USMLE STEP 1 Pathology Flashcards
Acute phase reactants
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)
Acute radiation syndrome
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
Acute vs chronic inflammatory mediators
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
Amyloidosis
abnormal aggregation of proteins into B-pleated linear sheets —> insoluble fibrils —> cellular damage and apoptosis
Atrophy
Decrease in tissue mass due to decrease in size and/or number of cells
Cancer incidence and mortality
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
Carcinoma vs sarcoma
Carcinoma: implies endothelial origin
Sarcoma: mesenchymal origin (connective tissue, blood vessels, lymphatic tissues)
Common types of amyloidosis
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
Dysplasia
Disordered, precancerous epithelial cell growth; loss of uniformity of cell size and shape (pleomorphism), loss of tissue orientation, nuclear changes
ESR
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
Free radical injury
Damage cells via membrane lipid peroxidation, protein modification, DNA breakage
Granulomatous inflammation
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
Hamartoma vs Chortistoma
Terms for non-neoplastic malformaions
Hamartoma: disorganized overgrowth of tissues in native location
Choristoma: normal tissue in a foreign location
Hypertrophy vs Hyperplasia
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
Immune evasion of cancer
- 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
Metaplasia
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)
Necrosis
Exogenous injury –> plasma membrane damage —> cell undergoes enzymatic degradation and protein denaturation, intracellular components leak —> local inflammatory reaction
Neoplasia
uncontrolled, monoclonal proliferation of cells; can be benign or malignant.
Two components: parenchyma (neoplastic cells) and supporting storm (blood vessels, connective tissue)
Neoplastic progression
- Dysplasia: loss of uniformity in cell size and shape (pleomorphism), loss of orientation, nuclear changes
- Carcinoma in situ/preinvasive: irreversible dysplasia of entire thickness of epithelium
- Invasive carcinoma: invade basement membrane using collagenases and hydrolyses, cell-cell contacts lost by inactivation of E-cadhirin
- Metastasis: spread to distant organ(s) via lymphatics or blood
Reversible vs irreversible cell damage
Reversible: decrease in ATP and activity —> cell swelling —> decreased protein synthesis
Irreversible: breakdown of plasma membrane —> enzymes leak —>activation of degradative enzymes —> nuclear degradation
Scar formation
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)
Tumor grade vs stage
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)
Warburg Effect
Shift of glucose metabolism away from mitochondrial oxidative phosphorylation toward glycolysis
Which cells are most susceptible to radiation therapy
Stem cells of rapidly regenerating tissues:
Skin, bone marrow, GI tract, gonads
are the most susceptible to radiation injury
