46) Blood pressure and the kidneys

Question 1

What is osmoregulation?

Answer 1

• Regulation of the amount of water in the body to maintain constant ECF osmolarity

Question 2

What is volume regulation?

Answer 2

• The regulation of ECF volume and is accomplished by regulating the amount of Na+ in the ECF
• This in turn determines the blood volume and in turn determines the blood pressure
• An effective circulating volume is important in effective tissue perfusion
• The amount of Na+ in the ECF determines the volume of the ECF

Question 3

What happens when salt and water are added to the ECF?

Answer 3

• When salt and water are added to the ECF it will be retained within the ECF as Na+ and other electrolytes are unable to cross the cell membrane
• There is also no osmotic gradient as the concentration of salt has stayed the same which means the solution will remain within the ECF
• As a result the ECF volume will expand

Question 4

How does blood volume link to blood pressure?

Answer 4

• An increase in ECF volume will increase volume in the plasma compartment and via Starling’s forces will increase venous return
• This increases the amount of filling that takes place and so with Starling’s law of the heart (increased stretch causes increased contraction) will increase cardiac output
• This increase in cardiac output causes an increase in blood pressure (due to the equation BP = CO x TPR)

Question 5

How is ECF volume determined?

Answer 5

• It is determined by the amount of Na+ in the ECF

- An increase in Na+ will increase ECF and vice versa

Question 6

How is a change in ECF counteracted?

Answer 6

• A change in Na+ intake is balanced out by a change in Na+ output

Question 7

How is amount of Na+ in ECF kept constant?

Answer 7

• A change in Na+ corresponds to a change in ECF which is detected by sensors
• These sensors send an impulse and cause effectors to elicit a change in Na+ and H2O excretion
• Causing Na+ to return back to normal

Question 8

How is ECF volume sensed?

Answer 8

• Atrial stretch receptors
• Atrial baroreceptors
• Afferent arterioles
• NaCl delivery to the DT

Question 9

What effectors respond to change in ECF?

Answer 9

• RAAS: Sodium retaining

- ANP: Sodium excreting

Question 10

How does the Renin Angiotensin Aldosterone System (RAAS) work?

Answer 10

• Renin is produced by juxtaglomerular cells which line the afferent arterioles
• Renin is released into the plasma where it cleaves angiotensinogen (produced by the liver) into angiotensin I
• Angiotensin I is not very active so is further cleaved by Angiotensin Converting Enzyme (ACE) into Angiotensin II and takes place in the lungs
• Angiotensin II is active and can cause vasoconstriction, can mediate thirst and can activate aldosterone secretion from the adrenal cortex which increases Na+ retention

Question 11

What increases renin secretion?

Answer 11

• Reduced renal profusion sensed by mechanoreceptors in the afferent arterioles
• Increased sympathetic activity caused by a decrease in blood pressure
• Decreased NaCl in circulation detected by the macula densa cells

Question 12

What factors decrease renin secretion?

Answer 12

• Increased perfusion pressure

- Increased amount of Na+ in distal tubule

Question 13

How is aldosterone secretion increased?

Answer 13

• RAAS

- Increased plasma [K+]

Question 14

How is Na+ renal excretion controlled?

Answer 14

• Most of the filtered salt and water is reabsorbed in the PT
• The fraction of this reabsorption increases with RAAS activity
• Smaller and variable fractions of Na and water are absorbed from the DT and CD
• In the distal tubule there is selective absorption of Na+ (through aldosterone) and water (through ADH). Hence reabsorption of these components are separate
• Aldosterone-mediated absorption of Na+ increases plasma-osmolarity which is then adjusted by the reabsorption of H2O through ADH.
• This results in increased Na and H2O reabsorption in the ECF with little or no change in plasma [Na] and osmolarity

Question 15

What cells does aldosterone act on?

Answer 15

• Principle cells lining the CD

- Intercalated cells of the CD

Question 16

What are the effects of aldosterone on principle cells?

Answer 16

• Increases Na+/K+ ATPase expression (where Na+ moves out and K+ moves in) and allows for a Na+ electrochemical gradient to form which allows it to be reabsorbed into the cell
• It also increases the expression of ENaC channels on the luminal membrane which provides a pathway for Na+ to move into the cell
• Overall this increases Na+ reabsorption and increases K+ secretion through K+ channels located in the membrane

Question 17

What effects does aldosterone have on intercalated cells in the CD?

Answer 17

• It increases the expression of H+ ATPase which transports H+ out of the cell into the tubular fluid causing increased acid secretion
• As this occurs there is an increase in HCO3- reabsorption.
• This is because as H+ is expelled the equilibrium between of H2O and CO2 with H+ and HCO3- is shifted leading to the production of more H+ and more HCO3-
• The HCO3- produced diffuses out of the intercalated cells via HCO3- channels and so is how aldosterone promotes HCO3- retention
• Ultimately this results in increases H+ secretion and increased HCO3- reabsorption

Question 18

What is pressure natriuresis?

Answer 18

• If mean arterial blood pressure rises then renal artery pressure also rises
• In response to this the kidney increases Na+ excretion which will reduce ECFV and bring blood pressure back to normal
• It is intrinsic and so does not need extrinsic hormonal regulation (i.e. there are local mechanisms in the kidney that mediates the response)
• It is thought that increased perfusion of the vasa recta releases paracrine factors which interacts with transport mechanisms and inhibit them leading to increases Na+ excretion
• It is also thought that increasing interstitial hydrostatic pressure will impair Starling’s forces for reabsorption from the renal tubule and so less H2O and Na+ are reabsorbed

Question 19

What is hypertension?

Answer 19

• Hypertension is present when Systolic > 140 mmHg and/or disatolic 90> mmHg

Question 20

How is hypertension subdivided?

Answer 20

• Secondary: Identifiable cause

- Essential: Unknown cause (more common)

Question 21

What is Liddle’s syndrome?

Answer 21

• A rare genetic disease including several mutations which involve a gain-of-function in the ENaCs
• This causes overexpression of ENaCs causing increased renal Na+ retention (through increased reabsorption), increased ECFV and increase in BP.
• Furthermore there would also be low renin as stimuli which trigger renin secretion (e.g. low BP, low ECFV and low NA+) are all turned off independent of renin
• Low renin leads to low aldosterone
• Low aldosterone can impair K+ balance leading to hyperkalaemia

Question 22

What is Conn’s syndrome?

Answer 22

• It is also known as primary hyperaldosteronism which is caused often by an adenoma of the adrenal cortex
• This adenoma is benign and located in the aldosterone secreting layer of the adrenal cortex and leads to hypersecretion of aldosterone
• This excess aldosterone increases renal Na+ retention which increases ECFV and increases BP
• The excess aldosterone will also decrease plasma [K+] by increasing K+ secretion leading to hypokalaemia
• Renin levels will also be low because RAAS activation is bypassed and instead the adrenal cortex itself releases excess aldosterone

Question 23

What is renal artery stenosis?

Answer 23

• An abnormal narrowing of the blood vessel leading to reduced perfusion of the kidney
• This causes the kidneys to think there is a loss in blood volume and so causes increased renin secretion in response
• This activates RAAS fully and so will increase Na+ retention and cause an increased BP
• In this case the inappropriate activation of RAAS causes renin and aldosterone levels to rise

Question 24

What is Addison’s disease?

Answer 24

• It is progressive failure of the adrenal cortex leading to insufficient cortisol and insufficient aldosterone formation
• This will lead to adrenal crisis which is fatal if not treated.
• Adrenal crisis leads to hypotension, hypovolemia, hyperkalaemia and hyponatremia