Hormonal control of blood pressure Flashcards
what are the two systems that regulate blood pressure
- neuronal system - fast acting
- hormonal system - slow acting
what does the juxtaglomerular apparatus consist of
three structures
- afferent arteriole
- efferent arteriole
- distal tubule
what lines the wall of the distal tubule
macula densa cells
what are macula densa cells
- these are the sodium sensors
where are the juxtaglomerular cells
they are around the end of the proximal tubule
what do the juxtaglomerular cells contain
they contain the enzyme renin
what happens when the sodium concentration is too low
- the macular densa cells act via local hormones
- the local hormones cause the relaxation of the smooth muscle of the afferent arterioles this increases the GFR
- they then signal the juxtaglomerular cells which increase the release of renin into the blood stream
- renin released from the juxtaglomeruar cells pass into the Venus blood where it meets the globular protein angiotensinogen
- the renin enzyme splits of a decapeptide called angiotensin I from the angiotensinogen precursor
- when angiotensin I passes through the lungs it is further cleaved by endothelial bound angiotensin-converting enzymes (ACE) into an octave-tide angiotensin II
- angiotensin II passes into the arterial blood in the arterioles and acts on a G protein coupled receptor which activates phospholipase C and increases the cytosolic calcium concentrations which triggers the constriction of the smooth muscle of systemic arterioles therefore increasing the blood pressure
what secretes angiotensinogen
liver
describe the steps of the angiotensinogen pathway
- renin released from the juxtaglomeruar cells pass into the Venus blood where it meets the globular protein angiotensinogen
- the renin enzyme splits of a decapeptide called angiotensin I from the angiotensinogen precursor
- when angiotensin I passes through the lungs it is further cleaved by endothelial bound angiotensin-converting enzymes (ACE) into an octave-tide angiotensin II
- angiotensin II passes into the arterial blood in the arterioles and acts on a G protein coupled receptor which activates phospholipase C and increases the cytosolic calcium concentrations which triggers the constriction of the smooth muscle of systemic arterioles therefore increasing the blood pressure
how does renin increase blood pressure
renin via its product angiotensin II raises the total peripheral resistance and after load
- therefore it assumes a constant cardiac output and raises blood pressure
what are the ways in which renin can be released
- sympathetic activation
- juxtaglomerular cells
How is renin released by sympathetic activation
- there are sympathetic nerves to the kidney via the renal nerve (sympathetic efferent) and there are beta receptors on the juxtaglomerular cells which when stimulated causes renin release
- this means that in addition to the vasoconstriction due to noradrenaline the sympathetic nervous system can produce further vasoconstriction via increased renin and angiotensin release
what receptors do the juxtaglomerular cells have
beta receptors
what type of feedback is renin angiotensin
negative feedback system for hormonal control of blood pressure
how is blood pressure controlled by GFR
- a decrease in blood pressure causes a decrease in GFR which causes renin angiotensin release which raises blood pressure and restores GFR therefore in this case the renin angiotensin acts as a negative feedback loop
what is a problem with the theory that blood pressure is controlled by the GFR
- GFR is autoregulated by the local tubulglomerular feedback
- this means that rises in blood pressure triggered by angiotensin II do not increase GFR unless the blood pressure rise is so high that it is outside the autoregulation range
what is a better theory than blood pressure being controlled by the GFR
better idea is that the renin-angiotensin system is involved in the control of blood volume
- this is because angiotensin receptors are found on cells in the adrenal cortex as well as vascular smooth muscle
- these cells secrete the mineralocorticoid steroid hormone aldosterone in to the blood stream
what is the action of aldosterone
- acts on the channel proteins in wall of of the distal tubule of the kidney
- the channels when stimulated by aldosterone increase reabsorption of sodium from the tubular fluid back into the blood
- this increases water reabsorption by osmosis
- so the net result is a decrease in urinary loss of sodium and water and an increase in circulating blood volume
what is the action of channel proteins in the distal tubule of the kidney
- the channel proteins can take up sodium from the tubular fluids and pump it back into the blood
what is renin release increased by
low sodium in the distal tubular fluid
what causes low sodium in the distal tubular fluid
low sodium int he arterial blood which is called hyponatremia
what happens if blood levels of sodium are low
- the renin-angiotensin-aldosterone system acts to increase sodium reabsorption in the kidney which restores the level to normal
- as sodium is reabsorbed water follows by osmosis and so both water and sodium are retained in the body and the blood volume increases
- this is a negative feedback system for control of blood volume
why does the renin angiotensin aldosterone (RAA)
- if the blood pressure is too low water can move from the interstitial spaces into the blood as the blood passes through the capillaries
- this dilutes the blood and cause hyponatremia
- by raising the systemic blood pressure the renin-angiotensin-aldosterone system pushes the water back into the interstitial space where it belongs and restores the balance between plasma and interstitial water
what is the overall RAA effect on sodium reabsorption
- overall by mainpulating sodium reabsorption and blood pressure the RAA system keeps the interstitial fluid and circulating blood volumes at correct levels and therefore ensures adequate perfusion of all organs
How can the RAA system malfunction
- renal artery or afferent arterioles are narrowed due to atheroma formation
- this reduces the GFR at normal blood pressure so more sodium is absorbed in the proximal tubule this leads to the reduced sodium concentration in the distal tubule
- juxtaglomerular cells release renin, causing a chronically raised systemic blood pressure.
- Excess aldosterone actions will cause excess sodium retention and thus excess total body water.
- The person will have chronic hypertension and excess body water and salt.
what are the drugs used to block hypertension If hypertension Is due to excess renin release
- ACE inhibitors
- angiotensin receptor antagonists
what is the mechanism of action of ACE inhibitors
eg captopril). These block angiotensin converting enzyme and thus prevent formation of Angiotensin II.
name an example of an ACE inhibitor
captopril
what is the mechanism of action of angiotensin receptor antagonists
These block angiotensin receptors
name an example of an angiotensin receptor antagonists
losartan
what are drugs used to reduce hypertension due to excess aldosterone levels
diuretics such as ..
- thiazide derivative
- aldosterone antagonists
- loop diuretics
what is the mechanism of action of Thiazide derivatives
eg bendroflumethiazide) these block a sodium-chloride symporter in the distal tubule (not the Enac channel)
name an example of Thiazide derivatives
eg bendroflumethiazide)
name an example of a aldosterone antagonist
eg spironolactone
what are the adverse effects of ACE inhibitors
Bradykinin is a peptide derived from endothelium- believed to be the cause of dry cough
- bradykinin is converted to inactive metabolites by ACE therefore inhibition of this leads to increased levels of bradykinin which causes a dry cough through bronchoconstriction
- bradykinin may also result in angloedema, this is deem in the subcutaneous tissues
- effect afro0caribbean patents more therefore ACE inhibitors are not the first line of defence for treating these patients
