Human Physiology

Nutrition

Balanced Diet

A balanced diet provides all essential nutrients in the correct proportions to maintain health. The seven classes of food are:

Nutrient	Function	Sources
Carbohydrates	Primary energy source; spare protein from being used as energy	Rice, bread, pasta, potatoes
Proteins	Growth and repair of tissues; enzyme and hormone synthesis	Meat, fish, eggs, beans, milk
Lipids	Energy reserve; insulation; structural component of cell membranes	Butter, oils, cheese, nuts
Vitamins	Regulate metabolic processes; prevent deficiency diseases	Fruits, vegetables, dairy
Minerals	Bone formation; nerve function; enzyme cofactors	Milk, spinach, meat, salt
Water	Solvent for biochemical reactions; transport medium; temperature regulation	Drinking water, food, metabolic water
Dietary fibre	Adds bulk to food; stimulates peristalsis; prevents constipation	Whole grains, vegetables, fruits

Energy Requirements

Basal Metabolic Rate (BMR) is the minimum energy required to maintain vital functions at rest. Total daily energy expenditure depends on:

$\mathrm{Total Energy} = \mathrm{BMR} + \mathrm{Physical Activity} + \mathrm{SDA (Specific Dynamic Action)}$

Average daily energy requirements:

Group	Energy (kJ/day)
Sedentary adult	8000 - 10000
Active adult male	12000 - 15000
Active adult female	10000 - 12000
Growing teenager	10000 - 13000

Worked Example: Energy Requirements

A 65 kg male office worker has a BMR of approximately 7000 kJ/day. His physical activity accounts for 3000 kJ/day and SDA accounts for 1000 kJ/day.

(a) Calculate his total daily energy requirement.

(b) If he starts marathon training and his physical activity doubles, what is his new total energy requirement?

(c) Explain why athletes often consume high-carbohydrate diets before competition.

Solution

(a) $\mathrm{Total Energy} = \mathrm{BMR} + \mathrm{Physical Activity} + \mathrm{SDA} = 7000 + 3000 + 1000 = 11\,000 \mathrm{ kJ/day}$

(b) If physical activity doubles to 6000 kJ/day: $\mathrm{Total Energy} = 7000 + 6000 + 1000 = 14\,000 \mathrm{ kJ/day}$. This is a 27% increase, demonstrating that physical activity is a major component for active individuals.

(c) Carbohydrates are the primary energy source for exercise. A high-carbohydrate diet maximises glycogen stores in muscles and the liver, providing readily available energy during prolonged exercise. This spares protein from being broken down for energy, preserving muscle mass. Carbohydrates also yield more energy per unit of oxygen consumed than fats, making them more efficient during intense exercise.

Malnutrition

Undernutrition: Insufficient intake of calories or specific nutrients.

Deficiency	Disease	Symptoms
Protein-energy	Kwashiorkor	Swollen abdomen, oedema, poor growth
Protein-energy	Marasmus	Severe weight loss, muscle wasting
Vitamin A	Night blindness	Inability to see in low light
Vitamin C	Scurvy	Bleeding gums, poor wound healing
Vitamin D	Rickets	Soft, deformed bones
Iron	Anaemia	Fatigue, pale skin, shortness of breath
Iodine	Goitre	Enlarged thyroid gland
Calcium	Osteoporosis	Weak, brittle bones
Vitamin B1 (thiamine)	Beri-beri	Nerve damage, muscle weakness

Overnutrition: Excessive intake leading to obesity, cardiovascular disease, Type 2 diabetes.

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The Digestive System

Overview of the Digestive Tract

The digestive system is a muscular tube running from mouth to anus, with accessory glands (salivary glands, liver, pancreas) secreting enzymes into the tract.

Region	Major Functions
Mouth	Mechanical digestion (chewing); chemical digestion (salivary amylase)
Oesophagus	Peristalsis moves food to stomach
Stomach	Protein digestion (pepsin); churning; acid kills bacteria
Small intestine	Complete digestion; absorption of nutrients into blood
Large intestine	Water reabsorption; formation of faeces
Rectum	Storage of faeces
Anus	Expulsion of faeces

The Mouth

Mechanical digestion:

• Teeth cut, tear, and grind food into smaller pieces (increases surface area)
• Tongue manipulates food and mixes it with saliva

Chemical digestion:

• Salivary glands produce saliva containing:
  • Salivary amylase: Breaks down starch into maltose (optimal pH ~6.8)
  • Mucus: Lubricates food for swallowing
  • Water: Dissolves food molecules for taste

$\mathrm{Starch} \xrightarrow{\mathrm{salivary amylase}} \mathrm{Maltose}$

The Stomach

• Gastric glands in the stomach wall secrete gastric juice containing:
  • Hydrochloric acid (HCl): pH ~2; denatures proteins; activates pepsinogen to pepsin; kills bacteria
  • Pepsinogen: Inactive precursor; activated to pepsin by HCl; digests protein into polypeptides
  • Mucus: Protects the stomach lining from acid and enzymes

$\mathrm{Proteins} \xrightarrow{\mathrm{pepsin (pH 2)}} \mathrm{Polypeptides}$

The stomach churns food with gastric juice to form chyme, a semi-liquid acidic mixture. The pyloric sphincter controls the release of chyme into the duodenum.

The Small Intestine

The small intestine is the primary site of both digestion and absorption. It is divided into:

1. Duodenum: Where most digestion occurs; receives bile and pancreatic juice
2. Jejunum and Ileum: Where most absorption occurs

Bile (produced by the liver, stored in the gall bladder):

• Emulsifies fats -- breaks large fat droplets into smaller droplets (increases surface area for lipase)
• Contains no enzymes -- it is not a digestive enzyme
• Neutralises stomach acid (alkaline, pH ~8)
• Contains bile pigments (bilirubin from haemoglobin breakdown) excreted in faeces

Pancreatic juice (produced by the pancreas):

• Pancreatic amylase: Starch to maltose
• Trypsin: Proteins/polypeptides to smaller peptides
• Lipase: Fats to fatty acids and glycerol

Intestinal enzymes (produced by cells on the villi):

Enzyme	Substrate	Product(s)
Maltase	Maltose	Glucose
Sucrase	Sucrose	Glucose + Fructose
Lactase	Lactose	Glucose + Galactose
Peptidases	Peptides	Amino acids
Lipase	Fats	Fatty acids + Glycerol

Summary of Enzyme Digestion

Enzyme	Source	Substrate	Product(s)	Optimal pH
Salivary amylase	Salivary glands	Starch	Maltose	~6.8
Pepsin	Stomach	Protein	Polypeptides	~2
Pancreatic amylase	Pancreas	Starch	Maltose	~7-8
Trypsin	Pancreas	Protein	Peptides	~8
Lipase	Pancreas	Lipids	Fatty acids + Glycerol	~8
Maltase	Small intestine	Maltose	Glucose	~7-8
Sucrase	Small intestine	Sucrose	Glucose + Fructose	~7-8
Lactase	Small intestine	Lactose	Glucose + Galactose	~7-8

Worked Example: Enzyme Digestion Pathway

A student eats a meal containing starch, protein, and fat. Trace the complete digestion of each nutrient from the mouth to the small intestine, naming the enzyme(s), substrate(s), and product(s) at each stage.

Solution

Starch digestion:

1. Mouth: Salivary amylase breaks down starch into maltose (pH ~6.8)
2. Stomach: No further starch digestion (acidic pH denatures salivary amylase)
3. Small intestine (duodenum): Pancreatic amylase breaks down remaining starch into maltose (pH ~7-8)
4. Small intestine (ileum): Maltase breaks down maltose into glucose

Protein digestion:

1. Mouth: No protein digestion
2. Stomach: Pepsin breaks down proteins into polypeptides (pH ~2; pepsinogen activated by HCl)
3. Small intestine (duodenum): Trypsin breaks down polypeptides into smaller peptides (pH ~8)
4. Small intestine (ileum): Peptidases break down peptides into amino acids

Fat digestion:

1. Mouth and stomach: No significant fat digestion
2. Small intestine (duodenum): Bile emulsifies fats into smaller droplets (physical, not enzymatic)
3. Small intestine (duodenum): Pancreatic lipase breaks down fats into fatty acids and glycerol

Absorption

The small intestine is adapted for absorption through structural features:

Villi: Finger-like projections of the intestinal wall that increase surface area. Each villus contains:

• A dense network of blood capillaries (absorb glucose, amino acids -- carried to liver via hepatic portal vein)
• A lacteal (lymphatic capillary) that absorbs fatty acids and glycerol (re-formed into triglycerides, packaged into chylomicrons, transported via the lymphatic system)

Microvilli: Tiny projections on the epithelial cells of the villi, further increasing surface area.

Features for efficient absorption:

1. Large surface area (villi + microvilli)
2. Thin walls (single layer of epithelial cells)
3. Dense blood capillary network (maintains concentration gradient)
4. Lacteal for lipid absorption
5. Short diffusion distance

Absorption mechanisms:

• Diffusion: From high to low concentration (e.g., fatty acids, glycerol)
• Facilitated diffusion: Via carrier proteins (e.g., fructose)
• Active transport: Against concentration gradient, requires ATP (e.g., glucose, amino acids)
• Co-transport: Na$^+$ gradient drives glucose/amino acid uptake via SGLT1 transporter

The Large Intestine

• Colon: Absorbs water and mineral ions from remaining indigestible material
• Caecum/Appendix: Vestigial in humans; contains gut bacteria that synthesise some vitamins (e.g., vitamin K, some B vitamins)
• Rectum: Stores faeces until defaecation

Egestion

Faeces consist of undigested food (mainly dietary fibre), dead cells, bacteria, bile pigments, and water.

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Gas Exchange

Structure of the Human Respiratory System

Structure	Function
Nasal cavity	Warms, moistens, and filters air; lined with mucus and ciliated epithelium
Trachea	Carries air to and from lungs; C-shaped cartilage rings keep it open
Bronchi	Branches of the trachea leading to each lung; also contain cartilage
Bronchioles	Smaller branches within the lungs; walls contain smooth muscle
Alveoli	Tiny air sacs; site of gas exchange; surrounded by capillaries
Diaphragm	Dome-shaped muscle; contracts and flattens during inhalation
Intercostal muscles	Muscles between ribs; external intercostals aid inhalation, internal aid exhalation
Ribcage	Protects the lungs; moves up and out during inhalation

Ventilation Mechanism

Inhalation (inspiration):

1. External intercostal muscles contract
2. Ribs move up and out
3. Diaphragm contracts and flattens
4. Volume of thorax increases
5. Pressure in lungs decreases below atmospheric pressure
6. Air rushes in

$P_{\mathrm{lung}} \lt P_{\mathrm{atm}} \implies \mathrm{air flows in}$

Exhalation (expiration) -- at rest (passive):

1. External intercostal muscles relax
2. Ribs move down and in
3. Diaphragm relaxes and returns to dome shape
4. Volume of thorax decreases
5. Pressure in lungs increases above atmospheric pressure
6. Air is pushed out

$P_{\mathrm{lung}} \gt P_{\mathrm{atm}} \implies \mathrm{air flows out}$

Forced exhalation: Internal intercostal muscles and abdominal muscles contract actively.

Gas Exchange in the Alveoli

Features of alveoli adapted for efficient gas exchange:

1. Large surface area: Millions of alveoli provide enormous total surface area (~70 m$^2$)
2. Thin walls: Alveolar epithelium is one cell thick
3. Dense capillary network: Each alveolus surrounded by capillaries; capillary walls are also one cell thick
4. Short diffusion path: Total distance between air and blood is ~1 micrometre
5. Moist surface: Gases dissolve before diffusing; moisture maintains the diffusion gradient
6. Maintained concentration gradient: Continuous blood flow and ventilation refresh the gradient

Diffusion of gases:

$\mathrm{O}_2 \mathrm{ (alveolar air, } pO_2 \approx 13.3 \mathrm{ kPa)} \to \mathrm{O}_2 \mathrm{ (blood, } pO_2 \approx 5.3 \mathrm{ kPa)}$

$\mathrm{CO}_2 \mathrm{ (blood, } pCO_2 \approx 6.0 \mathrm{ kPa)} \to \mathrm{CO}_2 \mathrm{ (alveolar air, } pCO_2 \approx 5.3 \mathrm{ kPa)}$

Oxygen diffuses from alveolar air into the blood; carbon dioxide diffuses from blood into alveolar air. Both movements are down their respective partial pressure gradients.

Respiratory Diseases

Asthma:

• Inflammation and constriction of bronchioles
• Excess mucus production
• Symptoms: wheezing, shortness of breath, coughing
• Triggers: allergens, exercise, cold air, stress
• Treatment: bronchodilator inhalers (relax smooth muscle), steroid inhalers (reduce inflammation)

Chronic Obstructive Pulmonary Disease (COPD):

• Includes chronic bronchitis and emphysema
• Chronic bronchitis: inflammation and mucus hypersecretion in bronchi; "smoker's cough"
• Emphysema: destruction of alveolar walls; reduced surface area for gas exchange; loss of elasticity
• Symptoms: persistent cough, breathlessness, fatigue
• Primary cause: smoking

Tuberculosis (TB):

• Caused by bacterium Mycobacterium tuberculosis
• Transmitted by droplet infection
• Infected lung tissue is destroyed by white blood cells, forming cavities
• Symptoms: persistent cough, blood-tinged sputum, weight loss, night sweats
• Treatment: long-term antibiotics (6-9 months)

Lung cancer:

• Uncontrolled cell division in lung tissue
• Strongly linked to smoking (carcinogens in tar)
• Symptoms: persistent cough, coughing up blood, chest pain, weight loss
• Treatment: surgery, chemotherapy, radiotherapy

Effects of Smoking

Substance	Effect
Nicotine	Addictive; increases heart rate and blood pressure; narrows blood vessels
Tar	Contains carcinogens; paralyses cilia; coats alveoli, reducing gas exchange
Carbon monoxide	Binds to haemoglobin with 250x affinity of O$_2$; reduces O$_2$ transport
Smoke particles	Irritate airways; damage ciliated epithelium; cause chronic inflammation

Carbon monoxide reduces the oxygen-carrying capacity of blood because it binds to haemoglobin forming carboxyhaemoglobin, which is stable and does not readily release the CO.

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Transport in Humans

The Circulatory System

Humans have a closed, double circulatory system:

1. Pulmonary circulation: Right ventricle to lungs to left atrium (deoxygenated blood to lungs for gas exchange, then oxygenated blood returns)
2. Systemic circulation: Left ventricle to body to right atrium (oxygenated blood to tissues, deoxygenated blood returns)

Structure of the Heart

The heart is a four-chambered muscular pump.

Chambers:

• Right atrium: Receives deoxygenated blood from the body via the vena cava
• Right ventricle: Pumps deoxygenated blood to the lungs via the pulmonary artery
• Left atrium: Receives oxygenated blood from the lungs via the pulmonary vein
• Left ventricle: Pumps oxygenated blood to the body via the aorta

Valves:

Valve	Location	Function
Tricuspid valve	Between right atrium and ventricle	Prevents backflow
Bicuspid (mitral) valve	Between left atrium and ventricle	Prevents backflow
Semilunar valves	In the pulmonary artery and aorta	Prevents backflow into ventricles

Valves open and close due to pressure differences. They ensure one-way blood flow.

Why the left ventricle has a thicker wall:

The left ventricle pumps blood to the entire body (systemic circulation) against high resistance, so it needs to generate much higher pressure than the right ventricle, which only pumps blood to the nearby lungs (pulmonary circulation).

Cardiac Cycle

1. Atrial systole: Atria contract; blood is forced through AV valves into ventricles
2. Ventricular systole: Ventricles contract; AV valves close ("lub" sound); semilunar valves open; blood is ejected into arteries
3. Diastole: Heart muscle relaxes; semilunar valves close ("dub" sound); blood flows into atria from veins

Blood Vessels

Feature	Arteries	Veins	Capillaries
Wall thickness	Thick (muscle + elastic tissue)	Thin	One cell thick
Lumen	Narrow (relatively)	Wide (relatively)	Very narrow
Valves	None (except semilunar in heart)	Present (prevent backflow)	None
Blood pressure	High	Low	Very low
Blood flow	Pulsatile	Steady	Slow
Direction	Away from heart	Towards heart	Between arteries and veins
Tissue layers	Thick smooth muscle, elastic fibres	Thin smooth muscle, elastic fibres	Endothelium only

Blood Composition

Blood consists of:

1. Plasma (55%): Liquid portion containing water, dissolved substances (glucose, amino acids, urea, hormones), plasma proteins (albumin, fibrinogen, globulins)
2. Red blood cells (erythrocytes, ~44%): Transport oxygen via haemoglobin
3. White blood cells (leucocytes, ~1%): Defence against pathogens
4. Platelets (thrombocytes, ~0.5%): Blood clotting

Red blood cells:

• Biconcave disc shape: increases surface area to volume ratio for gas exchange
• No nucleus: more space for haemoglobin
• Contain haemoglobin: iron-containing protein that binds oxygen
• Flexible: can squeeze through narrow capillaries
• Produced in red bone marrow; destroyed in the spleen and liver (lifespan ~120 days)

White blood cells:

• Phagocytes (neutrophils, macrophages): Engulf and digest pathogens by phagocytosis
• Lymphocytes: Produce antibodies; recognise specific antigens

Platelets:

• Cell fragments (no nucleus) produced in bone marrow
• Involved in blood clotting:
  1. Platelets accumulate at the wound site
  2. Thromboplastin is released
  3. Thromboplastin converts prothrombin to thrombin (with calcium ions)
  4. Thrombin converts soluble fibrinogen to insoluble fibrin
  5. Fibrin forms a mesh that traps red blood cells, forming a clot

Blood Groups

Blood groups are determined by antigens on the surface of red blood cells and antibodies in the plasma.

Blood Group	Antigen on RBC	Antibody in Plasma	Can Donate To	Can Receive From
A	A	Anti-B	A, AB	A, O
B	B	Anti-A	B, AB	B, O
AB	A and B	None	AB	A, B, AB, O
O	None	Anti-A and Anti-B	A, B, AB, O	O

Universal donor: O (no antigens on RBC surface)

Universal recipient: AB (no antibodies in plasma)

Rhesus factor (RhD): An additional antigen. Rh+ individuals have the D antigen; Rh- do not. An Rh- mother carrying an Rh+ foetus may produce anti-D antibodies during a second pregnancy (haemolytic disease of the newborn).

Worked Example: Blood Transfusion Compatibility

A hospital has the following blood supplies: 5 units of type A, 3 units of type B, 2 units of type AB, and 8 units of type O. Three patients arrive simultaneously:

• Patient 1: Blood group A, needs 2 units
• Patient 2: Blood group B, needs 1 unit
• Patient 3: Blood group AB, needs 2 units

(a) Which blood types can each patient safely receive?

(b) Can all three patients be treated with the available supply? Justify your answer.

Solution

(a) Using the blood group compatibility rules:

• Patient 1 (blood group A, has anti-B antibodies): Can receive A or O (no foreign antigens to trigger anti-B)
• Patient 2 (blood group B, has anti-A antibodies): Can receive B or O (no foreign antigens to trigger anti-A)
• Patient 3 (blood group AB, has no antibodies): Can receive A, B, AB, or O (universal recipient)

(b) Patient 1 needs 2 units: use 2 units of type A (3 remaining). Patient 2 needs 1 unit: use 1 unit of type B (2 remaining). Patient 3 needs 2 units: use 2 units of type AB (0 remaining). All patients can be treated. Remaining supply: 3 units A, 2 units B, 0 units AB, 8 units O. Alternatively, Patient 3 could receive O blood to conserve the limited AB supply.

Haemoglobin and Oxygen Transport

Each haemoglobin molecule can carry up to 4 oxygen molecules:

$\mathrm{Hb} + 4\mathrm{O}_2 \rightleftharpoons \mathrm{HbO}_8$

In the lungs (high $pO_2$), oxygen binds to haemoglobin (loading). In the tissues (low $pO_2$), oxygen dissociates from haemoglobin (unloading).

The Oxygen Dissociation Curve

The oxygen dissociation curve is an S-shaped (sigmoid) curve showing the relationship between the partial pressure of oxygen ($pO_2$) and the percentage saturation of haemoglobin.

$\mathrm{Percentage saturation of Hb vs } pO_2$

Key points:

• At high $pO_2$ (lungs): haemoglobin is nearly fully saturated (~97%)
• At low $pO_2$ (tissues): haemoglobin releases oxygen
• The steep part of the curve means small changes in $pO_2$ cause large changes in oxygen unloading

Factors shifting the curve:

Factor	Effect	Physiological significance
High $pCO_2$ (Bohr effect)	Curve shifts right	More O$_2$ released to actively respiring tissues
Low pH / high [H$^+$]	Curve shifts right	More O$_2$ released in acidic conditions
High temperature	Curve shifts right	More O$_2$ released to warm, active tissues
High 2,3-BPG concentration	Curve shifts right	More O$_2$ unloading (adaptation to altitude)
Fetal haemoglobin (HbF)	Curve shifts left	Higher affinity for O$_2$; extracts O$_2$ from maternal blood

A right shift = lower affinity for O$_2$ = more O$_2$ released to tissues.

A left shift = higher affinity for O$_2$ = less O$_2$ released to tissues.

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Excretion

Excretion vs Egestion

• Excretion: Removal of metabolic waste products (e.g., CO$_2$, urea, excess water) from the body. This is distinct from egestion.
• Egestion: Removal of undigested food (faeces) from the body. Faeces have never been part of metabolism, so egestion is NOT excretion.

The Kidney

Structure:

• Outer region: cortex (contains Bowman's capsules, convoluted tubules)
• Inner region: medulla (contains loops of Henle, collecting ducts)
• Central cavity: renal pelvis (collects urine)
• Ureter: Carries urine from kidney to bladder
• Bladder: Stores urine
• Urethra: Releases urine from the body

The Nephron

The nephron is the functional unit of the kidney. Each kidney contains approximately one million nephrons.

Components:

1. Renal (Bowman's) capsule: Cup-shaped structure surrounding the glomerulus
2. Glomerulus: Knot of capillaries inside the Bowman's capsule
3. Proximal convoluted tubule (PCT): Highly coiled tube after the capsule
4. Loop of Henle: U-shaped tube extending into the medulla
5. Distal convoluted tubule (DCT): Coiled tube in the cortex
6. Collecting duct: Receives fluid from several nephrons; passes through the medulla

Ultrafiltration

Ultrafiltration occurs at the glomerulus and Bowman's capsule.

Mechanism:

• Blood enters the glomerulus via the afferent arteriole (wider) and leaves via the efferent arteriole (narrower)
• The narrower efferent arteriole creates high hydrostatic pressure in the glomerulus
• This pressure forces small molecules (water, glucose, amino acids, urea, ions) through the capillary wall and the podocytes of the Bowman's capsule into the capsular space
• Large molecules (proteins, blood cells) remain in the blood

What is filtered: Water, glucose, amino acids, urea, salts, vitamins (all small solutes)

What is NOT filtered: Large proteins, red blood cells, white blood cells, platelets

The filtrate produced is called glomerular filtrate, which is similar in composition to blood plasma minus proteins.

Selective Reabsorption

As the filtrate passes along the nephron, useful substances are reabsorbed back into the blood.

Proximal Convoluted Tubule (PCT):

• All glucose is reabsorbed (by active transport and co-transport)
• All amino acids are reabsorbed (by active transport)
• Most water (by osmosis, following the reabsorption of solutes)
• Most salts/ions (Na$^+$, K$^+$, Cl$^-$) by active transport
• The PCT reabsorbs approximately 85% of the filtrate

Loop of Henle:

• Descending limb: Permeable to water but not to salts. Water moves out by osmosis into the increasingly concentrated medullary tissue fluid.
• Ascending limb: Impermeable to water but actively transports Na$^+$ and Cl$^-$ out into the medullary tissue fluid. This creates a sodium gradient in the medulla.
• The counter-current multiplier mechanism maintains a high solute concentration in the medulla, which is essential for water reabsorption from the collecting duct.

Distal Convoluted Tubule (DCT):

• Selective reabsorption of ions (Na$^+$, K$^+$, Ca$^{2+}$) regulated by hormones
• Water permeability controlled by ADH

Collecting duct:

• Water reabsorption controlled by antidiuretic hormone (ADH)
• In the presence of ADH, the collecting duct becomes more permeable to water, and water is reabsorbed into the concentrated medullary tissue fluid by osmosis
• Produces concentrated urine (small volume)

Osmoregulation

Osmoregulation is the control of water balance in the body.

Mechanism (negative feedback):

1. Blood water potential decreases (blood becomes more concentrated, e.g., after sweating or not drinking)
2. Osmoreceptors in the hypothalamus detect the decrease in water potential
3. The hypothalamus stimulates the posterior pituitary gland to release more ADH into the blood
4. ADH increases the permeability of the collecting duct to water (by inserting aquaporin channels)
5. More water is reabsorbed from the collecting duct into the blood
6. Urine becomes more concentrated and lower in volume
7. Blood water potential returns to normal; osmoreceptors are no longer stimulated; ADH secretion decreases

Condition	Blood Water Potential	ADH Level	Urine Volume	Urine Concentration
Dehydrated	Low	High	Low	High
Well hydrated	Normal	Normal	Normal	Normal
Drunk excess water	High	Low	High	Low

Worked Example: Osmoregulation and ADH

A person drinks 2 litres of water within 30 minutes on a hot day after exercising. Describe the sequence of physiological events that restores their blood water potential to normal.

Solution

1. Drinking 2 litres of water increases blood water potential (blood becomes more dilute)
2. Osmoreceptors in the hypothalamus detect the increase in blood water potential
3. The hypothalamus reduces its stimulation of the posterior pituitary gland
4. Less ADH is released into the blood; ADH level decreases
5. The collecting duct walls become less permeable to water (fewer aquaporin channels)
6. Less water is reabsorbed from the collecting duct into the blood
7. A large volume of dilute urine is produced (high volume, low concentration)
8. Excess water is excreted, and blood water potential gradually returns to normal
9. Once normal, osmoreceptors detect the restored water potential and ADH secretion returns to baseline

Note: On a hot day after exercise, the person would also have lost water through sweating. This means the initial blood water potential may not have been as high as expected, and the osmoregulatory response would be moderated. The kidneys cannot excrete water faster than approximately 1 litre per hour, so drinking 2 litres in 30 minutes exceeds the maximum excretion rate.

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Nervous Coordination

The Nervous System

The nervous system has two main divisions:

1. Central Nervous System (CNS): Brain and spinal cord -- processes information and coordinates responses
2. Peripheral Nervous System (PNS): All nerves outside the CNS -- transmits signals between the CNS and the rest of the body

The PNS is further divided into:

• Somatic nervous system: Controls voluntary actions (conscious)
• Autonomic nervous system: Controls involuntary actions (unconscious)
  • Sympathetic: "Fight or flight" -- increases heart rate, dilates pupils, inhibits digestion
  • Parasympathetic: "Rest and digest" -- decreases heart rate, constricts pupils, stimulates digestion

Neurons

Neurons are specialised cells that transmit electrical impulses.

Type	Structure	Function
Sensory neuron	Long axon, cell body off-centre	Transmits impulses from receptors to CNS
Relay neuron	Short axon, many dendrites	Connects sensory and motor neurons in CNS
Motor neuron	Long axon, cell body in CNS	Transmits impulses from CNS to effectors

Structure of a motor neuron:

• Cell body: Contains nucleus and organelles
• Dendrites: Receive impulses from other neurons
• Axon: Long fibre that carries impulses away from the cell body; insulated by myelin sheath (made by Schwann cells)
• Myelin sheath: Fatty layer that insulates the axon; allows saltatory conduction (impulses jump between Nodes of Ranvier), increasing the speed of transmission
• Nodes of Ranvier: Gaps in the myelin sheath where action potentials are regenerated
• Motor end plates: Connections to muscle fibres at the neuromuscular junction

Nerve Impulses

Resting potential: The inside of the neuron is negatively charged relative to the outside (~-70 mV). This is maintained by the sodium-potassium pump (pumps 3 Na$^+$ out for every 2 K$^+$ in) and the permeability of the membrane to K$^+$.

Action potential:

1. Stimulus causes voltage-gated Na$^+$ channels to open
2. Na$^+$ rushes in, depolarising the membrane (inside becomes positive, ~+40 mV)
3. Voltage-gated K$^+$ channels open
4. K$^+$ rushes out, repolarising the membrane
5. The Na$^+/K^+$ pump restores the resting potential (refractory period)

Propagation: The action potential travels along the axon. In myelinated neurons, it jumps between Nodes of Ranvier (saltatory conduction), which is faster than continuous conduction in unmyelinated neurons.

Synapses

A synapse is the junction between two neurons or between a neuron and an effector.

Structure:

• Pre-synaptic neuron: Terminal knob containing synaptic vesicles filled with neurotransmitter
• Synaptic cleft: Gap (~20 nm) between the two neurons
• Post-synaptic neuron: Membrane contains receptor proteins specific to the neurotransmitter

Transmission across a synapse:

1. Action potential arrives at the pre-synaptic terminal
2. Voltage-gated Ca$^{2+}$ channels open; Ca$^{2+}$ enters the terminal
3. Ca$^{2+}$ causes synaptic vesicles to fuse with the pre-synaptic membrane and release neurotransmitter into the synaptic cleft (exocytosis)
4. Neurotransmitter diffuses across the synaptic cleft
5. Neurotransmitter binds to specific receptors on the post-synaptic membrane
6. This triggers ion channels to open, generating a new action potential in the post-synaptic neuron
7. The neurotransmitter is broken down by enzymes or reabsorbed (taken up by the pre-synaptic neuron)

Key properties of synapses:

• Unidirectional: Impulses travel in one direction only (pre- to post-synaptic)
• Slow: Transmission is slower than along an axon (diffusion takes time)
• Summation: Multiple impulses may be needed to trigger an action potential (spatial summation from multiple neurons; temporal summation from rapid firing of one neuron)
• Inhibition: Some neurotransmitters are inhibitory (e.g., GABA), making the post-synaptic neuron less likely to fire

Reflex Arc

A reflex arc is the pathway taken by nerve impulses in an automatic, involuntary response (reflex).

Components:

1. Receptor: Detects the stimulus
2. Sensory neuron: Transmits impulse to the CNS
3. Relay neuron: In the spinal cord (or brain); connects sensory to motor neuron
4. Motor neuron: Transmits impulse from CNS to effector
5. Effector: Muscle or gland that produces the response

Example: Withdrawal reflex

• Touch a hot object
• Pain receptors in the skin detect heat
• Sensory neuron transmits impulse to the spinal cord
• Relay neuron passes impulse to motor neuron
• Motor neuron stimulates biceps to contract (withdraw hand) and triceps to relax
• The action is involuntary and rapid; the brain is informed afterwards

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Sense Organs

The Eye

Structure:

Part	Function
Sclera	Tough, white outer layer; protects the eye
Cornea	Transparent front part; refracts light
Iris	Coloured part; controls the size of the pupil
Pupil	Hole in the iris; allows light to enter
Lens	Focuses light onto the retina; changes shape for accommodation
Retina	Light-sensitive layer; contains rods and cones; photoreceptors
Fovea	Area of sharpest vision; highest concentration of cones
Optic nerve	Transmits electrical impulses to the brain
Blind spot	Where the optic nerve leaves the eye; no photoreceptors
Conjunctiva	Thin membrane covering the front of the sclera; protects the eye
Aqueous humour	Watery fluid between cornea and lens; maintains pressure, refracts light
Vitreous humour	Jelly-like fluid behind the lens; maintains the shape of the eye
Ciliary body	Contains ciliary muscles; attaches suspensory ligaments to the lens
Suspensory ligaments	Hold the lens in position; connect lens to ciliary body

Accommodation

Accommodation is the process of changing the shape of the lens to focus on objects at different distances.

Focusing on a distant object:

1. Light rays from a distant object are nearly parallel
2. Ciliary muscles relax
3. Suspensory ligaments are pulled taut
4. Lens becomes thin (less curved)
5. Light is focused on the retina

Focusing on a near object:

1. Light rays from a near object are diverging
2. Ciliary muscles contract
3. Suspensory ligaments slacken
4. Lens becomes fat (more curved, more powerful refraction)
5. Light is focused on the retina

Photoreceptors

Feature	Rods	Cones
Sensitivity	High (work in dim light)	Low (work in bright light)
Colour	Cannot distinguish colour	Distinguish red, green, blue
Visual acuity	Low (many rods share one neuron)	High (one cone per neuron in fovea)
Distribution	Concentrated at periphery of retina	Concentrated at fovea
Pigment	Rhodopsin	Iodopsin (three types)

The Ear

Structure:

Part	Function
Pinna (auricle)	Collects and directs sound waves into the ear canal
Ear canal (auditory canal)	Directs sound waves to the eardrum
Eardrum (tympanum)	Thin membrane that vibrates when sound waves hit it
Ossicles	Three tiny bones (malleus, incus, stapes) that amplify vibrations
Oval window	Transmits vibrations from ossicles to the cochlea
Cochlea	Fluid-filled spiral structure containing hair cells (sound receptors)
Round window	Releases pressure from the cochlear fluid
Auditory nerve	Transmits impulses from cochlea to the brain
Semicircular canals	Detect rotational movement (balance)
Eustachian tube	Connects middle ear to throat; equalises pressure

Hearing Mechanism

1. Sound waves are collected by the pinna and directed along the ear canal
2. Sound waves cause the eardrum to vibrate
3. Vibrations are transmitted and amplified by the ossicles (malleus, incus, stapes)
4. The stapes pushes against the oval window, creating pressure waves in the cochlear fluid
5. Pressure waves cause the basilar membrane in the cochlea to vibrate
6. Hair cells on the basilar membrane are bent, generating nerve impulses
7. Impulses travel along the auditory nerve to the brain, where sound is interpreted
8. The round window allows the cochlear fluid to dissipate the pressure waves

Skin Receptors

The skin contains various sensory receptors:

Receptor Type	Detected Stimulus
Pain receptors	Pain, tissue damage
Thermoreceptors	Temperature changes
Pressure receptors	Pressure, touch
Mechanoreceptors	Mechanical deformation

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Hormonal Coordination

The Endocrine System

The endocrine system consists of endocrine glands that secrete hormones directly into the bloodstream. Hormones are chemical messengers that travel in the blood to target organs.

Comparison: Nervous vs Hormonal Coordination

Feature	Nervous System	Endocrine System
Speed	Very fast (milliseconds)	Slower (seconds to hours to days)
Duration	Short-lived	Longer-lasting
Transmission	Electrical impulses along neurons	Chemical (hormones in blood)
Target	Specific effectors (muscles/glands)	Target organs with specific receptors
Pathway	Along neurones via synapses	Via bloodstream
Example	Reflex arc	Blood glucose regulation

Major Endocrine Glands and Hormones

Gland	Hormone(s)	Function
Hypothalamus	Releasing hormones, ADH	Controls pituitary gland; regulates water balance
Pituitary (anterior)	FSH, LH, TSH, ACTH, GH	Controls other glands; growth; reproductive cycle
Pituitary (posterior)	ADH, oxytocin	Water reabsorption; uterine contractions during labour
Thyroid	Thyroxine	Regulates basal metabolic rate; growth and development
Adrenal cortex	Cortisol, aldosterone	Stress response; regulates Na$^+$ and water balance
Adrenal medulla	Adrenaline	"Fight or flight" response; increases heart rate and BP
Pancreas (islets of Langerhans)	Insulin, glucagon	Blood glucose regulation
Ovaries	Oestrogen, progesterone	Female secondary sexual characteristics; menstrual cycle
Testes	Testosterone	Male secondary sexual characteristics; sperm production

Blood Glucose Regulation

Blood glucose concentration is normally maintained at approximately 90 mg/100 cm$^3$.

If blood glucose rises (e.g., after a meal):

1. Detected by beta ($\beta$) cells in the islets of Langerhans (pancreas)
2. $\beta$ cells secrete more insulin
3. Insulin stimulates:
   • Liver and muscle cells to take up glucose
   • Conversion of glucose to glycogen (glycogenesis) in liver and muscles
   • Increased rate of glucose respiration in cells
4. Blood glucose level decreases back to normal

If blood glucose falls (e.g., between meals or during exercise):

1. Detected by alpha ($\alpha$) cells in the islets of Langerhans (pancreas)
2. $\alpha$ cells secrete more glucagon
3. Glucagon stimulates:
   • Conversion of glycogen to glucose (glycogenolysis) in the liver
   • Conversion of amino acids and fats to glucose (gluconeogenesis) in the liver
4. Blood glucose level increases back to normal

This is an example of negative feedback.

Worked Example: Blood Glucose Regulation

After a 12-hour fast, a student's blood glucose concentration is 85 mg/100 cm$^3$. They then drink a solution containing 50 g of glucose. Describe the hormonal response over the next 3 hours.

Solution

Immediately after drinking (0-30 minutes):

• Glucose is absorbed from the small intestine into the blood
• Blood glucose concentration rises rapidly, exceeding the normal range of ~90 mg/100 cm$^3$
• Beta cells in the islets of Langerhans detect the elevated blood glucose
• Beta cells secrete more insulin; alpha cells secrete less glucagon

30 minutes to 2 hours:

• Insulin stimulates liver cells to take up glucose and convert it to glycogen (glycogenesis)
• Insulin stimulates muscle cells to take up glucose and convert it to glycogen
• Insulin increases the rate of glucose respiration in cells
• Blood glucose concentration decreases back towards normal
• As blood glucose falls, insulin secretion decreases (negative feedback)

2-3 hours:

• Blood glucose returns to approximately 90 mg/100 cm$^3$
• If it drops below normal, alpha cells detect this and secrete glucagon
• Glucagon stimulates the liver to convert glycogen back to glucose (glycogenolysis)
• Blood glucose is maintained within the normal range by this negative feedback mechanism

Diabetes

Type 1 Diabetes (insulin-dependent):

• Autoimmune destruction of $\beta$ cells in the pancreas
• No insulin is produced
• Usually develops in childhood
• Treated with insulin injections

Type 2 Diabetes (non-insulin-dependent):

• Body cells become less responsive to insulin (insulin resistance)
• $\beta$ cells may produce less insulin over time
• Usually develops in adults; linked to obesity and lifestyle
• Treated with dietary control, exercise, and oral medication; insulin may be needed later

Symptoms of diabetes:

• High blood glucose concentration (hyperglycaemia)
• Glucose in urine (kidneys cannot reabsorb all glucose above the renal threshold of ~180 mg/100 cm$^3$)
• Frequent urination (excess water follows glucose osmotically)
• Excessive thirst (dehydration from frequent urination)
• Weight loss (body breaks down fat and protein for energy)
• Fatigue

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Human Reproduction

Male Reproductive System

Structure	Function
Testes	Produce sperm (in seminiferous tubules) and testosterone
Scrotum	Holds testes outside the body (2-3 degrees C below core temperature for sperm development)
Epididymis	Stores and matures sperm
Vas deferens	Carries sperm from epididymis to urethra during ejaculation
Seminal vesicles	Produce seminal fluid (fructose for energy, prostaglandins)
Prostate gland	Produces alkaline fluid (neutralises vaginal acidity)
Urethra	Passageway for both semen and urine
Penis	Inserts semen into the vagina during intercourse

Sperm structure:

• Head: Contains the haploid nucleus (23 chromosomes) and the acrosome (contains enzymes to penetrate the egg)
• Middle piece: Packed with mitochondria to provide ATP for tail movement
• Tail (flagellum): Whiplash movement propels the sperm

Female Reproductive System

Structure	Function
Ovaries	Produce ova (eggs) and hormones (oestrogen, progesterone)
Oviduct (fallopian tube)	Carries the ovum from ovary to uterus; site of fertilisation
Uterus	Implantation of embryo; development of foetus
Endometrium	Lining of the uterus; thickens and is shed during menstruation
Cervix	Ring of muscle at the entrance to the uterus
Vagina	Receives the penis during intercourse; birth canal

The Menstrual Cycle

The menstrual cycle is approximately 28 days and is controlled by four hormones:

1. FSH (Follicle-Stimulating Hormone): Produced by the anterior pituitary gland; stimulates the development of a follicle in the ovary; stimulates the ovaries to produce oestrogen
2. Oestrogen: Produced by the developing follicle; causes the endometrium to thicken; inhibits FSH production (negative feedback); stimulates LH release (positive feedback when level is high enough)
3. LH (Luteinising Hormone): Produced by the anterior pituitary gland; triggers ovulation (day 14); stimulates the remains of the follicle to develop into the corpus luteum
4. Progesterone: Produced by the corpus luteum; maintains the thickened endometrium; inhibits FSH and LH production

Day(s)	Event
1-5	Menstruation: endometrium is shed (if no implantation occurs)
1-13	Follicular phase: follicle develops; oestrogen rises; endometrium thickens
~14	Ovulation: LH surge causes the follicle to rupture; ovum is released
15-28	Luteal phase: corpus luteum forms; progesterone rises; endometrium maintained
25-28	If no implantation: corpus luteum degenerates; progesterone drops; cycle restarts

Fertilisation and Implantation

1. Sperm are deposited in the vagina during intercourse
2. Sperm swim through the cervix and uterus into the oviduct
3. One sperm penetrates the zona pellucida of the ovum (acrosome reaction)
4. The sperm nucleus fuses with the ovum nucleus -- fertilisation produces a zygote
5. The zygote divides by mitosis as it travels along the oviduct (forms a ball of cells called a morula, then a blastocyst)
6. The blastocyst implants into the thickened endometrium (~7 days after fertilisation)
7. The placenta forms, providing nutrients and gas exchange between mother and foetus

Contraception

Method	Mechanism
Condom	Physical barrier; prevents sperm reaching the ovum
Diaphragm/cap	Physical barrier over the cervix
Oral contraceptive pill (combined)	Contains oestrogen and progesterone; inhibits ovulation; thickens cervical mucus
Mini-pill	Progesterone only; thickens cervical mucus
Intrauterine device (IUD)	Prevents implantation; may also affect sperm
Sterilisation	Surgical cutting/tying of vas deferens (male) or oviducts (female)
Rhythm method	Avoiding intercourse during the fertile window
Injection/implant	Slow-release progesterone; prevents ovulation

Sexually Transmitted Diseases (STDs)

Disease	Pathogen	Symptoms
HIV/AIDS	Human Immunodeficiency Virus (retrovirus)	Destroys helper T cells; immune system collapses; opportunistic infections
Syphilis	Treponema pallidum (bacterium)	Painless sores, rash, organ damage if untreated
Gonorrhoea	Neisseria gonorrhoeae (bacterium)	Painful urination, discharge; may cause infertility
Chlamydia	Chlamydia trachomatis (bacterium)	Often asymptomatic; can cause infertility
HPV (Human Papillomavirus)	Virus	Genital warts; linked to cervical cancer

Prevention: Use of condoms; vaccination (HPV); monogamy; regular testing.

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Common Pitfalls

1. Confusing excretion and egestion: Egestion (removal of faeces) is not excretion. Faeces never entered the body's metabolic processes. CO$_2$ from respiration and urea from deamination are excretory products.

2. Stating bile digests fat: Bile emulsifies fat (physical breakdown into droplets). It does NOT chemically digest fat. Lipase digests fat.

3. Mixing up ventilation pressures: During inhalation, lung pressure is LOWER than atmospheric pressure. During exhalation, lung pressure is HIGHER. The volume-pressure relationship is inverse (Boyle's law).

4. Saying veins carry deoxygenated blood: The pulmonary vein carries oxygenated blood from the lungs to the heart. Always specify pulmonary vs systemic.

5. Confusing osmoregulation direction: High ADH means concentrated urine (less water excreted), not dilute urine. ADH promotes water reabsorption.

6. Confusing antagonistic hormones: Insulin LOWERS blood glucose. Glucagon RAISES blood glucose. Students often swap them.

7. Mixing up sympathetic and parasympathetic: Sympathetic = fight or flight (pupil dilation, heart rate up). Parasympathetic = rest and digest (pupil constriction, heart rate down).

8. Forgetting that sensory neurons carry impulses TO the CNS: The direction of impulse travel matters. Sensory: receptor to CNS. Motor: CNS to effector.

9. Writing that the loop of Henle reabsorbs water in both limbs: Only the descending limb is permeable to water. The ascending limb actively transports Na$^+$ and Cl$^-$ and is impermeable to water.

10. Confusing the roles of FSH and LH: FSH stimulates follicle development. LH triggers ovulation and maintains the corpus luteum. Do not swap them.

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Problem Set

Problem 1: A student sets up an experiment to investigate the effect of pH on the activity of salivary amylase. Test tubes containing starch solution and amylase are incubated at different pH values. After 10 minutes, the presence of starch is tested with iodine solution.

pH	Starch remaining after 10 min
3	++++
5	++
7	-
9	+
11	++++

(a) At which pH is amylase most active? Explain.

(b) Explain why starch remains at pH 3.

(c) If the temperature were raised to 80 degrees C at pH 7, what would happen to the results? Why?

If you get this wrong, revise: Digestive System -- The Mouth; Enzymes

Solution

(a) pH 7, because no starch remains after 10 minutes, indicating that amylase has completely broken down the starch into maltose. This is close to the optimum pH of salivary amylase (~6.8).

(b) At pH 3, the enzyme is in a highly acidic environment far from its optimum pH. The extreme pH alters the tertiary structure of the enzyme, changing the shape of the active site. The substrate can no longer bind to the active site, so the enzyme is denatured and cannot catalyse the reaction.

(c) At 80 degrees C, the enzyme would be denatured by the high temperature. The increased kinetic energy would break the bonds maintaining the tertiary structure of the protein, permanently altering the active site shape. Starch would remain in all tubes because the enzyme can no longer function.

Problem 2: Explain how the structure of an alveolus is adapted for efficient gas exchange. Refer to at least three structural features in your answer.

If you get this wrong, revise: Gas Exchange -- Gas Exchange in the Alveoli

Solution

1. Large surface area: Millions of alveoli in each lung provide a total surface area of approximately 70 m$^2$, maximising the area available for diffusion of O$_2$ and CO$_2$.

2. Thin walls: The alveolar epithelium is only one cell thick, and each alveolus is surrounded by a capillary wall that is also one cell thick. The total diffusion distance is approximately 1 micrometre, minimising the distance gases must travel.

3. Dense capillary network: Each alveolus is surrounded by many capillaries. Continuous blood flow maintains a steep concentration gradient by removing oxygenated blood and bringing deoxygenated blood to the alveoli.

4. Moist inner surface: The lining of the alveoli is moist, allowing gases to dissolve before diffusing across the membrane.

Problem 3: A person produces 180 dm$^3$ of glomerular filtrate per day but only excretes 1.5 dm$^3$ of urine per day.

(a) Calculate the percentage of filtrate that is reabsorbed.

(b) Which part of the nephron is primarily responsible for this reabsorption? Explain the mechanism.

If you get this wrong, revise: Excretion -- Ultrafiltration; Selective Reabsorption

Solution

(a) Percentage reabsorbed = $\frac{180 - 1.5}{180} \times 100 = \frac{178.5}{180} \times 100 = 99.2\%$

(b) The proximal convoluted tubule (PCT) is the primary site of reabsorption. It reabsorbs approximately 85% of the glomerular filtrate, including all glucose (by active transport and co-transport), all amino acids (by active transport), most water (by osmosis following solute reabsorption), and most mineral ions (Na$^+$, K$^+$, Cl$^-$ by active transport). The loop of Henle, DCT, and collecting duct provide further fine-tuning, with the collecting duct regulated by ADH.

Problem 4: A patient with blood group B requires a blood transfusion. Explain why blood group O can be used but blood group A cannot.

If you get this wrong, revise: Transport in Humans -- Blood Groups

Solution

Blood group O red blood cells have no antigens (A or B) on their surface. When transfused into a blood group B recipient, there are no foreign antigens for the recipient's anti-A antibodies to attack. Therefore, the donor red blood cells will not be destroyed.

Blood group A red blood cells carry A antigens on their surface. The blood group B recipient has anti-A antibodies in their plasma. When blood group A blood is transfused, the anti-A antibodies will bind to the A antigens on the donor red blood cells, causing agglutination (clumping) of the red blood cells. This blocks blood vessels and can be fatal.

Problem 5: Describe the roles of FSH, oestrogen, LH, and progesterone in the menstrual cycle.

If you get this wrong, revise: Human Reproduction -- The Menstrual Cycle

Solution

FSH (Follicle-Stimulating Hormone): Produced by the anterior pituitary gland; stimulates the development of a follicle in the ovary; stimulates the follicle to produce oestrogen.

Oestrogen: Produced by the developing follicle; causes the endometrium to thicken; inhibits FSH production (negative feedback) at low levels; at high levels around day 12-13, stimulates LH release (positive feedback), triggering the LH surge.

LH (Luteinising Hormone): Produced by the anterior pituitary gland; surges around day 14 due to positive feedback from high oestrogen; triggers ovulation (follicle ruptures, releasing the ovum); stimulates the follicle remnant to develop into the corpus luteum.

Progesterone: Produced by the corpus luteum from day 15 onwards; maintains the thickened endometrium; inhibits both FSH and LH production (negative feedback); if no implantation occurs, the corpus luteum degenerates around day 25-28, progesterone drops, and menstruation begins.

Problem 6: A myelinated neuron has nodes of Ranvier spaced 1.5 mm apart. The action potential travels at 120 m/s in myelinated regions. An equivalent unmyelinated neuron conducts at 0.5 m/s. Compare the time for an impulse to travel 30 mm in each neuron.

If you get this wrong, revise: Nervous Coordination -- Nerve Impulses

Solution

Myelinated neuron: The action potential jumps between nodes of Ranvier (saltatory conduction). Number of internodes = $30 / 1.5 = 20$. Time per internode = $1.5 \times 10^{-3} / 120 = 12.5 \times 10^{-6}$ s. Total internode time = $20 \times 12.5 \times 10^{-6} = 2.5 \times 10^{-4}$ s = 0.25 ms. The myelinated neuron is much faster because saltatory conduction skips the membrane between nodes.

Unmyelinated neuron: Time = distance / speed = $30 \times 10^{-3} / 0.5 = 0.06$ s = 60 ms.

The myelinated neuron transmits the impulse approximately 240 times faster than the unmyelinated neuron over this distance (60 ms vs ~0.25 ms). This demonstrates why myelination is critical for rapid neural communication.

Problem 7: Explain why the oxygen dissociation curve shifts to the right during exercise. What is the significance of this shift?

If you get this wrong, revise: Transport in Humans -- The Oxygen Dissociation Curve

Solution

During exercise, respiration rate increases, producing more CO$_2$ as a waste product. Increased CO$_2$ raises blood $pCO_2$, which lowers blood pH (more H$^+$ ions from carbonic acid: $\mathrm{CO}_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$). Muscle temperature also rises due to increased metabolic activity.

These factors (high $pCO_2$, low pH, high temperature) cause the oxygen dissociation curve to shift to the right (the Bohr effect). A rightward shift means that at any given $pO_2$, haemoglobin has a lower affinity for oxygen and releases more oxygen to the tissues. This ensures that more oxygen is unloaded precisely where and when it is needed most -- the actively respiring muscles.

Problem 8: A person with Type 1 diabetes has a fasting blood glucose level of 280 mg/100 cm$^3$. The renal threshold for glucose is approximately 180 mg/100 cm$^3$.

(a) Explain why glucose is present in the urine.

(b) Explain why this person feels thirsty and produces large volumes of urine.

(c) How does insulin injection help to correct this condition?

If you get this wrong, revise: Hormonal Coordination -- Blood Glucose Regulation; Diabetes

Solution

(a) The blood glucose concentration (280 mg/100 cm$^3$) exceeds the renal threshold (180 mg/100 cm$^3$). The proximal convoluted tubule normally reabsorbs all glucose from the filtrate via carrier proteins. However, when the blood glucose level exceeds the renal threshold, the carrier proteins become saturated and cannot reabsorb all the glucose. The excess glucose remains in the filtrate and is excreted in the urine (glycosuria).

(b) The excess glucose in the filtrate lowers the water potential of the tubule fluid. Less water is reabsorbed from the nephron by osmosis, producing a large volume of dilute urine (polyuria). The loss of excess water reduces blood volume and increases blood osmolarity, which is detected by osmoreceptors in the hypothalamus, triggering thirst (polydipsia).

(c) Insulin injections increase the amount of insulin in the blood. Insulin stimulates cells (especially liver and muscle cells) to take up glucose and convert it to glycogen. This lowers the blood glucose concentration. When blood glucose drops below the renal threshold, the kidneys can once again fully reabsorb all glucose, eliminating glucose from the urine and restoring normal water reabsorption.

Problem 9: Explain why the left ventricle has a thicker muscular wall than the right ventricle, and explain the role of valves in the heart.

If you get this wrong, revise: Transport in Humans -- Structure of the Heart; Cardiac Cycle

Solution

The left ventricle pumps oxygenated blood to the entire body through the systemic circulation. The systemic circulation has a much larger network of blood vessels and much higher resistance than the pulmonary circulation. To overcome this resistance and generate sufficient pressure, the left ventricle needs a thicker, more muscular wall. The right ventricle only pumps deoxygenated blood to the lungs via the shorter, lower-resistance pulmonary circuit, so its wall is thinner.

Heart valves ensure one-way blood flow. They open when the pressure behind them is greater than the pressure in front, and close when the pressure gradient reverses. AV valves (tricuspid and bicuspid) prevent backflow from ventricles into atria during ventricular systole ("lub" sound). Semilunar valves (in the aorta and pulmonary artery) prevent backflow from arteries into ventricles during diastole ("dub" sound).

Problem 10: Explain how a nerve impulse is transmitted across a synapse. Why is transmission in one direction only?

If you get this wrong, revise: Nervous Coordination -- Synapses

Solution

1. An action potential arrives at the pre-synaptic terminal knob.
2. Depolarisation causes voltage-gated Ca$^{2+}$ channels to open; Ca$^{2+}$ diffuses into the terminal.
3. Ca$^{2+}$ causes synaptic vesicles to fuse with the pre-synaptic membrane, releasing neurotransmitter into the synaptic cleft (exocytosis).
4. The neurotransmitter diffuses across the synaptic cleft (~20 nm).
5. The neurotransmitter binds to specific receptor proteins on the post-synaptic membrane.
6. This binding causes ion channels to open. If excitatory neurotransmitters (e.g., acetylcholine) are released, Na$^+$ flows in, depolarising the post-synaptic membrane and potentially triggering a new action potential.
7. The neurotransmitter is quickly removed -- either broken down by enzymes (e.g., acetylcholinesterase) or taken back up by the pre-synaptic neuron (reuptake).

Unidirectional transmission occurs because only the pre-synaptic terminal contains synaptic vesicles, only the post-synaptic membrane has the specific receptor proteins, and Ca$^{2+}$ channels (which trigger release) are only present on the pre-synaptic side.

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The Digestive System in Detail

Large Intestine (Colon)

The large intestine is approximately 1.5 metres long. Its primary functions are water reabsorption and faeces formation.

Region	Function
Caecum	Small pouch at the start; contains the appendix (no significant digestive function in humans)
Ascending colon	Water reabsorption; movement of contents upwards by peristalsis
Transverse colon	Water reabsorption; movement of contents across the abdomen
Descending colon	Water reabsorption; movement of contents downwards
Sigmoid colon	Storage of faeces; connects to the rectum
Rectum	Storage of faeces prior to defaecation
Anus	Sphincter muscles (internal: involuntary; external: voluntary) control defaecation

Key processes:

1. Water reabsorption: Approximately 90% of remaining water is reabsorbed by osmosis
2. Mineral absorption: $\mathrm{Na}^+$ and $\mathrm{Cl}^-$ are actively absorbed
3. Vitamin synthesis: Commensal bacteria synthesise vitamins K and B, which are absorbed
4. Mucus secretion: Goblet cells secrete mucus to lubricate faeces
5. Faeces composition: Undigested fibre, bacteria, water, bile pigments (stercobilin)

The Liver

Liver Function	Description
Bile production	Hepatocytes produce bile (bile salts, bile pigments, cholesterol, phospholipids)
Glycogen storage	Stores glycogen; releases glucose when blood glucose drops
Deamination	Converts excess amino acids to keto acids and ammonia; ammonia to urea (ornithine cycle)
Detoxification	Converts harmful substances (alcohol, drugs) into less harmful forms
Plasma protein synthesis	Synthesises albumin, fibrinogen, and other plasma proteins

Bile is NOT an enzyme. It emulsifies fats physically (increases surface area) but does NOT chemically digest fats. Lipase chemically digests fats.

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Gas Exchange in Detail

Partial Pressures and Gas Exchange

Location	$p\mathrm{O}_2$ (kPa)	$p\mathrm{CO}_2$ (kPa)
Inspired air	21.2	0.04
Alveolar air	13.3	5.3
Deoxygenated blood	5.3	6.1
Oxygenated blood	13.3	5.3
Tissue capillaries	2.0-5.3	6.0-7.3

Factors Affecting the Oxygen Dissociation Curve

Factor	Effect on Curve	Explanation
Increased $p\mathrm{CO}_2$	Shifts right (Bohr effect)	Carbonic acid lowers pH; H$^+$ reduces haemoglobin's affinity for $\mathrm{O}_2$
Decreased pH	Shifts right	H$^+$ ions bind to haemoglobin, reducing its affinity for $\mathrm{O}_2$
Increased temperature	Shifts right	Higher temperature reduces haemoglobin's affinity for $\mathrm{O}_2$
Fetal haemoglobin	Shifts left	Higher affinity for $\mathrm{O}_2$ than adult haemoglobin; allows efficient transfer across the placenta

Carbon Dioxide Transport

Method	Percentage	Description
Dissolved in plasma	~5%	Small amount dissolves directly in blood plasma
Bound to haemoglobin	~10-15%	$\mathrm{CO}_2$ binds to globin chains (NOT the haem group)
Hydrogen carbonate ($\mathrm{HCO}_3^-$)	~70-80%	Carbonic anhydrase converts $\mathrm{CO}_2$ to $\mathrm{H}_2\mathrm{CO}_3$, which dissociates to $\mathrm{H}^+$ and $\mathrm{HCO}_3^-$

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tip

tip Ready to test your understanding of Human Physiology? The diagnostic test contains the hardest questions within the DSE specification for this topic, each with a full worked solution.

Unit tests probe edge cases and common misconceptions. Integration tests combine Human Physiology with other biology topics to test synthesis under exam conditions.

See Diagnostic Guide for instructions on self-marking and building a personal test matrix.

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The Heart in Detail

Cardiac Cycle

The cardiac cycle is the sequence of events in one complete heartbeat. It consists of three main phases:

Phase	Atria	Ventricles	AV Valves	Semilunar Valves	Blood Movement
Atrial systole	Contract; push remaining blood into ventricles	Relax; passively fill from atria	Open	Closed	~25% of ventricular filling is from atrial contraction (the "atrial kick"); the remaining 75% occurred passively during ventricular diastole
Ventricular systole	Relax; fill from veins	Contract; pressure rises rapidly	Close (first heart sound, S1 "lub")	Open (when ventricular pressure exceeds arterial pressure)	Blood is ejected into the aorta and pulmonary artery; not all blood is expelled -- approximately 60% is ejected (ejection fraction); the remaining 40% is the end-systolic volume
Ventricular diastole	Relax; fill from veins	Relax; pressure drops below arterial pressure	Closed	Close (second heart sound, S2 "dub")	Both atria and ventricles relax; blood flows from veins into atria and passively into ventricles; the heart is filling

Key pressure relationships:

Event	Pressure Condition	Result
AV valves open	Atrial pressure > ventricular pressure	Blood flows from atria to ventricles
AV valves close	Ventricular pressure > atrricular pressure (at the start of ventricular systole)	Prevents backflow into atria
Semilunar valves open	Ventricular pressure > arterial pressure (aortic/pulmonary)	Blood is ejected into arteries
Semilunar valves close	Ventricular pressure < arterial pressure (at the start of ventricular diastole)	Prevents backflow into ventricles

Cardiac Output

$\text{Cardiac output} = \text{Heart rate} \times \text{Stroke volume}$

Component	Normal Value (at rest)	During Exercise
Heart rate	60-80 bpm	Increases to 150-200 bpm
Stroke volume	~70 mL	Increases to ~100-120 mL (due to increased venous return and stronger contraction)
Cardiac output	~5 L/min	Increases to ~15-25 L/min (up to 5x resting)

Factors affecting cardiac output:

Factor	Effect on Cardiac Output	Mechanism
Exercise	Increases significantly	Sympathetic nervous system releases adrenaline; increases heart rate and stroke volume; increased venous return (muscle pump)
Increased venous return	Increases (Frank-Starling law)	More blood entering the heart stretches the ventricular walls, causing a stronger contraction (Starling's law of the heart)
Adrenaline	Increases	Binds to beta-1 receptors in the heart; increases heart rate and force of contraction
Acetylcholine (vagus nerve)	Decreases	Binds to muscarinic receptors in the heart; decreases heart rate (parasympathetic effect)
Body temperature	Increases	Higher temperature increases metabolic rate and heart rate; for every 1 degrees C increase in body temperature, heart rate increases by approximately 10 bpm
Age	Generally decreases with age	Reduced maximum heart rate and stroke volume capacity with aging
Fitness level	Resting cardiac output is similar but stroke volume is higher and resting heart rate is lower (more efficient heart)	Athletic heart is larger and stronger; can pump more blood per beat, so it needs fewer beats at rest

Coronary Heart Disease (CHD)

Atherosclerosis: The build-up of fatty deposits (atheroma/plaque) in the walls of the coronary arteries, narrowing the lumen and restricting blood flow to the heart muscle.

Stage	Description
Endothelial damage	Damage to the inner lining of the artery (caused by high blood pressure, smoking, high cholesterol)
Lipid deposition	LDL cholesterol infiltrates the damaged endothelium and accumulates in the arterial wall
Inflammatory response	White blood cells (macrophages) migrate to the site, engulf the lipids, and become foam cells (forming a fatty streak)
Plaque formation	Smooth muscle cells migrate to the area and form a fibrous cap over the lipid core, creating an atheroma (plaque)
Plaque growth	The plaque gradually enlarges, narrowing the lumen of the artery and restricting blood flow
Thrombosis	If the fibrous cap ruptures, a blood clot (thrombus) forms at the site, potentially completely blocking the artery

Risk factors for CHD:

Risk Factor	Mechanism
High LDL cholesterol	LDL deposits cholesterol in arterial walls, promoting plaque formation
High blood pressure	Damages the endothelial lining of arteries, making it easier for cholesterol to infiltrate
Smoking	Carbon monoxide reduces oxygen-carrying capacity of blood; nicotine increases heart rate and blood pressure; chemicals in smoke damage endothelium
Diabetes	High blood glucose damages blood vessels; diabetics often have abnormal lipid profiles
Obesity	Associated with high blood pressure, high cholesterol, and diabetes
Sedentary lifestyle	Lack of exercise is associated with higher blood pressure, higher cholesterol, and obesity
Family history	Genetic predisposition to high cholesterol or other risk factors
High saturated fat diet	Increases LDL cholesterol levels
Stress	Chronic stress increases blood pressure and heart rate; may promote inflammation in arteries

Treatments for CHD:

Treatment	Description
Statins	Drugs that reduce cholesterol synthesis in the liver (inhibit HMG-CoA reductase); lower LDL cholesterol levels
Antihypertensives	Drugs that lower blood pressure (ACE inhibitors, beta-blockers, calcium channel blockers)
Anticoagulants	Drugs that prevent blood clot formation (aspirin, warfarin, heparin)
Angioplasty	A balloon catheter is inserted into the narrowed artery and inflated to compress the plaque and widen the lumen; a stent is usually inserted to keep the artery open
Coronary artery bypass graft (CABG)	A blood vessel (usually from the leg or chest) is grafted to bypass the blocked section of the coronary artery
Lifestyle changes	Healthy diet (low saturated fat, high fibre), regular exercise, stopping smoking, reducing alcohol intake, weight management

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Blood Pressure

Measurement

Blood pressure is measured using a sphygmomanometer and is expressed as two values:

$\text{Blood pressure} = \frac{\text{Systolic pressure}}{\text{Diastolic pressure}} \text{ mmHg}$

Component	Description	Normal Value
Systolic pressure	Maximum pressure during ventricular systole (when blood is ejected into the aorta)	~120 mmHg
Diastolic pressure	Minimum pressure during ventricular diastole (when the heart is relaxing)	~80 mmHg

Classification

Category	Systolic (mmHg)	Diastolic (mmHg)
Normal	Below 120	Below 80
Elevated	120-129	Below 80
Hypertension Stage 1	130-139	80-89
Hypertension Stage 2	140 or above	90 or above
Hypotension	Below 90	Below 60

Factors Affecting Blood Pressure

Factor	Effect	Mechanism
Cardiac output	Increased CO increases blood pressure	More blood pumped into arteries per unit time increases pressure
Peripheral resistance	Increased resistance increases blood pressure	Narrower arteries (vasoconstriction) or thicker blood increase resistance; higher resistance = higher pressure for the same flow
Blood volume	Increased volume increases blood pressure	More fluid in the blood vessels increases pressure against the walls
Exercise	Increases systolic, slightly increases or maintains diastolic	Increased cardiac output; vasodilation in exercising muscles offsets some of the pressure increase
Stress	Increases blood pressure (short-term)	Sympathetic nervous system activation; adrenaline and noradrenaline cause vasoconstriction and increased heart rate
Age	Generally increases with age (arteries become less elastic)	Reduced elasticity means arteries cannot expand to accommodate the pulse of blood, increasing systolic pressure
Diet (salt)	High salt intake increases blood pressure	Excess sodium causes water retention (osmosis), increasing blood volume

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Common Pitfalls

• The left ventricle has a thicker muscular wall than the right ventricle because it needs to generate a higher pressure to pump blood to the entire body (systemic circulation), whereas the right ventricle only needs to pump blood to the nearby lungs (pulmonary circulation)
• Systolic pressure is the HIGHER number; diastolic is the LOWER number. Students often confuse these. Remember: "systolic = squeeze" (ventricles contracting)
• Cardiac output = heart rate $\times$ stroke volume, NOT heart rate $\times$ blood volume. Stroke volume is the volume of blood ejected per beat, not the total blood volume
• Veins have valves to prevent backflow; arteries do NOT have valves. Arteries have thick, elastic walls that maintain blood pressure; veins rely on valves and the skeletal muscle pump to return blood to the heart

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The Digestive System in Detail

Structure of the Alimentary Canal

Layer	Description	Function
Mucosa (innermost)	Epithelial tissue; may be simple columnar (stomach, intestines) or stratified squamous (oesophagus, mouth)	Secretion of mucus, enzymes, and digestive juices; absorption of nutrients; protection against self-digestion and pathogens
Submucosa	Connective tissue containing blood vessels, lymphatic vessels, and nerves (submucosal plexus)	Nourishment of the gut wall; transport of absorbed nutrients into blood and lymph
Muscularis externa	Two layers of smooth muscle: inner circular layer and outer longitudinal layer (except in the stomach, which has a third oblique layer)	Peristalsis (rhythmic wave of contraction) moves food along the canal; segmentation mixes food with digestive juices
Serosa (adventitia)	Thin outer layer of connective tissue; covered by peritoneum (a serous membrane)	Protection; reduces friction between digestive organs and surrounding tissues

Enzymes of Digestion

Location	Enzyme	Substrate	Product(s)	Optimal pH
Mouth	Salivary amylase	Starch	Maltose	~6.8 (neutral)
Stomach	Pepsin	Proteins	Polypeptides	~1.5-2.0 (acidic)
Small intestine (duodenum)	Pancreatic amylase	Starch	Maltose	~7.5-8.5 (alkaline)
Small intestine (duodenum)	Pancreatic trypsin	Proteins/polypeptides	Shorter peptides/amino acids	~7.5-8.5
Small intestine (duodenum)	Pancreatic lipase	Lipids (triglycerides)	Fatty acids and glycerol	~7.5-8.5
Small intestine (ileum)	Maltase	Maltose	Glucose	~7.5-8.5
Small intestine (ileum)	Sucrase	Sucrose	Glucose and fructose	~7.5-8.5
Small intestine (ileum)	Lactase	Lactose	Glucose and galactose	~7.5-8.5
Small intestine (ileum)	Peptidases (erepsin)	Peptides	Amino acids	~7.5-8.5

Absorption in the Small Intestine

The small intestine is the primary site of nutrient absorption. It is highly adapted for this function:

Adaptation	Description	Benefit
Villi	Finger-like projections of the mucosa (~5 mm long); greatly increase the surface area for absorption	More surface area = more efficient absorption
Microvilli	Microscopic hair-like projections on the epithelial cells of the villi (forming the "brush border"); further increase surface area	Surface area is increased by an additional ~600x
Single layer of epithelial cells	The villi are lined by a single layer of simple columnar epithelium, creating a short diffusion distance	Nutrients only need to diffuse across one cell layer to reach the blood
Dense capillary network	Each villus contains a network of blood capillaries	Amino acids and glucose are absorbed into the blood and carried to the liver via the hepatic portal vein
Lacteal	Each villus contains a lacteal (a small lymphatic vessel)	Fatty acids and glycerol are absorbed into the lacteal and transported via the lymphatic system
Mitochondria	Epithelial cells have many mitochondria	Provide ATP for active transport of nutrients against concentration gradients

Mechanisms of absorption:

Mechanism	Description	Substances Absorbed
Diffusion	Movement from high to low concentration down a concentration gradient	Small lipids (glycerol, short-chain fatty acids); some water-soluble vitamins
Facilitated diffusion	Movement through carrier proteins or channel proteins, down the concentration gradient	Fructose; some amino acids
Active transport	Movement against the concentration gradient, using ATP and carrier proteins	Glucose; amino acids; ions (Na$^+$, K$^+$, Ca$^{2+}$); vitamins
Co-transport	Secondary active transport; Na$^+$ moves down its concentration gradient, dragging glucose or amino acids with it (SGLT1 and other co-transporters)	Glucose; galactose; amino acids
Endocytosis	The cell membrane engulfs the substance, forming a vesicle inside the cell	Cholesterol; some vitamins; antibodies in newborns (from breast milk)

Co-transport of Glucose

The mechanism by which glucose is absorbed from the small intestine (and reabsorbed in the kidney):

1. Na$^+$/K$^+$-ATPase pump on the basolateral membrane actively transports Na$^+$ OUT of the epithelial cell into the blood, maintaining a low Na$^+$ concentration inside the cell
2. This creates a concentration gradient for Na$^+$ from the intestinal lumen (high) into the cell (low)
3. The SGLT1 co-transporter on the apical membrane transports Na$^+$ down its concentration gradient into the cell, simultaneously transporting glucose AGAINST its concentration gradient (secondary active transport)
4. Glucose exits the cell through the basolateral membrane via facilitated diffusion (GLUT2 transporter) into the blood
5. Both Na$^+$ and glucose are now in the blood and can be transported to the liver via the hepatic portal vein

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The Liver

Functions of the Liver

Function	Description
Metabolism of carbohydrates	Stores glucose as glycogen (glycogenesis); breaks down glycogen to glucose when needed (glycogenolysis); converts amino acids/lactate to glucose (gluconeogenesis); maintains blood glucose levels
Metabolism of proteins	Deamination of excess amino acids (removal of the amino group, producing ammonia, which is converted to urea in the ornithine cycle); transamination (transfer of amino groups between amino acids)
Detoxification	Converts harmful substances (alcohol, drugs, toxins) into less harmful, water-soluble compounds that can be excreted by the kidneys
Production of bile	Bile is produced by hepatocytes and stored in the gall bladder; contains bile salts (emulsify fats), bile pigments (bilirubin from haemoglobin breakdown), and cholesterol
Storage	Stores glycogen, vitamins (A, D, B12), iron (as ferritin), and minerals
Synthesis of plasma proteins	Produces albumin (maintains blood osmotic pressure), fibrinogen and prothrombin (blood clotting factors), and globulins (antibodies and transport proteins)
Immune function	Kupffer cells (specialised macrophages in the liver sinusoids) phagocytose bacteria and old/damaged red blood cells
Breakdown of hormones	Inactivates and breaks down hormones such as insulin, glucagon, and steroid hormones

Ornithine (Urea) Cycle

The liver converts toxic ammonia (produced by deamination) into less toxic urea, which is transported to the kidneys for excretion:

1. Ammonia ($\mathrm{NH_3}$) combines with CO$_2$ and the amino acid ornithine to form citrulline
2. Citrulline combines with more ammonia to form arginine
3. Arginine is broken down by arginase to produce urea and regenerate ornithine (the cycle continues)

$2\mathrm{NH_3} + \mathrm{CO_2} \rightarrow \mathrm{CO(NH_2)_2} + \mathrm{H_2O}$

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Common Pitfalls

• Bile is NOT an enzyme. It emulsifies fats (breaks large fat droplets into smaller droplets, increasing surface area for lipase action), but it does NOT chemically digest fats. Emulsification is a PHYSICAL process, not a chemical one
• Trypsin is produced as trypsinogen (an inactive precursor) by the pancreas. It is activated by enterokinase (an enzyme on the intestinal wall). This prevents the pancreas from digesting itself. Pepsin is similarly produced as pepsinogen and activated by the acidic environment of the stomach
• The hepatic portal vein carries blood FROM the intestines TO the liver (not from the liver to the heart). This allows the liver to process absorbed nutrients and detoxify harmful substances before they enter the general circulation
• Glucose absorption in the small intestine is primarily by ACTIVE transport (co-transport with Na$^+$), NOT by diffusion. This is why glucose can be absorbed even when its concentration in the blood is already higher than in the gut lumen**
• Deamination occurs in the LIVER, not in the kidneys. The liver removes the amino group from excess amino acids and converts the resulting ammonia to urea. The kidneys excrete urea but do not produce it**