Assessment Bank

1.1 b — each level is built from the one below and shows emergent properties; the others invert that order. 1.2 b — with palms facing forward the thumb is the most lateral digit. Anatomical position exists precisely so this answer is unambiguous. 1.3 c — oxytocin increases contractions, which increase cervical stretch, which increases oxytocin. The other three oppose their stimulus and are negative feedback. 1.4 b — the pericardial cavity lies in the mediastinum, within the thoracic cavity of the ventral body cavity. 1.5 Effector: cutaneous arteriolar smooth muscle (plus sweat glands). Control system: the sympathetic division of the autonomic nervous system. The skin is chosen because its blood flow is largely thermoregulatory rather than metabolic, so it can be sacrificed to preserve brain and myocardial perfusion. 1.6 Fever is a set-point shift, not a control failure. Pyrogens raise the hypothalamic set point; at 38.9 °C the patient is still below the new set point, so the loop correctly generates heat by shivering and conserves it by vasoconstriction. Look for the phrase "the thermostat was moved, not broken." 1.7 Full credit requires mechanism and direction. Examples: cardiovascular — the heart generates the pressure, and stroke volume × rate sets it; nervous — baroreceptors sense pressure and adjust sympathetic outflow, which changes resistance; urinary — the kidney adjusts blood volume, which changes preload, which changes stroke volume, which changes pressure; endocrine — aldosterone retains sodium, which retains water, which raises volume.

2.1 d — mass number counts protons plus neutrons. Electrons contribute negligible mass. 2.2 c — pH is a base-10 logarithmic scale, so two units is a hundredfold difference. 2.3 b — high specific heat means large energy input produces small temperature change; this is why water is a thermal buffer as well as a solvent. 2.4 c — a covalent peptide bond forms by dehydration synthesis between an amino group and a carboxyl group. 2.5 Ketoacids (acetoacetate, β-hydroxybutyrate) donate hydrogen ions that bicarbonate buffers and is consumed doing so. Kussmaul respiration blows off CO₂, driving the carbonic acid equilibrium leftward and raising pH — a respiratory compensation for a metabolic acidosis. 2.6 Roughly 40% of serum calcium is bound to albumin. With hypoalbuminemia the bound fraction falls, so total calcium is low while the physiologically active ionized fraction — which is what the parathyroid glands regulate — is normal. This is why symptoms track ionized calcium. 2.7 Receptors: central chemoreceptors in the medulla (H⁺/CO₂) and peripheral chemoreceptors; control centers: the respiratory centers of the medulla and, separately, the renal tubule cells; effectors: the lungs, which adjust CO₂ within minutes, and the kidneys, which adjust bicarbonate reabsorption and hydrogen secretion over hours to days.

3.1 c — primary active transport hydrolyzes ATP at the carrier itself; facilitated diffusion and osmosis are passive, and secondary active transport uses a gradient rather than ATP directly. 3.2 b — smooth ER carries the enzymes for lipid and steroid synthesis and for drug detoxification; rough ER is studded with ribosomes and makes secreted protein. 3.3 b — 3% NaCl is hypertonic to plasma, so water leaves the cell and the membrane crenates. 3.4 b — the name is the clue, and the spindle checkpoint operates here. 3.5 Ischemia halts ATP production; without ATP the Na⁺/K⁺-ATPase fails, the cell swells, the membrane loses integrity, and cytosolic contents including troponin escape into the interstitium and then the blood. The lag reflects the time required for irreversible membrane failure plus diffusion and lymphatic and venous transport to a sampling site. 3.6 CFTR normally secretes chloride onto the airway surface; sodium and then water follow osmotically, keeping the periciliary layer hydrated. Without chloride secretion — and with increased sodium absorption — water is not drawn out, the surface layer dehydrates, and mucus becomes viscous and defeats ciliary clearance. 3.7 ATP failure stops the pump. Sodium accumulates intracellularly, the cell becomes hypertonic relative to the interstitium, water follows osmotically, and the cell swells. This is oncotic (hydropic) swelling and is the first structural sign of ischemic injury — the same sequence that liberates troponin in 3.5.

4.1 b — a single flattened layer minimizes diffusion distance; this is the thread "structure determines function" in its cleanest form. 4.2 c — blood is a connective tissue whose matrix is plasma and whose fibers are the soluble clotting proteins. 4.3 c — tight junctions fuse adjacent membranes into a belt; desmosomes provide mechanical anchorage, gap junctions provide communication. 4.4 b — nutrients diffuse across the basement membrane from capillaries in the underlying connective tissue, which is why epithelia are thin or organized around that limit. 4.5 Metaplasia — the replacement of one differentiated tissue by another. Columnar epithelium with mucus-secreting goblet cells tolerates acid better, so the change is adaptive in the short term. What is lost is the abrasion resistance of a stratified squamous surface, and the proliferating population is more prone to dysplasia and adenocarcinoma. 4.6 Mechanical: scar is non-contractile and stiffer than myocardium, so regional wall motion is lost and ventricular compliance falls, which raises filling pressures. Electrical: fibrous tissue is non-conducting, creating a zone of slow or blocked conduction that supports reentrant arrhythmia. 4.7 Gut epithelial stem cells remain in the cell cycle and divide continuously. Mature cardiac myocytes are permanently in G₀; having exited the cycle, they cannot re-enter it at any meaningful rate, so the healing response falls to fibroblasts and yields scar.

5.1 c — the basale sits on the basement membrane and is the only mitotic layer; cells move outward and die as they keratinize. 5.2 b — melanocytes synthesize it and transfer pigment granules to keratinocytes, which is why skin color differences reflect melanin type and distribution rather than melanocyte number. 5.3 c — sebum, secreted holocrine into the hair follicle. 5.4 b — 7-dehydrocholesterol becomes cholecalciferol (D₃), which is then hydroxylated in liver and kidney to calcitriol. 5.5 Anterior trunk 18% plus one whole arm 9% equals about 27%. Full-thickness burn destroys the epidermal barrier, so evaporative and exudative fluid loss is immediate and massive; plasma volume falls, and hypovolemic shock kills within hours, whereas burn wound infection is a threat over days. 5.6 Pallor is reduced cutaneous blood flow — vasoconstriction — and can occur with entirely normal arterial oxygen saturation. Cyanosis is a change in the color of blood present, caused by an absolute quantity of deoxygenated hemoglobin in the superficial vessels, so it reports saturation and hemoglobin concentration rather than flow. 5.7 Thermoregulation defends core temperature; the baroreflex and sympathetic perfusion response defend arterial pressure and central perfusion. The distinguishing evidence is core temperature and the rest of the picture: a cold patient who is pale is thermoregulating; a normothermic pale patient with tachycardia and cool sweat is defending perfusion.

6.1 c — osteoclasts are large multinucleate cells of monocyte lineage; osteoblasts build, osteocytes maintain and sense strain. 6.2 b — PTH acts on bone and kidney directly and on gut indirectly through calcitriol. Calcitonin opposes it and is physiologically minor in adults. 6.3 b — the plate; appositional growth at the periosteum increases width, not length. 6.4 c — type I collagen supplies tensile strength; hydroxyapatite supplies compressive strength. The composite argument is the point of §6.3. 6.5 The T-score is bone mineral density expressed in standard deviations from the mean of a young adult reference population; −2.8 is 2.8 SD below that mean and meets the criterion for osteoporosis. Estrogen normally restrains osteoclast formation and lifespan; after menopause, resorption outpaces formation, trabeculae are perforated and lost, and strength falls faster than density alone predicts. 6.6 Both are failures of matrix mineralization from inadequate vitamin D or phosphate. In a child the growth plates are open, so unmineralized cartilage accumulates and the soft metaphyses bow — hence bowed legs and costochondral beading. In an adult the plates are closed, so the result is diffuse bone pain, weakness, and pseudofractures rather than deformity. 6.7 Bone is highly vascular and contains osteoprogenitor cells at the periosteum and endosteum, so a fracture recruits a blood clot, inflammatory cells, and a cellular callus. Articular cartilage is avascular, aneural, and alymphatic, its chondrocytes are trapped in lacunae, and a lesion that does not reach subchondral bone recruits nothing.

7.1 b — the axial skeleton is skull, vertebral column, and thoracic cage; the other three are appendicular girdle bones. 7.2 b — the atlanto-occipital joint carries the "yes" nod; rotation on the dens is the "no" shake at the atlanto-axial joint. 7.3 d — a deep acetabulum trades range of motion for stability, which is exactly the opposite trade from the shoulder. 7.4 b — the ACL runs anteriorly from the tibia; the PCL resists posterior translation. 7.5 A planted foot with a decelerating, rotating body applies valgus and rotational torque that exceeds the ACL's tensile capacity. The ACL is intra-articular and vascularized, so rupture bleeds into the joint — a hemarthrosis fills the capsule in one to two hours, whereas a reactive effusion takes a day. The medial meniscus is attached to the medial collateral ligament and is loaded by the same valgus-rotation mechanism, producing the classic triad. 7.6 Force travels from the palm through the carpals to the distal radius, which is largely trabecular bone at the metaphysis and fails in extension with dorsal angulation. It shares its epidemiology with osteoporotic hip and vertebral fracture because trabecular bone is lost first and fastest. 7.7 Density falls — disuse osteopenia, measurable within weeks. Osteocytes sense mechanical strain and, when strain falls, signal to reduce formation and permit resorption; the skeleton maintains only the mass its loading history demands. This is Wolff's law running backwards, and it is why early weight-bearing is prescribed whenever the fracture allows.

8.1 c — calcium binds troponin C, which moves the troponin–tropomyosin complex off the myosin-binding sites on actin. Calcium never binds myosin. 8.2 d — the A band is the length of the thick filament and is constant. Filaments slide; they do not shorten. This item is written specifically to catch that misconception. 8.3 b — the power stroke follows phosphate release; ATP binding releases the head, and its hydrolysis re-cocks it. 8.4 a — slow oxidative fibers, with high myoglobin, capillary density, and mitochondrial content. 8.5 Fewer functional receptors mean each vesicle of acetylcholine produces a smaller end-plate potential, so the safety margin at the neuromuscular junction is reduced. Repeated activity depletes the readily releasable vesicle pool, so successive potentials fall below threshold and weakness accumulates with use. An acetylcholinesterase inhibitor prolongs acetylcholine's residence in the cleft, raising the chance it finds a surviving receptor. 8.6 Rhabdomyolysis. Myoglobin released from lysed fibers is filtered and turns urine red-brown, and it is nephrotoxic in the tubule. Potassium released from the same cells is the lethal element: hyperkalemia depolarizes the resting membrane, inactivates sodium channels, and produces asystole or ventricular arrhythmia. 8.7 Calcium must be pumped back into the sarcoplasmic reticulum against its gradient by SERCA, a primary active transporter, and myosin heads require ATP binding to detach from actin. After death, ATP synthesis stops; calcium leaks into the cytosol and cannot be recovered, and the heads that attach cannot release. The muscle locks in the attached state until proteolysis dissolves the bridges.

9.1 b — brachialis inserts on the ulna and so is unaffected by pronation or supination; biceps brachii loses leverage when pronated, and brachioradialis is strongest in mid-position. 9.2 d — action (extensor), region (carpi, radialis), and relative size (longus) are all encoded. Number of origins would be a prefix such as biceps or triceps. 9.3 c — effort between fulcrum and load: fast and wide-ranging but mechanically disadvantageous, which is why muscles generate forces far larger than the loads they move. 9.4 b — an active lengthening, or eccentric, contraction. It is the antagonist to gravity, not to itself. 9.5 Supraspinatus. Its tendon passes beneath the coracoacromial arch, and between roughly 60° and 120° of abduction the tendon and subacromial bursa are compressed against the acromion. Resisted abduction at 90° with the arm internally rotated reproduces it, as does passive impingement testing. 9.6 The safe zone is 2–3 finger-widths below the acromion, within the thick upper deltoid. The axillary nerve and posterior circumflex humeral artery wrap the surgical neck of the humerus below that level, and injection there risks nerve injury and deltoid denervation. 9.7 Eccentric contraction produces high force across fewer active cross-bridges, so individual sarcomeres — particularly weaker ones in series — are strained and disrupted. The resulting damage triggers inflammation, swelling, and sensitization of nociceptors over 24–48 hours. Lactate cannot be the cause because it is cleared within roughly an hour of exercise, long before soreness peaks, and because eccentric work produces less lactate than concentric work at equal load.

10.1 b — the resting membrane is most permeable to potassium, so E_K dominates. 10.2 b — voltage-gated sodium channels open first and fastest. 10.3 b — myelin insulates; only nodes regenerate the impulse, so it jumps between them. 10.4 c — voltage-gated calcium channels open on depolarization and calcium triggers vesicle fusion. This is the same calcium-as-trigger logic as in muscle. 10.5 A raised extracellular potassium reduces the potassium gradient, so the resting potential becomes less negative. Sustained depolarization drives voltage-gated sodium channels into their inactivated state, and inactivated channels cannot open, so fewer are available to fire — excitable tissue becomes inexcitable. This is why hyperkalemia produces weakness and asystole. 10.6 Conduction slows or fails entirely in demyelinated segments, and current leaks across the now-uninsulated internode. Marginal fibers conduct only within a narrow temperature range, so a small rise in body temperature — a hot bath, a fever — pushes them into block and symptoms return (Uhthoff's phenomenon). 10.7 Blocking the pump raises intracellular sodium. The Na⁺/Ca²⁺ exchanger, which normally extrudes calcium using the inward sodium gradient, loses its driving force and slows. Calcium accumulates in the cytosol and in the sarcoplasmic reticulum, so more is released per beat and contractility rises.

11.1 b — postcentral is sensory, precentral is motor; the central sulcus separates them. 11.2 b — choroid plexus in the ventricles; arachnoid granulations reabsorb it. 11.3 b — olfaction is the classic exception. 11.4 c — the cerebellum coordinates rather than commands, so its lesions produce incoordination without weakness. 11.5 Left hemisphere, middle cerebral artery territory, involving Broca's area and the lateral motor cortex. Corticospinal fibers decussate in the medullary pyramids, so a lesion above that crossing produces deficits on the opposite side of the body. 11.6 The cranium is a rigid box containing brain, blood, and CSF in a fixed total volume; an added mass must be offset by displacing CSF and venous blood. Those buffers accommodate slow growth almost linearly until they are exhausted, after which the pressure–volume curve turns steeply upward and a small further increase produces a large pressure rise. 11.7 Continuous capillaries in the CNS are sealed by tight junctions between endothelial cells, and astrocyte end-feet induce and maintain that phenotype. Only small lipid-soluble molecules and substrates with specific carriers cross freely, so many drugs — most antibiotics, most chemotherapy — reach the CNS poorly and must be dosed higher or delivered intrathecally.

12.1 d — the vagus, which supplies thoracic and most abdominal viscera. 12.2 b — hence "thoracolumbar"; parasympathetic outflow is craniosacral. 12.3 b — nicotinic cholinergic at every ganglion; the divisions differ at the target, not at the ganglion. 12.4 b — segmental, and the map is why a sensory level localizes a cord lesion. 12.5 Reduced heart rate and reduced contractility. Both lower myocardial oxygen demand, and a slower rate lengthens diastole — which is when the coronary arteries actually fill, since systolic compression of intramural vessels nearly halts left ventricular perfusion. Demand falls and supply time rises simultaneously. 12.6 Horner syndrome, from interruption of sympathetic supply to the head — ptosis from loss of the superior tarsal muscle, miosis from unopposed parasympathetic constriction, anhidrosis from loss of sudomotor fibers. 12.7 Visceral afferents from the heart enter the cord at roughly T1–T5 and synapse on second-order neurons that also receive somatic afferents from the corresponding dermatomes. The brain has no separate pathway for cardiac pain and interprets the input as coming from the better-represented somatic territory — the medial arm, shoulder, and, through convergence with upper cervical afferents, the jaw.

13.1 b — three cone classes, low sensitivity, high acuity; rods are monochromatic. 13.2 a — the sphincter-like ciliary muscle contracts, reducing tension on the zonules and letting the elastic lens round up. 13.3 c — on the basilar membrane, with stereocilia contacting the tectorial membrane. 13.4 c — the maculae of utricle and saccule detect linear acceleration and head tilt. 13.5 Presbyopia is loss of lens elasticity, so the near point recedes and reading glasses help — it does not affect color or glare. Cataract is opacification and yellowing of the lens protein, which scatters light: hence the need for more illumination, the yellow cast, and halos around point sources. 13.6 The basilar membrane is narrow and stiff at the base and wide and floppy at the apex, so high frequencies peak at the base. Basal hair cells are exposed to every sound the ear ever transduces and are first in line for noise and ischemic injury, so high-frequency loss appears first. 13.7 A stimulus changes the conformation or gating of a receptor protein; ion flow changes; this produces a graded receptor potential proportional to stimulus intensity; if the graded potential reaches threshold at a trigger zone — or, at a hair cell or photoreceptor, if it modulates transmitter release onto an afferent — action potentials are generated at a frequency encoding intensity. Intensity is coded by frequency and by population size, never by action potential amplitude.

14.1 b — lipid-soluble, so they cross the membrane; effects are slow in onset and long-lasting because they require gene transcription and protein synthesis. 14.2 c — ADH and oxytocin are synthesized in hypothalamic neurons and transported down axons for storage and release. The others are anterior pituitary products. 14.3 b — TSH acts on another endocrine gland; the rest act on non-endocrine targets. 14.4 b — glomerulosa makes aldosterone, reticularis makes androgens, medulla makes catecholamines. "Salt, sugar, sex — the deeper you go, the sweeter it gets." 14.5 Patient one has primary hypothyroidism: the thyroid has failed, negative feedback is released, and pituitary TSH rises. Patient two has secondary (central) hypothyroidism: an inappropriately normal or low TSH in the face of a low T4 means the pituitary or hypothalamus is the failing element, since a healthy pituitary would be shouting. 14.6 Cortisol. It opposes insulin by stimulating hepatic gluconeogenesis and by inducing peripheral insulin resistance in muscle and adipose tissue, reducing glucose uptake; it also promotes lipolysis and visceral fat deposition, which adds a second, inflammatory route to resistance. Night shift flattens and shifts the diurnal curve so cortisol is elevated at times when it should be low. 14.7 Serum calcium falls within hours and reaches its nadir in one to three days. PTH normally does three things: mobilizes calcium from bone, promotes distal tubular reabsorption of calcium, and drives renal 1α-hydroxylation of vitamin D for intestinal absorption. All three stop. The first sign is neuromuscular hyperexcitability — perioral tingling, then carpopedal spasm — because low ionized calcium lowers the threshold for sodium channel opening.

15.1 b — about 60% of plasma protein; hypoalbuminemia therefore causes edema. 15.2 c — peritubular interstitial cells sense oxygen delivery, which makes the kidney the body's oxygen sensor. 15.3 c — type O expresses neither antigen, so both antibodies are present. This is why O is the universal red-cell donor and the universal plasma recipient. 15.4 b — vascular spasm is immediate, the platelet plug forms in seconds, and the fibrin mesh takes minutes. 15.5 Iron-deficiency anemia. Iron limits heme synthesis; developing erythroblasts undergo extra divisions before reaching their hemoglobin threshold, so cells are small and pale. In an adult, occult gastrointestinal blood loss must be considered first — including loss from chronic aspirin or NSAID use. 15.6 Aspirin irreversibly acetylates cyclooxygenase-1, blocking thromboxane A₂ synthesis; clopidogrel blocks the P2Y12 ADP receptor. Platelet activation has redundant pathways, so blocking two independently reduces stent thrombosis more than blocking either alone. 15.7 Diseased kidneys secrete less erythropoietin, so marrow stimulation falls and red cell production declines despite adequate iron. Erythropoietin is the link; shortened red cell survival in uremia and iron handling defects compound it.

16.1 b — two cusps, and the higher-pressure side of the heart. 16.2 b — atrial repolarization is buried within it. 16.3 b — what went in minus what stayed behind. 16.4 c — L-type calcium current sustains depolarization, producing the long refractory period. 16.5 Troponin is a structural protein of cardiac myocytes; its presence in plasma proves myocyte death, which the ECG cannot show. Absence of ST elevation implies the infarct is subendocardial rather than transmural — the inner wall is the last-perfused, first-injured layer. 16.6 Ejection fraction is a ratio, not a volume. A stiff, hypertrophied ventricle fills poorly, so end-diastolic volume is small; ejecting 58% of a small volume gives a small stroke volume, while the high filling pressure required to fill it is transmitted back to the pulmonary veins, producing congestion. Diastole has failed, not systole. 16.7 The cardiac action potential's calcium plateau extends the absolute refractory period to nearly the full duration of contraction, so a second stimulus cannot arrive before relaxation begins. Summation is therefore impossible — which is essential, because a tetanized ventricle cannot fill and would eject nothing.

17.1 b — diastole occupies about two-thirds of the cycle at rest, which is what the weighting reflects. 17.2 c — arterioles are the resistance vessels; their radius is the main adjustable variable in the circuit because resistance varies with the fourth power of radius. 17.3 b — the Starling forces. Filtration dominates at the arteriolar end, reabsorption at the venular end, and the small excess is returned as lymph. 17.4 a — baroreceptors sense stretch; the carotid and aortic bodies are chemoreceptors. 17.5 Pulse pressure 70 mm Hg; MAP ≈ 98 + 23 = 121 mm Hg. Arteriolar dilation lowers systemic vascular resistance; cardiac output would be unchanged by that manoeuvre alone. 17.6 Baroreceptor unloading has produced intense sympathetic outflow: tachycardia, increased contractility, and arteriolar and venous constriction, which raises resistance and preserves venous return. Narrow pulse pressure means stroke volume has fallen and resistance has risen to mask it — compensated shock. Systolic pressure falls only when compensation fails, which it does abruptly. 17.7 Reduced renal perfusion pressure, reduced NaCl delivery to the macula densa, or increased sympathetic tone triggers renin from juxtaglomerular cells (kidney). Renin cleaves angiotensinogen (liver) to angiotensin I, which ACE (pulmonary endothelium) converts to angiotensin II. Angiotensin II constricts arterioles directly, raising resistance; and it stimulates aldosterone (adrenal cortex), which increases distal sodium reabsorption (kidney), raising blood volume and therefore preload and cardiac output.

18.1 a — MHC I is on all nucleated cells and displays intracellular (viral, tumor) peptides. 18.2 c — pentameric IgM; class switching to IgG follows. 18.3 b — fast, non-specific, no memory. 18.4 b — the thoracic duct drains everything except the right upper quadrant of the body. 18.5 Necrotic myocytes release damage-associated molecular patterns; neutrophils clear debris and macrophages phagocytose it and secrete growth factors that recruit fibroblasts. Without this, the infarct would not be structurally sealed and rupture risk would be higher. The same signals drive collagen deposition, so the healed region is non-contractile, non-conducting fibrous scar — healing and scarring here are literally one process. 18.6 IgE bound to mast cells, cross-linked by antigen, degranulating histamine and other mediators. Epinephrine acts on α₁ receptors to constrict arterioles and restore pressure and reduce mucosal edema, and on β₂ receptors to relax bronchial smooth muscle; it also stabilizes mast cells. One drug, two receptor families, both problems. 18.7 Capillary filtration continues normally, but the excess interstitial fluid and the protein that escapes with it can no longer be returned. Interstitial protein accumulates, raising interstitial colloid osmotic pressure, which opposes reabsorption and increases net filtration further. The result is a protein-rich, non-pitting lymphedema that does not resolve with elevation alone.

19.1 b — via central chemoreceptors responding to CSF hydrogen ion. Hypoxic drive becomes significant only below a PO₂ of about 60 mm Hg. 19.2 b — it reduces the collapsing pressure of small alveoli and, because it concentrates as an alveolus shrinks, stabilizes alveoli of unequal size against Laplace's law. 19.3 b — about 98.5%; the dissolved fraction is what a PO₂ measures. 19.4 c — roughly 70%, formed in the erythrocyte by carbonic anhydrase and exported by the chloride shift. 19.5 Airway collapse causes hypoxemia and hypercapnia, which trigger a strong sympathetic surge and an arousal that terminates the apnea. Repeated hundreds of times a night, these surges raise sympathetic tone chronically, impair endothelial function, activate the RAAS, and reset the baroreflex — so pressure remains elevated during the day when the airway is patent. 19.6 Left ventricular filling pressure rises and is transmitted back through the left atrium to the pulmonary veins and capillaries, raising capillary hydrostatic pressure. When it exceeds the plasma colloid osmotic pressure, net filtration into the interstitium exceeds lymphatic clearance; fluid then floods alveoli, where surfactant makes it foam. 19.7 Saturation reports the percentage of hemoglobin binding sites occupied in arterial blood. Delivery is content × flow. Downstream of a stenosed coronary artery, flow can approach zero while every hemoglobin molecule in the systemic arteries remains 96% saturated. Content without flow delivers nothing.

20.1 b — surface area, transit time, and enzyme delivery all peak there. 20.2 b — chief cells secrete pepsinogen; G cells secrete gastrin. 20.3 c — the gallbladder concentrates and stores it. 20.4 b — emulsification is mechanical, not chemical; lipase does the hydrolysis, and emulsification simply multiplies the surface available to it. 20.5 Cyclooxygenase-1 generates prostaglandins that maintain the gastric mucus and bicarbonate layer and mucosal blood flow. Aspirin inhibits COX-1 irreversibly and systemically, so protection falls while acid secretion continues — the defect is defensive, not secretory. 20.6 Without lactase, lactose is not hydrolyzed and remains in the lumen as an osmotically active solute, holding water and causing distension and diarrhea; colonic bacteria ferment it, producing gas and short-chain acids. Osmotic load scales with dose, so small amounts are often tolerated. 20.7 Iron, absorbed in the duodenum, gives a microcytic anemia. Vitamin B₁₂, absorbed in the terminal ileum and requiring intrinsic factor from gastric parietal cells, gives a macrocytic anemia; folate deficiency does the same by the same DNA-synthesis mechanism.

21.1 a — four made, two invested. The large yields require the mitochondrion. 21.2 c — the electron transport chain and ATP synthase are embedded there; the citric acid cycle runs in the matrix. 21.3 b — insulin promotes glycogenesis, lipogenesis, and protein synthesis simultaneously; it is a state signal, not merely a glucose-lowering agent. 21.4 c — the crossover concept: fat dominates at low intensity, carbohydrate above roughly 60–65% of VO₂max. 21.5 Metabolic syndrome; she meets all five criteria (central adiposity, high triglycerides, low HDL, hypertension, impaired fasting glucose). Insulin resistance with visceral adiposity unifies them: excess free fatty acid delivery to the liver drives triglyceride production and lowers HDL, while resistance and its associated sympathetic and RAAS activation raise pressure and glucose. 21.6 Muscle and liver glycogen are depleted. Fat oxidation continues but its maximal ATP production rate is far lower than glycolytic flux, and fat oxidation itself requires a supply of citric-acid-cycle intermediates from carbohydrate. Power output therefore falls to what fat alone can sustain — roughly the intensity of a slow jog. 21.7 Hepatic insulin resistance means the liver does not receive the "fed" signal: gluconeogenesis and glycogenolysis continue despite hyperinsulinemia. Elevated glucagon and free fatty acid flux reinforce it, so fasting glucose rises even though beta cells are secreting maximally.

22.1 b — driven by hydrostatic pressure across a three-layer filtration barrier. 22.2 c — bulk, isosmotic reabsorption; fine control happens distally. 22.3 b — inserted into the apical membrane of collecting duct principal cells. 22.4 b — the NKCC2 cotransporter is the single "engine" of the multiplier; everything else amplifies or exploits what it establishes. 22.5 Creatinine and GFR are related hyperbolically, not linearly. Because the remaining nephrons hyperfiltrate, roughly half of renal function can be lost before creatinine leaves its reference interval; a rise from 0.9 to 1.4 therefore represents a large loss, not a small one. Creatinine also varies with muscle mass, so it overestimates function in a small or elderly patient. 22.6 Furosemide blocks NKCC2 in the thick ascending limb, so sodium and chloride remain in the tubule and much more sodium reaches the distal nephron. There, principal cells reabsorb sodium through ENaC and secrete potassium in exchange down the resulting electrical gradient — amplified by the secondary hyperaldosteronism that volume loss provokes. The potassium is lost distally, not at the site of the blockade. 22.7 Falling cardiac output reduces renal perfusion pressure and baroreceptor stretch. The kidney responds as it would to hemorrhage: renin, angiotensin II, and aldosterone rise, sodium and water are retained, and sympathetic tone increases. The retained volume raises preload, which in a failing ventricle raises filling pressure without improving output, and raises afterload through angiotensin II vasoconstriction. Congestion worsens, output falls further, and the loop tightens.

23.1 b — the LH surge follows an estrogen-driven switch from negative to positive feedback. 23.2 b — Sertoli cells nurse the germ cells; Leydig cells make testosterone. 23.3 b — with some estrogen; progesterone maintains the secretory endometrium. 23.4 b — sperm appear after immune self-tolerance is established, so they must be sequestered. 23.5 Estrogen promotes endothelial nitric oxide production, favoring vasodilation, and favorably shifts the lipid profile by increasing LDL receptor expression and raising HDL. Losing it therefore raises vascular tone and raises LDL — two independent contributions to cardiovascular risk that appear together in the same decade. 23.6 Low energy availability suppresses hypothalamic GnRH pulsatility, so LH and FSH fall and ovarian estrogen production collapses. Estrogen restrains osteoclast activity; without it, resorption exceeds formation and bone density falls — in a young athlete this occurs during the years when peak bone mass should be accruing, so the deficit is permanent. 23.7 Hypothalamic GnRH (pulsatile) → anterior pituitary LH and FSH → testis: LH drives Leydig testosterone, FSH plus intratesticular testosterone drives Sertoli support of spermatogenesis. Exogenous testosterone raises serum levels, which suppress GnRH and LH/FSH. Serum testosterone is high but intratesticular testosterone collapses, and spermatogenesis requires the local concentration, not the systemic one.

24.1 b — the distal third of the tube, within about 24 hours of ovulation. 24.2 c — around day 6–7, via the trophoblast. 24.3 b — sustaining progesterone until the placenta takes over near week 10. It is also what a pregnancy test detects. 24.4 b — bypassing the high-resistance fetal lung; the foramen ovale shunts right atrium to left atrium. 24.5 Preeclampsia. Shallow trophoblastic invasion leaves the spiral arteries incompletely remodeled, so the placenta is underperfused; it releases antiangiogenic factors that produce systemic endothelial dysfunction. The result is generalized vasoconstriction (hypertension) and glomerular endothelial injury (proteinuria) — a systemic disease of placental origin, which is why delivery is the definitive treatment. 24.6 The neural tube closes at the end of the fourth week after fertilization, which is roughly when a first missed period occurs. By the time a test is positive, the window in which folate can influence closure has already passed. 24.7 Hematocrit falls — the physiologic anemia of pregnancy, a dilutional effect rather than a red cell deficit. Cardiac output must rise (mostly by stroke volume, with a modest rate increase) to perfuse the placenta and to carry the same oxygen in more dilute blood; systemic vascular resistance falls in parallel, which is why blood pressure normally drops in the second trimester.

25.1 b — two different alleles at one locus. 25.2 a — males are hemizygous, so a single recessive allele on the X is expressed. 25.3 b — nonsense creates a stop, frameshift alters the reading frame downstream. 25.4 c — many loci of small effect plus environment, which is why they show continuous variation rather than discrete categories. 25.5 Familial hypercholesterolemia is autosomal dominant, usually an LDL receptor defect, with untreated LDL often above 190–250 mg/dL in heterozygotes and premature coronary disease. Its pedigree shows affected individuals in every generation, male and female, with roughly half of each affected person's children affected. Polygenic hypercholesterolemia clusters in families without that vertical pattern, has more modest LDL elevation, and responds more to diet. 25.6 A single A→T substitution in the sixth codon of the β-globin gene replaces glutamate with valine. The hydrophobic valine allows deoxygenated hemoglobin S molecules to polymerize into fibers, which distort the red cell into a rigid sickle shape. Sickled cells adhere to endothelium and obstruct microvessels, producing ischemia and the pain of a vaso-occlusive crisis. 25.7 Heterozygotes make both HbA and HbS. Infected cells sickle preferentially and are cleared early, interrupting the parasite's cycle, while enough normal hemoglobin remains that cells do not sickle under ordinary conditions. Homozygotes have no HbA: polymerization occurs routinely, cells become rigid and are destroyed within 10–20 days rather than 120, and chronic hemolytic anemia results.

26.1 b — elastin fragments and collagen cross-links accumulate. 26.2 b — fast fibers and their motor neurons are lost first, which is why power declines faster than strength and why falls follow. 26.3 a — roughly 8 mL/min per decade after 40, while residual volume rises. 26.4 b — the lens hardens and the ciliary muscle can no longer round it up. 26.5 Glomerular filtration rate falls with age, so renally cleared drugs accumulate; and total body water and lean mass fall while fat rises, changing volumes of distribution — water-soluble drugs reach higher peak concentrations, lipid-soluble drugs have longer half-lives. Serum creatinine may look normal because muscle mass is low, masking both. 26.6 Nervous — slowed proprioceptive conduction and reaction time. Musculoskeletal — type II fiber loss reduces the rapid power needed for a corrective step. Cardiovascular — impaired baroreflex sensitivity produces orthostatic hypotension on standing. Special senses (cataract, vestibular hair cell loss) and medications are equally defensible answers. 26.7 A stiff aorta cannot expand to accommodate the stroke volume, so systolic pressure spikes higher; and it cannot recoil during diastole to sustain pressure, so diastolic pressure falls or stays flat. Pulse pressure therefore widens. This is a compliance problem, not a resistance problem, which is why it responds differently to treatment than the hypertension of middle age.

27.1 c — about two-thirds of total body water; plasma is under 8%. 27.2 b — a range of 0.10 pH units, defended against a continuous acid load. 27.3 b — pH low with a high PCO₂ is a primary respiratory acidosis; bicarbonate is barely moved, so it is acute and uncompensated. 27.4 b — hyperkalemia gives the peaked T waves; the pair is worth teaching together. 27.5 Loop blockade delivers a large sodium load distally, where aldosterone-driven sodium reabsorption exchanges for potassium and hydrogen secretion — so potassium and acid are lost together. Volume contraction concentrates the remaining bicarbonate and stimulates further aldosterone, and hypokalemia itself shifts hydrogen into cells and enhances renal bicarbonate reabsorption. One drug, three converging routes to the same alkalosis. 27.6 Primary metabolic acidosis: pH is low and bicarbonate is low. Compensation is present — the PCO₂ of 30 is below normal, so the lungs are hyperventilating to lower carbonic acid. Compensation is partial, since pH has not returned to 7.35. 27.7 The lungs control PCO₂ — the volatile acid — by adjusting alveolar ventilation. They act within minutes and can change pH quickly, but they cannot excrete fixed acid such as ketoacids, lactate, or sulfate. The kidneys control bicarbonate reabsorption and generation and secrete fixed acid buffered by phosphate and ammonia; they can excrete the daily fixed acid load completely, but they take hours to days.

28.1 b — reduced renal perfusion is read as volume depletion, and the RAAS responds as though it were. 28.2 b — the variable the whole second half of the book converges on. 28.3 b — the fast electrical controller and the slow chemical one. 28.4 b — contractility is not the defect; filling is. Volume reduction and afterload control lower filling pressures without impairing an already adequate ejection fraction. 28.5 Weight rises (retained sodium and water, roughly 1 kg per litre); jugular venous pressure rises (higher right atrial pressure); crackles appear (pulmonary capillary hydrostatic pressure exceeds plasma colloid osmotic pressure); exercise tolerance falls (congestion plus inability to raise stroke volume). Serum creatinine may fall slightly, because stopping the diuretic increases plasma volume and renal perfusion — which is the trap in the question: an improving creatinine here does not mean improving kidneys. 28.6 Any three: lower resting and submaximal heart rate through increased vagal tone and reduced sympathetic drive, so rate–pressure product falls; increased skeletal muscle capillary density and mitochondrial content, so the same work extracts more oxygen at lower cardiac output; reduced systemic vascular resistance through improved endothelial nitric oxide function, lowering afterload; and improved insulin sensitivity, reducing the metabolic drivers of progression. 28.7 A defensible chain: circadian disruption (nervous) flattens the cortisol rhythm (endocrine) → cortisol and short sleep promote visceral adiposity and insulin resistance (metabolic) → hyperinsulinemia and sympathetic activation raise sodium retention and vascular tone (renal, cardiovascular) → sustained hypertension raises left ventricular afterload, producing concentric hypertrophy and diastolic dysfunction (cardiac) → dyslipidemia and endothelial dysfunction accelerate coronary atherosclerosis, culminating in infarction and scar (cardiac, immune) → reduced cardiac output and elevated venous pressure lower renal perfusion and raise renal venous pressure (renal) → RAAS activation retains sodium, raising preload and worsening congestion → chronic glomerular hypertension and hypoperfusion reduce GFR. Grade for the number of correctly directed links, not for the number of nouns.

Cardiovascular: coronary narrowing → myocyte ischemia → troponin release (cell, tissue). Nervous: sympathetic activation → tachycardia, vasoconstriction, diaphoresis. Integumentary: cutaneous vasoconstriction → pallor and coolness — a low-priority bed sacrificed. Respiratory: rate up to maximize loading. The harmful compensation: tachycardia and raised pressure increase myocardial oxygen demand and shorten diastolic filling time for the coronaries, so the correction worsens the deficit. Full marks require naming that loop.

Immune: pathogen-associated molecular patterns → cytokine release → widespread nitric oxide production. Cardiovascular: profound vasodilation lowers systemic vascular resistance, so pressure falls despite a raised cardiac output — hence warm skin, unlike hypovolemic shock. Renal: low perfusion pressure → GFR falls → oliguria and rising creatinine. Metabolic: inadequate tissue oxygen delivery → anaerobic metabolism → lactate. Fever is a set-point shift (Chapter 1), not a failure.

Endocrine: absolute insulin deficiency → unrestrained lipolysis → hepatic ketogenesis → fixed acid load. Renal: glucose exceeds the transport maximum → osmotic diuresis → water and electrolyte loss → weight loss and hypovolemia. Respiratory: Kussmaul breathing lowers PCO₂ to compensate. Potassium: serum K⁺ is high because acidosis and insulin lack shift it out of cells, while total body potassium is severely depleted — which is why it falls dangerously once insulin is given. That distinction is the point of the case.

Muscular: sustained compression → ischemic myocyte necrosis → release of potassium, myoglobin, CK, and phosphate. Cardiovascular/nervous: hyperkalemia depolarizes the resting membrane, inactivates sodium channels, and produces asystole. Renal: myoglobin is filtered, precipitates in tubules, and causes pigment nephropathy; hypovolemia from third-spacing compounds it. Fluid: massive fluid sequestration into damaged muscle. Note the timing — the arrest often follows reperfusion, when the contents reach the circulation.

Cardiac: stiff ventricle → high filling pressure → pressure transmitted to pulmonary veins. Renal: reduced effective perfusion → RAAS activation → sodium and water retention → 1 kg per litre of weight. Respiratory: raised pulmonary capillary hydrostatic pressure → filtration exceeds lymphatic clearance → interstitial then alveolar edema; recumbency redistributes venous return centrally, hence orthopnea. Lymphatic: pulmonary lymphatics initially compensate. The paradox: diuresis lowers renal perfusion further before congestion relief improves it — a correctly directed short-term worsening.

Respiratory: airflow obstruction → alveolar hypoventilation and V/Q mismatch → CO₂ retention and hypoxemia → respiratory acidosis. Renal: chronic bicarbonate retention partially compensates — the elevated HCO₃⁻ dates the problem as chronic. Blood: chronic hypoxemia → renal EPO release → secondary polycythemia → raised viscosity. Cardiovascular: chronic hypoxic pulmonary vasoconstriction → pulmonary hypertension → right ventricular failure (cor pulmonale) → systemic venous congestion and peripheral edema.

Renal/endocrine: prolonged exercise stimulates non-osmotic ADH release, so free water cannot be excreted. Fluid: intake exceeds sweat losses — the weight gain is diagnostic — so extracellular osmolality falls. Nervous: water moves osmotically into brain cells; cerebral edema produces confusion and can produce seizure. Integumentary: sweat is hypotonic to plasma, so sodium losses alone do not explain the number; the dominant mechanism is dilution. Treatment is hypertonic saline, not more fluid.

Digestive: prostaglandin-depleted gastric mucosa ulcerates and bleeds; luminal blood is digested and absorbed as protein, raising urea production — hence a high BUN with a normal creatinine. Blood: acute loss plus impaired platelet function from dual antiplatelet therapy. Cardiovascular: baroreflex-driven tachycardia and vasoconstriction, narrow pulse pressure. Renal: reduced perfusion → sodium and urea reabsorption rise, amplifying the BUN further.

Predisposing: skeletal — estrogen loss → osteoclast excess → trabecular thinning, so a low-energy fall fractures. Nervous — slowed reaction time and proprioceptive loss. Cardiovascular — impaired baroreflex → orthostatic hypotension. Special senses and medications are equally valid. Recovery: muscular — sarcopenia and rapid disuse atrophy; and nervous/metabolic — reduced cognitive reserve plus anesthesia and opioids producing delirium. Add immune (healing) and skeletal (remodeling under load) for a fuller answer.

Developmental: incomplete spiral artery remodeling → placental hypoperfusion → release of antiangiogenic factors. Cardiovascular: systemic endothelial dysfunction → vasoconstriction → hypertension. Renal: glomerular endothelial injury (endotheliosis) → proteinuria. Blood: endothelial injury activates and consumes platelets → thrombocytopenia; microangiopathic hemolysis and hepatic involvement complete the HELLP picture. One endothelial lesion, four organ manifestations.

Immune: antigen cross-links IgE on mast cells → degranulation → histamine, tryptase, leukotrienes. Cardiovascular: vasodilation and increased capillary permeability → distributive shock. Respiratory: bronchial smooth muscle constriction and laryngeal edema. Integumentary: dermal vasodilation and wheal formation. Epinephrine: α₁ vasoconstriction restores pressure and reduces airway edema; β₂ relaxes bronchial smooth muscle; β₁ supports cardiac output; and it stabilizes mast cells.

Nervous: the lesion is above the thoracolumbar sympathetic outflow, so sympathetic tone is lost below it while vagal (cranial) parasympathetic tone is intact. Cardiovascular: unopposed vagal tone → bradycardia; loss of vasomotor tone → vasodilation → neurogenic shock with warm, dry skin. Urinary: loss of descending control → detrusor areflexia and retention. Integumentary: no sweating and no vasoconstriction below the lesion → poikilothermia. Contrast explicitly with hypovolemic shock, where the heart rate is high.

Endocrine: excess T3/T4 → increased transcription of Na⁺/K⁺-ATPase and of β₁-adrenergic receptors. Metabolic: raised basal metabolic rate → heat production exceeds dissipation → fever without infection. Cardiovascular: increased β-receptor density amplifies catecholamine effect → tachycardia, increased contractility, atrial fibrillation, and a widened pulse pressure from reduced peripheral resistance. Nervous: increased sympathetic responsiveness → tremor, agitation. A suppressed TSH confirms the problem is primary and the feedback loop is intact.

Blood: reduced EPO production → normocytic anemia. Endocrine/skeletal: reduced 1α-hydroxylation → low calcitriol → reduced intestinal calcium absorption → hypocalcemia; reduced phosphate excretion → hyperphosphatemia, which further lowers ionized calcium and raises FGF23. Both drive secondary hyperparathyroidism → sustained PTH → high bone turnover and renal osteodystrophy. Cardiovascular: calcium–phosphate product favors vascular calcification, which is why these patients die of cardiac disease rather than of uremia.

Integumentary/cardiovascular: heat production exceeds dissipation; skin blood flow and cardiac output compete with muscle for a contracting plasma volume, and high humidity defeats evaporative loss. Nervous: hypothalamic dysfunction and direct thermal neuronal injury → confusion. Muscular: thermal and ischemic myocyte injury → rhabdomyolysis. Renal: myoglobin plus hypovolemia → acute kidney injury. Blood: endothelial injury → disseminated intravascular coagulation. Cooling rate, not any drug, determines outcome — the mechanism explains the treatment.

1. Sodium and chloride stay in the tubule; the medullary gradient collapses, so ADH cannot concentrate urine. Large diuresis, distal sodium delivery rises, potassium and hydrogen are lost distally → hypokalemic metabolic alkalosis and volume contraction. 2. PTH falls to zero. Bone resorption, distal renal calcium reabsorption, and calcitriol synthesis all stop → ionized calcium falls within hours → neuromuscular hyperexcitability, perioral tingling, carpopedal spasm, laryngospasm. Phosphate rises. 3. Plasma colloid osmotic pressure falls, so capillary reabsorption falls and net filtration rises everywhere → generalized edema and ascites. Effective circulating volume falls → RAAS activation → sodium retention that worsens the edema. 4. Alveolar surface tension rises; small alveoli collapse into large ones (Laplace), work of breathing rises steeply, compliance falls, and V/Q mismatch produces hypoxemia refractory to oxygen. This is neonatal and acute respiratory distress syndrome. 5. Resting heart rate rises to the SA node's intrinsic rate of about 100/min. Heart rate variability collapses, the diving and baroreflex bradycardias are lost, and the rate can no longer be slowed rapidly. 6. Conduction velocity falls from tens of metres per second to about one; conduction may block entirely. Weakness, loss of the deep tendon reflex served by that nerve, and — because large myelinated fibers go first — loss of proprioception and vibration before pain. 7. Sodium and potassium gradients dissipate. Resting potentials depolarize and excitable tissue becomes inexcitable; secondary active transport (glucose, amino acid, calcium extrusion) fails; cells swell osmotically and lyse. This is the final common path of ischemic cell death. 8. Sodium retention raises extracellular volume and pressure — then aldosterone escape occurs: rising pressure causes pressure natriuresis and atrial natriuretic peptide release, so volume plateaus. Potassium and hydrogen loss continue, giving persistent hypokalemia and metabolic alkalosis with hypertension but without gross edema. 9. Saturation is a percentage of available binding sites, so it is normal while oxygen content is halved. Delivery falls; compensations are increased cardiac output and a rightward shift of the dissociation curve via 2,3-BPG. The patient is hypoxic with a reassuring pulse oximeter — the trap of Chapter 22. 10. Longitudinal growth stops permanently while appositional (width) growth continues → short stature with normal proportions of thickness. The commonest cause is premature exposure to sex steroids, which is why precocious puberty produces a tall child and a short adult.