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CARDIAC OUTPUT - 10 Marks

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1. Definition

CO = Heart Rate (HR) × Stroke Volume (SV)

• Output of both ventricles is exactly equal
• Each ventricle pumps 5-6 L of blood per minute

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2. Distribution of Cardiac Output

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3. Control of Cardiac Output

A. Control of Heart Rate (Extrinsic Autoregulation)

• Origin: Intermediolateral horn, T1-T5 spinal segments
• Supplies: SA node, AV node, atria, ventricles (epicardial fibers)
• Effects:
  • Positive chronotropic - increases HR
  • Positive inotropic - increases force of contraction
  • Positive dromotropic - increases conductivity
  • Positive bathmotropic - increases excitability

• Origin: Nucleus ambiguus of medulla
• Supplies: SA node, AV node, atrial muscles (endocardial fibers) - NOT ventricles
• Effects:
  • Negative chronotropic - decreases HR
  • Negative dromotropic - decreases conductivity
  • Negative inotropic - decreases atrial contraction only
  • No effect on ventricular contraction

• Vasomotor Centre (Sympathetic): Located in reticular formation, floor of 4th ventricle. On stimulation: vasoconstriction, increased BP, increased HR, increased force of contraction
• Cardiac Vagal Centre (Parasympathetic): Includes dorsal motor nucleus of vagus, nucleus ambiguus, nucleus tractus solitarius. Responsible for vagal tone. On stimulation: reduces HR

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B. Control of Stroke Volume (Intrinsic Autoregulation)

• EDV = 120-140 ml; ~65% is ejected = SV
• End Systolic Volume (ESV) = ~50 ml remaining

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1. Heterometric Regulation (Starling's Law of Heart)

• Force of contraction depends on the initial length of cardiac muscle fiber (pre-load)
• Pre-load = End Diastolic Volume (EDV)
• More venous return → More EDV → More stretching of myocardium → More force of contraction
• This is Starling's Law: "The energy of contraction is proportional to the initial length of the cardiac muscle fiber"

1. Thoracic/Respiratory pump - inspiration lowers intrathoracic pressure, increases venous return
2. Cardiac pump - suction effect during diastole
3. Muscle pump - skeletal muscle contractions compress veins
4. Total blood volume - increased blood volume → increased VR
5. Capacity of venous system - venoconstriction increases VR
6. Body position - lying flat increases VR
7. Ventricular compliance - more compliant ventricle accommodates more blood

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2. Homometric Regulation

• Myocardial contractility increases without an increase in the initial length of muscle fibers
• Ventricles develop tension more rapidly; ejection of blood is faster

1. Catecholamines - act via β1-adrenergic receptors
2. Sympathetic nerve stimulation
3. Increased heart rate - within limits, increased HR increases contractility
4. Drugs:
   • Caffeine, theophylline - positive inotropic effect
   • Glucagon - increases cAMP formation
   • Digitalis - inhibits Na⁺-K⁺ pump

1. Vagal stimulation - negative inotropic effect
2. Heart failure - intrinsic myocardial depression
3. Myocardial infarction - fibrotic, non-functional myocardium
4. Hypercapnia, hypoxia, acidosis - negative inotropic effect
5. Barbiturates - drug-induced depression

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4. Factors Affecting Heart Rate

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5. Methods of Measurement of Cardiac Output

• Based on Fick's Principle: Amount of substance taken up by an organ per unit time = (Arterial level - Venous level) of that substance
• Formula:

CO = Amount of O₂ consumed per min / (A-V O₂ difference)

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Summary Table

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Key Diagrams to Draw (as mentioned in PDF):

1. Heterometric regulation of cardiac output (Starling's curve)
2. Homometric regulation of cardiac output (Pressure-volume loop or contractility curve)

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FACTORS AFFECTING HEART RATE - In Depth

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1. AGE

• At birth, the SA node has high intrinsic automaticity and vagal tone is minimal, hence HR is very high
• As age increases from birth to adulthood, vagal tone progressively increases due to maturation of the parasympathetic nervous system - so HR gradually falls
• In old age, vagal tone declines again (autonomic dysfunction / decreased baroreceptor sensitivity), causing HR to rise slightly back toward 100 bpm
• Exercise training can also cause downregulation of the "funny current" (I_f) ion channels in the SA node, contributing to lower resting HR in athletes

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2. SEX (GENDER)

• Females have a slightly higher HR than males at the same age
• Mechanism: Females have lower resting vagal tone compared to males
• Difference is typically 2-7 bpm higher in females
• Also attributed to smaller heart size in females requiring higher rate to maintain same CO
• Hormonal influences (estrogen vs. testosterone) also play a minor modulatory role on autonomic balance

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3. BODY TEMPERATURE

• Rise in temperature → Tachycardia
• Fall in temperature → Bradycardia

• For every 1°F rise in body temperature, HR increases by ~10 bpm
• For every 1°C rise, HR increases by ~18 bpm
• This is due to the direct effect of heat on the SA node - elevated temperature accelerates the rate of ionic metabolism and depolarization of pacemaker cells
• Temperature above 105°F (40.5°C) may eventually decrease HR due to progressive debility of the heart muscle from fever
• Rise in temperature also causes peripheral vasodilation and fall in BP, which reflexly stimulates the sympathetic system, further increasing HR
• Fall in temperature causes vasoconstriction and rise in BP → reflex bradycardia

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4. EMOTIONAL STIMULI

• Emotional stimuli are processed in the limbic cortex (amygdala, cingulate cortex)
• Signals pass to the hypothalamus, which relays to the Rostral Ventrolateral Medulla (RVLM) - the sympathetic center
• Excitement, fear, anger → RVLM activation → sympathetic outflow → positive chronotropic effect on SA node → tachycardia + rise in BP
• Grief, shock → Vagal center activation → negative chronotropic effect → bradycardia + fall in BP
• This is the physiological basis of the "fight or flight" response

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5. DRUGS

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6. DISEASES

• Thyrotoxicosis (Hyperthyroidism): Excess thyroid hormone has a direct chronotropic effect on SA node and potentiates catecholamines → persistent tachycardia. High resting HR is a hallmark sign.
• Hypoxia: Low oxygen → chemoreceptor stimulation → initially tachycardia via sympathetic activation. Severe/prolonged hypoxia can cause bradycardia.
• Anemia: Reduced O₂ carrying capacity → compensatory tachycardia
• Dehydration / Blood loss: Decreased blood volume → fall in BP → sympathetic reflex → tachycardia

• Increased intracranial pressure (ICP): Cushing's reflex - raised ICP → brainstem compression → massive sympathetic response → severe hypertension → reflex vagal bradycardia (the classic triad: hypertension + bradycardia + irregular respiration)
• Hypothyroidism: Reduced metabolic rate, reduced SA node automaticity → bradycardia
• Jaundice: Bile salts deposit in tissues including the SA node and slow its automaticity
• Congestive Heart Failure (CHF): Weakened heart → inadequate CO → compensatory tachycardia initially, but in advanced CHF the overworked heart may fail to compensate. Digitalis is used to give a slow, steady but stronger beat.

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7. EXERCISE

• HR increases linearly with the severity of exercise
• During maximal exercise, HR can reach 180-200 bpm

• Anticipatory tachycardia: Even before exercise starts, HR rises via higher cortical (limbic/motor cortex) stimulation of the RVLM - this is a conditioned reflex
• During exercise:
  • Muscle proprioceptors and chemoreceptors send afferents to RVLM → sympathetic activation
  • Circulating catecholamines (epinephrine from adrenal medulla) increase SA node firing
  • Simultaneous withdrawal of vagal tone contributes significantly, especially in early stages
  • Rising body temperature during exercise also directly stimulates SA node
• After exercise: HR returns to baseline - rapid initial fall due to vagal reactivation, then slower normalization

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8. PAINFUL STIMULI

• Superficial pain during a procedure → reflex tachycardia (e.g., skin incision)
• Deep visceral pain (e.g., myocardial infarction) → can cause profound bradycardia + hypotension (vasovagal syncope)
• Prolonged severe pain → can cause fainting through vasodilation and fall in BP

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9. RESPIRATION (Sinus Arrhythmia)

• Inspiration → HR increases
• Expiration → HR decreases
• This rhythmic variation in HR with breathing is called Sinus Arrhythmia - a completely normal phenomenon

• Inspiration: Expansion of lungs → stretch of pulmonary receptors → vagal afferents to medulla → inhibition of the cardiac vagal centre → reduced vagal tone → SA node fires faster → tachycardia
• Additionally, during inspiration, intrathoracic pressure falls → venous return increases → atrial stretch receptors (Bainbridge reflex) → reflex tachycardia
• Expiration: Vagal tone restored → HR decreases
• Sinus arrhythmia is more pronounced in young adults and children, and diminishes with age or in autonomic neuropathy (e.g., diabetics)

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Summary Diagram

FACTORS AFFECTING HEART RATE
├── INCREASE HR (Tachycardia)
│   ├── Age: fetal/neonatal, old age
│   ├── Female sex
│   ├── Rise in body temperature (1°F → +10 bpm via SA node)
│   ├── Excitement / Fear / Anger (limbic → sympathetic)
│   ├── Exercise (catecholamines + vagal withdrawal)
│   ├── Superficial pain (somatosympathetic reflex)
│   ├── Inspiration (vagal inhibition + Bainbridge reflex)
│   ├── Diseases: thyrotoxicosis, hypoxia, anemia, dehydration
│   └── Drugs: epinephrine, atropine, caffeine, thyroid hormone
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└── DECREASE HR (Bradycardia)
    ├── Increasing vagal tone (adult age progression)
    ├── Male sex
    ├── Fall in body temperature (vasoconstriction → reflex)
    ├── Grief / Shock / Apprehension (vagal predominance)
    ├── Deep/visceral pain (vagal afferents)
    ├── Expiration (vagal tone restored)
    ├── Athletes (enlarged heart + I_f channel downregulation)
    ├── Diseases: raised ICP (Cushing's reflex), hypothyroidism, jaundice
    └── Drugs: digitalis, beta-blockers, barbiturates

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Key exam points:

• Temperature: 1°F rise = +10 bpm; direct effect on SA node
• Superficial pain = tachycardia; deep pain = bradycardia
• Sinus arrhythmia: inspiration = fast, expiration = slow
• Cushing's reflex: raised ICP → hypertension + bradycardia
• Digitalis: slow, steady, stronger beat in CHF