Lect 13: Regulating ECF Volume

Question 1

We regulate the plasma osmolarity by regulating the amount of Na in the ECF. Not water

Answer 1

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

Question 2

Sensors for volume/pressure

Answer 2

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)

Question 3

Effector organs of osmolarity are

Answer 3

kidney, brain. Osmolarity effectors short term is heart, blood vessels and long term is the kidneys

Question 4

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?

Answer 4

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

Question 5

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.

Answer 5

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

Question 6

The kidneys increase Na excretion in response to an increase in ECF volume

Answer 6

NOT AN INCREASE IN Na CONC

Question 7

The positive Na balance effectively increases the amount of NaCl in the ECF, resulting in an isosmotic expansion of the ECF volume.

Answer 7

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)

Question 8

Effective Circulating Volume

Answer 8

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.

Question 9

Diuretic drugs decrease plasma volume by

Answer 9

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

Question 10

ECF Volume baroreceptors are important!

Answer 10

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

Question 11

Feedback control of ECVolume

Answer 11

Four systems make this work: RAA, SNS, ADH/AVP, ANP all serve to INCREASE renal Na reabsorption and decrease renal Na excretion.

Question 12

Renin-Angiotensin-Aldosterone hormonal system

Answer 12

angiotensin II:
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

Question 13

How does aldosterone affect Na reabsorption?

Answer 13

Aldosterone induces an increase in Na reabsorption by the late distal tubule and early collecting ducts

Question 14

Increased renal sympathetics, how do they cause us to retain Na

Answer 14

induces renal vasoconstriction and increased Na reabsorption which reduces renal Na excretion

Question 15

ADH gets released and

Answer 15

promote water reabsorption in the cortical collecting ducts

Question 16

Reduced ECF volume decreases the release of ANP which does what?

Answer 16

reduces Na excretion (the opposit is true as well. if the ECV goes up the kidney would respond by increasing excretion

Question 17

RAA System

Answer 17

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.

Question 18

3 Mechanisms governing Renin release

Answer 18

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

Question 19

Angiotensin II (AII)

Answer 19

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

Question 20

Hormonal Control of electrolytes: Aldosterone is the primary long term regulator of salt balance and ECF volume, and therefor BP

Answer 20

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.

Question 21

Solute absorption and how they differ by segment: action of aldosterone

Answer 21

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

Question 22

The difference in the solute absorption arises from separate venous circulations in the cortex and vasa recta of the medulla where

Answer 22

the solutes absorbed into the vasa recta are recycled within the medulla to maintain the interstitial cortico-medullary gradient

Question 23

How do different parts handle Na? Proximal tubule

Answer 23

67% of filtered Na are reabsorbed isosmotically without a change in the osmolarity of the remaining 33%

Question 24

How do different parts handle Na? Thick Ascending Loop

Answer 24

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.

Question 25

How do different parts handle Na? Late Distal Tubule and CCTT and CD

Answer 25

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

Question 26

What is the only way to increase Na excretion

Answer 26

by increasing consumption of it or a decrease in the amount of Na reabsorbed, mostly in the late DT (due to aldosterone)

Question 27

NaCl transport in principal cells of the CCT

Answer 27

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.

Question 28

Coupling Na reabsorption with K secretion in the late DT and early CD is good because

Answer 28

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.

Question 29

Transepithelial lumen is EN (—) which serves as a driving force pushing transepithelial transport

Answer 29

of the anion Cl between cells (paracellular) rather than through cells (transcellular) by uptake at the apical and efflux at the basolateral

Question 30

When your salt intake is more than your sodium excretion, aldosterone levels are reduced, which reduces Na reabsorption and increases Na excretion to an amount equal to Na consumed.

Answer 30

Regulating Na balance. When in neg Na balance, aldosterone is high, increasing reabsorption, decreasing excretion to an amount equal to that consumed. The consequence of losing Na from the ECF is an ECF volume contraction

Question 31

Secretagogues for Aldosterone

Answer 31

ANG II increases ACTH release by the ant pit, which in addition to other ACTG-specific actions, increases aldosterone release by the adrenal cortex

Question 32

Hormonal control of plasma Na

Answer 32

plasma volume or BP can be regulated by the amount of Na. The renal vasculature sense the increased or decreased BP resulting in an incr or decreased activity of RAA. Changes in Na reabsorption directly affects changes in water reabsorption

Question 33

Hypernatremia: increased plasma sodium; how is it caused?

Answer 33

loss of water in excess of solutes from the plasma due to inadequate consumption or and inappropriate renal excretion

Question 34

hypovolemic hypernatremia may result from

Answer 34

extreme sweating, severe diarrhea, excessive renal free water excrerion- which may result from diabetes mellitus where plasma glucose conc is elevated and the filtered load of glucose rises to a level saturating and exceeding the capacity of the PT to reabsorb glucose. More gluclose around in TF raises osmolarity in the PT and to oppose free water reabsorption in the distal nephron segments are induced by ADH. An ensuring glucosuria occurs with excretion of a larger volume of less conc urine and lack of water reabsorption decreases plasma volume while increasing plasma Na conc

Question 35

hypovolemic hypernatremia may result from

Answer 35

Excessive renal water excretion due to central diabetes insipidus. This is caused bu inadequate ADH release in response to increased plasma osmolarity. As a result the increased plasma and Na osmolarity are not corrected by an increase in free water reabsorption because the collecting duct is not permeable to water.
Polyuria occurs with excretion of large volume of dilute urine and the lack of free water reabsorption decreases plasma volume while increasing plasma Na conc.

Question 36

hypovolemic hypernatremia may result from

Answer 36

nephrogenic diabetes insipidus: CD not able to respond to ADH

Question 37

HYPERvolemic hypernatremia (less common)

Answer 37

due to excessive consumption of highly conc or hyper tonic NaCl solution (seawater) or by IV infusion
–both plasma volume & Na osmolarity will increase.
the compensatory increase in renal water and Na excrewtion does not happen fast enough to prevent the increase in plasma volume so the hypervolemic hypernatremia occurs

Question 38

HYPERvolemic hypernatremia may also result from

Answer 38

hyperaldosteronism: increased circulating levels of aldosterone induces a inappropriate increase in the amount of Na in the plasma and a chronic volume expansion due to an inability of the kidney to excrete a greater volume of dilute urine in response to volume expansion.
Chronic volume expansion decreases the sensitivity of the central osmoreceptors to changes in plasma osmolarity. For a gven increase in plasma osmolarity, secondary to an increase in renal Na reabsorption and plasma Na conc, is not corrected for in free water reabsorption where plasma volume expansion has occurred

Question 39

hypoNATREMIA

Answer 39

YOU drink too much water, you dilute the plasma and decrease Na osmolarity. So since this is low, no ADH wil be activated and no water reabsorption will take place so you will excrete a dilute urine of low osmolarity…not SIADH (because adh levels here are fine)

Question 40

Hypervolemic hyponatremia

Answer 40

an inappropriate reabsorption of water from TF to the plasma increasing plasma volume and diluting plasma Na

–occurs in CHF, kidney failure or SIADH, polydipsia

Question 41

hypovolemic hyponatremia

Answer 41

occurs with hemorrhage, prolnged exercise in the heat or diuretic drugs, where consumption of water as well as increased water reabsorption by the kidney is insufficient to correct volume depletion but is sufficient to decrease plasma sodium conc

…can happen with Addison’s dz (adrenal insufficiency hypoaldosteronism or severe vomiting or diarrhea