Excretion

Excretion is the removal from the body of waste products of metabolism — substances that were MADE INSIDE the body's cells during chemical reactions. Examples:

• Carbon dioxide from aerobic respiration (excreted by the lungs).
• Urea from deamination of amino acids in the liver (excreted by the kidneys).
• Excess water and mineral ions (excreted by the kidneys and a small amount by sweat).
• Bile pigments (e.g. bilirubin) from breakdown of haemoglobin in old red blood cells (excreted in bile, which leaves the body in faeces — the faeces is mixed egestion + excretion).

Egestion is the removal of undigested food from the alimentary canal as faeces. The food never crossed the gut wall into the body's cells, so it was never part of the body's metabolism. Faeces consists of fibre, dead gut bacteria, dead gut-lining cells and bile pigments — it is mostly EGESTION (not excretion).

Key distinction. Look at WHERE the substance came from:

• Made inside cells → excretion.
• Never absorbed into cells → egestion.

Three main excretory organs in humans:

Organ	Waste excreted	Source
Lungs	CO₂, water vapour	Aerobic respiration in all cells
Skin	Water, mineral ions, urea (in sweat)	Sweat for thermoregulation; small excretory role
Kidneys	Urea, excess water, excess ions, drugs/toxins	Main excretory organ

The liver isn't usually counted as an excretory organ on its own, but it PRODUCES urea (by deamination) which the kidneys then excrete. The liver also breaks down hormones and toxins (e.g. alcohol).

The body cannot store excess amino acids the way it stores glucose (as glycogen) or fats (in adipose tissue). Excess amino acids must therefore be broken down. This happens in the LIVER.

Step 1 — Deamination.

• The amino (NH₂) group is removed from the amino acid, leaving a residual organic acid (a carbon-containing molecule).
• The freed amino group becomes ammonia (NH₃), which is highly toxic and water-soluble.

Step 2 — Urea synthesis (ornithine cycle).

• Ammonia is combined with carbon dioxide in the liver to form urea ((NH₂)₂CO).
• Urea is much less toxic than ammonia and can be safely transported in the blood.

Step 3 — Excretion.

• Urea travels in the blood plasma to the kidneys.
• It is filtered out and excreted in urine.

What happens to the residual organic acid?

• Some is fed into respiration (the Krebs cycle) to release ATP.
• Some is converted into glucose (gluconeogenesis) or fat for storage.

Why bother converting ammonia to urea?

• Ammonia is far too toxic to allow to accumulate in the blood. Aquatic animals (e.g. fish) can excrete ammonia directly because the surrounding water dilutes it. Land mammals need urea, which is safer to carry but still water-soluble enough to be filtered by the kidneys.

The liver has many other excretory-adjacent roles: breakdown of hormones, breakdown of toxins (alcohol → acetaldehyde → acetate), and breakdown of old red blood cells (releasing bile pigments).

The urinary system consists of two kidneys, two ureters, the bladder and the urethra.

• Blood enters each kidney via the renal artery (oxygenated, contains urea).
• Filtered blood leaves via the renal vein (urea removed).
• Urine drains from the kidney via the ureter → bladder (storage) → urethra → outside.

Gross kidney structure (3 regions, outside in):

1. Cortex — outer region. Contains Bowman's capsules, PCTs and DCTs.
2. Medulla — middle region. Contains loops of Henle and collecting ducts. Has a salty interstitium (which drives water reabsorption from the collecting duct).
3. Pelvis — inner cavity. Collects urine from collecting ducts and funnels it into the ureter.

Each kidney contains ~1 million NEPHRONS — the functional units of filtration.

Nephron structure (start → finish):

Part	Location	Function
Bowman's capsule + glomerulus	Cortex	Ultrafiltration under high pressure
Proximal convoluted tubule (PCT)	Cortex	Selective reabsorption (glucose, amino acids, water, ions)
Loop of Henle	Descends into medulla and returns	Builds salt gradient in medulla → enables water reabsorption later
Distal convoluted tubule (DCT)	Cortex	Fine-tunes salt and water reabsorption
Collecting duct	Cortex through medulla → pelvis	Final water reabsorption (controlled by ADH) → urine

The afferent arteriole (blood IN to glomerulus) is WIDER than the efferent arteriole (blood OUT of glomerulus). This mismatch is what generates the high hydrostatic pressure required for ultrafiltration.

Each nephron is wrapped in peritubular capillaries that pick up reabsorbed substances and return them to the renal vein.

Ultrafiltration happens at the glomerulus inside the Bowman's capsule.

The driving force. Blood enters the glomerulus via the wider afferent arteriole and leaves via the narrower efferent arteriole. Because the exit is squeezed, hydrostatic pressure inside the glomerular capillaries is HIGH.

The filter — three layers in series:

1. Capillary endothelium — has small pores (fenestrations) letting plasma through.
2. Basement membrane — the main size filter; a meshwork of glycoproteins. Anything larger than ~70 kDa (e.g. plasma proteins, blood cells) cannot pass.
3. Podocyte slits — the cells lining the inside of the Bowman's capsule (podocytes) have foot-like extensions with narrow slits between them.

What is filtered into the Bowman's capsule (glomerular filtrate):

• Water ✓
• Glucose ✓
• Amino acids ✓
• Urea ✓
• Mineral ions (Na⁺, K⁺, Cl⁻, HCO₃⁻) ✓
• Vitamins, small toxins ✓

What is NOT filtered (stays in the blood):

• Plasma proteins (e.g. albumin) — too large to cross the basement membrane.
• Red blood cells, white blood cells, platelets — far too large.

The glomerular filtrate therefore has the same composition as plasma, MINUS plasma proteins. From here, the filtrate flows into the proximal convoluted tubule.

Why this is so important. Filtering blood once a day at this scale (~180 litres of filtrate per day!) lets the body remove urea, drugs and excess salts efficiently. Almost all of the filtrate is reabsorbed in the next stage — the body excretes only ~1.5 litres of urine per day.

After ultrafiltration, the filtrate is full of useful substances that the body wants to KEEP. Selective reabsorption is the process of taking these back into the blood.

Site: mostly the proximal convoluted tubule (PCT) in the cortex. Some reabsorption also happens in the loop of Henle, the DCT and the collecting duct.

What's reabsorbed in the PCT:

Substance	How?	Where to?
Glucose	Active transport (against gradient — ALL of it)	Peritubular capillaries → blood
Amino acids	Active transport (ALL of them)	Peritubular capillaries → blood
Water	Osmosis (follows solutes; ~80% of filtrate water)	Blood
Useful mineral ions	Active transport / facilitated diffusion	Blood
Urea	NOT REABSORBED	Continues down the tubule → urine

PCT cell adaptations:

• Microvilli on the luminal (filtrate-facing) surface → huge surface area for reabsorption.
• Many mitochondria → ATP for active transport.
• Tight junctions to neighbouring cells → prevent backward leak.
• Basal infoldings on the blood-facing surface → also increase SA.

Why active transport for glucose?

• After filtration, glucose concentration in the filtrate ≈ glucose concentration in blood. As the PCT cells take glucose IN, the gradient quickly reverses (more glucose in cells than filtrate). To finish the job, glucose must be moved AGAINST its concentration gradient → requires ATP.

Why does glucose appear in urine in diabetes?

• In uncontrolled diabetes mellitus, blood glucose is very high (e.g. 15-20 mmol/dm³ vs normal 4-6). The filtered load of glucose exceeds the capacity of the PCT transporters → the excess passes through into urine. This is one of the classic diagnostic features of diabetes (sweet-tasting urine, hence 'diabetes mellitus' = 'honey-sweet').

After the PCT, the filtrate is mostly water + urea + some ions. The loop of Henle, DCT and collecting duct fine-tune the water and ion balance before urine reaches the renal pelvis.

Osmoregulation is the control of the water content (and solute concentration) of the blood. It's an example of homeostasis — keeping the internal environment within a narrow range.

The hormone responsible is ADH (antidiuretic hormone), also called vasopressin. ADH is made in the hypothalamus and released from the posterior pituitary gland into the blood.

The negative-feedback loop:

When blood becomes TOO CONCENTRATED (e.g. after sweating, low fluid intake, salty meal):

1. Solute concentration of plasma RISES (water potential falls).
2. Osmoreceptors in the HYPOTHALAMUS detect this change.
3. The hypothalamus signals the posterior pituitary to release MORE ADH.
4. ADH travels in the blood to the kidneys.
5. ADH binds to receptors on collecting duct (and DCT) cells.
6. Aquaporins (water channels) are inserted into the cell membrane → membrane becomes MORE PERMEABLE to water.
7. More water moves from the filtrate INTO the collecting duct cells and onward into the blood, by osmosis (down the water-potential gradient set up by the salty medulla).
8. Result: small volume of CONCENTRATED (dark yellow) urine. Blood water content rises back toward the set point.

When blood becomes TOO DILUTE (e.g. after drinking a lot of water):

1. Solute concentration of plasma FALLS (water potential rises).
2. Osmoreceptors detect the change.
3. Pituitary releases LESS ADH.
4. Collecting duct becomes LESS PERMEABLE to water (aquaporins removed).
5. LESS water is reabsorbed; more stays in the filtrate.
6. Result: large volume of DILUTE (pale yellow / clear) urine. Blood water content falls back toward the set point.

Negative feedback in action. In both cases the response REVERSES the change — that's the defining feature of negative feedback and what keeps blood concentration stable.

Why this matters. Cells in tissues need their surroundings to have a stable water potential. If blood becomes too concentrated, cells lose water by osmosis and shrivel; if too dilute, cells take in water and may lyse (especially RBCs). Stable blood water content keeps cells working properly.

If the kidneys fail (chronic kidney disease, polycystic kidney disease, severe injury, etc.), urea and excess water and salts build up to toxic levels (uraemia). Two treatments are used.

Treatment 1 — Haemodialysis.

• Patient's blood is taken from an artery (via a fistula in the arm) and passed through a dialysis machine.
• Inside, blood flows on one side of a partially permeable membrane; dialysate fluid flows on the other side.
• Dialysate contains the CORRECT concentrations of glucose, mineral ions and water, but no urea.
• Substances move by diffusion down their concentration gradients:
  • Urea: high in blood, none in dialysate → diffuses OUT of blood into dialysate.
  • Excess ions and water: also diffuse out into dialysate (if blood has too much).
  • Glucose: same concentration on both sides → no net movement.
  • Proteins: too large to pass through the membrane → stay in blood.
• Cleaned blood is returned to a vein.
• Typically 3 × 4-hour sessions per week.

Advantages of dialysis: available immediately; no surgery; no rejection; can be a bridge to transplant.

Disadvantages of dialysis: time-consuming; strict diet (low salt, low potassium, low protein, controlled fluid intake); risk of infection at fistula; expensive long-term.

Treatment 2 — Kidney transplant.

• A healthy donor kidney (from a living relative or a deceased donor) is surgically implanted into the patient.
• The donor's artery, vein and ureter are connected to the patient's blood vessels and bladder.
• Diseased kidneys are usually left in place (not removed).
• Patient takes immunosuppressant drugs for life to prevent the immune system from rejecting the donor kidney.

Advantages of transplant: long-term solution; no need for ongoing dialysis; near-normal lifestyle and diet; cheaper long-term.

Disadvantages of transplant: shortage of donor kidneys (long waiting list); major surgery with surgical risks; lifelong immunosuppression → higher risk of infections and some cancers; risk of rejection (acute or chronic); donor kidney won't last forever.

Choosing between them. Many patients start on dialysis while waiting for a transplant. Younger / healthier patients are prioritised for transplant. Tissue typing helps match donor to recipient to minimise rejection.