Hormonal Control of Blood Pressure Flashcards
What did Harry Goldblatt notice in post-mortems in 1934? What did this lead him yo discover?
Narrowing of the renal (kidney) blood vessels in patients who had died of hypertension.
This made him think “Could renal ischemia cause hypertension??”
He did experiments where he constricted the major renal arteries of dogs using a home-made adjustable silver clamp.
Partial constriction of both renal arteries resulted in a reproducible and persistent rise in blood pressure.
Goldblatt’s explanation for this rise in blood pressure was that the ischemic kidneys produced an “internal secretion” that caused hypertension.
Goldblatt’s discovery was spectacular, but nobody believed it at first
The scepticism was largely because of the technical difficulty of Goldblatt’s procedure, which few could reproduce.
However Goldblatt was proved right in 1939 when the identity of the “internal secretion” as the enzyme renin was confirmed.
Goldblatt was nominated in 1940 for a Nobel Prize for his work, but unfortunately the war intervened and he never received a prize.
What is hormonal control of blood pressure mediated by?
The kidney
Where does the main renal artery go as it enters the kidney? Where do these vessels terminate?
Divides into interlobar vessels
These divide into small arcuate (arch-shaped) arteries in the renal cortex
The arcuate arteries terminate in a little clump of capillaries in the cortex called a glomerulus
What is each capillary glomerulus enclosed in?
Each capillary glomerulus is enclosed inside a bag of tissue called BOWMAN’S CAPSULE. The first stage of urine formation is the filtering of plasma from the glomerular capillaries into the space of the capsule
Where does blood enter the glomerulus of each nephron? Where does it leave?
About 20% of the blood plasma is filtered through the glomerulus and enters the capsular space which empties into the proximal tubule.
The remaining 80% leaves in the efferent arteriole
What does the difference in diameter between afferent and efferent arterioles cause?
Afferent arterioles have larger diameters than efferent arterioles, so there is considerable drop (???) in pressure between afferent and efferent arteriole.
This is the filtration pressure driving fluid through the endothelium of the capillaries into the capsular space
Where do water and electrolytes from the plasma pass through?
They pass into the proximal (convoluted) tubule and through other parts of the kidney [discussed in a later lecture] to reach the distal (convoluted) tubule.
What does a part of the distal tubule contact?
The point where the afferent and efferent arterials enter the glomerulus.
What do the afferent and efferent arterioles, together with the distal tubule, form?
The juxtaglomerular apparatus (JGA)
What cells line the distal tubule at the JGA? What do these cells control?
Special epithelial cells called the macula densa
These macula densa cells control the activity of a second set of specialised epithelial cells, the juxtaglomerular cells
How is the proportion of plasma water filtered into the proximal tubule (glomerular filtration rate or GFR) kept constant?
By a process linking sodium concentration in the distal tubule fluid to vasoconstriction or dilation in the afferent arterioles; this is called tubuloglomerular feedback
How does tubuloglomerular feedback maintain a constant glomerular filtration rate?
Sodium is absorbed at a fixed rate from the fluid filtered into the proximal tubule.
Thus a low sodium level in the distal tubule may be an index of a low glomerular filtration rate:
Because a fixed amount of sodium is being removed by uptake from the proximal tubule per minute, if the amount of sodium delivered to the tubule per minute in filtered fluid decreases (due to reduced filtration) then less sodium is left in the fluid reaching the distal tubule.
A low sodium concentration in the distal tubule triggers relaxation of the vascular smooth muscle of the afferent arteriole.
This increases the pressure in the glomerulus, increases filtration and thus increases delivery of sodium to the tubule.
What else could a low sodium level in the distal tubule indicate? What does this cause?
A low sodium level in the distal tubule could also indicate a low concentration of sodium in the arterial blood.
When the sodium concentration in the distal tubular falls below a certain threshold, as well as initiating tubuloglomerular feedback the macula densa cells activate the juxtaglomerular cells to release the enzyme renin into the blood stream
What happens to the renin released from the juxtaglomerular cells?
It passes into the venous blood, where it reacts with a globular protein angiotensinogen secreted by the liver.
Renin enzymically splits off a decapeptide angiotensin I from the angiotensinogen precursor.
What happens when angiotensin I passes through the lungs?
It is further cleaved by endothelial-bound angiotensin-converting enzyme (ACE) into an octapeptide angiotensin II
What happens when angiotensin II passes into the arterial blood?
In the arterioles it acts on a G-protein coupled receptor Angiotensin receptor 1 (AT1r) which activates phospholipase C and increases the cytosolic Ca2+ concentrations, which in turn triggers constriction of the smooth muscle of systemic arterioles.
What is the overall function of renin, via its product angiotensin II?
It raises total peripheral resistance and afterload, and thus, assuming a constant cardiac output, raises blood pressure
What is circulating blood volume partly controlled by?
Plasma sodium concentration
What are normal serum levels? What happens if they are below this?
Between approximately 135 and 145 mmol/L
If blood plasma levels are below 135 mmol/L, this is hyponatremia
What does low blood sodium cause?
Decreases the osmotic pressure of plasma
This osmotic pressure keeps water in the blood and if low it allows plasma water to move out of the blood into the extravascular interstitial space in tissues.
The tissues swell and the blood volume shrinks
What can mild hyponatraemia cause? What about severe?
Mild hyponatremia can cause: o Loss of energy and fatigue o Confusion, Muscle weakness, Severe hyponatremia: o is serious as it can cause a rise in intracranial pressure this leads to Nausea and vomiting, headache, Spasms o Restlessness and irritability o If prolonged, Seizures & Coma
How does angiotensin stimulate sodium reabsorption from tubular fluid?
Angiotensin II receptors are found on cells in the adrenal cortex as well as vascular smooth muscle.
These cells secrete the mineralocorticoid steroid hormone aldosterone into the bloodstream.
Aldosterone stimulates epithelial channel proteins (ENACs) in the epithelial cells lining the walls of the distal tubule downstream from the juxtaglomerular apparatus.
These channel proteins take up sodium from the fluid in the distal tubule and pump it back into the interstitial fluid.
The increased sodium reabsorption in the interstitial space passes down its concentration gradient into the renal venous blood
How does low blood sodium decrease blood volume?
If plasma sodium levels are low, low osmotic pressure (OP) means water is lost from blood due to hydrostatic pressure (HP) as it passes through capillaries: circulating blood volume is reduced
What happens to fluid exchange in normal state? What about in decreased plasma sodium concentration? And increased plasma sodium concentration?
Normal state: water flows out of initial part of capillary where HP>OP and back in at end where OP>HP ; no change in blood volume at end of capillary
Decreased plasma sodium concentration: more water flows out of initial part of capillary due to decreased osmotic pressure; this is not compensated by inflow of water in final part of capillary: net loss of water from blood
Increased plasma sodium concentration: less water flows out of initial part of capillary due to increased osmotic pressure, more water flows back in in later part of capillary; net gain of water into blood
