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Mechanisms of Disease

by: Bonita Witting

Mechanisms of Disease BLD 204

Bonita Witting
GPA 3.79


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This 67 page Class Notes was uploaded by Bonita Witting on Saturday September 19, 2015. The Class Notes belongs to BLD 204 at Michigan State University taught by Staff in Fall. Since its upload, it has received 160 views. For similar materials see /class/207496/bld-204-michigan-state-university in Biomedical Sciences at Michigan State University.

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Date Created: 09/19/15
Exam 1 Information Exxon I Ii39iiln39ri39i Jinn Exam 3 Information BLD204 Mechanisms of Disease Objectives Upon completion of the unit on cells and cell injury the student should be able 1 Describe the composition of the cell membrane and state at least 3 physiologic functions a The cell membrane is considered to be a uid mosaic It is composed of several different things such as different forms of proteins lipids and carbohydrates b 3 physiological functions include i Regulation the membrane is selectively permeable and allows simple and active diEfusion Maintain osmotic relationships between the intercellular and extracellular environments iii Receptor and transduction functions 2 Explain the function of each of the following cytoplasmic organelles a Mitochondria i Cellular power plant Produce energy for the cell b Endoplasmic Reticulum i MHC class II assembly c Ribosomes i Site of protein synthesis d Golgi complex i Packages proteins and prepares them for secretion to there designated areas e Lysosomes i The stomach ofthe cell f Peroxisomes i Break down chains of long fatty acids g Microtubles and microfilaments i Maintain shape of cell and act as a track for transportation in cell 3 Define lysosome phagolysosome and autolysosome a Lysosomes Break down Digest Destroy i Injury Site storage disease single gene defect ii When injured release digestive enzymes into the cellBAD b Phagolysosome fusion of lysosome with phagosome i Work together to phagocytize ii Common function of c Autolysosome i Function of the lysosome ii self digestion e De ne etiology and pathogenesis and be able to use these de nitions to differentiate between the inciting agent of the disease and the response of the organism a Etiology is the cause ot a disease what caused the injury i Initiator b Pathogenesis is the path a disease is most likely to follow It is the sequence of events that occurs from the initial injury i Responder ii Knowing this can help prevention and treatment V39 List the common types of celldamaging factors responsible for cell injury and death and give an example of each a Hy poxiaaiioxia extreme hypoxia i Not enough Oxygen in the blood ii Due to ischemia b Reoxygenation i Too much Oxygen ii Leads to free radicals Affects the membrane of the cell a Disrupts receptors and osmotics 2 Superoxide s 3 Peroxides damages proteins calcium disrupts membrane bleb c Temperature Mast Cells Present i Extreme 1101 bum ii Extreme cold frost bite d Chemical i Chemotherapy 1 Nucleus prevent cells from dividing ii Radiation 1000 Radiation Sickness 2 1000 Necrosis ofhematopoietic stem cellsgtpancytopenia loss of gut epithelium death in 2 weeks 3 10000 Sever CNS death in a few hours 4 100000 instant death 5 MAffect cells the most when they are dividing e hradiation f nfectious Agents i Bacteria 1 Triggers immunity 2 Toxins releasedbad a Endotoxins part of organism structure i Released by bacteria after they die ii Can cause shock b Exotoxins i Secreted by organism 9 gt1 8 ii Enzymes and protein the bacteria are making need to get resources and migrate tliru body ii Viral 1 Direct damage g Nutritional de ciencies i Distupts cellular function 1 Not enough folic acid B12 2 Nucleus cannot mature a Pernicious anemia not enough red blood cells Compare and contrast the mechanisms of cellular injury due to hypoxia and chemical damage to the cell a Hypoxia cellular injury is due to the lack of oxygen in the blood which could be the result of ischemja When oxygen is reintroduced at a fast rate re oxygenation injuries can occur free radicals b Chemical injuries can be the result of many different agents It is the direct damage to the cell either during cell division or by free radicals i Chemotherapy ii Radiation Define and differentiate between necrosis and apoptosis a Apoptosis is PROGRAMMED cell death 39 Cell undergoes normal activity i39 No break down of energy supply iii No failure to maintain cell volume iv No membrane rupture V No acute in ammation Energy Dependent Involves Protein syntheses H Outpace mitosislose tissue Outpace apoptosis liyperplasia Vi Morphology 1 Separates from neighbors Keep a Steady 03 POPUIMlO11 2 PyknosiszNucleus J 3 Kalyorrhexis Cell breaks into membrane bound fragments 4 Karyolysis Phagocytized but differentautolysis vii Short time 12 hours viii Present in normal tissue at 1 ix Has genetic control b Necrosis death WITHOUT isolation i Destruction ii Exposure to surrounding tissue iii Triggers the immune system iv Acute in ammation Describe the characteristic nuclear changes that can occur during cell death a Pyknosis Condensation gets more dense and shrinks b Karyorrhexis Fragmentation caused by enzymatic digestion c Karyolysis Fading things are digested and removed 9 Compare and contract the four types of necrosis a Coagulation i Firm ii Swollen iii Protein denatured iv Mostly normal appearanceresult of ischemia injury b Caseation i Classic TB ii Structureless iii Lots oflipids iv Cheesy appearance V dissolves everything into a mess c Liquefaction i Hydrolytic enzymatic digestion ii Protein rich uid iii Primary in BRAIN iv Secondary in PUS Traumatic Fat i Mainly breasts ii Adipocyte rupture iii Lipolysis 1 Fatty acids 2 Glycerol iv Perceived as lumps malignancy e Enzyme Mediated Fat i Acute Pancreatits 2 1 1 Proteolytic 2 Lipolytic 3 Fatty acids plus Ca 4 Blocks pancreas from being able to use extretionary function gt digestive enzymes leak out into surrounding tissue the pancreas thinks there isn t enough therefore it continues to make more f Gangrene i Pathogen blockage of air supply 1 Clostridium 2 Anaerobic strep 3 Bacteriodaceae ii NASTY massive destruction iii Bad Oder iv Can spread to other limbs 10 De ne the following types of cellular adaptations a Atrophy Decrease in size of individual cells due to loss of cellular substance i Cause decrease in function aging decrease in nutritionblood supply and loss of endocrine stimulation b Hypertrophy Increase in size of individual cells Hypoplasia Decrease number of cells Hyperplasia Increase number of cells i Benign tumor e Aplasia Incomplete or deformed development of an Occurs when the cells are put under some form of stress change 9 organ or tissue Lack of development f Metaplasia the reversible change when an adult cell is replaced by another adult cell g Dysplasia abnormal development ofan organ or part of the body 11 Differentiate between and give examples of both exogenous and endogenous pigments a Exogenous from outside of the cell b Endogenous from inside the cell 12 State the two changes as a result in injury a Change in StI39UCtUre I Can go hand and hand but NOT ALWAYS b Change in function i Gain function loss in function hyperplasia hypertrophy metaplasia dysplasia aplasia hypoplasia etc may occur 13 State the overall objective of a cell and what that means 0 Maintain stability d Preserve DNA e Enzymes i Complementrangemenu ii Amount f Membrane Integrity i Needed for energy transport communication receptors ii Osmotic and uid homeostasis iii Maintains 1 Substrates 2 Prevent reoxygenation and hypoxia 14 De ne the role of pathology in terms of basic science and medicine g Pathology provides the link between biology and medicine i New fact discovered by biology pathology nds a way to use it ii The study of disease 16 Compare and contrast necrosis vs apoptosis in terms of initiating stimulus and ability to promote in ammation a Apoptosis is a normal cellular function i Does not promote in ammation ii Stimulate 1 Genetic control 2 Bad cell doesn t past the test b Necrosis i Stimulated by pathological reasons ii Promotes in ammation Upon completion of the unit on in ammation the student should be able to 1 List the 5 cardinal signs of in ammation and provide an explanation for each a Redness i Due to vasodilation increase blood ow in the area b Heat i Increased metabolic rate heat ii Vasodilation l The widening of blood vessels 2 Vessels moving into the tissue friction heat c Pain i Caused by tissue tension 1 Swelling ofthe tissue being compressed d Swelling i Increase of uids into the cells 1 Due to vasodilation a Exudate any uid that lters from the circulatory system into the lesion b Edema abnormal build up of uids e Loss offunction i Depends on how severe ii Result of failure to remove stimulus 2 Describe the hemodynamic vascular changes occurring with in ammation a Vasodilation the widening of blood vessels b Increased vascular permeability allows for leakage across the cell membrane c Increase blood ow Bring more uids to the lesion 3 List 5 ways uid exudates can participate in in ammation a Serous exudate Low protein i Jointsbendinggtpressure pain iii Clear uid iv Easy to cleanremove v High volume v39 Example blisters b Fibrinous Exudate i High Protein 1 Food source for bacteria increase infection H ii Low volume iii Sticky iv Painful V If not removed scarring loss of function vi Example Cavity linings pleura pericardium peritoneum Hemorrhagic exudate i Damage to small blood vessel allows red blood cells to escape from lumen into extravascular space ii Packet of blood sitting somewhere BLOODY iii Example Bacterialanthrax Rickettsia typhus rocky mountain spotted fever viralin uenza Catarrhal i Mucus 1 Mucus membrane in amed ii Similar to serous Mucus converts to sticky viscous material iii Example upper respiratory tract infections cold Purulent Exudate i Combines with brinous ii Opaque appearance neutrophil dominant iii Pus lots of dead cells and neutrophil debris Membranous i Pseudo membrane false membrane 1 Fibrin sheets combined with neutrophils9 looks like tissue 0 3 1 Fquot quot1 4 List the major cells involved in in ammation and brie y describe the characteristics of each as well as what they contribute to the in ammatory process Differentiate between PMN s and mononuclear cells passed on their approximate time of arrival at the site of in ammation a Neutrophils Early stage of inflammation ACUTE i Objective Removal Destruction and Recruitment ii Useddeath Lots of granules iii High number in perihal blood9easily replaced always some acute in am iv Chemical Mediators 1 Formulated peptide 2 F MetLeuPhe9Has receptors for this a Aids with migration and adherence to endothelium b Selections members Ig supergene i Linked to IL1 and TNA 1 ii E selectins and P selectins c Integrin s d Emigration 3 Fonns of inflammation a Suppurative i Huge number present b Membranous i Make up pseudomembrane with cell debris c Purulent Exudate i Neutrophil dominant pus 4 Anatomical In ammation a Abscess Zone i Center of liqui cation with dead cells V Complement Cascade 1 C3a induce release from bone marrow vi Tissue deprived mediators 1 Lysosomes9 makes acid protease work by decreasing pH vii Protein Mediators 1 Attracts and activates ILl b Macrophage i Objectives Removal Destruction Recruitment ii Driving force of CHRONIC in ammation Can activate the complement cascade iv Produces TNF or 9 enhances their killing v Involved with heterolysis vi Works with lymphocytes 1 Caratenic proteins attract them to an injury 2 They present antigen to lymphocyte showing immune system what they have 3 Responds to lymphokines a MCF Microchemotic Factor9 draws more macrophages b MIF Macrophage inhibiting factor tells macro where to g0 55 vii After injury 1 Removal of in ammation exudate 2 Wound healing a Release growth factorsmakes PDGF b Dermal events in ltrates 12 days c Granulomatous In ammation see below viii Synthesizes and Secretes 1 In ammatory mediators Cytokines a TGF A mediated killing b IL19 increases cytotoxicin i Stimulates production of neutrophils and IL1 c Chemokjnes i Excited them i i Bcyscys terminus iii Macrophage inhibiting factor 5 De ne margination emigration and chemotaxis a Margination i Movement through the body b Emigration i Crossing the endothelium and through tissue C ChemotaXis i The driving force chemically driven 6 List the 3 principle steps involved in phagocytosis and describe 2 mechanisms that the cell has for killing andor degrading ingested material a b C d Macrophagesneutrophils are attracted by a chemical receptor or signal i fpeptideCia Engulfment i Opsonization 1 Provides a handle for the macrophage to hold on to 2 CRP or MBP Create phagosome encloses bacteria in a bag of what got ingested Fuse to lysosome Makes a big bag that gets processed and destroyed 7 Brie y explain the effects of and the contribution that each of the following groups of chemical mediators has on the in ammatory response a GOAL Increase vasodilation N v and macrophages Form a clot Recruit neutrophils Fquot C Vasoactive Anunes i Histamines linked to acute in ammation tend to live near small blood vessels 1 can cause vascular dilation and increase vascular permeability 2 Antihistamines inhibit this response ii Mast Cells 1 Line small vessels 2 Triggers the release of mediators from granules of mast cells for chemical injuries a Immunoglobins Venom C3a CSb Chymotryspintryspin Cationic lysosomal proteins Harp 10 3 Physical injuries heat cold irradiation and mechanical The complement system i Complements the ability of lhe antibodies and phagenetic cells ii Yields particles that coat and function as adhesion molecules for neutrophils and macrophages 1 Ospsonins 2 Chemotaxis iii Leads to lysis ofbacterial membranes iv Forms the Membrane Attack Complex MAC C6789 v C3aC5a anaphylatoxins systematic vasodilation and vascular perm l C3a induce the release of neutrophils from bone barrow 2 C5a induce the release oflysosome enzymes The kinin system i Can activate complement cascade ii Releases Bradykin 1 Increases vasodilation 2 Increases vascular permability 3 Hyp otens ive iii Start clotting factor X11 1 Activate factor XI a Intrinsic clotting cascade activate 11 i M39 es a clot 8 Li 1 din nal al cv ll 2 ml Lurjjhi fu 1TH 9 Define exudate and transudate a Exudate anv uid that ows through the circulatory system and into a lesion or site of b Transudate a uid that which lters out much of the protein and cellular elements to yield a watery solution It occurs due to increased pressure in the veins 11 Differentiate between acute and chronic in ammation based on duration of cellular injury and the primary cell type involved a Acute few days neutrophils b Subacute weeks c Chronic monthsyears macrophages 12 Describe Chronic Granulomatous In ammation a Macrophages and lymphocytes recruited b LOTS ofnecrosis c Body cannot remove stimulus therefore puts it in one area It will just sit there and go unnoticed until the body is stressed the right way i Example TB or Lepmsy 13 Name and describe the two types of giant cells a B Cells i Process 1 Start in bone marrow 2 Gene arrangement a How to generate Bcell receptors need gene that codes for receptor 3 Make successful B Cell Receptor BCR 4 Training for selftolerance 5 Move to secondary lyphnoid organs ii MAKES IMMUNOGLOBLINS iii Not linear protein 3D b T Cells i Process C Start in bone marrow Gene arrangement Successful T cell receptor 0L and B Move to thymus Educatetrain for tolerance of self in thymus Move to secondary lymphoid glands ii Linear short proteins iii CD8 Cytolytic T Cells Tc 1 Killer 2 Problem blow upnecrosis iV CD4 helper T Cells Th 1 Help things happen 2 Make cytokjnes of all kinds 3 In uences macrophages and other T cells a T111 cell mediated response help i Help make macrophage better b T112 humoral response helper i B cell presents antigen oweWNr Macrophages 14 Describe the constituents of each of the following exudates and the situations andor tissues where they are most likely to be seen a Serous exudate Low protein i1 Jointsbendingpressure9 pain iii Clear uid iv Easy to cleanremove V High volume vi Example blisters b Fibrinous Exudate i High Protein 1 Food source for bacteria increase infection ii Low volume iii Sticky iv Painful V If not removed scarring loss of function vi Example Cavity linings pleura pericardium peritoneum c Hemorrhagic exudate i Damage to small blood vessel allows red blood cells to escape from lumen into extravascular space ii Packet of blood sitting somewhere BLOODY iii Example Bacterialanthrax Rickettsia typhus rocky mountain spotted fever viralin uenza d Catarrhal i Mucus l Mucus membrane in amed ii Similar to serous Mucus converts to sticky viscous material iii Example upper respiratory tract infections cold e Purulent Exudate i Combines with brinous ii Opaque appearance 9 neutrophil dominant iii Pus lots of dead cells and neutrophil debris f Membranous i Pseudo membrane false membrane 1 Fibrin sheets combined with neutrophilsgt looks like tissue b I 14 Describe the morphology of the in ammatory reaction associated with the following a Abscesses i In ammation lesion ii Occurs when there is a injury to a solid block of tissue dermis liver kidney brain iii Zones clearly de ned 1 Center is lique ed dead tissue and neutrophils 2 Layer of fribrin and living neutrophils 3 Periphery proliferating broblasts new capillaries and new college a Represents repair process 12 Possible pathogen in ammation BARRIER FOR further spread PREVENTS discharge Can prevent resolution f Open or removal may be needed iv Process dea cells9 neutrophils trying to keep contained V Looks like purulent9 pus F9999quot b Ulcers i located at epitheliumlined tissue skin gut pharynx larynx trachea ii Pseudomembranous reaction iii BAD blockage iv Could be from an abscess c Membranous Pseudomembranous in ammation 15 List and describe the function of the important protein mediators of localized acute in ammation a Cytokines i IL1 1 Fever 2 Endotheljum increase leukocyte adhesion 3 Macrophage a Stimulates their production which lead to neutrophils thru chemokine IL8 b Increase ILl expression and macrophage cytotoxicin 4 Neutrophils basophjl mast cell a Increases chemotaxis b Increases thromboxane c Increases histamine dilation of microvessels 5 Immune system a Increase T cell activateion Increase B cell Activation Increase NK activation Increase Lymphokine expression Increase IFN B DP09quot b Chemokjne s i FMetLeuPhe 1 Attracts neutrophils Attracts monocytes iii Excites macrophages iv Gets released by cells during inflammatory response V L 1 cysxcys temiinus 2 Produced by monocytes t lymph endothelium and epithelium 3 IL8 mediates the rapid accumulation of neutrophils vi B l cyscys terminus 2 macrophage activating factor 3 RANTES Regulated on Activeation Nonnal T Cells Expressed Secreted attracts memory T cells and monocytes c TNFot i Leads to apoptosis i Activation ofB lymphocytes iii T Cell proliferation iv Cytokine production V Produced by macrophages mast cells and T Cells vi Enhance macrophage and CD8 T Cell killing vii Fever viii Up regulate MHC class 1 ix Clot formation downstram from site of in ammation d Lymphokines i Affects macrophages 1 MCF attracts macrophages 2 MIFdirect Macrophages to location 3 Stimulates the production of hydrolytic enzymes e lnterferons i In uence in ammation and cells ii a B y CRP C Reactive protein triggers in ammation response MBP Will only bind to mandin in bacterial cell walls BOTH i Look similar ii Look and act like C lqrs l Activate complement cascade iii Opsonaization 90quot Upon completion of the unit on repair and heanng the student should be able to 1 De ne and give an example of labile stable and permanent cells a Labile can be regenerated i Mitosis from stem cells skin gut blood 1 Stem cells not temiinally differentiated no capacity limit on how many times they can divide give rise ot more cells or cells heading down a different temlinal b Stable Mitosis ofmature cells Ari chetechFrame workKey i Cell and tissue replaced ii Signaling by act Near can still stimulate labile c Permanent never divide i Nerve cells muscles cells ii Can under RIGHT conditions 2 De ne and describe granulation tissue a Granulation tissue the scab that follows after a brin clot i Scab falls off and there are white spots underneath 3 Describe the function of brin broblasts and angioblasts in the repair process a Fibrin produced by brinogen the mesh that forms the clot b Fibroblasts provides the structural matrix for wound healing and synthesizes collagen c Angioblasts a cell taking paJt in blood cell formation 4 De ne and contrast healing by rst intention primary union and second intention secondary union a First intention i Best resolution ii Healing of a cleanly incised easily structurable wound where edges are CLOSE b Second Intention i Extensive loss of epithelium large subepi tissue defect that has to be lled wth scar tissue and edges cannot be closed 5 Explain the term organization within the context of tissue repair a Organization occurs when demolition fails and exudate persists i The exudate is in ltrated by numerous macrophages then migration of broblasts Angioblasts tissue induced to produce buds to make new blood vessels iii Get well vasculated comiective tissue iv Eventually lose blood supply scar tissue rigid b Triggered by i Persistant in animation exudate ii Unlysed blood clots or thrombi iii Necrotic tissue c Consequences i Peritoneal cavity adhesions may lead to obstruction ii Serosal take up space iii Lungs loss ofproper tissue 6 Differentiate between the following responses a brous and brinous i Fibrous collagen for connective tissue ii Fibrinous brin for wound healing b granulomatous and granulation Granulomatous part of in ammatory response Chronic Surrounded by lymphoc ytes Granulation part of repair process contains small blood vessels and broblasts Scab 7 State the major protein component of a scar a The major protein component of a scar is collagen 8 State general mediators of cell growth and proliferation a Platelet Derived Growth Factor i Secreted by platelets ii Made by macrophages endothelium cells tumors iii Mitogenic iv chemotaxis b Fibroblast growth factor i Covers wound so it can heal c Epidermal Growth Factor i Connective tissue ii Platelet tissue iii Lickjng your wound iv mitogen 9 Differentiate between a keloid and proud flesh a Keloid rigid scar b Proud Flesh flesh that surrounds a healing wound Upon completion of the unit on immunity the student should be able to De ne antigen and antibody a Antigen Protein9 best leads to good memory i gt40000 mw ii Repetitive epitopes iii Multiple epitopes b Antibody 3 major functions i Complement activation ii Opsinization iii Neutralization 1 Preventative 2 Differentiate between a humoral and cellular immune response based on cell type involved and rate of response to antigen challenge a Humoral immune Response Antibody production i Blymphocytes recognize antigen tth receptor ii Present it to T cell iii T Cell drives B cells to make plasma cells iv Plasma cells make antibodies b Cell Mediated i B Cells 1 Process a Start in bone marrow b Gene arrangement i How to generate B cell receptors need gene that codes for receptor c Make successful B Cell Receptor BCR d Training for selftolerance e Move to secondary lyph noid organs 2 MAKES LMMUNOGLOBLINS 3 Not linear protein 3D ii T Cells 1 Process Start in bone marrow Gene arrangement Successful T cell receptor or and B Move to thymus Educatetrain for tolerance of self in thymus f Move to secondary lymphoid glands 2 Linear short proteins 3 CD8 Cytolytic T Cells Tc a Killer b Problem blow upnecr0sis 4 CD4 helper T Cells Th a Help things happen b Make cytokines of all kinds c Influences macrophages and other T cells i Thl cell mediated response help 1 Help make macrophage better ii Th2 humoral response helper 1 B cell presents antigen rep99 3 List ve different types of antibodies and state the cell type involved in their 39gt production a IgG Gamma i Serum and tissue ii Not good at activating complement cascade iii Readily diffuses iv CROSSES placenta activate transport IgA Alpha i Seretionsmucus ii Can be found in circulatory system c IgM Mue 39 FIRST to respond When B cell triggered i39 rst time teenager iii BIG iv Very low af nity v Lots of binding sites Fquot H vi Stays in vascular vii Gets process going viii Neutralizes iX Activates Complement Cascade d IgE epsilon i Mast Cells ii Allergies e IgD Delta i Surface Receptors ii Signaling mechanism iii Not in circulation Describe the function of the macrophage as it relates to the development of an immune response a Works With lymphocytes i Caratenjc proteins attract them to an injury ii They present antigen to lymphocyte showing immune system What they have iii Responds to lymphokines l MCF Microchemotic Factor draws more macrophages 2 MIF Macrophage inhibiting factorgt tells macro where to go b After injury i Removal of in ammation exudate ii Wound healing 1 Release growth factorsmakes PDGF 2 Dermal events in ltrates 12 days 3 Granulomatous In ammation V39 Compare and contrast the type of immune response cellular or humoral histologic lesion rate of development and pathogenesis of the following hypersensitivity reactions a Type IAnaphylactic i Immune system not really doing anything wrong ii Excessive amounts of IgE 1 Allergy 9 Allergic Reaction 2 Mast cells are triggered runny nose 3 Over reaction 4 Treatment a Build up tolerance b Calcium c Steroids Humoral Response 5 Example Hay Fever a Anaphylaxis bee sting pollen b Type II Antibody dependent i Antibody cell mediated 1 IgM or IgG or Complement Cascade a Example Complement lysis of cell membrane i IgG9 Autoimmunity l SLE and Type 1 diabetes IDDM 2 Examples a Heinolytic Disease of New Born HDN i Mom has antibodies against newborn platelets or RBC death b Neonatal isothrombocytopenia NIST c Adverse Transfusion outcome c Type III Immune ComplexMediated i Immune complex deposition 1 Release of lysosomal contents from the neutrophils 2 Release of histamines vasoactive amines 3 Aggregation of platelets ii Large or small complexes trap structures iii Immunoglobins involved 1 IgG and IgM iv Exogenous antigen v Can activate complement system vi Macrophages try to clear but can t spills lysosomes and histamines aggregates platelets vii Autoimmune diseases 1 RheumatoidA hritis 2 SLE 3 Drug induced Cellular d Type IV CellMediated Response i No Ig involvement ii Cell Mediated iii In ammation response swelling iv Caused by microbial agents 1 Bacteria TB Leprosy 2 Viruses small pox herpes measles 3 Fungi candidiasis histoplasmoisis V Rejection of tissue graft or organ graft V Contact dermatitis 1 Exposure to chemicals plant prod metals 2 Examples Poison Ivy 6 Given a particular disorder and the etiology of that disorder be able to classify it based on the most likely hypersensitivity reaction involved 909quot g ext rpm 29 Hay Fever Anaphylaxis bee sting pollen SLE and Type 1 diabetes IDDM Hemolytic Disease of New Born HDN i Mom has antibodies against newborn platelets or RBC9 death Neonatal isothrombocytopenia NIST Adverse Transfusion outcome Rheumatoid Arthritis SLE Drug induced Bacteria TB Leprosy Viruses small pox herpes measles Fungi candidiasis histoplasmoisis Poison Ivy 7 Describe each of the following patterns of transplantation rejection with regard to the type of immune response time course and histologic appearance a b C Hyperacute i Result of incompatible ABO groups ii Complement becomes activated 1 Activated platelets and clotting system leading to blood vessel occlusion in the graft and to ischaemic necrosis a Turns black Acute i Early acute 710 days 1 Not doomed to fail 2 Antibody mediated 3 Result of cellular response mediated by T cells or a vascular response mediated by antibodies ii Late Acute 11 days 6 weeks 1 Occurs in patients with immunosuppressions 2 Characterize by oral vascular damage mediated by antibody and complement Chronic 20 i How well did you keep the immune system at bay ii Needs to be challenged the right way 8 De ne autoimmunity a Autoimmunity the failure of an organism in recognizing its own constituent parts as self which allows an immune response against its own cells and tissues b Any chronic disease is involved c Very common d You are always capable of attacking yourself just isn t always stimulated 9 Describe 3 general mechanisms for the loss of selftolerance and the development of autoimmunity a To get to autoimmune you MUST have i Genetic susceptibility 1 HLA type can you present the right peptide 2 Loss oftolerance 3 Associated with type one diabetes ii Environmental involvement 1 Some type of infectious diseaseoutside source 2 Most autoimmune diseases start here 3 Concept of Danger vs Safe 4 Exposure of yourselfto your immune system thru necrosis iii Host status state 10 For each of the following autoimmune disorders describe the antigen etiology whether it is primarily humoral or cell mediated and the pathogenesis a Systemic Lupus erythematosus SLE i Cell mediated ii Classic autoimmune disease 1 Lesions are caused by immune complex disposition and excessive autoantibody production 2 Diagnostic Nightmare a Normally starts with some problem and you begin to have other problems moves around body b Always a different antigen 3 Schizophrenic immune system a 18 different menu items b Changes a lot mimics acid Mostly females in late adolescents early adulthood 5 Two theories for hyperactivity of B cells a Decline in suppressor Tcells allows B cells to produce large amounts of autoantibodies Direct polyclonal activation of B cells therefor by passing the need for nonspeci c signal for T helper cells 5 0quot 21 6 Class 2 and 3 hypersensitivity t H t39t39UHH am limit wazm 1 c Rheumatoid arthritis RA i Cell mediated ii Class 3 hypersensitivity iii Pathogenesis 1 Release of lysosomal content 2 Release of histamines 3 Aggregation of platelets ll Differentiate between primary and secondary lymphoid tissue and list two examples of each a Primary generates lymphocytes i Bone marrow and thymus b Secondary maintain mature naive lymphocytes and initiate an adaptive immune response i Spleen Skin 12 De ne self and why the need exists for tolerance to self a Great concept keep your body from attacking itself Upon completion of the module on transplantation and MHC the participant should be able to 1 State the role of MHC in the immune response Antigen Presentation Aka Human Leukocytelymphocyte antigen Up regulated by ILl Pocket with anchors Each individual allele can bind to a variety of peptides Potentially 6 different alleles expressed multiples of each each with potentially different peptide 9 diversity 1 molecule can bind to different peptides or get a diff group of molecules from MHC Class 1 i Three major loci rump96x Pquot 9 2 B 3 C 4 Two alleles from each parent 3 loci x 2 alleles 6 Highly polymorphic Important for virus protection iv All nucleated cells of the body 1 Does not include RBC v Need active protein synthese to keep it in epithelium cell 22 vi Endogenous Ag Presentation 1 From within the cell 2 Cymosolic proteins a Every protein being made gets presented and placed on a cell saW antigen through HLA class 1 3 Degradation 4 Process LMPS and TAPS a Fragments of proteins in cystol by proteasomes b Change shape for protection c Fragments are transported across membrane to ER i Transported by TAPS Transporter associated with Antigen presentation along the ER d Fragments are processed e Translocated to surface 5 Results a Loaded peptide to class 1 b interacts with TCR of CD8 lymphocytes i TCR must recognize that it is itself ii TCR must recognize the peptide 1 Sees that it is wrong kill it 2 Don t recgon no reaction 3 Most don t make it past here c If CD8 recognizes MHC and Ag i Cell is activated ii Becomes effector from na39139ve iii Activated CD8 1 Move to periphery kill i Class2 i Three Loci 1 DR 2 DQ 3 DP ii Expressed on Antigen Presentation Cell iii Exogenous Presentation From outside the cell Utilized by APC to present peptides derived from proteins the cell has endocytized a Macrophages Dendritic Cells B Cells 3 Process a Exogenous proteins taken by endocytosis are fragmented by proteases in an endosome Alpha and Beta chains of MHS class 2 are synthesized in the ER Transported through golgi to reach endosome Where the chain is ingested Peptide fragments are associated are MHC class 2 Transported to cell surface N Fquot 0 3 1 4 Result 23 a Class 2 MHC loaded with peptide i Presents too 1 Thl cell mediated macro dendrit 2 Th2 interact with b cell b Interacts With CD4 i TCR must recognize MHC ii TCR must recognize peptide iii Activated l Thl or Th2 2 Cytokine production 3 Move to periphery or stay with B cells 2 State the role of MHC in transplantation a MHC is a major barrier to transplantation b Dominant group of antigen governing rejection antigens c Matching at different degrees i High Bone Marrow ii Low Solid Organs 3 State the role of the histocompatibility laboratory 4 State the histocompatibility testing needed for the major transplanted organs Serological antigenantibody 9 class 1 Molecular DNA Cellular mixed lymphocyte culture class 2 Solid Organ i Check ABO compatibility ii Check for HLA matching 1 Kidneys 6 antigen match a HLAA B DR 2 of each 2 Bone Marrow 10 antigen match a HLAA 13 DR C DQ 2 of each 999 iii UNOS 1 United Network for Organ Sharing 2 OPO Organ Procurement Organization 3 Transplant Program iv NMDP 1 National Marrow Donor Program a Keeper of bone marrow samples and registry 5 Describe and recognize the major types of rejection episodes a Types i Cell mediated l Granuloma formation cells involved ii Humoral l Antibody production antibodies react with donor cells b Classi cations i Hyperacute 24 1 Result of ABO incompatible 2 Complement Activated a Organ turns black due to clots and decrease blood ow ii Acute 1 Early a Antibody mediated cell response mediated byt cells 2 Late a Due to immunosuppresses iii Chronic 1 How well can you keep immune system in check 6 Discuss GVHD a Result of rejection b Viable lymphocytes amount immune response by removing host cells c Occurs during bone marrow transplants and attack on epithelial cells i Prevented by pre training cells to recognize donor cells ad donor cells to not attack host cells d Graft versus Leukemia i Purposefully mismatch bone marrow in patient with leukemia 1 Allow GVHD to happen to help remove tumorslymphocytes 7 Name the major anti rej ection drugs and their modes of action and side effects Upon completion of the unit on viral infections the student should be able to 1 State two major groupings of viruses based on nucleic acid content a DNA i ntranuclear 1 Except Pox ii Covered by capsid 1 All Icosahedral a Except Pox ii Most have NO envelope 1 Except Herpes b RNA i Cytoplasm 1 Except Orthomyixo and retro 2 Covered by capsid a Either helical or icosahedral 3 Have envelop a EXCEPT picorna and reo 2 State the major shapes of viral capsids and how this may lead to viral ID a Icosahedral i All DNA except Pox b Helical i RNA can be helical or icosahedral 25 3 State what the infective particle of a virus is composed of and how it can differ between the two major types of viruses a The infective particle ofa virus is called the Viron i Genome capsid DNA ii Genomecapsid envelope RNA 4 State the effects of a viral infection on a cell or tissue a Damage or kill infected cell directly by virus 39 Target cell had correct receptor ii Viius causes it to explode ii39 Persistant without damaging cell 1 Stays a long time depends on percersure iv Transformation of the cells 1 Lead to tumor and be contagious Cancer HBV b Host Reaction to change c Immune response towards virus and cellular change cell death 5 State the five steps of a viral infection and the effects on the tissue at each step a Viral Transmission i Attachment to cell surface 1 Contact is random 2 Attach via a specific receptor a Surface of cell must have the speci c viral receptor ii Virus penetrates cell wall 1 If receptor is triggered right the target cell will engulf the viron via Endocytosis and cell will pull it in 2 Envelop viruses fuse with plasma membrane 3 RNA to cytoplasm DNA to Nucleus iii Uncoat Genome 1 Physical separation of viral nucleic acid iv Viral Replication l a Early nucleus mRNA9 early proteins b Late late mRNA transcribed cytoplasm9 late proteins RNA9 within cytoplasm Retrovirus insert RNA directly into host membrane 99 6 State 6 morphologic or functional effects of a virus on a host cell a Cell Death i Cell lysis caused by release of large of virons ii Cessation of normal function iii Immune mediated 1 Tc will react with CD8 MHC class 1 that cell is presenting 2 NK 3 ADCC b No Change latent c Cell alterations 26 d Cause fusion between infected and noninfected ecllls i Gian Cells 1 Measles multiple nucleuses in one membrane e Formation of inclusion bodies 39 Become esinophilic Intercytoplasmic inclusions found in cells infected with Fox Virus ParamyXOViIus reOVirures Intranuclear inclusions 1 Herpes and adenovirus iV Cell Proliferation Neoplastic transformation i ii39 lt State one main outcome from an acute productive Viral infection and what are the effects on the cell and host a The main outcome is usually febrile fever from increased macrophages b Virus is not help back State the 4 situations that can result from the failure to eliminate a Virus and what the effect is on the host a Latent i Very commone ii Occult iii Quiet iV Self limiting episodes V Hidden 1 Latent Herpes cold sores Vi Remain latent with in trigeminal ganglion 1 Varicella Zoster a Chicken Fox and shingles b Chronic i Continuous detection ii Little symptoms iii You are INFECTIVE iV Its replicating but you aren t responded Why you don t feel sick V Examples LentiVirus infants with HBV c Persistant i Slow ii Prolong iii INFECTIVE iV You feel kind of sick V Replicate slow Examples HBV cytomega10Virus CMV Epstein Barr 1 CMV and Epstein Barr a Most people are and haVe antibodies against b Only problem when someone that doesn t have it and recienves a transplant from someone that does S d Oncogenic 27 9 State the 3 types of interferon s and their sources a Alpha lymphocytes b Beta 9 broblasts c Gamma activated Tlymphocytes 10 State the effects of interferons on a virusvirally infected cell a Counter acts viral activity i Increases levels of alpha decrease cell pro iferation ii Increase IFN9 lots of Tc NK decrease in Ig b Trigger proteins that will block viral replication c Does not block viral attachment or penetration d Makes cell do things it couldn t because of virus i MHC antigen presentation upregulates it 11 De ne and recognize tropism when described a Viruses are speci c to a speci c cell species and receptors 12 State what type of virus the following are a DNA Viruses RNA Viruses a Poxvirus g Picomavirus b Herpes virus h Orthymyxovirus c Adenovirus I Paramyxovirus d Papovavirus j Rhabdovirus e Parvovirus k Arenavirus f Hepadnovirus l Coronavirus m Togavirus n Reovirus o Retrovirus p Oncomavirus 13 State what virus causes which disease from the following list a smallpox b Poxv1rus vacc1n1a c cold sores d genital blisters e shingles f infectious mononucleosis g conjunctivitis pneumonia Ad h stuffy nose cough sore throat enovmls I r 39 IA39L I I j fth disease ParvoviIus k Hepatitis B Hepadnovirus l Polio m Myocarditis n In uenza Orthymyxovirus 1quot MeaSIe Paramvxovirus q Mumps r Lassa fever Arenavirus Herpes virus I u 1 1 J Papovav1rus 28 s Common cold9C0r01iavirus t Yellow fever u Rubella TOgavmlS V Colorado tick fever Reovirus w HTL X HIV y Neoplasms and malignant transformations Oncomavirus etrovirus Upon completion of the unit on amyloid the student should be able to l N E Describe the physical characteristics of an organ that has signi cant amounts of amyloid deposition a The organ is larger rmer and paler i Retains uid due to bad circulation ii Structural change9 functional change Describe the microscopic features and staining properties of an organ that has significant amounts of amyloid deposition a The staining properties are known as H and E Stain i Hemotaoxic basic and Eosin acidic ii Dichrosism Congo red iii Metachromasia methylene blue b Esinophilic becomes pink State the unifying feature of amyloid proteins a The unitfying feature of amyloid proteins is the Beta Sheets i Gives the staining properties ii Fibrillar ultra structure iii Resistant to physiological solvents iv Resistant to preteolytic digestion Define and give examples of primary and secondary amyloidosis a Primary i Absence or a recognizable disease b Secondary i Followsassociates with a disease c Based on i Pattern or protein denaturation ii Aquired or inherited iii Nature of amyloid protein State the origin of amyloid proteins in a Immune origin amyloidosis 39 Systematic i1 Aminoterminal fragment iii Bence Jones Protein iv Ig Light chain 29 9 FL Hemodialysisassociated amyloidosis i B2 microglobin 1 B2 uglobin Reactive systemic amyloidosis i AA type of amyloid ii Circulation of acute phase proteins Hereditary systemic amyloidosis i All autosomal dominant except familial meditrainian Endocrinerelated amyloidosis i Pancreatic insulits Intracerebral amyloidosis i Neuron loss ii Reactive proliferation of astrocytes iii Associated with blood vessel State the relationship if SAA With in ammation a b 99 SAA is high under normal in ammation SAA under Basal conditions very low i Triggers IL 1 IL6 TNF Alpha T is a apolopproprotein HDL RA and Crohn s Disease 30 Upon completion of the unit on hemodynarnic derangements the student should be able to 1 De ne the following terms a Edema i Fluid in the extravascular ii Amount of total water in body 49 liters l 35L intracellular 2 3L intravascular 3 ll Liters extravascular b Ascites i Free uid in peritoneal cavity c Hyperemia i Greater amount of blood than normal in a given tissue 1 Two causes a Increased arterial ow i Due to arterial dialation ii Active hyperemia b Decrease in Outflow i Obtrusive functional vs structural ii Example Chronin bronchitis iii Passive congestionobstructive nature of pne d Hydrothorax i Presence of uid in one or both pleural cavities usually resulting from cardiac failure e Anasarca i severe generalized massive edema Anasarca often occurs in congestive heart failure liver failure or renal disease 11 An accumulation of serous uid in various tissues and cavities of the body f Pericardial effusion i abnormal accumulation of uid in the pericardial cavity Because of the limited amount of space in the pericardial cavity uid accumulation leads to an increased intrapericardial pressure which can negatively affect heart function A pericardial effusion with enough pressure to adversely affect heart function is called cardiac tamponade 2 Describe primary causes of edema a Raised intracapillary pressure b Low plasma oncotic pressure c Retention of salt and water 3 Differentiate between active hyperemia and congestion or passive hyperemia a Active hyperemia i Hyperemia due to increased ow of arterial blood in dilated capillaries b Passive Hyperemia Venous Congestion Disruption of blood ow to an area Can be sudden ir Usually chronic iv Results from increase pulmonary and systematic venous pressure Example Pneumonia lt 31 4 Differentiate between hyperemia and hemorrhage a Hyperanemia ACTIVE increase in the volume of blood in tissues red gt caused by arteriolar dilation gt physiological blushing skeletal muscle during exercise pathological in ammation b Hemorrhageextravasation of blood to the exterior of the body or into nonvascular body space due to rupture of blood vessels gt trauma atherosclerosis aneurysms bleeding disorders gt in soft tissues is called hematoma 5 De ne a Epistaxis b Hemothorax c Hemoptysis d Hemopericardium e Hematemesis f Hemoperitoneum g Enterorrhagia h Petechiae i Metrorrhagia j Purpura k Hematuria l Ecchymoses 6 List the major components involved in hemostasis 7 List two agents capable of initiating the formation of a clot 8 Differentiate between localized clot formation and disseminated coagulation 9 Define embolus and list 3 types of emboli a Massive pulmonary Emboli i From the legs sudden ii Associated with straining stool iii Acute Right heart failure 1 Vagal re ex with spasms of coronarypulmonary arteries 2 Re ex producing marked peripheral vasodilation 3 Re ex producing cardiac arrest 4 Massive release of prostaglandins which provokes a vasospasm b Medium Size i Localized necrosis ii Infarcts or necrosis secondary to ischemia iii Block 029 tissue dies c Small size Clinically silent don t really know it happened Multiple and recurrent Retraction of the emboli and organization may leave small fibrinous tissue cords criss crossing the vessel decreases the exibility iv Can get hammered into vessel leads to mural type thrombus that leads to smooth muscle layering and thickening and eventually pulmonary hypertension 10 Describe the development of an infarct a Infarct localized ischemia due to ischemia ii39 32 b It occurs when there is a decreased about ofblood ow to tissue as a result ofa block such as clot thrombus or emboli 11 De ne arteriosclerosis and atherosclerosis Describe the most important risk factors associated with the development of atherosclerosis N L a Describe the development of an atheromatous plaque based on the reaction to injury hypothesis 14 Describe clinical manifestations resulting from the development of an atheroma De ne and describe and development of shock a Shock clinical syndrome characterized by systemic underperfusion of tieesues due to prolonged hypotension 15 Given a cause of shock categorize it according to the following a Hypovolemia i Severe hemorrhage ii Diarrheavomiting iii Loss of skin b Cardiogenic i Acute myocardial event c Redistrubutive speptic shock i Sepsis may occur as a result of ii Systemic infections from pathogenic microorgansms 1 Lead to caused by a DIC b Adult respiratory distress c Bacertial d Endotoxins released i TNFA ILl IL6 IFN G DAF NO Prostoglandin leukotrienes 16 Describe the pathogenesis of the following consequences of shock a Renal failure b Acidbase imbalance c GI hemorrhage Upon completion of the section on thrombosis the participant should be able to 1 Compare and contrast clots and thrombi in terms of origin and the hemostatic system involved a Thrombi Solid mass or plug within heartarteries veins or capillaries from components of streaming blood i Clotting is the activation of a protein cascade within the blood leading to the formation of thrombin which convert fibrinogen to fibrin b Thrombosis is platelet activation and clotting i Occurs when plaque is unstable and cap releases c Thrombosis hard to get rid of i Clotting can dissolve with enzymes easier 33 2 The four contributions of platelets to hemostasis a Adhere to underlying vessel wall Adhere platelet and collagen something to bind with i b Release phar quot y active c Aggregate Aggregate platelet and platelet binding d Provide cofactors for clotting 39 Don t make platelet growth factor only store it Can lead to clots o Platelet microanatomy o In the circulation Flat disc i 1 ii 0 4 major zones I r peripheral Solgel surface membrane and structures close to surface GlycocalyX exterior coat 0 Houses receptors for signals triggering platelet activation and substrates from adhesion and aggregation Important for plateletplatelet or plateletvessel 0 Wrong bleeding Lack components and get dysfunction Contains laments to maintain shape Open canalicular system invaginations of the cell surface that increase the surface area like a sponge 0 Push membrane into center surface becomes internal 0 Don t work as well but move through body easier Fibers to maintain discoid shape and for internal contraction 3 systems 0 the submembrane fibers 0 microtubules around circumference to maintain shape 0 microfilament actin and myosin for contraction Organelle Like most cells 0 Mitochondria o Lysosomes o Peroxisomes Alpha granules Dense bodies Membrane Surface connected open canalicular system 0 Tunnels through the cytoplasm of platelet serpentine manner 0 Increases surface area Channels for release 0 34 o Dense tubular system 0 Consists of smooth endoplasmic reticulum 3 Detail the actions of adhesion release aggregation and interaction with the clotting system that platelets provide to hemostasis including the result if any of the processes or integral components or process are lacking a Adhesion 39 Binding to something Binding to damaged endothelium cells or exposed subendothelium most common characteristics 1 Bind to glycoprotein receptors derived from vessel walls 2 Collagen now exposed b IDi i iii Exposed collagen binds with glycoprotein receptors GPLa platelet 1 Von Willebrand Factor VWF binds to glycoprotein receptor GPlb endothelium a Bleeding defects ifno GPla or GPlb i Incorrect receptors platelets won t bind b Release i Platelet adherence leads to shape change ii Release preformed and denova compounds that affect homeostasis and the metabolism of the vessel wall 1 Release of storage granules anything involved with Coag a Alpha Granules PDGF thrombospondin platelet factor 4 fibrinogen Fibrinection VWF b Dense Bodies ATP ADP GDP GTP serotonin calcium i THINK ENERGY drive reaction forward iii Release of he used in synthesis of prostaglandins that both promote and prevent aggregation 1 Checks and balances c Aggregation result of shape change i Ilium Sleixr lsui lat mass body forms using fibrinogen as a bridge ii Fibrinogen binds using GPIIB and Illa Integrin iii Receptors may also bind VWF which adds to adhesion l Stimulus is ADP and thromboxane 2 iv Result Plug to keep endothelium intact d Co factors for clotting i Interact with coag factors VVIII IX and X l Serves as surface for clotting cascade triggers it ii One mechanism is the inversion ipping of phospholipids from interior to exterior o PlateletActivation o Adhesion I Platelets interact with exposed subendothelium tissue 39 Lose change shape from discoid round with pseudopdra l Fibrin and collagen have the same effect 0 Release Phase I Result of shape change 35 I Release of the contents of the intracellular granules o Involvestriggers aggregation 4 Describe the contents and function of platelet alpha granules and dense bodies a Alpha Granules substrates involved with clotting i PDGF ii Thrombospondin iii Platelet Factor 4 iv Fibrino gen V Fibrinectin vi vWF b Dense Bodies substrates that drive the reaction forward 1 ii ADP iii GPD iv GTP v Serotonin vi Calcium vii Platelets contract on stimulus l Actinmyosin modulated by Cal F a Signaled through via open canalicular and communicates with dense tubular i Excursion of Cal F to the cytoplasm CONTRACTION 5 Name three states that will promote thrombosis a Virchow s Triad b Change in intimal surface endothelium i Atherosclerosis most important change ii In ammation iii Endocarditis heart infection neoplasms exposure to collagen iv Immune complexes interact With exposed endothelium v Neoplasms change rate of blood vi Most likely involves endothelial cell loss which exposes sub endothelium and collagen vii Injury or trauma viii Bumfrost bite ix Mechanical trauma crushing x Cannulas increase risk sliding tube in you risk scraping and exposing the surface xi Chemical injuries 36 0 gt1 c Changes in blood ow i Changes in speed i Changes in pattern iii Slowing leads to venous thrombosis iv Turbulence leads to atrial or cardiac thrombosis V Reduction of blood ow vi Often occurs in the leg veins Prolong dependence on a limb viii Decrease muscular pumping ix Proximal occlusion to drainage d Constituent changes of the blood ow rate of movement i Slow blood ow is worse increases chance ofthrombosis 1 Forms pockets ofblood 2 Platelets numbers and actions Aggregatability somewhat active 1 Release Reaction can be monitored iii Adhesiveness increase leads to rest of process iv Numbers relate to bleeding or thrombosis v Very ne line 1 Increase number decreases their function because there is not enough calcium 2 Independent of each other 3 Formed object will effect how things ow whip up blood denature proteins brombosis Occurs a lot with bed ridden people Describe how injury trauma in ammation or changes in blood ow or pattern will promote thrombosis a Injury trauma in ammation will change the endothelium surface Changing the endothelium surface can impact how the blood ows through the body Ifthe blood slows down it can form pockets Turbulence can lead to atrial or cardiac thrombosis i In ammation forms i Endocarditis heart infection ii1 Immune complexes can interact with endothelium iv Neoplasms expose collagen v Changes the rate and ow Define the term hypercoaguable and how platelets can contribute to it a Hypercoaguable up regulation of vessel wall interaction in which thrombosis is favored i Increased procoagulant factors Fibronogen ii Decreased natural anticoagulants iii Increased viscosity iv Stasis blocking blood ow v Increased plateletvessel interaction most important cause of this 37 vii Super cial or deep injury to plaque cap viii Increased platelet count not extreme 39X Increased platelet function over active 0 Other Causes of thrombosis o Inherited disorders which increase risk I Antithrombin III ATIII9 Autosomal dominant 0 Increase concentration of prothrombin fragments I Protein C De ciency 9 Autosomal Dominant 0 Life long thrombosis I Protein S De ciency Autosomal Dominant o Abnormal resistance to form thrombosis o Inherited Disorders affecting fibrinolysis I Rare and affects levels of fibrinogen and plasminogen 0 Cannot dissolve things 0 Elevated levels of Fibrinogen and FVIIIc see below 0 Acquired Disorders see below 8 State how age obesity oral contraceptives cigarette smoking or malignancy can contribute to the generation of thrombi a Age obesity oral contraceptives cigarette smoking or malignancy elevate the Fibrinogen and factor VIIc concentrations b Elevated levels increase the chance of thrombosis State how thrombi can be lysed a 3 ways i By Plasmin occurs naturally ii By Streptokinase dissolving thrombosis iii Plasminogen Activator genetically engineered b Embolization worry about i Detaches from wall and travels through circulation l Eventually thrombi will get somewhere it cant get through 2 Occulsion occurs a Leads to collagen plug blocks circulation b No 02 cell death 10 State and recognize how thrombi are related to emboli and occlusion of blood vessel Look above 0 Thrombi Removal 0 Recanalization get some blood ow to return 0 Mural just at the surface blood ow passes by 50 Upon completion of the section on embolism the participant shall be able to 1 Define what an embolism is a Embolism is mass in blood stream solid or gaseous and clogs vessel 38 2 E 4 State at least 8 materials that can cause or be incorporated into emboli a Thrombus b Thrombusclot c Air d Nitrogen e Fat f Bone marrow g Debris from base of Atherosclerotic plaque h Tumor Cells Describe and recognize the contribution factors to the development of pulmonary emboli a Pulmonary emboli b Venous in origin c Most common form of embolization d Most dangerous form of embolization 1 600000 yr N 2050k are fatal 39 2 Random autopsy found 10 had them present ii Effects depend on 1 Sizeamount of obstruction 2 Presence or absence of congestion when impacted State the three categories for a pulmonary emboli based on size and what their clinical impact are a Massive pulmonary Emboli i From the legs sudden ii Associated with straining stool iii Acute Right heart failure 3 Vagal re ex with spasms of coronarypulmonary arteries 4 Re ex producing marked peripheral vasodilation 5 Re ex producingcardiac arrest 6 Massive release of prostaglandins which provokes avasospasm b Medium Size i Localized necrosis ii Infarcts or necrosis secondary to ischemia iii Block 029 tissue dies c Small size Clinically silent don t really know it happened Multiple and recurrent Retraction of the emboli and organization may leave small fibrinous tissue cords criss crossing the vessel decreases the exibility iv Can get hammered into vessel leads to mural type thrombus that leads to smooth muscle layering and thickening and eventually pulmonary hypertension ii 39 V39 Describe how systemic emboli differ from pulmonary in terms of origin and placement a Pulmonary emboliright side venous in origin b Systemic emboli left side i transmural myocardial infraction ii congestion cardiomyopathy 9 and detail the outcome of infective endocarditis and how it is linked to in ammation c Infective endocarditis occurs in the brain lower limbs spleen and kidneys Changes vessel wall Virchow s triad Disorder induced by combo of haemodynamically induced endocardial injury and bacterium Leads to localized in ammation 7 Leads to mycotic aneyrysm ii39 gt1 De ne what platelet thrombi are and Where they are most often lodged and the clinical outcome d Platelet thrombi i From plaques in the neck ii Related to atherosclerosis plaque in the neck iii Deposition in the brain i Permanent or transient ischemia attacks strokes TIA s a Air gaseous emboli i Results from 8 Head and neck injury 9 Blood transfusions 10 Hemodialysis 11 Air into fallopian tubes 12 Placental disruptions ii How 13 Air can enter into right ventricle and whipped into a frothy mess 14 From the heart action blood and air is turning causing proteins to break down and stick together a 40 mLs not good b 100 mLs Fatal 9 Detail how nitrogen or other inert gases could lead to an emboli b Nitrogen gaseous emboli iii Occurs in decompression sickness 15 High atmospheric conditions returning to normal 16 Under increased pressure inert gases dissolve into plasma and tissue adipose 40 iv Example Divers diving deep coming up fast the bends 10 Detail how fat could lead to an emboli discuss both the mechanical and biochemical theories c 90 of patients with signi cant trauma v fracture of long bones Anythmg that dlsmpts V severe burns fat depos1ts v11 severe excess1ve soft t1ssue viii hyperlipediemia ix ischemic bone marrow necrosis with sickle cell disease x joint reconstruction x39 cardiopulmonary bypass xi 39 intramedullary nailing xiii liposuction d Mechanical Theory xiv Bone marrow derived fat globules enter the venous system and lodge in the pulmonary vasculature as fat emboli e Biochemical Theory xv Circulation free fatty acids affect cell lining the air spaces and produces abnormalities in gas exchange H 11 Link atherosclerosis to emboli f Atherosclerosis plaque can lead to an emboli xvi Debris from brolipid xvii Atherosclerosis is the hardening of veins hence the plaque If part 0 the clot or ulcer breaks off and reaches an opening in cannot pass through it will lead to embolization 17 From embolization occlusion will occur and lead to a collagenous plug blocking the circulation system a Blockage means 02 which means cell death 0 Other Forms of Embolism 0 Bone marrow derived I Result from trauma to the ribs CPR Upon completion of the section on ischemia and infarction the participant shall be able to 1 De ne the terms infarct and ischemia a Ischemia decreased perfusion not meeting metabolic needs of the tissue b Infarct localized ischemia due to ischemia 2 Discuss causes of local ischemia a Causes of local ischemia i Atherosclerosis ii Thrombosis 41 ii Emboli can be from anywhere iv Arterial smooth muscle spasm V Pressure from within V Pathological change to a vessel doing drugs like heroine Discuss the role of venous occlusion a Occurs when blood cannot bypass obstruction i Leads to intensely congested b Hemorrhagic c Seen in ii Extensive mesenteric venous thrombosis iii Strangulation of hernias intestines drop down twisted which then disrupts the blood ow d Decreases blood ow Discuss the role of capillary obstruction a Physical damage to capillaries frost bite b Parasitescerebral malaria c Abnormal red cells sickle cell anemia d Fibrin i Disseminated intravascular coagulation 1 Little dots everywhere screwing with capillaries 2 Leads to formation of small blood clots throughout the body a These clots use up platelets and coagulation b No more left death 3 Can t really fix it ii Example being shot by shotgun 1 You won t die from shot but rather the DIC e AgAb Complexes i Interact with basement membrane leads to in ammation 2 Makes it so blood cannot not circulate f Fat gaseous emboli i External pressurebed sores 3 Must keep turning in order to prevent pressure or cut off blood supply Discuss the role of arterial obstruction a Wide range of cause and effect b no effects result of good collateral circulation or insignificant reduction of blood ow i more an one entry for arterial blood to tissue Describe the functional evidence of ischemia a You are okay until stressed demand for O2 increases9 most of the time you don t know you have tissues that could be ischemic until stressed b Angina or intermittent claudication 42 i Chest pain from stress ii Sign ofplaque build up c Remove source of stress and symptoms go away d Eventually loss of tissue or abnormal or de cient function iii Example in heart get electrical disturbanaces leading to arrhythmias e Diff tissues stress diff and at diff times 7 Describe the structural evidence of ischemia a Lost tissue leads to Fibrosis from necrosis resolution to injury incomplete b If slow onset little damage or loss c Sudden pulmonary emboli 8 What variables can determine the degree of ischemia and how do they interact d Degree of postischemia necrosis is proportional to the degree of ischemia i Decrease damage Decrease ischemia e Determined by interacting variables i Metabolic needs of the tissue 1 Tissues vary in their capacity to Withstand decreased arterial perfusion a Brain in most sensitive 34 mins brain damage b Myocardium i BOTH have poor collateral circulation ii Regeneration is not easy Speed of onset 2 Sudden is bad Degree of blockage 3 More proximal effects larger area c Example more damage to the body when the clot causing the ischemia is closer to the heart iv Local anatomy 4 Varies by organ 5 Some have none 6 Others have double circulation lungs ii v State of collateral coagulation 7 Stenosis 8 Fibrolipid plaques 9 Good collateral circulation supply can compensate for blockage in the main arterial tree only if the collateral vessels themselves are neither stenosed by atherosclerotic plaques nor spasms 9 Describe the relationship of ischemia to infarct a Infarction coagulative necrosis vi May be bloody from congestion b Infarction is the result of decrease arterial blood supply aka ischemia Tissues die off from the lack of supply of blood that surround the area of blockage 10 Given specific anatomical sites of infarct What type of necrosis would be expected 43 a CNS necrosis is liquefaction not coagulativecavity formation b Heart angia arrhythmia s necrosis failure of muscular activity vii Deterioration of a beating heart c Lung wedgeshape lt10 emboli due to circulatory d Liver rare e Intestine Strangulating hernia Volvus intussusception viii Twisted block 2 E Upon completion of the section on uid distribution and disturbances the participant shall be able to 5 Discuss factors that cause uid to leave the vasculature a Abnormal b Increased vasculature pressure causing leakage c Increased colloids in extravascular increases pressure leakage Discuss factors that cause uids to stay in the vasculature a Normal b Albuminmost important i Low molecular weight and high concenstration compared to plasma proteins ii Decrease in albumin in plasma concentration leads to 1 Reduced synthesisChronic liver disease 2 Excessive loss kidney disease and sever edema c Selective vascular permeability i Keeps albumin inside d Tissue tension in the interstial tissue Limits the leaving of uidfrom the microvasculature Normal tension is below 1 kPa Normal net loss from vasculature to the tissue and then back through the lympthnodes NO edema develops because excess uid drains away via lymphatics from the site where it might accumulate a Obstruct this then you will get an edema Compare and contrast exudates to transudate and their causes a Exudates if the uid is there because of increased vascular permeability and contains large amounts of macromolecules Fibrinogen b Transudate mechanism is hydrostatic protein count decreases ii39 Discuss cardiac renal nephritic and nephrotic nutritional chronic liver and pulmonary systemic edema including underlying causes principles and outcomes a Cardiac Edema i Redistribution and retention of uidgt increased body weight ii Distribution has a lot to do with gravity 1 Patient ambulant the legs are first to be involved 44 2 Patient bed ridden the edema appears in genital area iii Excess retention by renal tubules 1 Sodium and Water 2 Failure of the heart as a pump pressure on capillaries restriction causes reduction of renal perfustion a Leads to ride of angiotension 19 increase rentention of Na and H20 b Renal Edema i Nephritic 1 Associated with acute glomerulonephritis 2 Caused by sodium retention fall in glomerular ltration rate 3 Transudate characteristics a Indicates no change in permeability ii Nephrotic 1 Heavy proteinuria excess due to ability of liver to synthesize albumin a Hypoalbuminaemia losing albumin faster than the liver can make b Leads to decreased plasma oncotic pressure c Nutritional Edema i Prolonged starvation l Cause loss of subcutaneous fat a The subcutaneous tissue is looser and there is no decline in tissue tension ii Treated with bed rest iii Connected to Kwashiorkor l Decrease protein and calorie undemutrition children in economically deprived countries d Chronic Liver Disease Edema i Appears as ascites Free uid in peritoneal cavity ii Pathogenesis Increased intracapillary pressure 2 Decrease plasma albumin leading too 3 Decreased oncotic pressure 4 Increased formation of hepatic liver Na retention w cirrhosis e Pulmonary Edema i Distribution of uid between intravascular and extravascular compartments ii Balance of intracapillary hydrostatic pressure and capillary permeability 1 Increase of either leads to edema 2 Increase intracapillary pressure contributes too a Intravenous uid overload b Severe anemia c Renal failure d Increase altitude 3 Increase capillary permeability V39 45 a Aspiration b c Pneumonia d Severe Trauma e Bacterium f ARDS Adult Respiratory Distress Syndrome 5 Discuss the three types of disturbances in uid distribution seen in local edema a Increased hydrostatic pressure within microcirculation i Occurs in pregnancy ii Occurs in patients with occlusive venous thrombosis iii Occurs in those with varicose veins Increased local vascular permeability i Occurs in acute in ammation ii Occurs in hypersensitivity c Lymphedema 39 Obstruction to normal lymphatic ow 1 From surgery or in ammation Example Patients undergo radial sugery with axillary clearance for carcinoma of the breast develop severe edema on arm of the side of the operation 0quot Objectives for pigmentation and calci cation 1 List three sources of pigment for endogenous pigmentation a Melanin i Gives hair skin and eyes their color ii Melanocytes produce melanin l Concentrated in the basil layer of the epidermis 2 Constant number across races 3 Albinismnone b Hemoglobin c Fat 2 Discuss abnormal melanin pigmentation both generalized and focal a General Hyperpigmentation i Addison s disease ii Acromegaly Chronic arsenic poisoning 1v Hemochromatosis v Chlorpromazine violet grey sunlight exposure vi Large dose of estrogen 1 Given for treatment of prostate cancer 39EE 2 Pregnancy b Focal Hyperpigmentation i Freckles 46 Cafe au lait spots increased number of melanocytes l Neuro bromatosis multiple tumors derived from brous element in nerve sheet 2 Albright s syndrome PeutzJeghers Syndrome autosomal dominant l 2 main characteristics a curious focal hyperpigmentation involving lips and skin around mouth b multiple polyps in GI tract iv Lengtiginosis 1 Multiple hyperpigmentated spots characterized with increased amounts of melanocytes ii39 v Melanocyte Tumors l Commonly seen on skin a Benignmoles vi Can result from ionizing radiation UV light hear and chronic irritation 3 Discuss both local and generalized hypopigmentation a LocalFocal Vitiligo i Well de ned areas of pigmentation b General Albinism i Skin very white hair translucent pink eyes ii De ciency of tyrosine 4 State how iron can be involved in pigmentation and the possible outcomes a Excess iron is stored in the form of ferritin b Excess hemosiderin i Why 1 Increased abosorption 2 Decreased excretion 3 Impaired utilization 4 Excess breakdown of hemoglobin c Local with bruise i Pattern of deposition of excess hemosiderin l Parenchymatous 2 reticuloendothelial 5 Discuss how fats can be involved in pigmentation a lipofusion 6 Discuss how bilirubin breakdown products are involved in pigmentation 7 Compare and contrast dystrophic vs metastatic calci cation listing both a Dystropic i Serum calcium levels are normal ii Calcium salts are deposited in dead or degenerate tissue 47 b 8 Causes iii Occurs under the following circumstances Caseous necrosis Fat necrosis Thrombosis Hematosis Atherosclerotic plaque Chronic in ammatory granulation Monckebuers sclerorsis Degenerative collide goiters Cysts 10 Degenerative tumors Metastic Calci cation i Increased calcium levels 1 Due to bone resportion 2 Calcium deposits in a Kindey stone 509 gt OV39gtP Nt b Lung c Stomach d Blood vessel e Cornea 3 5 causes a Primary hyperthyroidism b Increases absorption from diet c Hypohosphatisia i Inborn error in metabolism d Destructive bone lesions e Renal tubular acidose outcomes and relative levels of Ca in the plasma serum 9 Detail the connection between necrosis and calcium deposition 10 De ne 0quot P39P qorhrvpdo Hemosiderosis Hemochromatosis i Increased absorption and deposition in the liver and hear 1 Scarring damage Anthracosis Kemicterus Siderosis Silicosis Hemolytic jaundice prehepatic Toxic jaundice intrahepatic Obstructive jaundice posthepatic 48 Upon completion of the unit on neoplasia and carcinogenesis the student should be able to ef1ne a Neoplasm i New growth ii Alterations of genes that alternate proteins therefore alternates functions 1 Result abnormal mass of tissue iii You will see 1 Increased proliferation 2 Decreased differenetiation 3 Individual cell function 4 No relationship with other cells 5 Increase mitosis with abnormalities a Tripolar quadpolar b Oncology i The study of cancer tumors and treatment c Carcinoma i Malignant tumor of epithelial origin Tumor Benign i No tendency to invade spread pushes tissue out of the way ii Surrounded by connective tissue capsule iii Get pressure atrophy around border cells dying in around tissue iv Growth rate usually slow v Don t get mestatases unless physical action f Sarcoma i Malignant tumor of connective tissue origine Cancer Malignant 39 Invasive moves through tissue i Separation from surroundings iii Grows in an irregular pattern iv Gains access to lymphatics and vasculature 1 Problem becomes way of transportation for tumor a Cannot move forward in ammation and cells proliferate v Metastases 1 Example lung cell found in spleen 2 Primary seed to secondary tumors 2 Describe the system of nomenclature used to name neoplasms and be able to differentiate benign from malignant and mesenchymal from epithelial tumors given speci c tumor names we 590 3 List and discuss each of the criteria used to differentiate benign from malignant neoplasms a Benign i No tendency to invade spread pushes tissue out of the way ii Surrounded by connective tissue capsule 49 iii Get pressure atrophy around border cells dying in around tissue iv Growth rate usually slow V Don t get mestatases unless physical action b Malignant i Invasive moves through tissue ii Separation from surroundings iii Grows in an irregular pattern iv Gains access to lymphatics and vasculature 1 Problem becomes way of transportation for tumor a Cannot move forward in ammation and cells proliferate v Metastases 1 Example lung cell found in spleen 2 Primary seed to secondary tumors 3 After a tumor splits 4 Embolic process thru vascular and lymphatic vi Dysplasia 1 Steps towards malignancy 2 Cells change with no invasion 3 Maybe a continuum vi1 Cells 1 Larger 2 Greater variation 3 Nuclei are larger 4 Greater nuclearcytoplasm ratio 5 Moves fast through division viii Loss of differentiation 1 Orderly relationship gone 2 Structure and structures become unrecognizable 3 Cells misbehaving 4 4 Describe and discuss the morphologic changes associated with anaplasia a 5 Describe the mechanisms by which malignant neoplasms spread within the body a Directly through tissue 1 ii Involves invasion of tissues adjacent to the original lesion MUST HAVE 1 Adequate blood supply a Maintains health of tumor b New growth angiogenesis i Higher the angio increase risk of malignancy c Stimulated by chemical signals i TGFA ii Angiogenin iii Inhibited by TGFB 2 Decreased adhesion to other tumor cells 50 a Loss of homotypic adhesion i Infiltrating malignant cells are shed from original primary 1 Indicates reduced cell adhesion ii Lose interaction with normal cells 3 Adhesion or basement membrane and extracellular matrix Active movement tumor mass spreadingexpanding not crawling iii How 1 The stimulated endothelial cells in capillaries and vessels adjacent to tumors a Degrade their own basement membrane b Migrate through extravascular space c Form capillary beds 2 Endothelium cells breaking a away and making a pipeline iv Invasion requires 1 Crossing connective tissue barriers 2 BM 4 3 Tumor cell interaction involves a Attachment of tumor cells to BM i Adhesion to collagen and fibrinogen b Lysis of the basement membrane i Needs protein to break thru BM Metalloproteinase 2 Heparanases 3 Serine dependent proteinases 4 Thiol dependent proteinases 5 Plasminogen activator v Movement 1 Active 2 Random kinesis 3 Directedtaxis 4 In uenced by a Intact fragmented proteins of extracellular matrix b Tumor autocrin motility factor taxis c Scatter factor from fibroblasts vi Tumor will take path of least resistance vii RESULT 1 Changes in the extracellular matrix a Destroyed matrix by tumor cells b Increase production of matric by host body trying to heal c Increased synthesis by tumor b Lymphatic s i Invasion of the lymphatic channels c Blood streams 51 i May invade small new vessels win the substance of the tumor itself or the host blood vessels near edge oftumor d Body cavities 6 Describe the speci c set of criteria that must be met before atumor Will metastasize a Steps i Liberation of cells from primary tumor mass ii Invasion of blood vessels and vasculurature iii Transfer to tumor cells iv Adhesion to endothelium v Migration from vessel which emboli have impacted Survival vii Multiplication 7 List at least 3 categories of carcinogenic agents a Remote car in g uparent 39 i Metabolized b Proximate carcinogen i Greater carcinogen ii Metabolized c Ultimate Carcinogen i Interacts with DNA 1 Types of carcinogen 39 Remote 7 parent compound 1 Metabolized then becomes carcinogen ii Proximate carcinogen l Metabolized iii Ultimate carcinogen l Interacts with DNA iv Carcinogens are taken in and processed to the point of Where they react v Goes from remote to proximate to ultimate S 2quot 9 Differentiate between directacting chemical carcinogens and procarcinogens giving examples of each 9 Brie y describe a proposed mechanism by which remote carcinogens are converted to ultimate carcinogens a Metabolizes 10 Discuss initiation and promotion as they relate to the steps involved in chemical carcinogenesis List examples of promoters a Carcinogenisis i Multistep ii Imtiation is change in genome of target cell 1 Promotion a Stimulate normal and abnormal cells b Can be broken down into 2 stages c 52 11 Discuss the following in relationship to their contribution or signi cance in the development of chemical carcinogenesis a Cell replication b Safe threshold for carcinogenic agents c Diverse in uences additional contributing factors d Multistage process hyperplasia dysplasia and anaplasia 12 Describe two theories by which radiation acts as a carcinogen a Free radicals b Thorotrast 13 Give examples of the development of cancer as a result of both RNA oncogenic viruses retroviruses and DNA viruses a i Papova l Papilloma 2 Polyoma 3 Simian Vaculating SV40 ii Herpes b RNA i EBV ii HBV iii HTLV 14 Discuss the effects that heredity has on the development of cancer and state 1 type of cancer that has been shown to be related to a speci c cytogenetic alteration a No single cause BINGOH b Genetic factors i Can see in family lines 7 breast cancer ii Inherited syndromes fall into two groups 1 Major recognizable abnormality 2 Single gene abnormality c Chromosomally determined syndromes i Downs syndrome 1 Extra 21 acute leukemia ii Klinefelter s 1 Extra X 2 Male breast cancer iii Gonadal dys genesis l Abnormal hormone soup 2 Unresponsive target d Single gene abnormalities i Xeroderma pigmentosum 1 Lack repair enzyme ii Familial adenomatous polyposis coli 1 Autosomal dominant 53 2 Tumor suppressor gene 3 Issues with colin cancer 15 State 3 additional factors that can be related to the etiology of cancer but do not fall directly into the categories of chemical radiation heredity or Viruses a Natural alfotoxins peanuts b Polycyclic hyrdocarbons grilling meat 1 Aromatic amines nitrosamines nitrosamides direct alkylating agents c Hormones 1 Good at inducing tumors ii Usually a stimulation 1 Start proliferating 2 Make this product iii Example breast cancer d Physical Agents e Foreign Material 1 Plastic 16 List possible effects that benign and malignant neoplasms have on their hosts as well as effects that the host has on the tumor I Effects of neoplasm in host 0 Wide variety 0 Depends on malignant 0 Or benign I Has no metastatic potential I Local 0 Mechanical pressure I Obstruction Increased pressure I Size Site I Brain is worse not a lot of space Tissue destruction 0 I May be a result of I Pressure I Aggressive invasive propertles of tumor 0 Hypercalcemia I Ectopic hormone production I Outside of place it should be I Bone loss 0 Hemorrhage I Epithelial surface neoplasms or just beneath surface often ulcerate and bleed I Blood loss I Chronic loss may produce severe anemia 54 0 Infection I In relation to malignancy is common and may determine time of death I Occurs I Obstructs drainage system retention of secretions I Ulceration I Immune suppression I Run risk of infection because tumors impact how bloodlymphatics ow I Body is not sterile Systemic manifestations of cancer 0 Fever I Mediated by release of cytokines I ILl I TNTa I Tumors give fevers you cant explain 0 Cachexia I Anorexia I Malabsorption I TNFa aka cachectin I Have no interest in food I Body trying to starve the tumor Effects on the immune system 0 If lymphoid neoplasia I Immunocomprimised o Humeral and Cell mediated I Can be depressed o If cell mediated I Tuberculosis I Fungal I Viral I NOTE get increased risk of all these 0 Maybe related to treatment I Chemo radiation immune 0 CLASS notes I Tumors may make you more susceptible to things viruses that went latent may appear I Have to get really close to dead to get rid of tumor I Immune response doesn t work as well 0 Autoimmunity can occur I Right antigen in right place at right time Hematologic effects of neoplasms o Anemia I Blood loss iron deficiency I Poor nutrition cachexiamalabsorption I Malabsorption macrocytic 55 I Autoimmunitydestruction I Decreased erythropoietin secretion I Treatment Polycythemia 7 ectopic erythropmetin O o Platelets I Thrombocytopenia purpura I Less platelets circulating I Hypercoaguabletoo many platelets 0 Note platelets are big problem I Tend to lose them With treatment worry about bleeding to death I Endocrine effects of neoplasms 0 Two main groups I Appropriate I Normal productionnormal site of hormone production 0 Tumor don t have feedback control 0 Abnormal amount I Ectopics I Wrong place 0 No control abnormal amount I Effect of Host 011 neoplasms I Tumor vs immune system I Immune surveillance 0 Tumor regression o Immune response to presence of tumor 0 Immunocompromisedtumors 0 Tumor rejection by animal hosts Mechanisms by which the immune system can combat tumor growth 0 Macrophage system 0 Effector Tc cells 0 lgs antibodies 0 NK cells 17 Describe the diagnostic signi cance and origin of alphafetoprotein carcinoembryonic antigen and pancreatic oncofetal antigen 18 Besides the appearance of fetal antigens discuss other means of diagnosing cancer I Biological markers c Tumorassociated antigens 39 Oncofetal antigens AF P 7 alpha fetoprotein iii CEA carcinoembryonic antigen iv HCG Note protein expression but not specific solely to tumors Fire 56 19 Differentiate between lymphoma and leukemia a Both are cancers that affect a part ofa human s immune system i Leukemia and Lymphoma are diseases of compromised immune system caused by tumor growth and their distinction lies in which cells are initially affected ii RNA retroviruses slow and irregular b Leukemia effects blood cells or bone marrow c Lymphoma effects lymph nodes 57 Upon completion of the unit on genetic mechanisms of disease the student should be able to 1 Define the following terms a Congenital vs Hereditary disease i Congenital Present at birth ii Hereditary Disease disease passed down in families b Autosom a1 Dominant one i You have it9 it will be the phenotype you see overrides second gene ii Both parents see it in every generation iii 29z1000 iv The single mutated gene is expressed even though there is a normal present v Exception of de novo vi More severe homozygous vii Male and female same rate viii Penetrance 1 Dominant mutant genotype with normal phenotype 2 Incomplete penetrance Can be variable c Autosomal Recessive two i Not expressed unless you have two effective alleles ii Parents may be normal iii Parents are at least heterozygous iv Penetrance usually complete v Male and female equal rate d Genotype i the genetic makeup of a cell an organism or an individual ie the specific allele makeup of the individual e Phenotype i result from the expression of an organism39s genes as well as the in uence of environmental factors and the interactions between the two f Sexlinked Recessive i Few exceptions it is the X ii Seen in ma es 1 Hemizygous iii Seen in females 1 homozygous g Karyotyping 1 Stimulate cells to go into division ii Stop at metaphase 39 Stain iv Bandin v d large to small vi long arms are 1 vii short arms are p h Aneuploidy i Abnormal number of chromosomes ii Trisomy9common 1 Down s people a 321 s b most common c related to age ofmom i lt20111550 ii gt45 128 Most survive P 58 e Multiple effects at different levels variation 13 6 a wouldn t know it HLA and MHC iii Monosomy9not as often Usually not alive 2 Severe defects iv Sex Chromosomes 1 More common than autosomes 2 Ylittle genetic material 3 X a lot of genetic material 4 5 2 18 XOlive Turners YO die i Mutation i Change inDNA ii Missense 1 Base substitution that leads to different amino acids 2 Not all bad 3 Bul there are outcomes like sickle cell 4 Single base mutation iii Nonsense 1 Make premature stop codon 2 Beta thalassemia 3 Stop earlyMAJ OR iv Stop codon mutation l Opposite of nonsense 2 Convert stop to regular amino acid 3 Protein continues to be made through what is usually untranslated 4 Example is constant spring v Frameshift 1 Insert or deletion vi RNA splice mutations 1 How genes are made 2 Read exon remove intron vii Consensus sequence Mutations l Borders between intron and exon 2 Donor between last 3 codons in exon and first 6 intron 3 Acceptor is last 10 codons of intron first triplet of exon 4 Mutations lead to splicing problem viii Transcriptional mutations 1 Blocks of DNA upstream or 5 end 2 Regulatory 3 Promotor mutations 4 Can go either way 5 Example in cytokines ix Mtochondrial Each mito has several copies of cicular chromosome Proteins for respiratory chain and oxidative phosphorylation Special RNA 2 RNA genes 22tRNA 13 proteins Maternal inherited mtDNA higher rate of mutation Normal population considerable variations Often late onset of disease Follows maternal line HHWWSQM W E t O 59 x Fusion Mutations nequal cross over between non homologous genes Leukemias and lymphomas xi Point Mutations l urine to purine or pyrimidine to pyrimidine are transitions 2 Purine for pyrimidine is a transversion 3 Because of dengeracy or redundancy win the coding for amino acidsi 13 have an effect Switching what beinds to what SNPS r e j Mendelian Inheritance i Law of Segregation ii Law of Independent Assortment 1 Separate genes for separate traits are passed independently of one another from parents to offspring W Nondisjunction 39 Is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2 specifically in the anaphase This could arise from a failure of homologous chromosomes to separate in meiosis I or the failure of sister chromatids to separate during meiosis II or mitosis Deletion i Deletion of region of same chromosome from different pareng different disease ii Need 4Mb to see under microscope in karyotype 1 Children not developing correctly 2 Staging issuewhat to do Should parent have more kids m Inversion i 2 breaks on single X some ii 180 degree rotation iii usually no phenotype change iv unusual gamates only seen during bondingsequencing n Translocation i Balanced 1 No loss 2 Increased risk for kids ii Example Robertsonian a Balance translocation b Two acrocentrics i One large One small Using chronic myelocytic leukemia as the example explain the chromosomal alteration associated with this type of leukemia and give the name specifically associated with this chromosoma alteration Chronic myelocytic leukemia is cancer of the white blood cells List 6 different factors that are known to be associated with variations in the genetic structure eletions of region of same chromosome from different parent different disease i Need 4Mb to see under microscope in karyotype 1 Children not developing correctly ii Staging issue what to do Should parent have more kids in b Rings i Chromosome breaks at both ends and fuses together ii DNA is sticky not supposed to have rings Okay until mitosis or if they re gametes 60 c Translocations alanced Segments break off from two separate chromosomes and are reciprocally transferred 2 No loss of genetic material for individual 3 Bad for kids ii Robertsonian Translocation Balanced translocation between two acrocentric chromosomes 2 Breaks ususally affect long arms in one chromosome and short arm in 1 1 3 d Isochromosome the other Kids have issues Endresult of the loss of either a short or a long arm of a chromosome and duplication of the lost material ii Consists of two short arms or two long arms iii Centromere off centered e Inversion 1 Results from the occurrence of two breaks withing a single chromosome ii 180 degree rotation iii Usually phenotype change iv Unusual Gametes f Aneuploidy 1 Abnormal number of chromosomes ii Trisomy9common 1 Down s people 2 3 a b c d 321 5 most common related to age ofmom i lt2011550 ii gt45 128 Most survive Multiple effects at different levels variation e 18 Edwards syndrome 13 Patau s syndrome a wouldn t know it HLA and MHC iii Monosomy9not as often Usually not alive Severe defects Exception of chromosome 21 iv Sex Chromosomes More common than autosom es Y little genetic material X a lot of genetic material XOlive Turners 1 2 3 1 7 2 3 4 5 6 YO die Klinefelter s XXY 06x XYY 090579 1600 850 live births males phenotypically look like a male 11000 NOT superman Lil bigger phenotypically Lil slower Associated with prisoners 61 8 Super females a XXX v g Polyploidy 4 Define and describe Down s Syndrome and Klinefelter s Syndrome based onthe following criteria Down Syndrome a Cytogenetic alteration observed with karyotyping i 95 show trisomy of 21 b Proposed mechanism by which this alteration occurred i Result of nondisjunction of chromosome 21 either at the first or second stage of meiotic division ii Where the nondysfunction ahs taken place at the second meiotic division the fetus carries two copies of one of the parental chromosome 21 and one copy from the other parental chromosome 21 iii The cause for the nondisjunction and the correlation of maternal age is unknown iv 4 result from Robertsonian translocation within either the maternal or the parental germ ecll line of the long arm chromosome 21 to either chromosome 22 or 1 this provides the extra genetic material v Remaining 1 of case the cause is of nondisjunction of chromosome 21 at the zygoat level c Major clinical features of each i Face Facetends to be fat with low bridged nose and oblique palpebral and prominent epicanthic folds 2 The mouth is often enlarged possible protruding tongue 3 Tongue itself lacks central groove ii Hands 1 There is a horizontal palmer crease sometimes called simian crease 2 The middle phalanx of the little finer is shorter than normal 3 Fingers curve inward iii Long bones 1 Shorter than normal 2 Effects height Abnormalities in rub cage and pelvis can be seen iv Haematological 1 Increase risk of acute leukemia v Immune 1 Increased chance of infection especially in lungs vi Central Nervous Syndrome Severe degree of mental retardation Iq of 50 2 Eventually develop Alzjeimers at around 40 d Incidence of each syndrome and its relationship to age i At about age 40 develop Alziemers ii Born with it iii related to age ofmom 1 lt20 11550 2 gt45 128 e Life expectancy i Over 40 f Prenatal screening procedures i At this time the most commonly used screening test is The Triple Screen This is a combination of three tests that measure quantities of various substances in the blood These tests are usually done between 15 and 20 weeks of gestation 62 ii Sonograms ultrasounds are usually performed in conjunction with other screenings These can show some physical traits that are helpful in calculating the risk of Down syndrome iii Screening tests do not accurately confirm the diagnosis of Down syndrome In fact false positives and false negatives frequently occur Klinefelter s syndrome st common cause of male hypogonadism Most common chromosome disorder affecting the sex chromosome Cytogenetic alteration observed with karyotyping 1 y 19 Sex Chromosome Aneuplmd l XXY 2 Male phenotypically one X becomes inactivated 3 1600850 briths ii Total of 47 instead of 46 Proposed mechanism by which this alteration occurred i Most commonly when non disjunction of the X chromosome in the mother gives rise to the karyotype in the child of 47XXY ii Rare but could be XXXY or more Major clinical features of each i Males are tall height due to disproportion of length of lower limbs Patients have a eunuchoid appearance of the lower limbs The testes are atrophic and the penis is small iv Hair resembles that of a female Gynaecomastia may be present due to high plasma oestradiol concetrations 1 defined as benign proliferation of male breast glandular vi Some show minor degree of mental retardation j Incidence of each syndrome and its relationship to age i Parental age has no in uence k Life expectancy 39 Full life ii No kids 1 Prenatal screening procedures 39 Diagnosis is made easy by finding Barr bodies in the cells of phenotypically male 5 Differentiate between autosomal and sex linked disorders based on the chromosomes involved a Autosom al Disorders i Carried through Genes ii Mostly Recessive 1 Examples Alibism Cystic fibrosis TaySachs iii Dominant alleles Examples Huntingtons disease Sickel Cell 1v Not Gender specific b Sexlinked Disorders 39 Carried through chromosomes Seen in males 1 Hemizygous iii Seen in females omozygous iv Xlinked I Q 1 If from the dad L a Daughters are carriers 12 4 b Sons are okay I Mama O Knawn miner Fr lt I 63 2 v Fragile l WWSQMer N H 0 If from mom a 50 sons are affected b 50 daughters are carriers X Severe mental retardation Acts like anX linked Normal males transmit to grandchildren Concept of premuation Common Broken X s Hard to test for If known already too late CGG repeat a Number of copies relates to disease i Normal is 30 with range of 654 ii Permutation 60200 setting stage b 140 or more indication ofhigh risk c stable make meiosis increase in female Premutations a In malesParkinson s b In femalepremature ovarian failure i Sterile 6 List criteria that can be used to differentiate between an autosomal dominant mode of inheritance and an autosomal recessive pattern a Autosomal Dominant 39 29 1000 The single mutated gene expressed even though there is a normal present Parent affected Exception is de nova More severe if homozygous Male and female rate the same Present in every generation Penetrance Dominant mutant genotype with normal phenotype Incomplete penetrance Can be variable Example if a mutation in the gene responsible for a particular autosomal dominant disorder has 95 penetrance then 95 of those with the mutation Will develop the disease While 5 will not Aulusomal Dominant Conditions Huntington Diseas ho acondroplasia s dwar 5m polycysiic kidney disease e rt limbed 64 gt1 00 b Autosomal Recessive i arents maybe normal Parents at least heterozygous in Penetrance usually complete Lose function therefor no variation iv Male and female equal rate SIZE Affected individuals are indicated by solid black symbols and un ec le rriers are indicated by the half black symbols hemochrom as s phenylkelonuria PKU Describe the mode of inheritance the specific metabolic alteration and the clinical symptoms and consequences of familial hypercholesterolemia a Genetic disorder characterized by high cholesterol levels specifically LDL b Mutations in the LDLR gene that encodes the LDL receptor protein i Mutations in the APOB LDLR LDLRAPI and PCSK9 genes cause hypercholesterolemia c Mode of inheritance autosom al dominant d Clinical symptoms 1 Very high cholesterol levels in the blood 11 iii Yellow patches above eye e Consequences i Increases the risk of developing heart disease Specifically coronary artery disease ii Build cholesterol in other tissues that could lead to tendon xanthom as For each of the following inborn errors of metabolism state the mode of inheritance the specific metabolic pathway affected the enzyme defect the clinical manifestations and treatment where applicable a Phenylketonuria 39 Mode of inheritance l Autosomal recesiive metabolic genetic disorder ii Specific metabolic pathway affected 1 The enzyme phenylalanine hydroylase normally coverts the amino acid phenylalanine into the amino acide tyrosine 2 If the reaction doesn t occur a Increase amount of phenylalanine b Defiency oftyrosine iii Enzyme defect l Defected enzyme Phenylalanine hydroxylase PAH iv Clinical manifestations 1 Initially infants don t have symptpms without treatment develop Mental retardation Behavioral or social problems Hana 9017 mm Ewe quotO on H m o 5 lt amp Skin rashes eczema 65 0 Small head size microcephaly A musty odor in the child39s breath skin or urine caused by too much phenylalanine in the bod Fair skin and blue eyes because phenylalanine cannot transform into melanin the pigment responsible for hair and skin tone 93 t v Treatment 1 Diagnosed early enough an affected newborn can grow up with normal brain development a Must control Phe levels through diet and medication i Low in P e 2 Medication tetradrobioprterin BH4 Reduces blood levels of this amino acid in certain patients 3 Gene therapy b Albinism i Mode of inheritance l Congenital disorder 2 Inheritance of recessive gene alleles ii Specific metabolic pathway affected 1 The production of melanin 2 Melanin is not produced if the enzyme is tyrosinase is absent iii Enzyme defect Absents of the enzyme Tyrosinase leads to the full inability to produce melanin iv Clinical manifestations 1 Visual impairment a Rapid involuntary backandforth movement of the eyes nystagmus b Inability of both eyes to stay directed at the same point or to move in unison strabismus c Extreme nearsightedness or farsightedness d Sensitivity to light photophobia e Astigmatism Milky white skin Hair color varies from white to brown some yellow Eye color ranges from blue to brown with age a Can appear red awn v Treatment 1 Eye treatments a Visual rehabilitation b Surgery Glasses Taysachs disease is a lysosomal storage disease39 discuss the mode of inheritance the specific metabolic defect the clinical manifestations and the prognosis a Mode of inheritance i Autosomal recessive ii Rare iii Causes deterioration of nerve cells and mental and physical abilities that commence around 6 months of age usually result in death at about 4 years old b Speci c metabolite defect 39 Result of the mutations in the HEXA gene on human chromosome 15 ii This encodes the alphasubunit of betaNacetylhexosaminidase a a Lysosomal enzyme c Clinical manifestationsseveral forms based off age 1 Infantile infants appear normal at first till about 6 months after birth I Becomes blind deaf unable to swallow atrophied and paralytic 66 2 Death at 4 ii Juvenile l Rarer 2 Initially seen between ages two through ten years old 3 Develop cognitive and motor skill deterioration dysarthria dysphagia ataxia and spasticity 4 Death between age 5 and 14 iii AdultLate onset I First sympoms at age 30s to 40s Usually not fatal effects can stop progressing Frequently misdiagnoised IT quot of gait p 39 39 deterioration Symptoms can be seen in adolescence or early adulthood a Speech and swallowing difficulties unsteadiness of gait spasticity cognitive decline and psychiatric illness particularly a schizophrenia 6 Fulltime wheel chair users d Prognosis above 10 Discuss the mode of inheritance the metabolic defect in carbohydrate metabolism the clinical features the urine laboratory findings and the treatment for galactosemia Galactosemiacannot fully break down sugar Diagnosised withNBS Newborn Screening Mode of inheritance i Rare ii Autosomal recessive iii l60000 Metabolic defect in carbohydrate metabolism i Deficiency in an enzyme responsible for adequate galactose degradation ii Lactose in food such as dairy products is broken down by the enzyme lactase into glucose and galactose In individuals with galactosemia the enzymes needed for further metabolism of galactose are severely diminished or missing entirely leading to toxic levels of galactose lphosphate in various tissues as in the case of classic galactosemia Clinical features 39 in hepatomegaly an enlarged liver cirrhosis renal failure cataracts brain damage and ovarian failure Without treatment mortality in infants with galactosemia is about 75 ii Jaundice yellowish discoloration of the skin and the whites of the eyes Vomiting Poor feeding baby refusing to drink milkcontaining formula Poor weight gain Lethargy Irritability Convulsions Urinary laboratory findings i checks for three enzymes that are needed to change galactose sugar that is found in milk and milk productsinto glucose a sugar that your body uses for energy I A person with galactosemia doesn39t have one of these enzymes This causes high levels of galactose in the blood or urine 2 3 4 5 ST 0 Equot P F Treatment i Avoid all milk containing products and other foods containing galactose ii Feed infants with soy formula meat based or nutramigen ll Describe the genetic basis of hemophilia A state which clotting factor is missing and give the clinical consequences of this abnormality State an appropriate method for treating this disorder Hemophilia A a Which clotting factor is missing i Lacking factor VIII ii Causes increased bleeding usually in males iii Xlinked recessive trait l Occurs in males 67


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