Structure and integrative functions of the main organ systems

Deoxygenated blood enters the right atrium (via the venae cavae), passes the tricuspid valve to the right ventricle, and is pumped through the pulmonary arteries to the lungs. Oxygenated blood returns to the left atrium, crosses the mitral (bicuspid) valve to the left ventricle, and is forced out the aorta to the body. Semilunar valves (pulmonary, aortic) guard the ventricular exits. Systole is contraction, diastole is relaxation. The heartbeat is myogenic, set by the conduction chain SA node (pacemaker) → AV node → bundle of His (in the interventricular septum) → Purkinje fibers.

Arteries withstand and smooth out the pressure pulse; arterioles control flow by constricting/dilating. Capillaries are where O₂, CO₂, nutrients, and wastes diffuse between blood and tissue — their thin walls and huge total cross-sectional area (slow flow) optimize exchange. Veins hold most of the blood volume and rely on one-way valves and skeletal-muscle squeezing to push blood back to the heart against gravity.

Erythrocytes (red cells) are biconcave, lack nuclei and mitochondria in mammals, and are packed with hemoglobin. O₂ binds hemoglobin cooperatively (the sigmoidal curve from hemoglobin); CO₂ is carried ~70% as bicarbonate (HCO₃⁻), formed by carbonic anhydrase in red cells — which also makes blood the body's main pH buffer (the carbonic-acid/bicarbonate system). The Bohr effect: high CO₂/low pH in active tissue shifts the curve right, releasing more O₂ where it's needed. Clotting is a cascade ending in fibrin mesh over a platelet plug.

A typical resting CO is ~5 L/min (e.g. SV ≈ 70 mL/beat × HR ≈ 70 beats/min). Output rises during exercise by increasing either factor. Frank–Starling's law ties SV to filling: greater venous return stretches the ventricle more (greater preload), and a more-stretched cardiac muscle contracts more forcefully — so more blood in means more blood out. This auto-matches the heart's output to the volume returning to it.

Blood (hydrostatic) pressure is high at the arteriolar end, so fluid filters out into the tissue there. As blood moves along the capillary, hydrostatic pressure falls, but the oncotic pull stays roughly constant (large plasma proteins like albumin can't leave), so at the venular end fluid is reabsorbed in. Net filtration slightly exceeds reabsorption; the lymphatic system returns the leftover fluid (see lymphatic system), preventing edema.

The largest single pressure drop occurs across the arterioles — the chief resistance vessels, which control flow and pressure by constricting or dilating. Pressure is high and pulsatile in the arteries, drops sharply at the arterioles, is low in the capillaries, and is nearly zero in the veins (hence veins need valves and muscle squeezing to return blood). This follows ΔP = Q × R: the high resistance of the narrow arterioles consumes most of the pressure.

Type O is the universal donor (no A/B antigens to attack), type AB the universal recipient (no anti-A/anti-B antibodies); mismatched ABO transfusion causes agglutination/hemolysis. Rh sensitization matters in pregnancy: an Rh⁻ mother carrying an Rh⁺ fetus can be exposed to fetal Rh⁺ cells (usually at delivery) and make anti-Rh antibodies. The first pregnancy is usually fine, but in a later Rh⁺ pregnancy those IgG antibodies cross the placenta and attack fetal red cells — hemolytic disease of the newborn (prevented by giving the mother anti-Rh, RhoGAM).

At the alveolus, O₂ is high in air and low in returning (deoxygenated) blood, so O₂ diffuses in; CO₂ is high in blood and low in air, so it diffuses out. Efficiency comes from surface area (millions of alveoli), thinness (one cell each side), and moisture. The alveoli are kept open by surfactant, which lowers surface tension so they don't collapse.

Breathing is negative-pressure ventilation: enlarging the thoracic cavity lowers intrapulmonary pressure so air rushes in (Boyle's law — volume up, pressure down). Quiet exhalation just reverses by elastic recoil. Surfactant (made by alveolar cells) reduces surface tension, preventing the smallest alveoli from collapsing — its absence in premature infants causes respiratory distress syndrome.

The respiratory center in the medulla oblongata (brainstem) sets the automatic rhythm of breathing. Central chemoreceptors in the medulla and peripheral chemoreceptors in the aortic arch and carotid bodies monitor blood chemistry. The strongest day-to-day driver is CO₂, because dissolved CO₂ forms carbonic acid and lowers blood pH; rising CO₂ (or falling pH) signals the medulla to increase ventilation, blowing off CO₂ and restoring pH — a classic negative-feedback loop tied to the bicarbonate buffer. O₂ is only a backup trigger, sensed peripherally and only when it falls very low.

Spirometry partitions lung air into volumes and capacities (sums of volumes). Tidal volume (TV) is the air moved in a normal resting breath. Inspiratory reserve volume (IRV) is the extra you can forcibly inhale beyond a normal breath; expiratory reserve volume (ERV) is the extra you can forcibly exhale. Residual volume (RV) is the air left after a maximal exhale — it cannot be expelled and keeps the alveoli from collapsing. Vital capacity (VC) = TV + IRV + ERV = the largest breath you can move; total lung capacity (TLC) = VC + RV. So VC = TLC − RV.

The conducting zone (nose/nares through the terminal bronchioles) warms, humidifies, and filters incoming air but does no gas exchange — its volume is anatomical dead space. The respiratory zone starts where alveoli first appear on the airway walls: the respiratory bronchioles, then alveolar ducts and alveoli, where O₂ and CO₂ actually diffuse across the thin walls. Cartilage and smooth muscle change along the path: the trachea and bronchi are held open by cartilage rings, while bronchioles are cartilage-free and rely on smooth muscle (which constricts in asthma).

The adaptive response splits into two arms: humoral immunity (B cells make antibodies that tag/neutralize extracellular pathogens) and cell-mediated immunity (T cells — helper T cells coordinate the response, cytotoxic T cells kill infected cells). Memory cells from either arm enable the rapid secondary response.

Antibodies (immunoglobulins) bind antigens to neutralize them, tag them for phagocytosis (opsonization), or activate complement. Cells display protein fragments on MHC molecules: MHC I (on all nucleated cells) shows internal proteins to cytotoxic T cells (flagging virus-infected or cancerous cells); MHC II (on antigen-presenting cells) shows engulfed antigens to helper T cells. This display-and-inspect system is how the body distinguishes self from non-self.

Activated in sequence, complement proteins assemble into the membrane attack complex (MAC) — a pore punched into the pathogen's membrane that lets water rush in and osmotically lyses the cell. Along the way, C3b coats the pathogen as an opsonin (marking it for phagocytes), and other fragments recruit immune cells and drive inflammation. Though made of soluble proteins, complement is part of the innate system (no antigen specificity, no memory), but it is also recruited by antibodies of the adaptive response.

Cytotoxic T cells need to see a foreign peptide on MHC I to kill, so viruses (and tumors) often downregulate MHC I to hide. NK cells are the failsafe: rather than recognizing a specific antigen, they kill any cell missing the normal "self" MHC I signal. They induce apoptosis in the target. NK cells belong to the innate system — fast and nonspecific, with no memory — despite being lymphocytes.

When a cell detects it is infected, it secretes interferons that bind receptors on nearby uninfected cells, switching on an antiviral state (e.g., degrading viral RNA and blocking viral protein synthesis) so the virus cannot replicate if it reaches them. They also activate immune cells like NK cells. Interferons are part of the innate antiviral response — the answer when a stem asks which molecule lets an infected cell protect its neighbors.

Active immunity comes from your B cells responding to an antigen — naturally (getting sick) or artificially (a vaccine) — and it lays down memory cells for long-lasting protection. Passive immunity is borrowed: antibodies transferred from another source, such as a mother's across the placenta or in breast milk, or an injected antiserum/antivenom. Because your own cells never learn the antigen, passive immunity fades as the donated antibodies degrade.

Each Y-shaped antibody has two identical antigen-binding sites at the tips of its arms, formed by the variable regions — their sequence varies enormously, which is what gives each antibody its specificity. The constant region stem is the same across antibodies of a given class and is what phagocytes and complement recognize. The specific spot on the antigen that is recognized is the epitope; the matching pocket on the antibody is the paratope — they fit like lock and key.

Before any infection, the body holds a vast pool of lymphocytes, each pre-committed to a single antigen specificity. When an antigen appears, it "selects" the lymphocyte bearing the matching receptor; that cell undergoes clonal expansion (rapid division) to produce many identical cells — some become effector cells (e.g., plasma cells) that fight now, others become memory cells retained for the future. This one idea ties together adaptive immunity's specificity, amplification, and memory.

All immune cells originate from hematopoietic stem cells in the bone marrow. T cells migrate to the thymus for screening: positive selection keeps T cells that can recognize self-MHC (so they can read displayed antigens at all), while negative selection destroys T cells that bind self-antigens too strongly. This builds self-tolerance. When tolerance fails, the immune system attacks the body's own cells — autoimmunity (e.g., type 1 diabetes, multiple sclerosis).

A naive B cell circulates with a unique receptor but does nothing until it meets its matching antigen (usually with helper-T-cell help). It then expands and splits its fate: most become plasma cells, effector cells packed with rough ER that secrete large amounts of antibody but die in days, while a few become memory B cells that persist for years and respond rapidly on re-exposure. "B cells make antibodies" really means plasma cells do the secreting.

On first contact with an antigen, naive lymphocytes must find, activate, and expand before antibodies appear, so the antibody titer climbs only after a days-to-week lag and peaks modestly. On re-exposure, pre-existing memory cells respond almost immediately, driving a much higher, faster antibody titer — this is what vaccines exploit. On a titer-vs-time graph, the secondary curve is the tall, early, steep peak; the primary is the small, delayed one.

Chemical digestion in the mouth is carbohydrate only — salivary amylase starts starch (and lingual lipase begins a little fat); protein digestion does not begin until the stomach. The stomach's low pH (HCl from parietal cells) kills microbes and activates pepsin for protein. The small intestine is the main event: it neutralizes acid, receives pancreatic enzymes (amylase, lipase, proteases) and bile, and absorbs sugars, amino acids, and fats across a vast surface of villi and microvilli (the brush border). Final cleavage happens at that membrane: brush-border disaccharidases (maltase, sucrase, lactase) split disaccharides into monosaccharides and dipeptidases finish protein into single amino acids — so a missing lactase leaves lactose uncleaved, causing lactose intolerance. The large intestine mainly reabsorbs water and hosts gut flora.

The pancreas is both exocrine (enzymes + HCO₃⁻ into the duodenum) and endocrine (insulin/glucagon into blood). The liver is the body's metabolic hub: it makes bile (which emulsifies fats, aiding lipase), stores glycogen, detoxifies, and is the first stop for nutrient-rich blood from the gut (hepatic portal system). Bile is stored in the gallbladder and released into the small intestine after a fatty meal. (Bile emulsifies; it doesn't chemically digest.)

A meal triggers an endocrine relay. Gastrin (from stomach G cells) drives parietal cells to secrete HCl. As acidic chyme enters the duodenum, secretin signals the pancreas to release HCO₃⁻ (raising duodenal pH) and dials gastric acid back down. Fats and amino acids release CCK (cholecystokinin), which makes the gallbladder contract to release bile and the pancreas release digestive enzymes — and it promotes satiety. Longer-term appetite is set by ghrelin (stomach, the "hunger" hormone, rising before meals) and leptin (adipose, the "satiety" hormone) — see the endocrine system.

Each gastric cell type does one job. Parietal cells pump out HCl (the acid that denatures protein and activates pepsin) and also secrete intrinsic factor, a protein required to absorb vitamin B12 in the ileum — so losing parietal cells (e.g., in pernicious anemia/autoimmune gastritis) causes B12 deficiency. Chief cells secrete pepsinogen, the inactive zymogen of pepsin. G cells release the hormone gastrin, which drives parietal cells to make more acid (see gut hormones). Mucous cells coat the lining with bicarbonate-rich mucus that protects the epithelium from self-digestion.

Proteases are dangerous, so the body ships them as zymogens (proenzymes) and switches them on only at the worksite (general principle in enzyme regulation). In the stomach, HCl's low pH cleaves pepsinogen to active pepsin (and pepsin then autoactivates more pepsinogen) — note the activator here is acid, not another enzyme. In the duodenum, the brush-border enzyme enteropeptidase (enterokinase) cleaves pancreatic trypsinogen to trypsin. Trypsin is the master switch: it cleaves and activates the remaining pancreatic zymogens — chymotrypsinogen → chymotrypsin and procarboxypeptidases → carboxypeptidases — and more trypsinogen, an amplifying cascade.

Blood is filtered under pressure in the glomerulus into Bowman's capsule (small molecules pass; cells and proteins stay). The filtrate then travels the tubule: the proximal tubule reabsorbs most nutrients, ions, and water; the loop of Henle acts as a countercurrent multiplier that builds the medullary osmotic gradient — its descending limb is permeable to water but not salt, so water leaves and the filtrate concentrates, while its ascending limb is permeable to salt but not water and actively pumps out NaCl, diluting the filtrate and loading the medulla with solute. That standing gradient is what later lets the distal tubule and collecting duct pull water back out (under ADH/aldosterone control) to fine-tune Na⁺, K⁺, acid, and water. What's left is urine.

When you're dehydrated, the posterior pituitary releases ADH (vasopressin), which inserts water channels (aquaporins) in the collecting duct so more water is reabsorbed — small volume of concentrated urine. When blood pressure/volume is low, the RAAS pathway releases aldosterone (adrenal cortex), which drives Na⁺ reabsorption in the distal nephron, and water follows the salt. Both raise blood volume, but by different levers.

Erythropoietin (EPO) is secreted by the kidney in response to low blood O₂ and stimulates the bone marrow to make more red blood cells (erythropoiesis) — the missing driver behind the erythrocytes in blood composition. When blood pressure/volume falls, the juxtaglomerular apparatus (JGA) releases renin, which cleaves angiotensinogen toward angiotensin II (vasoconstriction) and triggers aldosterone release — the RAAS pathway behind osmoregulation: ADH & aldosterone — all of which raise blood pressure. Opposing it, stretched cardiac atria (high volume) release atrial natriuretic peptide (ANP), which promotes Na⁺ and water excretion and vasodilation to lower blood pressure.

When the atria are over-filled (volume too high), stretch-sensitive cells secrete atrial natriuretic peptide. ANP promotes natriuresis (Na⁺ excretion) and diuresis, and opposes the RAAS — it inhibits renin and aldosterone release and relaxes vascular smooth muscle. Net effect: less salt and water reabsorbed → blood volume and pressure fall. It is the body's main "BP too high" counter-regulator.

This is the upstream trigger behind aldosterone. Low blood pressure/volume → renin is secreted → renin converts angiotensinogen (from the liver) into angiotensin I → ACE (mostly in the lungs) converts it to angiotensin II. Angiotensin II raises BP two ways: it constricts blood vessels (raising resistance) and it stimulates the adrenal cortex to release aldosterone (→ Na⁺ and water retention). It also stimulates ADH and thirst. So the bare acronym from osmoregulation unpacks as Renin–Angiotensin–Aldosterone System.

Blood enters the glomerulus through the afferent arteriole and leaves through the efferent arteriole — unusual, because the efferent is an arteriole exiting a capillary bed, which lets the kidney sandwich and regulate glomerular pressure. Constricting the efferent arteriole dams blood inside the glomerulus → higher glomerular pressure → raises GFR; constricting the afferent arteriole throttles inflow → lowers GFR. GFR rises and falls with blood pressure overall, and angiotensin II preferentially constricts the efferent arteriole to defend GFR when BP drops.

Blood pH is held by the bicarbonate buffer system, and two organs adjust it. The lungs act in minutes by blowing off or retaining CO₂ (respiratory compensation). The kidney acts over hours to days: to fight acidosis it reabsorbs HCO₃⁻ in the proximal tubule and secretes H⁺ in the distal nephron/collecting duct (raising blood pH); to fight alkalosis it does the reverse — excreting HCO₃⁻ and retaining H⁺. Because it changes the actual amount of buffer in the blood, the renal route is powerful but slow.

Skeletal muscle moves the skeleton on command and shows clear striations from ordered sarcomeres. Cardiac muscle is also striated but involuntary and myogenic (the SA node sets the beat); its intercalated discs with gap junctions sync contraction. Smooth muscle lines the gut, blood vessels, and bladder, contracts slowly and involuntarily, and lacks striations.

Excitation–contraction coupling: a motor neuron's action potential triggers ACh release → muscle-fiber depolarization → Ca²⁺ released from the sarcoplasmic reticulum. Ca²⁺ binds troponin, moving tropomyosin off actin's myosin-binding sites. Myosin heads bind actin, pivot (the power stroke, pulling the thin filaments toward the center), then ATP binds to release and re-cock the head for another cycle. The I-band and H-zone shrink while the A-band stays constant — the signature of sliding filaments. Relaxation comes when Ca²⁺ is pumped back and the sites are re-blocked.

Type I (slow oxidative) fibers have a dense capillary supply, many mitochondria, and high myoglobin (the red color), so they make ATP by oxidative phosphorylation and sustain prolonged activity without tiring — think marathon/posture muscles. Type II (fast) fibers split into IIa (fast oxidative-glycolytic), an intermediate that uses both pathways, and IIb/IIx (fast glycolytic), the largest, strongest, fastest-contracting fibers that rely on anaerobic glycolysis, accumulate lactic acid, and fatigue rapidly — think sprinting/jumping. The trade-off is force-and-speed versus endurance.

In striated (skeletal/cardiac) muscle, Ca²⁺ acts on the thin filament by binding troponin to move tropomyosin off actin. Smooth muscle instead regulates the thick filament: Ca²⁺ binds calmodulin, and Ca²⁺–calmodulin activates MLCK, which phosphorylates the myosin light chain so cross-bridging can occur (relaxation comes via myosin light-chain phosphatase). Smooth muscle also lacks T-tubules and draws much of its Ca²⁺ from the extracellular space (plus some from the SR), which is why it contracts more slowly and in a sustained, graded way.

Blood calcium is tightly regulated because it's essential for nerves, muscle, and clotting. When blood Ca²⁺ falls, parathyroid hormone (PTH) stimulates osteoclasts to resorb bone (and the kidney/gut to retain/absorb Ca²⁺), raising it; when Ca²⁺ is high, calcitonin favors osteoblast deposition, lowering it. Bone thus doubles as the body's calcium bank.

The cycle is a hormonal relay: FSH drives follicle growth → the follicle secretes estrogen (thickening the endometrium). Estrogen peaking flips to positive feedback, causing the pituitary LH surge → ovulation (~day 14). The ruptured follicle becomes the corpus luteum, secreting progesterone (and estrogen) to sustain the endometrium. No fertilization → the corpus luteum degenerates → progesterone/estrogen drop → menstruation, and the cycle restarts. Pregnancy maintains the corpus luteum via hCG (what pregnancy tests detect).

Pregnancy hand-off. hCG (from the implanting embryo/placenta) mimics LH to rescue the corpus luteum, keeping progesterone/estrogen high so the endometrium isn't shed — the testable causal chain. After roughly the first trimester, the placenta itself takes over progesterone/estrogen production and the corpus luteum regresses. Organogenesis occurs mainly in the first trimester, when the embryo is most vulnerable to teratogens.

After S phase the primary cell is diploid (2n, replicated). Meiosis I halves the chromosome number, so the secondary cell is haploid (n) but still carries sister chromatids; meiosis II separates those chromatids to give the mature haploid gamete. The primary oocyte arrests in prophase I from birth and only resumes at ovulation, dividing into a secondary oocyte that arrests again in metaphase II; meiosis II completes only if a sperm fertilizes it — otherwise the unfertilized cell degenerates. (Meiosis itself is covered in 1C.)

On contact, the sperm's acrosome (an enzyme-filled cap) bursts, releasing hydrolytic enzymes that drill through the egg's zona pellucida to reach the membrane. Fusion of the first sperm causes a spike in egg intracellular Ca²⁺, which triggers cortical granules to exocytose and chemically modify the zona pellucida — the cortical reaction, the slow block to polyspermy. Completing fertilization restarts the egg's stalled meiosis II (see gametogenesis) and forms the diploid zygote (see cleavage).

Inside each seminiferous tubule, spermatogenesis proceeds against the supporting Sertoli cells, which feed the germ cells and form the blood–testis barrier; FSH acts on Sertoli cells. Between the tubules sit the Leydig (interstitial) cells, which secrete testosterone in response to LH. Immature sperm leave the testis and are stored/matured in the epididymis, where they acquire motility before ejaculation through the vas deferens.

Because the fetus gets oxygen at the placenta (not the lungs), HbF binds O₂ more tightly than adult HbA, letting it strip O₂ across the placental gradient. Since the lungs aren't ventilated, blood is routed around them: the ductus venosus sends oxygenated umbilical-vein blood past the liver to the inferior vena cava; the foramen ovale shunts blood right atrium → left atrium; and the ductus arteriosus diverts pulmonary artery → aorta. At birth these close as the lungs inflate.