Lecture 6: Fluid and Electrolyte Disturbance - Ca, Mg, PO Flashcards
Free Ca2+ is important for what part of tissue excitability/AP’s?
Effect of low and high Ca2+ levels?
- Calcium controls the AP threshold
- ↓ Ca2+ lowers threshold
- ↑ Ca2+ raises threshold
What is the effect of hypoalbuminemia on serum Ca2+ levels?
- Decreases TOTAL serum [Ca2+]
- WITHOUT affecting ionized Ca2+ level
*Ionized Ca2+ is free and unbound!
If serum albumin is abnormal, clinical decisions should be based on which level of Ca2+?
IONIZED Ca2+ levels
Which 3 hormones regulate Ca2+ levels?
- Calcitriol (1,25 OH Vit D3) –> works to ↑Ca2+
- PTH –> works to ↑Ca2+
- Calcitonin –> ↓Ca2+
3 major sites of regulation for Ca2+?
1) Kidney
2) Bone
3) Intestine
What are the main effects of PTH on serum ion levels?
↑ plasma [Ca2+] and ↓ plasma [PO43-] —> increased ionized plasma Ca2+
What are the 3 main sites of action for PTH?
- Distal nephron to increase Ca2+ reabsorption
- Inhibits PO43- reabsorption in proximal tubule
- Enhances bone release of Ca2+
Secretion of PTH is controlled chiefy by serum [Ca2+] acting where?
Calcium-sensing receptors on parathyroid cells
65% of filtered calcium is reabsorbed where?
Predominantly by which type of transport?
- Proximal tubule
- Predominantly paracellular (passive)
Where in the nephron is the major site of calcium regulation?
Distal tubule
How is calcium reabsorbed in the distal tubule, the major site of regulation?
Regulated by which hormone?
- Renal epithelial Ca2+ channel (TRPV5) - along with calnindin
- Regulated by 1,25 vitamin D3 (calcitriol)
What are major causes of Hypercalcemia?
- Primary hyperparathyroidism
- Thiazide diuretics
- Milk-alkali syndrome (i.e., antacids)
- Malignancy
- Immobilization syndrome
- Granulomatous Dz
Hypercalcemia is almost always causes by increased entry of calcium into the ECF due to what 2 factors?
- Bone resorption
- Intestinal absorption
Severe hypercalcemia is often associated with symptoms related to what 2 systems and what are they?
- GI sx’s = anorexia, N/V, and constipation
- Neuro = weakness, fatigue, confusion, stupor, and coma
How does polyuria, nausea and vomiting associated with hypercalcemia contribute to worseing sx’s?
Cause marked hypovolemia, resulting in impaired calcium excretion, thereby worsening the hypercalcemia
What are drugs/treatments that can be given for the management of hypercalcemia?
- ECF volume replacement w/ 0.9% saline
- Furosemide = Ca2+ losing diuretic
- Calcitonin
- Glucocorticoids
- Hemodialysis
For hypercalcemia not responding to saline diuresis, and especially if secondary to malignancy, therapy with what is required?
Bisphosphonates
True hypocalcemia is present only when which level is reduced?
Ionized calcium
Common causes of hypocalcemia?
- Hypoparathyroidism
- Acute pancreatitis
- Chronic kidney disease
- Rhabdomyolysis = Ca2+ in injured ms.
- Parathyroidectomy
- Pseudohypoparathyroidism –> failure to respond to PTH
- Familial hypocalcemia
- Vit D deficiency
- Septic shock
Major cardiovascular signs/sx’s of hypocalcemia?
- Hypotension
- CHF
- Dysrhythmias
Major neuromuscular irritability signs/sx’s of hypocalcemia?
- Paresthesias, numbness
- Muscle twitching and cramping
- Tetany
- General fatigability and muscle weakness
- Seizures
Trousseau’s sign and Chvostek’s sign will be (+) in which settings?
- Hypocalcemia
- Hypomagnesemia
- Alkalosis (decreases ionized Ca2+)
In an emergency situation in which hypocalcemia is suspected and seizures, tetany, hypotension, or cardiac arrhythmias are present what is the treatment?
IV calcium
Pts w/ chronic, mild hypocalcemia or hypoparathyroidism can be managed how?
Calcium and vitamin D supplements
What % of body phosphorous is in the ECF?
1%
Effect on serum phosphate levels with CHO or glucose infusion?
Decreased
What are the 4 major regulatory hormones for Phosphate?
Which decrease and which increase levels?
- PTH –> ↓ serum PO43- and ↑ renal excretion
- FGF-23 –> ↓ serum PO43- and ↑ renal excretion
- 1,25(OH)D3 —> ↑ PO43- and ↑ intestinal phosphate absorption
- Insulin —> ↓ serum PO43- and shifts phosphate into cells
Where is FGF-23 released from and what is its effect on serum PO43- levels?
Promotes PO43- excretion by the kidney = decreased serum levels
A major portion of phosphate is reabsorbed in the PCT by which transporter?
What 2 hormones regulate this transpoter?
NaPi2 = highly regulated by PTH and FGF-23
Why is a fall in GFR highly problematic for phosphate regulation?
Kidneys excrete 900 mg/day or about 65% of our intake!
What are 2 major causes of decreased renal excretion of phosphorous leading to hyperphosphatemia?
- CKD stages 3-5
- Acute renal failure/AKI
Many of the signs and sx’s of an acute rise in serum phosphate are the result of what?
Concomitant hypocalcemia due to deposition of calcium in soft tissues and a resultant fall in ECF ionized Ca2+
Severe hyperphosphatemia may result in what tissue manifestations?
Tissue ischemia or calciphylaxis (vascular calcification/necrosis)
Chronic hyperphosphatemia contributes to what disorder?
Renal osteodystrophy
How is acute hyperphosphatemia managed clinically?
Saline diuresis
How is hyperphosphatemia managed in end-stag kidney disease?
Reduce dietary intake/intestinal absorption (phosphate binders)
What is Renal Osteodystophy?
How does CKD contribute to its development?
- Bone demineralization due to CKD
- Due to HYPERparathyroidismsecondary toHYPERphosphatemia… kidney unable to excrete phosphate
- Combined w/ HYPOcalcemia –> kidney unable to activate vit D to calcitriol needed for Ca2+ absorption from diet
What are the treatment options for Renal Osteodystrophy associated w/ CKD?
- Ca2+/Vit D supplementation
- Restriction of dietary phosphate, use of phosphate binders
- Hemodialysis/renal transplantation
- Cinacalet (calcium sensitizer drug, lowers PTH)
What is often times a cause of death in starving people/anorexics when given a large bolus of food too quickly?
- Re-feeding HYPOphosphatemia
- Too much phosphate will be taken up into cell as hexokinase phosphorylates glucose
What are some of the major causes of Hypophosphatemia?
- re-feeding hypophosphatemia
- Alcohol-related
- Diabetes mellitus –> Tx w/ large dose of insulin
- Urinary loss —> Fanconi syndrome
- Oncogenic osteomalacia –> tumor making FGF-23
Chronic hypophosphatemia causes what in children and adults?
- Rickets in children
- Osteomalacia in adults
What are some of the muscular and CV abnormalities causes by hypophosphatemia?
- Weakness
- Rhabdomyolysis
- Impaired diaphragmatic function
- Respiratory and Heart failure
What are 2 hemologic abnormalities caused by hypophosphatemia?
- Hemolysis
- Platelet dysfunction
Hypophosphatemic patients frequently have low levels of what other ions that need to be corrected?
- Hypokalemic
- Hypomagnesemic
What is the function of ionized magnesium found intracellularly?
Crucial role as cofactor in many biochemical and physiological processes such as ATPases, reg. of ion channels and translational processes
What is the major site of magnesium reabsorption in the nephron?
Thick ascending limb
*Hence why loop diuretics cause hypomagnesemia, although thiazides cause more severe hypomagnesemia
What is the site of magnesium fine-tuning in the nephron?
Primary driver of cellular Mg2+ influx?
- DCT
- Electrical potential is primary driver
Hypomagnesemia is most often seen in which patients?
ICU patients (60%)
Hypomagnesemia in ICU patients is primarily caused by what 5 factors?
Which drugs can caused decreased reabsorption?
- Decreased nutrition
- Diuretics
- Decreased reabsorption due to PPIs = IMPORTANT!!!
- Decreased albumin
- Aminoglycosides
How common is hypermagnesemia?
Rarely seen, due to efficient elimination by kidneys!
Although rare, what are 3 causes of Hypermagnesemia?
- End-stage renal disease
- Massive intake i.e., Epsom salt
- Magnesium infusion i.e., in pregnant women w/ pre-ecclampsia/ecclampsia to limit neuromuscular excitability
If plasma magnesium is >12 mg/dL what signs/sx’s will occur?
Muscle paralysis –> flaccid quadriplegia, apnea and respiratory failure, complete heart block, and cardiac arrest
Treatment of hypermagnesemia in pt w/ normal renal function vs. reduced renal function vs. end-stage renal disease?
- Normal = stop administration and wait and/or add loop or thiazide diuretic
- Reduced funtion = same as above + add saline infusion
- End-stage = dialysis
