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Pathology Flashcards

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1
Q

Apoptosis findings

A
  • Cell shrinkage
  • Chromatin condensation
  • Membrane blebbing
  • Formation of apoptotic bodies (which are then phagocytosed)
  • Eosinophilic cytoplasm
  • Basophilic nucleus
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2
Q

Sensitive indicator of apoptosis

A

DNA laddering (fragments in multiples of 180 bp)

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3
Q

Occurs when a regulating factor is withdrawn from a proliferating cell population

A

Intrinsic (mitochondrial) apoptotic pathway

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4
Q

BAK

A

Pro-apoptotic

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5
Q

What makes bcl-2 anti-apoptotic

A

Bcl-2 prevent cytochrome c release by binding to and inhibiting APAF-1. APAF-1 normally binds to cytochrome c and induces activation of caspase 9, inhibiting caspase cascade.

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6
Q

Extrinsic (death receptor) apoptotic pathway

A

2 pathways:

  • Ligand receptor interactions (FasL binding to Fas [CD95] or TNF-α binding to TNF)
  • Immune cell (cytotoxic T-cell release of perforin and granzyme B)

Fas-FasL interaction is necessary in thymic medullary negative selection. Mutations in Fas ↑ numbers of circulating self reacting lymphocytes due to failure of clonal deletion.

Defective Fas-FasL interactions cause AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME

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7
Q

Autoimmune lymphoproliferative syndrome caused by

A

Defective Fas-FasL interactions (form of extrinsic apoptotic pathway)

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8
Q

Compare coagulative and liquefactive necrosis

A

Coagulative → proteins denature then enzymatic degradation

Liquefactive → enzymatic degradation first then proteins denature

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9
Q

Compare wet and dry gangrenous necrosis

A

Dry → ischemia; coagulative necrosis

Wet → superinfection; liquefactive superimposed on coagulative

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10
Q

Ischemia of kidney

A
  • Straight segment of proximal tubule (medulla)

- Thick ascending limb (medulla)

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11
Q

Cellular injury reversible with O2

A
  • Cellular/ mitochondrial swelling (↓ ATP → ↓ activity of Na+/K+ pumps)
  • Nuclear chromatin clumping
  • Membrane blebbing
  • ↓ glycogen
  • Fatty change
  • Ribosomal/ polysomal detachment (↓ protein synthesis)
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12
Q

Irreversible cellular injury

A
  • Mitochondrial permeability/ vacuolization; phospholipid-containing amorphous densities within mitochondria (swelling alone is reversible)
  • Nuclear pyknosis (condensation), karyorrhexia (fragmentation), karyolysis (fading)
  • Plasma membrane damage (degradation of membrane phospholipid)
  • Lysosomal rupture
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13
Q

Contains multiple blood supplies

A
  • Liver
  • Lung
  • Intestine
  • Testes
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14
Q

Solid organs with single (end-arterial) blood supply

A
  • Heart
  • Kidney
  • Spleen
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15
Q

Functio laesa

A
  • Loss on function

- Characterization of inflammation

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16
Q

Chronic inflammation

A
  • Mononuclear (monocyte/macrophage, lymphocytes, plasma cells) and fibroblast mediated
  • Characterized by persistent destruction and repair
  • Associated with blood vessel proliferation, fibrosis
  • Granuloma: nodular collections of epithelioid macrophages and giant cells
  • Outcomes include scarring and amyloidosis
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17
Q

Chromatolysis

A

Reaction of neuronal cell body to axonal injury. Changes reflect ↑ protein synthesis in effort to repair damaged axon. Characterized by:

  • Round cellular swelling
  • Displacement of the nucleus to the periphery
  • Dispersion of Nissl substance through cytoplasm

Concurrent with Wallerian degeneration → degeneration of axon distal to site of injury; macrophages remove debris and myelin

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18
Q

Dystrophic calcification

A
  • Ca2+ deposition in abnormal tissues secondary to injury or necrosis
  • Seen in TB (lungs and pericardium), liquefactive necrosis of chronic abscesses, fat necrosis, infarcts, thrombi, schistosomiasis, Monckeberg arteriolosclerosis, congenital CMV + toxoplasmosis, psammoma bodies
  • Normocalcemic
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19
Q

Metastatic calcification

A
  • Widespread (ie diffuse, metastatic) deposition of Ca2+ in normal tissue secondary to hypercalcemia or high calcium-phosphate product levels
  • Ca2+ deposits predominantly in interstitial tissues of kidney, lung, and gastric mucosa (these tissues lose acid quickly; ↑ pH favors deposition)
  • NOT normocalcemic
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20
Q

Step 1 Extravasation: Margination and rolling

A
  • Defective in leukocyte adhesion deficiency type 2 (↓ Sialyl-Lewis-x)

Vascular/stroma: Leukocyte

  • E-selectin: Sialyl-Lewis-x
  • P-selectin: Sialyl-Lewis-x
  • GlyCAM-1, CD34: L-selectin
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21
Q

Step 2 Extravasation: Tight-binding

A
  • Defective in leukocyte adhesion deficiency type 1 (↓ CD18 integrin subunit)

Vascular/stroma: Leukocyte

  • ICAM-1 (CD54): CD11/18 integrins (LFA-1, Mac-1)
  • VCAM-1 (CD106): VLA-4 integrin
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22
Q

Step 3 Extravasation: Diapedesis

A
  • WBC travels between endothelial cells and exits blood vessel

Vascular/stroma: Leukocyte
- PECAM-1 (CD31): PECAM-1 (CD31)

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23
Q

Step 4 Extravasation: Migration

A

Chemotactic products released in response to bacteria:

  • C5a
  • IL-8
  • LTB4
  • Kallikrein
  • Platelet-activating factor
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24
Q

Inhalation injury and sequelae

A
  • Pulmonary complication associated with smoke and fire

- Caused by heat, particulates (

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25
Tensile strength after scar formation
70-80% of tensile strength regained at 3 months, little additional tensile strength will be regained afterward
26
Compare collagen organization of hypertrophic and keloid scars
Hypertrophic → parallel organization | Keloid → disorganized
27
PDGF
- Secreted by activated platelets and macrophages - Induces vascular remodeling and smooth muscle migration - Stimulates fibroblast growth for collagen synthesis
28
FGF
Stimulates angiogenesis
29
EGF
Stimulates cell growth via tyrosine kinases (eg EGFR, ErbB1)
30
TGF-β
- Angiogenesis - Fibrosis - Cell cycle arrest
31
Metalloproteinases
Tissue remodeling
32
VEGF
Stimulates angiogenesis
33
Inflammatory stage of wound healing
- Up to 3 days after wound - Effector cells → platelets, neutrophils, macrophages - Clot formation - ↑ vessel permeability and neutrophil migration into tissue - Macrophages clear debris 2 days later
34
Proliferative stage of wound healing
- Day 3 - weeks after wound - Effector cells → fibroblasts, myofibroblasts, endothelial cells, keratinocytes, macrophages - Deposition of granulation tissue and type III collagen - Angiogenesis - Epithelial cell proliferation - Dissolution of clot - Wound contraction (mediated by myofibroblasts)
35
Remodeling stage of wound healing
- 1 week - 6+ months after wound - Effector cells → fibroblasts - Type III collagen replaced by type I collagen - ↑ tensile strength of tissue
36
Bacterial infections that cause granuloma formation
- Mycoplasma - Bartonella henselae - Listeria monocytogenes - Treponema pallidum
37
Parasitic infections that cause granuloma formation
Schistosomiasis
38
Fungal infections that cause granuloma formation
Endemic mycoses
39
Granuloma formation
- TH1 cells secrete IFN-gamma, activating macrophages | - TNF-alpha from macrophages induces and maintains granuloma formation
40
Compare causes of exudate and transudate accumulation
Exudate → lymphatic obstruction (chylous), inflammation/infection, malignancy Transudate → ↑ hydrostatic pressure (eg HF, Na+ retention), ↓ oncotic pressure (eg cirrhosis, nephrotic syndrome)
41
How does ESR work
Products of inflammation (eg fibrinogen) coat RBCs and cause aggregation. The denser RBCs aggregate and fall at a faster rate within a pipetic tube. Often co-tested with CRP levles.
42
↑ ESR
- Most anemias - Infections - Inflammation (eg giant cell arteritis, polymyalgia rheumatica) - Cancer (eg metastases, multiple myeloma) - Renal disease (end-stage or nephrotic syndrome) - Pregnancy
43
↓ ESR
- Sickle cell anemia (altered shape) - Polycythemia (↑ RBCs "dilute" aggregation factors) - HF - Microcytosis - Hypofibrinogenemia
44
AL (primary) amyloidosis
- Due to deposition of proteins from Ig Light chains - Can occur as a plasma cell disorder or associated with multiple myeloma - Often affects multiple organ systems, including renal (nephrotic syndrome), cardiac (restrictive cardiomyopathy, arrhythmia), hematologic (easy bruising, splenomegaly), GI (hepatomegaly) and neurologic (neuropathy)
45
AA (secondary) amyloidosis
- Seen with chronic inflammatory conditions such as rheumatoid arthritis, IBD, spondyloarthropathy, familial Mediterranean fever, protracted infection - Fibrils composed of serum Amyloid A - Often multisystem like AL amyloidosis
46
Dialysis-related amyloidosis
- Fibrils composed of β2-microglobulin in patients with ESRD and/or on long-term dialysis - MAY PRESENT AS CARPAL TUNNEL SYNDROME
47
Heritable amyloidosis
Heterogeneous group of disorders, including familial amyloid polyneuropathies due to transthyretin gene mutation
48
Age-related (senile) amyloidosis
- Due to deposition of normal (wild-type) transthyretin (TTR) predominantly in cardiac ventricles - Slower progression of cardiac dysfunction relative to AL amyloidosis
49
Organ specific amyoidosis
- Amyoid deposition localized to a single organ - Most important form is amyloidosis in Alzhemier disease due to deposition of beta-amyloid protein cleaved from APP - TIIDM → islet amyloid polypeptide (IAPP) → amylin in pancreatic islets - Normal aging → atrial amyloidosis → atrial natriuretic peptide
50
Lipofuscin
- A yellow-brown "wear and tear" pigment associated with normal aging - Formed by oxidation and polymerization of autophagocytosed organellar membranes - Autopsy of elderly person will reveal deposits in heart, colon, liver, kidney, eye and other organs
51
Compare grade and stage
Grade → degree of cellular differentiation and mitotic activity on histology Stage → degree of localization/spread based on site and size of primary lesion, spread to regional lymph nodes, presence of metastases; TNM, where M is often most important
52
Compare hamartoma and choristoma
Hamartoma → disorganized overgrowth of tissues in their native location) Choristoma → normal tissue in a foreign location
53
Paraneoplastic hypercalcemia
PTHrP → squamous cell carcinomas of lung, head and neck; renal, bladder, breast and ovarian carcinomas ↑ 1,25-(OH)2 vitamin D3 (calcitriol) → lymphoma
54
Paraneoplastic polycythemia
↑ EPO → renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma, pheochromocytoma, leiomyoma
55
Paraneoplastic pure red cell aplasia
Anemia with LOW reticulocytes → thymoma
56
Good syndrome
Paraneoplastic hypogammaglobulinemia → thymoma
57
Trosseau syndrome
Migratory superficial thrombophlebitis → adenocarcinomas, especially pancreatic
58
Paraneoplastic nonbacterial thrombotic (marantic) endocarditis
Deposition of sterile platelet thrombi on heart valves → adenocarcinomas, especially pancreatic
59
Anti-NMDA receptor encephalitits
Psychiatric disturbance, memory deficits, seizures, dyskinesias, autonomic instability, language dysfunction → ovarian teratoma
60
Opsoclonus-myoclonus ataxia syndrome
"Dancing eyes, dancing feet" → neuroblastoma (children), small cell lung cancer (adults)
61
Paraneoplastic cerebellar degeneration
Antibodies against Hu, Yo, Tr antigens in Purkinje cells → Small cell lung cancer, gynecologic and breast cancers, and Hodgkin lymphoma
62
Paraneoplasic encephalitis
Antibodies against Hu antigens in neurons → small cell lung cancer
63
ALK
- Oncogene - Receptor tyrosine kinase - Lung adenocarcinoma
64
BCR-ABL
- Oncogene - Tyrosine kinase - CML, ALL
65
BCL-2
- Oncogene - Anti-apoptotic molecule - Follicular and diffuse large B cell lymphoma
66
BRAF
- Oncogene - Serine/threonine kinase - Melanoma, non-Hodgkin lymphoma
67
c-KIT
- Oncogene - Cytokine receptor - Gastrointestinal stromal tumor (GIST)
68
c-MYC
- Oncogene - Transcription factor - Burkitt lymphoma
69
HER2/neu (c-erbB2)
- Oncogene - Tyrosine kinase - Breast and gastric carcinomas
70
JAK2
- Oncogene - Tyrosine kinase - Chronic myeloproliferative disorders
71
KRAS
- Oncogene - GTPase - Colon cancer, lung cancer, pancreatic cancer
72
MYCL1
- Oncogene - Transcription factor - Lung tumor
73
MYCN
- Oncogene - Transcription factor - Neuroblastoma
74
RET
- Oncogene - Tyrosine kinase - MEN 2A and 2B, medullary thyroid cancer
75
APC
- Tumor suppressor gene | - Colorectal cancer (associated with FAP)
76
BRCA1/BRCA2
- Tumor suppressor gene - Breast and ovarian cancer - DNA repair protein
77
CDKN2A
- Tumor suppressor gene - Melanoma, pancreatic cancer - p16, blocks G1 → S phase
78
DCC
- Tumor suppressor gene - Colon cancer - DCC → deleted in colon cancer
79
DPC4/SMAD4
- Tumor suppressor gene - Pancreatic cancer - DPC → deleted in pancreatic cancer
80
MEN1
- Tumor suppressor gene - MEN1 - Menin
81
NF1
- Tumor suppressor gene - NF1 - Ras GTPase activating protein (neurofibromin)
82
NF2
- Tumor suppressor gene - NF2 - Merlin (schwannomin) protein
83
PTEN
- Tumor suppressor gene | - Breast cancer, prostate cancer, endometrial cancer
84
Rb
- Tumor suppressor gene | - Retinoblastoma, osteosarcoma
85
TP53
- Tumor suppressor gene - Most human cancers, Li-Fraumeni syndrome - p53, activates p21, blocks G1 → S phase
86
TSC1
- Tumor suppressor gene - Tuberous sclerosis - Hamartin protein
87
TSC2
- Tumor suppressor gene - Tuberous sclerosis - Tuberin protein
88
VHL
- Tumor suppressor gene - von Hippel-Lindau disease, renal cell carcinoma - Inhibits hypoxia inducible factor 1a
89
WT1/WT2
- Tumor suppressor gene | - Wilms tumor (nephroblastoma)
90
2nd leading cause of lung cancer after cigarette smoke
Radon
91
Alkaline phosphatase
- Metastases to bone or liver - Paget disease of bone - Seminoma (placental ALP)
92
AFP
- Hepatocellular caricnoma - Hepatoblastoma - Yolk sac (endodermal sinus) tumor - Mixed germ cell tumor Normally made by fetus. Transiently elevated in pregnancy. High levels associated with neural tube and abdominal wall defects, low levels associated with Down syndrome.
93
hCG
- Hydatiform mole - Choriocarcinoma - Testicular cancer - Mixed germ cell tumor Produced by synciotrophoblasts of the plascenta
94
CA 15-3/ CA 27-29
Breast cancer
95
CA 19-9
Pancreatic adenocarcinoma
96
CA 125
Ovarian cancer
97
Calcitonin
Medullary thyroid carcinoma
98
CEA
CarcinoEmbryonic Antigen Very nonspecific but produced by around 70% of colorectal and pancreatic cancers. Also produced by gastric, breast and medullary thyroid carcinomas.
99
PSA
- Prostate specific antigen - Prostate cancer Can also be elevated in BPH and prostatitis. Questionable risk/benefit for screening.
100
P-glycoprotein
- Multidrug resistance protein 1 (MDR1) - Classically seen in adrenal cell carcinoma but also expressed by other cancer cells (eg colon, liver) - Used to pump out toxins, including chemotherapeutic agents (one mechanism of ↓ responsiveness or resistance to chemotherapy over time)
101
Cachexia
Weight loss, muscle atrophy, and fatigue that occur in chronic disease (eg cancer, AIDS, heart failure, COPD) Mediated by TNF, INF-gamma, IL-1, IL-6
102
Sarcomas generally spread
Hematogenously
103
Carcinomas generally spread
Lymphatically
104
Carcinomas that spread hematogenously
- Renal cell carcinoma - Choriocarcinoma - Hepatocellular carcinoma - Follicular thyroid carcinoma
105
Site of metastases → brain
Lung > breast > prostate > melanoma > GI
106
Site of metastases → liver
Colon >> stomach > pancreas
107
Site of metastases → bone
Prostate, breast > lung, thyroid, kidney ``` Breast → mixed Lung → mixed Thyroid → lytic Kidney → lytic Prostate → blastic ``` Predilection for axial skeleton
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