ECF Volume Regulation 1 & 2 Flashcards
One of the most important aspects of the ECF regulated by the kidney is its ______
volume
Since H2O can freely cross all cell membranes, the body fluids are in osmotic equilibrium, so that the distribution of TBW between cells and ECF is determined by what?
the number of osmotically active particles in each compartment
name major ECF and ICF osmoles
Na+ and Cl- are the major ECF osmoles. K+ salts are the major ICF osmoles
Regulation of ECF volume = Regulation of body ___
Na+
describe the distribution of body water
what will changes in Na+ content of the ECF lead to?
changes in ECF volume and therefore will affect the volume of blood perfusing the tissues = effective circulating volume and therefore BP
what is regulation of Na+ dependent on?
Na+ is basically dependent on high and low P baroreceptors
Describe the renal response to a decreased ECF volume (hypovolaemia)?
increase salt and H2O loss as in vomiting, diarrhoea or excess sweating = decreased PV = decreased venous P = decreased VR = decreased atrial P = decreased EDV = decreased SV = decreased CO = decreased BP = decreased carotid sinus baroreceptor inhibition of sympathetic discharge.
= increased Sympathetic discharge = increased VC = increased TPR = increased BP towards normal
what does increased sympathetic discharge cause on the kidney?
- increased renal VC nerve activity = increased renal arteriolar constriction and an increase in renin
- increased renin = increased angiotensin II = decreased peritubular capillary hydrostatic P (+ the increased osmotic pressure) = increase Na+ reabsorption from the proximal tubule and therefore less Na+ excreted
increased renin = increased angiotensin II = increased aldosterone = increased distal tubule Na+ reabsorption and therefore less Na+ excreted
what are changes in the proximal tubule Na+ reabsorption due to?
Changes in proximal tubule Na+ reabsorption are due to changes in the rate of uptake by the peritubular capillaries.
Determined by osmotic pressure
increase in Na+ reabsorption is because of greater reabsorptive forces in the peritubular capillaries
what happens if If have lost NaCl and H2O is lost
more of the “wet stuff”, then osmotic pressure increases even more than normal (ie > than that due to loss of filtration fraction) so can reabsorb up to 75% of the filtrate at the proximal tubule
(So reabsorptive range in proximal tubule; 65% in volume excess to 75% in volume deficit. Big range of volume just because of changes in Starling’s forces.)
GFR remains largely unaffected
How is GFR maintained in time of excess or deficits in volume
Autoregulation maintains GFR and the VC of afferent and efferent means little effect on GFR until volume depletion severe enough to cause considerable decreased MBP
when volume compromised:
Oncotic pressure is ______ as we are volume compromised and volume of blood protein stays the same so higher ______ pressure so drive to take up water is even bigger
higher
oncotic
Regulation of distal tubule Na+ reabsorption is under the control of what?
the adrenal cortical steroid hormone, aldosterone
Very important in the long-term regulation of Na+ and ECF volume
Aldosterone secretion is controlled by reflexes involving what?
Aldosterone secretion controlled by reflexes involving the kidneys themselves
what are Juxtaglomerular cells (JG)?
Smooth muscle of the media of the afferent arteriole, just before it enters the glomerulus has become specialized, containing large epithelial cells with plentiful granules = Juxtaglomerular cells (JG)
what are JG associated with and what does it form?
They are closely associated with a histologically specialized loop of the distal tubule = the macula densa
The two together form the Juxtaglomerular apparatus
what do JG cells produce?
JG cells produce the hormone renin
what does renin act on?
a proteolytic enzyme which acts on a large protein in the a2-globulin fraction of the plasma proteins = angiotensinogen
Renin splits off the decapeptide angiotensin I which is then converted by enzymes in the endothelium to the active octapeptide = angiotensin II
what is the rate limiting step invovle dinth e prodcution of angiotensin 2?
ACE enzyme found everywhere
How much renin is present is the only rate limiting step
whata re all the effects of angiotensin 2?
Vasoconstrictor
Increased cardiovascular response like heart rate
Increased the release of ADH to maintain volume and reabsorb everything and also increase thirst to increase intake, aiming to restoring volume
AGN 2 also stimulates adrenal cortex to release aldosterone and this increases sodium reabsorption in distal tubule cells
Close relationship between afferent arteriole with JG cells and macula densa provides mechanism for controlling input and output of tubules and basis of tubuloglomerular balance
Angiotensin II is fundamentally important in the body’s response to hypovolaemia, why is this?
- It stimulates aldosterone and therefore NaCl and H2O retention
- It is a very potent biological vasoconstrictor, 4-8 x more potent than NE, therefore contributes to increased TPR
- It acts on the hypothalamus to stimulate ADH secretion = increased H2O reabsorption from CD
- It stimulates the thirst mechanism and the salt appetite (in the hypothalamus)
describe the process of what would happen in the kidneys if there was an increase in volume
Consider a person suffering from severe diarrhoea, who has lost 3l of salt and water (from ECF) and drinks 2l of pure water. There will be opposing inputs to ADH secreting cells:
decrease ECF osmolarity = inhibition of ADH via osmoreceptors
decrease ECF volume = increase ADH via baroreceptors
what takes priority?
Volume considerations have primacy if ECV is compromised, so that ADH will increase because of the baroreceptors, even though this is associated with hypoosmolarity
What are the levels of sodium and potassium like in patients with Conns syndrome?
Similarly in patients with Conn’s syndrome, 1° hyperaldosteronism, due to a tumour of the adrenal cortex, they are K+ depleted, but not hypernatraemic
ANP is secreted by atrial cells in response to expansion of ECF volume and causes natriuresis, loss of Na+ and H2O in urine
Actions may be to inhibit secretion of renin, generally oppose the actions of angiotensin II
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 therefore causing what?
Glucose remains in the tubule and exerts an osmotic effect to retain H2O in the tubule
thereofre [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
and therefore decreased ability to reabsorb glucose since it shares a symport with Na+
how does uncontorlled DM affect the descending loop of henle?
In the descending limb of the loop of Henle, movement of H2O out of the tubule into the interstitium is reduced because the glucose and excess Na+ exert an osmotic effect to retain H20
therefore fluid in the descending limb is not so concentrated
how does uncontorlled DM affect the ascending loop of henle?
Due to fluid in the descending limb being not so concentrated, this means that the fluid delivered to the ascending limb is less concentrated
Since the NaCl pumps in 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 from the loops of Henle,
so a large volume of NaCl and H2O is delivered to the distal tubule
AND the interstitial gradient is gradually abolished
Summary of the osmolarity in the different parts of the kidney
Note the 200mOsmole gradient at each horizontal level of the ascending limb of the loop of Henle reflects the pumping of the active pumps
Under normal conditions, a large volume of NaCl and H2O delivered to the distal tubule means there is excess ECF volume and therefore need to get rid of NaCl and H2O
what would this cause?
The macula densa will detect the high rate of delivery of NaCl so that renin secretion will be suppressed and
Therefore Na+ reabsorption at the distal tubule will be decreased
normal reflex works in the wrong way and now the system works incorrectly
Already have impaired reabsorption abilities now RAAS says just get rid of it
Produces massive dehydration
Summary of effects of uncontrolled diabetes
normal on the left
The active transport mechanism that operates on the luminal surface of the thick ascending loop of Henle, actually involves __ ions as well as NaCl, ie Na+-__-2Cl- co-transporter
K+
K+
This is a passive process, energy is provided by active transport, Na+/K+ATPase on the basolateral membrane
Makes no difference to story, but important to know because loop diuretics can cause K+ ion wasting
