Homeostasis
Homeostasis is the maintenance of a stable internal environment despite fluctuations in the external one. The AAMC MCAT content outline expects you to handle excretion (especially nitrogenous waste), the structure and function of the human kidney, and thermoregulation in mammals. This is a high-yield area for the Bio/Biochem section.
Feedback Loops
Homeostasis is maintained by feedback control. A generic loop has a stimulus (a change in a variable), a receptor/sensor that detects it, a control center (often the hypothalamus) that compares the value with a set point, and an effector (muscle or gland) that produces a response.
The response opposes and reverses the original change, driving the variable back toward the set point. Most homeostatic systems are negative-feedback loops. Examples: thermoregulation (a rise in core temperature triggers sweating and vasodilation), blood glucose (insulin lowers it, glucagon raises it), blood osmolarity (ADH), and blood pressure (baroreceptor reflex and RAAS). Negative feedback keeps variables oscillating in a narrow range around the set point.
The response reinforces and amplifies the original stimulus, pushing the variable further from baseline until an end point is reached. These loops are self-limiting events, not steady-state regulation. Classic MCAT examples: oxytocin during childbirth (uterine stretch → oxytocin → stronger contractions → more stretch), the clotting cascade, the action-potential upstroke (Na+ influx opens more Na+ channels), and the LH surge that triggers ovulation.
Excretion
Excretion is the elimination of metabolic wastes from the body. The most important excretory product in mammals is urea, formed in the liver via the ornithine (urea) cycle from the breakdown of amino acids. Carbon dioxide, bile pigments and excess water/salts are also excreted.
- Ammonotelic
- Organisms that excrete ammonia directly. Highly toxic but very water-soluble — only feasible for aquatic animals (bony fish, amphibian larvae).
- Ureotelic
- Excrete urea. Less toxic, moderately soluble — mammals, adult amphibians, cartilaginous fish.
- Uricotelic
- Excrete uric acid as a semi-solid paste. Almost insoluble — conserves water. Birds, reptiles, insects.
Kidneys remove urea, excess water, salts and toxins. Lungs excrete CO2 and water vapor. Skin loses water, salts and small amounts of urea via sweat. Liver excretes bile pigments (bilirubin, biliverdin) into the gut.
Homeostasis (Kidney)
The kidney is the master regulator of plasma composition. Each human kidney contains roughly 1 million nephrons — the structural and functional units that filter blood and form urine.
Gross structure
A kidney shows an outer cortex, an inner medulla divided into pyramids, and a central pelvis that drains urine into the ureter. Blood enters via the renal artery and leaves via the renal vein.
A nephron has six parts in sequence: Bowman’s capsule (with glomerulus inside) → proximal convoluted tubule (PCT) → descending limb of loop of Henle → ascending limb → distal convoluted tubule (DCT) → collecting duct. Cortical nephrons are short; juxtamedullary nephrons have long loops that dip deep into the medulla and create the osmotic gradient needed for urine concentration.
Three steps of urine formation
- 1. Ultrafiltration
- Occurs in the glomerulus. High hydrostatic pressure (~55 mmHg) forces water and small solutes through the basement membrane into Bowman’s capsule. Cells, platelets and large proteins are retained. Glomerular filtration rate (GFR) is about 125 mL/min (180 L/day).
- 2. Selective reabsorption
- ~99% of the filtrate is reabsorbed. The PCT reclaims all glucose and amino acids (active transport via Na+ co-transporters), most Na+, Cl−, HCO3− and water (osmosis). The descending limb is permeable to water only; the ascending limb pumps out Na+/Cl− but is impermeable to water (counter-current multiplier).
- 3. Tubular secretion
- The DCT and collecting duct actively secrete K+, H+, ammonia, creatinine and certain drugs into the filtrate. This fine-tunes blood pH and removes substances that escaped filtration.
| Region | Location | Permeability | Main function | Key transports |
|---|---|---|---|---|
| Bowman's capsule (glomerulus) | Cortex | Highly permeable to small solutes | Ultrafiltration | Water, glucose, urea, ions filter out; cells/proteins retained |
| Proximal convoluted tubule (PCT) | Cortex | Highly permeable to water | Bulk reabsorption (~65% of filtrate) | All glucose, all amino acids, Na+/Cl−, HCO3−, water (osmosis) |
| Descending limb of Loop of Henle | Medulla (deep) | Permeable to water only | Water leaves → filtrate becomes hypertonic | Passive water exit |
| Ascending limb of Loop of Henle | Medulla (returning) | Impermeable to water; permeable to ions | NaCl pumped out → filtrate becomes hypotonic | Active Na+/Cl−/K+ efflux (loop diuretics target this) |
| Distal convoluted tubule (DCT) | Cortex | Variable (hormone-controlled) | Fine-tuning of Na+, K+, pH, Ca2+ | Aldosterone → Na+ in / K+ out; H+ secretion; PTH → Ca2+ reabsorption |
| Collecting duct | Cortex → medulla | Permeability set by ADH | Final water reabsorption — concentrates urine | ADH → aquaporin-2 insertion; aldosterone → Na+ reabsorption |
| Type | Waste excreted | Toxicity | Water needed | Examples |
|---|---|---|---|---|
| Ammonotelic | Ammonia (NH3) | Very high | Lots (must be diluted) | Bony fish, amphibian larvae, aquatic invertebrates |
| Ureotelic | Urea | Moderate | Moderate | Mammals, adult amphibians, cartilaginous fish |
| Uricotelic | Uric acid | Low (insoluble paste) | Very little | Birds, reptiles, insects, snails |
Released from the posterior pituitary when osmoreceptors in the hypothalamus detect rising blood osmolarity. ADH increases water permeability of the collecting duct by inserting aquaporin-2 channels. Result: more water reabsorbed, concentrated urine, blood volume restored. Lack of ADH causes diabetes insipidus (large volumes of dilute urine).
Triggered by a fall in blood pressure or Na+. Juxtaglomerular cells release renin, which converts angiotensinogen to angiotensin I. ACE in the lungs converts it to angiotensin II — a potent vasoconstrictor that also stimulates the adrenal cortex to release aldosterone. Aldosterone makes the DCT/collecting duct reabsorb more Na+ (and water follows), restoring pressure.
Counter-current multiplier
The loop of Henle establishes a steep osmotic gradient in the medulla (300 → 1200 mOsm). The descending limb is water-permeable; the ascending limb pumps out NaCl. This makes the medulla hypertonic, so when urine flows down the collecting duct (under ADH influence) water is osmotically pulled out, producing concentrated urine.
Thermoregulation
Mammals are endotherms — they maintain core body temperature (~37°C) regardless of ambient conditions. The hypothalamus acts as the body’s thermostat, comparing actual temperature with the set point and triggering corrective responses.
The skin contains thermoreceptors, sweat glands, hair follicles with erector pili muscles, and a network of arterioles. It is the major effector for heat loss and heat conservation.
Responses when too hot
- Vasodilation of skin arterioles → more blood near surface → more heat radiated.
- Sweating → evaporation of water absorbs latent heat from the skin.
- Hair lies flat (relaxation of erector pili) → trapped insulating air layer is reduced.
- Behaviour: seeking shade, reduced activity.
Responses when too cold
- Vasoconstriction of skin arterioles → blood diverted away from surface.
- Shivering — rapid involuntary muscle contractions release heat.
- Hair erection (piloerection) → thicker insulating air layer (more visible in furry mammals; in humans we call them goosebumps).
- Increased metabolic rate via thyroxine and adrenaline; non-shivering thermogenesis in brown adipose tissue (in infants).
Acid-Base Balance
Arterial blood pH is held in a very tight range, 7.35–7.45. Because metabolism constantly generates acid (CO2 and non-volatile acids), three lines of defense keep pH stable: chemical buffers (seconds), the respiratory system (minutes), and the kidneys (hours to days).
The dominant extracellular buffer:
CO2 + H2O ⟶carbonic anhydrase H2CO3 ↔ H+ + HCO3−
Its power comes from being open: the lungs independently control CO2 (the acid side) while the kidneys control HCO3− (the base side). The Henderson-Hasselbalch relationship shows pH rises when the HCO3−/CO2 ratio rises. Other buffers include hemoglobin, plasma proteins and the phosphate system.
Respiratory control is fast: acidosis stimulates chemoreceptors → hyperventilation blows off CO2 → pH rises. Renal control is slow but powerful: tubular cells secrete H+ (buffered by phosphate and ammonia) and reabsorb or generate HCO3−. A respiratory problem is compensated by the kidneys and vice versa; full renal compensation takes days.
| Disorder | Primary problem | pH | Typical cause | Compensation |
|---|---|---|---|---|
| Respiratory acidosis | ↑ CO2 (hypoventilation) | Low | COPD, opioid overdose, airway obstruction | Kidneys retain HCO3− |
| Respiratory alkalosis | ↓ CO2 (hyperventilation) | High | Anxiety, high altitude, fever | Kidneys excrete HCO3− |
| Metabolic acidosis | ↓ HCO3− or ↑ acid | Low | Diabetic ketoacidosis, lactic acidosis, diarrhea | Hyperventilation (Kussmaul breathing) |
| Metabolic alkalosis | ↑ HCO3− or ↓ acid | High | Vomiting, excess antacids | Hypoventilation retains CO2 |
Worked MCQs
Five MCQs covering the high-yield testing patterns for homeostasis. Read every explanation — the deeper concept lives there.
Q1. ADH (vasopressin) increases water reabsorption primarily by acting on which part of the nephron?
ADH inserts aquaporin-2 channels into the apical membrane of the collecting duct, making it permeable to water. Water moves osmotically into the hypertonic medulla, producing concentrated urine. The PCT reabsorbs water constitutively (not ADH-dependent).
Q2. A patient hyperventilates during a panic attack, exhaling large amounts of CO2. The most likely acid-base disturbance is:
Blowing off CO2 lowers H2CO3, so [H+] falls and pH rises — a respiratory (CO2-driven) alkalosis. The kidneys compensate slowly by excreting HCO3−. Metabolic disturbances arise from HCO3−/acid changes, not from CO2.
Q3. A drop in blood pressure activates the RAAS pathway. Which hormone, released as a result, increases Na+ reabsorption from the DCT?
Renin is an enzyme, not a hormone target. Angiotensin II stimulates the adrenal cortex to release aldosterone, which acts on the DCT and collecting duct to reabsorb Na+ (water follows). ADH conserves water but not Na+.
Q4. Which of the following is an example of positive feedback?
Positive feedback amplifies the stimulus: uterine stretch triggers oxytocin, which strengthens contractions, causing more stretch — escalating until birth. The other three are negative-feedback loops, where the response opposes and reverses the original change.
Q5. Glucose normally appears in urine of healthy adults at what level?
Glucose is freely filtered at the glomerulus but is then completely reabsorbed in the PCT by Na+-glucose co-transporters (SGLT2). Glucose only appears in urine when the renal threshold (~180 mg/dL) is exceeded, as in untreated diabetes mellitus.
Quick Recap
- Negative feedback opposes the change (thermoregulation, glucose, ADH); positive feedback amplifies it (oxytocin/childbirth, clotting, action potential).
- Mammals = ureotelic; birds/reptiles = uricotelic; bony fish = ammonotelic.
- Nephron = Bowman’s capsule → PCT → loop of Henle → DCT → collecting duct.
- Three steps: ultrafiltration (glomerulus), selective reabsorption (mostly PCT), tubular secretion (DCT).
- ADH from posterior pituitary → collecting duct → water reabsorption.
- RAAS: low BP → renin → angiotensin II → aldosterone → Na+ & water retention.
- Thermoregulation = hypothalamus + skin (vasodilation/constriction, sweat, shivering, piloerection).
- Blood pH 7.35–7.45; bicarbonate buffer (CO2/HCO3−) with fast respiratory and slow renal compensation.