The internal environment

Homeostasis is the regulatory process that keeps an organism’s internal environment within preset limits, even when conditions outside or inside the organism change. In a multicellular animal, most cells do not touch air, food or water directly. They sit in tissue fluid, an extracellular fluid that surrounds body cells and exchanges substances with blood.

Why does this matter? Enzymes, membranes and transport proteins work best within a narrow range of conditions. If the internal environment shifts too far, metabolism runs less efficiently, or cells may be damaged.

Homeostatic variables in humans

A homeostatic variable is a measurable feature of the internal environment that is regulated around acceptable limits. In humans, the syllabus examples are:

• core body temperature, because enzyme activity and membrane behaviour are temperature-sensitive;
• blood pH, because changes in hydrogen ion concentration alter protein shape and enzyme activity;
• blood glucose concentration, because glucose is a major respiratory substrate, especially important for the brain;
• blood osmotic concentration, because water movement by osmosis affects cell volume and pressure.

A set point is the reference value for a regulated variable, and control systems tend to bring the variable back towards it. Don’t picture one perfectly fixed number. In real bodies, regulation usually works across a narrow range, not at a single mathematical dot. Blood glucose, for example, rises after a meal and falls during fasting, but normally stays within limits that allow cells to function normally.

Why negative feedback is used

Feedback control is a regulatory system in which information about the output of a process affects the future operation of that process. In homeostasis, receptors detect a change, an integrating centre compares the change with the set point, and effectors produce a response.

Negative feedback is a feedback mechanism in which a change in a variable triggers responses that reduce the change and return the variable towards its set point. It works if the variable rises too high or falls too low. That makes it the basic logic of homeostasis: it keeps conditions stable.

Positive feedback is a feedback mechanism in which a change in a variable triggers responses that amplify the change. It helps when the body needs a rapid, self-reinforcing process. It does not maintain constant internal conditions well, because it pushes variables away from the set point.

The usual loop

A homeostatic negative feedback loop normally has four parts:

1. a receptor, which is a sensory cell or protein that detects a change in a variable;
2. an integrating centre, often in the nervous system or an endocrine gland, which compares the detected value with the set point;
3. an effector, which is a cell, tissue or organ that carries out the corrective response;
4. a response that reduces the original deviation.

For example, if a variable rises above the set point, the response lowers it. If the same variable falls below the set point, another response raises it. That two-direction correction is the key point.

Hormones and pancreatic endocrine cells

A hormone is a chemical messenger secreted by endocrine cells into the blood that changes the activity of target cells with specific receptors. The blood part matters. Insulin and glucagon aren't delivered through ducts to a single place; they travel widely in the circulation, but only target cells with the correct receptors respond.

Small clusters of endocrine tissue, called islets, are found in the pancreas. Two pancreatic endocrine cell types are central to blood glucose control:

• alpha cells are pancreatic endocrine cells that secrete glucagon when blood glucose concentration falls below the set point;
• beta cells are pancreatic endocrine cells that secrete insulin when blood glucose concentration rises above the set point.

Insulin lowers blood glucose

Insulin is a peptide hormone secreted by beta cells that lowers blood glucose concentration by increasing glucose uptake and storage in target tissues. After a meal, glucose absorbed from the gut enters the blood. Beta cells detect this increase and release insulin into the bloodstream.

Insulin acts on target cells, especially liver cells, skeletal muscle cells and adipose cells. In many cells it increases glucose uptake and the use of glucose in cell respiration. It also promotes conversion of glucose to glycogen in liver and skeletal muscle. In adipose tissue, it favours conversion of excess glucose into fats. Blood glucose concentration then falls back towards the set point.

Glucagon raises blood glucose

Glucagon is a peptide hormone secreted by alpha cells that raises blood glucose concentration by stimulating glucose release from stores. During fasting or exercise, blood glucose may fall. Alpha cells respond by secreting glucagon into the blood.

Glucagon mainly targets liver cells. It stimulates breakdown of glycogen into glucose, then release of glucose into the bloodstream. When necessary, it also supports production of glucose from non-carbohydrate substrates. Blood glucose concentration then rises back towards the set point.

A balance, not a flat line

Blood glucose control shows homeostasis well because the concentration is not perfectly constant. It fluctuates around a regulated range as glucose is added from digestion or liver stores and removed by respiration, glycogen synthesis and fat synthesis. The body keeps balancing input and output.

What diabetes is

Diabetes mellitus is a metabolic disorder where blood glucose concentration stays abnormally high because the body does not secrete enough insulin or does not respond to insulin properly. When blood glucose remains high for a long time, glucose can pass into the urine. Less water is then reabsorbed in the kidney, so the person may produce large volumes of urine and become dehydrated.

Long-term hyperglycaemia damages tissues, partly because it alters proteins. So diabetes is not just “too much sugar in the blood”. It can seriously affect blood vessels, kidneys, nerves and other tissues.

Type 1 diabetes

Type 1 diabetes is an autoimmune form of diabetes. The immune system destroys pancreatic beta cells, so too little insulin is produced. The physiological change is therefore a failure of insulin secretion. It often appears relatively suddenly in childhood or young adulthood.

Treatment mainly involves regular monitoring of blood glucose and injection or infusion of insulin. Insulin is often given before meals to reduce the rise in glucose after digestion and absorption. Since injected insulin lowers blood glucose whether or not food has been absorbed as expected, the dose and timing have to be managed carefully.

Type 1 diabetes cannot be prevented simply by changing diet or exercise habits, because the underlying problem is immune destruction of beta cells. Research into improved delivery systems and replacement beta cells aims to make treatment closer to normal pancreatic control.

Type 2 diabetes

Type 2 diabetes is a form of diabetes where target cells respond weakly to insulin, often followed later by reduced insulin secretion. The physiological change is mainly insulin resistance: target cells may have fewer effective insulin receptors, impaired signalling pathways or reduced insertion of glucose transporters.

Risk factors include prolonged obesity, diets high in sugar or fat, low physical activity and genetic predisposition affecting energy metabolism. For prevention, the focus is on maintaining a healthy body mass, doing regular physical activity and following dietary patterns that avoid repeated large glucose peaks.

Treatment usually starts with lifestyle measures: weight loss where appropriate, exercise, smaller and more frequent meals, reduced intake of high-sugar foods, and foods with a low glycaemic index because they are digested and absorbed more slowly. Some patients also need medication or insulin if blood glucose cannot be controlled sufficiently.

Glucose tolerance testing

A glucose tolerance test tracks blood glucose concentration after a person drinks a glucose solution. In an unaffected person, blood glucose rises and then returns towards the starting level as insulin acts. In a person with diabetes, the starting concentration may be higher, the peak is usually higher, and return towards the starting concentration is slower. It’s a useful data skill because the diagnosis comes from the shape of the response curve, not just one reading.

Core temperature as a controlled variable

Thermoregulation is a homeostatic process that keeps core body temperature close to a set point by adjusting heat gain, heat production and heat loss. Birds and mammals control body temperature through physiological responses as well as behaviour. In humans, core temperature normally stays close to $37^\circ\text{C}$, although fever shifts the defended temperature upwards during some infections.

Temperature matters because many biological systems are sensitive to it. Enzyme rates change with temperature, and at high temperatures enzymes can lose their functional shape. Membrane fluidity, diffusion rates, respiration, photosynthesis in plants, and muscle function all depend on temperature. Homeothermy costs a lot of energy, but it gives cells a relatively stable biochemical environment to work in.

Receptors and the hypothalamus

A thermoreceptor is a sensory receptor that detects temperature or a change in temperature. Peripheral thermoreceptors in the skin detect temperatures shaped by the external environment, so they help the body anticipate heat loss or heat gain. Central thermoreceptors in the body core, including the hypothalamus, monitor the internal environment more directly.

The hypothalamus is a brain region that brings together sensory information and coordinates homeostatic responses. In thermoregulation, it compares temperature information with the set point and starts responses when the body is becoming too cold or too hot.

Pituitary gland, thyroxin and metabolic heat

The hypothalamus can change metabolic heat production through the pituitary gland and thyroid gland. When the body needs more heat production, the hypothalamus stimulates the pituitary gland to release thyroid-stimulating hormone. This causes the thyroid gland to secrete thyroxin, a hormone that increases metabolic rate in many cells.

Muscle and adipose tissue act as important effectors. Muscle produces heat when it contracts, especially during shivering. Subcutaneous adipose tissue reduces heat loss by insulation. Brown adipose tissue can generate heat quickly through uncoupled respiration, which is especially useful in infants.

Physiological and behavioural control

Birds and mammals keep body temperature under control in two main ways: physiological mechanisms inside the body, and behavioural responses such as seeking shade, adding clothing, huddling, changing posture, drinking water or moving into warmer places. For IB detail, make sure you know the human physiological mechanisms well.

Changing blood flow through the skin

Vasoconstriction is the narrowing of arterioles caused by contraction of circular smooth muscle in their walls. In cold conditions, arterioles supplying the skin vasoconstrict, so less blood flows through skin capillaries. The skin cools, the temperature gradient between skin and surroundings becomes smaller, and less heat is lost.

Vasodilation is the widening of arterioles caused by relaxation of circular smooth muscle in their walls. In hot conditions, arterioles supplying the skin vasodilate, so more blood flows through skin capillaries. The skin warms, the temperature gradient between skin and surroundings becomes larger, and more heat is lost.

Blood vessels do not shift closer to or further from the skin surface. The change is in how much blood flows through capillary beds near the surface.

Responses to cold

Shivering is rapid, involuntary contraction and relaxation of skeletal muscles that generates heat without producing useful movement. It only works as a short-term response because it uses respiratory substrates quickly and is hard to sustain.

Uncoupled respiration is respiration in which energy released by oxidation of substrates is converted to heat rather than being conserved in ATP. Brown adipose tissue has many mitochondria and can use uncoupled respiration to warm the body. This matters especially in babies, who lose heat rapidly because of their large surface area relative to volume.

Hair erection is the raising of hairs by contraction of tiny erector muscles in the skin. In furry mammals, raised hairs trap a thicker insulating layer of air. In humans, body hair is sparse, so it has little warming effect; goose bumps are the visible remains of that response.

Responses to heat

Sweating is secretion of watery fluid onto the skin surface by sweat glands. As water in sweat evaporates, it removes heat from the skin because evaporation requires energy. Blood flowing through the skin cools, which helps cool the body core.

Sweating works best when sweat actually evaporates. In very humid air, evaporation is reduced, so cooling is less effective even if sweat production is high. That is why hot, humid conditions are more dangerous than the thermometer alone suggests.

Two roles of the kidney

Osmoregulation is the homeostatic regulation of the osmotic concentration of body fluids. Osmotic concentration is measured in osmoles per litre, written $\mathrm{osmol}\,\mathrm{L}^{-1}$; in human physiology, smaller units such as milliosmoles per litre are more common. Osmotic concentration is the total concentration of solute particles in a fluid that can influence water movement by osmosis.

Excretion is the removal of toxic metabolic waste products from the body. Keep the two ideas separate: osmoregulation deals with water and solute balance, while excretion removes unwanted substances made by metabolism.

The kidney carries out both roles by filtering blood plasma, then selectively reabsorbing useful substances. Final urine contains excess water and salts when these need to be removed, plus metabolic wastes and other unwanted solutes.

Nitrogenous wastes and unwanted solutes

When excess amino acids are broken down, they produce nitrogen-containing waste. In mammals, much of this nitrogen is excreted as urea. The kidney can also remove substances absorbed from the gut that the body does not use, including some drugs and pigments from food.

The nephron

A nephron is a microscopic kidney tubule that filters blood plasma and modifies the filtrate to form urine. Each nephron starts with a Bowman’s capsule surrounding a glomerulus, then continues through tubular regions with different roles. Blood vessels closely associated with the nephron allow filtration first and reabsorption later.

Ultrafiltration in the glomerulus

Ultrafiltration is pressure-driven filtration of blood plasma in the glomerulus. Water and small solutes can pass into Bowman’s capsule, while blood cells and most plasma proteins stay in the blood. The glomerulus itself is a knot of capillaries, supplied by an afferent arteriole and drained by a narrower efferent arteriole. Because the exit is narrow, hydrostatic pressure remains high inside the capillaries.

The filtration barrier is made up of fenestrated capillary walls, a basement membrane and podocyte slit gaps. Podocytes are specialised epithelial cells of Bowman’s capsule that wrap around glomerular capillaries, leaving narrow filtration slits between their foot processes. Ions, glucose, urea and other small solutes enter the filtrate; cells and most proteins do not.

Bowman’s capsule collects the filtrate

Bowman’s capsule is a cup-shaped part of the nephron that surrounds the glomerulus and receives glomerular filtrate. Its outer wall is relatively impermeable, so the filtrate is directed into the proximal convoluted tubule instead of leaking away.

Ultrafiltration does not sort substances by whether the body needs them. Glucose, salts, urea and water all enter the filtrate. After that, the body must reabsorb useful materials and leave toxins and excess substances to be excreted.

Selective reabsorption in the proximal convoluted tubule

Selective reabsorption is the movement of useful substances from nephron filtrate back into the blood. The proximal convoluted tubule is built for this job: it is long and folded, its cells have microvilli to increase surface area, many mitochondria to supply ATP, and close contact with peritubular capillaries.

Pump proteins in the membranes of tubule cells actively transport sodium ions out of the filtrate. Chloride ions follow because of electrical gradients. Glucose and amino acids move back into the blood by cotransport with sodium ions. Water then follows the solutes by osmosis. By the end of the proximal convoluted tubule, all glucose and amino acids should normally have been reabsorbed, along with much of the water and mineral ions.

Creating a salty medulla

The loop of Henle is a hairpin-shaped part of the nephron. It helps build a high osmotic concentration in the kidney medulla. Stay within the syllabus limit here: focus on active transport of sodium ions in the ascending limb, which maintains high osmotic concentration in the medulla and therefore facilitates water reabsorption in collecting ducts.

Filtrate travels down into the medulla through the descending limb, then back towards the cortex through the ascending limb. Because the flow runs in opposite directions, it helps maintain a medullary gradient: lower osmotic concentration near the cortex, higher osmotic concentration deeper in the medulla.

Ascending limb: sodium out, water stays in

Cells in the ascending limb actively transport sodium ions from the filtrate into the surrounding medullary tissue. Water cannot follow, because the ascending limb is effectively impermeable to water. As a result, the medulla becomes more concentrated, while the filtrate leaving the loop becomes less concentrated.

This concentrated medulla matters later, when the collecting duct passes through it. If the collecting duct is permeable to water, water moves out of the filtrate by osmosis into the medulla and then into the blood. In this way, the kidney conserves water and produces concentrated urine.

Detecting blood osmotic concentration

An osmoreceptor is a sensory receptor that detects changes in osmotic concentration of body fluids. In the hypothalamus, osmoreceptors monitor the osmotic concentration of the blood. If the blood becomes too concentrated, usually because of water loss or low water intake, the hypothalamus makes the pituitary gland increase secretion of antidiuretic hormone.

Antidiuretic hormone is a peptide hormone released from the pituitary gland that increases water reabsorption by making collecting duct cells more permeable to water. The name helps: “anti-diuretic” means it reduces urine production.

Aquaporins switch location

An aquaporin is a membrane channel protein that allows water molecules to cross a membrane rapidly. ADH binds to receptors on cells of the distal convoluted tubule and collecting duct. In response, aquaporins move from intracellular vesicles into the cell surface membrane.

With more aquaporins in the membrane, the collecting duct becomes more permeable to water. As filtrate passes through the concentrated medulla, water moves out by osmosis and returns to the blood. This produces a small volume of more concentrated urine and lowers blood osmotic concentration towards normal.

When blood osmotic concentration is too low, ADH secretion decreases. Aquaporins are removed from the membrane and stored in intracellular vesicles. The collecting duct becomes less permeable to water, so less water is reabsorbed and a larger volume of dilute urine is produced.

Why the loop of Henle and ADH belong together

The loop of Henle creates the medullary osmotic gradient. ADH controls whether the collecting duct lets water move down that gradient. Without the gradient, ADH would have little osmotic pull to use. Without ADH, the gradient would still exist, but the collecting duct would not let much water leave the filtrate.

Why blood distribution has to change

Cardiac output is the volume of blood pumped by one side of the heart per minute. Even if cardiac output rises, the body still can’t send blood to every organ at its maximum possible rate all at once. It has to direct blood where it is needed for the current activity.

Organisms need to distribute materials and energy because cells require oxygen, respiratory substrates, ions, hormones and heat transfer, while wastes such as carbon dioxide and urea must be removed. In humans, changing blood flow helps match supply and removal to the demand of each tissue.

Arterioles control local blood supply

Blood supply to an organ is adjusted mainly by smooth muscle in arteriole walls. Vasoconstriction narrows the lumen diameter and restricts blood flow. Vasodilation widens the lumen diameter, so blood flow increases. Some tissues also use shunt vessels to redirect blood past capillary beds.

The same terms used in thermoregulation apply here, although the purpose may change. In skin, vasodilation can increase heat loss. In skeletal muscle during exercise, vasodilation increases delivery of glucose and oxygen and removal of carbon dioxide and heat.

Patterns during activity, rest and sleep

During vigorous physical activity, skeletal muscles get a greatly increased blood supply because ATP demand is high and respiration needs more oxygen and glucose. Blood flow to the gut is reduced, since digestion can be slowed temporarily. Blood flow to the kidneys also falls, lowering filtration rate for a time. Brain blood supply remains high or may increase because brain cells need a continuous supply of oxygen and glucose.

During wakeful rest, skeletal muscles still need a moderate supply for posture and small movements. The gut receives variable supply depending on whether food is present. The kidneys receive a large share of cardiac output, allowing filtration and homeostatic adjustment of blood composition. The brain receives a steady supply.

During sleep, skeletal muscle blood supply is reduced because movement is minimal. In adults, kidney blood supply is reduced, helping avoid excessive urine production overnight. Brain supply remains substantial and may increase in some phases of sleep, supporting continued activity and waste removal.

Relative blood supply to selected organs in activity, rest and sleep.

Reading percentage-change data

When blood-flow data are shown as percentage change, calculate it as the change from the original value divided by the original value, then multiplied by 100. A negative percentage means the later value is lower than the original; a positive percentage means it is higher. Check which condition is being used as the reference, because “asleep compared with awake” and “awake compared with asleep” reverse the sign.