Thermoregulation MCQ Example
McArdle’s Maximum Allowable Sweat Rate (P4SR)
- McArdle → Muscle → sweating
Zone | Predicted 4-hr Sweat Rate |
Comfort | 1 – 3 L |
Just tolerable | 3 – 4.5 L |
Intolerable | > 4.5 L |
- Normal body temperature:
- Approx. 98.8°F (36.8 +/- 0.4°C)
Site | Difference from Core Temp |
Axillary | 0.5 – 1°C lower than core temp |
Rectal | 0.5 – 1°C higher than core temp |
- Thermoregulatory gain:Â - 33
- Very powerful
Sensation | TRP Channels | ã…¤ |
For Heat | • TRP V1 (Vanilloid) | V1 A1 M2 M3 |
ㅤ | • TRP M2 | ㅤ |
ㅤ | • TRP M3 | ㅤ |
For Cold | • TRP M8 (Menthol) | 8 → snowman → cold |
ㅤ | • TRP A1 | ㅤ |
- Note: Thermoregulation uses both feed forward and feedback systems.
- Feedforward system:
- Predictive control.
- Based on skin temperature changes.
- Hypothalamus raises core body temperature before it actually falls.
- Activates heat conservation/generation mechanisms early by hypothalamus
- Example: shivering, vasoconstriction.
- Feedback system:
- Responds to actual changes like ↑↑ metabolic rate, behavioral changes like seeking warmth
Pyrogens
- Substances that cause fever
- Types
Type of Pyrogen | Examples |
Exogenous Pyrogens | • Endotoxins of gram-negative bacteria |
Endogenous Pyrogens | • IL-1 |
ㅤ | • IL-6 |
ㅤ | • TNF - α |
ㅤ | • INF-α (used in treatment of hepatitis) |
Mechanism of Pyrogen Action
Pyrogen Pathophysiology
- Pyrogens cannot cross BBB
- Act outside the BBB
- Organum Vasculosum Laminae Terminalis (OVLT)
- Close to the hypothalamic temperature regulation area.
- Mechanism Pathway:
- Pyrogens produce PGE2
- PGE2 binds to EP3 receptor
- Results in ↑↑ cAMP.
- Clinical Outcomes: Fever, Arthritis, Myalgia.
- Treatment:
- Antipyretics
- Mechanism: ↓↓ PGE2
Nucleus | Phase of fever | Physiological Responses | Mechanism |
Posterior Nucleus | 1. Fever Onset [Exposure to Pyrogen] | Hypothalamic set point ↑↑↑↑ Heat generating mechanism • Shivering • Vasoconstriction • ↑ Micturition frequency | Back of car → exhaust → heat up |
Anterior Nucleus | 2. Fever resolves | Hypothalamic set point ↓↓↓ Heat dissipating mechanism • Sweating • Vasodilation • ↑ Thirst | Front of Car → Cools down |
Cold Disorders
Feature | Accidental Hypothermia | Therapeutic Hypothermia |
Description | Occurs unintentionally | Induced |
Uses | Causes: - Cold environment. - Barbiturates | Uses: • Minimize blood loss in neurosurgical procedures Principle: • For every 1°C ↓ body temperature ↳ Cerebral blood flow ↓ by 7%. • Cardiomyocyte cooling. |
Cardiomyocyte Cooling
- Purpose: To prevent death following MI.
- Mechanism:
- Normal
- MI → ROSC → ↑ Metabolic needs → Oxidative stress → Death.
- Cardiomyocyte cooling:
- ↓ body temperature by 5°C
- Activates Reperfusion Injury Salvage Kinase (RISK).
- RISK activates:
- Survival KinaseÂ
- Akt phosphorylationÂ
- Mitochondrial protectionÂ
- ↑ Survival
- Heat shock protein HSP A7Â
- Positive regulator of Akt
- Akt phosphorylation
- Mnemonic:
- Take RISK (RIS kinase) and Act (Akt) Coldly (Cool) → to ↑ survival (survival kinase)
Heat Disorders
Feature | Heat Cramps | Heat Syncope | Heat Exhaustion / Heat Collapse | Heat Stroke | Malignant Hyperthermia |
Severity | Very mild | Mild | Moderate | Medical emergency | Most severe |
Seen in | Hot environment | Prolonged standing in hot environment | Classic form: Old age Exertion form: Young athletes, soldiers | Classic form: Old age Exertion form: Young athletes, soldiers | Succinylcholine Halothane |
Pathology | Profuse sweating → Loss of Sodium → Muscle cramps | Vasodilation → Venous pooling • Loss of Na & water → ↓ CO → ↓ Brain BF | Extensive vasodilation → ↓ Diastolic filling of heart | Sweating is absent | Overactivity of ryanodine receptor → ↑↑ Release of calcium |
Presentation | Muscle pain & cramps | Syncope → LOC | LOC | Triad: 1. Hot dry skin 2. Coma 3. Rectal temp > 106°F | Sustained muscle contraction → ↑ Heat → ↑ Body temperature |
Thermo regulation | Intact | Intact | Intact | Not intact | - |
Treatment | Electrolyte replacement fluid | Spontaneous recovery on lying down | Lying down + fluid replacement | Active cooling: • Cool place • Cool water • Cold clothes • Fluid replacement | Dantrolene Sodium: (Ryanodine receptor blocker) |
Mutation of RyR1 | Gain of function | Loss of function |
Disease | Malignant Hyperthermia | Central Core Disease |
Effect | Excessive calcium release ↳ Severe muscle contraction ↳ Heat production | Less calcium release ↳ hypotonia ↳ weakness |
Treatment | Dantrolene ↳ RyR1 antagonist | No specific treatment |
Precipitated by | Anesthetic agents (e.g., halothane) | ã…¤ |
Mnemonic | Ryan has gained fever and cancer (malignant hyperthermia) and dandruff (Dantrolene) | Ryan already lost (Loss of function) his Core strength (Central core disease) when born → hypotonia, weakness |
Malignant Hyperthermia
- Mortality rate: 70 - 100 %
- Autosomal dominant
- Etiology: All inhalational agents (halothane, isoflurane) & succinylcholine.
- Risk factor: Family history of muscular dystrophy.
- Pathophysiology:
- Ryanodine receptor mutation (Sarcoplasmic Reticulum)
- Gain of function
- Uncontrolled release of calcium
- vigorous muscle contractions.
- Presentation:
- Initial:
- locked jaw (masseter spasm).
- Sudden tachycardia, HTN, ↑ temp,
- ↑ EtCO₂ (most sensitive)
- Step ladder.
- ventricular arrhythmias (hyperkalemia),
- cardiac arrest.
- Management:
- First step / Immediate step
- 100% Oâ‚‚
- DOC:
- Dantrolene sodium 2.5 mg/kg
- diluted in distilled water
- Hyperkalemia:
- Calcium gluconate, Insulin + dextrose, or Salbutamol.
- Hyperventilation/acidosis:
- Sodium bicarbonate.
- Post-op complication:
- Acute tubular necrosis (myoglobin release)
- monitor urine output.
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