Volume Regulation - Blood Pressure & The Kidneys Flashcards
Define osmoregulation and volume regulation
- Osmoregulation -
- Regulation of the amount of water in the body to maintain constant ECF osmolarity
- Changes in osmolarity will shows as changes in NaCl concentration as this is the most predominant salt
- E.g. if osmolarity increases pure water will increase to dilute this ECF to decrease osmolarity again and vice versa
- Volume regulation -
- Regulation of blood volume and pressure to ensure effective circulating volume
- Accomplished by regulating the total amount of sodium in the ECF
How does the amount of Na+ determine ECF volume?
The total amount of sodium in the ECF determines its volume -
- When NaCl and water are added to the ECF they are retained within it
- There is no osmotic gradient as [Na+] stays the same so only the ECF is expanded
Describe how BP is linked to blood volume?
- The ECF volume increases
- This increases the venous return via starling’s forces (expansion of ECF volume is distributed between interstitial and plasma compartment)
- This increases filling and via starling’s law (the more stretched the ventricle the more force with which it contracts) leads to increased cardiac output, which then increases blood pressure
BP = CO x TPR
How is ECF volume sensed?
- There is a change in the amount of Na+ in the ECF
- This changes the ECF volume
- This is detected by receptors, namely- atrial stretch receptors, arterial baroreceptors, receptors in afferent arterioles and based on the amount of NaCl delivery to DT
- This then signals effectors including RAAS which is sodium retaining and ANP which is sodium excreting
- This leads to a change in renal sodium and water excretion which matches output to intake
RAAS is activated and inhibited by what?
RAAS is activated by -
1. Reduced renal perfusion due to decreased perfusion pressure
2. Increased sympathetic activity
3. Decreased Na+/Cl- in distal tubule caused by decreased renal perfusion - macula densa activated from this to stimulate juxtaglomerular cells
RAAS is inhibited by -
1. An increased renal perfusion due to increased perfusion pressure
2. Decreased sympathetic activity
3. Increased Na+ in the distal tubule
Describe the RAAS system
- Renin is released by juxtaglomerular cells which causes the conversion of angiotensinogen in the liver to angiotensin I by cleaving it
- Angiotensin I is then converted to angiotensin II by ACE which cleaves it
- Angiotensin II then acts to increase feelings of thirst in the brain as well as act on blood vessels to cause vasoconstriction
- Angiotensin II also acts of ATI receptors to cause the adrenal cortex to increase aldosterone secretion which can also be stimulated by increased K+
How is renal Na+ excretion controlled?
- Most filtered NaCl and H2O is reabsorbed in the PT which increases with RAAS activity
- There is a much smaller variable fraction reabsorbed in the DCT and CD
- Reabsorption of Na+ and solute free water are separated
- Aldosterone mediated Na+ reabsorption increases plasma osmolarity which is then adjusted by pure water reabsorption via the ADH system
- Results in increased Na+ and water in the ECF with little to no change in plasma [Na] or osmolarity
Describe the effects of aldosterone
- Acts on principal cells lining the CD
- Increases Na+/K+ ATPase which increases the Na+ concentration gradient so there is low intracellular [Na+] so Na+ moves into the cells
- Increases expression of ENaC channels on luminal membrane by changing the transcription of the proteins that form the channel after binding to a nuclear receptor
- Results in -
- Increases Na+ reabsorption
- Increased K+ secretion
- Acts on intercalated cells of CD -
- Increases H+ ATPase that pumps H+ ions out of the cells
- Results in -
- Increased H+ secretion
- Increased HCO3- reabsorption
Describe the pressure natriuresis
- If blood pressure increases so does renal artery pressure
- Kidney responds by increasing Na excretion which decreases ECF volume
- Occurs intrinsically without the need for extrinsic hormonal control
Mechanism is not fully understood but thought to include several mechanisms - increased perfusion of the vasa recta (releases paracrine factors which interacts with transport mechanisms to inhibit them e.g. inhibits Na+ reabsorption) and also changes the balance of starling’s forces (increases interstitial hydrostatic pressure particularly within the PCT which impairs reabsorption forces so less water and Na+ reabsorption overall)
What is hypertension and its classification?
- Hypertension -
- Present when systolic is over 140 mmHg and or diastolic is above 90 mmHg
- Classified as -
- Secondary - identifiable cause in 5 to 10% of cases
- Essential - unknown cause in over 90% of cases
Describe what liddles syndrome is and what it leads to
Rare genetic gain of function mutation in epithelial sodium channel (ENaC) -
- Increased renal Na retention
- Increased ECF volume
- Increased blood pressure
- Low renin because it is independent of RAAS control
- Low aldosterone due to low renin
- This can impair K+ secretion - hyperkalaemia
Describe what conns syndrome is and what it leads to
- Primary hyperaldosteronism
- Often due to adenoma of adrenal cortex
- Increases renal Na+ retention
- Increases ECF volume
- Increases BP
- Decreases plasma [K+]
- Low renin - despite high aldosterone as it is independent of RAAS system activation
- High aldosterone
Describe what renal artery stenosis is and what it leads to
- Abnormal narrowing of the blood vessel
- Reduced blood flow to stenotic kidney which acts as a signal for low ECF volume
- Increased renin as RAAS is stimulated
- This increased angiotensin II which increases aldosterone and vasoconstriction
- Leads to Na+ retention and high blood pressure
Describe what Addisons disease is and what it leads to
- Progressive failure of adrenal cortex -
- Insufficient cortisol
- Insufficient aldosterone
- Eventually leads to an adrenal crisis which can be fatal if not treated:
- There is a lack of cortisol and aldosterone
- Hypotension, hypovolemia, hyperkalaemia all due to aldosterone absence as there is less Na+ retention and maintenance of ECF volume and hyponatremia - lack of aldosterone leads to lesser amount of sodium and less water- not change in Na+ concentration but a change in amount - cortisol changes [Na+]
