Renal Physiology – Part 1 Study Notes

Functions of the Kidney

• Excretion of metabolic waste/toxins:

  • Urea (amino acid metabolism)

  • Creatinine (muscle breakdown)

  • Uric acid (nucleic acid breakdown)

  • Bilirubin (hemoglobin breakdown)

• Water & electrolyte balance (adjusts to intake changes)

• Arterial pressure regulation:

  • Short-term: Renin–angiotensin system

  • Long-term: Sodium & water balance

• Acid–base balance: excretes acids, regulates buffers

• Erythropoiesis regulation: secretes erythropoietin → RBC production

• Hormones & glucose: Vitamin D activation, gluconeogenesis

Anatomy & Filtration

• Glomerulus: capillary network at start of nephron → filtrate enters Bowman’s capsule

• Filtrate = water + solutes (no proteins, protein-bound solutes, cells, or most negatively charged molecules)

• Blood supply: Afferent arteriole → glomerulus → efferent arteriole (unlike typical venules)

• ~1 million nephrons per kidney (non-regenerative if destroyed)

Excretion = Filtration + Secretion – Reabsorption

• Filtration: glomerular capillaries → Bowman’s capsule

• Reabsorption: nephron → blood

• Secretion: peritubular capillaries → renal tubules

Urinary Tract

• Bladder: smooth muscle storage chamber

• Ureters: drain urine into bladder

• Urethra: exits bladder; innervated by sympathetic & parasympathetic nerves

Glomerular Filtration Rate (GFR)

• Definition: Flow rate of filtered fluid through kidneys; indicator of renal function (important for drug dosing)

• Normal: 125 mL/min (~180 L/day)

• Renal blood flow (RBF): ~1100 mL/min (~22% CO)

• Renal plasma flow: RBF × (1 – hematocrit) ≈ 660 mL/min

• Filtration fraction: GFR / RPF ≈ 20%

• Reabsorption: ~124 mL/min → net urine output ≈ 1 mL/min

Determinants of GFR

• Hydrostatic pressure

• Oncotic pressure

• Causes of ↓ GFR:

  • Renal disease/diabetes (membrane damage)

  • Hypotension (↓ hydrostatic pressure)

  • ↑ resistance in afferent arteriole (↓ flow in; e.g., vasopressors, sympathetic tone)

  • ↓ resistance in efferent arteriole (blood leaves too quickly; low Ang II)

  • ↑ plasma oncotic pressure (opposes filtration)

  • ↑ Bowman’s capsule pressure (e.g., obstruction/stone)

Autoregulation

• Maintains constant RBF & GFR despite MAP changes (70–170 mmHg)

• Mechanisms:

  • Tubuloglomerular feedback (macula densa senses NaCl in distal tubule)

  • Adjusts afferent/efferent resistance

  • Renin release from juxtaglomerular cells

• Net effect: as MAP ↑ → urine output ↑ (RBF & GFR constant)

Clearance

• Definition: volume of plasma completely cleared of a substance per unit time

• Theoretical concept → substance passes repeatedly until cleared

• Example: If [substance] = 1 mg/mL in plasma & 1 mg/min excreted → clearance = 1 mL/min

Creatinine & GFR

• Creatinine: freely filtered, slight secretion → good approximation of GFR

• Methods:

  • 24-hour urine collection → precise Cr clearance

  • Serum creatinine (inverse relationship with GFR)

• Equations:

  • Cockcroft–Gault (older, still used for drug dosing)

  • MDRD & CKD-EPI (preferred in modern practice)

Clinical note: Drugs with renal clearance require dose adjustment if creatinine clearance is low.