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what is the linking molecule between aggregating platelets
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Section 1
(50 cards)
what is the linking molecule between aggregating platelets
fibrinogen - platelets aggregate at the site of injury via GPIIb/IIIa using fibrinogen as a linking molecule, forming the platelet plug
BCL2
anti-apoptotic ("prosurvival") protein that resides in the outer mitochondrial membrane and blocks apoptotic cell death by preventing leakage of cytochrome c (and other death-inducing proteins) into the cytosol
hallmark of reversible cell injury
Cellular swelling (including loss of microvilli, membrane blebbing, and decreased protein synthesis due to ribosomes popping off ER)
superoxide radical
O₂°⁻ eliminated by superoxide dismutase (SOD - in mitochondria)
infarction
focal zone of TISSUE death due to ischemia
what is the morphologic hallmark of cell death?
loss of the nucleus
Barrett esophagus
classic example of metaplasia - esophagus is normally lined with non-keratinizing squamous epithelium, but chronic gastric acid caused by gastric reflux from the stomach causes metaplasia: squamous epithelium of the esophagus becomes non-ciliated, mucin-producing (glandular) columnar cells better able to handle stress of acid (may progress to adenocarcinoma)
hallmark of irreversible cell injury
membrane damage (plasma membrane - cytosolic enzymes out and more Ca2+ in; mitochondrial membrane damage - loss of ETC and cyto C leakage; lysosome membrane - hydrolytic enzymes in acidic/high Ca2+ cytosol)
where is von Willebrand factor derived from?
Weibel-Palade bodies of endothelial cells and alpha-granules of platelets
how does low ATP affect cellular functions?
-Na/K pump needs ATP - sodium and water build up in cell causing swelling -Ca2+ pump needs ATP - calcium builds up in cytoplasm -switch to anaerobic glycolysis and lactic acid building causes decrease in pH which denatures proteins
ischemia
decreased blood flow through an organ
which type of cell death causes inflammation?
necrosis
hydroxyl radical
OH°⁻ most reactive free radical! can be eliminated by glutathione peroxidase (in mitochondria)
hyaline inclusions
cytoplasmic eosinophilic homogeneous bodies that consist of denatured proteins that are resistant to the UPR and aggregate into large complexes ex. mallory hyaline (liver), Lewy bodies in Parkinson's (stain strongly with Ubiquitin antibodies)
reperfusion injury
caused by return of blood to ischemic tissue, which results in the production of free radicals that further damage tissue (inflammatory cells + oxygen = free radicals) ex. why you see a continued rise in cardiac enzymes (troponin) after reperfusion of infarcted myocardial tissue
white thrombi
composed of predominantly platelets and tend to form in the arterial system
hydrogren peroxide
H₂O₂ longest half-life free radical produced by SOD and eliminated by catalase (in peroxisomes)
NRF2
transcription factor that serves as a sensor for oxidants in cells; KEAP1 is an E3 complex that keeps NRF2 inactive by ubiquitination, but with ROS NRF2 induces genes that protect cells from oxidative damage (SOD, glutathione peroxidase, phase II enzymes, etc.)
Bax, Bak
pro-apoptotic members of Bcl-2 family that increase outer mitochondrial membrane permeability
hyperplasia
increase in the number of cells via production of new cells from stem cells (permanent tissues = cardiac muscle, skeletal muscle, and nerve CANNOT undergo hyperplasia)
hypoxia
low oxygen delivery to tissue and an important cause of cellular injury because decreased oxygen impairs OXPHOS resulting in decreased ATP; causes of hypoxia include ischemia, hypoxemia, and decreased O2-carrying capacity (Hb problem)
necroptosis
a hybrid form of cell death that has features of both necrosis and apoptosis - like apoptosis, it utilizes death receptors and genetically programmed signaling pathway; but the degradation process is like necrosis = reduced ATP, increased ROS, cell swelling and rupture, NO specific proteases
hypertrophy
increase in the size of cells ex. cardiac myocytes undergo hypertrophy (NOT hyperplasia) in response to systemic hypertension
caspase 3
executioner
acetaminophen toxicity
cytochrome P450 enzymes in liver metabolize drug generating free radicals causing oxidative cellular damage - membrane lipid peroxidation, DNA mutation
Bim, Bid, Bad
pro-apoptotic "sensors" that block bcl-2 and allow cytochrome c to leak into cytoplasm and activate caspases
unfolded protein response (UPR)
un-folded or mis-folded proteins accumulate in the ER which triggers signaling pathways that increase the production of chaperones, enhance proteasomal degradation of abnormal proteins, and slow secretory protein translation
Von Hippel Lindau (VHL) Disease
autosomal dominant disease resulting from mutations in the VHL tumor suppressor gene; VHL protein is an E3 enzyme part of the hypoxia sensing system that recognizes hypoxia-induced factor I (HIF-1) - HIF-1 is a transcription factor that induces vascular growth factors (erythropoietin) and cell growth factors = tumors
karyolysis
dissolution of nucleus
ER stress
condition in which improperly folded proteins accumulate in the ER and can result in apoptotic cell death
what causes fatty change in tissues?
cell injury causes swelling of the RER and ribosome detachment which impairs protein synthesis - this results in the inability to reprocess lipids into lipoproteins for secretion (in the liver - called abnormal fat accumulation = steatosis)
autophagy
involves generation of autophagic vaculoes (autophagosomes that fuse with lysosomes) from fragments of smooth ER membrane
hypoxemia
low partial pressure of oxygen in the blood
red thrombi
composed of predominantly red blood cells and form in veins
ischemic pre-conditioning
if a tissue is under a low level stress or insult, protective cellular processes (unfolded protein response, ER unfolded protein response) are induced which means that a subsequent high level insult to the tissue that normally would have produced irreversible injury or death, only produces reversible damage
lipofuscin
yellow-brown granules in cells consisting of remnants of damaged organelles that can't be digested to constituent lipids and amino acids by the autophagosome
first step of primary hemostasis
vasoconstriction of damaged vessel
karyorrhexis
fragmentation of nucleus
ATM
(ataxia-telangiectasia mutated) protein that senses double-stranded DNA breaks and recruits double-strand repair enzymes such as BRCA1 and 2 plus p53; can stimulate apoptosis if repair is not effective (mutations = cancer)
caspases 8, 9, 10
initiators
extrinsic activation of caspases
aka death receptor pathway; death receptors (like Fas CD95 and tumor necrosis factor receptor TNFR) bind their ligands (FasL /TNF) and their death domains come together which leads to cleavage and activation of initiator caspases 8 and 10 which then actives executioner caspases leading to apoptosis
mTOR
mammalian Target of Rapamycin; causes physiologic hypertrophy by increasing protein translation
NADPH oxidase
a bacteriocidal enzymes that produces superoxide ions during oxygen-dependent killing of bacteria = "oxidative burst"
pyknosis
condensation of nucleus
caspases
proteases that mediate apoptosis; characterized as either initiators (cleave other pro-caspases) or executioners (cleave cellular proteins); promote DNA cleavage, degradation of structural components, and fragmentation of nuclei
thromboxane A2 is synthesized by
platelet cyclooxygenase (COX)
metals that generate free radicals
copper and iron
platelets bind vWF using what receptor?
GPIb
metaplasia
a change in cell type due to a change in stress on an organ; most commonly involves change of one type of surface epithelium to another *reversible proces
intrinsic activation of caspases
aka mitochondrial pathway; apoptotic stimuli (Bax, Bak or inactivation of Bcl-2) triggers the release of cytochrome c from the mitochondria, cyto c associates with Apaf-1 and forms an apoptosome with initiator caspase 9 which activates it and then caspase 9 cleaves caspase 3 leading to apoptosis
Section 2
(50 cards)
prothrombin time (PT)
screens the extrinsic pathway (PT/INR used for monitoring warfarin anticoagulation)
thrombomodulin
redirects thrombin to activate protein C, which cleaves factors V and VIII
heparin-like molecules
increase activity of antithrombin III (ATIII) which inactivates thrombin
ecchymoses
(aka bruises) large (over 1 cm) subcutaneous hemorrhages that go from red-blue to blue-green to gold-brown as the hemoglobin breaks down to hemosiderin
disorders of primary hemostasis are usually due to?
platelet defects
most common manifestations of arterial thrombosis
stroke and MI
Clopidogrel (Plavix)
anti-platelet medication that blocks ADP and inhibits platelet activation and aggregation
anticoagulant factors produced by endothelial cells
PGI2, NO, adenosine diphosphatase, heparin-like molecules, thrombomodulin, tPA, and tissue factor pathway inhibitor
common pathway of coagulation cascade
factors X, V, II, and I
protein C
produced in the liver and inhibits clotting factors V and VIII; requires protein S as cofactor and is vitamin K dependent (production inhibited by warfarin)
coagulation factors that require vitamin k for carboxylation
factors II, VII, IX, and X
thrombin
factor II that converts fibrinogen in the platelet plug to fibrin
most common manifestations of venous thrombosis
DVT and PE
hemophilia B
genetic factor IX deficiency
hemothorax
hemorrhage into a pleural cavity
prolonged PT (and normal aPTT)
suggests deficiency of factor VII
why can a prolonged aPTT suggest von Willebrand's disease?
vWF stabilizes factor VIII (which is an intrinsic factor that aPTT screens for)
clinical features of secondary hemostasis disorders
deep tissue bleeding into soft tissue or joints and rebleeding after surgical procedures
Glazmann thrombasthenia
a rare bleeding disorder that results from a hereditary deficiency of GpIIb/IIIa receptor (needed for platelet aggregation)
clinical features of primary hemostasis disorders
mucosal and skin bleeding
prolonged closure time indicates
lower platelet function (count or abnormal function), or if anti-platelet medications are present
petechiae
tiny (1-2 mm) hemorrhages; usually caused by platelet deficiency or dysfunction of vascular wall support (vitamin C deficiency)
purpura
medium (3-5 mm) hemorrhages; can also be caused by vasculitis, trauma
closure time
a test which measures the time required for the platelets in a sample of blood to plug a small hole in a tiny tube after being exposed to various activating substances
warfarin (coumadin)
an anticoagulant that blocks epoxide reductase (the enzyme that creates vitamin K), which therefore blocks the post-translational gamma-carboxylation of vitamin k dependent clotting proteins = factors, II, VII, IX, and X and proteins C and S
tissue plasminogen activator
tPA - synthesized by endothelial cells and converts plasminogen to plasmin
epistaxis
nose bleeding
contents of dense granules of platelets
contain ADP and ATP, calcium, serotonin and epinephrine.
prolonged aPTT
suggests deficiency in any of the intrinsic factors, von Willebrand's disease, and lupus anticoagulant
heparin
an anticoagulant that potentiates ATIII activity (which inactivates thrombin)
von Willebrand disease
a bleeding disorder that results from a deficiency or abnormal function of von Willebrand antigen (vWA) that leads to a platelet adhesion problem; prolonged closure time and prolonged aPTT (because vWA binds and stabilizes factor VIII - intrinsic pathway)
hemoplilia A
x-linked recessive deficiency in factor VIII that presents with deep tissue, joint, and post-surgical bleeding along with elevated aPTT, normal PT, and normal platelet count and closure time
three major risk factors for thrombosis
(Virchow's triad) endothelial cell damage, abnormal blood flow (turbulence or stasis), and hypercoagulability
ristocetin test
ristocetin induces platelet aggregation by causing vWF to bind platelet GP1b; an abnormal ristocetin test indicates von Willebrand disease because a lack of vWF leads to impaired aggregation and an abnormal test
activated partial thromboplastin time (aPTT)
screens for factors in the intrinsic pathway (XII, XI, IX, and VIII) (used for heparin monitoring, but anti-Xa is better)
plasmin
major factor in fibrinolysis that breaks down fibrin to fibrin degradation products (D-dimer)
antithrombin III
produced by the liver and activated by HLM on endothelial cells; inactivates thrombin, as well as factors IX, X, XI, and XII (heparin potentiates its activity)
aspirin
anti-platelet medication that acts as an irreversible cyclooxygenase inhibitor that blocks the synthesis of TXA2 and therefore impairs platelet aggregation
hematoma
accumulation of blood within a tissue
endothelial prostacylin and nitric oxide
PGI2 and NO - vasodilators that inhibit platelet aggregation
extrinsic pathway of coagulation cascade
factor VII
intrinsic pathway of coagulation cascade
factors XII, XI, IX, and VIII
hemoptysis
coughing up blood
prothrombin gene variant mutation
(20210A) an inherited point mutation in prothrombin that results in increased expression - increased thrombin promotes thrombus formation (fibrinogen --> fibrin)
factor V leiden
most common primary(inherited) hyper-coagulable disorder that results from a mutated factor V that is unable to be cleaved by protein C
contents of alpha granules of platelets
contain fibrinogen, factors V, vWF and VIII, fibronectin, platelet factor 4, platelet derived growth factor (PDGF), P-selectin.
ATIII deficiency
hypercoagulable condition that decreases the protective effect of heparin-like molecules produced by the endothelium, increasing risk for thrombosis and results in the highest risk of venous thrombosis; aPTT does NOT rise with standard Heparin dosing because heparin works by activating ATIII
Bernard-Soulier disease
a rare bleeding disorder caused by a deficiency of the Gp1b receptor (needed for platelets to bind vWF)
NSAIDs
Non-steroidal Anti-inflammatory Drugs; act as nonselective inhibitors of COX
disorders of secondary hemostasis are usually due to?
coagulation factor abnormalities
Section 3
(50 cards)
anaphylactic shock
shock caused by systemic allergic reaction
lines of Zahn
characteristic of thrombi (versus blood clot, postmortem clot) - consists of alternating layers of of platelets/fibrin and RBCs
liquefactive necrosis
necrotic tissue becomes liquefied due to enzymatic lysis of cells and proteins which results in the tissue losing its architecture characteristic of infection (abscess), pancreatitis, and brain infarct
Lupus anticoagulant
???
disseminated intravascular coagulation (DIC)
a pathologic activation of the coagulation cascade that results in both 1) widespread microthrombi resulting in ischemia and infarction and 2) consumption of platelets and factors that results in bleeding; almost always secondary to another disease process (ex. sepsis - bacterial endotoxins and cytokines)
shock
state of reduced cardiac output, reduced circulating blood volume, or reduced systemic vascular resistance that leads to diminished tissue perfusion and cellular hypoxia
three stages of shock
non-progressive phase, progressive stage, and irreversible stage
why cover warfarin therapy with heparin?
warfarin works by blocking epoxide reductase which decreases vitamin K levels - vitamin k is needed to carboxylate factors II, VII, IX, and X and proteins C and S; because proteins C and S have a shorter half-life than the coagulation factors, there is a temporary deficiency of these coagulation inhibitors during the initial stage of warfarin anticoagulation
classical finding in an acute MI (type of necrosis)
coagulative necrosis
coagulative necrosis
the most common histological form of infarction in which the necrotic tissue remains firm and cell shape and organ structure are preserved due to coagulation of proteins BUT nucleus disappears - area of infarct is often wedge-shaped characteristic of ischemic infarction of any organ EXCEPT brain
thrombus
a pathological formation of an intravascular blood clot that can occur in an artery or vein (most common DVT) and characterized by lines of Zahn and attachment to vessel wall
cardinal signs of acute inflammation
swelling, red, heat, pain
mixing study
patient's plasma is mixed with normal plasma with normal factors - if the aPTT does NOT correct upon mixing, then the problem must be do to an inhibitor or antibody
heparin-induced thrombocytopenia (HIT)
an acquired (secondary) hypercoagulable condition that occurs in 4-5% of patients exposed to heparin and is characterized by the development of antibodies that bind complexes of heparin-platelet membrane protein resulting in platelet destruction -- the fragments of destroyed platelets may activate remaining platelets leading to thrombosis
SIRS
systemic inflammatory response syndrome - a nonspecific clinical response to either infection OR a non-infectionous inflammatory process
irreversible stage of shock
organ dysfunction and shutdown due to pronounced cell and tissue death (often leads to death)
margination
vasodilation slows blood flow and allows cells to migrate from the center of the vessel to the periphery
hypovolemic shock
shock resulting from loss of blood or plasma volume (not enough blood)
ischemic necrosis in _____ results in liquefactive necrosis (not coagulative)
brain
ascites
peritoneal effusion - fluid in abdominal cavity
protein C or S deficiency
autosomal dominant hypercoagulable condition that decreases the negative feedback on the coagulation cascade (protein C inhibits FV and FVIII); can result in warfin induced skin necrosis
caseous necrosis
a combination of coagulative and liquefactive necrosis that results in soft and friable necrotic tissue with a "cottage cheese-like" appearance; characteristic of granulomatous inflammation due to TB or fungal infection
progressive state of shock
organ perfusion is compromised (tissue hypoperfusion) and persistent hypoxia results in anaerobic metabolism which can lead to lactic acidosis
white infarct
pale, anemic infarct typical of solid organs with end-arterial circulation (heart, spleen, kidney, brain)
fat necrosis
necrotic adipose tissue with a chalky-white appearance due to deposition of calcium; fatty acids are released by trauma to fat (breast) or by lipase (pancreatitis) and the FAs join with calcium via saponification characteristic of trauma to fat and pancreatitis-mediated damage of peripancreatic fat
red infarct
hemorrhagic infarcts that arise when blood re-enters loosely organized tissue because of venous occlusion, dual/anastomosing blood supply, or reperfusion (liver, lung, intestine)
fibrinoid necrosis
necrotic damage to blood vessel wall (bright pink staining under microscope) characteristic of malignant hypertension and vasculitis(autoimmune Abs build up in blood vessel walls)
neutrophilia
elevated neutrophils in acute inflammation
septic shock
type of distributive shock (reduced systemic vascular resistance - not enough pressure) caused by a massive outpouring of inflammatory mediators due to bacterial or fungal infections
selectin
"speed bumps" that become upregulated on endothelial cells and bind sialyl Lewis X on leukocytes which results in rolling of leukocytes along vessel wall
Dohle bodies
blue inclusions in neutrophils seen on peripheral blood smear during acute inflammation - reflects increased RNA and therefore protein production https://p5759554.vo.llnwd.net/e1/courses/imgs/600-663991.jpg
warfarin skin necrosis
increased clotting instead of anticoagulation seen in patients with protein C deficiency soon after starting warfarin; in the initial stage of warfarin therapy there is a temporary deficiency in proteins C and S (before decreased levels of coagulation factors II, VII, IX, and X) and in a preexisting protein C deficiency, there is a severe deficiency at the onset of warfarin therpay increasing risk for thrombosis in skin
gangrenous necrosis
a form of coagulative necrosis that resembles mummified tissue (blackening and shrinkage) that is characteristic of ischemia of the lower limb (and GI tract)
neutrophilic left shift
an increase in immature (band-form vs. segments) neutrophilic cells in the peripheral blood seen during acute inflammation because of the increased stimulus for bone marrow neutrophil production (relates to illustrations of leukocyte maturation that show more mature cells on the right and less mature cells on the left)
right heart failure leads to what type of edema?
lower body edema
vegatation
thrombi on heart valve
exudate
extracellular fluid with high protein content and containing cellular debris due to increased vascular permeability (as in acute inflammation)
P-selectin
released from Weibel-Palade bodies of endothelial cells and is mediated by histamine
nonprogressive stage of shock
vital organ perfusion is maintained (due to reflex mechanism - vasoconstriction, redistribution of blood flow, increase cardiac output)
anti-phospholipid antibody syndrome (APS)
an acquired (secondary) hyper-coagulable condition that predisposes to both venous and arterial thrombosis and pregnancy complications; can be secondary to an underlying autoimmune disease
infarct
area of ischemic necrosis usually due to blockage of a blood vessels and subsequent ischemia, resulting in cell death
tissues with dual/anastomosing blood supply
liver, lung, intestine
transudate
extracellular fluid that is low in protein content and lacks cellular material
embolism
an intravascular mass that travels and occludes downstream vessels; most common form is a thromboembolus - due to thrombus that dislodges
E-selectin
induced by TNF and IL-1
pus
(aka purulent or suppurative exudate) an exudate rich in neutrophils, including dead and dying cells, as well as microbes (CULTURE!)
Waterhouse-Friderichsen syndrome
adrenal gland hemorrhage, often due to septic shock
left heart failure leads to what type of edema?
pulmonary edema
cardiogenic shock
shock resulting from low cardiac output due to pump failure (hear not working) causes = MI, cardiac tamponade, pulmonary embolus, ventricular arrhythmia
type of necrosis in pancreatitis
liquefactive necrosis of pancreas - proteolytic enzymes from the pancreas liquefy the parenchyma fat necrosis of peripancreatic fat - lipase releases fatty acids outside the pancrease and the FAs join calcium and saponify
Section 4
(50 cards)
TGF-alpha
a chemotactic factor for macrophages that attracts them to different tissues
lymphocytes histology
smallest WBCs with small round nuclei, dense chromatin, and little cytoplasm (secrete INF-gamma which activates macrophages)
which leukotriene attracts/activates neutrophils
LTB4
suppurative/purulent inflammation
production of large amounts of pus - neutrophils, liquefactive necrosis, and edema fluid - usually caused by pyogenic bacteria
chronic granulomatous disease (CGD)
a recessive condition characterized by poor oxygen-dependent killing of microbes due to a defect in NADPH oxidase (first enzyme in oxidative burst that converts O2 to superoxide) - leads to recurrent infect and granuloma formation with catalase-positive organisms (ex. staph aureus, psedomonas cepacis, etc.) because catalase destroys the H2O2 produced by bacteria that neutrophils could use; colorless NBT test
unwanted side effects of NSAIDs
stomach ulcers and bleeding - overlap between inflammatory response and blood clotting = NSAIDs interfere with the production of prostaglandins which reduces pain and fever, but also interferes with prostaglandins that protect the stomach and support platelets and blood clotting (TXA2)
antipyretic
reduces fever
corticosteroids
broad spectrum anti-inflammatory agents that block production/release/activity of arachidonic acid, prostaglandins, leukotrienes, lipotoxins, kinins, histamine, etc. and therefore have more widespread effects and side effects compared to NSAIDs; can cause increased susceptibility to infections via immunosuppression and mask the sign and symptoms of inflammation
complement system
a group of more than 20 plasma proteins (C1-C9 and others) that "complement" inflammation and can be triggered by several stimuli, including microbes
IL-12
produced by macrophages and stimulates T cell response (CD4+ helper T cells --> TH1 subtype that secrete INF-gamma)
TNF and IL-1
cytokines produced mainly by macrophages that stimulate expression of cellular adhesion molecules (ICAM and VCAM) and E-selectin and secretion of other cytokines; also involved in production of fever
non-caseating granulomas
aka non-necrotizing, LACK central necrosis seen in reaction of foreign material, sarcoidosis, Chrons disease, cat scratch disease
serous inflammation
thin fluid, often derived from plasma, which accumulated in serous cavities such as pleural, pericardial, or peritoneal cavities = effusion
CD14
a TLR on macrophages that recognizes lipopolysaccharide (LPS), a PAMP on the outer membrane of gram-negative bacteria
MPO deficiency
defective conversion of H2O2 to HOCl increases risk for candida infections but most asymptomatic; normal NBT test
Mediators that attract neutrophils (4)
LTB4, C5a, IL-8, and bacterial products
C5a
chemoattractant for neutrophils
leukocyte adhesion deficiency (LAD)
most commonly due to an autosomal recessive defect of integrins (type 1, vs. type 2 - selectins) clinical features: -delayed separation of umbilical cord (necrotic tissue attracts neutrophils which usually destroy tissue causing it to fall off) -increased circulating neutrophils (impaired adhesion of marginated pool of leukocytes) -recurrent bacterial infections WITHOUT pus (no dead neutrophils)
abcess
a collection of purulent inflammation in a tissue or organ; contains neutrophils, cellular debris, and is surrounded by congested blood vessels
cell mediators of chronic inflammation
macrophages, lymphocytes, and plasma cells
function of prostaglandins
vasodilation, increased vascular permeability, pain and fever, and also vasoconstriction and platelet aggregation (TXA2)
toll-like receptors (TLRs)
receptors present on cells of the innate immune system (leukocytes) that are activated by pathogen-associated molecular patterns (PAMPs) on microbes; activation results in up-regulation of NF-kB which activates immune response genes leading to production of multiple immune mediators
function of leukotrienes
chemotaxis of neutrophils and vasoconstriction, bronchospasm, and increased vascular permeability (anaphylaxis)
fibrinous inflammation
characteristic of inflammation of the lining of the body cavities that is an exudate containing the large protein molecule fibrinogen due to a pronounced increase in vascular permeability histologically - eosinophilic meshwork of fibers
function of bradykinin
mediates vasodilation and increased vascular permeability and pain
C3b
complement protein that is an opsonin for phagocytosis - it is deposited on the microbe and signals to the neutrophil to consume it
TGF-beta
secreted by macrophages and is the most important cytokine for synthesis and deposition of connective tissue proteins and fibrosis for healing - stimulates fibroblasts migration and proliferation, increased synthesis of collagen, and decreased breakdown of ECM by activating tissue inhibitors of metalloproteinases (TIMPs)
eosinophils histology
small granulocytes with bilobed nucleus and bright eosinophilic (red) granules (parasitic infections and allergic reactions)
caseating granulomas
aka necrotising, exhibit central necrosis and are characteristic of TB and fungal infections
C3a and C5a
complement proteins, specifically anaphylatoxins, that trigger mast cell degranulation resulting in histamine-mediated vasodilation and increased vascular permeability
which prostaglandin mediates pain and fever?
PGE2
production of fever
pyrogens (from bacteria) cause macrophages to release IL-1 and TNF which increase COX activity in the perivascular cells of the hypothalamus - this increases PGE2 which raises the temperature set point
histiocyte
tissue macrophage
multinucleated giant cells
(MNGCs) macrophages that form by the fusion of macrophages or reduplication of the nucleus, commonly seen in granulomatous inflammation
NBT test
nitroblue tetrazolium test used to screen for CGD - leukocytes are incubated with NBT dye which turns blue if NADPH oxidase can convert O2 to O₂°⁻, but is colorless if NADPH oxidase is defective (MPO deficiency would have normal NBT test)
non-steroidal anti-inflammatory drugs
(NSAIDs) act by inhibiting cylooxygenase (COX) enzymes that generate prostaglandins and are useful analgesics and antipyretics
pyogenic
pus producing
MAC
membrane attack complex form when C5b complexes with C6-C9; lyses microbes by creating a hole in the cell membrane
kinin system
kinin cleaves high molecular weight kininogen (HMWK) to bradykinin
Hageman factor (factor XII)
an inactive pro-inflammatory protein produced in the liver that is activated upon exposure to subendothelial or tissue collagen and activates the coagulation/fibrinolytic system, the complement system, and the kinin system
function of integrins
up-regulated on leukocytes during acute inflammation and interact with cellular adhesion molecules (CAM) on the endothelium which results in the firm adhesion of leukocytes to the vessel wall
phagolysosome
cytoplasmic vacuole formed by fusion of a phagosome containing an engulfed particle and a lysozyme - ingested particle is then destroyed by lysosomal enzymes or reactive oxygen species
interferon-gamma
(INF-gamma) a cytokine released by CD4+ T-cells that activates macrophages (convert to epitheliod histiocytes and giant cells)
plasma cells histology
small/medium size, round nucleus with clock-face chromatin clumping and a perinuclear hof (white space near nucleus due to prominent Golgi)
arachidonic acid metabolites
prostaglandins (produced by cylooxygenase) and leukotrienes (produced by 5-lipoxygenase)
granuloma
a collection of epithelioid histiocytes (macrophages), usually surrounded by multi-nucleated giant cells and a rim of lymphocytes
transmigration
(aka diapedesis) migration of leukocytes through the endothelium
histamine
one of the first mediators released during acute inflammation that is pre-stored in mast cell granules and causes vasodilation of arterioles and increased vascular permeability of venules
oxygen-dependent killing
neutrophils most effective mechanism of killing in which HOCl is generated via oxidative burst in the phagolysosome and destroys the phagocytosed microbe
macrophages histology
largest WBCs with large reinform (kidney-shaped/oval nucleus), abundant cytoplasm with vacuoles
Section 5
(50 cards)
AFB stain
TB
formation of granuloma
1) macrophages find antigen and present it to helper T cells 2) macrophages secrete IL-12 which causes T cells to differentiate into TH1 subtype 3) TH1 cells secrete INF-gamma, which converts macrophages to epithelioid histiocytes and giant cells
malignant hyperthermia
inherited condition associated with mutation in the RYR ryanodine receptor characterized by a "heat-stroke-like" rise in core body temperature (greater then 104F) and muscle contractures following exposure to common anesthetics
determination of clonality with G6PDH isoforms
gene for G6PDH is located on the X-chromosome and one of the two inherited isoforms is inactivated resulting in normal ratio of 1:1 (50% have isoform A, 50% have isoform B) in any tissue; however, one ONE isoform is present in neoplasia because all of the neoplastic cells are derived from a single mother cell
mercury poisoning
mercury binds to sulfhydryl groups on proteins leading to CNS and kidney damage; main source of exposure is contaminated fish
well differentiated
tumor resembles normal parent tissue
immunohistological stain - keratin
epithelial tissue
keloid
excessive production of scar tissue consisting of type III collagen that is out of proportion to the wound boundaries; more common in African Americans and classically affects the earlobes, face, and upper extremities
compensatory hyperplasia
regeneration of liver after partial resection - the amount of liver mass lost is restored through regeneration/proliferation of all different liver cells, but liver shape is NOT restored, adult stem cells are NOT involved, and fibrosis does NOT occur (each hepatocyte produces additional cells and then reenters quiescence)
benign tumor
-well differentiated (resemble normal tissue) -organized cell growth -uniform nuclei -low N/C ratio minimal mitotic activity -lack of invasion and NO metastatic potential
type II collagen
cartilage ("car-two-lage"
VEGF
vascular endothelial growth factor - important for angiogenesis
stable tissues
(aka quiescent) comprised of cells that are quiescent (G0), but can reenter the cell cycle to generate tissue when necessary (ex. liver)
type I collagen
bone (bone) - strong tensile strength
major carcinogens in cigarette smoke
polycyclic hydrocarbons (most carcinogenic), arsenic, napthylamine (derived from the smoke)
why is there a mixed wound healing response with deep skin wound?
epidermis - regenerates dermis - heals by scarring
carbon tetrachloride
organic solvent used in the dry cleaning industry that is converted to its free radical form (CCl3) by CYP450; results in cell injury and swelling of RER, ribosome detachment, decrease in synthesis of of apolipoproteins leading to fatty change in the liver
non-ionzing radiation
carcinogenic agent in UVB sunlight that results in formation of pyrimidine dimers in DNA which are normally excised by NER enzyme, however can lead to basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin
arsenic
found in soil and water around mines and interferes with mitochondrial OXPHOS; presents with neurological effects, skin hyperpigmentation and hyperkeratosis, and also results in increase risk for development of squamous cell carcinoma of skin, lung cancer, and angiosarcoma of the liver present in cigarette smoke also
lead poisoning
lead interferes with calcium metabolism resulting in CNS defects in children (peripheral neuropathy in adults), abdominal pain, increased bone density as seen by "lead lines", and microcytic hypochromic anemia with basophilic stippling (decrease in heme synthesis); treated with chelation therapy
ionizing radiation
a carcinogenic agent that generates hydroxyl free radicals which damages DNA (rapidly dividing cells are more susceptible to damage; associated with AML, CML (leukemias), and papillary carcinoma of the thyroid
type III collagen
pliable - present in granulation tissue, embryonic tissue, uterus, and keloids
type IV collagen
basement membrane
neoplasia
"new growth" that is unregulated, irreversible, and monoclonal
what type of collagen is present in granulation tissue?
type III collagen (replaced by type I in scar formation)
vinyl chloride
used to make PVC pipes; associated with angiosarcoma of the liver
primary intention/union
wound healing that occurs after a clean surgical incision in which there is minimal defect because wound edges are brought together leading to minimal inflammation and minimal scar formation (ex. suturing of surgical incision)
dehiscence
rupture of a wound, most commonly seen after abdominal surgery as a result of increased intra-abdominal pressure; due to inadequate granulation tissue formation or inadequate scarring
FGF
fibroblast growth factor - important for angiogenesis
granulation tissue
a provisional matrix formed in the initial phase of tissue repair that consists of capillaries, fibroblasts, and myofibroblasts
location of small and large bowel stem cells
stem cells in mucosal crypts
fibrosis/scarring
occurs if a tissue cannot regenerate or can do so only in a limited fashion and the area of tissue loss must be filled in by deposition of collagen and other ECM material
what is the KEY distinguishing feature between benign and malignant tumors
metastatic potential
labile tissues
(continuously dividing) posses stem cells that continuously cycle to regenerate the tissue
tumor differentiation
the degree to which the parenchyma (neoplastic cells) resembles its normal counterpart
dystrophic calcification
occurs in patients with normal serum calcium and phosphate when calcium deposits on dead/necrotic tissue leading to fat necrosis
silicosis
common lung disease associated with occupations involving sandblasting, stone carving, etc. caused by inhalation of pro-inflammatory crystalline silicon dioxide; presents after decades of exposure as slowly progressing, nodular, fibrosing lung disease- also associated with increased risk of TB because of altered macrophage functioning *characterized histologically by an area of whorled collagen fibers with a more peripheral zone of dust-laden macrophages
wound contracture
diminishment in size of the wound during the healing process that occurs due to myofibroblast contraction (specialized fibroblasts that express smooth muscle actin)
technical difference between fibrosis and scarring
fibrosis - active process leading to the abnormal deposition of collagen and ECM in internal organs in response to chronic (persistent or recurring) injury scar - the end result of wound healing when the inciting injurious agent has been removed, contained, or walled off
polycyclic hydrocarbons
most potent carcinogens, associated with lung and bladder cancer, present in cigarette smoke
secondary intention/union
wound healing that occurs after large cutaneous defects in which the wound edges are not approximated and granulation tissue instead fills the defect - this results in possible infection and inflammation and wound contracture is needed to form prominent scar (ex. punch biopsy)
stem cells of bone marrow
hemopoietic stem cells
GMS stain
silver stain - fungus
which tissues in the body are able to regenerate?
bone marrow, skin, and gastrointestinal mucosa (also liver but regeneration does NOT depend on stem cells)
metastatic calcification
occurs when HIGH serum calcium or phosphate levels lead to calcium deposition in normal tissues (gastric mucosa, kidneys, lungs)
location of skin stem cells
stem cells in basal layer of the epidermis
permanent tissues
lack significant regenerative potential (myocardium, skeletal muscle, and neurons)
adhesions
fibrous bands that form between tissues that are not normally connected (especially bowel loops) usually after surgery or infection (can lead to bowel obstruction)
malignant tumor
-poorly differentiated -disorganized growth and loss of polarity -nuclear pleomorphism -nuclear hyperchromasia -high N/C ratio -mitotic figures -invasion and metastatic potential
poorly differentiated
tumor does NOT resemble parent tissue
Section 6
(50 cards)
EBV
(Epstein-Barr virus) associated with Burkitt lymphoma
choristoma
a congenital abnormality in which a collection of cells or tissues forms a tumor in a location where they would not normally be found ex. small nodules of ectopic gastric mucosa found in duodenum (normal gastric glands but in wrong location) - NOT a neoplasm
seeding of body cavities is characteristic of what neoplasm?
ovarian carcinoma - seeding of peritoneum "omental caking"
lymphatic spread
neoplasm spreads via lymphatic channels; characteristic of carcinomas
silica
associated with lung carcinoma (occupational exposure - sandblasting, stone carving)
myeloma
cancer from plasma cells
barrett esophagus (associated cancer)
associated with esophageal carcinoma
teratoma
"monstrous tumor" a tumor composed of several tissue types from different embryological layers that arises from totipotent cells (germ cells in gonads) and results in a strange mixtures of tissues (skin, hair, fat, nervous, teeth) can be mature - benign or immature - malignant
pap smear
detects cervical dysplasia (CIN) before it becomes carcinoma
benign tumor ending
-oma
hematogenous spread
neoplasm spreads via blood vessels characteristic of sarcomas and some carcinomas
immunohistological stain - vimentin
mesenchyme tissue
polyp
a visible projection of a collection of tissue above the mucosa of an organ into the lumen inside the organ; may be benign, pre-neoplastic, or malignant
immunohistological stain - PSA
prostatic epithelial tissue
cancer is the ___ leading cause of death in both adults and children
2nd
malignant tumor of mesothelium
mesothelioma (mesothelium = layer that lines the pleura, pericardium, and peritoneum)
immunohistological stain - ER
breast epithelial tissue
immunohistological stain - chromogranin
neuroendrocrine cells
desmoplasia
the reactive stroma that surrounds the invading edge of tumor (fibrous tissue, new collagen, blood vessels, lymphocytes and plasma cells etc.) - NOT part of the neoplasm, but form part of palpable tumor
dysplasia
disordered cellular growth, most often referring to the proliferation of PREcancerous cells that arises from longstanding pathologic hyperplasia or metaplasia (ex. cervical intraepithelial neoplasia (CIN) is a dysplasia that arises from squamous metaplasia and is a precursor to cervical cancer)
malignant tumor from mesenchyme lineage
-sarcoma (connective tissue - bone, cartilage, blood vessels, fat)
HPV
(human papillomavirus) associated with adenocarcinoma of cervix, squamous cell carcinoma of the vulva, vagina, anus, and cervix
chole-
gall, bile
exceptions - carcinomas that travel via hematogenous spread
-renal cell carcinoma (renal vein) -hepatocellular carcinoma (hepatic vein) -follicular carcinoma of the thyroid -choriocarcinoma = malignancy of placental tissues
immunohistological stain - S-100
melanoma
sentinel node
the first lymph nodes in a regional lymphatic area that receives lymph flow from a primary tumor (often removed with the primary tumor)
low grade tumor
well differentiated (resembles normal parent tissue); better prognosis
hamartoma
a developmental abnormality that leads to a benign mass of mature but disorganized tissue indigenous to its site - NOT a neoplasm
prostate specific antigen (PSA) and digital rectal exam
detects prostate carcinoma before it spreads
grading cancer
based on the degree of tumor differentiation (extent to which tumor cells resemble their normal counterparts) taking into account the number of mitotic figures, amount of tumor necrosis, and architectural features
anaplastic
"backwards growth" undifferentiated (no recognizable features of a specific cell type), pleomorphic tumors characteristic of malignant neoplasms
malignant tumor from epithelial lineage
-carcinoma (inner/outer mucosal/epidermal surfaces = digestive tract, pulmonary tract, genitourinary system, skin, glands = adeno-, pancreas, adrenal glands)
leukemia
cancer of white blood cells
immunohistological stain - desmin
muscle tissue
mammography
detects in situ breast cancer (ductal carcinoma in situ - DCIS) before it invades and also detects invasive carcinoma before it becomes clinically palpable (2 cm)
malignant tumor of lymphocytes
lymphoma/leukemia
3 most common cancers (by mortality)
lung, breast/prostate, colorectal
gastrointestinal tumors tend to metastasize to
the liver (via portal circulation)
HBV and HCV
(hepatitis B and C virus) associated with hepatocellular carcinoma
example of benign hyperplasia
uterine lining (endometrium) undergoes normal hyperplasia during pregnancy
high grade tumor
poorly differentiated (does NOT resemble parent tissue - anaplastic); worse prognosis
3 most common cancers (by incidence)
breast/prostate, lung, colorectal
asbestos
associated with lung carcinoma and mesothelioma (more likely to lead to lung cancer)
most common tumor of liver
a metastatic malignancy (GI tumor --> liver)
benign tumor of lymphocytes
DNE!
staging of cancer
assessment of tumor size and spread taking into account the degree of lymph node metastasis and more distant metastasis
carcinoma in situ (CIS)
an epithelial neoplasm with all the features and abilities of malignancy, but it has not yet begun to invade the surrounding tissues - the entire "full thickness" epithelium is replaced by neoplasia but the cells are still bound by basement membrane ex. cervical intraepithelial neoplasia (CIN)
malignant melanocyte tumor
melanoma
iatrogenic
produced by a physician
benign melanocyte tumor
nevus (mole)
Section 7
(5 cards)