46) Blood pressure and the kidneys Flashcards
1
Q
What is osmoregulation?
A
- Regulation of the amount of water in the body to maintain constant ECF osmolarity
2
Q
What is volume regulation?
A
- 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
3
Q
What happens when salt and water are added to the ECF?
A
- 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
4
Q
How does blood volume link to blood pressure?
A
- 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)
5
Q
How is ECF volume determined?
A
- It is determined by the amount of Na+ in the ECF
- An increase in Na+ will increase ECF and vice versa
6
Q
How is a change in ECF counteracted?
A
- A change in Na+ intake is balanced out by a change in Na+ output
7
Q
How is amount of Na+ in ECF kept constant?
A
- 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
8
Q
How is ECF volume sensed?
A
- Atrial stretch receptors
- Atrial baroreceptors
- Afferent arterioles
- NaCl delivery to the DT
9
Q
What effectors respond to change in ECF?
A
- RAAS: Sodium retaining
- ANP: Sodium excreting
10
Q
How does the Renin Angiotensin Aldosterone System (RAAS) work?
A
- 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
11
Q
What increases renin secretion?
A
- 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
12
Q
What factors decrease renin secretion?
A
- Increased perfusion pressure
- Increased amount of Na+ in distal tubule
13
Q
How is aldosterone secretion increased?
A
- RAAS
- Increased plasma [K+]
14
Q
How is Na+ renal excretion controlled?
A
- 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
15
Q
What cells does aldosterone act on?
A
- Principle cells lining the CD
- Intercalated cells of the CD
16
Q
What are the effects of aldosterone on principle cells?
A
- 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
17
Q
What effects does aldosterone have on intercalated cells in the CD?
A
- 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
18
Q
What is pressure natriuresis?
A
- 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
19
Q
What is hypertension?
A
- Hypertension is present when Systolic > 140 mmHg and/or disatolic 90> mmHg
20
Q
How is hypertension subdivided?
A
- Secondary: Identifiable cause
- Essential: Unknown cause (more common)
21
Q
What is Liddle’s syndrome?
A
- 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
22
Q
What is Conn’s syndrome?
A
- 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
23
Q
What is renal artery stenosis?
A
- 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
24
Q
What is Addison’s disease?
A
- 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
