USMLE STEP 1 Pathology

Question 1

Acute phase reactants

Answer 1

Increase in response to inflammation:

C-reactive protein (opsonin, facilitated phagocytosis)
Ferritin (sequesters iron)
Fibrinogen (coagulation factor, promotes endothelial repair)
Haptoglobin (binds extracell Hb, protects oxidative stress)
Hepcidin (decreases iron absorption and release **anemia of chronic disease)
Procalcitonin (only increases in bacterial infections)
Serum amyloid A
Negative (down regulated):
Albumin (conserve GAs for positive reactants)
Transferrin (internalized by macrophages to sequester Fe)
Transthyretin (pre-albumin)

Question 2

Acute radiation syndrome

Answer 2

develops after sudden whole-body exposure to high doses of ionizing radiation; nausea, vomiting, diarrhea, hair loss, erythema, cytopenias (decrease in blood cells), headache, altered mental status

Question 3

Acute vs chronic inflammatory mediators

Answer 3

Acute: early response neutrophils, macrophages predominate late stages of acute (2-3 days) and secrete cytokines

Chronic: mononuclear infiltration (macrophages, lymphocytes, plasma cells) —> tissue destruction and repair

Question 4

Amyloidosis

Answer 4

abnormal aggregation of proteins into B-pleated linear sheets —> insoluble fibrils —> cellular damage and apoptosis

Question 5

Atrophy

Answer 5

Decrease in tissue mass due to decrease in size and/or number of cells

Question 6

Cancer incidence and mortality

Answer 6

MALES (I;M)
1. Prostate; Lung
2. Lung; prostate
3. Colon/rectum;colon/rectum

FEMALES (I;M)
1. Breast; lung
2. Lung; breast
3. Colon/rectum;colon/rectum

CHILDREN
1. Leukemia; leukemia
2. CNS;CNS
3. Neuroblastoma/ neuroblastoma

Question 7

Carcinoma vs sarcoma

Answer 7

Carcinoma: implies endothelial origin

Sarcoma: mesenchymal origin (connective tissue, blood vessels, lymphatic tissues)

Question 8

Common types of amyloidosis

Answer 8

Primary: AL (IgG light chains); seen in plasma cell disorders (ex. Multiple myeloma)

Secondary: serum amyloid A (AA); seen in chronic inflammatory conditions

Dialysis-related amyloidosis: B2-microglobulin; seen in end stage renal failure (ESRF) or on long term dialysis

Question 9

Dysplasia

Answer 9

Disordered, precancerous epithelial cell growth; loss of uniformity of cell size and shape (pleomorphism), loss of tissue orientation, nuclear changes

Question 10

ESR

Answer 10

Erythrocyte sedimentation rate: inflammation products coat RBCs —> decrease (-) charge —> increase RBC aggregation —> increase ESR

Increased ESR:
- Most anemias
- Infections
- Inflammation
- Cancer
- Renal disease
- Pregnancy

Decreased ESR:
- Sickle cell anemia
- Polycythemia (more RBCs dilute aggregation factors)
- HF
- Microcytosis
- Hypofibrinogenemia

Question 11

Free radical injury

Answer 11

Damage cells via membrane lipid peroxidation, protein modification, DNA breakage

Question 12

Granulomatous inflammation

Answer 12

A pattern of chronic inflammation; wall off a resistant stimulus without completely eradicating/degrading it —> persistent inflammation —> fibrosis, organ damage

Bacterial :Thanks buddy., leprosy, cat scratch disease
Fungus: endemic plasmosis
Parasitic: schistosomiasis
Immune: sarcoidosis, Crohn’s
Vasculitis

Question 13

Hamartoma vs Chortistoma

Answer 13

Terms for non-neoplastic malformaions

Hamartoma: disorganized overgrowth of tissues in native location
Choristoma: normal tissue in a foreign location

Question 14

Hypertrophy vs Hyperplasia

Answer 14

Hypertrophy: increase in cell size due to increase in structural proteins and organelles

Hyperplasia: increase in number of cells due to controlled proliferation of stem cells and differentiated cells; excessive stimulation leads to pathologic hyperplasia

Question 15

Immune evasion of cancer

Answer 15

• Decreased MHC I expression on tumor cells –> cytotoxic Ts unable to recognize
• Secrete immunosuppressive factors (TGF-B) and recruit regulatory T cells to down regulate immune response
• Up regulate immune checkpoint molecules to inhibit immune response

Question 16

Metaplasia

Answer 16

reprogramming of stem cells leading to the replacement of one cell type by another that can adapt to a new stress

Usually due to an irritant (gastric acid —> Barrett esophagus, tobacco smoke —> ciliated columnar ep cells to stratified squamous epithelium)

Question 17

Necrosis

Answer 17

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

Question 18

Neoplasia

Answer 18

uncontrolled, monoclonal proliferation of cells; can be benign or malignant.
Two components: parenchyma (neoplastic cells) and supporting storm (blood vessels, connective tissue)

Question 19

Neoplastic progression

Answer 19

1. Dysplasia: loss of uniformity in cell size and shape (pleomorphism), loss of orientation, nuclear changes
2. Carcinoma in situ/preinvasive: irreversible dysplasia of entire thickness of epithelium
3. Invasive carcinoma: invade basement membrane using collagenases and hydrolyses, cell-cell contacts lost by inactivation of E-cadhirin
4. Metastasis: spread to distant organ(s) via lymphatics or blood

Question 20

Reversible vs irreversible cell damage

Answer 20

Reversible: decrease in ATP and activity —> cell swelling —> decreased protein synthesis

Irreversible: breakdown of plasma membrane —> enzymes leak —>activation of degradative enzymes —> nuclear degradation

Question 21

Scar formation

Answer 21

Excess TGF-B associated with aberrant scarring, such as hypertrophic and keloid scars

Hypertrophic scar: increased type III collagen in parallel; confined to borders of original wound

Keloid scar: types I and III collagen disorganized; extends beyond borders of original wound with “claw-like” projections (increased incidents in people with darker skin)

Question 22

Tumor grade vs stage

Answer 22

GRADE
Degree of cell differentiation (tissue of origin resemblance) and mitotic activity on histology; higher grade often correlates with higher aggressiveness

STAGE
Degree of invasion and spread from initial site
TMN —> M > N > T —> primary Tutor size/invasion, regional lymph Node metastasis, distant Metastasis
Stage usually more prognostic value than grade (Stage determines Survival)

Question 23

Warburg Effect

Answer 23

Shift of glucose metabolism away from mitochondrial oxidative phosphorylation toward glycolysis

Question 24

Which cells are most susceptible to radiation therapy

Answer 24

Stem cells of rapidly regenerating tissues:
Skin, bone marrow, GI tract, gonads
are the most susceptible to radiation injury