Week 4 - Control of BP Flashcards
What are the 4 mechanisms of long-term control of blood pressure?
- Renin-Angiotensin-Aldosterone-System
- Sympathetic Nervous System
- Anti-Diuretic Hormone
- Atrial Natiuretic hormone
Where is renin released from? What 3 mechanisms stimulate its release?
- Granular cells of JGA
1) Reduced NaCl in DCT detected by MD ->Cause afferent arteriole to release PGs ->PGs cause granular cells to release renin
2) Reduced perfusion pressure detected by baroreceptors in afferent arteriole
3) Sympathetic stimulation of JGA
What is angiotensinogen and where is it made?
- Precursor
- In the liver at a constant rate
Where is angiotensin I in high conc?
-Lungs
What are the functions of angiotensin II?
- Stimulates aldosterone production from adrenal cortex
- Stimulates Na resorption in PCT (stimulate NHE)
- Stimulates vasoconstriction of afferent and efferent arteriole to decrease GFR and thus decrease excretion
Describe the pathway of aldosterone stimulation by RAAS
- Angiotensinogen->Angiotensin I by renin
- Angiotensin I ->Angiotensin II by Angiotensin Converting Enzyme
- Angiotensin II stimulates aldosterone
What is the aim of RAAS?
-To increase BP by increasing fluid volume
What is the main angiotensin II receptor? What type of receptor is it?
- AT1
- GPCR
Describe the actions of aldosterone on the kidney
- Acts on principle cells of collecting duct and stimulates Na and thus water resorption
- Increases expression of ENaC and NaKATPase and apical K channel
How does aldosterone reach the priciple cells?
-Can diffuse directly through cell membrane as steroid hormone
Why does an ACE inhibitor cause a dry cough?
-Decreased bradykinin in lungs as ACE breaks it down
What is bradykinin?
-Vasodilator
Explain how the sympathetic nervous system stimulates renin release from JGA
- In response to low bp, High levels of sympathetic stimulation reduces renal blood flow via vasoconstriction of the arterioles
- This causes a decrease in GFR and thus a decrease in the filtration fraction
- This causes less Na to be delivered to DCT which is detected by MD of JGA
- MD causes afferent arteriole to release prostaglandins which cause vasodilation and stimulates the release of renin from granular cells
In what 3 ways does the sympathetic nervous system reduce Na excretion
- Directly acts on PCT to activate NHE and NaKATPase
- Causes vasoconstriction of afferent arteriole to reduce GFR -> reduced Na Excretion
- Stimulate Renin release from JGcells
How does antidiuretic hormone act as a long-term regulator of BP?
-ADH stimulates Na resorption in thick ascending limb through NKCC2
How does atrial natiuretic peptide act as a long-term regulator of BP?
- ANP acts to reduce bp by promoting Na excretion and thus water excretion
- ANP (which is sythesised and stored in atrial myocytes) is released from atrial cells in response to stretch -> Increased blood volume -> increased SV -> increased stretch
- When corculating vol reduced -> less stretch -> less ANP released
- ANP acts as a vasodilator of afferent arteriole which increases renal perfusion = increased GFR = increased excretion
- ANP also inhibits Na reabsorption along the nephron
What is the general action of prostaglandins?
-Vasodilator
What effect do NSAIDs have on prostaglandins?
-Inhibit cyclo-oxygenase pathway involved in prostaglandin synthesis -> decreased PGs
What is the danger of adminstering NSAIDs in Acute Kidney Injury?
-Further increase the injury by inhibiting PGs and causing a reduction in renal blood flow -> decreases GFR further
What effect does dopamine have on the BP?
- Dopamine formed locally in the kidney from L-DOPA
- Acts on dopamine receptors on renal BVs and cells of PCT and TAL
- Causes vasodilation and increases renal blood flow
- Causes reduces reabsorption of NaCl by inhibiting NHA and NaKATPase
What is hypertension?
-Sustained increase in BP over 140/90
What is primary hypertension?
-Hypertension with no definitive cause
What is secondary hypertension?
-Hypertension secondary to disease eg cushings, chronic renal disease
How does renovascular disease cause hypertension?
- Occlusion of renal artery/renal artery stenosis causes a fall in perfusion pressure
- Decreased perfusion leads to an increase in renin
- Increase in renin results in an increased aldosterone
- Increased Na and Water reabsorption -> Hypertension
What is Conn’s syndrome?
-Hypertension and hypokalaemia caused by an aldosterone secreting adenoma
Why does pheochromocytoma cause hypertension?
- Excess production of NA and A
- Increased action of sympathetic nervous system
- Increased vasoconstriction -> Hypertension
What is the eqn for calculating BP? What is the eqn for calculating CO?
- CO x TPR
- CO=SV x HR
How is hypertension treated pharmacologically?
- ACE inhibitors
- AngIIR antagonists
- Thiazide Diuretics or Spironolactone
- L-Type Ca Channel blockers
- a1-receptor blockers
- b-blockers if previous MI
How do L-type Calcium Channel blockers reduce hypertension?
- Reduce Ca entry into vascular smooth muscle of cells
- Relaxation of vascular smooth muscle
How do a1-receptor blocers decrease hypertension?
-Reduce sympatheric tone by blocking NA
Describe non-pharmacological approaches to treating hypertension
- Diet
- Exercise
- Stop smoking
- Reduce alcohol intake
- Reduced Na intake
What is the short-term regulator of BP? Explain it
- Baroreceptor reflex
- Baroreceptors are stretch receptors located in aortic arch and the carotid which adjust symp and parasymp input to the heart to alter CO and adjust symp input to vessels
- They are sensitive to pressure. Increased pressure on the receptors causes increased signals to be sent to the medulla -> increased parasympathetic input -> decreased CO and TPR
- Decrease in blood pressure decreases signals sent to medulla -> decreased parasymp and increased symp (if needed) and vasoconstriction occurs
