ECF Volume Regulation Flashcards
What is one of the most important aspects of the ECF regulated by the kidney?
Volume
Why is the distribution of TBW between the cells and the ECF determined by the number of active osmotic particles in each compartment?
H2O can freely cross all cell membranes so the body fluids are in osmotic equilibrium
What are the major ECF osmoles?
Na and Cl
What are the major ICF osmoles?
K salts
What is regulation of ECF volume regulated by?
Regulation of body Na
How is water distributer within the body?
Water (60%)
TBW = 42l
- ICF (2/3) = 28l
- ECF (1/3) = 14l
- plasma = 3l
- interstitial fluid = 11l
How do changes in Na content of the ECF affect BP?
changes in Na+ content of the ECF = changes in ECF volume
- affects volume of blood perfusing tissues
- determines circulating volume and therefore BP
What is regulation of Na basically dependent on?
High and low pressure baroreceptors
Hypovolaemia?
Low ECF volume
What happens to the body in hypovolaemia?
- Increases in salt and H2O loss
- Decrease in pulse volume
- Decrease in venous pressure
- Decrease in venous return
- Decrease in atrial pressure
- Decrease in End diastolic volume
- Decrease in stroke volume
- Decrease in cardiac output
- Decrease in BP
- Decrease in carotid sinus baroreceptor inhibition of sympathetic discharge
How does the body compensate for hypovolaemia?
- decreases carotid sinus barocreceptor inhibition of sympathetic discharge = increased sympathetic discharge
- increase VC
- increase TPR
- increase BP towards normal
Give examples when there might be increase salt and water loss?
- Vomiting/diarrhoea
- Excess sweating
How does the renal system respond to comepensation for hypovolaemia?
- increase ADH
- increases renal arterial constriction
- increases renin
- increase angiotensin II
- increased NaCl and H2O reabsorption in proximal tubule
- increased aldosterone which increases NaCl and H2O reabsorption in the distal tubule
What effect does increased renin have on the proximal tubule of the kidney?
- Increases angiotensin II
- Decreases peritubular capillary hydrostatic pressure (+ the osmotic pressure)
- Increased Na reabsorption from the proximal tubule and less Na excreted
What effect does renin have on the distal tubule of the kidney?
- Increased renin
- Increased angiotensin II
- Increased aldosterone
- Increased distal tubule Na reabsorption and less Na excreted
What is the sympathetic discharhe on the kidney determined by?
Osmotic pressure
What are changes in proximal tubule Na reabsorption due to?
Changes in the rate of uptake by the peritubular capillaries
What are increases in Na reabsorption due to?
Greater reabsorptive forces in the peritubular capillaries
What is the reabsorptive range of the proximal tubule?
- 65% in volume excess
- 75% in volume deficit.
- Big range of volume just because of changes in Starling’s forces.)
Why is GFR largely unaffected by changes in ECF?
Autoregulation maintains GFR and the VC of afferent and efferent means little effect on GFR until volume depletion severe enough to cause considerable decrease in MBP.
What maintains GFR in ECF loss?
- Constriction of afferent due to sympathetic VC
- Constriction of efferent mediated by angiotensin II
What is regulation of distal tubule Na reabsorption under control of?
Adrenal cortical steroid hormone aldosterone
What hormone is very important in the long-term regulation of Na and ECF volume?
Aldosterone
What is aldosterone secretion controlled by?
Reflexes involving the kidneys themselves
What cells are present in the smooth muscle media of the afferent arteriole just before it enters the glomerulus?
Juxtaglomerular cells (JG): specialized, containing large epithelial cells with plentiful granules
What are the 2 components of the juxtaglomerular apparatus?
- Juxtaglomerular cells
- Macula densa
What are the JG cells closely associated with?
A histologically specialized loop of the distal tubule known as the macula densa
What do JG cells produce?
Renin
What is renin?
A proteolytic enzyme which acts on a large protein in the 2-globulin fraction of the plasma proteins known as angiotensinogen.
What does renin do the angiotensinogen?
Renin splits off the decapeptide angiotensin I which is then converted by enzymes in the endothelium to the active octapeptide = angiotensin II
What does ACE stand for?
Angiotensin converting enzyme
Where is ACE found?
It is found throughout the vascular endothelium, but the greatest proportion of the conversion occurs as the blood passes through the pulmonary circuit, but all of the endothelium is important.
What does angiotensin II do?
Angiotensin II stimulates the aldosterone- secreting cells in the zona glomerulosa of the adrenal cortex
What does aldosterone do?
The aldosterone passes in the blood to the kidney where it stimulates distal tubular Na+ ion reabsorption
What is the rate-limiting step in the renin-angiotensin-aldosterone system?
The rate limiting-step is the release of renin since angiotensinogen is always present in plasma.
When is renin release increased?
When the pressure in afferent arteriole at the level of the JG cells is decreased
How do JG cells act as renal baroreceptors?
Less distension leads to increased secretion of renin. Intrinsic property occurs if denervated
Why does increased sympathetic nerve activity cause increases in renin?
Via B1 effect
What is rate of renin secretion inversely proportional to?
Rate of delivery of NaCl at the macula densa (specialised distal tubule)
What inhibits renin?
- Angiotensin II feed back
- ADH r
What does the close relationship between the afferent arteriole with JG cells and the macula densa provide a mechanism for?
Controlling input and output of tubules and basis of tubuloglomerular balance
How are volume deficits restored in hypovolaemia?
Increases in proximal AND distal tubule Na+ reabsorption together with osmotic equivalents of H2O, helps restore volume deficits, mediated by CV reflexes
Why is angiotensin II fundamentally important in the body’s response to hypovolaemia
- It stimulates aldosterone and therefore NaCl and H2O retention
- It is a very potent biological vasoconstrictor, 4-8x more potent than norepinephrine therefore contributes too increased TPR
- It acts on the hypothalamus to stimulate ADH secretion which increases H2O reabsorption from CD
- It stimulates the thirst mechanism and the salt appetite
What does tubuloglomerular feedback contribute to?
GFR constancy
If there is conflicting information received by osmoreceptors and baroreceptors what happens?
Volume considerations have primacy if ECV is compromised
What is normally the main determinant of [ADH]?
Osmolarity
When does volume become the primary driver of [ADH]?
If there is sufficient volume change to compromise brain perfusion
What is the simple rule when it comes to normalising ECF?
Simple rule, lose salt and water, replace salt and water.
What does aldosterone promote?
Na reabsorption
What is ANP?
Atrial natriuretic peptide
What does ANP promote?
Na excretion
What effect does aldosterone have at the distal tubule?
- Increased Na reabsorption
- Increased K secretion
What does administering aldosterone lead to?
- Increased weight because of retention of H2O with increased Na
- Volume expansion
- Stimulation of release of ANP from atrial cells
- Loss of Na and H20
- Continued K loss due to increased K secretion
What is aldosterone escape?
ANP overrides aldosterone effects on Na+ reabsorption because of volume expansion
When is ANP secreted?
ANP is secreted by atrial cells in response to expansion of ECF volume and causes natriuresis, loss of Na+ and H2O in urine
When is osmotic diuresis particularly important to consider?
In uncontrolled diabetes (hyperglycaemic coma)
What happen in uncontrolled DM where [BG] is not kept within strict control?
The high plasma glucose level exceeds the maximum reabsorptive capacity in the proximal tubule
What happens when glucose levels exceed the maximum reabsorptive capacity?
Glucose remains in the tubule and exerts an osmotic effect to retain H2O in the tubule.
Why is there a decreased ability to reabsorb glucose in uncontrolled diabetes?
- [Na+] in the lumen is decreased because the Na+ is present in a larger volume.
- Since Na+ gains access to the proximal tubule cells by passive diffusion down a concentration gradient created by the active transport out of the basolateral surfaces, Na+ reabsorption will be decreased
- This decreases the ability to reabsorbe glucose since it shares a symport with Na
In uncontrolled diabetes, why is the movement of H2O out of the tubule into the interstitium reduced in the descending loop of Henle?
The glucose and excess Na exert an osmotic effect to retain H2O therefore fluid in the descending limb is not so concentrated
If the fluid in the descending loop of Henle is less concentrated in uncontrolled diabetes, what does that mean for the ascending limb?
The fluid delivered to the ascending limb is less concentrated
Why is there a large volume of NaCl and H2O delivered to the distal tubule and the interstitial gradient is gradually abolished in uncontrolled diabetes?
- Since the NaCl pumps in the ascending limb are gradient limited, medullary interstitial gradient is much less
- Therefore there is a considerable reduction in the volume of NaCl and H2O reabsorbed fro the loops of Henle
Under normal conditions what does a large volume of NaCl and H2O delivered to the distal tubule mean?
There is excess ECF volume and therefore the need to get rid of NaCl and H2O
What detects high rates of delivery of NaCl to the distal tubule?
The macula densa
How does the macula densa respond to high rates of NaCl delivery to the distal tubule?
- Renin secretion is supressed
- Na reabsorption at the distal tubule is decreased
What type of urine do uncontrolled diabetics produce?
Large volumes of nearly isotonic urine which decreases the PV
What will decreased PV stimulate in uncontrolled diabetes?
ADH release via baroreceptors but they cannot be effective because the interstitial gradient has run down
How much urine can a patient with uncontrolled diabetes produce?
Up to 6-8l per day causing slat and water depletion
What is one of the first signs of DM?
Raging thirst
Why does hyperglycaemic comas occur?
Hypotension may become so severe
What is a hyperglycaemic coma due to?
Inadequate blood flow to the brain
What is a hypoglycaemic coma due to?
Inadequate glucose to the brain
What can cause an osmotic diuresis in uncontrolled diabetes?
Any solute which remains in the tubule can cause an osmotic diuresis eg NaCl or urea but this helps to eliminate their excess.
Why is osmotic diuresis not self-limiting in uncontrolled diabetes?
The liver keeps producing glucose
What affect can loop diuretics have on K?
Can cause K wasting
