General Principles of Foundational Science
Cell and tissue biology
Mitochondria perform oxidative phosphorylation and release cytochrome c during apoptosis; rough ER synthesizes protein; smooth ER handles detoxification and steroid synthesis; the Golgi modifies and sorts; lysosomes contain acid hydrolases; the proteasome degrades ubiquitin-tagged proteins. Apoptosis shows cell shrinkage, blebbing, and no inflammation and is caspase-dependent; necrosis shows swelling and inflammation. Reversible injury causes swelling and fatty change; irreversible injury causes membrane rupture and mitochondrial failure.
Inflammation and repair
Histamine from mast cells causes vasodilation and increased permeability; prostaglandins mediate pain and fever (blocked by NSAIDs); leukotrienes cause bronchoconstriction and chemotaxis. Neutrophils arrive first (6–24 hours), macrophages later. Chronic inflammation features lymphocytes, plasma cells, and fibrosis. Healing occurs by primary or secondary intention depending on tissue loss.
Immunology
IgG crosses the placenta and dominates the secondary response; IgM appears first and is the best agglutinin; IgA protects secretions; IgE mediates allergy and parasite defense. MHC I on all nucleated cells presents to CD8 T cells; MHC II on antigen-presenting cells presents to CD4 T cells. Hypersensitivity: type I IgE (anaphylaxis), type II antibody-mediated (autoimmune hemolysis, Goodpasture), type III immune complex (SLE, post-streptococcal glomerulonephritis), type IV delayed (tuberculin test, contact dermatitis). SCID affects both arms; DiGeorge affects T cells with hypocalcemia; Bruton affects B cells.
Pharmacology and genetics
First-order elimination removes a constant fraction per unit time; zero-order elimination (phenytoin, ethanol, high-dose aspirin) removes a constant amount and saturates. Volume of distribution = dose ÷ plasma concentration. Potency reflects EC50; efficacy reflects maximal effect. Expect questions on autosomal dominant and recessive, X-linked, mitochondrial (maternal), imprinting (Prader-Willi, Angelman), and trinucleotide repeat disorders.
Rule of thumb
If a drug's half-life lengthens as the dose increases, suspect saturable zero-order kinetics and titrate cautiously.