https://librepathology.org/w/api.php?action=feedcontributions&feedformat=atom&user=Tate 2026-05-16T08:09:42Z User contributions MediaWiki 1.36.3 https://librepathology.org/w/index.php?title=Robbins_and_Cotran_9th_Edition_Questions&diff=39568 2015-09-03T13:03:30Z

<p>Tate: /* Chapter 11: Blood Vessels */</p> <hr /> <div>== Chapter 1: The Cell as a Unit of Health and Disease==<br /> <br /> {{hidden| Short Answer Questions |<br /> {{hidden|How much of the human genome is coding and what does it code?|Of the 3.2b basepairs, there are 20,000 genes that comprise about 1.5% of the genome that code for proteins (enzymes, structural components, and signaling molecules used to assemble and maintain all the cells in the body}}<br /> <br /> {{hidden|What do we think that the rest of the genome does?|80% of the genome binds proteins, implying that it is involved in regulating gene expression, related to the regulation of gene expression, often in a cell-type specific fashion.}}<br /> <br /> {{hidden|List the major classes of functional non-protein-coding sequences found in the human genome.|<br /> *1. Promoter &amp; enhancer<br /> *2. Chromatin binding site structures<br /> *3. non-coding regulatory RNAs<br /> *4. Mobile genetic elements (transposons)<br /> *5. telomeres<br /> *6. centromers. }}<br /> <br /> {{hidden|What are the two most common forms of DNA variation in the human genome?|<br /> *1) Single nucleotide polymorphisms (SNPs)<br /> *2) copy number variations (CNVs)}}<br /> <br /> {{hidden|What are the possible implications of SNPs.|<br /> *1) regulatory = alters gene expression<br /> *2) Correlation with disease states when in close proximity with altered genes<br /> *3) association used to define linkage disequilibrium,?}}<br /> <br /> {{hidden|Define epigenetics.|Heritable changes in gene expression which are not caused by alterations in DNA sequence.}}<br /> <br /> {{hidden|List the 6 types of epigenetic changes.|<br /> *1) Histone &amp; histone modifying factors (Histones organize chromatin into heterochromatin and euchromatin <br /> *2) histone methylation <br /> *3) histone acteylation<br /> *4)histone phosphorylation<br /> *5) DNA methylation<br /> *6) Chromatin organizing factors.}}<br /> <br /> {{hidden|What is the function of micro-RNA (mi-RNA)?|It does not encode protein, instead they function primarily to modulate the translation of target mRNAs into their corresponding proteins, and are responsible for post-transcriptional silencing of gene expression.}}<br /> <br /> {{hidden|What is knockdown technology?|The use of synthetic si-RNA (short RNA sequences) introduced into cells that serve as substrates for Dicer and interact with the RISC complex in a manner analogous to endogenous miRNAs, and are used to study gene function, and are being developed as therapeutic agents to silence pathogenic genes, e.g. oncogenic in neoplasms.}}<br /> <br /> {{hidden|What is long non coding RNA?|Lnc-RNA modulate gene expression by binding to regions of chromatin, restricting RNA polymerase access to coding genes within the region, and may exceed the number of mRNA's by 10-20 fold.}}<br /> <br /> {{hidden|What is XIST?|XIST is a lnc-RNA which is transcribed from the X-chromosome and plays an essential role in physiologic X chromosome inactivation, though not inactivated itself, it forms a repressive cloak on the X chromosome from which it is transcribed resulting in gene silencing.}}<br /> <br /> {{hidden|What are the cellular housekeeping functions?|1) protection from the environment, 2) nutrient acquisition, 3) communication, 4) movement, 5) renewal of senescent molecules, 6) molecular catabolism, 7) energy generation.}}<br /> <br /> {{hidden|List the cellular compartments and the role in the cell.|1) cytosol = metabolism, transport, protein translation, 2) Mitochondria = energy generation, apoptosis, 3) Rough ER = synthesis of membrane and secreted proteins, 4) Smooth ER / Golgi = protein modification, sorting, catabolism, 5)Nucleus = cell regulation, proliferation, DNA transcription, 6) Endosomes = intracellular transport and export, ingestion of extracellular substances, 7) Lysosomes = cellular catabolism, 8) peroxisomes = very long-chain fatty acid metabolism}}<br /> <br /> {{hidden|Describe the basic structure and functions of the cell membrane.| The plasma membrane is composed of a lipid bilayer of phospholipids studded with a variety of proteins and glycoproteins involved in ion and metabolite transport, fluid phase and receptor-mediated uptake of macromolecules, cell-ligand/cell matrix/cell-cell interactions.}}<br /> <br /> {{hidden|How are the large complexes in the plasma membrane formed?|They aggregate under the control of chaperone molecules in the RER or by lateral diffusion in the plasma membrane followed by complex formation in situ.}}<br /> <br /> {{hidden|What are aquaporins?|Special integral membrane proteins which augment passive water transport in tissues where water is transported in large volumes.}}<br /> <br /> {{hidden|How are channel and carrier proteins different?|Channel proteins created hydrophilic pores, permit rapid movement of solutes, restricted by size and charge, where Carrier proteins bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane, relatively slow transport.}}<br /> <br /> {{hidden|What is the &quot;multidrug resistance (MDR) protein&quot;?|A type of transporter ATPases which pumps polar compounds (e.g. chemo drugs) out of cells which may render cancer cells resistant to treatment.}}<br /> <br /> {{hidden|What are the two fundamental mechanisms of fluid or macromolecules by the cell (endocytosis)?|1)Caveolae -invaginations of the plasma membrane, 2) Pinocytosis/receptor mediated endocytosis - macromolecules bind to receptor and membranes invaginate around it.}}<br /> <br /> {{hidden|What is exocytosis?|It is the opposite process of pinocytosis, where the receptor bound macromolecule is move to the cell surface and released.}}<br /> <br /> {{hidden|Describe the difference between phagocytosis and transcytosis.|In phagocytosis microbes are ingested forming phagosomes, which fuse with lysosomes and become phagylosomes, releasing undigested residual material when fusing again with the external membrane, in contrast transcytosis the materials are carried across the cell membrane unaltered.}}<br /> <br /> {{hidden|List the three major classes of 3 cytoskeleton proteins.|1) Actin, 2)Intermediate filaments, 3)Microtubules}}<br /> <br /> {{hidden|Describe actin.|Actin - 5 to 9nm diam fibrils, G-actin polymerized into F-actin, the form double strands helices, which interact with myosin (filamentous protein).}}<br /> <br /> {{hidden|List the various intermediate filaments, which are 10nm in diameter.|1) Lamin A, B, and C (nuclear lamins of all cells, 2) Vimentin (mesenchymal), 3)Desmin (scaffold for actin/myosin), 4) Neurofilaments (axons of neurons), 5) Glial filament protein (glial cells), 6)Cytokeratins (acid and basic and vary based on cell type). }}<br /> <br /> {{hidden|Describe microtubules.|Microtubules are 25nm diam fibrils of dimers of a and b tubulin, with a negative end embedded in the centrosome near the nucleus, the + end grows or shrinks as needed. There are kinesins and dyneins motors that move stuff around the cell, also found in cilia and flagella.}}<br /> <br /> {{hidden|What is clatharin?|A molecule found in the cell membrane that when the cell membrane invaginates forming a basket like structure.}}<br /> <br /> {{hidden|List and describe the 3 main classifications of cell junctions.|1) Tight /occluding junctions - form a high resistance barrier to solute movement, and allows the cell to maintain polarity, 2) anchoring junctions / desmosomes - mechanically attach the cell and their cytoskeleton to other cells and the ECM (hemidesmosome), 3)communicating/gap junctions - mediate the passage of chemical or electrical signals from one cell to another.}}<br /> <br /> {{hidden|What is the &quot;unfolded protein response&quot;?| Excess accumulation of misfolded protiens, which exceed the capacity of the ER to edit and degrade them, leads to the the ER stress response (UPR) that triggers cell death through apoptosis.}}<br /> <br /> {{hidden|What cell organelle has a reactive hyperplasia with repeated exposure to phenobarbitol catabolism in the cytocrhome p450 system?|Smooth endoplasmic reticulum.}}<br /> <br /> {{hidden|List three main functions of mitochondria.|1) Energy generation, 2) intermediate metabolism (instead of ATP make intemediate that can be used to make lipids, nucleic acids, and proteins), 3) Cell death ( necrosis &amp; apoptosis)}}<br /> <br /> {{hidden|List and describe the four extracellular cell-cell signaling pathways based on the distance the signal travels.|1)Paracrine (immediate vicinity), 2) Autocrine (cell affecting itself), 3) Synaptic (neurons sending neurotransmitters at synapse), 4) endocrine (signals released elsewhere into bloodstream).}}<br /> <br /> {{hidden|What are the two characterizing features of stem cells?|Self renewal and asymmetric division (one daughter cell stays a stem cell)}}<br /> <br /> {{hidden|What are the two types of stem cells?|embryonic stem cells (inner cell mass of the blastocyst, totipotent), and tissue/adult stem cells (found in stem cell niches associated with specialized tissues, limited repetoire of differentiation = multipotent)}}<br /> <br /> {{hidden|What is the Warburg effect?|Increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation by the cell.}}<br /> <br /> {{hidden|Which CDKI's have selective effects on CDK4 and CDK6?|p15,p16,p17,and p19}}<br /> <br /> {{hidden|List some examples of signal transduction pathways.|1) Receptor tyrosine kinases (RTKs), 2) Nonreceptor tyrosine kinase, 3) G-protein coupled receptors, 4) nuclear receptors, 5)Notch family receptors, 6) Wnt protein ligands (Frizzled family receptors).}}<br /> <br /> {{hidden|Why does nuclear beta catenin occur in some neoplasms?|When Wnt ligand bins to frizzled it recruits Disheveled, this leads to the disruption of the wnt-ubiquitin complex, this stabilized pool of b-catening is then translocated to the nucleus forming a transcriptional complex}}<br /> <br /> {{hidden|On Page 19 there is a table of growth factors involved in regeneration and repair, please review.|}}<br /> <br /> {{hidden|Describe the function of cadherin.|}}<br /> <br /> {{hidden|What are the functions of the extracellular matrix?|Mechanical support, control of cell proliferation, scaffolding for tissue renewal, establishment of tissue microenvironments}}<br /> <br /> {{hidden|What are the two basic forms of the ECM?|interstitial matrix (fibrillar and non fibrillar collagen, fibronectin, elastin, proteoglycans, hyloronate, and other stuff), basement membrane (type IV collagen and laminin) }}<br /> <br /> {{hidden|What are the three proteins groups in the ECM?|1) fibrous structural proteins (collagen, elastins), 2) water hydrated gels (proteoglycans and hyaluronan), 3) adhesive glycoproteins (connect ECM to each other and other cells)}}<br /> <br /> {{hidden|Describe the structure of a protein that is dependent on vitamin C.|Collagen is composed of 3 seprate polypeptide chains braided into a rope like triple helix, lateral cross linking of the triple helices by lysyl oxidase (requires vitamin C) give it it's tensile strength. }}<br /> <br /> {{hidden|List three non-fibrillar collagens.|Type IV -basement membrane, Type IX - Fibrillar associated collagen with interrupted triple helices (FACIT), Type VII (provides anchoring fibrils to basement membrane beneath skin)}}<br /> <br /> {{hidden|Which structural protein is associated with Marfan syndrom?|Fibrillin synthetic defects, which wrap the elastin core. }}}}<br /> <br /> == Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury and Death ==<br /> Experimenting, please ignore<br /> {{hidden <br /> | headerstyle = text-align: left;<br /> | header = What are the four aspects of a disease?<br /> | content = *1. Etiology<br /> **Genetic - Inherited mutations and disease-associated gene variants, or polymorphisms.<br /> **Acquired - Infectious, nutritional, chemical and physical.<br /> *2. Pathogenesis - The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.<br /> *3. Morphological changes - The structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process.<br /> *4. Clinical Manifestations - Symptoms and signs of disease, as well as its clinical course and outcome.}}<br /> <br /> == Chapter 3 ==<br /> == Chapter 4 ==<br /> == Chapter 5 ==<br /> {{hidden|MC cause of spontaneous abortion is ?|&lt;center&gt;[[ A demonstrable chromosomal abnormality.]]&lt;/center&gt;}}<br /> <br /> {{hidden|1% of all newborn infants possess a gross chromosomal abnormality and 5% of people &lt;25y present with |&lt;center&gt;[[a genetic disease. ]]&lt;/center&gt;}}<br /> <br /> {{hidden|Mutation|&lt;center&gt;[[permanent change in the DNA, if affect germ cells are transmitted to the progeny ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe 4 broad categories of human genetic disorders:|&lt;center&gt;[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance<br /> ii. Often highly penetrant (large proportion of pop with gene has disease)<br /> b. Chromosomal disorders<br /> i. Structural or numerical alterations in autosomes and sex chromosomes<br /> ii. Uncommon, high penetrance<br /> c. Complex multigenic disorders<br /> i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present<br /> d. Single gene disorders with nonclassic patterns of inheritance (not mendelian)<br /> i. Disorders resulting from triplet repeat mutations<br /> ii. Mutations in mitochondrial DNA<br /> iii. Those influenced by genomic imprinting<br /> iv. Those influenced by gonadal mosaicism]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of a point mutation in a coding region?|[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid, b. Nonsense mutation – makes a stop codon ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of point mutation or deletion in a non-coding region.|&lt;center&gt;[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing &gt; failure to make mature RNA &gt; no translation]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of deletions and insertions.|&lt;center&gt;[[a.Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon<br /> i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene ]]}}<br /> <br /> {{hidden|List and describe the possible outcomes of trinucleotide repeat mutations.|[[a. Usually G&amp;C, dynamic and increase during gametogenesis, “RNA stutters”,b. Fragile X – CGG 250-4000, Huntinton’s Disease ]]}}<br /> <br /> {{hidden|List and describe three examples of inheritance of single gene mutations|[[a. AD – manifested in the heterologous state, one parent of index case is usually affected, males and females affected and both can transmit conditioni. De novo cases may not have affected parentii. Penetrance = fraction of people with gene who have the traitiii. Variable expressivity = those with mutant gene have variety of phenotypesiv. Often age of onset is delayed so can reproduce before die from diseasev. Biochem mechanisms1. Reduced production of a protein or dysfunctional/inactive protein2. Involved in regulation of complex metabolic pathyway subject to feedback inhibition3. Key structural proteins (collagen and cytoskeleton of RBC)a. May be a dominant negative , e.g. osteogenesis imperfecta4. Gain of function are rare, 2 formsa. Increased in proteins normal function (excess enzyme activity)b. Huntinton’s diseas (abn protein accumulates, toxic to neurons)b. ARi. Largest category – both alleles at a locus are mutated1. Expression is uniform, complete penetrance common, early onset, unaffected carrier family members, mostly enzymesc. X Linkedi. All sex linked, and almost all are recessive , if Y Chromosome affected usually infertile males &gt; no progenyii. Male expression b/c hemizygous, daughter carriers with variable phenotype because of lionization of 2nd X e.g G6DPiii. Dominant . vitamin D resistant rickets]]&lt;/center&gt;}}<br /> <br /> Stopped at P142<br /> <br /> == Chapter 6 ==<br /> == Chapter 7 ==<br /> == Chapter 8 ==<br /> == Chapter 9 ==<br /> == Chapter 10 ==<br /> == Chapter 11: Blood Vessels==<br /> * Describe the two principal mechanisms underlying vascular disease. <br /> * Describe the four main disease mechanisms and the vessels for which they have a predicliction. <br /> * Describe the three layers of artery/vein walls.<br /> * Describe how the media of arteries changes as one gets further away from the heart. <br /> * List 5 differences between arterial vessels and venous vessels. <br /> * List and briefly describe three vascular anomalies. <br /> * List 5 functions of endothelial cells. <br /> * List 5 factors which activate endothelial cells.<br /> * List 6 features of an activated endothelial cell. <br /> * Define endothelial dysfunction. <br /> * List 5 functions of vascular smooth muscle cells. <br /> * Describe how intimal thickening occurs in a healing vessel. <br /> * List 5 difference between neointimal and medial smooth muscle cells. <br /> * In a non diabetic what are the thresholds for diastolic and systolic blood pressure associated with increased atherosclerotic disease.<br /> * List 5 causes of secondary hypertension. <br /> * List 5 diseases resulting from hypertension. <br /> * About 50% of patients with hypertension die from what 3 diseases. <br /> * Define malignant hypertension, and list 3 ocular findings. <br /> * Describe how cardiac function affects blood pressure. <br /> * Describe how blood volume affects blood pressure. <br /> * Describe how peripheral resistance affects blood pressure<br /> * Describe the pathophysiological mechanisms associated with renovascular hypertension. <br /> * List some single gene disorders which cause secondary hypetension. <br /> * List four factors are mechanisms of essential hypertension. <br /> * List five vascular changes associated with hypertension. <br /> * Describe the differences between hyaline and hyperplastic arteriosclerosis. <br /> * List three types of arteriosclerosis. <br /> * What is Monckeberg medial sclerosis and how is it different from atherosclerosis?<br /> * What disease causes more morbidity and mortality than any other in the western world?<br /> * What is an atheromatous plaque?<br /> * List four constituitive risk factors for atherosclerosis.<br /> * List 5 modifiable risk factors for atherosclerosis.<br /> * List five non constituituve and non modifiable risk factors for atherosclerosis. <br /> * Briefly describe the pathogenic steps in atherosclerosis. <br /> * What are the two most important causes of endothelial dysfunction?<br /> * Briefly describe the role of LDL in atherosclerosis.<br /> * How does inflammation contribute to atherosclerosis?<br /> * List three viruses for which there is limited evidence of contribution to atherosclerosis.<br /> * How do smooth muscle cells contribute to atherosclerosis?<br /> * What are the differences between a fatty streak and a atherosclerotic plaque?<br /> * List five most common locations of atherosclerotic plaques.<br /> * What are the three main components of an atherosclerotic plaque.<br /> * What is neovascularization of an atherosclerotic plaque?<br /> * What four clinically significant changes can occur in an atherosclerotic plaque?<br /> * What are the four major consequences of atherosclerosis?<br /> * Define critical stenosis and the possible sequelae there of?<br /> * What is the catch 22 of a fibrous plaque?<br /> * What is one possible explanation for the abrupt rise in MIs after 9-11.<br /> * What four basic mechanisms cause vasoconstriction?<br /> * What are the possible sequelae of thrombi in a coronary artery?<br /> * Classify aneurysms.<br /> * List three syndromes where the connective tissue quality results in aneurysms.<br /> * Briefly describe how collagen degradation and synthesis maintained.<br /> * What is cystic medial degeneration and how does it relate to aneurysm formation?<br /> * How does syphilis cause aneurysms of the aorta, and how to most of the patients die?<br /> * What are the two most important causes of aortic aneurysms?<br /> * What is a mycotic aneuryms and what are the three possible origins?<br /> * Who most classically gets a AAA and where is it?<br /> * List three variants of AAA and briefly describe each.<br /> * What are the four most common clinical manifestations of a AAA aside from a palpable pulsating abdominal mass. <br /> * Describe how the risk of rupture of a AAA increases with size. <br /> * What is the most common cause of thoracic aneurysm, and describe 5 features of this syndrome. <br /> * List 5 signs or symptoms of thoracic aneurysm.<br /> * What two groups of patients have aortic dissections?<br /> * What is the most significant risk factor for aortic dissection?<br /> * Describe the difference between an aneurysm and a dissection.<br /> * Classify aortic dissections. <br /> * Classify vasculitides.<br /> * List 5 defining features of Giant cell arteritis.<br /> * List 5 defining features of granulomatosis with polyangitis. <br /> * List 5 defining features of Churg-Strauss syndrome. <br /> * List 5 defining features of Polyarteritis nododum.<br /> * List 5 defining features of Leukocytoclastic vasculitis. <br /> * List 5 defining features of Beurger disease.<br /> * List 5 defining features of Behcet disease. <br /> * List 5 defining features of Takayasu arteritis. <br /> * List 5 defining features of microscopic polyangitis.<br /> * List 5 defining features of Kawasaki disease. <br /> * List 5 immune complext mediated vasculitides. <br /> * List 3 granulomatous vasculitides. <br /> * What is a pauci immune vasculitis and give three examples. <br /> * List some causes of infectious vasculitis.<br /> * List 5 features of Raynaud's phenomenon. <br /> * What is the difference between primary and secondary Raynaud's?<br /> * What is Takotsubo cardiomyopathy?<br /> * List 5 causes of myocardial vessel vasospasm.<br /> * What are varicose veins? List three risk factors. List 5 clinical feautures. <br /> * What three sites are venous varicosities most commonly found?<br /> * What are the 5 most common sites of venous thrombosis?<br /> *<br /> <br /> == Chapter 12 ==<br /> == Chapter 13 ==<br /> == Chapter 14 ==<br /> == Chapter 15 ==<br /> == Chapter 16 ==<br /> == Chapter 17 ==<br /> == Chapter 18 ==<br /> == Chapter 19 ==<br /> == Chapter 20 ==<br /> == Chapter 21 ==<br /> == Chapter 22 ==<br /> ==[[Breast (CH 23)]]==<br /> <br /> == Chapter 24 ==<br /> == Chapter 25 ==<br /> == Chapter 26 ==<br /> == Chapter 27 ==<br /> == Chapter 28 ==<br /> == Chapter 29 ==</div>

Tate https://librepathology.org/w/index.php?title=Robbins_and_Cotran_9th_Edition_Questions&diff=39567 2015-09-03T12:58:41Z

<p>Tate: /* Chapter 11: Blood Vessels */</p> <hr /> <div>== Chapter 1: The Cell as a Unit of Health and Disease==<br /> <br /> {{hidden| Short Answer Questions |<br /> {{hidden|How much of the human genome is coding and what does it code?|Of the 3.2b basepairs, there are 20,000 genes that comprise about 1.5% of the genome that code for proteins (enzymes, structural components, and signaling molecules used to assemble and maintain all the cells in the body}}<br /> <br /> {{hidden|What do we think that the rest of the genome does?|80% of the genome binds proteins, implying that it is involved in regulating gene expression, related to the regulation of gene expression, often in a cell-type specific fashion.}}<br /> <br /> {{hidden|List the major classes of functional non-protein-coding sequences found in the human genome.|<br /> *1. Promoter &amp; enhancer<br /> *2. Chromatin binding site structures<br /> *3. non-coding regulatory RNAs<br /> *4. Mobile genetic elements (transposons)<br /> *5. telomeres<br /> *6. centromers. }}<br /> <br /> {{hidden|What are the two most common forms of DNA variation in the human genome?|<br /> *1) Single nucleotide polymorphisms (SNPs)<br /> *2) copy number variations (CNVs)}}<br /> <br /> {{hidden|What are the possible implications of SNPs.|<br /> *1) regulatory = alters gene expression<br /> *2) Correlation with disease states when in close proximity with altered genes<br /> *3) association used to define linkage disequilibrium,?}}<br /> <br /> {{hidden|Define epigenetics.|Heritable changes in gene expression which are not caused by alterations in DNA sequence.}}<br /> <br /> {{hidden|List the 6 types of epigenetic changes.|<br /> *1) Histone &amp; histone modifying factors (Histones organize chromatin into heterochromatin and euchromatin <br /> *2) histone methylation <br /> *3) histone acteylation<br /> *4)histone phosphorylation<br /> *5) DNA methylation<br /> *6) Chromatin organizing factors.}}<br /> <br /> {{hidden|What is the function of micro-RNA (mi-RNA)?|It does not encode protein, instead they function primarily to modulate the translation of target mRNAs into their corresponding proteins, and are responsible for post-transcriptional silencing of gene expression.}}<br /> <br /> {{hidden|What is knockdown technology?|The use of synthetic si-RNA (short RNA sequences) introduced into cells that serve as substrates for Dicer and interact with the RISC complex in a manner analogous to endogenous miRNAs, and are used to study gene function, and are being developed as therapeutic agents to silence pathogenic genes, e.g. oncogenic in neoplasms.}}<br /> <br /> {{hidden|What is long non coding RNA?|Lnc-RNA modulate gene expression by binding to regions of chromatin, restricting RNA polymerase access to coding genes within the region, and may exceed the number of mRNA's by 10-20 fold.}}<br /> <br /> {{hidden|What is XIST?|XIST is a lnc-RNA which is transcribed from the X-chromosome and plays an essential role in physiologic X chromosome inactivation, though not inactivated itself, it forms a repressive cloak on the X chromosome from which it is transcribed resulting in gene silencing.}}<br /> <br /> {{hidden|What are the cellular housekeeping functions?|1) protection from the environment, 2) nutrient acquisition, 3) communication, 4) movement, 5) renewal of senescent molecules, 6) molecular catabolism, 7) energy generation.}}<br /> <br /> {{hidden|List the cellular compartments and the role in the cell.|1) cytosol = metabolism, transport, protein translation, 2) Mitochondria = energy generation, apoptosis, 3) Rough ER = synthesis of membrane and secreted proteins, 4) Smooth ER / Golgi = protein modification, sorting, catabolism, 5)Nucleus = cell regulation, proliferation, DNA transcription, 6) Endosomes = intracellular transport and export, ingestion of extracellular substances, 7) Lysosomes = cellular catabolism, 8) peroxisomes = very long-chain fatty acid metabolism}}<br /> <br /> {{hidden|Describe the basic structure and functions of the cell membrane.| The plasma membrane is composed of a lipid bilayer of phospholipids studded with a variety of proteins and glycoproteins involved in ion and metabolite transport, fluid phase and receptor-mediated uptake of macromolecules, cell-ligand/cell matrix/cell-cell interactions.}}<br /> <br /> {{hidden|How are the large complexes in the plasma membrane formed?|They aggregate under the control of chaperone molecules in the RER or by lateral diffusion in the plasma membrane followed by complex formation in situ.}}<br /> <br /> {{hidden|What are aquaporins?|Special integral membrane proteins which augment passive water transport in tissues where water is transported in large volumes.}}<br /> <br /> {{hidden|How are channel and carrier proteins different?|Channel proteins created hydrophilic pores, permit rapid movement of solutes, restricted by size and charge, where Carrier proteins bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane, relatively slow transport.}}<br /> <br /> {{hidden|What is the &quot;multidrug resistance (MDR) protein&quot;?|A type of transporter ATPases which pumps polar compounds (e.g. chemo drugs) out of cells which may render cancer cells resistant to treatment.}}<br /> <br /> {{hidden|What are the two fundamental mechanisms of fluid or macromolecules by the cell (endocytosis)?|1)Caveolae -invaginations of the plasma membrane, 2) Pinocytosis/receptor mediated endocytosis - macromolecules bind to receptor and membranes invaginate around it.}}<br /> <br /> {{hidden|What is exocytosis?|It is the opposite process of pinocytosis, where the receptor bound macromolecule is move to the cell surface and released.}}<br /> <br /> {{hidden|Describe the difference between phagocytosis and transcytosis.|In phagocytosis microbes are ingested forming phagosomes, which fuse with lysosomes and become phagylosomes, releasing undigested residual material when fusing again with the external membrane, in contrast transcytosis the materials are carried across the cell membrane unaltered.}}<br /> <br /> {{hidden|List the three major classes of 3 cytoskeleton proteins.|1) Actin, 2)Intermediate filaments, 3)Microtubules}}<br /> <br /> {{hidden|Describe actin.|Actin - 5 to 9nm diam fibrils, G-actin polymerized into F-actin, the form double strands helices, which interact with myosin (filamentous protein).}}<br /> <br /> {{hidden|List the various intermediate filaments, which are 10nm in diameter.|1) Lamin A, B, and C (nuclear lamins of all cells, 2) Vimentin (mesenchymal), 3)Desmin (scaffold for actin/myosin), 4) Neurofilaments (axons of neurons), 5) Glial filament protein (glial cells), 6)Cytokeratins (acid and basic and vary based on cell type). }}<br /> <br /> {{hidden|Describe microtubules.|Microtubules are 25nm diam fibrils of dimers of a and b tubulin, with a negative end embedded in the centrosome near the nucleus, the + end grows or shrinks as needed. There are kinesins and dyneins motors that move stuff around the cell, also found in cilia and flagella.}}<br /> <br /> {{hidden|What is clatharin?|A molecule found in the cell membrane that when the cell membrane invaginates forming a basket like structure.}}<br /> <br /> {{hidden|List and describe the 3 main classifications of cell junctions.|1) Tight /occluding junctions - form a high resistance barrier to solute movement, and allows the cell to maintain polarity, 2) anchoring junctions / desmosomes - mechanically attach the cell and their cytoskeleton to other cells and the ECM (hemidesmosome), 3)communicating/gap junctions - mediate the passage of chemical or electrical signals from one cell to another.}}<br /> <br /> {{hidden|What is the &quot;unfolded protein response&quot;?| Excess accumulation of misfolded protiens, which exceed the capacity of the ER to edit and degrade them, leads to the the ER stress response (UPR) that triggers cell death through apoptosis.}}<br /> <br /> {{hidden|What cell organelle has a reactive hyperplasia with repeated exposure to phenobarbitol catabolism in the cytocrhome p450 system?|Smooth endoplasmic reticulum.}}<br /> <br /> {{hidden|List three main functions of mitochondria.|1) Energy generation, 2) intermediate metabolism (instead of ATP make intemediate that can be used to make lipids, nucleic acids, and proteins), 3) Cell death ( necrosis &amp; apoptosis)}}<br /> <br /> {{hidden|List and describe the four extracellular cell-cell signaling pathways based on the distance the signal travels.|1)Paracrine (immediate vicinity), 2) Autocrine (cell affecting itself), 3) Synaptic (neurons sending neurotransmitters at synapse), 4) endocrine (signals released elsewhere into bloodstream).}}<br /> <br /> {{hidden|What are the two characterizing features of stem cells?|Self renewal and asymmetric division (one daughter cell stays a stem cell)}}<br /> <br /> {{hidden|What are the two types of stem cells?|embryonic stem cells (inner cell mass of the blastocyst, totipotent), and tissue/adult stem cells (found in stem cell niches associated with specialized tissues, limited repetoire of differentiation = multipotent)}}<br /> <br /> {{hidden|What is the Warburg effect?|Increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation by the cell.}}<br /> <br /> {{hidden|Which CDKI's have selective effects on CDK4 and CDK6?|p15,p16,p17,and p19}}<br /> <br /> {{hidden|List some examples of signal transduction pathways.|1) Receptor tyrosine kinases (RTKs), 2) Nonreceptor tyrosine kinase, 3) G-protein coupled receptors, 4) nuclear receptors, 5)Notch family receptors, 6) Wnt protein ligands (Frizzled family receptors).}}<br /> <br /> {{hidden|Why does nuclear beta catenin occur in some neoplasms?|When Wnt ligand bins to frizzled it recruits Disheveled, this leads to the disruption of the wnt-ubiquitin complex, this stabilized pool of b-catening is then translocated to the nucleus forming a transcriptional complex}}<br /> <br /> {{hidden|On Page 19 there is a table of growth factors involved in regeneration and repair, please review.|}}<br /> <br /> {{hidden|Describe the function of cadherin.|}}<br /> <br /> {{hidden|What are the functions of the extracellular matrix?|Mechanical support, control of cell proliferation, scaffolding for tissue renewal, establishment of tissue microenvironments}}<br /> <br /> {{hidden|What are the two basic forms of the ECM?|interstitial matrix (fibrillar and non fibrillar collagen, fibronectin, elastin, proteoglycans, hyloronate, and other stuff), basement membrane (type IV collagen and laminin) }}<br /> <br /> {{hidden|What are the three proteins groups in the ECM?|1) fibrous structural proteins (collagen, elastins), 2) water hydrated gels (proteoglycans and hyaluronan), 3) adhesive glycoproteins (connect ECM to each other and other cells)}}<br /> <br /> {{hidden|Describe the structure of a protein that is dependent on vitamin C.|Collagen is composed of 3 seprate polypeptide chains braided into a rope like triple helix, lateral cross linking of the triple helices by lysyl oxidase (requires vitamin C) give it it's tensile strength. }}<br /> <br /> {{hidden|List three non-fibrillar collagens.|Type IV -basement membrane, Type IX - Fibrillar associated collagen with interrupted triple helices (FACIT), Type VII (provides anchoring fibrils to basement membrane beneath skin)}}<br /> <br /> {{hidden|Which structural protein is associated with Marfan syndrom?|Fibrillin synthetic defects, which wrap the elastin core. }}}}<br /> <br /> == Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury and Death ==<br /> Experimenting, please ignore<br /> {{hidden <br /> | headerstyle = text-align: left;<br /> | header = What are the four aspects of a disease?<br /> | content = *1. Etiology<br /> **Genetic - Inherited mutations and disease-associated gene variants, or polymorphisms.<br /> **Acquired - Infectious, nutritional, chemical and physical.<br /> *2. Pathogenesis - The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.<br /> *3. Morphological changes - The structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process.<br /> *4. Clinical Manifestations - Symptoms and signs of disease, as well as its clinical course and outcome.}}<br /> <br /> == Chapter 3 ==<br /> == Chapter 4 ==<br /> == Chapter 5 ==<br /> {{hidden|MC cause of spontaneous abortion is ?|&lt;center&gt;[[ A demonstrable chromosomal abnormality.]]&lt;/center&gt;}}<br /> <br /> {{hidden|1% of all newborn infants possess a gross chromosomal abnormality and 5% of people &lt;25y present with |&lt;center&gt;[[a genetic disease. ]]&lt;/center&gt;}}<br /> <br /> {{hidden|Mutation|&lt;center&gt;[[permanent change in the DNA, if affect germ cells are transmitted to the progeny ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe 4 broad categories of human genetic disorders:|&lt;center&gt;[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance<br /> ii. Often highly penetrant (large proportion of pop with gene has disease)<br /> b. Chromosomal disorders<br /> i. Structural or numerical alterations in autosomes and sex chromosomes<br /> ii. Uncommon, high penetrance<br /> c. Complex multigenic disorders<br /> i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present<br /> d. Single gene disorders with nonclassic patterns of inheritance (not mendelian)<br /> i. Disorders resulting from triplet repeat mutations<br /> ii. Mutations in mitochondrial DNA<br /> iii. Those influenced by genomic imprinting<br /> iv. Those influenced by gonadal mosaicism]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of a point mutation in a coding region?|[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid, b. Nonsense mutation – makes a stop codon ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of point mutation or deletion in a non-coding region.|&lt;center&gt;[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing &gt; failure to make mature RNA &gt; no translation]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of deletions and insertions.|&lt;center&gt;[[a.Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon<br /> i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene ]]}}<br /> <br /> {{hidden|List and describe the possible outcomes of trinucleotide repeat mutations.|[[a. Usually G&amp;C, dynamic and increase during gametogenesis, “RNA stutters”,b. Fragile X – CGG 250-4000, Huntinton’s Disease ]]}}<br /> <br /> {{hidden|List and describe three examples of inheritance of single gene mutations|[[a. AD – manifested in the heterologous state, one parent of index case is usually affected, males and females affected and both can transmit conditioni. De novo cases may not have affected parentii. Penetrance = fraction of people with gene who have the traitiii. Variable expressivity = those with mutant gene have variety of phenotypesiv. Often age of onset is delayed so can reproduce before die from diseasev. Biochem mechanisms1. Reduced production of a protein or dysfunctional/inactive protein2. Involved in regulation of complex metabolic pathyway subject to feedback inhibition3. Key structural proteins (collagen and cytoskeleton of RBC)a. May be a dominant negative , e.g. osteogenesis imperfecta4. Gain of function are rare, 2 formsa. Increased in proteins normal function (excess enzyme activity)b. Huntinton’s diseas (abn protein accumulates, toxic to neurons)b. ARi. Largest category – both alleles at a locus are mutated1. Expression is uniform, complete penetrance common, early onset, unaffected carrier family members, mostly enzymesc. X Linkedi. All sex linked, and almost all are recessive , if Y Chromosome affected usually infertile males &gt; no progenyii. Male expression b/c hemizygous, daughter carriers with variable phenotype because of lionization of 2nd X e.g G6DPiii. Dominant . vitamin D resistant rickets]]&lt;/center&gt;}}<br /> <br /> Stopped at P142<br /> <br /> == Chapter 6 ==<br /> == Chapter 7 ==<br /> == Chapter 8 ==<br /> == Chapter 9 ==<br /> == Chapter 10 ==<br /> == Chapter 11: Blood Vessels==<br /> * Describe the two principal mechanisms underlying vascular disease. <br /> * Describe the four main disease mechanisms and the vessels for which they have a predicliction. <br /> * Describe the three layers of artery/vein walls.<br /> * Describe how the media of arteries changes as one gets further away from the heart. <br /> * List 5 differences between arterial vessels and venous vessels. <br /> * List and briefly describe three vascular anomalies. <br /> * List 5 functions of endothelial cells. <br /> * List 5 factors which activate endothelial cells.<br /> * List 6 features of an activated endothelial cell. <br /> * Define endothelial dysfunction. <br /> * List 5 functions of vascular smooth muscle cells. <br /> * Describe how intimal thickening occurs in a healing vessel. <br /> * List 5 difference between neointimal and medial smooth muscle cells. <br /> * In a non diabetic what are the thresholds for diastolic and systolic blood pressure associated with increased atherosclerotic disease.<br /> * List 5 causes of secondary hypertension. <br /> * List 5 diseases resulting from hypertension. <br /> * About 50% of patients with hypertension die from what 3 diseases. <br /> * Define malignant hypertension, and list 3 ocular findings. <br /> * Describe how cardiac function affects blood pressure. <br /> * Describe how blood volume affects blood pressure. <br /> * Describe how peripheral resistance affects blood pressure<br /> * Describe the pathophysiological mechanisms associated with renovascular hypertension. <br /> * List some single gene disorders which cause secondary hypetension. <br /> * List four factors are mechanisms of essential hypertension. <br /> * List five vascular changes associated with hypertension. <br /> * Describe the differences between hyaline and hyperplastic arteriosclerosis. <br /> * List three types of arteriosclerosis. <br /> * What is Monckeberg medial sclerosis and how is it different from atherosclerosis?<br /> * What disease causes more morbidity and mortality than any other in the western world?<br /> * What is an atheromatous plaque?<br /> * List four constituitive risk factors for atherosclerosis.<br /> * List 5 modifiable risk factors for atherosclerosis.<br /> * List five non constituituve and non modifiable risk factors for atherosclerosis. <br /> * Briefly describe the pathogenic steps in atherosclerosis. <br /> * What are the two most important causes of endothelial dysfunction?<br /> * Briefly describe the role of LDL in atherosclerosis.<br /> * How does inflammation contribute to atherosclerosis?<br /> * List three viruses for which there is limited evidence of contribution to atherosclerosis.<br /> * How do smooth muscle cells contribute to atherosclerosis?<br /> * What are the differences between a fatty streak and a atherosclerotic plaque?<br /> * List five most common locations of atherosclerotic plaques.<br /> * What are the three main components of an atherosclerotic plaque.<br /> * What is neovascularization of an atherosclerotic plaque?<br /> * What four clinically significant changes can occur in an atherosclerotic plaque?<br /> * What are the four major consequences of atherosclerosis?<br /> * Define critical stenosis and the possible sequelae there of?<br /> * What is the catch 22 of a fibrous plaque?<br /> * What is one possible explanation for the abrupt rise in MIs after 9-11.<br /> * What four basic mechanisms cause vasoconstriction?<br /> * What are the possible sequelae of thrombi in a coronary artery?<br /> * Classify aneurysms.<br /> * List three syndromes where the connective tissue quality results in aneurysms.<br /> * Briefly describe how collagen degradation and synthesis maintained.<br /> * What is cystic medial degeneration and how does it relate to aneurysm formation?<br /> * How does syphilis cause aneurysms of the aorta, and how to most of the patients die?<br /> * What are the two most important causes of aortic aneurysms?<br /> * What is a mycotic aneuryms and what are the three possible origins?<br /> * Who most classically gets a AAA and where is it?<br /> * List three variants of AAA and briefly describe each.<br /> * What are the four most common clinical manifestations of a AAA aside from a palpable pulsating abdominal mass. <br /> * Describe how the risk of rupture of a AAA increases with size. <br /> * What is the most common cause of thoracic aneurysm, and describe 5 features of this syndrome. <br /> * List 5 signs or symptoms of thoracic aneurysm.<br /> * What two groups of patients have aortic dissections?<br /> * What is the most significant risk factor for aortic dissection?<br /> * Describe the difference between an aneurysm and a dissection.<br /> * Classify aortic dissections. <br /> * Classify vasculitides.<br /> * List 5 defining features of Giant cell arteritis.<br /> * List 5 defining features of granulomatosis with polyangitis. <br /> * List 5 defining features of Churg-Strauss syndrome. <br /> * List 5 defining features of Polyarteritis nododum.<br /> * List 5 defining features of Leukocytoclastic vasculitis. <br /> * List 5 defining features of Beurger disease.<br /> * List 5 defining features of Behcet disease. <br /> * List 5 defining features of Takayasu arteritis. <br /> * List 5 defining features of microscopic polyangitis.<br /> * List 5 defining features of Kawasaki disease. <br /> * List 5 immune complext mediated vasculitides. <br /> * List 3 granulomatous vasculitides. <br /> * What is a pauci immune vasculitis and give three examples. <br /> * List some causes of infectious vasculitis.<br /> * List 5 features of Raynaud's phenomenon. <br /> * What is the difference between primary and secondary Raynaud's?<br /> * What is Takotsubo cardiomyopathy?<br /> * List 5 causes of myocardial vessel vasospasm.<br /> <br /> == Chapter 12 ==<br /> == Chapter 13 ==<br /> == Chapter 14 ==<br /> == Chapter 15 ==<br /> == Chapter 16 ==<br /> == Chapter 17 ==<br /> == Chapter 18 ==<br /> == Chapter 19 ==<br /> == Chapter 20 ==<br /> == Chapter 21 ==<br /> == Chapter 22 ==<br /> ==[[Breast (CH 23)]]==<br /> <br /> == Chapter 24 ==<br /> == Chapter 25 ==<br /> == Chapter 26 ==<br /> == Chapter 27 ==<br /> == Chapter 28 ==<br /> == Chapter 29 ==</div>

Tate https://librepathology.org/w/index.php?title=Robbins_and_Cotran_9th_Edition_Questions&diff=39560 2015-09-03T11:19:05Z

<p>Tate: /* Chapter 11 */</p> <hr /> <div>== Chapter 1: The Cell as a Unit of Health and Disease==<br /> <br /> {{hidden| Short Answer Questions |<br /> {{hidden|How much of the human genome is coding and what does it code?|Of the 3.2b basepairs, there are 20,000 genes that comprise about 1.5% of the genome that code for proteins (enzymes, structural components, and signaling molecules used to assemble and maintain all the cells in the body}}<br /> <br /> {{hidden|What do we think that the rest of the genome does?|80% of the genome binds proteins, implying that it is involved in regulating gene expression, related to the regulation of gene expression, often in a cell-type specific fashion.}}<br /> <br /> {{hidden|List the major classes of functional non-protein-coding sequences found in the human genome.|<br /> *1. Promoter &amp; enhancer<br /> *2. Chromatin binding site structures<br /> *3. non-coding regulatory RNAs<br /> *4. Mobile genetic elements (transposons)<br /> *5. telomeres<br /> *6. centromers. }}<br /> <br /> {{hidden|What are the two most common forms of DNA variation in the human genome?|<br /> *1) Single nucleotide polymorphisms (SNPs)<br /> *2) copy number variations (CNVs)}}<br /> <br /> {{hidden|What are the possible implications of SNPs.|<br /> *1) regulatory = alters gene expression<br /> *2) Correlation with disease states when in close proximity with altered genes<br /> *3) association used to define linkage disequilibrium,?}}<br /> <br /> {{hidden|Define epigenetics.|Heritable changes in gene expression which are not caused by alterations in DNA sequence.}}<br /> <br /> {{hidden|List the 6 types of epigenetic changes.|<br /> *1) Histone &amp; histone modifying factors (Histones organize chromatin into heterochromatin and euchromatin <br /> *2) histone methylation <br /> *3) histone acteylation<br /> *4)histone phosphorylation<br /> *5) DNA methylation<br /> *6) Chromatin organizing factors.}}<br /> <br /> {{hidden|What is the function of micro-RNA (mi-RNA)?|It does not encode protein, instead they function primarily to modulate the translation of target mRNAs into their corresponding proteins, and are responsible for post-transcriptional silencing of gene expression.}}<br /> <br /> {{hidden|What is knockdown technology?|The use of synthetic si-RNA (short RNA sequences) introduced into cells that serve as substrates for Dicer and interact with the RISC complex in a manner analogous to endogenous miRNAs, and are used to study gene function, and are being developed as therapeutic agents to silence pathogenic genes, e.g. oncogenic in neoplasms.}}<br /> <br /> {{hidden|What is long non coding RNA?|Lnc-RNA modulate gene expression by binding to regions of chromatin, restricting RNA polymerase access to coding genes within the region, and may exceed the number of mRNA's by 10-20 fold.}}<br /> <br /> {{hidden|What is XIST?|XIST is a lnc-RNA which is transcribed from the X-chromosome and plays an essential role in physiologic X chromosome inactivation, though not inactivated itself, it forms a repressive cloak on the X chromosome from which it is transcribed resulting in gene silencing.}}<br /> <br /> {{hidden|What are the cellular housekeeping functions?|1) protection from the environment, 2) nutrient acquisition, 3) communication, 4) movement, 5) renewal of senescent molecules, 6) molecular catabolism, 7) energy generation.}}<br /> <br /> {{hidden|List the cellular compartments and the role in the cell.|1) cytosol = metabolism, transport, protein translation, 2) Mitochondria = energy generation, apoptosis, 3) Rough ER = synthesis of membrane and secreted proteins, 4) Smooth ER / Golgi = protein modification, sorting, catabolism, 5)Nucleus = cell regulation, proliferation, DNA transcription, 6) Endosomes = intracellular transport and export, ingestion of extracellular substances, 7) Lysosomes = cellular catabolism, 8) peroxisomes = very long-chain fatty acid metabolism}}<br /> <br /> {{hidden|Describe the basic structure and functions of the cell membrane.| The plasma membrane is composed of a lipid bilayer of phospholipids studded with a variety of proteins and glycoproteins involved in ion and metabolite transport, fluid phase and receptor-mediated uptake of macromolecules, cell-ligand/cell matrix/cell-cell interactions.}}<br /> <br /> {{hidden|How are the large complexes in the plasma membrane formed?|They aggregate under the control of chaperone molecules in the RER or by lateral diffusion in the plasma membrane followed by complex formation in situ.}}<br /> <br /> {{hidden|What are aquaporins?|Special integral membrane proteins which augment passive water transport in tissues where water is transported in large volumes.}}<br /> <br /> {{hidden|How are channel and carrier proteins different?|Channel proteins created hydrophilic pores, permit rapid movement of solutes, restricted by size and charge, where Carrier proteins bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane, relatively slow transport.}}<br /> <br /> {{hidden|What is the &quot;multidrug resistance (MDR) protein&quot;?|A type of transporter ATPases which pumps polar compounds (e.g. chemo drugs) out of cells which may render cancer cells resistant to treatment.}}<br /> <br /> {{hidden|What are the two fundamental mechanisms of fluid or macromolecules by the cell (endocytosis)?|1)Caveolae -invaginations of the plasma membrane, 2) Pinocytosis/receptor mediated endocytosis - macromolecules bind to receptor and membranes invaginate around it.}}<br /> <br /> {{hidden|What is exocytosis?|It is the opposite process of pinocytosis, where the receptor bound macromolecule is move to the cell surface and released.}}<br /> <br /> {{hidden|Describe the difference between phagocytosis and transcytosis.|In phagocytosis microbes are ingested forming phagosomes, which fuse with lysosomes and become phagylosomes, releasing undigested residual material when fusing again with the external membrane, in contrast transcytosis the materials are carried across the cell membrane unaltered.}}<br /> <br /> {{hidden|List the three major classes of 3 cytoskeleton proteins.|1) Actin, 2)Intermediate filaments, 3)Microtubules}}<br /> <br /> {{hidden|Describe actin.|Actin - 5 to 9nm diam fibrils, G-actin polymerized into F-actin, the form double strands helices, which interact with myosin (filamentous protein).}}<br /> <br /> {{hidden|List the various intermediate filaments, which are 10nm in diameter.|1) Lamin A, B, and C (nuclear lamins of all cells, 2) Vimentin (mesenchymal), 3)Desmin (scaffold for actin/myosin), 4) Neurofilaments (axons of neurons), 5) Glial filament protein (glial cells), 6)Cytokeratins (acid and basic and vary based on cell type). }}<br /> <br /> {{hidden|Describe microtubules.|Microtubules are 25nm diam fibrils of dimers of a and b tubulin, with a negative end embedded in the centrosome near the nucleus, the + end grows or shrinks as needed. There are kinesins and dyneins motors that move stuff around the cell, also found in cilia and flagella.}}<br /> <br /> {{hidden|What is clatharin?|A molecule found in the cell membrane that when the cell membrane invaginates forming a basket like structure.}}<br /> <br /> {{hidden|List and describe the 3 main classifications of cell junctions.|1) Tight /occluding junctions - form a high resistance barrier to solute movement, and allows the cell to maintain polarity, 2) anchoring junctions / desmosomes - mechanically attach the cell and their cytoskeleton to other cells and the ECM (hemidesmosome), 3)communicating/gap junctions - mediate the passage of chemical or electrical signals from one cell to another.}}<br /> <br /> {{hidden|What is the &quot;unfolded protein response&quot;?| Excess accumulation of misfolded protiens, which exceed the capacity of the ER to edit and degrade them, leads to the the ER stress response (UPR) that triggers cell death through apoptosis.}}<br /> <br /> {{hidden|What cell organelle has a reactive hyperplasia with repeated exposure to phenobarbitol catabolism in the cytocrhome p450 system?|Smooth endoplasmic reticulum.}}<br /> <br /> {{hidden|List three main functions of mitochondria.|1) Energy generation, 2) intermediate metabolism (instead of ATP make intemediate that can be used to make lipids, nucleic acids, and proteins), 3) Cell death ( necrosis &amp; apoptosis)}}<br /> <br /> {{hidden|List and describe the four extracellular cell-cell signaling pathways based on the distance the signal travels.|1)Paracrine (immediate vicinity), 2) Autocrine (cell affecting itself), 3) Synaptic (neurons sending neurotransmitters at synapse), 4) endocrine (signals released elsewhere into bloodstream).}}<br /> <br /> {{hidden|What are the two characterizing features of stem cells?|Self renewal and asymmetric division (one daughter cell stays a stem cell)}}<br /> <br /> {{hidden|What are the two types of stem cells?|embryonic stem cells (inner cell mass of the blastocyst, totipotent), and tissue/adult stem cells (found in stem cell niches associated with specialized tissues, limited repetoire of differentiation = multipotent)}}<br /> <br /> {{hidden|What is the Warburg effect?|Increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation by the cell.}}<br /> <br /> {{hidden|Which CDKI's have selective effects on CDK4 and CDK6?|p15,p16,p17,and p19}}<br /> <br /> {{hidden|List some examples of signal transduction pathways.|1) Receptor tyrosine kinases (RTKs), 2) Nonreceptor tyrosine kinase, 3) G-protein coupled receptors, 4) nuclear receptors, 5)Notch family receptors, 6) Wnt protein ligands (Frizzled family receptors).}}<br /> <br /> {{hidden|Why does nuclear beta catenin occur in some neoplasms?|When Wnt ligand bins to frizzled it recruits Disheveled, this leads to the disruption of the wnt-ubiquitin complex, this stabilized pool of b-catening is then translocated to the nucleus forming a transcriptional complex}}<br /> <br /> {{hidden|On Page 19 there is a table of growth factors involved in regeneration and repair, please review.|}}<br /> <br /> {{hidden|Describe the function of cadherin.|}}<br /> <br /> {{hidden|What are the functions of the extracellular matrix?|Mechanical support, control of cell proliferation, scaffolding for tissue renewal, establishment of tissue microenvironments}}<br /> <br /> {{hidden|What are the two basic forms of the ECM?|interstitial matrix (fibrillar and non fibrillar collagen, fibronectin, elastin, proteoglycans, hyloronate, and other stuff), basement membrane (type IV collagen and laminin) }}<br /> <br /> {{hidden|What are the three proteins groups in the ECM?|1) fibrous structural proteins (collagen, elastins), 2) water hydrated gels (proteoglycans and hyaluronan), 3) adhesive glycoproteins (connect ECM to each other and other cells)}}<br /> <br /> {{hidden|Describe the structure of a protein that is dependent on vitamin C.|Collagen is composed of 3 seprate polypeptide chains braided into a rope like triple helix, lateral cross linking of the triple helices by lysyl oxidase (requires vitamin C) give it it's tensile strength. }}<br /> <br /> {{hidden|List three non-fibrillar collagens.|Type IV -basement membrane, Type IX - Fibrillar associated collagen with interrupted triple helices (FACIT), Type VII (provides anchoring fibrils to basement membrane beneath skin)}}<br /> <br /> {{hidden|Which structural protein is associated with Marfan syndrom?|Fibrillin synthetic defects, which wrap the elastin core. }}}}<br /> <br /> == Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury and Death ==<br /> Experimenting, please ignore<br /> {{hidden <br /> | headerstyle = text-align: left;<br /> | header = What are the four aspects of a disease?<br /> | content = *1. Etiology<br /> **Genetic - Inherited mutations and disease-associated gene variants, or polymorphisms.<br /> **Acquired - Infectious, nutritional, chemical and physical.<br /> *2. Pathogenesis - The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.<br /> *3. Morphological changes - The structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process.<br /> *4. Clinical Manifestations - Symptoms and signs of disease, as well as its clinical course and outcome.}}<br /> <br /> == Chapter 3 ==<br /> == Chapter 4 ==<br /> == Chapter 5 ==<br /> {{hidden|MC cause of spontaneous abortion is ?|&lt;center&gt;[[ A demonstrable chromosomal abnormality.]]&lt;/center&gt;}}<br /> <br /> {{hidden|1% of all newborn infants possess a gross chromosomal abnormality and 5% of people &lt;25y present with |&lt;center&gt;[[a genetic disease. ]]&lt;/center&gt;}}<br /> <br /> {{hidden|Mutation|&lt;center&gt;[[permanent change in the DNA, if affect germ cells are transmitted to the progeny ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe 4 broad categories of human genetic disorders:|&lt;center&gt;[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance<br /> ii. Often highly penetrant (large proportion of pop with gene has disease)<br /> b. Chromosomal disorders<br /> i. Structural or numerical alterations in autosomes and sex chromosomes<br /> ii. Uncommon, high penetrance<br /> c. Complex multigenic disorders<br /> i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present<br /> d. Single gene disorders with nonclassic patterns of inheritance (not mendelian)<br /> i. Disorders resulting from triplet repeat mutations<br /> ii. Mutations in mitochondrial DNA<br /> iii. Those influenced by genomic imprinting<br /> iv. Those influenced by gonadal mosaicism]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of a point mutation in a coding region?|[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid, b. Nonsense mutation – makes a stop codon ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of point mutation or deletion in a non-coding region.|&lt;center&gt;[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing &gt; failure to make mature RNA &gt; no translation]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of deletions and insertions.|&lt;center&gt;[[a.Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon<br /> i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene ]]}}<br /> <br /> {{hidden|List and describe the possible outcomes of trinucleotide repeat mutations.|[[a. Usually G&amp;C, dynamic and increase during gametogenesis, “RNA stutters”,b. Fragile X – CGG 250-4000, Huntinton’s Disease ]]}}<br /> <br /> {{hidden|List and describe three examples of inheritance of single gene mutations|[[a. AD – manifested in the heterologous state, one parent of index case is usually affected, males and females affected and both can transmit conditioni. De novo cases may not have affected parentii. Penetrance = fraction of people with gene who have the traitiii. Variable expressivity = those with mutant gene have variety of phenotypesiv. Often age of onset is delayed so can reproduce before die from diseasev. Biochem mechanisms1. Reduced production of a protein or dysfunctional/inactive protein2. Involved in regulation of complex metabolic pathyway subject to feedback inhibition3. Key structural proteins (collagen and cytoskeleton of RBC)a. May be a dominant negative , e.g. osteogenesis imperfecta4. Gain of function are rare, 2 formsa. Increased in proteins normal function (excess enzyme activity)b. Huntinton’s diseas (abn protein accumulates, toxic to neurons)b. ARi. Largest category – both alleles at a locus are mutated1. Expression is uniform, complete penetrance common, early onset, unaffected carrier family members, mostly enzymesc. X Linkedi. All sex linked, and almost all are recessive , if Y Chromosome affected usually infertile males &gt; no progenyii. Male expression b/c hemizygous, daughter carriers with variable phenotype because of lionization of 2nd X e.g G6DPiii. Dominant . vitamin D resistant rickets]]&lt;/center&gt;}}<br /> <br /> Stopped at P142<br /> <br /> == Chapter 6 ==<br /> == Chapter 7 ==<br /> == Chapter 8 ==<br /> == Chapter 9 ==<br /> == Chapter 10 ==<br /> == Chapter 11: Blood Vessels==<br /> <br /> == Chapter 12 ==<br /> == Chapter 13 ==<br /> == Chapter 14 ==<br /> == Chapter 15 ==<br /> == Chapter 16 ==<br /> == Chapter 17 ==<br /> == Chapter 18 ==<br /> == Chapter 19 ==<br /> == Chapter 20 ==<br /> == Chapter 21 ==<br /> == Chapter 22 ==<br /> ==[[Breast (CH 23)]]==<br /> <br /> == Chapter 24 ==<br /> == Chapter 25 ==<br /> == Chapter 26 ==<br /> == Chapter 27 ==<br /> == Chapter 28 ==<br /> == Chapter 29 ==</div>

Tate https://librepathology.org/w/index.php?title=Sudden_Death_Questions&diff=39184 2015-08-12T17:36:31Z

<p>Tate: </p> <hr /> <div># List 2 autopsy findings in a type 1 diabetic from diabetic ketoacidosis.<br /> ## Armanni-Epstein lesion: subnuclear vacuoles in the proximal tubule<br /> ## Vitreous fluid glucose levels &gt;&gt;200mg/DL (11mM), falls with time after death...</div>

Tate https://librepathology.org/w/index.php?title=Transportation_related_Deaths_Questions&diff=39183 2015-08-12T17:23:15Z

<p>Tate: </p> <hr /> <div>Death by motor vehicle collision<br /> <br /> # List 5 reasons autopsies are performed in motor vehicle deaths.<br /> ## to determine the cause of death<br /> ## to confirm if death was caused by injuries suffered in the accident<br /> ## to determine extent of injuries<br /> ## to detect any diseases or other factor which could have precipitated or contributed to the accident or death<br /> ## to detect any criminal activity associated with the death<br /> ## to document all findings for subsequent use in criminal or civil actions<br /> ## to establish positive identification of body, especially if burnt or mutilated<br /> # What are the four mechanisms of injuries in motor vehicle crashes?<br /> ## impact on some portion of interior of vehicle<br /> ## violation of integrity of the passenger compartment by another object<br /> ## ejection from the motor vehicle, part or entire<br /> ## fire<br /> # What is the most common cause of fatal motor vehicle crashes in north America?<br /> ## impairment of the driver by alcohol, drugs or combination of both &gt;&gt; human error (speed, recklessness, falling asleep)<br /> # List the 4 categories of motor vehicle crashes.<br /> ## front impact<br /> ## side impact<br /> ## read impact<br /> ## roll overs<br /> # List and briefly describe 3 main sites injuries of an unrestrained driver in a front impact motor vehicle crash.<br /> ## knees hitting dashboard (fractures of femurs, pelvix, tibia)<br /> ## chest hitting steering column (fractures or ribs, pulmonary and cardiac contusions, impaling, transection of aorta,...)<br /> ## head hitting windshield, frame or A pillar (lacerations, abrasions, contusions, soft tissue injuries, transection of cervical spine)<br /> # List 5 fatal internal thoro-abdominal injuries of a driver in a motor vehicle crash resulting from impact with a steering column. <br /> ## pulmonary and cardiac contusions<br /> ## laceration of lungs or heart from fractures or objects<br /> ## splenic or hepatic lacerations or contusions<br /> ## transection of the aorta<br /> ## <br /> # List 5 safety features of modern motor vehicles<br /> ## air bags<br /> ## three point restraints<br /> ## tempered glass side windows<br /> ## laminated windshields<br /> ## energy absorbing rear and front bumper design<br /> # A pedestrian is killed by a person driving a sedan, list 5 differences between the injuries of an adult and a child. <br /> ## adult will tend to be thrown on top of the vehicle while a child will be pushed under and may have tire tread marks <br /> ## adult will have secondary injuries due other contacts with the vehicle<br /> # A pedestrian is killed, list five difference between the injuries if they are hit by a sedan moving a 30km/hr vs 100km/hr.<br /> # A pedestrian is killed what would you expect if he were running vs walking?<br /> ## walking: the bumper fractures tend to be at the same height on both legs, where as in running they tend not to be<br /> # A pedestrian is killed, his is struck while walking, his body lands on the roof of the sedan, and he then falls of onto the road on the passenger side. Describe the primary, secondary and tertiary injuries that you might expect. <br /> ## primary injuries: bumper fractures to the lower legs, laceration of the lower legs<br /> ## secondary injuries: skull fracture from striking the windshield<br /> ## tertiary injuries: road rash and other fractures from hitting ground or other objects<br /> # What is the &quot;Locus minoris resistentiae&quot; if the aorta?<br /> # What is the most common location of the transsection of the aorta? Immediately distal to the left subclavian artery origin (peri-isthmus, at the ligamentum arteriosum)<br /> # Describe the cause and features of dicing injuries.<br /> # You have a scene with multiple unrestrained victims, describe three ways you might be able to determine who the driver of the vehicle was?<br /> # List 5 scenarios where air bags can cause immediate death in a motor vehicle crash. <br /> # What four factors determine the pattern and severity of pedestrian injuries when struck by a motor vehicle?<br /> # What four injuries are correlated with impact velocity?<br /> # In what circumstances is a child likely be thrown forward when struck by a vehicle?<br /> # What is a bumper fracture?<br /> # There are no fractures seen in a pedestrian victim of a motor vehicle collision, what should you now look for in the lower limbs and how?<br /> # Describe the mechanism by which striae are formed on pedestrian victims of motor vehicle collisons.<br /> # Describe 4 routes by which the abdominal contents may exit the abdominal cavity during a motor vehicle crash.</div>

Tate https://librepathology.org/w/index.php?title=Transportation_related_Deaths_Questions&diff=39182 2015-08-12T17:02:50Z

<p>Tate: </p> <hr /> <div>Death by motor vehicle collision<br /> <br /> # List 5 reasons autopsies are performed in motor vehicle deaths.<br /> ** to determine the cause of death<br /> ** to confirm if death was caused by injuries suffered in the accident<br /> ** to determine extent of injuries<br /> ** to detect any diseases or other factor which could have precipitated or contributed to the accident or death<br /> ** to detect any criminal activity associated with the death<br /> ** to document all findings for subsequent use in criminal or civil actions<br /> ** to establish positive identification of body, especially if burnt or mutilated<br /> # What are the four mechanisms of injuries in motor vehicle crashes?<br /> ** impact on some portion of interior of vehicle<br /> ** violation of integrity of the passenger compartment by another object<br /> ** ejection from the motor vehicle, part or entire<br /> ** fire<br /> # What is the most common cause of fatal motor vehicle crashes in north America?<br /> ** impairment of the driver by alcohol, drugs or combination of both &gt;&gt; human error (speed, recklessness, falling asleep)<br /> # List the 4 categories of motor vehicle crashes.<br /> ** front impact<br /> ** side impact<br /> ** read impact<br /> ** roll overs<br /> # List and briefly describe 3 main sites injuries of an unrestrained driver in a front impact motor vehicle crash.<br /> ** knees hitting dashboard (fractures of femurs, pelvix, tibia)<br /> ** chest hitting steering column (fractures or ribs, pulmonary and cardiac contusions, impaling, transection of aorta,...)<br /> ** head hitting windshield, frame or A pillar (lacerations, abrasions, contusions, soft tissue injuries, transection of cervical spine)<br /> # List 5 internal injuries of a driver in a motor vehicle crash resulting from impact with a steering column. <br /> ** rib and sternal fractures<br /> ** pulmonary and cardiac contusions<br /> ** laceration of lungs or heart<br /> ** <br /> # List 5 safety features of modenr <br /> # A pedestrian is killed by a person driving a sedan, list 5 differences between the injuries of an adult and a child. <br /> # A pedestrian is killed, list five difference between the injuries if they are hit by a sedan moving a 50km/hr vs 100km/hr.<br /> # A pedestrian is killed what would you expect if he were running vs walking?<br /> # A pedestrian is killed, his is struck while walking, his body lands on the roof of the sedan, and he then falls of onto the road on the passenger side. Describe the primary, secondary and tertiary injuries that you might expect. <br /> # What is the &quot;Locus minoris resistentiae&quot; if the aorta?<br /> # What is the most common location of the transsection of the aorta? Immediately distal to the left subclavian artery origin (peri-isthmus, at the ligamentum arteriosum)<br /> # Describe the cause and features of dicing injuries.<br /> # You have a scene with multiple unrestrained victims, describe three ways you might be able to determine who the driver of the vehicle was?<br /> # List 5 scenarios where air bags can cause immediate death in a motor vehicle crash. <br /> # What four factors determine the pattern and severity of pedestrian injuries when struck by a motor vehicle?<br /> # What four injuries are correlated with impact velocity?<br /> # In what circumstances is a child likely be thrown forward when struck by a vehicle?<br /> # What is a bumper fracture?<br /> # There are no fractures seen in a pedestrian victim of a motor vehicle collision, what should you now look for in the lower limbs and how?<br /> # Describe the mechanism by which striae are formed on pedestrian victims of motor vehicle collisons.<br /> # Describe 4 routes by which the abdominal contents may exit the abdominal cavity during a motor vehicle crash.</div>

Tate https://librepathology.org/w/index.php?title=Sudden_Death_Questions&diff=39179 2015-08-12T14:44:24Z

<p>Tate: </p> <hr /> <div># List 5 autopsy findings in a type 1 diabetic from diabetic ketoacidosis.</div>

Tate https://librepathology.org/w/index.php?title=Asphyxia_Questions&diff=39178 2015-08-12T14:42:32Z

<p>Tate: </p> <hr /> <div>[[Asphyxia]]<br /> # Explain how visceral congestions occurs in asphyxia deaths.<br /> # Under what circumstances might one expect to find petechiae of the conjunctiva and sclera?<br /> # When petechaie become larger or confluent they are called ecchymoses, describe a circumstance where you might expect this to occur.<br /> # What are three categories of asphyxia death.<br /> # List 6 general forms of suffocation and give an example of each. <br /> ## Entrapment/Environmental suffocation<br /> ## Smothering<br /> ## Choking<br /> ## Mechanical asphyxia (traumatic/positional/riot crush)<br /> ## Traumatic with smothering (overlay/ Burking)<br /> ## Suffocating gases (methane, CO2)<br /> # List and describe three forms of strangulation<br /> ## Hanging<br /> ## Ligature strangulation<br /> ## Manual strangulation<br /> # Jugular veins 4.4llbs, carotid artery compression occurs at 11lbs, the trachea 33lbs, vertebral arteries 66lb; describe how any of this makes sense and matters… <br /> # List 4 circumstances when you would expect to find fractures of the cervical spine in a hanging?<br /> # Describe the features of a typical suicidal hanging furrow?<br /> # List five features consistent with manual strangulation. <br /> # List three chemical asphyxiants and three suffocating gases and explain the difference between a suffocating gas and a chemical asphyxiant.<br /> # Describe 5 features of sexual asphyxiation. <br /> # Describe 5 features of crucifixion and explain the mechanisms leading to death. <br /> # Describe the differences between a choke hold and a carotid hold used by law enforcement personnel.</div>

Tate https://librepathology.org/w/index.php?title=Sudden_Death_Questions&diff=39177 2015-08-12T14:39:38Z

<p>Tate: Created page with &quot;*List 5 autopsy findings in a type 1 diabetic from diabetic ketoacidosis.&quot;</p> <hr /> <div>*List 5 autopsy findings in a type 1 diabetic from diabetic ketoacidosis.</div>

Tate https://librepathology.org/w/index.php?title=Forensic_Pathology&diff=39176 2015-08-12T14:39:07Z

<p>Tate: </p> <hr /> <div>===[[Transportation related Deaths Questions]]===<br /> ===[[Asphyxia Questions]]===<br /> ===[[Sudden Death Questions]]===</div>

Tate https://librepathology.org/w/index.php?title=Forensic_Pathology&diff=39175 2015-08-12T14:38:52Z

<p>Tate: </p> <hr /> <div>===[[Transportation related Deaths Questions]]===<br /> ===[[Asphyxia Questions]]===<br /> <br /> ===[[Sudden Death Questions]]==</div>

Tate https://librepathology.org/w/index.php?title=Forensic_pathology&diff=39174 2015-08-12T14:26:00Z

<p>Tate: /* Aortic trauma */</p> <hr /> <div>'''Forensic pathology''' is figuring-out why, when, where and how people died, if the manner of death is ''not'' obviously natural.<br /> <br /> =Death categorization=<br /> Deaths are categorized foremost by the '''manner of death'''. The manner is the single most important legal categorization for a death. <br /> The '''cause of death''' is important for understanding what happened. The '''mechanism of death''' is the pathophysiologic reason for death and can be inferred from the cause.<br /> <br /> Examples:<br /> {| class=&quot;wikitable sortable&quot; <br /> !Cause of death <br /> !Manner of death<br /> !Mechanism of death<br /> !Scenario<br /> |-<br /> | [[Electrocution]]<br /> | accident<br /> | [[cardiac arrhythmia]]<br /> | man struck by lightening<br /> |-<br /> | Hyperthermia<br /> | accident<br /> | arrhythmias, seizures&lt;ref name=fmuk&gt;URL: [http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ http://www.forensicmed.co.uk/pathology/mechanisms-of-death/]. Accessed on: 19 April 2012.&lt;/ref&gt;<br /> | man lost on hiking trip in desert<br /> |-<br /> | [[Epidural hemorrhage]] due to [[blunt force trauma]] to the head<br /> | homicide<br /> | brain stem compression or cerebral vascular spasm leading to autonomic dysregulation<br /> | man hit with a hammer in the head<br /> |-<br /> | [[Carbon monoxide toxicity]]<br /> | suicide<br /> | cerebral hypoxia (CO binds to hemoglobin impairing oxygen transport)<br /> | woman found in car with suicide note, long history of depression, previous suicide attempts<br /> |-<br /> | [[Atherosclerotic heart disease]]<br /> | natural<br /> | cardiac arrhythmia due to ischemia<br /> | man found dead in bed, apartment locked, 95% stenosis of LMCA at autopsy, no other significant autopsy findings<br /> |- &lt;!--<br /> | [[Peritonitis]] due to duodenal perforation as a consequence of [[peptic ulcer disease]]<br /> | natural<br /> | cerebral hypoxia secondary to hypotension<br /> | man found in locked apartment, complained of abdominal pain before dead<br /> |-<br /> | Coronary artery stent thrombosis complicating the treatment of a [[myocardial infarction]] due to atherosclerotic heart disease<br /> | natural<br /> | cardiac arrhythmia due to ischemia<br /> | woman found dead following hospital stay for a myocardial infarction, post-angioplasty and coronary stenting --&gt;<br /> |}<br /> <br /> ==Manner of death==<br /> The manner of death is a legislatively defined classification. It varies slightly between jurisdictions. <br /> &lt;!--<br /> MANNER OF DEATH<br /> --&gt;<br /> {{familytree/start}}<br /> {{familytree | | | | | | | | | A | | | | | | | | |A=Manner}}<br /> {{familytree | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| |}}<br /> {{familytree | B | | C | | D | | E | | F |B=Homicide|C=Suicide|D=Natural|E=Accident|F=Undetermined}}<br /> {{familytree/end}}<br /> <br /> Notes:<br /> *''Undetermined'' - is a waste basket category.<br /> *''Homicide'' - not necessarily murder.<br /> *Can be group into three:<br /> *#Intent to kill (homicide, suicide).<br /> *#No intent to kill (natural, accidental).<br /> *#Undetermined.<br /> <br /> ==Mechanism of death==<br /> This is occasionally of interest. It is usually based on physiology. <br /> <br /> The mechanism is often asked for [[asphyxial death]]s. The short answer it is: brain stem hypoxia due to ischemia caused by venous obstruction in the neck.&lt;ref&gt;URL: [http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ http://www.forensicmed.co.uk/pathology/mechanisms-of-death/]. Accessed on: 1 May 2012.&lt;/ref&gt;&lt;ref&gt;URL: [http://www.forensicmed.co.uk/pathology/pressure-to-the-neck/ http://www.forensicmed.co.uk/pathology/pressure-to-the-neck/]. Accessed on: 1 May 2012.&lt;/ref&gt;<br /> <br /> ==Cause of death==<br /> *Abbreviated ''COD''.<br /> ===General===<br /> *The cause of death should be what started the sequence of events that lead to death.<br /> <br /> ====Word form for cause of death====<br /> Examples:<br /> *''[[C. difficile colitis]] complicating antibiotic treatment for a dental abscess''.&lt;ref&gt;MSP. 8 September 2010.&lt;/ref&gt;<br /> *''Complications of laparoscopic cholecystectomy for ascending cholangitis with [[mesothelioma]] and atherosclerotic heart disease''.&lt;ref&gt;TR. 3 September 2010.&lt;/ref&gt;<br /> <br /> General forms:<br /> *''A'' complicating ''B'' for the treatment of ''C''.<br /> *''A'' complicating ''B'' for the treatment of ''C'' with ''D'' and ''E''.<br /> <br /> ====World Health Organization form for cause of death====<br /> General form:&lt;ref name=pmid15914304&gt;{{cite journal |author=Pollanen MS |title=Deciding the cause of death after autopsy--revisited |journal=J Clin Forensic Med |volume=12 |issue=3 |pages=113–21 |year=2005 |month=June |pmid=15914304 |doi=10.1016/j.jcfm.2005.02.004 |url=}}&lt;/ref&gt;<br /> *1a = ''immediate cause of death''.<br /> *1b = what lead to the ''immediate cause of death''.<br /> *1c... 1[x] -- where 'x' is the last letter used; 1x = What started the sequence of events. This is known as the ''underlying cause of death''.<br /> *2 = contributing factors.<br /> <br /> Example 1:<br /> *1a. [[Ketoacidosis]].<br /> *1b. [[Diabetes mellitus]].<br /> *2. [[Alcoholism]] and acute [[bronchopneumonia]].<br /> <br /> Example 2:<br /> *1a. Hemoperitoneum.<br /> *1b. [[Splenic laceration]].<br /> *1c. Blunt force trauma.<br /> *2. Liver [[cirrhosis]].<br /> <br /> ===Natural deaths===<br /> {{Main|Natural death}}<br /> *The cause should be a medical diagnosis, '''not''' the mechanism (e.g. ''cardiac arrest'', ''cachexia'', ''kidney failure'').<br /> *The [[mechanism of death|mechanism]] is irrelevant.<br /> <br /> Notes:<br /> *Unnatural causes trump natural ones. If a guy with (nothing more than) a 70% proximal LAD stenosis and an old [[myocardial infarct]] is found in the water, they are usually called [[drowning]].<br /> *[[Cancer]] is rarely the immediate cause of death - it is usually something else.&lt;ref&gt;Shannon, P. 2009.&lt;/ref&gt;<br /> *Things (mechanisms) that shouldn't be used: [http://www.pallimed.org/2008/03/unacceptable-causes-of-death-other-web.html http://www.pallimed.org/2008/03/unacceptable-causes-of-death-other-web.html]<br /> <br /> ===Legal frame work===<br /> ====General====<br /> *In Ontario, the ''manner'' is determined by the coroner.<br /> *Coroners, in Ontario, are MDs -- usually [[family docs]].<br /> *The cause (e.g. &quot;gunshot wound to the head&quot;) is determined by the pathologist.<br /> <br /> NB - the word ''coroner'' is not synoymous with MD. British Columbia has coroners that aren't MDs.<br /> <br /> ====Case classification (Ontario)====<br /> Cases are classified as:<br /> *''A case'' = homicide and suspicious for homicide, (all) gunshot wounds.<br /> *''B case'' = adult, non-suspicious.<br /> *''C case'' = child, non-suspicious.<br /> <br /> Notes:<br /> *All ''A cases'' are done at regional centers by certified forensic pathologists.<br /> <br /> =Forensic golden triangle=<br /> *History.<br /> *Scene.<br /> *[[Autopsy]].<br /> <br /> =Forensic diagnostic triangle=<br /> Most general differential diagnosis:<br /> *Natural:<br /> **Haemorrhage (e.g. cerebral bleed, gastrointestinal bleed, aortic aneurysm).<br /> **Infection (e.g. [[pneumonia]]).<br /> **[[Coronary artery atherosclerosis]] ([[cardiac arrhythmia]]s - more common in the forensic context than [[myocardial infarction]] (MI); individuals with MIs don't usu. drop dead-- they go to the ER).<br /> ***Post [[myocardial infarction]] (free wall rupture).<br /> ***Ruptured (atherosclerotic) plaque.<br /> *Toxic (memory device: ''PAIRO''):<br /> **Poisons.<br /> **[[Alcohol]] (EtOH). <br /> **Illicit (e.g. [[cocaine]], heroin, LSD). <br /> **Rx. <br /> **Over-the-counter (OTC) (e.g. acetaminophen, warfarin).<br /> *Trauma (memory device ''AGE BS''):<br /> **[[asphyxial deaths|Asphyxial]]. <br /> **[[Gunshot wounds]] (GSWs). <br /> **Environmental (e.g. hypothermia, hyperthermia, [[drowning]], lack of oxygen, [[electrocution]]).<br /> **[[Blunt force trauma]]. <br /> **[[Sharp force trauma]]. <br /> <br /> Difficulties arise when more than one point of the triangle is in play, i.e. the forensic pathologist has to earn their pay when an old man with a heart condition is known to be into erotic asphyxia, and dies after doing some drugs and whilst indulging in erotic asyphxiation with a friend...<br /> <br /> *If he had an arrhythmia and there was no stressor... ''natural'' death.<br /> *If he over did it with the drugs, it is an overdose, ergo ''accidental''.<br /> *If he did the erotic asphyxia a bit too long it is ''accidental''.<br /> *If the friend held the plastic bag over his head just a bit long to asphyxiate him... it is a ''homicide''.<br /> *If he was a lone and depressed... he might have been trying to kill himself, ergo ''suicide''.<br /> <br /> =Death-related changes=<br /> ===Rigor mortis===<br /> Definition: <br /> *Muscle rigidity following death (caused by depletion of ATP).<br /> <br /> Dependent on:<br /> *Temperature of patient at death.<br /> *Temperature variations in the environment since death.<br /> *Presence of some medical conditions.<br /> *May never develop!<br /> <br /> It is the explanation for post-mortem goose bumps.<br /> <br /> ====Summary====<br /> *Its onset &amp; presence is ''highly variable''.<br /> *Forensic pathologists do '''not''' comment on time of death, as the above times are subject to such a large degree of variability, i.e. the estimates are essentially useless.<br /> <br /> ====Time estimates====<br /> A crude guess for time of death based on rigor:&lt;ref name=Ref_KFP61&gt;{{Ref KFP|61}}&lt;/ref&gt;<br /> *Warm &amp; flaccid &lt;3 h.<br /> *Warm &amp; stiff 3-8 h. <br /> *Cold &amp; stiff 8-36 h. <br /> *Cold &amp; flaccid &gt; 36 h.<br /> <br /> Notes:<br /> *Memory device: '''3s''': cut points are at ''3 hours'', ''1/3 of a day'', ''3/2 of a day.''<br /> ===Livor mortis===<br /> Definition: pooling of blood in the dependent position, due to blood stasis. <br /> *Onset may preceed death in the context of congestive heart failure.<br /> *If pressure is applied to a dependent area-- no blood can enter there; thus, a pressure area is blanched (i.e. white).<br /> <br /> *Can be seen externally, i.e. on the skin, and internally.<br /> *Liver mortis becomes fixed some time after death. <br /> **Liver mortis does NOT tell one the position the decedent was in at the time of death-- only the position the decedent was at the time liver mortis became fixed. '''If''' the decedent wasn't moved liver mortis can help determine the position the person was in when they died.<br /> <br /> Averages:<br /> *Start: 30 minutes to 2 hours<br /> *Fixed: 8-12 hours.<br /> <br /> DDx:<br /> *[[Blunt force trauma]] - especially to the inexperienced eye.<br /> *Post-mortem hypostatic bruising.<br /> <br /> ===Tache noire===<br /> Literally ''black spot''.<br /> <br /> Features:&lt;ref name=emed1680032&gt;URL: [http://emedicine.medscape.com/article/1680032-overview http://emedicine.medscape.com/article/1680032-overview]. Accessed on: 6 March 2012.&lt;/ref&gt;<br /> *Brown/black horizontal line of the eye due to drying.<br /> **Arises if the eye remains open after death.<br /> **May mimic a traumatic injury. <br /> <br /> Images:<br /> *[http://img.medscape.com/pi/emed/ckb/pathology/1603817-1607640-1680032-1714463.jpg Tache noire (medscape.com)].&lt;ref name=emed1680032/&gt;<br /> *[http://www.demussen.net/carbon-monoxide/images/1856_23_12-vitreous-potassium.jpg Tache noire (demussen.net)].&lt;ref&gt;URL: [http://www.demussen.net/carbon-monoxide/chemical-changes-in-body-fluids.html http://www.demussen.net/carbon-monoxide/chemical-changes-in-body-fluids.html]. Accessed on: 6 March 2012.&lt;/ref&gt;<br /> <br /> ===Post-mortem decomposition/preservation===<br /> One of three things happens post-mortem:&lt;reF name=Ref_HospAuto102&gt;{{Ref HospAuto|102}}&lt;/ref&gt;<br /> #Mummification.<br /> #Putrefaction (skeletonisation).<br /> #*Green colour due to break down of hemoglobin (biliverdin).&lt;ref&gt;{{cite journal |author=NOIR BA, GARAY ER, ROYER M |title=SEPARATION AND PROPERTIES OF CONJUGATED BILIVERDIN |journal=Biochim. Biophys. Acta |volume=100 |issue= |pages=403–10 |year=1965 |month=May |pmid=14347937 |doi= |url=linkinghub.elsevier.com/retrieve/pii/0304416565900097}}&lt;/ref&gt;<br /> #Adipocere - transformation into wax (due to anaerobic bacterial hydrolysis of fat).<br /> #*Useless for toxicology and DNA.<br /> <br /> *A mix of the above often occur, i.e. part of the corpse is mummified... part of it decomposed through putrefaction.<br /> <br /> Mummification:<br /> *Predominant in dry environments.<br /> *Body becomes dry and leathery.<br /> <br /> Putrefaction:<br /> *Body wet/moist after death -- ideal environment for putrefactive bacteria and organisms.<br /> <br /> ===Artefacts===<br /> *Prinsloo and Gordon artefact = artefactual post-morten haemorrhage on the posterior surface of the esophagus.&lt;ref name=pmid16378701&gt;{{cite journal |author=Piette MH, De Letter EA |title=Drowning: still a difficult autopsy diagnosis |journal=Forensic Sci. Int. |volume=163 |issue=1-2 |pages=1–9 |year=2006 |month=November |pmid=16378701 |doi=10.1016/j.forsciint.2004.10.027 |url=}}&lt;/ref&gt;<br /> **Minimized by removing cranial contents &amp; thoracic contents ''before'' undertaking neck dissection.&lt;ref name=Ref=HospAuto118&gt;{{Ref HospAuto|118}}&lt;/ref&gt;<br /> *Artefactual fractures (see fractures).<br /> *Dilated anus (in isolation).&lt;ref&gt;URL: [http://www.kingstonwhigstandard.com/ArticleDisplay.aspx?archive=true&amp;e=736464 http://www.kingstonwhigstandard.com/ArticleDisplay.aspx?archive=true&amp;e=736464]. Accessed on: 6 October 2010.&lt;/ref&gt;&lt;ref name=pmid17961873 &gt;{{Cite journal | last1 = Elder | first1 = DE. | title = Interpretation of anogenital findings in the living child: Implications for the paediatric forensic autopsy. | journal = J Forensic Leg Med | volume = 14 | issue = 8 | pages = 482-8 | month = Nov | year = 2007 | doi = 10.1016/j.jflm.2007.03.005 | PMID = 17961873 }}&lt;/ref&gt;<br /> *Towel clip injury, usu. paired (in organ donors) - may be mistaken for an electroshock weapon (e.g. Taser) wound.&lt;ref&gt;MSP. 12 October 2010.&lt;/ref&gt;<br /> *Subclavian stab for vascular access - may be confused with a gunshot exit wound.<br /> <br /> ====Infants====<br /> *Lumpy neck - small superficial nodules on anterior neck ~2-5 mm (???).&lt;ref&gt;MSP. 6 October 2010.&lt;/ref&gt;<br /> *Intussusception of small bowel - often multiple.<br /> <br /> =Wounds=<br /> ==General==<br /> *''Wound'' - definition: defect in skin or mucous membrane&lt;ref&gt;URL: [http://dictionary.reference.com/browse/wound http://dictionary.reference.com/browse/wound]. Accessed on: 20 April 2012.&lt;/ref&gt; - usually due to trauma.<br /> <br /> Special types of wounds:<br /> *[[Gunshot wounds]].<br /> *Incised wounds - see [[sharp force trauma]].<br /> <br /> ===Gross pathologic classification of injuries===<br /> Mnemonic ''CALI'':<br /> *'''C'''ontusion - &quot;bruise&quot;, [[hematoma]].<br /> **Age (usual colour change sequence): red, blue, green, yellow, brown.&lt;ref name=Ref_HospAuto108&gt;{{Ref HospAuto|108}}&lt;/ref&gt;<br /> **Etiology: bleeding from arterioles or venules (not capillaries).&lt;ref name=Ref_HospAuto105&gt;{{Ref HospAuto|105}}&lt;/ref&gt;<br /> *'''A'''brasion - &quot;scrape&quot;, e.g. motorcyclist slide across the roadway... skin scraped-off.<br /> **Can be subclassified as ''brush abrasions'' (has skin tags) and ''crush abrasions'' (do not have skin tags).<br /> ***Skin tags suggest directionality; they are found at the distal point / point of last contact.&lt;ref name=Ref_HospAuto105&gt;{{Ref HospAuto|105}}&lt;/ref&gt;<br /> *'''L'''aceration - &quot;tear&quot;, indicates blunt force trauma; contact point may be distant from where skin splits.<br /> *'''I'''ncised - &quot;cut&quot;, e.g. caused by a knife,&lt;ref name=Ref_HoFP154&gt;{{Ref_HoFP|154}}&lt;/ref&gt; subdivided as follows:<br /> *#&quot;Cut&quot; or &quot;slash&quot; = length &gt; depth.<br /> *#&quot;Stab&quot; = depth &gt; length.<br /> *#&quot;Chop&quot; = typically have a contusion at the margin of the wound, classically caused by an axe. May be caused by a propeller.&lt;ref name=pmid19733336&gt;{{Cite journal | last1 = Ihama | first1 = Y. | last2 = Ninomiya | first2 = K. | last3 = Noguchi | first3 = M. | last4 = Fuke | first4 = C. | last5 = Miyazaki | first5 = T. | title = Fatal propeller injuries: three autopsy case reports. | journal = J Forensic Leg Med | volume = 16 | issue = 7 | pages = 420-3 | month = Oct | year = 2009 | doi = 10.1016/j.jflm.2009.04.006 | PMID = 19733336 }}&lt;/ref&gt;<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image:Hand_Abrasion_-_32_minutes_after_injury.JPG | Abrasion. (WC)<br /> Image:Black_eye_2.jpg | Contusion (&quot;black eye&quot;). (WC)<br /> &lt;/gallery&gt;<br /> ====DDx====<br /> How to decide what you're looking at:<br /> *Contusion: <br /> **Can be demonstrated histologically... there are extravascular RBCs.<br /> ***If pre-morten there is vital reaction, i.e. WBCs come to clean-up the trauma.<br /> **If the post mortem interval is not known and long-- differentiation from decomposition may be non-trivial/impossible.<br /> <br /> *Abrasion vs. contusion:<br /> **Contusions skin is intact... in abrasion it is not.<br /> **Abrasions and contusions may be co-localized, i.e. in the same place.<br /> <br /> *Laceration vs. incision:<br /> **Lacerations have &quot;bridges&quot;, incisions do NOT have bridges.<br /> ***Bridges are fine strands of tissue that cross the long axis of the skin defect.<br /> ****You can think of the wound as partially &quot;sutured&quot; by the bridges of tissue.<br /> **Lacerations are usually associated with a contusion and/or crush and have an irregular margin.&lt;ref name=Ref_HospAuto109&gt;{{Ref HospAuto|109}}&lt;/ref&gt;<br /> **Lacerations are classically on the skull and face. They are rarely on the abdomen.<br /> <br /> ===Wound dating===<br /> *Colour is somewhat useful for contusions (bruises).<br /> *Post-mortem injuries tend to be orange-yellow.&lt;ref name=pmid19237864&gt;{{Cite journal | last1 = Campobasso | first1 = CP. | last2 = Marchetti | first2 = D. | last3 = Introna | first3 = F. | last4 = Colonna | first4 = MF. | title = Postmortem artifacts made by ants and the effect of ant activity on decompositional rates. | journal = Am J Forensic Med Pathol | volume = 30 | issue = 1 | pages = 84-7 | month = Mar | year = 2009 | doi = 10.1097/PAF.0b013e318187371f | PMID = 19237864 }}&lt;/ref&gt;<br /> *Wounds age is difficult to determine as [[wound healing]] is affected by a large number of variables.<br /> *Old wounds (scars), generally, cannot be dated - one can only say they are ''old''.<br /> <br /> ===Microscopic===<br /> Wounds can be grouped into:<br /> *Pre-mortem.<br /> *Post-mortem.<br /> <br /> Signs a wound was inflicted during life:<br /> *Blood.<br /> **Hypostasis/decomposition can mess with this, i.e. blood oozing out of vessels post-mortem shouldn't be called an injury.<br /> **Hemosiderin demonstrated by an iron stain - hard sign.<br /> *Inflammation:&lt;ref name=Ref_PCPBoD8_26&gt;{{Ref PCPBoD8|26}}&lt;/ref&gt;<br /> **[[PMN]]s 6-24 hours after injury.<br /> **PMNs replaced monocytes in 24-48 hours.<br /> <br /> ===Stains===<br /> *[[Iron stain]] for siderophages (hemosiderin-laden macrophages) -- presence suggests 2-3 days or older.&lt;ref name=pmid7529545&gt;{{Cite journal | last1 = Betz | first1 = P. | title = Histological and enzyme histochemical parameters for the age estimation of human skin wounds. | journal = Int J Legal Med | volume = 107 | issue = 2 | pages = 60-8 | month = | year = 1994 | doi = | PMID = 7529545 }}&lt;/ref&gt;<br /> <br /> =Bone fractures=<br /> *[[AKA]] ''fractures''.<br /> *[[AKA]] ''fracture of bone''.<br /> <br /> ==Artefactual fractures==<br /> *&quot;Undertaker's fracture&quot; - cervical fracture due to rough handling.&lt;ref&gt;URL: [http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html]. Accessed on: 29 September 2010.&lt;/ref&gt;<br /> *Basal skull fracture due to opening of skull.&lt;ref&gt;MSP. 29 September 2010.&lt;/ref&gt;<br /> **Classically does not cross sella turcica.<br /> **Notably absent features of a real (ante-mortem) fracture: hematoma, brain injury.<br /> **Mechanism to explain trauma not present in history; a fall/tripping not sufficient.<br /> <br /> ==Healing of fractures==<br /> ===Simplified classification===<br /> *Primary callus (cartilaginous) - early.<br /> *Secondary callus (bone) - late.<br /> <br /> ===Microscopic===<br /> Features:<br /> *Fragmentation of bone.<br /> *+/-Dead bone = lacunae have no osteocytes.&lt;ref name=pmid22460748&gt;{{Cite journal | last1 = Fondi | first1 = C. | last2 = Franchi | first2 = A. | title = Definition of bone necrosis by the pathologist. | journal = Clin Cases Miner Bone Metab | volume = 4 | issue = 1 | pages = 21-6 | month = Jan | year = 2007 | doi = | PMID = 22460748 }}&lt;/ref&gt;<br /> **Takes days for osteocyte loss.<br /> *+/-Inflammatory cells.<br /> *+/-Hemosiderin-laden macrophages.<br /> *+/-Osteoblastic rimming.<br /> <br /> DDx:<br /> *Fracture secondary to a tumour:<br /> **Metastatic carcinoma.<br /> **[[Osteosarcoma]] - typically does '''not''' have osteoblastic rimming. <br /> <br /> Notes:<br /> *Radiology is not good at dating fratures;&lt;ref name=pmid15788611&gt;{{Cite journal | last1 = Prosser | first1 = I. | last2 = Maguire | first2 = S. | last3 = Harrison | first3 = SK. | last4 = Mann | first4 = M. | last5 = Sibert | first5 = JR. | last6 = Kemp | first6 = AM. | title = How old is this fracture? Radiologic dating of fractures in children: a systematic review. | journal = AJR Am J Roentgenol | volume = 184 | issue = 4 | pages = 1282-6 | month = Apr | year = 2005 | doi = | PMID = 15788611 | url=http://www.ajronline.org/cgi/content/full/184/4/1282 }}<br /> &lt;/ref&gt; however, it is good at finding 'em.<br /> <br /> ==Pattern and cause==<br /> ===Child abuse-related===<br /> *Paravertebral (bony) nodules = classic location for rib fractures in child abuse.<br /> *Metaphyseal fractures - &quot;classical metaphyseal lesions&quot;.&lt;ref name=pmid8615271&gt;{{Cite journal | last1 = Kleinman | first1 = PK. | last2 = Marks | first2 = SC. | title = A regional approach to classic metaphyseal lesions in abused infants: the distal tibia. | journal = AJR Am J Roentgenol | volume = 166 | issue = 5 | pages = 1207-12 | month = May | year = 1996 | doi = | PMID = 8615271 }}&lt;/ref&gt;<br /> <br /> ===Motor vehicle versus pedestrian===<br /> If the pedestrian is standing during the initial impact one classically finds, at bumper level, a lower limb fracture with a ''Messerer wedge'' (German: ''Messerer-Kiel'');&lt;ref name=pmid11376986&gt;{{Cite journal | last1 = Karger | first1 = B. | last2 = Teige | first2 = K. | last3 = Fuchs | first3 = M. | last4 = Brinkmann | first4 = B. | title = Was the pedestrian hit in an erect position before being run over? | journal = Forensic Sci Int | volume = 119 | issue = 2 | pages = 217-20 | month = Jun | year = 2001 | doi = | PMID = 11376986 }}<br /> &lt;/ref&gt; the wedge points in the direction of the (impact) force.<br /> <br /> ==Location or type==<br /> ===Orbital floor fractures===<br /> *[[AKA]] ''blow-out fractures''.&lt;ref name=pmid17333039&gt;{{Cite journal | last1 = Punke | first1 = C. | last2 = Fritsche | first2 = A. | last3 = Martin | first3 = H. | last4 = Schmitz | first4 = KP. | last5 = Pau | first5 = HW. | last6 = Kramp | first6 = B. | title = [Investigation of the mechanisms involved in isolated orbital floor fracture. Simulation using a finite element model of the human skull]. | journal = HNO | volume = 55 | issue = 12 | pages = 938-44 | month = Dec | year = 2007 | doi = 10.1007/s00106-007-1545-5 | PMID = 17333039 }}&lt;/ref&gt;<br /> ====General====<br /> *Classically due to fights, followed by traffic accidents.&lt;ref name=pmid20165966&gt;{{Cite journal | last1 = Gosau | first1 = M. | last2 = Schöneich | first2 = M. | last3 = Draenert | first3 = FG. | last4 = Ettl | first4 = T. | last5 = Driemel | first5 = O. | last6 = Reichert | first6 = TE. | title = Retrospective analysis of orbital floor fractures--complications, outcome, and review of literature. | journal = Clin Oral Investig | volume = 15 | issue = 3 | pages = 305-13 | month = Jun | year = 2011 | doi = 10.1007/s00784-010-0385-y | PMID = 20165966 }}&lt;/ref&gt;<br /> *Thought to result from loading on the orbital rim directly or the orbit - both are transmitted to the orbital floor.&lt;ref name=pmid17333039/&gt;<br /> <br /> Note:<br /> *The orbital floor tends to the be weaker than other components of the orbital cavity wall; thus, it is the most common site of fracture in the orbital cavity wall.<br /> <br /> ===Basal skull fracture===<br /> ====General====<br /> Etiology:<br /> *Blunt force trauma - high energy &amp; velocity.<br /> **Seen in ''motor vehicle collisions'', ''descent from height''.<br /> <br /> Clinical/external findings:<br /> *Raccoon eyes = periorbital ecchymosis.<br /> *Battle sign = mastoid ecchymosis.<br /> **Associated with orbital roof fractures.&lt;ref&gt;URL: [http://emedicine.medscape.com/article/1680107-overview#showall http://emedicine.medscape.com/article/1680107-overview#showall]. Accessed on: 28 March 2012.&lt;/ref&gt;<br /> *Cerebrospinal fluid rhinorrhea.<br /> *Hemorrhage from nose and ears.<br /> *Hemotympanum.<br /> <br /> Note:<br /> *There is a dictum that states ''bilateral petrous bone fractures are due to impact to the side of the head'' - it isn't true.&lt;ref name=pmid7391790&gt;{{Cite journal | last1 = Harvey | first1 = FH. | last2 = Jones | first2 = AM. | title = Typical basal skull fracture of both petrous bones: an unreliable indicator of head impact site. | journal = J Forensic Sci | volume = 25 | issue = 2 | pages = 280-6 | month = Apr | year = 1980 | doi = | PMID = 7391790 }}&lt;/ref&gt;<br /> <br /> ===Hinge fracture of the skull===<br /> *A special type of [[basal skull fracture]].<br /> *Complete hinge fractures are considered severe; they are a 4 on the ''abbreviated injury scale'' (AIS).&lt;ref&gt;{{Cite journal | last1 = Adams | first1 = VI. | last2 = Carrubba | first2 = C. | title = The Abbreviated Injury Scale: application to autopsy data. | journal = Am J Forensic Med Pathol | volume = 19 | issue = 3 | pages = 246-51 | month = Sep | year = 1998 | doi = | PMID = 9760090 }}&lt;/ref&gt;<br /> *Classically due to a blow to the chin - resulting in a fracture across the medial fossa and sella turcica.&lt;ref&gt;URL: [http://wiki.answers.com/Q/Hinge_fracture_of_skull_is_seen_in_accidents_involving http://wiki.answers.com/Q/Hinge_fracture_of_skull_is_seen_in_accidents_involving]. Accessed on: 28 March 2012.&lt;/ref&gt;<br /> <br /> ===Pathologic fracture===<br /> {{Main|Pathologic fracture}}<br /> *A fracture due to an underlying pathology.<br /> <br /> ===Hip fractures===<br /> *[[Traumatic fracture of the femoral neck]].<br /> <br /> =Autopsy=<br /> {{Main|Autopsy}}<br /> The ''autopsy'' article covers procedural things. Heart dissection is covered in the ''[[heart]]'' article.<br /> <br /> ===Types===<br /> Forensic vs. hospital:<br /> *Forensic autopsies are focused on the external exam.<br /> <br /> ===Marking conventions for common findings===<br /> There are no universal marking conventions for injuries.<br /> <br /> One system in use (the ''Rose system'') is:&lt;ref&gt;TR. 1 September 2010.&lt;/ref&gt;<br /> *One red line for an incised wound.<br /> *Multiple closely spaced red lines, i.e. red hatching, for abrasions.<br /> *Multiple closely-spaced blue lines, i.e. blue hatching, for contusions.<br /> <br /> The above makes sense in that:<br /> *Abrasions and incised wounds typically bleed - are red.<br /> *Contusions (bruises) don't classically bleed and are classically blue.<br /> <br /> ===External exam findings===<br /> Colour of the corpse:&lt;ref name=Ref_Shkrum33&gt;{{Ref Shkrum|33}}&lt;/ref&gt;<br /> *Red (Pink) = [[carbon monoxide toxicity|carbon monoxide]], cyanide, fluoroacetate,&lt;ref name=pmid17288493&gt;{{cite journal |author=Proudfoot AT, Bradberry SM, Vale JA |title=Sodium fluoroacetate poisoning |journal=Toxicol Rev |volume=25 |issue=4 |pages=213–9 |year=2006 |pmid=17288493 |doi= |url=}}&lt;/ref&gt; [[hypothermia]].<br /> *Purple (intense) = propane.<br /> *Green = [[hydrogen sulfide]].<br /> *Brown = nitrites (methemoglobinemia).<br /> <br /> ===Autopsy terminology===<br /> *''Gutter butter'' = adipose tissue in a decomp case; looks like butter topping put on popcorn. A Toronto-ism.<br /> *''Gutter blood'' = blood in the empty thorax - after extraction of the organ block.<br /> *''Tardieu spots'' = postmortem hypostatic hemorrhages;&lt;ref name=pmid19901802&gt;{{cite journal |author=Pollanen MS, Perera SD, Clutterbuck DJ |title=Hemorrhagic lividity of the neck: controlled induction of postmortem hypostatic hemorrhages |journal=Am J Forensic Med Pathol |volume=30 |issue=4 |pages=322–6 |year=2009 |month=December |pmid=19901802 |doi=10.1097/PAF.0b013e3181c17ec2 |url=}}&lt;/ref&gt; look like petechiae - in dependent areas, i.e. in the zone of livity.<br /> <br /> ===Autopsy on decomposed remains===<br /> *[[AKA]] &quot;decomp autopsy&quot; or simply &quot;decomp&quot;.<br /> ====General====<br /> *Histology usually very limited ''or'' useless.<br /> *Often done to exclude trauma.<br /> *Typical scenario: decedent lives alone -- body not discovered for prolonged period of time.<br /> *More likely to be a ''[[negative autopsy]]'' than non-decomp cases.<br /> <br /> ====Suspicious decomp====<br /> Common sense rules for if skin is '''not''' intact:<br /> #Blunt dissection (to avoid artefactual injuries to the bones).<br /> #Clean the bones (''not'' with bleach)<br /> #*Bones cooked for 1+ hours... with frequent checks to avoid that they become mushy.<br /> <br /> =Causes of death=<br /> <br /> ==Environmental==<br /> {{Main|Environmental causes of death}}<br /> They include: <br /> *[[Hypothermia]]. <br /> *[[Hyperthermia]]. <br /> *Drowning - see [[asphyxial deaths]].<br /> *Lack of oxygen - see [[asphyxial deaths]]. <br /> *[[Electrocution]].<br /> <br /> =Gunshot wounds=<br /> {{main|Gunshot wounds}}<br /> Gunshot wounds (GSWs) are a relatively uncommon finding in Canada. They are dealt within a separate article.<br /> <br /> =Asphyxia=<br /> {{main|Asphyxial deaths}}<br /> <br /> *This is a big topic and covered by a separate article.<br /> <br /> ===Classification=== <br /> *''Strangulation'' - where there are signs of neck compression.<br /> **Includes: ganging, ligature strangulation and manual strangulation.<br /> *''Chemical asphyxia'' - usually no signs of neck compression.<br /> **Includes: carbon monoxide poisoning.<br /> *''Suffocation'' - usually no signs of neck compression.<br /> **Includes: smothering, [[choking]], positional asphyxia, [[drowning]].<br /> <br /> =Blunt force injury=<br /> *[[AKA]] ''blunt force trauma''.<br /> ==General==<br /> Classification:<br /> *Contusions.<br /> *Laceration.<br /> *Acceleration/deceleration injury, e.g. [[diffuse axonal injury]].<br /> <br /> Weapons: <br /> *Fist.<br /> *Foot.<br /> *Baseball bat... pretty much anything.<br /> *Beer bottles are common... and strong enought to fracture a skull.<br /> **Empty bottles have a higher fracture energy than full ones.&lt;ref name=pmid19239964&gt;{{cite journal |author=Bolliger SA, Ross S, Oesterhelweg L, Thali MJ, Kneubuehl BP |title=Are full or empty beer bottles sturdier and does their fracture-threshold suffice to break the human skull? |journal=J Forensic Leg Med |volume=16 |issue=3 |pages=138–42 |year=2009 |month=April |pmid=19239964 |doi=10.1016/j.jflm.2008.07.013 |url=}}&lt;/ref&gt;<br /> <br /> ==Cause of death==<br /> ===Commotio cordis===<br /> Features:&lt;ref name=pmid11334832&gt;{{cite journal |author=Kohl P, Nesbitt AD, Cooper PJ, Lei M |title=Sudden cardiac death by Commotio cordis: role of mechano-electric feedback |journal=Cardiovasc. Res. |volume=50 |issue=2 |pages=280–9 |year=2001 |month=May |pmid=11334832 |doi= |url=}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |author=Maron BJ, Estes NA |title=Commotio cordis |journal=N. Engl. J. Med. |volume=362 |issue=10 |pages=917–27 |year=2010 |month=March |pmid=20220186 |doi=10.1056/NEJMra0910111 |url=http://www.nejm.org/doi/full/10.1056/NEJMra0910111}}&lt;/ref&gt;<br /> *Often negative autopsy; no cardiac pathology.<br /> *Etiology: [[cardiac arrhythmia|arrhythmia]].<br /> *History: trauma to chest.<br /> <br /> Note:<br /> *May be spelled ''Commodio cordis''.&lt;ref name=pmid11555799&gt;{{cite journal |author=Perron AD, Brady WJ, Erling BF |title=Commodio cordis: an underappreciated cause of sudden cardiac death in young patients: assessment and management in the ED |journal=Am J Emerg Med |volume=19 |issue=5 |pages=406–9 |year=2001 |month=September |pmid=11555799 |doi=10.1053/ajem.2001.24455 |url=}}&lt;/ref&gt;<br /> *Analogous to ''[[commotio medullaris]]''.<br /> <br /> ==Scenarios==<br /> ===Motor vehicle collisions===<br /> *Pedestrian vs. motor vehicle: heel to injury measurement, remember to include the thickness of the heel/sole of shoe.&lt;ref&gt;{{Ref OPMfP|18}}&lt;/ref&gt;<br /> *Dicing injuries: tempered glass used in side window construction fragments into cubes when fractured causing L-shaped wounds.<br /> <br /> ===Descent from height===<br /> *Relatively common way to suicide.<br /> **May be an ''accident'', e.g. decedent thought they can fly (due to a psychosis).<br /> **May be a ''homicide'', e.g. decedent was pushed.<br /> <br /> ====Gross====<br /> Features:<br /> *Multiple injuries - often including multiple fractures, e.g. basal skull fracture, flail chest.<br /> *+/-Haemothorax - can be proved with a large bore needle.<br /> **Sufficient for cause of death - can be used to do an abbreviated post-mortem.<br /> *+/-Haemoaspiration (due to facial trauma) - presence suggest that decendent was alive shortly after landing/impact and thus likely very alive during the descent.<br /> **Patchy red centrilobular spots on gross examination.<br /> <br /> ==Injury patterns==<br /> ===Seromuscular tear===<br /> * [[AKA]] ''seatbeat syndrome''.<br /> * Intestinal injury associated with motor vehicle collisions and more specifically seatbelts. <br /> <br /> Features:<br /> * Def'n: separation of (inner) muscularis propria from submucosa.&lt;ref name=pmid12198344&gt;{{Cite journal | last1 = Slavin | first1 = RE. | last2 = Borzotta | first2 = AP. | title = The seromuscular tear and other intestinal lesions in the seatbelt syndrome: a clinical and pathologic study of 29 cases. | journal = Am J Forensic Med Pathol | volume = 23 | issue = 3 | pages = 214-22 | month = Sep | year = 2002 | doi = 10.1097/01.PAF.0000023001.32202.2D | PMID = 12198344 }}&lt;/ref&gt;<br /> <br /> ===Bite injury===<br /> *A special type of [[blunt force trauma]].<br /> *May be seen in the context of a sexual assault.<br /> *A ''forensic dentist'' may be able to assist.<br /> <br /> In the context of a suspicious case:<br /> *Human vs. animal.<br /> *Bite marks, as evidence, have a limited value for identification purposes.<br /> **In the context of identifying a potential perpetrator, it is essential to swab the bite mark for saliva, which is rich in DNA.&lt;ref&gt;{{Cite journal | last1 = Pretty | first1 = IA. | title = Forensic dentistry: 2. Bitemarks and bite injuries. | journal = Dent Update | volume = 35 | issue = 1 | pages = 48-50, 53-4, 57-8 passim | month = | year = | doi = | PMID = 18277695 }}&lt;/ref&gt;<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image: Dog_bite.JPG | Bite injury. (WC)<br /> &lt;/gallery&gt;<br /> <br /> ===Aortic trauma===<br /> *Classic location of transection of the aorta is distal the the left subclavian branch point near the insertion of the ligamentum arteriosum (e.g. peri-isthmus).&lt;ref name=pmid1934437&gt;{{cite journal |author=Kodali S, Jamieson WR, Leia-Stephens M, Miyagishima RT, Janusz MT, Tyers GF |title=Traumatic rupture of the thoracic aorta. A 20-year review: 1969-1989 |journal=Circulation |volume=84 |issue=5 Suppl |pages=III40–6 |year=1991 |month=November |pmid=1934437 |doi= |url=}}&lt;/ref&gt;<br /> *[[Aortic dissection]] due to trauma is often catastrophic. Several mechanisms have been proposed and there is a body of trauma biomechanics research that explores this.<br /> <br /> ==Trauma with delayed death==<br /> *[[Epidural hemorrhage]] with a lucid interval.<br /> *Subcapsular splenic hematoma with subsequent rupture.<br /> *Subcapsular hepatic hematoma with subsequent rupture.<br /> *[[Aortic dissection]] with subsequent rupture.<br /> <br /> =Sharp force injury=<br /> *[[AKA]] ''sharp force trauma''.<br /> ===General===<br /> Injuries caused by:&lt;ref name=Ref_HospAuto111-2&gt;{{Ref HospAuto|111-2}}&lt;/ref&gt;<br /> *Knife.<br /> *Scissors - classic &quot;Z&quot; shape.<br /> *Screwdriver.<br /> *Glass.<br /> <br /> ===Gross===<br /> Features:&lt;ref name=Ref_HospAuto111-2&gt;{{Ref HospAuto|111-2}}&lt;/ref&gt;<br /> *Incised wound (see: ''[[Wounds|Classification of wounds]]'').<br /> **&quot;Clean&quot; edge (no contusion, no abrasion).<br /> **Well-demarcated edges.<br /> *+/-Hilt mark.<br /> **Due to contact of hilt.<br /> <br /> Subclassified into - see ''[[Wounds|classification of wounds]]'':<br /> *''Cut/slash''. <br /> *''Stab''. <br /> *''Chop'' - a mixed injury, sharp force and blunt force.<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image: Thorax-Messerstichwunden.jpg | Sharp force trauma - thorax. (WC)<br /> &lt;/gallery&gt;<br /> <br /> =Head injuries=<br /> ===Accidental vs. intentional===<br /> Features of non-accidental injuries:&lt;ref name=pmid20141554&gt;{{cite journal |author=Guyomarc'h P, Campagna-Vaillancourt M, Kremer C, Sauvageau A |title=Discrimination of falls and blows in blunt head trauma: a multi-criteria approach |journal=J. Forensic Sci. |volume=55 |issue=2 |pages=423–7 |year=2010 |month=March |pmid=20141554 |doi=10.1111/j.1556-4029.2009.01310.x |url=}}&lt;/ref&gt;<br /> *Lacerations:<br /> **More than three.<br /> **Length &gt;= 7 cm or more.<br /> **Location:<br /> ***Above hat brim line (HBL).<br /> ***[[Ear]].<br /> ***Left-sided.<br /> *Fractures:<br /> **Comminuted or depressed calvarial fractures. <br /> **Location:<br /> ***Fractures located above the HBL.<br /> ***Left-sided fractures.<br /> ***Facial fractures.<br /> *Contusions:<br /> **Greater than four facial contusions.<br /> *Other:<br /> **&quot;Postcranial osseous&quot; [sic] (non-rib, non-skull) and/or visceral trauma.<br /> <br /> Note: The paper doesn't give odds ratios for the the different features -- like in the rational clinical exam series... it is a shame.<br /> <br /> ==Diffuse axonal injury==<br /> *Abbreviated ''DAI''.<br /> ===General===<br /> Clinical:<br /> *Vegetative state. <br /> *Imaging findings: no anatomical cause apparent (in some cases).<br /> <br /> Etiology:<br /> *Hypothesized to arise from high shear loading of white mater tracts.&lt;ref name=pmid2769276&gt;{{cite journal |author=Blumbergs PC, Jones NR, North JB |title=Diffuse axonal injury in head trauma |journal=J. Neurol. Neurosurg. Psychiatr. |volume=52 |issue=7 |pages=838–41 |year=1989 |month=July |pmid=2769276 |pmc=1031929 |doi= |url=}}&lt;/ref&gt;<br /> <br /> ===Gross===<br /> Macroscopic findings:&lt;ref name=pmid2769276/&gt;<br /> *Tears - corpus callosum.<br /> *Haemorrhage.<br /> <br /> Other (chronic) changes:&lt;ref name=Ref_AoGP639&gt;{{Ref AoGP|639}}&lt;/ref&gt;{{fact}}<br /> *Thalamus - shrinkage.<br /> *Enlargement of third ventricle.<br /> <br /> DDx (medical imaging):&lt;ref name=pmid22406792&gt;{{Cite journal | last1 = Kumar | first1 = S. | last2 = Gupta | first2 = V. | last3 = Aggarwal | first3 = S. | last4 = Singh | first4 = P. | last5 = Khandelwal | first5 = N. | title = Fat embolism syndrome mimicker of diffuse axonal injury on magnetic resonance imaging. | journal = Neurol India | volume = 60 | issue = 1 | pages = 100-2 | month = | year = | doi = 10.4103/0028-3886.93597 | PMID = 22406792 }}&lt;/ref&gt;<br /> *[[Cerebral fat embolism]].<br /> <br /> ===Microscopic===<br /> Microscopic findings:&lt;ref name=pmid2769276/&gt;<br /> *Axonal retraction balls.<br /> *&quot;Microglial stars&quot;.<br /> *Degeneration of fibre tracts.<br /> <br /> Grading:&lt;ref&gt;URL: [http://wiki.cns.org/wiki/index.php/Diffuse_axonal_injury_%28DAI%29 http://wiki.cns.org/wiki/index.php/Diffuse_axonal_injury_%28DAI%29]. Accessed on: 13 February 2012.&lt;/ref&gt;<br /> *Grade 1: only microscopic findings.<br /> *Grade 2: macroscopic corpus callosum injury + microscopic findings of DAI. <br /> *Grade 3: macroscopic corpus callosum and midbrain injuries + microscopic findings of DAI.<br /> <br /> ===Stains===<br /> *[[Bielschowsky stain]] to highlight axonal swellings - appear 12-18 hours after injury.&lt;ref name=Ref_Shkrum_562&gt;{{Ref Shkrum|562}}&lt;/ref&gt;<br /> <br /> ===IHC===<br /> *Beta-amyloid precursor protein (beta-APP ''or'' APP).&lt;ref name=pmid10050789&gt;{{cite journal |author=Gleckman AM, Bell MD, Evans RJ, Smith TW |title=Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining |journal=Arch. Pathol. Lab. Med. |volume=123 |issue=2 |pages=146–51 |year=1999 |month=February |pmid=10050789 |doi= |url=}}&lt;/ref&gt;&lt;ref name=pmid17368446&gt;{{Cite journal | last1 = Mac Donald | first1 = CL. | last2 = Dikranian | first2 = K. | last3 = Song | first3 = SK. | last4 = Bayly | first4 = PV. | last5 = Holtzman | first5 = DM. | last6 = Brody | first6 = DL. | title = Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury. | journal = Exp Neurol | volume = 205 | issue = 1 | pages = 116-31 | month = May | year = 2007 | doi = 10.1016/j.expneurol.2007.01.035 | PMID = 17368446 | PMC = 1995439 }}&lt;/ref&gt;<br /> *NF.&lt;ref name=pmid17368446/&gt;<br /> <br /> ==Intracranial hemorrhage==<br /> {{main|Intracranial hematoma}}<br /> Intracranial hemorrhage may be a consequence of blunt force trauma.<br /> <br /> Classification:<br /> *[[Epidural hematoma]].<br /> *[[Subdural hematoma]].<br /> *[[Subarachnoid hematoma]].<br /> *[[Intracerebral hematoma]].<br /> <br /> ==Cerebral contusion==<br /> ===General===<br /> *Due to blunt force trauma.<br /> <br /> ===Gross===<br /> Features:<br /> *Focal superficial hemorrhage.<br /> *Location, usually, ''frontal lobe'' and ''temporal lobe''.&lt;ref name=Ref_HoFP_102&gt;{{Ref HoFP|102}}&lt;/ref&gt;<br /> <br /> Notes:<br /> *Classically, come in pairs:&lt;ref name=Ref_HoFP_102&gt;{{Ref HoFP|102}}&lt;/ref&gt;<br /> *#''Coup contusion'' - at the site of the (primary) impact<br /> *#''Contrecoup contusion'' - secondary internal impact.<br /> **Example - fall on back of head: <br /> ***Occipital lobe contusion = coup contusion.<br /> ***Frontal lobe contusion = contrecoup contusion.<br /> *May be associated with contusions of the:&lt;ref name=Ref_HoFP_103&gt;{{Ref HoFP|103}}&lt;/ref&gt; <br /> **Deep brain structures, known as an &quot;intermediary coup&quot;.<br /> **Dorsal surface of the cerebral hemispheres, known as &quot;gliding contusions&quot;.<br /> *Resolve as a yellow lesion (like at other sites), known as a ''[[plaque]] jaune'' in the brain.<br /> **Classically, inferior aspect of the frontal lobe.<br /> <br /> DDx:<br /> *Hemorrhagic [[stroke]] - usually temporal lobe and/or parietal lobe.<br /> <br /> ==Traumatic brain injury in infants==<br /> {{main|Traumatic brain injury in infants}}<br /> <br /> *Shaken-impact syndrome, [[AKA]] shaken baby syndrome.<br /> <br /> ==Commotio medullaris==<br /> Features:&lt;ref name=Ref_Shkrum613&gt;{{Ref Shkrum|613}}&lt;/ref&gt;<br /> *Sudden death after head trauma that is insufficient to explain death.<br /> *Etiology: unknown - thought to be related to apnea.<br /> <br /> Note:<br /> *Analogous to ''[[commotio cordis]]''.<br /> <br /> =Excited delirium=<br /> *[[AKA]] ''agitated delirium''.&lt;ref name=pmid8768172&gt;{{cite journal |author=Wetli CV, Mash D, Karch SB |title=Cocaine-associated agitated delirium and the neuroleptic malignant syndrome |journal=Am J Emerg Med |volume=14 |issue=4 |pages=425–8 |year=1996 |month=July |pmid=8768172 |doi= |url=}}&lt;/ref&gt;<br /> ===General===<br /> *[[Diagnosis]] is considered somewhat controversial outside of the forensic pathology community.&lt;ref name=pmid18450833&gt;{{Cite journal | last1 = Stanbrook | first1 = MB. | last2 = Hébert | first2 = PC. | last3 = Kale | first3 = R. | last4 = Sibbald | first4 = B. | last5 = Flegel | first5 = K. | last6 = MacDonald | first6 = N. | title = Tasers in medicine: an irreverent call for proposals. | journal = CMAJ | volume = 178 | issue = 11 | pages = 1401-2, 1403-4 | month = May | year = 2008 | doi = 10.1503/cmaj.080592 | PMID = 18450833 |PMC = 2374865 }}&lt;/ref&gt;<br /> *The [[diagnosis]] has garnered attention in the context of electroshock weapon use, as ''Taser International'' (a manufacturer of electroshock weapons) has often ascribed the deaths involving its weapons to it - when it is alleged that their electroshock weapon caused the death.<br /> <br /> *There is no &quot;official&quot; definition for ''excited delirium''.<br /> **Most agree it includes fever.<br /> <br /> One paper defines it in relation ''neuroleptic malignant syndrome'':&lt;ref name=pmid8768172/&gt;<br /> *Fever.<br /> *Disorientation and confusion.<br /> *Increased energy/superhuman strength.<br /> <br /> Excited delirium - hypothesis:<br /> *Thought to arise in the context of severe chronic mental disorders (e.g. schizophrenia) and protracted [[cocaine]] binges.&lt;ref name=pmid9645173&gt;{{Cite journal | last1 = Pollanen | first1 = MS. | last2 = Chiasson | first2 = DA. | last3 = Cairns | first3 = JT. | last4 = Young | first4 = JG. | title = Unexpected death related to restraint for excited delirium: a retrospective study of deaths in police custody and in the community. | journal = CMAJ | volume = 158 | issue = 12 | pages = 1603-7 | month = Jun | year = 1998 | doi = | PMID = 9645173 | PMC = 1229410 | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1229410}}&lt;/ref&gt;<br /> *Thought to result from alteration of dopamine receptor density. The D2 receptor in particular, which is thought to be important in temperature regulation, is decreased in psychotic cocaine abusers.&lt;ref name=pmid8768172/&gt;<br /> <br /> =Toxicology &amp; biochemistry=<br /> ===General===<br /> Things usually collected at autopsy:<br /> #Blood in EDTA tube (genetic testing).<br /> #Urine toxicology:<br /> #*Useful to evaluate ''myoglobin''.<br /> #Vitreous:<br /> #*Biochemistry.<br /> #*Ketones.<br /> #*Urea (???).<br /> #Bile:&lt;ref&gt;{{Ref HospAuto|220}}&lt;/ref&gt;<br /> #*Acetaminophen overdoses.<br /> #*Opiate overdoses.<br /> <br /> Myoglobin DDx:<br /> *Neuroleptic malignant syndrome.<br /> *Malignant hyperthermia.<br /> *Serotonin syndrome.<br /> <br /> ===Biochemistry===<br /> *[[Diabetes mellitus]]:&lt;ref name=Ref_HospAuto221&gt;{{Ref HospAuto|221}}&lt;/ref&gt;<br /> **Plasma:<br /> ***Hemoglobin A1c - increased.<br /> ***Acetone - increased.<br /> ***Beta-hydroxybutyrate - increased.<br /> ****Also increased in alcoholic ketoacidosis (though ketones low).<br /> **Urine:<br /> ***Aceto-acetate - increased.<br /> <br /> Death by insulin overdose:&lt;ref name=Ref_HospAuto224&gt;{{Ref HospAuto|224}}&lt;/ref&gt;<br /> *C-peptide - low.<br /> *Insulin - high.<br /> <br /> ====Serum====<br /> *Potassium - rises quickly and rapidly after death; completely useless.<br /> *Sodium - tends to decrease after death; usually useless.<br /> *Glucose - drops quickly; useless unless sky high.<br /> *Urea, creatinine and urate - stable for ~48 hours post-mortem.&lt;ref name=Ref_HospAuto222&gt;{{Ref HospAuto|222}}&lt;/ref&gt;<br /> <br /> ===Vitreous===<br /> *Creatinine and urea - approximate those at time of death.&lt;ref name=Ref_HospAuto222&gt;{{Ref HospAuto|222}}&lt;/ref&gt;<br /> *Glucose - used to assess for hyperglycemia (due to [[diabetes mellitus|diabetic coma]]) in life.&lt;ref name=pmid19167848&gt;{{Cite journal | last1 = Zilg | first1 = B. | last2 = Alkass | first2 = K. | last3 = Berg | first3 = S. | last4 = Druid | first4 = H. | title = Postmortem identification of hyperglycemia. | journal = Forensic Sci Int | volume = 185 | issue = 1-3 | pages = 89-95 | month = Mar | year = 2009 | doi = 10.1016/j.forsciint.2008.12.017 | PMID = 19167848 }}&lt;/ref&gt;<br /> <br /> ===Toxicology===<br /> *Should be submitted with anatomical findings and history.<br /> <br /> Common submissions:<br /> #Alcohol only.<br /> #Suspected toxicologic death - need details on drugs.<br /> <br /> ====Mandated by case====<br /> In Ontario, the following are mandated by the case:&lt;ref&gt;{{Ref OPMfP|14}}&lt;/ref&gt;<br /> *Sudden death of child under five years old.<br /> *Workplace death.<br /> *Fatal motor vehicle collision - esp. driver.<br /> *Aviation death - esp. pilot &amp; co-pilot.<br /> *Fire-related death (carboxyhemoglobin).<br /> <br /> ===Toxins===<br /> ====Ethanol toxicity====<br /> {{Main|Ethanol abuse}}<br /> *Usually measured (in Canada) as: ''mass of EtOH (mg)/volume of blood (mL)''.<br /> **Limit (Ontario): 80 milligrams of alcohol in 100 millilitres of blood (0.08 gm/100 mL).&lt;ref&gt;URL: [http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml]. Accessed on: 28 September 2010.&lt;/ref&gt;<br /> **Enough to be fatal ~ 350 mg/dL ~= 76 mmol/L.<br /> <br /> =====Ethanol intoxication as a table&lt;ref name=southendnhs&gt;URL: [http://www.southend.nhs.uk/pathologyhandbook/clinical_chemistry/Guidelines/ethanol_poisoning.htm http://www.southend.nhs.uk/pathologyhandbook/clinical_chemistry/Guidelines/ethanol_poisoning.htm]. Accessed on: 19 October 2010.&lt;/ref&gt;===== <br /> {| class=&quot;wikitable&quot;<br /> |<br /> |Concentration<br /> |Concentration<br /> |Concentration<br /> |Concentration<br /> |-<br /> |Legal limit - Ontario&lt;ref&gt;URL: [http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml]. Accessed on: 28 September 2010.&lt;/ref&gt;<br /> | 80 mg/dL<br /> | ~17 mmol/L<br /> | 0.8 g/L<br /> | 0.08 g/dL<br /> |-<br /> |Mild<br /> | &lt; 180 mg/dL<br /> | &lt; 39 mmol/L<br /> | &lt; 1.8 g/L <br /> | &lt; 0.18 g/dL <br /> |-<br /> |Moderate<br /> | 180-350 mg/dL <br /> | 39-76 mmol/L<br /> | 1.8-3.5 g/L <br /> | 0.18-0.35 g/dL<br /> |-<br /> |Severe<br /> | 350-450 mg/dL <br /> | 76-98 mmol/L<br /> | 3.5-4.5 g/L <br /> | 0.35-0.45 g/dL <br /> |}<br /> <br /> Notes:<br /> *1 mg/dL = 1/4.607 mmol/L.<br /> **Ethanol's molar mass = 46.07 g/mol.<br /> <br /> ====Methanol toxicity====<br /> *Minimum lethal dose: 40 mg/dl.&lt;ref&gt;URL: [http://path.upmc.edu/cases/case242/dx.html http://path.upmc.edu/cases/case242/dx.html. Accessed on: 13 January 2012.&lt;/ref&gt;<br /> <br /> *Typically an accidental death; person consumes methanol as an ethanol substitute. <br /> *Blindness.<br /> *[[Putamen]] [[necrosis]] (bilateral).&lt;ref name=pmid16484428&gt;{{Cite journal | last1 = Blanco | first1 = M. | last2 = Casado | first2 = R. | last3 = Vázquez | first3 = F. | last4 = Pumar | first4 = JM. | title = CT and MR imaging findings in methanol intoxication. | journal = AJNR Am J Neuroradiol | volume = 27 | issue = 2 | pages = 452-4 | month = Feb | year = 2006 | doi = | PMID = 16484428 }}&lt;/ref&gt;<br /> *+/-Pancreatic injury.&lt;ref name=pmid10866330&gt;{{Cite journal | last1 = Hantson | first1 = P. | last2 = Mahieu | first2 = P. | title = Pancreatic injury following acute methanol poisoning. | journal = J Toxicol Clin Toxicol | volume = 38 | issue = 3 | pages = 297-303 | month = | year = 2000 | doi = | PMID = 10866330 }}&lt;/ref&gt;<br /> <br /> ====Cocaine toxicity====<br /> *No agreed upon toxic dose&lt;ref name=pmid15075681&gt;{{cite journal |author=Stephens BG, Jentzen JM, Karch S, Wetli CV, Mash DC |title=National Association of Medical Examiners position paper on the certification of cocaine-related deaths |journal=Am J Forensic Med Pathol |volume=25 |issue=1 |pages=11–3 |year=2004 |month=March |pmid=15075681 |doi= |url=}}&lt;/ref&gt; - due to tolerance.<br /> *Usual mechanism ''cardiac failure''.<br /> <br /> Features - heart:<br /> *Usually anatomically normal heart.<br /> **+/-Advanced [[coronary artery atherosclerosis]] for age.<br /> **+/-[[Myocardial infarction]].<br /> ***+/-Contraction band necrosis.<br /> **+/-Cardiac hypertrophy.<br /> <br /> Other:<br /> *+/-Nasal septum perforation.<br /> *+/-Track marks (other drug use).<br /> *+/-Finger burns (during preparation of crack).<br /> *+/-Drug paraphernalia, e.g. crack pipe.<br /> <br /> ====Ethylene glycol toxicity====<br /> :For a more general discussion see ''[[Crystals_in_body_fluids#Urine_crystals|urine crystals]]''<br /> *Not done in routine toxicology screening.<br /> *Birefringent calcium oxalate crystals found in kidney (with polarized light).&lt;ref name=Ref_KFP589&gt;{{Ref KFP|589}}&lt;/ref&gt;<br /> <br /> ====Anaphylaxis====<br /> *Allergic reaction, e.g. peanut allergy.<br /> <br /> Diagnosis - serology:&lt;ref name=pmid20176258&gt;{{cite journal |author=Simons FE |title=Anaphylaxis |journal=J. Allergy Clin. Immunol. |volume=125 |issue=2 Suppl 2 |pages=S161–81 |year=2010 |month=February |pmid=20176258 |doi=10.1016/j.jaci.2009.12.981 |url=}}&lt;/ref&gt;<br /> *IgE.<br /> *Tryptase.<br /> <br /> =Natural death=<br /> {{main|Natural death}}<br /> There is a lot that can kill ya... but only a few of those are quickly, i.e. within a hour or so.<br /> <br /> Generally, these things are:<br /> *Cardiovascular:<br /> **[[Cardiac arrhythmia|Arrhythmia]].<br /> **[[Myocardial infarction]].<br /> **Haemorrhage.<br /> ***Ruptured aneurysm.<br /> **[[Hypertensive heart disease]].<br /> *Respiratory:<br /> **[[Pulmonary embolism]] (PE).<br /> **[[Asthma]].<br /> *GI:<br /> **Haemorrhage.<br /> ***[[Esophageal varices]].<br /> ***Gastric varices.<br /> *Neurologic:<br /> **Intracranial haemorrhage.<br /> ***Ruptured aneurysm.<br /> ***Spontaneous [[subdural hemorrhage]].<br /> **[[Stroke]]:<br /> ***Haemorrhagic.<br /> ***Thrombotic (more common than hemorrhagic).<br /> <br /> =Forensic entomology=<br /> {{main|Forensic entomology}}<br /> *Study of the bugs that eat corpses.<br /> *Bugs may hide a wound... it is important to know where they like to be.<br /> <br /> =Forensic anthropology=<br /> {{main|Forensic anthropology}}<br /> Forensic anthropology is looking at skeletal remains. It may be useful of [[decendent identification|identification]] and, rarely, the cause of death. Important in skeletonized remains and decomp cases.<br /> <br /> =Forensic taphonomy=<br /> *The study of post-mortem decay to assist in a medicolegal investigation.<br /> **''Taphonomy'' = postmortem fate of biological remains; derived from the Greek word ''taphos'' (grave).&lt;ref&gt;{{cite journal |author=Milroy CM |title=Forensic taphonomy: the postmortem fate of human remains |journal=BMJ |volume=319 |issue=7207 |pages=458 |year=1999 |month=August |pmid=10445946 |pmc=1127062 |doi= |url=}}&lt;/ref&gt;<br /> <br /> =See also=<br /> *[[Forensic entomology]].<br /> *[[Autopsy]].<br /> *[[Heart]].<br /> <br /> =References=<br /> {{reflist|2}}<br /> <br /> =External links=<br /> *[http://cap-acp.org/forensic.cfm Forensic pathology (cap-acp.org)].<br /> *[http://neurobio.drexelmed.edu/goldmanweb/forensicanthro/trauma.pdf Fractures (drexelmed.edu)].<br /> *[http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ Mechanisms of death (forensicmed.co.uk)].<br /> <br /> ==Post-mortem changes==<br /> *[http://emedicine.medscape.com/article/1680032-overview#showall Post-mortem changes (emedicine.medscape.com)].<br /> *[http://emedicine.medscape.com/article/1680107-overview#showall Autopsy of blunt force trauma (emedicine.medscape.com)].<br /> *[http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html Post-mortem changes (the-crankshaft.info)].<br /> <br /> [[Category:Autopsy]]<br /> [[Category:Forensic pathology]]</div>

Tate https://librepathology.org/w/index.php?title=Forensic_pathology&diff=39173 2015-08-12T14:21:05Z

<p>Tate: /* Motor vehicle collisions */</p> <hr /> <div>'''Forensic pathology''' is figuring-out why, when, where and how people died, if the manner of death is ''not'' obviously natural.<br /> <br /> =Death categorization=<br /> Deaths are categorized foremost by the '''manner of death'''. The manner is the single most important legal categorization for a death. <br /> The '''cause of death''' is important for understanding what happened. The '''mechanism of death''' is the pathophysiologic reason for death and can be inferred from the cause.<br /> <br /> Examples:<br /> {| class=&quot;wikitable sortable&quot; <br /> !Cause of death <br /> !Manner of death<br /> !Mechanism of death<br /> !Scenario<br /> |-<br /> | [[Electrocution]]<br /> | accident<br /> | [[cardiac arrhythmia]]<br /> | man struck by lightening<br /> |-<br /> | Hyperthermia<br /> | accident<br /> | arrhythmias, seizures&lt;ref name=fmuk&gt;URL: [http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ http://www.forensicmed.co.uk/pathology/mechanisms-of-death/]. Accessed on: 19 April 2012.&lt;/ref&gt;<br /> | man lost on hiking trip in desert<br /> |-<br /> | [[Epidural hemorrhage]] due to [[blunt force trauma]] to the head<br /> | homicide<br /> | brain stem compression or cerebral vascular spasm leading to autonomic dysregulation<br /> | man hit with a hammer in the head<br /> |-<br /> | [[Carbon monoxide toxicity]]<br /> | suicide<br /> | cerebral hypoxia (CO binds to hemoglobin impairing oxygen transport)<br /> | woman found in car with suicide note, long history of depression, previous suicide attempts<br /> |-<br /> | [[Atherosclerotic heart disease]]<br /> | natural<br /> | cardiac arrhythmia due to ischemia<br /> | man found dead in bed, apartment locked, 95% stenosis of LMCA at autopsy, no other significant autopsy findings<br /> |- &lt;!--<br /> | [[Peritonitis]] due to duodenal perforation as a consequence of [[peptic ulcer disease]]<br /> | natural<br /> | cerebral hypoxia secondary to hypotension<br /> | man found in locked apartment, complained of abdominal pain before dead<br /> |-<br /> | Coronary artery stent thrombosis complicating the treatment of a [[myocardial infarction]] due to atherosclerotic heart disease<br /> | natural<br /> | cardiac arrhythmia due to ischemia<br /> | woman found dead following hospital stay for a myocardial infarction, post-angioplasty and coronary stenting --&gt;<br /> |}<br /> <br /> ==Manner of death==<br /> The manner of death is a legislatively defined classification. It varies slightly between jurisdictions. <br /> &lt;!--<br /> MANNER OF DEATH<br /> --&gt;<br /> {{familytree/start}}<br /> {{familytree | | | | | | | | | A | | | | | | | | |A=Manner}}<br /> {{familytree | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| |}}<br /> {{familytree | B | | C | | D | | E | | F |B=Homicide|C=Suicide|D=Natural|E=Accident|F=Undetermined}}<br /> {{familytree/end}}<br /> <br /> Notes:<br /> *''Undetermined'' - is a waste basket category.<br /> *''Homicide'' - not necessarily murder.<br /> *Can be group into three:<br /> *#Intent to kill (homicide, suicide).<br /> *#No intent to kill (natural, accidental).<br /> *#Undetermined.<br /> <br /> ==Mechanism of death==<br /> This is occasionally of interest. It is usually based on physiology. <br /> <br /> The mechanism is often asked for [[asphyxial death]]s. The short answer it is: brain stem hypoxia due to ischemia caused by venous obstruction in the neck.&lt;ref&gt;URL: [http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ http://www.forensicmed.co.uk/pathology/mechanisms-of-death/]. Accessed on: 1 May 2012.&lt;/ref&gt;&lt;ref&gt;URL: [http://www.forensicmed.co.uk/pathology/pressure-to-the-neck/ http://www.forensicmed.co.uk/pathology/pressure-to-the-neck/]. Accessed on: 1 May 2012.&lt;/ref&gt;<br /> <br /> ==Cause of death==<br /> *Abbreviated ''COD''.<br /> ===General===<br /> *The cause of death should be what started the sequence of events that lead to death.<br /> <br /> ====Word form for cause of death====<br /> Examples:<br /> *''[[C. difficile colitis]] complicating antibiotic treatment for a dental abscess''.&lt;ref&gt;MSP. 8 September 2010.&lt;/ref&gt;<br /> *''Complications of laparoscopic cholecystectomy for ascending cholangitis with [[mesothelioma]] and atherosclerotic heart disease''.&lt;ref&gt;TR. 3 September 2010.&lt;/ref&gt;<br /> <br /> General forms:<br /> *''A'' complicating ''B'' for the treatment of ''C''.<br /> *''A'' complicating ''B'' for the treatment of ''C'' with ''D'' and ''E''.<br /> <br /> ====World Health Organization form for cause of death====<br /> General form:&lt;ref name=pmid15914304&gt;{{cite journal |author=Pollanen MS |title=Deciding the cause of death after autopsy--revisited |journal=J Clin Forensic Med |volume=12 |issue=3 |pages=113–21 |year=2005 |month=June |pmid=15914304 |doi=10.1016/j.jcfm.2005.02.004 |url=}}&lt;/ref&gt;<br /> *1a = ''immediate cause of death''.<br /> *1b = what lead to the ''immediate cause of death''.<br /> *1c... 1[x] -- where 'x' is the last letter used; 1x = What started the sequence of events. This is known as the ''underlying cause of death''.<br /> *2 = contributing factors.<br /> <br /> Example 1:<br /> *1a. [[Ketoacidosis]].<br /> *1b. [[Diabetes mellitus]].<br /> *2. [[Alcoholism]] and acute [[bronchopneumonia]].<br /> <br /> Example 2:<br /> *1a. Hemoperitoneum.<br /> *1b. [[Splenic laceration]].<br /> *1c. Blunt force trauma.<br /> *2. Liver [[cirrhosis]].<br /> <br /> ===Natural deaths===<br /> {{Main|Natural death}}<br /> *The cause should be a medical diagnosis, '''not''' the mechanism (e.g. ''cardiac arrest'', ''cachexia'', ''kidney failure'').<br /> *The [[mechanism of death|mechanism]] is irrelevant.<br /> <br /> Notes:<br /> *Unnatural causes trump natural ones. If a guy with (nothing more than) a 70% proximal LAD stenosis and an old [[myocardial infarct]] is found in the water, they are usually called [[drowning]].<br /> *[[Cancer]] is rarely the immediate cause of death - it is usually something else.&lt;ref&gt;Shannon, P. 2009.&lt;/ref&gt;<br /> *Things (mechanisms) that shouldn't be used: [http://www.pallimed.org/2008/03/unacceptable-causes-of-death-other-web.html http://www.pallimed.org/2008/03/unacceptable-causes-of-death-other-web.html]<br /> <br /> ===Legal frame work===<br /> ====General====<br /> *In Ontario, the ''manner'' is determined by the coroner.<br /> *Coroners, in Ontario, are MDs -- usually [[family docs]].<br /> *The cause (e.g. &quot;gunshot wound to the head&quot;) is determined by the pathologist.<br /> <br /> NB - the word ''coroner'' is not synoymous with MD. British Columbia has coroners that aren't MDs.<br /> <br /> ====Case classification (Ontario)====<br /> Cases are classified as:<br /> *''A case'' = homicide and suspicious for homicide, (all) gunshot wounds.<br /> *''B case'' = adult, non-suspicious.<br /> *''C case'' = child, non-suspicious.<br /> <br /> Notes:<br /> *All ''A cases'' are done at regional centers by certified forensic pathologists.<br /> <br /> =Forensic golden triangle=<br /> *History.<br /> *Scene.<br /> *[[Autopsy]].<br /> <br /> =Forensic diagnostic triangle=<br /> Most general differential diagnosis:<br /> *Natural:<br /> **Haemorrhage (e.g. cerebral bleed, gastrointestinal bleed, aortic aneurysm).<br /> **Infection (e.g. [[pneumonia]]).<br /> **[[Coronary artery atherosclerosis]] ([[cardiac arrhythmia]]s - more common in the forensic context than [[myocardial infarction]] (MI); individuals with MIs don't usu. drop dead-- they go to the ER).<br /> ***Post [[myocardial infarction]] (free wall rupture).<br /> ***Ruptured (atherosclerotic) plaque.<br /> *Toxic (memory device: ''PAIRO''):<br /> **Poisons.<br /> **[[Alcohol]] (EtOH). <br /> **Illicit (e.g. [[cocaine]], heroin, LSD). <br /> **Rx. <br /> **Over-the-counter (OTC) (e.g. acetaminophen, warfarin).<br /> *Trauma (memory device ''AGE BS''):<br /> **[[asphyxial deaths|Asphyxial]]. <br /> **[[Gunshot wounds]] (GSWs). <br /> **Environmental (e.g. hypothermia, hyperthermia, [[drowning]], lack of oxygen, [[electrocution]]).<br /> **[[Blunt force trauma]]. <br /> **[[Sharp force trauma]]. <br /> <br /> Difficulties arise when more than one point of the triangle is in play, i.e. the forensic pathologist has to earn their pay when an old man with a heart condition is known to be into erotic asphyxia, and dies after doing some drugs and whilst indulging in erotic asyphxiation with a friend...<br /> <br /> *If he had an arrhythmia and there was no stressor... ''natural'' death.<br /> *If he over did it with the drugs, it is an overdose, ergo ''accidental''.<br /> *If he did the erotic asphyxia a bit too long it is ''accidental''.<br /> *If the friend held the plastic bag over his head just a bit long to asphyxiate him... it is a ''homicide''.<br /> *If he was a lone and depressed... he might have been trying to kill himself, ergo ''suicide''.<br /> <br /> =Death-related changes=<br /> ===Rigor mortis===<br /> Definition: <br /> *Muscle rigidity following death (caused by depletion of ATP).<br /> <br /> Dependent on:<br /> *Temperature of patient at death.<br /> *Temperature variations in the environment since death.<br /> *Presence of some medical conditions.<br /> *May never develop!<br /> <br /> It is the explanation for post-mortem goose bumps.<br /> <br /> ====Summary====<br /> *Its onset &amp; presence is ''highly variable''.<br /> *Forensic pathologists do '''not''' comment on time of death, as the above times are subject to such a large degree of variability, i.e. the estimates are essentially useless.<br /> <br /> ====Time estimates====<br /> A crude guess for time of death based on rigor:&lt;ref name=Ref_KFP61&gt;{{Ref KFP|61}}&lt;/ref&gt;<br /> *Warm &amp; flaccid &lt;3 h.<br /> *Warm &amp; stiff 3-8 h. <br /> *Cold &amp; stiff 8-36 h. <br /> *Cold &amp; flaccid &gt; 36 h.<br /> <br /> Notes:<br /> *Memory device: '''3s''': cut points are at ''3 hours'', ''1/3 of a day'', ''3/2 of a day.''<br /> ===Livor mortis===<br /> Definition: pooling of blood in the dependent position, due to blood stasis. <br /> *Onset may preceed death in the context of congestive heart failure.<br /> *If pressure is applied to a dependent area-- no blood can enter there; thus, a pressure area is blanched (i.e. white).<br /> <br /> *Can be seen externally, i.e. on the skin, and internally.<br /> *Liver mortis becomes fixed some time after death. <br /> **Liver mortis does NOT tell one the position the decedent was in at the time of death-- only the position the decedent was at the time liver mortis became fixed. '''If''' the decedent wasn't moved liver mortis can help determine the position the person was in when they died.<br /> <br /> Averages:<br /> *Start: 30 minutes to 2 hours<br /> *Fixed: 8-12 hours.<br /> <br /> DDx:<br /> *[[Blunt force trauma]] - especially to the inexperienced eye.<br /> *Post-mortem hypostatic bruising.<br /> <br /> ===Tache noire===<br /> Literally ''black spot''.<br /> <br /> Features:&lt;ref name=emed1680032&gt;URL: [http://emedicine.medscape.com/article/1680032-overview http://emedicine.medscape.com/article/1680032-overview]. Accessed on: 6 March 2012.&lt;/ref&gt;<br /> *Brown/black horizontal line of the eye due to drying.<br /> **Arises if the eye remains open after death.<br /> **May mimic a traumatic injury. <br /> <br /> Images:<br /> *[http://img.medscape.com/pi/emed/ckb/pathology/1603817-1607640-1680032-1714463.jpg Tache noire (medscape.com)].&lt;ref name=emed1680032/&gt;<br /> *[http://www.demussen.net/carbon-monoxide/images/1856_23_12-vitreous-potassium.jpg Tache noire (demussen.net)].&lt;ref&gt;URL: [http://www.demussen.net/carbon-monoxide/chemical-changes-in-body-fluids.html http://www.demussen.net/carbon-monoxide/chemical-changes-in-body-fluids.html]. Accessed on: 6 March 2012.&lt;/ref&gt;<br /> <br /> ===Post-mortem decomposition/preservation===<br /> One of three things happens post-mortem:&lt;reF name=Ref_HospAuto102&gt;{{Ref HospAuto|102}}&lt;/ref&gt;<br /> #Mummification.<br /> #Putrefaction (skeletonisation).<br /> #*Green colour due to break down of hemoglobin (biliverdin).&lt;ref&gt;{{cite journal |author=NOIR BA, GARAY ER, ROYER M |title=SEPARATION AND PROPERTIES OF CONJUGATED BILIVERDIN |journal=Biochim. Biophys. Acta |volume=100 |issue= |pages=403–10 |year=1965 |month=May |pmid=14347937 |doi= |url=linkinghub.elsevier.com/retrieve/pii/0304416565900097}}&lt;/ref&gt;<br /> #Adipocere - transformation into wax (due to anaerobic bacterial hydrolysis of fat).<br /> #*Useless for toxicology and DNA.<br /> <br /> *A mix of the above often occur, i.e. part of the corpse is mummified... part of it decomposed through putrefaction.<br /> <br /> Mummification:<br /> *Predominant in dry environments.<br /> *Body becomes dry and leathery.<br /> <br /> Putrefaction:<br /> *Body wet/moist after death -- ideal environment for putrefactive bacteria and organisms.<br /> <br /> ===Artefacts===<br /> *Prinsloo and Gordon artefact = artefactual post-morten haemorrhage on the posterior surface of the esophagus.&lt;ref name=pmid16378701&gt;{{cite journal |author=Piette MH, De Letter EA |title=Drowning: still a difficult autopsy diagnosis |journal=Forensic Sci. Int. |volume=163 |issue=1-2 |pages=1–9 |year=2006 |month=November |pmid=16378701 |doi=10.1016/j.forsciint.2004.10.027 |url=}}&lt;/ref&gt;<br /> **Minimized by removing cranial contents &amp; thoracic contents ''before'' undertaking neck dissection.&lt;ref name=Ref=HospAuto118&gt;{{Ref HospAuto|118}}&lt;/ref&gt;<br /> *Artefactual fractures (see fractures).<br /> *Dilated anus (in isolation).&lt;ref&gt;URL: [http://www.kingstonwhigstandard.com/ArticleDisplay.aspx?archive=true&amp;e=736464 http://www.kingstonwhigstandard.com/ArticleDisplay.aspx?archive=true&amp;e=736464]. Accessed on: 6 October 2010.&lt;/ref&gt;&lt;ref name=pmid17961873 &gt;{{Cite journal | last1 = Elder | first1 = DE. | title = Interpretation of anogenital findings in the living child: Implications for the paediatric forensic autopsy. | journal = J Forensic Leg Med | volume = 14 | issue = 8 | pages = 482-8 | month = Nov | year = 2007 | doi = 10.1016/j.jflm.2007.03.005 | PMID = 17961873 }}&lt;/ref&gt;<br /> *Towel clip injury, usu. paired (in organ donors) - may be mistaken for an electroshock weapon (e.g. Taser) wound.&lt;ref&gt;MSP. 12 October 2010.&lt;/ref&gt;<br /> *Subclavian stab for vascular access - may be confused with a gunshot exit wound.<br /> <br /> ====Infants====<br /> *Lumpy neck - small superficial nodules on anterior neck ~2-5 mm (???).&lt;ref&gt;MSP. 6 October 2010.&lt;/ref&gt;<br /> *Intussusception of small bowel - often multiple.<br /> <br /> =Wounds=<br /> ==General==<br /> *''Wound'' - definition: defect in skin or mucous membrane&lt;ref&gt;URL: [http://dictionary.reference.com/browse/wound http://dictionary.reference.com/browse/wound]. Accessed on: 20 April 2012.&lt;/ref&gt; - usually due to trauma.<br /> <br /> Special types of wounds:<br /> *[[Gunshot wounds]].<br /> *Incised wounds - see [[sharp force trauma]].<br /> <br /> ===Gross pathologic classification of injuries===<br /> Mnemonic ''CALI'':<br /> *'''C'''ontusion - &quot;bruise&quot;, [[hematoma]].<br /> **Age (usual colour change sequence): red, blue, green, yellow, brown.&lt;ref name=Ref_HospAuto108&gt;{{Ref HospAuto|108}}&lt;/ref&gt;<br /> **Etiology: bleeding from arterioles or venules (not capillaries).&lt;ref name=Ref_HospAuto105&gt;{{Ref HospAuto|105}}&lt;/ref&gt;<br /> *'''A'''brasion - &quot;scrape&quot;, e.g. motorcyclist slide across the roadway... skin scraped-off.<br /> **Can be subclassified as ''brush abrasions'' (has skin tags) and ''crush abrasions'' (do not have skin tags).<br /> ***Skin tags suggest directionality; they are found at the distal point / point of last contact.&lt;ref name=Ref_HospAuto105&gt;{{Ref HospAuto|105}}&lt;/ref&gt;<br /> *'''L'''aceration - &quot;tear&quot;, indicates blunt force trauma; contact point may be distant from where skin splits.<br /> *'''I'''ncised - &quot;cut&quot;, e.g. caused by a knife,&lt;ref name=Ref_HoFP154&gt;{{Ref_HoFP|154}}&lt;/ref&gt; subdivided as follows:<br /> *#&quot;Cut&quot; or &quot;slash&quot; = length &gt; depth.<br /> *#&quot;Stab&quot; = depth &gt; length.<br /> *#&quot;Chop&quot; = typically have a contusion at the margin of the wound, classically caused by an axe. May be caused by a propeller.&lt;ref name=pmid19733336&gt;{{Cite journal | last1 = Ihama | first1 = Y. | last2 = Ninomiya | first2 = K. | last3 = Noguchi | first3 = M. | last4 = Fuke | first4 = C. | last5 = Miyazaki | first5 = T. | title = Fatal propeller injuries: three autopsy case reports. | journal = J Forensic Leg Med | volume = 16 | issue = 7 | pages = 420-3 | month = Oct | year = 2009 | doi = 10.1016/j.jflm.2009.04.006 | PMID = 19733336 }}&lt;/ref&gt;<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image:Hand_Abrasion_-_32_minutes_after_injury.JPG | Abrasion. (WC)<br /> Image:Black_eye_2.jpg | Contusion (&quot;black eye&quot;). (WC)<br /> &lt;/gallery&gt;<br /> ====DDx====<br /> How to decide what you're looking at:<br /> *Contusion: <br /> **Can be demonstrated histologically... there are extravascular RBCs.<br /> ***If pre-morten there is vital reaction, i.e. WBCs come to clean-up the trauma.<br /> **If the post mortem interval is not known and long-- differentiation from decomposition may be non-trivial/impossible.<br /> <br /> *Abrasion vs. contusion:<br /> **Contusions skin is intact... in abrasion it is not.<br /> **Abrasions and contusions may be co-localized, i.e. in the same place.<br /> <br /> *Laceration vs. incision:<br /> **Lacerations have &quot;bridges&quot;, incisions do NOT have bridges.<br /> ***Bridges are fine strands of tissue that cross the long axis of the skin defect.<br /> ****You can think of the wound as partially &quot;sutured&quot; by the bridges of tissue.<br /> **Lacerations are usually associated with a contusion and/or crush and have an irregular margin.&lt;ref name=Ref_HospAuto109&gt;{{Ref HospAuto|109}}&lt;/ref&gt;<br /> **Lacerations are classically on the skull and face. They are rarely on the abdomen.<br /> <br /> ===Wound dating===<br /> *Colour is somewhat useful for contusions (bruises).<br /> *Post-mortem injuries tend to be orange-yellow.&lt;ref name=pmid19237864&gt;{{Cite journal | last1 = Campobasso | first1 = CP. | last2 = Marchetti | first2 = D. | last3 = Introna | first3 = F. | last4 = Colonna | first4 = MF. | title = Postmortem artifacts made by ants and the effect of ant activity on decompositional rates. | journal = Am J Forensic Med Pathol | volume = 30 | issue = 1 | pages = 84-7 | month = Mar | year = 2009 | doi = 10.1097/PAF.0b013e318187371f | PMID = 19237864 }}&lt;/ref&gt;<br /> *Wounds age is difficult to determine as [[wound healing]] is affected by a large number of variables.<br /> *Old wounds (scars), generally, cannot be dated - one can only say they are ''old''.<br /> <br /> ===Microscopic===<br /> Wounds can be grouped into:<br /> *Pre-mortem.<br /> *Post-mortem.<br /> <br /> Signs a wound was inflicted during life:<br /> *Blood.<br /> **Hypostasis/decomposition can mess with this, i.e. blood oozing out of vessels post-mortem shouldn't be called an injury.<br /> **Hemosiderin demonstrated by an iron stain - hard sign.<br /> *Inflammation:&lt;ref name=Ref_PCPBoD8_26&gt;{{Ref PCPBoD8|26}}&lt;/ref&gt;<br /> **[[PMN]]s 6-24 hours after injury.<br /> **PMNs replaced monocytes in 24-48 hours.<br /> <br /> ===Stains===<br /> *[[Iron stain]] for siderophages (hemosiderin-laden macrophages) -- presence suggests 2-3 days or older.&lt;ref name=pmid7529545&gt;{{Cite journal | last1 = Betz | first1 = P. | title = Histological and enzyme histochemical parameters for the age estimation of human skin wounds. | journal = Int J Legal Med | volume = 107 | issue = 2 | pages = 60-8 | month = | year = 1994 | doi = | PMID = 7529545 }}&lt;/ref&gt;<br /> <br /> =Bone fractures=<br /> *[[AKA]] ''fractures''.<br /> *[[AKA]] ''fracture of bone''.<br /> <br /> ==Artefactual fractures==<br /> *&quot;Undertaker's fracture&quot; - cervical fracture due to rough handling.&lt;ref&gt;URL: [http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html]. Accessed on: 29 September 2010.&lt;/ref&gt;<br /> *Basal skull fracture due to opening of skull.&lt;ref&gt;MSP. 29 September 2010.&lt;/ref&gt;<br /> **Classically does not cross sella turcica.<br /> **Notably absent features of a real (ante-mortem) fracture: hematoma, brain injury.<br /> **Mechanism to explain trauma not present in history; a fall/tripping not sufficient.<br /> <br /> ==Healing of fractures==<br /> ===Simplified classification===<br /> *Primary callus (cartilaginous) - early.<br /> *Secondary callus (bone) - late.<br /> <br /> ===Microscopic===<br /> Features:<br /> *Fragmentation of bone.<br /> *+/-Dead bone = lacunae have no osteocytes.&lt;ref name=pmid22460748&gt;{{Cite journal | last1 = Fondi | first1 = C. | last2 = Franchi | first2 = A. | title = Definition of bone necrosis by the pathologist. | journal = Clin Cases Miner Bone Metab | volume = 4 | issue = 1 | pages = 21-6 | month = Jan | year = 2007 | doi = | PMID = 22460748 }}&lt;/ref&gt;<br /> **Takes days for osteocyte loss.<br /> *+/-Inflammatory cells.<br /> *+/-Hemosiderin-laden macrophages.<br /> *+/-Osteoblastic rimming.<br /> <br /> DDx:<br /> *Fracture secondary to a tumour:<br /> **Metastatic carcinoma.<br /> **[[Osteosarcoma]] - typically does '''not''' have osteoblastic rimming. <br /> <br /> Notes:<br /> *Radiology is not good at dating fratures;&lt;ref name=pmid15788611&gt;{{Cite journal | last1 = Prosser | first1 = I. | last2 = Maguire | first2 = S. | last3 = Harrison | first3 = SK. | last4 = Mann | first4 = M. | last5 = Sibert | first5 = JR. | last6 = Kemp | first6 = AM. | title = How old is this fracture? Radiologic dating of fractures in children: a systematic review. | journal = AJR Am J Roentgenol | volume = 184 | issue = 4 | pages = 1282-6 | month = Apr | year = 2005 | doi = | PMID = 15788611 | url=http://www.ajronline.org/cgi/content/full/184/4/1282 }}<br /> &lt;/ref&gt; however, it is good at finding 'em.<br /> <br /> ==Pattern and cause==<br /> ===Child abuse-related===<br /> *Paravertebral (bony) nodules = classic location for rib fractures in child abuse.<br /> *Metaphyseal fractures - &quot;classical metaphyseal lesions&quot;.&lt;ref name=pmid8615271&gt;{{Cite journal | last1 = Kleinman | first1 = PK. | last2 = Marks | first2 = SC. | title = A regional approach to classic metaphyseal lesions in abused infants: the distal tibia. | journal = AJR Am J Roentgenol | volume = 166 | issue = 5 | pages = 1207-12 | month = May | year = 1996 | doi = | PMID = 8615271 }}&lt;/ref&gt;<br /> <br /> ===Motor vehicle versus pedestrian===<br /> If the pedestrian is standing during the initial impact one classically finds, at bumper level, a lower limb fracture with a ''Messerer wedge'' (German: ''Messerer-Kiel'');&lt;ref name=pmid11376986&gt;{{Cite journal | last1 = Karger | first1 = B. | last2 = Teige | first2 = K. | last3 = Fuchs | first3 = M. | last4 = Brinkmann | first4 = B. | title = Was the pedestrian hit in an erect position before being run over? | journal = Forensic Sci Int | volume = 119 | issue = 2 | pages = 217-20 | month = Jun | year = 2001 | doi = | PMID = 11376986 }}<br /> &lt;/ref&gt; the wedge points in the direction of the (impact) force.<br /> <br /> ==Location or type==<br /> ===Orbital floor fractures===<br /> *[[AKA]] ''blow-out fractures''.&lt;ref name=pmid17333039&gt;{{Cite journal | last1 = Punke | first1 = C. | last2 = Fritsche | first2 = A. | last3 = Martin | first3 = H. | last4 = Schmitz | first4 = KP. | last5 = Pau | first5 = HW. | last6 = Kramp | first6 = B. | title = [Investigation of the mechanisms involved in isolated orbital floor fracture. Simulation using a finite element model of the human skull]. | journal = HNO | volume = 55 | issue = 12 | pages = 938-44 | month = Dec | year = 2007 | doi = 10.1007/s00106-007-1545-5 | PMID = 17333039 }}&lt;/ref&gt;<br /> ====General====<br /> *Classically due to fights, followed by traffic accidents.&lt;ref name=pmid20165966&gt;{{Cite journal | last1 = Gosau | first1 = M. | last2 = Schöneich | first2 = M. | last3 = Draenert | first3 = FG. | last4 = Ettl | first4 = T. | last5 = Driemel | first5 = O. | last6 = Reichert | first6 = TE. | title = Retrospective analysis of orbital floor fractures--complications, outcome, and review of literature. | journal = Clin Oral Investig | volume = 15 | issue = 3 | pages = 305-13 | month = Jun | year = 2011 | doi = 10.1007/s00784-010-0385-y | PMID = 20165966 }}&lt;/ref&gt;<br /> *Thought to result from loading on the orbital rim directly or the orbit - both are transmitted to the orbital floor.&lt;ref name=pmid17333039/&gt;<br /> <br /> Note:<br /> *The orbital floor tends to the be weaker than other components of the orbital cavity wall; thus, it is the most common site of fracture in the orbital cavity wall.<br /> <br /> ===Basal skull fracture===<br /> ====General====<br /> Etiology:<br /> *Blunt force trauma - high energy &amp; velocity.<br /> **Seen in ''motor vehicle collisions'', ''descent from height''.<br /> <br /> Clinical/external findings:<br /> *Raccoon eyes = periorbital ecchymosis.<br /> *Battle sign = mastoid ecchymosis.<br /> **Associated with orbital roof fractures.&lt;ref&gt;URL: [http://emedicine.medscape.com/article/1680107-overview#showall http://emedicine.medscape.com/article/1680107-overview#showall]. Accessed on: 28 March 2012.&lt;/ref&gt;<br /> *Cerebrospinal fluid rhinorrhea.<br /> *Hemorrhage from nose and ears.<br /> *Hemotympanum.<br /> <br /> Note:<br /> *There is a dictum that states ''bilateral petrous bone fractures are due to impact to the side of the head'' - it isn't true.&lt;ref name=pmid7391790&gt;{{Cite journal | last1 = Harvey | first1 = FH. | last2 = Jones | first2 = AM. | title = Typical basal skull fracture of both petrous bones: an unreliable indicator of head impact site. | journal = J Forensic Sci | volume = 25 | issue = 2 | pages = 280-6 | month = Apr | year = 1980 | doi = | PMID = 7391790 }}&lt;/ref&gt;<br /> <br /> ===Hinge fracture of the skull===<br /> *A special type of [[basal skull fracture]].<br /> *Complete hinge fractures are considered severe; they are a 4 on the ''abbreviated injury scale'' (AIS).&lt;ref&gt;{{Cite journal | last1 = Adams | first1 = VI. | last2 = Carrubba | first2 = C. | title = The Abbreviated Injury Scale: application to autopsy data. | journal = Am J Forensic Med Pathol | volume = 19 | issue = 3 | pages = 246-51 | month = Sep | year = 1998 | doi = | PMID = 9760090 }}&lt;/ref&gt;<br /> *Classically due to a blow to the chin - resulting in a fracture across the medial fossa and sella turcica.&lt;ref&gt;URL: [http://wiki.answers.com/Q/Hinge_fracture_of_skull_is_seen_in_accidents_involving http://wiki.answers.com/Q/Hinge_fracture_of_skull_is_seen_in_accidents_involving]. Accessed on: 28 March 2012.&lt;/ref&gt;<br /> <br /> ===Pathologic fracture===<br /> {{Main|Pathologic fracture}}<br /> *A fracture due to an underlying pathology.<br /> <br /> ===Hip fractures===<br /> *[[Traumatic fracture of the femoral neck]].<br /> <br /> =Autopsy=<br /> {{Main|Autopsy}}<br /> The ''autopsy'' article covers procedural things. Heart dissection is covered in the ''[[heart]]'' article.<br /> <br /> ===Types===<br /> Forensic vs. hospital:<br /> *Forensic autopsies are focused on the external exam.<br /> <br /> ===Marking conventions for common findings===<br /> There are no universal marking conventions for injuries.<br /> <br /> One system in use (the ''Rose system'') is:&lt;ref&gt;TR. 1 September 2010.&lt;/ref&gt;<br /> *One red line for an incised wound.<br /> *Multiple closely spaced red lines, i.e. red hatching, for abrasions.<br /> *Multiple closely-spaced blue lines, i.e. blue hatching, for contusions.<br /> <br /> The above makes sense in that:<br /> *Abrasions and incised wounds typically bleed - are red.<br /> *Contusions (bruises) don't classically bleed and are classically blue.<br /> <br /> ===External exam findings===<br /> Colour of the corpse:&lt;ref name=Ref_Shkrum33&gt;{{Ref Shkrum|33}}&lt;/ref&gt;<br /> *Red (Pink) = [[carbon monoxide toxicity|carbon monoxide]], cyanide, fluoroacetate,&lt;ref name=pmid17288493&gt;{{cite journal |author=Proudfoot AT, Bradberry SM, Vale JA |title=Sodium fluoroacetate poisoning |journal=Toxicol Rev |volume=25 |issue=4 |pages=213–9 |year=2006 |pmid=17288493 |doi= |url=}}&lt;/ref&gt; [[hypothermia]].<br /> *Purple (intense) = propane.<br /> *Green = [[hydrogen sulfide]].<br /> *Brown = nitrites (methemoglobinemia).<br /> <br /> ===Autopsy terminology===<br /> *''Gutter butter'' = adipose tissue in a decomp case; looks like butter topping put on popcorn. A Toronto-ism.<br /> *''Gutter blood'' = blood in the empty thorax - after extraction of the organ block.<br /> *''Tardieu spots'' = postmortem hypostatic hemorrhages;&lt;ref name=pmid19901802&gt;{{cite journal |author=Pollanen MS, Perera SD, Clutterbuck DJ |title=Hemorrhagic lividity of the neck: controlled induction of postmortem hypostatic hemorrhages |journal=Am J Forensic Med Pathol |volume=30 |issue=4 |pages=322–6 |year=2009 |month=December |pmid=19901802 |doi=10.1097/PAF.0b013e3181c17ec2 |url=}}&lt;/ref&gt; look like petechiae - in dependent areas, i.e. in the zone of livity.<br /> <br /> ===Autopsy on decomposed remains===<br /> *[[AKA]] &quot;decomp autopsy&quot; or simply &quot;decomp&quot;.<br /> ====General====<br /> *Histology usually very limited ''or'' useless.<br /> *Often done to exclude trauma.<br /> *Typical scenario: decedent lives alone -- body not discovered for prolonged period of time.<br /> *More likely to be a ''[[negative autopsy]]'' than non-decomp cases.<br /> <br /> ====Suspicious decomp====<br /> Common sense rules for if skin is '''not''' intact:<br /> #Blunt dissection (to avoid artefactual injuries to the bones).<br /> #Clean the bones (''not'' with bleach)<br /> #*Bones cooked for 1+ hours... with frequent checks to avoid that they become mushy.<br /> <br /> =Causes of death=<br /> <br /> ==Environmental==<br /> {{Main|Environmental causes of death}}<br /> They include: <br /> *[[Hypothermia]]. <br /> *[[Hyperthermia]]. <br /> *Drowning - see [[asphyxial deaths]].<br /> *Lack of oxygen - see [[asphyxial deaths]]. <br /> *[[Electrocution]].<br /> <br /> =Gunshot wounds=<br /> {{main|Gunshot wounds}}<br /> Gunshot wounds (GSWs) are a relatively uncommon finding in Canada. They are dealt within a separate article.<br /> <br /> =Asphyxia=<br /> {{main|Asphyxial deaths}}<br /> <br /> *This is a big topic and covered by a separate article.<br /> <br /> ===Classification=== <br /> *''Strangulation'' - where there are signs of neck compression.<br /> **Includes: ganging, ligature strangulation and manual strangulation.<br /> *''Chemical asphyxia'' - usually no signs of neck compression.<br /> **Includes: carbon monoxide poisoning.<br /> *''Suffocation'' - usually no signs of neck compression.<br /> **Includes: smothering, [[choking]], positional asphyxia, [[drowning]].<br /> <br /> =Blunt force injury=<br /> *[[AKA]] ''blunt force trauma''.<br /> ==General==<br /> Classification:<br /> *Contusions.<br /> *Laceration.<br /> *Acceleration/deceleration injury, e.g. [[diffuse axonal injury]].<br /> <br /> Weapons: <br /> *Fist.<br /> *Foot.<br /> *Baseball bat... pretty much anything.<br /> *Beer bottles are common... and strong enought to fracture a skull.<br /> **Empty bottles have a higher fracture energy than full ones.&lt;ref name=pmid19239964&gt;{{cite journal |author=Bolliger SA, Ross S, Oesterhelweg L, Thali MJ, Kneubuehl BP |title=Are full or empty beer bottles sturdier and does their fracture-threshold suffice to break the human skull? |journal=J Forensic Leg Med |volume=16 |issue=3 |pages=138–42 |year=2009 |month=April |pmid=19239964 |doi=10.1016/j.jflm.2008.07.013 |url=}}&lt;/ref&gt;<br /> <br /> ==Cause of death==<br /> ===Commotio cordis===<br /> Features:&lt;ref name=pmid11334832&gt;{{cite journal |author=Kohl P, Nesbitt AD, Cooper PJ, Lei M |title=Sudden cardiac death by Commotio cordis: role of mechano-electric feedback |journal=Cardiovasc. Res. |volume=50 |issue=2 |pages=280–9 |year=2001 |month=May |pmid=11334832 |doi= |url=}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |author=Maron BJ, Estes NA |title=Commotio cordis |journal=N. Engl. J. Med. |volume=362 |issue=10 |pages=917–27 |year=2010 |month=March |pmid=20220186 |doi=10.1056/NEJMra0910111 |url=http://www.nejm.org/doi/full/10.1056/NEJMra0910111}}&lt;/ref&gt;<br /> *Often negative autopsy; no cardiac pathology.<br /> *Etiology: [[cardiac arrhythmia|arrhythmia]].<br /> *History: trauma to chest.<br /> <br /> Note:<br /> *May be spelled ''Commodio cordis''.&lt;ref name=pmid11555799&gt;{{cite journal |author=Perron AD, Brady WJ, Erling BF |title=Commodio cordis: an underappreciated cause of sudden cardiac death in young patients: assessment and management in the ED |journal=Am J Emerg Med |volume=19 |issue=5 |pages=406–9 |year=2001 |month=September |pmid=11555799 |doi=10.1053/ajem.2001.24455 |url=}}&lt;/ref&gt;<br /> *Analogous to ''[[commotio medullaris]]''.<br /> <br /> ==Scenarios==<br /> ===Motor vehicle collisions===<br /> *Pedestrian vs. motor vehicle: heel to injury measurement, remember to include the thickness of the heel/sole of shoe.&lt;ref&gt;{{Ref OPMfP|18}}&lt;/ref&gt;<br /> *Dicing injuries: tempered glass used in side window construction fragments into cubes when fractured causing L-shaped wounds.<br /> <br /> ===Descent from height===<br /> *Relatively common way to suicide.<br /> **May be an ''accident'', e.g. decedent thought they can fly (due to a psychosis).<br /> **May be a ''homicide'', e.g. decedent was pushed.<br /> <br /> ====Gross====<br /> Features:<br /> *Multiple injuries - often including multiple fractures, e.g. basal skull fracture, flail chest.<br /> *+/-Haemothorax - can be proved with a large bore needle.<br /> **Sufficient for cause of death - can be used to do an abbreviated post-mortem.<br /> *+/-Haemoaspiration (due to facial trauma) - presence suggest that decendent was alive shortly after landing/impact and thus likely very alive during the descent.<br /> **Patchy red centrilobular spots on gross examination.<br /> <br /> ==Injury patterns==<br /> ===Seromuscular tear===<br /> * [[AKA]] ''seatbeat syndrome''.<br /> * Intestinal injury associated with motor vehicle collisions and more specifically seatbelts. <br /> <br /> Features:<br /> * Def'n: separation of (inner) muscularis propria from submucosa.&lt;ref name=pmid12198344&gt;{{Cite journal | last1 = Slavin | first1 = RE. | last2 = Borzotta | first2 = AP. | title = The seromuscular tear and other intestinal lesions in the seatbelt syndrome: a clinical and pathologic study of 29 cases. | journal = Am J Forensic Med Pathol | volume = 23 | issue = 3 | pages = 214-22 | month = Sep | year = 2002 | doi = 10.1097/01.PAF.0000023001.32202.2D | PMID = 12198344 }}&lt;/ref&gt;<br /> <br /> ===Bite injury===<br /> *A special type of [[blunt force trauma]].<br /> *May be seen in the context of a sexual assault.<br /> *A ''forensic dentist'' may be able to assist.<br /> <br /> In the context of a suspicious case:<br /> *Human vs. animal.<br /> *Bite marks, as evidence, have a limited value for identification purposes.<br /> **In the context of identifying a potential perpetrator, it is essential to swab the bite mark for saliva, which is rich in DNA.&lt;ref&gt;{{Cite journal | last1 = Pretty | first1 = IA. | title = Forensic dentistry: 2. Bitemarks and bite injuries. | journal = Dent Update | volume = 35 | issue = 1 | pages = 48-50, 53-4, 57-8 passim | month = | year = | doi = | PMID = 18277695 }}&lt;/ref&gt;<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image: Dog_bite.JPG | Bite injury. (WC)<br /> &lt;/gallery&gt;<br /> <br /> ===Aortic trauma===<br /> *Classic location of injury is subclavian branch point.&lt;ref name=pmid1934437&gt;{{cite journal |author=Kodali S, Jamieson WR, Leia-Stephens M, Miyagishima RT, Janusz MT, Tyers GF |title=Traumatic rupture of the thoracic aorta. A 20-year review: 1969-1989 |journal=Circulation |volume=84 |issue=5 Suppl |pages=III40–6 |year=1991 |month=November |pmid=1934437 |doi= |url=}}&lt;/ref&gt;<br /> *[[Aortic dissection]] due to trauma is often catastrophic.<br /> <br /> ==Trauma with delayed death==<br /> *[[Epidural hemorrhage]] with a lucid interval.<br /> *Subcapsular splenic hematoma with subsequent rupture.<br /> *Subcapsular hepatic hematoma with subsequent rupture.<br /> *[[Aortic dissection]] with subsequent rupture.<br /> <br /> =Sharp force injury=<br /> *[[AKA]] ''sharp force trauma''.<br /> ===General===<br /> Injuries caused by:&lt;ref name=Ref_HospAuto111-2&gt;{{Ref HospAuto|111-2}}&lt;/ref&gt;<br /> *Knife.<br /> *Scissors - classic &quot;Z&quot; shape.<br /> *Screwdriver.<br /> *Glass.<br /> <br /> ===Gross===<br /> Features:&lt;ref name=Ref_HospAuto111-2&gt;{{Ref HospAuto|111-2}}&lt;/ref&gt;<br /> *Incised wound (see: ''[[Wounds|Classification of wounds]]'').<br /> **&quot;Clean&quot; edge (no contusion, no abrasion).<br /> **Well-demarcated edges.<br /> *+/-Hilt mark.<br /> **Due to contact of hilt.<br /> <br /> Subclassified into - see ''[[Wounds|classification of wounds]]'':<br /> *''Cut/slash''. <br /> *''Stab''. <br /> *''Chop'' - a mixed injury, sharp force and blunt force.<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image: Thorax-Messerstichwunden.jpg | Sharp force trauma - thorax. (WC)<br /> &lt;/gallery&gt;<br /> <br /> =Head injuries=<br /> ===Accidental vs. intentional===<br /> Features of non-accidental injuries:&lt;ref name=pmid20141554&gt;{{cite journal |author=Guyomarc'h P, Campagna-Vaillancourt M, Kremer C, Sauvageau A |title=Discrimination of falls and blows in blunt head trauma: a multi-criteria approach |journal=J. Forensic Sci. |volume=55 |issue=2 |pages=423–7 |year=2010 |month=March |pmid=20141554 |doi=10.1111/j.1556-4029.2009.01310.x |url=}}&lt;/ref&gt;<br /> *Lacerations:<br /> **More than three.<br /> **Length &gt;= 7 cm or more.<br /> **Location:<br /> ***Above hat brim line (HBL).<br /> ***[[Ear]].<br /> ***Left-sided.<br /> *Fractures:<br /> **Comminuted or depressed calvarial fractures. <br /> **Location:<br /> ***Fractures located above the HBL.<br /> ***Left-sided fractures.<br /> ***Facial fractures.<br /> *Contusions:<br /> **Greater than four facial contusions.<br /> *Other:<br /> **&quot;Postcranial osseous&quot; [sic] (non-rib, non-skull) and/or visceral trauma.<br /> <br /> Note: The paper doesn't give odds ratios for the the different features -- like in the rational clinical exam series... it is a shame.<br /> <br /> ==Diffuse axonal injury==<br /> *Abbreviated ''DAI''.<br /> ===General===<br /> Clinical:<br /> *Vegetative state. <br /> *Imaging findings: no anatomical cause apparent (in some cases).<br /> <br /> Etiology:<br /> *Hypothesized to arise from high shear loading of white mater tracts.&lt;ref name=pmid2769276&gt;{{cite journal |author=Blumbergs PC, Jones NR, North JB |title=Diffuse axonal injury in head trauma |journal=J. Neurol. Neurosurg. Psychiatr. |volume=52 |issue=7 |pages=838–41 |year=1989 |month=July |pmid=2769276 |pmc=1031929 |doi= |url=}}&lt;/ref&gt;<br /> <br /> ===Gross===<br /> Macroscopic findings:&lt;ref name=pmid2769276/&gt;<br /> *Tears - corpus callosum.<br /> *Haemorrhage.<br /> <br /> Other (chronic) changes:&lt;ref name=Ref_AoGP639&gt;{{Ref AoGP|639}}&lt;/ref&gt;{{fact}}<br /> *Thalamus - shrinkage.<br /> *Enlargement of third ventricle.<br /> <br /> DDx (medical imaging):&lt;ref name=pmid22406792&gt;{{Cite journal | last1 = Kumar | first1 = S. | last2 = Gupta | first2 = V. | last3 = Aggarwal | first3 = S. | last4 = Singh | first4 = P. | last5 = Khandelwal | first5 = N. | title = Fat embolism syndrome mimicker of diffuse axonal injury on magnetic resonance imaging. | journal = Neurol India | volume = 60 | issue = 1 | pages = 100-2 | month = | year = | doi = 10.4103/0028-3886.93597 | PMID = 22406792 }}&lt;/ref&gt;<br /> *[[Cerebral fat embolism]].<br /> <br /> ===Microscopic===<br /> Microscopic findings:&lt;ref name=pmid2769276/&gt;<br /> *Axonal retraction balls.<br /> *&quot;Microglial stars&quot;.<br /> *Degeneration of fibre tracts.<br /> <br /> Grading:&lt;ref&gt;URL: [http://wiki.cns.org/wiki/index.php/Diffuse_axonal_injury_%28DAI%29 http://wiki.cns.org/wiki/index.php/Diffuse_axonal_injury_%28DAI%29]. Accessed on: 13 February 2012.&lt;/ref&gt;<br /> *Grade 1: only microscopic findings.<br /> *Grade 2: macroscopic corpus callosum injury + microscopic findings of DAI. <br /> *Grade 3: macroscopic corpus callosum and midbrain injuries + microscopic findings of DAI.<br /> <br /> ===Stains===<br /> *[[Bielschowsky stain]] to highlight axonal swellings - appear 12-18 hours after injury.&lt;ref name=Ref_Shkrum_562&gt;{{Ref Shkrum|562}}&lt;/ref&gt;<br /> <br /> ===IHC===<br /> *Beta-amyloid precursor protein (beta-APP ''or'' APP).&lt;ref name=pmid10050789&gt;{{cite journal |author=Gleckman AM, Bell MD, Evans RJ, Smith TW |title=Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining |journal=Arch. Pathol. Lab. Med. |volume=123 |issue=2 |pages=146–51 |year=1999 |month=February |pmid=10050789 |doi= |url=}}&lt;/ref&gt;&lt;ref name=pmid17368446&gt;{{Cite journal | last1 = Mac Donald | first1 = CL. | last2 = Dikranian | first2 = K. | last3 = Song | first3 = SK. | last4 = Bayly | first4 = PV. | last5 = Holtzman | first5 = DM. | last6 = Brody | first6 = DL. | title = Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury. | journal = Exp Neurol | volume = 205 | issue = 1 | pages = 116-31 | month = May | year = 2007 | doi = 10.1016/j.expneurol.2007.01.035 | PMID = 17368446 | PMC = 1995439 }}&lt;/ref&gt;<br /> *NF.&lt;ref name=pmid17368446/&gt;<br /> <br /> ==Intracranial hemorrhage==<br /> {{main|Intracranial hematoma}}<br /> Intracranial hemorrhage may be a consequence of blunt force trauma.<br /> <br /> Classification:<br /> *[[Epidural hematoma]].<br /> *[[Subdural hematoma]].<br /> *[[Subarachnoid hematoma]].<br /> *[[Intracerebral hematoma]].<br /> <br /> ==Cerebral contusion==<br /> ===General===<br /> *Due to blunt force trauma.<br /> <br /> ===Gross===<br /> Features:<br /> *Focal superficial hemorrhage.<br /> *Location, usually, ''frontal lobe'' and ''temporal lobe''.&lt;ref name=Ref_HoFP_102&gt;{{Ref HoFP|102}}&lt;/ref&gt;<br /> <br /> Notes:<br /> *Classically, come in pairs:&lt;ref name=Ref_HoFP_102&gt;{{Ref HoFP|102}}&lt;/ref&gt;<br /> *#''Coup contusion'' - at the site of the (primary) impact<br /> *#''Contrecoup contusion'' - secondary internal impact.<br /> **Example - fall on back of head: <br /> ***Occipital lobe contusion = coup contusion.<br /> ***Frontal lobe contusion = contrecoup contusion.<br /> *May be associated with contusions of the:&lt;ref name=Ref_HoFP_103&gt;{{Ref HoFP|103}}&lt;/ref&gt; <br /> **Deep brain structures, known as an &quot;intermediary coup&quot;.<br /> **Dorsal surface of the cerebral hemispheres, known as &quot;gliding contusions&quot;.<br /> *Resolve as a yellow lesion (like at other sites), known as a ''[[plaque]] jaune'' in the brain.<br /> **Classically, inferior aspect of the frontal lobe.<br /> <br /> DDx:<br /> *Hemorrhagic [[stroke]] - usually temporal lobe and/or parietal lobe.<br /> <br /> ==Traumatic brain injury in infants==<br /> {{main|Traumatic brain injury in infants}}<br /> <br /> *Shaken-impact syndrome, [[AKA]] shaken baby syndrome.<br /> <br /> ==Commotio medullaris==<br /> Features:&lt;ref name=Ref_Shkrum613&gt;{{Ref Shkrum|613}}&lt;/ref&gt;<br /> *Sudden death after head trauma that is insufficient to explain death.<br /> *Etiology: unknown - thought to be related to apnea.<br /> <br /> Note:<br /> *Analogous to ''[[commotio cordis]]''.<br /> <br /> =Excited delirium=<br /> *[[AKA]] ''agitated delirium''.&lt;ref name=pmid8768172&gt;{{cite journal |author=Wetli CV, Mash D, Karch SB |title=Cocaine-associated agitated delirium and the neuroleptic malignant syndrome |journal=Am J Emerg Med |volume=14 |issue=4 |pages=425–8 |year=1996 |month=July |pmid=8768172 |doi= |url=}}&lt;/ref&gt;<br /> ===General===<br /> *[[Diagnosis]] is considered somewhat controversial outside of the forensic pathology community.&lt;ref name=pmid18450833&gt;{{Cite journal | last1 = Stanbrook | first1 = MB. | last2 = Hébert | first2 = PC. | last3 = Kale | first3 = R. | last4 = Sibbald | first4 = B. | last5 = Flegel | first5 = K. | last6 = MacDonald | first6 = N. | title = Tasers in medicine: an irreverent call for proposals. | journal = CMAJ | volume = 178 | issue = 11 | pages = 1401-2, 1403-4 | month = May | year = 2008 | doi = 10.1503/cmaj.080592 | PMID = 18450833 |PMC = 2374865 }}&lt;/ref&gt;<br /> *The [[diagnosis]] has garnered attention in the context of electroshock weapon use, as ''Taser International'' (a manufacturer of electroshock weapons) has often ascribed the deaths involving its weapons to it - when it is alleged that their electroshock weapon caused the death.<br /> <br /> *There is no &quot;official&quot; definition for ''excited delirium''.<br /> **Most agree it includes fever.<br /> <br /> One paper defines it in relation ''neuroleptic malignant syndrome'':&lt;ref name=pmid8768172/&gt;<br /> *Fever.<br /> *Disorientation and confusion.<br /> *Increased energy/superhuman strength.<br /> <br /> Excited delirium - hypothesis:<br /> *Thought to arise in the context of severe chronic mental disorders (e.g. schizophrenia) and protracted [[cocaine]] binges.&lt;ref name=pmid9645173&gt;{{Cite journal | last1 = Pollanen | first1 = MS. | last2 = Chiasson | first2 = DA. | last3 = Cairns | first3 = JT. | last4 = Young | first4 = JG. | title = Unexpected death related to restraint for excited delirium: a retrospective study of deaths in police custody and in the community. | journal = CMAJ | volume = 158 | issue = 12 | pages = 1603-7 | month = Jun | year = 1998 | doi = | PMID = 9645173 | PMC = 1229410 | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1229410}}&lt;/ref&gt;<br /> *Thought to result from alteration of dopamine receptor density. The D2 receptor in particular, which is thought to be important in temperature regulation, is decreased in psychotic cocaine abusers.&lt;ref name=pmid8768172/&gt;<br /> <br /> =Toxicology &amp; biochemistry=<br /> ===General===<br /> Things usually collected at autopsy:<br /> #Blood in EDTA tube (genetic testing).<br /> #Urine toxicology:<br /> #*Useful to evaluate ''myoglobin''.<br /> #Vitreous:<br /> #*Biochemistry.<br /> #*Ketones.<br /> #*Urea (???).<br /> #Bile:&lt;ref&gt;{{Ref HospAuto|220}}&lt;/ref&gt;<br /> #*Acetaminophen overdoses.<br /> #*Opiate overdoses.<br /> <br /> Myoglobin DDx:<br /> *Neuroleptic malignant syndrome.<br /> *Malignant hyperthermia.<br /> *Serotonin syndrome.<br /> <br /> ===Biochemistry===<br /> *[[Diabetes mellitus]]:&lt;ref name=Ref_HospAuto221&gt;{{Ref HospAuto|221}}&lt;/ref&gt;<br /> **Plasma:<br /> ***Hemoglobin A1c - increased.<br /> ***Acetone - increased.<br /> ***Beta-hydroxybutyrate - increased.<br /> ****Also increased in alcoholic ketoacidosis (though ketones low).<br /> **Urine:<br /> ***Aceto-acetate - increased.<br /> <br /> Death by insulin overdose:&lt;ref name=Ref_HospAuto224&gt;{{Ref HospAuto|224}}&lt;/ref&gt;<br /> *C-peptide - low.<br /> *Insulin - high.<br /> <br /> ====Serum====<br /> *Potassium - rises quickly and rapidly after death; completely useless.<br /> *Sodium - tends to decrease after death; usually useless.<br /> *Glucose - drops quickly; useless unless sky high.<br /> *Urea, creatinine and urate - stable for ~48 hours post-mortem.&lt;ref name=Ref_HospAuto222&gt;{{Ref HospAuto|222}}&lt;/ref&gt;<br /> <br /> ===Vitreous===<br /> *Creatinine and urea - approximate those at time of death.&lt;ref name=Ref_HospAuto222&gt;{{Ref HospAuto|222}}&lt;/ref&gt;<br /> *Glucose - used to assess for hyperglycemia (due to [[diabetes mellitus|diabetic coma]]) in life.&lt;ref name=pmid19167848&gt;{{Cite journal | last1 = Zilg | first1 = B. | last2 = Alkass | first2 = K. | last3 = Berg | first3 = S. | last4 = Druid | first4 = H. | title = Postmortem identification of hyperglycemia. | journal = Forensic Sci Int | volume = 185 | issue = 1-3 | pages = 89-95 | month = Mar | year = 2009 | doi = 10.1016/j.forsciint.2008.12.017 | PMID = 19167848 }}&lt;/ref&gt;<br /> <br /> ===Toxicology===<br /> *Should be submitted with anatomical findings and history.<br /> <br /> Common submissions:<br /> #Alcohol only.<br /> #Suspected toxicologic death - need details on drugs.<br /> <br /> ====Mandated by case====<br /> In Ontario, the following are mandated by the case:&lt;ref&gt;{{Ref OPMfP|14}}&lt;/ref&gt;<br /> *Sudden death of child under five years old.<br /> *Workplace death.<br /> *Fatal motor vehicle collision - esp. driver.<br /> *Aviation death - esp. pilot &amp; co-pilot.<br /> *Fire-related death (carboxyhemoglobin).<br /> <br /> ===Toxins===<br /> ====Ethanol toxicity====<br /> {{Main|Ethanol abuse}}<br /> *Usually measured (in Canada) as: ''mass of EtOH (mg)/volume of blood (mL)''.<br /> **Limit (Ontario): 80 milligrams of alcohol in 100 millilitres of blood (0.08 gm/100 mL).&lt;ref&gt;URL: [http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml]. Accessed on: 28 September 2010.&lt;/ref&gt;<br /> **Enough to be fatal ~ 350 mg/dL ~= 76 mmol/L.<br /> <br /> =====Ethanol intoxication as a table&lt;ref name=southendnhs&gt;URL: [http://www.southend.nhs.uk/pathologyhandbook/clinical_chemistry/Guidelines/ethanol_poisoning.htm http://www.southend.nhs.uk/pathologyhandbook/clinical_chemistry/Guidelines/ethanol_poisoning.htm]. Accessed on: 19 October 2010.&lt;/ref&gt;===== <br /> {| class=&quot;wikitable&quot;<br /> |<br /> |Concentration<br /> |Concentration<br /> |Concentration<br /> |Concentration<br /> |-<br /> |Legal limit - Ontario&lt;ref&gt;URL: [http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml]. Accessed on: 28 September 2010.&lt;/ref&gt;<br /> | 80 mg/dL<br /> | ~17 mmol/L<br /> | 0.8 g/L<br /> | 0.08 g/dL<br /> |-<br /> |Mild<br /> | &lt; 180 mg/dL<br /> | &lt; 39 mmol/L<br /> | &lt; 1.8 g/L <br /> | &lt; 0.18 g/dL <br /> |-<br /> |Moderate<br /> | 180-350 mg/dL <br /> | 39-76 mmol/L<br /> | 1.8-3.5 g/L <br /> | 0.18-0.35 g/dL<br /> |-<br /> |Severe<br /> | 350-450 mg/dL <br /> | 76-98 mmol/L<br /> | 3.5-4.5 g/L <br /> | 0.35-0.45 g/dL <br /> |}<br /> <br /> Notes:<br /> *1 mg/dL = 1/4.607 mmol/L.<br /> **Ethanol's molar mass = 46.07 g/mol.<br /> <br /> ====Methanol toxicity====<br /> *Minimum lethal dose: 40 mg/dl.&lt;ref&gt;URL: [http://path.upmc.edu/cases/case242/dx.html http://path.upmc.edu/cases/case242/dx.html. Accessed on: 13 January 2012.&lt;/ref&gt;<br /> <br /> *Typically an accidental death; person consumes methanol as an ethanol substitute. <br /> *Blindness.<br /> *[[Putamen]] [[necrosis]] (bilateral).&lt;ref name=pmid16484428&gt;{{Cite journal | last1 = Blanco | first1 = M. | last2 = Casado | first2 = R. | last3 = Vázquez | first3 = F. | last4 = Pumar | first4 = JM. | title = CT and MR imaging findings in methanol intoxication. | journal = AJNR Am J Neuroradiol | volume = 27 | issue = 2 | pages = 452-4 | month = Feb | year = 2006 | doi = | PMID = 16484428 }}&lt;/ref&gt;<br /> *+/-Pancreatic injury.&lt;ref name=pmid10866330&gt;{{Cite journal | last1 = Hantson | first1 = P. | last2 = Mahieu | first2 = P. | title = Pancreatic injury following acute methanol poisoning. | journal = J Toxicol Clin Toxicol | volume = 38 | issue = 3 | pages = 297-303 | month = | year = 2000 | doi = | PMID = 10866330 }}&lt;/ref&gt;<br /> <br /> ====Cocaine toxicity====<br /> *No agreed upon toxic dose&lt;ref name=pmid15075681&gt;{{cite journal |author=Stephens BG, Jentzen JM, Karch S, Wetli CV, Mash DC |title=National Association of Medical Examiners position paper on the certification of cocaine-related deaths |journal=Am J Forensic Med Pathol |volume=25 |issue=1 |pages=11–3 |year=2004 |month=March |pmid=15075681 |doi= |url=}}&lt;/ref&gt; - due to tolerance.<br /> *Usual mechanism ''cardiac failure''.<br /> <br /> Features - heart:<br /> *Usually anatomically normal heart.<br /> **+/-Advanced [[coronary artery atherosclerosis]] for age.<br /> **+/-[[Myocardial infarction]].<br /> ***+/-Contraction band necrosis.<br /> **+/-Cardiac hypertrophy.<br /> <br /> Other:<br /> *+/-Nasal septum perforation.<br /> *+/-Track marks (other drug use).<br /> *+/-Finger burns (during preparation of crack).<br /> *+/-Drug paraphernalia, e.g. crack pipe.<br /> <br /> ====Ethylene glycol toxicity====<br /> :For a more general discussion see ''[[Crystals_in_body_fluids#Urine_crystals|urine crystals]]''<br /> *Not done in routine toxicology screening.<br /> *Birefringent calcium oxalate crystals found in kidney (with polarized light).&lt;ref name=Ref_KFP589&gt;{{Ref KFP|589}}&lt;/ref&gt;<br /> <br /> ====Anaphylaxis====<br /> *Allergic reaction, e.g. peanut allergy.<br /> <br /> Diagnosis - serology:&lt;ref name=pmid20176258&gt;{{cite journal |author=Simons FE |title=Anaphylaxis |journal=J. Allergy Clin. Immunol. |volume=125 |issue=2 Suppl 2 |pages=S161–81 |year=2010 |month=February |pmid=20176258 |doi=10.1016/j.jaci.2009.12.981 |url=}}&lt;/ref&gt;<br /> *IgE.<br /> *Tryptase.<br /> <br /> =Natural death=<br /> {{main|Natural death}}<br /> There is a lot that can kill ya... but only a few of those are quickly, i.e. within a hour or so.<br /> <br /> Generally, these things are:<br /> *Cardiovascular:<br /> **[[Cardiac arrhythmia|Arrhythmia]].<br /> **[[Myocardial infarction]].<br /> **Haemorrhage.<br /> ***Ruptured aneurysm.<br /> **[[Hypertensive heart disease]].<br /> *Respiratory:<br /> **[[Pulmonary embolism]] (PE).<br /> **[[Asthma]].<br /> *GI:<br /> **Haemorrhage.<br /> ***[[Esophageal varices]].<br /> ***Gastric varices.<br /> *Neurologic:<br /> **Intracranial haemorrhage.<br /> ***Ruptured aneurysm.<br /> ***Spontaneous [[subdural hemorrhage]].<br /> **[[Stroke]]:<br /> ***Haemorrhagic.<br /> ***Thrombotic (more common than hemorrhagic).<br /> <br /> =Forensic entomology=<br /> {{main|Forensic entomology}}<br /> *Study of the bugs that eat corpses.<br /> *Bugs may hide a wound... it is important to know where they like to be.<br /> <br /> =Forensic anthropology=<br /> {{main|Forensic anthropology}}<br /> Forensic anthropology is looking at skeletal remains. It may be useful of [[decendent identification|identification]] and, rarely, the cause of death. Important in skeletonized remains and decomp cases.<br /> <br /> =Forensic taphonomy=<br /> *The study of post-mortem decay to assist in a medicolegal investigation.<br /> **''Taphonomy'' = postmortem fate of biological remains; derived from the Greek word ''taphos'' (grave).&lt;ref&gt;{{cite journal |author=Milroy CM |title=Forensic taphonomy: the postmortem fate of human remains |journal=BMJ |volume=319 |issue=7207 |pages=458 |year=1999 |month=August |pmid=10445946 |pmc=1127062 |doi= |url=}}&lt;/ref&gt;<br /> <br /> =See also=<br /> *[[Forensic entomology]].<br /> *[[Autopsy]].<br /> *[[Heart]].<br /> <br /> =References=<br /> {{reflist|2}}<br /> <br /> =External links=<br /> *[http://cap-acp.org/forensic.cfm Forensic pathology (cap-acp.org)].<br /> *[http://neurobio.drexelmed.edu/goldmanweb/forensicanthro/trauma.pdf Fractures (drexelmed.edu)].<br /> *[http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ Mechanisms of death (forensicmed.co.uk)].<br /> <br /> ==Post-mortem changes==<br /> *[http://emedicine.medscape.com/article/1680032-overview#showall Post-mortem changes (emedicine.medscape.com)].<br /> *[http://emedicine.medscape.com/article/1680107-overview#showall Autopsy of blunt force trauma (emedicine.medscape.com)].<br /> *[http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html Post-mortem changes (the-crankshaft.info)].<br /> <br /> [[Category:Autopsy]]<br /> [[Category:Forensic pathology]]</div>

Tate https://librepathology.org/w/index.php?title=Forensic_pathology&diff=39172 2015-08-12T14:19:10Z

<p>Tate: /* Motor vehicle collisions */</p> <hr /> <div>'''Forensic pathology''' is figuring-out why, when, where and how people died, if the manner of death is ''not'' obviously natural.<br /> <br /> =Death categorization=<br /> Deaths are categorized foremost by the '''manner of death'''. The manner is the single most important legal categorization for a death. <br /> The '''cause of death''' is important for understanding what happened. The '''mechanism of death''' is the pathophysiologic reason for death and can be inferred from the cause.<br /> <br /> Examples:<br /> {| class=&quot;wikitable sortable&quot; <br /> !Cause of death <br /> !Manner of death<br /> !Mechanism of death<br /> !Scenario<br /> |-<br /> | [[Electrocution]]<br /> | accident<br /> | [[cardiac arrhythmia]]<br /> | man struck by lightening<br /> |-<br /> | Hyperthermia<br /> | accident<br /> | arrhythmias, seizures&lt;ref name=fmuk&gt;URL: [http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ http://www.forensicmed.co.uk/pathology/mechanisms-of-death/]. Accessed on: 19 April 2012.&lt;/ref&gt;<br /> | man lost on hiking trip in desert<br /> |-<br /> | [[Epidural hemorrhage]] due to [[blunt force trauma]] to the head<br /> | homicide<br /> | brain stem compression or cerebral vascular spasm leading to autonomic dysregulation<br /> | man hit with a hammer in the head<br /> |-<br /> | [[Carbon monoxide toxicity]]<br /> | suicide<br /> | cerebral hypoxia (CO binds to hemoglobin impairing oxygen transport)<br /> | woman found in car with suicide note, long history of depression, previous suicide attempts<br /> |-<br /> | [[Atherosclerotic heart disease]]<br /> | natural<br /> | cardiac arrhythmia due to ischemia<br /> | man found dead in bed, apartment locked, 95% stenosis of LMCA at autopsy, no other significant autopsy findings<br /> |- &lt;!--<br /> | [[Peritonitis]] due to duodenal perforation as a consequence of [[peptic ulcer disease]]<br /> | natural<br /> | cerebral hypoxia secondary to hypotension<br /> | man found in locked apartment, complained of abdominal pain before dead<br /> |-<br /> | Coronary artery stent thrombosis complicating the treatment of a [[myocardial infarction]] due to atherosclerotic heart disease<br /> | natural<br /> | cardiac arrhythmia due to ischemia<br /> | woman found dead following hospital stay for a myocardial infarction, post-angioplasty and coronary stenting --&gt;<br /> |}<br /> <br /> ==Manner of death==<br /> The manner of death is a legislatively defined classification. It varies slightly between jurisdictions. <br /> &lt;!--<br /> MANNER OF DEATH<br /> --&gt;<br /> {{familytree/start}}<br /> {{familytree | | | | | | | | | A | | | | | | | | |A=Manner}}<br /> {{familytree | |,|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| |}}<br /> {{familytree | B | | C | | D | | E | | F |B=Homicide|C=Suicide|D=Natural|E=Accident|F=Undetermined}}<br /> {{familytree/end}}<br /> <br /> Notes:<br /> *''Undetermined'' - is a waste basket category.<br /> *''Homicide'' - not necessarily murder.<br /> *Can be group into three:<br /> *#Intent to kill (homicide, suicide).<br /> *#No intent to kill (natural, accidental).<br /> *#Undetermined.<br /> <br /> ==Mechanism of death==<br /> This is occasionally of interest. It is usually based on physiology. <br /> <br /> The mechanism is often asked for [[asphyxial death]]s. The short answer it is: brain stem hypoxia due to ischemia caused by venous obstruction in the neck.&lt;ref&gt;URL: [http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ http://www.forensicmed.co.uk/pathology/mechanisms-of-death/]. Accessed on: 1 May 2012.&lt;/ref&gt;&lt;ref&gt;URL: [http://www.forensicmed.co.uk/pathology/pressure-to-the-neck/ http://www.forensicmed.co.uk/pathology/pressure-to-the-neck/]. Accessed on: 1 May 2012.&lt;/ref&gt;<br /> <br /> ==Cause of death==<br /> *Abbreviated ''COD''.<br /> ===General===<br /> *The cause of death should be what started the sequence of events that lead to death.<br /> <br /> ====Word form for cause of death====<br /> Examples:<br /> *''[[C. difficile colitis]] complicating antibiotic treatment for a dental abscess''.&lt;ref&gt;MSP. 8 September 2010.&lt;/ref&gt;<br /> *''Complications of laparoscopic cholecystectomy for ascending cholangitis with [[mesothelioma]] and atherosclerotic heart disease''.&lt;ref&gt;TR. 3 September 2010.&lt;/ref&gt;<br /> <br /> General forms:<br /> *''A'' complicating ''B'' for the treatment of ''C''.<br /> *''A'' complicating ''B'' for the treatment of ''C'' with ''D'' and ''E''.<br /> <br /> ====World Health Organization form for cause of death====<br /> General form:&lt;ref name=pmid15914304&gt;{{cite journal |author=Pollanen MS |title=Deciding the cause of death after autopsy--revisited |journal=J Clin Forensic Med |volume=12 |issue=3 |pages=113–21 |year=2005 |month=June |pmid=15914304 |doi=10.1016/j.jcfm.2005.02.004 |url=}}&lt;/ref&gt;<br /> *1a = ''immediate cause of death''.<br /> *1b = what lead to the ''immediate cause of death''.<br /> *1c... 1[x] -- where 'x' is the last letter used; 1x = What started the sequence of events. This is known as the ''underlying cause of death''.<br /> *2 = contributing factors.<br /> <br /> Example 1:<br /> *1a. [[Ketoacidosis]].<br /> *1b. [[Diabetes mellitus]].<br /> *2. [[Alcoholism]] and acute [[bronchopneumonia]].<br /> <br /> Example 2:<br /> *1a. Hemoperitoneum.<br /> *1b. [[Splenic laceration]].<br /> *1c. Blunt force trauma.<br /> *2. Liver [[cirrhosis]].<br /> <br /> ===Natural deaths===<br /> {{Main|Natural death}}<br /> *The cause should be a medical diagnosis, '''not''' the mechanism (e.g. ''cardiac arrest'', ''cachexia'', ''kidney failure'').<br /> *The [[mechanism of death|mechanism]] is irrelevant.<br /> <br /> Notes:<br /> *Unnatural causes trump natural ones. If a guy with (nothing more than) a 70% proximal LAD stenosis and an old [[myocardial infarct]] is found in the water, they are usually called [[drowning]].<br /> *[[Cancer]] is rarely the immediate cause of death - it is usually something else.&lt;ref&gt;Shannon, P. 2009.&lt;/ref&gt;<br /> *Things (mechanisms) that shouldn't be used: [http://www.pallimed.org/2008/03/unacceptable-causes-of-death-other-web.html http://www.pallimed.org/2008/03/unacceptable-causes-of-death-other-web.html]<br /> <br /> ===Legal frame work===<br /> ====General====<br /> *In Ontario, the ''manner'' is determined by the coroner.<br /> *Coroners, in Ontario, are MDs -- usually [[family docs]].<br /> *The cause (e.g. &quot;gunshot wound to the head&quot;) is determined by the pathologist.<br /> <br /> NB - the word ''coroner'' is not synoymous with MD. British Columbia has coroners that aren't MDs.<br /> <br /> ====Case classification (Ontario)====<br /> Cases are classified as:<br /> *''A case'' = homicide and suspicious for homicide, (all) gunshot wounds.<br /> *''B case'' = adult, non-suspicious.<br /> *''C case'' = child, non-suspicious.<br /> <br /> Notes:<br /> *All ''A cases'' are done at regional centers by certified forensic pathologists.<br /> <br /> =Forensic golden triangle=<br /> *History.<br /> *Scene.<br /> *[[Autopsy]].<br /> <br /> =Forensic diagnostic triangle=<br /> Most general differential diagnosis:<br /> *Natural:<br /> **Haemorrhage (e.g. cerebral bleed, gastrointestinal bleed, aortic aneurysm).<br /> **Infection (e.g. [[pneumonia]]).<br /> **[[Coronary artery atherosclerosis]] ([[cardiac arrhythmia]]s - more common in the forensic context than [[myocardial infarction]] (MI); individuals with MIs don't usu. drop dead-- they go to the ER).<br /> ***Post [[myocardial infarction]] (free wall rupture).<br /> ***Ruptured (atherosclerotic) plaque.<br /> *Toxic (memory device: ''PAIRO''):<br /> **Poisons.<br /> **[[Alcohol]] (EtOH). <br /> **Illicit (e.g. [[cocaine]], heroin, LSD). <br /> **Rx. <br /> **Over-the-counter (OTC) (e.g. acetaminophen, warfarin).<br /> *Trauma (memory device ''AGE BS''):<br /> **[[asphyxial deaths|Asphyxial]]. <br /> **[[Gunshot wounds]] (GSWs). <br /> **Environmental (e.g. hypothermia, hyperthermia, [[drowning]], lack of oxygen, [[electrocution]]).<br /> **[[Blunt force trauma]]. <br /> **[[Sharp force trauma]]. <br /> <br /> Difficulties arise when more than one point of the triangle is in play, i.e. the forensic pathologist has to earn their pay when an old man with a heart condition is known to be into erotic asphyxia, and dies after doing some drugs and whilst indulging in erotic asyphxiation with a friend...<br /> <br /> *If he had an arrhythmia and there was no stressor... ''natural'' death.<br /> *If he over did it with the drugs, it is an overdose, ergo ''accidental''.<br /> *If he did the erotic asphyxia a bit too long it is ''accidental''.<br /> *If the friend held the plastic bag over his head just a bit long to asphyxiate him... it is a ''homicide''.<br /> *If he was a lone and depressed... he might have been trying to kill himself, ergo ''suicide''.<br /> <br /> =Death-related changes=<br /> ===Rigor mortis===<br /> Definition: <br /> *Muscle rigidity following death (caused by depletion of ATP).<br /> <br /> Dependent on:<br /> *Temperature of patient at death.<br /> *Temperature variations in the environment since death.<br /> *Presence of some medical conditions.<br /> *May never develop!<br /> <br /> It is the explanation for post-mortem goose bumps.<br /> <br /> ====Summary====<br /> *Its onset &amp; presence is ''highly variable''.<br /> *Forensic pathologists do '''not''' comment on time of death, as the above times are subject to such a large degree of variability, i.e. the estimates are essentially useless.<br /> <br /> ====Time estimates====<br /> A crude guess for time of death based on rigor:&lt;ref name=Ref_KFP61&gt;{{Ref KFP|61}}&lt;/ref&gt;<br /> *Warm &amp; flaccid &lt;3 h.<br /> *Warm &amp; stiff 3-8 h. <br /> *Cold &amp; stiff 8-36 h. <br /> *Cold &amp; flaccid &gt; 36 h.<br /> <br /> Notes:<br /> *Memory device: '''3s''': cut points are at ''3 hours'', ''1/3 of a day'', ''3/2 of a day.''<br /> ===Livor mortis===<br /> Definition: pooling of blood in the dependent position, due to blood stasis. <br /> *Onset may preceed death in the context of congestive heart failure.<br /> *If pressure is applied to a dependent area-- no blood can enter there; thus, a pressure area is blanched (i.e. white).<br /> <br /> *Can be seen externally, i.e. on the skin, and internally.<br /> *Liver mortis becomes fixed some time after death. <br /> **Liver mortis does NOT tell one the position the decedent was in at the time of death-- only the position the decedent was at the time liver mortis became fixed. '''If''' the decedent wasn't moved liver mortis can help determine the position the person was in when they died.<br /> <br /> Averages:<br /> *Start: 30 minutes to 2 hours<br /> *Fixed: 8-12 hours.<br /> <br /> DDx:<br /> *[[Blunt force trauma]] - especially to the inexperienced eye.<br /> *Post-mortem hypostatic bruising.<br /> <br /> ===Tache noire===<br /> Literally ''black spot''.<br /> <br /> Features:&lt;ref name=emed1680032&gt;URL: [http://emedicine.medscape.com/article/1680032-overview http://emedicine.medscape.com/article/1680032-overview]. Accessed on: 6 March 2012.&lt;/ref&gt;<br /> *Brown/black horizontal line of the eye due to drying.<br /> **Arises if the eye remains open after death.<br /> **May mimic a traumatic injury. <br /> <br /> Images:<br /> *[http://img.medscape.com/pi/emed/ckb/pathology/1603817-1607640-1680032-1714463.jpg Tache noire (medscape.com)].&lt;ref name=emed1680032/&gt;<br /> *[http://www.demussen.net/carbon-monoxide/images/1856_23_12-vitreous-potassium.jpg Tache noire (demussen.net)].&lt;ref&gt;URL: [http://www.demussen.net/carbon-monoxide/chemical-changes-in-body-fluids.html http://www.demussen.net/carbon-monoxide/chemical-changes-in-body-fluids.html]. Accessed on: 6 March 2012.&lt;/ref&gt;<br /> <br /> ===Post-mortem decomposition/preservation===<br /> One of three things happens post-mortem:&lt;reF name=Ref_HospAuto102&gt;{{Ref HospAuto|102}}&lt;/ref&gt;<br /> #Mummification.<br /> #Putrefaction (skeletonisation).<br /> #*Green colour due to break down of hemoglobin (biliverdin).&lt;ref&gt;{{cite journal |author=NOIR BA, GARAY ER, ROYER M |title=SEPARATION AND PROPERTIES OF CONJUGATED BILIVERDIN |journal=Biochim. Biophys. Acta |volume=100 |issue= |pages=403–10 |year=1965 |month=May |pmid=14347937 |doi= |url=linkinghub.elsevier.com/retrieve/pii/0304416565900097}}&lt;/ref&gt;<br /> #Adipocere - transformation into wax (due to anaerobic bacterial hydrolysis of fat).<br /> #*Useless for toxicology and DNA.<br /> <br /> *A mix of the above often occur, i.e. part of the corpse is mummified... part of it decomposed through putrefaction.<br /> <br /> Mummification:<br /> *Predominant in dry environments.<br /> *Body becomes dry and leathery.<br /> <br /> Putrefaction:<br /> *Body wet/moist after death -- ideal environment for putrefactive bacteria and organisms.<br /> <br /> ===Artefacts===<br /> *Prinsloo and Gordon artefact = artefactual post-morten haemorrhage on the posterior surface of the esophagus.&lt;ref name=pmid16378701&gt;{{cite journal |author=Piette MH, De Letter EA |title=Drowning: still a difficult autopsy diagnosis |journal=Forensic Sci. Int. |volume=163 |issue=1-2 |pages=1–9 |year=2006 |month=November |pmid=16378701 |doi=10.1016/j.forsciint.2004.10.027 |url=}}&lt;/ref&gt;<br /> **Minimized by removing cranial contents &amp; thoracic contents ''before'' undertaking neck dissection.&lt;ref name=Ref=HospAuto118&gt;{{Ref HospAuto|118}}&lt;/ref&gt;<br /> *Artefactual fractures (see fractures).<br /> *Dilated anus (in isolation).&lt;ref&gt;URL: [http://www.kingstonwhigstandard.com/ArticleDisplay.aspx?archive=true&amp;e=736464 http://www.kingstonwhigstandard.com/ArticleDisplay.aspx?archive=true&amp;e=736464]. Accessed on: 6 October 2010.&lt;/ref&gt;&lt;ref name=pmid17961873 &gt;{{Cite journal | last1 = Elder | first1 = DE. | title = Interpretation of anogenital findings in the living child: Implications for the paediatric forensic autopsy. | journal = J Forensic Leg Med | volume = 14 | issue = 8 | pages = 482-8 | month = Nov | year = 2007 | doi = 10.1016/j.jflm.2007.03.005 | PMID = 17961873 }}&lt;/ref&gt;<br /> *Towel clip injury, usu. paired (in organ donors) - may be mistaken for an electroshock weapon (e.g. Taser) wound.&lt;ref&gt;MSP. 12 October 2010.&lt;/ref&gt;<br /> *Subclavian stab for vascular access - may be confused with a gunshot exit wound.<br /> <br /> ====Infants====<br /> *Lumpy neck - small superficial nodules on anterior neck ~2-5 mm (???).&lt;ref&gt;MSP. 6 October 2010.&lt;/ref&gt;<br /> *Intussusception of small bowel - often multiple.<br /> <br /> =Wounds=<br /> ==General==<br /> *''Wound'' - definition: defect in skin or mucous membrane&lt;ref&gt;URL: [http://dictionary.reference.com/browse/wound http://dictionary.reference.com/browse/wound]. Accessed on: 20 April 2012.&lt;/ref&gt; - usually due to trauma.<br /> <br /> Special types of wounds:<br /> *[[Gunshot wounds]].<br /> *Incised wounds - see [[sharp force trauma]].<br /> <br /> ===Gross pathologic classification of injuries===<br /> Mnemonic ''CALI'':<br /> *'''C'''ontusion - &quot;bruise&quot;, [[hematoma]].<br /> **Age (usual colour change sequence): red, blue, green, yellow, brown.&lt;ref name=Ref_HospAuto108&gt;{{Ref HospAuto|108}}&lt;/ref&gt;<br /> **Etiology: bleeding from arterioles or venules (not capillaries).&lt;ref name=Ref_HospAuto105&gt;{{Ref HospAuto|105}}&lt;/ref&gt;<br /> *'''A'''brasion - &quot;scrape&quot;, e.g. motorcyclist slide across the roadway... skin scraped-off.<br /> **Can be subclassified as ''brush abrasions'' (has skin tags) and ''crush abrasions'' (do not have skin tags).<br /> ***Skin tags suggest directionality; they are found at the distal point / point of last contact.&lt;ref name=Ref_HospAuto105&gt;{{Ref HospAuto|105}}&lt;/ref&gt;<br /> *'''L'''aceration - &quot;tear&quot;, indicates blunt force trauma; contact point may be distant from where skin splits.<br /> *'''I'''ncised - &quot;cut&quot;, e.g. caused by a knife,&lt;ref name=Ref_HoFP154&gt;{{Ref_HoFP|154}}&lt;/ref&gt; subdivided as follows:<br /> *#&quot;Cut&quot; or &quot;slash&quot; = length &gt; depth.<br /> *#&quot;Stab&quot; = depth &gt; length.<br /> *#&quot;Chop&quot; = typically have a contusion at the margin of the wound, classically caused by an axe. May be caused by a propeller.&lt;ref name=pmid19733336&gt;{{Cite journal | last1 = Ihama | first1 = Y. | last2 = Ninomiya | first2 = K. | last3 = Noguchi | first3 = M. | last4 = Fuke | first4 = C. | last5 = Miyazaki | first5 = T. | title = Fatal propeller injuries: three autopsy case reports. | journal = J Forensic Leg Med | volume = 16 | issue = 7 | pages = 420-3 | month = Oct | year = 2009 | doi = 10.1016/j.jflm.2009.04.006 | PMID = 19733336 }}&lt;/ref&gt;<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image:Hand_Abrasion_-_32_minutes_after_injury.JPG | Abrasion. (WC)<br /> Image:Black_eye_2.jpg | Contusion (&quot;black eye&quot;). (WC)<br /> &lt;/gallery&gt;<br /> ====DDx====<br /> How to decide what you're looking at:<br /> *Contusion: <br /> **Can be demonstrated histologically... there are extravascular RBCs.<br /> ***If pre-morten there is vital reaction, i.e. WBCs come to clean-up the trauma.<br /> **If the post mortem interval is not known and long-- differentiation from decomposition may be non-trivial/impossible.<br /> <br /> *Abrasion vs. contusion:<br /> **Contusions skin is intact... in abrasion it is not.<br /> **Abrasions and contusions may be co-localized, i.e. in the same place.<br /> <br /> *Laceration vs. incision:<br /> **Lacerations have &quot;bridges&quot;, incisions do NOT have bridges.<br /> ***Bridges are fine strands of tissue that cross the long axis of the skin defect.<br /> ****You can think of the wound as partially &quot;sutured&quot; by the bridges of tissue.<br /> **Lacerations are usually associated with a contusion and/or crush and have an irregular margin.&lt;ref name=Ref_HospAuto109&gt;{{Ref HospAuto|109}}&lt;/ref&gt;<br /> **Lacerations are classically on the skull and face. They are rarely on the abdomen.<br /> <br /> ===Wound dating===<br /> *Colour is somewhat useful for contusions (bruises).<br /> *Post-mortem injuries tend to be orange-yellow.&lt;ref name=pmid19237864&gt;{{Cite journal | last1 = Campobasso | first1 = CP. | last2 = Marchetti | first2 = D. | last3 = Introna | first3 = F. | last4 = Colonna | first4 = MF. | title = Postmortem artifacts made by ants and the effect of ant activity on decompositional rates. | journal = Am J Forensic Med Pathol | volume = 30 | issue = 1 | pages = 84-7 | month = Mar | year = 2009 | doi = 10.1097/PAF.0b013e318187371f | PMID = 19237864 }}&lt;/ref&gt;<br /> *Wounds age is difficult to determine as [[wound healing]] is affected by a large number of variables.<br /> *Old wounds (scars), generally, cannot be dated - one can only say they are ''old''.<br /> <br /> ===Microscopic===<br /> Wounds can be grouped into:<br /> *Pre-mortem.<br /> *Post-mortem.<br /> <br /> Signs a wound was inflicted during life:<br /> *Blood.<br /> **Hypostasis/decomposition can mess with this, i.e. blood oozing out of vessels post-mortem shouldn't be called an injury.<br /> **Hemosiderin demonstrated by an iron stain - hard sign.<br /> *Inflammation:&lt;ref name=Ref_PCPBoD8_26&gt;{{Ref PCPBoD8|26}}&lt;/ref&gt;<br /> **[[PMN]]s 6-24 hours after injury.<br /> **PMNs replaced monocytes in 24-48 hours.<br /> <br /> ===Stains===<br /> *[[Iron stain]] for siderophages (hemosiderin-laden macrophages) -- presence suggests 2-3 days or older.&lt;ref name=pmid7529545&gt;{{Cite journal | last1 = Betz | first1 = P. | title = Histological and enzyme histochemical parameters for the age estimation of human skin wounds. | journal = Int J Legal Med | volume = 107 | issue = 2 | pages = 60-8 | month = | year = 1994 | doi = | PMID = 7529545 }}&lt;/ref&gt;<br /> <br /> =Bone fractures=<br /> *[[AKA]] ''fractures''.<br /> *[[AKA]] ''fracture of bone''.<br /> <br /> ==Artefactual fractures==<br /> *&quot;Undertaker's fracture&quot; - cervical fracture due to rough handling.&lt;ref&gt;URL: [http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html]. Accessed on: 29 September 2010.&lt;/ref&gt;<br /> *Basal skull fracture due to opening of skull.&lt;ref&gt;MSP. 29 September 2010.&lt;/ref&gt;<br /> **Classically does not cross sella turcica.<br /> **Notably absent features of a real (ante-mortem) fracture: hematoma, brain injury.<br /> **Mechanism to explain trauma not present in history; a fall/tripping not sufficient.<br /> <br /> ==Healing of fractures==<br /> ===Simplified classification===<br /> *Primary callus (cartilaginous) - early.<br /> *Secondary callus (bone) - late.<br /> <br /> ===Microscopic===<br /> Features:<br /> *Fragmentation of bone.<br /> *+/-Dead bone = lacunae have no osteocytes.&lt;ref name=pmid22460748&gt;{{Cite journal | last1 = Fondi | first1 = C. | last2 = Franchi | first2 = A. | title = Definition of bone necrosis by the pathologist. | journal = Clin Cases Miner Bone Metab | volume = 4 | issue = 1 | pages = 21-6 | month = Jan | year = 2007 | doi = | PMID = 22460748 }}&lt;/ref&gt;<br /> **Takes days for osteocyte loss.<br /> *+/-Inflammatory cells.<br /> *+/-Hemosiderin-laden macrophages.<br /> *+/-Osteoblastic rimming.<br /> <br /> DDx:<br /> *Fracture secondary to a tumour:<br /> **Metastatic carcinoma.<br /> **[[Osteosarcoma]] - typically does '''not''' have osteoblastic rimming. <br /> <br /> Notes:<br /> *Radiology is not good at dating fratures;&lt;ref name=pmid15788611&gt;{{Cite journal | last1 = Prosser | first1 = I. | last2 = Maguire | first2 = S. | last3 = Harrison | first3 = SK. | last4 = Mann | first4 = M. | last5 = Sibert | first5 = JR. | last6 = Kemp | first6 = AM. | title = How old is this fracture? Radiologic dating of fractures in children: a systematic review. | journal = AJR Am J Roentgenol | volume = 184 | issue = 4 | pages = 1282-6 | month = Apr | year = 2005 | doi = | PMID = 15788611 | url=http://www.ajronline.org/cgi/content/full/184/4/1282 }}<br /> &lt;/ref&gt; however, it is good at finding 'em.<br /> <br /> ==Pattern and cause==<br /> ===Child abuse-related===<br /> *Paravertebral (bony) nodules = classic location for rib fractures in child abuse.<br /> *Metaphyseal fractures - &quot;classical metaphyseal lesions&quot;.&lt;ref name=pmid8615271&gt;{{Cite journal | last1 = Kleinman | first1 = PK. | last2 = Marks | first2 = SC. | title = A regional approach to classic metaphyseal lesions in abused infants: the distal tibia. | journal = AJR Am J Roentgenol | volume = 166 | issue = 5 | pages = 1207-12 | month = May | year = 1996 | doi = | PMID = 8615271 }}&lt;/ref&gt;<br /> <br /> ===Motor vehicle versus pedestrian===<br /> If the pedestrian is standing during the initial impact one classically finds, at bumper level, a lower limb fracture with a ''Messerer wedge'' (German: ''Messerer-Kiel'');&lt;ref name=pmid11376986&gt;{{Cite journal | last1 = Karger | first1 = B. | last2 = Teige | first2 = K. | last3 = Fuchs | first3 = M. | last4 = Brinkmann | first4 = B. | title = Was the pedestrian hit in an erect position before being run over? | journal = Forensic Sci Int | volume = 119 | issue = 2 | pages = 217-20 | month = Jun | year = 2001 | doi = | PMID = 11376986 }}<br /> &lt;/ref&gt; the wedge points in the direction of the (impact) force.<br /> <br /> ==Location or type==<br /> ===Orbital floor fractures===<br /> *[[AKA]] ''blow-out fractures''.&lt;ref name=pmid17333039&gt;{{Cite journal | last1 = Punke | first1 = C. | last2 = Fritsche | first2 = A. | last3 = Martin | first3 = H. | last4 = Schmitz | first4 = KP. | last5 = Pau | first5 = HW. | last6 = Kramp | first6 = B. | title = [Investigation of the mechanisms involved in isolated orbital floor fracture. Simulation using a finite element model of the human skull]. | journal = HNO | volume = 55 | issue = 12 | pages = 938-44 | month = Dec | year = 2007 | doi = 10.1007/s00106-007-1545-5 | PMID = 17333039 }}&lt;/ref&gt;<br /> ====General====<br /> *Classically due to fights, followed by traffic accidents.&lt;ref name=pmid20165966&gt;{{Cite journal | last1 = Gosau | first1 = M. | last2 = Schöneich | first2 = M. | last3 = Draenert | first3 = FG. | last4 = Ettl | first4 = T. | last5 = Driemel | first5 = O. | last6 = Reichert | first6 = TE. | title = Retrospective analysis of orbital floor fractures--complications, outcome, and review of literature. | journal = Clin Oral Investig | volume = 15 | issue = 3 | pages = 305-13 | month = Jun | year = 2011 | doi = 10.1007/s00784-010-0385-y | PMID = 20165966 }}&lt;/ref&gt;<br /> *Thought to result from loading on the orbital rim directly or the orbit - both are transmitted to the orbital floor.&lt;ref name=pmid17333039/&gt;<br /> <br /> Note:<br /> *The orbital floor tends to the be weaker than other components of the orbital cavity wall; thus, it is the most common site of fracture in the orbital cavity wall.<br /> <br /> ===Basal skull fracture===<br /> ====General====<br /> Etiology:<br /> *Blunt force trauma - high energy &amp; velocity.<br /> **Seen in ''motor vehicle collisions'', ''descent from height''.<br /> <br /> Clinical/external findings:<br /> *Raccoon eyes = periorbital ecchymosis.<br /> *Battle sign = mastoid ecchymosis.<br /> **Associated with orbital roof fractures.&lt;ref&gt;URL: [http://emedicine.medscape.com/article/1680107-overview#showall http://emedicine.medscape.com/article/1680107-overview#showall]. Accessed on: 28 March 2012.&lt;/ref&gt;<br /> *Cerebrospinal fluid rhinorrhea.<br /> *Hemorrhage from nose and ears.<br /> *Hemotympanum.<br /> <br /> Note:<br /> *There is a dictum that states ''bilateral petrous bone fractures are due to impact to the side of the head'' - it isn't true.&lt;ref name=pmid7391790&gt;{{Cite journal | last1 = Harvey | first1 = FH. | last2 = Jones | first2 = AM. | title = Typical basal skull fracture of both petrous bones: an unreliable indicator of head impact site. | journal = J Forensic Sci | volume = 25 | issue = 2 | pages = 280-6 | month = Apr | year = 1980 | doi = | PMID = 7391790 }}&lt;/ref&gt;<br /> <br /> ===Hinge fracture of the skull===<br /> *A special type of [[basal skull fracture]].<br /> *Complete hinge fractures are considered severe; they are a 4 on the ''abbreviated injury scale'' (AIS).&lt;ref&gt;{{Cite journal | last1 = Adams | first1 = VI. | last2 = Carrubba | first2 = C. | title = The Abbreviated Injury Scale: application to autopsy data. | journal = Am J Forensic Med Pathol | volume = 19 | issue = 3 | pages = 246-51 | month = Sep | year = 1998 | doi = | PMID = 9760090 }}&lt;/ref&gt;<br /> *Classically due to a blow to the chin - resulting in a fracture across the medial fossa and sella turcica.&lt;ref&gt;URL: [http://wiki.answers.com/Q/Hinge_fracture_of_skull_is_seen_in_accidents_involving http://wiki.answers.com/Q/Hinge_fracture_of_skull_is_seen_in_accidents_involving]. Accessed on: 28 March 2012.&lt;/ref&gt;<br /> <br /> ===Pathologic fracture===<br /> {{Main|Pathologic fracture}}<br /> *A fracture due to an underlying pathology.<br /> <br /> ===Hip fractures===<br /> *[[Traumatic fracture of the femoral neck]].<br /> <br /> =Autopsy=<br /> {{Main|Autopsy}}<br /> The ''autopsy'' article covers procedural things. Heart dissection is covered in the ''[[heart]]'' article.<br /> <br /> ===Types===<br /> Forensic vs. hospital:<br /> *Forensic autopsies are focused on the external exam.<br /> <br /> ===Marking conventions for common findings===<br /> There are no universal marking conventions for injuries.<br /> <br /> One system in use (the ''Rose system'') is:&lt;ref&gt;TR. 1 September 2010.&lt;/ref&gt;<br /> *One red line for an incised wound.<br /> *Multiple closely spaced red lines, i.e. red hatching, for abrasions.<br /> *Multiple closely-spaced blue lines, i.e. blue hatching, for contusions.<br /> <br /> The above makes sense in that:<br /> *Abrasions and incised wounds typically bleed - are red.<br /> *Contusions (bruises) don't classically bleed and are classically blue.<br /> <br /> ===External exam findings===<br /> Colour of the corpse:&lt;ref name=Ref_Shkrum33&gt;{{Ref Shkrum|33}}&lt;/ref&gt;<br /> *Red (Pink) = [[carbon monoxide toxicity|carbon monoxide]], cyanide, fluoroacetate,&lt;ref name=pmid17288493&gt;{{cite journal |author=Proudfoot AT, Bradberry SM, Vale JA |title=Sodium fluoroacetate poisoning |journal=Toxicol Rev |volume=25 |issue=4 |pages=213–9 |year=2006 |pmid=17288493 |doi= |url=}}&lt;/ref&gt; [[hypothermia]].<br /> *Purple (intense) = propane.<br /> *Green = [[hydrogen sulfide]].<br /> *Brown = nitrites (methemoglobinemia).<br /> <br /> ===Autopsy terminology===<br /> *''Gutter butter'' = adipose tissue in a decomp case; looks like butter topping put on popcorn. A Toronto-ism.<br /> *''Gutter blood'' = blood in the empty thorax - after extraction of the organ block.<br /> *''Tardieu spots'' = postmortem hypostatic hemorrhages;&lt;ref name=pmid19901802&gt;{{cite journal |author=Pollanen MS, Perera SD, Clutterbuck DJ |title=Hemorrhagic lividity of the neck: controlled induction of postmortem hypostatic hemorrhages |journal=Am J Forensic Med Pathol |volume=30 |issue=4 |pages=322–6 |year=2009 |month=December |pmid=19901802 |doi=10.1097/PAF.0b013e3181c17ec2 |url=}}&lt;/ref&gt; look like petechiae - in dependent areas, i.e. in the zone of livity.<br /> <br /> ===Autopsy on decomposed remains===<br /> *[[AKA]] &quot;decomp autopsy&quot; or simply &quot;decomp&quot;.<br /> ====General====<br /> *Histology usually very limited ''or'' useless.<br /> *Often done to exclude trauma.<br /> *Typical scenario: decedent lives alone -- body not discovered for prolonged period of time.<br /> *More likely to be a ''[[negative autopsy]]'' than non-decomp cases.<br /> <br /> ====Suspicious decomp====<br /> Common sense rules for if skin is '''not''' intact:<br /> #Blunt dissection (to avoid artefactual injuries to the bones).<br /> #Clean the bones (''not'' with bleach)<br /> #*Bones cooked for 1+ hours... with frequent checks to avoid that they become mushy.<br /> <br /> =Causes of death=<br /> <br /> ==Environmental==<br /> {{Main|Environmental causes of death}}<br /> They include: <br /> *[[Hypothermia]]. <br /> *[[Hyperthermia]]. <br /> *Drowning - see [[asphyxial deaths]].<br /> *Lack of oxygen - see [[asphyxial deaths]]. <br /> *[[Electrocution]].<br /> <br /> =Gunshot wounds=<br /> {{main|Gunshot wounds}}<br /> Gunshot wounds (GSWs) are a relatively uncommon finding in Canada. They are dealt within a separate article.<br /> <br /> =Asphyxia=<br /> {{main|Asphyxial deaths}}<br /> <br /> *This is a big topic and covered by a separate article.<br /> <br /> ===Classification=== <br /> *''Strangulation'' - where there are signs of neck compression.<br /> **Includes: ganging, ligature strangulation and manual strangulation.<br /> *''Chemical asphyxia'' - usually no signs of neck compression.<br /> **Includes: carbon monoxide poisoning.<br /> *''Suffocation'' - usually no signs of neck compression.<br /> **Includes: smothering, [[choking]], positional asphyxia, [[drowning]].<br /> <br /> =Blunt force injury=<br /> *[[AKA]] ''blunt force trauma''.<br /> ==General==<br /> Classification:<br /> *Contusions.<br /> *Laceration.<br /> *Acceleration/deceleration injury, e.g. [[diffuse axonal injury]].<br /> <br /> Weapons: <br /> *Fist.<br /> *Foot.<br /> *Baseball bat... pretty much anything.<br /> *Beer bottles are common... and strong enought to fracture a skull.<br /> **Empty bottles have a higher fracture energy than full ones.&lt;ref name=pmid19239964&gt;{{cite journal |author=Bolliger SA, Ross S, Oesterhelweg L, Thali MJ, Kneubuehl BP |title=Are full or empty beer bottles sturdier and does their fracture-threshold suffice to break the human skull? |journal=J Forensic Leg Med |volume=16 |issue=3 |pages=138–42 |year=2009 |month=April |pmid=19239964 |doi=10.1016/j.jflm.2008.07.013 |url=}}&lt;/ref&gt;<br /> <br /> ==Cause of death==<br /> ===Commotio cordis===<br /> Features:&lt;ref name=pmid11334832&gt;{{cite journal |author=Kohl P, Nesbitt AD, Cooper PJ, Lei M |title=Sudden cardiac death by Commotio cordis: role of mechano-electric feedback |journal=Cardiovasc. Res. |volume=50 |issue=2 |pages=280–9 |year=2001 |month=May |pmid=11334832 |doi= |url=}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |author=Maron BJ, Estes NA |title=Commotio cordis |journal=N. Engl. J. Med. |volume=362 |issue=10 |pages=917–27 |year=2010 |month=March |pmid=20220186 |doi=10.1056/NEJMra0910111 |url=http://www.nejm.org/doi/full/10.1056/NEJMra0910111}}&lt;/ref&gt;<br /> *Often negative autopsy; no cardiac pathology.<br /> *Etiology: [[cardiac arrhythmia|arrhythmia]].<br /> *History: trauma to chest.<br /> <br /> Note:<br /> *May be spelled ''Commodio cordis''.&lt;ref name=pmid11555799&gt;{{cite journal |author=Perron AD, Brady WJ, Erling BF |title=Commodio cordis: an underappreciated cause of sudden cardiac death in young patients: assessment and management in the ED |journal=Am J Emerg Med |volume=19 |issue=5 |pages=406–9 |year=2001 |month=September |pmid=11555799 |doi=10.1053/ajem.2001.24455 |url=}}&lt;/ref&gt;<br /> *Analogous to ''[[commotio medullaris]]''.<br /> <br /> ==Scenarios==<br /> ===Motor vehicle collisions===<br /> *Pedestrian vs. motor vehicle: heel to injury measurement, remember to include the thickness of the heel/sole of shoe.&lt;ref&gt;{{Ref OPMfP|18}}&lt;/ref&gt;<br /> <br /> ===Descent from height===<br /> *Relatively common way to suicide.<br /> **May be an ''accident'', e.g. decedent thought they can fly (due to a psychosis).<br /> **May be a ''homicide'', e.g. decedent was pushed.<br /> <br /> ====Gross====<br /> Features:<br /> *Multiple injuries - often including multiple fractures, e.g. basal skull fracture, flail chest.<br /> *+/-Haemothorax - can be proved with a large bore needle.<br /> **Sufficient for cause of death - can be used to do an abbreviated post-mortem.<br /> *+/-Haemoaspiration (due to facial trauma) - presence suggest that decendent was alive shortly after landing/impact and thus likely very alive during the descent.<br /> **Patchy red centrilobular spots on gross examination.<br /> <br /> ==Injury patterns==<br /> ===Seromuscular tear===<br /> * [[AKA]] ''seatbeat syndrome''.<br /> * Intestinal injury associated with motor vehicle collisions and more specifically seatbelts. <br /> <br /> Features:<br /> * Def'n: separation of (inner) muscularis propria from submucosa.&lt;ref name=pmid12198344&gt;{{Cite journal | last1 = Slavin | first1 = RE. | last2 = Borzotta | first2 = AP. | title = The seromuscular tear and other intestinal lesions in the seatbelt syndrome: a clinical and pathologic study of 29 cases. | journal = Am J Forensic Med Pathol | volume = 23 | issue = 3 | pages = 214-22 | month = Sep | year = 2002 | doi = 10.1097/01.PAF.0000023001.32202.2D | PMID = 12198344 }}&lt;/ref&gt;<br /> <br /> ===Bite injury===<br /> *A special type of [[blunt force trauma]].<br /> *May be seen in the context of a sexual assault.<br /> *A ''forensic dentist'' may be able to assist.<br /> <br /> In the context of a suspicious case:<br /> *Human vs. animal.<br /> *Bite marks, as evidence, have a limited value for identification purposes.<br /> **In the context of identifying a potential perpetrator, it is essential to swab the bite mark for saliva, which is rich in DNA.&lt;ref&gt;{{Cite journal | last1 = Pretty | first1 = IA. | title = Forensic dentistry: 2. Bitemarks and bite injuries. | journal = Dent Update | volume = 35 | issue = 1 | pages = 48-50, 53-4, 57-8 passim | month = | year = | doi = | PMID = 18277695 }}&lt;/ref&gt;<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image: Dog_bite.JPG | Bite injury. (WC)<br /> &lt;/gallery&gt;<br /> <br /> ===Aortic trauma===<br /> *Classic location of injury is subclavian branch point.&lt;ref name=pmid1934437&gt;{{cite journal |author=Kodali S, Jamieson WR, Leia-Stephens M, Miyagishima RT, Janusz MT, Tyers GF |title=Traumatic rupture of the thoracic aorta. A 20-year review: 1969-1989 |journal=Circulation |volume=84 |issue=5 Suppl |pages=III40–6 |year=1991 |month=November |pmid=1934437 |doi= |url=}}&lt;/ref&gt;<br /> *[[Aortic dissection]] due to trauma is often catastrophic.<br /> <br /> ==Trauma with delayed death==<br /> *[[Epidural hemorrhage]] with a lucid interval.<br /> *Subcapsular splenic hematoma with subsequent rupture.<br /> *Subcapsular hepatic hematoma with subsequent rupture.<br /> *[[Aortic dissection]] with subsequent rupture.<br /> <br /> =Sharp force injury=<br /> *[[AKA]] ''sharp force trauma''.<br /> ===General===<br /> Injuries caused by:&lt;ref name=Ref_HospAuto111-2&gt;{{Ref HospAuto|111-2}}&lt;/ref&gt;<br /> *Knife.<br /> *Scissors - classic &quot;Z&quot; shape.<br /> *Screwdriver.<br /> *Glass.<br /> <br /> ===Gross===<br /> Features:&lt;ref name=Ref_HospAuto111-2&gt;{{Ref HospAuto|111-2}}&lt;/ref&gt;<br /> *Incised wound (see: ''[[Wounds|Classification of wounds]]'').<br /> **&quot;Clean&quot; edge (no contusion, no abrasion).<br /> **Well-demarcated edges.<br /> *+/-Hilt mark.<br /> **Due to contact of hilt.<br /> <br /> Subclassified into - see ''[[Wounds|classification of wounds]]'':<br /> *''Cut/slash''. <br /> *''Stab''. <br /> *''Chop'' - a mixed injury, sharp force and blunt force.<br /> <br /> ====Images====<br /> &lt;gallery&gt;<br /> Image: Thorax-Messerstichwunden.jpg | Sharp force trauma - thorax. (WC)<br /> &lt;/gallery&gt;<br /> <br /> =Head injuries=<br /> ===Accidental vs. intentional===<br /> Features of non-accidental injuries:&lt;ref name=pmid20141554&gt;{{cite journal |author=Guyomarc'h P, Campagna-Vaillancourt M, Kremer C, Sauvageau A |title=Discrimination of falls and blows in blunt head trauma: a multi-criteria approach |journal=J. Forensic Sci. |volume=55 |issue=2 |pages=423–7 |year=2010 |month=March |pmid=20141554 |doi=10.1111/j.1556-4029.2009.01310.x |url=}}&lt;/ref&gt;<br /> *Lacerations:<br /> **More than three.<br /> **Length &gt;= 7 cm or more.<br /> **Location:<br /> ***Above hat brim line (HBL).<br /> ***[[Ear]].<br /> ***Left-sided.<br /> *Fractures:<br /> **Comminuted or depressed calvarial fractures. <br /> **Location:<br /> ***Fractures located above the HBL.<br /> ***Left-sided fractures.<br /> ***Facial fractures.<br /> *Contusions:<br /> **Greater than four facial contusions.<br /> *Other:<br /> **&quot;Postcranial osseous&quot; [sic] (non-rib, non-skull) and/or visceral trauma.<br /> <br /> Note: The paper doesn't give odds ratios for the the different features -- like in the rational clinical exam series... it is a shame.<br /> <br /> ==Diffuse axonal injury==<br /> *Abbreviated ''DAI''.<br /> ===General===<br /> Clinical:<br /> *Vegetative state. <br /> *Imaging findings: no anatomical cause apparent (in some cases).<br /> <br /> Etiology:<br /> *Hypothesized to arise from high shear loading of white mater tracts.&lt;ref name=pmid2769276&gt;{{cite journal |author=Blumbergs PC, Jones NR, North JB |title=Diffuse axonal injury in head trauma |journal=J. Neurol. Neurosurg. Psychiatr. |volume=52 |issue=7 |pages=838–41 |year=1989 |month=July |pmid=2769276 |pmc=1031929 |doi= |url=}}&lt;/ref&gt;<br /> <br /> ===Gross===<br /> Macroscopic findings:&lt;ref name=pmid2769276/&gt;<br /> *Tears - corpus callosum.<br /> *Haemorrhage.<br /> <br /> Other (chronic) changes:&lt;ref name=Ref_AoGP639&gt;{{Ref AoGP|639}}&lt;/ref&gt;{{fact}}<br /> *Thalamus - shrinkage.<br /> *Enlargement of third ventricle.<br /> <br /> DDx (medical imaging):&lt;ref name=pmid22406792&gt;{{Cite journal | last1 = Kumar | first1 = S. | last2 = Gupta | first2 = V. | last3 = Aggarwal | first3 = S. | last4 = Singh | first4 = P. | last5 = Khandelwal | first5 = N. | title = Fat embolism syndrome mimicker of diffuse axonal injury on magnetic resonance imaging. | journal = Neurol India | volume = 60 | issue = 1 | pages = 100-2 | month = | year = | doi = 10.4103/0028-3886.93597 | PMID = 22406792 }}&lt;/ref&gt;<br /> *[[Cerebral fat embolism]].<br /> <br /> ===Microscopic===<br /> Microscopic findings:&lt;ref name=pmid2769276/&gt;<br /> *Axonal retraction balls.<br /> *&quot;Microglial stars&quot;.<br /> *Degeneration of fibre tracts.<br /> <br /> Grading:&lt;ref&gt;URL: [http://wiki.cns.org/wiki/index.php/Diffuse_axonal_injury_%28DAI%29 http://wiki.cns.org/wiki/index.php/Diffuse_axonal_injury_%28DAI%29]. Accessed on: 13 February 2012.&lt;/ref&gt;<br /> *Grade 1: only microscopic findings.<br /> *Grade 2: macroscopic corpus callosum injury + microscopic findings of DAI. <br /> *Grade 3: macroscopic corpus callosum and midbrain injuries + microscopic findings of DAI.<br /> <br /> ===Stains===<br /> *[[Bielschowsky stain]] to highlight axonal swellings - appear 12-18 hours after injury.&lt;ref name=Ref_Shkrum_562&gt;{{Ref Shkrum|562}}&lt;/ref&gt;<br /> <br /> ===IHC===<br /> *Beta-amyloid precursor protein (beta-APP ''or'' APP).&lt;ref name=pmid10050789&gt;{{cite journal |author=Gleckman AM, Bell MD, Evans RJ, Smith TW |title=Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining |journal=Arch. Pathol. Lab. Med. |volume=123 |issue=2 |pages=146–51 |year=1999 |month=February |pmid=10050789 |doi= |url=}}&lt;/ref&gt;&lt;ref name=pmid17368446&gt;{{Cite journal | last1 = Mac Donald | first1 = CL. | last2 = Dikranian | first2 = K. | last3 = Song | first3 = SK. | last4 = Bayly | first4 = PV. | last5 = Holtzman | first5 = DM. | last6 = Brody | first6 = DL. | title = Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury. | journal = Exp Neurol | volume = 205 | issue = 1 | pages = 116-31 | month = May | year = 2007 | doi = 10.1016/j.expneurol.2007.01.035 | PMID = 17368446 | PMC = 1995439 }}&lt;/ref&gt;<br /> *NF.&lt;ref name=pmid17368446/&gt;<br /> <br /> ==Intracranial hemorrhage==<br /> {{main|Intracranial hematoma}}<br /> Intracranial hemorrhage may be a consequence of blunt force trauma.<br /> <br /> Classification:<br /> *[[Epidural hematoma]].<br /> *[[Subdural hematoma]].<br /> *[[Subarachnoid hematoma]].<br /> *[[Intracerebral hematoma]].<br /> <br /> ==Cerebral contusion==<br /> ===General===<br /> *Due to blunt force trauma.<br /> <br /> ===Gross===<br /> Features:<br /> *Focal superficial hemorrhage.<br /> *Location, usually, ''frontal lobe'' and ''temporal lobe''.&lt;ref name=Ref_HoFP_102&gt;{{Ref HoFP|102}}&lt;/ref&gt;<br /> <br /> Notes:<br /> *Classically, come in pairs:&lt;ref name=Ref_HoFP_102&gt;{{Ref HoFP|102}}&lt;/ref&gt;<br /> *#''Coup contusion'' - at the site of the (primary) impact<br /> *#''Contrecoup contusion'' - secondary internal impact.<br /> **Example - fall on back of head: <br /> ***Occipital lobe contusion = coup contusion.<br /> ***Frontal lobe contusion = contrecoup contusion.<br /> *May be associated with contusions of the:&lt;ref name=Ref_HoFP_103&gt;{{Ref HoFP|103}}&lt;/ref&gt; <br /> **Deep brain structures, known as an &quot;intermediary coup&quot;.<br /> **Dorsal surface of the cerebral hemispheres, known as &quot;gliding contusions&quot;.<br /> *Resolve as a yellow lesion (like at other sites), known as a ''[[plaque]] jaune'' in the brain.<br /> **Classically, inferior aspect of the frontal lobe.<br /> <br /> DDx:<br /> *Hemorrhagic [[stroke]] - usually temporal lobe and/or parietal lobe.<br /> <br /> ==Traumatic brain injury in infants==<br /> {{main|Traumatic brain injury in infants}}<br /> <br /> *Shaken-impact syndrome, [[AKA]] shaken baby syndrome.<br /> <br /> ==Commotio medullaris==<br /> Features:&lt;ref name=Ref_Shkrum613&gt;{{Ref Shkrum|613}}&lt;/ref&gt;<br /> *Sudden death after head trauma that is insufficient to explain death.<br /> *Etiology: unknown - thought to be related to apnea.<br /> <br /> Note:<br /> *Analogous to ''[[commotio cordis]]''.<br /> <br /> =Excited delirium=<br /> *[[AKA]] ''agitated delirium''.&lt;ref name=pmid8768172&gt;{{cite journal |author=Wetli CV, Mash D, Karch SB |title=Cocaine-associated agitated delirium and the neuroleptic malignant syndrome |journal=Am J Emerg Med |volume=14 |issue=4 |pages=425–8 |year=1996 |month=July |pmid=8768172 |doi= |url=}}&lt;/ref&gt;<br /> ===General===<br /> *[[Diagnosis]] is considered somewhat controversial outside of the forensic pathology community.&lt;ref name=pmid18450833&gt;{{Cite journal | last1 = Stanbrook | first1 = MB. | last2 = Hébert | first2 = PC. | last3 = Kale | first3 = R. | last4 = Sibbald | first4 = B. | last5 = Flegel | first5 = K. | last6 = MacDonald | first6 = N. | title = Tasers in medicine: an irreverent call for proposals. | journal = CMAJ | volume = 178 | issue = 11 | pages = 1401-2, 1403-4 | month = May | year = 2008 | doi = 10.1503/cmaj.080592 | PMID = 18450833 |PMC = 2374865 }}&lt;/ref&gt;<br /> *The [[diagnosis]] has garnered attention in the context of electroshock weapon use, as ''Taser International'' (a manufacturer of electroshock weapons) has often ascribed the deaths involving its weapons to it - when it is alleged that their electroshock weapon caused the death.<br /> <br /> *There is no &quot;official&quot; definition for ''excited delirium''.<br /> **Most agree it includes fever.<br /> <br /> One paper defines it in relation ''neuroleptic malignant syndrome'':&lt;ref name=pmid8768172/&gt;<br /> *Fever.<br /> *Disorientation and confusion.<br /> *Increased energy/superhuman strength.<br /> <br /> Excited delirium - hypothesis:<br /> *Thought to arise in the context of severe chronic mental disorders (e.g. schizophrenia) and protracted [[cocaine]] binges.&lt;ref name=pmid9645173&gt;{{Cite journal | last1 = Pollanen | first1 = MS. | last2 = Chiasson | first2 = DA. | last3 = Cairns | first3 = JT. | last4 = Young | first4 = JG. | title = Unexpected death related to restraint for excited delirium: a retrospective study of deaths in police custody and in the community. | journal = CMAJ | volume = 158 | issue = 12 | pages = 1603-7 | month = Jun | year = 1998 | doi = | PMID = 9645173 | PMC = 1229410 | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1229410}}&lt;/ref&gt;<br /> *Thought to result from alteration of dopamine receptor density. The D2 receptor in particular, which is thought to be important in temperature regulation, is decreased in psychotic cocaine abusers.&lt;ref name=pmid8768172/&gt;<br /> <br /> =Toxicology &amp; biochemistry=<br /> ===General===<br /> Things usually collected at autopsy:<br /> #Blood in EDTA tube (genetic testing).<br /> #Urine toxicology:<br /> #*Useful to evaluate ''myoglobin''.<br /> #Vitreous:<br /> #*Biochemistry.<br /> #*Ketones.<br /> #*Urea (???).<br /> #Bile:&lt;ref&gt;{{Ref HospAuto|220}}&lt;/ref&gt;<br /> #*Acetaminophen overdoses.<br /> #*Opiate overdoses.<br /> <br /> Myoglobin DDx:<br /> *Neuroleptic malignant syndrome.<br /> *Malignant hyperthermia.<br /> *Serotonin syndrome.<br /> <br /> ===Biochemistry===<br /> *[[Diabetes mellitus]]:&lt;ref name=Ref_HospAuto221&gt;{{Ref HospAuto|221}}&lt;/ref&gt;<br /> **Plasma:<br /> ***Hemoglobin A1c - increased.<br /> ***Acetone - increased.<br /> ***Beta-hydroxybutyrate - increased.<br /> ****Also increased in alcoholic ketoacidosis (though ketones low).<br /> **Urine:<br /> ***Aceto-acetate - increased.<br /> <br /> Death by insulin overdose:&lt;ref name=Ref_HospAuto224&gt;{{Ref HospAuto|224}}&lt;/ref&gt;<br /> *C-peptide - low.<br /> *Insulin - high.<br /> <br /> ====Serum====<br /> *Potassium - rises quickly and rapidly after death; completely useless.<br /> *Sodium - tends to decrease after death; usually useless.<br /> *Glucose - drops quickly; useless unless sky high.<br /> *Urea, creatinine and urate - stable for ~48 hours post-mortem.&lt;ref name=Ref_HospAuto222&gt;{{Ref HospAuto|222}}&lt;/ref&gt;<br /> <br /> ===Vitreous===<br /> *Creatinine and urea - approximate those at time of death.&lt;ref name=Ref_HospAuto222&gt;{{Ref HospAuto|222}}&lt;/ref&gt;<br /> *Glucose - used to assess for hyperglycemia (due to [[diabetes mellitus|diabetic coma]]) in life.&lt;ref name=pmid19167848&gt;{{Cite journal | last1 = Zilg | first1 = B. | last2 = Alkass | first2 = K. | last3 = Berg | first3 = S. | last4 = Druid | first4 = H. | title = Postmortem identification of hyperglycemia. | journal = Forensic Sci Int | volume = 185 | issue = 1-3 | pages = 89-95 | month = Mar | year = 2009 | doi = 10.1016/j.forsciint.2008.12.017 | PMID = 19167848 }}&lt;/ref&gt;<br /> <br /> ===Toxicology===<br /> *Should be submitted with anatomical findings and history.<br /> <br /> Common submissions:<br /> #Alcohol only.<br /> #Suspected toxicologic death - need details on drugs.<br /> <br /> ====Mandated by case====<br /> In Ontario, the following are mandated by the case:&lt;ref&gt;{{Ref OPMfP|14}}&lt;/ref&gt;<br /> *Sudden death of child under five years old.<br /> *Workplace death.<br /> *Fatal motor vehicle collision - esp. driver.<br /> *Aviation death - esp. pilot &amp; co-pilot.<br /> *Fire-related death (carboxyhemoglobin).<br /> <br /> ===Toxins===<br /> ====Ethanol toxicity====<br /> {{Main|Ethanol abuse}}<br /> *Usually measured (in Canada) as: ''mass of EtOH (mg)/volume of blood (mL)''.<br /> **Limit (Ontario): 80 milligrams of alcohol in 100 millilitres of blood (0.08 gm/100 mL).&lt;ref&gt;URL: [http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml]. Accessed on: 28 September 2010.&lt;/ref&gt;<br /> **Enough to be fatal ~ 350 mg/dL ~= 76 mmol/L.<br /> <br /> =====Ethanol intoxication as a table&lt;ref name=southendnhs&gt;URL: [http://www.southend.nhs.uk/pathologyhandbook/clinical_chemistry/Guidelines/ethanol_poisoning.htm http://www.southend.nhs.uk/pathologyhandbook/clinical_chemistry/Guidelines/ethanol_poisoning.htm]. Accessed on: 19 October 2010.&lt;/ref&gt;===== <br /> {| class=&quot;wikitable&quot;<br /> |<br /> |Concentration<br /> |Concentration<br /> |Concentration<br /> |Concentration<br /> |-<br /> |Legal limit - Ontario&lt;ref&gt;URL: [http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml http://www.mto.gov.on.ca/english/safety/impaired/fact-sheet.shtml]. Accessed on: 28 September 2010.&lt;/ref&gt;<br /> | 80 mg/dL<br /> | ~17 mmol/L<br /> | 0.8 g/L<br /> | 0.08 g/dL<br /> |-<br /> |Mild<br /> | &lt; 180 mg/dL<br /> | &lt; 39 mmol/L<br /> | &lt; 1.8 g/L <br /> | &lt; 0.18 g/dL <br /> |-<br /> |Moderate<br /> | 180-350 mg/dL <br /> | 39-76 mmol/L<br /> | 1.8-3.5 g/L <br /> | 0.18-0.35 g/dL<br /> |-<br /> |Severe<br /> | 350-450 mg/dL <br /> | 76-98 mmol/L<br /> | 3.5-4.5 g/L <br /> | 0.35-0.45 g/dL <br /> |}<br /> <br /> Notes:<br /> *1 mg/dL = 1/4.607 mmol/L.<br /> **Ethanol's molar mass = 46.07 g/mol.<br /> <br /> ====Methanol toxicity====<br /> *Minimum lethal dose: 40 mg/dl.&lt;ref&gt;URL: [http://path.upmc.edu/cases/case242/dx.html http://path.upmc.edu/cases/case242/dx.html. Accessed on: 13 January 2012.&lt;/ref&gt;<br /> <br /> *Typically an accidental death; person consumes methanol as an ethanol substitute. <br /> *Blindness.<br /> *[[Putamen]] [[necrosis]] (bilateral).&lt;ref name=pmid16484428&gt;{{Cite journal | last1 = Blanco | first1 = M. | last2 = Casado | first2 = R. | last3 = Vázquez | first3 = F. | last4 = Pumar | first4 = JM. | title = CT and MR imaging findings in methanol intoxication. | journal = AJNR Am J Neuroradiol | volume = 27 | issue = 2 | pages = 452-4 | month = Feb | year = 2006 | doi = | PMID = 16484428 }}&lt;/ref&gt;<br /> *+/-Pancreatic injury.&lt;ref name=pmid10866330&gt;{{Cite journal | last1 = Hantson | first1 = P. | last2 = Mahieu | first2 = P. | title = Pancreatic injury following acute methanol poisoning. | journal = J Toxicol Clin Toxicol | volume = 38 | issue = 3 | pages = 297-303 | month = | year = 2000 | doi = | PMID = 10866330 }}&lt;/ref&gt;<br /> <br /> ====Cocaine toxicity====<br /> *No agreed upon toxic dose&lt;ref name=pmid15075681&gt;{{cite journal |author=Stephens BG, Jentzen JM, Karch S, Wetli CV, Mash DC |title=National Association of Medical Examiners position paper on the certification of cocaine-related deaths |journal=Am J Forensic Med Pathol |volume=25 |issue=1 |pages=11–3 |year=2004 |month=March |pmid=15075681 |doi= |url=}}&lt;/ref&gt; - due to tolerance.<br /> *Usual mechanism ''cardiac failure''.<br /> <br /> Features - heart:<br /> *Usually anatomically normal heart.<br /> **+/-Advanced [[coronary artery atherosclerosis]] for age.<br /> **+/-[[Myocardial infarction]].<br /> ***+/-Contraction band necrosis.<br /> **+/-Cardiac hypertrophy.<br /> <br /> Other:<br /> *+/-Nasal septum perforation.<br /> *+/-Track marks (other drug use).<br /> *+/-Finger burns (during preparation of crack).<br /> *+/-Drug paraphernalia, e.g. crack pipe.<br /> <br /> ====Ethylene glycol toxicity====<br /> :For a more general discussion see ''[[Crystals_in_body_fluids#Urine_crystals|urine crystals]]''<br /> *Not done in routine toxicology screening.<br /> *Birefringent calcium oxalate crystals found in kidney (with polarized light).&lt;ref name=Ref_KFP589&gt;{{Ref KFP|589}}&lt;/ref&gt;<br /> <br /> ====Anaphylaxis====<br /> *Allergic reaction, e.g. peanut allergy.<br /> <br /> Diagnosis - serology:&lt;ref name=pmid20176258&gt;{{cite journal |author=Simons FE |title=Anaphylaxis |journal=J. Allergy Clin. Immunol. |volume=125 |issue=2 Suppl 2 |pages=S161–81 |year=2010 |month=February |pmid=20176258 |doi=10.1016/j.jaci.2009.12.981 |url=}}&lt;/ref&gt;<br /> *IgE.<br /> *Tryptase.<br /> <br /> =Natural death=<br /> {{main|Natural death}}<br /> There is a lot that can kill ya... but only a few of those are quickly, i.e. within a hour or so.<br /> <br /> Generally, these things are:<br /> *Cardiovascular:<br /> **[[Cardiac arrhythmia|Arrhythmia]].<br /> **[[Myocardial infarction]].<br /> **Haemorrhage.<br /> ***Ruptured aneurysm.<br /> **[[Hypertensive heart disease]].<br /> *Respiratory:<br /> **[[Pulmonary embolism]] (PE).<br /> **[[Asthma]].<br /> *GI:<br /> **Haemorrhage.<br /> ***[[Esophageal varices]].<br /> ***Gastric varices.<br /> *Neurologic:<br /> **Intracranial haemorrhage.<br /> ***Ruptured aneurysm.<br /> ***Spontaneous [[subdural hemorrhage]].<br /> **[[Stroke]]:<br /> ***Haemorrhagic.<br /> ***Thrombotic (more common than hemorrhagic).<br /> <br /> =Forensic entomology=<br /> {{main|Forensic entomology}}<br /> *Study of the bugs that eat corpses.<br /> *Bugs may hide a wound... it is important to know where they like to be.<br /> <br /> =Forensic anthropology=<br /> {{main|Forensic anthropology}}<br /> Forensic anthropology is looking at skeletal remains. It may be useful of [[decendent identification|identification]] and, rarely, the cause of death. Important in skeletonized remains and decomp cases.<br /> <br /> =Forensic taphonomy=<br /> *The study of post-mortem decay to assist in a medicolegal investigation.<br /> **''Taphonomy'' = postmortem fate of biological remains; derived from the Greek word ''taphos'' (grave).&lt;ref&gt;{{cite journal |author=Milroy CM |title=Forensic taphonomy: the postmortem fate of human remains |journal=BMJ |volume=319 |issue=7207 |pages=458 |year=1999 |month=August |pmid=10445946 |pmc=1127062 |doi= |url=}}&lt;/ref&gt;<br /> <br /> =See also=<br /> *[[Forensic entomology]].<br /> *[[Autopsy]].<br /> *[[Heart]].<br /> <br /> =References=<br /> {{reflist|2}}<br /> <br /> =External links=<br /> *[http://cap-acp.org/forensic.cfm Forensic pathology (cap-acp.org)].<br /> *[http://neurobio.drexelmed.edu/goldmanweb/forensicanthro/trauma.pdf Fractures (drexelmed.edu)].<br /> *[http://www.forensicmed.co.uk/pathology/mechanisms-of-death/ Mechanisms of death (forensicmed.co.uk)].<br /> <br /> ==Post-mortem changes==<br /> *[http://emedicine.medscape.com/article/1680032-overview#showall Post-mortem changes (emedicine.medscape.com)].<br /> *[http://emedicine.medscape.com/article/1680107-overview#showall Autopsy of blunt force trauma (emedicine.medscape.com)].<br /> *[http://www.the-crankshaft.info/2010/07/postmortem-changes_29.html Post-mortem changes (the-crankshaft.info)].<br /> <br /> [[Category:Autopsy]]<br /> [[Category:Forensic pathology]]</div>

Tate https://librepathology.org/w/index.php?title=Transportation_related_Deaths_Questions&diff=39170 2015-08-12T13:40:55Z

<p>Tate: Created page with &quot;Death by motor vehicle collision 1. List 5 reasons autopsies are perfomed in motor vehicle deaths. 2. What are the four mechanisms of injuries in motor vehicle crashes? 3. Wh...&quot;</p> <hr /> <div>Death by motor vehicle collision<br /> <br /> 1. List 5 reasons autopsies are perfomed in motor vehicle deaths.<br /> 2. What are the four mechanisms of injuries in motor vehicle crashes?<br /> 3. What is the most common cause of fatal motor vehicle crashes in north America?<br /> 4. List the 4 categories of motor vehicle crashes.<br /> 5. List 5 injuries and briefly describe the mechanism of a driver in a front impact motor vehicle crash. <br /> 6. List 5 internal injuries of a driver in a motor vehicle crash resulting from impact with a steering column. <br /> 7. A pedestrian is killed by a person driving a sedan, list 5 differences between the injuries of an adult and a child. <br /> 8. A pedestrian is killed, list five difference between the injuries if they are hit by a sedan moving a 50km/hr vs 100km/hr.<br /> 9. A pedestrian is killed what would you expect if he were running vs walking?<br /> 10. A pedestrian is killed, his is struck while walking, his body lands on the roof of the sedan, and he then falls of onto the road on the passenger side. Describe the primary, secondary and tertiary injuries that you might expect. <br /> 11. What is the &quot;Locus minoris resistentiae&quot; if the aorta?<br /> 12. What is the most common location of the transsection of the aorta? Immediately distal to the left subclavian artery origin (peri-isthmus, at the ligamentum arteriosum)<br /> 13. Describe the cause and features of dicing injuries.<br /> 14. You have a scene with multiple unrestrained victims, describe three ways you might be able to determine who the driver of the vehicle was?<br /> 15. List 5 scenarios where air bags can cause immediate death in a motor vehicle crash. <br /> 16. What four factors determine the pattern and severity of pedestrian injuries when struck by a motor vehicle?<br /> 17. What four injuries are correlated with impact velocity?<br /> 18. In what circumstances is a child likely be thrown forward when struck by a vehicle?<br /> 19. What is a bumper fracture?<br /> 20. There are no fractures seen in a pedestrian victim of a motor vehicle collision, what should you now look for in the lower limbs and how?<br /> 21. Describe the mechanism by which striae are formed on pedestrian victims of motor vehicle collisons.<br /> 22. Describe 4 routes by which the abdominal contents may exit the abdominal cavity during a motor vehicle crash.</div>

Tate https://librepathology.org/w/index.php?title=Asphyxia_Questions&diff=39169 2015-08-12T13:33:59Z

<p>Tate: </p> <hr /> <div>[[Asphyxia]]<br /> 1. Explain how visceral congestions occurs in asphyxia deaths.<br /> 2. Under what circumstances might one expect to find petechiae of the conjunctiva and sclera?<br /> 3. When petechaie become larger or confluent they are called ecchymoses, describe a circumstance where you might expect this to occur.<br /> 4. What are three categories of asphyxia death.<br /> 5. List 7 general forms of suffocation and give an example of each. <br /> a. Entrapment<br /> b. Environmental suffocation<br /> c. Smothering<br /> d. Choking<br /> e. Mechanical asphyxia (traumatic/positional/riot crush)<br /> f. Traumatic with smothering (overlay/ Burking)<br /> g. Suffocating gases (methane, CO2)<br /> 6. List and describe three forms of strangulation<br /> a. Hanging<br /> b. Ligature strangulation<br /> c. Manual strangulation<br /> 7. Jugular veins 4.4llbs, carotid artery compression occurs at 11lbs, the trachea 33lbs, vertebral arteries 66lb; describe how any of this makes sense and matters… List 4 circumstances when you would expect to find fractures of the cervical spine in a hanging?<br /> 8. Describe the features of a typical suicidal hanging furrow?<br /> 9. List five features consistent with manual strangulation. <br /> 10. List three chemical asphyxiants and three suffocating gases and explain the difference between a suffocating gas and a chemical asphyxiant.<br /> 11. Describe 5 features of sexual asphyxiation. <br /> 12. Describe 5 features of crucifixion and explain the mechanisms leading to death. <br /> 13. Describe the differences between a choke hold and a carotid hold used by law enforcement personnel. <br /> 14.</div>

Tate https://librepathology.org/w/index.php?title=Asphyxia_Questions&diff=39168 2015-08-12T13:33:37Z

<p>Tate: Created page with &quot;Asphyxia 1. Explain how visceral congestions occurs in asphyxia deaths. 2. Under what circumstances might one expect to find petechiae of the conjunctiva and sclera? 3. When p...&quot;</p> <hr /> <div>Asphyxia<br /> 1. Explain how visceral congestions occurs in asphyxia deaths.<br /> 2. Under what circumstances might one expect to find petechiae of the conjunctiva and sclera?<br /> 3. When petechaie become larger or confluent they are called ecchymoses, describe a circumstance where you might expect this to occur.<br /> 4. What are three categories of asphyxia death.<br /> 5. List 7 general forms of suffocation and give an example of each. <br /> a. Entrapment<br /> b. Environmental suffocation<br /> c. Smothering<br /> d. Choking<br /> e. Mechanical asphyxia (traumatic/positional/riot crush)<br /> f. Traumatic with smothering (overlay/ Burking)<br /> g. Suffocating gases (methane, CO2)<br /> 6. List and describe three forms of strangulation<br /> a. Hanging<br /> b. Ligature strangulation<br /> c. Manual strangulation<br /> 7. Jugular veins 4.4llbs, carotid artery compression occurs at 11lbs, the trachea 33lbs, vertebral arteries 66lb; describe how any of this makes sense and matters… List 4 circumstances when you would expect to find fractures of the cervical spine in a hanging?<br /> 8. Describe the features of a typical suicidal hanging furrow?<br /> 9. List five features consistent with manual strangulation. <br /> 10. List three chemical asphyxiants and three suffocating gases and explain the difference between a suffocating gas and a chemical asphyxiant.<br /> 11. Describe 5 features of sexual asphyxiation. <br /> 12. Describe 5 features of crucifixion and explain the mechanisms leading to death. <br /> 13. Describe the differences between a choke hold and a carotid hold used by law enforcement personnel. <br /> 14.</div>

Tate https://librepathology.org/w/index.php?title=Forensic_Pathology&diff=39167 2015-08-12T13:33:30Z

<p>Tate: </p> <hr /> <div>===[[Transportation related Deaths Questions]]===<br /> ===[[Asphyxia Questions]]===</div>

Tate https://librepathology.org/w/index.php?title=Transportation_related_Deaths&diff=39166 2015-08-12T13:32:37Z

<p>Tate: Created page with &quot;1. List 5 reasons autopsies are perfomed in motor vehicle deaths. 2. What are the four mechanisms of injuries in motor vehicle crashes? 3. What is the most common cause of fat...&quot;</p> <hr /> <div>1. List 5 reasons autopsies are perfomed in motor vehicle deaths.<br /> 2. What are the four mechanisms of injuries in motor vehicle crashes?<br /> 3. What is the most common cause of fatal motor vehicle crashes in north America?<br /> 4. List the 4 categories of motor vehicle crashes.<br /> 5. List 5 injuries and briefly describe the mechanism of a driver in a front impact motor vehicle crash. <br /> 6. List 5 internal injuries of a driver in a motor vehicle crash resulting from impact with a steering column. <br /> 7. A pedestrian is killed by a person driving a sedan, list 5 differences between the injuries of an adult and a child. <br /> 8. A pedestrian is killed, list five difference between the injuries if they are hit by a sedan moving a 50km/hr vs 100km/hr.<br /> 9. A pedestrian is killed what would you expect if he were running vs walking?<br /> 10. A pedestrian is killed, his is struck while walking, his body lands on the roof of the sedan, and he then falls of onto the road on the passenger side. Describe the primary, secondary and tertiary injuries that you might expect. <br /> 11. What is the &quot;Locus minoris resistentiae&quot; if the aorta?<br /> 12. What is the most common location of the transsection of the aorta? Immediately distal to the left subclavian artery origin (peri-isthmus, at the ligamentum arteriosum)<br /> 13. Describe the cause and features of dicing injuries.<br /> 14. You have a scene with multiple unrestrained victims, describe three ways you might be able to determine who the driver of the vehicle was?<br /> 15. List 5 scenarios where air bags can cause immediate death in a motor vehicle crash. <br /> 16. What four factors determine the pattern and severity of pedestrian injuries when struck by a motor vehicle?<br /> 17. What four injuries are correlated with impact velocity?<br /> 18. In what circumstances is a child likely be thrown forward when struck by a vehicle?<br /> 19. What is a bumper fracture?<br /> 20. There are no fractures seen in a pedestrian victim of a motor vehicle collision, what should you now look for in the lower limbs and how?<br /> 21. Describe the mechanism by which striae are formed on pedestrian victims of motor vehicle collisons.<br /> 22. Describe 4 routes by which the abdominal contents may exit the abdominal cavity during a motor vehicle crash.</div>

Tate https://librepathology.org/w/index.php?title=Forensic_Pathology&diff=39165 2015-08-12T13:32:24Z

<p>Tate: Created page with &quot;===Transportation related Deaths=== ===Asphyxia===&quot;</p> <hr /> <div>===[[Transportation related Deaths]]===<br /> ===[[Asphyxia]]===</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39164 2015-08-12T13:31:16Z

<p>Tate: </p> <hr /> <div>===[[Forensic Pathology]]===<br /> <br /> ===[[Molecular Pathology Rotation Notes]]===<br /> <br /> ===[[Robbins and Cotran 9th Edition Questions]]===<br /> <br /> ===[[Cytogenetics Review Questions]]===<br /> <br /> <br /> === [[Molecular Genetic Diagnosis]]===<br /> <br /> ===[[CAP Molecular Diagnosis of Lung Cancer]]===<br /> <br /> ===[[CAP Molecular Diagnosis of AML]]===<br /> <br /> ===[[CAP Breast Cancer and Molecular]]===</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39163 2015-08-12T13:31:03Z

<p>Tate: </p> <hr /> <div>===[[Forensic Pathology]]==<br /> <br /> ===[[Molecular Pathology Rotation Notes]]===<br /> <br /> ===[[Robbins and Cotran 9th Edition Questions]]===<br /> <br /> ===[[Cytogenetics Review Questions]]===<br /> <br /> <br /> === [[Molecular Genetic Diagnosis]]===<br /> <br /> ===[[CAP Molecular Diagnosis of Lung Cancer]]===<br /> <br /> ===[[CAP Molecular Diagnosis of AML]]===<br /> <br /> ===[[CAP Breast Cancer and Molecular]]===</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39162 2015-08-12T13:30:31Z

<p>Tate: </p> <hr /> <div><br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ===[[Molecular Pathology Rotation Notes]]===<br /> <br /> ===[[Robbins and Cotran 9th Edition Questions]]===<br /> <br /> ===[[Cytogenetics Review Questions]]===<br /> <br /> <br /> === [[Molecular Genetic Diagnosis]]===<br /> <br /> ===[[CAP Molecular Diagnosis of Lung Cancer]]===<br /> <br /> ===[[CAP Molecular Diagnosis of AML]]===<br /> <br /> ===[[CAP Breast Cancer and Molecular]]===</div>

Tate https://librepathology.org/w/index.php?title=Libre_Pathology_talk:Study_Group&diff=39161 2015-08-12T13:29:46Z

<p>Tate: </p> <hr /> <div>==Michael's thoughts on the exam==<br /> *I wrote it and passed it in 2012. I also did the American exam the same year and passed that.<br /> *The pass rate for the FRCPC exam is pretty high.<br /> **2009-2011 it was 96+/-3.9% for Canadian medical school grads on their first attempt.<br /> <br /> ===Written===<br /> *I though it was picking at details. Some things are very relevant to practise... other less so.<br /> **The pocketbook version of [[Robbins]] covers most of it.<br /> <br /> ===Practical (slide) exam===<br /> *You should know the answer almost immediately.<br /> **If you don't know, write something down and move on.<br /> *It is set to broadly cover everything.<br /> *If it isn't a [[spot diagnosis]]... it should not be on.<br /> *Somethings are PGY2/PGY3 stuff. One should not overthink things.<br /> *Anecdotally, the first impression is usually the right one.<br /> **I think one should stick with the first impression. <br /> <br /> ===Gross exam===<br /> *Go with the most probable if you're uncertain.<br /> *I worked through the ''Atlas of Gross Pathology with Histologic Correlation'' (see [[Pathology books]] for the reference).<br /> **I am not sure this is necessary... but I thought it was useful.<br /> *Flickr.com/Google images has a lot to offer in this respect.<br /> *[[Gross spot diagnosis]].<br /> <br /> ===Forensic exam===<br /> *I thought this was tricky... and I liked forensics.<br /> *Residents that took the exam prior to me said the same.<br /> <br /> ===Cytology exam===<br /> *Some of the cases have several images.<br /> *I remember being confused... the first three images were from one case. I remember thinking... I have the same diagnosis three times.<br /> *Like the forensics and gross sections - this section isn't too long. From an exam strategy point-of-view, this makes it less likely that a diagnosis is repeated.<br /> <br /> ===Oral exam===<br /> *I think this is to test if you are safe and useful.<br /> **By &quot;safe&quot; I mean: knowing your limits and consulting with a colleague when appropriate.<br /> **By &quot;useful&quot; I mean: you don't need to consult on everything.<br /> *The examiners ask a pre-determined list of questions.<br /> **Questions may depend on one another and, in fairness, they are told to redirect you.<br /> ***Example: You see a lung biopsy with hyaline material... and you go down the fibrosis route-- but it is really amyloidosis.<br /> ****The examiners will say something like &quot;how would one work-up suspected amyloid?&quot; or &quot;lets assume this is amyloid...&quot;<br /> *If you're a Canadian resident, you cannot be examined by someone within your residency program.<br /> *As far as I know, examiners are told to be stone-faced, i.e. show no emotion.<br /> *Some of the cases were very straight forward.<br /> *I didn't think anything was really exotic.<br /> <br /> [[User:Michael|Michael]] ([[User talk:Michael|talk]]) 23:43, 25 October 2014 (EDT)<br /> <br /> = [[Short answer questions submitted by Tate]]=</div>

Tate https://librepathology.org/w/index.php?title=CAP_Breast_Cancer_and_Molecular&diff=39160 2015-08-12T13:29:02Z

<p>Tate: Created page with &quot; {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}...&quot;</p> <hr /> <div><br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39159 2015-08-12T13:28:52Z

<p>Tate: </p> <hr /> <div><br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == [[Molecular Genetic Diagnosis]]==<br /> <br /> ==[[CAP Molecular Diagnosis of Lung Cancer]]==<br /> <br /> ==[[CAP Molecular Diagnosis of AML]]==<br /> <br /> ==[[CAP Breast Cancer and Molecular]]==</div>

Tate https://librepathology.org/w/index.php?title=CAP_Molecular_Diagnosis_of_AML&diff=39158 2015-08-12T13:28:10Z

<p>Tate: Created page with &quot; {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}} {{hidden|...&quot;</p> <hr /> <div><br /> {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}}<br /> <br /> {{hidden|List the 5 main categories of classification of Acute Myeloid Leukemia|1. AML with recurrent genetic abnormalities, 2. AML with myelodysplasia-related changes, 3. Therapy related myeloid neoplasms, 4. AML, NOS, 5. Myeloid sarcoma}}<br /> <br /> {{hidden|Give any three translocations identified in AML.|t(8,21), inv (16), t(15,17), t(9,11), t(6,9), inv(3), t(1,22), mutated NPM1, mutated CEBPA}}<br /> <br /> {{hidden|What entities are fall under the AML, NOS classification?|AML with minimal differentiation, AML without maturation, AML with maturation, Acute myelomonocytic leukemia, Acute monoblastic/monocytic leukemia, Acute erythroid leukemias (pure erythroid, erythroleukemia, erythroid/myeloid), Acute Megakaryoblastic leukemia, Acute basophilic leukemia, Acte panmyelosis with myelofibrosis}}<br /> <br /> {{hidden|List 2 genes which confer a poor prognostic impact vs 2 which confer a good prognostic impact.|Poor: KIT, FLT3, Good: NPM1, CEBPA}}</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39157 2015-08-12T13:28:04Z

<p>Tate: </p> <hr /> <div><br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == [[Molecular Genetic Diagnosis]]==<br /> <br /> <br /> <br /> ==[[CAP Molecular Diagnosis of Lung Cancer]]==<br /> <br /> ==[[CAP Molecular Diagnosis of AML]]==<br /> <br /> === CAP Breast Cancer and Molecular ===<br /> <br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=CAP_Molecular_Diagnosis_of_Lung_Cancer&diff=39156 2015-08-12T13:27:38Z

<p>Tate: Created page with &quot; {{hidden|List 5 treatment defining molecular transformation, the neoplasm, and the genetic alteration|1. 100% of CML: BRR-ABL &gt; Imatinib, 2. 20% of Lung Adenocarcinoma: EGFR...&quot;</p> <hr /> <div><br /> {{hidden|List 5 treatment defining molecular transformation, the neoplasm, and the genetic alteration|1. 100% of CML: BRR-ABL &gt; Imatinib, 2. 20% of Lung Adenocarcinoma: EGFR &gt; Erlotinib/Gefitinib, 3. 25% Infiltrative ductal carcinoma of breast HER2&gt;Trastuzumab, 4. 50% of Melanoma, BRAF v600E &gt; PLX4032, 5. 4% of Lung Adenocarcinoma: ALK &gt; Crizotinib}}<br /> <br /> {{hidden|List and describe 5 areas of Genetic characaterization of tumours for personalized medicine|DNA mutations, DNA chromosomal alterations, mRNA and MiRNA profiling, Proteomics, DNA epigenetics}}<br /> <br /> {{hidden|What fraction of Lung adenocarcinomas have no known detactable mutations|42%}}<br /> <br /> {{hidden|What are the three most common molecular alterations of Lung Adenocarcinoma|KRAS 23%, EGFR 15%, TP53 5%}}<br /> <br /> {{hidden|What is the two most common molecular alteration makes patients with EGFR mutations resistant to targetted therapies?|KRAS (primary) and T790M (primary and acquired)}}<br /> <br /> {{hidden|List two EGFR kinase inhibitors.|Gefitinib/Iressa, Erlotinib/Tarceva}}<br /> <br /> {{hidden|What are the three most common cancers associated with KRAS mutations?|Pancreatic 90%, Colon 50%, Lung NSCLC 30%}}<br /> <br /> {{hidden|Why don't KRAS + tumours respond to Anti EGFR therapies?|KRAS is downstream from EGFR, so changing the function of EFGR would not have any effect on mutated KRAS}}<br /> <br /> {{hidden|Explain the cost effectiveness of genetic testing for targetted therapies?|Most molecular tests cost $200-1000, vs one month of targetted therapy $2000-10000/month}}<br /> <br /> {{hidden|What are the three most common cancers associated with BRAF mutations?|Melanoma 70%, Papillary Thyroid Carcinoma 50%, Ovarian serious carcinoma 30%, Colon cancer 10%, Hint Papillary architecture}}<br /> <br /> {{hidden|Beta catenin/CTNNB1 expression is found with which histological pattern of lung adenocarcinoma?|Low grade adenocarcinoma of fetal type, poor px, &lt;40yo, and has glycogen rich glandular formations, may occur in FAP patients}}<br /> <br /> {{hidden|What is the most common ALK rearrangement found in NSCLC?|EML4-ALK (90% of the 13% of lung cancers found to due to ALK fusions)}}<br /> <br /> {{hidden|List some pros and cons of ALK FISH.|Pros: commercial FDA approved probes available, not too expensive, moderately easy to disseminate screening, clinically validated, and failed tests on poorly preserved tissues are not reported as negative. Cons: need fish lab expertise (including pathologist and PhD), can be tricky if genes are close}}<br /> <br /> {{hidden|List some pros and cons of ALK IHC.|Pros: fast, cheap, easy to disseminate screening, Cons: commercial antibodies sub-optimal, poorly preserved tissues (esp bx) may give false negative results due to loss of antigenicity, no internal control}}<br /> <br /> {{hidden|What is a positive count in the ALK-FISH?|Signal split &gt;2 probe diameters}}</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39155 2015-08-12T13:27:31Z

<p>Tate: </p> <hr /> <div><br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == [[Molecular Genetic Diagnosis]]==<br /> <br /> <br /> <br /> ==[[CAP Molecular Diagnosis of Lung Cancer]]==<br /> <br /> ===CAP Molecular Diagnosis of AML===<br /> <br /> {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}}<br /> <br /> {{hidden|List the 5 main categories of classification of Acute Myeloid Leukemia|1. AML with recurrent genetic abnormalities, 2. AML with myelodysplasia-related changes, 3. Therapy related myeloid neoplasms, 4. AML, NOS, 5. Myeloid sarcoma}}<br /> <br /> {{hidden|Give any three translocations identified in AML.|t(8,21), inv (16), t(15,17), t(9,11), t(6,9), inv(3), t(1,22), mutated NPM1, mutated CEBPA}}<br /> <br /> {{hidden|What entities are fall under the AML, NOS classification?|AML with minimal differentiation, AML without maturation, AML with maturation, Acute myelomonocytic leukemia, Acute monoblastic/monocytic leukemia, Acute erythroid leukemias (pure erythroid, erythroleukemia, erythroid/myeloid), Acute Megakaryoblastic leukemia, Acute basophilic leukemia, Acte panmyelosis with myelofibrosis}}<br /> <br /> {{hidden|List 2 genes which confer a poor prognostic impact vs 2 which confer a good prognostic impact.|Poor: KIT, FLT3, Good: NPM1, CEBPA}}<br /> <br /> <br /> === CAP Breast Cancer and Molecular ===<br /> <br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=Molecular_Genetic_Diagnosis&diff=39154 2015-08-12T13:26:59Z

<p>Tate: Created page with &quot;{{hidden|List three basic molecular diagnostic techniques|a. Karyotyping, b. Southern blot, c. Sanger DNA sequencing, d. Polymerase chain reaction}}&quot;</p> <hr /> <div>{{hidden|List three basic molecular diagnostic techniques|a. Karyotyping, b. Southern blot, c. Sanger DNA sequencing, d. Polymerase chain reaction}}</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39153 2015-08-12T13:26:52Z

<p>Tate: </p> <hr /> <div><br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == [[Molecular Genetic Diagnosis]]==<br /> <br /> <br /> <br /> ===CAP Molecular Diagnosis of Lung Cancer===<br /> <br /> {{hidden|List 5 treatment defining molecular transformation, the neoplasm, and the genetic alteration|1. 100% of CML: BRR-ABL &gt; Imatinib, 2. 20% of Lung Adenocarcinoma: EGFR &gt; Erlotinib/Gefitinib, 3. 25% Infiltrative ductal carcinoma of breast HER2&gt;Trastuzumab, 4. 50% of Melanoma, BRAF v600E &gt; PLX4032, 5. 4% of Lung Adenocarcinoma: ALK &gt; Crizotinib}}<br /> <br /> {{hidden|List and describe 5 areas of Genetic characaterization of tumours for personalized medicine|DNA mutations, DNA chromosomal alterations, mRNA and MiRNA profiling, Proteomics, DNA epigenetics}}<br /> <br /> {{hidden|What fraction of Lung adenocarcinomas have no known detactable mutations|42%}}<br /> <br /> {{hidden|What are the three most common molecular alterations of Lung Adenocarcinoma|KRAS 23%, EGFR 15%, TP53 5%}}<br /> <br /> {{hidden|What is the two most common molecular alteration makes patients with EGFR mutations resistant to targetted therapies?|KRAS (primary) and T790M (primary and acquired)}}<br /> <br /> {{hidden|List two EGFR kinase inhibitors.|Gefitinib/Iressa, Erlotinib/Tarceva}}<br /> <br /> {{hidden|What are the three most common cancers associated with KRAS mutations?|Pancreatic 90%, Colon 50%, Lung NSCLC 30%}}<br /> <br /> {{hidden|Why don't KRAS + tumours respond to Anti EGFR therapies?|KRAS is downstream from EGFR, so changing the function of EFGR would not have any effect on mutated KRAS}}<br /> <br /> {{hidden|Explain the cost effectiveness of genetic testing for targetted therapies?|Most molecular tests cost $200-1000, vs one month of targetted therapy $2000-10000/month}}<br /> <br /> {{hidden|What are the three most common cancers associated with BRAF mutations?|Melanoma 70%, Papillary Thyroid Carcinoma 50%, Ovarian serious carcinoma 30%, Colon cancer 10%, Hint Papillary architecture}}<br /> <br /> {{hidden|Beta catenin/CTNNB1 expression is found with which histological pattern of lung adenocarcinoma?|Low grade adenocarcinoma of fetal type, poor px, &lt;40yo, and has glycogen rich glandular formations, may occur in FAP patients}}<br /> <br /> {{hidden|What is the most common ALK rearrangement found in NSCLC?|EML4-ALK (90% of the 13% of lung cancers found to due to ALK fusions)}}<br /> <br /> {{hidden|List some pros and cons of ALK FISH.|Pros: commercial FDA approved probes available, not too expensive, moderately easy to disseminate screening, clinically validated, and failed tests on poorly preserved tissues are not reported as negative. Cons: need fish lab expertise (including pathologist and PhD), can be tricky if genes are close}}<br /> <br /> {{hidden|List some pros and cons of ALK IHC.|Pros: fast, cheap, easy to disseminate screening, Cons: commercial antibodies sub-optimal, poorly preserved tissues (esp bx) may give false negative results due to loss of antigenicity, no internal control}}<br /> <br /> {{hidden|What is a positive count in the ALK-FISH?|Signal split &gt;2 probe diameters}}<br /> <br /> ===CAP Molecular Diagnosis of AML===<br /> <br /> {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}}<br /> <br /> {{hidden|List the 5 main categories of classification of Acute Myeloid Leukemia|1. AML with recurrent genetic abnormalities, 2. AML with myelodysplasia-related changes, 3. Therapy related myeloid neoplasms, 4. AML, NOS, 5. Myeloid sarcoma}}<br /> <br /> {{hidden|Give any three translocations identified in AML.|t(8,21), inv (16), t(15,17), t(9,11), t(6,9), inv(3), t(1,22), mutated NPM1, mutated CEBPA}}<br /> <br /> {{hidden|What entities are fall under the AML, NOS classification?|AML with minimal differentiation, AML without maturation, AML with maturation, Acute myelomonocytic leukemia, Acute monoblastic/monocytic leukemia, Acute erythroid leukemias (pure erythroid, erythroleukemia, erythroid/myeloid), Acute Megakaryoblastic leukemia, Acute basophilic leukemia, Acte panmyelosis with myelofibrosis}}<br /> <br /> {{hidden|List 2 genes which confer a poor prognostic impact vs 2 which confer a good prognostic impact.|Poor: KIT, FLT3, Good: NPM1, CEBPA}}<br /> <br /> <br /> === CAP Breast Cancer and Molecular ===<br /> <br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=Short_answer_questions_submitted_by_Tate&diff=39152 2015-08-12T13:26:22Z

<p>Tate: Created page with &quot; == Short answer questions on genetics and molecular pathology. == These are some questions I came up with that are plausible to me... let me know if they are out to lunch....&quot;</p> <hr /> <div><br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == Molecular Genetic Diagnosis==<br /> {{hidden|List three basic molecular diagnostic techniques|a. Karyotyping, b. Southern blot, c. Sanger DNA sequencing, d. Polymerase chain reaction}}<br /> <br /> <br /> ===CAP Molecular Diagnosis of Lung Cancer===<br /> <br /> {{hidden|List 5 treatment defining molecular transformation, the neoplasm, and the genetic alteration|1. 100% of CML: BRR-ABL &gt; Imatinib, 2. 20% of Lung Adenocarcinoma: EGFR &gt; Erlotinib/Gefitinib, 3. 25% Infiltrative ductal carcinoma of breast HER2&gt;Trastuzumab, 4. 50% of Melanoma, BRAF v600E &gt; PLX4032, 5. 4% of Lung Adenocarcinoma: ALK &gt; Crizotinib}}<br /> <br /> {{hidden|List and describe 5 areas of Genetic characaterization of tumours for personalized medicine|DNA mutations, DNA chromosomal alterations, mRNA and MiRNA profiling, Proteomics, DNA epigenetics}}<br /> <br /> {{hidden|What fraction of Lung adenocarcinomas have no known detactable mutations|42%}}<br /> <br /> {{hidden|What are the three most common molecular alterations of Lung Adenocarcinoma|KRAS 23%, EGFR 15%, TP53 5%}}<br /> <br /> {{hidden|What is the two most common molecular alteration makes patients with EGFR mutations resistant to targetted therapies?|KRAS (primary) and T790M (primary and acquired)}}<br /> <br /> {{hidden|List two EGFR kinase inhibitors.|Gefitinib/Iressa, Erlotinib/Tarceva}}<br /> <br /> {{hidden|What are the three most common cancers associated with KRAS mutations?|Pancreatic 90%, Colon 50%, Lung NSCLC 30%}}<br /> <br /> {{hidden|Why don't KRAS + tumours respond to Anti EGFR therapies?|KRAS is downstream from EGFR, so changing the function of EFGR would not have any effect on mutated KRAS}}<br /> <br /> {{hidden|Explain the cost effectiveness of genetic testing for targetted therapies?|Most molecular tests cost $200-1000, vs one month of targetted therapy $2000-10000/month}}<br /> <br /> {{hidden|What are the three most common cancers associated with BRAF mutations?|Melanoma 70%, Papillary Thyroid Carcinoma 50%, Ovarian serious carcinoma 30%, Colon cancer 10%, Hint Papillary architecture}}<br /> <br /> {{hidden|Beta catenin/CTNNB1 expression is found with which histological pattern of lung adenocarcinoma?|Low grade adenocarcinoma of fetal type, poor px, &lt;40yo, and has glycogen rich glandular formations, may occur in FAP patients}}<br /> <br /> {{hidden|What is the most common ALK rearrangement found in NSCLC?|EML4-ALK (90% of the 13% of lung cancers found to due to ALK fusions)}}<br /> <br /> {{hidden|List some pros and cons of ALK FISH.|Pros: commercial FDA approved probes available, not too expensive, moderately easy to disseminate screening, clinically validated, and failed tests on poorly preserved tissues are not reported as negative. Cons: need fish lab expertise (including pathologist and PhD), can be tricky if genes are close}}<br /> <br /> {{hidden|List some pros and cons of ALK IHC.|Pros: fast, cheap, easy to disseminate screening, Cons: commercial antibodies sub-optimal, poorly preserved tissues (esp bx) may give false negative results due to loss of antigenicity, no internal control}}<br /> <br /> {{hidden|What is a positive count in the ALK-FISH?|Signal split &gt;2 probe diameters}}<br /> <br /> ===CAP Molecular Diagnosis of AML===<br /> <br /> {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}}<br /> <br /> {{hidden|List the 5 main categories of classification of Acute Myeloid Leukemia|1. AML with recurrent genetic abnormalities, 2. AML with myelodysplasia-related changes, 3. Therapy related myeloid neoplasms, 4. AML, NOS, 5. Myeloid sarcoma}}<br /> <br /> {{hidden|Give any three translocations identified in AML.|t(8,21), inv (16), t(15,17), t(9,11), t(6,9), inv(3), t(1,22), mutated NPM1, mutated CEBPA}}<br /> <br /> {{hidden|What entities are fall under the AML, NOS classification?|AML with minimal differentiation, AML without maturation, AML with maturation, Acute myelomonocytic leukemia, Acute monoblastic/monocytic leukemia, Acute erythroid leukemias (pure erythroid, erythroleukemia, erythroid/myeloid), Acute Megakaryoblastic leukemia, Acute basophilic leukemia, Acte panmyelosis with myelofibrosis}}<br /> <br /> {{hidden|List 2 genes which confer a poor prognostic impact vs 2 which confer a good prognostic impact.|Poor: KIT, FLT3, Good: NPM1, CEBPA}}<br /> <br /> <br /> === CAP Breast Cancer and Molecular ===<br /> <br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=Libre_Pathology_talk:Study_Group&diff=39151 2015-08-12T13:25:20Z

<p>Tate: </p> <hr /> <div>==Michael's thoughts on the exam==<br /> *I wrote it and passed it in 2012. I also did the American exam the same year and passed that.<br /> *The pass rate for the FRCPC exam is pretty high.<br /> **2009-2011 it was 96+/-3.9% for Canadian medical school grads on their first attempt.<br /> <br /> ===Written===<br /> *I though it was picking at details. Some things are very relevant to practise... other less so.<br /> **The pocketbook version of [[Robbins]] covers most of it.<br /> <br /> ===Practical (slide) exam===<br /> *You should know the answer almost immediately.<br /> **If you don't know, write something down and move on.<br /> *It is set to broadly cover everything.<br /> *If it isn't a [[spot diagnosis]]... it should not be on.<br /> *Somethings are PGY2/PGY3 stuff. One should not overthink things.<br /> *Anecdotally, the first impression is usually the right one.<br /> **I think one should stick with the first impression. <br /> <br /> ===Gross exam===<br /> *Go with the most probable if you're uncertain.<br /> *I worked through the ''Atlas of Gross Pathology with Histologic Correlation'' (see [[Pathology books]] for the reference).<br /> **I am not sure this is necessary... but I thought it was useful.<br /> *Flickr.com/Google images has a lot to offer in this respect.<br /> *[[Gross spot diagnosis]].<br /> <br /> ===Forensic exam===<br /> *I thought this was tricky... and I liked forensics.<br /> *Residents that took the exam prior to me said the same.<br /> <br /> ===Cytology exam===<br /> *Some of the cases have several images.<br /> *I remember being confused... the first three images were from one case. I remember thinking... I have the same diagnosis three times.<br /> *Like the forensics and gross sections - this section isn't too long. From an exam strategy point-of-view, this makes it less likely that a diagnosis is repeated.<br /> <br /> ===Oral exam===<br /> *I think this is to test if you are safe and useful.<br /> **By &quot;safe&quot; I mean: knowing your limits and consulting with a colleague when appropriate.<br /> **By &quot;useful&quot; I mean: you don't need to consult on everything.<br /> *The examiners ask a pre-determined list of questions.<br /> **Questions may depend on one another and, in fairness, they are told to redirect you.<br /> ***Example: You see a lung biopsy with hyaline material... and you go down the fibrosis route-- but it is really amyloidosis.<br /> ****The examiners will say something like &quot;how would one work-up suspected amyloid?&quot; or &quot;lets assume this is amyloid...&quot;<br /> *If you're a Canadian resident, you cannot be examined by someone within your residency program.<br /> *As far as I know, examiners are told to be stone-faced, i.e. show no emotion.<br /> *Some of the cases were very straight forward.<br /> *I didn't think anything was really exotic.<br /> <br /> [[User:Michael|Michael]] ([[User talk:Michael|talk]]) 23:43, 25 October 2014 (EDT)<br /> <br /> = [[Short answer questions submitted by Tate]]=<br /> <br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == Molecular Genetic Diagnosis==<br /> {{hidden|List three basic molecular diagnostic techniques|a. Karyotyping, b. Southern blot, c. Sanger DNA sequencing, d. Polymerase chain reaction}}<br /> <br /> <br /> ===CAP Molecular Diagnosis of Lung Cancer===<br /> <br /> {{hidden|List 5 treatment defining molecular transformation, the neoplasm, and the genetic alteration|1. 100% of CML: BRR-ABL &gt; Imatinib, 2. 20% of Lung Adenocarcinoma: EGFR &gt; Erlotinib/Gefitinib, 3. 25% Infiltrative ductal carcinoma of breast HER2&gt;Trastuzumab, 4. 50% of Melanoma, BRAF v600E &gt; PLX4032, 5. 4% of Lung Adenocarcinoma: ALK &gt; Crizotinib}}<br /> <br /> {{hidden|List and describe 5 areas of Genetic characaterization of tumours for personalized medicine|DNA mutations, DNA chromosomal alterations, mRNA and MiRNA profiling, Proteomics, DNA epigenetics}}<br /> <br /> {{hidden|What fraction of Lung adenocarcinomas have no known detactable mutations|42%}}<br /> <br /> {{hidden|What are the three most common molecular alterations of Lung Adenocarcinoma|KRAS 23%, EGFR 15%, TP53 5%}}<br /> <br /> {{hidden|What is the two most common molecular alteration makes patients with EGFR mutations resistant to targetted therapies?|KRAS (primary) and T790M (primary and acquired)}}<br /> <br /> {{hidden|List two EGFR kinase inhibitors.|Gefitinib/Iressa, Erlotinib/Tarceva}}<br /> <br /> {{hidden|What are the three most common cancers associated with KRAS mutations?|Pancreatic 90%, Colon 50%, Lung NSCLC 30%}}<br /> <br /> {{hidden|Why don't KRAS + tumours respond to Anti EGFR therapies?|KRAS is downstream from EGFR, so changing the function of EFGR would not have any effect on mutated KRAS}}<br /> <br /> {{hidden|Explain the cost effectiveness of genetic testing for targetted therapies?|Most molecular tests cost $200-1000, vs one month of targetted therapy $2000-10000/month}}<br /> <br /> {{hidden|What are the three most common cancers associated with BRAF mutations?|Melanoma 70%, Papillary Thyroid Carcinoma 50%, Ovarian serious carcinoma 30%, Colon cancer 10%, Hint Papillary architecture}}<br /> <br /> {{hidden|Beta catenin/CTNNB1 expression is found with which histological pattern of lung adenocarcinoma?|Low grade adenocarcinoma of fetal type, poor px, &lt;40yo, and has glycogen rich glandular formations, may occur in FAP patients}}<br /> <br /> {{hidden|What is the most common ALK rearrangement found in NSCLC?|EML4-ALK (90% of the 13% of lung cancers found to due to ALK fusions)}}<br /> <br /> {{hidden|List some pros and cons of ALK FISH.|Pros: commercial FDA approved probes available, not too expensive, moderately easy to disseminate screening, clinically validated, and failed tests on poorly preserved tissues are not reported as negative. Cons: need fish lab expertise (including pathologist and PhD), can be tricky if genes are close}}<br /> <br /> {{hidden|List some pros and cons of ALK IHC.|Pros: fast, cheap, easy to disseminate screening, Cons: commercial antibodies sub-optimal, poorly preserved tissues (esp bx) may give false negative results due to loss of antigenicity, no internal control}}<br /> <br /> {{hidden|What is a positive count in the ALK-FISH?|Signal split &gt;2 probe diameters}}<br /> <br /> ===CAP Molecular Diagnosis of AML===<br /> <br /> {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}}<br /> <br /> {{hidden|List the 5 main categories of classification of Acute Myeloid Leukemia|1. AML with recurrent genetic abnormalities, 2. AML with myelodysplasia-related changes, 3. Therapy related myeloid neoplasms, 4. AML, NOS, 5. Myeloid sarcoma}}<br /> <br /> {{hidden|Give any three translocations identified in AML.|t(8,21), inv (16), t(15,17), t(9,11), t(6,9), inv(3), t(1,22), mutated NPM1, mutated CEBPA}}<br /> <br /> {{hidden|What entities are fall under the AML, NOS classification?|AML with minimal differentiation, AML without maturation, AML with maturation, Acute myelomonocytic leukemia, Acute monoblastic/monocytic leukemia, Acute erythroid leukemias (pure erythroid, erythroleukemia, erythroid/myeloid), Acute Megakaryoblastic leukemia, Acute basophilic leukemia, Acte panmyelosis with myelofibrosis}}<br /> <br /> {{hidden|List 2 genes which confer a poor prognostic impact vs 2 which confer a good prognostic impact.|Poor: KIT, FLT3, Good: NPM1, CEBPA}}<br /> <br /> <br /> === CAP Breast Cancer and Molecular ===<br /> <br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=Robbins_and_Cotran_9th_Edition_Questions&diff=39053 2015-07-28T00:25:24Z

<p>Tate: </p> <hr /> <div>== Chapter 1: The Cell as a Unit of Health and Disease==<br /> <br /> {{hidden| Short Answer Questions |<br /> {{hidden|How much of the human genome is coding and what does it code?|Of the 3.2b basepairs, there are 20,000 genes that comprise about 1.5% of the genome that code for proteins (enzymes, structural components, and signaling molecules used to assemble and maintain all the cells in the body}}<br /> <br /> {{hidden|What do we think that the rest of the genome does?|80% of the genome binds proteins, implying that it is involved in regulating gene expression, related to the regulation of gene expression, often in a cell-type specific fashion.}}<br /> <br /> {{hidden|List the major classes of functional non-protein-coding sequences found in the human genome.|<br /> *1. Promoter &amp; enhancer<br /> *2. Chromatin binding site structures<br /> *3. non-coding regulatory RNAs<br /> *4. Mobile genetic elements (transposons)<br /> *5. telomeres<br /> *6. centromers. }}<br /> <br /> {{hidden|What are the two most common forms of DNA variation in the human genome?|<br /> *1) Single nucleotide polymorphisms (SNPs)<br /> *2) copy number variations (CNVs)}}<br /> <br /> {{hidden|What are the possible implications of SNPs.|<br /> *1) regulatory = alters gene expression<br /> *2) Correlation with disease states when in close proximity with altered genes<br /> *3) association used to define linkage disequilibrium,?}}<br /> <br /> {{hidden|Define epigenetics.|Heritable changes in gene expression which are not caused by alterations in DNA sequence.}}<br /> <br /> {{hidden|List the 6 types of epigenetic changes.|<br /> *1) Histone &amp; histone modifying factors (Histones organize chromatin into heterochromatin and euchromatin <br /> *2) histone methylation <br /> *3) histone acteylation<br /> *4)histone phosphorylation<br /> *5) DNA methylation<br /> *6) Chromatin organizing factors.}}<br /> <br /> {{hidden|What is the function of micro-RNA (mi-RNA)?|It does not encode protein, instead they function primarily to modulate the translation of target mRNAs into their corresponding proteins, and are responsible for post-transcriptional silencing of gene expression.}}<br /> <br /> {{hidden|What is knockdown technology?|The use of synthetic si-RNA (short RNA sequences) introduced into cells that serve as substrates for Dicer and interact with the RISC complex in a manner analogous to endogenous miRNAs, and are used to study gene function, and are being developed as therapeutic agents to silence pathogenic genes, e.g. oncogenic in neoplasms.}}<br /> <br /> {{hidden|What is long non coding RNA?|Lnc-RNA modulate gene expression by binding to regions of chromatin, restricting RNA polymerase access to coding genes within the region, and may exceed the number of mRNA's by 10-20 fold.}}<br /> <br /> {{hidden|What is XIST?|XIST is a lnc-RNA which is transcribed from the X-chromosome and plays an essential role in physiologic X chromosome inactivation, though not inactivated itself, it forms a repressive cloak on the X chromosome from which it is transcribed resulting in gene silencing.}}<br /> <br /> {{hidden|What are the cellular housekeeping functions?|1) protection from the environment, 2) nutrient acquisition, 3) communication, 4) movement, 5) renewal of senescent molecules, 6) molecular catabolism, 7) energy generation.}}<br /> <br /> {{hidden|List the cellular compartments and the role in the cell.|1) cytosol = metabolism, transport, protein translation, 2) Mitochondria = energy generation, apoptosis, 3) Rough ER = synthesis of membrane and secreted proteins, 4) Smooth ER / Golgi = protein modification, sorting, catabolism, 5)Nucleus = cell regulation, proliferation, DNA transcription, 6) Endosomes = intracellular transport and export, ingestion of extracellular substances, 7) Lysosomes = cellular catabolism, 8) peroxisomes = very long-chain fatty acid metabolism}}<br /> <br /> {{hidden|Describe the basic structure and functions of the cell membrane.| The plasma membrane is composed of a lipid bilayer of phospholipids studded with a variety of proteins and glycoproteins involved in ion and metabolite transport, fluid phase and receptor-mediated uptake of macromolecules, cell-ligand/cell matrix/cell-cell interactions.}}<br /> <br /> {{hidden|How are the large complexes in the plasma membrane formed?|They aggregate under the control of chaperone molecules in the RER or by lateral diffusion in the plasma membrane followed by complex formation in situ.}}<br /> <br /> {{hidden|What are aquaporins?|Special integral membrane proteins which augment passive water transport in tissues where water is transported in large volumes.}}<br /> <br /> {{hidden|How are channel and carrier proteins different?|Channel proteins created hydrophilic pores, permit rapid movement of solutes, restricted by size and charge, where Carrier proteins bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane, relatively slow transport.}}<br /> <br /> {{hidden|What is the &quot;multidrug resistance (MDR) protein&quot;?|A type of transporter ATPases which pumps polar compounds (e.g. chemo drugs) out of cells which may render cancer cells resistant to treatment.}}<br /> <br /> {{hidden|What are the two fundamental mechanisms of fluid or macromolecules by the cell (endocytosis)?|1)Caveolae -invaginations of the plasma membrane, 2) Pinocytosis/receptor mediated endocytosis - macromolecules bind to receptor and membranes invaginate around it.}}<br /> <br /> {{hidden|What is exocytosis?|It is the opposite process of pinocytosis, where the receptor bound macromolecule is move to the cell surface and released.}}<br /> <br /> {{hidden|Describe the difference between phagocytosis and transcytosis.|In phagocytosis microbes are ingested forming phagosomes, which fuse with lysosomes and become phagylosomes, releasing undigested residual material when fusing again with the external membrane, in contrast transcytosis the materials are carried across the cell membrane unaltered.}}<br /> <br /> {{hidden|List the three major classes of 3 cytoskeleton proteins.|1) Actin, 2)Intermediate filaments, 3)Microtubules}}<br /> <br /> {{hidden|Describe actin.|Actin - 5 to 9nm diam fibrils, G-actin polymerized into F-actin, the form double strands helices, which interact with myosin (filamentous protein).}}<br /> <br /> {{hidden|List the various intermediate filaments, which are 10nm in diameter.|1) Lamin A, B, and C (nuclear lamins of all cells, 2) Vimentin (mesenchymal), 3)Desmin (scaffold for actin/myosin), 4) Neurofilaments (axons of neurons), 5) Glial filament protein (glial cells), 6)Cytokeratins (acid and basic and vary based on cell type). }}<br /> <br /> {{hidden|Describe microtubules.|Microtubules are 25nm diam fibrils of dimers of a and b tubulin, with a negative end embedded in the centrosome near the nucleus, the + end grows or shrinks as needed. There are kinesins and dyneins motors that move stuff around the cell, also found in cilia and flagella.}}<br /> <br /> {{hidden|What is clatharin?|A molecule found in the cell membrane that when the cell membrane invaginates forming a basket like structure.}}<br /> <br /> {{hidden|List and describe the 3 main classifications of cell junctions.|1) Tight /occluding junctions - form a high resistance barrier to solute movement, and allows the cell to maintain polarity, 2) anchoring junctions / desmosomes - mechanically attach the cell and their cytoskeleton to other cells and the ECM (hemidesmosome), 3)communicating/gap junctions - mediate the passage of chemical or electrical signals from one cell to another.}}<br /> <br /> {{hidden|What is the &quot;unfolded protein response&quot;?| Excess accumulation of misfolded protiens, which exceed the capacity of the ER to edit and degrade them, leads to the the ER stress response (UPR) that triggers cell death through apoptosis.}}<br /> <br /> {{hidden|What cell organelle has a reactive hyperplasia with repeated exposure to phenobarbitol catabolism in the cytocrhome p450 system?|Smooth endoplasmic reticulum.}}<br /> <br /> {{hidden|List three main functions of mitochondria.|1) Energy generation, 2) intermediate metabolism (instead of ATP make intemediate that can be used to make lipids, nucleic acids, and proteins), 3) Cell death ( necrosis &amp; apoptosis)}}<br /> <br /> {{hidden|List and describe the four extracellular cell-cell signaling pathways based on the distance the signal travels.|1)Paracrine (immediate vicinity), 2) Autocrine (cell affecting itself), 3) Synaptic (neurons sending neurotransmitters at synapse), 4) endocrine (signals released elsewhere into bloodstream).}}<br /> <br /> {{hidden|What are the two characterizing features of stem cells?|Self renewal and asymmetric division (one daughter cell stays a stem cell)}}<br /> <br /> {{hidden|What are the two types of stem cells?|embryonic stem cells (inner cell mass of the blastocyst, totipotent), and tissue/adult stem cells (found in stem cell niches associated with specialized tissues, limited repetoire of differentiation = multipotent)}}<br /> <br /> {{hidden|What is the Warburg effect?|Increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation by the cell.}}<br /> <br /> {{hidden|Which CDKI's have selective effects on CDK4 and CDK6?|p15,p16,p17,and p19}}<br /> <br /> {{hidden|List some examples of signal transduction pathways.|1) Receptor tyrosine kinases (RTKs), 2) Nonreceptor tyrosine kinase, 3) G-protein coupled receptors, 4) nuclear receptors, 5)Notch family receptors, 6) Wnt protein ligands (Frizzled family receptors).}}<br /> <br /> {{hidden|Why does nuclear beta catenin occur in some neoplasms?|When Wnt ligand bins to frizzled it recruits Disheveled, this leads to the disruption of the wnt-ubiquitin complex, this stabilized pool of b-catening is then translocated to the nucleus forming a transcriptional complex}}<br /> <br /> {{hidden|On Page 19 there is a table of growth factors involved in regeneration and repair, please review.|}}<br /> <br /> {{hidden|Describe the function of cadherin.|}}<br /> <br /> {{hidden|What are the functions of the extracellular matrix?|Mechanical support, control of cell proliferation, scaffolding for tissue renewal, establishment of tissue microenvironments}}<br /> <br /> {{hidden|What are the two basic forms of the ECM?|interstitial matrix (fibrillar and non fibrillar collagen, fibronectin, elastin, proteoglycans, hyloronate, and other stuff), basement membrane (type IV collagen and laminin) }}<br /> <br /> {{hidden|What are the three proteins groups in the ECM?|1) fibrous structural proteins (collagen, elastins), 2) water hydrated gels (proteoglycans and hyaluronan), 3) adhesive glycoproteins (connect ECM to each other and other cells)}}<br /> <br /> {{hidden|Describe the structure of a protein that is dependent on vitamin C.|Collagen is composed of 3 seprate polypeptide chains braided into a rope like triple helix, lateral cross linking of the triple helices by lysyl oxidase (requires vitamin C) give it it's tensile strength. }}<br /> <br /> {{hidden|List three non-fibrillar collagens.|Type IV -basement membrane, Type IX - Fibrillar associated collagen with interrupted triple helices (FACIT), Type VII (provides anchoring fibrils to basement membrane beneath skin)}}<br /> <br /> {{hidden|Which structural protein is associated with Marfan syndrom?|Fibrillin synthetic defects, which wrap the elastin core. }}}}<br /> <br /> == Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury and Death ==<br /> Experimenting, please ignore<br /> {{hidden <br /> | headerstyle = text-align: left;<br /> | header = What are the four aspects of a disease?<br /> | content = *1. Etiology<br /> **Genetic - Inherited mutations and disease-associated gene variants, or polymorphisms.<br /> **Acquired - Infectious, nutritional, chemical and physical.<br /> *2. Pathogenesis - The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.<br /> *3. Morphological changes - The structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process.<br /> *4. Clinical Manifestations - Symptoms and signs of disease, as well as its clinical course and outcome.}}<br /> <br /> == Chapter 3 ==<br /> == Chapter 4 ==<br /> == Chapter 5 ==<br /> {{hidden|MC cause of spontaneous abortion is ?|&lt;center&gt;[[ A demonstrable chromosomal abnormality.]]&lt;/center&gt;}}<br /> <br /> {{hidden|1% of all newborn infants possess a gross chromosomal abnormality and 5% of people &lt;25y present with |&lt;center&gt;[[a genetic disease. ]]&lt;/center&gt;}}<br /> <br /> {{hidden|Mutation|&lt;center&gt;[[permanent change in the DNA, if affect germ cells are transmitted to the progeny ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe 4 broad categories of human genetic disorders:|&lt;center&gt;[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance<br /> ii. Often highly penetrant (large proportion of pop with gene has disease)<br /> b. Chromosomal disorders<br /> i. Structural or numerical alterations in autosomes and sex chromosomes<br /> ii. Uncommon, high penetrance<br /> c. Complex multigenic disorders<br /> i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present<br /> d. Single gene disorders with nonclassic patterns of inheritance (not mendelian)<br /> i. Disorders resulting from triplet repeat mutations<br /> ii. Mutations in mitochondrial DNA<br /> iii. Those influenced by genomic imprinting<br /> iv. Those influenced by gonadal mosaicism]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of a point mutation in a coding region?|[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid, b. Nonsense mutation – makes a stop codon ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of point mutation or deletion in a non-coding region.|&lt;center&gt;[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing &gt; failure to make mature RNA &gt; no translation]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of deletions and insertions.|&lt;center&gt;[[a.Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon<br /> i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene ]]}}<br /> <br /> {{hidden|List and describe the possible outcomes of trinucleotide repeat mutations.|[[a. Usually G&amp;C, dynamic and increase during gametogenesis, “RNA stutters”,b. Fragile X – CGG 250-4000, Huntinton’s Disease ]]}}<br /> <br /> {{hidden|List and describe three examples of inheritance of single gene mutations|[[a. AD – manifested in the heterologous state, one parent of index case is usually affected, males and females affected and both can transmit conditioni. De novo cases may not have affected parentii. Penetrance = fraction of people with gene who have the traitiii. Variable expressivity = those with mutant gene have variety of phenotypesiv. Often age of onset is delayed so can reproduce before die from diseasev. Biochem mechanisms1. Reduced production of a protein or dysfunctional/inactive protein2. Involved in regulation of complex metabolic pathyway subject to feedback inhibition3. Key structural proteins (collagen and cytoskeleton of RBC)a. May be a dominant negative , e.g. osteogenesis imperfecta4. Gain of function are rare, 2 formsa. Increased in proteins normal function (excess enzyme activity)b. Huntinton’s diseas (abn protein accumulates, toxic to neurons)b. ARi. Largest category – both alleles at a locus are mutated1. Expression is uniform, complete penetrance common, early onset, unaffected carrier family members, mostly enzymesc. X Linkedi. All sex linked, and almost all are recessive , if Y Chromosome affected usually infertile males &gt; no progenyii. Male expression b/c hemizygous, daughter carriers with variable phenotype because of lionization of 2nd X e.g G6DPiii. Dominant . vitamin D resistant rickets]]&lt;/center&gt;}}<br /> <br /> Stopped at P142<br /> <br /> == Chapter 6 ==<br /> == Chapter 7 ==<br /> == Chapter 8 ==<br /> == Chapter 9 ==<br /> == Chapter 10 ==<br /> == Chapter 11 ==<br /> == Chapter 12 ==<br /> == Chapter 13 ==<br /> == Chapter 14 ==<br /> == Chapter 15 ==<br /> == Chapter 16 ==<br /> == Chapter 17 ==<br /> == Chapter 18 ==<br /> == Chapter 19 ==<br /> == Chapter 20 ==<br /> == Chapter 21 ==<br /> == Chapter 22 ==<br /> ==[[Breast (CH 23)]]==<br /> <br /> == Chapter 24 ==<br /> == Chapter 25 ==<br /> == Chapter 26 ==<br /> == Chapter 27 ==<br /> == Chapter 28 ==<br /> == Chapter 29 ==</div>

Tate https://librepathology.org/w/index.php?title=Molecular_Pathology_Rotation_Notes&diff=39052 2015-07-28T00:23:42Z

<p>Tate: </p> <hr /> <div>===UNIT 1===<br /> <br /> {{hidden|List three differences between DNA and RNA.|[[DNA (double stranded, thymine, deoxyribose, more stable; RNA single stranded, ribose, uracil]]}}<br /> <br /> {{hidden|What are the three stop codons?|[UAA, UGA, UAG]]}}<br /> <br /> {{hidden|Where does transcription begin?|[[promoters at the 5' end before the coding region]]}}<br /> <br /> {{hidden|List 2 enzymes necessary for transcription and their function. |[[helicase, polymerase]]}}<br /> <br /> {{hidden|List and describe three post transcription modifications of RNA.|[[Splicing, cappping, 3'polyadenylation, ]]}}<br /> <br /> {{hidden| Why is alternative splicing important?|[[Using the basic construction blocks of coding sequences allows a large variety of recombinations, more efficient coding (e.g. creating functions to call))]]}}<br /> <br /> {{hidden|List three differences between somatic and germline mutations. |&lt;center&gt;[[Somatic: not passed on to progeny, only tumour or particular tissue cells with mutation, Germline: passed onto progeny, all cells have mutation * unless mosaicism or chimerism]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is the difference between a missense and a non-sense mutation?|&lt;center&gt;[[Missense the new base pair does not change the amino acid found in the protein at that location, non-sense changes the amino acid in the protein at that location]]&lt;/center&gt;}}<br /> <br /> {{hidden|Define a frameshift mutation. |&lt;center&gt;[[deletion of a non-multiple of 3 which causes all further trinucleotide combinations to no longer code for the correct amino acid, often results in a premature stop codon]]&lt;/center&gt;}}<br /> <br /> {{hidden|Why are inversion mutations difficult to detect?|&lt;center&gt;[[When the are smal, e.g. only a few base pairs]]&lt;/center&gt;}}<br /> <br /> {{hidden|Describe the potential sequelae of a translocation mutation. |&lt;center&gt;[[when a segment on one chromosome is transferred to another, make a gene non-functional or can result in a fusion gene]]&lt;/center&gt;}}<br /> <br /> ===UNIT 2===<br /> {{hidden|Translate the following: c.1524_1527delCGTA.|&lt;center&gt;[[a small deletion of CGTA between the 1524 and 1527 base pairs]]&lt;/center&gt;}}<br /> <br /> {{hidden|List 5 features of SNPs.|[[Most common DNA sequence variation in humans, must occur in &gt;=1% of a particular population, frequency of SNPs varies by groups, but responsible for &gt;90% of human genetic variation, an can be found in any region of genome]]}}<br /> <br /> {{hidden|Define a regulatory SNP versus a synonymous SNP?|[[Regulatory SNP: occur in non-coding regions e.g. promoters where they affect mRNA expression and stability, as occur in the splice site where can result in abnormal protein production]]}}<br /> <br /> {{hidden|What is the difference between a microstalellite and a minisattelite?|&lt;center&gt;[[Microsatellite = stretches of DNA with sequences of 2-4 base pairs repeated a few dozen times (STRP), minisatellite = variable number of tandem repeats 10-100bp in lenght]]&lt;/center&gt;}}<br /> <br /> {{hidden|Describe Hardy-Weinberg Equilibrium?|&lt;center&gt;[[Mathematical probability function to describe allelic and genotype frequency in a random mating scenario]]&lt;/center&gt;}}<br /> <br /> {{hidden|What factors can disrupt the H-W equilibrium?|&lt;center&gt;[[non random mating, migration, genetic drift, founder effects, mutation, natural selection]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is linkage disequilibrium?|&lt;center&gt;[[The closer two genes are together on the chromosome the more likely they are to be found toghether in a population, during meiosis some exchange of material happens between the two chromosomes]]&lt;/center&gt;}}<br /> <br /> ===UNIT 3===<br /> {{hidden|What are the three major steps of PCR?|&lt;center&gt;[[denaturing, primer annealing, strand extending]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is the hallmark of PCR?|&lt;center&gt;[[The cycling at different temperatures, in the presence of key reaction components to traget and exponentially amplify a specific DNA target sequence]]&lt;/center&gt;}}<br /> <br /> {{hidden|What factors affect the method of genotyping chosen?|&lt;center&gt;[[throughput, type of variants that can be genotyped, equipment and costs, TAT, technical expertise, and multiplex ability]]&lt;/center&gt;}}<br /> <br /> {{hidden|Define sensitivity, specificity, positive predictive value and negative predictive value. |&lt;center&gt;[[Sensitivity = probability of a positive test in a disease, specificity = probability of a negative dest in a non-diseased patient ]]&lt;/center&gt;}}<br /> <br /> {{hidden|Define reproduciblity and accuracy of an analytical test. |&lt;center&gt;[[Reproducability = probability of the test repeatedly producing the same reults in the same person, Accuracy = the degree to which the observed genotype matches the true genotype]]&lt;/center&gt;}}<br /> <br /> {{hidden|Describe briefly Sanger sequencing.|&lt;center&gt;[[DIdeoxynucleotides are used in a mix with deoxynucleotides, the Di*** terminate the chain, and so you get all possible lengths of chains so then you put them all in order and you can read (based on weight) which one is at each position]]&lt;/center&gt;}}<br /> <br /> {{hidden|Describe briefly how Taqman automated genotyping is used for allele detection. |&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|How are DNA microarrays used to identify drug disposition or responses?|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> ===UNIT 4===<br /> {{hidden|Describe the procedure for submitting FFPE slides for KRAS for colorectal cancer.|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|Compare and contrast uniplex versus multiplex genotyping. |&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|Compare and contrast conventional vs massively parallel sequencing. |&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is multiplex ligation-dependent ligation (MLPA)?|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is fragment analysis?|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|Compare and contrast RT-PCR vs qRTPCR.|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is MSI?|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is methylation analysis?|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> ===UNIT 5===<br /> {{hidden|What are the four test features required to be documented by the CLIA?|&lt;center&gt;[[]]&lt;/center&gt;}}<br /> <br /> {{hidden|What are &quot;in vitro diagnostics&quot; vs &quot;laboratory developed tests&quot;?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What does validation mean? |&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What are the four performance characteristics that need to be verified for FDA cleared/approved tests?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What are the six performance characteristics that need to be verified for FDA cleared LDTs or modified FDA cleared/approved tests?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> ===UNIT 6===<br /> {{hidden|List the components of a molecular pathology report.|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|Define analytical sensitivity and clinical sensitivity. |&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What should be said in a report of a molecular test on a patient for residual disease if no previous positive assay was confirmed?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|Define ammended report versus addendum report.|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|Whose responsibility is it to sythesize the test results with other clinico-pathological information?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|How long are cytogenetic reports required to be kept by CAP?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is the recommended process to use test results if an assay is not yet validated for clinical use?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|Give three examples of &quot;grey areas&quot; which warrant discretion of professionals involved to use a non-validated test?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What reference standard is available for gene nomenclature?|&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|Create a table of the most common gene rearrangements associated with heme and soft tissue diseases. |&lt;center&gt;[[Microsatellite instability]]&lt;/center&gt;}}<br /> <br /> {{hidden|What is a &quot;DNA fingerprint&quot; and what can it be used for?|&lt;center&gt;[[A method that examines multiple areas of short tandem repeats to identify paternity, mosaicism, chimerism, and identity in forensics cases]]<br /> &lt;/center&gt;}}</div>

Tate https://librepathology.org/w/index.php?title=Libre_Pathology_talk:Study_Group&diff=39051 2015-07-28T00:13:20Z

<p>Tate: </p> <hr /> <div>==Michael's thoughts on the exam==<br /> *I wrote it and passed it in 2012. I also did the American exam the same year and passed that.<br /> *The pass rate for the FRCPC exam is pretty high.<br /> **2009-2011 it was 96+/-3.9% for Canadian medical school grads on their first attempt.<br /> <br /> ===Written===<br /> *I though it was picking at details. Some things are very relevant to practise... other less so.<br /> **The pocketbook version of [[Robbins]] covers most of it.<br /> <br /> ===Practical (slide) exam===<br /> *You should know the answer almost immediately.<br /> **If you don't know, write something down and move on.<br /> *It is set to broadly cover everything.<br /> *If it isn't a [[spot diagnosis]]... it should not be on.<br /> *Somethings are PGY2/PGY3 stuff. One should not overthink things.<br /> *Anecdotally, the first impression is usually the right one.<br /> **I think one should stick with the first impression. <br /> <br /> ===Gross exam===<br /> *Go with the most probable if you're uncertain.<br /> *I worked through the ''Atlas of Gross Pathology with Histologic Correlation'' (see [[Pathology books]] for the reference).<br /> **I am not sure this is necessary... but I thought it was useful.<br /> *Flickr.com/Google images has a lot to offer in this respect.<br /> *[[Gross spot diagnosis]].<br /> <br /> ===Forensic exam===<br /> *I thought this was tricky... and I liked forensics.<br /> *Residents that took the exam prior to me said the same.<br /> <br /> ===Cytology exam===<br /> *Some of the cases have several images.<br /> *I remember being confused... the first three images were from one case. I remember thinking... I have the same diagnosis three times.<br /> *Like the forensics and gross sections - this section isn't too long. From an exam strategy point-of-view, this makes it less likely that a diagnosis is repeated.<br /> <br /> ===Oral exam===<br /> *I think this is to test if you are safe and useful.<br /> **By &quot;safe&quot; I mean: knowing your limits and consulting with a colleague when appropriate.<br /> **By &quot;useful&quot; I mean: you don't need to consult on everything.<br /> *The examiners ask a pre-determined list of questions.<br /> **Questions may depend on one another and, in fairness, they are told to redirect you.<br /> ***Example: You see a lung biopsy with hyaline material... and you go down the fibrosis route-- but it is really amyloidosis.<br /> ****The examiners will say something like &quot;how would one work-up suspected amyloid?&quot; or &quot;lets assume this is amyloid...&quot;<br /> *If you're a Canadian resident, you cannot be examined by someone within your residency program.<br /> *As far as I know, examiners are told to be stone-faced, i.e. show no emotion.<br /> *Some of the cases were very straight forward.<br /> *I didn't think anything was really exotic.<br /> <br /> [[User:Michael|Michael]] ([[User talk:Michael|talk]]) 23:43, 25 October 2014 (EDT)<br /> <br /> === Short answer questions submitted by Tate ===<br /> <br /> == Short answer questions on genetics and molecular pathology. ==<br /> <br /> These are some questions I came up with that are plausible to me... let me know if they are out to lunch. <br /> <br /> ==[[Molecular Pathology Rotation Notes]]==<br /> <br /> ==[[Robbins and Cotran 9th Edition Questions]]==<br /> <br /> ==[[Cytogenetics Review Questions]]==<br /> <br /> <br /> == Molecular Genetic Diagnosis==<br /> {{hidden|List three basic molecular diagnostic techniques|a. Karyotyping, b. Southern blot, c. Sanger DNA sequencing, d. Polymerase chain reaction}}<br /> <br /> <br /> ===CAP Molecular Diagnosis of Lung Cancer===<br /> <br /> {{hidden|List 5 treatment defining molecular transformation, the neoplasm, and the genetic alteration|1. 100% of CML: BRR-ABL &gt; Imatinib, 2. 20% of Lung Adenocarcinoma: EGFR &gt; Erlotinib/Gefitinib, 3. 25% Infiltrative ductal carcinoma of breast HER2&gt;Trastuzumab, 4. 50% of Melanoma, BRAF v600E &gt; PLX4032, 5. 4% of Lung Adenocarcinoma: ALK &gt; Crizotinib}}<br /> <br /> {{hidden|List and describe 5 areas of Genetic characaterization of tumours for personalized medicine|DNA mutations, DNA chromosomal alterations, mRNA and MiRNA profiling, Proteomics, DNA epigenetics}}<br /> <br /> {{hidden|What fraction of Lung adenocarcinomas have no known detactable mutations|42%}}<br /> <br /> {{hidden|What are the three most common molecular alterations of Lung Adenocarcinoma|KRAS 23%, EGFR 15%, TP53 5%}}<br /> <br /> {{hidden|What is the two most common molecular alteration makes patients with EGFR mutations resistant to targetted therapies?|KRAS (primary) and T790M (primary and acquired)}}<br /> <br /> {{hidden|List two EGFR kinase inhibitors.|Gefitinib/Iressa, Erlotinib/Tarceva}}<br /> <br /> {{hidden|What are the three most common cancers associated with KRAS mutations?|Pancreatic 90%, Colon 50%, Lung NSCLC 30%}}<br /> <br /> {{hidden|Why don't KRAS + tumours respond to Anti EGFR therapies?|KRAS is downstream from EGFR, so changing the function of EFGR would not have any effect on mutated KRAS}}<br /> <br /> {{hidden|Explain the cost effectiveness of genetic testing for targetted therapies?|Most molecular tests cost $200-1000, vs one month of targetted therapy $2000-10000/month}}<br /> <br /> {{hidden|What are the three most common cancers associated with BRAF mutations?|Melanoma 70%, Papillary Thyroid Carcinoma 50%, Ovarian serious carcinoma 30%, Colon cancer 10%, Hint Papillary architecture}}<br /> <br /> {{hidden|Beta catenin/CTNNB1 expression is found with which histological pattern of lung adenocarcinoma?|Low grade adenocarcinoma of fetal type, poor px, &lt;40yo, and has glycogen rich glandular formations, may occur in FAP patients}}<br /> <br /> {{hidden|What is the most common ALK rearrangement found in NSCLC?|EML4-ALK (90% of the 13% of lung cancers found to due to ALK fusions)}}<br /> <br /> {{hidden|List some pros and cons of ALK FISH.|Pros: commercial FDA approved probes available, not too expensive, moderately easy to disseminate screening, clinically validated, and failed tests on poorly preserved tissues are not reported as negative. Cons: need fish lab expertise (including pathologist and PhD), can be tricky if genes are close}}<br /> <br /> {{hidden|List some pros and cons of ALK IHC.|Pros: fast, cheap, easy to disseminate screening, Cons: commercial antibodies sub-optimal, poorly preserved tissues (esp bx) may give false negative results due to loss of antigenicity, no internal control}}<br /> <br /> {{hidden|What is a positive count in the ALK-FISH?|Signal split &gt;2 probe diameters}}<br /> <br /> ===CAP Molecular Diagnosis of AML===<br /> <br /> {{hidden|List 6 genes associated with Acute Myeloid Leukemia that have been identified by cloning translocation break points|RUNX1, RUNX1T1, PML, CBFB, ETV6, MLL}}<br /> <br /> {{hidden|List the 5 main categories of classification of Acute Myeloid Leukemia|1. AML with recurrent genetic abnormalities, 2. AML with myelodysplasia-related changes, 3. Therapy related myeloid neoplasms, 4. AML, NOS, 5. Myeloid sarcoma}}<br /> <br /> {{hidden|Give any three translocations identified in AML.|t(8,21), inv (16), t(15,17), t(9,11), t(6,9), inv(3), t(1,22), mutated NPM1, mutated CEBPA}}<br /> <br /> {{hidden|What entities are fall under the AML, NOS classification?|AML with minimal differentiation, AML without maturation, AML with maturation, Acute myelomonocytic leukemia, Acute monoblastic/monocytic leukemia, Acute erythroid leukemias (pure erythroid, erythroleukemia, erythroid/myeloid), Acute Megakaryoblastic leukemia, Acute basophilic leukemia, Acte panmyelosis with myelofibrosis}}<br /> <br /> {{hidden|List 2 genes which confer a poor prognostic impact vs 2 which confer a good prognostic impact.|Poor: KIT, FLT3, Good: NPM1, CEBPA}}<br /> <br /> <br /> === CAP Breast Cancer and Molecular ===<br /> <br /> {{Hidden|List 3 patient and 4 tumour features that affect Prognosis and treatment.|Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade}}<br /> <br /> {{hidden|Describe the histological grading system used for breast cancer.|Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)}}<br /> <br /> {{hidden|Describe the genomic grading system used for breast cancer.|Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)}}<br /> <br /> {{hidden|What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy?|&gt;=1% of invasive tumour cells nuclear positivity}}<br /> <br /> {{hidden|what defines a positive HER2 for the purpose of treatment with Herceptin?|HER2 IHC &gt;30% with complete membranous staining OR HER2/CEP17 &gt;2.2}}<br /> <br /> {{hidden|What are the indications for chemotherapy for breast cancer patients?|Low expression of ER/PR, Grade 3 histology, Ki67&gt;20%, 4+ nodes positive, +LVI, and tumour &gt;5cm]}}<br /> <br /> {{hidden|What are the indications for hormonal therapy alone?|high expression of ER, Grade 1, Ki67&gt;40%, Node negative, LVI not identified, and tumour 1-2cm}}<br /> <br /> {{hidden|What are the four categories of breast cancer using the molecular classification of gene expression?|Luminal A, Luminal B, Basal, and Her2 OverExpression}}<br /> <br /> {{hidden|What is the difference between unsupervised and supervised molecular classification of tumours?|Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.}}<br /> <br /> {{hidden|What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model.|Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)}}<br /> <br /> {{hidden|What are the features of Luminal A breast cancer?|High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.}}<br /> <br /> {{hidden|What are the features of Luminal B breast cancer?|low ER/PR expression (may be PR neg), over expression GFR(Her2 &amp; EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)}}<br /> <br /> {{hidden|What are the features of Luminal B HER2| ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen}}<br /> <br /> {{hidden|What are the features of Her2 Enriched breast cancers?| GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin}}<br /> <br /> <br /> {{hidden|What are the features of Basal breast cancer?|}}</div>

Tate https://librepathology.org/w/index.php?title=Robbins_and_Cotran_9th_Edition_Questions&diff=39022 2015-07-26T21:46:20Z

<p>Tate: /* Chapter 23 */</p> <hr /> <div>== Chapter 1: The Cell as a Unit of Health and Disease==<br /> <br /> {{hidden| Short Answer Questions |<br /> {{hidden|How much of the human genome is coding and what does it code?|Of the 3.2b basepairs, there are 20,000 genes that comprise about 1.5% of the genome that code for proteins (enzymes, structural components, and signaling molecules used to assemble and maintain all the cells in the body}}<br /> <br /> {{hidden|What do we think that the rest of the genome does?|80% of the genome binds proteins, implying that it is involved in regulating gene expression, related to the regulation of gene expression, often in a cell-type specific fashion.}}<br /> <br /> {{hidden|List the major classes of functional non-protein-coding sequences found in the human genome.|<br /> *1. Promoter &amp; enhancer<br /> *2. Chromatin binding site structures<br /> *3. non-coding regulatory RNAs<br /> *4. Mobile genetic elements (transposons)<br /> *5. telomeres<br /> *6. centromers. }}<br /> <br /> {{hidden|What are the two most common forms of DNA variation in the human genome?|<br /> *1) Single nucleotide polymorphisms (SNPs)<br /> *2) copy number variations (CNVs)}}<br /> <br /> {{hidden|What are the possible implications of SNPs.|<br /> *1) regulatory = alters gene expression<br /> *2) Correlation with disease states when in close proximity with altered genes<br /> *3) association used to define linkage disequilibrium,?}}<br /> <br /> {{hidden|Define epigenetics.|Heritable changes in gene expression which are not caused by alterations in DNA sequence.}}<br /> <br /> {{hidden|List the 6 types of epigenetic changes.|<br /> *1) Histone &amp; histone modifying factors (Histones organize chromatin into heterochromatin and euchromatin <br /> *2) histone methylation <br /> *3) histone acteylation<br /> *4)histone phosphorylation<br /> *5) DNA methylation<br /> *6) Chromatin organizing factors.}}<br /> <br /> {{hidden|What is the function of micro-RNA (mi-RNA)?|It does not encode protein, instead they function primarily to modulate the translation of target mRNAs into their corresponding proteins, and are responsible for post-transcriptional silencing of gene expression.}}<br /> <br /> {{hidden|What is knockdown technology?|The use of synthetic si-RNA (short RNA sequences) introduced into cells that serve as substrates for Dicer and interact with the RISC complex in a manner analogous to endogenous miRNAs, and are used to study gene function, and are being developed as therapeutic agents to silence pathogenic genes, e.g. oncogenic in neoplasms.}}<br /> <br /> {{hidden|What is long non coding RNA?|Lnc-RNA modulate gene expression by binding to regions of chromatin, restricting RNA polymerase access to coding genes within the region, and may exceed the number of mRNA's by 10-20 fold.}}<br /> <br /> {{hidden|What is XIST?|XIST is a lnc-RNA which is transcribed from the X-chromosome and plays an essential role in physiologic X chromosome inactivation, though not inactivated itself, it forms a repressive cloak on the X chromosome from which it is transcribed resulting in gene silencing.}}<br /> <br /> {{hidden|What are the cellular housekeeping functions?|1) protection from the environment, 2) nutrient acquisition, 3) communication, 4) movement, 5) renewal of senescent molecules, 6) molecular catabolism, 7) energy generation.}}<br /> <br /> {{hidden|List the cellular compartments and the role in the cell.|1) cytosol = metabolism, transport, protein translation, 2) Mitochondria = energy generation, apoptosis, 3) Rough ER = synthesis of membrane and secreted proteins, 4) Smooth ER / Golgi = protein modification, sorting, catabolism, 5)Nucleus = cell regulation, proliferation, DNA transcription, 6) Endosomes = intracellular transport and export, ingestion of extracellular substances, 7) Lysosomes = cellular catabolism, 8) peroxisomes = very long-chain fatty acid metabolism}}<br /> <br /> {{hidden|Describe the basic structure and functions of the cell membrane.| The plasma membrane is composed of a lipid bilayer of phospholipids studded with a variety of proteins and glycoproteins involved in ion and metabolite transport, fluid phase and receptor-mediated uptake of macromolecules, cell-ligand/cell matrix/cell-cell interactions.}}<br /> <br /> {{hidden|How are the large complexes in the plasma membrane formed?|They aggregate under the control of chaperone molecules in the RER or by lateral diffusion in the plasma membrane followed by complex formation in situ.}}<br /> <br /> {{hidden|What are aquaporins?|Special integral membrane proteins which augment passive water transport in tissues where water is transported in large volumes.}}<br /> <br /> {{hidden|How are channel and carrier proteins different?|Channel proteins created hydrophilic pores, permit rapid movement of solutes, restricted by size and charge, where Carrier proteins bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane, relatively slow transport.}}<br /> <br /> {{hidden|What is the &quot;multidrug resistance (MDR) protein&quot;?|A type of transporter ATPases which pumps polar compounds (e.g. chemo drugs) out of cells which may render cancer cells resistant to treatment.}}<br /> <br /> {{hidden|What are the two fundamental mechanisms of fluid or macromolecules by the cell (endocytosis)?|1)Caveolae -invaginations of the plasma membrane, 2) Pinocytosis/receptor mediated endocytosis - macromolecules bind to receptor and membranes invaginate around it.}}<br /> <br /> {{hidden|What is exocytosis?|It is the opposite process of pinocytosis, where the receptor bound macromolecule is move to the cell surface and released.}}<br /> <br /> {{hidden|Describe the difference between phagocytosis and transcytosis.|In phagocytosis microbes are ingested forming phagosomes, which fuse with lysosomes and become phagylosomes, releasing undigested residual material when fusing again with the external membrane, in contrast transcytosis the materials are carried across the cell membrane unaltered.}}<br /> <br /> {{hidden|List the three major classes of 3 cytoskeleton proteins.|1) Actin, 2)Intermediate filaments, 3)Microtubules}}<br /> <br /> {{hidden|Describe actin.|Actin - 5 to 9nm diam fibrils, G-actin polymerized into F-actin, the form double strands helices, which interact with myosin (filamentous protein).}}<br /> <br /> {{hidden|List the various intermediate filaments, which are 10nm in diameter.|1) Lamin A, B, and C (nuclear lamins of all cells, 2) Vimentin (mesenchymal), 3)Desmin (scaffold for actin/myosin), 4) Neurofilaments (axons of neurons), 5) Glial filament protein (glial cells), 6)Cytokeratins (acid and basic and vary based on cell type). }}<br /> <br /> {{hidden|Describe microtubules.|Microtubules are 25nm diam fibrils of dimers of a and b tubulin, with a negative end embedded in the centrosome near the nucleus, the + end grows or shrinks as needed. There are kinesins and dyneins motors that move stuff around the cell, also found in cilia and flagella.}}<br /> <br /> {{hidden|What is clatharin?|A molecule found in the cell membrane that when the cell membrane invaginates forming a basket like structure.}}<br /> <br /> {{hidden|List and describe the 3 main classifications of cell junctions.|1) Tight /occluding junctions - form a high resistance barrier to solute movement, and allows the cell to maintain polarity, 2) anchoring junctions / desmosomes - mechanically attach the cell and their cytoskeleton to other cells and the ECM (hemidesmosome), 3)communicating/gap junctions - mediate the passage of chemical or electrical signals from one cell to another.}}<br /> <br /> {{hidden|What is the &quot;unfolded protein response&quot;?| Excess accumulation of misfolded protiens, which exceed the capacity of the ER to edit and degrade them, leads to the the ER stress response (UPR) that triggers cell death through apoptosis.}}<br /> <br /> {{hidden|What cell organelle has a reactive hyperplasia with repeated exposure to phenobarbitol catabolism in the cytocrhome p450 system?|Smooth endoplasmic reticulum.}}<br /> <br /> {{hidden|List three main functions of mitochondria.|1) Energy generation, 2) intermediate metabolism (instead of ATP make intemediate that can be used to make lipids, nucleic acids, and proteins), 3) Cell death ( necrosis &amp; apoptosis)}}<br /> <br /> {{hidden|List and describe the four extracellular cell-cell signaling pathways based on the distance the signal travels.|1)Paracrine (immediate vicinity), 2) Autocrine (cell affecting itself), 3) Synaptic (neurons sending neurotransmitters at synapse), 4) endocrine (signals released elsewhere into bloodstream).}}<br /> <br /> {{hidden|What are the two characterizing features of stem cells?|Self renewal and asymmetric division (one daughter cell stays a stem cell)}}<br /> <br /> {{hidden|What are the two types of stem cells?|embryonic stem cells (inner cell mass of the blastocyst, totipotent), and tissue/adult stem cells (found in stem cell niches associated with specialized tissues, limited repetoire of differentiation = multipotent)}}<br /> <br /> {{hidden|What is the Warburg effect?|Increased cellular uptake of glucose and glutamine, increased glycolysis, and decreased oxidative phosphorylation by the cell.}}<br /> <br /> {{hidden|Which CDKI's have selective effects on CDK4 and CDK6?|p15,p16,p17,and p19}}<br /> <br /> {{hidden|List some examples of signal transduction pathways.|1) Receptor tyrosine kinases (RTKs), 2) Nonreceptor tyrosine kinase, 3) G-protein coupled receptors, 4) nuclear receptors, 5)Notch family receptors, 6) Wnt protein ligands (Frizzled family receptors).}}<br /> <br /> {{hidden|Why does nuclear beta catenin occur in some neoplasms?|When Wnt ligand bins to frizzled it recruits Disheveled, this leads to the disruption of the wnt-ubiquitin complex, this stabilized pool of b-catening is then translocated to the nucleus forming a transcriptional complex}}<br /> <br /> {{hidden|On Page 19 there is a table of growth factors involved in regeneration and repair, please review.|}}<br /> <br /> {{hidden|Describe the function of cadherin.|}}<br /> <br /> {{hidden|What are the functions of the extracellular matrix?|Mechanical support, control of cell proliferation, scaffolding for tissue renewal, establishment of tissue microenvironments}}<br /> <br /> {{hidden|What are the two basic forms of the ECM?|interstitial matrix (fibrillar and non fibrillar collagen, fibronectin, elastin, proteoglycans, hyloronate, and other stuff), basement membrane (type IV collagen and laminin) }}<br /> <br /> {{hidden|What are the three proteins groups in the ECM?|1) fibrous structural proteins (collagen, elastins), 2) water hydrated gels (proteoglycans and hyaluronan), 3) adhesive glycoproteins (connect ECM to each other and other cells)}}<br /> <br /> {{hidden|Describe the structure of a protein that is dependent on vitamin C.|Collagen is composed of 3 seprate polypeptide chains braided into a rope like triple helix, lateral cross linking of the triple helices by lysyl oxidase (requires vitamin C) give it it's tensile strength. }}<br /> <br /> {{hidden|List three non-fibrillar collagens.|Type IV -basement membrane, Type IX - Fibrillar associated collagen with interrupted triple helices (FACIT), Type VII (provides anchoring fibrils to basement membrane beneath skin)}}<br /> <br /> {{hidden|Which structural protein is associated with Marfan syndrom?|Fibrillin synthetic defects, which wrap the elastin core. }}}}<br /> <br /> == Chapter 2: Cellular Responses to Stress and Toxic Insults: Adaptation, Injury and Death ==<br /> Experimenting, please ignore<br /> {{hidden <br /> | headerstyle = text-align: left;<br /> | header = What are the four aspects of a disease?<br /> | content = *1. Etiology<br /> **Genetic - Inherited mutations and disease-associated gene variants, or polymorphisms.<br /> **Acquired - Infectious, nutritional, chemical and physical.<br /> *2. Pathogenesis - The sequence of cellular, biochemical, and molecular events that follow the exposure of cells or tissues to an injurious agent.<br /> *3. Morphological changes - The structural alterations in cells or tissues that are either characteristic of a disease or diagnostic of an etiologic process.<br /> *4. Clinical Manifestations - Symptoms and signs of disease, as well as its clinical course and outcome.}}<br /> <br /> == Chapter 3 ==<br /> == Chapter 4 ==<br /> == Chapter 5 ==<br /> {{hidden|MC cause of spontaneous abortion is ?|&lt;center&gt;[[ A demonstrable chromosomal abnormality.]]&lt;/center&gt;}}<br /> <br /> {{hidden|1% of all newborn infants possess a gross chromosomal abnormality and 5% of people &lt;25y present with |&lt;center&gt;[[a genetic disease. ]]&lt;/center&gt;}}<br /> <br /> {{hidden|Mutation|&lt;center&gt;[[permanent change in the DNA, if affect germ cells are transmitted to the progeny ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe 4 broad categories of human genetic disorders:|&lt;center&gt;[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance<br /> ii. Often highly penetrant (large proportion of pop with gene has disease)<br /> b. Chromosomal disorders<br /> i. Structural or numerical alterations in autosomes and sex chromosomes<br /> ii. Uncommon, high penetrance<br /> c. Complex multigenic disorders<br /> i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present<br /> d. Single gene disorders with nonclassic patterns of inheritance (not mendelian)<br /> i. Disorders resulting from triplet repeat mutations<br /> ii. Mutations in mitochondrial DNA<br /> iii. Those influenced by genomic imprinting<br /> iv. Those influenced by gonadal mosaicism]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of a point mutation in a coding region?|[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid, b. Nonsense mutation – makes a stop codon ]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of point mutation or deletion in a non-coding region.|&lt;center&gt;[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing &gt; failure to make mature RNA &gt; no translation]]&lt;/center&gt;}}<br /> <br /> {{hidden|List and describe the possible outcomes of deletions and insertions.|&lt;center&gt;[[a.Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon<br /> i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene ]]}}<br /> <br /> {{hidden|List and describe the possible outcomes of trinucleotide repeat mutations.|[[a. Usually G&amp;C, dynamic and increase during gametogenesis, “RNA stutters”,b. Fragile X – CGG 250-4000, Huntinton’s Disease ]]}}<br /> <br /> {{hidden|List and describe three examples of inheritance of single gene mutations|[[a. AD – manifested in the heterologous state, one parent of index case is usually affected, males and females affected and both can transmit conditioni. De novo cases may not have affected parentii. Penetrance = fraction of people with gene who have the traitiii. Variable expressivity = those with mutant gene have variety of phenotypesiv. Often age of onset is delayed so can reproduce before die from diseasev. Biochem mechanisms1. Reduced production of a protein or dysfunctional/inactive protein2. Involved in regulation of complex metabolic pathyway subject to feedback inhibition3. Key structural proteins (collagen and cytoskeleton of RBC)a. May be a dominant negative , e.g. osteogenesis imperfecta4. Gain of function are rare, 2 formsa. Increased in proteins normal function (excess enzyme activity)b. Huntinton’s diseas (abn protein accumulates, toxic to neurons)b. ARi. Largest category – both alleles at a locus are mutated1. Expression is uniform, complete penetrance common, early onset, unaffected carrier family members, mostly enzymesc. X Linkedi. All sex linked, and almost all are recessive , if Y Chromosome affected usually infertile males &gt; no progenyii. Male expression b/c hemizygous, daughter carriers with variable phenotype because of lionization of 2nd X e.g G6DPiii. Dominant . vitamin D resistant rickets]]&lt;/center&gt;}}<br /> <br /> Stopped at P142<br /> <br /> == Chapter 6 ==<br /> == Chapter 7 ==<br /> == Chapter 8 ==<br /> == Chapter 9 ==<br /> == Chapter 10 ==<br /> == Chapter 11 ==<br /> == Chapter 12 ==<br /> == Chapter 13 ==<br /> == Chapter 14 ==<br /> == Chapter 15 ==<br /> == Chapter 16 ==<br /> == Chapter 17 ==<br /> == Chapter 18 ==<br /> == Chapter 19 ==<br /> == Chapter 20 ==<br /> == Chapter 21 ==<br /> == Chapter 22 ==<br /> == Chapter 23 ==<br /> 1. Describe the physiological changes of breast tissue with puberty, menstrual cycle, pregnancy and aging. <br /> 2. List and describe three disorders of breast development.<br /> 3. Describe the impact and limitations of self breast examination on breast cancer detection and death.<br /> 4. Describe the impact and limitations of screening mammography on breast cancer detection and death.<br /> 5. List three clinical symptoms of breast cancer and what is the associated rate of breast cancer associated with each.<br /> 6. What are the mammographic features which are suspicious for breast cancer?<br /> 7. List 6 benign inflammatory conditions which may mimic breast cancer and briefly describe each.<br /> 8. Define and give examples of non-proliferative breast changes.<br /> 9. What is a lactational adenoma and what is the increased risk of breast cancer associated with it?<br /> 10. What is flat epithelial atypia and what is the increased risk of breast cancer associated with it?<br /> 11. Categorize proliferative breast diseases and give several examples of each.<br /> 12. Define and describe gynecomastia.<br /> 13. Compare and contrast ADH and ALH. <br /> 14. What is the increased risk of breast cancer with proliferative breast disease (with and without atypia)?<br /> 15. What percentage of women with atypical hyperplasia develop breast cancer?<br /> 17. What are the three major biological subgroups of breast cancer, describe each and the classic patient. <br /> 18. Describe the ethnic variation in breast cancer incidence and type. <br /> 19. List and briefly describe 10 risk factors for breast cancer (which increase risk and which decrease risk?).<br /> 20. What are the clinical history features that would suggest a hereditary breast cancer?<br /> 21. What happens to patients in which a BRCA1 or BRCA2 gene is identified?<br /> 22. Compare BRCA1 and BRCA2 breast cancers.<br /> 23. List three other tumour suppressor genes that are found in breast cancer, and what is their normal function. <br /> 24. What is a driver mutation?<br /> 25. List the 6 most common driver mutations in breast cancer.<br /> <br /> == Chapter 24 ==<br /> == Chapter 25 ==<br /> == Chapter 26 ==<br /> == Chapter 27 ==<br /> == Chapter 28 ==<br /> == Chapter 29 ==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38292 2015-05-29T01:07:49Z

<p>Tate: </p> <hr /> <div>==Lecture 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|Which family members should have chromosomal analysis?|<br /> *1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and <br /> *2. all family members at risk of having a chromosome rearrangement.}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|<br /> *1. Advanced maternal age (Greater than 35 years old) <br /> *2. Previous pregnancy with chromosomal disorder<br /> *3. One parent is a known carrier (or other relative*)<br /> *4. Couples at risk of x-linked disorders for which a molecular test is not available<br /> *5. Fetal defects on ultrasound, <br /> *6. Prenatal screen high risk pregnancies<br /> *7. couples with 2+ spontaneous abortions <br /> *8. infertility. }}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|<br /> *1)Abortuses (missed abortions) of unknown reason, <br /> *2)Malformed stillbirths, <br /> *3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|<br /> *1)Suspicion of chromosomal mosaicism, <br /> *2) blood is not available (e.g. POC), <br /> *3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|<br /> *1) Geimsa / G-Banding, <br /> *2) Quinacrin / Q-banding <br /> *3) Reverse / R-banding, <br /> *4)Centromere / C-banding, <br /> *5)NOR staining (nucleolus organizer regions), <br /> *6)DAPI staining, <br /> *7) Chromosomal breakage, <br /> *8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|<br /> *1)FISH (flourescence in situ hybridization), <br /> *2) Multi-colour FISH, <br /> *3) SKY (spectral karyotyping), <br /> *4) CGH (comparative genomic hybridization), <br /> *5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|<br /> *1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), <br /> *2) Chromosome elongation Thymidine BrdU, <br /> *3) Metaphase arrest with Colcemide, <br /> *4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* <br /> *5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), <br /> *6) Slide making (chromosome spread with ideal temperature and humidity), <br /> *7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), <br /> *8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|<br /> *1. Chromosome number, <br /> *2) short or long arm, <br /> *3) region on that arm, <br /> *4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|<br /> *1)suspected classic chromosome syndrome, <br /> *2) Mental retardation of undetermined etiology, <br /> *3) dysmophic features, <br /> *4) multiple congenital abnormalities, <br /> *5) abnormalities of sexual development, <br /> *6) ambiguous genitalia, <br /> *7)pubertal failure, <br /> *8)abnormalities of growth, <br /> *9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.|Cultured cells are treated with Diepoxybutane, or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> <br /> ==Lecture 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|<br /> *Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), <br /> *Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?|<br /> *1) dysmophy<br /> *2) Visceral malformations, <br /> *3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|<br /> *1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), <br /> *2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|<br /> *1) Deletion, <br /> *2) Duplication, <br /> *3) Rearrangement (inversion or insertion), <br /> *4) Translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|<br /> *deletion<br /> *duplication<br /> *derivative chromsome<br /> *recombination chromosome<br /> *marker chromosome<br /> *ring chromosome<br /> *Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> <br /> ==Lecture 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|<br /> *1)Probes for repetitive sequences (Centromeres, telomeric sequences), <br /> *2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, <br /> *3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| <br /> *1) Microdeletion syndromes, <br /> *2) Characterization of chromosomal structural abnormalities, <br /> *3) identification of marker chromosomes, <br /> *4) Aneuploidy detection, <br /> *5) Cancer cytogenetics, <br /> *6) Gene mapping, <br /> *7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|<br /> *1) Trisomic rescue (loss of a chromosome from a trisomic zygote), <br /> *2) monosomic rescue (duplication of a chromosome from a monosomic zygote), <br /> *3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|<br /> *95% 22q11.2 deletion, 5% FISH negative; AD inherit; <br /> *1) Conotruncal heart defects, <br /> *2)uropathy, <br /> *3)polyhydramnios,<br /> *4)increased nuchal translucency, <br /> *5) IUGR, <br /> *6)thymic hypoplasia, <br /> *7) characteristic facies, <br /> *8) hypoparathyroidism, <br /> *9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|<br /> *1) translocations, <br /> *2) insertions, <br /> *3)marker chromosome identification, <br /> *4) cancer tumour genetics}}<br /> {{hidden|What are thelimitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Lecture 4==<br /> {{hidden|List 3 solid tumours for which cancer cytogenetics are currently used in prognosis and treatment.|<br /> *1. Lymphoma<br /> *2. Breast cancer<br /> *3. Bladder carcinoma}}<br /> {{hidden|What is a chromosomal instability syndrome?|There are several rare single gene syndromes in which there is a characteristic cytogenetic abnormality; affected individuals exhibit elevated rates of chromosome instability, leading to chromosomal rearrangements.}}<br /> {{hidden|What are the features of ataxia telangiectasia?|<br /> *1) AR inhertiance 1/40,000, ATM:11q22.3-q23.1<br /> *2) Cerebellar ataxia<br /> *3) Telangiectasia<br /> *4) Growth retardation<br /> *5) Immunodeficiency<br /> *6) Radiosensitivity *tx with conventional radiation doses, could be fatal<br /> *7) Cytogenetics: Chromosomal breakages, telomere instability, radiation sensitivity t(7;14)}}<br /> {{hidden|What is Nijmegen Breakage Syndrome?|<br /> *1. microcephaly<br /> *2. Bird like face<br /> *3. Radiosensitivity<br /> *4. rearrangements between 7 and 14, AR, rare NBS1(8q21.3)<br /> *5. sensitive to x-rays and bleomycin<br /> *6. Growth and mental retardation<br /> *7. Ovarian failure<br /> *8. Prone to b-cell lymphomas}}<br /> {{hidden|What is Bloom syndrome?|<br /> *AR inheritance, rare (1/160,000, BLM:15q26.1, SCE and quadrils<br /> * growth retartdation/ short stature<br /> * sun sensitivity / facial lesions<br /> *Ashkenazi jews}}<br /> {{hidden|What is Xeroderma pigmentosum?|}}<br /> {{hidden|What is Fanconi Anemia?|}}<br /> {{hidden|What is ICF Syndrome?|}}<br /> {{hidden|What is Roberts Syndrome?|}}<br /> {{hidden|What karytype is most at risk of gonadoblastoma?|}}<br /> {{hidden|What cancer are Kleinfelters patients at increased risk of?|}}<br /> {{hidden|What lymphoproliferative disorders are associated with Down's Syndrome?|}}<br /> {{hidden|<br /> <br /> == Lecture 5 ==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What are the steps in preparing a cytogenetics tissue specimen?|<br /> *1. Specimen received in flow medium and accessioned asap. <br /> *2. Specimen cut-up (+/- treated with collagenase), filtered /18G needle<br /> *3. Seeded into flask <br /> *4. Cultured at 37C 5% CO2 x 48hours<br /> *5. Flask flooded with 2ml of media<br /> *6. Cultured at 37C 5% CO@ x 2-10days<br /> *7. Trypsinize to coverslip when flask growth is confluent<br /> *8. Colcemid added to the coverslip x 30min (1/12 dilution)<br /> *9. Aspirate off colcemid <br /> *10. Add hypo (1/2 0.54 KCl, 1/2 0.75 NaCitrate) x 30 min<br /> *11. Add 2mL of fix (1/3 Methanol, 1/3 }}<br /> <br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> <br /> <br /> <br /> ==Peripheral Blood Culture and Harvest==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38291 2015-05-29T00:53:49Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|Which family members should have chromosomal analysis?|<br /> *1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and <br /> *2. all family members at risk of having a chromosome rearrangement.}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|<br /> *1. Advanced maternal age (Greater than 35 years old) <br /> *2. Previous pregnancy with chromosomal disorder<br /> *3. One parent is a known carrier (or other relative*)<br /> *4. Couples at risk of x-linked disorders for which a molecular test is not available<br /> *5. Fetal defects on ultrasound, <br /> *6. Prenatal screen high risk pregnancies<br /> *7. couples with 2+ spontaneous abortions <br /> *8. infertility. }}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|<br /> *1)Abortuses (missed abortions) of unknown reason, <br /> *2)Malformed stillbirths, <br /> *3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|<br /> *1)Suspicion of chromosomal mosaicism, <br /> *2) blood is not available (e.g. POC), <br /> *3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|<br /> *1) Geimsa / G-Banding, <br /> *2) Quinacrin / Q-banding <br /> *3) Reverse / R-banding, <br /> *4)Centromere / C-banding, <br /> *5)NOR staining (nucleolus organizer regions), <br /> *6)DAPI staining, <br /> *7) Chromosomal breakage, <br /> *8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|<br /> *1)FISH (flourescence in situ hybridization), <br /> *2) Multi-colour FISH, <br /> *3) SKY (spectral karyotyping), <br /> *4) CGH (comparative genomic hybridization), <br /> *5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|<br /> *1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), <br /> *2) Chromosome elongation Thymidine BrdU, <br /> *3) Metaphase arrest with Colcemide, <br /> *4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* <br /> *5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), <br /> *6) Slide making (chromosome spread with ideal temperature and humidity), <br /> *7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), <br /> *8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|<br /> *1. Chromosome number, <br /> *2) short or long arm, <br /> *3) region on that arm, <br /> *4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|<br /> *1)suspected classic chromosome syndrome, <br /> *2) Mental retardation of undetermined etiology, <br /> *3) dysmophic features, <br /> *4) multiple congenital abnormalities, <br /> *5) abnormalities of sexual development, <br /> *6) ambiguous genitalia, <br /> *7)pubertal failure, <br /> *8)abnormalities of growth, <br /> *9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.|Cultured cells are treated with Diepoxybutane, or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> <br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|<br /> *Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), <br /> *Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?|<br /> *1) dysmophy<br /> *2) Visceral malformations, <br /> *3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|<br /> *1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), <br /> *2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|<br /> *1) Deletion, <br /> *2) Duplication, <br /> *3) Rearrangement (inversion or insertion), <br /> *4) Translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|<br /> *deletion<br /> *duplication<br /> *derivative chromsome<br /> *recombination chromosome<br /> *marker chromosome<br /> *ring chromosome<br /> *Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> <br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|<br /> *1)Probes for repetitive sequences (Centromeres, telomeric sequences), <br /> *2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, <br /> *3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| <br /> *1) Microdeletion syndromes, <br /> *2) Characterization of chromosomal structural abnormalities, <br /> *3) identification of marker chromosomes, <br /> *4) Aneuploidy detection, <br /> *5) Cancer cytogenetics, <br /> *6) Gene mapping, <br /> *7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|<br /> *1) Trisomic rescue (loss of a chromosome from a trisomic zygote), <br /> *2) monosomic rescue (duplication of a chromosome from a monosomic zygote), <br /> *3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|<br /> *95% 22q11.2 deletion, 5% FISH negative; AD inherit; <br /> *1) Conotruncal heart defects, <br /> *2)uropathy, <br /> *3)polyhydramnios,<br /> *4)increased nuchal translucency, <br /> *5) IUGR, <br /> *6)thymic hypoplasia, <br /> *7) characteristic facies, <br /> *8) hypoparathyroidism, <br /> *9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|<br /> *1) translocations, <br /> *2) insertions, <br /> *3)marker chromosome identification, <br /> *4) cancer tumour genetics}}<br /> {{hidden|What are thelimitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> {{hidden|List 3 solid tumours for which cancer cytogenetics are currently used in prognosis and treatment.|<br /> *1. Lymphoma<br /> *2. Breast cancer<br /> *3. Bladder carcinoma}}<br /> {{hidden|What is a chromosomal instability syndrome?|There are several rare single gene syndromes in which there is a characteristic cytogenetic abnormality; affected individuals exhibit elevated rates of chromosome instability, leading to chromosomal rearrangements.}}<br /> {{hidden|What are the features of ataxia telangiectasia?|<br /> *1) AR inhertiance 1/40,000, ATM:11q22.3-q23.1<br /> *2) Cerebellar ataxia<br /> *3) Telangiectasia<br /> *4) Growth retardation<br /> *5) Immunodeficiency<br /> *6) Radiosensitivity *tx with conventional radiation doses, could be fatal<br /> *7) Cytogenetics: Chromosomal breakages, telomere instability, radiation sensitivity t(7;14)}}<br /> {{hidden|What is Nijmegen Breakage Syndrome?|}}<br /> {{hidden|What is Bloom syndrome?|}}<br /> {{hidden|What is Xeroderma pigmentosum?|}}<br /> {{hidden|What is Fanconi Anemia?|}}<br /> {{hidden|What is ICF Syndrome?|}}<br /> {{hidden|What is Roberts Syndrome?|}}<br /> {{hidden|What karytype is most at risk of gonadoblastoma?|}}<br /> {{hidden|What cancer are Kleinfelters patients at increased risk of?|}}<br /> {{hidden|What lymphoproliferative disorders are associated with Down's Syndrome?|}}<br /> {{hidden|<br /> <br /> ==Miscellaneous==<br /> {{hidden|What are the steps in preparing a cytogenetics tissue specimen?|<br /> *1. Specimen received in flow medium and accessioned asap. <br /> *2. Specimen cut-up (+/- treated with collagenase), filtered /18G needle<br /> *3. Seeded into flask <br /> *4. Cultured at 37C 5% CO2 x 48hours<br /> *5. Flask flooded with 2ml of media<br /> *6. Cultured at 37C 5% CO@ x 2-10days<br /> *7. Trypsinize to coverslip when flask growth is confluent<br /> *8. Colcemid added to the coverslip x 30min (1/12 dilution)<br /> *9. Aspirate off colcemid <br /> *10. Add hypo (1/2 0.54 KCl, 1/2 0.75 NaCitrate) x 30 min<br /> *11. Add 2mL of fix (1/3 Methanol, 1/3 }}<br /> <br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> === Unit 5 ==<br /> <br /> <br /> ==Peripheral Blood Culture and Harvest==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38260 2015-05-27T19:36:02Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|Which family members should have chromosomal analysis?|<br /> *1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and <br /> *2. all family members at risk of having a chromosome rearrangement.}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|<br /> *1. Advanced maternal age (Greater than 35 years old) <br /> *2. Previous pregnancy with chromosomal disorder<br /> *3. One parent is a known carrier (or other relative*)<br /> *4. Couples at risk of x-linked disorders for which a molecular test is not available<br /> *5. Fetal defects on ultrasound, <br /> *6. Prenatal screen high risk pregnancies<br /> *7. couples with 2+ spontaneous abortions <br /> *8. infertility. }}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|<br /> *1)Abortuses (missed abortions) of unknown reason, <br /> *2)Malformed stillbirths, <br /> *3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|<br /> *1)Suspicion of chromosomal mosaicism, <br /> *2) blood is not available (e.g. POC), <br /> *3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|<br /> *1) Geimsa / G-Banding, <br /> *2) Quinacrin / Q-banding <br /> *3) Reverse / R-banding, <br /> *4)Centromere / C-banding, <br /> *5)NOR staining (nucleolus organizer regions), <br /> *6)DAPI staining, <br /> *7) Chromosomal breakage, <br /> *8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|<br /> *1)FISH (flourescence in situ hybridization), <br /> *2) Multi-colour FISH, <br /> *3) SKY (spectral karyotyping), <br /> *4) CGH (comparative genomic hybridization), <br /> *5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|<br /> *1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), <br /> *2) Chromosome elongation Thymidine BrdU, <br /> *3) Metaphase arrest with Colcemide, <br /> *4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* <br /> *5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), <br /> *6) Slide making (chromosome spread with ideal temperature and humidity), <br /> *7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), <br /> *8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|<br /> *1. Chromosome number, <br /> *2) short or long arm, <br /> *3) region on that arm, <br /> *4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|<br /> *1)suspected classic chromosome syndrome, <br /> *2) Mental retardation of undetermined etiology, <br /> *3) dysmophic features, <br /> *4) multiple congenital abnormalities, <br /> *5) abnormalities of sexual development, <br /> *6) ambiguous genitalia, <br /> *7)pubertal failure, <br /> *8)abnormalities of growth, <br /> *9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> <br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|<br /> *Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), <br /> *Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?|<br /> *1) dysmophy<br /> *2) Visceral malformations, <br /> *3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|<br /> *1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), <br /> *2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|<br /> *1) Deletion, <br /> *2) Duplication, <br /> *3) Rearrangement (inversion or insertion), <br /> *4) Translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|<br /> *deletion<br /> *duplication<br /> *derivative chromsome<br /> *recombination chromosome<br /> *marker chromosome<br /> *ring chromosome<br /> *Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> <br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|<br /> *1)Probes for repetitive sequences (Centromeres, telomeric sequences), <br /> *2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, <br /> *3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| <br /> *1) Microdeletion syndromes, <br /> *2) Characterization of chromosomal structural abnormalities, <br /> *3) identification of marker chromosomes, <br /> *4) Aneuploidy detection, <br /> *5) Cancer cytogenetics, <br /> *6) Gene mapping, <br /> *7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|<br /> *1) Trisomic rescue (loss of a chromosome from a trisomic zygote), <br /> *2) monosomic rescue (duplication of a chromosome from a monosomic zygote), <br /> *3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|<br /> *95% 22q11.2 deletion, 5% FISH negative; AD inherit; <br /> *1) Conotruncal heart defects, <br /> *2)uropathy, <br /> *3)polyhydramnios,<br /> *4)increased nuchal translucency, <br /> *5) IUGR, <br /> *6)thymic hypoplasia, <br /> *7) characteristic facies, <br /> *8) hypoparathyroidism, <br /> *9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|<br /> *1) translocations, <br /> *2) insertions, <br /> *3)marker chromosome identification, <br /> *4) cancer tumour genetics}}<br /> {{hidden|What are thelimitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> {{hidden|List 3 solid tumours for which cancer cytogenetics are currently used in prognosis and treatment.|<br /> *1. Lymphoma<br /> *2. Breast cancer<br /> *3. Bladder carcinoma}}<br /> {{hidden|What is a chromosomal instability syndrome?| There are several rare single-gene syndromes in which there is a characteristic cytogenetic abnormality; affected individuals exhibit elevated rates of chromosome instability, leading to chromosomal rearrangements.}}<br /> {{hidden|What are the features of ataxia telangiectasia?|<br /> *1) AR inhertiance 1/40,000, ATM:11q22.3-q23.1<br /> *2) Cerebellar ataxia<br /> *3) Telangiectasia<br /> *4) Growth retardation<br /> *5) Immunodeficiency<br /> *6) Radiosensitivity *tx with conventional radiation doses, could be fatal<br /> *7) Cytogenetics: Chromosomal breakages, telomere instability, radiation sensitivity t(7;14)}}<br /> {{hidden|What is Nijmegen Breakage Syndrome?|}}<br /> {{hidden|What is Bloom syndrome?|}}<br /> {{hidden|What is Xeroderma pigmentosum?|}}<br /> {{hidden|What is Fanconi Anemia?|}}<br /> {{hidden|What is ICF Syndrome?|}}<br /> {{hidden|What is Roberts Syndrome?|}}<br /> {{hidden|What karytype is most at risk of gonadoblastoma?|}}<br /> {{hidden|What cancer are Kleinfelters patients at increased risk of?|}}<br /> {{hidden|What lymphoproliferative disorders are associated with Down's Syndrome?|}}<br /> {{hidden|<br /> <br /> ==Miscellaneous==<br /> {{hidden|What are the steps in preparing a cytogenetics tissue specimen?|<br /> *1. Specimen received in flow medium and accessioned asap. <br /> *2. Specimen cut-up (+/- treated with collagenase), filtered /18G needle<br /> *3. Seeded into flask <br /> *4. Cultured at 37C 5% CO2 x 48hours<br /> *5. Flask flooded with 2ml of media<br /> *6. Cultured at 37C 5% CO@ x 2-10days<br /> *7. Trypsinize to coverslip when flask growth is confluent<br /> *8. Colcemid added to the coverslip x 30min (1/12 dilution)<br /> *9. Aspirate off colcemid <br /> *10. Add hypo (1/2 0.54 KCl, 1/2 0.75 NaCitrate) x 30 min<br /> *11. Add 2mL of fix (1/3 Methanol, 1/3 <br /> <br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> === Unit 5 ==<br /> <br /> <br /> ==Peripheral Blood Culture and Harvest==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38242 2015-05-27T15:36:18Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|Which family members should have chromosomal analysis?|<br /> *1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and <br /> *2. all family members at risk of having a chromosome rearrangement.}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|<br /> *1. Advanced maternal age (Greater than 35 years old) <br /> *2. Previous pregnancy with chromosomal disorder<br /> *3. One parent is a known carrier (or other relative*)<br /> *4. Couples at risk of x-linked disorders for which a molecular test is not available<br /> *5. Fetal defects on ultrasound, <br /> *6. Prenatal screen high risk pregnancies<br /> *7. couples with 2+ spontaneous abortions <br /> *8. infertility. }}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|<br /> *1)Abortuses (missed abortions) of unknown reason, <br /> *2)Malformed stillbirths, <br /> *3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|<br /> *1)Suspicion of chromosomal mosaicism, <br /> *2) blood is not available (e.g. POC), <br /> *3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|<br /> *1) Geimsa / G-Banding, <br /> *2) Quinacrin / Q-banding <br /> *3) Reverse / R-banding, <br /> *4)Centromere / C-banding, <br /> *5)NOR staining (nucleolus organizer regions), <br /> *6)DAPI staining, <br /> *7) Chromosomal breakage, <br /> *8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|<br /> *1)FISH (flourescence in situ hybridization), <br /> *2) Multi-colour FISH, <br /> *3) SKY (spectral karyotyping), <br /> *4) CGH (comparative genomic hybridization), <br /> *5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|<br /> *1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), <br /> *2) Chromosome elongation Thymidine BrdU, <br /> *3) Metaphase arrest with Colcemide, <br /> *4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* <br /> *5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), <br /> *6) Slide making (chromosome spread with ideal temperature and humidity), <br /> *7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), <br /> *8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|<br /> *1. Chromosome number, <br /> *2) short or long arm, <br /> *3) region on that arm, <br /> *4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|<br /> *1)suspected classic chromosome syndrome, <br /> *2) Mental retardation of undetermined etiology, <br /> *3) dysmophic features, <br /> *4) multiple congenital abnormalities, <br /> *5) abnormalities of sexual development, <br /> *6) ambiguous genitalia, <br /> *7)pubertal failure, <br /> *8)abnormalities of growth, <br /> *9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> <br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|<br /> *Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), <br /> *Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?|<br /> *1) dysmophy<br /> *2) Visceral malformations, <br /> *3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|<br /> *1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), <br /> *2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|<br /> *1) Deletion, <br /> *2) Duplication, <br /> *3) Rearrangement (inversion or insertion), <br /> *4) Translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|<br /> *deletion<br /> *duplication<br /> *derivative chromsome<br /> *recombination chromosome<br /> *marker chromosome<br /> *ring chromosome<br /> *Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> <br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|<br /> *1)Probes for repetitive sequences (Centromeres, telomeric sequences), <br /> *2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, <br /> *3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| <br /> *1) Microdeletion syndromes, <br /> *2) Characterization of chromosomal structural abnormalities, <br /> *3) identification of marker chromosomes, <br /> *4) Aneuploidy detection, <br /> *5) Cancer cytogenetics, <br /> *6) Gene mapping, <br /> *7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|<br /> *1) Trisomic rescue (loss of a chromosome from a trisomic zygote), <br /> *2) monosomic rescue (duplication of a chromosome from a monosomic zygote), <br /> *3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|<br /> *95% 22q11.2 deletion, 5% FISH negative; AD inherit; <br /> *1) Conotruncal heart defects, <br /> *2)uropathy, <br /> *3)polyhydramnios,<br /> *4)increased nuchal translucency, <br /> *5) IUGR, <br /> *6)thymic hypoplasia, <br /> *7) characteristic facies, <br /> *8) hypoparathyroidism, <br /> *9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|<br /> *1) translocations, <br /> *2) insertions, <br /> *3)marker chromosome identification, <br /> *4) cancer tumour genetics}}<br /> {{hidden|What are thelimitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> === Unit 5 ==<br /> <br /> <br /> ==Peripheral Blood Culture and Harvest==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38241 2015-05-27T15:35:44Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|Which family members should have chromosomal analysis?|<br /> *1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and <br /> *2. all family members at risk of having a chromosome rearrangement.}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|<br /> *1. Advanced maternal age (Greater than 35 years old) <br /> *2. Previous pregnancy with chromosomal disorder<br /> *3. One parent is a known carrier (or other relative*)<br /> *4. Couples at risk of x-linked disorders for which a molecular test is not available<br /> *5. Fetal defects on ultrasound, <br /> *6. Prenatal screen high risk pregnancies<br /> *7. couples with 2+ spontaneous abortions <br /> *8. infertility. }}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|<br /> *1)Abortuses (missed abortions) of unknown reason, <br /> *2)Malformed stillbirths, <br /> *3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|<br /> *1)Suspicion of chromosomal mosaicism, <br /> *2) blood is not available (e.g. POC), <br /> *3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|<br /> *1) Geimsa / G-Banding, <br /> *2) Quinacrin / Q-banding <br /> *3) Reverse / R-banding, <br /> *4)Centromere / C-banding, <br /> *5)NOR staining (nucleolus organizer regions), <br /> *6)DAPI staining, <br /> *7) Chromosomal breakage, <br /> *8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|<br /> *1)FISH (flourescence in situ hybridization), <br /> *2) Multi-colour FISH, <br /> *3) SKY (spectral karyotyping), <br /> *4) CGH (comparative genomic hybridization), <br /> *5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|<br /> *1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), <br /> *2) Chromosome elongation Thymidine BrdU, <br /> *3) Metaphase arrest with Colcemide, <br /> *4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* <br /> *5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), <br /> *6) Slide making (chromosome spread with ideal temperature and humidity), <br /> *7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), <br /> *8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|<br /> *1. Chromosome number, <br /> *2) short or long arm, <br /> *3) region on that arm, <br /> *4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|<br /> *1)suspected classic chromosome syndrome, <br /> *2) Mental retardation of undetermined etiology, <br /> *3) dysmophic features, <br /> *4) multiple congenital abnormalities, <br /> *5) abnormalities of sexual development, <br /> *6) ambiguous genitalia, <br /> *7)pubertal failure, <br /> *8)abnormalities of growth, <br /> *9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> <br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|<br /> *Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), <br /> *Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?<br /> *1) dysmophy, <br /> *2) Visceral malformations, <br /> *3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|<br /> *1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), <br /> *2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|<br /> *1) Deletion, <br /> *2) Duplication, <br /> *3) Rearrangement (inversion or insertion), <br /> *4) Translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|<br /> *deletion<br /> *duplication<br /> *derivative chromsome<br /> *recombination chromosome<br /> *marker chromosome<br /> *ring chromosome<br /> *Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> <br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|<br /> *1)Probes for repetitive sequences (Centromeres, telomeric sequences), <br /> *2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, <br /> *3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| <br /> *1) Microdeletion syndromes, <br /> *2) Characterization of chromosomal structural abnormalities, <br /> *3) identification of marker chromosomes, <br /> *4) Aneuploidy detection, <br /> *5) Cancer cytogenetics, <br /> *6) Gene mapping, <br /> *7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|<br /> *1) Trisomic rescue (loss of a chromosome from a trisomic zygote), <br /> *2) monosomic rescue (duplication of a chromosome from a monosomic zygote), <br /> *3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|<br /> *95% 22q11.2 deletion, 5% FISH negative; AD inherit; <br /> *1) Conotruncal heart defects, <br /> *2)uropathy, <br /> *3)polyhydramnios,<br /> *4)increased nuchal translucency, <br /> *5) IUGR, <br /> *6)thymic hypoplasia, <br /> *7) characteristic facies, <br /> *8) hypoparathyroidism, <br /> *9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|<br /> *1) translocations, <br /> *2) insertions, <br /> *3)marker chromosome identification, <br /> *4) cancer tumour genetics}}<br /> {{hidden|What are thelimitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> === Unit 5 ==<br /> <br /> <br /> ==Peripheral Blood Culture and Harvest==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38240 2015-05-27T15:34:21Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|Which family members should have chromosomal analysis?|<br /> *1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and <br /> *2. all family members at risk of having a chromosome rearrangement.}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|<br /> *1. Advanced maternal age (Greater than 35 years old) <br /> *2. Previous pregnancy with chromosomal disorder<br /> *3. One parent is a known carrier (or other relative*)<br /> *4. Couples at risk of x-linked disorders for which a molecular test is not available<br /> *5. Fetal defects on ultrasound, <br /> *6. Prenatal screen high risk pregnancies<br /> *7. couples with 2+ spontaneous abortions <br /> *8. infertility. }}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|<br /> *1)Abortuses (missed abortions) of unknown reason, <br /> *2)Malformed stillbirths, <br /> *3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|<br /> *1)Suspicion of chromosomal mosaicism, <br /> *2) blood is not available (e.g. POC), <br /> *3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|<br /> *1) Geimsa / G-Banding, <br /> *2) Quinacrin / Q-banding <br /> *3) Reverse / R-banding, <br /> *4)Centromere / C-banding, <br /> *5)NOR staining (nucleolus organizer regions), <br /> *6)DAPI staining, <br /> *7) Chromosomal breakage, <br /> *8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|<br /> *1)FISH (flourescence in situ hybridization), <br /> *2) Multi-colour FISH, <br /> *3) SKY (spectral karyotyping), <br /> *4) CGH (comparative genomic hybridization), <br /> *5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|<br /> *1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), <br /> *2) Chromosome elongation Thymidine BrdU, <br /> *3) Metaphase arrest with Colcemide, <br /> *4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* <br /> *5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), <br /> *6) Slide making (chromosome spread with ideal temperature and humidity), <br /> *7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), <br /> *8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|<br /> *1. Chromosome number, <br /> *2) short or long arm, <br /> *3) region on that arm, <br /> *4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|<br /> *1)suspected classic chromosome syndrome, <br /> *2) Mental retardation of undetermined etiology, <br /> *3) dysmophic features, <br /> *4) multiple congenital abnormalities, <br /> *5) abnormalities of sexual development, <br /> *6) ambiguous genitalia, <br /> *7)pubertal failure, <br /> *8)abnormalities of growth, <br /> *9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constitutive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright fluorescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> <br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|<br /> *Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), <br /> *Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]<br /> *1) dysmophy, <br /> *2) Visceral malformations, <br /> *3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|<br /> *1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), <br /> *2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|<br /> *1) Deletion, <br /> *2) Duplication, <br /> *3) Rearrangement (inversion or insertion), <br /> *4) Translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|<br /> *deletion<br /> *duplication<br /> *derivative chromsome<br /> *recombination chromosome<br /> *marker chromosome<br /> *ring chromosome<br /> *Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|<br /> *1)Probes for repetitive sequences (Centromeres, telomeric sequences), <br /> *2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, <br /> *3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| <br /> *1) Microdeletion syndromes, <br /> *2) Characterization of chromosomal structural abnormalities, <br /> *3) identification of marker chromosomes, <br /> *4) Aneuploidy detection, <br /> *5) Cancer cytogenetics, <br /> *6) Gene mapping, <br /> *7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|<br /> *1) Trisomic rescue (loss of a chromosome from a trisomic zygote), <br /> *2) monosomic rescue (duplication of a chromosome from a monosomic zygote), <br /> *3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|<br /> *95% 22q11.2 deletion, 5% FISH negative; AD inherit; <br /> *1) Conotruncal heart defects, <br /> *2)uropathy, <br /> *3)polyhydramnios,<br /> *4)increased nuchal translucency, <br /> *5) IUGR, <br /> *6)thymic hypoplasia, <br /> *7) characteristic facies, <br /> *8) hypoparathyroidism, <br /> *9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|<br /> *1) translocations, <br /> *2) insertions, <br /> *3)marker chromosome identification, <br /> *4) cancer tumour genetics}}<br /> {{hidden|What are thelimitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> === Unit 5 ==<br /> <br /> <br /> ==Peripheral Blood Culture and Harvest==</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38229 2015-05-27T14:56:35Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden| List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> <br /> {{hidden|Which family members should have chromosomal analysis?|1. Both parents of a child with structural chromosome rearrangement, deletion, duplication, and 2. all family members at risk of having a chromosome rearrangement.}}<br /> <br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|1. Advanced maternal age (&gt;=35yo), 2. Previous pregnancy with chromosomal disorder, 3. One parent is a known carrier (or other relative*), 4. Couples at risk of x-linked disorders for which a molecular test is not available, 5. Fetal defects on ultrasound, 6. Prenatal screen high risk pregnancies, 7. couples with 2+ spontaneous abortions, 8. infertility.}}<br /> <br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|1)Abortuses (missed abortions) of unknown reason, 2)Malformed stillbirths, 3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|1)Suspicion of chromosomal mosaicism, 2) blood is not available (e.g. POC), 3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|1) Geimsa / G-Banding, 2) Quinacrin / Q-banding 3) Reverse / R-banding, 4)Centromere / C-banding, 5)NOR staining (nucleolus organizer regions), 6)DAPI staining, 7) Chromosomal breakage, 8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|1)FISH (flourescence in situ hybridization), 2) Multi-colour FISH, 3) SKY (spectral karyotyping), 4) CGH (comparative genomic hybridization), 5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), 2) Chromosome elongation Thymidine BrdU, 3) Metaphase arrest with Colcemide, 4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* 5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), 6) Slide making (chromosome spread with ideal temperature and humidity), 7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), 8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|1. Chromosome number, 2) short or long arm, 3) region on that arm, 4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|1)suspected classic chromosome syndrome, 2) Mental retardation of undetermined etiology, 3) dysmophic features, 4) multiple congenital abnormalities, 5) abnormalities of sexual development, 6) ambiguous genitalia, 7)pubertal failure, 8)abnormalities of growth, 9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constituitive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright flourescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|1) Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]1) dysmophy, 2) Visceral malformations, 3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), 2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|1) Deletion, 2) duplication, 3) rearrangement (inversion or insertion), 4) translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|deletion, duplication, derivative chromsome, recombination chromosome, marker chromosome, ring chromosome, Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|1)Probes for repetative sequences (Centromeres, telomeric sequences), 2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, 3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| 1) Microdeletion syndromes, 2) Characterization of chromosomal structural abnormalities, 3) identification of marker chromosomes, 4) Aneuploidy detection, 5) Cancer cytogenetics, 6) Gene mapping, 7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|1) Trisomic rescue (loss of a chromosome from a trisomic zygote), 2) monosomic rescue (duplication of a chromosome from a monosomic zygote), 3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|95% 22q11.2 deletion, 5% FISH negative; AD inherit; 1) Conotruncal heart defects, 2)uropathy, 3)polyhydramnios,4)increased nuchal translucency, 5) IUGR, 6)thymic hypoplasia, 7) characteristic facies, 8) hypoparathyroidism, 9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|1) translocations, 2) insertions, 3)marker chromosome identification, 4) cancer tumour genetics}}<br /> {{hidden|What are three limitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> ==Peripheral Blood Culture and Harvest==<br /> {{hidden|<br /> {{hidden|</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38228 2015-05-27T14:53:23Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden|List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|1. Advanced maternal age (&gt;=35yo), 2. Previous pregnancy with chromosomal disorder, 3. One parent is a known carrier (or other relative*), 4. Couples at risk of x-linked disorders for which a molecular test is not available, 5. Fetal defects on ultrasound, 6. Prenatal screen high risk pregnancies, 7. couples with 2+ spontaneous abortions, 8. infertility}}<br /> {{hidden|Which family members should have chromosomal analysis?|Both parents of a child with structural chromosome rearrangement, deletion, duplication 2) all family members at risk of having a chromosome rearrangement}}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|1)Abortuses (missed abortions) of unknown reason, 2)Malformed stillbirths, 3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|1)Suspicion of chromosomal mosaicism, 2) blood is not available (e.g. POC), 3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|1) Geimsa / G-Banding, 2) Quinacrin / Q-banding 3) Reverse / R-banding, 4)Centromere / C-banding, 5)NOR staining (nucleolus organizer regions), 6)DAPI staining, 7) Chromosomal breakage, 8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|1)FISH (flourescence in situ hybridization), 2) Multi-colour FISH, 3) SKY (spectral karyotyping), 4) CGH (comparative genomic hybridization), 5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), 2) Chromosome elongation Thymidine BrdU, 3) Metaphase arrest with Colcemide, 4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* 5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), 6) Slide making (chromosome spread with ideal temperature and humidity), 7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), 8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|1. Chromosome number, 2) short or long arm, 3) region on that arm, 4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|1)suspected classic chromosome syndrome, 2) Mental retardation of undetermined etiology, 3) dysmophic features, 4) multiple congenital abnormalities, 5) abnormalities of sexual development, 6) ambiguous genitalia, 7)pubertal failure, 8)abnormalities of growth, 9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constituitive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright flourescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|1) Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]1) dysmophy, 2) Visceral malformations, 3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), 2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|1) Deletion, 2) duplication, 3) rearrangement (inversion or insertion), 4) translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|deletion, duplication, derivative chromsome, recombination chromosome, marker chromosome, ring chromosome, Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|1)Probes for repetative sequences (Centromeres, telomeric sequences), 2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, 3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| 1) Microdeletion syndromes, 2) Characterization of chromosomal structural abnormalities, 3) identification of marker chromosomes, 4) Aneuploidy detection, 5) Cancer cytogenetics, 6) Gene mapping, 7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|1) Trisomic rescue (loss of a chromosome from a trisomic zygote), 2) monosomic rescue (duplication of a chromosome from a monosomic zygote), 3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|95% 22q11.2 deletion, 5% FISH negative; AD inherit; 1) Conotruncal heart defects, 2)uropathy, 3)polyhydramnios,4)increased nuchal translucency, 5) IUGR, 6)thymic hypoplasia, 7) characteristic facies, 8) hypoparathyroidism, 9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|1) translocations, 2) insertions, 3)marker chromosome identification, 4) cancer tumour genetics}}<br /> {{hidden|What are three limitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> ==Peripheral Blood Culture and Harvest==<br /> {{hidden|<br /> {{hidden|</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38222 2015-05-22T18:13:27Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden|List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|1) Advanced maternal age (&gt;=35yo), 2) Previous pregnancy with chromosomal disorder, 3)one parent is a known carrier (or other relative*), 4)couples at risk of x-linked disorders for which a molecular test is not available, 5) fetal defects on ultrasound, 6)prenatal screen high risk pregnancies, 7) couples with 2+ spontaneous abortions, 8) infertility}}<br /> {{hidden|Which family members should have chromosomal analysis?|Both parents of a child with structural chromosome rearrangement, deletion, duplication 2) all family members at risk of having a chromosome rearrangement}}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|1)Abortuses (missed abortions) of unknown reason, 2)Malformed stillbirths, 3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|1)Suspicion of chromosomal mosaicism, 2) blood is not available (e.g. POC), 3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|1) Geimsa / G-Banding, 2) Quinacrin / Q-banding 3) Reverse / R-banding, 4)Centromere / C-banding, 5)NOR staining (nucleolus organizer regions), 6)DAPI staining, 7) Chromosomal breakage, 8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|1)FISH (flourescence in situ hybridization), 2) Multi-colour FISH, 3) SKY (spectral karyotyping), 4) CGH (comparative genomic hybridization), 5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), 2) Chromosome elongation Thymidine BrdU, 3) Metaphase arrest with Colcemide, 4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* 5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), 6) Slide making (chromosome spread with ideal temperature and humidity), 7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), 8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|1. Chromosome number, 2) short or long arm, 3) region on that arm, 4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|1)suspected classic chromosome syndrome, 2) Mental retardation of undetermined etiology, 3) dysmophic features, 4) multiple congenital abnormalities, 5) abnormalities of sexual development, 6) ambiguous genitalia, 7)pubertal failure, 8)abnormalities of growth, 9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constituitive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright flourescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|1) Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]1) dysmophy, 2) Visceral malformations, 3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), 2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|1) Deletion, 2) duplication, 3) rearrangement (inversion or insertion), 4) translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|deletion, duplication, derivative chromsome, recombination chromosome, marker chromosome, ring chromosome, Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|1)Probes for repetative sequences (Centromeres, telomeric sequences), 2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, 3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| 1) Microdeletion syndromes, 2) Characterization of chromosomal structural abnormalities, 3) identification of marker chromosomes, 4) Aneuploidy detection, 5) Cancer cytogenetics, 6) Gene mapping, 7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|1) Trisomic rescue (loss of a chromosome from a trisomic zygote), 2) monosomic rescue (duplication of a chromosome from a monosomic zygote), 3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|Features: hypotonia, obesity, developmental delay, hypogonadism, short stature, 70%: del(15q11-13), 25% uniparental disomy, 2%:other, diagnoses by FISH for microdeletion, or DNA methylation; due to absence of paternally derived PWS/AS gene }}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Describe DeGeorge Syndrome.|95% 22q11.2 deletion, 5% FISH negative; AD inherit; 1) Conotruncal heart defects, 2)uropathy, 3)polyhydramnios,4)increased nuchal translucency, 5) IUGR, 6)thymic hypoplasia, 7) characteristic facies, 8) hypoparathyroidism, 9)MR/DD}}<br /> {{hidden|What is SKY?|A chromosomal analysis technique that has the ability to paint each pair of chromosomes and the sex chromosomes a different flourescing colour.}}<br /> {{hidden|What kinds of chromosomal transformations is SKY used for?|1) translocations, 2) insertions, 3)marker chromosome identification, 4) cancer tumour genetics}}<br /> {{hidden|What are three limitations of SKY?|1) cannot detect del,dup,inv, 2) interpretation difficult if colours too similar}}<br /> {{hidden|Explain the basic principle of Comparative Genomic Hybridization.|References genomes and the index genome are mixed, if the index genome substantially differs from the reference genome then there will be a neg signal loss or gain for that probe's flourescence, this can be used to determine if there is one allele in the index case that is missing or in excess compared to the reference genome.}}<br /> {{hidden|How do CGH arrays work?|CGH arrays allow hundreds-thousands of probes to be used to compare the index and the reference genome, giving a complete chromosomal analysis that depends on the resolution of the probe.}}<br /> <br /> ==Unit 4==<br /> <br /> ==Miscellaneous==<br /> {{hidden|What is Allerdice or Sandy Point Syndrome?|It is a chromosomal disorder discovered in Sandy Point, NL by Dr. Penny Allderdice, inv(3)(p25q21) characterized by affected offspring with multiple congenital anomalies with surviving children exhibiting severe growth and developmental delays.}}<br /> {{hidden|What is the most common robertsonian translocation?|Translocation between the long arms of 13 and 14.}}<br /> {{hidden|What is the most common non-robertsonian translocation?|t(11;22)(q23;q11)}}<br /> {{hidden|What is a marker chromosome?|A structurally abnormal chromosome in which no part can be identified cytogenetically.}}<br /> {{hidden|What is the most common chromosomal abnormality in humans?|Aneuploidy - about 5% of pregnancies.}}<br /> {{hidden|What is the most common cause of triploidy?|Dispermy in 60%}}<br /> {{hidden|What is the recurrence risk for parents of Down's syndrome child with a &quot;free chromosome&quot;?|1%}}<br /> {{hidden|List 5 features of Trisomy 8.|}}<br /> {{hidden|List 5 features of Trisomy 9.|}}<br /> {{hidden|List 5 features of Trisomy 13.|}}<br /> {{hidden|List 5 features of Trisomy 14.|}}<br /> {{hidden|List 5 features of Trisomy 18.|}}<br /> {{hidden|List 5 features of Trisomy 21.|}}<br /> {{hidden|What is the most common outcome of a pregnancy when the parent has a balanced translocation?|Misscarriage}}<br /> <br /> ==Peripheral Blood Culture and Harvest==<br /> {{hidden|<br /> {{hidden|</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38221 2015-05-22T16:37:39Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden|List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|1) Advanced maternal age (&gt;=35yo), 2) Previous pregnancy with chromosomal disorder, 3)one parent is a known carrier (or other relative*), 4)couples at risk of x-linked disorders for which a molecular test is not available, 5) fetal defects on ultrasound, 6)prenatal screen high risk pregnancies, 7) couples with 2+ spontaneous abortions, 8) infertility}}<br /> {{hidden|Which family members should have chromosomal analysis?|Both parents of a child with structural chromosome rearrangement, deletion, duplication 2) all family members at risk of having a chromosome rearrangement}}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|1)Abortuses (missed abortions) of unknown reason, 2)Malformed stillbirths, 3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|1)Suspicion of chromosomal mosaicism, 2) blood is not available (e.g. POC), 3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|1) Geimsa / G-Banding, 2) Quinacrin / Q-banding 3) Reverse / R-banding, 4)Centromere / C-banding, 5)NOR staining (nucleolus organizer regions), 6)DAPI staining, 7) Chromosomal breakage, 8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|1)FISH (flourescence in situ hybridization), 2) Multi-colour FISH, 3) SKY (spectral karyotyping), 4) CGH (comparative genomic hybridization), 5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), 2) Chromosome elongation Thymidine BrdU, 3) Metaphase arrest with Colcemide, 4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* 5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), 6) Slide making (chromosome spread with ideal temperature and humidity), 7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), 8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|1. Chromosome number, 2) short or long arm, 3) region on that arm, 4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|1)suspected classic chromosome syndrome, 2) Mental retardation of undetermined etiology, 3) dysmophic features, 4) multiple congenital abnormalities, 5) abnormalities of sexual development, 6) ambiguous genitalia, 7)pubertal failure, 8)abnormalities of growth, 9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constituitive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright flourescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|1) Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]1) dysmophy, 2) Visceral malformations, 3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), 2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|1) Deletion, 2) duplication, 3) rearrangement (inversion or insertion), 4) translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|deletion, duplication, derivative chromsome, recombination chromosome, marker chromosome, ring chromosome, Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|1)Probes for repetative sequences (Centromeres, telomeric sequences), 2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, 3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| 1) Microdeletion syndromes, 2) Characterization of chromosomal structural abnormalities, 3) identification of marker chromosomes, 4) Aneuploidy detection, 5) Cancer cytogenetics, 6) Gene mapping, 7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Cri-du Chat Syndrome|}}<br /> {{hidden|Describe 3 mechanisms by which uniparental disomy occurs.|1) Trisomic rescue (loss of a chromosome from a trisomic zygote), 2) monosomic rescue (duplication of a chromosome from a monosomic zygote), 3)Gamete complementation (fertilization of a gamete with two copies of a chromosome with no copies from other parent)}}<br /> {{hidden|What is imprinting?|Normally we inherit one copy of each gene from each parent, some genes are only expressed when they are inherited paternally, some only when maternally, this differential expression based on inheritance is called imprinting, and changes generation to generation.}}<br /> {{hidden|Which chromosomes are known to have imprinted genes?|Chromosomes 6,7,11,14,and 15.}}<br /> {{hidden|Describe Prader-Willi Syndrome.|<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38220 2015-05-22T16:29:56Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden|List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|1) Advanced maternal age (&gt;=35yo), 2) Previous pregnancy with chromosomal disorder, 3)one parent is a known carrier (or other relative*), 4)couples at risk of x-linked disorders for which a molecular test is not available, 5) fetal defects on ultrasound, 6)prenatal screen high risk pregnancies, 7) couples with 2+ spontaneous abortions, 8) infertility}}<br /> {{hidden|Which family members should have chromosomal analysis?|Both parents of a child with structural chromosome rearrangement, deletion, duplication 2) all family members at risk of having a chromosome rearrangement}}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|1)Abortuses (missed abortions) of unknown reason, 2)Malformed stillbirths, 3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|1)Suspicion of chromosomal mosaicism, 2) blood is not available (e.g. POC), 3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|1) Geimsa / G-Banding, 2) Quinacrin / Q-banding 3) Reverse / R-banding, 4)Centromere / C-banding, 5)NOR staining (nucleolus organizer regions), 6)DAPI staining, 7) Chromosomal breakage, 8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|1)FISH (flourescence in situ hybridization), 2) Multi-colour FISH, 3) SKY (spectral karyotyping), 4) CGH (comparative genomic hybridization), 5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), 2) Chromosome elongation Thymidine BrdU, 3) Metaphase arrest with Colcemide, 4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* 5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), 6) Slide making (chromosome spread with ideal temperature and humidity), 7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), 8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|1. Chromosome number, 2) short or long arm, 3) region on that arm, 4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|1)suspected classic chromosome syndrome, 2) Mental retardation of undetermined etiology, 3) dysmophic features, 4) multiple congenital abnormalities, 5) abnormalities of sexual development, 6) ambiguous genitalia, 7)pubertal failure, 8)abnormalities of growth, 9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constituitive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright flourescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|1) Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]1) dysmophy, 2) Visceral malformations, 3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), 2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|1) Deletion, 2) duplication, 3) rearrangement (inversion or insertion), 4) translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|deletion, duplication, derivative chromsome, recombination chromosome, marker chromosome, ring chromosome, Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|1)Probes for repetative sequences (Centromeres, telomeric sequences), 2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, 3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| 1) Microdeletion syndromes, 2) Characterization of chromosomal structural abnormalities, 3) identification of marker chromosomes, 4) Aneuploidy detection, 5) Cancer cytogenetics, 6) Gene mapping, 7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}</div>

Tate https://librepathology.org/w/index.php?title=Cytogenetics_Review_Questions&diff=38219 2015-05-22T16:29:19Z

<p>Tate: </p> <hr /> <div>==Unit 1==<br /> {{hidden|List the three broad categories of clinical indications for chromosomal analysis.|Prenatal, Constitutional, Cancer/Acquired}}<br /> {{hidden|List 5 prenatal indications for cytogenetics analysis.|1) Advanced maternal age (&gt;=35yo), 2) Previous pregnancy with chromosomal disorder, 3)one parent is a known carrier (or other relative*), 4)couples at risk of x-linked disorders for which a molecular test is not available, 5) fetal defects on ultrasound, 6)prenatal screen high risk pregnancies, 7) couples with 2+ spontaneous abortions, 8) infertility}}<br /> {{hidden|Which family members should have chromosomal analysis?|Both parents of a child with structural chromosome rearrangement, deletion, duplication 2) all family members at risk of having a chromosome rearrangement}}<br /> {{hidden|What are the indications for chromosomal analysis of products of conception?|1)Abortuses (missed abortions) of unknown reason, 2)Malformed stillbirths, 3)Stillbirth of undetermined etiology}}<br /> {{hidden|Compare amniocentesis and chorionic villus sampling with regards to gestational age, complication rate, turn around time, and false results|}}<br /> {{hidden|What are the clinical indications for tissue sampling instead of blood for cytogenetic analysis?|1)Suspicion of chromosomal mosaicism, 2) blood is not available (e.g. POC), 3) surgical or post-mortem tissue.}}<br /> {{hidden|List 8 standard techniques for cytogenetics analysis.|1) Geimsa / G-Banding, 2) Quinacrin / Q-banding 3) Reverse / R-banding, 4)Centromere / C-banding, 5)NOR staining (nucleolus organizer regions), 6)DAPI staining, 7) Chromosomal breakage, 8) Sister chromatid Exchange (SCE)}}<br /> {{hidden|List 5 Molecular cytogenetics techniques.|1)FISH (flourescence in situ hybridization), 2) Multi-colour FISH, 3) SKY (spectral karyotyping), 4) CGH (comparative genomic hybridization), 5) CGH array}}<br /> {{hidden|What is g-banding?|Chromosomes are treated with trypsine and then stained with Geimsa (or wrights) which darkly stains the AT rich regions (heterochromatin), and lightly stains the GC rich regions of the chromosome.}}<br /> {{hidden|Outline the general procedure for cytogenetics study.|1) cell culture at 37C 5%CO2 in medium (dividing and stimulation), 2) Chromosome elongation Thymidine BrdU, 3) Metaphase arrest with Colcemide, 4) Cell swelling with hypotonic KCl,* Hardening with acetic acid* 5) Fixation with Cournay's (Methanol: Acetic acid, 3:1), 6) Slide making (chromosome spread with ideal temperature and humidity), 7) Slide aging (air dry slide warmer), 8)Staining (G, Q, C, R-banding), 8) Molecular cytogenetic technique (FISH, multi-FISH, CGH, SKY, array CGH).}}<br /> {{hidden|Broadly what at the three main morphological groups of chromosomes?|Metacentric, acrocentric, submetacentric.}}<br /> {{hidden|What are the 4 minimum items included in a standard banding nomenclature?|1. Chromosome number, 2) short or long arm, 3) region on that arm, 4) band number within that region}}<br /> {{hidden|What are the clinical indications for an individual to have chromosomal analysis?|1)suspected classic chromosome syndrome, 2) Mental retardation of undetermined etiology, 3) dysmophic features, 4) multiple congenital abnormalities, 5) abnormalities of sexual development, 6) ambiguous genitalia, 7)pubertal failure, 8)abnormalities of growth, 9) certain types of malignancies.}}<br /> {{hidden|What is q-banding?|Chromosomes are prepared with quinacrine which produces flourescent bands in the AT rich regions, particularly useful in identifying polymorphisms on the acrocentric chromosomes ( ) and the Y chromosome.}}<br /> {{hidden|What is R-banding?|Darkly stains the GC rich regions of the chromosome (Euchromatin), aka Reverse-banding, and is used to detect subtle deletions or rearrangements that may not be detected by Q or G banding.}}<br /> {{hidden|What is C-banding?|C-Banding stains the constituitive heterochromatin that is localized to the pericentromeric regions of all chromosomes and on the distal long arm of Y. Used to identify pericentric inversions and polymorphisms in centromeric regions of 1,9,16, and Yq, as well as confirming translocations of Y}}<br /> {{hidden|What is NOR?|NOR is a silver staining procedure which stains the nucleolus organizer regions of satellited chromosomes (used to study the size of stalks and satellites in the acrocentric chromosomes)}}<br /> {{hidden|List the metacentric chromosomes.|}}<br /> {{hidden|List the submetacentric chromosomes.|}}<br /> {{hidden|List the acrocentric chromosomes.|}}<br /> {{hidden|What is Bloom syndrome?|Bloom syndrome is a rare AR genetic disorder with a defect in the BLM gene with a phenotype of short stature, tendency to sunburn, increased risk of malignancy, reduced or absent fertility, and prone to sister chromatid exchange [[http://ghr.nlm.nih.gov/condition/bloom-syndrome]] }}<br /> {{hidden|What is SCE (Sister chromatid exchange?|SCE (sister chromatid exchange) is the interchange of homologous segments between two chromatids of one chromosome, grow the cells under special conditions to produce a differential staining of sister chromatids.}}<br /> {{hidden|What is DAPI staining?|DAPI staining produces bright flourescence of the heterochromatin regions of 1,9,16, and Y, as well as the centromere of 15, and is used to id marker chromosomes or translocations of Y.}}<br /> {{hidden|Explain how chromosomal breakage studies are used to diagnose Fanconi's anemia.| Cultured cells are treated with DEB (Diepoxybutane) or mitomycin C to induce breakage, those cells with chromosomes prone to breakage are especially susceptible and this can be seen as gaps, breaks, deletions, triradial, quadriradial, dicentric, and complex figure in the metaphase.}}<br /> ==Unit 2==<br /> {{hidden|Describe the 4 steps of mitosis.|Prophase, metaphase, anaphase, telophase}}<br /> {{hidden|List the 8 steps of meiosis.|Meiosis 1(Prophase 1, Metaphase 1, Anaphase 1, Telophase 1), Meiosis 2( Prophase 2, Metaphase 2, Anaphase 2, Telophase 2).}}<br /> {{hidden|What is the main difference between constitutional and acquired chromosome anomalies.|1) Constitutional affects the whole patient, acquired usually limited to 1 organ.}}<br /> {{hidden|What at the three main categories of patient features associated with unbalanced constitutional chromosomal anomalies?]1) dysmophy, 2) Visceral malformations, 3) developmental/psychomotor delay.}}<br /> {{hidden|What is meant by a homogeneous chromosomal anomaly?|Homogeneous chromosomal anomalies mean that all the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What is meant by a mosaic chromosomal anomaly?|Mosaic chromosomal anomalies mean that only some of the cells STUDIED carry the anomaly, may be constitutional or acquired.}}<br /> {{hidden|What are chromosomal polymorphisms?|Chromosomal polymorphisms are variants of chromosomes that are widespread in a particular population which to date are not known to have any effect on the phenotype, they vary in size, position, and staining properties but must occur in heterochromatin regions usually near the centromere.}}<br /> {{hidden|List 3 known chromosomal polymorphisms, according to ISCN 2013.|[[Chromosomal polymorphisms]]}}<br /> {{hidden|Classify numerical abnormalities of chromosomes.|1) polyploidy (multiple complete sets of chromosomes, e.g. 3N), 2) Aneuploidy (monosomy (e.g. Turner's syndrome), trisomy (e.g. trisomy 18, 13, or 21), tetrasomy))}}<br /> {{hidden|What are the four main types of abnormalities in chromosome structure?|1) Deletion, 2) duplication, 3) rearrangement (inversion or insertion), 4) translocation}}<br /> {{hidden|What is the key difference between a balanced and an unbalanced chromosomal rearrangement?|Balanced translocations imply that there is no missing or excess genetic material, while unbalanced translocations have either missing or excess genetic material from that of a normal genotype.}}<br /> {{hidden|List three types of balanced chromosomal rearrangements.|Translocation, inversion, insertion.}}<br /> {{hidden|List three unbalanced numerical chromosomal rearrangements.|trisomy, monosomy, multiploidy}}<br /> {{hidden|List 5 structural unbalanced chromosomal rearrangements.|deletion, duplication, derivative chromsome, recombination chromosome, marker chromosome, ring chromosome, Dm &amp; HSR}}<br /> {{hidden|What is the karyotype for a female infant with cri-du-chat?|46,XX,del(5)(p15.1)}}<br /> ==Unit 3==<br /> {{hidden|What is FISH?|FISH is a molecular cytogenetic technique in which flourescently labelled DNA probes are hybridized to metaphase spreads or interphase nuclei.}}<br /> {{hidden|When is interphase FISH more helpful than metaphase?|Interphase FISH is particularly useful in samples where there is poor culture growth such as bone marrow or cancer tissue.}}<br /> {{hidden|What is the approximate resolution of cytogenetic FISH?|3-5Mb}}<br /> {{hidden|What are the three types of FISH probes?|1)Probes for repetative sequences (Centromeres, telomeric sequences), 2) Unique sequence probes hybridized to a single copy of DNA sequences in a specific gene or chromosome, 3) Whole chromosome paints (or arms) which are cocktails of probes that are chromosome specific and cover the entire length.}}<br /> {{hidden|List 7 applications of FISH technology?| 1) Microdeletion syndromes, 2) Characterization of chromosomal structural abnormalities, 3) identification of marker chromosomes, 4) Aneuploidy detection, 5) Cancer cytogenetics, 6) Gene mapping, 7)Rapid detection of sex chromosomes and the SRY gene}}<br /> {{hidden|List 5 microdeletion syndromes.|[[List of Microdeletion Syndromes]]}}<br /> {{hidden|Briefly describe William's Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)}}<br /> {{hidden|Briefly describe Williams Syndrome.|Deletion of one elastin allele (7q11.23 = 96% of cases), multi-system d/o characterized by: Growth &amp; developmental delay, characteristic facies &amp; personality, supra valvular stenosis, idiopathic infantile hypercalcemia (connective tissue / vascular)</div>

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