Endocrinology: Renal and Cardiovascular Physiology

Question 1

Role of baroreceptors and autonomic nervous system in low BP

Answer 1

Short term regulation of BP and CO
Baroreceptor mediated via autonomic nervous system
- Arterial baroreceptors located in carotid artery and aortic arch detect pressure changes: afferent signalling –> medulla oblongata vasomotor centre
- Low BP detected:
o Relayed to CNS
o ANS –> decreases parasympathetic tone (i.e., cardiac vagal tone, tachycardia) and increases sympathetic output (increase in noradrenaline secretion –> peripheral vascular contraction) –> Elevated BP
o SNS –> adrenal gland adrenaline release –> increases cardiac contractile force and rate –> elevates BP

Question 2

Role of baroreceptors and autonomic nervous system in high BP

Answer 2

Short term regulation of BP and CO
Baroreceptor mediated via autonomic nervous system
- Arterial baroreceptors located in carotid artery and aortic arch detect pressure changes: afferent signalling  medulla oblongata vasomotor centre
- High BP detected:
o Relayed to CNS
o ANS –> increase parasympathetic tone (Ach release at sinus node decreased HR) and decrease sympathetic output (decrease in noradrenaline secretion) –> vasodilation and reduction in cardiac contractile force) decreased CO and peripheral resistance

Question 3

Fluid and ion balance when BP is too low

Answer 3

• GFR is controlled by the afferent arterioles of the glomerulus
• When BP is too low:
  o Afferent arteriole constriction –> lower GFR
  o SNS local noradrenaline release –> beta 1 receptors

Question 4

Fluid and ion balance when BP is too high

Answer 4

GFR is controlled by the afferent arterioles of the glomerulus
When BP is too high: Afferent arteriole dilation (loss of SNS stimulation and ANP) –> increase GFR

Question 5

Vasopressin and BP control

Answer 5

• When osmolarity is high or BP is very low, osmoreceptors in the hypothalamus activated and vasopressin secreted
• Binds with V2 receptors on basolateral membrane of collecting duct
• Stimulates insertion of aquaporin 2 into tubular luminal membrane of collecting duct and distal tubule
• Reabsorption of water by osmosis
• Restores BP
• Stimulates arteriolar vasoconstriction elevating BP

Question 6

Long term regulation of BP and CO

Answer 6

Renal fluid and ion balance
- Glomerular filtration rate = flow rate of filtered through both kidneys per minute (mL/min). approximately 125mL/min
- Granular cells secrete renin in response to: decrease NaCl/ ECF volume/ BP
- 3 mechanisms of renin release:
o Granular cells are baroreceptors
o Macula densa cells detect NaCl in tubule
o Granular cells are innovated by the SNS releases noradrenalin locally (beta 1 receptors)
- Activates renin via renin-angiotensin-aldosterone-system (RAAS) –> Na+ reabsorption
o Activated by low BP, dehydration, low salt, high potassium
o Also stimulates vasopressin secretion: directly increases water reabsorption in the nephron
- Aldosterone and the renal handling of Na+ and K+
o Aldosterone combines with cytoplasmic receptor
o Hormone-receptor complex initiates transcription
o New protein channels and pumps are synthesised
o Aldosterone induced proteins modification
o Result increased Na+ reabsorption and K+ secretion

Question 7

3 mechanisms of renin release

Answer 7

o Granular cells are baroreceptors
o Macula densa cells detect NaCl in tubule
o Granular cells are innovated by the SNS releases noradrenalin locally (beta 1 receptors)

Question 8

Aldosterone and renal handling of Na+ and K+

Answer 8

o Aldosterone combines with cytoplasmic receptor
o Hormone-receptor complex initiates transcription
o New protein channels and pumps are synthesised
o Aldosterone induced proteins modification
o Result increased Na+ reabsorption and K+ secretion

Question 9

Impact on aging on renal mass and functional tissue

Answer 9

Renal mass and functional tissue decrease
- Reduced functioning Nephrons, increase tubulointerstitial fibrosis
- Reduced functioning glomeruli, increase in sclerotic glomeruli
- Reduced afferent arteriole resistance control
- Reduced filtration coefficient

Decreased endocrine synthesis
- Lower plasma renin
- Lower plasma angiotensin II
- Lower plasma aldosterone

Hypothalamic osmoreceptor
- Low thirst response
- Low vasopressin secretion

Question 10

What does decreased renal mass and functional tissue with age lead to?

Answer 10

impaired filtration
- Glomerular filtration rate gradually declines: >40 years old declines by 1mL/min/year, 70yrs GFR will be ~70mL/min

Question 11

Proteinuria

Answer 11

impaired fluid balance

Question 12

What does decreased endocrine synthesis with aging lead to?

Answer 12

electrolyte disturbances
- Hyponatremia (low Na)
- Hyperkalaemia (high K)
- Poor fluid regulation

Question 13

What does hypothalamic osmoreceptor with aging lead to?

Answer 13

• Low thirst response
• Low vasopressin secretion

Question 14

Onset of symptoms of chronic kidney disease

Answer 14

Symptoms of chronic kidney disease (elevated blood creatinine and urea) only occur once GFR is less than 50%

Question 15

Impact of aging on the BP

Answer 15

High BP and aging: and the vascular system
- Diuretic medications: inhibit renal effects which lead to blood volume regulation
- Vascular changes in hypertension mimic those found in arteries with aging
- Aging: endothelial dysfunction, vascular remodelling, increased stiffness, vascular inflammation, calcification
- Decreased lumen of blood vessels
Targeting medication to vasodilation and HR
- Calcium channel blockers: reduce vasoconstriction, reduce SNS effects on HR and CO

Question 16

Orthostatic hypotension/ syncope with aging

Answer 16

Orthostatic hypotension/ syncope
- Syncope can occur rapidly upon standing due to: actual or relative volume depletion (dehydration, excessive diuresis, GI bleeding, vasodilatory anti-hypertensive drugs), abnormal vasomotor compensatory mechanisms to an orthostatic challenge
- Not associated with vagal hyperactivity: rather an insufficient (baroreceptor-mediated) sympathetic response to standing
- Older patients are at particular risk of orthostatic hypotension and syncope because of altered baroreceptor responsiveness, polypharmacy, and the increased risk of volume depletion

Question 17

Diuretics

Answer 17

pharmaceuticals used to treat BP problems or fluid retention through elevating urine production and fluid loss.
Generally: decrease renal reabsorption of sodium (and therefore water) in the kidney.

Question 18

ACE inhibitors and angiotensin II receptor blocks

Answer 18

ACE (angiotensin converting enzyme) inhibitors (Captopril) and angiotensin II receptor blocks (Valsartan): decrease NaCl and water retention and reduce vessel tone by inhibiting production or action of angiotensin II.

Question 19

Aldosterone antagonists

Answer 19

Hypertensive medication: Aldosterone antagonists (Spironolactone): decrease NaCl reabsorption and K+ secretion but don’t influence blood vessel tone as angiotensin still released.

Question 20

Potential unwanted effects of ACE inhibitors

Answer 20

• Decreased water reabsorption and dehydration
• Electrolyte imbalance
  o Reduced NaCl reabsorption of hyponatraemia
  o Reduced K+ secretion = hyperkalaemia
• Excessive vasodilation (flushing, headaches)
• Orthostatic hypotension
• Dry cough (bradykinin accumulation as ACE inactivates bradykinin causes airway fluid accumulation)

Question 21

Calcium channel blockers

Answer 21

Calcium channel blockers (Amlodipine) = hypertensive medications
- Promote relaxation of vascular smooth muscle as interfere with calcium entry
- Reduce noradrenalin release (impacts on renin release and cardiac contractility)

Question 22

Potential adverse effects of calcium channel blockers

Answer 22

• Low BP: low of muscular contractility
• Bradycardia (HR below 60bpm): reduced muscular contractility
• Flushing and headaches: vasodilation leads to increase in cerebral blood flow
• Dizziness/ syncope: insufficient/ SNS response to standing
• Abdominal discomfort (constipation): relaxes GIT smooth muscle reduces contractility
• Ankle oedema: fluid accumulation in the lower limbs due to reduced venous return and vasodilation

Question 23

Beta blockers

Answer 23

Hypertensive medication
- Beta 1 and beta 2 receptor blocker
- Adrenalin alpha 1 and 2, beta 1 and 2
- Noradrenalin alpha 1 and 2 and beta 1
- Influence regulatory pathway
- Adrenalin beta 1: decreased heart rate, contractility, and BP
- Noradrenalin beta 1: decreased afferent arteriole vasoconstriction, increased GFR, decreased renin secretion (diuretic), decreased angiotensin II (vasodilation)
- All this leads to reduced BP

Question 24

Potential adverse effects of beta blockers

Answer 24

• Bradycardia: block action of adrenaline on beta receptors in the heart, leads to decreased HR. excessive slowing can lead to fatigue, dizziness, and fainting
• Hypotension: decrease in BP if too much can lead to dizziness, light-headedness, weakness, and fainting
• Fatigue and weakness
• Cold extremities: reduced blood flow to the extremities