Cell adaptation - hypertrophy - hyperplasia - atrophy - metaplasia - dysplasia

- increase in structural proteins and organelle which increases size of cell - controlled proliferation of stem cells -> increase in amnt of cells - decrease in tissue mass because decrease in size or number of cells - reprogramming of stem cells causing replacement of one cell type to another because it is better at adapting to certain stressor - disordered precancerous epi cell growth characterized by loss of uniformity of cell size and shape

Injury - reversible: ATP, ribosomes, membrane, nuclear, function - irreversible: membrane, mito, lysosome, nuclear

- decrease in ATP -> decrease Ca activity and Na/K pmp -> cellular swelling; ribosomal detachment -> decrease protein synthesis; plasma membrane changes; nuclear changes; rapid loss of function - breakdown of plasma membrane -> Ca into cell -> activates proteases; mito damage dysfunction -> loss of ETC -> low ATP; rupture of lysosomes -> autolysis; nuclear degradation

Apoptosis - intrinsic: what is it, regulated by, Function of apoptotic, Function of anti-apoptotic - extrinsic: 2 pathways

- regulating factor is withdrawn from proliferating cell causing apoptosis; BCL2 family, BAX and BAK: form pores into mito membrane -> release of cyto C from inner mito membrane to cytoplasm -> activation of capases; BCL2: keep mito membrane impermeable - ligand binding receptor (Fas-FasL or TNF-alpha) or immune cell mediated (CD8+ or NK)

Types of Necrosis - coagulative: seen in, due to, histo - liquefactive - caseous - fat - fibrinoid - gangrenous

- ischemia / infarct; injury that denatures proteins; preserved cell architecture but nuclei disappear - bacterial abcesses or brain infarcts; PMN release lysosomal enzymes that digest tissue; cellular debris and macro -> cystic spaces and cavitations - TB, systemic fungi; macro wall off infecting organism -> granular debris; fragmented cells and debris surrounded by lymphocytes - enzymatic: acute pancreatitis, non-enzymatic: trauma; damaged pancreatic cells release lipase which breaks down trigly and FFA binds to CA -> causing chalk white appearance of fat; outline of dead fat cell w/o peripheral nuclei - immune vascular reaction; immune complex deposition and or plasma protein leakage from damaged vessel; vessel walls are thick and pink - distal extremity and GI tract after chronic ischemia; Dry: ischemia, wet: super-infection; coagulative or liquefactive on top of coagulative

Ischemia - what is it - mechanism

- inadequate blood supply to meet demand - decrease arterial perfusion, decreased venous drainage, shock

Type of infarct - red - white

- occurs in venous occlusions and tissues w/ multiple blood supplies and with re-perfusion - occurs in solid organ with single blood supply

Free radical injury - function - caused by

- damage cell membrane by lipid peroxidation - radiation, meds, redox reactions, NO - scavenging enzymes, spontaneous decay, anti-oxidant

Type of calcification - dystrophic: cell type, extent, etiology, serum Ca levels, associated conditions - metastatic: cell type, extent, etiology, serum Ca levels, associated conditions

- in diseased tissue; localized; secondary to injury or necrosis; normal; TB, chronic abcess, fat necrosis, infarct - in normal tissue; widespread; secondary to hyper Ca; abnormal; in interstitum of kidney, lung, GI mucosa,

Lipofuscin - what is it - cause - found in

- yellow-brown wear and tear pigment associated w/ normal aging - oxidation and polymerization og autophagocytosed organellar membranes - heart, colon, liver, kidney, eye of elederly on autopsy

Amyloidosis - what is it/ pathogenesis - visualized w/ - location

- abnormal aggregation of proteins into beta pleated linear sheets -> insoluble fibrils -> cell damage and apoptosis - congo-red stain - glomerular mesangial areas

Systemic amyloidosis - primary: fibril protein, seen in - secondary - dialysis

- AL protein, seen in plasma cell disorders - serum amyloid A, seen in chronic inflamm conditions - B2 microglobulin, seen in pts with ESRD

Localized amyloidosis - Alzheimers: protein, from - Type II DM: protein, cause - Medullary thyroid CA: protein - Isolated atrial amyloidosis: protein, pathogenesis, risk - systemic senile amyloidosis: protein, location

- Beta amyloid protein; cleaved from amyloid precursor protein - Islet amyloid polypeptide; caused by deposition of amylin in pancreatic islet cells - calcitonin - ANP, common in normal aging but puts at risk for a fib - transthyretin, seen predominantly in cardiac ventricles

Hereditary amyloidosis - familial amyloid cardiomyopathy: protein, location, causes - familial amyloid polyneuropathy: protein

- mutated transthyretin, ventricular endocardium -> restrictive cardiomyopathy - mutated transthyretin -> caused by tranthyretin gene mutation

Inflammation - what is it - signs - acute phase - fever

- response to eliminate cause of cell injury, remove necrotic cells and initiate tissue repair - erythema / heat (histamine/ prostaglandin/ bradykinin causing increase in vasodilation), tumor / swelling (leukotrienes, hitamine, serotonin causeeing endothelial disruption allowing for leakage of proteins and increasing interstial oncotic pressure), pain (bradykinin, PGE2, histamine causing sensitization of nerve endings), loss of function - fever, leukocytosis, increase in plasma acute phase protein produced by liver - pyrogens cause macro to release IL-1 and TNF -> increase COX -> in pervacsular cells in hypothal -> increase PGE2 -> increase set point - elevation of WBC count and type of cell depends on inciting agent

Acute phase reactants - ferritin - fibrinogen - serum amyloid A - hepcidin - CRP - albumin - transferrin

- upreg, binds and sequesters iron to inhibit microbial iron scavenging - upreg, coag factor, promotes endo repain, correlates with ESR - upreg, prolonged leads to amyloidosis - upreg, decrease iron absorption and release - upreg, opsonin - down reg, conserves AA - down reg, internalized by macrophages to sequester iron

Pathology Flashcards by Nyssa Saenz

Cell adaptation

hypertrophy
hyperplasia
atrophy
metaplasia
dysplasia

increase in structural proteins and organelle which increases size of cell
controlled proliferation of stem cells -> increase in amnt of cells
decrease in tissue mass because decrease in size or number of cells
reprogramming of stem cells causing replacement of one cell type to another because it is better at adapting to certain stressor
disordered precancerous epi cell growth characterized by loss of uniformity of cell size and shape

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Injury

reversible: ATP, ribosomes, membrane, nuclear, function
irreversible: membrane, mito, lysosome, nuclear

decrease in ATP -> decrease Ca activity and Na/K pmp -> cellular swelling; ribosomal detachment -> decrease protein synthesis; plasma membrane changes; nuclear changes; rapid loss of function
breakdown of plasma membrane -> Ca into cell -> activates proteases; mito damage dysfunction -> loss of ETC -> low ATP; rupture of lysosomes -> autolysis; nuclear degradation

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Apoptosis

intrinsic: what is it, regulated by, Function of apoptotic, Function of anti-apoptotic
extrinsic: 2 pathways

regulating factor is withdrawn from proliferating cell causing apoptosis; BCL2 family, BAX and BAK: form pores into mito membrane -> release of cyto C from inner mito membrane to cytoplasm -> activation of capases; BCL2: keep mito membrane impermeable
ligand binding receptor (Fas-FasL or TNF-alpha) or immune cell mediated (CD8+ or NK)

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Types of Necrosis

coagulative: seen in, due to, histo
liquefactive
caseous
fat
fibrinoid
gangrenous

ischemia / infarct; injury that denatures proteins; preserved cell architecture but nuclei disappear
bacterial abcesses or brain infarcts; PMN release lysosomal enzymes that digest tissue; cellular debris and macro -> cystic spaces and cavitations
TB, systemic fungi; macro wall off infecting organism -> granular debris; fragmented cells and debris surrounded by lymphocytes
enzymatic: acute pancreatitis, non-enzymatic: trauma; damaged pancreatic cells release lipase which breaks down trigly and FFA binds to CA -> causing chalk white appearance of fat; outline of dead fat cell w/o peripheral nuclei
immune vascular reaction; immune complex deposition and or plasma protein leakage from damaged vessel; vessel walls are thick and pink
distal extremity and GI tract after chronic ischemia; Dry: ischemia, wet: super-infection; coagulative or liquefactive on top of coagulative

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Ischemia

what is it
mechanism

inadequate blood supply to meet demand

- decrease arterial perfusion, decreased venous drainage, shock

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Type of infarct

red
white

occurs in venous occlusions and tissues w/ multiple blood supplies and with re-perfusion
occurs in solid organ with single blood supply

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Free radical injury

function
caused by

damage cell membrane by lipid peroxidation
radiation, meds, redox reactions, NO
scavenging enzymes, spontaneous decay, anti-oxidant

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Type of calcification

dystrophic: cell type, extent, etiology, serum Ca levels, associated conditions
metastatic: cell type, extent, etiology, serum Ca levels, associated conditions

in diseased tissue; localized; secondary to injury or necrosis; normal; TB, chronic abcess, fat necrosis, infarct
in normal tissue; widespread; secondary to hyper Ca; abnormal; in interstitum of kidney, lung, GI mucosa,

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Lipofuscin

what is it
cause
found in

yellow-brown wear and tear pigment associated w/ normal aging
oxidation and polymerization og autophagocytosed organellar membranes
heart, colon, liver, kidney, eye of elederly on autopsy

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Amyloidosis

what is it/ pathogenesis
visualized w/
location

abnormal aggregation of proteins into beta pleated linear sheets -> insoluble fibrils -> cell damage and apoptosis
congo-red stain
glomerular mesangial areas

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Systemic amyloidosis

primary: fibril protein, seen in
secondary
dialysis

AL protein, seen in plasma cell disorders
serum amyloid A, seen in chronic inflamm conditions
B2 microglobulin, seen in pts with ESRD

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Localized amyloidosis

Alzheimers: protein, from
Type II DM: protein, cause
Medullary thyroid CA: protein
Isolated atrial amyloidosis: protein, pathogenesis, risk
systemic senile amyloidosis: protein, location

Beta amyloid protein; cleaved from amyloid precursor protein
Islet amyloid polypeptide; caused by deposition of amylin in pancreatic islet cells
calcitonin
ANP, common in normal aging but puts at risk for a fib
transthyretin, seen predominantly in cardiac ventricles

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Hereditary amyloidosis

familial amyloid cardiomyopathy: protein, location, causes
familial amyloid polyneuropathy: protein

mutated transthyretin, ventricular endocardium -> restrictive cardiomyopathy
mutated transthyretin -> caused by tranthyretin gene mutation

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Inflammation

what is it
signs
acute phase
fever

response to eliminate cause of cell injury, remove necrotic cells and initiate tissue repair
erythema / heat (histamine/ prostaglandin/ bradykinin causing increase in vasodilation), tumor / swelling (leukotrienes, hitamine, serotonin causeeing endothelial disruption allowing for leakage of proteins and increasing interstial oncotic pressure), pain (bradykinin, PGE2, histamine causing sensitization of nerve endings), loss of function
fever, leukocytosis, increase in plasma acute phase protein produced by liver
pyrogens cause macro to release IL-1 and TNF -> increase COX -> in pervacsular cells in hypothal -> increase PGE2 -> increase set point
elevation of WBC count and type of cell depends on inciting agent

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Acute phase reactants

ferritin
fibrinogen
serum amyloid A
hepcidin
CRP
albumin
transferrin

upreg, binds and sequesters iron to inhibit microbial iron scavenging
upreg, coag factor, promotes endo repain, correlates with ESR
upreg, prolonged leads to amyloidosis
upreg, decrease iron absorption and release
upreg, opsonin
down reg, conserves AA
down reg, internalized by macrophages to sequester iron

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Erythrocyte sedimentation rate

- what is it

RBC normally able to remain separated by neg charge but with inflammation fibrinogen will coat RBC and decrese negative charge -> increase in RBC aggregation

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Exudate vs Transudate

exudate: cell, protein, caused by
transudate
light criteria

cellular (cloudy), high protein, lymph obstruction/ inflammation/ infection/ malignancy
hypocellular (clear), low protein, increase in hydrostatic pressure or decrease in oncotic pressure
pleural fluid is exudative if more than 1 of following criteria is met: has fluid/serum protein ration > 0.5, fluid/serum LDH ration > .6, pleural fluid LDH > 2/3 of upper limit of normal serum LDH

Acute inflammation

what is it
characterized by
stimuli
mediators
vascular component
cellular component
outcomes

transient and early response to injury or infection
PMNs in tissue and edema
infection, trauma, necrosis, foreign bodies
TLR, arachadonic acid metabolites, PMN, eosinophil
vasodilation and increase in endothelial permeability
extravasion of leukocytes from post-cap venules and accumulation in location of injury
resolution and healing, abcess, scarring

Leukocyte extravasion

margination and rolling: endo cells express, leukocytes express
tight binding: endo cells express, leukocytes express
diapedesis: what is it, endo cells express, leukocytes express
migration: what is it, endo cells express, leukocytes express

endo: E-selectin, P-selecting, GlyCAM1; Leuko: Sialyl lewis and L-selectin; leukocyte adhesion deficiency type 2 bs of decrease in sialyl lewis
endo: ICAM and VCAM; Leukocyte: CD11/12 and VLA4; defective in leukoocyte adhesion deificiency type 1
WBC travel between endo cell and exits blood vessel; PECAM-1 (both endo and leuko)
WBC travels in interstitium to site of injury or infection guided by chemotactic signal; endo: C5a, IL8

Wound healing tissue mediators

FGF
TGF beta
VEGF
PDGF
Metalloproteinases
EGF

stimulates angiogenesis
angiogenesis and fibrosis
stimulate angiogenesis
secreted by platelets, induces vascular remodeling and smooth muscle cell migration, stimulates fibroblast growth for collagen synthesis
tissue remodeling
stimulates cell growth via tyrosine kinase

Phase of wound healing

inflammatory
proliferative
remodeling

immediate to 3 days after wound; pleatelets, PMN, macro; clot formation, increase vessel permeability and PMN migration into tissue, macro clear debris 2 days later
3 days to weeks after wound; fibroblasts, myofibrblasts, endothelial cells, keratinocytes, macro; deposition of granulation tissue and type III collagen, angiogenesis, epi cell proliferation, dissolution of clot and wound contraction
1 week to 6 month; fibroblasts; type III colagen replaced by type I collagen to increase tensile strength of tissue, collagenases, zinc deficiency

Phase of wound healing

inflammatory: time frame, cells involved, characteristics
proliferative: time frame, cells involved, characteristics
remodeling: time frame, cells involved, characteristics

immediate to 3 days after wound; pleatelets, PMN, macro; clot formation, increase vessel permeability and PMN migration into tissue, macro clear debris 2 days later
3 days to weeks after wound; fibroblasts, myofibrblasts, endothelial cells, keratinocytes, macro; deposition of granulation tissue and type III collagen, angiogenesis, epi cell proliferation, dissolution of clot and wound contraction
1 week to 6 month; fibroblasts; type III colagen replaced by type I collagen to increase tensile strength of tissue, collagenases, zinc deficiency

Granulomatous inflammation

what is it
caused by
used for
histo
types
mechanism
anti TNF

pattern of chronic inflammation
by persistent T-cell response to certain infections
wall off a resistant stimulus w/o completely eradicating or degrading it
activated macrophage w/ abundant pink cytoplasm surrounded by lymphocytes lymphocytes and giant cells
caseating w/ central necrosis or non caseating w/o necrosis
APC present antigens to CD4 helper T cells and secrete IL-2 -> differentiate into Th1 cells -> secrete INF gamma -> macrophages activated -> macrophage increase cytokine secretion -> formation of giant cells
cause sequestering granulomas to break down -> disseminated disease

Scar formation

what?
hypertrophic
keloid

occurs when repair cannot be accomplished by cell regeneration, non-regenerated cells replaced by CT
increased type III collagen, collagen is parallel, scar confined to to borders of original wound, infrequent recurrence and no predispostion
very high type I and III collagen, disorganized collagen organization, extends beyond border of original would with claw like projections typically on earlobes, face, UE, frequently recur, increase incidence in ethnic groups w/ darker skin

Neoplasia - what is it - components - dysplasia - carcinoma in situ - invasive carcinoma - mets

- uncontrolled, monoclonal proliferation of cells, can be malignant or benign - parenchyma (neoplastic cells) and supporting stroma (blood vessels, CT) - loss of uniformity in cell size and shape, loss of tissue orientation, nuclear changes - irreversible severe dysplasia that involves the entire thickness of epi but the basement membrane is intact - cells have invaded the basement membrane using collagenases and hydrolases, cell-cell contacts lost bu inactivation of E-cadherin - spread to distant organs via lymphatics or blood

Tumor nomenclature - carcinoma - sarcoma - benign - malignant - hamartoma - choriostoma

- epthelial origin - mesenchymal origin - well differentiated and wll demarcated, low mitotic activity, no mets, no necrosis - poor diferentiation, erratic growth, local invasion, mets, decreased apoptosis - disorganized growth of tissue in native location - normal tissue in foreign location

Cell type and types of CA - Epi: benign, malignant - blood cells: malignant - blood vessels: benign, malignant - SM: benign, malignant - Striated muscle: benign, malignant - CT: benign, malignant - Bone: benign, malignant - Fat: benign, malignant - Melanocyte: benign, malignant

- adenoma, papilloma; adenocarcinoma, papillary carcinoma - leukemia, lymphoma - hemangioma; angiosarcoma - leiomyoma; leiomyosarcoma - rhabdomyoma; rhabdomyosarcoma - fibroma; fibrosarcoma - osteoma; osteosarcoma - lipoma; liposarcoma - nevus; melanoma

Tumor grade vs Stage - grade - stage

- degree of cellular differentiation (how much it looks like tissue of origin) on histo - degree of localization/ spread based on site and size of primary location, spread to regional LN, presence of mets; determines survival

Immune evasion in CA - what happens - escape mechanisms

- immune cells can recognize and attack tumor cells - decreased MHC class I expression -> cytotoxic T cells unable to recognize tumor cells, secrete immunosuppressive factors, up-reg immune chekpoint mutations

Common Mets - sarcoma - carcinoma - four carcinoma route hemato

- hematogenously - lymph - follicular thyroid, choriocarcinoma, renal cell, and heptaocellular

Oncogenic Microbes - EBV - HBV, HCV - HHV-8 - HPV - H pylori - HTLV-1 - Liver fluke - Schistosoma

- Burkitt lymphoma - Heptaocellular carcinoma - Kaposi sarcoma - Cervical and penile/anal carcinoma, head and neck CA - gastric adenocarcinoma and MALT lymphoma - adult t-cell leukemia - cholangiocarcinoma - squamous cell bladder CA

Serum tumor marker - alk phos - alpha fetoprotein - hCG - CA-15/ CA 27-29 - CA 19-9 - CA 125 - Calcitonin - CEA - chromogranin - LDH - Neuron specific enolase - PSA

- mets to bone or liver, pagets dx, seminoma - hepatocellular carcinoma, mixed germ cell tumor, neural tube defects - hydatidiform mole and choriocarcinoma - breast CA - pancreatic adenocarcinoma - ovarian carcinoma - medullary thyroid carcinoma - colorectal and pancreatic carcinoma - neuroendocrine tumor - testicular germ cell tumors, ovarian dysgerminoma - neuroendocrine tumor - prostate CA

IHC stains - chromogranin - cytokeratin - desmin - GFAP - neurofilament - s-100 - TRAP

- neuroendocrine cells -> small cell carcinoma of lung - epithelial cells - muscle - neuroglia -> astrocytoma, glioblastoma - neurons - neural crest cells - hair cell leukemia

P- glycoprotein - in - for

- in adrenocortical carcinoma | - used to pump out toxins including chemo agents

Psammoma bodies - histo - which cancers

- laminated, concentric spherules w/ dystrophic calcification - papillary carcinoma of thyroid, somatostatinoma, meningioma, mesothelioma, ovarian serous papillary cystadenocarcinoma, prolactinma

Cachexia - what is it - caused by

- weight loss, muscle atrophy, and fatigue that occurs w/ chronic dx - TNF alpha, IFN gamma, IL-1 and 6

Paraneoplastic Syndrome MS and cutaneous - dermatomyositis: description/ mechanism; most common tumor - acanthosis nigricans - sign of leser-trelat - hypertrophic osteoathropathy

- progressive proximal muscle waekness, gottron papules, heliotrope rash - hyperpigmented velvety plaques in axilla and neck - sudden onset of mult seborrheic keratoses - abnrml proliferation of skin and bone at distal extremities

Paraneoplastic Syndrome endocrine - hypercalcemia: description/ mechanism; most common tumor - cushing syndrome - hyponatremia

- PTHrP; suamous cell carcinoma of lung, head, and neck - high ACTH, small cell lung CA - High ADH, small cell lung CA

Paraneoplastic Syndrome hematologic - polycythemia: description/ mechanism; most common tumor - pure red cell plasia - good syndrome - trosseau syndrome - nonbacterial throbmotic endocarditis

- increased erythropoietin; pheochromocytoma, renal cell carcinoma - anemia w/ low reticulocytes; thymoma - hypogammaglobulinemia; thymoma - migratory superficial thrombophlebitis; adenocarcinoma - deposition of sterile platelet thrombi on heart valves; adenocarcinoma

Paraneoplastic Syndrome Neuromuscular - anti NMDA receptor encephalitis: description/ mechanism; most common tumor - opsoclonus-myoclonus ataxia syndrome - paraneoplastic cerebellar degeneration - paraneoplastic encephalomyelitis - lamber-eatn myasthenic syndrome - myasthenia gravis

- psych disturbances, memory deficits, seizures; ovarian teratoma - dancing eyes and feet; neuroblastoma and small cell lung - antibodies against purkinje cells; small cell, gycenologic and breast CA - antibodies against Hu antigen in neuron; small cell lung CA - antibodies against pre-synaptic channels at NMJ; small cell lung CA - antibodies against postsynaptic Ach receptors at NMJ; thymoma