16.6 Exercise Physiology, Thermoregulation & Bone Mechanobiology

16.6 Exercise Physiology, Thermoregulation & Bone Mechanobiology

The physiology outline lists exercise physiology (thermoregulation and exercise) and bone metabolism (osteoclast, osteoblast and stress/strain). Hormonal control of calcium and bone remodeling (PTH, vitamin D, calcitonin) is in 16.3, and bone cell histology is in 14.1. This section adds the integrated response to exercise, temperature regulation and bone mechanics, which apply to sports medicine, diabetic exercise prescription, cold injuries and stress fractures.

Energy Systems in Exercise

As intensity rises, lactate production outpaces clearance at the lactate threshold, and ventilation increases disproportionately at the ventilatory threshold. Maximal oxygen uptake (VO2max) reflects cardiovascular capacity:

$$\dot{V}O_2 = \text{CO} \times (C_aO_2 - C_{\bar{v}}O_2)$$

Muscle Fiber Types

Cardiovascular and Respiratory Responses

• Cardiac output rises from about 5 L/min to as much as 20–30 L/min in trained athletes, through increases in heart rate and stroke volume (more venous return, sympathetic inotropy and the muscle pump).
• Blood flow redistribution: local metabolites (adenosine, K+, H+, CO2, lactate, nitric oxide) dilate muscle arterioles, while sympathetic vasoconstriction reduces splanchnic and renal flow.
• Blood pressure: systolic pressure rises, and diastolic pressure stays about the same or falls in dynamic exercise because systemic vascular resistance decreases.
• Ventilation rises with CO2 production and stays matched to it until the ventilatory threshold.
• Training adaptations: endurance training increases stroke volume, capillary density, mitochondrial content and fat oxidation, and lowers resting heart rate. Resistance training mainly causes muscle hypertrophy and neural adaptation.
• Eccentric contractions (for example, downhill running) produce delayed-onset muscle soreness that peaks 24–72 hours later.

Clinical applications:

• In diabetes, contraction moves GLUT4 to the membrane independently of insulin (through AMPK, 15.1), so exercise lowers glucose. Hypoglycemia can follow in patients on insulin or sulfonylureas, and protective footwear and foot inspection are essential with neuropathy.
• In peripheral artery disease, supervised exercise therapy is a first-line treatment for claudication because it improves collateral flow and muscle oxidative capacity.

Thermoregulation

Control center. The preoptic anterior hypothalamus compares core temperature with its set point (about 37°C). Warm signals trigger heat loss and cold signals trigger heat conservation and production.

Effectors:

• Skin blood flow: sympathetic adrenergic vasoconstriction conserves heat, and active vasodilation (sympathetic cholinergic) releases it. Arteriovenous anastomoses in the glabrous skin of the hands and feet (14.2) are the main thermoregulatory vessels.
• Sweating: eccrine glands are driven by sympathetic cholinergic M3 fibers. Heat acclimatization over about 1–2 weeks produces earlier, greater and more dilute sweating (aldosterone-mediated salt conservation).
• Heat production: shivering, nonshivering thermogenesis (brown fat in infants) and thyroid hormone.

Fever is a raised set point. IL-1, IL-6 and TNF-alpha induce hypothalamic PGE2, which is why NSAIDs and acetaminophen reduce fever. This differs from hyperthermia, where the set point is normal but heat gain overwhelms heat loss.

Heat Illness

• Heat exhaustion: fatigue, nausea and headache with core temperature usually below 40°C and normal mental status.
• Exertional heat stroke: core temperature above about 40°C with central nervous system dysfunction (confusion, collapse, seizures), often with rhabdomyolysis, AKI and DIC. Treatment is immediate cold-water immersion or other rapid cooling.
• Drug-related hyperthermic syndromes (malignant hyperthermia, serotonin syndrome, neuroleptic malignant syndrome) are covered in 11.4 and 12.1.

Cold Injury

• Frostnip: superficial and reversible.
• Frostbite: ice crystal formation and microvascular thrombosis. Rewarm rapidly in water at about 37–39°C only when refreezing can be prevented, protect blisters, give analgesia and defer debridement until demarcation, which can take weeks.
• Non-freezing cold injury (trench or immersion foot): prolonged cold, wet exposure above freezing causes neurovascular damage with painful hyperemia afterward. It is classically seen in military personnel and people experiencing homelessness.
• Chilblains (pernio): inflammatory, pruritic or painful violaceous lesions on the toes after cold, damp exposure.

Bone Mechanobiology

Stress and strain:

• Stress = force / area (pascals; 1 MPa = 1 N/mm²)
• Strain = change in length / original length (dimensionless or %)
• Young's modulus = stress / strain in the elastic region (stiffness)

The stress-strain curve shows an elastic region (full recovery), a yield point, a plastic region (permanent deformation), ultimate strength and failure. Cortical bone is anisotropic (strongest in compression, weaker in tension and weakest in shear) and viscoelastic (stiffer and stronger at higher loading rates). Tendon shows an initial "toe region" as crimped collagen straightens, then a linear region.

Worked examples:

• A 700-N load on a cross-sectional area of 350 mm² produces a stress of 700 / 350 = 2 N/mm², or 2 MPa.
• A 200-mm tendon that lengthens by 8 mm has a strain of 8 / 200 = 4%.

Adaptation:

• Wolff's law: bone remodels to match its loading.
• Mechanostat: strain above a modeling threshold adds bone, and disuse below a lower threshold causes resorption.
• Osteocytes sense fluid shear in canaliculi and reduce sclerostin when loaded, which releases Wnt signaling and stimulates osteoblasts.
• Unloading (casting, non-weight-bearing, bed rest) raises sclerostin and RANKL-driven osteoclast activity, causing disuse osteopenia.
• The Hueter-Volkmann principle: increased compression across a growth plate slows growth and reduced compression speeds it.

Stress fractures:

• Fatigue fractures: abnormal or repetitive loading of normal bone. Second metatarsal "march" fractures, calcaneal and tibial fractures are typical. High-risk sites include the navicular body, the proximal fifth metatarsal metadiaphysis (1.2), the anterior tibial cortex and the medial malleolus.
• Insufficiency fractures: normal loading of weakened bone (osteoporosis, CKD-mineral bone disorder, long-term corticosteroids).
• Relative energy deficiency in sport (RED-S), which includes the female athlete triad (low energy availability, menstrual dysfunction, low bone density), predisposes athletes to recurrent stress fractures.