Usmle Step 1: Pathology

Front 1

Apoptosis

Back 1

- Programmed cell death; ATP required. Mediated by caspases.
- Characterized by cell shrinkage, chromatin condensation (pyknosis), membrane blebbing, DNA fragmentation (karyorrhexis), nuclear fragmentation (karyolysis), and formation of apoptotic bodies, which are then phagocytosed. No significant inflammation.

- Occurs during embryogenesis, hormone induction (menstruation), immune cell–mediated death, injurious stimuli (e.g., radiation, hypoxia), atrophy (e.g.,endometrial lining during menopause).

Front 2

Necrosis

Back 2

- Enzymatic degradation of a cell resulting from exogenous injury.
- Characterized by enzymatic digestion and protein denaturation, with release of intracellular components.
- Inflammatory.
- Morphologically occurs as coagulative (heart, liver, kidney), liquefactive (brain), caseous (tuberculosis), fat (pancreas), fibrinoid (blood vessels), or gangrenous (limbs, GI tract).

Front 3

Inflamation

Back 3

- Characterized by rubor (redness), dolor (pain), calor (heat), tumor (swelling), and functio laesa (loss of function).

- Fluid exudation: ↑ vascular permeability, vasodilation, endothelial injury.
- Leukocyte activation: Emigration (rolling, tight binding, diapedesis); chemotaxis (bacterial products, complement, chemokines); phagocytosis and killing.
- Fibrosis: Fibroblast emigration and proliferation; deposition of ECM.

- Acute: Neutrophil, eosinophil, and antibody mediated.
- Chronic: Mononuclear cell mediated - characterized by persistent destruction/repair, granuloma (nodular collections of epitheloid macrophages and giant cells)

Front 4

Transudate vs Exudate

Back 4

Transudate
- hypocellular, protein poor, specific gravity < 1.012
- due to increased hydrostatic pressure, increased oncotic pressure, Na retention

Exudate
- cellular, protein rich, specific gravity > 1.020
- due to lymphatic obstruction and inflammation

Front 5

Leukocyte extravasation

Back 5

1. Rolling––mediated by E-selectin and P-selectin on vascular endothelium binding to sialyl LewisX on the leukocyte
2. Tight binding––mediated by ICAM-1 on vascular endothelium binding to LFA-1 (Integrin) on the leukocyte
3. Diapedesis––leukocyte travels between endothelial cells and exits blood vessel
4. Migration––leukocyte travels through the interstitium to the site of injury or infection guided by chemotactic signals (e.g., cytokines)

Front 6

Free radical injury

Back 6

- Initiated via radiation exposure, metabolism of drugs (phase I), redox reaction, nitric oxide, transition metals, leukocyte oxidative burst.

- Induces cell injury through membrane lipid peroxidation, protein modification, DNA breakage.

- Free radical degradation produced through enzymes (catalase, superoxide dismutase, glutathione peroxidase), spontaneous decay, antioxidants (vitamins E and A).

- Reperfusion after anoxia induces free radical production (e.g., superoxide) and is a major cause of injury after thrombolytic therapy.

Front 7

Neoplastic progression

Back 7

1. normal
2. hyperplasia (increased cell number) and dysplasia (loss of size, shape and orientation specificity)
3. in situ carcinoma: neoplastic cells have failed to breach the basement membrane; high nuclear cytoplasmic ratio
4. Cells invade basement membrane using collagenases/hydrolases
5. Metastasis: spread to distant organ(s)

Front 8

hyperplasia

Back 8

increase in number of cells.

reversible

Front 9

metaplasia

Back 9

1 adult cell type is replaced by another. often secondary to irritation and/or environmental exposure (e.g., squamous metaplasia in trachea and bronchi of smokers).

reversible

Front 10

dysplasia

Back 10

abnormal growth with loss of cellular orientation, shape and size in comparison to normal tissue maturation

reversible

Front 11

anaplasia

Back 11

abnormal cells lacking differentiation;like primative cells of the same tissue, often equated with undifferentiated malignant neoplasms

irreversible

Front 12

neoplasia

Back 12

a clonal proliferation of cells that is uncontrolled and excessive

irreversible

Front 13

desmoplasia

Back 13

fibrous tissue formation in response to neoplasm

irreversible

Front 14

Tumor grade vs. stage

Back 14

- Grade: degree of cellular differentiation based on histologic appearance. Usually graded I-IV based on degree of differentiation and number of mitoses per high-power field; character of tumor itself

- Stage: degree of localization/spread based on site and size of primary lesion, spread to regional lymph nodes, presense of metastases; spread of tumor in a specific patient

- stage usually has more prognostic value than grade

- TNM staging system
- T = size of Tumor
- N = Node involvement
- M = Metastases

Front 15

Benign vs. Malignant

Back 15

- Benign: usually well differentiated, slow growing, well demarcated, no metastasis

- Malignant: may be poorly differentiated, erratic growth, locally invasive/diffuse, may metastisize

Front 16

Oncogenic Viruses

Back 16

- HTLV-1: adult T-cell leukemia
- HBV, HCV: hepatocellular carcinoma
- EBV: Burkitt's lymphoma, nasopharyngeal carcinoma
- HPV: cervical carcinoma, penile/anal carcinoma
- HHV-8: Kaposi's sarcoma, body cavity fluid B-cell lymphoma

Front 17

Chemical carcinogens

Back 17

Aflatoxins - Liver (hepatocellular carcinoma)
Vinyl chloride - Liver (angiosarcoma)
CCl4 - Liver (centrilobular necrosis, fatty change)
Nitrosamines (e.g., in smoked foods) - Esophagus, stomach
Cigarette smoke - Larynx, lung, renal cell carcinoma, transitional cell carcinoma
Asbestos - Lung (mesothelioma and bronchogenic carcinoma)
Arsenic - Skin (squamous cell carcinoma)
Naphthalene (aniline) dyes - Bladder (transitional cell carcinoma)
Alkylating agents - Blood (leukemia),

Front 18

Paraneoplastic effects of tumors

Back 18

- Small cell lung carcinoma: ACTH or ACTH-like peptide (Cushing’s syndrome)
- Small cell lung carcinoma and intracranial neoplasms: ADH (SIADH)
- Squamous cell lung carcinoma, renal cell carcinoma, and breast carcinoma: PTH-related peptide, TGF-β, TNF, IL-1 (Hypercalcemia)
- Renal cell carcinoma, hemangioblastoma: Erythropoietin (Polycythemia)
- Thymoma, small cell lung carcinoma: Antibodies against presynaptic Ca2+ channels at neuromuscular junction (Lambert-Eaton syndrome - muscle weakness)
- Leukemias and lymphomas: Hyperuricemia due to excess nucleic acid turnover (i.e., cytotoxic therapy) Gout, urate nephropathy

Front 19

Psammoma bodies

Back 19

Laminated, concentric, calcific spherules seen in
- papillary adenocarcinoma of thyroid
- serous papillary cystadenocarcinoma of ovary
- meningioma
- malignant mesothelioma

- PSaMMoma: papillary (thyroid), serous (ovary), miningioma, mesothelioma

Front 20

Metastasis to brain

Back 20

- Primary tumors that metastasize to brain: lung, breast, skin, kidney, GI

- Lots of Bad Stuff Kills Glia

Front 21

Metastasis to liver

Back 21

- Primary tumors that metastisize to liver: colon > stomach > pancreas > breast > lung

- Cancer Sometimes Penetrates Benign Liver