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Unit XII: The Integrated Physiology

MBBS 1st Year - Complete Chapter Notes

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Chapter 102: Regulation of Body Temperature in Humans

Normal Body Temperature

• Core temperature (deep tissues): highly regulated, normally 97°F - 99.5°F (36°C - 37.5°C). This remains stable within ±0.6°C in health.
• Skin (shell) temperature: fluctuates freely with the environment, and is important for heat exchange.

Factors Affecting Body Temperature

1. Basal metabolic rate (BMR) of all cells
2. Muscle activity - exercise and shivering are major sources
3. Thyroid hormones (thyroxine) - increase cellular metabolism
4. Epinephrine/norepinephrine and sympathetic stimulation
5. Cell temperature - higher temperature accelerates chemical reactions
6. Thermogenic (specific dynamic) effect of food - digestion generates heat

Temperature Regulating Mechanisms

"When the rate of heat production in the body is greater than the rate at which heat is being lost, heat builds up in the body, and the body temperature rises. Conversely, when heat loss is greater than heat production, body temperature decreases." - Guyton & Hall

• The anterior hypothalamus is the body's thermoregulatory center (the "thermostat")
• It receives input from:
  • Peripheral thermoreceptors in the skin (warm & cold receptors)
  • Central thermoreceptors in the anterior hypothalamus itself monitoring blood/core temperature
• The hypothalamus compares sensed temperature against a set-point (~37°C) and activates corrective responses

• Shivering - rapid involuntary muscle contractions generate heat
• Vasoconstriction of skin blood vessels (sympathetic tone increase) - reduces heat loss from skin
• Increased metabolic rate via thyroid hormones
• Piloerection (goosebumps) - traps insulating air layer

• Sweating - evaporation is the most powerful heat loss mechanism
• Vasodilation of skin vessels (reduced sympathetic tone) - brings warm blood to skin surface for radiation, conduction, convection
• Increased respiration (minor effect in humans; major in panting animals)

Applied Aspects

• Defined as core temperature above normal due to resetting of the hypothalamic set-point upward by pyrogens
• Pyrogens (e.g., bacterial lipopolysaccharide endotoxins) stimulate macrophages to release cytokines, especially Interleukin-1 (IL-1), which is also called endogenous pyrogen
• IL-1 acts on the anterior hypothalamus to increase local prostaglandin synthesis, which raises the set-point
• The body then activates heat-generating mechanisms (shivering, vasoconstriction) until the new, higher set-point is reached - this is the "chills" phase
• Aspirin reduces fever by inhibiting cyclooxygenase (COX), blocking prostaglandin synthesis - this lowers the set-point back to normal, triggering heat-loss mechanisms (sweating, vasodilation) - Costanzo Physiology 7th Ed., p. (block2)

• Core temperature below 35°C
• At <32°C: loss of shivering (heat production fails), cardiac arrhythmias risk
• At <20°C: potentially fatal
• Causes: exposure to extreme cold, immersion in cold water, anesthesia

• Occurs when core temperature rises to levels causing tissue damage, due to failure of heat-dissipating mechanisms
• If sweating fails, heat cannot be released and temperature rises uncontrolled
• Medical emergency requiring rapid cooling

• A rare but life-threatening condition triggered by certain inhalation anesthetics in susceptible individuals
• Causes massive increase in skeletal muscle metabolic rate, extreme heat production that overwhelms dissipating mechanisms

• Frostnip - mild, reversible freezing of superficial skin
• Frostbite - ice crystal formation in tissues causing cell damage and vascular injury

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Chapter 103: Physiology of Exercise

Grading of Exercise

• Light exercise: <3 METs (e.g., slow walking)
• Moderate exercise: 3-6 METs (e.g., brisk walking, cycling)
• Vigorous/Hard exercise: >6 METs (e.g., running, sports)

• Type I (slow-twitch) fibers - recruited first, high oxidative capacity, fatigue-resistant - used for sustained activities
• Type IIa (fast-twitch oxidative) - intermediate
• Type IIx (fast-twitch glycolytic) - recruited last, powerful but fatigue quickly

"Physical exercise is often the greatest stress that the body encounters in the course of daily life... the body must make rapid, integrated adjustments at the level of cells and organ systems." - Medical Physiology (Boron & Boulpaep)

Cardio-respiratory Adaptation to Exercise

• Heart rate (HR) increases - due to withdrawal of vagal tone and increased sympathetic activity
• Stroke volume increases - due to increased venous return (Frank-Starling mechanism) and sympathetic stimulation of the heart
• Cardiac output (CO = HR × SV) can increase from 5 L/min at rest to 20-25 L/min during maximal exercise
• Blood pressure rises - systolic increases more than diastolic
• Vasodilation in active muscles (due to local metabolites: CO₂, H⁺, adenosine, K⁺) and vasoconstriction in visceral organs - blood is redirected to muscles

• Respiratory rate and tidal volume both increase
• Minute ventilation can rise from 5-6 L/min at rest to >100 L/min during maximal exercise
• Increased ventilation matches increased CO₂ production and O₂ demand
• Ventilatory threshold (anaerobic threshold): point at which lactic acid accumulates faster than it can be cleared; ventilation rises disproportionately to clear excess CO₂ from lactate buffering

Physiological Effects of Physical Training

• Musculoskeletal: increased muscle strength, bone density, joint flexibility
• Cardiovascular: lower resting HR, larger stroke volume, reduced cardiovascular disease risk
• Metabolic: improved insulin sensitivity, better glucose and lipid metabolism, increased fat oxidation
• Respiratory: improved efficiency, larger vital capacity
• Psychological: reduced anxiety and depression, improved mood (endorphin release)

Exercise under Heat and Cold

• Competing demands between muscles (needing blood flow) and skin (needing blood flow for cooling) create cardiovascular strain
• Core temperature rises faster; risk of heat exhaustion and heat stroke
• Fluid replacement (hydration) and acclimatization are essential
• Acclimatization over 7-14 days increases plasma volume, improves sweating efficiency and earlier onset of sweating

• Shivering increases heat production
• Vasoconstriction protects core temperature but peripheral extremities are at risk of cold injury
• Wet cold and wind greatly increase heat loss

Consequences of Sedentary Lifestyle

• Cardiovascular disease: sedentary lifestyle is associated with increased inflammation, insulin resistance, decreased wall shear stress, and heightened vascular disease risk
• Obesity and metabolic syndrome: reduced caloric expenditure, impaired glucose metabolism
• Osteoporosis: reduced mechanical loading leads to bone loss
• Muscle atrophy (disuse atrophy)
• Depression and anxiety
• Increased all-cause mortality

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Chapter 104: Physiology of Yoga

General Introduction

Types of Yogic Exercises

• Relaxative (e.g., Shavasana)
• Meditative (e.g., Padmasana)
• Cultural/corrective - for posture and organ function

Health Benefits of Yoga Practice

• Reduces resting heart rate and blood pressure
• Improves heart rate variability (reflects improved parasympathetic tone)
• Lowers cholesterol and triglycerides

• Pranayama improves lung volumes - vital capacity (VC) and tidal volume increase
• Improves respiratory muscle strength and efficiency

• Increases flexibility and range of joint motion
• Strengthens postural muscles and core stability
• Helps prevent and manage low back pain

• Reduces cortisol (stress hormone) levels
• Improves insulin sensitivity; beneficial in Type 2 diabetes
• Balances thyroid function

• Stimulates parasympathetic nervous system (rest-and-digest), countering chronic sympathetic over-activation
• Reduces anxiety, depression, and perceived stress
• Improves sleep quality
• Increases GABA levels in the brain (anti-anxiety)

Yoga in Health and Disease

• Hypertension: yoga's parasympathomimetic effect reduces sympathetic drive and lowers BP
• Diabetes mellitus: improves glycemic control and insulin sensitivity
• Asthma and COPD: pranayama improves breathing efficiency
• Depression/anxiety: meditative practices reduce cortisol, increase serotonin
• Obesity: combined effect of physical activity + stress reduction + improved eating behaviors
• Osteoporosis: weight-bearing asanas stimulate bone formation
• Arthritis: gentle movement improves joint lubrication and reduces stiffness

Yoga vs. Conventional Exercises

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Chapter 105: Physiology of Infancy and Aging

Physiology of Infancy

• Circulatory transition: The foramen ovale and ductus arteriosus close (functional closure within hours, anatomical within weeks), converting from parallel fetal circulation to adult serial circulation
• Respiratory onset: First breath is triggered by hypoxia, hypercarbia, cold stimulation, and tactile stimulation at birth
• Thermoregulation: Neonates are poikilothermic - they lose heat rapidly due to high surface area:body mass ratio and thin subcutaneous fat. Brown adipose tissue (BAT) - unique to neonates - provides non-shivering thermogenesis via uncoupling of oxidative phosphorylation

Aging and Free Radicals and Antioxidants

• Normal byproduct of mitochondrial oxidative phosphorylation (electron leakage)
• Inflammatory reactions
• UV radiation, ionizing radiation
• Environmental toxins, cigarette smoke
• Ischemia-reperfusion injury

• DNA damage: strand breaks, base modifications - leads to mutations and cancer
• Lipid peroxidation: damage to cell membranes
• Protein oxidation: inactivates enzymes
• Mitochondrial damage: creates a vicious cycle of more ROS production

• Cardiovascular: Reduced cardiac output, arterial stiffening (atherosclerosis), hypertension
• Respiratory: Reduced vital capacity, decreased elastic recoil of lungs
• Renal: Reduced GFR (decreases ~1% per year after age 40), reduced tubular function
• Nervous system: Neuronal loss, reduced neurotransmitter levels, slowed conduction velocities, memory decline
• Musculoskeletal: Sarcopenia (muscle wasting), osteoporosis, joint degeneration
• Immune system: Immunosenescence - reduced T-cell function, increased autoimmunity and infection susceptibility
• Hormonal: Menopause (women), andropause (men), reduced growth hormone and IGF-1

Brain Death

1. Coma - completely unresponsive to all external stimuli
2. Absence of all brainstem reflexes:
   • No pupillary light reflex (pupils fixed and dilated)
   • No corneal reflex
   • No oculovestibular (caloric) reflex
   • No gag or cough reflex
   • No oculocephalic reflex (doll's eye absent)
3. Apnea test positive - no spontaneous breathing even when PaCO₂ rises to ≥60 mmHg, confirming complete loss of respiratory drive
4. Irreversibility confirmed - known cause, reversible causes ruled out (hypothermia, drug intoxication, metabolic disturbances excluded)

• EEG - shows electrocerebral silence (flat trace)
• Cerebral angiography - no intracranial blood flow
• Transcranial Doppler - absent cerebral blood flow
• Radionuclide scan (SPECT) - no cerebral perfusion

• In PVS, the brainstem functions are preserved (breathing, reflexes intact), but higher cortical functions are lost
• Brain death is complete and irreversible loss including brainstem - PVS is not brain death

• Brain death declaration allows discontinuation of mechanical ventilation
• It is the medical and legal prerequisite for organ donation
• Two independent physicians must certify brain death

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Quick Revision Summary for Exams