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Pathology Flashcards

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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 When regulating factor is withdrawn from a proliferating cell population or after exposure to injurious stimuli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
Alzheimer disease amyloidosis
B amyloid protein cleaved from amyloid precursor protein
26
T2DM amyloidosis
islet amyloid polypeptide | deposition of amylin in pancreatic islets
27
Medullary thyroid cancer amyloidosis
Calcitonin
28
Isolated atrial amyloidosis
ANP common in normal aging | increased risk of A fib
29
systemic senile amyloidosis
normal in cardiac ventricles cardiac dysfunction more insidious than AL
30
Familial amyloid cardiomyopathy
mutated ATTR | ventricular endomyocardium deposition --> restrictive cardiomyopathy, arrhythmias
31
Familial amyloid polyneuropathies
mutated ATTR
32
Inflammation
Response to eliminated initial cause of cell injury, remove necrotic cells, initiate tissue repair Harmful if reaction is excessive or prolonged
33
Cardinal signs of inflammation
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
34
Fever
Pyogens induce macrophages to release IL1 and TNF --> increase COX in perivascular cells of hypothalamus --> increase PGE2 --> increase temp set point
35
Leukocytosis
elevated WBC
36
increase plasma acute phase proteins
factors whose serum concentrations change in response to inflammation produced by liver (IL6)
37
Acute phase reactants that are upregulated
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
38
Acute phase reactants that are down regulated
Albumin- to conserve AA | Transferrin- internalized by macrophages to sequester iron
39
ESR
RBC normally - charge | inflammation --> decrease - charge --> aggregation --> increase ESR
40
High ESR
``` anemia infection inflammation cancer renal disease pregnancy ```
41
Low ESR
``` SCD polycythemia HF microcytosis hypofibrinogenemia ```
42
Acute inflammation
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
43
Leukocyte extravasation
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
44
Chronic inflammation
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
45
Tissue mediators for would healing
``` 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 ```
46
Inflammatory wound healing phase
3 days after Platelets, neutrophils, macrophages clot formation, increase vessel permeability and neutrophil migration into tissue. macrophage clean up debris
47
Proliferative wound healing phase
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
48
Remodeling wound healing phase
``` 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 ```
49
Granulomatous inflammation
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
50
Histology of Granulomatous inflammation
epithelioid cells surrounded by lymphocytes and multinucleated giant cells Caseating- central necrosis (TB, fungal) Non caseating- no central necrosis (autoimmune diseases)
51
Mechanism Granulomatous inflammation
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
52
Scar formation
occurs when repair cannot be accomplished by cell regeneration alone Nonregenerated cells are replaced by connective tissue Associated with excess TGFB
53
Hypertrophic scar
``` Increase Type 3 collagen Parallel collagen Confined to borders of original wound infrequent recurrence No prediposition ```
54
Keloid Scar
``` 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 ```
55
Neoplasia and Neoplastic progression
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
56
Tumor Grade
degree of cellular differentiation and mitotic activity on histo
57
Tumor Stage
degree of localization based on site and size of primary lesion, spread to regional LN, metastasis More prognostic TNM- tumor size, node, metastasis
58
Hallmarks of cancer
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)
59
Immune checkpoint interactions
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)
60
Common metastases
Sarcomas - via blood | Carcinomas- via lymphatics except follicular thyroid, choriocarcinoma, RCC, hepatocellular
61
Metastasis to brain
Lung > breast > melanoma, colon, kidney
62
Metastasis to Liver
Colon >> stomach > pancreas
63
Metastasis to Bone
Prostate, breast > kidney, thyroid, lung
64
Oncogene
Gain of function | Damage to one allele
65
ALK
oncogene TKR lung adenocarcinoma
66
BCR-ABL
oncogene nonreceptor TK CML, ALL
67
BCL-2
oncogene anti apoptotic follicular and diffuse large B cell lymphoma
68
BRAF
oncogene serine-threonine kinase melanoma, NHL, papillary thyroid carcinoma, hairy cell leukemia
69
c-KIT
oncogene cytokine receptor Gastrointestinal stromal tumor
70
c-MYC
oncogene transcription factor Burkitt lymphoma
71
HER2
oncogene TKR breast and gastric carcinoma
72
JAK2
oncogene TK chronic myeloproliferative disorders
73
KRAS
oncogene GTPase colon cancer, lung cancer, pancreatic cancer
74
MYCL1
oncogene transcription factor lung tumor
75
N myc
oncogene transcription factor Neuroblastoma
76
RET
oncogene TKR MEN2A and 2B, papillary thyroid carcinoma, pheochromocytoma
77
Tumor suppressor gene
loss of function | both alleles must be lost
78
APC
Tumor suppressor Negative regulator of B catenin. Wnt colorectal cancer
79
BRCA1/2
Tumor suppressor | Breast, ovarian, pancreatic cancer
80
CDK2NA
Tumor suppressor p16 block G1 --> S melanoma, pancreatic cancer
81
DCC
Tumor suppressor deleted in colon cancer colon cancer
82
SMAD4
Tumor suppressor deleted in pancreatic cancer pancreatic cancer
83
MEN 1
Tumor suppressor menin MEN1
84
NF1
Tumor suppressor Ras GTPase activating protein NF1
85
NF2
Tumor suppressor merlin protein NF2
86
PTEN
Tumor suppressor negative regulator p13k/AKT prostate, breast, endometrial cancer
87
Rb
Tumor suppressor inhibit E2F, block G1 --> S retinoblastoma, osteosarcome
88
TP53
Tumor suppressor p53 activate p21, block G1 --> S Li fraumeni, SBLA
89
TSC1
Tumor suppressor Hamartin protein Tuberous sclerosis
90
TSC2
Tumor suppressor Tuberin protein Tuberous sclerosis
91
VHL
Tumor suppressor | inhibit hypoxia inducible factor 1a
92
WT1
Tumor suppressor urogenital development transcription factor wilms tumor
93
Aflatoxin
Carcinogen stored grains and nuts hepatocellular carcinoma
94
Alkylating agents
Carcinogen chemo leukemia/ lymphoma
95
Aromatic amines
Carcinogen textile, cigarette transition cell carcinoma in bladder
96
Arsenic
Carcinogen herbicides, metal smelting angiosarcoma in liver, lung cancer, SCC in skin
97
Asbestos
Carcinogen old roofing, shipyard bronchogenic carcinoma > mesothelioma
98
Cigarette
Carcinogen Transitional cell carcinoma in bladder, SCC in cervix, esophagus, larynx, lung, RCC, oropharyngeal cancer, pancreatic adenocarcinoma
99
Ethanol
Carcinogen | SCC esophagus, hepatocellular carcinoma
100
Ionizing radiation
Carcinogen | papillary thyroid carcinoma, leukemia
101
Nickel, chromium, beryllium, silica
Carcinogen occupational lung cancer
102
Nitrosamines
Carcinogen smoked foods gastric cancer
103
Radon
Carcinogen basement lung cancer
104
Vinyl chloride
Carcinogen PVC angiosarcoma in liver
105
EBV cancer
Burkitt, hodgkin, nasopharyngeal carcinoma, primary CNS lymphoma
106
HBV, HCV cancer
Hepatocellular
107
HHV8 cancer
kaposi
108
HPV cancer
cervical, penile/anal, head and neck
109
H. pylori cancer
gastric adenocarcinoma and MALT lymphoma
110
Liver fluke cancer
cholangiocarcinoma
111
Schistosoma cancer
SCC bladder
112
ALK phos in cancer
metastases to bone or liver, Paget disease of bone, seminoma
113
AFP in cancer
Hepatocellular carcinoma, endodermal sinus tumor, mixed germ cell tumor, ataxia telangiectasia, neural tube defect
114
hCG in cancer
Hydatidiform moles and choriocarcinoma, testicular cancer, mixed germ cell tumor
115
CA 15-3/ 27-29 in cancer
breast
116
CA 19-9
pancreatic adenocarcinoma
117
CA 125
ovarian cancer
118
Calcitonin in cancer
medullary thyroid carcinoma, MEN 2A and 2B
119
CEA in cancer
colorectal and pancreatic
120
chromogranin in cancer
neuroendocrine tumors
121
LDH in cancer
testicular germ cell tumors, ovarian dysgerminoma
122
Neuron specific enolase in cancer
neuroendocrine tumor
123
PSA
prostate cancer
124
Chromogranin and synaptophysin stain
neuroendocrine cells | small cell lung carcinoma, carcinoid tumor
125
Cytokeratin statin
epithelial cells | SCC
126
Desmin stain
muscle | rhabdomyosarcomas
127
GFAP stain
neuroglia | astrocytoma, glioblastoma
128
Neurofilament stain
neurons | neuronal tumors
129
PSA stain
prostatic epithelium | prostate cancer
130
S100 stain
NCC | melanoma, schwannoma, langerhans histiocytosis
131
TRAP stain
hairy cell leukemia
132
Vimentin stain
mesenchymal tissue
133
p- glycoprotein
MDR1 adrenocortical carcinoma pump out toxins aka chemo
134
Psammoma bodies
laminated concentric spherules with dystrophic calcifications papillary carcinoma of thyroid somastostatinoma meningioma malignant mesothelioma ovarian serous papillary cystadenocarcinoma prolactinoma
135
Cachexia
weight loss, muscle atrophy and fatigue that occur in chronic disease via TNFa, IFNy, IL1, IL6
136
Dermatomyositis
progressive proximal muscle weakness, Gottron papules, heliotrope rash adenocarcinomas (ovarian)
137
Acanthosis nigricans
Hyperpigmented velvet plaque in axilla dn neck | gastric adenocarcinoma
138
Sign of Leser Trelat
sudden onset of multiple seborrheic keratoses | GI adenocarcinoma
139
Hypertrophic osteoarthropathy
Abnormal proliferation of skin and bone at distal extremities --> clubbing, arthralgia, joint effusion, periostosis adenocarcinoma of lung
140
Hypercalcemia
PTHrP- SCC of lung head and neck, renal bladder, breast and ovarian carcinoma increase calcitriol- lymphoma
141
Cushing
increase ACTH | small cell lung
142
SIADH
increase ADH | small cell lung
143
Polycythemia
increase EPO | pheochromocytoma, RCC, HPP, hemangioblastoma, leiomyoma
144
Pure red cell aplasia
anemia with low reticulocytes | thymoma
145
Good syndrome
Hypogammaglobulinemia | Thymoma
146
Trousseau syndrome
migratory superficial thrombophlebitis | Thymoma
147
Nonbacterial thrombotic endocarditis
deposition of sterile platelet thrombi on heart valves | adenocarcinoma
148
Anti NMDA encephalitis
psych disturbance, memory deficit, seizures, dyskinesias, autonomic instability, language dysfunction ovarian teratoma
149
Opsoclonus myoclonus ataxia syndrome
dancing eyes, dancing feet | neuroblastoma, small cell lung
150
paraneoplastic cerebellar degeneration
Ab against Ag in Purkinje cells | small cell lung (anti-Hu), gynecologic and breast (anti- Yo), Hodgkin (anti- Tr)
151
Paraneoplastic encephalomyelitis
Ab against Hu Ag in neurons | small cell lung
152
Lambert Eaton Myasthenia
Ab against presynaptic Ca2+ channels at NMJ | small cell lung
153
Myasthenia gravis
Ab against postsynaptic AChR at NMJ | thymoma

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