Neuronal + Hormonal control of blood pressure

Question 1

what is blood pressure + how do we calculate it?

Answer 1

blood pressure= Force per unit area exerted by blood on arterial walls - pressure exerted by circulating blood on artery walls

blood pressure= systemic vascular resistance(aka TPR) x cardiac output

BP= TPR x CO

n.b. systemic vascular resistance (SVR)= total peripheral resistance (TPR)

Question 2

what factors determine the following:
* cardiac output (CO)
*Systemic Vascular resistance (SVR)/ Total Peripheral resistance (TPR)

Answer 2

CO
* stroker volume/volume status
* heart rate (HR)
* cardiac contractility

Systemic Vascular Resistance
*blood vessel length
*arterial smooth muscle tone
* arterial cross-sectional area (Poiseuille’s law= as radius of tube decreases the resistance to flow increases– by the fourth power)
*blood viscosity

Question 3

in the neural control of blood pressure is mediated via the autonomic nervous system; which branch are the following innervated :
* heart
*blood vessels
*kindeys
*adrenal glands

Answer 3

• Heart (parasympathetic + sympathetic innervation)
• Blood vessels (mainly sympathetic innervation)
• Kidneys (sympathetic innervation)
• Adrenal glands (sympathetic innervation)

Question 4

what is orthostatic hypotension

Answer 4

Orthostatic hypotension — also called postural hypotension — is a form of low blood pressure that happens when standing after sitting or lying down. Orthostatic hypotension can cause dizziness or lightheadedness and possibly fainting

Question 5

where are the sensors for neural control of blood pressure located?

Answer 5

The primary sensors for the neural control of blood pressure = baroreceptors these communicate with the brainstem. Baroreceptors are specialized neurons that detect changes in blood pressure and are located in both:

Carotid Sinuses: These are located in the internal carotid artery right after the bifurcation of the common carotid artery; the walls of the carotid arteries, which are the main arteries supplying blood to the brain. The carotid sinuses are sensitive to changes in the arterial blood pressure of the blood going to the brain.
n.b. sensory innervation of the carotid sinus is the carotid branch of CN IX (glossopharyngeal nerve)

Aortic Arch:There are also baroreceptors located in the aortic arch, the part of the aorta that bends between the ascending and descending aorta. These receptors are sensitive to the blood pressure of the blood being pumped out of the heart to the rest of the body.
n.b. aortic arch is innervated by vagus nerve (CN X)

Question 6

• walls of carotid sinus contain sensory endings of carotid sinus nerve– these ending are sensitive to [__________] (altered by blood pressure) in sinus wall

N.B. BP= BLOOD PRESSURE

Answer 6

• walls of carotid sinus contain sensory endings of carotid sinus nerve– these ending are sensitive to stretch (altered by blood pressure) in sinus wall

*continuous baseline train of action potentials present in nerve fibres; increases in frequency during systole, decreases in frequency during diastole– i.e. in response to increased BP (increased firing=sympathetic) and decreased BP (decreased firing =parasympathetic)

Question 7

Where do those sensory (afferent) nerves (from the baroreceptors) go with their info about blood pressure?

Answer 7

Where do those sensory (afferent) nerves go with their info about blood pressure?
nucleus of solitary tract (NuTS) found in brainstem specifically posterior aspect of medulla

Question 8

Describe the neural control of blood pressure

Answer 8

Baroreceptors in ARTERIES THEMSELVES is -ve feedback system - vasomotor centre contains “set point” for BP at ~ 120/80 mmHg

• NuST(nucleus of the solitary tract) is integrating centre - gets afferents from baroreceptors in aortic arch and carotid sinus
• NuST projects to rostral ventrolateral medulla (RVLM) and the caudal ventrolateral medulla (CVLM) to the nucleus ambiguus
• RVLM is where bodies of SNS located - increase SNS output to heart and peripheral vasculature
• CVLM is where bodies of PSNS located - basically vagus (CN X)
  *The NuST will increase the activity of one centre and decrease the other depending on what it wants to do to the blood pressure!

If baroreceptor firing rate too low (not stretched enough) - indicates BP too low
* NuST must increase BP - does this by signalling RVLM to increase SNS activity, causes:
* Arteriolar vasoconstriction - raises TPR (through alpha-adrenoceptors)
* Increases HR and cardiac contractility - increases CO
* Increases venous constriction - increases blood return to heart (preload) therefore increased SV so increased CO
*Inhibits nucleus ambiguus

If baroreceptor firing rate too high (too much stretch) - indicates BP too high
* RVLM inhibited - reduced SNS outflow
* Reduced HR and cardiac contractility - decreases CO
* Relaxation of arterioles - reduces TPR
* Lowers BP back to set level
* Baroreceptor afferents also have excitatory influences on nucleus ambiguus in CVLM - aka cardioinhibitory centre - increases vagal output to heart
* Vagus acts on SA node to slow down HR and reduce CO - reduced CO leads to reduced BP
*PSNS don’t affect peripheral vascular resistance
* parasympathetic outflow arising from the nucleus ambiguus and dorsal motor nucleus of the vagus nerve acts to decrease cardiac activity in response to fast increases in blood pressure

Question 9

what enzyme secreted by the kidneys cleaves angiotensinogen into angiotensin I?

Answer 9

Blood pressure falls - kidneys secrete renin which cleaves angiotensinogen (peptide made by liver) into angiotensin I

Question 10

what is the role of the RAAS system?

Answer 10

RAAS= the Renin-Angiotensin-Aldosterone System; regulates blood pressure

• Blood pressure falls - kidneys secrete renin which cleaves angiotensinogen (peptide made by liver) into angiotensin I; then angiotensin converting enzyme (which lives in lungs) converts angiotensin I into angiotensin II
• Angiotensin II is most potent vasoconstrictor body makes
• Angiotensin II binds to angiotensin receptors and acts on arteriole smooth muscle to vasoconstrict them; this increases SVR/TPR
• Angiotensin II also acts on adrenal glands to secrete more aldosterone which increases Na+ reabsorption which also brings water in
  *K+ gets excreted as a result

Question 11

blood enters glomerulus (capillary network) of each nephron in afferent arteriole- 20% of blood plasma is filtered through glomerulus + enters the Bowman’s capsule which empties into proximal tubules of nephron. Remaining 80% leaves in efferent arteriole.

which ateriole has a larger diameter and why?

Answer 11

blood enters glomerulus of each nephron in afferent arteriole- 20% of blood plasma is filtered through glomerulus + enters the Bowman’s capsule which empties into proximal tubules of nephron. Remaining 80% leaves in efferent arteriole.

Afferent arterioles have a larger diameter than efferent arterioles- considerable drop in pressure between afferent + efferent arteriole- filtration pressure driving fluid through capillary endothelium into capsular space then to proximal convoluted tubule

Question 12

• how does angiotensin II increase glomerular filtrate rate?

Answer 12

Angiotensin II increases glomerular filtration rate - acts on afferent/efferent arteriole
* Angiotensin II constricts efferent arteriole (vasoconstriction) more than afferent due to their being more angiotensin II receptors in the efferent arteriole - so efferent arteriole width of vessel decreases (more than afferent)- efferent vasoconstricting + decreasing blood flow so there is greater pressure at glomerulus.
* Angiotensin II increases blood pressure, therefore increasing blood flow to kidneys, therefore increases GFR
*Increases TPR (total peripheral resistance)

Question 13

what is the function of the macula densa cells

Answer 13

macula densa cells are specialized cells line the distal convoluted tubule; specifically at the point where the tubule contacts the glomerular arterioles (the afferent and efferent arterioles){this point is called juxtaglomerular apparatus}. Function of macula densa:

• sense the amount of sodium in the distal convoluted tubule

*Regulating Glomerular Filtration Rate (GFR)

• When they detect low sodium levels, macula densa cells can stimulate the juxtaglomerular cells (located in the afferent arteriole) to secrete renin. Renin is an enzyme that initiates a cascade leading to the production of angiotensin II, which ultimately increases blood pressure

Question 14

what is tubulo-glomerular feedback?

Question 15

what does eGFR actually measure?

Answer 15

estimated Glomerular filtration rate (eGFR) is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the glomeruli each minute

*remember a lot of factors effect GFR: sex, race, age!

Question 16

what are the 3 factors that affect SVR (systemic vascular resistance aka TPR- total peripheral resistance)

Answer 16

3 factors which affect SVR/TPR:
* blood viscosity
vessel length**; the longer the vessel, the greater the resistance and the lower the flow
**vessel diameter {greatest effect}

Question 17

*what are the vascular effects of angiotensin II?

*what are the renal effects of angiotensin II

*what are the neural effects of angiotensin II

Answer 17

vascular effects:

*angiotensin II acts on G-protein coupled receptor 1 that activates phospholipase C and increases cytosolic Ca2+ concentrations= this triggers constriction of smooth muscle of systemic arterioles= raising the systemic vascular resistance (aka PVR peripheral vascular resistance/TPR total peripheral resistance)= INCREASES BLOOD PRESSURE

*angiotensin II constricts the arterioles.. this reduces water coming in.. so hydrostatic pressure in capillaries decreases.. this means more water to move in to blood from tissues= increase CIRCULATING BLOOD VOLUME

renal effects
* angiotensin II acts directly on nephron proximal convoluted tubule cells to increase sodium reabsorption by stimulating Na+/H+ antiporter activity and Na+/K+ activity= this increased Na+ level increases blood osmolarity leading to shift of water/fluid into plasma volume= increased blood volume= increased blood pressure

*angiotensin II acts on adrenal cortex through angiotensin receptor 1 causing increase aldosterone release = aldosterone increases Na+ reabsorption in distal convoluted tubule {does this by stimulating ENACS/ epithelial channel proteins}= water follows Na+= increase water= increase blood volume= increase blood pressure

neural effects
* angiotensin II acts on posterior pituitary gland and increases the secretion of ADH= ADH acts on distal convoluted tubules (DCT) + collecting ducts(CD). ADH acts through a G-protein coupled receptor to increase transcription + insertion of aquaporin 2 channels to apical membrane of DCT + CD cells increasing their permeability to water= increasing water reabsorption= increased blood volume= increased blood pressure.
n.b. more ADH= more conc urine..

*stimulates thirst (angiotensin II) acts on hypothalamus to tell u to drink more water as wants to increase BP

*angiotensin II acts of symapthetic nervous system (SNS) to facilitate release of noradrenaline/norepinephrine to stimulate increased blood pressure..increased heart rate

Question 18

what is the difference between a symporter and an antiporter?

Answer 18

Proteins that move two molecules in the same direction across the membrane are called symports (also called synporters, synports, or symporters). If two molecules are moved in opposite directions across the bilayer, the protein is called an antiport (e.g. Na+/K+ ATPase antiporter and Na(+)/H(+) antiporter). Proteins involved in moving ions are called ionophores

n.b. transmembranal Na(+)/H(+) antiporters transport sodium (or several other monovalent cations) in exchange for H(+) across lipid bilayers in all kingdoms of life.

Question 19

the sympathetic nervous system (SNS) has a direct influence on renin release.. how?

Answer 19

*Renin release from the renal juxtaglomerular cells (JG) is stimulated by the SNS via beta 1-adrenoceptors.

*intrarenal baroreceptors within afferent arterioles- juxtaglomerular cells are innervated by these sympathetic nerve fibres

*activation of renal sympathetic nerves increases release of renin through beta-adrenergic receptors– activated by decreased renal perfusion

*reduced sympathetic nerve activity will diminish renin secretion

Question 20

what is hyponatremia + its cause + causes

Answer 20

hyponatremia= low sodium levels in blood plasma. Hyponaetremia decreases osmotic pressure of plasma; if osmotic pressure low plasma water moves out of blood into extravascular interstitial space in tissues= tissue swells + blood volume shrink

*circulating blood volume is partly controlled by Na+ plasma levels cuz water follow Na+

mild hyponatremia causes: fatigue, confusion, muscle weakness + cramps

severe hyponatremia causes: rise in intracranial pressure because cells SWELL (cerebral oedema)= nausea, vomiting, headache, spasms, restlessness, irritabilty and if prolonged seizures, coma + death

Question 21

what are the pharmacological treatments for elevated blood pressure (hypertension)

Answer 21

hypertensive meds usually target the RAAS system:

drugs that target reinin-angiotensin system:
* ACE inhibitors; Angiotensin-converting enzyme (ACE) inhibitors (e.g. enalopril) are medicines that help relax the veins and arteries to lower blood pressure. These block angiotensin converting enzyme + thus prevent formation of angiotensin II

• Angiotensin receptor antagonists (e.g. losartan) these block angiotensin receptors

drugs that target renin-angiotensin-aldosterone system: diuretics

• thiazide derivatives e.g. bendroflumethiazide; these block sodium-chloride symporter in the distal tubule (not the ENAC channels)
  aldosterone antagonist** e.g. spironolactone
  **loop diuretics

Question 22

what is angioedema?

Answer 22

angioedema= increased fluid in submucosa (interstitial space) causing swelling

causes:
severe allergic reaction
=elevation of bradykinin; ACE inhibitors can induce elevation of bradykinin if patient has this angioedema the warning sign is a persistent cough u have to stop the meds immediately and put them on an angiotensin II receptor antagonist instead of the ACE inhibitor

n.b. ACE inhibitors are therefore not the first line drugs for treating hypertension in Afro-caribbean patients UNLESS they also have diabetes mellitus{renal protective effects}

Question 23

when there’s low sodium; low blood pressure; renal stenosis; poorly controlled diabetics have high levels of glucose in blood which can trigger disrupt of basement membrane of glomerulus (sometimes this can cause blood in urine) what does this trigger in body?

Answer 23

all of these factors cause low blood pressure which all of these factors lead to activation of RAAS system

as macula densa cells sense low sodium in the distal tubule; as DCT is pressing against macula densa cells (stretch sensitive baroreceptors) this triggers SNS activation of beta adrenoceptors to stimulate JG cells to release renin

Question 24

why do diabetics have glucose in urine?

Answer 24

glycosuria because there either isn’t enough insulin, or your body can’t use what’s available. WIthout insulin, blood glucose levels become too high, and your kidneys can’t filter and reabsorb it.