Blood Pressure: Physiology and Clinical Aspects

1. Definition and Units

• Guyton and Hall Textbook of Medical Physiology, p. 2075

2. Physiological Determinants

Cardiac Output

• CO = Heart Rate × Stroke Volume
• The most important determinant of stroke volume is filling pressure, regulated through sodium homeostasis and blood volume
• Heart rate and myocardial contractility are controlled by α- and β-adrenergic systems

Peripheral Vascular Resistance

• Regulated predominantly at the arteriolar level by neural and humoral inputs
• Vascular tone = balance between:
  • Vasoconstrictors: Angiotensin II, catecholamines, endothelin, thromboxane, leukotrienes
  • Vasodilators: Kinins, prostaglandins, nitric oxide (NO)
• Blood vessels exhibit autoregulation: increased flow triggers vasoconstriction to protect tissues from hyperperfusion
• Fine-tuned by local tissue pH and hypoxia
• Robbins & Kumar Basic Pathology, p. 2501-2512

3. Anatomic Sites of BP Control

1. Resistance arterioles - primary site of peripheral vascular resistance
2. Capacitance venules - regulate venous return and preload
3. Heart (pump output) - cardiac output
4. Kidneys (volume control) - via the renin-angiotensin-aldosterone system

• Katzung's Basic and Clinical Pharmacology, 16e, p. 2905

4. Regulatory Mechanisms

A. Baroreceptor Reflex (Short-term)

• Baroreceptor activation decreases → sympathetic discharge increases
• Reflex responses: arteriolar constriction (↑ PVR), venoconstriction (↑ venous return), and cardiac stimulation (↑ CO)
• This rapid, moment-to-moment system is responsible for postural BP homeostasis

• Katzung's Basic and Clinical Pharmacology, 16e, p. 2908-2910

B. Renin-Angiotensin-Aldosterone System (Long-term)

• Juxtaglomerular cells of the kidney release renin in response to low renal perfusion pressure or low distal tubular sodium
• Renin cleaves angiotensinogen → angiotensin I → ACE converts to angiotensin II (Ang II)
• Ang II is the key effector: ~40× more potent than norepinephrine as a pressor agent
• Ang II actions:
  • Direct arteriolar vasoconstriction
  • Stimulates aldosterone release → sodium and water retention → increases blood volume
  • Acts on CNS to reset the baroreceptor reflex to higher pressure
  • Stimulates sympathetic ganglia and adrenal medulla (epinephrine/norepinephrine release)
  • Is mitogenic for vascular and cardiac muscle (mediates hypertensive remodeling)
• Atrial natriuretic peptide (ANP) counteracts this system by promoting sodium excretion in response to volume overload
• Katzung's Basic and Clinical Pharmacology, 16e, p. 323-350
• Robbins & Kumar Basic Pathology, p. 2516-2520

C. Sodium Homeostasis

5. BP Measurement

Clinical Auscultatory Method

• Korotkoff sounds heard during cuff deflation
• Systolic BP = first Korotkoff sound
• Diastolic BP = disappearance of sounds (Phase V)
• White coat hypertension: alerting reaction causes BP rise during physician measurement

Home Blood Pressure Monitoring (HBPM)

• Proper technique is mandatory; average home BP goal is <135/85 mm Hg

Ambulatory Blood Pressure Monitoring (ABPM)

• 24-hour average goal: <130/80 mm Hg
• ABPM is the gold standard to rule out white coat hypertension and detect masked hypertension

High-Fidelity Methods

• Guyton & Hall, p. 2079-2104
• Textbook of Family Medicine, 9e, p. 3210

6. Normal Values and Classification

• Textbook of Family Medicine, 9e, p. 2456

7. Hypertension: Clinical Aspects

Epidemiology

• Affects approximately one third of the adult population
• Only ~50% of hypertensive patients achieve BP goals in the US
• Leading modifiable risk factor for stroke, heart attack, heart failure, and CKD

Causes

• Primary (essential) hypertension: ~95% of cases; polygenic, no single identifiable cause; influenced by genetics, salt intake, obesity, stress, and the RAAS
• Secondary hypertension (~5%): identifiable causes include:
  • Renovascular hypertension (renal artery stenosis)
  • Primary hyperaldosteronism (Conn syndrome)
  • Pheochromocytoma
  • Cushing syndrome
  • Obstructive sleep apnea
  • Coarctation of the aorta
  • Drug-induced (NSAIDs, OCPs, stimulants, decongestants)

Hypertension as a Risk Factor

• Peripheral arterial disease (PAD): 2.5-fold age-adjusted risk in men, 3.9-fold in women
• Stroke, coronary artery disease, heart failure, CKD
• Each 20 mmHg rise in systolic (or 10 mmHg in diastolic) above 115/75 mm Hg doubles cardiovascular mortality risk (data from 1 million adults across 61 prospective studies - Lewington et al.)
• Textbook of Family Medicine, 9e, p. 974

8. Treatment of Hypertension

BP Targets

• General population <60 years: <140/90 mm Hg
• Age >60 years (JNC 8): <150/90 mm Hg; most other guidelines prefer <140/90 mm Hg in this group too
• Diabetics/CKD with significant proteinuria (>500 mg/day): <130/80 mm Hg may offer additional renal protection
• Home BP goal: <135/85 mm Hg | 24-hour ABPM goal: <130/80 mm Hg

Lifestyle Modifications (first-line for all)

• Dietary sodium restriction
• Weight reduction (DASH diet)
• Regular aerobic exercise
• Limiting alcohol
• Smoking cessation

Drug Therapy

• Thiazide/thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide)
• ACE inhibitors (e.g., lisinopril, ramipril)
• Angiotensin receptor blockers (ARBs, e.g., losartan, irbesartan)
• Calcium channel blockers (CCBs, e.g., amlodipine)

Compelling Indications (JNC 7) - Drug Selection by Comorbidity

• Textbook of Family Medicine, 9e, p. 3453-3464

Resistant Hypertension

• Defined as BP above goal on ≥3 antihypertensive medications (including a diuretic)
• Affects ~10% of the hypertensive population
• Empirical use of spironolactone (2.5-50 mg/day) has demonstrated efficacy as add-on therapy
• CPAP therapy helps in resistant hypertension with obstructive sleep apnea (HIPARCO trial)

9. Hypotension and Shock

Clinical Importance of Hypotension

• Hypotension is one of the last signs of shock
• Children and fit young adults can maintain BP until the final stages of shock through increased stroke volume and vasoconstriction - they can be in profound shock with a "normal" BP
• Elderly patients who are chronically hypertensive may be hypotensive at "normal" population values (e.g., 120/80 in a patient whose usual BP is 160/90)
• Beta-blockers or other medications may prevent the expected tachycardic response, masking the diagnosis

Hypertension in Heart Failure (AHF)

• Most patients with acute heart failure present with elevated BP and benefit from vasodilator therapy
• In AHF with pulmonary edema, vasodilators (nitroglycerin, nitroprusside) are primary therapy
• SBP <85-90 mm Hg or peripheral hypoperfusion are poor prognostic signs in AHF
• IV catecholamines (dopamine, dobutamine, norepinephrine) carry increased in-hospital mortality risk and should be used only when necessary
• Braunwald's Heart Disease, p. 3078-3080
• Bailey and Love's Surgery, 28e, p. 1003-1013

10. Special Populations

Pregnancy

Older Adults

Recent Evidence Update (2025)

Summary