Renal Physiology and Regulation

•    Glomerular Filtration Rate (GFR)

o    GFR ≈ 120 mL/min; represents the volume of plasma filtered per minute by both kidneys.

o    Controlled by afferent/efferent arteriolar tone and glomerular capillary pressure.

o    ↓ GFR seen in hypoperfusion, renal artery stenosis, or intrinsic renal disease.

o    Estimation via serum creatinine (affected by muscle mass) and equations (e.g. MDRD, CKD-EPI).

•    RAAS (Renin–Angiotensin–Aldosterone System)

o    Triggered by low renal perfusion, low sodium, or sympathetic stimulation.

o    Renin from JG cells converts angiotensinogen → angiotensin I → (ACE) angiotensin II.

o    Angiotensin II: systemic vasoconstriction, efferent arteriole constriction, stimulates aldosterone.

o    Aldosterone: from adrenal cortex; ↑ Na⁺ reabsorption and K⁺ secretion in DCT/CD.

•    Tubular Function Breakdown

o    Proximal Convoluted Tubule (PCT):

    Reabsorbs ~65% of filtered Na⁺ and water, all glucose and amino acids, most HCO₃⁻.

    Target for carbonic anhydrase inhibitors (e.g. acetazolamide).

o    Loop of Henle (LoH):

    Descending limb: water permeable, passive reabsorption, concentrates filtrate.

    Thick ascending limb: impermeable to water; active reabsorption of Na⁺, K⁺, Cl⁻ via NKCC2.

    Site of action of loop diuretics (e.g. furosemide).

o    Distal Convoluted Tubule (DCT):

    Further Na⁺ and Cl⁻ reabsorption; site of thiazide action.

    Calcium reabsorption under PTH control.

o    Collecting Duct (CD):

    Aldosterone increases Na⁺ reabsorption, K⁺ and H⁺ secretion.

    ADH (vasopressin) promotes water reabsorption by inserting aquaporins.

•    ADH (Antidiuretic Hormone)

o    Synthesised in hypothalamus, stored/released from posterior pituitary.

o    Released in response to ↑ plasma osmolality or ↓ volume (e.g. haemorrhage).

o    Acts on V2 receptors in collecting duct → aquaporin insertion → concentrated urine.

o    Inhibited in diabetes insipidus (cranial or nephrogenic).

•    Urea and Creatinine

o    Urea: produced from protein metabolism; reabsorbed passively in PCT.

    Rises in hypovolaemia or upper GI bleeding.

o    Creatinine: from muscle metabolism; filtered by glomerulus, not reabsorbed.

    ↑ with renal dysfunction, but influenced by age, sex, and muscle mass.

    Used to calculate eGFR; eGFR less accurate in AKI or extremes of body habitus.