Hypertension - MBBS Physiology

Reference: Sembulingam's Essentials of Medical Physiology, 6th Edition

Definition

Normal BP: Systolic < 120 mm Hg | Diastolic < 80 mm Hg

Classification of Hypertension

1. Primary (Essential) Hypertension

• Elevated blood pressure in the absence of any underlying disease
• Cause is unknown
• Arterial pressure increases due to increased peripheral resistance from an unknown cause
• Accounts for ~90-95% of all hypertension cases

2. Secondary Hypertension

i. Cardiovascular Hypertension

• Coarctation of aorta
• Arteriosclerosis

ii. Endocrine Hypertension

• Pheochromocytoma - tumor of adrenal medulla causing excess catecholamine secretion
• Hyperaldosteronism - excess aldosterone from adrenal cortex (causes Na+ and water retention)
• Cushing's Syndrome - excess glucocorticoids from adrenal cortex

iii. Renal Hypertension

• Stenosis of renal arteries (Goldblatt hypertension)
• Tumor of juxtaglomerular cells - excess angiotensin II production
• Glomerulonephritis

iv. Neurogenic Hypertension

• Increased intracranial pressure
• Lesion in tractus solitarius (NTS)
• Sectioning of nerve fibers from carotid sinus

Pathophysiology of Primary Hypertension

1. Increased Peripheral Resistance

• Increased sympathetic activity
• Excess circulating catecholamines
• Excess angiotensin II

2. Renin-Angiotensin-Aldosterone System (RAAS) Activation

• Renal ischemia or excess renin secretion triggers angiotensin II formation
• Angiotensin II causes:
  1. Immediate effect - Arteriolar vasoconstriction → raises TPR → raises BP
  2. Long-term effect - Stimulates aldosterone secretion → Na+ and water retention → raises blood volume → raises cardiac output → raises BP
• This two-step mechanism is central to renovascular and endocrine hypertension

3. Impaired Renal Pressure Natriuresis

• Normally, the kidney excretes excess salt and water when BP rises ("pressure natriuresis"), resetting BP toward normal
• In hypertension, this mechanism is blunted - the kidney requires a higher set-point pressure to excrete adequate salt and water
• This is the fundamental long-term mechanism for sustained hypertension (Guyton's concept)

4. Sympathetic Nervous System Overactivity

• Increases heart rate and contractility → raises CO
• Increases arteriolar tone → raises TPR
• Stimulates renal renin release
• Particularly prominent in obesity-related hypertension

5. Volume Loading (Salt-Sensitive Hypertension)

• Excess salt intake → expanded extracellular fluid and blood volume → raised cardiac output → raised BP
• Especially prominent when renal mass is reduced

Effects / Complications of Hypertension (Sembulingam)

1. Renal failure - hypertensive nephropathy
2. Left ventricular failure - from chronically increased afterload
3. Myocardial infarction - accelerated coronary atherosclerosis
4. Cerebral hemorrhage - rupture of cerebral vessels ("stroke")
5. Retinal hemorrhage - hypertensive retinopathy

Treatment Overview (Sembulingam)

• Secondary hypertension - treat the underlying cause
• Primary hypertension - can be controlled but not cured

1. Beta-blockers - block beta-adrenoceptors; reduce cardiac output and vasoconstriction
2. Diuretics - reduce blood volume
3. ACE inhibitors / ARBs - block RAAS
4. Calcium channel blockers - reduce arteriolar tone
5. Alpha-blockers - reduce peripheral resistance

Summary Diagram

Quick Reference Table

• Essentials of Medical Physiology by K. Sembulingam & Prema Sembulingam, 6th Edition - Section 8, Cardiovascular System (Applied Physiology: Hypertension, p. 614 onwards)
• Guyton and Hall Textbook of Medical Physiology, 14th Edition - Chapter 19 (Role of the Kidneys in Long-Term Arterial Pressure Control and Hypertension) - used to supplement and cross-verify mechanism details

Coronary Circulation - MBBS Physiology

Reference: Sembulingam's Essentials of Medical Physiology, 6th Ed. - Chapter 108

Introduction

I. DISTRIBUTION OF CORONARY BLOOD VESSELS

A. Coronary Arteries

1. Right Coronary Artery (RCA)

• Arises from the right aortic sinus
• Runs in the right atrioventricular (AV) groove
• Supplies:
  • Right atrium
  • Right ventricle
  • Posterior wall of the left ventricle (in 80-90% of people - "right dominant")
  • SA node (in ~60% of people) and AV node (in ~80% of people)
• Main branch: Posterior descending artery (PDA)

2. Left Coronary Artery (LCA)

• Arises from the left aortic sinus
• A short left main stem (~2-3 cm) divides into:
  • Left Anterior Descending (LAD) - also called "widow maker"; supplies anterior wall of LV, interventricular septum (anterior 2/3), and apex
  • Left Circumflex (LCX) - runs in left AV groove; supplies lateral and posterior wall of left ventricle and left atrium
• Supplies anterior and left lateral portions of the left ventricle

Clinical Point (Sembulingam): The LAD is the most commonly occluded coronary artery. Its blockage causes extensive anterior wall myocardial infarction.

B. Venous Drainage

C. Physiological Shunt

• A small portion of aortic blood flows directly into the myocardium via the thebesian veins (venae cordis minimae), bypassing the coronary arteries
• This represents a right-to-left shunt - it returns deoxygenated blood to the left heart, slightly reducing the oxygen saturation of arterial blood
• This is called the physiological shunt in the heart

II. CORONARY BLOOD FLOW

A. Normal Coronary Blood Flow

• At rest: ~70 mL/min per 100 g of heart weight
• Total resting coronary flow: approximately 225 mL/min (~4-5% of cardiac output)
• During strenuous exercise: increases 3 to 4 times (coronary reserve)
• The heart consumes ~8-10 mL O₂/min/100g of tissue at rest (much higher than most other organs)
• 70-80% of oxygen is extracted from coronary blood (compared to ~25% in skeletal muscle)

B. Measurement of Coronary Blood Flow

• Fick's principle - using oxygen consumption
• Electromagnetic flowmeter on coronary arteries
• Thermodilution method
• Radioactive microspheres

III. PHASIC CHANGES IN CORONARY BLOOD FLOW

Left Ventricle (Sembulingam, Fig. 108.1)

Key Point: The left ventricle receives most of its blood supply during diastole. This is why a fast heart rate (short diastole) or low diastolic BP can critically reduce coronary perfusion.

Right Ventricle

• Right ventricular muscle contracts with much less force than the left
• Intramural pressure rise during systole is smaller
• Therefore, phasic changes in the right coronary artery are less pronounced
• Some flow continues even during systole

Epicardial vs. Subendocardial Blood Flow

• Epicardial coronary arteries lie on the surface and are less affected by myocardial compression
• Subendocardial arteries are most susceptible to systolic compression
• A subendocardial plexus of vessels compensates for the reduced systolic flow
• In disease (e.g., hypertrophy, high diastolic pressure), subendocardial ischemia occurs first - this is why subendocardial MI is more common than epicardial MI in diffuse disease

IV. FACTORS REGULATING CORONARY BLOOD FLOW

1. Need for Oxygen (Most Important - Sembulingam)

• Oxygen is the single most important factor regulating coronary blood flow
• Coronary blood flow is directly proportional to oxygen consumption of cardiac muscle
• Even at rest, 70-80% of oxygen is extracted - almost maximal
• When oxygen demand increases, the only way to supply more O₂ is to increase flow
• Any decrease in O₂ triggers vasodilation immediately

2. Metabolic Factors

Adenosine mechanism (Guyton): When O₂ falls in muscle cells, ATP degrades to AMP, then to adenosine. Adenosine leaks out of cells and causes arteriolar vasodilation, increasing coronary flow to match metabolic needs. This is the primary local regulatory mechanism.

3. Coronary Perfusion Pressure

• Coronary Perfusion Pressure = Aortic Diastolic Pressure - Left Ventricular End-Diastolic Pressure (LVEDP)
• Flow increases when aortic diastolic pressure rises
• Flow decreases when LVEDP rises (e.g., heart failure) - this is why cardiac failure worsens coronary ischemia
• Coronary autoregulation: blood flow remains constant over a mean arterial pressure range of 60-180 mmHg (autoregulatory plateau)

4. Nervous Factors

Sympathetic Stimulation:

• Direct effect: Norepinephrine acts on:
  • Alpha receptors (predominant on epicardial arteries) → vasoconstriction
  • Beta-2 receptors (predominant on intramuscular arteries) → vasodilation
• Indirect (dominant) effect: Increased heart rate and contractility → increased metabolism → metabolic vasodilation overrides direct constriction
• Net result: Coronary flow increases (metabolic override prevails)

Sembulingam: Stimulation of sympathetic nerves increases rate and force of cardiac contraction → liberation of more metabolites → vasodilation → increased coronary flow.

Parasympathetic (Vagal) Stimulation:

• Direct effect: Acetylcholine → mild coronary vasodilation
• Indirect (dominant) effect: Slows heart rate, decreases contractility → less O₂ demand → less metabolites → coronary vasoconstriction
• Net result: Coronary flow decreases

V. SPECIAL FEATURES OF CARDIAC METABOLISM

• At rest, cardiac muscle derives ~70% energy from fatty acids, ~30% from glucose
• During ischemia or anaerobiosis, switches to glucose utilization
• Heart has minimal anaerobic capacity - very sensitive to ischemia
• Energy stored as creatine phosphate (short-term reserve only)
• Capillary density in myocardium is much higher than skeletal muscle - optimises O₂ delivery

VI. APPLIED PHYSIOLOGY - CORONARY ARTERY DISEASE (Sembulingam, Chapter 108)

A. Coronary Occlusion

• Atherosclerosis (most common) - plaque formation narrows lumen
• Thrombosis - clot forms on ruptured atheromatous plaque
• Embolism - thrombus or detached plaque fragment blocks smaller vessels
• Coronary vasospasm - especially with sympathetic excess (Prinzmetal/variant angina)

B. Myocardial Ischemia and Necrosis

Myocardial Ischemia

• Defined as reaction of myocardium to hypoxia due to severely reduced coronary flow
• Develops when blood flow decreases but cell death has not yet occurred
• Reversible if blood flow is restored quickly (especially within 20-40 minutes)
• Small areas of ischemia may recover via coronary collateral circulation

Myocardial Stunning

• Transient mechanical dysfunction of the heart caused by a mild reduction in coronary blood flow
• Insufficient to cause necrosis but causes brief contractile dysfunction
• Heart recovers completely once flow is restored

Necrosis

• Death of myocardial cells - occurs when ischemia is severe and prolonged
• Irreversible once completed
• Leads to myocardial infarction

C. Myocardial Infarction (Heart Attack) - Sembulingam

1. Cardiac pain (severe, crushing chest pain)
2. Nausea
3. Vomiting
4. Palpitations
5. Difficulty in breathing (dyspnea)
6. Extreme weakness
7. Sweating
8. Anxiety

• ECG changes: ST elevation, Q waves, T-wave inversion
• Cardiac enzymes rise: Troponin I/T (most specific), CK-MB, LDH
• Collateral vessels may develop if occlusion is gradual
• In sudden complete occlusion - no time for collaterals → large infarct

D. Cardiac Pain - Angina Pectoris (Sembulingam)

• Starts beneath the sternum (retrosternal)
• Radiates to the left arm, left shoulder, jaw, and neck
• Described as crushing, tightening, or pressure-like
• Lasts 2-15 minutes (if longer, suspect MI)
• Relieved by rest and nitrates

• The heart and left arm develop from the same dermatomal segment in the embryo (C8-T4)
• Pain impulses from the heart travel via cardiac sympathetic nerves to T1-T5 spinal segments
• The brain interprets these as arising from the somatic areas of the same segments - hence referred to left arm and chest wall

Summary Flow Chart

Coronary Occlusion (Atherosclerosis/Thrombus)
        ↓
Reduced Coronary Blood Flow
        ↓
Myocardial Hypoxia → Release of Adenosine, CO₂, H⁺, K⁺
        ↓
↑ Coronary vasodilation (compensatory) ←→ If inadequate → Ischemia
        ↓                                             ↓
 Restored blood flow                     Angina Pectoris (Pain)
  (Myocardial Stunning)                              ↓
                                           Necrosis → Infarction

Quick Revision Points for Exams

• Essentials of Medical Physiology - K. Sembulingam & Prema Sembulingam, 6th Edition, Chapter 108: Coronary Circulation (pp. 629-633)
• Guyton and Hall Textbook of Medical Physiology, 14th Edition, Chapter 21 - used to cross-verify and supplement regulation details

Conducting System of the Heart - Origin and Propagation of Cardiac Impulse

Reference: Sembulingam's Essentials of Medical Physiology, 6th Ed. - Chapters 90 & 96

Introduction

Components of the Conducting System (Sembulingam)

1. Sinoatrial (SA) node - the primary pacemaker
2. Internodal fibers - connect SA node to AV node
3. Atrioventricular (AV) node - delays conduction
4. Bundle of His (AV bundle) - common bundle
5. Right and Left Bundle Branches - divide at the interventricular septum
6. Purkinje fibers - terminal distribution to ventricular myocardium

1. Sinoatrial (SA) Node - The Primary Pacemaker

Location

• Situated in the right atrium, just below (inferior to) the opening of the superior vena cava
• Also called the Keith and Flack's node

Structure (Sembulingam)

• Spindle-shaped collection of specialized muscle cells
• Cells are small, poorly striated, with fewer myofibrils
• Surrounded by fibrous connective tissue
• Richly supplied by both sympathetic and parasympathetic nerve fibers

Why is the SA Node the Pacemaker?

• All parts of the conductive system can generate impulses spontaneously (automaticity)
• The SA node discharges at the fastest intrinsic rate (70-80/min), outpacing all others
• Because it fires fastest, it depolarizes all other pacemaker tissues before they can fire spontaneously
• Therefore, SA node sets the rhythm for the entire heart

Intrinsic Rates of Different Parts (Sembulingam)

Key concept: If the SA node fails, the next fastest site takes over - this is the escape pacemaker or latent pacemaker.

2. Origin of the Cardiac Impulse

Ionic Mechanism - Pacemaker Potential (Sembulingam + Ganong)

Phases of SA Node Action Potential

Important distinction: The SA/AV node action potential is driven by Ca²⁺ (not Na⁺). That is why:

• There is no sharp spike before the plateau
• Ca²⁺ channel blockers (verapamil, diltiazem) slow the SA and AV nodes
• TTX (Na⁺ channel blocker) does not affect nodal tissue

3. Propagation of the Cardiac Impulse

Step-by-Step Sequence (Sembulingam)

SA Node
   ↓  (via internodal fibers)
Atrial Myocardium (simultaneous R and L atria)
   ↓
AV Node (DELAY - 0.09 sec)
   ↓
Bundle of His (common bundle)
   ↓  (at top of interventricular septum)
Left Bundle Branch → Left and Right ventricles
Right Bundle Branch ↗
   ↓
Purkinje Fibers (rapid spread)
   ↓
Ventricular Myocardium (from apex → base)

Internodal Fibers (Sembulingam - Chapter 90)

• Conduction through atrial muscle also occurs but is slower
• The Bachmann bundle provides the fastest inter-atrial conduction

AV Node - The Gatekeeper

• Allows the atria to complete their contraction and empty blood into ventricles first
• Prevents too-rapid ventricular filling and protects against atrial arrhythmias flooding the ventricles

• Fewer gap junctions between cells → high resistance to ionic spread
• Smaller cells with higher internal resistance
• Ca²⁺-dependent action potentials (slower than Na⁺-dependent)

This 0.16 sec = PR interval on ECG

Bundle of His (AV Bundle)

• Direct continuation of the AV node
• Runs along the lower border of the membranous interventricular septum
• Surrounded by fibrous connective tissue - insulated from surrounding myocardium
• Only electrically active connection between atria and ventricles (normally)
• Divides into Right Bundle Branch and Left Bundle Branch at the top of the muscular interventricular septum

Bundle Branches

Right Bundle Branch (RBB)

• Runs down the right side of the interventricular septum
• Reaches the apex
• Enters the moderator band (septomarginal trabecula)
• Reaches the anterior papillary muscle and spreads to the right ventricular wall

Left Bundle Branch (LBB)

• Runs down the left side of the interventricular septum
• Divides into two fascicles:
  • Left Anterior Fascicle (LAF) - supplies anterior and superior wall of LV
  • Left Posterior Fascicle (LPF) - supplies posterior and inferior wall of LV

Purkinje Fibers

• Arise from the terminal ends of the bundle branches
• Spread as a subendocardial network over both ventricular walls
• Largest cells in the conductive system (larger than ventricular myocytes)
• Rich in gap junctions → very high conduction velocity
• First reach papillary muscles and apex, then spread toward the base

4. Conduction Velocities at Different Parts (Sembulingam - Chapter 90)

5. ECG Correlation with Impulse Propagation

6. Applied Physiology - Arrhythmias of the Conducting System (Sembulingam - Chapter 96)

A. Heart Block

i. Sinoatrial (SA) Block

• Failure of impulse transmission from SA node → AV node
• Heart momentarily stops → AV node takes over as pacemaker
• Produces AV nodal rhythm at 40-60/min
• On ECG: P wave absent in affected beats

ii. Atrioventricular (AV) Block

iii. Infranodal Block (Bundle Branch Block)

• Block in branches of Bundle of His (below AV node)
• Purkinje fibers become pacemaker → rate ~35/min
• If ventricular muscle takes over → rate ~20/min
• Right bundle branch block (RBBB): Wide QRS with RSR' pattern in V1
• Left bundle branch block (LBBB): Wide QRS with broad notched R in V5-V6

B. Ectopic Pacemakers

SA node fails
    ↓
AV node (40-60/min) → "Junctional rhythm"
    ↓ (if also blocked)
Bundle of His (40/min)
    ↓
Purkinje fibers (35/min) → "Ventricular escape rhythm"
    ↓
Ventricular muscle (20/min) → "Idioventricular rhythm"

C. Other Important Arrhythmias (Sembulingam)

D. WPW Syndrome (Wolff-Parkinson-White)

• An accessory pathway (Bundle of Kent) bypasses the AV node
• Impulse reaches ventricles earlier (pre-excitation) → delta wave on ECG
• Short PR interval + wide QRS + delta wave
• Can cause re-entrant tachycardia

Summary - Impulse Propagation Sequence

SA Node (70-80/min)
    ↓ 0.03 sec
Internodal tracts (Bachmann, Wenckebach, Thorel)
    ↓
Both Atria depolarize simultaneously → P wave on ECG
    ↓
AV Node (DELAY: 0.09 sec → total PR = 0.16 sec)
    ↓
Bundle of His (common bundle)
    ↓
Right Bundle Branch          Left Bundle Branch
        ↓                          ↓
Right ventricle         Left anterior + posterior fascicles
        ↓                          ↓
                Purkinje fibers (4 m/sec)
                        ↓
        Apex → base ventricular contraction → QRS complex

Quick Revision Table

• Essentials of Medical Physiology - K. Sembulingam & Prema Sembulingam, 6th Edition, Chapter 90 (Conducting System) and Chapter 96 (Arrhythmia)
• Ganong's Review of Medical Physiology, 26th Edition, Chapter 29 - Origin and Spread of Cardiac Excitation
• Guyton and Hall Textbook of Medical Physiology, 14th Edition, Chapter 10 - Rhythmical Excitation of the Heart