path 1 exam 5 Flashcards

Question

what is pyroptosis?

Answer 1

activation of inflammasome causing activation of CASPASES --> production of cytokines --> inflammation with FEVER --> apoptosis

Answer 2

reversible = inflammation irreversible = membrane damage with end result of cell death

Answer 3

death of cells by necrosis due to deficiency of O2 levels that result in failure of energy-dependent metabolic pathways

Answer 4

decrease activity of PM ATP-dependent sodium pumps increase anaerobic glycolysis structural disruption of protein syntehtic apparatus increase accumulation of ROS damage to mt and lysosomal membranes

Answer 5

brain --> ACA,MCA,PCA - watershed areas --> susceptible to ischemia from hypoperfusion due to receiving blood from most distal branches of 2 arteries with limit collateral vascularity - neurons most vulnerable = PURKINJE CELLS of cerebellum and PYRAMIDAL CELLS of hippocampus and neocortex heart --> subendocardium kidney--> medulla (straight segment of prox tubule and thick ascending limb) liver --> around central vein (zone 3) colon = splenic flexure, rectum

Answer 6

arterial perfusion (atherosclerosis) venous drainage (testicular torsion, Budd Chiari syndrome) shock

Answer 7

in certain cases, restoration of blood flow to ischemic but viable tissues results in increase cell injury due to increase generation of ROS inflammation enhances influx of leukocytes and plasma proteins causing additional damage activation of complement system exacerbates cell injury and inflammation usually after myocardial or cerebral ischemia

Answer 8

red infarct (reperfusion) occurs in VENOUS OCCLUSION and tissues with MULTIPLE blood supplies and with reperfusion --> reperfusion injury due to damage by free radicals pale infarct occurs in solid organs with SINGLE blood supply (heart and kidney)

Answer 9

phagocytic leukocytes, mainly NEUTROPHILS and MACROPHAGES (O2-, H2O2 and OH) NO produced in macrophages and other leukocytes

Answer 10

absorption of RADIANT ENERGY (ionizing radiation hydrolyze water into hydroxyl and hydrogen) enzymatic metabolism of EXOGENOUS CHEMICALS (CCl4) INFLAMMATION in which free radicals are produced by LEUKOCYTES REPERFUSION of ischemic tissues

Answer 11

- spontaneous decay - glutathione peroxidases --> present in cytoplasm of all cells and protect them from oxidative damage by catalyzing breakdown of H2O2 - catalase --> present in peroxisomes, catalyzes decomposition of H2O2 - endogenous or exogenous antioxidants may block formation of free radicals or scavenge them after they have formed

Answer 12

lipid peroxidation of membranes crosslinking and other changes in proteins DNA damage --> SS breaks --> apoptosis, aging, malignant transmission

Answer 13

direct-acting toxins = mercuric chloride poisoning (eating contaminated seafood) --> mercury binds to sulfhydryl groups of cell membrane proteins --> inhibition of ATP dependent transport and increase membrane permeability, many anti-neoplastic chemotherapeutic agents and toxins made by microogs act similarly latent toxins = affects cells that are activated by cytochrome P-450 in SER of liver and other orgs --> formation of free radicals like CCl4 (causes fatty liver) and acetaminophen (analgesic)

Answer 14

DNA damage --> accumulation of p53 which arrest cell cycle in G1 to allow cells to repair DNA damage if damage too great to be repaired, p53 triggers apoptosis by activating Bax and Bak (proapoptotic of Bcl2 fam) when p53 mutated or absent, cells with damaged DNA will survive and DNA damage results in DNA rearrangements --> neoplastic proliferation

Answer 15

cytochrome C released into cytoplasm activates APOPTOSIS

Answer 16

mt membrane damage = decrease ATP --> necrosis (increased permeability of PM and lysosomal membranes is NOT a feature of apoptosis) PM damage --> loss of osmotic balance, influx of fluids and ions, loss of cell contents injury to lysosomal membranes --> leakage of their enzymes into cytoplasm and activation of ACID HYDROLASES in acidic intracell pH --> enzymatic digestion of cell components --> necrosis

Answer 17

hypertrophy hyperplasia atrophy metaplasia

Answer 18

increase SIZE of cells or organs can be physiologic or pathologic due to increase functional demand or by GF or hormonal stimulation physiologic hypertrophy - pregnancy (estrogen-stimulated smooth muscle hypertrophy and smooth muscle hyperplasia) - striated skeletal muscle and heart undergo only hypertrophy in response to increase workload due to limited capacity of adult muscle cells to divide pathological --> cardiac enlargement in HTN or aortic valve disease

Answer 19

increase in NUMBER OF CELLS process remains controlled cells that are capable of replication can be physiologic or pathologic --> both have cell prolif stim by GFs physiologic - hormonal hyperplasia --> prolif of glandular epi of female breast at puberty and during pregnancy - compensatory hyperplasia, residual tissue grows after removal or loss of an organ --> when part of liver is resected, mitotic activity in remaining cells begin as early as 12 hours later, eventually restoring liver to its normal sieze pathologic caused by excessive hormonal or GF stim - endometrial hyperplasia = induced by unopposed estrogens (can progress to malignancy) - prostatic hyperplasia = induced by androgens - GFs = papillomaviruses cause skin warts

Answer 20

shrinkage of size of cells by loss of cell substance causes: decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, aging due to decreased protein synthesis and increase protein degradation - reduced metabolic activity --> decrease protein synthesis - ubiquitin-proteasome pathway (increased by neutrient deficiency and disuse) --> degradation of cell proteins - associated with autophagy --> starved cells eat their own cells in attempt to survive physiologic = normal development, embryonic structures, thymus, post-partum uterus, lactating breast, bone marrow in long bones pathologic = disuse, loss of innervation, diminished blood supply, loss of hormone stimulation, diminished blood supply, inadequate nutrition-malnutrition, aging, pressure

Answer 21

one adult cell type is REPLACED by another cell type one sensitive to stress is replaced by one better able to withstand adverse environment ex: smokers (ciliated columnar epi --> stratified squamous epi), vit A deficiency (also induced squamous metaplasia), GERD (stratified squamous to gastric/intestinal columnar epi aka Baret's esophagus), bone formation in soft tissues as a response to stress if persistent, may predispose to malignant transformation

Answer 22

dysplasia --> malignant transformation Barrett's esophagus --> adenocarcinoma apocrine metaplasia of breast --> no increased risk of cancer

Answer 23

required for differentiation of specialized epi surfaces columnar epi of conjuctiva to keratinizing squamous epi dry eyes (xeropthalmia) --> destrction of cornea and blindness

Answer 24

myositis ossifcans --> muscle to bone during healing following trauma with intramuscular hemorrhage

Answer 25

change in cell type formed in bone marrow with consequent extramedullary hematopoiesis in spleen or liver

Answer 26

failure of cell production during embryogenesis (thymic aplasia/renal agenesis) decrease cell production during embryogenesis (testes in Klinfelter syndrome and streak ovary in Turner's) --> small organ

Answer 27

disordered cell growth proliferation of cancerous cells --> cervical intraepi neoplasia can progress cervical carcinoma persistent hyperplasia or metaplasia --> endometrial hyperplasia or intestinal metaplasia reversible irreversible if persists then it can progress to cancer

Answer 28

exogenous material like - fat change - cholesterol and cholesteryl esters - glycogen (diabetes, glycogen storage disorders) - protein pigments exogenous = anthracosis (smokers), tattoo endogenous = lipofuscin (aging and atrophy), melanin (Peutz-Jeghers - GI polyps, hyperpig macules on lips and oral mucosa), hemosiderin (hemosiderosis and hereditary hemochromatosis)

Answer 29

abnormal metabolism = fatty liver lack of enzyme = lysosomal storage disease resulting in accumulation of endogenous materials protein mutation = defect in protein folding and transport resulting in accumulation abnormal proteins ingestion of indigestible materials = accumulation of exogenous materials

Answer 30

normocalcemia late complication in areas of necrosis common finding in complex atheromas of advanced atherosclerosis aging or damaged heart valves in TB and other granulomatous diseases, fat necrosis, infarcts, thrombi, CMV, toxoplasmosis, and CREST syndrome

Answer 31

hypercalcemia deposits of calcium precipitate in normal tissue due to persistent hypercalcemia or hyperphosphatemia calcification in bv in stomach, kidney, lung all these sites lose acid and alkaline milieu promotes calcium deposits causes of hypercalcemia - elevated PTH or PTH-related protein - destruction of bone --> primary tumors of bone marrow (multiple myeloma), diffuse skeletal metastasis after immobilization, accelerated bone turnover (Paget's disease) - vit D disorders (hypervitaminosis, sarcoidosis) cause of hyperphosphatemia - renal failure = secondary hyperparathyroidism

Answer 32

result of progressive decline in life span and functional activity of cells contributing factors - accumulations of mut in DNA - decrease cell rep - defective protein homeostasis -persistent inflammation replicative senescence occurs in aging cells because of PROFRESSIVE SHORTENING OF TELOMERES which ultimately results in cell cycle arrest

Answer 33

calorie restriction which decrease insulin/IGF signaling and decrease TOR --> alters transcription --> increase DNA repair and protein homeostasis

Answer 34

- Smooth muscle can undergo hypertrophy and hyperplasia - Straited muscle can undergo only hypertrophy

Answer 35

Mild ER stress: - Reduced protein synthesis and increased protein degradation - Reduced load of misfolded proteins Severe ER stress: - Activation of caspases and apoptosis

Answer 36

acute --> initial rapid response that develops in minutes to hours and last hours to days, exudation of fluids and plasma proteins (edema) and migration of leukocytes (mainly neutrophils aka polymorphonuclear leukocytes) --> when acute inflammation achieve its goal of removing the offending agent then rxn will terminate and residual injury is repaired chronic --> longer duration, associated with more tissue destruction, presence of lymphocytes and macrophages, proliferation of blood vessels and FIBROSIS, may follow acute inflam or arise de novo

Answer 37

redness swelling pain heat loss of function

Answer 38

disease where inflammatory reaction if excessively prolonged --> infections by which microbes resist eradication disease with defective inflammation --> too little inflammation leads to increase susceptibility to infections diseases in which inflammatory reaction is misdirected --> against self tissues (autoimmune disease) and against harmless environmental substances (allergies)

Answer 39

by cell receptors for microbes --> in PMs, endosomes, and cytoplasm of phagocytes, DCs and other cells, these receptors recognize motifs common to many microbes (PAMPs) by sensors of cell damage --> in cytosol of all cells (detect DAMP) like acid uric, ATP, reduced K+ --> DNA which activate multiprotein cytosolic complex --> inflammasome --> IL-1 --> recruitment of leukocytes --> inflammation - mut in cytosolic receptors = autoinflammatory syndromes (spontaneous inflam) - inflammasome implicated in inflammatory reactions in gout, atherosclerosis, metabolic syndrome, and obesity-associated diabetes, amyloid deposition in brain (AD) - IL-1 antagonist therapy by circulating proteins --> complement system, mannose binding lectin, collections recognize microbes that entered blood

Answer 40

dilation of small vessels = increase blood flow increase permeability enabling leukocytes and plasma proteins to leave circulation emigration of leukocytes from microcirculation, their accumulation in focus of injury in tissues, and activation to eliminate offending agent

Answer 41

exudate = escape of fluid, proteins, and blood cells from vascular system into interstitial tissue or body cavities --> extravascular fluid with INCREASED PROTEIN conc and CELL DEBRIS, presence implies increase permeability of small bvs sum: PROTEIN AND NEUTROPHIL RICH, increase vascular permeability, and cloudy transudate = ultrafiltrate of blood plasma produced as a result of OSMOTIC HYDROSTATIC IMBALANCE across vessels with norm vascular permeability --> fluid with DECREASED PROTEIN conc and LITTLE/NO CELL MATERIAL, low specific gravity --> EDEMA sum: PROTEIN POOR, increased hydrostatic pressure WITHOUT increased vascular permeability, low specific gravity, clear

Answer 42

exudative = acute inflammation nonexudative = chronic inflammation with fibrosis and scarring

Answer 43

vasodilation due to histamine affect on vascular smooth muscle of arterioles --> opening of new capillary beds --> increase blood flow --> heat and redness (erythema) increase permeability of microvasculature --> protein rich fluids exit vessel loss of fluid and increase vessel diameter --> slow blood flow, concentration of RBCs in small vessels and increase viscosity of blood --> stasis --> vascular congestion and externally localized redness (erythema) blood leukocytes accumulate along vascular endo and adhere to it --> migrate out into interstitial tissue retraction of endo cells --> opening interendo spaces (by histamine, bradykinin, leukotrienes within 15-30 mins, immediate transient response) --> leakage endo injury --> endo cell and detachment --> leakage (starts immediately and lasts for several hours until vessels are repaired or thromobosed)

Answer 44

lymph flow increases in inflammation to help drain edema fluid lymph nodes drain fluid, leukocytes, cell debris, and microbes lymphatic vessels, like bvs proliferate to handle increase load

Answer 45

red streak that follows the course of a lymphatic channel may be a sign of infection of wound

Answer 46

loose attachment, margination, rolling mediated by selectins firm attachment mediated by integrins

Answer 47

chemotaxis is directional chemokinesis is bidrectional

Answer 48

interendo gaps --> PECAM-1 (CD 31)

Answer 49

bacterial products cytokines complement components (specifically C5a) products of lipooxygenase pathway of AA metabolism (LTB4)

Answer 50

early (6-24 hrs) = neutrophils late (24-48 hrs) = monocytes-derived macrophages

Answer 51

produced by activation of NADPH oxidase --> superoxide produced by phagolysosomes, acts on ingested particles only, no damage of host cells superoxide is converted to H2O2 with no killing effect MPO in neutrophil granules, in presence of Cl- converts H2O2 to OCl2- --> destroys microbes by halogenationo or oxidation oof proteins and lipids H2O2-MPO-halide system = most effiency BACTERICIDAL system of neutrophils H2O2 conveted to OH

Answer 52

3 types of NO endothelial neuronal inducible which is involved in MICROBIAL DEGRADATION and expressed when macrophages are activated by cytokines (IFN-gamma) or microbial products and induces production of NO in macrophages, NO reacts with superoxide to make OONO RNSs damage lipids, proteins, and nucleic acids of microbes and host cells NO produced by endothelial cells relaxes smooth muscle = vasodilation

Answer 53

and prevent spread of microbes by trapping them in fibrils

Answer 54

ppl are susceptible to fungal and bacterial infections, and skin abscesses that develop are called COLD ABSCESSES that lack classic features of acute inflam warmth and redness

Answer 55

histamine, PG, leukotrienes, cytokines, chemokines, PAF, complement, kinins

Answer 56

histamine = vasodilation, increase vascular permeability, endo activation PG = vasodilation, PAIN, and FEVER cytokines = local --> endo activation, systemic --> fever, metabolic abnormalities, hypotension (shock) chemokines = chemotaxis, leukocyte activation PAF = vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst complement = leukocyte chemotaxis and activation, direct target killing (membrane attack complex), and vasodilation kinins = increased vascular permeability, smooth muscle contraction, vasodilation, pain

Answer 57

in mast cells in blood - basophils and platelets released by degranulation in response to: - physical injury - binding of Ab to mast cells - products of complement (anaphylatoxins) - neuropeptides and cytokines dilation of arterioles increase permeability of venules by creating interendo gaps and binding to H1 receptors on microvascular endo cells H1 receptor antagonists used to treat inflam rxns like allergies

Answer 58

preformed vasoactive mediator present in platelets and certain neuroendocine cells nt in GI VASOCONSTRICTOR

Answer 59

cyclooxygenase = PG lipooxygenase = leukotrienes and lipoxins

Answer 60

vasodilation = PGI2, PGE1, PGE2, PGD2 vasoconstriction = thromboxane A2, leukotrienes C4, D4, E4 increased vascular permeability = leukotrienes C4,D4, E4 chemotaxis, leukocyte adhesion = leukotriene B4 smooth muscle contraction = PGC4, PGD4, PGE4

Answer 61

mast cells, macrophages, endothelial cells vascular and systemic rxns of inflammation generated by 2 cyclooxygenases (COX 1 and 2) COX2 induced by inflammatory stimuli generates PGs involved in inflammatory rxns and LOW/ABSENT in norm tissues most important PGs in inflam = PGE2, PGD2, PGF2, PGI2, and TXA2 - PGD2 (PGE2) = produced by mast cells, vasodilation, increases permeability of postcapillary venules, exudation, edema, chemoattractant for neutrophils - platelets = synthesis of TXA2, platelet AGGREGATION and VASOCONSTRICTOR - vascular endo = PGI2, VASODILATION and INHIBITOR OF PLATELET AGGREGATION, prevents thrombosis

Answer 62

TXAs which causes platelet aggregation and vasoconstriction PGI2 which inhibits platelet aggregation, preventing thrombosis and causes vasodilation

Answer 63

leukocytes and mast cells by lipoxygenase vascular and smooth muscle reactions and leukocyte recruitment LTB4 = neutrophils and macrophages, chemotactic agent, activator of neutrophils, aggregation and adhesion, gen of ROSs, release of lysosomal enzymes LTC4 = as well as LTD4 and LTE4, mast cells, VASOCONSTRICTION, BRONCHOSPASM (asthma), increase permeability of venules use LTC4 antagonist to treat asthma

Answer 64

generated from lipoxygenase pathway -suppress inflammation by inhibiting recruitment of leukocytes - inhibit neutrophil chemotaxis and adhesion to endothelium NEUTROPHILS and PLATELETS needed for their production

Answer 65

aspirin and other NSAIDS which inhibit both COX 1 and 2, so blocks all PG synthesis aspirin IRREVERSIBLY inactivates COX selective COX2 inhibitors, may increase risk of cardiovascular and cerebrovascular events lipoxygenase inhibitor = ZILEUTON (tx of asthma) corticosteroids = broad spectrum anti-inflam agents leukotriene receptor antagonists = MONTELUKAST (tx of asthma)

Answer 66

leukocyte recruitment, produced by macrophages and DCs TNF also produced by T lymphocytes, mast cells, and some epi cells secretion stim by microbial products, foreign bodies, necrotic cells actions = local and systemic reactions of inflammation - endo activation - activation of leukocytes and other cells - systemic acute phase response = fever, SIRS TNF suppresses appetite --> cachexia (weight loss, muscle atrophy, anorexia) seen in cancers TNF antagonists = tx of chronic inflam diseases, complication increase susceptibility to mycobacterial infection

Answer 67

acting on neutrophils --> IL-8 --> chemotaxis of neutrophils acting on monocytes, eosinophils, basophils, and lymphocytes acting on lymphocytes acting on lymphocytes and T cells 2 main functions = acute inflammation and maintenance of tissue architecture

Answer 68

IL-6 made by macrophages, involved in local and system reactions --> IL-6 receptor antagonist tx for RA IL-17 made by T lymphocytes, involved in neutrophil recruitment --> IL-17 antagonist tx for PSORIASIS type 1 interferons inhibit VIRAL rep, contribute to some systemic manifestations of inflam

Answer 69

inactivate in plasma

Answer 70

cleavage of C3 component

Answer 71

classical pathway = triggered by faxation of C1 to ANTIBODY (IgM or IgG combined to Ag) alternative pathway = triggered by microbial surface molecules (no Ab) lectin pathway = plasma MANNOSE-BINDING LECTINS bind to carbs on microbes and DIRECTLY ACTIVATES C1 all 3 paths = formation of C3 convertase which splits C3 into 2 functionally distinctive frags = C3a and C3b

Answer 72

inflam - C5a (C4a and C3a) stimulate histamine release from mast cells --> increase vascular permeability and vasodilation, can also act as chemotactic agent for NEUTROPHILS, monocytes, eosinosphils, and basophils opsonization and phagocytosis - C3b and its cleavage product inactive C3b when fixed to a microbial cell wal act as opsonins --> phagocytosis cell lysis deposition of MAC on cell drills holes in cell mem, making cells permeable to water and ions --> osmotic death important for killing microbes with thin cell walls (Neisseria species --> meninigococci and gonococci) these microbes can cause serious disseminated infections in persons with deficiency of terminal components of complement

Answer 73

inflammation

Answer 74

phagocytosis

Answer 75

increase vascular permeability and contraction of smooth muscle, dilation of blood vessels, and PAIN when injected into skin mediator of anaphylaxis

Answer 76

exudation of cell poor fluid into spaces created by injury to surface epithelia or into body cavities lined by peritoneum, pleura, or pericardium usually not infected by destructive orgs and does not contain large numbers of leukocytes in body vacities --> fluid may derived from plasma or from secretions of mesothelial cells as a result of local irritation, accum of fluid in these cavities is called effusion effusion consisting of transudates also occur in noninflam conditions like in HF and kidney and liver diseases skin blister result from burn or viral effect (early stage) represents accum of serious fluid within or immediately beneath damage epi of skin

Answer 77

inflam in lining of body cavities histo = fibrin = eosinophilic meshwork of threads or amorphous materil

Answer 78

production of pus, liquefied debris of necrotic cells and edema fluid ABSCESSES are localized collections of pus caused by suppuration buried in tissue, organ, or confined space, produced by seeding of pyogenic bacteria into tissue

Answer 79

t lymphocyte becomes activated by TNF which leads to inflammation or becomes macrophage by IFN-gamma macrophage can then be activated by TNF and IL-1, also present to t lymphocytes

Answer 80

acute pul inflammation - neutrophils in alveolar spaces - congested bvs - resolution is POSSIBLE chronic pul inflammation - chronic inflammatory cells - destruction of parenchyma - FIBROSIS - resolution is IMPOSSIBLE

Answer 81

pattern of chronic inflammation aggregates of epithelioid macrophages mononuclear leukocytes specifically lymphocytes and plasma cells fibrosis variable NOT THE SAME AS GRANULATION TISSUE

Answer 82

macrophage with MHC will encounter Ag, phagocytose it and process --> MHCII will allow it to present to Th1 via IL-12 (formation of Th1 cells) and IL-1 (activation of Th1 cells, fever) Th1 can proliferate via IL-2 which then leads to IFN-gamma (activation of epitheloid cells, giant cells) and MIF (accumulation)

Answer 83

CRP and mannose-binding lectin

Answer 84

cells that constantly dividing hematopoietic cells and surface epithelia

Answer 85

parenchyma of most solid tissues, endothelial cells, fibroblasts, and SMCs ex: hypertrophy and hyperplasia of proximal duct in contralateral kidney --> if you remove one kidney the other one will increase in size due to increased workload these tissues can be pushed to divide and re-enter cell cycle

Answer 86

neurons, cardiac muscle, and skeletal muscle these tissues are terminally differentiated

Answer 87

priming phase = cytokines like IL-6 produced mainly by Kupffer cells act on hepatocytes to make parencymal cells COMPETENT to receive and respond to GFs GF phase = GFs like HGF and TGF-alpha act on primed hepatocytes to stimulate CELL METABOLISM and entry of cells into CELL CYCLE termination phase = TGF-beta?

Answer 88

replacement of injured cells with CT leads to formation of a scar nondividing cells are injured due to severe or chronic tissue injury, resulting in damage to PARENCHYMAL CELLS, EPITHELIA, and CT framework angiogenesis formation of granulation tissue remodeling of CT (produce scar)

Answer 89

immediately you form a blood clot that stops the bleeding and provides a scaffold for the infiltrating inflammatory cells 1-3 days = acute and chronic inflammation where chemotactic agents from the platelets will recruit neutrophils and monocytes --> these cells will eliminate the offending agent 3-5 days = macrophage recruitment --> M1 clears the microbes and necrotic tissue and promotes inflammation, M2 produces GFs that stimulate fibroblast proliferation and CT synthesis 7-14 days = granulation tissue via proliferating fibroblasts, loose CT, new bvs, and scattered chronic inflammatory cells 2 weeks and after = scar tissue and CT remodeling

Answer 90

epi cells response to locally produced GFs and migrate over the wound to cover it endo cells proliferate to form new bvs aka angiogensis fibroblasts proliferate and migrate into site of injury and lay down collagen fibers that form the scar

Answer 91

vasodilation due to NO separation of pericytes and breakdown of BM migration of endo cells toward area of tissue injury prolif of endo cells, just behind leading front tip of migrating cells remodeling into capillary tubes recruitment of periendothelial cells suppression of endo prolif deposition of BM

Answer 92

endothelial migration endothelial proliferation increase permeability

Answer 93

endothelial proliferation migration of fibroblasts, macrophages, and epidermal cells

Answer 94

angiogenesis recruits --> pericytes, SMCs, and CT

Answer 95

stimulates fibroblast migration and proliferation, synthesis of collage --> fibrosis in organs after prolonged inflammation or scar formation after injury inhibits degradation of collagen, inflammation, endothelial proliferation, and endothelial migration

Answer 96

surgical incision --> bleeding clot, inflammation, proliferation of epithelial and other cells, granulation tissue and fibrosis, maturation of CT scar blood clot stops bleeding, scaffold for migrating cells as a result of cytokines, chemokines and GFs 24-28 hrs = neutrophils and basal cell prolif 3-7 days = macrophages clearing and promoting angiogenesis and ECM deposition --> granulation tissue 2 weeks = collagen accumulation (beginning of scar) --> blanching 1 month = scar --> DERMAL APPENDAGES WON'T REGEN, intact dermis, strength of scar will increase over time

Answer 97

tissue loss is MORE EXTENSIVE regen and scarring larger fibrin clot, more exudate/necrotic debris, more inflammation, larger granulation tissue, larger scar first = provisional matrix containing fibrin, fibronectin, and type III collagen 24 hrs = acute inflammation of granulation tissue 3-14 days = larger amount of granulation tissue 2 weeks = replaced by matrix composed of type I collage (initial scar) converted into pale, avascular scare composed of sphindle-shaped fibroblasts, dense collagen, frags of elastic tissue, and other ECM components 1m = acellular CT devoid of inflammatory infiltrate, covered by intact epidermis wound contraction (occurs in large wounds) where myofibroblasts will pull the wound edges closer together to close the gap fibroblasts --> myofibroblasts with actin --> contract --> shrink wound

Answer 98

diabetes glucocorticoids/antiinflammatory effect, inhibition of TGF-beta production (negative/positive) poor perfusion --> arteriosclerosis, diabetes, and venous insufficiency defective fibrillary collagen synthesis by nutritional deficiency or constitutional --> protein and vit C deficiency (required for cross-linking of fibrillary collagen --> scurvy) and Ehlers-Danlos syndrome

Answer 99

infection, prolonged inflammation, local tissue injury mechanical factors (like px lying in one area for a long time which can lead to ischemia) foreign bodies type of tissue (labile and stable vs permanent) extent of injury location of injury

Answer 100

excessive deposition of collagen and other ECM components in tissue and internal organs lung and kidney = myofibroblasts are main source of collagen liver = stellate cells persistent injurious stimuli --> cell death by necrosis or apoptosis and production of ROS results in production of TGF-beta associated with loss of tissue

Answer 101

inadequate formation of granulation tissue or scar uncommon/rare, occurs most frequestly after ab surgery and is due to increased ab pressure (vomiting, coughing, ileus)

Answer 102

edema is fluid accumulation in tissues effusion is fluid accumulation within body space or cavity --> may be transudative (protein poor) or exudative (protein rich)

Answer 103

due to increased hydrostatic pressure and decreases colloid pressure moving fluid out of vessels increased hydrostatic pressure due to IMPAIRED VENOUS RETURN, localized or systemic reduced colloid pressure --> albumin --> liver disease --> decrease synthesis, nephrotic syndrome = loss

Answer 104

arteriolar constriction primary hemostasis --> platelets form a plug secondary hemostasis --> coagulation cascade forming an insoluble fibrin meshwork clot stabilization and resorption

Answer 105

platelets have alpha granules (fibrinogen, FV, and vWF) and delta granules (Ca2+ and ADP) --> sites of damage expose vWF and collagen, vWF will bind to platelet surface Gplb (platelet adhesion) --> Gplb-vWF ACTIVATES platelets leads to shape change by increasing SA and NEGATIVE CHARGE at surface, degranulation, production and release of TXA2 (platelet activation and aggregation, requires COX which is inhibited by aspirin) platelets binds fibrinogen to GpIIb-IIIa aggregated platelets, linked by fibrinogen, form temporary clot at site of injury

Answer 106

vWF binds to exposed collagen and elongates, exposing binding sites for platelets (GPIb) and ADAMTS13 vWF can form multimers, resulting in large vWF-platelet complexes ADAMTS13 binds to elongated vWF, cleaves deficiency of ADAMTS13 = unregulated platelet adhesion and aggregation

Answer 107

goal = form thrombin from prothrombin thrombin converts fibrinogen into fibrin --> promotes further platelet activation, aggregation, and contraction acts on normal endo to limit clot size

Answer 108

initiated by injury to endo, esxposed TISSUE FACTOR and NEGATIVELY CHARGED platelet TF-VIIa complex activates IX and X leading to small amount of thrombi thrombin feeds back and amplifies cascade by activating XI, VIII, V

Answer 109

measures fibrin clotting time PT = extrinsic pathways --> add TF, phospholipids, and Ca2+ PTT = intrinsic pathway --> add negatively charged surface, phospholipids, and Ca2+

Answer 110

wash out of factors need for negatively charges surface normal endo - prostacyclin, NO --> inhibit platelet activation and aggregation - shields platelets from vWF and coagulation factors from TF - thrombin induces release of tPA, promoting fibrinolysis - anticoagulant effects, including production of thrombomodulin and protein C receptor inactivates thrombin and clotting factors, inactivate TF-VIIa complexes thrombomodulin activates protein C to inactivate FV and FVIII which inhibits intrinsic pathway

Answer 111

plasminogen is cleaved into plasmin by tPA or fibrin which splits fibrin products

Answer 112

endo injury, hypercoagulability, and abnorm blood all lead to thrombosis end inury = procoagulant effects like decrease thrombomodulin (no fibrinolysis), decrease protein C (can't inactivate V and VIII), decrease TF inhibitor (inhibit inhibitor) as well as antifibrinolytic effects like decrease tPA (can't convert plasminogen into plasmin to dissolve clot) prothrombic environment = chronic inflammation, HTN, hyperlipidemia, and circulating toxins

Answer 113

arterial thrombi arise at sites of turbulence --> goes against norm blood flow common sites = coronary, cerebral, and femoral aa venous thrombi arise at sites of stasis --> travels with blood flow and richer in RBCS common sites = veins of legs and UE thrombi are laminated with lines of Zahn (indicates thrombus formed in flowing blood)

Answer 114

thrombi occurring in hear or within aorta occur in setting of MI or aortic aneurysm

Answer 115

propagation embolize dissolution by fibrinolysis --> most easily accomplished with younger thrombi organization --> thrombus replaced by fibroblasts, smooth muscle and endo cells recanalization --> new capillaries and small vessels grow thru structure

Answer 116

joints and soft tissues

Answer 117

Ab to coagulation factor most common factor to be inhibited is FVIII may occur in multiple clinical scenarios like B-cell lymphoma/plasma cell neoplasms and amyloidosis MIXING STUDY may help determine whether abnorm clotting time sare due to decreased amount of factor (no Ab present) or presence of an inhibitor

Answer 118

red (hemorrhagic) infarcts - in tissue with DUAL blood supply - venous occlusion (torsion) - previously cogested tissue - reperfused necrotic tissue after arterial occlusion white (anemic) infarcts - arterial occlusions in solid organs with END-ARTERIAL occlusions - spleen, kidney, and heart ischemia coagulate infarcts except for brain which is liquefactive infarcts are replaced by scar

Answer 119

anatomy of affected vessels --> presence or absence dual blood supply (red/white) rate of occlusion --> slow rate may allow time for COLLATERAL circ to develop tissue vulnerability to hypoxia

Answer 120

initial stage characterized by comp mechanisms - sympathetic discharge --> catecholamines - renal conservation of vol progressive stage characterized increase tissue HYPOperfusion and widespread hypoxia aerobic --> anaerobic metabolism further vasodilation, peripheral pooling and stasis irreversible stage = irreversible organ failure cardiogenic/hypovolemic shock may present differently than septic --> COOL, CLAMMY, and CYANOTIC, hypotensice, and tachycardic

Answer 121

- For a mixing study, we take a patient sample, and we run a PT and PTT - Then, mix in normal plasma and repeat the PT and PTT - If the PT and PTT improve when the normal plasma is added, then it must be a deficiency of a factor - If the PT and PTT don't improve when the normal plasma is added, then the patient must have Ab to a factor. The patient's Ab must have inhibited the factor in the normal plasma, causing no improvement in the PT and PTT.

Answer 122

(SD/mean)*100

Answer 123

within-run = analyze 20 specimens in same run between run = analyze once over 21 days imprescision over time, with within run < between run because less variables

Answer 124

absolute more important at low levels percentage more important at high levels

Answer 125

many pxs are taking biotin for beauty but it interferes with biotin-streptavidin interaction that is in many immunoassays in sandwich assay, free biotin BLOCKS binding of Ab complex --> reduced signal = falsely LOW value in competitive assay, reduced signal --> falsely HIGH value only because Ab complex can't bind

Answer 126

Ab bound to well, add Ag (TSH), then add enzyme labelled Ab to Ag amount of signal is directly proportional to amount of analyte

Answer 127

Ab bound to well, add 2 samples where one is competitive amount of signal is INVERSELY proportional to amount of analyte

Answer 128

occurs when captured and labeled Ab are added at the same time and there is HIGH conc of analyte Ab react simultaneously with analyte and sandwiches are NOT formed --> falsely LOW value --> because every Ab and labeled Ab gets their own Ag so no sandwiches - Normally, we would have a bead + prolactin Ab, and a prolactin Ab + alk phos for the signal - When prolactin is added, it will bind both Ab and make a sandwich (see image below) - In the hook effect, we have a high amount of prolactin, so it will bind to the capture Ab and signal Ab at the same time. This means we can not make sandwiches - Everything is washed away, and a lower signal is made because few sandwiches are produced, causing a falsely low result

Answer 129

positivity of a lab test in PRESENCE of disease (true positive/(true positive + false negative))*100 id fraction of population WITH DISEASE that will test POSITIVE tests with high sensitivity are more likely to be positive when px has disease sensitivity is INVERSELY related to false negatives

Answer 130

negativity in ABSENCE of disease (true negatives/(true negatives+false positives))*100 id fraction of population WITHOUT disease that will test NEGATIVE tests with high specificity are more likely to be negative when px does NOT have disease specificity is INVERSELY proportional to false positives

Answer 131

line closer to upper left hand corner of graph if the slope is 1, it's not good because it's 50/50

Answer 132

percentage of px with pos test who actually have disease (true pos/(true pos+false pos))*100

Answer 133

percentage of px with negative test who DO NOT have disease (true neg/(true neg+false neg))*100

Answer 134

predictive values of pos and neg tests can be combined to give efficiency of tests (true pos+true neg/(true pos+false pos+true neg+false neg+))*100 prevalence of disease can affect rate of FALSE POSITIVE results --> even test with high sensitivity and specificity is more likely to give false result if condition is rare (if disease is low prevalence then you know it has to be a false pos) ,

Answer 135

formed in distal tubules and collecting ducts increased formation LOW pH, NEPHRON OBSTRUCTION, and INCREASED PLASMA PROTEINS Tamm-Horsfall protein, which is secreted in ascending loop of Henle

Answer 136

hyaline --> Tam-Horsfall protein only, translucent and colorless RBC --> indicates glomerular damager from RBCs passing into tubules WBC --> indicates interstitial infections, WBC entering thru and btwn tubular epi granular --> graules of degenerating plasma proteins or cells, indicates sig renal disease waxy --> RENAL FAILURE, associated with obstruction of nephrons

Answer 137

creatinine = muscle breakdown, conc increases are kidney function decreases BUN = proteins, increases are kidney function decreases cystatin-c = protein produced by all nucleated cells, less influenced by muscle mass or diet, increases as kidney function decreases NGAL = protein bound to gelatinase, MARKED OF AKI, increases more quickly than creatinine GFR (>90 mL/min/1.73 m2 = norm)

Answer 138

albumin ALP ALT and AST bilirubin total protein can detect chronic or acute liver issues

Answer 139

heme --> biliverdin --> bilirubin --> free bilirubin that goes to brain and placenta or bilirubin-albumin that goes to liver direct bilirubin = conjugated (does not need accelerator) indirect bilirubin = unconjugated (need accelerator to proceed to completion)

Answer 140

prealbumin albulim a1 a2 beta gamma

Answer 141

prealbumin aka transtyretin synthesized by liver and choroid plexus (prominent in CSF SPEP) functions as carrier for THYROXINE rapidly degraded in nutritional deficit NEGATIVE APR RBP transports retinol (vit A) cleared via renal excretion (increased conc in renal insufficiency) decreased conc indicates liver failure and protein malnutrition

Answer 142

most abundant protein carrier protein for many molecules absorbed in the healthy proximal tubules --> urine excretion indicates renal tubule injury) assessment of nutritional status, glomerular fxn, and hepatic synthetic fxn major cause of hyperalbuminemia = DEHYDRATION NEGATIVE APR

Answer 143

a1 antitrypin inhibitor of trypsin gene is highly polymorphic --> PiZZ homozygous genotype will have DIMINISHED band on SPEP (associated with EMPHYSEMA, CIRRHOSIS HEPATOCELLULAR CARCINOMA POSITIVE APR a1 acid glycoprotein synthesized by liver, granulocytes, and monocytes useful for monitoring ULCERATIVE COLLTIS POSITIVE APR

Answer 144

haptoglobin produced in liver binds to free Hb --> sensitive marker of INTRAVASCULAR HEMOLYSIS a2 macroglobulin produced in liver very large protein that inhibits proteases increased in NEPHROTIC SYNDROME NEGATIVE APR ceruloplasmin contains 95% of plasma copper useful screening for Wilson's diseases where's its conc is decreases POSITIVE APR

Answer 145

b2 microglobulin part of HLA complex increased in concs in UPEP in autoimmune diseases, renal failure, and lymphoproliferative diseases too low to be seen in SPEP transferrin binds and transports iron concentration is INVERSELY related to iron availability CSF contains 2 forms of transferrin --> reg form and tau protein, id of tau protein can id fluid as CSF especially in drainages NEGATIVE APR fibrinogen key role in coagulation with platelets absent in SPEP due to consumption during clotting process but can be seen in HEPARINIZED PLASMA SAMPLES - can be confused with Ig monoclonal spike - if band disappears from recollected serum sample, confirms it as fibrinogen

Answer 146

CRP POSITIVE APR marker of inflammation norm levels have high negative predictive value for infection high sensitivity CRP - very precise measurements in nrom referencei nterval can be used to estimate LONG TERM RISK OF CARDIOVASCULAR DISEASE IG represent majority of proteins in this region and show homogenous protein staining appear washed out in IMMUNODEFICIENCY IgA,D,E,G,M

Answer 147

oligoclonal banding on CSF PEP and IFE

Answer 148

multiple myeloma AL amyloidosis Waldenstrom macroglobulinemia MGUS

Answer 149

both require pyridoxal 5'-P liver disease is most important cause of elevated AST/ALT, ALT if higher than AST except alcoholic hepatitis, cirrhosis, and liver neoplasia persistent elevation of ALT for 6 months diagnose chronic hepatitis AST can appear elevated in myocardial injury, progressive muscular dystrophy, and dermatomyositis AST <35 U/L ALT <45 U/L

Answer 150

tartrate ions but bone is not

Answer 151

detection of rise and/or fall of cardiac biomarkers (troponin) above 99th percentile with evidence of ischemia and at least one of the following - ischemic symps - ECG changes of new ischemia - development of pathologic Q waves - imaging evidence of new loss of viable myocardium or new regional wall motion abnormality monitor troponin values at presentation, 3 hrs, and 6 hrs

Answer 152

inhibitor of lipoprotein lipase which cleaves TG into FA to be taken up by other cells

Answer 153

more susceptible to premature CHD

Answer 154

comprised of Kringle domains elevated risk for CHD genetically determined

Answer 155

found in px with cholestatic or obstructive liver disease

Answer 156

indicative of primary hypercholesterolemia

path 1 exam 5 Flashcards

(180 cards)