Renal physiology

Clearance

• Clearance = (urine concentration × urine flow) ÷ plasma concentration: the volume of plasma completely cleared of a substance per minute.
• Inulin is filtered but neither secreted nor reabsorbed, so its clearance equals GFR and is the best measure of GFR: 60 mg/mL × 2 mL/min ÷ 1 mg/mL = 120 mL/min.
• Creatinine clearance is the practical clinical estimate (normal about 95–140 mL/min); it slightly overestimates GFR because some creatinine is secreted. Example: 8 mmol/L × 1.5 L ÷ 0.1 mmol/L = 120 L/day, about 83 mL/min.
• Clearance above inulin means the substance is filtered and secreted (PAH, many drugs); below inulin means net reabsorption. Order: PAH > creatinine > inulin > urea > glucose (zero).
• PAH clearance gives effective renal plasma flow (about 650 mL/min). Renal blood flow = RPF ÷ (1 − haematocrit): 600 ÷ 0.6 = 1000 mL/min.
• Volume of distribution by indicator dilution = amount given ÷ concentration reached: 100 mg giving 0.01 mg/mL means a 10 L space.

Filtered load and Tmax

• Filtered load = GFR × plasma concentration; excretion = filtered load − reabsorption (+ secretion).
• Example: GFR 125 mL/min, Tm 125 mg/min, plasma 200 mg/100 mL (2 mg/mL): filtered 250 mg/min, reabsorbed 125 mg/min (capped at Tm), excreted 125 mg/min.
• Glucose is reabsorbed in the proximal tubule by secondary active transport with Na⁺ (SGLT2, then SGLT1); the Na⁺ gradient is made by the basolateral Na⁺/K⁺-ATPase, and glucose leaves by GLUT2. Glycosuria appears when the filtered load exceeds Tmax (renal threshold about 10 mmol/L, 180 mg/dL) or GFR rises (pregnancy). SGLT2 inhibitors make the urinary tract fill with FDG on PET.

Glomerular filtration and autoregulation

• Filtration falls if Bowman's space pressure rises (obstruction).
• Prostaglandins dilate the afferent arteriole; angiotensin II constricts the efferent. NSAIDs with ACE inhibitors and diuretics remove both supports and GFR collapses.
• Autoregulation keeps RBF and GFR steady between a mean arterial pressure of about 80 and 180 mmHg by two mechanisms:
• Myogenic: stretch of the afferent arteriole makes it contract.
• Tubuloglomerular feedback: the macula densa senses NaCl delivery to the distal tubule. High delivery (high GFR) releases adenosine, which constricts the afferent arteriole and lowers GFR; low delivery dilates it and releases renin from juxtaglomerular cells.
• After major blood loss, GFR and urine output fall; the juxtaglomerular apparatus (macula densa and JG cells) restores GFR through renin, angiotensin II (efferent constriction) and afferent dilation.
• Pregnancy: GFR rises about 50%, so creatinine and urate fall. Physiological hydronephrosis (right more than left) is caused mainly by progesterone relaxing ureteric smooth muscle, helped by the enlarging uterus compressing the right ureter at the pelvic brim.

What each segment does

• Water reabsorption: most water (65%) is reabsorbed in the proximal tubule whether or not ADH is present; the ADH-regulated water is taken up in the collecting duct.
• Passive reabsorption: water, urea (half the filtered load, following water) and chloride move passively.
• Potassium: urinary K⁺ rises when distal secretion rises: aldosterone, high distal Na⁺ delivery and flow (loop and thiazide diuretics), alkalosis. Acidosis and low aldosterone reduce it. Because ECF K⁺ sets the resting membrane potential, a rise in extracellular potassium has the most dangerous effect on the heart.
• Countercurrent multiplier (loop of Henle) builds the hyperosmotic medulla; the vasa recta, straight vessels alongside the loops, act as a countercurrent exchanger that prevents washout.
• Acute tubular necrosis: damaged tubules cannot concentrate or retain sodium (urine osmolality about 300, FENa above 2%).
• Uric acid stones form in persistently acidic urine (pH below 5.5), as in gout, because uric acid is poorly soluble when protonated; they are radiolucent on X-ray but visible on non-contrast CT. Alkalinising the urine dissolves them.

ADH and water balance

• ADH is made in the supraoptic and paraventricular nuclei and carried down the hypothalamo-neurohypophyseal tract to the posterior pituitary. Injury to this tract (sellar fracture, surgery) causes cranial DI: dilute urine (90 mOsm/kg) with high plasma osmolality that concentrates after desmopressin. The anterior pituitary depends on portal blood instead.
• Release is triggered by a rise in osmolality (most sensitive) or a fall in volume. Non-osmotic release: pain, surgery, nausea, heart failure. Alcohol inhibits it.

Hyponatraemia

• After surgery, ADH and aldosterone rise for 24–48 hours; hypotonic fluids then risk hyponatraemia.

Fluid compartments and infusions

• Total body water is about 60% of weight: two-thirds intracellular, one-third extracellular (ECF = interstitial fluid about three-quarters plus plasma about one-quarter, with a small transcellular part).
• Plasma osmolality = 2Na⁺ + glucose + urea (mmol/L), about 285–295 mOsm/kg.

Micturition

• Storage: sympathetic (T10–L2) acts on beta-3 receptors to relax the detrusor; mirabegron, a beta-3 agonist, treats overactive bladder without antimuscarinic dry mouth (it can raise blood pressure). Alpha-1 receptors close the bladder neck; the pudendal nerve keeps the external sphincter shut.
• Voiding: parasympathetic pelvic splanchnic nerves (S2–4) contract the detrusor through M3 receptors. The reflex is self-reinforcing once started.
• The pontine micturition centre co-ordinates detrusor contraction with sphincter relaxation; the frontal cortex gives voluntary control.
• Ureteric peristalsis starts from pacemaker cells in the renal pelvis, so it works in a denervated transplant.

Renal tracers

Remember Clearance above inulin means secretion; below inulin means reabsorption. Inulin measures GFR best; creatinine estimates it.

Exam trap Saline expands only the extracellular space; 5% dextrose behaves as pure water and ends up mostly inside cells.

Exam trap The macula densa constricts the afferent arteriole when distal NaCl is high; it does not act on the efferent arteriole.

How FCPS asks about this

• Best measure of GFR and RPF: inulin clearance and PAH clearance; creatinine clearance is the clinical estimate.
• Filtered load: GFR × plasma concentration; excretion is filtered load minus Tm once saturated.
• Glucose reabsorption: secondary active transport with Na⁺ (SGLT2).
• Tubuloglomerular feedback: macula densa senses NaCl and adjusts afferent arteriolar tone.
• Straight vessels that keep the medullary gradient: vasa recta (countercurrent exchange).
• Polyuria after sellar fracture, corrected by desmopressin: hypothalamo-neurohypophyseal tract injury.
• Mirabegron receptor: beta-3 adrenoceptor.