blood pressure regulation

likely incomplete

parasympathetic innervation of the heart

• SA node and AV node

• Releases acetylcholine which binds to muscarinic receptors (M2)

• Slows the heart rate and rhythm

mechanism:

• inhibits cyclic AMP (cAMP) (by inhibiting adenylyl cyclase, the enzyme responsible for its production)

• intracellular Ca2+ levels decreases (calcium channels close) (slows AV node conduction)

• K+ conductance increased leading to hyperpolarisation of membrane (slows heart rate)

sympathetic regulation of blood pressure

• Responsible for immediately increasing blood pressure
  e.g. Exercise, standing, etc.

• Releases noradrenaline →

• Heart:

  • NA acts on β1-receptors in heart to increase heart rate and contractility

• Blood vessels:

  • α1-receptors vasoconstriction (TPR) → increased cardiac output

  • parasympathetic: β2-receptors vasodilation (rarely)

• Kidneys:

  • α1-receptors → renin/angiotensin/aldosterone
    secretion

blood volume

controlled by kidneys

high blood volume = high bp

hypotension risks

• Circulatory collapse (vessels collapse)

• Tissue ischemia/hypoxia

• No filtration in the kidney

• MAP below 60mmHg can cause syncope (fainting)

hypertension risks

• Retinal, renal damage

• Oedema

• MAP above 160mmHg can result in cerebral oedema

• Aneurysm/haemorrhage

• Heart hypertrophy/failure

main factors influencing blood pressure

• Blood volume (kidneys)

• Total peripheral resistance (TPR) (SNS + blood vessels)

• Cardiac output (SNS + blood vessels)

stroke volume

volume of blood ejected per beat (mL)

usually approx. 70mL/beat

EDV (end diastolic volume) - ESV (end systolic volume)

NA acts on β1-receptors in the heart to increase SV

heart rate

number of beats per minute

NA acts on β1-receptors in the heart to increase HR

cardiac output

heart rate X stroke volume

the volume of blood flowing through the circulation in one minute (L/min)

determined by blood vessels (due to venous return) and SNS

nerve regulation of heart rate

• SA node innervated by the parasympathetic nervous system via the vagus nerve

  • cranial nerve

  • direct innervation

  • decrease HR

• SA and AV nodes innervated by the sympathetic nervous system via the cardiac accelerator nerve

  • through spinal cord

  • Increase HR

factors affecting stroke volume

• preload

  • amount of ventricular stretch after diastole  (Frank-Starling mech)

• contractility

  • controlled by SNS

• afterload

  • amount of resistance heart must overcome to open aortic valve (inverse to stroke volume)

(not affected by heart rate)

preload

• the amount of sarcomere stretch experienced by cardiomyocytes, at the end of ventricular filling during diastole

  • i.e. the stretch that the blood places on the walls of the ventricles when it’s maximally filled (EDV)

• Frank-Starling law: the more you stretch the heart, the greater the reflexive contraction of the heart will be, and the more blood that will be ejected (until plateau)

• directly related to venous return

contractility

the relative ability of the heart to eject a stroke volume (SV) at a given prevailing afterload and preload (end-diastolic volume)

impacted by sympathetic activation - contractile strength increasing

afterload

the resistance the blood experiences as it leaves the ventricle

increased afterload = decreased stroke volume

atherosclerosis effect on stroke volume

plaques in the walls of arteries

→ narrowed diameter of the arteries

→ increased afterload

→ decreased stroke volume

inotropic agents

influence contractile force

positive inotropic agents: factors increasing the availability of Ca2+

• noradrenaline

• thyroid hormone

negative inotropic agents: factors decreasing the availability of Ca2+

• calcium blockers

• electrolyte imbalances

chronotropic effects

• influence heart rate

• positive chronotropic effect:

  • sympathetic stimulation

  • anticholinergics (block acetylcholine)

• negative chronotropic effect:

  • parasympathetic stimulation

  • beta-blockers

total peripheral resistance (TPR)

The sum of the resistance encountered throughout the circulation

For the blood to overcome the resistance and keep flowing forwards, a pressure gradient is required

Controlled by blood vessels and SNS 

mean arterial pressure (MAP)

the average pressure exerted by the blood
against the vessels

MAP = diastolic pressure + 1/3 pulse pressure

determined by: cardiac output & total peripheral resistance

systolic blood pressure

pressure exerted against the walls of the arteries during systole

diastolic blood pressure

pressure exerted against the walls of the arteries during diastole

elastic arteries purpose (maybe only Y1)

maintain constant pressure gradient despite pumping action

experience high pressure - Windkessel effect

• distension accommodates increased volume with only moderate increase in pressure

• recoil maintains relatively high pressure as blood flows away and volume is reduced

muscular arteries purpose (maybe only Y1)

• distribute blood flow to muscles/organs

• dampen pulsatility

• (don’t have to withstand as much pressure as elastic arteries)

arterioles

regulate blood flow to capillaries

• innervated by sympathetic system (only)

  • a1 → vasoconstriction (SNS)

    • vasodilates in response to hormones, metabolic controls but NO ß2 for vasodilation (PNS)

• short-term blood pressure regulation

  • regulate blood flow + TPR

• ensure effective capillary exchange

(think kidneys afferent and efferent arterioles)

baroreceptors

• detect blood pressure

• high pressure baroreceptors:

  • located in arteries (carry blood away from the heart under high pressure):

    • aortic arch (CNX sensory fibres)

    • carotid sinus (CNIX sensory fibres)

• high pressure baroreceptors send information → cardiovascular centre in the medulla

  → adjusts sympathetic and parasympathetic activity appropriately

• low pressure baroreceptors:

  • located in veins and atria (blood returning to the heart at much lower pressure)

    • venous system

    • right atrium

  • → pituitary gland releases ADH when blood volume is low

autonomic innervation of the circulatory system

SNS and PNS:

• SA and AV nodes

SNS only:

• ventricles

• blood vessels

baroreceptor reflex - low BP

Reduced MAP

→ decreased baroreceptor firing rate

→ medulla cardioacceleratory center

• sympathetic impulses to heart increasing:

  • heart rate

  • contractility

• resulting in increased cardiac output

+ vasomotor center activates

• increased: total peripheral resistance (vasoconstriction)

baroreceptor reflex - high BP

Increases in MAP

→ increased firing rate of baroreceptors

→ activate the medulla cardioinhibitory centre (parasympathetic),

• decreasing

  • heart rate

  • cardiac contractility

• therefore decreasing cardiac output

+ vasomotor centre inhibited

• decrease total peripheral resistance (vasodilation)

Forces pushing and pulling fluid into the capillary (maybe only Y1)

pushing: interstitial fluid hydrostatic pressure

pulling: capillary oncotic pressure

(nutrient exchange at capillaries)

nephron

• structural and functional unit of the kidney

• glomerulus: high pressure capillary bed, fluid and dissolved solutes diffuse from blood into glomerular/bowman’s capsule

• produced filtrate passes through renal tubule (composition continues to be altered)

renal tubule

1. proximal convoluted tubule (PCT)

   • substantial water and solute reenters bloodstream (reabsorbs)

2. loop of Henle (descending and ascending limb)

   • descending: only water permeable/reabsorbed (lots of aquaporins)

   • ascending: only solutes reabsorbed (little to no aquaporins)

3. distal convoluted tubule (DCT)

   • hormonal control for what is being reabsorbed

4. collecting duct

   • hormonal control for what is being reabsorbed

cortical nephrons

• most abundant

• found in cortex (outside) of the kidney (except loop of henle that dips into medullary portion)

juxtamedullary nephron

• less common

• glomerulus and Bowman’s capsule arise near cortex-medullary junction

• loops of Henle deeply invade renal medulla

• important in producing concentrated urine

glomerulus

• high pressure capillaries

• site of filtration

  • fluids and solutes forced into glomerular capsule

• fed by afferent arterioles

• drained by efferent arterioles

peritubular capillaries

• arise from efferent arteriole

• low pressure porous capillaries

  • filter waste from blood

  • reabsorb water and solutes from filtrate back into blood

  • vasa recta - long straight vessels serving juxtamedullary nephrons

juxtaglomerular apparatus

region where distal portion of ascending limb lies against afferent arteriole

contains:

• juxtaglomerular/granular cells

• macula densa

juxtaglomerular/granular cells

• enlarged smooth muscle cells

• secretory granules producing and storing renin

• mechanoreceptor that sense BP in afferent arteriole (low BP increases renin release)

  • controls arteriole diameter to regulate blood flow

• NA

  → ß1 receptors

  → renin secretion

macula densa cells

• specialised epithelial cells

• closely packed cells of ascending limb

• chemoreceptors - monitor changes in NaCl in distal part of nephron

• responsible for vasoconstricting afferent arteriole to regulate blood flow/filtrate into glomerulus

glomerular filtration

BP forced fluids and solutes across glomerular capillaries into glomerular capsule

• passive process

• leaky glomerular capillaries made of fenestrated endothelial cells (open windows)

• high pressure and large surface area increases filtration efficiency

• small molecules move down pressure gradient across filtration membrane

glomerular blood pressure

filtration rate mainly dependent on BP

• afferent arterioles: short, large diameter

• efferent arterioles: smaller diameter

therefore high rate of blood flow into glomerulus, low rate out of glomerulus

glomerular filtration rate (GFR)

indicator of kidney function: volume of filtrate produced by all the glomeruli in both kidneys per minute

• Intrinsic mechanisms (renal autoregulation) maintain stable filtration under normal conditions.

• Extrinsic mechanisms prioritize systemic blood pressure and survival during emergencies, sometimes at the cost of kidney filtration

Intrinsic renal mechanisms

alter blood volume

• increased blood pressure + renal blood flow increase water + sodium excretion (urine production)

• two mechanisms:

  • pressure diuresis

    • high pressure

      → more filtrate formed

      → more urine formed 

  • pressure natriuresis

    • sodium excretion:

      • filtrate is formed faster and pushed through nephron faster

      • not much time for sodium reabsorption

      • electrolytes remain in filtrate and water follows and remains so more urine formed

hormones regulating the reabsorption in distal convoluted tubule and collecting duct

• Aldosterone

• ADH

• ANP

• Parathyroid hormone (PTH)

anti-diuretic hormone

• Hypothalamic neurons called osmoreceptors monitor solute concentrations in the blood

• If blood becomes too concentrated OR if BP is low:

  • ADH released by posterior pituitary

  • Targets collecting ducts (via cAMP system)

  • Water reabsorbed from filtrate

ACE

• Angiotensin Converting Enzyme (RAAS system)

  • Angiotensin I → Angiotensin II

  • ALSO: Bradykinin → inactive metabolites

    • ACE inhibitors lead to the accumulation of bradykinin in lungs → cough

• found in endothelial cells of all tissues

• AI → AII primarily converted in the lungs (due to their dense vasculature and high ACE expression)

RAAS system

aldosterone

• regulates amount of Na+ reabsorption (Na+ decrease = aldosterone release)

• Zona Glomerulosa in adrenal cortex releases aldosterone in response to

  • Decreased blood volume or BP

  • renin-angiotensin system

  • Angiotensin II

  • Increased Potassium

  • Adrenocorticotropic hormone

  • Atrial natriuretic peptide

• action: DCT (distal convoluted tubule) and collecting duct

  • Increases blood volume

    • Na+ reabsorption

    • Water reabsorption

    • K+ & H+ excretion

atrial natriuretic peptide

• secreted by specialized cardiac muscle cells in the atria

  • triggered by increased BP

• Inhibits the renin-angiotensin system and release of aldosterone

• Inhibits Na⁺ and water reabsorption

• ↓ blood volume and BP

Antidiuretic hormone (ADH)/vasopressin

• secreted by posterior pituitary after

  • increased osmolality of bodily fluids

  • decreased volume and pressure of vascular system

• increases permeability of collecting ducts to:

  • water (primary action) (via aquaporins)

  • urea (accumulates with NaCl - adding to osmotic gradient)

• stimulates reabsorption of NaCl by thick ascending limb of Loop of Henle, DT and collecting duct

Synthesised in the hypothalamus
- paraventricular nucleus
- supraoptic nucleus
➢ Released from the posterior pituitary
➢ Acts on
➢ V2 receptors in the kidney induce water retention
➢ V1 receptors on blood vessels cause vasoconstriction
➢ Antidiuretic effect
Increases water permeability in distal convoluted
tubule and collecting ducts (by increasing number of
water channels (aquaporins)

how is ADH triggered to release

• 1% rise in osmolality can significantly increase ADH secretion

  • detected by osmoreceptors in hypothalamus

• 10% drop in blood volume stimulates low pressure baroreceptors (atria and veins) to send signals to release ADH

• signal sent to synthesising cells located in hypothalamus:

  • supraoptic nuclei

  • paraventricular nuclei

• released from posterior pituitary

actions of ADH

• V1 receptors on blood vessels cause vasoconstriction

• V2 receptors in the kidney induce water retention

  • Increases water permeability in distal convoluted
    tubule and collecting ducts (by increasing number of water channels (aquaporins)

ATP binds to

P2X receptors (pyronergic)

Adenosine binds to

A1 receptors