Revise Homeostasis in mammals for Cambridge 9700 (14.1)

Homeostasis is the maintenance of a relatively constant internal environment within strict limits, despite changes in external conditions. For mammals, this includes regulating factors like body temperature, blood glucose concentration, blood water potential, pH, and carbon dioxide levels. This stable internal state is crucial because enzymes and other proteins function optimally only within very narrow physiological ranges. Deviations can lead to reduced enzyme efficiency, cell damage, organ failure, or even death.

The primary mechanism for maintaining homeostasis is negative feedback. This is a self-regulating system where a change in a physiological variable triggers a response that counteracts the initial change, bringing the variable back towards its set point. The general sequence is:

1. Stimulus: A change in the internal environment (e.g., rise in body temperature).
2. Receptor: Detects the change (e.g., thermoreceptors in the hypothalamus).
3. Coordinator: Processes the information and signals a response (e.g., the hypothalamus).
4. Effector: A muscle or gland that carries out the response (e.g., sweat glands, skin arterioles).
5. Response: The action that counteracts the stimulus (e.g., sweating, vasodilation). This response reduces the initial stimulus, thus turning off the pathway. This is why it's called 'negative' feedback.

Maintaining a constant core body temperature (around 37°C in humans) is vital for optimal enzyme activity. The hypothalamus in the brain acts as the primary thermoregulatory centre. It receives input from thermoreceptors in the skin (detecting external temperature) and in the hypothalamus itself (detecting core blood temperature).

Responses to High Body Temperature (Hyperthermia)

Responses to Low Body Temperature (Hypothermia)

Osmoregulation is the homeostatic control of the water potential of the blood and body fluids. The kidneys are the primary effectors in this process. Each kidney contains millions of microscopic filtering units called nephrons, which filter blood and adjust the amount of water and solutes reabsorbed to produce urine.

The Role of the Nephron and ADH

Blood is filtered under high pressure in the glomerulus (ultrafiltration), and the filtrate passes into the Bowman's capsule. As this filtrate moves through the proximal convoluted tubule, Loop of Henle, and distal convoluted tubule, essential substances are reabsorbed. The final adjustment of water content occurs in the distal convoluted tubule and the collecting duct, under the control of antidiuretic hormone (ADH).

The control loop is as follows:

• Stimulus: A change in blood water potential is detected by osmoreceptors in the hypothalamus.
• Low Water Potential (Dehydration): If blood water potential is low, the hypothalamus stimulates the posterior pituitary gland to release more ADH. ADH travels in the blood to the kidneys and binds to receptors on the cells of the collecting ducts and distal convoluted tubules. This increases their permeability to water by promoting the insertion of aquaporins into the cell membranes. More water moves by osmosis from the filtrate back into the blood. This produces a small volume of concentrated urine and restores blood water potential.
• High Water Potential (Hydration): If blood water potential is high, less ADH is released. The collecting ducts become less permeable to water, so less water is reabsorbed. This produces a large volume of dilute urine.

Maintaining a stable blood glucose concentration (around 90 mg/100 cm³ or 4-6 mmol/dm³) is critical for providing a constant energy supply to cells, especially brain cells which rely almost exclusively on glucose. The pancreas is the key organ, containing clusters of endocrine cells called the Islets of Langerhans.

Response to High Blood Glucose (Hyperglycaemia)

After a carbohydrate-rich meal, blood glucose levels rise.

1. Receptor: Beta (β) cells in the Islets of Langerhans detect the high glucose concentration.
2. Response: β-cells secrete the hormone insulin into the bloodstream.
3. Effect: Insulin binds to receptors on liver, muscle, and adipose tissue cells. This triggers:
   • An increase in the number of GLUT4 glucose transporter proteins in the cell membranes of muscle and fat cells, increasing glucose uptake from the blood.
   • Stimulation of glycogenesis: the conversion of glucose into glycogen for storage in the liver and muscles.
   • Increased rate of glucose use in respiration.
   • Conversion of glucose to fatty acids in the liver and adipose tissue. These actions rapidly lower blood glucose concentration back to the set point.

Response to Low Blood Glucose (Hypoglycaemia)

During fasting or strenuous exercise, blood glucose levels fall.

1. Receptor: Alpha (α) cells in the Islets of Langerhans detect the low glucose concentration.
2. Response: α-cells secrete the hormone glucagon into the bloodstream.
3. Effect: Glucagon primarily targets liver cells (hepatocytes). It binds to receptors, activating a G-protein and triggering a second messenger cascade (cAMP). This leads to:
   • Stimulation of glycogenolysis: the breakdown of stored glycogen into glucose.
   • Stimulation of gluconeogenesis: the synthesis of new glucose from non-carbohydrate sources like amino acids and glycerol. The liver releases this glucose into the blood, raising the blood glucose concentration back to the set point.