Physiology-review

Comprehensive Physiology Review · Hypertension

⚡ Comprehensive physiology review of hypertension

Hemodynamics · neural & hormonal regulation · endothelial function · vicious cycle & target organ damage

The Fundamental Equation (Hemodynamics)

Ohm’s Law analogy for the cardiovascular system:

Mean Arterial Pressure (MAP) = Cardiac Output (CO) × Total Peripheral Resistance (TPR)
  • Cardiac Output (CO) = Heart Rate (HR) × Stroke Volume (SV). Volume of blood pumped per minute.
  • Total Peripheral Resistance (TPR) = degree of arteriolar constriction (vasoconstriction) or dilation (vasodilation) — the “tap” of the circulatory system.

Therefore, hypertension must be caused by an increase in CO, an increase in TPR, or both.

The Short-Term Regulators (Minute-to-Minute)

Rapid, neural reflexes keep BP stable moment-to-moment, primarily mediated by the Autonomic Nervous System and Baroreceptors.

  • Baroreceptor Reflex: Located in carotid sinus and aortic arch. If BP drops, these stretch receptors fire less → signals Cardiovascular Center in medulla oblongata to:
    • ↑ Sympathetic output: releases Norepinephrine → binds to Beta-1 receptors on heart (↑ HR & contractility) and Alpha-1 receptors on arterioles (vasoconstriction, ↑ TPR).
    • ↓ Parasympathetic output: withdraws vagal tone on heart, allowing HR to rise further.
  • Chemoreceptors: sensitive to hypoxia, hypercapnia, acidosis. In severe cases, they override baroreceptors to prioritize breathing, stimulating sympathetic system to raise BP.
⏱️ Key takeaway: In early or labile hypertension, the issue is often sympathetic overactivity — “fight or flight” stuck in a higher gear.

The Long-Term Regulators (Hours to Days)

Because baroreceptor reflex resets to a new baseline after 24–48 hours, long-term BP control relies on Blood Volume and the Kidneys — governed by the Renin-Angiotensin-Aldosterone System (RAAS).

  1. Renin Release: Juxtaglomerular apparatus senses low renal perfusion pressure or low sodium → releases Renin.
  2. Angiotensin I: Renin cleaves Angiotensinogen (from liver) into Angiotensin I.
  3. ACE: Angiotensin-Converting Enzyme (mainly in lungs) converts Angiotensin I → Angiotensin II (powerful vasoconstrictor).
  4. Angiotensin II does three things:
    • Vasoconstricts arterioles (immediately raises TPR).
    • Stimulates Aldosterone from adrenal cortex → kidneys retain Sodium & excrete Potassium; water follows sodium → ↑ blood volume & CO.
    • Stimulates ADH (Vasopressin) from pituitary → water retention & further vasoconstriction.
🧠 Key takeaway: The kidneys hold the “master key” to BP. If they perceive low pressure, they raise volume and resistance. In chronic hypertension, this set-point is often faulty → salt-sensitivity & volume expansion.

The Local Regulators (Endothelial Function)

The vascular endothelium is a dynamic endocrine organ, producing local hormones that fine-tune TPR:

🟢 Vasodilators (Relaxers)

Nitric Oxide (NO)

Most important. Released in response to shear stress. Relaxes vascular smooth muscle via cGMP. In hypertension, NO bioavailability is severely reduced (Endothelial Dysfunction).

Prostacyclin (PGI2): inhibits platelet aggregation & dilates vessels.

🔴 Vasoconstrictors (Constrictors)

Endothelin-1 (ET-1)

Most potent vasoconstrictor known. Released by damaged endothelium to prevent bleeding; overproduction contributes to high TPR.

Angiotensin II (also produced locally in the vessel wall).

⚠️ Key takeaway: Hypertension is a state of endothelial dysfunction – a shift toward oxidative stress, where vasodilators (like NO) are destroyed by free radicals, leaving vasoconstrictors (ET-1 & Ang II) unopposed.

The Pathophysiology of Primary (Essential) Hypertension

In 90–95% of cases, no single identifiable cause — multifactorial vicious cycle. Consensus physiological model:

🔄 The “Vicious Cycle” Model

  1. Cardiac Output increases (mild hypervolemia or high sympathetic tone).
  2. Peripheral arterioles sense increased flow and autoregulate — constrict to protect downstream capillaries.
  3. Autoregulatory vasoconstriction increases Total Peripheral Resistance.
  4. Sustained high resistance causes structural remodeling: smooth muscle hypertrophy & collagen deposits (fibrosis).
  5. Wall-to-lumen ratio increases. Even if original trigger (high CO) goes away, physical narrowing keeps TPR permanently high.
  6. Reduced lumen → kidneys receive less blood flow → inappropriately activates RAAS → fluid retention → tries to raise CO again … restarting the cycle.

The “Pressure-Natriuresis” Relationship (Renal Set-Point)

  • Healthy: if BP rises, kidneys excrete more Sodium & Water (pressure-natriuresis), dropping volume and bringing BP back down.
  • Hypertensive: curve shifted to the right. Kidneys require a much higher arterial pressure to excrete the same amount of sodium.
  • Consequently, the patient must maintain a high BP just to clear the daily salt load. This is why salt restriction and diuretics (which artificially force the kidneys to excrete salt) are first-line treatments.

The Maladaptive Consequences (Target Organ Damage)

  • Increased Wall Tension (LaPlace's Law): Wall Tension = Pressure × Radius. High pressure forces LV to generate enormous tension → Left Ventricular Hypertrophy (LVH) – heart muscle thickens, becomes stiff (diastolic dysfunction) and outgrows its blood supply → ischemia.
  • Shear Stress & Atherosclerosis: High pressure damages endothelial lining at branch points → LDL infiltrates wall → atherosclerotic plaques (heart attacks & strokes).
  • Microvascular Damage: In brain and kidneys, high pressure forces arterioles to constrict so hard they undergo fibrinoid necrosis → lacunar strokes and renal scarring (nephrosclerosis).

📋 Summary Cheat Sheet for Physiology Review

ComponentNormal FunctionChange in Hypertension
Cardiac Output~5 L/minOften High early on (hyperdynamic); may fall later as LVH develops.
Systemic Vascular ResistanceRegulated by arteriolar toneExcessively High (dominant feature of established HTN).
RAAS SystemResponds to low volume/saltInappropriately activated despite normal or high volume.
Sympathetic Nervous SystemResponds to stress/postureOveractive (increased NE spillover from kidneys and heart).
EndotheliumProduces NO to keep vessels pliableDysfunctional (↓ NO, ↑ endothelin, oxidative stress).
Kidney Set-PointExcretes salt at normal BPResets to require higher BP to excrete sodium.

Where to go next clinically

If you are reviewing this for a test, remember that drug classes map directly to these physiological points:

💊 Diuretics kidney set-point (volume) 💊 Beta-blockers Cardiac Output (HR & contractility) 💊 ACE inhibitors / ARBs RAAS system 💊 CCBs vascular smooth muscle (TPR) & heart 💊 Alpha-blockers sympathetic tone (TPR)
🧬 Physiology review · Hypertension · 2026 comprehensive · from hemodynamics to target organ damage