Renal Physiology

Most people think of the kidneys mainly as waste-disposal organs — making urine to remove toxins. That's part of the story, but the kidneys are far more sophisticated than this. They are the body's master regulators of the internal environment. The kidneys are responsible for: 1. Excreting metabolic waste — urea (from protein metabolism), creatinine (from muscle), uric acid, bilirubin metabolites, and many drugs and their breakdown products 2. Regulating blood volume and blood pressure — by controlling how much water and sodium they retain or excrete 3. Regulating the electrolyte composition of blood — sodium, potassium, chloride, bicarbonate, calcium, phosphate — all tightly controlled 4. Maintaining acid-base balance — the kidneys can excrete H⁺ ions and reabsorb bicarbonate to keep blood pH at 7.35–7.45 5. Producing hormones: - Erythropoietin (EPO) — stimulates red blood cell production in the bone marrow (this is why kidney failure causes anaemia) - Renin — part of the RAAS system controlling blood pressure - Calcitriol — the active form of Vitamin D (essential for calcium absorption) This explains why kidney failure (renal failure) causes such wide-ranging problems: anaemia, high blood pressure, abnormal electrolytes, bone disease, and acid accumulation — all in one. You have two kidneys, each about the size of a fist, sitting behind the abdominal cavity on either side of the spine. Each kidney contains about one million nephrons — the functional units where all the filtering and regulating actually happens.

Urine formation involves three processes, all happening simultaneously in every nephron: 1. Filtration — the glomerulus Blood pressure drives fluid across the glomerular capillary wall. The GFR (glomerular filtration rate) is the volume of filtrate produced per minute — normally ~120 mL/min (or 180 L/day). GFR is THE most important measure of kidney function. When kidneys are damaged, GFR falls: - Normal: >90 mL/min - Mild CKD (chronic kidney disease): 60–89 - Moderate CKD: 30–59 - Severe CKD: 15–29 - Kidney failure (requiring dialysis): <15 2. Reabsorption — the tubules The tubules reclaim useful substances from the filtrate back into the blood. This is selective — the body reabsorbs what it needs and lets waste products pass through. Key substances reabsorbed: - ALL glucose (in healthy kidneys — appearance of glucose in urine = "glycosuria" = sign of diabetes with very high blood glucose overwhelming the transport capacity) - ALL amino acids - ~99% of filtered water - ~99% of filtered sodium - Bicarbonate (to maintain pH) 3. Secretion — the tubules Some substances are actively pumped FROM the blood INTO the tubular fluid (to be excreted in urine). This allows the kidneys to eliminate substances that weren't filtered in step 1: - H⁺ ions (acid — for pH regulation) - Potassium (K⁺) (under aldosterone's control) - Many drugs (penicillin, aspirin, metformin) — this is why kidney disease requires drug dose adjustments - Some toxins Creatinine is a waste product of muscle metabolism that is freely filtered and not reabsorbed — so blood creatinine level is a practical measure of GFR. High blood creatinine = kidneys not filtering = reduced GFR = kidney disease.

Blood pH must be maintained between 7.35–7.45. Even small deviations cause profound effects on enzyme function, nerve conduction, and heart rhythm. The kidneys and lungs work together to maintain pH — but in very different ways: The lungs control CO₂ — acting fast (seconds to minutes). CO₂ is acidic (CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻). Breathe faster → blow off more CO₂ → blood becomes less acidic. This is the fast regulatory system. The kidneys control bicarbonate (HCO₃⁻) — acting slowly (hours to days) but with greater precision: - Reabsorb bicarbonate (a base) to prevent it being lost in urine - Excrete H⁺ ions (acid) in urine — bound to phosphate or ammonia buffers - Generate new bicarbonate when pH is too low The four acid-base disorders: Respiratory acidosis — too much CO₂ in blood (pH falls). Caused by: respiratory failure, COPD, sedative overdose. The kidneys compensate over days by retaining more bicarbonate. Respiratory alkalosis — too little CO₂ (pH rises). Caused by: hyperventilation (anxiety, altitude, early salicylate overdose). Kidneys compensate by excreting more bicarbonate. Metabolic acidosis — too little bicarbonate or too many acids (pH falls). Caused by: diabetic ketoacidosis (DKA), kidney failure (can't excrete H⁺), lactic acidosis (shock, sepsis), severe diarrhoea (losing bicarbonate). Lungs compensate by breathing faster. Metabolic alkalosis — too much bicarbonate (pH rises). Caused by: vomiting (losing HCl), excess diuretics (losing Cl⁻ and H⁺). Lungs compensate by breathing slower. Reading an arterial blood gas (ABG): Blood pH + pCO₂ + HCO₃⁻ together tell you which of these disorders is present and whether compensation has occurred. ABG interpretation is a fundamental clinical skill built entirely on this physiology.

Kidney disease is one of the most common serious conditions worldwide, and understanding renal physiology makes its consequences immediately logical. Chronic Kidney Disease (CKD): Progressive loss of nephron function over months to years. The most common causes are diabetes (40%) and hypertension (25%) — both damage the small blood vessels supplying the glomeruli. As GFR falls, the consequences of losing each kidney function become apparent: - Waste accumulates — rising urea and creatinine → uraemia (symptoms: nausea, confusion, fatigue) - Blood pressure rises — kidneys cannot regulate volume → hypertension - Anaemia develops — less erythropoietin → bone marrow makes fewer red blood cells - Bone disease — less active Vitamin D → poor calcium absorption → secondary hyperparathyroidism → bone resorption - Potassium rises (hyperkalaemia) — kidneys cannot excrete it → dangerous heart rhythm abnormalities - Acid accumulates (metabolic acidosis) — kidneys cannot excrete H⁺ Acute Kidney Injury (AKI): A sudden fall in kidney function over hours to days. Causes are classified as: - Pre-renal — inadequate blood flow to kidneys (dehydration, heart failure, major haemorrhage). Most common. Often reversible if blood flow is restored quickly. - Intrinsic renal — direct kidney damage (glomerulonephritis, acute tubular necrosis from toxins or prolonged ischaemia) - Post-renal — blockage of urine flow (enlarged prostate, kidney stones, tumour). Pressure backs up → damages kidneys. Treat the obstruction. Dialysis replaces the filtration function of failed kidneys — either haemodialysis (blood is filtered externally by a machine) or peritoneal dialysis (fluid is washed in and out of the abdominal cavity). It does NOT replace the hormonal functions (EPO, Vitamin D) — these must be supplemented separately.