(a) Using a well labelled diagram, trace the taste pathway from circumvallate papillae of tongue to the cerebral cortex. 15…

(a) Taste pathway

The taste pathway from circumvallate papillae is a special visceral afferent (SVA) sequence. Taste buds in circumvallate papillae contain gustatory receptor cells (type II for sweet, umami and bitter; type III for sour) that transduce sweet, umami, bitter, sour and salty stimuli. Afferent fibres from these buds enter the glossopharyngeal nerve (CN IX), whose cell bodies lie in the petrosal (inferior glossopharyngeal) ganglion. In the medulla, fibres ascend in the solitary tract and synapse in the rostral nucleus solitarius. Second-order neurons ascend largely ipsilaterally in the central tegmental tract (in primates they bypass the pontine taste relay present in rodents) to the parvocellular part of the ventral posteromedial (VPMpc) nucleus of the thalamus. Collaterals from the nucleus solitarius also reach the salivatory nuclei and dorsal vagal nucleus for gustatory reflexes (salivation, gastric secretion), and the hypothalamus and amygdala for the affective component of taste. Third-order thalamocortical fibres reach the primary gustatory area in the anterior insular cortex and, for flavour integration, the orbitofrontal cortex. The labelled diagram shows: circumvallate papilla → taste bud → type III cell → CN IX → petrosal ganglion → solitary tract → nucleus solitarius → ipsilateral central tegmental tract → VPM → insular cortex → orbitofrontal cortex.

(b)(i) Renal tubular function tests

Five tests assess tubular function by measuring what tubules reabsorb, secrete or acidify. (1) Urine pH and PCO2 gap test: acetazolamide causes bicarbonaturia; a widened urine–blood PCO2 gap in the alkaline urine indicates intact distal acidification, while a small gap suggests distal tubular acidification failure. (2) Urine concentrating ability: Uosm/Posm and free-water clearance (CH2O) test ADH-dependent water reabsorption in collecting ducts; low Uosm in dehydration indicates impaired aquaporin-2/urea handling. (3) Urinary acidification (ammonium chloride loading test): after oral NH4Cl 0.1 g/kg, urine pH should fall below 5.3 with rising NH4+ and titratable acid; failure to acidify despite systemic acidosis indicates distal (type 1) renal tubular acidosis, while a normal response with bicarbonate wasting points to proximal (type 2) RTA. The urine anion gap (Na+ + K+ − Cl−) is a bedside surrogate of NH4+ excretion: negative is normal, positive suggests distal RTA. (4) Renal glycosuria/aminoaciduria: glucose or amino acids in urine despite normal plasma levels indicate proximal tubular reabsorptive defects, e.g. SGLT2 or amino acid transporter failure. (5) PAH clearance and TmPAH: para-aminohippurate is filtered and almost completely secreted by the proximal tubule, so its clearance at low plasma levels estimates effective renal plasma flow (about 600 mL/min), while the maximal secretory rate (TmPAH, about 80 mg/min) at high plasma levels measures proximal secretory capacity; a reduced TmPAH indicates loss of functioning tubular mass. Other useful tests are the fractional excretion of sodium (FENa <1% in prerenal azotaemia, >2% in acute tubular necrosis), the tubular maximum for phosphate (TmP/GFR), and urinary low-molecular-weight proteins (β2-microglobulin, retinol-binding protein) and N-acetyl-β-glucosaminidase as markers of proximal tubular injury. Glomerular filtration itself is measured separately by inulin or creatinine clearance.

(b)(ii) Biotin

Biotin is a water-soluble vitamin covalently attached to lysine residues of carboxylases as biocytin; the biotin moiety carries activated CO2. It is essential for pyruvate carboxylase in gluconeogenesis, acetyl-CoA carboxylase in fatty acid synthesis, propionyl-CoA carboxylase in odd-chain fatty acid/propionate metabolism to succinyl-CoA, and 3-methylcrotonyl-CoA carboxylase in leucine catabolism. Deficiency (raw-egg diets, long-term parenteral nutrition, anticonvulsants, biotinidase or holocarboxylase synthetase defects) causes dermatitis, alopecia, conjunctivitis, hypotonia, seizures, lactic and organic acidosis. Avidin, a biotin antagonist in raw egg white, binds biotin with Kd ~10^-15 M, outcompetes carboxylase biotin and causes deficiency. The avidin/streptavidin-biotin interaction is used in ELISA, immunohistochemistry and molecular diagnostics; biotinidase deficiency screening uses biotinidase activity and biotin metabolites to detect recycling defects.

(c)(i) Cardiac output

Cardiac output (CO) is the volume of blood pumped by the ventricle per minute, CO = HR × SV (about 5 L/min at rest, 70/min × 70 mL). In normal adults it is regulated by intrinsic Frank-Starling mechanism: increased end-diastolic volume/pressure stretches myocardium, increasing stroke volume via length-tension relationship. Extrinsic regulation includes sympathetic and parasympathetic autonomic control via baroreceptors, changes in contractility, heart rate, preload, afterload, and hormones such as angiotensin II, ADH and catecholamines. Cardiac Index is CO divided by body surface area, normally 2.5–4.0 L/min/m². Cardiac Reserve is the capacity to increase CO above the resting level, expressed as the difference between maximal and resting CO (about 15–20 L/min, i.e. 300–400% above rest, and up to 30–35 L/min in trained athletes); it is made up of heart-rate reserve and stroke-volume reserve, and is reduced in heart failure, where symptoms appear on exertion.

(c)(ii) Systemic vascular resistance

SVR is the resistance to flow in the systemic circulation, SVR = (MAP − CVP)/CO × 80 dyn·s·cm⁻⁵. Its determinants are vessel radius, vessel length and blood viscosity. Radius is dominant because resistance varies inversely with radius to the fourth power; it is regulated by local metabolites, endothelial factors and sympathetic tone. Length is fixed in adults, while viscosity depends on haematocrit and plasma proteins (polycythaemia raises and anaemia lowers SVR). Per Poiseuille's law, R = 8ηL/πr⁴, and the arterioles, the main resistance vessels, account for most of SVR; the normal value is about 800–1,200 dyn·s·cm⁻⁵.