Flashcards in Renal Control Of Blood Pressure And CO Deck (38):
What is used for short term control of BP? How does it work?
Nerve endings are sensitive to stretch caused by increased arterial pressure
Send signal along afferent pathway to medulla
Signals down efferent pathway adjust sympathetic input which adjusts TPR
Adjusts sympathetic and parasympathetic inputs to heart to alter cardiac output
Where are baroreceptors found?
How is the sympathetic NS used in long term renal control of BP?
High levels of sympathetic stimulation reduce renal blood flow by vasoconstriction (α1 receptor)
Decrease in GFR -> decrease in Na+ excretion
Activates apical Na-H exchanger and NaKATPase in PCT
Stimulates renin release
What are the ways for long-term control of BP?
Sympathetic nervous system
What does atrial natriuretic peptide (ANP) do?
Promotes Na+ excretion
Causes vasodilatation of afferent arteriole, increasing GFR
Inhibits Na reabsorption along the nephron
Where is ANP synthesised and stored?
What causes release and inhibition of release of ANP?
Stimulates release - Stretch
Inhibits release - low pressure volume sensors in atria detect reduced effective circulating volume (reduced filling of the heart)
Where is renin released from?
Granular cells of juxtaglomerular apparatus
What causes release of renin?
Reduced perfusion pressure in the kidney which is detected by baroreceptors in the afferent arteriole
Decreased NaCl concentration at the macula densa (due to low GFR) causes sympathetic stimulation to the JGA, increasing renin release.
Action of renin?
Converts angiotensin to angiotensin I
What receptors does angiotensin II act on?
AT1 (mostly) (GPCR)
Actions of angiotensin II?
Arterioles - vasoconstriction by working on smooth muscle cells, increasing TPR and BP. Also constricts afferent arteriole in kidney
Kidneys - enhanced Na+ reabsorption in PCT by stimulating NaH exchanger
Sympathetic NS - increases release of NA
Adrenal cortex - release of aldosterone
Hypothalamus - increased thirst sensation by stimulating ADH release
Action of aldosterone?
Acts on intracellular receptors
Increases expression of apical Na+ channel (ENaC) and NaKATPase in principal cells of collecting duct
What works against aldosterone?
What stimulates release of ADH
Increases in plasma osmolarity
What is the main role of anti-diuretic hormone?
Formation of concentrated urine by retaining water
Stimulates Na reabsorption
Acts on thick ascending limb to stimulate Na-K-Cl co-transporter (therefore less water can leave thin ascending limb due to less of a gradient)
How is ADH released?
Baroreceptors detect a 5-10% drop in BP
Signals to brain stem via vagus nerve
Modulates sympathetic nerve outflow
Secretion of ADH (and reduction of ANP)
Overall action of ANP?
What do prostaglandins do?
Locally - enhance glomerular filtration and reduce Na reabsorption
Act as a buffer to excessive vasoconstriction by sympathetic NS and RAAS
Important when angiotensin II is high
Overall action of prostaglandins?
Reduce blood pressure
What is pathway involved in the formation of prostaglandins? What can interfere with it?
Cyclo-oxygenase (COX) pathway
When can administration of NSAIDs be dangerous? Why?
When renal perfusion is compromised
They can further decrease GFR
Cause acute renal failure
Due to inhibition of prostaglandins
In heart failure/hypertensive patients, can worsen condition by increasing NaCl and water retention
What is hypertension?
Sustained increase in blood pressure
What is essential hypertension and what proportion of cases does this make up?
Where there is no definable cause
95% of cases
What factors could play a part in essential hypertension?
What are some causes of secondary hypertension?
Renovascukar and chronic renal disease
How can renovascular disease lead to hypertension?
Renal artery stenosis
Fall in perfusion pressure in that kidney
Detected as a low circulating volume
Increased renin production
Activation of RAAS
Vasoconstriction and Na+ retention in other kidney
How can renal parenchymal disease lead to hypertension?
Can cause a loss of vasodilator substances eg prostaglandins and dopamine (earlier stage)
Later stage - Na and water retention due to inadequate glomerular filtration
Leads to volume dependent hypertension
What is Conn's syndrome and how does it lead to hypertension?
Have an aldosterone-secreting adenoma
Causes hypertension and also hyperkalaemia
How does Cushing's syndrome lead to hypertension?
Excess secretion of cortisol
At high concs, acts on aldosterone receptors causing Na and water retention
How can pheochromocytoma lead to hypertension?
It is a tumour of the adrenal medulla
Secretes catecholamines such as NA and adrenaline
What can hypertension lead to?
For treating hypertension, how is the RAAS targeted?
Use of ACE-inhibitors or angiotensin II receptor antagonist
Blocking ang II has diuretic and vasodilator effects
How can diuretics be used to reduce blood pressure and which ones?
Thiazide - reduces circulating volume by inhibiting Na-Cl transporter in distal tubule
Mechanism of action of drug vasodilators?
Block L-type calcium channels
Reduce Ca entry into smooth muscle cells
Relaxation of smooth muscle
Also have alpha-1 receptor blockers which reduce sympathetic tone
How do β blockers work?
Block β1 receptors in the heart to reduce effects of sympathetic output
Reduces heart rate and contractility
What are some non-pharmacological approaches for reducing hypertension?
Reduce Na intake