Metabolism & Body Temperature

The whole reason you breathe and the whole reason you eat is to make ATP. Every cellular process that requires energy — muscle contraction, neuronal firing, active transport, protein synthesis — ultimately runs on ATP, and ATP is produced by oxidising fuel. The body keeps three fuel stores ready: glycogen (small, short-term, mostly in liver and muscle, ~400 g total), fat (massive, long-term, ~15 kg in an adult of normal weight, providing energy for weeks of starvation), and protein (mostly muscle, dipped into only in extreme deprivation). The interesting thing about fat is its energy density: at 9.3 kcal/g it carries more than twice the energy per gram of carbohydrate or protein. That is why evolution chose fat as the body’s main long-term energy store — you couldn’t carry around the equivalent weight of glycogen.

• Immediate fuel = glucose/ATP; the main long-term energy store of the body is FAT (energy-dense, 9.3 kcal/g) — glycogen stores are small.
• Caloric values: carbohydrate & protein ~4.1 kcal/g; fat ~9.3 kcal/g.

Specific dynamic action = the extra heat produced after eating, as the body processes the food. It is highest for protein (~30%), much less for carbohydrate & fat.

Even when you do absolutely nothing — lie still, don’t talk, don’t digest, don’t shiver — your body still burns about 1500-1800 kcal per day, just keeping itself alive: heart pumping, lungs breathing, brain working, ion gradients maintained, body temperature held at 37°C. This irreducible minimum is the basal metabolic rate (BMR), and it’s a useful clinical fingerprint of your overall metabolic state. Because BMR depends on body size, it’s reported per square metre of body surface area (~40 kcal/m²/h in a young man). The main determinant of BMR is thyroid hormone — raise it and BMR climbs (hyperthyroidism: hot, sweaty, restless, weight loss despite eating more); lower it and BMR falls (hypothyroidism: cold, tired, slow, weight gain despite eating less). BMR is also pushed up by catecholamines (fever, exercise), and is naturally higher in children (growth) and lower in elderly.

Basal conditions required:

• Awake but physically & mentally at rest, lying down (not standing).
• Post-absorptive — 12–14 hours after the last meal (no SDA).
• Thermoneutral environment (~20–25°C, quiet).
• Normal body temperature.

BMR is normally expressed per unit body surface area (kcal/m²/h or kJ/m²/h) rather than per kg, because heat exchange & metabolism scale with surface area. Adult ♂ ~40 kcal/m²/h, ♀ ~37; a 1.7 m² man ≈ 1600–1800 kcal/day.

• Direct calorimetry: measures the heat lost by a subject in an insulated chamber. Accurate but cumbersome — rarely used clinically.
• Indirect calorimetry: measures O₂ consumption (and CO₂ production) and converts using the energy equivalent of O₂ (~4.825 kcal/L O₂ on a mixed diet, depending on RQ). Most common.
• The Benedict–Roth spirometer (closed-circuit) and modern open-circuit metabolic carts both use indirect calorimetry.

A swimmer pulled from icy water has a hypothermic skin but his organs are still close to 37°C — for a while. That’s the core-shell distinction. The body protects the temperature of the core (brain, thorax, abdomen) ferociously, because enzymes work in a narrow temperature window and severe cooling or heating denatures them. The shell (skin, limbs) is allowed to wander — it acts as a buffer between the harsh outside world and the protected core. In the cold, the shell cools first (you go pale, fingers numb) before the core is touched; in the heat, the shell sweats and vasodilates so heat can leave before the core climbs. Rectal temperature most closely matches core; oral is ~0.5°C lower; axillary lower still. Core temperature has a daily rhythm: lowest at ~4 am, highest at ~6 pm, ~1°C swing.

• Core temperature (deep organs — brain, thorax, abdomen) is kept nearly constant ~37°C; this is the clinically relevant "body temperature".
• Shell temperature (skin, limbs) varies with the environment and acts as a heat buffer/radiator.
• Measurement sites: rectal (~37.1–37.5°C, closest to core) > oral (~37°C) > axillary (~36.5°C).

• At rest: the liver (and other viscera) is the main heat source.
• In cold / during activity: skeletal-muscle shivering is the chief way to increase heat production.
• Also: hormones (thyroxine, adrenaline → non-shivering thermogenesis), and the specific dynamic action of food.

Heat leaves the body by four routes — radiation (~60% at rest, infrared given off to cooler surroundings), conduction (small, by direct contact), convection (heat carried away by moving air or water; rises with wind), and evaporation (sweat). Three of these depend on a temperature gradient between skin and environment, which means when the room is hotter than your skin (~33°C), they go into reverse and you start gaining heat. At that point evaporation becomes the only route left — which is why sweating is your last defence against hyperthermia. A litre of sweat that fully evaporates carries away ~580 kcal, equivalent to about a third of your daily BMR. The catch: that evaporation only happens if the air is dry enough to accept it. In high humidity (e.g. tropical climates) sweat drips off without evaporating, and core temperature climbs — heat stroke risk soars.

The body keeps temperature within ~0.5°C of 37°C because the preoptic area of the hypothalamus works as a thermostat. Neurons there directly sense blood temperature and compare it with an internal set point. If body temp climbs above 37°C, the hypothalamus dispatches heat-loss orders: skin vasodilation, sweating, decreased heat production. If body temp falls below 37°C, the opposite happens: cutaneous vasoconstriction (you go pale), piloerection (goosebumps, useful in furred mammals), shivering (large skeletal muscle contractions that produce heat as a byproduct), and behavioural changes (huddle, put on a jumper). Fever is not a broken thermostat — it’s a thermostat reset to a higher set point by pyrogens (mainly prostaglandin E₂ in the hypothalamus, made in response to inflammatory cytokines like IL-1 and IL-6). The body then defends the new (higher) temperature exactly as if it were normal — you feel cold and shiver as it climbs. NSAIDs (aspirin, paracetamol) block PGE₂ synthesis, resetting the thermostat back to 37°C.

The thermoregulatory centre sits in the preoptic area of the (anterior) hypothalamus — neurons there respond directly to blood temperature and compare it with a set point (~37°C), driving negative feedback:

Pyrogens (from infection/inflammation, via prostaglandin E₂) raise the hypothalamic set point above 37°C. Now the actual body temperature is below the new set point, so the body behaves as if cold:

1. Onset (chill phase): vasoconstriction + shivering → heat is generated & conserved → temperature climbs to the new (higher) set point — the patient feels cold despite a rising fever.
2. Plateau: temperature held at the elevated set point.
3. Defervescence (crisis): when the set point falls back to normal (recovery or antipyretic), body temp is now above it → vasodilation + sweating → temperature falls.

• To heat: over days/weeks → sweat begins at a lower core temperature, sweat volume rises (up to 2 L/h), and sweat Na⁺ content falls (aldosterone) → salt conserved.
• To cold: increased non-shivering thermogenesis (brown fat in infants; thyroid up-regulation in adults), peripheral vasoconstriction, lower thermal comfort temperature.
• To altitude (covered in Unit 5): hyperventilation, ↑2,3-DPG, ↑EPO → polycythaemia, ↑capillary density.

• Glycolysis — cytosolic; 1 glucose → 2 pyruvate + 2 ATP + 2 NADH (anaerobic: pyruvate → lactate). Rate-limited by phosphofructokinase-1 (inhibited by ATP/citrate, activated by AMP/F2,6-BP).
• TCA cycle & oxidative phosphorylation — mitochondrial; complete oxidation yields ~30–32 ATP per glucose.
• Glycogenesis (liver, muscle) stores glucose as glycogen (insulin-driven). Glycogenolysis (glucagon, adrenaline) releases it. Liver glycogen ~100 g, muscle ~400 g.
• Gluconeogenesis (liver, renal cortex) makes glucose from lactate, glycerol & gluconeogenic amino acids in starvation. Driven by glucagon, cortisol.

Normal fasting plasma glucose ~70–100 mg/dL (3.9–5.6 mmol/L). Brain & RBCs depend almost exclusively on glucose; the brain uses ~120 g/day.

• Lipolysis in adipose → free fatty acids (FFA) + glycerol; activated by adrenaline, glucagon, cortisol; inhibited by insulin.
• β-oxidation (mitochondrial) yields ~106 ATP per palmitate (16C) — fat is the densest fuel.
• Ketogenesis (liver, starvation / DKA): acetyl-CoA → acetoacetate + β-hydroxybutyrate → brain & muscle fuel.
• Cholesterol made in liver (HMG-CoA reductase, statin target) → bile acids, steroid hormones, membrane component.
• Lipoproteins: chylomicrons (gut → tissue TG), VLDL (liver → tissue TG), LDL ("bad" — cholesterol to tissues), HDL ("good" — reverse cholesterol transport).

• Amino acids: 20 standard, 9 essential (cannot be synthesised — PVT TIM HALL: Phe, Val, Thr, Trp, Ile, Met, His, Arg*, Leu, Lys).
• Transamination & deamination → carbon skeleton (glucogenic / ketogenic) + NH₃.
• Urea cycle (liver): NH₃ + CO₂ → urea (excreted by kidney) — the body’s detoxification of nitrogen. Failure (liver failure, urea-cycle defects) → hyperammonaemia → encephalopathy.
• Nitrogen balance: positive (growth, pregnancy, recovery) vs negative (starvation, trauma, sepsis, glucocorticoids).