Blood Pressure and the Kidney

Question 1

How is blood pressure regulated in the short term

Answer 1

• Baroreceptor reflex
• Adjust sympathetic and parasympathetic inputs to the heart to alter cardiac output
• Adjust sympathetic input to peripheral resistance vessels to alter TPR

Question 2

How is blood pressure regulated in the medium-to-long term

Answer 2

Neurohormonal response to affect salt and water balance (thirst and increased sodium/water reabsorption)

Question 3

Explain how angiotensin II is formed from RAAS

Answer 3

• Renin released from granular cells of juxtaglomerular apparatus (JGA)
• Renin converts angiotensinogen made in the liver into angiotensin I
• Angiotensin converting enzyme converts angiotensin I to angiotensin II

Question 4

What factors stimulate renin release

Answer 4

• Reduced NaCl delivery to macula densa cells of distal tubule
• Reduced perfusion pressure in the kidney causes the release of renin - detected by baroreceptors in afferent arteriole
• Sympathetic stimulation to JGA increases release of renin

Question 5

What are the effects of angiotensin II on the kidney

Answer 5

• Vasoconstriction of efferent arteriole to decrease blood flow
• Enhanced sodium reabsorption at the PCT
  
  • Angiotensin II binds to AT1 receptor and stimulates Na-H exchanger (NHE3) in apical membrane
  • Also stimulates Na/K ATPase on basolateral membrane
  • This facilitates sodium reuptake and therefore water reuptake
• Increases ADH and aldosterone release

Question 6

What are the effects of aldosterone on the kidney

Answer 6

• Angiotensin II stimulates aldosterone release from adrenal cortex
• Acts on principal cells of collecting duct
• Stimulates sodium and therefore water reabsorption
  
  • Activates apical ENaC (epithelial Na channel) and apical potassium channel
  • Increases basolateral sodium extrusion via Na/K/ATPase

Question 7

What are the effects of sympathetic system on kidney

Answer 7

• High levels of sympathetic stimulation reduce renal blood flow
  
  • Vasoconstriction of arterioles and decrease GFR
• Activates apical Na/H exchanger (HNE3) and basolateral Na/K ATPase in PCT
• Stimulates renin release from JG cells

Question 8

What are the effects of prostaglandins on kidney

Answer 8

• Little effect under normal conditions
• Cause vasodilation of the afferent arteriole
  
  • Efferent arteriole constricted by other factors
• Release stimulated by vasoconstrictors - angiotensin II, noradrenaline, ADH
• Local release of prostaglandins also enhance renin release
• Prostaglandins and RAAS interact and stimulate each other
  
  • Net effect of both is systemic vasoconstriction, vasoconstriction of efferent arteriole and vasodilation of afferent arteriole
    
    • Preserves GFR

Question 9

What are the effects of ADH on kidney

Answer 9

• Formation of concentrated urine by retaining water to control plasma osmolarity
  
  • Increases water reabsorption in distal nephron (AQP2)
• ADH release is stimulated by increases in plasma osmolarity or severe hypovolaemia

Question 10

What is the effect of atrial natriuretic peptide

Answer 10

• Causes vasodilation of systemic circulation and afferent arteriole (increases GFR)
• Inhibits sodium reabsorption especially in collecting duct
  
  • Causes natriuresis
• If circulating volume is low, ANP release is inhibited

Question 11

Outline how renovascular disease can cause hypertension

Answer 11

• Renal artery stenosis due to atheroma (mostly) or fibromuscular dysplasia (FMD)
  
  • FMD leads to isolated areas of stenosis - common in distal artery
• Atheroma causes decrease in kidney volume
  
  • Atheroma tend to be proximal - at origin of renal artery
• In unilateral renal artery stenosis (1 kidney affected), sodium and water excretion still occurs and increased in healthy kidney
  
  • RAAS system activated in poorly perfused kidney causing possible decrease in arterial pressure
• Bilateral renal artery stenosis means poor renal perfusion causes impaired sodium and water excretion
  - RAAS system activated but impaired sodium and water excretion may lead to risk of hypertension and pulmonary oedema

Question 12

How can coarctation of the aorta lead to hypertension

Answer 12

• Coarctation = narrowing of aorta
• Hypertension due to reduced perfusion of kidneys
• Radio-femoral delay - delayed pulse in legs
• Hypertension but no fluid and U&E problems as kidneys normal

Question 13

How can primary hyperaldosteronism (conn’s syndrome) lead to hypertension

Answer 13

• Excess aldosterone due to adrenal adenoma or adrenal hyperplasia
• Leads to lower renin and angiotensin II and aldosterone increasing BP
• Causes hypertension and possibly hypokalaemia

Question 14

How can Cushing’s syndrome lead to hypertension

Answer 14

• Cortisol also acts on aldosterone receptor to increase sodium reabsorption in nephron
• Liquorice prevents conversion of cortisol to cortisone and thus may also lead to hypertension

Question 15

In terms of hydrostatic and oncotic pressure, how can this cause oedema

Answer 15

• Increased hydrostatic pressure - venous outflow obstruction due to congestive heart failure
  
  • In heart failure, fluid levels normal but body undergoes sympathetic innervation to increase CO from heart
  • Leads to oedema as fluid levels increase and create more pressure
• Decrease osmotic pressure - decrease protein synthesis in liver disease or increased protein loss in kidney disease

Question 16

How can chronic kidney disease cause hypertension

Answer 16

• Inability to excrete excess salt and water due to reduced kidney function (reduced GFR)
  
  • Maximum limit to which kidney can work
• Hypertension and oedema

Question 17

How can nephrotic syndome cause hypertension

Answer 17

• Mixture of reduced oncotic pressure causing reduced perfusion pressure and activation of RAAS, and alterations in sodium and water excretion due to reduced kidney function
• Proteinuria, hypoalbuminaemia, oedema

Question 18

List causes of secondary hypertension

Answer 18

• Renovascular disease
• Coarctation of the aorta
• Primary hyperaldosteronism (Conn’s)
• Cushing’s syndrome
• Chronic kidney disease
• Nephrotic syndrome