Blood Pressure Regulation, Hypertension, and Shock

Learning objectives

• Compare and contrast compliance and dispensability (dispensability is the term used in the slides).
• Describe how these two factors influence blood pressure.
• Define hypertension.
• Describe the pathophysiology of hypertension.
• Explain the mechanism(s) of circulatory shock.

Blood pressure recap: fundamental concepts

• Heart as reference pressure; gravity acts as a hydrostatic column.
• Transmural pressure: pressure within the vessel; ∆P = driving pressure for blood flow (arterial pressure minus venous pressure).

- Recumbent vs upright: arterial and venous pressures differ at head, heart, and feet, but driving pressures may remain similar.

ext{Transmural pressure} = P{ ext{inside}} - P{ ext{outside}}

• In orthostatic conditions, a redistribution of blood occurs; the model presents that driving pressures can be similar despite regional pressure differences.

Orthostatic redistribution and modelling (Prac 1, 2/3 link)

• Model: blood volume ~5 L in systemic veins; driving pressure ~7 mmHg.
• Blood pools in dependent regions (e.g., ankles) when standing, increasing local pressure.
• Model B predicts no venous return and thus no cardiac output (CO) if autoregulatory responses are not engaged.
• Model C predicts a physiological response to restore flow and maintain CO.

Factors contributing to orthostatic challenge

• Non-uniform distribution of blood: central blood volume initially increases with CO; venous return (VR) increases for the first beats.
• Non-uniform distensibility of vessels: leg veins vs central veins – as vessel size decreases, distensibility decreases.
• Skeletal muscle pumps and valves: contractions enhance venous return.
• Autonomic reflexes: baroreceptors sense low arterial pressure and change vessel tone and heart rate.
• Summary: 1+2 = anatomical factors; 3+4 = physiological responses.

Vascular distensibility vs vascular compliance

• All blood vessels are distensible.
• Arterial distensibility allows accommodation of pulsatile cardiac output.
• Venous distensibility provides a blood reservoir.
• Distensibility concept:

ext{Vascular distensibility} = ext{Increase in pressure} imes ext{Original volume}

• Veins are more distensible than arteries (approximately 8×) because vein walls are less muscular.
• For a given pressure increase, veins store ~8× the extra blood compared with arteries.

Vascular compliance

• Definition: The ability of a blood vessel wall to expand and contract in response to a change in pressure.

• Increased smooth muscle in vessel wall → decreased compliance.

• Compliance decreases with high pressure and high volume.

• Classic relation (as presented):

ext{Vascular compliance} = ext{distensibility} imes rac{ ext{Increase in volume}}{ ext{Increase in pressure}} imes rac{ ext{Original volume}}{ ext{Volume}}

• In practice (per slides):
  • Vein is 10–20× more compliant at low pressure than arteries.
  • Changes in myogenic tone affect compliance.

Distinguishing compliance and distensibility

• Compliance vs distensibility:
  • Compliance: tendency to resist change and recoil; relates to how much volume changes with pressure.
  • Distensibility: ability to stretch with pressure.
• Relative differences:
  • Veins: ~8× distensible; ~3× volume.
  • Overall, Vein compliance is much greater than arterial compliance for the same pressure range (per slides, compliance ≈ 24× greater than distensibility in some comparisons).

Effect of vascular tone on arterial and venous compliance

• Arterial system: operates over a small volume range – small volume changes yield large pressure changes.
• Venous system: acts as a reservoir – large volume changes yield small pressure changes.

Stress relaxation and venous accommodation

• Stress relaxation (creep): initial high pressure when volume increases, then gradual return toward normal without net volume shift.
• Allows veins to accommodate large volume shifts in both directions (important during hemorrhage).
• Key references: Guyton & Hall physiology text.

Arterial compliance and the arterial system

• Arterial compliance converts pulsatile flow into more continuous flow during systole and diastole.
• Function: stores a portion of stroke volume in the aorta during systole, then stretches and recoils to maintain flow during diastole.
• This stored volume and recoil help smooth arterial flow.

Pulse pressure determinants

• Pulse pressure (PP) is determined by:
  • Stroke volume of the heart (↑ SV → ↑ PP)
  • Compliance of the arterial tree (↓ compliance → ↑ PP)
  • Character of ejection (rapid vs. slow)
• Dichrotic notch: traditionally marks aortic valve closure; some contexts show a second wave where diastolic flow is represented rather than the classic notch.
• Pulse pressure formula (from slides):

ext{Pulse pressure} = SBP - DBP

• Clinical connection: radial pulse as a reflection of central arterial wave dynamics.

Transmission of pulse pressure and arterial waveforms

• During systole, blood ejected into proximal aorta creates a pressure pulse that travels faster than the moving blood.
• Velocity of the pressure pulse increases as arterial compliance decreases (stiff arteries transmit faster).
• Typical velocities:

ext{Blood velocity} \, \approx \, 1 \, \text{m/s}
ext{Pressure pulse velocity} \, \approx \, 5-6 \, \text{m/s in aorta}, \ 10-15 \, \text{m/s in arterioles}

• Result: pressure wave becomes steeper and narrower with distance from the heart; pulse pressure can increase with distance from the heart.

Flow and pressure profiles along the arterial tree

• Flow: peak flow is highest in the aorta during ventricular ejection and declines with distance.
• Pressure: distance from the heart correlates with pressure waveform distortion; the wave is not dampened, and PP tends to increase with distance.
• Practical note: the wave reflections and arterial stiffness contribute to PP and MAP dynamics; think about prac 1 connection.

Dampening of pulse pressure in smaller vessels

• As vessels become smaller, radius decreases and resistance increases, which would dampen flow.
• However, many vessels act in parallel and collectively increase total wall area, which can increase overall compliance in the microcirculation stage, impacting PP.
• The second wave discussed on slides is not the same as the classic dicrotic notch; it represents diastolic flow in later interpretation.

Pathologies related to arterial stiffness and pulse pressure

• Hardened and non-compliant arteries lead to lower diastolic pressure and higher systolic pressure (wider pulse pressure).
• Abnormal valve function can produce abnormal flow patterns: low aortic DBP, backflow, and loss of dicrotic notch.

Arterial blood pressure and aging

• BP tends to rise with age; there are sex differences that vary with age.
• After age ~60, systolic BP tends to rise more than diastolic BP.
• MAP tracks diastolic BP more closely than systolic BP.
• Clinical question: is an elderly patient more likely to present with systolic or diastolic hypertension? (Guided by aging-related arterial stiffness; typically systolic hypertension becomes more prominent.)

Hypertension: epidemiology and categories

• Framingham perspective: hypertension is a major CVD risk factor and often asymptomatic.
• Population trend: most people over 55 will develop hypertension.
• Systolic and diastolic BP categories (approximate thresholds from slides):

• Pathophysiology by age group:
  • Patients < 40 years: driven by high cardiac output with normal total peripheral resistance (TPR).
  • Older patients: normal or reduced cardiac output with increased TPR, often due to decreased lumen diameter of arterioles and increased arterial stiffness.
• 4 systems involved in BP regulation:
  1) Heart (pumping pressure),
  2) Vessels (resistance),
  3) Kidneys (volume),
  4) Hormones (modulation).

Essential vs secondary hypertension

• Essential hypertension (≈95% of patients): elevated BP with no readily definable cause.
• Heredity and environment contribute, with family history and twin concordance patterns noted.
• Secondary hypertension (≈5%): defined structural or hormonal causes such as:
  • Primary kidney disease or renal artery stenosis (atherosclerotic).
  • Catecholamine-secreting tumors affecting TPR.
  • Coarctation of the aorta (congenital narrowing).
  • Primary aldosteronism (adrenal adenoma or hyperplasia).

The Renin–Angiotensin–Aldosterone System (RAAS) and renal control of BP

• Key pathway (highlights from the slides):
  • Renin release from the kidney increases in response to reduced renal perfusion.
  • Renin converts angiotensinogen to angiotensin I; angiotensin-converting enzyme (ACE) in the lung converts Ang I to Ang II.
  • Ang II causes vasoconstriction and stimulates aldosterone release, promoting Na+/H2O retention and increased arterial pressure.
  • Angiotensinase inactivated Ang II.
• Normal renal function curve (as per slides):
  • 1× output at ~50 mmHg, 2× output at ~100 mmHg, 6–8× output above ~180 mmHg (illustrating renal perfusion and flow with MAP changes).
• One-kidney Goldblatt hypertension (classic experiment):
  1) Constrict renal artery → reduced distal renal artery pressure.
  2) Dramatic rise in systemic arterial pressure within the first hour due to increased renin release.
  3) Renin falls with restoration of renal artery pressure, followed by a slower rise in systemic pressure over days due to volume retention and autoregulation; TPR also contributes.
• Salt and hypertension: renal function and salt intake in volume regulation.
  • Normal: ~4–6 mmHg BP rise with 50× salt intake.
  • Blocked RAAS: BP can rise ~50–60 mmHg with the same salt intake due to failure to excrete excess salt/water.
• Primary role of RAAS: to regulate extracellular fluid volume and systemic pressure despite salt intake variations.

Renal function and volume regulation in hypertension – key concepts

• Volume-loading hypertension: increased extracellular fluid volume, blood volume (BV), and cardiac output (initial driver).
• Baroreceptor feedback: as BP rises, baroreceptors reset; autoregulation eventually sustains the higher BP at a new set point.
• In volume-loaded states, TPR may rise secondarily to sustained high BP to maintain flow.
• Acute vs chronic: rhange in renal mass and salt intake can shift renal function curves and influence long-term arterial pressure.

White coat hypertension and BP measurement accuracy

• White coat hypertension: elevated clinic BP without sustained elevation in other settings.
• About 20% of patients with mild hypertension are clinic-confined.
• Home monitoring and 24-hour ambulatory monitoring help differentiate true hypertension from white coat effects.
• False positives can be caused by speaking during measurement and other factors (reviewed in the cited Lancet article).

Stress and hypertension risk

• Acute stress raises BP transiently; chronic stress can influence other risk factors and lead to adverse cardiovascular outcomes.
• Mechanisms include catecholamine release (adrenaline) causing arterial spasm and reduced coronary perfusion, and hepatic release of cholesterol into blood (atherogenic profile).

Hypertension and organ damage

• Brain: stroke.
• Heart: hypertrophy, failure, ischemia, infarction.
• Kidney: nephrosclerosis, renal failure.
• Aorta: aneurysm/dissection.
• Vasculature: arteriosclerosis.
• Retina: arterial narrowing and hemorrhage.

Circulatory shock: definition, causes, and progression

• Definition (slides): peripheral circulatory failure with inadequate tissue perfusion and oxygen delivery, leading to tissue damage.
• Shock progression involves deterioration of vascular and myocardial function.
• Major causes:
  • Cardiac abnormalities reducing pumping ability (infarction, valve dysfunction, arrhythmias).
  • Factors reducing venous return (low blood volume, low venous tone).
• Sustained CO and tissue perfusion issues can create a negative feedback loop worsening shock.

Stages of circulatory shock

• 1) Non-progressive (reflex compensation): recovery possible with intervention.
• 2) Progressive: ongoing deterioration; may lead to death without intervention.
• 3) Irreversible: no salvage despite current life signs; outcome depends on intensity of progressive positive feedback vs negative feedback; energy reserves depletion (phosphate stores) is critical.

Non-progressive shock (reflex compensation)

• Mechanisms involved:
  • Baroreceptor reflexes raise MAP via increased heart rate, stroke volume, and arteriolar/venous tone.
  • CNS ischemic response when perfusion is compromised.
  • Stretch reflexes: renin-angiotensin system via low kidney blood flow; angiotensin and vasopressin release.
  • Blood volume adjustments (fluid shifts).
• Regulatory focus: reflexes aim to restore MAP, not necessarily CO.
• Negative feedback vs positive feedback: vasoconstriction and volume retention aim to raise MAP; however, if perfusion remains poor, a progressive decline can ensue.

Hypovolaemic shock (haemorrhage)

• Sensitivity to blood loss:
  • Up to ~10% blood loss: little effect on MAP.
  • >10% CO drop leads to MAP fall; major risk when ~35–45% blood loss occurs.
• Experimental data (dog models): arterial pressure reductions limit recovery; outcomes depend on degree and speed of pressure fall.
• Mechanisms in play:
  • Hemorrhage shifts blood away from central circulation toward peripheral veins, reducing central blood volume.
  • Compensatory mechanisms include increased heart rate, vasoconstriction, and sympathetic activation.
• The sequence involves changes in stroke volume, CO, arterial pressure, and venous return.

Mechanisms of shock progression and compensatory networks

• Progressive shock features:
  • Cardiac depression due to prolonged MAP reduction and ischemia of myocardium.
  • Vasomotor failure from reduced CNS perfusion impairing vasomotor center.
  • Microcirculatory collapse with low flow, capillary leakage, and tissue necrosis.
  • Release of toxins (e.g., histamine, endotoxins) from ischemic tissue, especially in septic contexts.
  • Acidosis (lactic acid accumulation) worsens cellular function.
• Irreversible shock: outcome depends on the balance of progressive positive feedback vs negative feedback; energy reserve depletion (phosphate) is particularly devastating.
• Sepsis, anaphylaxis, and neurogenic shock are additional categories with distinct pathophysiologies and management considerations.

Other types of shock and treatments

• Septic shock: inflammatory response with widespread tissue damage; most common shock after cardiogenic shock.
• Anaphylactic shock: histamine release causes vasodilation, reduced venous return, reduced MAP, and increased capillary permeability.
• Neurogenic shock: vasomotor tone loss due to deep anesthesia or spinal injuries.
• General treatment principles:
  • Fluids: oral/electrolyte solutions; transfusions (whole blood, plasma, or dextran) as indicated.
  • Positioning: head-down tilt (~12 inches) to improve venous return in certain hypotensive states.
  • Sympathomimetics (vasoconstrictors): useful in neurogenic and anaphylactic shock, less useful in pure hemorrhagic shock (to be used with caution and context).

Revision questions (unanswered in slides)

• Q1: In older patients with hypertension, which of the following contributes to the high blood pressure?
  • A. Increased cardiac output
  • B. Increased distensibility of the aorta
  • C. Increased total peripheral resistance
  • D. Decreased pulse pressure
  • E. Decreased cardiac output
• Q2: Non-progressive shock can include which of the following compensatory mechanisms?
  • A. Increased total peripheral resistance
  • B. Veno-constriction
  • C. Increased heart rate
  • D. Increased renin release
  • E. All of the above

Key formulas and quantitative points (summary)

• Driving pressure across the circulation:

\Delta P = P{\text{arterial}} - P{\text{venous}}

• Pulse pressure:

PP = SBP - DBP

• Aortic/arterial capacitance (as labeled in slides):

Ca = \frac{\Delta Va}{\Delta P_a}

• Renin–angiotensin cascade (conceptual steps): Renin → Angiotensin I → (ACE) → Angiotensin II → vasoconstriction and aldosterone-mediated volume retention.
• Normal renal function curve (illustrative):

1\times \text{output at } 50~\text{mmHg},\quad 2\times \text{output at } 100~\text{mmHg},\quad 6-8\times \text{output above } 180~\text{mmHg}

• Salt intake and BP response (RAAS context):
  • Normal: ~4–6 mmHg rise in BP with 50× salt intake.
  • Blocked RAAS: ~50–60 mmHg rise in BP for the same salt intake.

Connections to broader concepts

• The arterial system acts as a pressure reservoir to smooth flow (via compliance) and to convert pulsatile flow into a more continuous flow.
• The venous system serves as a major blood reservoir and plays a key role in venous return and orthostatic tolerance.
• Hypertension emerges from interactions among cardiac output, vascular resistance, kidney function (volume control), and hormonal regulation (RAAS, catecholamines, etc.).
• Aging and arterial stiffening shift the hemodynamic profile toward increased systolic BP and pulse pressure, with MAP influenced by diastolic pressure.
• Shock represents a breakdown of compensatory mechanisms and feedback loops, with organ perfusion failing progressively; management requires rapid restoration of perfusion and addressing the underlying cause.