Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Desmopressin may occasionally be administered to patients with substantial
polyuria caused by central diabetes insipidus. A risk associated with the use of
ADH in this context is that acute hyponatremia and volume expansion can
occur in a patient receiving IV fluids with consequent brain swelling and dath.
In this setting what terminates the physiologic effects of ADH?
1. Increase in plasma volume
2. 2. Decrease in plasma osmolarity
3. Inc levels of cAMP in collecting duct cells
4. Endocytosis of aquaporin water channels
5. Receptor-mediated endocytosis of ADH from the luminal surface
The thick ascending limb in the
loop of Henle is:
1. Permeable to water
2. Permeable to NH3
3. Permeable to H+
4. Impermeable to water
2. Permeable to NH3
3. Permeable to H+
A dec. in the conc. Of NaCl in
the intraluminal fluid causes
the juxtaglomerular apparatus
to release:
1. ADH
2. Aldosterone
3. Adenosine
4. Renin
5. Angiotensinogen
Factors that alter renal Ca2+ excretion
Mg2+
↓Calcium Excretion
↑Parathyroid hormone
(PTH)
↓ ECF Volume
↑Calcium Excretion
↓PTH
↑BP
↑ Plasma PO4Metabolic acidosis
Vitamin D3
↑BP
↓Plasma PO4Metabolic Alkalosis
•
As far as we know, there is NO hormone that has
direct control of Mg excetion and absorption. HE
WON’T ASK US QUESTIONS ON MG2+ EXCEPT IN
TERMS OF ION TRANSPORT FROM ANOTHER
LECTURE
•
>1/2 of body Mg++ is stored in bone
•
Mechanisms of Mg++ excretion are poorly defined
•
These disturbances lead to increased Mg++
↑ ECF Volume
excretion
•
Increased ECF Mg++
•
ECF volume expansion
•
Increased ECF Ca++ concentration
This schematic shows an illustration of Ca2+ balance in the
body. Under normal conditions, its interactions with the
bone and liberation of Ca2+ from bone (resorbption) or
formation.
Magnesium balance. IN calcium, PTH has well defined actions
on bone and kidney… magnesium is not that way.
Factors affecting Phosphate excretion
The primary hormone regulator is PTH
•
Dietary intake
•
Calcium levels
•
Acute hypercalcemia decreases
phospate excretion
•
Chronic hypercalcemia inhibits
excretion
•
Chronic hypercalcemia increases
reabsorption
Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Potassium








\
K+ input= output; you can increase intake a
lot without really affecting [plasma K+]
98% is intracellular (opp. Of Na+)
Severe hyperkalemia
o Partial depolarization of cell
membranes
o Cardiac toxicity
 ventricular fibrillation or
asystole
Severe hypokalemia
Hyperpolarization of cell membranes
Fatigue, muscle weakness
hypoventilation
delayed ventricular repolarization

Control of Principal cell K+ Secretion




Remember these factors! On the left favor
K+ movement into the cell. On the right, they
do the opposite movement out of the cell.
Secretion occurs in the cortical collecting
tubule: K+ secretion by principal cells: active
pumping followed by passive diffusion in to the
tubule
Inc. Extracellular K+ concentration : increases K+
secretion
Aldosterone : increases K+ secretion
o Without aldo system the more K+ you
intake, the higher the K+ concentration of
plasma.
Sodium (volume) delivery : increases K+ secretion
o Increase in Na volume (not the same as
increases in [Na]) increased delivery to
macula densa cellsincreases K secretion
Acid - base status:
- acidosis : decreases K+ secretion
- alkalosis : increases K+ secretion
Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Questions:
1. Fill in ↑ OR ↓ in table
↓Calcium
Excretion
__Parathyroid
hormone (PTH)
__ECF Volume





Increase the flow rate (water) and you “wash out of K+”
Remember that K will stay the same if Na intake is
increased.
H+ ions inhibit the ATPase mechanism inhibits K
secretion!
Alkalosis ↑K+ in cells↑K+ Secretion
↑K+Excretion K+ Depletion
**For K+, dietary intake is very important. If you
increase you intake, you’ll excrete the excess, but if
your on a chronically low K+ diet, that can cause
hypokalemia.
↑Calcium
Excretion
__PTH
__ECF Volume
__BP
__BP
__Plasma PO4- __Plasma PO42. What hormone is the primary
regulatory hormone for Ca2+?
3. T/F You can increase intake a lot
without really affecting [plasma K+]
4. K+ secretion by intercalated cells in
the cortical collecting tubule
Answers:
1.
↓Calcium
Excretion
↑Parathyroid
hormone (PTH)
↓ ECF Volume
↑Calcium
Excretion
↓PTH
↑BP
↑ Plasma PO4-
↑BP
↓Plasma PO4-
↑ ECF Volume
2. Parathyroid hormone
3. T
4. F. Secretion occurs by principal
cells.
Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Na2+ Volume Regulation
Sodium balance is maintained but at a higher AP.
This summarizes whats become known as RENAL-Body Fluid
Arterial Pressure Feedback. Na2+ intake or excretion interacts to
produce whatever EC fluid volume you have. CO*TPR=MAP
Regulation of arterial pressure long-term relies on proper renal
function. On top, it demonstrates that salt doesn’t affect BP that
much in healthy kidneys. The dotted line indicates a problem with
renal function  BP is raised.
Normal Water and Sodium Balance



Na+ is the primary solute in the ECF
Inextricably linked but at the same time separate
Na+ regulation can be thought of as two processes
o Proximal nephon: coupled changes in Na+ and
water excretion
o Distal nephron: Na+ can be reabsorbed
independently of water
Disorders of Na+ Balance are disorders of ECF volume


Hyponatremia
o Usually associated with hypoosmolality
o May occur with normal, excess or deficit of
Na+
Hypernatremia
o Usually a result of excess water loss
Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Remember that if filtration falls, the reabsorption needs to also
decrease (that’s occurring in the positive balance section.)
If reasborption dec, excretion would initially increase to
bring it back down to steady state.
Decrease initially in Na+ excretion until they reach a set point for
maintaining sodium balance but at a higher arterial pressure
Gerenally this is like when you give diuretics. Diuretic
therapy increases Na2+ excretion and decreases ECF
volume
Negative feedback loops involved
Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Regulation of Fluid Balance in Hypertension: When there is
a disturbance of kidney function that tends to cause sodium
and water retention, and if local and hormal mechanisms
are unable to maintain balance, increase BP (HTN) serves to
allow the kidney to “escape” from Na2+ and water
retention (a result of a nasty feedback loop.)
Decrease initially in Na+ excretion until they reach a set
point for maintaining sodium balance but at a higher
arterial pressure.
People with fewer glomeruli develop HTN, but they don’t
seem to be salt sensitive.
This can be a gradation, depending on the severity of the
disease.
Common example. CHF results in a dec. in CO; which in
the kidney is a dec in GFR, which results in dec. delivery
of NaCl at the macula densa.




These pateints have acites.
Similar response occurs for hemorrhage.
Minimal chenge disease loss of charges at basement
membrane excess filtration
With accumulating edema, kidney will see that as a dec. in
GFR and initiate the feedback mechanisms to retain Na and
expand plasma volume.
Gilbert: Mg2+, Ca2+, PO4- Handling & Na2+ Volume Regulation
Ruth Olson
Questions:
1. T/F Na+ is the primary solute in the ECF
2. Increased Na+ reabsorption is caused by all
but:
a) Small increase in blood pressure
b) Decreased peritubular capillary
pressure
c) Increased angiotensin II
d) Increased aldosterone
3. T/F People with fewer glomeruli develop
HTN and they seem to be salt sensitive.
4. Which of the following are systemic
mechanisms of body fluid regulation
a)
b)
c)
d)
e)
Changes in hormones
Changes in sympathetic activity
Changes in BP
Changes in Blood composition
All of the above
As Blood Pressure increases, initially, excretion is declining.
But as the volume expands, the P increases until it reaches a
steady state again.
Answers:
This gives you the benefit of seeing the time component.
1. T
If there is impaired renal function impaired ability to
excrete Na na is retained and H2O follows Plasma
volume expands  inc hydrostatic P and BP.
2. a. Small DECREASE in BP would be correct
Here you’re achieving a new set point to excrete Na+ at a
higher BP.
This is an example of renal ablation. Clinically it would be
more progressive.
3. F. People with fewer glomeruli develop
HTN, but they DON’T seem to be salt sensitive.
4. e