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Pathology Flashcards

1
Q

reversible cell injury

A

low ATP –> low Ca2+ and Na+/K+ pumps –> cellular swelling and mitochondrial swelling
Ribosomal/ polysomal detachment –> decrease protein synthesis
Blebbing
Nuclear change
Rapid loss of function
Myelin figures

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2
Q

Irreversible cell injury

A

breakdown of plasma membrane –> cytosolic enzymes leak outside of cell, influx of Ca2+ –> activate degradative enzymes
mitochondrial damage –> loss of ETC –> low ATP
cytoplasmic vacuolization (apoptosis)
Rupture of lysosomes –> autolysis
Nuclear degradation- pyknosis –> karyorrhexis –> karyolysis
Amorphous densities

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3
Q

Apoptosis

A

ATP dependent programmed cell death
Activate Caspases –> cellular breakdown
Deeply eosinophilic cytoplasm and basophilic nucleus, pyknosis and karyorrhexis
cell membrane intact without inflammation
DNA laddering

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4
Q

Intrinsic mitochondrial pathway

A

Tissue remodeling in embryogenesis. When regulating factor is withdrawn from a proliferating cell population or after exposure to injurious stimuli
Regulated by Bcl-2 family (BAX and BAK= pro and Bcl-2 and Bcl-xL= anti)
BAX and BAK –> form pores in mitochondrial membrane –> release cytochrome C –> activate caspases
Bcl-2 and Bcl-xL keep mitochondrial membrane impermeable –> prevent cytochrome C release

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5
Q

Extrinsic pathway

A

Ligand receptor interactions (FasL bind Fas or TNFa bind to its receptor) or via immune cell
Fas-FasL necessary in thymic medullary negative selection
Fas mutations increase numbers of circulating self reacting lymphocytes

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6
Q

Necrosis

A

Exogenous injury -> plasma membrane damage –> enzymatic degradation and protein denaturation, intracellular components leak –> local inflammatory reaction

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7
Q

Coagulative necrosis

A

Ischemic/ infarcts in most tissue
–> denature enzymes –> proteolysis blocked
Preserved cellular architecture but nuclei disappear
Increase cytoplasmic binding of eosin stain

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8
Q

Liquefactive necrosis

A

Bacterial abscesses, brain infarcts
Neutrophils release lysosomal enzymes –> digest
Early: cellular debris and macrophages
Late: cystic spaces and cavitation (brain)
Neutrophils and cell debris seen with bacterial infection

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9
Q

Caseous Necrosis

A

TB, Histoplasma, capsulatum, Nocardia
Macrophages wall off the infecting microorganism –> granular debris
Fragmented cells and debris surrounded by lymphocytes and macrophages

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10
Q

Fat Necrosis

A

Enzymatic- acute pancreatitis
Nonenzymatic- traumatic
Damaged pancreatic cells release lipase which break down TG –> bind calcium –> saponification
Outlines of dead fat cells without peripheral nuclei
Saponification appears blue

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11
Q

Fibrinoid Necrosis

A

Immune vascular reactions
Nonimmune vascular reactions
Immune complex deposition or plasma protein leakage from damaged vessel
Vessel walls are thick and pink

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12
Q

Gangrenous Necrosis

A

Distal extremity and GI tract, after chronic ischemia
Dry- ischemia –> coagulative
Wet- superinfection –> liquefactive superimposed on coagulative

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13
Q

Ischemia

A

inadequate blood supple to meet demand

decreased arterial perfusion, decrease venous drainage, shock

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14
Q

Watershed area

A

receive blood supple from most distal branches of 2 arteres with limited collateral vascularity
Susceptible to ischemia

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15
Q

Red infarct

A

venous occlusion and tissues with multiple blood supplies and with reperfusion injury

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16
Q

Pale infarct

A

occurs in solid organs with a single blood supply

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17
Q

Free radical injury

A

damage via membrane lipid peroxidation, protein modification, DNA breakage.
initiated via radiation exposure, metabolism of drugs, WBC oxidation burst
Eliminated by scavenging enzymes, spontaneous decay, antioxidants and metal carrier proteins

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18
Q

Dystrophic calcification

A 
In abnormal tissues
Tends to be localized 
TB, liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistasomiasis, congenital CMV, toxo, rubella, psammoma bodies, CREST, atherosclerotic plaques
Secondary to injury or necorisis
Normal serum Ca2+
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19
Q

Metastatic calcification

A

in normal tissues
Widespread
Interstitial tissues of kidney, lung and gastric mucosa
Secondary to hypercalcemia or high Calcium phosphate product levels
Abnormal Ca2+ in serum

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20
Q

Lipofuscin

A

yellow brown wear and tear pigment associated with normal aging
composed of polymers of lipids and phospholipids complexed with protein. May be derived through lipid peroxidation of polyunsaturated lipids and subcellular membranes
Autopsy of elderly person will reveal deposits in heart, colon, liver, kidney, eye

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21
Q

Amyloidosis

A

Abnormal aggregation of proteins into B pleated linear sheets –> insoluble fibrils –> cell damage and apoptosis.
Congo Red
Tubular BM enlarged on light microscopy

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22
Q

Primary Amyloidosis

A

AL protein seen in plasma cell disorder (multiple myeloma)

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23
Q

Secondary Amyloidosis

A

AA protein

seen in chronic inflammatory conditions

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24
Q

Dialysis related amyloidosis

A

B2 microglobulin

ESRD or long term dialysis

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25
Q

Alzheimer disease amyloidosis

A

B amyloid protein cleaved from amyloid precursor protein

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26
Q

T2DM amyloidosis

A

islet amyloid polypeptide

deposition of amylin in pancreatic islets

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27
Q

Medullary thyroid cancer amyloidosis

A

Calcitonin

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28
Q

Isolated atrial amyloidosis

A

ANP common in normal aging

increased risk of A fib

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29
Q

systemic senile amyloidosis

A

normal
in cardiac ventricles
cardiac dysfunction more insidious than AL

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30
Q

Familial amyloid cardiomyopathy

A

mutated ATTR

ventricular endomyocardium deposition –> restrictive cardiomyopathy, arrhythmias

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31
Q

Familial amyloid polyneuropathies

A

mutated ATTR

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32
Q

Inflammation

A

Response to eliminated initial cause of cell injury, remove necrotic cells, initiate tissue repair
Harmful if reaction is excessive or prolonged

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33
Q

Cardinal signs of inflammation

A

Rubor via vasodilation and increased blood flow (histamine, PG, bradykinin, NO)
Tumor via endothelial contration –> leak protein rich fluid –> increase interstitial oncotic pressure (leukotrienes, histamine, 5HT)
Dolor via sensitization of sensory nerve endings (bradykinin, PGE2, histamine)
Funtio laesa

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34
Q

Fever

A

Pyogens induce macrophages to release IL1 and TNF –> increase COX in perivascular cells of hypothalamus –> increase PGE2 –> increase temp set point

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35
Q

Leukocytosis

A

elevated WBC

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36
Q

increase plasma acute phase proteins

A

factors whose serum concentrations change in response to inflammation
produced by liver (IL6)

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37
Q

Acute phase reactants that are upregulated

A

Ferritin- bind and sequester iron
Fibrinogen- coagulation factor = ESR
Serum amyloid A- prolonged elevation –> amyloidosis
Hepcidin- decrease iron absorption and iron release –> anemia of chronic disease
CRP- opsonin (fix complement) nonspecific sign of ongoing inflammation

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38
Q

Acute phase reactants that are down regulated

A

Albumin- to conserve AA

Transferrin- internalized by macrophages to sequester iron

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39
Q

ESR

A

RBC normally - charge

inflammation –> decrease - charge –> aggregation –> increase ESR

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40
Q

High ESR

A 
anemia
infection
inflammation
cancer
renal disease
pregnancy
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41
Q

Low ESR

A 
SCD
polycythemia
HF
microcytosis
hypofibrinogenemia
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42
Q

Acute inflammation

A

transient and early response to injury or infection
Neutrophils
Rapid onset and short duration
via infection, trauma, necrosis, foreign bodies
Mediated by TLR, arachidonic acid, neutrophils, eosinophils, Ab, mast cells, basophils, complement
Vascular vasodilation and extravasation of leukocytes

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43
Q

Leukocyte extravasation

A
  1. Margination and rolling- E selectin and P selectin
  2. Tight binding- ICAM1 bind LFA1 and VCAM1 bind VLA4
  3. Diapedesis- PECAM1 bind PECAM
  4. Migration- C5a, IL8, LTB, kallikrein, PAF
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44
Q

Chronic inflammation

A

prolonged inflammation with mononuclear infiltration –> tissue destruction and repair
via persistent infection –> type IV hypersensitivity, autoimmune diseases, prolonged exposure to toxins and foreign material
Th1 cells –> IFNy –> macrophage classical activation
Th2 –> IL4/13 –> macrophage alternative activation
Lead to scarring amyloidosis and neoplastic transformation

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45
Q

Tissue mediators for would healing

A 
FGF --> angiogenesis
TGFB --> angiogenesis and fibrosis
VEGF --> angiogenesis
PDGF --> vascular remodeling and smooth muscle cell migration and fibroblast growth for collagen synthesis
metalloproteinases --> tissue remodeling
EGF --> cell growth via TK
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46
Q

Inflammatory wound healing phase

A

3 days after
Platelets, neutrophils, macrophages
clot formation, increase vessel permeability and neutrophil migration into tissue. macrophage clean up debris

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47
Q

Proliferative wound healing phase

A

day 3- weeks
fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages
Deposition of granulation tissue and Type 3 collagen, angiogenesis, epithelial cells proliferation, dissolution of clot, wound contraction
Delayed if Vitamin C or copper deficient

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48
Q

Remodeling wound healing phase

A 
1 week - 6 months
Fibroblasts
Type 3 collagen replaced by Type 1 collagen --> increase tensile strength
collagenases break down Type 3 collagen
Delayed if Zn deficient
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49
Q

Granulomatous inflammation

A

induced by T cell response to infection, immune mediated diseases and foreign bodies
wall off a resistant stimulus without completely eradicating or degrading it –> persistent inflammation –> fibrous organ damage

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50
Q

Histology of Granulomatous inflammation

A

epithelioid cells surrounded by lymphocytes and multinucleated giant cells
Caseating- central necrosis (TB, fungal)
Non caseating- no central necrosis (autoimmune diseases)

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51
Q

Mechanism Granulomatous inflammation

A
  1. APCs present Ag to CD4 –> secrete IL12 –> CD4 differentiate in th1 cells
  2. Th1 cells secrete IFNy –> macrophage activation
  3. macrophages increase cytokine secretion –> form epithelioid macrophages and giant cells
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52
Q

Scar formation

A

occurs when repair cannot be accomplished by cell regeneration alone
Nonregenerated cells are replaced by connective tissue
Associated with excess TGFB

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53
Q

Hypertrophic scar

A 
Increase Type 3 collagen
Parallel collagen 
Confined to borders of original wound
infrequent recurrence
No prediposition
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54
Q

Keloid Scar

A 
INCREASED Type 3 and 1 collagen
Disorganized collagen
extends beyond border of original wound with claw like projections
Frequent recurrence
Increased incidence in dark skin
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55
Q

Neoplasia and Neoplastic progression

A
  1. Normal cells
  2. Dysplasia- loss of uniformity in cell size and shape
  3. CIS- irreversible severe dysplasia that involves the entire thickness of epithelium but does not penetrate the BM
  4. Invasive carcinoma- invade BM using collagenases and hydrolases. inactivate E cadherin
  5. Metastasis- spread to distance organs via lymphatics or blood
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56
Q

Tumor Grade

A

degree of cellular differentiation and mitotic activity on histo

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57
Q

Tumor Stage

A

degree of localization based on site and size of primary lesion, spread to regional LN, metastasis
More prognostic
TNM- tumor size, node, metastasis

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58
Q

Hallmarks of cancer

A

Growth signal, self sufficiency (PDGF, HER2, RAS, MYC, CDK)
Anti growth signal insensitivity (Rb, NF2)
Evasion of apoptosis (TP53, BCL-2)
Limitless replication
Sustained angiogenesis (VEGF)
Tissue invasion (E- cadherin)
Metastasis
Warburg effect- shift glucose metabolism away from oxidative phosphorylation
Immune evasion (low MHC)

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59
Q

Immune checkpoint interactions

A

PD-1 and PDL- 1/2 –> T cell dysfunction (inhibit via PD 1 antag)
CTLA4 outcompetes CD28 for B7 on APCs –> loss of T cell costimulatory signal (inhibited by anti CTLA4)

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60
Q

Common metastases

A

Sarcomas - via blood

Carcinomas- via lymphatics except follicular thyroid, choriocarcinoma, RCC, hepatocellular

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61
Q

Metastasis to brain

A

Lung > breast > melanoma, colon, kidney

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62
Q

Metastasis to Liver

A

Colon&raquo_space; stomach > pancreas

63
Q

Metastasis to Bone

A

Prostate, breast > kidney, thyroid, lung

64
Q

Oncogene

A

Gain of function

Damage to one allele

65
Q

ALK

A

oncogene
TKR
lung adenocarcinoma

66
Q

BCR-ABL

A

oncogene
nonreceptor TK
CML, ALL

67
Q

BCL-2

A

oncogene
anti apoptotic
follicular and diffuse large B cell lymphoma

68
Q

BRAF

A

oncogene
serine-threonine kinase
melanoma, NHL, papillary thyroid carcinoma, hairy cell leukemia

69
Q

c-KIT

A

oncogene
cytokine receptor
Gastrointestinal stromal tumor

70
Q

c-MYC

A

oncogene
transcription factor
Burkitt lymphoma

71
Q

HER2

A

oncogene
TKR
breast and gastric carcinoma

72
Q

JAK2

A

oncogene
TK
chronic myeloproliferative disorders

73
Q

KRAS

A

oncogene
GTPase
colon cancer, lung cancer, pancreatic cancer

74
Q

MYCL1

A

oncogene
transcription factor
lung tumor

75
Q

N myc

A

oncogene
transcription factor
Neuroblastoma

76
Q

RET

A

oncogene
TKR
MEN2A and 2B, papillary thyroid carcinoma, pheochromocytoma

77
Q

Tumor suppressor gene

A

loss of function

both alleles must be lost

78
Q

APC

A

Tumor suppressor
Negative regulator of B catenin. Wnt
colorectal cancer

79
Q

BRCA1/2

A

Tumor suppressor

Breast, ovarian, pancreatic cancer

80
Q

CDK2NA

A

Tumor suppressor
p16 block G1 –> S
melanoma, pancreatic cancer

81
Q

DCC

A

Tumor suppressor
deleted in colon cancer
colon cancer

82
Q

SMAD4

A

Tumor suppressor
deleted in pancreatic cancer
pancreatic cancer

83
Q

MEN 1

A

Tumor suppressor
menin
MEN1

84
Q

NF1

A

Tumor suppressor
Ras GTPase activating protein
NF1

85
Q

NF2

A

Tumor suppressor
merlin protein
NF2

86
Q

PTEN

A

Tumor suppressor
negative regulator p13k/AKT
prostate, breast, endometrial cancer

87
Q

Rb

A

Tumor suppressor
inhibit E2F, block G1 –> S
retinoblastoma, osteosarcome

88
Q

TP53

A

Tumor suppressor
p53 activate p21, block G1 –> S
Li fraumeni, SBLA

89
Q

TSC1

A

Tumor suppressor
Hamartin protein
Tuberous sclerosis

90
Q

TSC2

A

Tumor suppressor
Tuberin protein
Tuberous sclerosis

91
Q

VHL

A

Tumor suppressor

inhibit hypoxia inducible factor 1a

92
Q

WT1

A

Tumor suppressor
urogenital development transcription factor
wilms tumor

93
Q

Aflatoxin

A

Carcinogen
stored grains and nuts
hepatocellular carcinoma

94
Q

Alkylating agents

A

Carcinogen
chemo
leukemia/ lymphoma

95
Q

Aromatic amines

A

Carcinogen
textile, cigarette
transition cell carcinoma in bladder

96
Q

Arsenic

A

Carcinogen
herbicides, metal smelting
angiosarcoma in liver, lung cancer, SCC in skin

97
Q

Asbestos

A

Carcinogen
old roofing, shipyard
bronchogenic carcinoma > mesothelioma

98
Q

Cigarette

A

Carcinogen
Transitional cell carcinoma in bladder, SCC in cervix, esophagus, larynx, lung, RCC, oropharyngeal cancer, pancreatic adenocarcinoma

99
Q

Ethanol

A

Carcinogen

SCC esophagus, hepatocellular carcinoma

100
Q

Ionizing radiation

A

Carcinogen

papillary thyroid carcinoma, leukemia

101
Q

Nickel, chromium, beryllium, silica

A

Carcinogen
occupational
lung cancer

102
Q

Nitrosamines

A

Carcinogen
smoked foods
gastric cancer

103
Q

Radon

A

Carcinogen
basement
lung cancer

104
Q

Vinyl chloride

A

Carcinogen
PVC
angiosarcoma in liver

105
Q

EBV cancer

A

Burkitt, hodgkin, nasopharyngeal carcinoma, primary CNS lymphoma

106
Q

HBV, HCV cancer

A

Hepatocellular

107
Q

HHV8 cancer

108
Q

HPV cancer

A

cervical, penile/anal, head and neck

109
Q

H. pylori cancer

A

gastric adenocarcinoma and MALT lymphoma

110
Q

Liver fluke cancer

A

cholangiocarcinoma

111
Q

Schistosoma cancer

A

SCC bladder

112
Q

ALK phos in cancer

A

metastases to bone or liver, Paget disease of bone, seminoma

113
Q

AFP in cancer

A

Hepatocellular carcinoma, endodermal sinus tumor, mixed germ cell tumor, ataxia telangiectasia, neural tube defect

114
Q

hCG in cancer

A

Hydatidiform moles and choriocarcinoma, testicular cancer, mixed germ cell tumor

115
Q

CA 15-3/ 27-29 in cancer

116
Q

CA 19-9

A

pancreatic adenocarcinoma

117
Q

CA 125

A

ovarian cancer

118
Q

Calcitonin in cancer

A

medullary thyroid carcinoma, MEN 2A and 2B

119
Q

CEA in cancer

A

colorectal and pancreatic

120
Q

chromogranin in cancer

A

neuroendocrine tumors

121
Q

LDH in cancer

A

testicular germ cell tumors, ovarian dysgerminoma

122
Q

Neuron specific enolase in cancer

A

neuroendocrine tumor

123
Q

PSA

A

prostate cancer

124
Q

Chromogranin and synaptophysin stain

A

neuroendocrine cells

small cell lung carcinoma, carcinoid tumor

125
Q

Cytokeratin statin

A

epithelial cells

SCC

126
Q

Desmin stain

A

muscle

rhabdomyosarcomas

127
Q

GFAP stain

A

neuroglia

astrocytoma, glioblastoma

128
Q

Neurofilament stain

A

neurons

neuronal tumors

129
Q

PSA stain

A

prostatic epithelium

prostate cancer

130
Q

S100 stain

A

NCC

melanoma, schwannoma, langerhans histiocytosis

131
Q

TRAP stain

A

hairy cell leukemia

132
Q

Vimentin stain

A

mesenchymal tissue

133
Q

p- glycoprotein

A

MDR1
adrenocortical carcinoma
pump out toxins aka chemo

134
Q

Psammoma bodies

A

laminated concentric spherules with dystrophic calcifications
papillary carcinoma of thyroid
somastostatinoma
meningioma
malignant mesothelioma
ovarian serous papillary cystadenocarcinoma
prolactinoma

135
Q

Cachexia

A

weight loss, muscle atrophy and fatigue that occur in chronic disease
via TNFa, IFNy, IL1, IL6

136
Q

Dermatomyositis

A

progressive proximal muscle weakness, Gottron papules, heliotrope rash
adenocarcinomas (ovarian)

137
Q

Acanthosis nigricans

A

Hyperpigmented velvet plaque in axilla dn neck

gastric adenocarcinoma

138
Q

Sign of Leser Trelat

A

sudden onset of multiple seborrheic keratoses

GI adenocarcinoma

139
Q

Hypertrophic osteoarthropathy

A

Abnormal proliferation of skin and bone at distal extremities –> clubbing, arthralgia, joint effusion, periostosis
adenocarcinoma of lung

140
Q

Hypercalcemia

A

PTHrP- SCC of lung head and neck, renal bladder, breast and ovarian carcinoma
increase calcitriol- lymphoma

141
Q

Cushing

A

increase ACTH

small cell lung

142
Q

SIADH

A

increase ADH

small cell lung

143
Q

Polycythemia

A

increase EPO

pheochromocytoma, RCC, HPP, hemangioblastoma, leiomyoma

144
Q

Pure red cell aplasia

A

anemia with low reticulocytes

thymoma

145
Q

Good syndrome

A

Hypogammaglobulinemia

Thymoma

146
Q

Trousseau syndrome

A

migratory superficial thrombophlebitis

Thymoma

147
Q

Nonbacterial thrombotic endocarditis

A

deposition of sterile platelet thrombi on heart valves

adenocarcinoma

148
Q

Anti NMDA encephalitis

A

psych disturbance, memory deficit, seizures, dyskinesias, autonomic instability, language dysfunction
ovarian teratoma

149
Q

Opsoclonus myoclonus ataxia syndrome

A

dancing eyes, dancing feet

neuroblastoma, small cell lung

150
Q

paraneoplastic cerebellar degeneration

A

Ab against Ag in Purkinje cells

small cell lung (anti-Hu), gynecologic and breast (anti- Yo), Hodgkin (anti- Tr)

151
Q

Paraneoplastic encephalomyelitis

A

Ab against Hu Ag in neurons

small cell lung

152
Q

Lambert Eaton Myasthenia

A

Ab against presynaptic Ca2+ channels at NMJ

small cell lung

153
Q

Myasthenia gravis

A

Ab against postsynaptic AChR at NMJ

thymoma

Step 1 (17 decks)

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