cardiovascular and renal physiology

• Renal and cardiovascular physiology

  
• Lecture objectives


  • Recap of how blood pressure and cardiac output is regulated in SHORT TERM (baroreceptor reflex and CV involvement) and LONG TERM (renal/endocrine involvement)
  • Impact of aging on the renal system function
  • Impact of aging and hypertension on the vascular system
  • Discuss diuretics and their use to treat hypertension
  • Highlight some other common hypertension medications: calcium channel blockers and Beta blockers, their mechanisms of action and potential adverse reactions

  
• Short term rapid regulation of blood pressure: AUTONOMIC PATHWAYS


  • Somatic
  • Sympathetic: release noradrenalines into tissues. Noradrenaline influences the ability of caclium and stimulates muscle contractions of tissues
  • Sympathoadrenal: activate adrenal medulla. Adrenaline released into circulation. Binds with receptors on tissues. Influence contraction of cardiac and smoothy muscles
  • Parasympathetic: counteracts. Reduces excitability of cardiovascular muscles

  
• Actions of catecholamines: interactions with the cardiovascular system and renal system(β receptor mediated)


  • ↑ force and rate of heart contractions
  • dilation of arterioles supplying skeletal muscle
  • ↑glycogenesis
  • ↑lipolysis
  • relaxation of bronchiole muscle (increased air flow into lungs)
  • ↓ Motility of gastrointestinal (β2)
  • relaxation of urinary bladder (β2)
  • relaxation of uterus (β2)
  • ↑ renin secretion (β1)
  • ↑ tension generation (β2)
  • ↓ neuromuscular transmission(β2)
• Regulation of blood pressure in the Short term: Baroreceptor mediated via Autonomic nervous system

  1. Arterial baroreceptors detect pressure changes

  2. Afferent signalling -> medulla oblongata vasomotor centre

  ANS:

  1. Low blood pressure -> decreases parasympathetic tone ( caridiac vagal tone, tachycardia)
  2. increases sympathetic output (↑noradrenaline secretion -> vascular contraction) -> elevates blood pressure

  SNS:

  1. adrenal gland releases adrenaline
  2. increase cardiac contractile force and rate

  
• Regulation of blood pressure in the Long term: renal Fluid and ion balance


  1. GFR is controlled by the afferent arterioles of the glomerulus

  2. When blood pressure is too low -> afferent arteriole constriction, ↓GFR

  3. When blood pressure is too high -> afferent arteriole dilation, ↑GRF

  
• Renal Fluid and ion balance. Na+, K+ and H2O

  
  

  constant %Na+, K+ and H2O reabsorption

  • Proximal tubule: 65% Na, 65% H2O, 100% K+
  • Descending Loop Henle: 0% Na, 15% H2O
  • Ascending Loop Henle: 25% Na+, 0% H2O

  variable % Na and H2O reabosrbtion and K+ secretion

  • Distal tubule and Collecting duct
  • reabsorption: 0-10% Na+, 10-19.7% H2O
  • secretion: 1-80% K+

  
• Regulation of blood pressure: renal Fluid and ion balance

  1. Short Term action: SNS Local NA release -> (β1 receptors) afferent arteriole vasoconstriction & ↓GFR ↓filtrate formation

  2. Long term action: Granular cells secrete Renin in response to: ↓NaCl / ↓ECF volume / ↓BP

  • 3 mechanisms of renin release:

  1. Granular cells are baroreceptors
  2. Macula Densa cells detect NaCl
  3. Granular cells are innovated by the SNS release NA locally (β1 receptors)

  
• Fluid balance: The RAAS system


  • Activated by: low blood pressure, Dehydration, Low salt, High potassium
  • Also stimulates vasopressin secretion -> increases water reabsorption in the nephron

  
• Aldosterone and the Renal Handling of Na+ and K+

  1. Aldosterone combines with cytoplasmic receptor

  2. Hormone-receptor complex initiates transcription

  3. New protein channels and pumps are synthesised

  4. Aldosterone induced proteins modification

  5. Result Increased Na+ reabsorption and K+ secretion
• Vasopressin and blood pressure control

  • When osmolarity is high or BP is very low osmoreceptors in hypothalamus activated and vasopressin secreted
  • Binds with V2 receptors on basolateral membrane of collecting duct
  • Stimulates insertion of aquaporin 2 into tubular luminal membrane -> Reabsorption of H2O by osmosis
  • restores blood volume
  • Stimulates arteriolar vasoconstriction elevating blood pressure
• Impact of aging on the renal system and fluid balance

  • Renal mass and functional tissue decreases
  • Glomerular filtration rate gradually declines
  • Reduced Afferent arteriole resistance control
  • Reduced filtration coefficient
  • Decreased endocrine synthesis: lower plasma renin, angiotension II, aldosterone
  • Hypothalamic Osmoreceptor Fluid balance: low thirst response, low fluid intake, low vasopressin secretion, poor renal water retention

  
• Aldosterone and Cardiac Failure: when the system goes into overdrive

  Aldosterone ↑ -> Plasma Volume ↓, Renin ↑, Angiotensin 2 ↑, Sodium Reabsorption ↑, Sodium Excretion ↓, ↑SNS, ↓GFR -> Fluid retention, Odema, VERY LOW BLOOD PRESSURE, Potassium secretion ↑, Potassium excretion ↑
• High blood pressure and aging: and the vascular system


  • Vascular changes in hypertension mimic those found in arteries with aging

  
• Diuretic medications


  Inhibit renal effects which lead to blood volume regulation

  
• Diuretics: Pharmaceuticals used to treat blood pressure problems or fluid retention through elevating urine production and fluid loss


  • Generally: decrease renal reabsorption of sodium (and therefore water) in the kidneys
  • ACE inhibitors (Captopril) & angiotensin II receptor blockers (Valsartan): Decrease NaCl and water retention and reduce vessel tone by inhibiting production or action of angiotensin II
  • Aldosterone antagonists (Spironolactone): Decrease NaCl reabsorption and K+ secretion but don't influence blood vessel tone as angiotensin still released

  
• Understanding ACE inhibitors


  1. Lung and kidney endothelium produce ACE

  2. ACE converts Angiotensin 1 to Angiotensin 2 which causes vasoconstriction and aldosterone release

  3. ACE inhibitors block this conversion, reducing blood pressure
• Potential unwanted effects of ACE inhibitors


  • Decreased water reabsorption and dehydration
  • Electrolyte imbalance: Reduced NaCl reabsorption = hyponatraemia, Reduced K+ secretion = hyperkalemia
  • Excessive vasodilation (flushing, headaches)
  • Orthostatic hypotension
  • Dry cough (bradykinin accumulation)
• High blood pressure and aging


  • Targeting medication to vasodilation and HR

  
• Calcium channel blockers


  Reduce vasoconstriction, Reduce SNS effects on HR and CO
• Calcium channel blockers (Amlodipine)


  1. Promote relaxation of vascular smooth muscle as interfere with calcium entry

  2. Reduce noradrenalin release (impacts on renin release and cardiac contractility)
• Potential adverse effects of Calcium Channel blockers


  • Low blood pressure: 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 reducing contractility
  • Ankle oedema: Fluid accumulation in the lower limbs due to reduced venous return and vasodilation
• Common hypertension medications which influence this regulatory pathway Beta blockers: Propranolol


  • Propranolol is a β1 +β2 receptor blocker
  • Adrenalin β1 -> ↓ Heart rate, ↓ Contractility, ↓ Blood pressure
  • Noradrenalin β1 -> ↓ afferent arteriole vasoconstriction, ↑GRF, ↓ renin secretion -> diuretic, ↓angiotensin II = vasodilation
• Reduced blood pressure from beta blockers can lead to orthostatic hypotension / syncope, especially in older patients
• Causes of orthostatic hypotension / syncope include: actual or relative volume depletion, abnormal vasomotor compensatory mechanisms, congenital, CNS damage, aging, diabetes, alcoholism, malnutrition, amyloidosis
• Actions of catecholamines: interactions with the cardiovascular system and renal system
(α receptor mediated)


  • constriction of most systemic arteries and veins (skin, renal, Splanchnic , genital)
  • ↑ gluconeogenesis
  • ↑gastrointestinal sphincter contraction
  • ↑urinary bladder sphincter contraction
  • sweating
  • pupil dilation (contraction of radial muscle)
• High blood pressure detected by baroreceptors 


  1. relayed to CNS
  2. ANS increase parasympathetic tone (acetylcholamine release at sinus node decreased heart rate
  3. decreased sympathetic output (decrease in noradrenaline secretion)
  4. vasodilation and reduction in cardiac contractile force
  5. decreased CO and peripheral resistance