6.2 Renal, Endocrine and Gastrointestinal Physiology

Renal Physiology

The functional unit is the nephron. Roughly 20% of renal plasma flow is filtered at the glomerulus, giving a normal glomerular filtration rate of about 90 to 120 mL/min/1.73 m². Filtration depends on the balance between glomerular hydrostatic pressure and plasma oncotic pressure across a barrier of fenestrated endothelium, basement membrane and podocyte slit diaphragms.

The renin-angiotensin-aldosterone system is the principal long-term regulator of blood pressure. Reduced renal perfusion triggers renin release from juxtaglomerular cells; renin cleaves angiotensinogen to angiotensin I; angiotensin-converting enzyme converts this to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release and sodium retention. ACE inhibitors block this pathway and cause a dry cough through bradykinin accumulation, which patients sometimes report to the dentist as a throat problem.

Kidney failure matters in dentistry because it produces anaemia from reduced erythropoietin, bleeding tendency from uraemic platelet dysfunction, renal osteodystrophy from failed vitamin D activation, and impaired clearance of renally excreted drugs.

Endocrine Physiology

Hormones act through three broad receptor mechanisms: cell-surface G-protein-coupled receptors (for example PTH), cell-surface tyrosine kinase receptors (insulin), and intracellular nuclear receptors for lipid-soluble hormones (steroids, thyroid hormone, calcitriol).

Insulin and glucose. Insulin from pancreatic beta cells promotes glucose uptake through GLUT4 transporters in muscle and adipose tissue, glycogen synthesis and lipogenesis. Glucagon from alpha cells opposes it. Normal fasting plasma glucose is 4.0 to 5.9 mmol/L. The counter-regulatory response to hypoglycaemia is glucagon, then adrenaline, then cortisol and growth hormone — which is why a patient on a beta blocker may lose the adrenergic warning symptoms of hypoglycaemia.

The hypothalamic-pituitary-adrenal axis. CRH from the hypothalamus drives ACTH from the anterior pituitary, which drives cortisol from the adrenal cortex. Cortisol exerts negative feedback at both levels. Exogenous corticosteroid suppresses the axis, so a patient on long-term steroid may be unable to mount a stress response — the basis of adrenal crisis.

Thyroid hormone. TSH drives T4 and T3 synthesis. Thyrotoxicosis raises the risk of arrhythmia and increases sensitivity to adrenaline; untreated severe hypothyroidism increases sensitivity to sedatives and central nervous system depressants.

Gastrointestinal Physiology

• Gastric secretion occurs in cephalic, gastric and intestinal phases. Parietal cells secrete hydrochloric acid through the H+/K+-ATPase proton pump, the target of proton pump inhibitors, driven by histamine at H2 receptors, gastrin and acetylcholine. Resting gastric pH is 1.0 to 2.0, far below the critical pH for enamel of 5.5.
• Intrinsic factor, also from parietal cells, is required for ileal vitamin B12 absorption. Loss of parietal cells in pernicious anaemia causes B12 deficiency, which presents orally as glossitis, angular cheilitis and recurrent oral ulceration.
• Iron is absorbed in the duodenum and proximal jejunum, and folate in the jejunum. Coeliac disease damages exactly this territory, which is why it presents with the haematinic deficiency triad that a dentist may detect before a physician does.
• The lower oesophageal sphincter is a physiological rather than anatomical sphincter. Its incompetence causes reflux and therefore intrinsic dental erosion, and it is also why a heavily sedated or supine patient is at risk of aspiration.

Exam link. A patient with recurrent aphthous ulceration, angular cheilitis and a smooth red tongue is a haematinic screening question, and the underlying physiology — where iron, folate and B12 are absorbed and what is required for each — is what makes coeliac disease and pernicious anaemia the two expected answers.

Applying Systems Physiology to Prescribing

The renal, endocrine and gastrointestinal systems are examined largely through drug handling. Glomerular filtration rate falls with age and with chronic kidney disease, and any drug cleared predominantly by the kidney accumulates when it falls. In dentistry the practical consequences are that non-steroidal anti-inflammatory drugs should be avoided in significant renal impairment because they reduce afferent arteriolar vasodilatation and can precipitate acute kidney injury, and that dose reduction is required for renally excreted antimicrobials.

Endocrine physiology is examined through the stress response. Cortisol secretion follows a diurnal rhythm peaking in the early morning and rises sharply with physiological stress; a patient on long-term systemic corticosteroids has a suppressed hypothalamic–pituitary–adrenal axis and may be unable to mount that rise, which is the mechanism underlying adrenal crisis. Thyroid hormone excess increases sensitivity to catecholamines, which is why an untreated thyrotoxic patient is a cautioned group for adrenaline-containing local anaesthetic.

Gastrointestinal physiology underpins absorption and first-pass metabolism. Oral drugs absorbed from the small intestine pass through the portal circulation and are metabolised by the liver before reaching the systemic circulation, whereas sublingual and buccal routes bypass first-pass metabolism — the reason glyceryl trinitrate and buccal midazolam act within minutes.