REGULATION OF BLOOD PRESSURE

Mechanisms, Hemodynamics, Neural Regulation and Hormonal Regulation

1. BLOOD PRESSURE REGULATION

Blood pressure is a continuously regulated physiological variable. The body constantly detects changes in arterial pressure and activates compensatory mechanisms to maintain adequate tissue perfusion.

A useful reference value for normal adult blood pressure is approximately:

BP = 120/80 mm Hg

120 mm Hg = Systolic blood pressure (SBP)
80 mm Hg = Diastolic blood pressure (DBP)

Blood pressure is primarily determined by two major variables:

Blood Pressure ≈ Cardiac Output × Total Peripheral Resistance

Two major determinants

Cardiac output (CO) – mainly influences the amount of blood ejected into the arterial system.
Total peripheral resistance (TPR) – mainly determined by arteriolar tone and strongly influences diastolic pressure.

2. SYSTOLIC AND DIASTOLIC PRESSURE

Systolic Blood Pressure

Systolic BP is the maximum pressure in the arteries during ventricular contraction.

It is influenced by:

Cardiac output
Stroke volume
Heart rate
Contractility
Arterial compliance

During systole:

Left ventricular contraction → Mitral valve closes → Aortic valve opens → Blood is ejected into aorta → Arterial pressure rises

An increase in cardiac output generally tends to increase systolic BP.

Diastolic Blood Pressure

Diastolic BP is the pressure remaining in the arteries during ventricular relaxation.

It is strongly influenced by:

Total peripheral resistance
Arteriolar tone
Heart rate
Arterial elastic recoil

During diastole:

Ventricle relaxes → Aortic valve closes → Elastic recoil of arteries maintains forward blood flow

Effect of vascular tone

Vasoconstriction → ↑ TPR → ↑ DBP

Vasodilation → ↓ TPR → ↓ DBP

Exam point

Vasodilation decreases peripheral resistance, whereas vasoconstriction increases peripheral resistance.

3. MEAN ARTERIAL PRESSURE (MAP)

Mean arterial pressure is the average pressure in the arterial system during one complete cardiac cycle.

MAP is not simply:

(SBP + DBP)/2

because systole and diastole do not occupy equal amounts of time.

Approximately:

Systole = 1/3 of cardiac cycle
Diastole = 2/3 of cardiac cycle

Therefore, MAP is closer to DBP than SBP.

Formula

MAP ≈ DBP + 1/3 (SBP − DBP)

Since:

SBP − DBP = Pulse Pressure (PP)

Therefore:

MAP ≈ DBP + 1/3 PP

Example

For BP = 120/80 mm Hg:

Pulse pressure:

PP = 120 − 80 = 40 mm Hg

Therefore:

MAP = 80 + 1/3(40)

MAP = 80 + 13.3

MAP ≈ 93.3 mm Hg

Clinical importance

MAP represents the average driving pressure available for systemic tissue perfusion.

If MAP becomes excessively low:

↓ Tissue perfusion → Ischemia

If MAP remains chronically elevated:

↑ Vascular stress → Target-organ damage

4. MEAN SYSTEMIC FILLING PRESSURE (MSFP)

Mean systemic filling pressure is the pressure that exists throughout the systemic circulation when the heart is stopped and there is no blood flow.

It is approximately 7–10 mm Hg, depending on the physiological conditions and definition used.

MSFP is determined mainly by:

Blood volume
Venous compliance
Venous tone

It contributes to the pressure gradient driving venous return.

Important distinction

Feature	MAP	MSFP
Main location	Arterial circulation	Systemic circulation
Main role	Drives systemic tissue perfusion	Contributes to venous return
Main determinants	CO and TPR	Blood volume and venous tone

Remember

MAP → drives blood toward tissues

MSFP → contributes to venous return

5. CARDIAC OUTPUT

Cardiac output is the volume of blood pumped by the heart per minute.

Formula

CO = Heart Rate × Stroke Volume

Where:

HR = beats/minute
SV = volume ejected per beat

Therefore:

↑ HR or ↑ SV → generally ↑ CO

However, an excessively high heart rate may reduce cardiac output because ventricular filling becomes inadequate.

6. FACTORS AFFECTING STROKE VOLUME

Stroke volume is influenced mainly by:

Preload
Contractility
Afterload

A. Preload

Preload is the degree of ventricular myocardial fiber stretch at the end of diastole and is related to ventricular filling.

It is influenced by:

Venous return
Blood volume
Venous tone
Right atrial pressure

Frank–Starling mechanism

↑ Venous return → ↑ Ventricular filling → ↑ Preload → ↑ Force of contraction → ↑ Stroke volume

B. Contractility

Contractility is the intrinsic ability of cardiac muscle to contract independently of changes in preload.

Increased contractility

↑ Contractility → ↑ Stroke volume → ↑ CO → ↑ BP

Examples:

Sympathetic stimulation
β1-adrenergic stimulation
Positive inotropic drugs

Decreased contractility

↓ Contractility → ↓ Stroke volume → ↓ CO → ↓ BP

Examples:

Myocardial infarction
Severe acidosis
Certain electrolyte disturbances
Severe myocardial dysfunction

C. Afterload

Afterload is the resistance against which the ventricle must eject blood.

For the left ventricle, it is strongly related to systemic vascular resistance and arterial pressure.

High afterload

↑ Afterload → ↑ Ejection resistance → ↓ Stroke volume

Reduced afterload

↓ Afterload → Easier ventricular ejection → ↑ Stroke volume

This is one reason why arterial vasodilators can improve cardiac output while simultaneously lowering blood pressure.

7. ROLE OF BLOOD VOLUME AND VENOUS TONE

Blood is distributed between:

Stressed volume

Blood that contributes significantly to vascular pressure.

Unstressed volume

Blood contained mainly in compliant veins at relatively low pressure.

The venous system acts as an important blood reservoir.

Venoconstriction

Venoconstriction → Blood shifts toward stressed volume → ↑ Venous return → ↑ Preload → ↑ SV → ↑ CO → ↑ BP

Venodilation

Venodilation → Blood pooling in veins → ↓ Venous return → ↓ Preload → ↓ SV → ↓ CO → ↓ BP

8. HEART RATE AND BLOOD PRESSURE

An important concept is that an increase in heart rate does not always increase blood pressure.

At moderate increases:

↑ HR → ↑ CO → ↑ BP

However, at very high heart rates:

↑ HR → ↓ Diastolic filling time → ↓ Ventricular filling → ↓ Preload → ↓ Stroke volume → ↓ CO → Possible ↓ BP

Therefore, severe tachycardia may produce hypotension.

Exam point

Very rapid heart rate can reduce cardiac output because of inadequate ventricular filling.

9. TOTAL PERIPHERAL RESISTANCE

Total peripheral resistance is determined mainly by the resistance offered by systemic arterioles.

Vasoconstriction

↓ Vessel radius → ↑ Resistance → ↑ TPR → ↑ BP

Vasodilation

↑ Vessel radius → ↓ Resistance → ↓ TPR → ↓ BP

Arterioles are therefore major regulators of systemic blood pressure.

10. OVERALL RELATIONSHIP

The central equation to remember is:

MAP ≈ CO × TPR

And:

CO = HR × SV

Therefore:

MAP ≈ HR × SV × TPR

Stroke volume is influenced by:

Preload + Contractility + Afterload

Thus, blood pressure is controlled by interacting:

Cardiac factors
Vascular factors
Blood-volume factors
Neural mechanisms
Hormonal mechanisms

11. SHORT-TERM AND LONG-TERM REGULATION

Blood pressure is regulated over different time scales.

Short-term regulation

Occurs within seconds to minutes.

Main mechanism:

Baroreceptor reflex

It primarily involves:

Baroreceptors
Autonomic nervous system
Sympathetic nervous system
Parasympathetic nervous system

Long-term regulation

Occurs over hours to days.

Major mechanisms include:

Renin–angiotensin–aldosterone system (RAAS)
Renal regulation of sodium and water
ADH
ANP

12. BARORECEPTOR REFLEX

The baroreceptor reflex is a rapid negative-feedback mechanism that stabilizes arterial blood pressure.

It prevents sudden fluctuations in BP.

Location of baroreceptors

Baroreceptors are stretch-sensitive mechanoreceptors located mainly in:

Carotid sinus
Aortic arch

They respond primarily to stretch of the arterial wall, which reflects arterial pressure.

13. AFFERENT PATHWAYS OF BARORECEPTORS

Carotid sinus

Afferent signal travels through:

Glossopharyngeal nerve – CN IX

Aortic arch

Afferent signal travels through:

Vagus nerve – CN X

Both signals reach the:

Nucleus of the tractus solitarius (NTS)

located in the medulla.

Very important exam point

Carotid sinus → CN IX

Aortic arch → CN X

Both → NTS

14. BARORECEPTOR RESPONSE TO INCREASED BLOOD PRESSURE

When BP increases:

↑ BP

↓
↑ Arterial wall stretch

↓
↑ Baroreceptor firing

↓
CN IX/CN X

↓
NTS in medulla

↓
↑ Parasympathetic activity + ↓ Sympathetic activity

↓
↓ Heart rate

↓ Contractility

↓ Cardiac output

Vasodilation

↓
↓ TPR

↓
↓ BP toward normal

Summary

High BP → ↑ Baroreceptor firing → ↑ Vagal activity + ↓ Sympathetic activity → ↓ CO + ↓ TPR → ↓ BP

15. BARORECEPTOR RESPONSE TO DECREASED BLOOD PRESSURE

When BP falls:

↓ BP

↓
↓ Arterial wall stretch

↓
↓ Baroreceptor firing

↓
↓ NTS input

↓
↓ Parasympathetic activity + ↑ Sympathetic activity

↓
↑ Heart rate

↑ Contractility

Vasoconstriction

↓
↑ CO + ↑ TPR

↓
↑ BP

The fall in BP also promotes:

↑ Renin release → RAAS activation → Na⁺ and water retention

16. AUTONOMIC CONTROL OF BLOOD PRESSURE

Sympathetic nervous system

Sympathetic activation generally:

↑ Heart rate
↑ Contractility
↑ Cardiac output
Causes arteriolar vasoconstriction
Causes venoconstriction
↑ TPR
↑ Venous return

Overall:

Sympathetic activation → ↑ BP

Parasympathetic nervous system

Parasympathetic activity, particularly through the vagus nerve:

↓ Heart rate
↓ Cardiac output

Overall:

↑ Parasympathetic activity → ↓ BP

17. CAROTID SINUS MASSAGE

Carotid sinus massage mechanically increases stretch of the carotid sinus.

Pathway

Carotid sinus stretch

↓
↑ Baroreceptor firing

↓
CN IX

↓
NTS

↓
↑ Parasympathetic + ↓ Sympathetic activity

↓
↓ Heart rate

Carotid sinus massage may therefore slow AV nodal conduction and can be used clinically in selected supraventricular tachyarrhythmias.

Important

The afferent limb is:

Glossopharyngeal nerve (CN IX)

18. INTERRUPTION OF CAROTID BARORECEPTOR AFFERENTS

If carotid sinus afferent signaling is reduced:

↓ Afferent input to CNS

The CNS may interpret this as reduced arterial pressure.

Therefore:

↑ Sympathetic activity → Vasoconstriction → ↑ HR → ↑ BP

This demonstrates the importance of the baroreceptor afferent pathway in maintaining normal BP.

19. ORTHOSTATIC HYPOTENSION

Orthostatic hypotension occurs when blood pressure falls excessively after standing.

On standing:

Gravity → Blood pools in lower extremities

↓
↓ Venous return

↓
↓ Preload

↓
↓ Stroke volume

↓
Transient ↓ CO and BP

Normally, the baroreceptor reflex compensates by increasing sympathetic activity.

Normal compensation

↑ Sympathetic activity → ↑ HR + Vasoconstriction → BP maintained

When compensation fails

Orthostatic hypotension may occur.

Possible causes include:

Volume depletion
Autonomic dysfunction
Certain medications
Excessive vasodilation
Impaired sympathetic responses

Symptoms

Dizziness
Light-headedness
Visual disturbance
Syncope/blackout

Important correction

A commonly used clinical definition is:

Fall in SBP ≥20 mm Hg OR fall in DBP ≥10 mm Hg within 3 minutes of standing

Therefore, a fall of >10 mm Hg in systolic BP alone is not the complete standard definition.

20. DRUGS THAT CAN WORSEN ORTHOSTATIC HYPOTENSION

Drugs that interfere with compensatory mechanisms include:

α1-adrenergic blockers
Sympatholytic drugs
Vasodilators
Diuretics and other drugs that reduce effective circulating volume

Mechanism:

Drug effect → Impaired vasoconstriction/volume compensation → ↓ BP on standing → Dizziness/syncope

21. RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM (RAAS)

The RAAS is an important long-term regulator of:

Blood pressure
Blood volume
Sodium balance
Water balance

It becomes particularly important during:

Hypotension
Reduced renal perfusion
Reduced effective circulating volume
Reduced sodium delivery to the macula densa

22. JUXTAGLOMERULAR APPARATUS

The juxtaglomerular apparatus is located near the vascular pole of the renal glomerulus.

Important components include:

1. Macula densa

Specialized cells of the distal tubule that sense tubular NaCl delivery.

2. Juxtaglomerular cells

Modified smooth muscle cells of the afferent arteriole that synthesize and release renin.

3. Extraglomerular mesangial/Lacis cells

Support communication within the juxtaglomerular apparatus.

23. STIMULI FOR RENIN RELEASE

Major stimuli include:

1. Reduced renal perfusion pressure

↓ Afferent arteriolar stretch → ↑ Renin

2. Reduced NaCl delivery to macula densa

↓ NaCl delivery → ↑ Renin

3. Sympathetic stimulation

β1-adrenergic stimulation of JG cells → ↑ Renin

24. RAAS CASCADE

↓ Blood pressure / ↓ renal perfusion

↓
Juxtaglomerular cells release RENIN

↓
Renin acts on:

ANGIOTENSINOGEN
(from liver)

↓
ANGIOTENSIN I

↓
ACE

↓
ANGIOTENSIN II

Angiotensin II produces:

Vasoconstriction
Aldosterone secretion
Increased sympathetic activity
Increased thirst
Increased sodium reabsorption

Overall:

↑ Blood volume + ↑ Vascular resistance → ↑ BP

25. RENIN

Renin is an enzyme, not a hormone.

It is secreted by:

Juxtaglomerular cells of the kidney

Renin converts:

Angiotensinogen → Angiotensin I

26. ANGIOTENSINOGEN

Angiotensinogen is synthesized primarily by the liver.

Renin cleaves angiotensinogen to form:

Angiotensin I

Angiotensin I is relatively inactive.

27. ACE

Angiotensin-converting enzyme converts:

Angiotensin I → Angiotensin II

ACE is widely expressed, particularly on vascular endothelial surfaces, with substantial activity in the pulmonary circulation.

Important

Angiotensin I:

10 amino acids = decapeptide

Angiotensin II:

8 amino acids = octapeptide

28. ACTIONS OF ANGIOTENSIN II

Angiotensin II is a powerful regulator of BP.

A. Vasoconstriction

Angiotensin II → AT1 receptor → Vasoconstriction → ↑ TPR → ↑ BP

This particularly increases diastolic pressure by increasing systemic vascular resistance.

B. Venoconstriction

Venoconstriction → ↑ Venous return → ↑ Preload → ↑ Stroke volume → ↑ CO

This can contribute to increased systolic pressure.

C. Aldosterone secretion

Angiotensin II → Adrenal cortex → Zona glomerulosa → ↑ Aldosterone

D. Thirst

Angiotensin II acts on the CNS and stimulates thirst.

↑ Thirst → ↑ Water intake → ↑ Blood volume

E. Sympathetic activity

Angiotensin II facilitates sympathetic activity and norepinephrine effects.

29. ALDOSTERONE

Aldosterone is a mineralocorticoid steroid hormone.

It is secreted from:

Zona glomerulosa of adrenal cortex

Major stimulus:

Angiotensin II

Other important stimulus:

Hyperkalemia

30. MECHANISM OF ACTION OF ALDOSTERONE

Aldosterone is lipid-soluble.

Therefore:

Aldosterone → Diffuses through cell membrane → Binds intracellular mineralocorticoid receptor → Hormone-receptor complex → Alters gene transcription → ↑ Transport proteins

Main target:

Principal cells of the late distal nephron/collecting duct

It increases:

ENaC activity/expression
Na⁺/K⁺-ATPase activity/expression
Potassium secretion pathways

Overall effect

↑ Na⁺ reabsorption

↑ Water retention

↑ K⁺ excretion

Therefore:

↑ Blood volume → ↑ BP

31. ALDOSTERONE – IMPORTANT MEMORY POINT

Remember:

ALDOSTERONE = Na⁺ RETENTION + K⁺ EXCRETION

Flowchart

Aldosterone

↓
↑ ENaC

↑ Na⁺/K⁺-ATPase

↓
↑ Na⁺ reabsorption

↓
Water retention

↓
↑ Blood volume

↓
↑ BP

At the same time:

↑ K⁺ secretion → ↑ K⁺ excretion

32. ANGIOTENSIN II AND THE PROXIMAL TUBULE

Angiotensin II also promotes sodium reabsorption in the proximal tubule.

It stimulates:

Na⁺/H⁺ exchanger

This promotes:

↑ Na⁺ reabsorption

and is associated with increased bicarbonate reabsorption.

Therefore:

Angiotensin II → ↑ Na⁺ and HCO₃⁻ reabsorption → ↑ Water retention → ↑ Blood volume

33. ANGIOTENSIN II AND EFFERENT ARTERIOLE

Angiotensin II preferentially constricts the efferent arteriole, particularly at physiologically relevant concentrations.

This helps maintain glomerular capillary pressure and GFR when renal perfusion pressure is reduced.

Important exam point

Angiotensin II → Efferent arteriolar constriction → Helps maintain glomerular pressure and GFR during reduced renal perfusion

34. ACE INHIBITORS

Examples:

Captopril
Enalapril
Lisinopril
Ramipril

Mechanism:

ACE inhibition

↓
↓ Angiotensin II formation

↓
↓ Vasoconstriction

↓ Aldosterone

↓ Sodium and water retention

↓
↓ BP

ACE inhibitors also increase bradykinin by reducing its breakdown.

Important adverse effects

Dry cough
Hyperkalemia
Hypotension
Rise in serum creatinine in susceptible patients
Angioedema

Contraindication/major caution

ACE inhibitors are contraindicated in pregnancy.

They should also be avoided in bilateral renal artery stenosis or significant stenosis of a solitary functioning kidney because loss of angiotensin II-mediated efferent constriction can markedly reduce GFR.

35. ARBs

Examples:

Losartan
Valsartan
Candesartan
Telmisartan

ARBs block the:

AT1 receptor

Therefore:

Angiotensin II cannot exert its major AT1-mediated effects

Result:

↓ Vasoconstriction

↓ Aldosterone effects

↓ BP

Unlike ACE inhibitors, ARBs do not directly inhibit bradykinin breakdown.

Therefore:

ARBs generally cause less cough than ACE inhibitors.

36. SPIRONOLACTONE

Spironolactone is a:

Mineralocorticoid receptor antagonist

It blocks aldosterone action.

Therefore:

↓ Na⁺ reabsorption

↓ Water retention

↑ Na⁺ excretion

↓ Blood volume

↓ BP

It is a potassium-sparing diuretic.

Important adverse effect

Hyperkalemia

Other adverse effects may include endocrine effects such as gynecomastia.

37. CHEMORECEPTORS AND BLOOD PRESSURE CONTROL

Chemoreceptors contribute to cardiovascular regulation, particularly during changes in blood gases.

There are two major types:

Peripheral chemoreceptors

Located in:

Carotid bodies
Aortic bodies

They respond particularly to:

↓ PaO₂

and also to changes in CO₂ and pH.

Central chemoreceptors

Located in the brainstem.

They respond mainly to changes in:

CO₂ / CSF H⁺

38. CENTRAL CHEMORECEPTORS

Central chemoreceptors respond primarily to increased CO₂ through the associated increase in hydrogen ion concentration in brain extracellular fluid/CSF.

Mechanism

↑ PaCO₂

↓
CO₂ enters CSF

↓
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

↓
↑ H⁺

↓
Central chemoreceptor stimulation

↓
↑ Ventilatory drive + cardiovascular responses

Important exam point

The key stimulus is the increase in H⁺ generated by CO₂ in the CNS, rather than CO₂ directly binding to the receptor.

39. PERIPHERAL CHEMORECEPTORS

Peripheral chemoreceptors are especially important in detecting:

↓ PaO₂

They are located in:

Carotid bodies
Aortic bodies

Afferent pathways:

Carotid bodies → CN IX

Aortic bodies → CN X

Signals reach the medulla and increase respiratory and sympathetic responses.

Response

↓ O₂ → Chemoreceptor activation → ↑ Sympathetic activity → Vasoconstriction → ↑ BP

40. CUSHING RESPONSE

The Cushing response occurs in the setting of significantly increased intracranial pressure.

Mechanism

↑ Intracranial pressure

↓
↓ Cerebral perfusion

↓
Brainstem ischemia / accumulation of CO₂ and H⁺

↓
Sympathetic activation

↓
Systemic vasoconstriction

↓
↑ Arterial BP

The increased arterial pressure activates the baroreceptor reflex:

↑ BP → ↑ Vagal activity → Bradycardia

Therefore, a classic feature is:

Hypertension + Bradycardia

Respiratory abnormalities may also occur.

Associated signs of raised ICP

Headache
Vomiting
Papilledema
Altered consciousness

Important

The classic Cushing triad is:

Hypertension with widened pulse pressure + Bradycardia + Irregular respirations

41. ADH / VASOPRESSIN

ADH is also called:

Antidiuretic hormone / Vasopressin

It is:

Synthesized in the hypothalamus → Transported to posterior pituitary → Stored and released from posterior pituitary

Major stimuli for release include:

Increased plasma osmolality
Significant reduction in effective circulating volume/BP

V2 receptor action

In the kidney:

ADH → V2 receptor → ↑ Aquaporin-2 insertion in collecting duct → ↑ Water reabsorption

Therefore:

↑ Water retention → ↑ Blood volume

At high concentrations, ADH also stimulates:

V1 receptors → Vasoconstriction → ↑ BP

42. ATRIAL NATRIURETIC PEPTIDE (ANP)

ANP is released mainly from:

Atrial myocytes

Stimulus:

↑ Atrial stretch due to increased blood volume

Actions:

↑ Na⁺ excretion
↑ Water excretion
Vasodilation
↓ Blood volume
↓ Blood pressure

Thus:

ANP opposes volume-retaining effects of RAAS and ADH.

43. ADH VS ANP

Feature	ADH	ANP
Main stimulus	↑ Osmolality / ↓ effective circulating volume	↑ Atrial stretch
Main effect	Water retention	Na⁺ and water excretion
Vascular effect	Vasoconstriction at high concentration	Vasodilation
Effect on BP	Increases/maintains BP	Decreases BP
Overall role	Defends volume	Removes excess volume

44. INTEGRATED REGULATION OF BLOOD PRESSURE

Blood pressure regulation involves several interconnected systems.

Immediate regulation

Baroreceptor reflex

Acts within:

Seconds

Intermediate/longer regulation

RAAS

ADH

Renal sodium and water handling

Additional regulation

Chemoreceptor reflexes
Sympathetic nervous system
ANP
Local vascular mechanisms

45. RESPONSE TO HEMORRHAGE

Consider a patient who loses a significant amount of blood.

Step 1 – Blood volume falls

Hemorrhage → ↓ Blood volume

↓
↓ Venous return

↓
↓ Preload

↓
↓ Stroke volume

↓
↓ Cardiac output

↓
↓ BP

Step 2 – Baroreceptor response

↓ BP → ↓ Baroreceptor stretch

↓
↓ Baroreceptor firing

↓
↓ Parasympathetic + ↑ Sympathetic activity

↓
↑ HR + ↑ Contractility + Vasoconstriction

↓
↑ CO + ↑ TPR

Step 3 – RAAS activation

↓ Renal perfusion → ↑ Renin

↓
↑ Angiotensin II

↓
Vasoconstriction + ↑ Aldosterone

↓
Na⁺ and water retention

↓
↑ Blood volume

Step 4 – ADH

↓ Effective circulating volume → ↑ ADH

↓
↑ Water retention

Overall

Hemorrhage → ↓ BP → Neural + hormonal compensation → Restoration of BP

46. RESPONSE TO STANDING

When a person suddenly stands:

Standing

↓
Gravity → Blood pooling in legs

↓
↓ Venous return

↓
↓ Preload

↓
↓ Stroke volume

↓
Transient ↓ CO

↓
↓ BP

Baroreceptor response:

↓ Baroreceptor firing

↓
↑ Sympathetic + ↓ Parasympathetic activity

↓
↑ HR + Vasoconstriction + Venoconstriction

↓
BP restored

47. RESPONSE TO VOLUME OVERLOAD

When blood volume increases:

↑ Blood volume

↓
↑ Venous return

↓
↑ Preload

↓
↑ Stroke volume / CO

↓
↑ BP

Compensatory responses include:

↑ ANP

↓ RAAS activity

↓ Sympathetic activity

↑ Renal Na⁺ and water excretion

Overall:

Excess volume → Natriuresis + Diuresis → ↓ Blood volume → ↓ BP

48. IMPORTANT EXAM FLOWCHARTS

A. Increased Blood Pressure

↑ BP

↓
↑ Baroreceptor stretch

↓
↑ Baroreceptor firing

↓
NTS

↓
↑ Parasympathetic + ↓ Sympathetic

↓
↓ HR + ↓ Contractility + Vasodilation

↓
↓ CO + ↓ TPR

↓
↓ BP

B. Decreased Blood Pressure

↓ BP

↓
↓ Baroreceptor stretch

↓
↓ Baroreceptor firing

↓
↓ Parasympathetic + ↑ Sympathetic

↓
↑ HR + ↑ Contractility + Vasoconstriction

↓
↑ CO + ↑ TPR

↑ Renin → RAAS

↑ ADH

↓
↑ BP

49. RAAS – COMPLETE FLOWCHART

↓ BP / ↓ Renal perfusion / ↓ NaCl delivery

↓
Juxtaglomerular cells

↓
RENIN

↓
Angiotensinogen

↓
Angiotensin I

↓ ACE

Angiotensin II

↓ ↓ ↓ ↓

Vasoconstriction

↑ Aldosterone

↑ Thirst

↑ Sympathetic activity

↓
↑ TPR + ↑ Blood volume + ↑ Venous return

↓
↑ BP

50. PHARMACOLOGICAL TARGETS IN RAAS

ACE inhibitors

↓ Angiotensin II formation

ARBs

Block AT1 receptor

Mineralocorticoid receptor antagonists

Block aldosterone action

Examples:

Spironolactone
Eplerenone

Direct renin inhibitor

Aliskiren

Blocks renin activity and therefore reduces downstream RAAS activation.

51. HIGH-YIELD EXAM POINTS

Remember these associations:

Carotid sinus → CN IX

Aortic arch → CN X

Both → NTS

Renin → Juxtaglomerular cells

Angiotensinogen → Liver

ACE → Converts Ang I to Ang II

Angiotensin II → Vasoconstriction + Aldosterone + Thirst + Sympathetic facilitation

Aldosterone → Na⁺ retention + K⁺ excretion

ADH → Water retention

ANP → Na⁺ and water excretion

Angiotensin II → Preferential efferent arteriolar constriction

ACE inhibitors → ↓ Ang II + ↑ Bradykinin

ARBs → AT1 receptor blockade

Spironolactone → Mineralocorticoid receptor blockade

52. IMPORTANT FORMULAS

Blood pressure

BP ≈ CO × TPR

Cardiac output

CO = HR × SV

Pulse pressure

PP = SBP − DBP

Mean arterial pressure

MAP ≈ DBP + 1/3(SBP − DBP)

MAP ≈ DBP + 1/3(PP)

Example

For 120/80 mm Hg:

PP = 40 mm Hg

MAP ≈ 93 mm Hg

53. COMMON CONCEPTUAL TRAPS

Trap 1

↑ HR does not always mean ↑ CO.

At very high HR:

↓ Filling time → ↓ SV → ↓ CO

Trap 2

Baroreceptors detect stretch, not pressure directly.

Trap 3

Carotid sinus = CN IX

Aortic arch = CN X

Trap 4

MAP is not simply the arithmetic average of SBP and DBP.

Because:

Diastole lasts longer than systole.

Trap 5

Renin is an enzyme, not a hormone.

Trap 6

Angiotensinogen comes from the liver.

Trap 7

Aldosterone is produced by the zona glomerulosa.

Trap 8

Aldosterone causes Na⁺ retention and K⁺ excretion.

Trap 9

ACE inhibitors can cause hyperkalemia.

Reason:

↓ Ang II → ↓ Aldosterone → ↓ K⁺ excretion

Trap 10

ACE inhibitors can cause cough because of increased bradykinin.

Trap 11

ARBs generally cause less cough than ACE inhibitors because they do not directly inhibit bradykinin breakdown.

Trap 12

Orthostatic hypotension is not simply any small fall in BP on standing.

A commonly used diagnostic criterion is:

SBP fall ≥20 mm Hg OR DBP fall ≥10 mm Hg within 3 minutes of standing.

54. ONE-PAGE CONCEPT SUMMARY

BLOOD PRESSURE

BP ≈ CO × TPR

↓

CO = HR × SV

↓

SV depends on Preload + Contractility + Afterload

SHORT-TERM CONTROL

Baroreceptors

Location:

Carotid sinus + Aortic arch

↓

CN IX + CN X

↓

NTS

↓

Autonomic nervous system

↓

HR + Contractility + Vascular tone

↓

BP stabilization

LONG-TERM CONTROL

↓ BP

↓

Renin

↓

Angiotensin I

↓

Angiotensin II

↓

Vasoconstriction

Aldosterone

Thirst

Sympathetic facilitation

↓

↑ Blood volume + ↑ TPR

↓

↑ BP

OTHER HORMONES

ADH → Water retention ± vasoconstriction

ANP → Natriuresis + diuresis + vasodilation

55. FINAL INTEGRATED FLOWCHART

DROP IN BLOOD PRESSURE

↓

FAST RESPONSE

↓ Baroreceptor firing

↓

↑ Sympathetic + ↓ Parasympathetic

↓

↑ HR

↑ Contractility

Vasoconstriction

Venoconstriction

↓

↑ CO + ↑ TPR

↓

SLOW RESPONSE

↓ Renal perfusion

↓

↑ Renin

↓

Angiotensin II

↓

Vasoconstriction

Aldosterone

Thirst

↑ Sympathetic activity

↓

Na⁺ + Water retention

↓

↑ Blood volume

↓

↑ Venous return

↓

↑ Preload

↓

↑ Stroke volume

↓

↑ Cardiac output

↓

RESTORATION OF BLOOD PRESSURE

QUICK VIVA REVISION

Q. What are the two major determinants of BP?
CO and TPR.

Q. What is the formula for CO?
CO = HR × SV.

Q. What is MAP?
Average arterial pressure during one cardiac cycle.

Q. Formula for MAP?
MAP ≈ DBP + 1/3(SBP − DBP).

Q. Where are baroreceptors located?
Carotid sinus and aortic arch.

Q. Which nerve carries carotid sinus afferents?
Glossopharyngeal nerve, CN IX.

Q. Which nerve carries aortic arch afferents?
Vagus nerve, CN X.

Q. Where do these signals terminate?
Nucleus of the tractus solitarius (NTS).

Q. What happens when BP rises?
↑ Baroreceptor firing → ↑ parasympathetic + ↓ sympathetic → ↓ HR, ↓ CO and vasodilation → ↓ BP.

Q. What happens when BP falls?
↓ Baroreceptor firing → ↓ parasympathetic + ↑ sympathetic → ↑ HR, ↑ contractility and vasoconstriction → ↑ BP.

Q. What stimulates renin release?
Reduced renal perfusion, reduced NaCl delivery to macula densa, and β1 sympathetic stimulation.

Q. Where is renin produced?
Juxtaglomerular cells.

Q. Where is angiotensinogen produced?
Liver.

Q. What converts Ang I to Ang II?
ACE.

Q. Major actions of Ang II?
Vasoconstriction, aldosterone secretion, thirst stimulation and sympathetic facilitation.

Q. Where is aldosterone produced?
Zona glomerulosa of adrenal cortex.

Q. Main action of aldosterone?
Na⁺ retention and K⁺ excretion.

Q. Main action of ADH?
Water retention.

Q. Main action of ANP?
Natriuresis, diuresis and vasodilation.

Q. Why can severe tachycardia reduce BP?
Because shortened diastolic filling time reduces ventricular filling, stroke volume and cardiac output.

Q. Why do ACE inhibitors cause cough?
Increased bradykinin.

Q. Why can ACE inhibitors cause hyperkalemia?
Reduced Ang II → reduced aldosterone → reduced K⁺ excretion.

Q. Why are ACE inhibitors dangerous in bilateral renal artery stenosis?
They remove Ang II-mediated efferent arteriolar constriction that helps maintain GFR.

Q. Why do ARBs cause less cough than ACE inhibitors?
They block AT1 receptors without directly inhibiting bradykinin breakdown.

Monday, September 28, 2026

Hypertension BP regulation

REGULATION OF BLOOD PRESSURE

Mechanisms, Hemodynamics, Neural Regulation and Hormonal Regulation

1. BLOOD PRESSURE REGULATION

Two major determinants

2. SYSTOLIC AND DIASTOLIC PRESSURE

Systolic Blood Pressure

Diastolic Blood Pressure

Effect of vascular tone

Exam point

3. MEAN ARTERIAL PRESSURE (MAP)

Formula

Example

Clinical importance

4. MEAN SYSTEMIC FILLING PRESSURE (MSFP)

Important distinction

Remember

5. CARDIAC OUTPUT

Formula

6. FACTORS AFFECTING STROKE VOLUME

A. Preload

Frank–Starling mechanism

B. Contractility

Increased contractility

Decreased contractility

C. Afterload

High afterload

Reduced afterload

7. ROLE OF BLOOD VOLUME AND VENOUS TONE

Stressed volume

Unstressed volume

Venoconstriction

Venodilation

8. HEART RATE AND BLOOD PRESSURE

Exam point

9. TOTAL PERIPHERAL RESISTANCE

Vasoconstriction

Vasodilation

10. OVERALL RELATIONSHIP

11. SHORT-TERM AND LONG-TERM REGULATION

Short-term regulation

Long-term regulation

12. BARORECEPTOR REFLEX

Location of baroreceptors

13. AFFERENT PATHWAYS OF BARORECEPTORS

Carotid sinus

Aortic arch

Very important exam point

14. BARORECEPTOR RESPONSE TO INCREASED BLOOD PRESSURE

Summary

15. BARORECEPTOR RESPONSE TO DECREASED BLOOD PRESSURE

16. AUTONOMIC CONTROL OF BLOOD PRESSURE

Sympathetic nervous system

Parasympathetic nervous system

17. CAROTID SINUS MASSAGE

Pathway

Important

18. INTERRUPTION OF CAROTID BARORECEPTOR AFFERENTS

19. ORTHOSTATIC HYPOTENSION

Normal compensation

When compensation fails

Symptoms

Important correction

20. DRUGS THAT CAN WORSEN ORTHOSTATIC HYPOTENSION

21. RENIN–ANGIOTENSIN–ALDOSTERONE SYSTEM (RAAS)

22. JUXTAGLOMERULAR APPARATUS

1. Macula densa

2. Juxtaglomerular cells

3. Extraglomerular mesangial/Lacis cells

23. STIMULI FOR RENIN RELEASE

1. Reduced renal perfusion pressure

2. Reduced NaCl delivery to macula densa

3. Sympathetic stimulation

24. RAAS CASCADE

25. RENIN

26. ANGIOTENSINOGEN

27. ACE

Important

28. ACTIONS OF ANGIOTENSIN II