HMA - Blood pressure and Blood flow Phys

High-pressure baroreceptors

stretch receptors located in the carotid sinus and aortic arch that increase firing with increases in arterial blood pressure, causing autonomic effects to the cardiovascular system.

Baroreceptor reflex

negative feedback loop in response to high or low blood pressure/volume, triggering changes sympathetic and parasympathetic activity to adjust HR, contractility and vascular resistance.

Low-pressure (volume) baroreceptors

stretch receptors located mainly in the atria and pulmonary circulation that increase firing with increases in blood volume/venous filling, causing inhibition of ADH and RAAS-mediated fluid retention.

Bainbridge reflex

increased atrial stretch due to blood volume increase leads to increased heart rate to pump blood from congested veins into arterial system for diuresis.

Pressure diuresis

with high blood pressure, increased renal perfusion causes an increase in water and sodium excretion by the kidneys, reducing blood volume.

Antidiuretic hormone (ADH)

reduced blood pressure/volume causing reduced baroreceptor during causes its secretion from the posterior pituitary gland, triggering increased water reabsorption by the kidneys and systemic vasoconstriction.

Atrial natriuretic peptide (ANP)

increased blood pressure/volume causing increased atrial stretch causes its secretion by atrial myocytes, triggering increased sodium and water excretion and systemic vasodilation.

Aldosterone

hormone produced in the adrenal cortex in response to angiotensin II, triggering sodium and water reabsorption by the kidneys.

Angiotensin II

hormone produced in pulmonary vasculature triggering systemic vasoconstriction, release of aldosterone, and thirst.

Renin-angiotensin-aldosterone system (RAAS)

hormonal mechanism activated in the kidneys in response to poor renal perfusion and sympathetic stimulation with low blood pressure.

Renin

enzyme secreted from juxtaglomerular apparatus (JGA) in kidney into blood, catalysing angiotensinogen (from liver) → angiotensin I.

Angiotensin-converting enzyme (ACE)

enzyme secreted by capillary endothelial cells of the lungs, catalysing angiotensin I → angiotensin II (active compound).

Right and left vagus (X) nerve

Describe the afferent pathway from aortic arch baroreceptor signals to brain stem.

Carotid sinus, then glossopharyngeal (IX) nerve

Describe the afferent pathway from carotid sinus baroreceptor signals to brain stem.

Medullary cardiovascular centre

consists of cardioinhibitor, vasoconstrictor, and vasodilator centre, integrating sensory information to initiate an autonomic response.

Cardioinhibitor centre

control centre for parasympathetic activity to the heart, responsible for slowing heart rate (bradycardia).

Vasoconstrictor centre

control centre for sympathetic activity to the heart and vessels, responsible for increasing heart rate and constricting blood vessels.

Vasodilator centre

control centre inhibiting sympathetic activity to the heart and vessels, responsible for dilating blood vessels.

Cardiac accelerator nerves from thoracic spinal cord

Describe the efferent pathway from the medullary cardiovascular centre to the heart, increasing heart rate and contractility via β₁-adrenoceptors.

Right and left vagus (X) nerves

Describe the efferent pathway from the medullary cardiovascular centre to the heart, decreasing heart rate via M₂ muscarinic receptors in the SA and AV nodes.

Sympathetic nerves from thoracic/lumbar spinal cord

Describe the efferent pathway from the medullary cardiovascular centre to blood vessels, causing vasoconstriction via α₁-adrenoceptors on vascular smooth muscle.

Orthostatic response

series of cardiovascular reflexes that maintain blood pressure and cerebral perfusion when moving from lying down to standing, preventing hypotension.

ACE inhibitor, ARB, calcium channel antagonist, diuretics

What are the 4 key first line anti-hypertensive therapies?

ACE inhibitor

first line anti-hypertensive that blocks conversion of angiotensin I to angiotensin II to reduce vasoconstriction and aldosterone-mediated water retention. Associated with dry cough, hyperkalaemia, hypotension, angioedema and contraindicated for those with renal impairment, taking NSAIDs, and pregnant women.

Angiotensin receptor blocker

first line anti-hypertensive that blocks binding to angiotensin II type 1 receptors (AT1R) in blood vessel wall and adrenal cortex, thus reducing vasoconstriction and aldosterone. Associated with hyperkalaemia and hypotension, can cause foetal malformation so contraindicated in pregnancy.

Angiotensin II type 1 receptors (AT1R)

What receptors do ARBs block binding to in the vessel wall and adrenal cortex.

Dihydropyridine (DHP) calcium channel antagonist

first line anti-hypertensive that blocks L-type Ca²⁺ channels in vascular smooth muscle, causing vasodilation. Associated with peripheral oedema, flushing, headache, and reflex tachycardia.

Non-DHP calcium channel antagonist

first-line anti-hypertensive that blocks L-type Ca²⁺ channels in the heart and vascular smooth muscle, causing reduced heartrate and contractility, and some vasodilation. Associated with bradycardia and irregular heart rhythms.

Thiazide

first-line anti-hypertensive diuretic blocking sodium/chloride co-transporter in the distal tubule to inhibit sodium reabsorption, leading to increased water excretion. Associated with hypokalaemia, hyponatraemia, and hyperuricaemia, and is contraindicated with diabetes.

K-sparing diuretic

diuretic blocking sodium channels OR aldosterone receptors in the collecting duct inhibiting sodium reabsorption, leading to increased water excretion without potassium loss. Associated with hyperkalaemia.

ACE inhibitor

What is enalapril or lisinopril?

Angiotensin receptor blocker

What is losartan, candesartan, or irbesartan?

Dihydropyridine (DHP) calcium channel antagonist

What is nifedipine or amlodipine?

Non-DHP calcium channel antagonist

What is diltiazem or verapamil?

Thiazide

What is hydrochlorothiazide?

K-sparing diuretic

What is amiloride or spironolactone?

Beta adrenoceptor antagonist

second line anti-hypertensive to reduce heart rate and contractility, and renin production, leading to reduced cardiac output to treat hypertension. Associated with bradycardia, fatigue, hypotension, and sexual dysfunction.

Selective beta 1 blocker for hypertension

What is atenolol or metoprolol?

Non selective beta blocker for hypertension

What is propranolol or timolol?

Alpha adrenoceptor antagonists

second line anti-hypertensive that inhibits postsynaptic α1 receptors, preventing noradrenaline binding, leading to vasodilation. Associated with postural hypotension, dizziness, and syncope.

Alpha blocker

What is prazosin or terazosin?

CNS acting agents

second line anti-hypertensive including α2-adrenoceptor agonists or imidazoline agonists that decrease sympathetic outflow. Associated with sedation, sleep disturbance, and depression.

CNS acting agents

What is clonidine or α-methyldopa (converted to α-methyl NA)?

Myogenic response, active/reactive hyperaemia

List key examples of local regulation of blood flow.

Sympathetic vasoconstriction/dilation, parasympathetic vasodilation

List key examples of neural regulation of blood flow.

Sympathetic vasoconstriction

NA binds to α₁ adrenoceptors on vascular smooth muscle, causing vasoconstriction and increasing systemic vascular resistance and blood pressure, e.g. skin, thoracic organs, where α₁ adrenoceptors predominate.

Sympathetic vasodilation

adrenaline acting on β₂ adrenoceptors causes vasodilation in skeletal muscle and coronary vessels, increasing blood flow during exercise or stress.

Parasympathetic vasodilation

ACh acting on endothelial cell muscarinic receptors to release NO causing local vascular smooth muscle relaxation, such as in face and genitalia.

Adrenaline, angiotensin II, antidiuretic hormone

List key examples of hormonal vasoconstrictors.

Natriuretic peptide, nitric oxide, bradykinin, histamines

List key examples of hormonal vasodilators.

Adrenaline

adrenal medulla hormone causing β₂-mediated vasodilation in skeletal muscle, α₁-mediated vasoconstriction elsewhere, and positive inotropic and chronotropic effects on the heart.

Angiotensin II

potent vasoconstrictor produced by the RAAS, also causing fluid retention and increasing cardiac sympathetic activity to increase systemic vascular resistance and blood pressure.

Vasopressin (anti-diuretic hormone)

hormone released from the posterior pituitary that causes vasoconstriction (esp in skin, skeletal muscles, and visceral organs) and promotes kidney water reabsorption, mainly stimulated by increases in plasma osmolarity.

Natriuretic peptide

hormone released in response to increase blood volume that promotes vasodilation, natriuresis, and diuresis, lowering blood volume.

Nitric oxide

vasodilator synthesised by eNOS in endothelial cells, diffusing to smooth muscle cells stimulating GTP → cGMP to cause smooth muscle relaxation.

Bradykinin

potent inflammatory vasodilator synthesised via kinin-kallikrein system in blood plasma and damaged tissue.

Histamine

potent local vasodilator released by tissues in inflammation and allergic reactions leading to redness (flash), local oedema (wheal), and spreading vasodilation (flare).

Reactive hyperaemia

temporary increase in blood flow that occurs after a brief period of ischaemia or arterial occlusion causing build up of metabolic waste products (e.g. adenosine, carbon dioxide) which act as local vasodilator.

Active (functional) hyperaemia

increased tissue metabolism causes causing build up of metabolic waste products (e.g. adenosine, carbon dioxide) which act as local vasodilator, increasing blood flow to meet metabolic demand, e.g. exercising skeletal muscle.

Autoregulation

intrinsic ability of an organ to maintain a steady blood level supply despite changes in blood pressure, e.g. brain, kidneys, heart.

Myogenic response

smooth muscle cells in arteriole walls intrinsically constrict or dilate in response to changes in intra-luminal pressure, i.e. increased pressure placed more tension of vascular walls, leading to vasoconstriction which decreases flow.

Coronary (heart) circulation

must maintain high O2 supply, and increase supply with metabolic demand, increasing flow via local metabolic regulation and with CO.

High capillary density, coronary artery anatomy, active hyperaemia, sympathetic vasodilation, myogenic response

List 5 factors that increase flow to coronary circulation.

Systolic compression, sympathetic vasoconstriction, pathologies

List 3 factors that decrease flow to coronary circulation.

Arterio-venous anastomoses

shunts connecting small arteries to veins found in apical skin (hands, feet, facial prominences), allowing blood to reach superficial venous plexuses for heat release if dilated.

Cutaneous (skin) circulation

primarily involved in temperature regulation involving strong sympathetic nerve control, linked to thermal receptors.

Sympathetic vasoconstriction

high NA activation of α₁ adrenoceptors in cutaneous circulation in cold temperatures to reduce radiant heat loss

Sympathetic withdrawal

reduced sympathetic vasoconstrictor tone in hot temperatures, leading to cutaneous circulation vasodilation to increase radiant heat loss.

Cerebral circulation

local metabolic autoregulation maintains constant oxygen and glucose supply and is effective at directing blood flow to the active part of the brain.

Active hyperaemia, myogenic response

List 2 factors regulating cerebral circulation.

70-80%

What is the proportion of cardiac output directed to skeletal muscle during exercise (from 15%)?

4-5 fold

What is the increase in cardiac output achieved during exercise?

Cardiac output

systolic blood pressure peaks during ejection phase, so is mainly influenced by changes in WHAT?

Total peripheral resistance

diastolic blood pressure occurs just before contraction, so is mainly influenced by changes in WHAT?

Heart rate

factor increasing in both aerobic and anaerobic exercise, but more so in anaerobic exercise due to skeletal muscles needing a very rapid supply of ATP.

Stroke volume

factor increasing mildly in both aerobic and aerobic exercise, but more so in anaerobic exercise due to greater skeletal muscle pumping action increasing venous return and greater ventricular filling time between contractions.

Cardiac output

factor increasing in both aerobic and anaerobic exercise, but more so in aerobic exercise.

Muscle contraction compressing vessels

Why do systolic, diastolic, and mean arterial pressure increase during anaerobic exercise?

Early integrated response

immediate, coordinated reaction at the onset of physical activity, where the motor cortex and hypothalamus initiate withdraw of parasympathetic activity, and increase of sympathetic activity.

Increased heart rate, contractility, visceral vasoconstriction, venoconstriction

What are the 4 main actions in the early integrated response to exercise.

Late integrated response

delayed physiological adjustments that occur during prolonged physical exertion to maintain blood flow, blood pressure and temperature.

Locally-mediated vasodilation, histamine release, adrenaline release, exercise pressor response, temperature regulation

What are the 5 main actions in the late integrated response to exercise.

Histamine release

local vasodilator in the late integrated response, also increases capillary permeability to support increased blood flow and exchange in active tissues.

Adrenaline

hormone responsible for β₂-mediated vasodilation in skeletal muscle and coronary arteries AND the increase in HR and contractility via β₁ receptors in the heart.

Active hyperaemia, NO release by shear stress

What 2 local factors lead to skeletal muscle vasodilation and capillary recruitment in the late integrated exercise response?

Capillary recruitment

dilation of upstream arterioles triggers perfusion of previously unperfused capillaries in response to increased tissue metabolic demand.

Exercise pressor response

sensory receptors in active skeletal muscle detect stretch and metabolic changes leading to increased sympathetic activity which continues to stimulate the heart, but also causes vasoconstriction in blood vessels preventing TPR and MAP from falling excessively.

Withdrawal from cutaneous circulation, stimulation of sweat glands

How does withdrawal or stimulation of sympathetic activity help with temperature regulation in the late integrated response to exercise?

Compensatory response

initial response to blood loss, involving maintaining blood pressure and volume via CNS and kidney stimulation/withdrawal by arterial baroreceptors, peripheral chemoreceptors, and volume receptors.

Peripheral and central chemoreceptors

in the carotid bodies and aortic bodies, ↑ firing when tissue perfusion becomes sufficiently reduced, causing ↓ arterial PO₂, ↑ PCO₂, and ↓ pH.

Transcapillary refill

reduction in capillary hydrostatic pressure (Pc) causes plasma colloid osmotic pressure (πp) to dominate, causing net reabsorption of fluid from interstitial space into the capillaries.

Hemodilution

decrease in haematocrit and haemoglobin levels during exercises as fluid shifts into the bloodstream or intravenous fluids are added.

Decompensatory response

vascular control has failed to maintain adequate blood pressure and tissue perfusion, leading to dropping blood pressure, cellular oxygen starvation, and potential progression to irreversible shock.

Lactic acidosis

poor tissue perfusion leading to hypoxia causes anaerobic metabolism, leading to lactic acid build up lowering blood pH, weakening the heart, and worsening organ failure.

Desensitisation to sympathetic transmitters, desensitisation of baroreceptors, end to transcapillary refill.

What contributes to the end of the compensatory response to haemorrhage?