Blood Pressure and the Kidneys

Question 1

How is blood volume linked to blood pressure?

Answer 1

If we accept that by adjusting the amount of sodium in the body and relying on the sodium to bring water with it thereby increasing the blood volume
If the ECF is increased, via Starling forces, this would increase the plasma volume which would distribute into the venous portion of the circulation, increasing venous return
Increased venous return to the heart increases the amount of filling of the chambers
In particular the increase in ventricular filling, the increased stretch would lead to a more forceful cardiac ventricular contraction via Starling’s law, increasing CO
Cardiac output is related to the mean arterial blood pressure so increased CO increases BP

Question 2

How is ECF volume sensed?

Answer 2

Suppose there is a change in the amount of sodium, there will also be a change in ECF volume
The sensors are:
Arterial stretch receptors- activated by increased atrial stretch when venous return increases
Arterial baroreceptors- located in the aortic arch and carotid arteries, increase firing rate as pressure rises and vice versa
Afferent arteriole of the nephron
NaCl delivery to DT
The effector systems are:
RAAS- sodium-retaining
ANP- sodium-excreting

Question 3

What is the renin-angiotensin-aldosterone? What does it do?

Answer 3

The macula densa senses changes in sodium, and via paracrine signalling, they influence the juxtaglomerular apparatus (on the afferent arteriole) which secretes renin
RAAS is activated by:
Reduced renal perfusion
Increased sympathetic activity
Both interpreted as a fall in blood volume
Renin is part of a cascade, catalyses a conversion of a precursor made by the liver, angiotensinogen to angiotensin I
Angiotensin I is converted to angiotensin II by and enzyme called ACE
Angiotensin II is a vasoconstrictor, it stimulates the adrenal cortex to increase aldosterone secretion which increases sodium reabsorption
Aldosterone secretion is increased by
RAAS
Increased plasma [K+]

Question 4

How is renal Na excretion controlled?

Answer 4

Most of the filtered salt and water is reabsorbed in the PT – this fraction increases with RAAS activity
Much smaller, variable fraction reabsorbed from DT and CD
Reabsorption of Na and solute-free water are separated
Aldosterone-mediated Na reabsorption increases plasma osmolarity, which is then adjusted by pure water reabsorption via ADH system
Result is increased Na and water in ECF with little or no change in plasma [Na] or osmolarity

Question 5

What is the effect of aldosterone on principal and intercalated cells?

Answer 5

Acts on principal cells lining CD:
Increases Na/K ATPase
Increases expression of ENaC channels on luminal membrane 
Resulting in
Increased Na+ reabsorption
Increased K+ secretion
Acts on intercalated cells of CD:
Increases H+ ATPase
Resulting in 
Increased H+ secretion
Increased HCO3- reabsorption

Question 6

What are the defences against volume depletion?

Answer 6

RAAS
Normal, continuous adjustment of Na excretion and ECF volume
Can reduce Na excretion to very low levels in hypovolemia​
ADH
Last line of defence against volume depletion
Non-osmotic ADH secretion if BP drops by ≈ 10-15%
RAAS is already fully activated

Question 7

What are the different types of hypertension?

Answer 7

Hypertension present when:​
Systolic > 140 mmHg and/ or diastolic > 90 mmHg​
Classified as:
Secondary (Identifiable cause ~ 5 - 10 % of cases )​
Essential (Unknown cause, > 90 % of cases)​

Question 8

What is Liddle’s syndrome?

Answer 8

Rare, genetic gain-of-function mutation in epithelial sodium channel (ENaC) where it is hyperactive/over-expressed 
↑ renal Na retention
↑ECVF 
↑ BP
Low renin
Low aldosterone​

Question 9

What is Conn’s syndrome?

Answer 9

Primary hyperaldosteronism
Often due to adenoma of adrenal cortex 
↑ renal Na retention
↑ECVF 
↑ BP
↓ plasma [K]
Low renin
High aldosterone​

Question 10

What is renal artery stenosis?

Answer 10

Abnormal narrowing of the blood vessel through the blockage
Reduced blood flow to the stenotic kidney
Increased renin secretion
The renin would then cause the usual RAAS cascade as well as increase vasoconstriction increasing blood pressure (from Ang2), and increased aldosterone and Na retention which also causes high blood pressure
So there is an over-activation of RAAS
This will also affect the other kidney to oppose this so different levels of aldosterone and renin

Question 11

How can Addison’s disease be linked to adrenal failure?

Answer 11

Progressive failure of adrenal cortex
Insufficient cortisol
Insufficient aldosterone
Eventually adrenal crisis – fatal if not treated
Lack of cortisol and aldosterone
Presenting with:
Hypotension
Hypovolemia 
Hyperkalaemia 
Hyponatremia