Fluid And Electrolyte Imbalance - Ca, Mg, PO4 Flashcards
60% of the plasma Ca is filtered across the glomerular capillaries. Together, the ___ and ____ reabsorb more than 90% of the filtered Ca by passive processes that are coupled to ____ reabsorption
PT; TAL; Na+
Note that together, the DT and CD reabsorb 8% of the filtered Ca by an active process
What effect do loop diuretics have on Ca reabsorption?
Because Ca reabsorption is linked Na reabsorption in the LoH, inhibiting Na reabsorption with a loop diuretic also inhibits Ca reabsorption
Thus, loop diuretics like furosemide increase Ca excretion
If volume is replaced, loop diuretics can be used to tx hypercalcemia
______ increases Ca reabsorption by activating adenylate cyclase in the distal tubule
PTH
[PTH also inhibits phosphate reabsorption in PT and enhances bone release of Ca]
PTH is activated when [Ca] is low
_____ diuretics increase Ca reabsorption in the DT and therefore decrease Ca excretion. For this reason, these are used in tx of idiopathic hypercalciuria
Thiazide
Besides PTH, other hormones involved in calcium regulation
Calcitriol (1,25-OH vit D3) — increases intestinal absorption of Ca, increases renal tubular reabsorption, and stimulates release of Ca from bone
Calcitonin (generally opposite effects of PTH) — lowers blood Ca by inhibiting absorption by intestines, inhibiiting osteoclasts, and inhibiting renal tubular absorption (increasing excretion)
The distal tubule is the site of 8% of calcium reabsorption but a major site of regulation. The renal epithelial channel ____ along with ____ is regulated by calcitriol
TRPV5; calbindin
Causes of hypercalcemia
Almost always caused by increased entry of Ca into ECF via bone resorption or intestinal absorption
May also be associated with decreased renal calcium clearance
Common causes include: Primary hyperparathyroidism Thiazide diuretics Milk-alkali syndrome Familial hypocalciuric hypercalcemia Malignancy Immobilization syndrome Granulomatous disease Vitamin D intoxication
Clinical features of hypercalcemia
Related to severity and how quickly serum levels rise
Mild hypercalcemia is generally asymptomatic
Severe hypercalcemia is often associated with neurologic and GI symptoms: anorexia, N/V, constipation, weakness, fatigue, confusion, stupor, coma
Note that polyuria, nausea, and vomiting cause marked hypovolemia, resulting in impaired Ca excretion thereby worsening hypercalcemia
Management of acute hypercalcemia [not an LO]
ECF volume replacement with normal saline
Furosemide
If secondary to malignancy, add bisphosphonates
Calcitonin, glucocorticoids, hemodialysis
Causes of hypocalcemia
Result of decreased Ca absorption from GI tract or decreased Ca reabsorption from bone
True hypocalcemia is present ONLY when ionized calcium concentration is reduced
Common causes include: Hypoparathyroidism Chronic kidney disease Familial hypocalcemia Rhabdomyolysis Septic shock Vit D deficiency Parathyroidectomy Pseudohypoparathyroidism Acute pancreatitis
Clinical features of hypocalcemia
Neuromuscular irritability (weakness, paresthesias, numbness, extremity tingling, muscle twitching/cramping, tetany, chvostek sign, trousseau sign, laryngeal and bronchial spasm)
Altered CNS function (irritability, depression, AMS, tonic-clonic seizure, papilledema, cerebral calcifications)
CV: lengthened QTc interval, dysrrhythmias, hypotension, CHF
Dermatologic and ocular: dry skin, coarse hair, brittle nails, cataracts
Trousseau’s sign and Chvostek’s sign are for latent tetany typically associated with hypocalcemia, but are also positive with ______ and _____
Hypomagnesemia
Alkalosis (which decreases ionized Ca)
Management of hypocalcemia (not an LO)
IV calcium should be administered if severe
Chronic, mild hypocalcemia can be tx with oral Ca supplements and Vit D
Pts with hypoparathyroidism tx with Ca and Vit D supplementation
85% of the filtered phosphate is reabsorbed in the proximal tubule by ____-phosphate cotransport. Because distal segments of the nephron do not reabsorb phosphate, 15% of the filtered load is excreted in urine
Na+
What effect does PTH have on phosphate reabsorption in the nephron?
PTH inhibits phosphate reabsorption in the PT by activating AC, generating cAMP, and inhibiting Na-phosphate cotransport
Therefore, PTH causes phosphaturia and increased urinary cAMP
What effect would a carbohydrate or glucose infusion have on serum phosphate?
Decreased serum phosphate
[serum phosphate would be increased by high-phosphate meal]
Major factors of phosphate regulation
PTH (decreases serum PO4)
FGF-23 (decreases serum PO4)
1,25(OH)2D3 (increases serum PO4)
Insulin (decreases serum PO4)
Also important are dietary intake and renal function
Explain pathophysiological mechanism responsible for hypocalcemia associated with chronic kidney disease
CKD —> hyperphosphatemia d/t decreased GFR —> secondary hypocalcemia
Causes of hyperphosphatemia
Decreased renal excretion of phosphorus (CKD stages 3-5, acute renal failure, AKI, hypoparathyroidism, acromegaly, tumoral calcinosis, FGF-23 inactivation, KLOTHO inactivating mutation, bisphosphonates)
Exogenous phosphorous admin (ingestion of phosphate, phosphate enemas, IV phosphate)
Redistribution of phosphorus (respiratory acidosis/metabolic alkalosis, tumor lysis syndrome, rhabdomyolysis, hemolytic anemia, catabolic state)
Pseudohyperphosphatemia (hyperglobulinemia, hyperlipidemia, hemolysis, hyperbilirubinemia)
Clinical features of hyperphosphatemia
Many of the signs/symptoms result from concomitant hypocalcemia d/t deposition of calcium in soft tissues and resultant fall in ECF ionized calcium
Severe hyperphosphatemia may result in tissue ischemia or calciphylaxis
Chronic hyperphosphatemia contributes to renal osteodystrophy
Management of hyperphosphatemia (not an LO)
Acute hyperphosphatemia reduced by saline diuresis
Tx of hyperphosphatemia in end stage kidney disease = reduce dietary intake/intestinal absorption (phosphate binders)
Bone demineralization disease d/t chronic kidney disease; can cause bone/joint pain, bone deformation or fracture
Renal osteodystrophy
[due to hyperparathyroidism secondary to hyperphosphatemia — kidney is unable to excrete phosphate; this is combined with hypocalcemia because kidney is unable to activate vit D to calcitriol needed for Ca absorption from diet]
Tx with Ca/Vit D supplements, restrict dietary phosphate, hemodialysis, renal transplant, cinacalcet
Causes of hypophosphatemia
Re-feeding hypophosphatemia (causes death in starving people or anorexics as hexokinase phosphorylates glucose taken into cells)
Alcohol-related (tend to be malnourished so re-feeding syndrome partially responsible)
DM (when tx with large doses of insulin)
Urinary loss (fanconi syndrome)
Oncogenic osteomalacia (tumor making FGF-23)
Clinical features of hypophosphatemia
S/s occur only if total body phosphate depletion is present
Muscular abnormalities include weakness, rhabdomyolysis, impaired diaphragmatic function, respiratory failure, and heart failure
Neuro: paresthesias, confusion, stupor, dysarthria, seizures, coma
Hemolysis and platelet dysfunction
Chronic hypophosphatemia —> rickets in children, osteomalacia in adults
In which parts of the nephron is Mg reabsorbed?
PT (15%), TAL (70%), and DT (10%)
In the TAL, Mg and ____ compete for reabsorption — what does this result in ?
Ca
Hypercalcemia causes increase in Mg excretion (by inhibiting Mg reabsorption)
Hypermagnesemia causes increase in Ca excretion (by inhibiting Ca reabsorption)
Causes of hypomagnesemia
Affects ~60% of ICU pts
Decreased nutrition
Diuretics
Decreased albumin
Aminoglycosides
Decreased reabsorption (e.g., d/t PPI use)
Clinical signs of hypomagnesemia
Neuromuscular: weakness, tremors, seizures, paresthesias, tetany, Chvostek and Trousseau, vertical and horizontal nystagmus
CV: nonspecific T wave changes, U waves, prolonged QT and QU, repolarization alternans, premature ventricular contractions, monomorphic ventricular tachycardia, torsade de pointes, vfib, enhanced digitalis toxicity
Other metabolic manifestations: hypokalemia, hypocalcemia
Causes of hypermagnesemia (although rare)
End-stage renal disease
Massive intake (e.g., epsom salts ingestion, enemas)
Magnesium infusion (e.g., administration to limit neuromuscular excitability in pregnant women with pre-eclampsia/ecclampsia)
Clinical signs of hypermagnesemia
[listed in order of severity]
Mild (<3.6) = asymptomatic
- 8-7.2 = nausea, flushing, HA, lethargy, drowsiness, diminished DTRs
- 2-12 = somnolence, hypocalcemia, absent DTRs, hypotension, bradycardia, ECG changes
> 12 = muscle paralysis —> flaccid quadriplegia, apnea, respiratory failure, complete heart block, and cardiac arrest
Why is hypermagnesemia relatively rare?
There is efficient elimination by the kidney
