Blood pressure and the kidneys Flashcards
What is the major electrolyte of ECFV?
→ Na
If you add Na+ to the blood why doesn’t hypernatremia happen (Increase in Na+ concentration)?
→ If Na+ increases
→ an equivalent amount of water is drawn with it
Equation for BP?
→ CO x TPR
What does an increase in blood volume lead to?
→ ventricular filling and increased stroke volume (Starlings law)
→ Increase cardiac output
→ Increase blood pressure
What is long term control of blood pressure?
→ regulating Na levels
What is short term control of blood pressure?
→ Baroreceptors
Flow chart for changes in Na balance
Changes in Na balance ↓ Changes in osmolarity ↓ ADH release ↓ H2O moves through ADH stimulated aquaporin channels in collecting duct
Why does resuscitation fluid not cause hypernatremia?
→ It is isotonic
→ Na+ cannot cross cell membranes
→ fluid will expand the ECFV
What is the effect of retained sodium the same as?
→ adding isotonic fluid
→ It draws an equivalent amount of water with it
→ Increase in blood pressure
How is Na+ sensed in the body?
→ Indirectly
→ A change in ECFV occurs (up or down)
→ Stretch and pressure receptors in CVS detect this
What are the afferent pathways for detecting indirect changes in Na+?
→ Cardiac volume receptord
→ Baroreceptors
→ Renal arterial pressure
What are the efferent pathways for responding to changes in Na+?
→ Neuronal : sympathetic nervous system
→ Hormonal : RAAS, ANP
→ Haemodynamic : + or - GFR, pressure natriuresis
How is sodium taken in the body?
→ Diet 10 to > 400 mMol a day
How is sodium removed from the body?
→ Sweat/faeces
→ Regulated renal excretion
What are mammals designed to do with Na+?
→ Conserve sodium
What is the Na+ conserving system called?
→ RAAS
How does RAAS work?
1) A loss of blood pressure stimulates the secretion of renin
2) Renin acts on a liver substrate called angiotensinogen and converts it to angiotensin I
3) Angiotensin I is converted to angiotensin II by angiotensin converting enzyme ( epithelial cells of the lung)
4) Angiotensin II acts on the AT1R receptor on the adrenal cortex and stimulates it to release aldosterone
5) Increases Na+ reabsorption in the nephron and increases K+ secretion
6) vascular smooth muscle contracts (vasoconstriction and BP increases)
Where is the macula densa?
→ The region of contact between the afferent arteriole and the distal tubule of the same nephron
What are renin secreting juxtaglomerular cells?
→ Modified smooth muscle cells along the afferent arteriole
What is renin secreted in response to?
1) decrease in BP and blood volume and renal blood flow detected by afferent arteriole mechanoreceptors
2) decrease Na levels at the macula densa
3) Sympathetic nerve activation of beta 1 adrenoceptors
What is aldosterone and where is it synthesized and what is it released by?
→ Steroid hormone
→synthesized in the zona glomerulosa of the adrenal gland
→ released by the action of angiotensin II
What does a decreased amount of Na+ at the macula densa mean?
→ Decreased GFR
Where does aldosterone act?
→ Nuclear receptors mainly on DCT cells
Where is Na+ and water mainly reabsorbed?
→ PCT
How does aldosterone increase Na+ retention?
→ increases the expression of eNAC channels
→ Increases activity of Na+/K+ pump
Where is the eNAC found?
→ Luminal side of the collecting duct
How does the Na+/K+ pump work to retain Na+?
→ Na+/K+ pump actively pumps sodium out
→ Low intracellular concentration of Na+
→ creates a diffusion gradient from the lumen of the tubule of the DCT
→ Na+ diffuses in via the eNAC
→ Na+ does not stay in the cell because the Na+/K+ pump is taking the Na+ out
What is Na+ absorption coupled with?
→ K+ excretion
What does excess aldosterone result in and why?
→ Hypokalaemia
→ K+ into the cell via Na+/K+ pump
→ K+ passively diffuses out of the cell into the lumen of tubule
Where are ANP and BNP found?
→ Specialized cardiac myocytes
What are ANP and BNP released in response to?
→ Increased cardiac filling pressures
What are the renal effects of ANP?
→ Increased natriuresis ( Na+ excretion)
→ Diuresis (H2O excretion)
What are the vasculature effects of ANP?
→ Vasodilation by stimulation of PKG in vascular smooth muscle cells
→ Decrease systemic BP
What are the hormonal effects of ANP?
→ Decrease renin secretion
→ Decreased aldosterone secretion
What is the main effect of ANP?
→ opposes RAAS
→ Na+ excreting system
What is pressure natriuresis?
→ Increase in Na+ renal excretion due to a rise in renal arterial pressure
What is the relationship between pressure and Na+ excretion?
→ The higher the pressure the higher the concentration of Na+ in the urine
How does pressure natriuresis occur?
→ A rise in medullary capillary pressure
→ causes an increase in fluid filtration and interstitial pressure
→ Prevents tubular reabsorption
Why is GFR not involved in pressure natriuresis?
→ Renal arterial pressure does not increase GFR
→ Due to powerful renal auto-regulation
What are the criteria for hypertension?
→ Diastolic > 90mmHg
→ Systolic > 140 mmHg
What are the classifications of hypertension?
→ Secondary - identifiable cause
→ Essential - unknown cause ( > 90% of cases)
What do secondary causes of hypertension involve?
→ Excess Na+ reabsorption and abnormalities in hormone secretion
→ Liddle’s syndrome
→ Conn’s syndrome
→ Renal artery stenosis
What can essential hypertension involve?
→ Abnormal handling of Na+ balance
What is Liddle’s syndrome?
→ Autosomal mutation that is rare → Genetic form of high blood pressure → Increases eNAC activity → Increases renal Na+ retention → Suppresses aldosterone/ renin
What are the effects of Liddle’s syndrome?
→ Increased ECFV
→ Increased BP
What is Conn’s syndrome caused by?
→ Overproduction of aldosterone by the adrenal gland tumor
What are the consequences of raised aldosterone?
→ Increase in ECFV
→ Renal sodium reabsorption increases
→ Increase eNAC / ATPase/ K+ excretion
→ decrease in renin secretion
What are the consequences of Addisons disease?
→ Insufficient release of aldosterone → Chronic Na+ loss → Decreased ECFV → Severe hypotension → Collapse and death
How does renal artery stenosis cause Na+ retention?
Decrease in renal artery pressure due to stenosis ↓ Decreased blood flow ↓ Renin secretion ↓ Angiotensin II production ↓ Increased aldosterone ↓ Increased vasoconstriction
How does congestive heart failure cause oedema?
LV failing to maintain enough pressure to maintain perfusion ↓ Arterial baroreceptors deactivated ↓ Body thinks blood volume is decreased ↓ Activates sympathetic output ↓ Increase RAAS system ↓ Stimulates Na+ retention ↓ ECFV expands ↓ Less arterial pressure ↓ Less hydrostatic pressure
What are environmental factors that can cause essential hypertension?
→ Life style
→ Diet
→ Diabetes
