Cardiovascular regulation
Cardiovascular regulatory mechanisms: reflexes, renin–angiotensin system and autoregulation
Blood pressure is defended within seconds by nervous reflexes, over hours to days by hormones that adjust salt and water, and locally by organs that keep their own flow constant. CPSP asks which receptor senses what, which nerve carries it, what drives renin, and what happens when a pressure goes outside an organ's autoregulatory range.
Time course of pressure control
| Speed | Mechanism |
|---|---|
| Seconds | Baroreceptor reflex (first and fastest), chemoreceptor reflex, CNS ischaemic response |
| Minutes to hours | Renin–angiotensin system, capillary fluid shift, stress relaxation of vessels |
| Days | Renal salt and water handling (pressure natriuresis), aldosterone, ADH |
Baroreceptors
- Stretch receptors in the carotid sinus (a dilatation at the origin of the internal carotid artery; afferents in the glossopharyngeal nerve) and aortic arch (vagus).
- They respond to mean pressure and, more strongly, to rapid pulsatile rises. Afferents go to the nucleus tractus solitarius; the vasomotor centre lies in the medulla and lower pons.
- A rise in pressure increases firing, increases vagal tone and reduces sympathetic outflow: slower heart, vasodilatation. Blood loss reduces firing, causing tachycardia and vasoconstriction.
- In chronic hypertension they reset to the higher pressure, so they do not correct sustained hypertension.
- Clinical examples: carotid sinus massage slows a supraventricular tachycardia; carotid sinus hypersensitivity (tight collar, shaving, plaque at the bulb) causes syncope; phenylephrine for spinal hypotension causes reflex bradycardia; damage to the sinus nerve at endarterectomy causes labile pressure.
- Valsalva: after release, venous return floods back into a constricted circulation; the pressure overshoot causes reflex bradycardia.
- Vasovagal syncope: sudden vagal bradycardia with loss of sympathetic tone (pain, fear, needle procedures).
Chemoreceptors and the CNS ischaemic response
| Receptor | Senses | Notes |
|---|---|---|
| Peripheral (carotid and aortic bodies) | Low PaO₂, also high PaCO₂ and H⁺ | Sense dissolved O₂, not O₂ content: anaemia and carbon monoxide do not stimulate them. When MAP falls below about 60–80 mmHg, stagnant hypoxia activates them and adds vasoconstriction after baroreceptors are maximally unloaded |
| Central (medulla) | H⁺ in CSF from raised arterial PCO₂ | CO₂ crosses the blood–brain barrier; H⁺ does not |
- CNS ischaemic response / Cushing reflex: raised intracranial pressure makes the brainstem ischaemic, causing a massive sympathetic surge and hypertension; baroreceptors then slow the heart. Irregular breathing follows.
- Delayed chemoreceptor feedback in heart failure produces Cheyne–Stokes breathing.
The renin–angiotensin–aldosterone system
- Renin from juxtaglomerular cells is released by:
| Stimulus | Example |
|---|---|
| Reduced stretch of the afferent arteriole | Renal artery stenosis (fibromuscular dysplasia with a beaded mid-artery in young women; atheroma at the origin in older smokers, with flash pulmonary oedema) |
| Sympathetic β1 stimulation | Haemorrhage, standing |
| Low NaCl at the macula densa | Loop diuretics block NKCC2, so the macula densa senses less chloride |
- Renin turns angiotensinogen (liver) into angiotensin I. ACE in pulmonary capillary endothelium converts most of it to angiotensin II.
- Angiotensin II: arteriolar vasoconstriction; constricts the efferent arteriole more than the afferent, preserving GFR; aldosterone release; ADH release; thirst (dominant in haemorrhage when osmolality is normal); proximal Na⁺ reabsorption; facilitates sympathetic transmission.
- Primary aldosteronism: volume expansion stretches the afferent arteriole, so renin is suppressed. Spironolactone raises renin and must be stopped before the aldosterone-to-renin ratio (false negative).
- Natriuretic peptides: ANP from atria and BNP from stretched ventricular myocytes cause natriuresis and vasodilatation and oppose renin.
Autoregulation
- Myogenic response: arteriolar smooth muscle contracts when stretched, so flow returns to baseline within a minute after a pressure rise, even in a denervated kidney.
- Metabolic control: adenosine, CO₂, H⁺, K⁺ and low O₂ dilate vessels (coronary and skeletal muscle).
- Kidney: myogenic response plus tubuloglomerular feedback (the macula densa senses NaCl delivery and adjusts afferent tone) keep GFR steady.
- Brain: flow is constant over a mean pressure of roughly 60–150 mmHg; arterial PCO₂ is the most powerful regulator. Hyperventilation to a PaCO₂ of 4.0 kPa (30 mmHg) constricts arterioles and lowers intracranial pressure for a time.
| Situation | What happens |
|---|---|
| Pressure above the upper limit | Forced dilatation, barrier breakdown, vasogenic oedema in posterior white matter (PRES in eclampsia) |
| Chronic hypertension | Curve shifts right; rapid lowering to "normal" causes cerebral ischaemia (restricted diffusion on MRI) |
| Uteroplacental circulation | No autoregulation: hypotension after spinal or hydralazine bolus causes fetal bradycardia |
Pregnancy
- Renin, angiotensin II and aldosterone are all raised, yet blood pressure falls in the second trimester because vessels become refractory to angiotensin II (prostacyclin, nitric oxide); twice the usual dose is needed to raise diastolic pressure.
- Women who develop pre-eclampsia lose this refractoriness weeks before hypertension appears, and their renin is lower than in normal pregnancy.
Remember Baroreceptors guard pressure, peripheral chemoreceptors guard PaO₂, central chemoreceptors guard CSF H⁺.
Exam trap Angiotensin I is converted mainly in the lungs, not the kidney.
Exam trap Anaemia does not stimulate the carotid bodies: they sense PaO₂, which is normal.
Test yourself on this topic
5 of the 43 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A 27-year-old woman with a ruptured ectopic pregnancy has a large haemoperitoneum and a mean arterial pressure of 50 mmHg. Besides the baroreceptors, which receptors now add strong drive to the vasomotor centre?
Answer: Carotid and aortic body chemoreceptors
Baroreceptors work best between about 60 and 180 mmHg. When mean pressure falls below about 80 mmHg, flow through the carotid and aortic bodies falls, and their cells become hypoxic and acidotic even if arterial PO2 is normal. The chemoreceptors then fire strongly and excite the vasomotor centre, adding to sympathetic vasoconstriction. They also stimulate breathing, which is why severe shock causes rapid breathing.
Chemoreceptor reflex in shock
- Works below about 80 mmHg
- Low flow: body cells hypoxic
- Adds sympathetic drive
- Also drives breathing
Remember When pressure is very low, the chemoreceptors join the baroreceptors.
Exam trap Chemoreceptors can be stimulated by low flow even when arterial PO2 is normal.
Why the other options are wrong
- Atrial low-pressure stretch receptors These fire less when volume falls and mainly affect ADH and heart rate.
- Pulmonary J receptors These respond to interstitial oedema and cause rapid shallow breathing.
- Muscle spindle afferents These are proprioceptors, not cardiovascular sensors.
- Hypothalamic osmoreceptors These respond to osmolality, not to arterial pressure.
A 22-year-old motorcyclist has diffuse brain swelling after a head injury. While awaiting surgery he is briefly hyperventilated to a PaCO2 of 4.0 kPa (30 mmHg), and his intracranial pressure falls. What is the mechanism?
Answer: Cerebral arteriolar constriction
Cerebral arterioles are very sensitive to PaCO2: CO2 crosses the blood-brain barrier and changes perivascular pH. A fall in PaCO2 raises local pH and constricts the arterioles, reducing cerebral blood flow and blood volume. Because the skull is a fixed box, a smaller blood volume lowers intracranial pressure. The effect is short-lived and too much hypocapnia can cause ischaemia.
PaCO2 and the brain
- Low PaCO2: vasoconstriction
- Less cerebral blood volume
- ICP falls briefly
- Too low: ischaemia
Remember CO2 is the strongest local dilator of brain vessels.
Exam trap Hyperventilation is a short bridge; prolonged hypocapnia worsens ischaemia.
Why the other options are wrong
- Reduced CSF production Hypocapnia has little rapid effect on CSF secretion.
- Increased venous outflow from the skull Venous drainage is helped by head position, not by hyperventilation.
- Osmotic shift of water out of the brain This is how mannitol works.
- Reduced cerebral oxygen demand Hypocapnia does not lower brain metabolism.
A 60-year-old man with long-standing untreated hypertension arrives with BP 230/130 mmHg and is given an infusion that lowers it to 120/70 mmHg within an hour. He becomes confused and develops infarcts in the border zones between the middle and posterior cerebral artery territories. Which of the following best explains this?
Answer: Right shift of autoregulation curve
Cerebral autoregulation keeps blood flow steady across a range of mean arterial pressures (roughly 60 to 150 mmHg in normal people). In chronic hypertension the arterioles remodel and the whole curve shifts to the right, so the lower limit is higher. A sudden fall to a pressure that a normal person would tolerate drops below this lower limit, and flow falls. The border zones at the ends of arterial territories suffer first.
Autoregulation in hypertension
- Normal range about 60 to 150 mmHg MAP
- Chronic hypertension: curve shifts right
- Fast BP drop: flow falls
- Border-zone infarcts
Remember Lower BP slowly in chronic hypertension.
Exam trap A blood pressure that looks normal can still be too low for a brain adapted to hypertension.
Why the other options are wrong
- Loss of carbon dioxide reactivity CO2 reactivity is usually preserved in hypertension.
- Cerebral vasospasm from the infusion Antihypertensive infusions dilate rather than constrict vessels.
- Embolism from the carotid arteries Emboli cause territorial, not border-zone, infarcts.
- Raised intracranial pressure No mass effect is described, and lower pressure would not raise ICP.
A 45-year-old man has a large extradural haematoma causing midline shift. Over an hour his blood pressure climbs from 130/80 to 200/110 mmHg. What is the cause of the rise in pressure?
Answer: Sympathetic surge from brainstem ischaemia
As intracranial pressure approaches arterial pressure, blood flow to the medulla falls. Ischaemia of the vasomotor centre produces intense sympathetic discharge, raising arterial pressure enough to push blood into the brain. This is the CNS ischaemic response, the hypertensive limb of the Cushing reflex. It appears late and signals impending herniation.
Cushing response
- Rising ICP: medullary ischaemia
- Massive sympathetic discharge
- Hypertension to perfuse brain
- Late sign of herniation
Remember The hypertension of raised ICP is a rescue attempt by the medulla.
Exam trap This response is a late warning sign, not a stable compensation.
Why the other options are wrong
- Pain from the scalp wound Pain does not produce progressive severe hypertension.
- Carotid baroreceptor reflex The baroreflex opposes, not causes, the rise.
- Release of ADH from the pituitary ADH has only a small pressor effect at these levels.
- Activation of renin by low renal flow Renal flow is not reduced in this setting.
A 40-year-old woman strains against a closed glottis for 15 seconds. A few seconds after she releases the strain, her blood pressure overshoots above baseline and her pulse slows to 55/min. What causes this slowing?
Answer: Baroreflex response to the pressure overshoot
During the strain, raised intrathoracic pressure cuts venous return, so cardiac output and blood pressure fall and heart rate rises reflexly with peripheral vasoconstriction. On release, venous return surges into a heart pumping against still-constricted arterioles, so pressure overshoots. The baroreceptors sense this and slow the heart through the vagus. This phase IV overshoot and bradycardia need an intact baroreflex, which is why the manoeuvre is used to test autonomic function.
Valsalva phase IV
- Strain: venous return falls, HR rises
- Release: venous return surges
- Vessels still constricted: BP overshoots
- Baroreflex bradycardia
Remember The slow pulse after release proves the baroreflex works.
Exam trap An absent overshoot and bradycardia suggests autonomic failure, not a normal response.
Why the other options are wrong
- Direct vagal stimulation by raised chest pressure Chest pressure is already back to normal at this point.
- Fall in venous return to the right heart Venous return is rising, not falling, after release.
- Peripheral chemoreceptor stimulation Chemoreceptors are not stimulated by a brief strain.
- Bainbridge reflex from atrial stretch Atrial stretch speeds rather than slows the heart.
Where this sits in the CPSP syllabus
- Diagnostic Radiology, Paper 2: Cardiovascular, respiratory and renal physiology, Cardiovascular regulatory mechanisms
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