Difficulty: Intermediate to Advanced | Prerequisites: Blood composition (Doc 1), cardiac output and blood flow (Doc 2), basic chemistry (gas laws, pH, enzyme kinetics).
This unit brings together four topics that rely heavily on the cardiovascular material. First, the respiratory system: how air gets into the lungs (ventilation), how O2 and CO2 cross between alveoli and blood (gas exchange), and how those gases are carried in the bloodstream. Second, how the brain controls breathing rate and depth. Third, cellular metabolism: how cells extract energy from carbohydrates, lipids and proteins, and the absorptive versus postabsorptive states. Fourth, thermoregulation: how the body produces, retains and dissipates heat. These topics are tested together because they share a common thread: oxygen delivery, CO2 removal and the energy budget of the body.
Air flows into the lungs when the diaphragm contracts and alveolar pressure drops below atmospheric pressure (Boyle's law). O2 diffuses into pulmonary capillaries and is carried mainly by haemoglobin (98.5%); CO2 returns mostly as bicarbonate ions (70%). The oxygen-haemoglobin dissociation curve shifts right (more O2 released) with lower pH, higher temperature or higher CO2 (Bohr effect). Cells harvest ATP from glucose (glycolysis, citric acid cycle, ETS), lipids (beta oxidation) and, as a last resort, proteins (transamination/deamination). The hypothalamus regulates body temperature by balancing heat production (metabolism, shivering, hormones) against heat loss (radiation, convection, evaporation, conduction).
Boyle's law
At constant temperature, the volume of a gas varies inversely with its pressure. This governs the pressure changes that drive inhalation and exhalation.
Dalton's law
Each gas in a mixture contributes to the total pressure in proportion to its fraction of the total number of molecules. Used to calculate partial pressures of O2, CO2, N2 and H2O in air.
Henry's law
At a given temperature, the amount of gas dissolved in a liquid is proportional to the partial pressure of that gas above the liquid. Solubility depends on the specific gas-liquid combination.
Tidal volume (Vt)
The volume of air moved into and out of the lungs with each normal breath, approximately 500 mL.
Alveolar ventilation (Va)
The volume of air per minute that reaches the respiratory zone and participates in gas exchange. Calculated as (tidal volume minus anatomic dead space) multiplied by respiratory rate.
Anatomic dead space
The volume of air in the conducting passages (nose to terminal bronchioles) that does not participate in gas exchange.
Compliance
The ease with which the lungs and thoracic wall can be expanded. High compliance requires less force; low compliance requires more.
Oxyhemoglobin dissociation curve
A sigmoidal graph relating haemoglobin saturation to PO2. The curve shape reflects cooperative binding: each O2 bound makes the next easier to bind.
Bohr effect
The effect of pH on haemoglobin's affinity for O2. Lower pH (more CO2, more H+) shifts the curve right, releasing more O2 to active tissues. Higher pH shifts the curve left.
Chloride shift
When HCO3- exits RBCs into plasma, Cl- moves in to maintain electrical balance.
Glycolysis
The anaerobic breakdown of glucose in the cytosol to two molecules of pyruvic acid, yielding a net 2 ATP.
Citric acid cycle (Krebs cycle)
An aerobic pathway in the mitochondrial matrix that processes acetyl-CoA, producing CO2, NADH, FADH2 and 2 ATP (via GTP) per glucose.
Electron transport system (ETS) / Oxidative phosphorylation
The mitochondrial process that uses NADH and FADH2 to generate approximately 28 ATP per glucose via chemiosmosis.
Beta oxidation
The mitochondrial breakdown of fatty acids into two-carbon acetyl-CoA fragments, each round yielding 12 ATP (from acetyl-CoA) plus 5 ATP (from NADH/FADH2).
Gluconeogenesis
The synthesis of glucose from non-carbohydrate precursors (lactic acid, glycerol, amino acids), mainly in the liver.
Basal metabolic rate (BMR)
The minimum resting energy expenditure of an awake, alert person, measured under standardised conditions. Proportional to oxygen consumption.
Thermoregulation
The homeostatic process of maintaining body temperature by balancing heat production and heat loss, coordinated by the hypothalamus.
Nonshivering thermogenesis
Heat production through hormonal stimulation of metabolic activity (epinephrine, thyroxine) without muscle contraction. In infants, brown fat provides this function.
Countercurrent exchange
Heat exchange between arterial blood flowing outward and venous blood returning from the extremities, trapping heat close to the body core in cold conditions.
Upper respiratory system: Nose, pharynx and associated structures.
Lower respiratory system: Larynx, trachea, bronchi, lungs.
Conducting zone: Trachea through terminal bronchioles. Warms, humidifies and filters air but no gas exchange occurs here.
Respiratory zone: Respiratory bronchioles, alveolar ducts, alveolar sacs. This is where gas exchange happens.
Bronchial tree branching: trachea, main bronchi, lobar bronchi, segmental bronchi, bronchioles, terminal bronchioles.
Two types of alveolar cells: type I (gas exchange surface) and type II (produce surfactant).
The respiratory membrane (the barrier gases cross) consists of: alveolar wall (type I and II cells plus macrophages), epithelial basement membrane, capillary basement membrane (often fused with the epithelial one), and capillary endothelium.
Air flows between the atmosphere and alveoli because of pressure gradients created by respiratory muscle contraction and relaxation.
Inhalation: Diaphragm contracts and flattens, external intercostals contract, chest cavity expands, alveolar pressure drops below atmospheric pressure, air flows in. Deep inhalation also uses scalene and sternocleidomastoid muscles.
Exhalation (quiet): Diaphragm relaxes, external intercostals relax, elastic recoil of lungs and chest wall increases alveolar pressure above atmospheric, air flows out. Forced exhalation uses internal intercostals and abdominal muscles.
Boyle's law: Volume up means pressure down (and vice versa). This drives the pressure changes of breathing.
Dalton's law: Total atmospheric pressure (760 mmHg) is the sum of partial pressures of N2 (78.6%), O2 (20.9%), H2O (0.5%) and CO2 (0.04%).
Henry's law: The amount of gas dissolved in liquid is proportional to the partial pressure of that gas. Solubility varies by gas.
Surface tension: The inward-directed force in alveoli that must be overcome during inspiration. Surfactant (from type II cells) reduces surface tension.
Elastic recoil: Returns alveoli to smaller size during expiration.
Compliance: Ease of lung expansion. Depends on elastic fibres, surfactant levels and thoracic cage mobility.
Intrapulmonary (intra-alveolar) pressure fluctuates slightly around atmospheric pressure: about -1 mmHg on inhalation, +1 mmHg on exhalation.
Intrapleural pressure (between parietal and visceral pleura) remains below atmospheric pressure throughout the respiratory cycle, keeping the lungs inflated.
Tidal volume (Vt): ~500 mL per breath.
Inspiratory reserve volume (IRV): 2,100 to 3,200 mL (extra air you can inhale beyond tidal volume).
Expiratory reserve volume (ERV): 1,000 to 1,200 mL (extra air you can forcibly exhale).
Residual volume (RV): ~1,200 mL (air that always stays in the lungs to keep alveoli open).
Respiratory minute volume (Ve) = respiratory rate x tidal volume.
Alveolar ventilation (Va) = (tidal volume minus anatomic dead space) x respiratory rate.
Eupnea: quiet breathing, 12 to 18 breaths/min in adults.
Apnea: cessation of breathing.
Dyspnea: laboured or difficult breathing.
Tachypnea: abnormally fast breathing.
Bradypnea: abnormally slow breathing.
External respiration (pulmonary): O2 diffuses from alveoli into pulmonary capillaries; CO2 moves the opposite way.
Internal respiration (tissue): O2 diffuses from systemic capillaries into tissue cells; CO2 moves into capillaries.
1.5% dissolved in plasma.
98.5% bound to haemoglobin as oxyhemoglobin (HbO2).
Fick equation: O2 consumption = CO x (arterial [O2] minus venous [O2]).
7% dissolved in plasma.
23% bound to Hb as carbaminohemoglobin.
70% converted to bicarbonate ions (HCO3-) in RBCs by carbonic anhydrase (CO2 + H2O becomes H2CO3, which dissociates into H+ and HCO3-).
In systemic capillaries, as HCO3- diffuses out of RBCs into plasma, Cl- moves into RBCs to maintain electrical neutrality.
Sigmoidal (S-shaped) because of cooperative binding: each O2 bound changes Hb's shape, making the next O2 easier to bind.
Standardised at pH 7.4 and 37 degrees C.
Right shift (more O2 released): Lower pH, higher temperature, higher PCO2. Occurs in metabolically active tissues.
Left shift (less O2 released, Hb holds tighter): Higher pH, lower temperature, lower PCO2.
CO2 enters RBCs, forms carbonic acid (via carbonic anhydrase), which dissociates into H+ and HCO3-.
The H+ ions lower pH, reducing Hb's affinity for O2 and shifting the curve right.
This ensures more O2 is released precisely where tissues are producing the most CO2.
Respiratory centres are located in the medulla oblongata and pons.
Dorsal respiratory group (DRG): Inspiratory centre; active in both quiet and forced breathing. When active, diaphragm and external intercostals contract (inhalation). When inactive, muscles relax and elastic recoil drives exhalation.
Ventral respiratory group (VRG): Functions only in forced breathing. Forceful inhalation neurons activate accessory muscles; forceful exhalation neurons activate internal intercostals and abdominal muscles.
Cortical influences: Voluntary control from the cerebral cortex (e.g. holding your breath).
Peripheral chemoreceptors (carotid and aortic arteries): Sense PO2, pH and PCO2.
Central chemoreceptors (medulla): Respond to CO2 changes in cerebrospinal fluid.
The most potent stimulus for increasing breathing rate and depth is rising PCO2 (hypercapnia): CO2 crosses into the brain, forms carbonic acid, H+ rises, central chemoreceptors activate respiratory centres.
Hypoxic hypoxia: Low arterial PO2 (high altitude, airway obstruction).
Anemic hypoxia: Decreased O2 bound to Hb (blood loss, anaemia, CO poisoning).
Ischemic hypoxia: Reduced blood flow (heart failure, shock, thrombosis).
Histotoxic hypoxia: Cells cannot use O2 (cyanide poisoning).
Stretch receptors in the pleurae and airways are stimulated by lung inflation.
They send inhibitory signals to the medullary respiratory centres, ending inhalation and allowing expiration.
Acts more as a protective response than a normal regulatory mechanism.
Metabolism encompasses all chemical reactions in the body. Cellular metabolism provides energy (ATP) to maintain homeostasis.
The nutrient pool contains the organic building blocks cells need, distributed via the bloodstream.
Overall equation: glucose + O2 becomes CO2 + H2O + ATP.
Glycolysis (cytosol, anaerobic): Breaks glucose into two pyruvic acid molecules. Net yield: 2 ATP.
Citric acid cycle (mitochondrial matrix, aerobic): Processes acetyl-CoA. Produces CO2, NADH, FADH2, and 2 ATP (via GTP) per glucose.
Electron transport system / oxidative phosphorylation (inner mitochondrial membrane): Uses NADH and FADH2 to produce ~28 ATP.
Total ATP per glucose: ~36 (2 from glycolysis + 4 from glycolysis NADH + 2 from citric acid cycle + 28 from ETS).
Gluconeogenesis: Liver synthesises glucose from non-carbohydrate precursors (lactic acid, glycerol, amino acids). Glucose is stored as glycogen in liver and skeletal muscle.
Lipolysis: Triglycerides are hydrolysed into glycerol (converted to pyruvate in the cytosol) and three fatty acids (converted to acetyl-CoA).
Beta oxidation (mitochondria): Chops fatty acids into two-carbon acetyl-CoA fragments.
Energy yield: Each two-carbon fragment yields about 17 ATP (12 from acetyl-CoA + 5 from NADH/FADH2). An 18-carbon fatty acid can yield ~144 ATP, about 1.5 times the energy of one glucose molecule.
Used for energy only when other sources are inadequate.
Transamination: Transfers the amino group to a keto acid, producing a new amino acid (available for protein synthesis) and a carbon skeleton that can enter the citric acid cycle.
Deamination: Removes the amino group as ammonium ion (NH4+), preparing the carbon skeleton for the citric acid cycle.
Ammonium ions are toxic. The liver converts them to urea via the urea cycle; urea is excreted in urine.
Three reasons the body avoids protein catabolism: proteins are harder to break down than carbohydrates or lipids; ammonium ions are toxic; proteins are critical structural and functional cell components.
Absorptive state: The period after a meal when nutrients are being absorbed. Glucose is the primary fuel; excess is stored as glycogen or fat.
Postabsorptive state: Between meals, when absorption is not occurring. The body relies on internal reserves. Liver conserves glucose by breaking down lipids and amino acids, which can produce ketone bodies.
Ketoacidosis: Dangerous drop in blood pH from high ketone levels. In severe cases, pH may fall below 7.05, risking coma, arrhythmias and death.
BMR: Minimum resting energy expenditure. Measured by monitoring O2 consumption.
Energy content of foods: lipids ~9.46 Cal/g; carbohydrates ~4.18 Cal/g; proteins ~4.32 Cal/g.
Hormonal regulation: Thyroxine controls overall metabolic rate. Leptin (from adipose tissue) and CCK suppress appetite. Ghrelin (from empty stomach) increases appetite.
The body produces heat as a by-product of metabolism. Enzymes operate within a narrow temperature range, so homeostatic mechanisms keep core temperature stable.
Core temperature (organs in skull, thorax, abdomen) is regulated and fairly constant. Rectal temperature is the best clinical indicator. Blood is the main agent of heat exchange between core and shell.
Shell temperature (skin) fluctuates between 20 and 40 degrees C depending on the environment.
Radiation (~50% of indoor heat loss): Warm objects emit infrared radiation.
Convection (~15% of indoor heat loss): Body heats the air near the skin; that air rises and is replaced by cooler air.
Evaporation (~20% of indoor heat loss from insensible water loss + variable sensible perspiration): 0.58 Cal absorbed per gram of water evaporated.
Conduction: Direct transfer of heat through physical contact. Generally not a major route of gain or loss.
The preoptic area of the anterior hypothalamus contains a heat gain centre and a heat loss centre. It receives input from peripheral thermoreceptors (skin) and central thermoreceptors (core).
Inhibition of the vasomotor centre causes peripheral vasodilation: warm blood flows to the skin surface, increasing radiation and convective losses.
Sweat glands increase secretory output, raising evaporative heat loss.
Respiratory centres are stimulated, increasing the depth of respiration.
Heat conservation: Sympathetic vasomotor centre decreases blood flow to the dermis, reducing radiation, convection and conduction losses.
Countercurrent exchange: In cold conditions, venous blood returning from the limbs is shunted to deep veins that wrap around arteries, trapping heat close to the core.
Shivering thermogenesis: Increased skeletal muscle tone produces heat. Can increase heat generation up to 400%.
Nonshivering thermogenesis: Epinephrine (released via sympathetic stimulation of the adrenal medulla) increases glycogenolysis and metabolic rate. The hypothalamus also stimulates TRH and TSH release, which increases thyroxine secretion and overall metabolic rate.
Infants cannot shiver. Instead, sympathetic fibres stimulate lipolysis in brown fat adipocytes, rapidly generating heat (up to 100% increase in metabolic heat).
Adults retain very little brown fat; shivering thermogenesis becomes the dominant mechanism.
Individuals with more subcutaneous fat shiver less because adipose tissue insulates.
Thermoregulatory responses differ due to acclimatisation and body size.
Larger body size means a lower surface-to-volume ratio, so heat is retained more efficiently.
The ovulatory cycle causes small temperature fluctuations in women.
Body temperature maintained above 37.2 degrees C. Usually temporary and not always pathological.
In young children, transient fevers can result from exercise in warm weather.
Hyperthermia (heat stroke): Core temperature reaches 41 degrees C, triggering a dangerous positive feedback loop: higher temperature raises metabolic rate, which raises temperature further. Skin becomes hot and dry. Can damage organs and be fatal.
Heat exhaustion: Collapse after vigorous exercise due to dehydration and low BP. Heat-loss mechanisms still functional. May progress to heat stroke if not treated.
Frostbite: Prolonged cold exposure restricts blood flow to skin, forming ice crystals in and around cells.
Hypothermia: Core temperature drops from cold exposure. Vital signs decrease. Shivering stops at 30 to 32 degrees C. Can progress to coma and cardiac arrest.
Students often think O2 is mostly dissolved in plasma. In fact, 98.5% is carried bound to haemoglobin; only 1.5% is dissolved.
Students confuse the Bohr effect with a general "pH affects everything" statement. The Bohr effect specifically describes how CO2-driven pH changes shift the O2-Hb dissociation curve right in active tissues, promoting O2 release where it is needed most.
Students sometimes believe glycolysis requires oxygen. It does not. Glycolysis is anaerobic and occurs in the cytosol. The aerobic steps (citric acid cycle, ETS) occur in the mitochondria.
Students frequently mix up heat stroke and heat exhaustion. In heat exhaustion, heat-loss mechanisms still work (sweating continues, dehydration and low BP cause collapse). In heat stroke, thermoregulation has failed (skin is hot and dry, positive feedback loop).
⚠️ Know the three gas laws (Boyle's, Dalton's, Henry's) and how each applies to ventilation and gas exchange.
⚠️ Be able to explain what shifts the O2-Hb dissociation curve right (lower pH, higher temp, higher PCO2) versus left.
⚠️ Understand the Bohr effect mechanism: CO2 enters RBCs, carbonic anhydrase produces H2CO3, which dissociates to H+ and HCO3-; H+ lowers pH and shifts the curve right.
⚠️ Know the three stages of glucose catabolism and ATP yield: glycolysis (2 ATP), citric acid cycle (2 ATP via GTP), ETS (28 ATP).
⚠️ Understand beta oxidation and why fats yield more ATP per gram than carbohydrates.
⚠️ Know the difference between the absorptive and postabsorptive states, and why ketoacidosis is dangerous.
⚠️ Distinguish the four mechanisms of heat transfer (radiation, convection, evaporation, conduction) and their approximate contributions to indoor heat loss.
⚠️ Understand the difference between shivering and nonshivering thermogenesis.
⚠️ Know how the DRG and VRG control quiet versus forced breathing.
⚠️ Be able to calculate alveolar ventilation: (Vt minus dead space) x respiratory rate.
Q: Using Boyle's law, explain what happens to alveolar pressure during inhalation and why air flows into the lungs.
A: When the diaphragm contracts and the chest cavity expands, lung volume increases. By Boyle's law, as volume increases, pressure decreases. Alveolar pressure drops below atmospheric pressure, creating a pressure gradient that drives air into the lungs.
Q: Describe the three forms in which CO2 is transported in the blood and state the approximate percentage for each.
A: 7% dissolved in plasma, 23% bound to haemoglobin as carbaminohemoglobin, 70% as bicarbonate ions (HCO3-) in plasma.
Q: Explain the Bohr effect and its physiological significance.
A: When CO2 enters RBCs, carbonic anhydrase converts it to carbonic acid (H2CO3), which dissociates into H+ and HCO3-. The increased H+ lowers pH, reducing haemoglobin's affinity for O2 (curve shifts right). This ensures more oxygen is released in metabolically active tissues that are producing the most CO2.
Q: How many ATP molecules are produced from the complete oxidation of one glucose molecule, and from which stages?
A: Approximately 36 ATP total: 2 from glycolysis, 4 from NADH produced in glycolysis, 2 from the citric acid cycle (via GTP), and 28 from the electron transport system.
Q: Compare heat stroke and heat exhaustion.
A: Heat exhaustion is heat-associated collapse due to dehydration and low BP after vigorous exercise; heat-loss mechanisms (sweating) are still functional, and it is treatable with cooling and rehydration. Heat stroke occurs when the core temperature reaches ~41 degrees C and thermoregulation fails: a positive feedback loop drives temperature higher, the skin becomes hot and dry, and organs can be damaged. Heat stroke is life-threatening.
Q: What is the primary chemical stimulus for increasing respiratory rate, and how does it work?
A: Rising blood PCO2 (hypercapnia). CO2 crosses into the brain and combines with water to form carbonic acid, which releases H+. The increased H+ stimulates central chemoreceptors in the medulla, which activate respiratory centres to increase the depth and rate of breathing, lowering blood PCO2 back to normal.
Gas exchange and transport tie directly back to the cardiovascular system (Doc 2): the blood vessels and cardiac output you studied are the delivery mechanism for the gases discussed here. The Bohr effect and chloride shift connect to acid-base balance, which appears in the renal unit. Metabolism connects to the digestive system (nutrient absorption feeds the nutrient pool) and to endocrine physiology (insulin, glucagon, thyroxine, leptin, ghrelin). Thermoregulation relies on concepts from the integumentary system (skin as a heat-exchange surface) and the autonomic nervous system (sympathetic and parasympathetic control of vasodilation, sweating and shivering).
Respiration, ventilation, breathing, inhalation, exhalation, upper respiratory system, lower respiratory system, conducting zone, respiratory zone, trachea, bronchi, bronchioles, terminal bronchioles, alveoli, alveolar cells type I, type II, surfactant, respiratory membrane, Boyle's law, Dalton's law, Henry's law, partial pressure, atmospheric pressure, diaphragm, external intercostals, internal intercostals, intrapulmonary pressure, intrapleural pressure, compliance, elastic recoil, surface tension, tidal volume, inspiratory reserve volume, expiratory reserve volume, residual volume, respiratory minute volume, alveolar ventilation, anatomic dead space, eupnea, apnea, dyspnea, tachypnea, bradypnea, external respiration, internal respiration, oxyhemoglobin, deoxyhemoglobin, carbaminohemoglobin, bicarbonate, chloride shift, oxygen-hemoglobin dissociation curve, Bohr effect, carbonic anhydrase, Fick equation, DRG, VRG, dorsal respiratory group, ventral respiratory group, chemoreceptor, central chemoreceptor, peripheral chemoreceptor, hypercapnia, hypoxia, hypoxic hypoxia, anemic hypoxia, ischemic hypoxia, histotoxic hypoxia, Hering-Breuer reflex, inflation reflex, metabolism, cellular metabolism, catabolism, anabolism, glycolysis, pyruvic acid, citric acid cycle, Krebs cycle, electron transport system, oxidative phosphorylation, ATP, NADH, FADH2, acetyl-CoA, beta oxidation, lipolysis, gluconeogenesis, transamination, deamination, urea cycle, ammonium ion, absorptive state, postabsorptive state, ketone bodies, ketoacidosis, basal metabolic rate, BMR, calorie, kilocalorie, thyroxine, leptin, ghrelin, CCK, thermoregulation, core temperature, shell temperature, radiation, convection, evaporation, conduction, insensible water loss, sensible perspiration, hypothalamus, preoptic area, heat gain centre, heat loss centre, vasodilation, vasoconstriction, countercurrent exchange, shivering thermogenesis, nonshivering thermogenesis, brown fat, epinephrine, thyroxine, TSH, TRH, pyrexia, fever, hyperthermia, heat stroke, heat exhaustion, frostbite, hypothermia