Every day your kidneys filter about 180 L of fluid out of your blood, more than your whole blood volume dozens of times over. Yet you make only about 1.5 L of urine. The kidneys pull back almost everything useful (water, glucose, salts) and let go of just the waste and the excess. By choosing how much water and salt to keep, they set your blood volume, blood pressure and blood pH. When they fail, waste and acid build up within days, which is why dialysis machines and transplants exist. The first problem is nitrogen. When cells break down excess amino acids for energy, the liver first removes the amino group (deamination), producing ammonia (). Ammonia is highly toxic, so animals either dilute it with lots of water or convert it into something safer, which costs energy. The form an animal excretes reflects a trade-off between water and energy.
| Waste | Toxicity | Water needed | Energy cost to make | Excreted by |
|---|---|---|---|---|
| Ammonia () | Very high | Very large volumes (must be diluted) | None | Most fish and aquatic invertebrates (diffuses out across gills) |
| Urea | Low | Moderate | Some ATP (made in the liver by the urea cycle from ammonia and ) | Mammals (including humans), adult amphibians, sharks |
| Uric acid | Very low | Very little (excreted as a paste or crystals) | Most ATP | Birds, reptiles, insects; allows waste to be stored safely inside a shelled egg |
The urinary system and the nephron
- Kidneys: two bean-shaped organs at the back of the abdomen. Together they receive about 20–25% of the blood pumped by the heart, through the renal arteries; filtered blood leaves through the renal veins.
- Ureters: tubes that carry urine from each kidney to the bladder by waves of smooth-muscle contraction (peristalsis).
- Urinary bladder: a muscular sac that stores urine; sphincter muscles control its release.
- Urethra: carries urine out of the body.
- Inside a kidney: the outer cortex (contains the glomeruli and convoluted tubules), the inner medulla (contains the loops of Henle and collecting ducts, arranged in cone-shaped renal pyramids) and the renal pelvis, a funnel that collects urine and drains into the ureter.
Each kidney contains about a million nephrons, microscopic tubules that each make urine. Blood enters through an afferent arteriole into a knot of capillaries, the glomerulus, which sits inside a cup-shaped Bowman's capsule. The blood leaves by a narrower efferent arteriole, which then branches into capillaries wrapped around the rest of the tubule. The tubule itself runs: Bowman's capsule → proximal convoluted tubule → loop of Henle (descending limb down into the medulla, ascending limb back up) → distal convoluted tubule → collecting duct, which is shared by many nephrons and carries urine down through the medulla to the renal pelvis.
| Process | Where | What happens |
|---|---|---|
| Filtration | Glomerulus → Bowman's capsule | Blood pressure (high because the efferent arteriole is narrower than the afferent) forces water and small solutes (glucose, amino acids, salts, urea) out of the capillaries into the capsule. Selection is by size only: blood cells and large plasma proteins stay in the blood. About 125 mL/min, or 180 L/day, of filtrate forms. |
| Reabsorption | Mostly the proximal tubule; also loop of Henle, distal tubule, collecting duct | Useful substances move from the filtrate back into the blood. In the proximal tubule, active transport of Na⁺ drives the reabsorption of all glucose and amino acids (by co-transport) and about two-thirds of the water and salt (water follows by osmosis). About 99% of the filtered water is eventually reabsorbed. |
| Secretion | Mainly the proximal and distal tubules | Cells actively move substances from the blood into the filtrate: H⁺, K⁺, ammonium, and foreign substances such as many drugs (e.g. penicillin). This clears things that were not filtered enough and adjusts pH and K⁺. |
Water, salt and pH balance
To make urine more concentrated than blood, the kidney needs somewhere salty enough to draw water out of the collecting duct by osmosis. The loop of Henle builds that salty region in the medulla. The ascending limb is impermeable to water but actively pumps Na⁺ and Cl⁻ out into the surrounding tissue. The descending limb is permeable to water but not to salt, so as it passes through that salty tissue, water leaves by osmosis and the filtrate inside becomes more concentrated at the bottom of the loop. That concentrated filtrate then flows up the ascending limb, which pumps out even more salt. Because the two limbs run side by side with fluid flowing in opposite directions, each small step adds up, building a gradient from about 300 mOsm/L in the cortex to about 1200 mOsm/L deep in the medulla (a countercurrent multiplier). Some urea also leaks out of the lower collecting duct and adds to the gradient. Animals that live in deserts, such as the kangaroo rat, have especially long loops and can make extremely concentrated urine.
- Renin–angiotensin–aldosterone system (RAAS): blood pressure or blood volume falls (for example after heavy bleeding or dehydration). Cells of the juxtaglomerular apparatus, where the distal tubule touches the afferent arteriole, detect the drop.
- They release the enzyme renin into the blood.
- Renin converts angiotensinogen (a plasma protein from the liver) into angiotensin I; angiotensin-converting enzyme (ACE), mostly in the lungs, converts it into angiotensin II.
- Angiotensin II constricts arterioles (raising pressure immediately), stimulates thirst and ADH release, and makes the adrenal cortex release aldosterone.
- Aldosterone makes the distal tubule and collecting duct reabsorb more Na⁺ (and secrete K⁺). Water follows the Na⁺ by osmosis, so blood volume and blood pressure rise back toward normal, and renin release falls.
ADH and aldosterone both increase water reabsorption, but they fix different problems. ADH responds to concentration: it saves water alone, which dilutes the blood. Aldosterone responds to volume and pressure: it saves salt and water together, so volume rises without changing concentration much. Many blood-pressure medications (ACE inhibitors) block this pathway. The kidneys also finish the job of pH control begun in the first topic: tubule cells secrete H⁺ into the filtrate (where it is buffered by phosphate and ammonia so urine does not become dangerously acidic) and reabsorb HCO₃⁻ into the blood. When blood is too acidic, more H⁺ is secreted; when it is too alkaline, more bicarbonate is excreted.
Diuretics, kidney disorders and treatment
- Diuretics increase urine volume. Alcohol inhibits ADH release, so fewer aquaporins are inserted and more water is lost; this dehydration contributes to hangovers. Caffeine is a mild diuretic, mainly because it reduces Na⁺ reabsorption in the tubule, so water follows the salt into the urine.
- Kidney stones are hard crystals (most often calcium oxalate, sometimes uric acid) that form when solutes in the urine become too concentrated. Dehydration raises the risk. A stone moving into a ureter blocks it and causes intense pain.
- Diabetes insipidus: the pituitary releases too little ADH, or the collecting ducts do not respond to it. Without aquaporins, the person produces large volumes (sometimes over 10 L a day) of very dilute urine and is constantly thirsty. There is no glucose in the urine.
- Diabetes mellitus (insulin problem): blood glucose rises so high that the filtered glucose exceeds what the proximal tubule's transporters can reabsorb (roughly above 10 mmol/L). Glucose stays in the filtrate and appears in the urine, and it holds water in the tubule by osmosis, so urine volume also rises.
- Kidney failure: the leading causes are diabetes and high blood pressure, which damage the glomeruli. As filtration falls, urea, K⁺ and acid build up, fluid is retained, blood pressure rises and red blood cell production drops. Protein in the urine is an early warning sign that the glomerular filter is leaking.
Dialysis replaces filtration with diffusion across a selectively permeable membrane. In hemodialysis, blood is pumped from a blood vessel in the arm through a dialyzer containing thousands of thin tubes of artificial membrane. Dialysate flows around the tubes in the opposite direction to the blood. The dialysate contains no urea, so urea diffuses out of the blood down its concentration gradient; it contains glucose and salts at normal blood concentrations, so these do not diffuse out (and excess K⁺ does). Blood cells and proteins are too large to cross. Countercurrent flow keeps a concentration gradient along the whole length of the dialyzer. A typical schedule is about 4 hours, 3 times a week. In peritoneal dialysis, dialysate is run through a tube into the abdominal cavity, where the peritoneum (the lining of the abdomen, rich in capillaries) acts as the membrane. After several hours the fluid, now carrying wastes, is drained and replaced. It can be done at home, often overnight by a machine.