requires knowledge of positive feedback examples (ovulation and childbirth are the most commonly tested). Remember: negative feedback maintains homeostasis; positive feedback amplifies change and does NOT maintain a constant internal environment.
Component Role Example Receptor Detects changes in the internal environment (stimuli) Thermoreceptors in the hypothalamus and skin detect temperature changes Coordinator Processes information from receptors and sends signals to effectors Hypothalamus processes temperature information and sends nerve impulses to effectors Effector Carries out the response that restores the variable to its set point Sweat glands secrete sweat; blood vessels dilate or constrict; muscles shiver Set point The normal value or range of the physiological variable Body temperature: 37 degrees C; blood glucose: approximately 90 mg/100 cm3 ^3 3 Feedback The output of the effector is monitored by the receptor, allowing the system to self-regulate As body temperature falls back to normal, thermoreceptors reduce their firing rate
Blood glucose concentration is maintained at approximately 90 mg/100 cm3 ^3 3 (range: approximately 70-110 mg/100 cm3 ^3 3
After a meal (blood glucose rises):
Blood glucose concentration increases as glucose is absorbed from the small intestine β \beta β β \beta β insulin into the bloodInsulin binds to receptors on target cells (liver, muscle, adipose tissue), triggering: Increased glucose uptake by cells (via GLUT4 transporter proteins, which are translocated to the cell membrane in response to insulin) Increased rate of glycolysis (glucose respiration within cells) Increased glycogenesis (conversion of glucose to glycogen for storage in liver and muscle) Decreased glycogenolysis (inhibition of glycogen breakdown) Increased lipogenesis (conversion of glucose to fat for long-term storage) Decreased gluconeogenesis (inhibition of new glucose synthesis) Blood glucose concentration decreases back to the set point As blood glucose falls, β \beta β negative feedback ) Between meals or during exercise (blood glucose falls):
Blood glucose concentration decreases as cells consume glucose α \alpha α α \alpha α glucagon into the bloodGlucagon binds to receptors on liver cells (hepatocytes), triggering: Increased glycogenolysis (breakdown of glycogen into glucose in the liver) Increased gluconeogenesis (conversion of amino acids and glycerol to glucose in the liver) Increased lipolysis (breakdown of fat into fatty acids and glycerol) Blood glucose concentration increases back to the set point As blood glucose rises, α \alpha α negative feedback ) The liver is the central organ in blood glucose homeostasis. It acts as a “glucose buffer,” removing glucose from the blood when levels are high and releasing glucose when levels are low.
Process Trigger Description Direction Glycogenesis High blood glucose Conversion of glucose to glycogen for storage Stores glucose Glycogenolysis Low blood glucose Breakdown of glycogen to glucose-6-phosphate, then to free glucose (liver has glucose-6-phosphatase) Releases glucose Gluconeogenesis Low blood glucose Synthesis of glucose from non-carbohydrate sources (lactate, amino acids, glycerol) Produces new glucose
Critical distinction — liver vs muscle:
The liver can both store glycogen AND release free glucose into the blood because hepatocytes possess the enzyme glucose-6-phosphatase , which removes the phosphate from glucose-6-phosphate, allowing free glucose to diffuse into the blood. Muscle cells can store glycogen and break it down for their own use (glycolysis), but they CANNOT release free glucose into the blood because they lack glucose-6-phosphatase. Muscle glycogenolysis produces glucose-6-phosphate, which can only be used within the muscle cell itself.The kidneys normally reabsorb all glucose from the glomerular filtrate in the proximal convoluted tubule (PCT). The maximum rate at which glucose can be reabsorbed is approximately 375 mg/min , corresponding to a blood glucose concentration of approximately 180 mg/100 cm3 ^3 3 (the renal threshold ).
If blood glucose is below 180 mg/100 cm3 ^3 3 If blood glucose exceeds 180 mg/100 cm3 ^3 3 glycosuria ) The hypothalamus contains the body’s thermostat . It receives input from two types of thermoreceptor:
Central thermoreceptors: Located in the hypothalamus itself, they monitor the temperature of the blood passing through the brainPeripheral thermoreceptors: Located in the skin (dermis), they monitor the external temperatureThe hypothalamus compares the input from these receptors with the set point (approximately 37 degrees C) and initiates corrective responses when the temperature deviates.
When the body temperature rises above the set point:
Response Mechanism Vasodilation Arterioles supplying the skin dilate, increasing blood flow to the skin surface. More heat is lost by radiation from the blood to the environment. Sweating Sweat glands secrete sweat onto the skin surface. Water in sweat evaporates, absorbing latent heat of vaporisation from the skin (approximately 2.4 kJ per gram of water). This cools the blood in the skin capillaries. Increased breathing Panting or faster breathing increases evaporative heat loss from the lungs and respiratory tract. Behavioural changes Removing clothing; seeking shade; drinking cold fluids Decreased metabolic rate Cells reduce their rate of respiration, producing less heat as a by-product
When the body temperature falls below the set point:
Response Mechanism Vasoconstriction Arterioles supplying the skin constrict, reducing blood flow to the skin surface. Less heat is lost from the blood to the environment. More blood is diverted to the core organs to maintain their temperature. Shivering (thermogenesis) Rapid, involuntary contractions of skeletal muscles. Muscle respiration generates heat as a by-product, warming the body. Shivering can increase heat production by 2-5 times the resting rate. Piloerection Hair erector muscles contract, causing body hairs to stand upright. This traps a layer of insulating air next to the skin (more significant in furry animals than in humans). Increased metabolic rate Thyroid gland releases more thyroxine, increasing the basal metabolic rate of cells. Cells respire more, producing more heat. Adrenaline also increases metabolic rate. Behavioural changes Putting on warm clothing; curling up to reduce surface area; seeking shelter; drinking hot drinks Brown fat metabolism Brown adipose tissue (especially in newborns) contains many mitochondria that can uncouple respiration from ATP production, releasing energy directly as heat (non-shivering thermogenesis).
A person produces 150 g of sweat per hour during exercise in a hot environment. The latent heat of vaporisation of water is 2.4 kJ/g. Calculate the rate of heat loss through sweating.
Solution Heat loss = mass of sweat × \times × 150 g × 2.4 k J / g = 360 k J / h o u r 150 \mathrm{ g} \times 2.4 \mathrm{ kJ/g} = 360 \mathrm{ kJ/hour} 150 g × 2.4 kJ/g = 360 kJ/hour
This is a significant contribution to heat loss. The basal metabolic rate produces approximately 300 kJ/hour, so sweating during exercise can remove more heat than the body produces at rest. This explains why adequate hydration is critical during exercise in hot environments — sweat that is not replaced leads to dehydration and reduced blood volume, impairing thermoregulation.
The kidneys regulate the water potential of the blood by adjusting the volume and concentration of urine produced. This process is called osmoregulation .
Key principle: If blood water potential is too low (blood is too concentrated), the kidneys produce a small volume of concentrated urine to conserve water. If blood water potential is too high (blood is too dilute), the kidneys produce a large volume of dilute urine to excrete excess water.
Antidiuretic hormone (ADH / vasopressin) is the key hormone in osmoregulation.
Synthesis and release:
ADH is produced by neurosecretory cells in the hypothalamus It is transported along their axons and stored in the posterior pituitary gland It is released into the blood when needed When blood water potential is low (dehydration):
Osmoreceptors in the hypothalamus detect the decreased blood water potential (increased solute concentration) The hypothalamus stimulates the posterior pituitary to release ADH into the blood ADH binds to receptors on the cells of the collecting duct This triggers the insertion of aquaporin (water channel) proteins into the collecting duct cell membrane The collecting duct becomes more permeable to water Water is reabsorbed from the collecting duct by osmosis into the concentrated medullary tissue fluid (maintained by the counter-current multiplier of the loop of Henle) Less water is lost in the urine: urine volume decreases, urine concentration increases Blood water potential increases back to normal (negative feedback) The osmoreceptors reduce their stimulation of the posterior pituitary, decreasing ADH release When blood water potential is high (over-hydration):
Osmoreceptors detect the increased blood water potential (decreased solute concentration) The hypothalamus reduces stimulation of the posterior pituitary Less ADH is released into the blood With less ADH, collecting duct cells remove aquaporin channels from their membranes The collecting duct becomes less permeable to water Less water is reabsorbed: urine volume increases, urine becomes more dilute Excess water is excreted, and blood water potential returns to normal (negative feedback) The nephron is the functional unit of the kidney. Each kidney contains approximately one million nephrons.
Region Function Renal (Bowman’s) capsule Ultrafiltration: high blood pressure in the glomerulus forces small molecules (water, glucose, urea, ions) out of the blood into the capsule Proximal convoluted tubule (PCT) Selective reabsorption: reabsorbs ALL glucose, ALL amino acids, approximately 85% of water, and most N a + \mathrm{Na}^+ Na + C l − \mathrm{Cl}^- Cl − Loop of Henle Creates a concentration gradient in the medulla via the counter-current multiplier. Descending limb: permeable to water (water out). Ascending limb: actively transports N a + \mathrm{Na}^+ Na + C l − \mathrm{Cl}^- Cl − Distal convoluted tubule (DCT) Fine-tuning of water and ion balance; regulated by aldosterone (N a + \mathrm{Na}^+ Na + Collecting duct Regulated by ADH: water reabsorption depends on ADH level; permeability controlled by aquaporin channels
The loop of Henle creates and maintains a concentration gradient in the medulla, with tissue fluid becoming progressively more concentrated from the cortex to the inner medulla (approximately 300 mOsm at the cortex to approximately 1200 mOsm at the inner medulla).
Mechanism:
Descending limb: Water passes out by osmosis into the increasingly concentrated medullary tissue fluid. The filtrate becomes more concentrated as it descends.Hairpin turn: At the bottom of the loop, the filtrate is at its most concentrated.Ascending limb (thin segment): N a + \mathrm{Na}^+ Na + C l − \mathrm{Cl}^- Cl − Ascending limb (thick segment): N a + \mathrm{Na}^+ Na + C l − \mathrm{Cl}^- Cl − Counter-current flow: Because the descending and ascending limbs flow in opposite directions (counter-current), the active transport of salt from the ascending limb continually adds to the concentration of the medullary tissue fluid adjacent to the descending limb. This amplifies the gradient (multiplier effect).Purpose of the medullary concentration gradient: The concentrated medullary tissue fluid provides the osmotic gradient that drives water reabsorption from the collecting duct when ADH is present. Without this gradient, the kidneys could not produce concentrated urine.
Blood pH is normally maintained between 7.35 and 7.45 . Enzymes and metabolic processes are highly sensitive to pH changes. A blood pH below 7.35 is called acidosis ; above 7.45 is called alkalosis . Either extreme can be fatal.
A buffer resists changes in pH by minimising the effect of adding acid or alkali.
The bicarbonate buffer system:
H + + H C O 3 − ⇌ H 2 C O 3 ⇌ C O 2 + H 2 O \mathrm{H}^+ + \mathrm{HCO}_3^- \rightleftharpoons \mathrm{H}_2\mathrm{CO}_3 \rightleftharpoons \mathrm{CO}_2 + \mathrm{H}_2\mathrm{O} H + + HCO 3 − ⇌ H 2 CO 3 ⇌ CO 2 + H 2 O
When H + \mathrm{H}^+ H + H C O 3 − \mathrm{HCO}_3^- HCO 3 − H 2 C O 3 \mathrm{H}_2\mathrm{CO}_3 H 2 CO 3 C O 2 \mathrm{CO}_2 CO 2 H 2 O \mathrm{H}_2\mathrm{O} H 2 O C O 2 \mathrm{CO}_2 CO 2 When H + \mathrm{H}^+ H + H 2 C O 3 \mathrm{H}_2\mathrm{CO}_3 H 2 CO 3 H + \mathrm{H}^+ H + Haemoglobin as a buffer:
Haemoglobin can bind H + \mathrm{H}^+ H + In the tissues: C O 2 \mathrm{CO}_2 CO 2 H C O 3 − \mathrm{HCO}_3^- HCO 3 − H + \mathrm{H}^+ H + H + \mathrm{H}^+ H + In the lungs: the reaction reverses; H + \mathrm{H}^+ H + H C O 3 − \mathrm{HCO}_3^- HCO 3 − C O 2 \mathrm{CO}_2 CO 2 Increased C O 2 \mathrm{CO}_2 CO 2 Chemoreceptors detect the decrease in pH and stimulate the ventilation centre in the medulla Breathing rate and depth increase, exhaling more C O 2 \mathrm{CO}_2 CO 2 Blood pH rises back to normal This is a rapid response (seconds to minutes) but can only compensate for changes related to C O 2 \mathrm{CO}_2 CO 2 The kidneys provide a slower but more powerful mechanism for pH regulation (takes hours to days):
In acidosis (low pH): the kidneys excrete more H + \mathrm{H}^+ H + H C O 3 − \mathrm{HCO}_3^- HCO 3 − N H 3 \mathrm{NH}_3 NH 3 H + \mathrm{H}^+ H + N H 4 + \mathrm{NH}_4^+ NH 4 + In alkalosis (high pH): the kidneys excrete more H C O 3 − \mathrm{HCO}_3^- HCO 3 − H + \mathrm{H}^+ H + Feature Detail Cause Autoimmune destruction of β \beta β Insulin NOT produced (absolute insulin deficiency) Onset in childhood or adolescence Treatment Insulin injections (lifelong); blood glucose monitoring; dietary management Mechanism Without insulin, cells cannot take up glucose; blood glucose rises; glucose appears in urine (glycosuria) when it exceeds the renal threshold (approximately 180 mg/100 cm3 ^3 3
Feature Detail Cause Body cells become resistant to insulin (reduced sensitivity of insulin receptors); β \beta β Insulin Initially produced (sometimes at higher levels than normal); eventually production may decrease Onset in adults (increasingly seen in younger people); strongly linked to obesity, physical inactivity, and diet Treatment Lifestyle changes (diet, exercise); oral medication (e.g., metformin, which increases insulin sensitivity and reduces hepatic glucose production); insulin may be needed in advanced cases Risk factors Obesity, sedentary lifestyle, family history, high-calorie diet, ageing
Symptom Mechanism Hyperglycaemia (high blood glucose) Insulin deficiency or resistance prevents glucose uptake by cells Glycosuria (glucose in urine) Blood glucose exceeds the renal threshold; PCT carrier proteins are saturated Polyuria (excessive urination) Excess glucose in the filtrate lowers water potential; less water reabsorbed by osmosis; large volume of urine produced Polydipsia (excessive thirst) Loss of water in urine reduces blood volume and increases blood osmolarity, detected by hypothalamic osmoreceptors, stimulating thirst Weight loss Body breaks down fat and protein for energy (since glucose cannot enter cells); loss of calories in urine (glucose) Fatigue Cells cannot use glucose efficiently for energy Blurred vision High blood glucose causes osmotic changes in the lens of the eye Slow wound healing High glucose impairs immune function and circulation
Complication Mechanism Cardiovascular disease Damage to blood vessels from chronic hyperglycaemia; increased atherosclerosis; increased risk of heart attack and stroke Kidney damage (nephropathy) High glucose damages the glomerular filtration membrane, reducing kidney function; can lead to kidney failure Nerve damage (neuropathy) High glucose damages peripheral nerves, causing numbness, tingling, and pain, especially in the extremities Retinopathy Damage to blood vessels in the retina; can cause blindness Foot ulcers and amputation Reduced sensation (neuropathy) and poor circulation lead to undetected injuries and poor healing
A patient with uncontrolled Type 1 diabetes has a fasting blood glucose concentration of 320 mg/100 cm3 ^3 3 3 ^3 3 3 ^3 3
(a) Calculate the mass of glucose filtered per day. (b) Calculate the mass of glucose reabsorbed per day. (c) Calculate the mass of glucose excreted in urine per day. (d) Explain why this patient produces large volumes of urine.
Solution (a) Glucose filtered per day = concentration × \times × 320 m g / 100 c m 3 × 180 × 10 d m 3 320 \mathrm{ mg/100 cm}^3 \times 180 \times 10 \mathrm{ dm}^3 320 mg/100cm 3 × 180 × 10 dm 3
= 320 × 10 m g / d m 3 × 180 d m 3 = 576 000 m g / d a y = 576 g / d a y = 320 \times 10 \mathrm{ mg/dm}^3 \times 180 \mathrm{ dm}^3 = 576\,000 \mathrm{ mg/day} = 576 \mathrm{ g/day} = 320 × 10 mg/dm 3 × 180 dm 3 = 576 000 mg/day = 576 g/day
(b) Maximum glucose reabsorption = 375 m g / m i n × 60 × 24 = 540 000 m g / d a y = 540 g / d a y 375 \mathrm{ mg/min} \times 60 \times 24 = 540\,000 \mathrm{ mg/day} = 540 \mathrm{ g/day} 375 mg/min × 60 × 24 = 540 000 mg/day = 540 g/day
(c) Glucose excreted = glucose filtered - glucose reabsorbed = 576 − 540 = 36 g / d a y 576 - 540 = 36 \mathrm{ g/day} 576 − 540 = 36 g/day
(d) The excess glucose in the filtrate (36 g/day that is not reabsorbed) lowers the water potential of the tubule fluid. Less water is reabsorbed from the nephron by osmosis (because the water potential gradient between the tubule fluid and the blood is reduced). This produces a large volume of dilute urine (polyuria). The loss of excess water reduces blood volume and increases blood osmolarity, which stimulates osmoreceptors in the hypothalamus, triggering thirst (polydipsia).
Life’s balancing act: Homeostasis is like a thermostat — the body constantly monitors conditions and adjusts to keep them stable. When blood sugar rises, insulin brings it down; when it falls, glucagon brings it back up.
Why it matters: From diabetes to climate adaptation, understanding homeostasis explains how the body maintains health and how disruptions cause disease.
The key insight: Negative feedback reverses changes, positive feedback amplifies them — knowing which is which prevents confusion in exams.
Confusing negative and positive feedback: Negative feedback reverses a change and maintains homeostasis (e.g., blood glucose regulation). Positive feedback amplifies a change and does not maintain homeostasis (e.g., ovulation, childbirth). Do not write that ovulation is controlled by negative feedback.
Writing that ADH is produced by the posterior pituitary: ADH is PRODUCED by neurosecretory cells in the HYPOTHALAMUS. It is STORED and RELEASED by the posterior pituitary. This distinction is frequently tested.
Confusing insulin and glucagon effects: Insulin LOWERS blood glucose (promotes uptake and storage). Glucagon RAISES blood glucose (promotes glycogenolysis and gluconeogenesis). Insulin is from β \beta β α \alpha α
Writing that muscle cells release glucose into the blood: Muscle cells break down glycogen for their own use but CANNOT release free glucose because they lack glucose-6-phosphatase. Only the liver can release glucose into the blood.
Stating that both limbs of the loop of Henle are permeable to water: Only the DESCENDING limb is permeable to water. The ASCENDING limb is impermeable to water but actively transports N a + \mathrm{Na}^+ Na + C l − \mathrm{Cl}^- Cl −
Writing that high ADH causes dilute urine: The opposite is true. High ADH causes concentrated urine (more water is reabsorbed). Low ADH causes dilute urine (more water is excreted).
Confusing the roles of receptors and effectors: Receptors DETECT changes; effectors CARRY OUT responses. Do not write that the skin “detects” cold (skin has thermoreceptors that detect cold, and the skin is also an effector — blood vessels constrict/dilate, sweat glands secrete).
Writing that temperature regulation is controlled by hormones alone: Temperature regulation is primarily controlled by the NERVOUS system (hypothalamus detects changes and sends nerve impulses to effectors). Thyroxine and adrenaline play supporting roles in the cold response but are not the primary mechanism.
Confusing acidosis and alkalosis: Acidosis = low blood pH (below 7.35); alkalosis = high blood pH (above 7.45). High C O 2 \mathrm{CO}_2 CO 2
Writing that Type 2 diabetes involves no insulin production: Type 2 diabetes involves insulin RESISTANCE, not absence of insulin. In the early stages, insulin levels may be normal or even elevated. Type 1 diabetes involves NO insulin production.
Problem 1: Explain the difference between negative and positive feedback. For each type, describe one example of its role in human physiology and explain why it is appropriate for that physiological process.
If you get this wrong, revise: Principles of Homeostasis — Negative Feedback; Positive Feedback
Solution Negative feedback reverses a deviation from the set point, restoring the variable to normal. Example: blood glucose regulation. After a meal, blood glucose rises; insulin is released, promoting glucose uptake and storage; blood glucose falls back to normal; insulin secretion decreases. This is appropriate because the body needs to maintain blood glucose within a narrow range for cellular function.
Positive feedback amplifies a deviation, pushing the variable further from the set point. Example: childbirth. Pressure of the baby’s head on the cervix triggers oxytocin release; oxytocin causes stronger uterine contractions; stronger contractions push the baby further against the cervix, stimulating more oxytocin release. This is appropriate because the process needs to reach completion (birth) rather than returning to a set point. Once the baby is born, the positive feedback loop ends.
Problem 2: Describe the mechanism by which ADH regulates water balance in the kidneys. Explain why a person in a hot desert environment would have high blood ADH levels.
If you get this wrong, revise: Osmoregulation — ADH and the Regulation of Water Balance
Solution ADH is released from the posterior pituitary when blood water potential is low. It binds to receptors on collecting duct cells, triggering the insertion of aquaporin channels into the cell membrane. This makes the collecting duct more permeable to water. Water is reabsorbed from the collecting duct by osmosis into the concentrated medullary tissue fluid (maintained by the loop of Henle counter-current multiplier). The result is a small volume of concentrated urine, conserving water in the body.
In a hot desert, the person loses water through sweating (thermoregulation) and exhalation. This reduces blood volume and increases blood solute concentration (lowers blood water potential). Osmoreceptors in the hypothalamus detect this and stimulate the posterior pituitary to release more ADH. The kidneys produce a small volume of concentrated urine to minimise further water loss, helping the person survive in the arid environment.
Problem 3: Compare Type 1 and Type 2 diabetes in terms of cause, insulin levels, age of onset, treatment, and the mechanism by which blood glucose rises to harmful levels.
If you get this wrong, revise: Diabetes Mellitus — Type 1 Diabetes; Type 2 Diabetes
Solution Feature Type 1 Diabetes Type 2 Diabetes Cause Autoimmune destruction of β \beta β Insulin resistance (reduced receptor sensitivity); genetic and lifestyle factors Insulin Not produced (absolute deficiency) Initially normal or elevated; may decrease over time (relative deficiency) Onset childhood/adolescence adulthood (but increasingly in younger people) Treatment Insulin injections (lifelong) Diet, exercise, oral medication; insulin in advanced cases Mechanism No insulin means cells cannot take up glucose; glucose accumulates in blood Cells become resistant to insulin; glucose uptake is impaired despite insulin presence
In both types, blood glucose rises because glucose cannot enter cells efficiently. Excess glucose is excreted in the urine (glycosuria), causing water loss (polyuria) and thirst (polydipsia). Long-term complications (cardiovascular disease, kidney damage, nerve damage, retinopathy) result from chronic hyperglycaemia damaging blood vessels and tissues.
Gestational diabetes mellitus (GDM) is a form of diabetes that develops during pregnancy and resolves after childbirth.
Feature Detail Cause Placental hormones (human placental lactogen, progesterone, cortisol) cause insulin resistance in maternal tissues; the pancreas may not produce enough additional insulin to compensate Onset during the second or third trimester (24-28 weeks) Risk factors Obesity, family history of Type 2 diabetes, previous GDM, maternal age over 35, certain ethnicities Risks to mother Increased risk of pre-eclampsia; increased risk of developing Type 2 diabetes later in life Risks to foetus Macrosomia (excessive birth weight); hypoglycaemia after birth; respiratory distress syndrome; increased risk of obesity and Type 2 diabetes in adulthood Management Dietary control; exercise; blood glucose monitoring; insulin if needed (oral hypoglycaemics are generally avoided in pregnancy)
Hyperthyroidism (overactive thyroid):
Feature Detail Cause Graves’ disease (autoimmune); thyroid nodule; excessive TSH Hormone Excess thyroxine (T 4 \mathrm{T}_4 T 4 T 3 \mathrm{T}_3 T 3 Symptoms Increased BMR; weight loss despite increased appetite; rapid heart rate (tachycardia); anxiety; tremor; heat intolerance; sweating; exophthalmos (bulging eyes in Graves’ disease) Treatment Anti-thyroid drugs (e.g., carbimazole); radioactive iodine; surgical removal of part or all of the thyroid
Hypothyroidism (underactive thyroid):
Feature Detail Cause Hashimoto’s thyroiditis (autoimmune); iodine deficiency; surgical removal; radioactive iodine treatment Hormone Insufficient thyroxine (T 4 \mathrm{T}_4 T 4 T 3 \mathrm{T}_3 T 3 Symptoms Decreased BMR; weight gain; fatigue; cold intolerance; dry skin; slow heart rate (bradycardia); depression; myxoedema (swelling of skin and tissues) Treatment Thyroxine replacement therapy (daily levothyroxine tablets)
Addison’s disease (adrenal insufficiency):
Destruction of the adrenal cortex (autoimmune or tuberculosis) Reduced production of cortisol and aldosterone Symptoms: fatigue, weight loss, low blood pressure, hyperpigmentation of skin, salt craving, hypoglycaemia Treatment: cortisol replacement (hydrocortisone); fludrocortisone (to replace aldosterone) Cushing’s syndrome:
Excess cortisol (from prolonged corticosteroid medication or adrenal tumour) Symptoms: weight gain (especially abdominal), moon face, buffalo hump, thin skin, easy bruising, high blood pressure, muscle weakness, hyperglycaemia A patient presents with weight gain, fatigue, cold intolerance, and a slow heart rate. Blood tests show elevated TSH and low T 4 \mathrm{T}_4 T 4
Solution Normal negative feedback loop:
The hypothalamus releases TRH (thyrotropin-releasing hormone), which stimulates the anterior pituitary The anterior pituitary releases TSH (thyroid-stimulating hormone), which stimulates the thyroid gland The thyroid gland produces and releases T 4 \mathrm{T}_4 T 4 T 3 \mathrm{T}_3 T 3 T 4 \mathrm{T}_4 T 4 T 3 \mathrm{T}_3 T 3 When T 4 \mathrm{T}_4 T 4 T 3 \mathrm{T}_3 T 3 In this patient (hypothyroidism):
The thyroid gland is not producing enough T 4 \mathrm{T}_4 T 4 T 4 \mathrm{T}_4 T 4 T 3 \mathrm{T}_3 T 3
Ectotherms (reptiles, amphibians, fish, invertebrates) rely primarily on behavioural and physiological mechanisms rather than metabolic heat production to regulate their body temperature.
Mechanism Description Example Basking Moving to a warm area and exposing the body surface to direct sunlight Lizards on rocks; snakes in sunlight Sheltering Moving to shade, burrows, or crevices during hot periods Snakes in rock crevices; toads in burrows Nocturnal activity Being active at night when temperatures are lower Geckos; desert rodents Countercurrent heat exchange Alternating the direction of blood flow in limbs to either conserve or lose heat depending on need Dolphin flukes; woodpecker feet Altering body shape Flattening the body to increase surface area for heat loss or reducing it to conserve heat Horned vipers flatten to increase surface area for heat absorption Adjusting heart rate Increasing heart rate to deliver more blood to the body surface for heat loss Lizards in sun increase heart rate Changing colour Some reptiles can darken their skin to absorb more heat Bearded dragons darken when cold
Birds and mammals generate heat internally through metabolism and use insulation and behavioural mechanisms to maintain body temperature.
Mechanism Description Example Shivering thermogenesis Rapid, involuntary muscle contractions that generate heat as a by-product of respiration Mammals in cold environments Non-shivering thermogenesis Brown adipose tissue (BAT) uncouples respiration from ATP production, releasing energy directly as heat; stimulated by sympathetic nervous system Newborn human infants; hibernating mammals Piloerection Hair erector muscles contract, trapping insulating air next to the skin Goosebumps in humans; mammals fluffing fur Vasoconstriction Reducing blood flow to the skin surface to reduce heat loss Mammals in cold environments Insulation (fur/blubber) Trapped air in fur or fat provides effective insulation against heat loss Arctic mammals have thick blubber layers Huddling Group behaviour to reduce surface area to volume ratio; reduces heat loss per individual Penguins in the Antarctic; macaques Nest building Constructing insulated structures to reduce heat loss Birds building insulated nests Countercurrent exchange Arterial blood flowing to limbs passes close to venous blood returning from limbs, allowing heat exchange between them Dolphin flukes; wolf paws
Hibernation: A state of reduced metabolic rate and body temperature during winter, allowing animals to survive when food is scarce.
Feature Description Body temperature Drops to near ambient (1-5 degrees C in many mammals); dramatically reduces metabolic rate (to approximately 2-5% of normal) Heart rate Drops to approximately 5% of normal Breathing rate Very slow and shallow Fat reserves Accumulated brown fat provides energy throughout hibernation Periodic arousal Animals periodically wake up to urinate, feed briefly, and restore normal body temperature Animals that hibernate Bats, hedgehogs, marmots, ground squirrels, dormice, bears (shallow hibernation)
Aestivation: A similar state of reduced metabolic rate during summer, triggered by heat and drought. Common in desert animals (e.g., desert tortoise, African lungfish).
Adaptation Mechanism for Heat Conservation Thick blubber layer 5-10 cm of subcutaneous fat; very effective insulation (thermal conductivity approximately 0.25 W/m/K) Dense underfur Trapped air in dense fur provides insulation; hollow guard hairs in polar bears increase insulation further Small ears and tail Reduced surface area to volume ratio minimises heat loss Counter-current heat exchange Arterioles in legs are wrapped by veins, allowing heat exchange; warm arterial blood transfers heat to returning venous blood near the body, minimising heat loss at the extremities Behavioural adaptations Huddling; building snow dens; reducing activity; sheltering from wind
Ectotherms (reptiles, amphibians, fish, invertebrates) rely primarily on behavioural and physiological mechanisms to regulate their body temperature rather than metabolic heat production.
Mechanism Description Example Basking Moving to a warm area and exposing the body surface to direct sunlight Lizards on rocks; snakes in sunlight Sheltering Moving to shade, burrows, or crevices during hot periods Snakes in rock crevices; toads in burrows Nocturnal activity Being active at night when temperatures are lower Geckos; desert rodents Countercurrent exchange Alternating the direction of blood flow in limbs to either conserve or lose heat depending on need Dolphin flukes; woodpecker feet Altering body shape Flattening the body to increase surface area for heat loss or reducing it to conserve heat Horned vipers flatten to absorb more heat Adjusting heart rate Increasing heart rate to deliver more blood to the body surface for heat loss Lizards in sun increase heart rate
Mechanism Description Example Shivering thermogenesis Rapid, involuntary muscle contractions that generate heat as a by-product of respiration Mammals in cold environments Non-shivering thermogenesis Brown adipose tissue (BAT) uncouples respiration from ATP production, releasing energy directly as heat; stimulated by sympathetic nervous system Newborn human infants; hibernating mammals Piloerection Hair erector muscles contract, trapping insulating air next to the skin Goosebumps in humans; mammals fluffing fur Vasoconstriction Reducing blood flow to the skin surface to reduce heat loss Mammals in cold environments Insulation (fur/blubber) Trapped air in fur or fat provides effective insulation against heat loss Arctic mammals have thick blubber layers Huddling Group behaviour to reduce surface area to volume ratio; reduces heat loss per individual Penguins in the Antarctic; macaques
Hibernation: A state of reduced metabolic rate and body temperature during winter.
Feature Description Body temperature Drops to near ambient (1-5 degrees C); metabolic rate drops to approximately 2-5% of normal Heart rate Drops to approximately 5% of normal Breathing rate Very slow and shallow Fat reserves Accumulated brown fat provides energy throughout hibernation Periodic arousal Animals periodically wake to urinate, feed briefly, and restore normal body temperature Animals that hibernate Bats, hedgehogs, marmots, ground squirrels, dormice, bears (shallow hibernation)
Aestivation: Similar state of reduced metabolic rate during summer, triggered by heat and drought. Common in desert animals (e.g., desert tortoise, African lungfish).
Adaptation Mechanism for Heat Conservation Thick blubber layer 5-10 cm of subcutaneous fat; very effective insulation (thermal conductivity approximately 0.25 W/m/K) Dense underfur Trapped air in dense fur provides insulation; hollow guard hairs in polar bears increase insulation further Small ears and tail Reduced surface area to volume ratio minimises heat loss Counter-current exchange Arterioles in legs wrapped by veins allows heat exchange; warm arterial blood transfers heat to returning venous blood near the body, minimising heat loss at extremities Behavioural adaptations Huddling; building snow dens; reducing activity; sheltering from wind
Component Location in Kidney Description Renal (Bowman’s) capsule Cortex Cup-shaped structure that surrounds the glomerulus; consists of an outer parietal layer (simple squamous epithelium) and an inner visceral layer (podocytes) Glomerulus Cortex Knot of capillaries between the afferent and efferent arterioles; high pressure due to the wide afferent and narrow efferent arteriole; site of ultrafiltration Proximal convoluted tubule (PCT) Cortex Highly coiled tube immediately after the renal capsule; lined with cuboidal epithelial cells with microvilli (brush border) and many mitochondria Loop of Henle Medulla (descending limb and thin ascending limb); cortex (thick ascending limb) Hairpin loop that creates a concentration gradient in the medulla; essential for producing concentrated urine Distal convoluted tubule (DCT) Cortex Coiled tube after the loop of Henle; lined with cuboidal epithelial cells (fewer microvilli than PCT); site of selective reabsorption and secretion Collecting duct Passes from cortex through the medulla to the renal pelvis Receives filtrate from multiple nephrons; permeability to water is controlled by ADH; delivers urine to the renal pelvis Peritubular capillaries Surround the PCT and DCT; arise from the efferent arteriole Reabsorb water, glucose, amino acids, and ions from the tubules back into the blood; secrete waste products into the tubules Vasa recta Hairpin-shaped capillaries that run alongside the loop of Henle Maintain the medullary concentration gradient by counter-current exchange
Ultrafiltration is the process by which blood is filtered in the glomerulus to form the glomerular filtrate (a protein-free, cell-free fluid similar to blood plasma).
Conditions for ultrafiltration:
Condition Description High blood pressure The afferent arteriole is wider than the efferent arteriole, creating high hydrostatic pressure (~55 mmHg) in the glomerulus that forces fluid out of the capillaries Fenestrated endothelium The capillary walls of the glomerulus have pores (fenestrations) that allow water and small solutes to pass through but restrict large molecules and cells Basement membrane A thick, negatively charged glycoprotein layer between the endothelium and the podocytes; acts as an additional filter; repels large proteins (which are negatively charged) Podocytes Specialised epithelial cells of the renal capsule with foot processes (pedicels) that wrap around the capillaries; filtration slits between the foot processes act as a final filter
What is filtered? Water, glucose, amino acids, urea, ions (Na+ ^+ + + ^+ + − ^- − 2 + ^{2+} 2 + 3 − _3^- 3 −
Substance PCT Reabsorption (approximate %) Mechanism Water ~65% Osmosis (following the reabsorption of solutes) Sodium ions (Na+ ^+ + ~65% Active transport (Na+ ^+ + + ^+ + Glucose 100% (in healthy kidneys) Secondary active transport (co-transport with Na+ ^+ + Amino acids 100% (in healthy kidneys) Secondary active transport (co-transport with Na+ ^+ + Potassium ions (K+ ^+ + ~65% Active transport and diffusion Calcium ions (Ca2 + ^{2+} 2 + ~65% Active transport (regulated by parathyroid hormone) Bicarbonate (HCO3 − _3^- 3 − ~85% Reabsorbed as CO2 _2 2 2 _2 2 3 _3 3 2 _2 2 2 _2 2 2 _2 2 3 − _3^- 3 − Urea ~50% Passive diffusion (reabsorbed along with water)
The loop of Henle acts as a countercurrent multiplier to create a concentration gradient in the medulla:
Descending limb: Permeable to water but NOT to ions. As the filtrate descends into the increasingly concentrated medulla, water leaves the filtrate by osmosis; the filtrate becomes more concentratedThin ascending limb: Permeable to ions (Na+ ^+ + − ^- − + ^+ + − ^- − Thick ascending limb: Impermeable to water; actively transports Na+ ^+ + + ^+ + − ^- − + ^+ + + ^+ + + ^+ + + ^+ + − ^- − The countercurrent flow (descending and ascending limbs flowing in opposite directions) amplifies the concentration gradient Result: the medullary interstitial fluid at the bottom of the loop is hypertonic (up to 1200 mOsm/L, compared to ~300 mOsm/L in the cortex) This gradient allows the collecting duct to reabsorb water and produce concentrated urine (when ADH is present) Layer Components Functions Epidermis Keratinocytes (produce keratin for water…/1-number-and-algebra/3_proof-and-logicing); melanocytes (produce melanin for UV protection); Langerhans cells (immune defence); Merkel cells (touch receptors) Water…/1-number-and-algebra/3_proof-and-logic barrier; protection against pathogens and UV radiation; vitamin D synthesis (7-dehydrocholesterol → \rightarrow → Dermis Blood vessels; nerves; hair follicles; sebaceous glands; sweat glands (eccrine and apocrine); sensory receptors (Meissner’s corpuscles, Pacinian corpuscles) Nourishment; sensation; thermoregulation; lubrication of hair and skin; structural support (collagen and elastin fibres) Hypodermis Adipose tissue (fat); connective tissue Insulation; energy storage; cushioning
When body temperature RISES (e.g., during exercise, in hot weather):
Response Mechanism Vasodilation Blood vessels in the dermis dilate (smooth muscle in the vessel walls relaxes); more blood flows near the skin surface; heat is lost by radiation and convection from the skin surface Sweating Sweat glands secrete sweat onto the skin surface; water in sweat evaporates, taking latent heat of vaporisation from the skin; this is the most effective cooling mechanism; can lose up to 1-2 litres of sweat per hour during intense exercise Decreased metabolic rate Cells reduce their rate of respiration, producing less heat as a by-product Behavioural responses Removing clothing; seeking shade; drinking cold fluids; fanning
When body temperature FALLS (e.g., in cold weather):
Response Mechanism Vasoconstriction Blood vessels in the dermis constrict (smooth muscle contracts); less blood flows near the skin surface; less heat is lost from the body surface; blood is diverted to the core to protect vital organs Shivering Rapid, involuntary contractions of skeletal muscles; respiration in the muscle cells increases, producing more heat as a by-product Piloerection Hair erector muscles contract; hairs stand upright, trapping a layer of still air next to the skin (insulating layer); effective in furry animals but limited effect in humans (goosebumps) Increased metabolic rate Cells increase their rate of respiration; thyroid hormones (T3, T4) stimulate basal metabolic rate; brown adipose tissue (in newborns and hibernating mammals) generates heat through non-shivering thermogenesis Behavioural responses Adding clothing; seeking shelter; curling up (reducing surface area to volume ratio); huddling
Normal body temperature: approximately 37 degrees C (core temperature)Temperature receptors: Thermoreceptors in the skin (detect external temperature changes) and in the hypothalamus (detect blood temperature changes) send nerve impulses to the thermoregulatory centre in the hypothalamusThermoregulatory centre: The hypothalamus processes the information and sends nerve impulses to effectors:Sweat glands (via sympathetic nervous system) Blood vessels in the skin (via sympathetic nervous system) Skeletal muscles (via motor neurons) Adrenal medulla (triggers adrenaline release for metabolic effects) Negative feedback: When the corrective response brings body temperature back to normal, the thermoreceptors detect this change and the hypothalamus reduces the corrective signalsUltrafiltration occurs in the glomerulus; selective reabsorption occurs primarily in the proximal convoluted tubule. Students often confuse the site of these two processesThe loop of Henle creates the concentration gradient in the medulla; the collecting duct USES this gradient to produce concentrated urine (when ADH is present). The loop does not reabsorb water; the collecting duct doesThe descending limb of the loop of Henle is permeable to water but NOT to ions; the ascending limb is permeable to ions but NOT to water. Getting these mixed up is a common errorADH increases water reabsorption, NOT decreases it. More ADH = more concentrated urine (less volume); less ADH = more dilute urine (more volume)Sweating cools the body through EVAPORATION, not through the production of sweat itself. If sweat drips off the skin without evaporating, it does not cool the body. This is why fans help with cooling (they increase evaporation rate)**:::tip Tip Ready to test your understanding of **Homeostasis**? Review the which covers homeostatic topics within the DSE specification.See for instructions on self-marking and building a personal test matrix.
When kidneys fail (renal failure), they can no longer:
Filter metabolic waste products (urea, creatinine, uric acid) Regulate water and ion balance Regulate blood pH Produce erythropoietin (leading to anaemia) If untreated, toxic levels of urea accumulate (uraemia ), causing nausea, confusion, seizures, and death.
Feature Description Principle Blood is pumped out of the body, passed through a dialyser (artificial kidney), and returned. Waste products diffuse from the blood across a partially permeable membrane into the dialysis fluid Dialysis membrane Made of cellulose acetate or synthetic polymer; permeable to small molecules (urea, ions, glucose) but not to large molecules (proteins, blood cells) Dialysis fluid (dialysate) Contains the same concentration of useful substances (glucose, ions) as normal blood plasma but NO urea — this creates a concentration gradient for urea to diffuse from blood into dialysate Flow Blood flows in one direction through the dialyser; dialysate flows in the opposite direction (counter-current exchange ) — this maintains the concentration gradient along the entire length of the dialyser, maximising diffusion efficiency Frequency 3 sessions per week, each lasting 3-5 hours Access An arteriovenous fistula (surgical connection between an artery and vein) provides a high-flow blood vessel for repeated needle insertion Anticoagulant Heparin is added to prevent blood clotting in the dialyser
Feature Description Principle The peritoneum (lining of the abdominal cavity) acts as the dialysis membrane. Dialysis fluid is introduced into the abdominal cavity through a catheter; waste products diffuse from the blood in the peritoneal capillaries into the dialysis fluid Exchange After several hours (dwell time), the dialysis fluid (now containing waste) is drained and replaced with fresh fluid Frequency Continuous (CAPD — continuous ambulatory peritoneal dialysis): 4-5 exchanges per day; automated (APD): machine performs exchanges overnight Advantages Can be performed at home; no need for a machine (CAPD); more gentle on the body; preserves remaining kidney function better Disadvantages Risk of peritonitis (infection of the abdominal cavity); less efficient than haemodialysis for large patients or those with high urea levels
Aspect Haemodialysis Peritoneal Dialysis Location Hospital or dialysis centre Home Membrane Artificial (dialyser) Natural (peritoneum) Efficiency Higher; removes waste more quickly Lower; slower process Convenience Requires travel to centre 3x/week Can be done at home; more independence Infection risk Low (sterile procedure) Higher (peritonitis risk) Diet restrictions Strict (fluid, potassium, phosphate) Less strict Suitable for Most patients; acute renal failure Patients who prefer home treatment; children
The best treatment for end-stage renal failure A healthy kidney from a living donor ( a relative) or a deceased donor is transplanted into the patient’s lower abdomen The donor kidney is connected to the recipient’s blood vessels and ureter Advantages over dialysis: no need for regular dialysis sessions; better quality of life; longer life expectancy; fewer dietary restrictions Disadvantages: risk of surgical complications; need for lifelong immunosuppressive drugs (increased risk of infections); risk of rejection; shortage of donor organs Success rate: approximately 95% survival at 1 year for kidneys from living donors Stimulus: Blood water potential decreases (blood becomes more concentrated; osmolarity increases above normal ~300 mOsm/L). This can be caused by:Sweating (water loss through skin) Insufficient water intake (dehydration) High salt intake (increases blood osmolarity) Diarrhoea or vomiting (water loss) Detection: Osmoreceptors in the hypothalamus detect the decrease in blood water potential. Osmoreceptors are specialised neurons that shrink when the surrounding fluid becomes more concentrated, triggering nerve impulses.
Coordination:
The hypothalamus sends nerve impulses to the posterior pituitary gland , stimulating it to release antidiuretic hormone (ADH, vasopressin) into the blood Simultaneously, the hypothalamus stimulates the thirst centre in the brain, creating the sensation of thirst and motivating water-drinking behaviour Effector response (kidneys): ADH binds to receptors on the cells of the collecting ducts and distal convoluted tubules in the nephrons This triggers the insertion of aquaporin water channels into the luminal membrane of these cells Water is now reabsorbed from the filtrate into the blood by osmosis (the medullary interstitial fluid is hypertonic due to the counter-current multiplier in the loop of Henle) More concentrated urine is produced (small volume, high urea concentration) Blood water potential returns to normal Negative feedback: As blood water potential returns to normal, osmoreceptors in the hypothalamus detect the change and reduce ADH secretion. Aquaporin channels are removed from the collecting duct membranes, reducing water reabsorption.Condition Blood Osmolarity ADH Level Aquaporin Channels Water Reabsorption Urine Volume Urine Concentration Dehydrated High High Many inserted High Low High (concentrated) Normal hydration Normal Normal Moderate Moderate Normal Normal Over-hydrated Low Low Few Low High Low (dilute)
A condition characterised by the inability to concentrate urine, resulting in the production of large volumes of dilute urine (up to 20 litres per day) Central diabetes insipidus: The hypothalamus or posterior pituitary does not produce or release sufficient ADH (caused by head injury, tumour, infection)Nephrogenic diabetes insipidus: The kidneys do not respond to ADH — the collecting duct cells lack functional receptors or aquaporin channels (caused by genetic mutations, certain drugs such as lithium)Treatment: desmopressin (synthetic ADH) for central DI; treating the underlying cause for nephrogenic DI The pancreas has both exocrine and endocrine functions:
Function Description Exocrine Acinar cells produce digestive enzymes (amylase, lipase, trypsinogen) and bicarbonate, secreted into the duodenum via the pancreatic duct Endocrine Islets of Langerhans produce hormones released into the blood: α \alpha α glucagon ; β \beta β insulin
Aspect Insulin (β \beta β Glucagon (α \alpha α Trigger Blood glucose concentration rises above normal (~5 mmol/L) Blood glucose concentration falls below normal (~5 mmol/L) Effect on blood glucose Decreases (lowers blood glucose) Increases (raises blood glucose) Target organs Liver, muscle cells, adipose tissue Liver Key mechanisms — Increases glucose uptake by cells (by stimulating translocation of GLUT4 transporters to the cell membrane in muscle and fat cells) — Stimulates glycogenolysis (breakdown of glycogen to glucose) in the liver — Stimulates glycogenesis (conversion of glucose to glycogen) in the liver and muscles — Stimulates gluconeogenesis (synthesis of glucose from amino acids and lactate) in the liver — Stimulates lipogenesis (conversion of glucose to fat for storage) in adipose tissue — Stimulates lipolysis (breakdown of fat to fatty acids and glycerol) in adipose tissue — Inhibits gluconeogenesis and glycogenolysis in the liver — Increases blood glucose — Increases rate of glucose uptake and use by cells (increases respiration rate)
Process Meaning Direction Stimulated By Inhibited By Glycogenesis Glycogen formation Glucose → \rightarrow → Insulin Glucagon Glycogenolysis Glycogen breakdown Glycogen → \rightarrow → Glucagon Insulin Gluconeogenesis New glucose synthesis Amino acids/lactate → \rightarrow → Glucagon Insulin
During the fight-or-flight response, the adrenal medulla releases adrenaline, which:
Stimulates glycogenolysis in the liver (rapidly increases blood glucose) Inhibits insulin secretion and stimulates glucagon secretion This ensures that muscles have an adequate supply of glucose for respiration during physical activity or stress The effect is short-lived compared to the effects of cortisol from the adrenal cortex Normally, all glucose is reabsorbed from the filtrate in the proximal convoluted tubule (via sodium-glucose co-transporters) The renal threshold for glucose is approximately 9-10 mmol/L — if blood glucose exceeds this level, the transporters become saturated and glucose appears in the urine (glycosuria) Glycosuria is a characteristic symptom of diabetes mellitus Insulin decreases blood glucose; glucagon increases it. Students often confuse the two — remember: “Insulin is IN, glucose goes IN to cells”Glucagon acts primarily on the liver, NOT on muscle cells. Muscle cells lack the receptor for glucagon. Only the liver can release glucose into the bloodInsulin and glucagon are antagonistic hormones — they have opposite effects on blood glucose concentrationType 1 diabetes is caused by autoimmune destruction of β \beta β (not α \alpha α Diabetes insipidus is NOT related to blood glucose. It is a disorder of water balance (ADH deficiency or resistance), causing dilute urine. It should not be confused with diabetes mellitusThe renal threshold is the blood glucose concentration at which glucose first appears in the urine (~9-10 mmol/L), NOT the normal blood glucose level (~5 mmol/L) ::: A[3_Homeostasis] --> B[Key Concepts]
A --> D[Practical Applications]
B --> E[Fundamental definitions]
D --> G[Real-world usage]
experimental evidence, and real-world applications.
Stashed changes:docs/docs_dse/Biology/homeostasis.md
Key concepts include:
photosynthesis (light-dependent and independent) transpiration and water transport plant hormones and tropisms reproduction in flowering plants plant responses to the environment Success requires the ability to recall specific factual content, apply knowledge to novel scenarios, and evaluate experimental evidence critically.
Stashed changes:docs/docs_dse/Biology/homeostasis.md
Worked examples demonstrating the application of key concepts are covered in the detailed sub-pages linked above.
