Disorders of Calcium and Phosphorous - Slotski Flashcards
What is the average intake and metabolism quantity of calcium and phosphorous in the body?
Calcium:
- Intake 1000 mg
- Absorbed 400-500 mg
- Lost in stools 300 mg
- Net absorption 100-200 mg
- Urine excretion 100-200 mg
Main stored form is hydroxyapatite in bone.
Phosphorous:
•Intake 800-1400 mg
•Absorbed 480-1120 mg
•Lost in stools 300 mg
•Net absorption 100-200 mg
•Urine excretion 100-200 mg
Main forms are hydroxyapatite in bone, also
intracellular eg ATP
Etiology of hypercalcemia
• Increased intestinal absorption
– Increased calcium intake
• Renal failure (difficulty excreting plus vit D supplt.)
• Milk alkali syndrome (used to be peptic ulcer treatment causes vicious cycle of renal insufficiency and calcium and alkalosis)
– Hypervitaminosis D*
• Exogenous
– Enhanced intake of vit D or metabolites
• Endogenous
– Chronic granulomatous disease (sarcoidosis)
– Malignant lymphoma
– Acromegaly (esp MEN type I)
• Increased bone resorption
– Primary and secondary hyperparathyroidism
– Malignancy
• TNFα
, IL1, PTH-RP (mimicks PTH)
– Hyperthyroidism (mild)
– Immobilization
– Other
• Paget’s disease (if immobilized), estrogens/antiestrogens in metastatic
breast cancer, hypervitaminosis A, retinoic acid
• Miscellaneous
– Chronic Li intake (→↑PTH)
– Thiazide diuretics (→↓Ca excretion)
– Pheochromocytomas (PTH-RP)
– Adrenal insufficiency
– Rhabdomyolysis and ARF
– Theophylline toxicity
– Familial hypocalcuric hypercalcemia
– Metaphyseal chondroplasia
– Congenital lactase deficiency
Clinical manifestations of hypercalcemia
Groans: • Gastrointestinal
– Constipation
– Anorexia
– Peptic ulcer?
– Acute pancreatitis
• Renal
– Nephrolithiasis
– Tubular dysfunction
• Distal RTA
• Nephrogenic diabetes insipidus
(via CaSR)
– Renal insufficiency (calcium receptor inhibits vasopressin–>ARF d/t Na/Ca exchanger)
Moans: anxiety, depression, psychosis, hallucinations, coma
• Cardiovascular
– Ca deposition in valves, coronary
arteries, myocardial fibres
– Shortening of myocardial action
potential-shortened QT interval
– Hypertension (1/3 of patients)
• Muscular
– Weakness
• Rheumatologic
– Gout
– Pseudogout (without uric acid crystals)
– Chondrocalcinosis
• Ocular
– Band keratopathy
Treatment of hypercalcemia
Practically:
• Mild (11-12.8 mg/dl)
– Glucocorticoids
– Oral P
• More severe or symptomatic (>12.8)
Short term: – Volume expansion + furosemide
– Salmon calcitonin
Long term: – Pamidronate
• Diminish intestinal Ca absorption
– ↓calcitriol production
• Glucocorticoids (main treatment)
• Chloroquine
• Hydroxychloroquine
• Ketoconazole
– Oral phosphate (causes constipation)
• Increase urinary Ca excretion
– IV saline (diuresis by flooding kidneys)
– Furosemide
• Inhibit bone resorption
– Calcitonin (short term)
– Biphosphonates (main method)
• Etidronate
• Pamidronate
• Alendronate
– Mithramycin
– Gallium nitrate
• Dialysis
• Chelation of ionized Ca (dangerous)
– EDTA
– IV phosphate
– Oral phosphate
• Novel approaches
– ↓PTH-related protein (22-oxocalcitriol)
– Calcimimetic (norcalcin-tricks PTh gland to think calcium is higher than it is)
– Anti-PTH antibodies
Etiologies of hypocalcemia
• Loss of calcium from circulation
– Extravascular deposition
• Hyperphosphatemia
– Renal insufficiency (kidneys don’t excrete P)
– Rhabdomyolysis(crush injuries)
– Tumor lysis syndrome (DNA breakdown)
– Hungry bone syndrome (after parathyroidectomy)
• Acute pancreatitis
• Osteoblastic metastases
– Intravascular complexing (rare)
• Citrate, lactate, foscarnet, EDTA
• Acute respiratory alkalosis
– Hypercalcuria (with hypoparathyroidism)
• Decreased entry of calcium into circulation
– Hypoparathyroidism
• After parathyroid, thyroid or radical neck surgery
• Idiopathic
– Autoimmune
– Congenital
» Autosomal dominant hypocalcemia
• Infiltration of parathyroids
• HIV infection
• Pseudohypoparathyoidism
– Type 1a, 1b, 2
• Decreased entry of calcium into
circulation (cont.)
– Disorders of Mg metabolism (treat with Mg not Ca)
– Vit D deficiency (most common)
• Multiple causes
– Other
• Sepsis
• Chemotherapy
• Fluoride intoxicatio
Clinical manifestations of hypocalcemia
• Neuromuscular
– Tetany
• Depends on
– Acid-base status
– Hypomagnesemia
– Hypokalemia
– Epinephrine
• Sensory (pins and needles in feet and perioral)
• Motor
– Trousseau’s sign (carpal spasm, feet with BP cuff)
– Chvostek’s sign (mouth corner twitches when facial nerve tapped)
– Seizures
– Intellectual impairment
– Extrapyramidal disorders (Parkinsonian like, rigidity)
– Papilledema
– Psychiatric manifestations
• Emotional instability, anxiety, depression
• Confusional states, hallucinations, psychosis
– Myopathy
• Ectodermal
– Dry, puffy, coarse skin
– Hyperpigmentation, dermatitis, eczema, psoriasis
– Coarse, brittle, sparse hair, patchy alopecia, brittle nails
+ characteristic transverse grooves
– Moniliasis
– Ocular
• Cataracts, keratoconjuntivitis
– Dental abnormalities
• Hypoplasia, failure of tooth eruption, defective enamel & root
formation, abraded carious teeth
• Cardiovascular
– Hypotension
– Myocardial insufficiency, CHF
– Prolonged QT interval
– Insensitivity to digitalis
• Gastrointestinal
– Steatorrhea
– Gastric achlorhydria
• Skeletal (hypoparathyroidism only)
– Increased BMD
– Osteosclerosis
• Endocrine
– Impaired insulin release
– Hypothyroidism, prolactin deficiency,
ovarian failure
• Renal
Treatment of hypocalcemia
Make sure it’s not a lab error and rule out underlying disorders
• Mild asymptomatic
– Diet (Ca, vitD and Mg if necessary)
• Symptomatic
– Intravenous 10% Ca gluconate or chloride
– Calcitriol
– MgSO4
– Correction of hyperphosphatemia
• Chronic hypocalcemia assoc. with
hypoparathyroidism
– Oral calcium
– Vitamin D
– Thiazides and salt restriction (to decrease calcium in the urine)
– PTH (expensive)
Etiology of hyperphosphatemia
• Massive acute phosphate load
– Tumor lysis syndrome
– Rhabdomyolysis
– Lactic acidosis
– Ketoacidosis
– Exogenous phosphate (used for colonoscopy before)
– Vit D toxicity
• Pseudohyperphosphatemia (lab interference)
– Hyperglobulinemia
– Hyperlipidemia
– Hemolysis (P release from red cells)
– Hyperbilirubinemia
Treatment of hyperphosphatemia
• Acute
– Saline infusion (dilute and wash)
– Carbonic anhydrase inhibitor (on proximal tubule P removal)
– Hemodialysis (last resort)
• Chronic
– Low phosphate diet
– Phosphate binders (prevent absorption in gut)
Etiology of hypophosphatemia
Mirror of hypercalcemia
• Internal redistribution
– Increased insulin secretion, esp refeeding (after starvation)
– Acute respiratory alkalosis
(overventilation)
– Hungry bone syndrome (after parathyroidectomy, goes to bones)
• Decreased intestinal reabsorption
– Inadequate intake (alcoholics)
– Antacids (Al or Mg containing now toxic and others used)
– Steatorrhea or chronic diarrhea (P and Vit D loss cause increased PTH–>decreased P absorption and urinary P loss)
• Increased urinary excretion
– Primary & secondary
hyperparathyroidism
– Vit D deficiency or resistance
– Primary renal phosphate wasting
– Fanconi syndrome (disorder of proximal tubule absorption)
– Miscellaneous
Vitamin D deficiency or resistance
• Deficient intake or absorption
– Dietary
– Inadequate sunlight exposure
– Malabsorption (IBD)
– Gastrectomy
– Small bowel disease
– Pancreatic disease
• Defective 25-hydroxylation
– Biliary cirrhosis
– Alcoholic cirrhosis
– Anticonvulsants (phenetoin effects liver)
• Loss of Vit D binding protein
– Nephrotic syndrome
• Defective 1-alpha-hydroxylation
– Hypoparathyroidism (physiological
– Renal failure (structural)
– Vit D dependent rickets type 1
• Defective target organ response
– Vit D dependent rickets type 2 (resistance)
How does FGF-23 contribute to hypophosphatemia
Secreted from osteoblasts
Stimulated by increased P and high calcitriol (feedback loop)
mainly accumulates in chronic kidney disease-independently predicts mortality
High levels may increase vascular calcification in coronary arteries and cardiac remodeling
1’ effect: phosphaturia through receptor in the distal tubule (Klotho-required for binding)
- Inhibits 1-alpha hydroxylase (inhibit calcitriol formation–> decreasing Ca and P absorption in bowel
- Directly inhibits bone mineralization of P (releases to urine)
- Direct stimulation of PTH at PTh
Clinical manifestatinos of hypophosphatemia
Severe cases:
If phosphate is low, decreased RBC 2,3-DPG levels–>
↑Affinity of Hb for O2–> decreasing O2 release to tissues–> tissue hypoxia, muscle weakness
Decreased Intracellular ATP–>
decreased Cell function (mostly in skeletal and cardiaac muscle) –> muscle weakness and heart failure
• Mineral metabolism (increased bone resorption causes rickets in children and osteomylacia in elderly (immobilized))
Hypercalcuria caused by decreased distal tubular Ca and Mg reabsorption, increased calcitriol synthesis and bone resorption. Can also cause hypocalcemia.
• CNS (severe like in alcoholism, up to coma)
• Cardiopulmonary (decreased myocardial contractility and CHF, diaphragmatic weakness <1mg/dL, stop breathing needs ventilation)
• Skeletal and smooth muscle (myopathy rhabdomyolysis)
• Hematologic (red cell hemolysis, WBC decreased granulocyte chemotaxis and phagocytosis, platelets decrease clot retraction and thrombocytopenia–> sepsis)
Diagnosis and Treatment of hypophosphatemia
Do 24h urinary P (N < 100mg/dl)
• FEPO4
(normal <5%)
• Other tubular mineral losses
- Vit D supplementation-chronic
- Oral phosphate
- IV phosphate ≤2.5 mg/kg bw
- Dipyridamole
