Calcium Metabolism and Hypocalcemia
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Transcript of Calcium Metabolism and Hypocalcemia
CALCIUM METABOLISM
& HYPOCALCEMIA
-Reshma Ann Mathew
Calcium Metabolism
■Food rich in Calcium- dark leafy greens, cheese, broccoli, green beans, almonds
■Normal serum calcium- 8.5-10.2 mg/dL
Calcium homeostasis
ECF CALCIUMGUT KIDNEY
BONE (1 kg)
Net 175 mg
Net 175 mg
500 mg500 mg
1000 mg
Distribution Of CalciumCALCIUM
ECF8.5-10.6 mg/dl
2.25-2.65 mmol//l
ICFCYTOPLASMIC
FREE50-100 nmol/l
PROTEIN BOUND45%
DIFFUSIBLEULTRAFILTRABLE
55%
IONIZED45%
COMPLEXED10%90% ALBUMIN
10% GLOBULIN
Protein binding of calcium■ Influenced by pH.■ Metabolic acidosis decrease protein binding increase
ionized calcium.■ Metabolic alkalosis increase protein binding decrease
ionized calcium.■ Fall in pH by o.1 increases serum calcium by 0.1 mmol/L■ Corrected calcium = (4.0 mg/dl - [plasma albumin]) X 0.8 +
[serum calcium]
Factors affecting calcium absorption in gut■ Increased ■ Decreased
• Vit D• Ingestion with alkali• PTH• GH• Acidic milieu
• High po4 content in diet
• High veg fibre• High fat content• Corticosteroid
treatment• Estrogen deficiency• Advanced age• Gastrectomy• Intestinal
malabsorption syndrome
• DM• Renal failure
RENAL HANDLING OF CALCIUM
■ 8-10 g calcium filtered across the glomerulus per day.■ 200 mg = 2 % is excreted■ Rest reabsorbed across renal tubules.
• PCT: 60-65%• mTALH: 20 %• DCT, CNT : 5%
PASSIVEACTIVE
8
CALCIUM PHYSIOLOGY: BLOOD CALCIUM
• Blood calcium is tightly regulated and maintained• Principle organ systems
Gut, Bone, Kidneys• Hormones
Parathyroid hormone (PTH), Vitamin D, Calcitonin (minor contribution)
FUNCTIONS■ Muscle contraction■ Neuromuscular / nerve conduction■ Intracellular signalling■ Bone formation■ Coagulation ■ Enzyme regulation
What is Hypocalcemia?
A decrease in the SERUM CALCIUM <8.5mg/dl or IONIZED CALCIUM <3-4.4mg/dL is termed hypocalcemia
Causes?
FUNCTIONAL CLASSIFICATIONPTH Absent 1) Hereditary hypoparathyroidism2) Acquired hypoparathyroidism3) HypomagnesaemiaPTH Ineffective
1) ACTIVE VITAMIN D LACKING• Dietary intake or sunlight2) DEFECTIVE METABOLISM• Anticonvulsant therapy• Vitamin D–dependent rickets type I
4) CHRONIC RENAL FAILURE
3) ACTIVE VITAMIN D INEFFECTIVE• Intestinal malabsorption• Vitamin D–dependent rickets type II
5) PSEUDOHYPOPARATHYROIDISM
PTH Overwhelmed 1) Severe, acute hyperphosphatemia2) Osteitis fibrosa after parathyroidectomy3) Tumour lysis4) Acute renal failure5) Rhabdomyolysis
OnsetACUTE- Critically ill patients Medications
CHRONIC- Chronic renal failure Hypoparathyroidism Vit D def Psedohypoparathyroidism Hypomagnesemia
TRANSIENT- Severe sepsis, burns Acute renal failure Transfusions Acute pancreatitis
PATHOPHYSIOLOGY
Decrease in extracellular Ca2+
The membrane potential on the outside becomes less negative
Less amount of depolarisation is required to initiate action potential
Increased excitability of muscle and nerve tissue
PTH ABSENT
HERIDITARY HYPOPARATHYROIDISM
Isolated
• Autosomal Dominant Hypocalcemia
With associated features
With associated features
Autosomal dominant Autosomal recessive Mitochondrial Autoimmune
• DiGeorge Syndrome• Kenney-Caffey
syndrome
• Sanjad-Sakatisyndrome
MELAS
Kearns-Sayre syndrome
• PolyglandularAutoimmune
Type Ideficiency
ACQUIRED HYPOPARATHYROIDISM
■Inadvertent surgical removal■Radiation induced■Haemochromatosis or Haemosidersosis
Treatment (Acquired And Hereditary Hypoparathyroidism)
1. VITAMIN D (1-3mg/day) or 1,25(OH)2D3(CALCITRIOL) [0.5-1micrograms/day]
2. High ORAL CALCIUM intake.
3. THIAZIDE DIURETICS(Hydrochlorothizide 12.5-50mg)
Chronic hypomagnesaemia
Intracellular magnesium deficiency
Interferes with secretion and peripheral response to PTH
HYPOMAGNAESEMIA
Treatment (Hypomagnesemia)
■Severe hypomagnaesemia (PARENTERAL treatment) IV MgCl2, continuous infusion, 50 mmol/d (GFR↓, 50-75% reduction in dose)■During therapy monitor serum Mg every 12-24hr
PTH INEFFECTIVE
When does it occur?
CHRONIC RENAL FAILURE• Phosphate retention
• Impaired production of 1,25(OH)2D
• Calcium deficiency• Secondary Hyperparathyroidism• Bone disease
Hyperphosphtemia (later stages)
Development of Hypocalcemia
causes
■Hyperphosphatemia lowers the blood calcium1. EXTRAOSSEUS DEPOSITION of calcium and phosphate2. IMPAIRMENT in bone resorbing action of PTH3. REDUCTION in the production of 1,25(OH)2D
Treatment (Chronic Renal Failure)■Diet: Phosphate restriction■Avoidance of antacids with phosphate■Calcium supplements (Oral): 1-2g/d■Calcitriol supplementation: 0.25-1microgram/d
VITAMIN D DEFICIENCY■ Inadequate diet and/or exposure to sunlight■ Investigations may show: ↓ Vitamin D, ↓ calcium, ↑ PTH, ↑phosphate
Treatment Adequate replacement with Vit D and Calcium until the deficiencies are corrected
DEFECTIVE VITAMIN D METABOLISM1. Anticonvulsant therapy
– Induces Vit D deficiency by increasing the CONVERSION of Vit D to inactive form
2. Vitamin D-dependent rickets type 1 a) Autosomal recessiveb) Mutations in genes coding 25-(OH)D-1α-hydroxylasec) Hypocalcemia, hyperphosphatemia, Hyperparathyroidism,
osteomalacia, ↑ ALPd) Reversible on calcitriol supplementation
VITAMIN D INEFFECTIVE1) Intestinal Malabsorption
Hypocalcemia
steatorrhea
Due to deficient production of pancreatic enzymes
2) Vitamin D dependent rickets type IIDue to end organ resistance to active metabolite [1,25(OH)2D3]
PTH OVERWHELMED
■Loss of Calcium from ECF is so severe that PTH cannot compensate
Severe acute Hyperphosphatemia-Impaired ability to excrete phosphorus due to renal failure
Hyperphosphatemia
Ca2+ loss from blood
Hypocalcemia
Treatment (Hyperphosphatemia)
1) LOWERING BLOOD PHOSPHATE- phosphate binding antacids or dialysis
2) In SEVERE hypocalcemia - Ca2+ administration
Osteitis FibrosisOccurs after parathyroidectomy
Severe hypocalcemia
Treatment- PARENTERAL administration of Ca
THANK YOU