Medicine & Anatomy

Medical Milestones & Discoveries

• Germ theory — Louis Pasteur’s swan-neck flask experiments (1859-1861) disproved spontaneous generation; he and Robert Koch established that specific microorganisms cause specific diseases.
• Koch’s postulates (1884) — four criteria to establish a microbe as the cause of a disease: isolate organism from diseased host; grow it in pure culture; reproduce disease in healthy host; re-isolate same organism.
• Vaccination / Edward Jenner (1796) — Jenner inoculated James Phipps with cowpox (Vaccinia) to protect against smallpox; the word “vaccine” derives from vacca (Latin: cow).
• Smallpox eradication (1980) — WHO declared global eradication after a 13-year campaign; the last natural case occurred in Somalia in 1977; Ali Maow Maalin was the final patient.
• Ether anesthesia / William Morton (1846) — Morton publicly demonstrated diethyl ether for surgical anesthesia at Massachusetts General Hospital on October 16, 1846 (“Ether Day”); Crawford Long had used ether privately in 1842 but did not publish.
• Antiseptic surgery / Joseph Lister (1867) — applied Pasteur’s germ theory; used carbolic acid (phenol) spray in the operating theatre, dramatically cutting post-operative mortality.
• Handwashing / Semmelweis — Ignaz Semmelweis showed in 1847 that chlorinated lime handwashing by physicians cut puerperal fever deaths in Vienna maternity wards from ~10% to ~1%; rejected by colleagues during his lifetime.
• X-ray discovery / Wilhelm Röntgen (1895) — discovered X-rays on November 8, 1895 while experimenting with cathode ray tubes; his wife’s hand was one of the first medical radiographs; awarded the first Nobel Prize in Physics (1901).
• Insulin isolation / Banting & Best (1921) — Frederick Banting and Charles Best (working in J.J.R. Macleod’s lab at the University of Toronto) extracted insulin from dog pancreas; first human patient (Leonard Thompson) treated January 1922; Banting and Macleod shared Nobel 1923.
• Penicillin / Fleming, Florey & Chain — Alexander Fleming noticed in 1928 that Penicillium notatum mold lysed Staphylococci on a contaminated plate; Howard Florey and Ernst Chain purified and tested penicillin clinically in 1940-1941; all three shared Nobel 1945.
• DNA double helix (1953) — James Watson and Francis Crick proposed the double-helix model of DNA in Nature (April 25, 1953); Rosalind Franklin’s X-ray diffraction image (Photo 51, taken by Raymond Gosling) was critical data; Maurice Wilkins shared Nobel 1962 with Watson and Crick (Franklin had died in 1958).
• Polio vaccine — Jonas Salk’s inactivated poliovirus vaccine (IPV) declared safe and effective in 1955; Albert Sabin developed the oral live-attenuated vaccine (OPV) used in mass immunization campaigns from the 1960s.
• First heart transplant / Christiaan Barnard (1967) — Barnard performed the first human-to-human heart transplant on December 3, 1967 at Groote Schuur Hospital, Cape Town; patient Louis Washkansky survived 18 days.
• In vitro fertilization (IVF, 1978) — Robert Edwards (embryologist) and Patrick Steptoe (gynecologist) achieved the first successful IVF birth: Louise Brown, born July 25, 1978 in Oldham, England; Edwards won Nobel 2010.
• HeLa cell line / Henrietta Lacks — first immortal human cell line, derived in 1951 from the cervical cancer of Henrietta Lacks (a Black patient at Johns Hopkins) without her knowledge or consent; cultured by George Gey; used in developing the polio vaccine and countless subsequent studies.
• Human Genome Project (HGP) — international consortium sequenced the human genome (completed draft 2000, finished 2003); ~3 billion base pairs; ~20,000-25,000 protein-coding genes; competitor Celera Genomics (Craig Venter) ran a parallel private effort.
• Monoclonal antibodies / Köhler & Milstein (1975) — Georges Köhler and César Milstein developed hybridoma technology to produce antibodies of a single specificity; Nobel 1984 (shared with Niels Jerne); now the largest drug class by revenue.
• Immune-checkpoint inhibitors — James Allison (CTLA-4 blockade, anti-CTLA-4 = ipilimumab) and Tasuku Honjo (PD-1 blockade, anti-PD-1 = pembrolizumab/nivolumab) established cancer immunotherapy via checkpoint release; Nobel 2018.
• CAR-T cell therapy — Chimeric Antigen Receptor T-cell therapy; patient’s own T cells engineered to express a receptor targeting a tumor antigen (e.g., CD19 for B-cell leukemia); tisagenlecleucel (Kymriah) was first FDA-approved CAR-T (2017).
• mRNA vaccines — Katalin Karikó and Drew Weissman showed that substituting pseudouridine for uridine in mRNA prevents innate immune activation (published 2005); this modification enabled the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 vaccines; Karikó and Weissman shared Nobel 2023.
• Broad Street pump / John Snow (1854) — Snow mapped cholera cases in London’s Soho and traced the outbreak to a contaminated water pump on Broad Street; removal of the pump handle ended the outbreak; founding act of modern epidemiology. (Vibrio cholerae was not identified until Koch, 1883.)
• 1918 influenza pandemic (“Spanish flu”) — caused by an H1N1 influenza A virus; killed an estimated 50-100 million people worldwide (more than World War I); unusually lethal in young adults (W-shaped mortality curve); re-constructed from Alaskan permafrost samples in the 2000s.
• HIV/AIDS — Human immunodeficiency virus identified independently ~1983 by Françoise Barré-Sinoussi and Luc Montagnier (Institut Pasteur, Nobel 2008); AIDS epidemic declared by CDC in 1981; HIV targets CD4+ T cells; AIDS defined by CD4 count <200 cells/µL or AIDS-defining illness; antiretroviral therapy (ART) transformed HIV from a death sentence to a manageable chronic illness.
• Epidemiologic transition — concept by Abdel Omran (1971): societies shift from infectious/famine mortality (pre-modern) to chronic non-communicable disease mortality as they develop.

Named Anatomical Structures

• Circle of Willis — arterial anastomosis at the base of the brain connecting the anterior and posterior cerebral circulations; components include the internal carotid arteries, anterior/middle/posterior cerebral arteries, and anterior/posterior communicating arteries; named for Thomas Willis (1664).
• Islets of Langerhans — clusters of endocrine cells in the pancreas; described by Paul Langerhans in 1869; contain alpha cells (glucagon), beta cells (insulin), delta cells (somatostatin), and PP cells.
• Loop of Henle — hairpin-shaped segment of the renal tubule (descending and ascending limbs) that creates the medullary osmotic gradient enabling urine concentration; named for Friedrich Gustav Jakob Henle.
• Nodes of Ranvier — gaps in the myelin sheath along myelinated axons where the axon membrane is exposed; saltatory conduction jumps from node to node, increasing speed; named for Louis-Antoine Ranvier.
• Bundle of His — specialized cardiac conduction tissue in the interventricular septum that carries the electrical impulse from the AV node to the Purkinje fibers and ventricles; named for Wilhelm His Jr.
• Organ of Corti — sensory epithelium within the cochlea of the inner ear; contains hair cells (inner and outer) that convert sound vibrations to neural signals; named for Alfonso Giacomo Gaspare Corti.
• Glomerulus — tuft of capillaries within Bowman’s capsule in the nephron; site of blood filtration under hydrostatic pressure; glomerulonephritis is inflammation of this structure.
• Sinoatrial (SA) node — the heart’s primary pacemaker, located in the right atrium near the superior vena cava junction; generates ~60-100 impulses per minute; also called the “sinus node.”
• Broca’s area — region in the posterior left inferior frontal gyrus essential for speech production; identified by Paul Broca in 1861 using the patient “Tan” (Louis Victor Leborgne) who could understand speech but not produce it.
• Wernicke’s area — posterior left superior temporal gyrus; essential for language comprehension; lesions cause fluent but nonsensical speech (Wernicke’s aphasia); identified by Carl Wernicke (1874).
• Hypothalamus — small region of the diencephalon forming the floor of the third ventricle; the master regulator of homeostasis (body temperature, hunger, thirst, circadian rhythm, emotion); links the nervous and endocrine systems by controlling the pituitary gland below it (connected via the infundibulum/pituitary stalk). Releasing/inhibiting hormones (e.g., GnRH, TRH, CRH, dopamine) reach the anterior pituitary through the hypophyseal portal system; the posterior pituitary stores hypothalamic ADH and oxytocin. Named nuclei: the suprachiasmatic nucleus (above the optic chiasm, the body’s master circadian clock, receiving direct retinal input and showing CLOCK-BMAL1 dimerization), the arcuate nucleus, and the supraoptic/paraventricular nuclei. The mammillary bodies and fornix are associated with it; lateral/posterior regions produce orexins (deficiency causes narcolepsy); damage can cause diabetes insipidus.

Cancer Biology

• Hallmarks of Cancer — framework by Douglas Hanahan and Robert Weinberg (Cell, 2000; updated 2011): sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion/metastasis; later additions include evading immune destruction and reprogramming energy metabolism.
• Oncogenes — mutated proto-oncogenes that drive cell proliferation; act in a dominant, gain-of-function manner; examples: RAS (most commonly mutated oncogene), MYC, HER2/ERBB2, BCR-ABL (Philadelphia chromosome in CML, targeted by imatinib/Gleevec).
• Tumor suppressor genes — loss-of-function mutations (both alleles typically needed: Knudson “two-hit hypothesis”); key examples: TP53 (most commonly mutated gene in cancer, “guardian of the genome”), RB1 (retinoblastoma), BRCA1/BRCA2 (breast/ovarian cancer risk).
• p53 protein — encoded by TP53; transcription factor that responds to DNA damage by arresting the cell cycle or triggering apoptosis; mutated in ~50% of all human cancers; Li-Fraumeni syndrome caused by germline TP53 mutation.
• Philadelphia chromosome — translocation t(9;22) creating the BCR-ABL fusion oncogene; found in >95% of CML cases; imatinib (Gleevec) was the first rationally designed kinase inhibitor targeting it.
• Warburg effect — cancer cells preferentially use aerobic glycolysis (producing lactate even in oxygen’s presence) rather than oxidative phosphorylation; described by Otto Warburg (~1924); exploited by FDG-PET imaging.

Genetic and Metabolic Disorders

• Cystic fibrosis — autosomal recessive; caused by mutations in the CFTR gene (chloride channel); most common lethal genetic disease in people of European descent; most common mutation is ΔF508; causes thick mucus in lungs, pancreas, GI tract; treated with CFTR modulators (ivacaftor, lumacaftor/tezacaftor/elexacaftor).
• Sickle cell disease — autosomal recessive; point mutation (Glu6Val) in the beta-globin gene (HBB); sickle-shaped RBCs cause vaso-occlusive crises, hemolytic anemia, organ damage; sickle trait confers partial malaria protection (heterozygous advantage).
• Huntington’s disease — autosomal dominant; CAG trinucleotide repeat expansion in the HTT gene on chromosome 4; progressive neurodegeneration affecting the striatum (caudate and putamen); onset typically in middle age; anticipation (repeat length increases in generations).
• Down syndrome (Trisomy 21) — most common chromosomal aneuploidy compatible with life; three copies of chromosome 21 (usually nondisjunction in meiosis); features include intellectual disability, characteristic facies, congenital heart defects, increased Alzheimer’s risk.
• Hemophilia A — X-linked recessive; deficiency of clotting factor VIII; characterized by prolonged bleeding after injury; treated with factor VIII replacement or emicizumab. Hemophilia B (Christmas disease) involves factor IX deficiency.
• PKU (phenylketonuria) — autosomal recessive; deficiency of phenylalanine hydroxylase (PAH); accumulation of phenylalanine causes intellectual disability if untreated; detected by newborn screening (Guthrie test); managed by low-phenylalanine diet.
• Marfan syndrome — autosomal dominant; mutation in FBN1 (fibrillin-1); affects connective tissue; tall stature, arachnodactyly, aortic root dilatation (risk of dissection), lens dislocation; Abraham Lincoln possibly affected.

Neurology & Psychiatry

• Concussion — a mild traumatic brain injury (TBI) caused by a biomechanical force to the head; results in a brief alteration of brain function (confusion, amnesia, headache, dizziness, light sensitivity) without necessarily involving loss of consciousness; neuropathologically involves diffuse axonal stretching and neurometabolic disruption rather than gross structural injury (thus CT/MRI are often normal); diagnosed clinically; repeated concussions are associated with chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease with tau pathology identified in contact-sport athletes and military veterans; managed with cognitive and physical rest followed by gradual return-to-play protocol.
• Macular degeneration — the leading cause of severe central vision loss in adults over 50 in developed countries; the macula is the central region of the retina responsible for high-acuity vision; dry (atrophic) AMD accounts for ~85–90% of cases and involves gradual accumulation of drusen and retinal pigment epithelium atrophy; wet (neovascular) AMD involves abnormal choroidal neovascularization causing rapid central vision loss and is treated with anti-VEGF injections (ranibizumab, bevacizumab, aflibercept); risk factors include age, smoking, genetics (CFH and ARMS2 gene variants), and UV exposure; affects central but not peripheral vision.
• Muscular dystrophy — a group of inherited genetic disorders characterized by progressive skeletal muscle weakness and degeneration; Duchenne muscular dystrophy (DMD) is the most common and severe form: X-linked recessive, caused by mutations in the DMD gene encoding dystrophin (largest known gene, on Xp21); presents in early childhood with proximal muscle weakness, Gowers’ sign (using hands to push up from the floor), calf pseudohypertrophy, and elevated creatine kinase; leads to wheelchair dependence and cardiorespiratory failure; Becker MD has milder dystrophin mutations; myotonic dystrophy (most common adult form) is autosomal dominant with CTG repeat expansion in DMPK.
• Obesity — defined by the World Health Organization as a BMI ≥30 kg/m²; results from a chronic positive energy balance; associated with type 2 diabetes, cardiovascular disease, hypertension, obstructive sleep apnea, nonalcoholic fatty liver disease (NAFLD/NASH), osteoarthritis, and multiple cancers; adipokines (leptin, adiponectin) link adipose tissue to metabolic regulation; GLP-1 receptor agonists (semaglutide, tirzepatide) have emerged as highly effective pharmacological treatments; bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) produces sustained weight loss and metabolic remission; worldwide prevalence has tripled since 1975.
• Alzheimer’s disease — most common dementia; hallmarks are extracellular amyloid-beta plaques and intracellular neurofibrillary tangles (hyperphosphorylated tau); APOE ε4 allele is the major genetic risk factor; early-onset familial forms involve APP, PSEN1, PSEN2 mutations.
• Parkinson’s disease — loss of dopaminergic neurons in the substantia nigra pars compacta; Lewy bodies (aggregated alpha-synuclein) are the pathological hallmark; cardinal features: resting tremor, rigidity, bradykinesia, postural instability; treated with levodopa/carbidopa.
• Multiple sclerosis (MS) — autoimmune demyelination of CNS axons; lesions (plaques) in white matter; most common disabling neurological disease in young adults in Western countries; relapsing-remitting is the most common form.
• Prion diseases — caused by misfolded PrP (prion protein); examples: Creutzfeldt-Jakob disease (CJD, humans), bovine spongiform encephalopathy (BSE/”mad cow disease”), scrapie (sheep), kuru (transmitted via ritual cannibalism); Stanley Prusiner proposed the prion hypothesis and won Nobel 1997.
• Epilepsy — recurrent, unprovoked seizures; classified as focal or generalized; generalized tonic-clonic seizures (formerly “grand mal”) involve whole-brain onset; absence seizures (formerly “petit mal”) show 3-Hz spike-and-wave on EEG; treated with antiepileptic drugs (e.g., phenytoin, valproate, levetiracetam).

Autoimmune & Inflammatory Diseases

• Systemic lupus erythematosus (SLE) — multisystem autoimmune disease; hallmark: antinuclear antibodies (ANA), especially anti-double-stranded DNA (anti-dsDNA); “butterfly” malar rash; affects kidneys (lupus nephritis), joints, skin, CNS; predominantly affects women of childbearing age.
• Rheumatoid arthritis (RA) — chronic autoimmune synovitis; symmetric small joint involvement; rheumatoid factor (RF) and anti-CCP antibodies are markers; treated with DMARDs (methotrexate) and biologics (anti-TNF agents like adalimumab).

Cardiovascular System

• Heart — four-chambered muscular organ; two atria (receiving) and two ventricles (pumping). The left ventricle pumps oxygenated blood into the aorta (systemic circulation); the right ventricle pumps deoxygenated blood to the lungs (pulmonary circulation).
• Cardiac cycle — systole (contraction/ejection) and diastole (relaxation/filling). A typical resting heart rate is 60-100 beats per minute.
• Conducting system — sinoatrial (SA) node sets the pace; signal passes through the atrioventricular (AV) node, Bundle of His, and Purkinje fibers.
• Blood vessels — arteries carry blood away from the heart; veins carry blood toward it; capillaries enable exchange of gases and nutrients with tissues.
• Blood pressure — expressed as systolic/diastolic (e.g., 120/80 mmHg); measured by sphygmomanometer.
• Coronary arteries — supply the heart muscle itself; left anterior descending (LAD), left circumflex, and right coronary artery.
• Major diseases — coronary artery disease (atherosclerotic plaque narrowing coronaries); myocardial infarction (heart attack, from blocked coronary flow); heart failure (inadequate cardiac output); atrial fibrillation (irregular atrial rhythm, stroke risk).

Blood composition

• Red blood cells (erythrocytes) — carry oxygen via hemoglobin; produced in red bone marrow; lack a nucleus at maturity; lifespan ~120 days.
• White blood cells (leukocytes) — immune function; types include neutrophils (most common, bacterial defense), lymphocytes (adaptive immunity), monocytes, eosinophils, basophils.
• Platelets (thrombocytes) — cell fragments essential for clotting (hemostasis).
• Plasma — liquid component (~55% of blood); water, proteins (albumin, globulins, fibrinogen), electrolytes, glucose.
• ABO blood groups — Karl Landsteiner (~1901); four groups (A, B, AB, O) based on surface antigens; AB = universal recipient for red cells; O = universal donor for red cells. The Rh factor is a separate antigen; Rh-negative individuals can develop antibodies against Rh-positive blood.

Respiratory System

• Airways — nasal cavity → pharynx → larynx → trachea → bronchi → bronchioles → alveoli.
• Alveoli — microscopic air sacs (~300 million in adults) where gas exchange occurs; surrounded by capillaries; walls one cell thick.
• Lungs — right lung has three lobes; left has two (to accommodate the heart).
• Diaphragm — dome-shaped muscle; contracts and flattens to increase thoracic volume, driving inspiration.
• Gas exchange — oxygen diffuses from alveolar air into blood; CO2 diffuses from blood into alveolar air and is exhaled.
• Spirometry terms — tidal volume (normal breath ~0.5 L); vital capacity (max exhale after max inhale); FEV1 (forced expiratory volume in 1 second); used to classify obstructive vs restrictive disease.
• Major diseases — asthma (reversible bronchospasm, inflammation); COPD (chronic obstructive pulmonary disease, largely due to smoking); pneumonia (lung infection, bacterial/viral/fungal); tuberculosis (Mycobacterium tuberculosis, spreads by airborne droplets).

Nervous System

• Central nervous system (CNS) — brain and spinal cord.
• Peripheral nervous system (PNS) — all nerves outside the CNS; divided into somatic (voluntary motor/sensory) and autonomic (involuntary: sympathetic “fight-or-flight” and parasympathetic “rest-and-digest”).
• Neuron — basic unit; cell body (soma), dendrites (input), axon (output). Signal is the action potential — a rapid reversal of membrane potential driven by sodium/potassium ion flow.
• Synapse — junction between neurons; most are chemical (neurotransmitter release); key neurotransmitters include acetylcholine, dopamine, serotonin, norepinephrine, GABA, glutamate.
• Brain regions — cerebral cortex (higher cognition); frontal lobe (executive function, motor); parietal lobe (sensory integration, spatial); temporal lobe (hearing, language, memory); occipital lobe (vision); cerebellum (motor coordination); brainstem (midbrain, pons, medulla — vital functions: breathing, heart rate); hypothalamus (homeostasis; links nervous and endocrine systems via the pituitary); hippocampus (memory consolidation); amygdala (emotion, fear).
• Cranial nerves — 12 pairs; include optic (II), oculomotor (III), trigeminal (V), facial (VII), vestibulocochlear (VIII), vagus (X).
• Major diseases — stroke (ischemic or hemorrhagic; time-sensitive treatment); Parkinson’s disease (dopamine neuron loss in substantia nigra); Alzheimer’s disease (amyloid plaques and tau tangles; most common dementia); multiple sclerosis (demyelination of CNS axons); epilepsy (recurrent seizures).

Digestive System

• Tract sequence — mouth → esophagus → stomach → small intestine (duodenum, jejunum, ileum) → large intestine (colon) → rectum → anus.
• Stomach — secretes HCl (pH ~2) and pepsinogen; begins protein digestion.
• Small intestine — primary site of digestion and nutrient absorption; ~6 m long; surface area vastly amplified by villi and microvilli.
• Large intestine — absorbs water and electrolytes; hosts gut microbiome; produces some vitamins (e.g., K2).
• Liver — produces bile (fat emulsification), processes absorbed nutrients, detoxifies, synthesizes clotting factors and plasma proteins.
• Pancreas — exocrine: digestive enzymes (amylase, lipase, proteases) secreted into duodenum; endocrine: islets of Langerhans secrete insulin (beta cells) and glucagon (alpha cells).
• Helicobacter pylori — bacterial cause of most peptic ulcers; discovered by Barry Marshall and Robin Warren (Nobel 2005); Marshall famously self-infected to demonstrate causation.
• Major diseases — Crohn’s disease and ulcerative colitis (inflammatory bowel diseases); celiac disease (gluten-triggered autoimmune damage to small intestinal villi); hepatitis (liver inflammation, viral types A/B/C/D/E).

Endocrine System

Gland	Key hormones	Main function
Pituitary (anterior)	GH, TSH, ACTH, FSH, LH, prolactin	“Master gland”; controls other endocrine glands
Pituitary (posterior)	ADH (vasopressin), oxytocin	Water retention; uterine contraction/bonding
Thyroid	T3, T4	Metabolic rate regulation
Parathyroid	PTH	Raises blood calcium
Adrenal cortex	Cortisol, aldosterone, androgens	Stress response; salt/water balance
Adrenal medulla	Epinephrine, norepinephrine	Fight-or-flight
Pancreas (islets)	Insulin, glucagon	Blood glucose regulation
Gonads	Estrogen, progesterone, testosterone	Reproduction and secondary sex characteristics
Pineal	Melatonin	Circadian rhythm

• Diabetes mellitus — type 1: autoimmune destruction of beta cells, requires insulin; type 2: insulin resistance, initially managed with lifestyle and oral agents.
• Hypothyroidism — low thyroid hormone; symptoms include fatigue, weight gain, cold intolerance. Hashimoto’s thyroiditis is the most common autoimmune cause.

Musculoskeletal System

• Skeleton — adult has 206 bones; axial (skull, vertebral column, ribcage) and appendicular (limbs and girdles). Bones serve support, protection, movement, hematopoiesis, and mineral storage.
• Muscle types — skeletal (striated, voluntary); cardiac (striated, involuntary, intercalated discs); smooth (involuntary, walls of organs/vessels).
• Sarcomere — functional unit of skeletal muscle; sliding filament model: myosin heads pull actin toward the center, shortening the fiber.
• Joints — fibrous (immovable, e.g., skull sutures), cartilaginous (slightly movable, e.g., intervertebral discs), synovial (freely movable, fluid-filled, e.g., knee, hip).
• Major bones — femur (longest/strongest); patella (largest sesamoid); ossicles of the ear (malleus, incus, stapes — smallest bones).
• Major diseases — osteoporosis (reduced bone density, fracture risk); rheumatoid arthritis (autoimmune synovial inflammation); osteoarthritis (joint cartilage wear); gout (urate crystal deposition, often in the first metatarsophalangeal joint).

Immune System

• Innate immunity — rapid, non-specific; includes skin barrier, neutrophils, macrophages, natural killer (NK) cells, complement system, and inflammatory cytokines.
• Adaptive immunity — specific and has memory; mediated by lymphocytes. B cells produce antibodies (humoral); T cells include CD4+ helper T cells (coordinate response) and CD8+ cytotoxic T cells (kill infected cells).
• Antibodies (immunoglobulins) — IgM (primary response), IgG (most abundant, secondary response, crosses placenta), IgA (mucosal secretions), IgE (allergic response), IgD.
• MHC (major histocompatibility complex) — cell-surface proteins presenting peptide antigens; MHC class I on all nucleated cells (recognized by CD8+ T cells); class II on antigen-presenting cells (recognized by CD4+ T cells). Called HLA in humans.
• Vaccines — stimulate adaptive immunity without disease; types include live-attenuated, inactivated, subunit, toxoid, and mRNA (COVID-19 vaccines from Moderna/Pfizer-BioNTech).
• Autoimmune diseases — immune system attacks self; examples: rheumatoid arthritis, lupus (SLE), type 1 diabetes, multiple sclerosis.

Renal and Urinary System

• Kidneys — paired, retroperitoneal; filter ~180 L of plasma per day; produce ~1.5 L urine. Functions: excrete nitrogenous waste, regulate fluid/electrolyte balance, regulate blood pressure (via renin-angiotensin-aldosterone system), produce erythropoietin (stimulates RBC production).
• Nephron — functional unit; ~1 million per kidney. Sequence: glomerulus → Bowman’s capsule → proximal convoluted tubule → loop of Henle → distal convoluted tubule → collecting duct.
• GFR — glomerular filtration rate; key measure of kidney function; normal ~90-120 mL/min.
• Urinary tract — urine passes from kidneys via ureters to the bladder; excreted via urethra.
• Major diseases — chronic kidney disease (progressive loss of GFR); nephrolithiasis (kidney stones, often calcium oxalate); urinary tract infections (UTIs; most commonly E. coli in women).

Anatomy

• Gallbladder — a small pear-shaped organ on the underside of the liver that stores and concentrates bile produced by the liver; releases bile into the duodenum via the common bile duct to aid fat digestion; bile is concentrated ~5–10-fold by absorption of water and electrolytes; cholecystitis is inflammation of the gallbladder, often caused by a gallstone (cholelithiasis) obstructing the cystic duct; surgical removal (cholecystectomy) is one of the most common abdominal operations.
• Glenohumeral joint — the ball-and-socket synovial joint between the head of the humerus and the glenoid cavity of the scapula; the most mobile joint in the body and the most commonly dislocated; stability provided primarily by the rotator cuff muscles (supraspinatus, infraspinatus, teres minor, subscapularis — “SITS”) and the glenoid labrum rather than bony congruence; subject to dislocations (usually anterior), impingement, and rotator cuff tears.
• Micturition — the act of urination; urine stored in the bladder is expelled via the urethra; controlled by the micturition reflex: bladder filling stretches the detrusor muscle, triggering parasympathetic contraction and relaxation of the internal urethral sphincter; the external sphincter is under voluntary somatic control; disrupted in spinal cord injury, multiple sclerosis, and benign prostatic hyperplasia.

Vitamins & Key Biomolecules

• Collagen — the most abundant protein in mammals and the main structural protein of connective tissue (skin, bone, tendon, cartilage, scar tissue); synthesized by fibroblasts (and osteoblasts in bone, as osteoid). Its triple helix (sometimes called the “Madras helix”) is built from three left-handed polypeptide chains coiled into a right-handed superhelix with a repeating Gly-X-Y sequence; the unusual amino acids hydroxyproline and hydroxylysine stabilize it. Hydroxylation of proline and lysine requires vitamin C, so its deficiency causes scurvy (defective collagen). Stained blue by Masson’s trichrome. There are many types: defects in types I and III cause Ehlers-Danlos syndrome; defective type I causes osteogenesis imperfecta (brittle bone disease); type IV (basement membrane) is implicated in Alport syndrome and Goodpasture syndrome. The marine sponge equivalent is spongin; collagen is widely used in cosmetic surgery and, when denatured, becomes gelatin.
• Vitamin C (ascorbic acid) — water-soluble vitamin; deficiency causes scurvy (bleeding gums, poor wound healing). Required as a cofactor for the hydroxylation of proline and lysine in collagen synthesis, and also for synthesizing norepinephrine and carnitine. Found in citrus fruits and other fresh produce; James Lind demonstrated in 1747 that citrus prevented scurvy in sailors; isolated/characterized by Albert Szent-Györgyi (Nobel 1937). Most animals synthesize it via L-gulonolactone oxidase, but humans, other primates, and guinea pigs cannot. Linus Pauling promoted megadoses.
• Vitamin D — fat-soluble vitamin (technically a prohormone); deficiency causes rickets in children and osteomalacia in adults. Forms include ergocalciferol (D2) and cholecalciferol (D3); synthesized in skin upon UV (sunlight) exposure, then activated by hydroxylation in the liver and kidney (to calcitriol). Promotes intestinal absorption of calcium and phosphate for bone mineralization. Found in fortified dairy, fatty fish, and mushrooms.
• Vitamin A (retinol) — fat-soluble, isoprenoid vitamin essential for vision; its derivative retinal is the chromophore of rhodopsin in the retina, so deficiency causes night blindness and xerophthalmia (with Bitot’s spots). Obtained as retinol from animal sources and as carotenoid precursors (beta-carotene) from carrots and other plants. Retinoic acid acts through nuclear receptors (RAR/RXR) to regulate gene transcription and development; all-trans retinoic acid (ATRA) is used to treat acute promyelocytic leukemia (with the t(15;17) translocation).
• Vitamin K — fat-soluble vitamin essential for blood clotting; required for the gamma-carboxylation of glutamate residues (forming the calcium-binding Gla domain) in clotting factors II (prothrombin), VII, IX, X and proteins C and S. Forms include phylloquinone (K1), found in leafy green vegetables, and menaquinone (K2), made by gut bacteria. Warfarin is an anticoagulant that works by inhibiting vitamin K epoxide reductase. Discovered by Henrik Dam (“K” for the Danish/German Koagulation), who shared the Nobel Prize.

Key Pathogens

Bacteria

• Staphylococcus aureus — gram-positive; causes skin infections, pneumonia, bacteremia; MRSA is methicillin-resistant.
• Streptococcus pyogenes (Group A Strep) — causes strep throat, scarlet fever, rheumatic fever, necrotizing fasciitis.
• Mycobacterium tuberculosis — tuberculosis; slow-growing, acid-fast; infects ~1/4 of the world’s population latently.
• Clostridium — gram-positive anaerobes; C. tetani (tetanus), C. botulinum (botulism), C. difficile (colitis after antibiotic disruption of gut flora).
• Yersinia pestis — bubonic plague (“Black Death”); transmitted by fleas; killed roughly 1/3 of Europe’s population in the 14th century.

• Treponema pallidum — syphilis; spirochete; progresses through primary (chancre), secondary (rash), and tertiary (gummas, cardiovascular/neurological) stages.

• Neisseria gonorrhoeae — gram-negative diplococcus; causes gonorrhea, one of the most common bacterial sexually transmitted infections; infects urogenital mucosa, throat, and conjunctiva; can cause pelvic inflammatory disease (PID) and disseminated gonococcal infection; rising antibiotic resistance is a major public health concern; treated with ceftriaxone.

Viruses

• Epstein-Barr virus (EBV) — a herpesvirus (human herpesvirus 4, HHV-4) that infects B lymphocytes and epithelial cells; transmitted via saliva; causes infectious mononucleosis (“mono” or “kissing disease”) with fever, sore throat, and lymphadenopathy; establishes lifelong latent infection in B cells; strongly associated with Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease; >90% of adults worldwide are seropositive; diagnosed by the monospot test (heterophile antibodies) and EBV-specific antibodies.
• Herpes simplex virus (HSV) — two closely related alphaherpesviruses: HSV-1 (typically oral herpes, causing cold sores/fever blisters on the lips; also a leading cause of herpes encephalitis) and HSV-2 (primarily genital herpes); both establish lifelong latent infection in sensory ganglia (trigeminal ganglion for HSV-1, sacral ganglia for HSV-2) and reactivate under stress, UV exposure, or immunosuppression; transmitted by direct mucosal contact; treated with nucleoside analogs (acyclovir, valacyclovir); HSV encephalitis targets the temporal lobes; neonatal herpes acquired during childbirth can be life-threatening.
• Measles — caused by the measles morbillivirus (genus Morbillivirus, family Paramyxoviridae); highly contagious airborne RNA virus (R₀ ~12–18, the highest of any known pathogen); presents with fever, cough, coryza, conjunctivitis, Koplik spots (pathognomonic white spots on buccal mucosa), and a maculopapular rash spreading cephalocaudally; can cause pneumonia, encephalitis, and subacute sclerosing panencephalitis (SSPE, years later); MMR vaccine is ~97% effective; responsible for ~100,000+ deaths annually in unvaccinated populations; measles infection causes transient immune amnesia (depleting pre-existing antibody memory).
• Influenza — RNA virus; antigenic drift (gradual mutations) and antigenic shift (reassortment of segments, can cause pandemics). The 1918 “Spanish flu” killed an estimated 50-100 million people.
• SARS-CoV-2 — coronavirus causing COVID-19 (pandemic declared March 2020); targets ACE2 receptors; mRNA vaccines developed within ~1 year.
• HIV — retrovirus; reverse transcriptase copies RNA genome into DNA for integration; identified ~1983 independently by Françoise Barré-Sinoussi and Luc Montagnier (Nobel 2008).
• Hepatitis B and C — blood-borne viruses causing chronic liver disease and hepatocellular carcinoma; HBV has an effective vaccine; HCV now curable with direct-acting antivirals.
• Variola (smallpox) — officially eradicated in 1980 (WHO declaration); the only human disease fully eradicated by vaccination. Last natural case in 1977.
• Ebola — filovirus; hemorrhagic fever; high case-fatality rate in outbreaks; rVSV-ZEBOV vaccine approved 2019.

History of Medicine

• Rudolf Virchow (1821–1902) — German pathologist and polymath; “Father of modern pathology”; established that disease arises at the cellular level (Cellularpathologie, 1858), articulating the principle that all cells come from pre-existing cells (“omnis cellula e cellula”); coined the terms “thrombosis,” “embolism,” “leukemia,” and “amyloid”; described Virchow’s triad (three factors predisposing to venous thrombosis: blood stasis, hypercoagulability, and endothelial injury); also a pioneering anthropologist and liberal political figure who opposed Bismarck.
• Hippocrates (~460-370 BCE) — ancient Greek physician; “Father of Medicine”; emphasized observation and prognosis over supernatural causes; the Hippocratic Corpus and the Hippocratic Oath bear his name.
• Galen (129-~216 CE) — Greek-Roman physician; systematic anatomy and physiology texts dominated European medicine for ~1,300 years despite numerous errors.
• Andreas Vesalius (1514-1564) — Flemish anatomist; De humani corporis fabrica (1543) revolutionized anatomy via human cadaver dissection, correcting many Galenic errors.
• William Harvey (1578-1657) — described the circulation of blood (De motu cordis, 1628); demonstrated that the heart pumps blood in a circuit.
• Edward Jenner (1749-1823) — demonstrated in 1796 that cowpox inoculation protected against smallpox; laid the foundation for vaccination (term from vacca, Latin for cow).
• Ignaz Semmelweis (1818-1865) — showed handwashing reduced puerperal (childbed) fever in Vienna; his findings were largely rejected during his lifetime.
• Louis Pasteur (1822-1895) — germ theory of fermentation and disease; swan-neck flask experiments disproved spontaneous generation; developed vaccines for anthrax and rabies.
• Robert Koch (1843-1910) — isolated the tuberculosis bacillus (1882) and cholera bacillus (1883); formulated Koch’s postulates to establish microbial causation of disease. Nobel 1905.
• Joseph Lister (1827-1912) — antiseptic surgery using carbolic acid (phenol), dramatically reducing post-operative infections; inspired by Pasteur’s germ theory.
• Wilhelm Röntgen (1845-1923) — discovered X-rays in 1895; first Nobel Prize in Physics (1901). X-rays were almost immediately applied in medicine.
• Alexander Fleming (1881-1955) — observed in 1928 that Penicillium mold inhibited Staphylococcus; this led to the development of penicillin. Howard Florey and Ernst Chain developed clinical penicillin; all three shared the Nobel Prize in Physiology or Medicine (1945).
• Frederick Banting and Charles Best — isolated insulin in 1921; first patient treated for type 1 diabetes in 1922. Banting and J.J.R. Macleod shared Nobel 1923.
• Jonas Salk — developed the first effective inactivated polio vaccine (1955); Albert Sabin developed the oral live-attenuated version.

Medical Imaging and Diagnostics

• X-ray (radiograph) — uses ionizing radiation; best for dense structures (bone, lungs); discovered by Röntgen (1895).
• CT (computed tomography) — multiple X-ray projections reconstructed into cross-sectional images; introduced clinically in the 1970s (Hounsfield and Cormack, Nobel 1979).
• MRI (magnetic resonance imaging) — uses strong magnetic fields and radiofrequency pulses to image soft tissues; no ionizing radiation. Peter Mansfield and Paul Lauterbur shared Nobel 2003.
• Ultrasound — sound waves (~2-18 MHz); real-time imaging; no radiation; widely used in obstetrics, cardiology (echocardiography), and abdomen.
• PET scan — positron emission tomography; uses radiotracer (commonly FDG); detects metabolic activity; useful in oncology and neurology.
• Electrocardiogram (ECG/EKG) — records cardiac electrical activity; PQRST wave sequence; diagnoses arrhythmias, MI, etc. Developed by Willem Einthoven (Nobel 1924).
• Endoscopy — fiber-optic or video camera to visualize GI tract, airway, joints (arthroscopy), etc.
• Blood tests — CBC (complete blood count), metabolic panels, lipid panels, troponin (cardiac injury), HbA1c (glycated hemoglobin, diabetes monitoring).

Pharmacology Basics

• Pharmacokinetics (PK) — what the body does to the drug: absorption, distribution, metabolism, excretion (ADME). Half-life (t½): time for plasma concentration to fall by 50%.
• Pharmacodynamics (PD) — what the drug does to the body; dose-response relationships, receptor binding (agonist vs. antagonist).
• Antibiotics — classes include penicillins/cephalosporins/carbapenems (beta-lactams, inhibit cell-wall synthesis), aminoglycosides (30S ribosome), macrolides/tetracyclines (protein synthesis), fluoroquinolones (DNA gyrase), vancomycin (cell wall, gram-positives).
• Antibiotic resistance — arises via mutation and horizontal gene transfer; ESKAPE pathogens are priority resistant organisms. Overuse and incomplete courses accelerate resistance.
• Statins — inhibit HMG-CoA reductase; lower LDL cholesterol; reduce cardiovascular events.
• NSAIDs (nonsteroidal anti-inflammatory drugs) — a broad class of drugs that inhibit cyclooxygenase enzymes (COX-1 and/or COX-2), reducing synthesis of prostaglandins and thromboxanes; effects include analgesia, antipyresis, and anti-inflammation; examples include ibuprofen, naproxen, aspirin, diclofenac, and selective COX-2 inhibitors (celecoxib); COX-1 inhibition reduces gastroprotective prostaglandins, causing ulcer risk; renal prostaglandin inhibition can impair kidney function; NSAIDs do not carry addiction risk unlike opioids; aspirin (irreversible COX inhibitor) is also antiplatelet.
• Aspirin — irreversibly inhibits COX-1/COX-2 (cyclooxygenase); analgesic, anti-inflammatory, and antiplatelet.
• Opioids — act on mu-, kappa-, delta-opioid receptors; analgesic; high addiction and respiratory depression risk.
• Vaccines — see Immune System section; mechanism: prime adaptive memory without causing disease.
• LD50 — dose lethal to 50% of a test population; standard measure of acute toxicity.

Epidemiology Terms

• Incidence — rate of new cases arising in a population over a defined period.
• Prevalence — proportion of a population with a condition at a given point (or period).
• Endemic / epidemic / pandemic — a disease present at a consistently expected level (endemic); suddenly above expected (epidemic); spread globally (pandemic).
• R0 (basic reproduction number) — average number of secondary cases from one infectious case in a fully susceptible population; R0 > 1 indicates spread.
• Herd immunity — indirect protection when sufficient population immunity (from infection or vaccination) blocks transmission.
• Sensitivity / specificity — sensitivity: true positive rate (probability of a positive test given disease present); specificity: true negative rate (probability of a negative test given disease absent).
• PPV / NPV — positive/negative predictive value; depend on prevalence (unlike sensitivity/specificity).
• Relative risk (RR) vs. odds ratio (OR) — RR is the ratio of incidence rates; OR is the ratio of odds; OR approximates RR when disease is rare.
• Confounding — a third variable that distorts the observed association; controlled by randomization, matching, or multivariable adjustment.
• John Snow — traced 1854 London cholera outbreak to the Broad Street pump by mapping cases; founding example of field epidemiology.

Nobel Prizes in Physiology or Medicine (Selected)

Year	Laureate(s)	Discovery
1901	Emil von Behring	Serum therapy for diphtheria
1905	Robert Koch	Tuberculosis bacterium
1923	Banting, Macleod	Insulin
1945	Fleming, Florey, Chain	Penicillin
1962	Watson, Crick, Wilkins	DNA double helix structure
1979	Cormack, Hounsfield	CT scanning
1984	Köhler, Milstein, Jerne	Monoclonal antibodies
2003	Lauterbur, Mansfield	MRI
2005	Marshall, Warren	H. pylori and peptic ulcer
2008	zur Hausen; Barré-Sinoussi, Montagnier	HPV causes cervical cancer; HIV discovery
2018	Allison, Honjo	Immune checkpoint therapy (cancer immunotherapy)
2023	Karikó, Weissman	mRNA nucleoside modification enabling COVID-19 vaccines

Key Figures

• Vesalius — modern human anatomy via dissection.
• Harvey — circulation of blood.
• Jenner — vaccination (smallpox via cowpox).
• Semmelweis — handwashing and antisepsis (largely ignored in his lifetime).
• Pasteur — germ theory, sterilization (pasteurization), anthrax and rabies vaccines.
• Koch — isolated TB and cholera bacilli; Koch’s postulates.
• Lister — antiseptic surgical technique.
• Röntgen — X-rays.
• Curie, Marie — radioactivity research; developed mobile X-ray units in WWI.
• Fleming / Florey / Chain — penicillin.
• Banting / Best — insulin.
• Salk / Sabin — polio vaccines.
• Crick, Watson, Franklin, Wilkins — DNA double helix (1953); Franklin’s X-ray data (Photo 51) was pivotal.
• Barré-Sinoussi, Montagnier — HIV isolation (1983).
• Marshall, Warren — H. pylori etiology of peptic ulcer.
• Karikó, Weissman — mRNA modification technology underpinning COVID-19 vaccines.