Regulation of ECF Volume Flashcards
Since H2O can freely cross all cell membranes, body fluids are all in…
Osmotic equilibrium meaning TBW distribution between cells and ECF is determined by osmotically active particles
What osmotically active particles regulate the ECF volume?
Na+ and Cl-
What ions regulate ICF?
K+
Changes in Na+ content of the ECF affects what?
ECF volume
Volume of blood perfusing tissues and circulating blood
Blood pressure
So if Na+ has such a large affect on blood volume and BP, what is regulation bound to be dependent on ?
High and low pressure baroreceptors
What is the response to a low ECF volume (hypovolaemia)?
A low ECF will result in low venous pressure = a low atrial pressure which decreases end diastolic volume, decreasing stroke volume, CO and BP
This reduces carotid baroreceptor inhibition of sympathetic discharge
The increase of S discharge results in vasoconstriction = an increase in total peripheral resistance which increases BP
How are some ways a low ECF can occur?
Salt and H2O loss via vomiting, diarrhoea or excess sweating
What does an increase of ADH do to the renal system?
Increases renal artery constriction -vasopressin
Increase in renin leading to increase in angiotensin 2
Angiotensin 2 increases proximal tubule salt and water reabsorption and increases aldosterone which acts on the distal tubule also increasing salt and water reabsorption
How does angiotensin 2 increase salt reabsorption from the proximal tubule?
It decreases peritubular capillary hydrostatic pressure (therefore increasing oncotic pressure favouring reabsorption)
How does vasoconstriction caused by ADH affect afferent and efferent arterioles and therefore glomerular filtration?
Autoregulation maintains GFR and the VC of afferent and efferent means little effect on GFR
Only causes an effect if volume depletion is so low that there is a large drop in mean BP
Regulation of distal tube reabsorption is under control of…
Aldosterone
What are juxtaglomerular cells?
Specialized smooth muscle cells of the afferent arteriole in the area of the glomerulus.
It contains large epithelial cells with plentiful granules
What are Juxta-glomerular cells (JG cells) closely related to?
The macula densa - a histologically specialized loop of the distal tubule
What do JG cells do?
Produce the hormone renin
What triggers JG cells to make renin ?
- A decrease in afferent arteriole pressure (decrease in BP)
- Increase sympathetic nerve activity via B1 effect
- In the macula densa cells in the distal tubule detect low levels of NaCl, which means a low BP
- Negative feedback loop of high levels of angiotensin 2
- ADH inhibits renin release
What does renin do?
Splits angiotensinogen into angiotensin 1
Angiotensin 1 is converted to 2 by ACE enzyme
Where is ACE enzyme found?
Where does most conversion take place?
In vascular endothelium - most conversion takes place in the pulmonary circulation
What does angiotensin 2 do?
Vasoconstriction and increased CV response to increase BP
Stimulates hypothalamus to make ADH and increase thirst
Stimulates adrenal cortex to made aldosterone
What does aldosterone do ?
Passes in the blood to the kidney where it stims distal tubule Na+ ion reabsorption
What is the rate limiting step of the RAAS system?
The release of renin since angiotensinogen is always present in the plasma
When the GFR increases as a result of angiotensin 2 - what is the feedback loop to stop it getting too high?
Since flow increases - flow past macula densa also increases
This sends signal to afferent arteriole constriction it which increases resistance, decreasing hydrostatic pressure which decreases GFR
Complex case - What happens to a person suffering from severe diarrhoea, who has lost 3l of salt and water (from ECF) and drinks 2 l of pure water (no salt)
Leads to opposing inputs to ADH secreting cells
- A decrease in the ECF osmolarity leads to inhibition of ADH via osmoreceptors
- A decrease in ECF volume (by 1L) will increase ADH via baroreceptors
So what ADH response is more important?
Normally osmolarity is the main determinant of ADH
But if there is sufficient volume change which compromises brain perfusion then ECF volume becomes the 1y drive
So body works to fix ECF volume first then regulates osmolarity
Start of lecture 2
OK
What is ANP and what does it do?
Atrial Natriuretic Peptide
Does opposite of aldosterone and causes excretion of Na+
What happens if you administer aldosterone to normal subjects on a good Na+ intake?
Na+ retention and K+ loss
2-3kg weight gain due to water reabsorption
After a couple of days there will be spontaneous diuresis due to ANP release which balances water and Na+ levels BUT K+ loss still persists
How does this affect Conn’s syndrome patients?
Since Conn’s is hyperaldosteroneism - they will have K+ depletion but not have high levels of Na+ (due to ANP)
What is osmotic diuresis
Is the increase of urination rate caused by the presence of certain substances, such as a high conc. of glucose, in the kidneys
How does uncontrolled DM wreak kidney function via osmotic diuresis?
The high plasma conc. of glucose exceeds the kidneys ability to reabsorb it all
So glucose in tubule exerts osmotic effect retaining H2O in tubule
This decreases Na conc. in tubule lumen creating a gradient from which Na will leave the intersitium and go into the tubule
= Increased retention of Na and H2O
How does this increased retention of Na and H2O in the proximal tubule due to osmotic diuresis affect the loop of henle function?
In descending limb - water doesn’t move out into interstitium as much due to glucose and excess Na+ exerting an osmotic effect
In ascending limb - fluid is now less concentrated - NaCl pumps cannot create a good medullary interstitium gradient
This leads to a reduced ability to reabsorb water and NaCl
If osmotic diuresis keeps up, what will happen in the loop of henle?
Medullary interstitium gradient is destroyed
What does osmotic diruesis do to the RAAS system?
Macula densa detects high flow of NaCl so thinks ECF volume is high and inhibits renin release
This further stops Na reabsorption at distal tubule
Why is ADH release ineffective against osmotic diuresis?
Because the loop of henle medullary interstitial gradient has been run down/abolished
So in uncontrolled diabetes why does a hyperglycemic coma happen?
Reduced ECF volume reduced O2 perfusion to brain
So in uncontrolled diabetes why does a hypoglycemic coma happen?
Reduced glucose levels for brain
What is an important point about K+ ions in the loop of henle?
The NaCl pumps in the ascending limb also involve K ions - which is why loop diuretics cause K+ ion wasting
