Midterm 2 Pathology

What is a paradoxical embolus?

-Any venous embolus that gains access to systemic circulation by crossing over from the right to the left side of the heart thru a septal defect

What are the 2 control points in the coagulation pathways and why?

-Factors 5 and factors 8 (both involve thrombin)

Healing from infarct: 1) How do most infarcts "heal"? Mechanism? Caveat to this?

-Heal by organization: ingrowth of fibroblasts and collagen (granulation) from periphery toward center *Person needs to live long enough for this to occur

What is a major difference between Type 2 and Type 3 hypersensitivity reactions?

-Type 3 can become systematic since it can travel thru blood vessels, whereas Type 2 is localized to a location/tissue

Chronic passive congestion-Due to right sided heart failure: Image* 1) What pathology can result from this in liver? What does this look like in tissue? 2) What does a slide of cells look like? 3) What type of injury does this cause and why? What type of environment is created? Right sided heart failure can do what to heart? 4) In foot, what occurs due to this chronic passive congestion (3)

1) "Nutmeg liver": portal triads resemble light tan/dark colored nutmeg pattern 2) See blood/pink color backing up into triads from central vein (large pink portal veins) 3) Hypoxic injury due to hepatocytes dumping CO2 here -Goes to anaerobic environment creating lactic acid -Cause cardiac sclerosis 3) Foot: Edema, thinning of skin, and ulcers

Systemic Lupus Erythematosus (SLE): 1) Incidence? 2) Female to male ratio? 3) When in life this most often occurs? 4) More common/severe in what ethnic group? 5) Pathogenesis: Failure of what? 6) What 4 things are antibodies directed to? What are 4 types of antibodies that target nucleolar antigens and % positive Abs made for each

1) 1/2500 2) Female to male ratio= 10:1 3) Teens or 20s (2nd/3rd decade) 4) More common/severe in African Americans 5) Pathogenesis: Failure of sustaining self-tolerance (recognizing self self-produced antigens as a non threat) 6) Antibodies directed toward: a) DNA b) Histones c) Nonhistone proteins bound to RNA d) Nucleolar antigens: -ANA: >95% -anti-dsDNA: 40-60% -anti-SM (smith): 20-30% -Anti-phospholipid antibody (40-50%)

HIV Virus: 1) What are the 2 causative agents in AIDS? What type of virus (DNA/RNA)? What is the specific genus of retrovirus? First type this genus were described in what? 2) What is another type of retrovirus that has ability to cause cellular transformation? What are the 4 viruses in this group?

1) 2 causative agents: Human retrovirus HIV-1 and HIV-2 -RNA viruses; cytopathic lentivirus (type of retrovirus) -First type of lenti viruses were described in non-primates 2) Human oncoviruses (leukemia viruses) -Mammalian and avian type C virus -feline leukemia virus -bovine leukemia virus

Image: 1) During the clinical course of HIV disease, how many viremias are seen? What 3 events occur in each? 2) What occurs after the first viremia? Significance of this timeframe (2)? 3) What is the most daunting problem in "curing" HIV infection?

1) 2 viremias: a) 6 weeks: First (transient viremia): acute HIV syndrome, wide dissemination of virus, and seeding of lymphoid organs b) 7-11 years: Second: Constitutional symptoms, opportunistic diseases, and death 2) 6 weeks-7 years: Clinical latency: After first viremia, immune response virtually clears virus from blood: virus enters a variety of cellular reservoirs (macs) and remains dormant as a provirus integrated in genome 3) Most daunting problem: little is known on how to clear provirus from eukaryotic genomes

Amyloid: 1) 3 components? 2) How is it arranged? 3) What type of birefringence (under polarization) of amyloid is seen when first stained with Congo Red? What does this look like? 4) What are the 2 chemically distinct insoluble amyloid fibril proteins? 5) 2 classifications of amyloidosis

1) 3 components: a) Fibrillary protein b) Amyloid P protein c) Glycosaminoglycan FAG 2) Arranged in beta pleated sheet 3) Green birefringence -Dichromism: bends light in a way where looks green in one view, and diff color in another view (glow in the dark look/apple-green) 4) Chemically distinct amyloid fibril proteins: a) Amyloid light chain (AL) b) Amyloid-Associated (AA) 5) 2 classifications: a) Systemic forms b) Localized forms

Amyloid (contin): 1) Significance of fibrillary protein's biochemical nature? 2) Amyloid P: Does this vary/stay constant in all amyloid? What is it derived from? 3) What is Glycosaminoglycan mostly composed of and responsible for?

1) 3 components: a) Fibrillary protein: biochemical nature varies with underlying disease b) Amyloid P protein: -Similar in all amyloid -derived from a serum protein called serum amyloid P component (SAP) c) Glycosaminoglycan: -Composed of heparin sulfate -Responsible for iodine staining properties of amyloid (starch like)

Platelet Hemostasis- Step 2 During Platelet Activation: What 3 things occur here

1) 3 things: a) Platelets undergo shape change and degranulation b) Platelet synthesize thromboxane A2 (vasoconstrictor and platelet aggregator) c) Membrane expression of phospholipid complex: important for coagulation cascade

Histo slides (113-114): 1) 3-5 days post-myocardial infarction, what abundant cell can you see on slide of cardiac tissue? What type of necrosis is this? 2) 14 days post-myocardial infarction, what can you see on a slide of cells? 3) What is a remote infarct? what does this look like within kidney?

1) 3-5 days: a) Lots of neutrophils *Coagulative necrosis! 2) 14 days post MI a) Macrophages (secrete VEGF) laying down b) Granulation tissue (new blood vessels forming) c) With collagen type 3 *More obvious coagulative necrosis at bottom of slide 3) Remote infarct=old -irreversible scar tissue

Septic (bacterial infection): 1) High levels of endotoxin (lipopolysaccharides) release leads to production of what 4 cytokines? 2) Depending how on low, moderate, and high quantities of cytokines, what 3 effects occur?

1) 4 cytokines: a) TNF (inflammation) b) IL-1 (inflammation) c) IL-6 (inflammation) d) IL-8 (neutrophil and other inflammatory cell recruitment) 2) Depending on how how much is released leads to: a) Local inflammation (low quantities) b) Systemic effects (moderate quantities) c) Septic shock (high quantities)

Transplantation: 5 important types of transplants that produce acquired immunodeficiencies; What are the 3 types of rejection?

1) 5 transplants a) Renal b) Heart and/or lung c) Bone Marrow d) Liver 2) 3 types of rejection: -Hyperacute rejection -Acute rejection -Chronic rejection

Malignant Lymphomas: 1) What % of AIDS patients get B cell lymphomas? 2) 4 locations these often occur 3) What are these lymphomas similar to (2)?

1) 6% of patients 2) 4 locations: a) Lungs b) GI tract c) Bone marrow d) Brain 3) Simliar to: a) Transplant lymphomas b) Lymphomas of congenital immunodeficiencies

Congestion: 1) AKA? Definition 2) What is passive and active congestion each due to? 3 causes/examples of passive? 2 causes/examples of active? 3) What physical symptom does active hyperemia cause? What is this brought about by (2)? 2 vasoactive substances?

1) AKA Hyperemia: Increased volume of blood within dilated vessels 2) 2 types: a) Passive hyperemia=Mechanical effect: -Right sided heart failure -Chronic congestion of liver and lungs -Venous thrombosis b) Active hyperemia=dilation of arterioles: -acute inflammation and hypersensitivity reaction type 1 3) Active hyperemia: Causes increased redness in affected part (due to arteriole dilation) -brought about by sympathetic neurogenic mechanisms or release of vasoactive substances: histamine and serotonin

Chemically distinct insoluble amyloid fibril proteins: 1) AL protein (amyloid light chain): a) What stimulus stimulates formation of the AL protein? b) What cell is amyloid light chain derived from? c) What soluble precursor misfolded protein is it made from? 2) AA protein (amyloid associated): a) What stimulus induces formation? b) What cells get activated subsequently? What 2 IL are release? c) What cells get activated by IL? d) What soluble precursor misolded protein is it made from?

1) AL: a) Stimulus unknown (potential carcinogen) b) Derived from plasma cells c) Misfolded Ig light chains 2) Amyloid-associated: a) Chronic inflammation b) Macrophages activated, releasing IL-1 and IL-6 c) Liver cells stimulated by IL d) SAA protein (non-Ig protein)* created by liver

Type 4 Hypersensivity Reaction: How is a granuloma formed (3 steps); what type of necrosis was this seen in?

1) APC presents antigen to CD4 T cell as well as stimulates more production of cell by releasing IL-12 2) CD4 T cell secretes IL-2 for self-proliferation and TNF/Interferon-gamma to recruit monocytes/diapedesis of cells into extravascular space 3) Macrophages/giant cells/epithelioid cells, fibroblasts and lymphocytes gather to create granuloma *Caseous necrosis

Edema: 1) Definition-where does this accumulate (2)? 2) 5 causes

1) Abnormal accumulation of water in tissue spaces and serous cavities 2) Causes: a) Endothelial cell wall/blood vessel wall damage b) Increased hydrostatic pressure c) Increased osmotic tension of ISF d) Decreased oncotic pressure of plasma (due to proteins such as albumin*) e) Lymphatic obstruction

Insoluble Amyloid Fibril Formation: 1) What 2 proteins are made from production of abnormal amounts of protein? 2) What protein is made from production of normal amounts of mutant* protein? Name of mutated protein?

1) Abnormal amounts of protein: AL (amyloid light chain) and AA protein (amyloid associated) 2) ATTR protein -made from mutated transthyretin protein*

Metabolic consequence of alcohol metabolism: 1) What is an important enzyme involved in alcohol metabolism? What type of enzyme is this- Therefore, what effect does it have on some people? 2) What is product made from breaking down alcohol? 3) What is an important product made from TCA cycle/Krebs and what is it used for? What happens if you increase products of TCA via increased alcohol consumption? What builds up and leads to immunosuppression ?

1) Acetaldehyde dehydrogenase -Potent vasodilator: Makes some people get very red in face 2) Creates acetate which is needed to create acetyl CoA: important starting product for TCA 3) Creation of NADH for oxidative phosphorylation to make ATP -If increase products of TCA (NADH), stops TCA; acetate will build back up--> immunosuppression

Sjogren Syndrome: 1) In a histological slide of parotid gland cells, what do the see? In an image of a person with malignant lymphoma (1% of pts), what is seen?

1) Acinar units are destroyed by influx of B/T cells (lots of inflammatory cells) 2) An even more enlarged parotid (salivary) gland that represents the influx of B cells making Ab to SSA/SSB to destroy acinar units

What are the 3 general types of bleeding disorders related to clotting factor abnormalities? 2 types of acquired bleeding disorders? 3 types of inherited bleeding disorders?

1) Acquired a) Vitamin K deficiency b) Liver failure or disease 2) Inherited a) von Willebrand disease b) Hemophilia A (Classic hemophilia) c) Hemophilia B (Christmas Disease) 3) Disseminated Intravascular Coagulation (DIC)

Platelet Hemostasis- Step 3 (Platelet aggregation): 1) 4 other steps that occur here

1) Activation of platelet aggregating factors: ADP, prostaglandin, thromboxane A2, endoperoxides 2) Activation of platelet clotting factors (platelet factor 3=thromboplastin and platelet factor 4=heparin neutralizing factor) 3) Activation of platelet thrombosthenin (cause clot retraction) 4) Platelets bind to eachother by binding to fibrinogen using Gp 2b-3a

Immune Thrombocytopenic Purpura (ITP): 1) Acute ITP: What group is this seen in? Significance of disorder? 2) Chronic ITP: What group is this seen in? May be the first manifestations of what 2 disorders? 4 symptoms that may result?

1) Acute ITP: -Seen in children following viral infection -Self-limited disorder 2) Chronic ITP -Seen in women in childbearing years -First manifestation of SLE and AIDS -Symptoms: a) Petechiae (pinpoint bruises) b) Ecchymoses (larger bruising) c) Menorrhagia (heavy vaginal bleeding) d) Nosebleeds

2 Stages of HIV Disease and what type of lymphadenopathy is seen in each? What are made in the first phase (how long does this take) and what is patient susceptible to in second phase?

1) Acute Phase -Viral mononucleosis syndrome (lymphadenopathy) (ex: EBV) -Seroconversion: Make Abs to virus in about 6-12 weeks 2) Chronic phase: -Persistent generalized lymphadenopathy -Minor opportunistic infections (oral candidiasis)

1) In a histology slide renal tubules, what will you see in acute vascular rejection? What will you see during acute cellular rejection? 2) In histology slide of renal tubules what will you see during chronic rejection?* (3)

1) Acute vascular rejection: Lumen of vessel is occluded due to thickening (cause decreased perfusion) -Acute cellular rejection: Lots of increased cyotoxic T cells around tubular cells 2) Chronic rejection: -Fibroblasts coming in and causes narrowing of blood vessels in lumen (ischemic damage) -Wall thickening of vessel -Light pink area=fibrosis/scarring

What 2 types of molecules do platelets contain? 6 examples of first, 6 examples of second

1) Alpha granules: -Fibrinogen -Fibronectin -Clotting Factors 5 and 8 -Platelet factor 4 (heparin-neutralizing factor/protein) -Platelet derived GF 2) Electron-dense bodies: -ADP, ATP -Ionized Ca2+ -Histamine -Serotonin (5HT) -Epinephrine

Complement System Disorders (contin): 1) What 2 factors are deficient in alternative pathway only and what type of infection is pt at risk of? 2) When classical complement regulatory protein ____ is deficient, what pathology does this lead to? What physical symptom does this cause at mucosal surfaces? What 2 types of complement levels are low

1) Alternative pathway only: a) Factor B and properdin: increased neisserial infections 2) Classical complement regulatory protein: a) C1-INH deficiency (C1 inhibitor protein): leads to hereditary angioedema -Causes edema at mucosal surfaces -C2 and C4 levels are low

DIC: 1) In lung alveoli cells, what do you see (2)? 2) In skin cells, what can you see? 3) In organs (kidneys, stomach, etc.), what is the common physical trait? 4) Meningococcemia: a) In a body section of someone with meningococcemia, what does skin and cross section of tissue look like (2)? b) What do cells of skin look like (3)

1) Alveoli: Vast amount of shistocytes in alveolar sacs with pink platelet thrombi between cells 2) Skin: Bright pink thrombi in dermis 3) Diffuse bleeding 4) Meningococcemia: a) See purpura: purple bruising with blood blisters on skin -See bleeding within the subcutaneous fat b) Cells of skin: See thrombi in dermis, basement membrane death, and epidermis lifting off dermis

Disseminated Intravascular Coagulation (DIC): 1) What is the significance of its cause? Release of what is key to begin DIC? 2) Release of this critical component leads to formation of what and where? 3) Fibrin-platelet thrombi formation directly leads to what 3 things (important bc this determines what you see on lab tests)? These ultimately cause what pathology?

1) Always secondary to another disorder! -Release of TF is key to DIC 2) Release of TF --> leads to extensive microvascular thromboses* (aka fibrin-platelet thrombi=small blood clots) that occur throughout bloodstream 3) Widespread Fibrin-Platelet Thrombi lead to: a) Fibrinolysis: Breakdown fibrinogen to fibrin split products b) Ischemic tissue injury c) Consumption of clotting factors* and platelets *All lead to HYPOXIC INJURY

Diffuse scleroderma: 1) What are antibodies against here (2 names)? Found in up to what % of patients with diffuse scleroderma? 2) Clinical characteristics (3)? 3) What 4 organs are involved and what happens to each of them clinically?

1) Anti-DNA topoisomerase 1 antibody (Anti-Scl-70: 40-70%) 2) Clinical characteristics: a) Widespread involvement of skin at onset** (diff than CREST) b) Early visceral involvement c) Rapid progression 3) Clinical Course: a) Renal: Renal failure b) Lung: Pulmonary insufficiency c) Intestine: Intestinal malabsorption d) Heart: Cardiac failure

CREST Syndrome: 1) What antibodies are made? 2) Clinical characteristics in terms of the acronym (5)? 3) Significance in terms of skin involvement? Does Visceral involvement occur-significance? 4) Significance regarding clinical course?

1) Anticentromere antibody (90%) 2) Clinical: a) Calcinosis (metastatic calficiation) b) Secondary Raynaud phenomenon (affects digits) c) Esophogeal dysmotility (dysphagia) d) Sclerodactlyly e) Telangiectasis (end blood vessels become dilated and blood backs up) 3) Skin involvement/Visceral: a) Limited skin involvement confined to face and fingers b) Visceral involvement occurs late* not early like diffuse scleroderma 4) Clinical course is relatively benign

Goodpasture Syndrome: 1) What are there autoantibodies against in this? 2) 6 steps that induce hypersensitivity reaction type 2 in glomerulus 3) What are the 3 consequences from in lung/kidney?

1) Autoantibodies against basement membrane in lungs and kidney 2) 6 steps: a) Anti-GBM antibodies form against basement membranes in renal glomeruli and lung b) Anti-GMB antibodies bind to GBM and trigger complement cascade (complement C2 and C4 are consumed) c) Chemotactic factors such as C5a attract neutrophils to glomerular capillaries d) PMNs attempt to phagocytize the anti-GBM and complement bound to the GMB and release lysosomal enzymes e) GMB disintegrates and allow plasma proteins to escape f) Subsequent coverage of the GMB with a continuous sheet of epi via fusion of epithelial foot processes 3) Consequences: Hemoptysis, hematuria, and renal failure

Wiskott-Aldrich Syndrome: 1) What cells are affected here? Therefore what is decreased and what is depleted? 2) What type of disorder (who is affected)? 3) 4 clinical presentations

1) B and T cell deficiency -Decreased level of serum IgM and depletion of T cell dependent paracortical areas of lymph nodes 2) X-linked recessive (males affected) 3) Clinical Presentation: a) Prone to develop malignant lymphoma b) Ezcema c) Thrombocytopenia d) Vulnerability to recurrent infection PETV

X-Linked Agammaglobulinemia of Bruton: 1) What is there a deficiency of and where (2)? 2) What type of cells are present?What is absent? 3) What cell function is intact? 4) What group is affected more? Time of onset? 5) 5 clinical pathologies? What 2 types of pyogenic bacteria is person susceptible to? 6) On physical exam, what would make you suspect primary B/T cell deficiency if pt is asymptomatic?

1) B cell deficiency in blood and lymphoid tissues 2) Pre-B cells with intracytoplasmic IgM -No surface immunoglobulins* 3) T cell function intact 4) Males affected more -Early onset (as soon as birth) 5) 5 clinical pathologies: a) Recurrent infections at 6-8 months of age (especially pyogenic organisms-staph and Haemophilus influenzae) b) Recurrent conjunctivitis c) Otitis media d) Bronchitis e) Pneumonia 6) Decreased size of lymph nodes/no tonsils due to decreased germinal centers (where B cells are located)

Review from last slide: 4 fates of a thrombus-which occur in small/large thrombi

1) Be removed by fibrinolysis (small thrombi)-resolution 2) Give rise to an embolus (potential to move back to lungs) 2) Organiziation and recanalization (large thrombi)

What are 3 Laboratory Tests for Platelet Function? What is the normal range for the first 2?

1) Bleeding time: normal (2-7 minutes) 2) Platelet count: normal (150,000 to 400,000 per mm^3) 3) Platelet aggregometry (see if platelets agglutinate in test tube)

Cell Mediated Hypersensitivity: Renal Allograft Rejection (7 steps)

1) Blood borne graft cells (dendritic cells/ monocytes) serve as initial APC 2) CD4 helper cells recognize HLA-D antigen differences between graft and host 3) CD8 or suppressor/cytotoxic cells recognize HLA-A, B, C differences bw the great and host 4) Sensitized CD4 cells secrete IL-2 which cause proliferation of cytotoxic CD8 cell and enhance B-cell humoral response (Ab production) 5) Sensitized cytotoxic CD8 cells recognize the original graft via HLA-A,B, and C antigens and specifically kill graft cells 6) During graft attack, CD8 cells also release IFN-alpha, activating macrophages (causes nonspecific damage to graft) 7) Abs recognizing graft can initiate Class 2 reactions via ADCC and complement

1) In a histological slide of GI tract of someone with amyloidosis stained with H&E and Congo Red, what do you notice in terms of blood vessels (2)? Therefore what condition may patient present with and why? 2) On presentation, what does pt present with physically? 3) If you suspect patient has amyloidosis, how do you check? You can also use this test to check what other condition?

1) Blood vessels have smaller lumen and thickened walls--> hypoxic damage -Present with diarrhea since cannot absorb nutrients 2) Purpuric lesions (bruising) 3) If suspect amyloidosis, pinch skin and if pt has spontaneous bleeding (palpable purpura), they have amyloidosis -Vasculitis--> also will have palpable pupura

Fibrinolysis: 1) What is the function of this? What occurs to fibrin? 2) What are 4 ways of breaking down fibrin?

1) Body's system of checks and balances to prevent too much clotting--> dissolves fibrin after it is formed 2) 4 ways of breaking down fibrin: a) Increased levels of circulating anticoagulants (heparin) after an episode of clotting b) Increased levels of enzymes that inactivate the activated clotting factors (thrombomodulin) c) Reticuloendothelial system: Removes particulate procoagulants like thromboplastin/tissue factor from circulation d) Fibrinolytic enzyme system: lyses fibrin after it is formed via plasmin (protease)

SLE Pathology of Skin (5)

1) Bullae (blisters >1 cm) 2) Urticaria (hives) 3) Ulcerations (vasculitis) 4) Mallar (cheek) rash: butterfly pattern 5) Maculopapular lesion (<1 cm+ raised): discoid lupus *BUUMM

What are 2 tissues that do not have lymphatics in body Lymphatics critical to return to what system and why?

1) CNS: has CSF instead 2) Cartilage *Lymphatics critical to return to venous system to reconstitute bile

1) Cardiogenic shock: 4 examples of cause? 2) Obstructive shock: cause? 3) Septic shock: What type of infection is this? 2 causes?

1) Cardiogenic (pump failure): -Myocardial infection -myocarditis -cardiac arrhythmia (hypotension) -cardiac tamponade (pressure on heart due to fluid filling pericardial sac--> cause decrease blood flow and BP drops) 2) Obstructive: Massive pulmonary embolism 3) Septic (bacterial infection): -Gram negative septicemia -Release of endotoxin (bacterial wall LPS**) into circulation

Disseminated Intravascular Coagulation (DIC): 1) 4 general causes?

1) Causes: a) Obstetric complications b) Infections c) Neoplasms d) Massive tissue injury *others as well

Hemostasis: *recording 1) Integrity of cell wall: What 4 examples of conditions can make wall weak/unstable? 2) Platelets: 2 categories hemostasic issues due to platelets? Example of each? 3) Coagulation cascade: Disease in what organ can compromise hemostasis by inhibiting coagulation cascade? Example of disorder?

1) Cell wall instability due to: a) Increase hydrostatic pressure b) Malnutrition b) Vasculitis (inflammation): due to collegenase/elastase from neutrophils->cause palpable purpura (bruising) in dermis and subQ d) Amyloidosis: abnormal extracellular protein deposited in wall of blood vessel (also cause palpable plura) 2) Platelets a) Qualitative: Plenty of platelets but no hemostatic plug formed -Aspirin (anticoagulant) makes platelets non functional b) Quantitative: Thrombocytopenia (decrease platelets) 3) Coagulation cascade: *Liver damage: Hepatocytes make most clotting factors, so if damage to liver (cirrhosis), will have bad hemostasis -ex: Cirrhosis

5 classes of renal pathology of SLE: 1) What occurs in each? Which is first and second most common to occur? What do all lead to?

1) Class 1: No morphologic changes 2) Class 2: Mesangial lupus nephritis (immune complexes deposit in mesangial cells of glomerulus) 3) Class 3: Focal glomerulonephritis (not all glomeruli are damaged) 4) Diffuse Proliferative glomerulonephritis (all glomeruli damaged) *most common (45-50%) 5) Class 5: Membranous glomerulopathy (immune complexes trapped in podocytes)* second most common *All lead to renal dysfunction

1) In images of cryptococcal meningitis, what does the brain look like (what should it look like)? 2) In toxoplasmosis, what is seen in a bisection of brain (2)? In histological slides, what is seen (2)

1) Clouding of the meninges (should be translucent) 2) Necrosis with yellow ring enhancing lesion -Histological: a) Plasma cells (making Abs to microorganism) b) Nurse cell (round cells that are immature organisms of toxoplasmosis)

Type 2 Hypersensitivity: 1) 3 pathologies that fall under Complement Dependent type 2 hypersensitivity reactions 2) 1 pathology that falls under of Antibody Dependent Cellular Cytotoxicity 3) 2 pathologies that fall under Antibody-Mediated Cellular dysfunction

1) Complement dependent: -Autoimmune hemolytic anemias -Erythroblastosis fetalis -Goodpasture syndrome 2) Ab-dependent cellular cytotoxicity -Pernicious anemia 3) Ab-mediated cellular dysfunction: -Graves Disease -Myasthenia gravis

1) What pathology is pitting edema due to? 2) Where is the greatest volume of blood-arterial or venous system? Significance?

1) Congestive heart failure 2) Venous system-if get CHF, veins get distended/blood backs up into veins, hydrostatic pressure in capillaries increases, and force fluid into tissue-->get edema here

von Willebrand Disease: Spontaneous bleeding from mucous membranes- 6 locations this can occur in body

1) Conjuctiva (eyes) 2) Oral cavity 3) Anus 4) Labia 5) Nasal cavity 6) Vagina *COALNV

Immune Thrombocytopenic Purpura (ITP): 3 Treatments? Function of each?

1) Corticosteroids: Decrease Ab production 2) Ig therapy: Bind Fc receptors on splenic macrophages 3) Splenectomy: Removes site of platelet destruction and Ab production

Neuropathology of HIV Disease: What are 5 Neuropathology disorders to know? Which one is important for driving neoplasia? Which is most common? Which is a demyelinating disease? Which one will you see diffuse lesions?

1) Cryptococcal meningitis 2) AIDS dementia: diffuse lesions* 3) Toxoplasmosis Encephalitis *most common 4) Progressive multifocal leukoencephalopathy: JC virus (demyelinating disease) 5) Malignant B cell Lymphoma (EBV)-drives neoplasia* *CATPM

1) What is hypovolemic shock 2) Caused by loss of what 4 things?

1) Decreased blood volume (hypovolemic): 2) Caused by: a) Loss of whole blood (hemorrhage) b) Loss of plasma c) Loss of fluids and electrolytes (severe dehydration) d) Loss of fluid secondary to severe burns

Thrombotic Thrombocytopenic Purpura (TTP) Lab findings: 1) What happens to platelet count and bleeding time? 2) What happens to PT and PTT? 3) What does peripheral blood smear show (3)

1) Decreased platelet and prolonged bleeding time 2) Normal PT and PTT 3) Peripheral blood smear shows thrombocytopenia, schistocytes, and reticulocytes (immature RBC)

Immune Thrombocytopenic Purpura (ITP): 1) What happens to # platelets? What happens to bleeding time? 2) What happens to prothrombin (PT) and partial thromboplastin time (PTT)? 3) What does peripheral blood smear show (2)? 4) What does BM biopsy show (2)? 5) Is there fibrinogen significance? What will you not see here?

1) Decreased platelets and prolonged bleeding time 2) Normal prothrombin time (PT) (extrinsic pathway) and partial thromboplastin time (PTT) (intrinsic pathway) *not an issue with clotting factors 3) Peripheral blood smears show thrombocytopenia with enlarged immature platelets (megakaryocytes) 4) BM biopsy shows increased # of megakaryocytes with immature forms 5) Fibrinogen is normal *Will not see schistocytes

Hemolytic Uremic Syndrome (HUS) Lab findings: 1) What happens to platelet count and bleeding time? 2) What happens to PT and PTT time? 3) Is there significance regarding fibrinogen?

1) Decreased platelets, increased bleeding time 2) PT and PTT normal 3) Fibrinogen normal

Thrombocytopenia (quantitative defect in platelets): 1) What are 2 common platelet disorders caused by decreased production of platelets? 2) What are 4 common platelet disorders caused by increased platelet destruction

1) Decreased production: a) Aplastic anemia (drugs, viruses, etc) b) Tumor (metastatic cancer) 2) Increased destruction a) Immune thrombocytopenia (ITP) b) Thrombotic Thrombocytopenic Purpura (TPP) c) Hemolytic Uremic Syndrome (HUS) d) Hypersplenism (large spleen traps platelets)

Hemophilia B (Christmas Disease): 1) What is this due to? 2) Type of inheritance? What gender does it affect 3) Clinical symptoms similar to what?

1) Deficiency in factor 9 2) X-linked recessive (males) 3) Clinically identical to hemophilia A

Shock: 1) Characterized by what (2)? Due to one of what 3 things? It results in (2) 2) Is cellular injury reversible? Explain.

1) Definition: -Characterized by (a) vascular collapse and (b) widespread hypoperfusion of cells/tissue -Due to: (a) reduction in blood volume (b) reduction of cardiac output (c) or redistribution of blood (vascular tone) -Resulting in (a) inadequate effective circulating volume leading to (b) systemic hypoxic injury!! 2) Initially is REVERSIBLE: -If hypoxia persists, cellular injury becomes IRREVERSIBLE, leading to death of cells (necrosis) and patient

Type 1 Immediate Hypersensitivity (Anaphylactic Type): 1) Definition 2) How long does this take and why? 3) What occurs right before sensitization phase? 4) What occurs during the sensitization phase? 5) During degranulation, what are the primary mediators of anaphylaxis that gets released (6)?

1) Definition: Antigen reacting to sensitized mast cells or basophils causing subsequent degranulation 2) Seconds to minutes: Preformed molecules give immediate effect 3) Before sensitization phase, TH2 releases cytokines to stimulate B cells to secrete IgE antibody in response to allergen 4) Sensitization: -Binding of IgE to mast cell surface; allergen binding to this results in degranulation and release of chemical mediators of inflammation 5) Primary mediators: a) Histamine b) Heparin c) Protease Enzymes: tryptase and glucosaminidase d) Eosinophilic chemotactic factor (ECF-A) and neutrophilic chemotactic factor (NCF)

AIDS (Acquired Immunodeficiency Syndrome): 1) Definition (2)? What 4 pathologies are included here? 2) What year did AIDS begin? How many reported cases were there? 3) What % of males and females were affected? 4) What age range did it affect most 5) What were the top 3 ethnic groups affected (%?)?

1) Definition: CD4 lymphocyte count of less than 200 cells per microliter or a total CD4 T lymphocyte count of <14% in individuals with: a) Severe immunosuppression b) Pulmonary TB c) Recurrent pneumonia d) Invasive cervical cancer 2) 1992 -~47,000 reported cases 3) Males=86%; females=14% 4) Affects 20-49 year olds (87%) -also affected teens and older adults however 5) Ethnic: -White, non-Hispanic: 47% -Black, non-hispanic: 33% -Hispanic: 18%

Immune Complex Mediated (Type 3 Hypersensitivity): 1) Definition? What type of necrosis? 2) 7 pathology examples? 3 types of chronic infections? 3) How long does it take to occur?

1) Definition: Deposition of antibody-antigen complexes in tissue with subsequent inflammation and tissue damage (fibrinoid necrosis) 2) 5 pathologies: a) Serum sickness b) SLE c) Arthus reaction (immune complex vasculitis) d) Other acute glomerulonephritis (immune complex in glomerulus) e) Multiple myeloma f) Cryoglobulinemia g) Chronic infections: HIV, hepatitis B, and syphilis SSOAMCC 3) Takes 2-6 hours*

Hemorrhage: 1) Definition? 2) Definition of following terms: a) What is petechiae b) What is ecchymosis c) What is purpura d) What is epistaxis? e) What is hematemesis? f) What is Hemoptysis

1) Definition: Escape of blood from the vascular system 2) Terms: a) Petechiae: small pin point bleeding b) Ecchymosis: larger bruised area (not due to trauma) c) Purpura: Bruising in flat area (usually due to trauma) d) Epistaxis: Bleeding from nose e) Hematemesis: Vomiting blood f) Hemoptysis: coughing blood

Coagulation (Hemostasis): 1) Coagulation: Definition? What 2 cellular constituents get trapped? 2) Coagulation factors: a) Where are majority of clotting factors synthesized? b) What type of enzymes are these and what must occur to them? c) 2 potential requirements for conversions?

1) Definition: Intravascular transformation of fluid blood into a gel matrix entrapping cellular constituents -constituents= RBCs and WBCs 2) Coagulation factors: a) Synthesized by liver b) Proenzymes that must be converted to active form c) 2 requirements: -Phospholipid surface OR -Require calcium (cofactor)

Infarct: 1) Definition? 2) Infarcts to what 3 locations account for more deaths than all forms of cancer/infectious disease put together in US? 3) 3 Causes of an infarct? Most common?

1) Definition: Localized area of necrosis resulting from circulatory insufficiency (ischemia) 2) Heart, brain and lungs 3) Etiology: a) Thrombus: 99% b) Embolus c) Shock (low cardiac output state)

Amyloidosis: 1) 4 ways to describe this substance and 2 locations it can be deposited in body? 2) Primary amyloidosis-what is this? 3) Secondary amyloidosis- what is this?

1) Definition: Pathologic, EXTRACELLULAR* (key), amorphous, proteinaceous substance, deposited in connective tissues and blood vessel walls in body 2) Primary amyloidosis: Amyloid deposition in patients who have underlying immunocyte dycrasias (mixture of disorders-ex: multiple myeloma) 3) Secondary amyloidosis: Patients who had some chronic inflammatory disease (ex: Crohn's, TB, RA, osteomyelitis)

Cell Mediated (Type 4) Hypersensitivity: 1) Definition-what 3 things get released? 2) What is the histological hallmark of this? 3) 2 types of Type 4 Hypersensitivity and what each are mediated by 4) What predicts how a person's immune response will respond?

1) Definition: Reaction of sensitized T lymphocytes with subsequent release of interleukins, lymphokines, and cytotoxins 2) Hallmark: Infiltration of tissue with lymphocytes 3) 2 types: a) Delayed type hypersensitivity (MHC 2): Mediated by CD4+ T cells that secrete cytokines leading to recruitment of major effector cells (eg macrophages) that causes tissue injury and inflammation b) T-cell mediated cytotoxicity (MHC 1): Mediated by CD8+ T cells that directly act as the effector cells to cause tissue injury and cell killing 4) Genetically determined

Hemostasis: 1) Definition: Sequence of events leading to ____ (3 words) by formation of a stable what? 2) 3 critical components to make it hemostatic plug occur (in sequential order of when they are activated)

1) Definition: Sequence of events leading to cessation of bleeding by formation of a stable fibrin-platelet hemostatic plug 2) 3 components: a) Vascular wall b) Platelets c) Coagulation cascade

Antibody-Mediated Hypersensitivity (Type 2): 1) Definition-what 3 things does it lead to? What type of necrosis? 2) 3 types? 3) How long does it take to occur?

1) Defintion: Formation of antibody (usually IgM or IgG) with subsequent binding of Ab to a cell or tissue surface* leading to lysis, phagocytosis, or tissue damage (fibrinoid necrosis*) -aka Ab targeted to a location 2) 3 types: a) Complement dependent b) Antibody dependent cellular cytotoxicity c) Antibody-mediated cellular dysfunction 3) Occurs in minutes to hours

What 6 factors determine whether an infarct occurs?

1) Degree of obstruction 2) Rate/acuteness of occlusion (seconds/mins/months) 3) Presence or absence of collateral circulation (portal vein, bronchial/pulmonary arteries in lung)-natural growth of arteries to areas of decreased perfusion 4) Pre-existing disease in organ (ex: atherosclerosis) 5) Oxygen-carrying capacity of blood (anemia) 6) Vulnerability of tissue to ischemia (cells that have a lot of mito: neurons, cardiac myocytes, epithelium, prox tubules, GI)

Cellular Trophism of HIV: 1) Cellular tropism of HIV dependent on presence of what molecule on target cell surface? 2) 2 types of CD4+ positive cells? 5 subtypes of second? 3) What is this significance of all the macrophage-like cells (2)? 4) By decreasing these 2 cell types, what do you do to immune system and what 2 things are you worried about?

1) Dependent on presence of CD4 molecule on target cell surface 2) 2 CD4+ positive cells: a) CD4+ cells: T-helper cells b) Macrophages (60-120 day lifespan): -Dendritic reticulum cells -Follicular dendritic cells -Langerhans cells (skin) -Microglial cells of brain -Fixed macrophages of liver and spleen 3) (1) Shown to be reservoirs of HIV and (2) help with resistance to HIV drugs (decrease # T cells via resistance) 4) Cripple immune system and worried about: a) Opportunistic infection b) Cancer/neoplasia

Clinical Course of Amyloidosis: 1) What symptoms does deposition in respiratory tract produce? 2) Diagnosis of amyloidosis is based upon what (2 types used)? 3) Prognosis of generalized amyloidosis-poor/good? Prognosis of immunocyte-derived amyloidosis (excluding multiple myeloma): what is the survival period after diagnosis?

1) Deposition produces no symptoms 2) Diagnosis based on biopsy: a) Rectal mucosa b) SubQ abdominal fat pad 3) Prognosis: a) Generalized amyloidosis: poor b) Immunocyte-derived amyloidosis (excluding MM): medial survival of 14 months after diagnosis

Acquired Immunodeficiencies-Systemic Diseases: 3 causes

1) Diabetes mellitus 2) Collagen vascular diseases (ex: SLE) 3) Effects of alcohol

Thrombus vs Blood clot: 1) How do these differ in terms of where they occur and when? 2) How do you describe a blood clot in terms of: a) Composition (3) b) Lines of Zahn c) Shape d) Color/Consistency 4) How do you describe a thrombus in terms of: a) Composition (3) b) Lines of Zahn c) Shape d) Color/Consistency

1) Differences: a) Thrombus: -Occurs when alive within intravascular space b) Blood clot: -Occurs within intravascular space (post-mortem) or extravascular space (body cavities/tissues) 2) Blood clot: a) Composition: -Lacks platelets -Fibrin -RBCs and WBCs b) Does not have Lines of Zahn c) Lacks shape -Has minimal number of platelets d) Dark red, jello-like 3) Thrombus: a) Composition: -Platelets* -Fibrin -RBCs and WBCs b) Has Lines of Zahn c) Has shape d) pale/gray-red and firm

Renal Allograft Rejection: 1) As said earlier, what are the 2 types of hypersensitivity reactions that can occur-what 2 pathways of rejection do these correspond with? a) What are each due to? b) What gets destroyed in each?

1) Direct Pathway: Cell mediated (Type 4) -Due to donor's APC (in graft) activating MHC class 1 and 2 -Destroys renal blood vessels first and then renal tubules due to CD8 cells 2) Indirect Pathway: Antibody mediated (Type 2) -Due to Recipient's APC activating MHC class 1 and 2 -Destroys renal blood vessels due to preformed antibodies

Complement System Disorders: 1) Disease of what organ? 2) What complement factors are deficient in BOTH the classical and alternative pathways and what 2 diseases/infections does each lead to (2 sets)? 3) What are the deficient complement factors in the classical pathway and what 2 diseases/infections does this lead to (1 set)?

1) Disease of liver 2) Deficiency of factors in both classical and alternative pathways: a) C3 deficiency: Recurrent bacterial infections and immune complex disease b) C5, C6, C7, C8 deficiencies: Recurrent meningococcal and gonococcal infections 3) Deficiency of factors in classical pathway only: a) C1q, C1r, C1s, C2, and C4: Increased immunocomplex diseases and pyogenic infections

Hemophilia A (Classic hemophilia): 1) What is this due to? 2) Type of inheritance? What gender is more common? 3) 4 clinical features? How does symptoms vary?

1) Due to deficiency in factor 8 2) X linked recessive *more common in males 3) 4 Clinical Features: a) Spontaneous hemorrhages into joints (hemarthrosis) *diff the vWF b) Easy bruising and hematoma formation after minor trauma c) Severe prolonged bleeding after surgery or lacerations d) Ptechiae (pin point bleeding) or ecchymoses (large bruising) can occur *Symptoms variable dependent on degree of deficiency

Renal Transplant Hyperacute rejection: 1) Due to (2)? 2) What is present here and what are they directed against? 2) How long does rejection take to occur? 3 characteristics of kidney? 3) What type of hypersensitivity reaction is this

1) Due to severe vasculitis within kidney and renal cortex infarcts 2) Presence of preformed circulating Abs in recipient directed against donor-specific antigens 2) Occurs in minutes -Hyperacutely rejecting kidney: cyanotic, mottled, and flaccid 3) Hypersensitivity reaction type 2

Hair leukoplakia: 1) What virus is this caused by? 2) What is this characterized by and where? Physical image characteristic of affected body part? 3) In a slide of cells of the tongue what do cells look like-aka? 4) In close up histology, what do EBV positive cells look like compared to normal cells?

1) EBV* virus 2) Squamous proliferation of the mouth: White like plaques ("corrugated ridges") that can grow on edge of tongue 3) Increased proliferation of squamous cells* in mouth (especially tongue)- aka hyperplasia (thickened cell wall) 4) EBV cells have dark purple nucleus compared to the normal cells that have light purple

What pathologies are the following herpes viruses associated with: 1) EBV (2) 2) HSV (3) 4) CMV (4)

1) EBV: -lymphoma -hairy leukoplakia 2) HSV: blisters/ulcers/encephlitis 3) CMV: -pneumonitis -retinitis -esophagitis -GI tract ulcers* *PREG

True Thrombus (how this differs from post-mortem blood clot): 1) What occurs early for formation of thrombus (3)? 2) What occurs later to thrombus? If a person survives the thrombotic event, over a period of time, thrombus can stimulates one of what 4 types of responses? What occurs one each?

1) Early: Enlarge, cause obstruction, and formation of Lines of Zahn 2) Later: Thrombus adherence to vascular endothelium -If person survives event, over a period of time, thrombus stimulates: a) Resolution b) Embolization to lungs c) Organization of thrombus into vessel wall: An inflammatory reparative response during which fibrin is removed and collagen laid down -*Macs involved, incorporating thrombus into wall)-thrombus not gone d) Recanalization of thrombus: Formation of new channel (vessels) thru an organizing thrombus (thrombus not gone)

Circulation pathology: 1) What is effusion? 2) What is transudate? What is its specific gravity less than? 3) What is exudate? What is its specific gravity greater than? 4 types of exudate? 4) What is the specific gravity of water?

1) Effusion: Fluid within the body cavities and joint space 2) Transudate: Edema fluid with low protein content -specific gravity <1.020 3) Exudate: Edema fluid with high protein contents and cells -Specific gravity >1.020 -Types of exudates: a) Purulent (pus) b) Fibrinous c) Hemorrhagic d) Eosinophilic 4) Specific gravity= 1.0

Embolus: 1) Definition-what 3 forms can it be in 2) 3 differences between thrombus and embolus? 3 examples of foreign material

1) Embolus: Detached intravascular mass (gas, liquid, or solid) that is carried to a site distant from the point of origin 2) Differences: a) Embolus may be composed of "foreign" material (amniotic fluid, bacteria, and tumor cells) b) Embolus may not conform to shape of blood vessel, while thrombus usually does c) Thrombus overlies an atherosclerotic artery, while an embolus overlies a normal vessel until organization occurs

Stage 3: During irreversible injury, what 3 things occur? What can patient not respond to at this point?

1) Endothelial damage 2) Release of endothelin-1 (potent vasoconstrictor) 3) Microcirculatory failure (lead to cellular membrane injury and cell death) *Necrosis in tissues *Patient cannot respond to therapy

3 layers of vascular wall

1) Endothelial lining (innermost) 2) Subendothelial connective tissue 3) Muscular layer (outermost)

Hemolytic Uremic Syndrome (HUS): 1) What disorder type is this an example of? 2) Occurs most commonly in what group? 3) Cause and a unique characteristic? What organism is involved and what does it produce? 4) Clinical findings (3)?

1) Example of thrombotic microangiopathy 2) Children 3) Cause: Gastroenteritis with bloody diarrhea -Organism: Verotoxin-producing E.coli 0157:H7 4) Clinical findings: a) Thrombocytopenia b) Microangiopathic hemolytic anemia c) Acute renal failure dominance

Anasarca: What are 2 general types of places you can find fluid in body? 3 subtypes of first?

1) Extracellular space: -Interstitium of tissue -Intravascular space -Body cavities/joint space 2) Intracellular space

Severe Combined Immunodeficiency: 5 clinical features; 6 types of opportunistic infections pt is susceptible to?

1) Failure to thrive 2) Adverse reactions to live virus immunization 3) Early onset of infection with virus, fungus, bacteria and protozoa (parasites) 4) Chronic fungal infection 5) Succumb to other opportunistic infections -Pseudomonas -Candida -CMV -VZV -HSV -Susceptible to pneumocystis carinii/jirovecii infection

Scleroderma (Progressive Systemic Sclerosis): 1) What is the female to male ratio? 2) When does the disease occur in life? 3) Pathogenesis: a) What is seen throughout body and why? b) 4 cytokines involved? 4) 2 types? What does one stand for

1) Female to male ratio= 3:1 2) Disease occurs in third and fifth decades of life (20s-40s) 3) Pathogenesis: a) Excessive fibrosis throughout the body via fibroblast activation b) Activated via IL-1, TNF-alpha, TGF-beta, and PDGF 4) 2 types: a) Diffuse scleroderm b) CREST syndrome (limited scleroderma): Stands for (Calcinosis, secondary Raynaud phenomenon, Esophogeal dysmotility, Sclerodactlyly, and Telangiectasis) -Telangiectasis=dilated blood vessels throughout body

Sjogren Syndrome: 1) Who does this affect (gender and age)? 2) 60% of cases are often associated with what type of disease-which disease most often? 3) 3 types clinical presentations and what do first 2 result from? 4) Pathogenesis: What type of cell is dysfunctional and what 2 Abs are made? 5) What is pt at increased risk for developing? What % develop this?

1) Females over 40 YO 2) 60% of cases associated with collagen vascular diseases -especially RA* 3) Clinical presentation: a) Dry eyes (keratoconjunctivitis sicca) b) Dry mouth (xerostomia) *Dry eyes/mouth results from immunologically mediated destruction of lacrimal and salivary glands c) Enlarged parotid gland 4) Pathogenesis: -B cell dysfunction -Anti-ribonucleoprotein Abs*: anti-SSA/(Ro) and anti-SSB/(La) 5) Increased risk for developing high grade B cell lymphoma (1%)

3 physical characteristics of Sclerodactyly (image); 3 reasons why scaling occurs

1) Flexed fingers due to contracture (increased fibrosis) 2) Deformed nails 3) Scaling/drying of skin due to destruction of blood vessels: a) Decreased blood flow to epidermis--> thin skin b) Destruction of sweat glands c) Decreased perfusion and decreased lipid in epidermis (no longer moist)

AIDS: 1) Free virus can cause what? Transmitted in what 2 types of blood components? 2) However, in sexual transmission, how is virus spread

1) Free virus can cause infection: virus transmitted in blood components such as: -cryoprecipitate -factor concentrates 2) Probably enters as an intracellular passenger (provirus in a T cell)

AIDS: 1) What polymicrobial infections is pt more susceptible to (2)? 2) 2 important opportunistic fungi affecting AIDs patients?

1) Fungi and viruses 2) Pneumocystis jiroveccii/carnii and toxoplasma gondi

1) In a histology slide of diffuse proliferative glomerulonephritis, what is seen? 2) What is seen on electron micrograph? Function of a podocyte and what happens when they are damaged

1) Glomeruli/tubules have increased number of inflammatory cells 2) Immunocomplexes trapped under endothelial cells (deposition) that damage podocytes -podocyte: maintain integrity of basement membrane--> damage allows inflammatory cells/proteins to leak out

Transplantation 1) What issue can arise during BM transplant? When does this occur? 2) 4 organs that are involved clinically in GVHD (and their respective cells)?

1) Graft versus host disease: Occurs when immunologically competent cells (donor) are transplanted into an immunosuppressed recipient 2) 3 organs: a) Skin: kertinocytes (rash) b) Liver: hepatocytes and bile duct cells c) Intestinal mucosa (epithelial cells) SLIm d) BM

In the following autoimmune diseases, what gets targeted: 1) Graves' syndrome 2) Idiopathic adrenocortical insufficiency 3) Autoimmune hemolytic anemia 4) Myasthenia gravis 5) Immune thrombocytopenia pupura 6) Primary biliary cirrhosis 7) Sjorgren's syndrome 8) RA (2) 9) Systemic lupus erythematosis (SLE) 11) Goodpasture syndrome 12) Hashimoto thyroiditis

1) Graves' syndrome: TSH receptor 2) Idiopathic adrenocortical insufficiency: adrenal cortex 3) Autoimmune hemolytic anemia: red cells 4) Myasthenia gravis: Ach receptor 5) Immune thrombocytopenia pupura: Platelets 6) Primary biliary cirrhosis: mitochondria 7) Sjorgren's syndrome: nucleoproteins 8) RA: Immunoglobulins/CD8 lymphocytes 9) Systemic lupus erythematosis (SLE): nucleic acids 10) Goodpasture syndrome: basement membrane 11) Hashimoto thyroiditis: thyroglobulin

Infarct: 1) Gross pathology-2 physical characteristics 2) 2 classifications based on color-what 2 colors? 3) Are these reversible?

1) Gross pathology: a) Wedge shaped (due to way its occluded) b) Apex of wedge points to occlusion 2) Classified by color as: a) Hemorrhagic: red b) Anemic: pale or white 3) NO--> dead (necrosis); permanent scar tissue

What are the 5 herpes viruses involved in AIDS?

1) HSV 2) VZV 3) CMV 4) EBV 5) KSHV (Kaposi's sarcoma associated herpesvirus)

Intrinsic pathway-9 steps (Draw out): *at what step does it converge with extrinsic path? What 4 locations is Ca2+ used?

1) Hageman factor/Factor 12 is activated by foreign surface (collagen, etc), kallikrein, and HMWK collagen type 4 to factor 12a 2) 12a activates 11-->11a 3) Factor 11a activates factor 9--> 9a 4) Factor 8 gets activated to 8a via activated 2a (thrombin*) 5) 8a + 9a + Ca2+ (on the phospholipid bilayer surface of platelet) activate factor 10-->10a *ACTIVATED 10a=CONVERGENCE of intrinsic/extrinsic 6) 2a activates 5--> 5a 7) factor 10a + 5a + Ca2 (on another phospholipid bilayer surface) activates 2 (prothrombin)--> 2a (thrombin) 8) Thrombin (2a) activates both: a) Factor 1 (fibrinogen)+ Ca2+--> 1a (fibrin) b) Factor 13+ Ca2+ -->13a 9) Fibrin (1a) + 13a leads to cross linked fibrin

There are several points where clotting system, fibrinolytic systems, and inflammatory response interact. What are 5 components/factors that are involved in all 3 and what do each do?

1) Hageman factor: common activator for all 3 systems 2) Platelets: Contain clotting factors, vasoactive agents, and other activators of inflammation 3) Fibrin degradation products: Vasoactive agents 4) Fibrin: End product of clotting; and important component of acute inflammatory response 5) Plasmin: Activates complement

1) Hemorrhagic infarcts: 3 areas of body these can occur in? Example of 2 organs do these occur in? 2) Anemic infarcts: 3 areas these occur in-what is most common? Example of 3 organs these occur in? 3) Are venous occlusions common causes of infarct? What are they classified as when it occurs? Common organ this can occur?

1) Hemorrhagic infarcts: a) Loose tissues b) Organs with dual blood supply (collateral circulation): lung and intestines c) Venous occlusion 2) Anemic infarcts: a) Solid organs or tissues with (b) single blood supply: spleen, kidney, and heart c) Arterial occlusion (most common) 3) Rare causes of infarct: Classified as hemorrhagic -testicular torsion

Severe Combined Immunodeficiency: Treatment (4)

1) Histocompatible bone marrow transplant 2) Gene therapy 3) Intramuscular gamma globulin 4) Supportive therapy against infection

Congestion Image: 1) Hyperemia-erythema: What is increased here? Is there increased or decreased O2 blood? 2) Cyanosis/hypoxia: What is decreased here? Is there increased or decreased O2? 3) Why do veins appear blue? Why do arteries appear white?

1) Hyperemia: Increased inflow -Increased O2 blood 2) Cyanosis/hypoxia: -Decreased outflow -Decreased O2 blood 3) Veins blue due to thin* protein structure: Absorbs all wavelengths of light except blue and de-O2 blood is getting closer to color black (absorbs light) -Arteries are red because they are thick* protein structures so absorb all wavelengths of light

Immune Complex-Mediated (Type 3): 4 consequences of post-streptococcal glomerulonephritis? Are these self-limiting or chronic? What happens in severe cases-3 characteristics?

1) Hypertension 2) Hematuria 3) Oliguria (low urine output) 4) Proteinuria *Usually self-limited (resolve on its own) but can lead to chronic renal failure (CRF) -Severe cases leading to CRF can feature "crescent formation": deposition of fibrin, damaged epi cells, and monocytes in Bowman space

Systemic (generalized) forms of amyloidosis (contin): 1) What protein is Immunocyte dyscrasias with amyloidosis associated with? 2 examples of dyscresias? 2) What is Reactive systemic amyloidosis associated with? These are what types of conditions-4 examples? 3) What protein is systemic senile amyloidosis associated with-function of protein? 4) What is hemodialysis associated amyloidosis associated with? What pathology does hemodialysis associated amyloidosis lead to?

1) Immunocyte dyscrasias with amyloidosis: -AL type: Ig light chains-lambda -Examples: multiple myeloma and other monoclonal B-cell proliferations 2) Reactive systemic amyloidosis: -AA type: serum amyloid associated protein -Chronic inflammatory conditions: TB, RA, osteomyelitis, and Crohn Disease 3) Systemic senile: Transthyretin: protein carrier of thyroxine and retinal in serum/CSF 4) Hemodialysis: -Associated with beta2-microglobulin -chronic renal failure

5 Systemic (generalized) forms of amyloidosis? Which is primary and secondary? Which is rare?

1) Immunocyte dyscrasias with amyloidosis: primary amyloidosis 2) Reactive systemic amyloidosis: secondary amyloidosis 3) Hemodialysis associated amyloidosis: beta 2 microglobulin 4) Heredofamilial amyloidosis (rare)*-don't look for on test 5) Systemic senile amyloidosis (elderly 70+ YO)

3 reasons diabetes mellitus can cause acquired immunodeficiency

1) Impaired migration: T cells have to bind to integrins (proteins) to get from intravascular to extravascular space--> high glucose and increased glycosylation of proteins (including HbA1C): impaired movement--> immunocompromised 2) Endothelial vessels get coated with glucose--> create polyalcohols (sorbitol) that brings water into endothelial cells--> dysfunction and walls get thicker leading to ischemia (non-healing ulcers) 3) Sorbitol also accumulates in neutrophils/monocytes/leukocytes and cause cellular dysfunction: immunocompromised

Metabolic consequence of alcohol metabolism: 1) As previously mentioned, what is increased during alcohol metabolism and what does this do to all upstream metabolic processes that convert it to this form? 2) 4 processes inhibited? 3) What cell gets affected? 4) What pathology can result?

1) Increase in NADH from alcohol metabolism leads to an inhibitory* effect on all upstream metabolic processes that convert NAD+ to NADH 2) 4 processes inhibited: a) Kreb cyccle b) Beta oxidation c) Conversion of glycerol to DHAP in glycolysis d) Conversion of pyruvate to acetyl CoA at end of glycolysis 3) Immunosuppressive effect on neutrophils 4) Alcoholic Cirrhosis of liver

Edema (contin): 1) 4 pathologies that caused increased hydrostatic pressure 2) What would cause increased osmotic tension of interstitial fluid and what is this due to? 3) What pathologies cause decreased oncotic pressure of plasma (4) 4) 2 types of edema

1) Increased hydrostatic pressure: Cirrhosis, CHF, constrictive pericarditis, and venous obstruction *CCCV 2) Increased osmotic tension: Sodium retention/increased interstitial sodium due to excess salt intake 3) Decreased oncotic pressure of plasma: Cirrhosis, nephrotic syndrome, malnutrition (albumin decrease-marker), and protein losing gastroenteropathy 4) 2 types: Local and systemic

Hypercoagulability of Blood: What 6 things/pathologies cause this? When does decreased fibrolytic activity occur (2)?

1) Increased levels of platelets or clotting factors 2) Decreased fibrolytic activity (late pregnancy and post partum) 3) Nephrotic syndrome 4) Severe trauma or burns 5) Disseminated cancer 6) Disseminated intravascular coagulation (DIC)

Edema formation (5 steps)

1) Increased permeability/flow 2) Increase hydrostatic pressure (increased fluid out of capillary into tissues) 3) Increased Na reabsorption into interstitium/tissues, so increased Na/H2O retention in interstitium 4) Decreased albumin in capillary which decrease plasma colloid osmotic pressure (unable to push fluid back into capillary) 5) Anything that deals with lymphatics to increase interstitial pressure--> Edema

Immune Complex-Mediated (Type 3): Post-streptococcal glomerulonephritis (7 steps) for inducing type 3 hypersensitivity reaction

1) Infection with nephritogenic strain of group A beta-hemolytic streptococci (skin infections account for 2/3 of cases) 2) Build up of anti-strep antibodies over course of weeks 3) Deposition of immune complexes in sub-epithelial GBM space 4) Activation of complement (depletion of C2, C4) and chemotaxis of neutrophils 5) Immune complexes and lysosomal enzymes of the activated neutrophils damage the GBM and lead to plasma protein loss 6) Protein loss causes foot pad fusion of epi membrane 7) Huge sub epithelial immune complexes now form (so-called "humps") *NECROSIS

von Willebrand Disease: 1) What is this due to (2)? 2) What cells produce vWF (2)? What is vWF necessary for? What factor is vWF necessary for transporting to the clotting cascade? What blood test is therefore affected? 3) Clinically characterized by what (3)? What is uncommon? 4) What gender does this occur in?

1) Inherited bleeding disorder characterized by a deficiency or defect in vWF 2) Produced by endothelial cells and megakaryocytes -Necessary for platelet adhesion to the endothelium -vWF necessary for transporting factor 8 to clotting cascade for PTT 3) Characterized by: a) Spontaneous bleeding from mucous membranes b) Excessive bleeding from wounds c) Menorrhagia in young females (spotting of blood when not on period) *Bleeding into joints is uncommon 4) Occurs in both males and females

Extrinsic pathway (Draw out): *at what step does it converge with intrinsic path? What 4 locations is Ca2+ used?

1) Injury to bilipid membrane of endothelium releases tissue factor 2) Tissue factor activates factor 7-->7a 3) Factor 7a+ Ca2+ activates 10--> 10a *Converges with intrinsic path (see above)

Edema: 1) Endothelial cell wall damage: 4 examples of causes? 2) Lymphatic obstructions: 4 causes?

1) Injury to endothelial cell/blood vessel wall -Causes: Burns, inflammation, trauma, and allergic reaction BITA 4) Lymphatic obstruction -Causes: Inflammation, subcutaneous fat via obesity, neoplastic, and post-surgical

Thrombus formation: 1) Injury to endothelium: What is this usually due to? Significance? 2) Changes in laminar flow: What 3 changes occur? Which is caused by polycythemia? Which is the most important cause of clotting in deep leg veins? Which is due to aneurysms? 3) Where is velocity highest in blood vessel? Slowest?

1) Injury: Atherosclerosis -Most important cause of arterial thrombosis* 2) Changes: *a) Increased viscosity of blood (due to polycythemia) *b) Stasis of blood (most important causing of clotting in deep leg veins*) c) Turbulence (aneurysms) *=Main ones 3) Highest=center, slowest on outside

Coagulation (contin): 1) What are the 2 pathways of coagulation? 2) What is the difference between each pathway in terms of substrates for clotting? What is difference in how each activates the coagulation cascade? What coagulation factor does each activate *What are 3 examples of foreign surfaces?

1) Intrinsic system: -All substrates necessary for clotting are present within circulating blood -Activated by contact with a foreign surface (usually collagen**, but also Ab-Ag complexes, glass, etc)--> activates factor 12 or Hageman Factor 2) Extrinsic system: -After tissue injury, phospholipid protein complex (tissue factor* aka thromboplastin=old name) is released into circulating blood to activate the extrinsic pathway -Activated by tissue injury where tissue injury can gain entrance -Tissue factor converts inactive factor 7 to active factor 7

Infarct Microscopic Pathology: 1) 4 characteristics- what organ is an exception to 2 of these?

1) Ischemic coagulative necrosis -Brain is exception*=liquefaction necrosis 2) Inflammatory response 3) Granulation tissue (proliferation of blood vessels and fibroblasts) surround infarct area 4) Fibrosis -Brain is exception: Becomes cystic surrounded by a glial scar

Clinical Presentation of SLE (7)

1) Joint pain 2) Skin rash (mallar skin rash) 3) Renal disease 4) Pleuritis and pericarditis 5) Neurological disorders 6) Hematologic (type 2 hypersensitivity reaction) *JRS PPNH

Pathology of shock: 1) What condition occurs in the kidney (3 names for same thing)? 2) What occurs in lung-2 names? 3) What 2 things occur to intestine? What may prolonged injury lead to?

1) Kidney: Acute tubular necrosis="shock kidney"=acute renal failure 2) Lungs: Undergo diffuse alveolar damage ("shock lung") 3) Intestines: a) Superficial mucosal ischemic necrosis and hemorrhages b) Prolonged injury: may lead to sepsis with bowel flora

Clinical Course of Amyloidosis: 1) What is the most common organ involved-significance? 2) Heart involvement: what type of amyloidosis does this occur in-most common in what type of disease? What 2 pathologies does it lead to? 3) What do liver and spleen show? 2 names for spleen pathology that occurs

1) Kidney: most common and potentially most serious 2) Heart: -Any form of systemic amyloidosis -More common with immunocyte-derived disease -Leads to restrictive cardiomyopathy and cardiac arrhythmias 3) Liver and spleen: moderate to marked hepatosplenomagaly -"sago spleen" or "lardaceous spleen"

DIC: 1) Laboratory Findings: a) What happens to platelet count and bleeding time? b) What happens to PT and PTT time? c) Fibrinogen changes? d) Unique/distinguishing characteristic of cells 2) Treatment (2)?

1) Lab findings: a) Decreased platelet count (increased bleeding time) b) PT and PTT abnormal (consume all clotting factors) c) Fibrinogen decreased and fibrin split products increased (D-dimers) d) Intravascular microthrombi (fibrin platelet thrombi*) aka schistocytes 2) Treatment: Treat underlying disorder and give clotting factors

Hemophilia A (Classic hemophilia): 1) Lab results: a) What happens to platelet count and bleeding time? b) What happens to PT and PTT? 2) Treatment?

1) Labs: a) Normal platelet count and bleeding time*** Different than vW disease and others!!! (since only a factor issue) b) Normal PT and prolonged PTT (>35 seconds bc of factor 8) 2) Tx: Factor 8 concentrate

von Willebrand Disease (contin) 1) Lab findings: a) What happens to platelet count and bleeding time? b) What happens to PT and PTT? c) Abnormal platelet response to what important diagnostic test-what is used and what does test determine? 2) Treatment-what does this treatment do?

1) Labs: a) Normal platelet count and prolonged bleeding time b) Normal PT with a prolonged PTT (interferes with factor 8) c) Negative ristocetin aggregation test* important: -Ristocetin: Ab that helps platelets agglutinate; if does not agglutinate, vWF may be missing* (negative test=no agglutination) 2) Treatment: -Treat mild cases with desmopressin (ADH hormone analogue), which releases vWF from Weibel-Palade bodies of endothelial cells

Pathology of shock: 1) What occurs in the liver? AKA? 2) Adrenals: What pathology/syndrome is caused by adrenal shock? What bacterial-causing septic shock is this commonly associated with? 2 things that occur

1) Liver: Centrilobular necrosis ("shock liver") 2) Adrenals: Waterhouse-Friderichsen syndrome -Commonly associated with meningococcal septic shock a) Bilateral hemorrhagic infarction b) Acute adrenal insufficiency

1) Local Edema: 4 causes? 2) Systemic edema: a) What its this AKA? b) 4 types/origins? What are each due to?

1) Local edema: a) Acute inflammation (exudate vs transexudate) b) Urticaria (hives)-allergy c) Venous thrombosis: Obstruction of venous outflow d) Left sided heart failure 2) Systemic Edema: a) AKA Anasarca b) 4 types: -Cardiac origin: Due to retention of Na+/H2O and increased capillary BP, leading to CHF -Hepatic origin: Due to decreased synthesis of plasma proteins, especially albumin -Renal origin: due to increased glomerular capillary permeability and loss of plasma albumin in urine -Iatrogenic: fluid resuscitation (giving too much fluid to pt to try and maintain BP)

1) Local inflammation: What 3 cells are activated? 2 other things that get activated? 2) Systemic effects: What 3 things result?

1) Local: -Monocyte/mac/neutrophil activation -Endothelial activation -Complement activation 2) Systemic: -Release of acute phase reactants from liver -Leukocyte release -Fever

Serious effects of hemorrhage are determined by what 2 things

1) Location 2) Amount of blood lost

1) What do fibrin-platelet thrombi look like? What can they do to RBC-name? 2) In a peripheral blood smear, what do these types of RBCs look like? 3) What is an example of a pathology with these types of RBCs? What are 3 potential real life causes of pathology? What happens to O2 carrying capacity?

1) Look like: Platelets with multiple fibrin strands, that trap RBCs -They can abuse RBCs and RBC becomes a schistocyte* 2) Blood smear: Schistocyte are abused/fragmented looking (slide 22) 3) Microangiopathic hemolytic anemia a) Causes: -Mechanical heart valves leading to trauma to RBC -Disseminated intravascular coagulation -Runners--> physical injury to RBCs via pounding on feet *O2 carrying capacity decreases=hypoxia

Hypovolemic shock: 1) What 2 things can cause loss of plasma? 2) What 3 things can cause loss of fluids/electrolytes 3) What is BP equation?

1) Loss of plasma: Severe burns and peritonitis 2) Loss of fluids/electrolytes: Diarrhea, vomiting, and anaphlyaxis 3) BP=cardiac output x peripheral resistance

In a slide of cells of the bronchus from someone who had asthma, what would you see (6)?

1) Lots of inflammatory cells (neutrophils/macs) 2) Eosinophils 3) Smooth muscle hyperplasia 4) Increase in goblet cells to make more mucin 5) Mucus plugs (diminish amount of air) 6) Edema (space bw cells)

Acute Hemorrhagic Infarcts (images) 1) What do acute hemorrhagic infarcts look like in lung (2)? 2) What does it look like in heart?3) What does it look like in small intestine?

1) Lung: Pulmonary artery completely occluded/filled with blood of PE and dark red-black area is infarct 2) Heart (normally a pale infarct): Dark brown/black hemorrhage in free wall and anterior septum (dark brown/black) 3) Small Intestine: Reddened due to acute hemorrhage

Immune Thrombocytopenic Purpura (ITP): 1) What is thrombocytopenia mediated by (2)? Where are antibodies made? 2) Etiology: a) Step 1: What type of Ab are made and against what 2 things? b) Step 2: How does destruction of platelets follow? Destroyed by what type of macrophages? 3) 2 forms of disorder?

1) Mediated by hormonal antiplatelet antibodies or Ag-Ab complexes -antibodies made in spleen 2) Etiology: a) Antiplatelet Abs (IgG) against platelet antigens such as Gp 2b-3a and Gp1b-9 b) After IgG coating of platelets, platelets are destroyed in reticuloendothelial system (splenic macrophages-have Fc receptors) 3) 2 forms: -Acute ITP -Chronic ITP

Hemorrhage-Definition of following terms: 1) Melena 2) Hematuria 3) Hemothorax, hemopericardium, hemoperitoneum 4) Hematoma-aka

1) Melena: Refers to dark color of partially digested blood in stool (dark tarry stools) 2) Hematuria: Blood in urine 3) Hemothorax, hemopericardium, hemoperitoneum: Bleeding into various serous cavities 4) Hematoma (blood clot): localized hemorrhage into tissues or tissue spaces -blood clot bc extravascular

Physiological steps to clotting cascade (4 general steps)

1) Microinjury to endothelium 2) Primary hemostasis 3) Secondary hemostasis 4) Thrombus and antithrombotic events

Physiological steps to clotting cascade (contin): 1) During micro injury to endothelium, what does this lead to in blood vessel? 2) Primary hemostasis: What 2 actions occur here? 3) Secondary hemostasis: What 3 actions occur here? 4) Thrombus/antithrombotic events: What 2 types of cells are trapped? Bc of this, what 2 things are released to break down polymerized fibrin? What do they block

1) Microinjury to endothelium (release of TF or collagen type 4 acts as substrate) leads to reflex vasoconstriction 2) Primary hemostasis: -Platelets get recruited and adhere to basement membrane -Granules release ADP and TXA2 (potent platelet aggregators; TXA also a vasoconstrictor) and platelets aggregate 3) Secondary hemostasis: a) Tissue factor is released, expressing phospholipid complex b) Thrombin is activated c) Fibrin polymerizes 4) Thrombus and antithrombotic events: a) Trapped neutrophils and RBCs b) Release of tPA and thrombomodulin: block coagulation cascade

AIDS: 1) Mode of transmission (4); which is most common and why? Which is now less common and why? 2 ways of acquiring contaminated blood products?

1) Mode of transmission: a) Sexual contact -#1 cause-> anal intercourse bc of 1 layer of simple columnar epi b) Intravenous drug use c) Perinatal transmission d) Contaminated blood products *Less common bc PCR decreased this -Factors for hemophiliacs -Blood transfusions

DIC (contin): 1) Neoplasms: 5 types of neoplasms that cause it? How? 2) 3 types of massive tissue injuries

1) Neoplasms: -Carcinoma of pancreas, prostate, lung, and stomach PPLS -Acute promyelocytic leukemia: AML M3* (cytoplasmic granules that activate clotting) 2) Massive tissue injuries: -Burns -Extensive surgery -Trauma

5 Causes of shock?

1) Neurogenic 2) Anaphylactic 3) Cardiogenic 4) Hypovolemic 5) Obstructive 6) Sepsis *NACHOS

1) Neurogenic shock: This is generalized _____. 2 examples of causes? 2) Anaphylactic Shock: This is generalized _____. What type of reaction is this?

1) Neurogenic=generalized vasodilation: -Causes: Brain trauma or general anesthesia 2) Anaphylactic shock (generalized vasodilation): -Cause: Type 1 hypersensitivity reaction

Anus: *Slide of cells: 1) Anus cells do not contain what? 2) What type of epithelium is it? 2) What does an organizing thrombosed hemorrhoid look like under the microscope (2)? How do other thromboses not further along compare?

1) No hair follicles 2) Simple columnar epi 3) See: a) Dilated veins with blood inside b) With narrowed lumen around vein (looks like small circle of white)-> (represents thrombus being organized) -Other thromboses not yet organized/not further along are larger and do not contain small white area of contraction

3 cardiac clinical presentations of pt with SLE (3) and 3 subtypes of third? Significance of cardiac pathology of SLE?

1) Nonbacterial verrucous endocarditis 2) Myocarditis 3) Pericarditis: -acute -subacute: healing -chronic: fibrotic *Significance: All 3 layers of heart are affected

Cardiac Pathology of SLE: 1) Nonbacterial verrucous endocarditis: What is this aka? 2 clinical presentations? 2) Myocarditis: What does this lead to pathologically (2)

1) Nonbacterial verrucous endocarditis (Libman-Sacks endocarditis): a) Vegetations (wart-like clusters) of immune complex gets stuck on endocardial surface (see image) b) Thickening of chordae tendinae 2) Myocarditis: leads to decreased contractility and arrhythmias

Pathology of shock: 1) Is this specific/nonspecific? 2) What 2 general systemic pathologies can occur? 3) 5 organs commonly affected? 3) Note: In many cases there is good clinical evidence that patient died as a result of shock but there are no ____ (2 words) suggestive of shock?

1) Nonspecific 2) 2 general pathologies: a) Congestion of viscera (obstruction of blood flow in organs) b) Thrombotic lesions* seen from endotoxin shock 3) Organs: -Kidneys -Adrenals -Liver -Lungs -Intestines *KALLI 3) No pathologic lesions suggestive of shock

Hemostatic Mechanism-Platelets: 1) What is the normal # of circulating platelets*? 2) What are they derived from and where? 3) What is thrombocytopenia and what is it due to (2)? 4) When vascular endothelium is damaged, what are the 3 main steps to platelet hemostasis? What 3 actions occur in second step? What 4 actions occur in 3rd step? 2 types of vasoactive amines? 4 types of platelet aggregating factors? 2 types of platelet clotting factors?

1) Normal #: 150,000-450,000 per mm^3 2) Derived from megakaryocytes in BM 3) Thrombocytopenia=decreased # of platelet due to: a) Decreased production b) Increased destruction 4) 6 steps: a) Platelet adhesion to underlying collagen b) Platelet activation (shape change) and degranulation -Release of vasoactive amines (serotonin and histamine) -Platelet synthesis of TXA2 -Expression of phospholipid complex for coagulation cascade c) Platelet aggregation -Activation of platelet aggregating factors: ADP, prostaglandin, thromboxane A2, endoperoxides -Activation of platelet clotting factors (platelet factor 3=thromboplastin/tissue factor and platelet factor 4=heparin neutralizing factor) -Activation of platelet thrombosthenin (cause clot retraction) -Platelets bind to eachother by binding to fibrinogen using Gp 2b-3a

CD4 Count Levels: 1) What is normal? 2) What pathologies occur at levels 200-500 (4) 3) What pathologies occur at 100-200 (2)? 4) What 3 organisms is pt susceptible to at <100? (3)? 5) What 3 pathologies occur at <50?

1) Normal: 700-1500 2) 200-500: -zoster -Oral thrush -TB -Kaposi sarcoma *ZOTK 3) 100-200: -Pneumocystis Jiroveci pneumonia -dementia PD 4) <100: -toxoplasmosis -cryptococcus -cryptosporidium 5) <50: -CMV -Mycobacterium-avium -Leukoencephalopathy

DIC (contin): 1) Obstetric complication: 5 pathologies that can lead to DIC? How? 2) Infections: 7 types? What cytokine activates clotting?

1) Obstetric: *ASTAR a) Amniotic fluid embolism b) Septic abortion c) Toxemia (characterized by high BP) d) Abruptio placentae (placenta disattaches from womb) e) Retained dead fetus *Placental TF activates clotting 2) Infections: a) Gram negative sepsis*: TNF activates clotting b) Meningococcemia* c) Rickettsia* d) Rocky Mountain spotted fever e) Histoplasmosis f) Aspergillosis g) Malaria GMRR HAM

Transplantation- Renal: Chronic Rejection: 1) How long does this take to occur after transplant and why? 2) What do the vessels demonstrate and what does this result in (2)-What 2 cells present in infiltrate?

1) Occurs months to years after transplantation -Why: patient's serum creatine progressively increases over a period of 4-6 months 2) Vessels demonstrate intimal fibrosis* (SCARRING) resulting in: a) Renal ischemia (glomerular/tubular atrophy and interstitial fibrosis) b) Interstitial mononuclear cell infiltrate (plasma cells and eosinophils)

Histology of SLE: 1) In a histology slide of a bullous/blister with SLE, what stain is used? 2) What can be used to show immune complexes? 3) What is seen (3)

1) PAS stain 2) Immunofluorescence to show immune complexes 3) Seen: a) Thickened basement membrane representing immune complexes b) Lots of dermal vessels c) Epidermis separating from dermis via the bulloid

1) PT: What pathway(s) does this test? What 5 factors? 2) PTT: What pathway(s) does this test? What 8 factors? 3) What does TT test for? 4) What does FDP test?

1) PT: Tests extrinsic (and common coagulation) pathways -Factors 5, 7, 10, prothrombin and fibrinogen 2) PTT: Tests intrinsic (and common coagulation pathways) -Factors: 5, 8, 9, 10, 11, 12, prothrombin, and fibrinogen 3) TT: Tests for adequate fibrinogen levels 4) FDP: Tests fibrinolytic system

What are 4 HIV associated Neoplasias; 2 types of Malignant lymphomas

1) Parasite derived cancer 2) Hairy leukoplakia* 3) Kaposi sarcoma* 4) Malignant lymphoma* a) Non-Hodgkin Lymphoma: primarily B cell (EBV associated) b) Hodgkin Lymphoma*

Thrombotic Thrombocytopenia Purpura (TPP): 1) Pathogenesis: what is this caused by deficiency/inactivity in? What does this result in? What is type of anemia is produced from thrombocytopenia? Name of cells created? 2) Clinical presentation: What type if pt is this most frequently seen in? What are the 5 "pentad" characteristics signs?

1) Pathogenesis: Deficiency/inactive form of a protease ADAMTS13 (normally cleaves vWF) -Results in fibrin-platelet thrombi: platelet aggregates surrounded by intravascular hyaline thrombi throughout microcirculation -Leads to microangiopathic hemolytic anemia -aka schistiocytes/helmet cells 2) Clinical presentation: -Seen in females -"Pentad" of characteristic signs: a) Fever b) Microangiopathic hemolytic anemia c) Neurologic deficits d) Thrombocytopenia e) Renal failure FMNTR

Severe Combined Immunodeficiency (SCID): 1) Lack of what cell type(s) and what is this due to? 2) 2 genetic inheritance patterns? Which is most common? What enzyme is there a lack of in the first pattern (what chromosome is this on?)? What does the second involve a mutation in (what 6 IL are involved)?

1) Pathogenesis: Lack of both T-cell mediated and B cell humoral immunity due to defects of lymphoid stem cells of both T cell and B cell precursors 2) 2 modes of transmission: a) Autosomal recessive: lack of adenosine deaminase--> chromosome 20q (long arm of chromosome 20) b) X linked: Mutation involving common gamma chain in IL receptors for IL-2, 4, 7, 9, 15, and 21 *most common

Pathogenesis of immunocomplex induced vasculitis (3 phases) *image

1) Phase 1: Immune complex formation -Antigen circulation attaches to free antibody--> antigen-antibody complex 2) Phase 2: Immune complex deposition -Ag-Ab complex attaches to wall of blood vessels 3) Phase 3: Immune complex-mediated Inflammation -Complement is activated, leading to complement/neutrophil activation and fibrinoid necrosis occurs--> ischemic injury

Fibrinolytic enzyme system: 1) What is plasmin derived from? What does it get activated/converted by (3)? 2) What is tissue plasminogen activator (tPA) derived from? What does it convert? 3) What does activated plasmin break down and to what (2 names)? 4) The fibrolytic pathway is only activated in what case?

1) Plasmin derived from plasminogen (inactive precursor in blood) -Activated by Hageman Factor (factor 12), tissue plasminogen activator (tPA), and insoluble fibrin 2) tPA derived from damaged vascular endothelium -Converts plasminogen to plasmin with help of Factor 12 and presence of insoluble fibrin 3) Activated plasmin breaks down cross linked fibrin to multiple soluble fibrin molecules (D-dimers*) 4) Olny activated in acute thrombus/coagulation*

Hemostatic Mechanism (in detail) Step 1: 1) At first, platelets are tight/loosely adherent to collagen and contain many what? 2) 2 steps here?

1) Platelets are loosely adherent and contain many intracytoplasmic granules 2) 2 steps: a) vWF adheres to subendothelial collagen b) Platelets then adhere to vWF by glycoprotein 1b

1) Pneumocystis Jiroveci Pneumonia: a) Where does this grow in body? b) What can this cause difficulty doing? c) What stain is used and what samples do you use (2)? 2) In Mycobacterium-Avium Intracellular Complex with TB, where is a common site of infection and what samples are used (2)

1) Pneumocystis a) Grows in lung alveolar spaces b) Causes breathing difficulties c) Giemsa Stain with lavage/sputum 2) Mycobacterium: lung; lavage/induced sputum

What are 5 important characteristic opportunistic infections in AIDS mentioned with histology slides? (take a look at slides)

1) Pneumocystis Jiroveci Pneumonia 2) CMV Pneumonia 3) Mycobacterium-Avium Intracellular Complex (TB) 4) Invasive Candida Esophagitis* 5) Herpetic Simplex Esophagitis*

Kaposi Sarcoma: 1) Physical presentation on patient? 2) Diagnostic problems can occur when lesions are confused with what 3 things? 3) What is BA caused by?

1) Presents as multiple red/purple patches/lesions all over body 2) Confused with: a) Granulation tissue b) Hemangiomas (benign tumor of blood vessels) c) Skin disease in AIDS called bacillary angiomatosis (BA) 3) Caused by a bacilli similar to cat scratch bacillus*

Immunodeficiency Syndromes: 5 types of primary immunodeficiencies (born with)

1) Primary B cell immunodeficiency disease (can't make Abs) 2) Primary T cell immunodeficiency disease (CD4/CD8) 3) Primary B and T cell disease (cant make both B/T cells) 4) Disorders of complement system 5) Disorders of phagocytes

What are the 2 types of Immune Deficiency Syndromes

1) Primary Immunodeficiencies 2) Acquired immunodeficiencies

Pathogenesis of HIV: 7 steps to AIDS beginning with primary infection of cells in blood/mucosa(image)

1) Primary infection of cells in blood/mucosa (this causes drainage to lymph nodes/spleen)--> 2) Infection established in lymphoid tissue--> 3) Viremia: Acute HIV syndrome, spread of infection throughout the body -flu like symptoms* --> 4) Immune response to antigen, with partial control of viral replication--> 5) Clinical latency (latent infection/low level of infection)--> 6) Dysregulation of B cell response 7) AIDS (depletion of lymphoid tissue-depletion of CD4 T cells) a) Opportunistic infections b) Opportunistic neoplasia

Autoimmune Diseases: 1) What type of process is this? 2) 3 generalizations of autoimmune diseases 3) What determines if a person will have an autoimmune disease?

1) Process by which immunocompetent cells and/or their products (ie autoantibodies) recognize and interact with self-antigens 2) 3 Generalizations: a) Autoimmune diseases tend to occur in women during reproductive age b) Underlying etiology for vast majority of autoimmune diseases is presently unknown, yet individual is genetically susceptible c) Complications include opportunistic infections and malignant melanomas 3) Genetically pre-determined

7 high risk factors for thrombosis

1) Prolonged immobilization 2) MI 3) Atrial fibrillation 4) Prosthetic cardiac valves 5) Tissue injury (surgery, fracture, burn) 6) Cancer 7) DIC

Anti-thrombogenic substances: 3 Examples of anti-platelet aggregating prostaglandins? Function of each?

1) Prostacyclin (PGI2): Inhibits platelet aggregation and is a vasodilator*know 2) Thrombomodulin: Bind thrombin and activates protein C (cofactor protein S), which inhibits clotting by enzymatic cleaving factors 5a and 8a* 3) Nitric Oxide: Vasodilation

What are 4 lab tests for coagulation? What are the normal range times for each? Which will be increased with DIC (disseminated intravascular coagulation)

1) Prothrombin time (PT) -Normal: 10-15 seconds 2) Partial thromboplastin time (PTT) -Normal: 25-35 seconds 3) Thrombin time (TT) -Normal: 9-13 seconds 4) Fibrin degradation products (FDP) -Increased with DIC (disseminated intravascular coagulation)

What are the 6 theories of autoimmunity

1) Release of sequestered antigens 2) Modification of self-constituents 3) Cross reactivity bw self and foreign antigens 4) Polyclonal B cell activation 5) Failure of suppressor function 6) Genetic susceptibility

Theories of autoimmunity: 1) Release of sequestered antigens: 2 examples of pathologies? 2) Modification of self-constituents: 2 examples? 3) Cross reactivity bw self and foreign antigens: 2 examples?

1) Release of sequestered antigens: -Ab to sperm after vasectomy -Ab to lens after eye surgery 2) Modification of self-constituents -Complexing with drugs: Ab to red cells after penicillin -Partial degradation of thyroglobulin during Hashimoto's Thyroidis 3) Cross reactivity bw self and foreign antigens -Group A strep/heart muscle (rheumatic heart disease) -Viral antigens/multiple sclerosis

Pulmonary embolus: 4 outcomes and % they each occur

1) Resolution in 70-80% 2) Infarction in 10-15% 3) Chronic pulmonary hypertension in 5% 4) Sudden death in 5% (massive pulmonary embolus) RISC

Type 1 Immediate Hypersensitivity (Anaphylactic Type): 1) What are the secondary mediators of inflammation (4)? And what cell each gets released from? 2) What do secondary mediators cause (4)? What 3 cell types get recruited? 3) What cell is the regulator of anaphylaxis? 4) 3 type 1 hypersensitivity reaction examples? 2 examples of what causes system anaphylaxis?

1) Secondary mediators: a) Leukotrienes (from AA)-from eosinophils b) Prostaglandins (from AA)-from eosinophils c) PAF-from eosinophils d) SRS-A (LTC4 and LTD4)-released from basophils -slow reacting substance of anaphylaxis 2) Cause: a) Smooth muscle contraction (bronchospasm*) b) Vasodilation and modification of platelet function (edema) c) Chemotaxis of neutrophils, macrophages, and eosinophils d) Mucus secretion 3) Eosinophils 4) Pathologies: a) Systemic anaphylaxis: -Proteins (antisera) -Drugs (penicillin) b) Skin and food allergies: local reaction (atopy-exzema) c) Asthma

3 types of localized amyloidosis

1) Senile cardiac 2) Senile cerebral 3) Endocrine

Localized amyloidosis: 1) Senile cardiac: What protein is this associated with increase of (AKA)? What function does it affect in heart? It can also affect what 2 things outside of heart? 2) Senile cerebral: What is this associated with (on what chromosome)? Leads to what disease? 3) Endocrine: What disorder is this associated with and what hormone is increased?

1) Senile cardiacs: -Transthyretin ("pre-albumin"): Effects DIASTOLIC function! -Also affects peripheral and autonomic nerves 2) Senile cerebral: -A4 (beta amyloid protein gene on chromosome 21) -Alzheimer's Disease* 3) Endocrine: -Medullary carcinoma of thyroid: leading to procalcitonin

Immune Complex Mediated (Type 3 Hypersensitivity): 1) Serum sickness: What is an example of what may cause this? 2) What is SLE? 3) What is the Arthus Reaction and what is it due to?

1) Serum sickness: From horse anti-tetanus serum 2) Systemic lupus erythematous: rapidly progressive glomerulonephritis 3) Arthus reaction: localized area of tissue necrosis due to an acute immune complex vasculitis*

Pulmonary embolus: 1) Clinical significance (2) 2) Origin (3)? 3) If more than 50% of vasculature is obstructed, what can it lead to? 4) What usually causes infarction here? 5) What causes hemorrhage here?

1) Significance: a) Often clinically silent b) Most commonly missed diagnosis in hospitalized patients 2) Origin: a) Deep leg veins b) Prostatic venous plexus c) Uterine venous plexus 3) If more than 50% of vasculature is obstructed, can lead to sudden cardiac death 4) Infarction: Obstruction of small sized pulmonary branches 5) Hemorrhage: Obstruction of medium sized pulmonary vascular

4 descriptions to describe a thrombus; What does a true thrombus look like (3)?

1) Size (12 cm length x 2.5 cm width, for example) 2) Shape: Has shape (cyclindrical, for example) 3) Color: Gray-red lines made of fibrin and platelets (Lines of Zahn)** look at on slides 4) Consistency: Firm *True thrombus: mottled, gray-red, and friable

Scleroderma contin: 1) In a histology slide of cells for systemic sclerosis, what characteristics do you see from a skin biopsy (4)? 2) What would be pt's complaint in an issue of the lung due to systemic sclerosis? 3) If pt had increased collagen in esophagus, would be pt present with? 4) Raynaud Phenomenon: Who was this first described in and when? What 2 things occur? What other autoimmune disease can this occur in?

1) Skin biopsy shows: a) Thickened layer of dermis* (can't even see the subcutaneous fat layer compared to normal) b) Lots of cross linked collagen in dermis c) Eccrine sweat gland is destroyed d) Inflammatory cells 2) Progressive onset of SOB due to fibrosis (decreased perfusion)--> respiratory acidosis and hypoxemia 3) Esophagus: Issues swallowing (dysphagia) 3) Raynaud: Described in women during cold seasons a) Blanching (whiteness) of hands followed by b) More blood flow/reperfusion (redness) during relaxation *Also occurs in SLE

Kaposi Sarcoma (HHV8): 1) Where does neoplasia occur in/on body? 2) 3 groups of people susceptible? 3) 3 steps to development of KS?

1) Skin malignancy 2) 3 groups: a) Elderly men of Mediterranean origin b) Sub-Saharan Africans c) Transplant recipients 3) 3 steps: a) HIV infected CD4+ cells release cytokines that recruit KSHV (herpesvirus) mesenchymal spindle cells b) Spindle cells cause proliferation/angiogenesis of lymphatic endothelial cells** (know) c) Cells form slit like vascular spaces with leakage of RBCs/fragments from vessel *get characterstic red spots

What 7 organs/systems are affected during SLE

1) Spleen 2) Skin 3) Renal 4) Lungs 5) CNS 6) Heart 7) Pericardium and other serosal surfaces

SLE: 1) Pathology of spleen? 2) 4 pathologies of lungs? 3) CNS?

1) Spleen: Moderately enlarged 2) Lungs: a) Pleural effusions b) Pleuritis c) Interstitial pneumonitis d) Diffuse fibrosing alveolitis 3) CNS: unclear

Acute pale infarcts: 1) What does this look like in spleen? 2) What does it look like in kidney?

1) Spleen: Wedge shaped pale infarct 2) Kidney: Wedge shaped pale infarct in cortex

Stages of Shock: 1) Stage 1: What 3 things occur in order to compensate for decreased perfusion 2) Stage 2: During decompensation, is this reversible/irreversible tissue injury? What 3 things develop?

1) Stage 1: a) Increased sympathetic tone: increase HR/stroke volume b) Release of catecholamines (increase BP) c) Activation of renin-angiotensin system (retain Na/H2O) 2) Stage 2: a) Progressive decrease in tissue perfusion (aerobic to anaerobic state) -Potentially reversible tissue injury occurs -Development of metabolic acidosis, electrolyte imbalances, and renal insufficiency

3 Stages of Shock: 1) Stage 1: Due to decreased cardiac output, vasodilation, or hypotension, what is main response to maintain perfusion? 2) What occurs in stage 2 and stage 3?

1) Stage 1: Reflex mechanisms (compensation)* occurs to maintain perfusion to vital organs 2) Stage 2: Decompensation or decreased perfusion 3) Stage 3: Irreversible Injury

Clinical Course of Amyloidosis: 1) In what layer does GI tract involvement start (2)? Where does it eventually extend (3)? 2) 7 physiological issues it can lead to? 3) Can further go on to cause what 2 pathologies?

1) Starts in vascular bed and/or epithelial basement membrane -Eventually extends into submucosa, muscularis, and subserosa 2) 7 physiological issues: -dysmotility, obstruction -hemorrhage, ulceration -malabsorption, diarrhea -protein loss 3) 2 pathologies: Macroglossia and "amyloid tumor"

Vascular Wall: 1) Subendothelial CT: What does this promote (2) 2) Muscular layer: What does this cause? Induced by what type of reflexes as well as release of what 2 vasoactive amines? What cell are vasoactive amines released from? Degree of vasoconstriction depends on what-significance?

1) Subendothelial CT: -Promotes platelet adherence and subsequent reactions 2) Muscular layer: -Cause constriction of blood vessels -Induced by pain reflexes and vasoactive amines (histamine and serotonin) released from platelets -Degree depends on amount of muscle in wall, so arteries constrict more than veins

Acquired immunodeficiencies: What are 4 types? 6 examples of transplants?

1) Systemic Diseases 2) Transplantation -Renal -Heart and/or lung -Liver -Bone Marrow 3) Drugs (Immunosuppression): steroids (sequester CD4 cells), etc 4) Acquired Immunodeficiency Syndrome (AIDS)

DiGeorge Syndrome: 1) What cell is deficient and why? 2) Therefore, what organ is absent-what does this mean for immunity? There is also a decrease in size of what organ? 3) Time of onset: early or late? 4) Clinical findings: a) Poor defense against what types of infections (2)? b) What are 3 physical symptoms?

1) T cell deficiency derived from failure of development of 3rd and 4th pharyngeal pouches 2) Absence of thymus: Total absence of T cell mediated immunity -also decrease in lymph node size (T cells formed in paracortex/medullary areas) 3) Early onset 4) Clinical findings: a) Poor defense against fungal/viral infections (since need Th1 to clear) b) 3 symptoms: -Congenital defects of heart and great vessels -Deficient, delayed type skin reactions -Tetany/spasms (hypocalcemia) due to lack of parathyroids (hypoparaythroidism)

1) What IL do Th1 cells need to be activated? 2) What IL does Th2 cells need to be activated? What type of hypersensitivity reaction are they important for? 3) Treg cells assist in suppression of both Th1 and Th2-what cytokine do they need to release to activate these cells?

1) Th1: Need IL-12 -Needed for all cell mediated hypersensitivity reactions (type 4) 2) Th2: Need IL-4 -Asthma & allergy 3) Treg: Need TGF-beta

Vascular Wall-Endothelial Lining: 1) What 2 types of substances do endothelial cells contain? 2-3 examples of each? 3 types of anti-platelet prostaglandins?

1) Thrombogenic substances: a) Thromboplastin (tissue factor): Potent thrombogenic factor b) Von Willenbrand's factor c) Thromboxane A2 (TXA2) 2) Anti-thrombogenic substances: a) Plasminogen activator b) Anti-platelet aggregating prostaglandins -prostacylin (PGI2): vasodilation and platelet inhibition -nitric oxide: vasodilation -thrombomodulin: binds thrombin, activating protein C (and cofactor S), which cleaves clotting factor 5a and 8a

Thrombus: 1) Definition-where does it occur? 2) Formation dependent on what 3 processes (what are these 3 processes combined called?)

1) Thrombus: Mass formed from the constituents of the blood within the (INTRAVASULAR) vessels or heart when alive* 2) 3 factors (Virchow's Triad): a) Injury to endothelium b) Changes in laminar flow c) Hypercoagulability

12 examples of Type 4 Hypersensitivity reactions; which 1 is delayed type 4 hypersensitivity reactions and which 10 are cell mediated?

1) Tuberculin test/TB (delayed type 4 aka CD4+ T cells)** 2) Crohn Disease (CD8 T cells)* 3) Contact dermatitis (CD8 T cells)* 4) Granulomatous disease (CD8 T cells)** 5) Graft-versus-host disease (CD8 T cells)* 6) Peripheral Neuropathy (CD8 T cells)* 7) Poison Ivy dermatitis (T cell Mediated) (CD8 T cells)* 8) Multiple sclerosis (demyelination) (CD8 T cells)* 9) RA (destruction of articular cartilage/bone) (CD8 T cells)* 10) Type 1 DM (destroys pancreatic beta cells) (CD8 T cells)* 11) Tumor associated antigens (CD8 T cells)* 12) Viral infections (CD8 T cells)* *CCGGPPMRTTV=CMI

Hypersensitivity Reactions: 4 types

1) Type 1: Immediate Hypersensitivity (anaphylactic type) 2) Type 2: Antibody-Mediated 3) Type 3: Immune Complex Mediated 3) Type 4: Cell mediated

What are the only hypersensivity reactions that can cause tissue damage (3)

1) Type 2 cytotoxicity 2) Type 3 immune complex disease 3) Type 4 cytotoxicity (cell mediated T-cell dependent)

Course of Scleroderma *image: 4 steps starting with trigger

1) Unknown Trigger (potentially by exogenous agent) leads to--> 2) 2 separate steps: a) Immune system activation (B/T cells)--> leads to release of cytokines/growth factors OR b) and Blood vessels injured/narrowed--> leads to ischemia 2) Ischemia and cytokines/GFs from the 2 steps above activate fibroblasts*--> 3) Increasing ECM (collagen/scarring)--> 3) Fibrosis

Transplantation- Renal: Acute Rejection: 1) How long does this take to occur in (a) untreated patient and (b) after terminating immunosuppressive drugs? TO CLASSIFY AS ACUTE, it takes less than how long normally? 2) What 2 subtypes of acute rejection both take place-2 names? 3) What hypersensitivity reaction is taking place?

1) Untreated pt= Occurs within days -After terminating drugs= months or years *Less than 6 months! 2) 2 subtypes: a) Cellular (interstitial mononuclear infiltrate) rejection b) Humoral (vascular) rejection 3) Hypersensitivity reaction type 4

Clinical course of SLE: 1) 2 ways to describe? 2) % survival rate and at how many years? 3) Therapy (2)? 4) Death from what (2)? Example?

1) Variable and unpredictable 2) 86% survival at 5 years 3) Therapy: steroids and immunosuppressive drugs 4) Death from renal failure and opportunistic infections* (disseminated candiasis-see image of epiglottis)

Review: 1) 2 types of vasoactive amines? 2) What are 4 types of platelet aggregating agents? 3) What are 3 types of platelet clotting factors and what each function is

1) Vasoactive amines: Histamine and serotonin 2) Platelet aggregating agents: a) ADP b) prostaglandin endoperoxidases c) thromboxane A2 3) Platelet clotting factors: a) Platelet factor 3 (platelet thromboplastin) b) Platlet factor 4 (heparin neutralizing factor) c) Platelet thrombosthenin (cause clot retraction)

What 4 physiological responses does septic shock cause? What is mortality rate?

1) Vasodilation and hypotension 2) Acute respiratory distress syndrome (ARDS) 3) DIC 4) Multisystem organ failure *Mortality rate: 50%

(Images): What are 4 examples of organs that can have thromboses

1) Vein-thrombosis 2) Heart-thrombosis 3) Anus (organizing thrombosed hemorrhoids) 4) Prostatic organizing thrombosis

1) Why is it important to put oysters on ice-what bacteria will grow? Where is it normally found? 2) 10 risk factors associated with this bacteria

1) Vibrio vulnificus -found in ocean and grows in heat 2) 10 risk factors: a) Diabetes mellitus b) Inflammatory bowel disease (or any person receiving immunosuppressive drugs c) Lymphoma, leukemia, AIDS, Hodgkin lymphoma d) Liver disease: cirrhosis and hemochromatosis (buildup of iron in body) e) Chronic alcohol use f) Chronic renal disease g) Cancer: If taking anti-cancer drugs or radiation tx h) Steroid dependency i) Antacids (excess) j) Thalassemia (decreased Hb) *DILL CCC SAT

Acquired Bleeding Disorders: 1) Vitamin K deficiency: This leads to decrease synthesis of what 6 coagulation factors/proteins? 2) Liver failure/disease: What clotting factors does this lead to decrease synthesis of?

1) Vitamin K: -Factors 2, 7, 9, 10, and protein C & S 2) Liver disease: decreased synthesis of all clotting factors

Potent thrombopenic substances: 1) What is the source of Von Willebrand's factor? What does it cause? 2) What does TXA2 cause (2)?* know

1) Von Willebrand's factor: Endothelial cells -Cause platelet adhesion to subepithelial collagen 2) TXA2: Vasoconstrictor and platelet aggregation

Disseminated Intravascular Coagulation (DIC): 2 main etiologies/characteristics

1) Widespread fibrin-platelet thrombi in blood 2) Consumption of platelets and clotting factors leading to diathesis (bleeding everywhere/anywhere)

What are the 5 primary immunodeficiency pathologies/diseases to know

1) X-linked Agammaglobulinemia of Bruton 2) Common variable immunodeficiency 3) DiGeorge Syndrome 4) Severe Combined Immunodeficiency (SCID) 5) Wiskott-Aldrich Syndrome

Hodgkin Lymphoma (HL): 1) Who is most prevalent in? 2) Significance in HIV-disease? 3) 3 important characteristics of disease

1) Young adults 2) Unclear if HL is increased in HIV 3) 3 characteristics: a) Aggressive b) Unusual presentation (not unlike the lymphomas) c) Tumor cells with EBV episomes

Images: 1) On AIDS virus (HTLV-3), what are the 2 important glycoproteins? Function of these? 2) On T-cell, what 2 structures are needed for AIDS virus to get in? 3) Once in cell, what occurs (4 steps)

1) gp120 and gp41: What virus uses attach and get into CD4 cells 2) Need CD4 and chemokine receptor (CCR5-macs and CXCR4-T cells) to attach to gp120 and gp41 on envelope protein to get into cell 3) In cell: a) HIV RNA genome undergoes reverse transcriptase to become proviral DNA b) Proviral DNA integrated into host cell genome--> becomes HIV DNA provirus c) HIV DNA provirus converted to HIV RNA transcript d) HIV RNA transcript gets assembled into proteins of virion and released from host

What are 5 common platelet disorders caused by qualitative defects? What are each caused by?

1) von Willebrand disease: Decrease/defect in vWF, leading to spontaneous bleeding 2) Bernard-Soulier syndrome: Involve deficiency in glycoprotein-1b complex (Gp1b complex/receptor) on platelets that bind fibrinogen 3) Glanzmann thrombasthenia: Involve deficiency in Gp2b-3a complex/receptor in platelets that bind fibrinogen 4) Uremia: High level of waste product in blood due to renal failure (electrolyte imbalance) 5) Drugs (aspirin)

1) There are about how many types of emboli? What makes up 98% of these-where are these found? 2) 4 emboli we should identify under a microscope-how do each occur?

1) ~8 types of emboli -Thrombus (98% of all emboli): deep leg veins 2) 3 emboli: a) Bone marrow embolus: fractures (ribs) and cardiopulmonary resuscitation b) Amniotic fluid embolus: labor and delivery c) Fat embolus: fractures and extensive crush injuries of soft tissues d) Pulmonary embolus

CD4 T cell Injury Image: What are 3 mechanisms to cell injury following HIV/chronic T cell activation; which 2 are cell mediated?

3 mechanisms: Chronic T cell activation leads to: 1) Viral replication in INFECTED CD4 T cells--> Death of infected cells via cytopathic effect of virus (virus overtakes machinery)* 2) Activation of UNINFECTED CD4+ T cells --> These T cells release FAS that induce cell death (apoptosis)* -cell mediated 3) HIV infected CD4 T cells activate CTL--> Killing of infected cells by virus-specific CTLs* -cell mediated

4) Polyclonal B cell activation: Pathology example? 5) Failure of suppressor function: Pathology example? What does it lead to? 6) Genetic susceptibility: 2 examples

4) Polyclonal B cell activation -EBV infection 5) Failure of suppressor function -HIV disease (CD4 decrease, and unable to amplify CD8 suppressor cells)--> lead to hypergammaglobulinemia 6) Genetic susceptibility: -HLA correlation -Defects in B cell function/maturation