Flashcards in Lect 13: Regulating ECF Volume Deck (41)
We regulate the plasma osmolarity by regulating the amount of Na in the ECF. Not water
the amount of Na determines the amount (conc x volume). We regulate it by Na which changes osmolarity which controls water. The amount of Na in the ECF determines ECF volume
Sensors for volume/pressure
stretch receptors volume and pressure goes up and down. They include carotid sinus, aortic arch, renal afferent arteriole and atria (ANP - increase in Na excretion)
Effector organs of osmolarity are
kidney, brain. Osmolarity effectors short term is heart, blood vessels and long term is the kidneys
Let's say that we are in sodium balance and then at day 0 we increase intake of Na from like 10mMol to 50. How does the kidney respond?
Initially it cannot compensate as quickly as the mouth is taking it in. So you will be in positive Na balance (more Na in than out). Where does the Na go? It goes into the ECF because 1L H20 is 1kg of body wt. This is seen as isosmotic retention of Na and is seen in the shaded area in the positive Na balance
Over a couple of days 4-5d, Na excretion begins to increase to a rate that is much higher than the amount that we are consuming and you get into NEGATIVE Na balance.
So you have corrected the osmolarity issue but have you corrected the volume issue? Volume still remains high because you see the increase in weight. Weight equals water
The kidneys increase Na excretion in response to an increase in ECF volume
NOT AN INCREASE IN Na CONC
The positive Na balance effectively increases the amount of NaCl in the ECF, resulting in an isosmotic expansion of the ECF volume.
The kidneys respond by increasing Na excretion, measured as urine Na x urine flow. The increase in Na excretion results from a decrease in reabsorption in one or more segments of the nephron. The excreted Na and water is ISOSMOTIC (equal proportions of Na and water in the urine)
Effective Circulating Volume
changes to this induces regualtion of Na excretion...it is a blood volume representing the extent of tissue perfusion where blood pressure is sensed. It me be less in dz states such as Edema (or CHF), where there is a shift from intravascular to extravascular space. WHEN THE EFV goes down that is sensed.
Diuretic drugs decrease plasma volume by
forcing the kidney to increase excretion of Na and water in the urine. This decreases hydrostatoc pressure in the capillaries and increases oncotic pressure, which favors absorption of edematous fluid in the EV space back into the IV space
ECF Volume baroreceptors are important!
Central vescular sensors sense two types of pressure: low and high
Low Pressure are in the atria and pulmonary vasculaure. if the blood pressure falls too low, then the organs wouldn't get perfused.
The ones that sense high pressure are in the carotid sinus, aortic arch and JGA
Feedback control of ECVolume
Four systems make this work: RAA, SNS, ADH/AVP, ANP all serve to INCREASE renal Na reabsorption and decrease renal Na excretion.
Renin-Angiotensin-Aldosterone hormonal system
1. promotes Na retention by stimulating Na/H exchange in proximal tubule cells and causes aldosterone release from the adrenals
2.induces an increase in renal plasma flow, which promotes increased Na reabsorption
How does aldosterone affect Na reabsorption?
Aldosterone induces an increase in Na reabsorption by the late distal tubule and early collecting ducts
Increased renal sympathetics, how do they cause us to retain Na
induces renal vasoconstriction and increased Na reabsorption which reduces renal Na excretion
ADH gets released and
promote water reabsorption in the cortical collecting ducts
Reduced ECF volume decreases the release of ANP which does what?
reduces Na excretion (the opposit is true as well. if the ECV goes up the kidney would respond by increasing excretion
angioteninogen is the substrate of the enzyme Renin. Renin is synthesized and stored by granular cells of the juxtaglomerular cells of the kidney. Decreased effective circulating volume increases renin release by the JGA. Renin is a protease that converts angiotensinogen into angiotensin 1
Angiotensnin 1 -->Angiotensin II by ACE
Most important factor controlling ANG II levels in the plasma is renin release from the granular cells of the JGA.
3 Mechanisms governing Renin release
1. Renal baroreceptors, when there is an increase in pressure there will be an increase in release; they are in the arterioles
2. low BP (stimulaes baroreceptors which increases sympahetic drive to JGA increasing renin secretion
3. macula densa cells sense the Na conc in the TF and if it is low, causes an increased release of renin
Angiotensin II (AII)
1. induces aldosterone release
2. acts on the hypothalamus to increase thirst and increase ADH/AVP from post pit.
3. vasoconstricts renal and other systemic vessels. in the kidney it constricts EFFERENT arterioles which increases GFR, increasing Starling forces favoring reabsorption of TF by the peritubular capillaries
Hormonal Control of electrolytes: Aldosterone is the primary long term regulator of salt balance and ECF volume, and therefor BP
It acts on the kidney tubules to increase the reabsorption of Na as well as water, due to the increase in osmolarity resulting from increased Na reabsorption
-it also acts on the distal nephron to increase the secretion of K.
Solute absorption and how they differ by segment: action of aldosterone
Aldosterone works on the principal cells of the late DT and the early collecting duct; both have intracellular aldosterone receptors. The Na reabsorbed rapidly exits the kidney into the circulation. Solutes reabsorbed in the medullary nephron participate in the countercurrent multiplication. But solutes reabsorbed from nephron segments in the renal cortex (PT, DT, CCD) do NOT participate in the multiplication
The difference in the solute absorption arises from separate venous circulations in the cortex and vasa recta of the medulla where
the solutes absorbed into the vasa recta are recycled within the medulla to maintain the interstitial cortico-medullary gradient
How do different parts handle Na? Proximal tubule
67% of filtered Na are reabsorbed isosmotically without a change in the osmolarity of the remaining 33%
How do different parts handle Na? Thick Ascending Loop
25% of the filtered Na is reabsorbed into 2 anatomically different artero-venous capillary networks depeniding on the medyllary or cortical location of the TAL. In the medulla, TAL, Na reabsorption drives the countercurrent multiplication of solute conc, generating and maintaing the interstitial solute conc gradient (300mOsm) surrounding the descending, ascending LH, collecting duct.
In cortex TAL, Na reabsorption from the TF into the surrounding cortical arterio-venous capillary network rapidle exits the kidney in the renal vein to the circ.
How do different parts handle Na? Late Distal Tubule and CCTT and CD
5% of the filtered Na is reabsorbed and its levels are increased or decreased based on the levels of aldosterone. In the collectign duct, 3% is reabsorbed. We reabsorb 99% of the Na
What is the only way to increase Na excretion
by increasing consumption of it or a decrease in the amount of Na reabsorbed, mostly in the late DT (due to aldosterone)
NaCl transport in principal cells of the CCT
passive lumenal to intracellular transport (Na channels). Na/K ATPase (basolateral) is actively pumping Na out of the cell. In the later distal tubule Na and CD is functionally coupled to K secretion. Na is pumped out while K is pumped in.
Coupling Na reabsorption with K secretion in the late DT and early CD is good because
an increased delivery of Na to these terminal nepron segments will not only result in a compensatory increase in Na reabsorption but also and increase in K secretion, which increases K loss in the urine and possible hypokalemia. Since aldosterone controls Na reabsorption, it controls K secretion...it causes more K channels to be put out.
Transepithelial lumen is EN (---) which serves as a driving force pushing transepithelial transport
of the anion Cl between cells (paracellular) rather than through cells (transcellular) by uptake at the apical and efflux at the basolateral