Excretory Products and their Elimination — NEET notes

Modes of Excretion — Ammonia, urea, or uric acid? Depends on the habitat

Animals are classified as ammonotelic (excrete ammonia — aquatic animals like bony fish), ureotelic (excrete urea — mammals, terrestrial amphibians), or uricotelic (excrete uric acid — birds, reptiles, insects). The strategy depends on water availability, toxicity tolerance, and energy budget for conversion.

Ammonotelism

Ammonia (NH₃) is the simplest nitrogenous waste. It's highly toxic and highly soluble, so it needs large volumes of water for dilution. Only aquatic animals can afford this strategy.

When amino acids are deaminated, the amino group is released as ammonia (NH₃). Ammonia is the most toxic nitrogenous waste but requires zero energy to produce — it's the direct product of deamination. The catch? It must be diluted with enormous amounts of water and excreted continuously.

• Ammonia is highly toxic — even small concentrations damage tissues and nervous system
• Ammonia is highly soluble in water — dissolves readily and diffuses across gill surfaces
• Requires ~500 ml water per gram of nitrogen excreted — only aquatic habitats provide this
• Excreted mainly through body surface and gills (not kidneys) in most ammonotelic animals
• Energy cost of production: zero (it's the raw deamination product)

Ammonotelic organisms: Bony fishes, aquatic amphibians (tadpoles), aquatic insects, crustaceans (prawns), many molluscs, and echinoderms. Freshwater fish excrete ammonia directly into surrounding water. Marine fish also excrete ammonia but additionally produce some urea via gills.

Ureotelism

Urea is synthesized in the liver via the ornithine (urea) cycle. It's 100,000× less toxic than ammonia and needs much less water for excretion — perfect for terrestrial mammals.

Urea is produced in the liver through the ornithine cycle (urea cycle) — discovered by Krebs and Henseleit. The liver converts 2 molecules of ammonia + 1 CO₂ into 1 urea molecule. This costs ATP but produces a waste product that's 100,000× less toxic than ammonia.

• Urea is synthesized in the liver via the ornithine (urea) cycle
• Urea is less toxic than ammonia → can be stored temporarily in the body
• Requires only ~50 ml water per gram of nitrogen — 10× less than ammonia
• Excreted by kidneys as urine (dissolved in water)
• Urea is freely filtered at the glomerulus and partially reabsorbed in collecting ducts

Ureotelic organisms: Mammals (humans, dogs, whales), adult amphibians (frogs — note: tadpoles are ammonotelic, adults are ureotelic!), cartilaginous fish (sharks, rays — they retain urea for osmoregulation), and terrestrial turtles.

Uricotelism

Uric acid is the most water-efficient nitrogenous waste. It's nearly insoluble and excreted as a semi-solid paste — ideal for egg-laying animals and desert dwellers.

Uric acid is practically insoluble in water. It crystallizes out and can be excreted as a semi-solid paste with minimal water loss. This is the costliest conversion (requires the most ATP) but the most water-efficient strategy.

• Uric acid is least toxic and least soluble of the three nitrogenous wastes
• Excreted as crystals or paste — needs almost no water (< 10 ml per gram nitrogen)
• Highest energy cost to produce — complex purine synthesis pathway
• Can be stored in cells without damage — some insects pack it into fat body cells
• The white part of bird droppings = uric acid

Uricotelic organisms: Birds, reptiles (lizards, snakes), land snails, insects, and some land crustaceans. Note: embryos developing inside eggs MUST be uricotelic — ammonia would poison the embryo, and urea would need water that isn't available inside a shell.

Comparing All Three

The choice of nitrogenous waste is a three-way tradeoff: toxicity (how dangerous), water requirement (how much water needed to excrete), and energy cost (how much ATP to synthesize).

• Many animals are NOT strictly one type — they use mixed strategies based on conditions
• Humans are primarily ureotelic but also excrete small amounts of ammonia (kidney tubules) and uric acid (from purine metabolism)
• Cockroach is uricotelic — uric acid is stored in fat bodies (uricose glands)
• Frog switches from ammonotelic (tadpole) to ureotelic (adult) during metamorphosis
• Crocodile is ureotelic (exception among reptiles — most reptiles are uricotelic)

Quick recall

A marine bony fish and a shark both live in the ocean. Do they excrete the same nitrogenous waste?

No! Marine bony fish are ammonotelic (excrete ammonia through gills). Sharks (cartilaginous fish) are ureotelic — they retain urea in blood to maintain osmolarity equal to seawater. Habitat alone doesn't decide the strategy.

Human Excretory System — Two kidneys, a million nephrons each, and the plumbing

The human excretory system consists of a pair of kidneys, ureters, a urinary bladder, and the urethra. Each kidney contains ~1 million nephrons — the structural and functional units. Nephrons are of two types: cortical (85%, short loops) and juxtamedullary (15%, long loops that dip deep into medulla for urine concentration).

Kidney

Each kidney is a bean-shaped organ located in the abdominal cavity, one on each side of the vertebral column. The right kidney is slightly lower than the left (the liver pushes it down).

Kidneys are reddish-brown, bean-shaped organs, each about 10-12 cm long, 5-7 cm wide, and weighing ~120-170 g. They lie retroperitoneally (behind the peritoneum) between T12 and L3 vertebrae. The right kidney is slightly lower than the left due to the liver above it.

• Each kidney is surrounded by three layers: renal capsule (fibrous), adipose capsule (fat for cushioning), renal fascia (outermost, anchors kidney)
• Hilum — the notch on the medial concave surface where renal artery enters, renal vein and ureter exit
• Internally divided into outer cortex (darker, contains Bowman's capsules and convoluted tubules) and inner medulla (lighter, contains loops of Henle and collecting ducts)
• Medulla is organized into medullary pyramids (8-18 per kidney) — cone-shaped structures whose tips (papillae) project into minor calyces
• Cortex extends between pyramids as columns of Bertini (renal columns)

The renal pelvis is a funnel-shaped space inside the hilum that collects urine from 2-3 major calyces, which in turn collect from 8-18 minor calyces. Each minor calyx cups a medullary pyramid's papilla. Urine flows: collecting duct → papilla → minor calyx → major calyx → renal pelvis → ureter.

Nephron

The nephron is the structural and functional unit of the kidney. Each kidney has ~1 million nephrons. A nephron consists of Bowman's capsule + glomerulus (together = Malpighian body/renal corpuscle) + tubular system (PCT, loop of Henle, DCT).

Each nephron has two parts: (1) Malpighian body (= renal corpuscle) = glomerulus + Bowman's capsule, located in the cortex, and (2) renal tubule = PCT → loop of Henle → DCT. The DCT opens into a collecting duct (shared by many nephrons, technically not part of the nephron itself).

• Glomerulus — a tuft of capillaries formed by afferent arteriole; blood exits via efferent arteriole (note: efferent is NARROWER → maintains high pressure for filtration)
• Bowman's capsule — double-walled cup surrounding the glomerulus; inner wall has podocytes with filtration slits
• PCT (Proximal Convoluted Tubule) — lined with brush border (microvilli) for maximum reabsorption; longest and most convoluted segment
• Loop of Henle — descending limb (thin, permeable to water) + ascending limb (thick, impermeable to water, actively pumps NaCl out)
• DCT (Distal Convoluted Tubule) — site of regulated reabsorption (aldosterone acts here); also secretes H⁺ and K⁺
• Collecting duct — runs through medulla; ADH controls water reabsorption here; shared by multiple nephrons

Cortical vs Juxtamedullary Nephrons

85% of nephrons are cortical (short loop of Henle, stays mostly in cortex) and 15% are juxtamedullary (long loop extending deep into medulla — essential for producing concentrated urine).

• Only juxtamedullary nephrons have vasa recta — cortical nephrons have peritubular capillaries instead
• Desert mammals (kangaroo rats) have a higher proportion of juxtamedullary nephrons → very concentrated urine → survive without drinking water
• Vasa recta participate in counter-current exchange (passive) — they don't create the gradient, they preserve it
• The loop of Henle + vasa recta together form the counter-current multiplier system

Quick recall

Which type of nephron is essential for concentrating urine, and why?

Juxtamedullary nephrons — their long loops of Henle dip deep into the medulla, creating the medullary osmotic gradient (300 → 1200 mOsm/L). The associated vasa recta preserve this gradient. Cortical nephrons have short loops that can't reach the hypertonic inner medulla.

Ureters, Bladder & Urethra

Urine exits the kidney through the renal pelvis → ureter (25-30 cm muscular tube) → urinary bladder (stores 300-800 ml) → urethra (exits body). Peristalsis in ureters pushes urine to the bladder.

Each ureter is a ~25-30 cm long muscular tube that carries urine from the renal pelvis to the urinary bladder by peristalsis (rhythmic muscular contractions). Ureters enter the bladder obliquely — this acts as a valve preventing backflow of urine.

• Urinary bladder — muscular, pear-shaped sac that stores urine; lined by transitional epithelium (stretches as bladder fills)
• Bladder wall has detrusor muscle (smooth muscle) — contracts during micturition
• Internal urethral sphincter (smooth muscle, involuntary) at bladder neck
• External urethral sphincter (skeletal muscle, voluntary) — gives conscious control over urination
• Urethra — male (~20 cm, shared with reproductive tract) vs female (~4 cm, separate from reproductive tract)

Urine Formation — Filter 180 litres, keep 178.5, excrete 1.5

Urine formation involves three steps: (1) glomerular filtration (125 ml/min GFR, ~180 L/day), (2) selective tubular reabsorption (99% of filtrate reabsorbed — glucose, amino acids, water, ions), and (3) tubular secretion (H⁺, K⁺, ammonia, drugs added to filtrate). The counter-current mechanism in the loop of Henle and vasa recta creates the medullary osmotic gradient (300→1200 mOsm/L) that concentrates urine.

GFR = 125 ml/min = 180 L/day

Glomerular Filtration

Blood is filtered under pressure in the glomerulus. The filtrate (called primary urine or glomerular filtrate) contains everything in plasma except proteins and blood cells. ~180 litres are filtered per day.

Blood enters the glomerulus via the afferent arteriole (wider) and exits via the efferent arteriole (narrower). The diameter difference creates high glomerular capillary pressure (~60 mmHg). This pressure forces water and small solutes through three filtration barriers into Bowman's capsule.

• Three filtration barriers: (1) Fenestrated endothelium of glomerular capillaries, (2) Basement membrane (acts as molecular sieve), (3) Podocytes with filtration slits (on inner wall of Bowman's capsule)
• Filtrate = plasma minus proteins — contains glucose, amino acids, urea, creatinine, ions, water
• GFR = 125 ml/min (both kidneys combined) = 7.5 L/hr = 180 L/day
• Only ~1.5 L is excreted as urine — rest (99%) is reabsorbed in tubules
• Filtration fraction = GFR/renal plasma flow ≈ 125/660 ≈ ~20% of plasma is filtered per pass

Net filtration pressure (NFP) drives ultrafiltration. It's the balance of pressures across the glomerular membrane: NFP = Glomerular hydrostatic pressure − (Bowman's capsule pressure + Colloidal osmotic pressure) = 60 − (18 + 32) = 10 mmHg

Tubular Reabsorption

99% of the filtrate is reabsorbed as it flows through the tubular system. PCT reabsorbs the bulk (~65-80%), loop of Henle handles water/NaCl, and DCT/collecting duct do fine-tuning under hormonal control.

Tubular reabsorption is the process of moving useful substances (glucose, amino acids, Na⁺, water) from tubular lumen back into peritubular capillaries. It occurs by active transport (needs ATP — Na⁺, glucose, amino acids) and passive transport (osmosis for water, diffusion for urea).

• Glucose reabsorption has a transport maximum (Tm) — if blood glucose exceeds ~180 mg/dL (renal threshold), carriers saturate → glucose appears in urine (glycosuria — seen in diabetes mellitus)
• Water reabsorption in PCT is obligatory (always happens); in collecting duct it's facultative (depends on ADH)
• Reabsorption is mostly by active transport in PCT (Na⁺-K⁺ ATPase drives it), passive in descending limb (osmosis)

Tubular Secretion

Tubular secretion is the reverse of reabsorption — substances are actively transported FROM peritubular capillaries INTO the tubular lumen. This helps maintain blood pH, K⁺ levels, and eliminates drugs/toxins.

Tubular secretion is the transfer of substances from blood → tubular fluid. It occurs mainly in the PCT and DCT. While filtration is non-selective and reabsorption rescues useful things, secretion is targeted — it actively pushes specific wastes and excess ions into the urine.

• H⁺ ions — secreted in PCT and DCT to maintain blood pH (acid-base balance)
• K⁺ ions — secreted in DCT and collecting duct (regulated by aldosterone)
• NH₃ (ammonia) — produced by deamination in tubular cells, secreted into lumen where it combines with H⁺ → NH₄⁺
• Drugs and toxins — penicillin, aspirin, uric acid are secreted in PCT
• Secretion is the reason some substances have clearance greater than GFR — they're both filtered AND secreted

Quick recall

What are the three processes involved in urine formation, in order?

1. Glomerular filtration (pressure-driven ultrafiltration in Bowman's capsule — 180 L/day) 2. Tubular reabsorption (useful substances recovered from filtrate — 99% reabsorbed) 3. Tubular secretion (extra waste/H⁺/K⁺ added to tubular fluid from blood) Final urine = Filtrate − Reabsorbed + Secreted ≈ 1.5 L/day

Counter-Current Mechanism

The counter-current multiplier (loop of Henle) and counter-current exchanger (vasa recta) together create and maintain a steep osmotic gradient from cortex (300 mOsm/L) to inner medulla (1200 mOsm/L). This gradient is what allows the collecting duct to concentrate urine.

The loop of Henle acts as a counter-current multiplier — the descending and ascending limbs run in opposite directions (counter-current) and their different permeabilities multiply a small single effect into a large osmotic gradient across the medulla.

• Descending limb — permeable to water, impermeable to NaCl → water leaves by osmosis → filtrate becomes MORE concentrated as it descends (from 300 → ~1200 mOsm/L at the tip)
• Ascending limb — impermeable to water, actively pumps NaCl OUT → NaCl enters medullary interstitium → filtrate becomes LESS concentrated as it ascends (from 1200 → ~100 mOsm/L)
• NaCl pumped out by ascending limb makes the interstitium salty → this pulls water out of descending limb → positive feedback loop = multiplier
• Vasa recta (counter-current exchanger) — blood flows in opposite directions in descending and ascending vasa recta → picks up salt going down, loses salt going up → NET effect: gradient preserved, not washed away
• Urea recycling contributes ~50% of inner medullary osmolarity — urea diffuses from inner medullary collecting duct into interstitium, then back into thin ascending limb

The final concentration happens in the collecting duct. When ADH is present, aquaporin channels are inserted into the collecting duct wall → water rushes OUT into the hypertonic medullary interstitium → urine becomes concentrated (up to 1200 mOsm/L). Without ADH, the collecting duct stays impermeable → dilute urine is excreted.

Regulation of Kidney Function — Hormones fine-tune every drop of urine

Kidney function is regulated by ADH (retains water → concentrated urine), aldosterone (retains Na⁺ → water follows), ANF (promotes Na⁺ excretion → dilute urine), and the RAAS (renin-angiotensin-aldosterone system) triggered by the juxtaglomerular apparatus (JGA). These hormones adjust urine volume and composition in response to blood pressure, osmolarity, and ion levels.

ADH (Antidiuretic Hormone)

ADH (also called vasopressin) is released by the posterior pituitary when blood osmolarity rises or blood volume drops. It inserts aquaporin-2 channels in the collecting duct, allowing water reabsorption and producing concentrated urine.

ADH is synthesized in the hypothalamus and stored/released from the posterior pituitary. When osmoreceptors in the hypothalamus detect high blood osmolarity (dehydration), ADH release increases. ADH travels via blood to the kidneys and acts on the collecting duct and late DCT.

• ADH makes the collecting duct wall permeable to water by inserting aquaporin-2 channels
• Water moves from collecting duct lumen → hypertonic medullary interstitium → vasa recta → blood
• Result: small volume of concentrated urine (up to 1200 mOsm/L)
• Low ADH (overhydration) → collecting duct stays impermeable → large volume of dilute urine (down to ~70 mOsm/L)
• Alcohol and caffeine INHIBIT ADH → that's why you urinate more after drinking — it's diuresis, not extra fluid intake

Diabetes insipidus results from ADH deficiency (central type — pituitary damage) or ADH resistance (nephrogenic type — kidneys don't respond). Patients excrete up to 20 litres of very dilute urine per day and are constantly thirsty.

Aldosterone

Aldosterone is a steroid hormone from the adrenal cortex that acts on the DCT and collecting duct to increase Na⁺ reabsorption (and K⁺ secretion). Water follows Na⁺ passively, increasing blood volume and pressure.

Aldosterone is released from the adrenal cortex (zona glomerulosa) in response to low blood Na⁺, high blood K⁺, or angiotensin II stimulation. It acts on the DCT and collecting duct, upregulating Na⁺-K⁺ ATPase pumps and epithelial sodium channels (ENaC).

• Increases Na⁺ reabsorption from tubular fluid → blood
• Increases K⁺ secretion from blood → tubular fluid (that's why excess aldosterone causes hypokalemia)
• Water follows Na⁺ by osmosis → increases blood volume and blood pressure
• Released in response to: (1) angiotensin II (RAAS), (2) high blood K⁺, (3) ACTH from pituitary
• Addison's disease = adrenal insufficiency → low aldosterone → Na⁺ loss, K⁺ retention, low BP

JGA & RAAS

The juxtaglomerular apparatus (JGA) is a specialized structure at the junction of DCT and afferent arteriole. When blood pressure drops, JGA cells release renin, triggering the renin-angiotensin-aldosterone system (RAAS) cascade.

The JGA (Juxtaglomerular Apparatus) sits where the DCT contacts the afferent arteriole of the same nephron. It has three components: (1) JG cells (modified smooth muscle in afferent arteriole wall — they secrete renin), (2) Macula densa (specialized DCT cells that sense NaCl concentration), (3) Extraglomerular mesangial cells (lacis cells).

• When blood pressure/GFR drops → JG cells release renin (a protease enzyme) into blood
• Renin converts angiotensinogen (from liver) → angiotensin I
• ACE (angiotensin converting enzyme, mainly in lung capillaries) converts angiotensin I → angiotensin II
• Angiotensin II does THREE things: (1) powerful vasoconstrictor → raises BP, (2) stimulates aldosterone release from adrenal cortex, (3) stimulates ADH release from pituitary
• Aldosterone → Na⁺/water retention → blood volume increases → BP restored
• This entire cascade = RAAS (Renin-Angiotensin-Aldosterone System)

The macula densa acts as a salt sensor. When it detects low NaCl in the tubular fluid (indicating low GFR), it signals JG cells to release renin. This is called tubuloglomerular feedback — the tubule talks back to the glomerulus to fix its own filtration rate.

ANF (Atrial Natriuretic Factor)

ANF is released by atrial heart cells when blood volume/pressure is too high. It opposes RAAS — causes vasodilation, inhibits NaCl reabsorption, and increases urine output to bring BP back down.

When blood volume increases and atrial walls stretch, atrial myocytes release ANF (Atrial Natriuretic Factor), also called ANP (Atrial Natriuretic Peptide). ANF is the body's natural 'anti-RAAS' — it acts to reduce blood volume and pressure.

• Released by atrial wall when stretched by excess blood volume
• Vasodilation of afferent arteriole → increases GFR → more filtrate → more urine
• Inhibits Na⁺ reabsorption in collecting duct → Na⁺ and water excreted → blood volume drops
• Inhibits renin release from JGA → suppresses entire RAAS cascade
• Inhibits aldosterone secretion from adrenal cortex → less Na⁺ retention
• Net effect: decreased blood pressure and blood volume (opposite of RAAS)

Micturition & Disorders — The reflex, the failures, and the fixes

Micturition (urination) is a reflex act controlled by the CNS. The stretch receptors in the bladder wall trigger the micturition reflex via the pelvic nerve. Kidney disorders include uremia (urea in blood), renal calculi (kidney stones), glomerulonephritis (inflammation of glomeruli). Treatments include hemodialysis (artificial kidney) and kidney transplant.

Micturition Reflex

Micturition is the process of voiding urine from the bladder. It involves both involuntary (autonomic reflex) and voluntary (cerebral cortex) control. The reflex is initiated when bladder volume reaches ~300-400 ml.

As the bladder fills, its wall stretches. Stretch receptors in the bladder wall are stimulated and send sensory signals via pelvic nerves to the micturition centre in the sacral spinal cord (S2-S4). This triggers motor signals back to the bladder.

• Stretch receptors in bladder wall detect filling (~300-400 ml triggers the urge)
• Sensory impulses travel via pelvic nerve to sacral spinal cord (S2-S4)
• Motor signals cause detrusor muscle contraction (bladder wall) and internal sphincter relaxation (smooth muscle, involuntary)
• External sphincter (skeletal muscle) is under voluntary control — cerebral cortex decides when to relax it
• Micturition reflex is a self-regenerating reflex — once started, contractions intensify until bladder empties completely
• Higher brain centres (cerebral cortex, pons) can inhibit or facilitate the reflex — that's why you can 'hold it'

The CNS passes on the signal to motor neurons of the bladder, producing simultaneous contraction of detrusor muscle and relaxation of both sphincters. The signal from pelvic nerve also causes the urethral sphincter to relax. Urine is expelled by the combined pressure of detrusor contraction and abdominal muscle contraction.

Kidney Disorders

Major disorders: uremia (urea accumulation in blood due to kidney failure), renal calculi (kidney stones from calcium oxalate/phosphate crystals), glomerulonephritis (inflammation of glomeruli), and renal failure (acute or chronic).

Kidney disorders range from stones blocking the plumbing to complete organ failure. Understanding each disorder requires knowing which part of the nephron/kidney is affected and how it disrupts normal urine formation.

Dialysis & Transplant

When kidneys fail, dialysis (hemodialysis or peritoneal) removes wastes artificially. Hemodialysis uses an external machine with a semi-permeable membrane. Kidney transplant is the definitive treatment for end-stage renal disease.

Hemodialysis uses an artificial kidney machine (dialyzer). Patient's blood is pumped through a system of tubes made of cellophane (semi-permeable membrane). These tubes are bathed in dialysing fluid (similar composition to normal plasma minus wastes). Urea, creatinine, and excess ions diffuse from blood → dialysing fluid along the concentration gradient.

• Hemodialysis — blood passes through cellophane tubes in dialysing fluid; wastes diffuse out, useful substances (glucose, amino acids) stay because they're already in the dialysing fluid at normal concentrations
• Typically done 3 times per week, 4 hours per session for chronic kidney failure patients
• Anti-coagulant (heparin) is added to prevent blood clotting in the machine
• Peritoneal dialysis — dialysing fluid is pumped into the abdominal cavity; the peritoneum acts as the semi-permeable membrane; can be done at home (CAPD — continuous ambulatory peritoneal dialysis)
• Kidney transplant — a healthy donor kidney replaces the failed kidney; patient needs immunosuppressive drugs lifelong to prevent rejection
• Transplanted kidney is usually placed in the iliac fossa (lower abdomen), not the normal kidney position

Accessory Excretory Organs — Lungs, liver, skin & intestine pitch in too

Kidneys are the primary excretory organs, but lungs (remove CO₂ and water vapour), liver (converts ammonia to urea, excretes bile pigments like bilirubin), skin (removes NaCl, urea, lactic acid via sweat), and intestine (excretes heavy metals, excess calcium, iron) also play important excretory roles.

Lungs

Lungs are the primary excretory organs for CO₂ (produced by cellular respiration) and water vapour. CO₂ is a metabolic waste that, if accumulated, would make blood dangerously acidic.

Every cell in your body produces CO₂ as a waste product of aerobic respiration. CO₂ dissolves in blood, forming carbonic acid (H₂CO₃), which would lower blood pH if not removed. The lungs excrete ~200 ml of CO₂ per minute at rest — about 18,000 ml (288 litres!) per day.

• CO₂ is the most abundant metabolic waste by volume — lungs handle it entirely
• CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ — if CO₂ accumulates, blood pH drops (respiratory acidosis)
• Water vapour is also lost via exhaled air — about 400 ml/day (that's why your breath fogs glass)
• Lungs remove CO₂ by diffusion — high pCO₂ in blood (46 mmHg) → low pCO₂ in alveolar air (40 mmHg)
• Regulation: if blood CO₂ rises → respiratory centre increases breathing rate → more CO₂ blown off

Liver

The liver converts toxic ammonia to urea (ornithine cycle), degrades hemoglobin to bile pigments (bilirubin, biliverdin), metabolizes drugs and hormones, and excretes cholesterol via bile.

The liver is the body's central detoxification organ. Its excretory roles include: (1) converting ammonia → urea via the ornithine (urea) cycle, (2) breaking down old RBCs' hemoglobin into bilirubin and biliverdin (bile pigments), (3) inactivating hormones and drugs, (4) excreting cholesterol into bile.

• Urea cycle (ornithine cycle) — 2 NH₃ + CO₂ → urea + H₂O; occurs in liver hepatocytes; urea is then carried by blood to kidneys for excretion
• Bile pigments — bilirubin (yellow) and biliverdin (green) are breakdown products of hemoglobin from dead RBCs; excreted via bile into intestine → give feces its brown colour (stercobilin)
• Bilirubin in urine (urobilinogen) → gives urine its yellow colour
• Jaundice = excess bilirubin in blood (>2 mg/dL) → skin and eyes turn yellow → indicates liver damage or excessive RBC breakdown
• Liver also detoxifies drugs (e.g., alcohol → acetaldehyde → acetic acid), steroid hormones, and various toxins

Skin

Sweat glands in the skin produce sweat containing water, NaCl, urea, lactic acid, and small amounts of amino acids. Sebaceous glands secrete sebum containing waxes and sterols. Skin is a secondary excretory organ.

The skin has two types of glands with excretory function: (1) Sweat glands (sudoriferous glands) — produce sweat containing water, NaCl, urea, lactic acid, and traces of amino acids and glucose. (2) Sebaceous glands — secrete oily sebum containing waxes, sterols, hydrocarbons, and fatty acids.

• Sweat is ~99% water + NaCl + urea + lactic acid + small amounts of K⁺, Ca²⁺
• An average person loses ~500-700 ml of sweat per day (much more during exercise or hot weather)
• Sweat glands are of two types: eccrine (all over body, thermoregulation) and apocrine (armpits/groin, scent-related)
• Sebaceous glands secrete sebum — eliminates some lipids, waxes, sterols; also lubricates skin and hair
• Skin excretes the same wastes as kidneys (NaCl, urea) but in much smaller quantities — it's supplementary, not primary

Intestine

The intestine excretes certain substances that the kidneys can't handle efficiently — including heavy metals (lead, mercury), excess calcium, iron, and bile pigments. These are eliminated with feces.

The large intestine (and to some extent, small intestine) serves as an excretory route for substances that are better eliminated via feces than urine. The liver sends bile (containing bilirubin, cholesterol, drug metabolites) into the intestine via the bile duct. The intestinal epithelium itself can secrete heavy metals and excess minerals.

• Bile pigments (bilirubin, biliverdin) — arrive via bile → converted to stercobilin in intestine → brown colour of feces
• Excess calcium and iron — excreted by intestinal epithelial cells into the lumen (especially when body stores are full)
• Heavy metals (lead, mercury, arsenic) — liver conjugates them → bile → intestine → feces
• Cholesterol — excess excreted via bile into intestine
• This is NOT the same as undigested food — excretion involves substances that were absorbed/metabolized and then actively secreted back into the gut