The Kidneys: Filtration and Homeostasis

The kidneys are a pair of bean-shaped organs, each approximately 11 cm long, 6 cm wide, and 3 cm thick, weighing 120–170 g. They lie retroperitoneally on the posterior abdominal wall at the T12–L3 vertebral level, with the right kidney slightly lower than the left (displaced by the liver). Their primary function is to filter the blood and excrete waste products in urine, but they also regulate fluid balance, electrolytes, acid-base status, and blood pressure, and have endocrine functions that affect red blood cell production and calcium metabolism. This guide is for educational purposes only.

## Gross Structure

Each kidney is surrounded by a fibrous renal capsule, embedded in perirenal fat, and enclosed within the renal fascia (Gerota's fascia), which also encloses the adrenal gland. On cut section, the kidney shows a reddish-brown outer cortex and a paler inner medulla. The medulla is organised into 8–18 renal pyramids, whose apices (papillae) project into the renal sinus, draining into minor calyces, which merge into 2–3 major calyces, which unite to form the renal pelvis — the funnel-shaped origin of the ureter.

The renal sinus, the central cavity of the kidney, contains the renal pelvis, calyces, vessels, nerves, and fat. The hilum on the medial border is the entry and exit point for the renal artery, renal vein, and ureter (from anterior to posterior: vein, artery, ureter — remember VAU).

## Nephron Anatomy

The nephron is the functional unit of the kidney; each kidney contains approximately 1–1.2 million nephrons. Each nephron consists of a renal corpuscle (Bowman's capsule enclosing the glomerulus) and a renal tubule (proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct).

The glomerulus is a tuft of fenestrated capillaries derived from the afferent arteriole, drained by the efferent arteriole. The glomerular filtration barrier consists of three layers: the fenestrated endothelium (prevents passage of red cells), the glomerular basement membrane (negatively charged, restricts passage of anionic proteins), and the podocytes (specialised epithelial cells with interdigitating foot processes, creating slit diaphragms that prevent large protein passage). The mesangial cells between capillary loops regulate glomerular blood flow and phagocytose material trapped in the basement membrane.

Nephrons are classified as cortical (short loops of Henle that do not reach deep medulla) or juxtamedullary (long loops that penetrate deep into the medulla and are essential for generating the corticomedullary osmotic gradient used to concentrate urine).

## Glomerular Filtration

The kidneys filter approximately 180 litres of plasma per day (glomerular filtration rate, GFR ~125 mL/min in a healthy adult). Of this, 99% is reabsorbed; only 1–2 litres is excreted as urine. The driving force for filtration is the net filtration pressure — the balance of hydrostatic pressure favouring filtration (glomerular capillary pressure ~60 mmHg) against oncotic pressure (opposing filtration, ~32 mmHg) and Bowman's capsule pressure (~18 mmHg).

GFR is tightly regulated by autoregulation (maintaining glomerular pressure as systemic blood pressure varies), tubuloglomerular feedback (the macula densa senses distal tubular NaCl delivery and adjusts afferent arteriolar tone), and hormonal signals (angiotensin II constricts efferent arterioles, increasing filtration pressure; prostaglandins dilate the afferent arteriole in ischaemic states). GFR is estimated clinically using serum creatinine and equations such as the CKD-EPI formula; the MDRD formula is also widely used. Cystatin C provides an alternative filtration marker less affected by muscle mass.

## Tubular Reabsorption and Secretion

The proximal convoluted tubule (PCT) reabsorbs approximately 65–70% of filtered sodium, chloride, bicarbonate, potassium, glucose, and amino acids, largely by sodium-coupled cotransporters. Glucose reabsorption saturates at a plasma glucose of approximately 10 mmol/L (the renal threshold), above which glycosuria occurs — exploited therapeutically by SGLT2 inhibitors, which block glucose reabsorption in the PCT to lower blood glucose in type 2 diabetes.

The loop of Henle descends into the medulla (thin descending limb, permeable to water but not salt) and ascends (thick ascending limb, impermeable to water but actively reabsorbs NaCl via the NKCC2 cotransporter — the target of loop diuretics such as furosemide). This countercurrent multiplication system generates the hyperosmotic medullary interstitium that enables urine concentration.

The distal convoluted tubule and collecting duct are the primary sites of fine-tuning. Aldosterone (from the adrenal cortex) stimulates sodium reabsorption and potassium secretion at the principal cells of the collecting duct via ENaC sodium channels. Antidiuretic hormone (ADH/vasopressin) increases the water permeability of the collecting duct via aquaporin-2 insertion, enabling water reabsorption in the hyperosmotic medulla.

## Hormonal Functions

The kidneys are not merely excretory organs — they have important endocrine roles. The juxtaglomerular apparatus (JGA), comprising the macula densa, juxtaglomerular cells, and extraglomerular mesangium, secretes renin in response to reduced renal perfusion pressure, low tubular NaCl delivery, or sympathetic stimulation. Renin cleaves angiotensinogen to angiotensin I, which is converted by ACE (angiotensin-converting enzyme, primarily in pulmonary endothelium) to angiotensin II — a potent vasoconstrictor and stimulator of aldosterone and ADH secretion. The RAAS (renin-angiotensin-aldosterone system) is a key target of antihypertensive therapy (ACE inhibitors, ARBs, renin inhibitors).

The kidneys also produce erythropoietin (EPO) — a glycoprotein hormone that stimulates red blood cell production in the bone marrow — primarily in the peritubular interstitial cells of the cortex and outer medulla, in response to hypoxia. Chronic kidney disease results in EPO deficiency and normocytic normochromic anaemia. Recombinant EPO is used therapeutically in renal anaemia and is notoriously abused in endurance sport.

Finally, the kidneys activate vitamin D: 25-hydroxyvitamin D (from liver hydroxylation of dietary and skin-derived vitamin D) is converted to the active 1,25-dihydroxyvitamin D (calcitriol) by 1-alpha-hydroxylase in the proximal tubular cells, stimulated by PTH and hypophosphataemia. Calcitriol promotes intestinal calcium and phosphate absorption and modulates PTH secretion; deficiency leads to renal osteodystrophy in chronic kidney disease.

## Renal Vasculature

The renal arteries arise from the abdominal aorta at the L1–L2 level. Each renal artery enters the hilum and divides into segmental arteries (5 per kidney: superior, anterosuperior, anteroinferior, inferior, posterior), which are end-arteries with no collateral anastomoses — occlusion causes segmental infarction. Segmental arteries give rise to interlobar arteries (running between the pyramids), which branch into arcuate arteries at the corticomedullary junction, and then into interlobular (cortical radiate) arteries, from which the afferent arterioles arise.

The efferent arterioles from cortical glomeruli supply the peritubular capillary network (which reabsorbs substances from the PCT and DCT). Efferent arterioles from juxtamedullary glomeruli descend as the vasa recta — long, hairpin-looped vessels that supply the medulla in a countercurrent arrangement preserving the osmotic gradient without washing it out.

## Common Conditions

Chronic kidney disease (CKD) — defined as GFR < 60 mL/min/1.73 m² or markers of kidney damage for > 3 months — affects 10–15% of adults globally. Common causes include diabetic nephropathy (leading cause in developed countries), hypertensive nephrosclerosis, glomerulonephritis, and polycystic kidney disease. Nephrolithiasis (kidney stones) most commonly involve calcium oxalate; they may obstruct the ureter, causing severe colicky pain radiating from loin to groin. Renal cell carcinoma arises from proximal tubular cells and classically presents with the triad of haematuria, flank pain, and palpable mass (though often asymptomatic at presentation); clear cell carcinoma is the most common subtype.