Excretion as an Example of Homeostatic Control¶

Part of Module 5: Communication, homeostasis and energy.

Excretion is the removal of metabolic waste products from the body. Because many of these products are toxic, their accumulation would disrupt homeostasis and eventually cause cell death. The two main excretory organs — the liver and the kidneys — are therefore central to homeostatic control. The kidney also regulates blood water potential (osmoregulation), making it a key effector in two separate homeostatic loops.

Learning Objectives¶

What Is Excretion?¶

Excretion is the removal from the body of the waste products of metabolism. It is distinct from egestion (removal of undigested food through the anus), which is the disposal of material that was never absorbed.

Major metabolic waste products include: - Carbon dioxide — produced by aerobic respiration in all cells; excreted via the lungs - Nitrogenous compounds — produced by deamination of excess amino acids in the liver; excreted by the kidneys as urea in urine - Bile pigments — breakdown products of haemoglobin from old red blood cells; excreted in bile

The focus of this topic is nitrogen-containing waste and the role of the liver and kidneys.

The Liver¶

Liver Structure¶

The liver is the largest internal organ and carries out a remarkable range of functions. Structurally it is divided into units called hepatic lobules.

Each lobule is a cylinder of hepatocytes (liver cells) arranged in radial rows around a central vein: - The hepatic artery supplies oxygenated blood to the lobule - The hepatic portal vein brings nutrient-rich blood from the gut (products of digestion) - Sinusoids are the modified capillaries running between rows of hepatocytes, connecting the portal vein and hepatic artery to the central vein - Kupffer cells are macrophages embedded in the sinusoid walls; they break down old red blood cells and remove bacteria from the blood - Bile canaliculi are tiny channels running alongside the sinusoids, collecting bile secreted by hepatocytes and draining it to the bile duct

Blood flows from the portal vein and hepatic artery inwards along the sinusoids, past the hepatocytes, and drains out through the central vein into the hepatic vein, which returns blood to the inferior vena cava.

Deamination and the Ornithine Cycle¶

When dietary protein provides more amino acids than the body requires for protein synthesis, the excess cannot be stored. Amino acids contain nitrogen in their amino group (–NH₂), and nitrogenous compounds are toxic at high concentrations. The liver therefore removes the amino group from excess amino acids in a two-stage process:

Stage 1 — Deamination: The amino group is removed from the amino acid, producing ammonia (NH₃) and an organic acid. The reaction occurs in hepatocytes.

amino acid → organic acid + ammonia

The organic acid can then enter aerobic respiration (e.g. as pyruvate or as an intermediate of the Krebs cycle — see 5.2.2 Respiration) to provide ATP, or be converted to carbohydrates for glycogen storage.

Stage 2 — Ornithine cycle: Ammonia is highly toxic even in low concentrations. It is converted to the less toxic compound urea in the hepatocytes by the ornithine cycle. Carbon dioxide combines with ammonia in a cyclic series of reactions:

2NH₃ + CO₂ → CO(NH₂)₂ + H₂O (ammonia + carbon dioxide → urea + water)

Urea is relatively soluble and much less toxic than ammonia. It is released from hepatocytes into the blood, transported to the kidneys, and filtered out into urine.

Detoxification¶

The liver also detoxifies other harmful substances:

• Alcohol (ethanol): Oxidised by liver enzymes first to ethanal (acetaldehyde) and then to acetic acid (acetate), which can enter the Krebs cycle. Ethanal is itself toxic and responsible for many effects of alcohol consumption.
• Drugs and other toxins: Liver enzymes (including cytochrome P450 enzymes) modify lipid-soluble toxins into more water-soluble forms that can be excreted by the kidneys.

The Kidneys¶

Overview of Kidney Function¶

The kidneys perform three interlinked roles: 1. Excretion of urea, excess ions and other water-soluble waste in urine 2. Osmoregulation — regulation of blood water potential and ion balance 3. pH regulation — selective retention or excretion of hydrogen ions and bicarbonate ions

Each kidney contains approximately one million nephrons — the functional units responsible for filtration and selective reabsorption. Blood enters each kidney via the renal artery and leaves via the renal vein. Urine drains from the collecting ducts through the ureter to the bladder.

Ultrafiltration¶

Filtration of blood occurs in the Malpighian body, which comprises: - Glomerulus: a knot of capillaries with high hydrostatic pressure - Bowman's capsule: a cup-shaped structure surrounding the glomerulus that collects the filtrate

Blood arrives at the glomerulus via the afferent arteriole and leaves via the efferent arteriole. Crucially, the afferent arteriole has a wider lumen than the efferent arteriole. This resistance to outflow forces blood pressure in the glomerulus to be high (~60 mmHg). This high hydrostatic pressure drives ultrafiltration: small molecules are forced out of the capillary blood and into the Bowman's capsule.

The filtrate passes through three barriers: 1. Fenestrated endothelium of the capillary wall (pores between endothelial cells) 2. Basement membrane (made of collagen and glycoproteins) — acts as a molecular sieve 3. Epithelium of the Bowman's capsule — podocytes with pedicels (foot processes) that leave narrow filtration slits

Molecules with molecular mass below ~69,000 Mr pass through freely. This includes water, glucose, urea, amino acids, ions and hormones. Red blood cells and plasma proteins cannot pass through due to their large size (and, in the case of proteins, negative charges on the basement membrane).

Worked example — why red blood cells are not filtered: Red blood cells have a diameter of ~8 µm. The filtration pores in the Bowman's capsule wall are far smaller (a few nm for the basement membrane). Physical exclusion by size prevents them passing through. Additionally, if red blood cells or plasma proteins appear in urine (haematuria or proteinuria), this indicates damage to the glomerular filtration barrier.

Selective Reabsorption¶

The filtrate entering the Bowman's capsule contains many useful substances that the body needs to retain. Selective reabsorption occurs primarily in the proximal convoluted tubule (PCT).

In the PCT: - 100% of glucose and amino acids are reabsorbed by active transport using co-transporter proteins (co-transported with Na⁺) - Large amounts of water are reabsorbed by osmosis (following the solute gradient created by ion transport) - Large amounts of Na⁺ and Cl⁻ are reabsorbed

Cells lining the PCT are adapted for this intense transport activity: - Microvilli on the luminal surface form a brush border, greatly increasing surface area - Abundant mitochondria supply ATP for active transport - Tight junctions between cells prevent filtrate bypassing through the paracellular route

The Loop of Henle¶

The loop of Henle descends from the cortex deep into the medulla and then ascends back to the cortex. Its function is to create a concentration gradient in the medulla — a region of very low water potential — which allows the production of concentrated urine later in the nephron.

The mechanism is called countercurrent multiplication:

Because filtrate in the descending and ascending limbs flows in opposite directions (countercurrent), salt pumped out of the ascending limb increases the concentration of the medulla, drawing more water out of the descending limb — the concentration is multiplied along the length of the loop.

Longer loops of Henle (found in desert-adapted mammals such as kangaroo rats) extend deeper into the medulla and produce even more concentrated urine.

The Distal Convoluted Tubule, Collecting Duct and ADH¶

After the loop of Henle, filtrate enters the distal convoluted tubule (DCT) and then the collecting duct, both of which pass through the concentrated medulla. Whether water is reabsorbed here is controlled by antidiuretic hormone (ADH).

ADH mechanism:

1. Osmoreceptors in the hypothalamus detect a fall in blood water potential (rise in blood osmolarity — as occurs in dehydration).
2. Nerve impulses travel to the posterior pituitary gland.
3. ADH is released into the blood.
4. ADH binds to receptors on the plasma membrane of collecting duct cells.
5. Binding activates adenylate cyclase, which converts ATP to cyclic AMP (cAMP) — a second messenger.
6. cAMP activates protein kinases that cause vesicles containing aquaporin water channel proteins to fuse with the apical (luminal) membrane.
7. Water channels are inserted into the membrane, making it highly permeable to water.
8. Water moves by osmosis from the collecting duct filtrate into the concentrated medulla and then into the blood.
9. A small volume of concentrated urine is produced.

When the body is well hydrated, ADH secretion falls, fewer aquaporins are inserted, the collecting duct is less permeable, less water is reabsorbed, and a large volume of dilute urine is produced. This is a textbook example of a negative feedback loop (see 5.1.1 Communication and homeostasis).

Kidney Failure¶

Kidney failure results when the kidneys can no longer adequately filter blood and regulate blood composition. Causes include: - Kidney infections causing inflammation and tissue damage - High blood pressure damaging glomerular capillaries, allowing proteins through the filtration barrier (proteinuria) - Diabetes mellitus causing damage to glomeruli over time

Consequences of untreated kidney failure: - Build-up of urea and other toxic waste products (causes nausea, vomiting, confusion) - Fluid retention and oedema (swelling) because excess water cannot be removed - Ionic imbalances leading to bone weakness (disrupted calcium/phosphate regulation) and dangerous cardiac arrhythmias - Death if untreated

Treatment options:

Transplant is generally the preferred long-term solution as it restores near-normal kidney function. Most donors are close relatives because of greater HLA (tissue-type) compatibility.

Urine as a Diagnostic Fluid¶

The composition of urine reflects blood composition and kidney function. Several diagnostic tests use urine samples:

• Pregnancy test: Monoclonal antibodies detect human chorionic gonadotropin (hCG), a hormone present in the urine of pregnant women from shortly after implantation.
• Anabolic steroid testing: Gas chromatography separates urine components; the retention time of steroids in the column is compared to known standards to identify banned substances.
• Glucose in urine (glycosuria): Normally all glucose is reabsorbed in the PCT. The presence of glucose in urine suggests blood glucose was so high that the transport capacity of the PCT was exceeded (renal threshold), consistent with uncontrolled diabetes mellitus.
• Proteins in urine (proteinuria): Indicates damage to the glomerular filtration barrier.
• Creatinine in urine: Elevated blood creatinine may suggest muscle and/or kidney damage; blood creatinine is also used to estimate the glomerular filtration rate (GFR), a key measure of kidney function. A low GFR indicates less effective filtration and may signal kidney disease.
• Drug detection: Urine testing involves an immunoassay (monoclonal antibodies bind drug molecules or their metabolites), followed by gas chromatography to separate components and mass spectrometry to identify molecular structures precisely. This method can detect anabolic steroids and recreational drugs.

Key Terms¶

• Excretion: removal from the body of the waste products of metabolism.
• Deamination: removal of the amino group from an amino acid in the liver, producing ammonia.
• Ornithine cycle: sequence of reactions in liver cells that converts toxic ammonia into urea.
• Hepatic lobule: cylindrical structural unit of the liver made of hepatocytes arranged around a central vein.
• Nephron: the functional unit of the kidney where ultrafiltration and selective reabsorption occur.
• Ultrafiltration: high-pressure filtration of blood from the glomerulus into the Bowman’s capsule.
• Podocyte: specialised cell of the Bowman’s capsule with filtration slits that help form the ultrafiltration barrier.
• Glomerular filtrate: fluid forced out of the blood into the nephron at the start of ultrafiltration.
• Selective reabsorption: uptake of useful substances from the filtrate back into the blood.
• Loop of Henle: nephron section that establishes a medullary salt gradient used to reabsorb water.
• ADH: antidiuretic hormone that increases water reabsorption in the distal convoluted tubule and collecting duct.
• Aquaporin: water channel protein inserted into the collecting duct cell membrane in response to ADH.
• GFR: glomerular filtration rate; the volume of filtrate formed per minute; used as an indicator of kidney health.
• Osmoregulation: control of the water potential of the blood and body fluids.

Connected Pages¶

• 5.1.1 Communication and homeostasis
• 5.1.4 Hormonal communication (blood glucose regulation)
• 5.2.2 Respiration (Krebs cycle — connection to organic acids from deamination)
• Negative feedback in homeostasis
• Module 5: Communication, homeostasis and energy