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