Fluid And Electrolyte Imbalance - Ca, Mg, PO4

Question 1

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

Answer 1

PT; TAL; Na+

Note that together, the DT and CD reabsorb 8% of the filtered Ca by an active process

Question 2

What effect do loop diuretics have on Ca reabsorption?

Answer 2

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

Question 3

______ increases Ca reabsorption by activating adenylate cyclase in the distal tubule

Answer 3

PTH

[PTH also inhibits phosphate reabsorption in PT and enhances bone release of Ca]

PTH is activated when [Ca] is low

Question 4

_____ diuretics increase Ca reabsorption in the DT and therefore decrease Ca excretion. For this reason, these are used in tx of idiopathic hypercalciuria

Answer 4

Thiazide

Question 5

Besides PTH, other hormones involved in calcium regulation

Answer 5

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)

Question 6

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

Answer 6

TRPV5; calbindin

Question 7

Causes of hypercalcemia

Answer 7

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

Question 8

Clinical features of hypercalcemia

Answer 8

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

Question 9

Management of acute hypercalcemia [not an LO]

Answer 9

ECF volume replacement with normal saline

Furosemide

If secondary to malignancy, add bisphosphonates

Calcitonin, glucocorticoids, hemodialysis

Question 10

Causes of hypocalcemia

Answer 10

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

Question 11

Clinical features of hypocalcemia

Answer 11

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

Question 12

Trousseau’s sign and Chvostek’s sign are for latent tetany typically associated with hypocalcemia, but are also positive with ______ and _____

Answer 12

Hypomagnesemia

Alkalosis (which decreases ionized Ca)

Question 13

Management of hypocalcemia (not an LO)

Answer 13

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

Question 14

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

Answer 14

Na+

Question 15

What effect does PTH have on phosphate reabsorption in the nephron?

Answer 15

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

Question 16

What effect would a carbohydrate or glucose infusion have on serum phosphate?

Answer 16

Decreased serum phosphate

[serum phosphate would be increased by high-phosphate meal]

Question 17

Major factors of phosphate regulation

Answer 17

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

Question 18

Explain pathophysiological mechanism responsible for hypocalcemia associated with chronic kidney disease

Answer 18

CKD —> hyperphosphatemia d/t decreased GFR —> secondary hypocalcemia

Question 19

Causes of hyperphosphatemia

Answer 19

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)

Question 20

Clinical features of hyperphosphatemia

Answer 20

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

Question 21

Management of hyperphosphatemia (not an LO)

Answer 21

Acute hyperphosphatemia reduced by saline diuresis

Tx of hyperphosphatemia in end stage kidney disease = reduce dietary intake/intestinal absorption (phosphate binders)

Question 22

Bone demineralization disease d/t chronic kidney disease; can cause bone/joint pain, bone deformation or fracture

Answer 22

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

Question 23

Causes of hypophosphatemia

Answer 23

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)

Question 24

Clinical features of hypophosphatemia

Answer 24

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

Question 25

In which parts of the nephron is Mg reabsorbed?

Answer 25

PT (15%), TAL (70%), and DT (10%)

Question 26

In the TAL, Mg and ____ compete for reabsorption — what does this result in ?

Answer 26

Ca

Hypercalcemia causes increase in Mg excretion (by inhibiting Mg reabsorption)

Hypermagnesemia causes increase in Ca excretion (by inhibiting Ca reabsorption)

Question 27

Causes of hypomagnesemia

Answer 27

Affects ~60% of ICU pts

Decreased nutrition

Diuretics

Decreased albumin

Aminoglycosides

Decreased reabsorption (e.g., d/t PPI use)

Question 28

Clinical signs of hypomagnesemia

Answer 28

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

Question 29

Causes of hypermagnesemia (although rare)

Answer 29

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)

Question 30

Clinical signs of hypermagnesemia

Answer 30

[listed in order of severity]

Mild (<3.6) = asymptomatic

4. 8-7.2 = nausea, flushing, HA, lethargy, drowsiness, diminished DTRs
5. 2-12 = somnolence, hypocalcemia, absent DTRs, hypotension, bradycardia, ECG changes

> 12 = muscle paralysis —> flaccid quadriplegia, apnea, respiratory failure, complete heart block, and cardiac arrest

Question 31

Why is hypermagnesemia relatively rare?

Answer 31

There is efficient elimination by the kidney