Regulation of Plasma Sodium and ECF volume

Question 1

How does regulation of blood volume occur mostly? What initially senses ECF osmolarity and volume changes? Given the sensors do their job, what are the efferent pathways? What do these efferent pathways affect in terms of organs? What are the regulated parameters?

Answer 1

By reg of plasma volume;
Osmoreceptors in hypothalamus (thirst and ADH/AVP) and volume receptors for stretch in carotid sinus, aortic arch, renal AA, atria;
ADH/AVP and thirst for osmolarity, with RAA (reg PVR and renal Na excretion), symp NS (change PVR and HR), ADH/AVP (free water excretion), and ANP (increase in Na excretion so more water leaves);
Osm with kidney and brain, with short term heart (CO) and bv’s (PVR), with long term by kidney (maintain BP and circulation)

Question 2

What results in larger or smaller ECF volumes? What does 1 L of water equal? What does a 1 L isosmotic expansion of ECF imply? What does abrupt increase in Na consumption lead to and what else is induced? How can this increased value decrease over time?

Answer 2

Presence of Na in ECF;
1 kg; means one is in positive Na balance of 140 mEq NaCl;
Means increased plasma osmolarity, meaning more ADH/AVP in the circulation;
As ADH/AVP could dilute osmolarity and increase plasma volume, volume can decrease slowly with less Na reabsorbed and more Na excreted

Question 3

What happens to the kidneys with increased or decreased dietary sodium intake? How long will this take to happen? What is the mech for regulating sodium balance? What does severe ECF volume contraction induce, and what is it equivalent to? What is abnormal gain in ECF volume?

Answer 3

Decrease or increase magnitude of sodium reabsorption over period of several days until higher or lower level of urinary Na output achieved; 4-5 days;
sensing expansion or contraction of ECF volume occurring secondary to increases and decreases in sodium intake, respectively;
lowered GFR, hemorrhage;
edema

Question 4

For ECF volume contraction, what will the kidney act on primarily and secondarily to promote Na and water reabsorption?

Answer 4

Proximal segment of nephron, distal segment of nephron

Question 5

When do kidneys increase Na excretion, as opposed to what else? What is the kidney effectively doing in e.g. positive Na balance in order to excrete Na?

Answer 5

Increase in ECF volume, NOT an increase in [Na];

it takes an excess of isosmotic volume from ECF and excreting it into the urine

Question 6

What induces regulation of sodium excretion? What is ECV defined as? What is its value normally? When is it less? When is ECV less than total ECF?

Answer 6

Changes in effective circulating volume, NOT total ECF volume;
Blood volume reflecting extent of tissue/organ perfusion where BP is sensed; parallels total ECF volume (IVV and EVV);
Disease states like CHF, pulmonary edema, liver disease, nephrotic syndrome

Question 7

In the four diseased states causing edema, what are the mechs?

Answer 7

CHF: increased capillary hydrostatic pressure;
Pulmonary edema: increased capillary hydrostatic pressure in the lungs;
Liver disease: not making albumin (oncotic pressure)
Nephrotic syndrome: filtration of albumin into ultrafiltrate and albuminuria

Question 8

What are the most important volume baroreceptors? What are the other ones?

Answer 8

Low pressure: atria and pulmonary vasculature;
High pressure: carotid sinus, Aortic Arch, juxtaglomerular apparatus;
sensors in CNS and liver

Question 9

What does a decrease in effective circulating volume stimulate?

Answer 9

1. RAA: Ang II stimulates Na/H exhcnage in prox tubule and decreases RPF, allowing for more Na reabsorption; aldosterone allows for Na reabsorption in late distal tubule and early CD
2. Renal SNS: renal vasoconstriction and Na reabsorption
3. PP: release ADH/AVP
4. Decrease release of ANP from cardiac atria;
   ALL help increase renal Na reabsorption and decrease Na renal excretion

Question 10

How does Ang II exert its effects on kidneys reducing Na excretion directly and indirectly? What is the most important factor controlling Ang II levels?

Answer 10

It can work through adrenals and leads to aldosterone being released to act on distal tubule, while directly signaling prox tubule to increase Na reabsorption;
Renin release from granular cells of JGA

Question 11

What are three ways to get renin release?

Answer 11

1. local renal baroreceptors in afferent arterioles responding to low BP
2. lower systemic arterial BP –> baroreceptor reflex (symp drive to JGA)
3. Macula densa senses sodium concentration (if low)

Question 12

Besides its effect on aldosterone, where else does Ang II act?

Answer 12

1. hypo: increase thirst and induce ADH/AVP release
2. renal and systemic vessels: vasoconstrict efferent arteriole to increase GFR and favor reabsorption of tubular fluid in peritubular caps
3. Prox tubule: enhance Na/H exchange
4. Renal tubule cells: hypertrophy

Question 13

What is aldosterone’s primary role? What does it do in the distal nephron as well?

Answer 13

Long term regulator of salt balance and ECF volume (ie BP);

increase secretion and excretion of K

Question 14

How does aldosterone allow for increased Na reabsorption? What cells help with this process? Do cortical nephron segments participate in anything else besides this solute reabsorption? Which circulation actually would promote maintaining the cortico-medullary solute gradient?

Answer 14

More basolateral Na/K pumps; more apical membrane Na channels, more mito enzymes (ATP for Na/K pumps);
principal cells in late distal tubule and early CD of renal cortex;
No, they do not participate in the counter-current multiplication of the cortico-medullary solute concentration gradient;
Vasa recta

Question 15

Where does aldosterone act?

Answer 15

DCT and cortical collecting tubule

Question 16

List the filtered load of Na and the percentages of how much is absorbed where. How much Na is ultimately reabsorbed? What renal process does not apply to Na? How can we divide the TAL with regards to sodium?

Answer 16

25,500 mmoles, 67% isosmotically in proximal tubule, 25% in TAL, 5% in the late distal and cortical collecting tubule, 3% in collecting duct;
99.6%, vs. .4% excreted;
Secretion;
cortical TAL will return Na to circulation quickly, whereas medullary TAL will help maintain cortico-medullary gradient

Question 17

In the cortical collecting tubule, how is Na taken in? How does K leave at luminal membrane? How is Na moved at basolateral membrane? What is its relationship with K in this part of the nephron? What does aldosterone help with? Why is there a lumen neg transcell voltage difference? What does this drive?

Answer 17

Passively down a channel; passively down its channel; Na/K pump with more Na out than K in; Na reabsorption is coupled with K secretion in this sgement;
Increased/decreased Na reabsorption with increased/decreased K secretion;
More positive charge moves into cells across apical membrane than positive charge moves out across apical membrane (Na and K respectively);
Cl movement between cells

Question 18

How does aldosterone exert its actions at the cellular level? What is the consequence of e.g. adding Na to the ECF if Na is not eliminated immediately?

Answer 18

Binds to IC aldosterone receptor to form complex, enters nucleus, helps with transcription of mRNA to code for membrane transport proteins and mito enzymes for oxphos;
ECV volume contraction

Question 19

What are the secretogogues for aldosterone?

Answer 19

Ang II, increased plasma K, ACTH (induced release by Ang II)

Question 20

What five things can contribute to lowered plasma K?

Answer 20

Increased Na and water reabsorption, increased K excretion, increased blood volume and BP

Question 21

What is the normal range for Na? What is the condition of having too much? Symptoms? When can it get severe? What causes it?

Answer 21

145-158 mEq/L; hypernatremia;
lethargy, weakness, irritable;
above 158 mEq/L;
Loss of water in excess of solutes because of not enough water drank relative to solute, or too much water excreted in excess of solute inappropriately

Question 22

What are the two subtypes of causing hypernatremia? Within these two subtypes?

Answer 22

Hypovolemic: not enough water drank, extreme sweating, sever diarrhea, polyuria (glucosuria or diabetes insipidus);
hypervolemic: hypertonic saline infused or drinking seawather; hyperaldosteronism

Question 23

How does one differentiate central vs. nephrogenic diabetes insipidus?

Answer 23

Central: PP can’t release ADH in response to increased osmolarity;
Nephrogenic: inability of CD to respond to ADH

Question 24

In hypervolemic hypernatremia, what process is not occurring fast enough?

Answer 24

Compensatory increase in renal water and Na excretion, which would otherwise prevent increase in plasma volume and Na concentration

Question 25

What are symptoms of hyponatremia? When can they become severe? What is hyponatremia typically caused by? What are main subtypes of hyponatremia?

Answer 25

Nausea, vomiting, headache, lethargy, fatigue, loss of appetite, restlessness and irritability, muscle weakness, spasms/cramps;
below 125 mEq/L;
gain of water in excess of solutes in plasma due to excess water consumption or SIADH;
hypervolemic hyponatremia and hypovolemic

Question 26

Hypervolemic hyponatremia can be caused by which five things?

Answer 26

CHF, kidney failure, liver failure, SIADH, polydipsia

Question 27

What can cause hypovolemic hyponatremia?

Answer 27

1. Plasma volume reduction is extreme (hemorrhage, prolonged exercisein heat, diuretic drug therapy) where water taken in in excess of solute by reabsorption can’t correct volume depletion but will decrease plasma Na
2. Addison’s disease
3. Severe vomiting/diarrhea