Download Calcium metabolism and its disorders

Dr Amir Babiker
MBBS, FRCPCH (UK), CCT (UK),
Msc in Endocrinology and Diabetes - Queen
Mary University, London (UK)
Consultant Paediatric Endocrinologist (KKUH)
Assistant Professor (KSU, KSA)
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Calcium metabolism

Calcium disorders (↓Ca, ↑Ca)
• Parathyroid disorders
• Vitamin D disorders

Rickets
Haversian canals within lamellae
Calcium salts in bone provide structural integrity of
the skeleton
 Calcium ions in extracellular and cellular fluids is
essential to normal function of a host of biochemical
processes

 Neuoromuscular excitability
 Blood coagulation
 Hormonal secretion
 Enzymatic regulation

Minerals; serum concentration
 Calcium (Ca2+); 2.2-2.6 mmol/l (total)
 Phosphate (HPO42-); 0.7-1.4 mmol/l
 Magnesium (Mg2+); 0.8-1.2 mmol/l

Organ systems that play an import role in Ca2+
metabolism
 Skeleton
 GI tract
 Kidney

Calcitropic Hormones
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Parathyroid hormone (PTH)
Calcitonin (CT)
Vitamin D (1,25 dihydroxycholecalciferol)
Parathyroid hormone related protein (PTHrP)

While PTH and vitamin D act to increase
plasma Ca++--

Calcitonin causes a decrease in plasma Ca++.

PTH is synthesized and secreted by the
parathyroid gland which lie posterior to the
thyroid glands.

The blood supply to the parathyroid glands is
from the thyroid arteries.

The dominant regulator of PTH is plasma Ca2+.

Secretion of PTH is inversely related to [Ca2+].

Vitamin D, after its activation to the hormone
1,25-dihydroxy Vitamin D3 is a principal
regulator of Ca++.

Vitamin D increases Ca++ absorption from the
intestine and Ca++ resorption from the bone .

Calcitonin acts to decrease plasma Ca++ levels.

Calcitonin is synthesized and secreted by the
parafollicular cells of the thyroid gland.

The major stimulus of calcitonin secretion is a rise in
plasma Ca++ levels

Calcitonin is a physiological antagonist to PTH with
regard to Ca++ homeostasis

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Intake = output
Negative calcium
balance: Output >
intake
Positive calcium
balance: Intake >
output
 Occurs during growth

Calcium is essential,
we can’t synthesize
it
Hypo
parathyroid
Postoperative
Non parathyroid
PTH Resistance
Vitamin D
deficiency
Pseudohypoparathyroidism
Idiopathic
Malabsorption
hypomagnesaemia
Post radiation
Liver disease
Congenital
Kidney disease
Vitamin D
resistance

PTH-deficiency: reduced or absent synthesis of PTH
 Congenital (DiGeorge syndrome) or Acquired
(Autoimmune or surgery)

Hypocalcaemia occurs when there is inadequate
response of the Vitamin D-PTH axis to hypocalcaemic
stimuli

Hypocalcemia is often bihormonal—concomitant
decrease in 1,25-(OH)2-D

PTH-resistant hypoparathyroidism
 Due to defect in PTH receptor-adenylate cyclase
complex

Mutation in Gas subunit

High or normal PTH, low Ca, high phosphate,
normal Vit D3

Clinical features: Hereditary Albright
osteodystrophy, obesity, SS, subcutaneous
nodules, short fourth metacarpal +/- intracranial
calcification
Similar clinical features
but normal biochemistry
(PTH, Ca and PO4)
Reduced mineralization of bone matrix due to
calcium deficiency.
Commonest cause is Vit D3 deficiency:
 Dietary lack of the vitamin
 Insufficient ultraviolet skin exposure
 Malabsorption of fats and fat-soluble
vitamins- A, D, E, & K.
 Abnormal metabolism of vitamin D
 Chronic renal failure.
Synthesis of
Vitamin D

Nutritional

Vitamin D deficient

Vitamin D dependant type I
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Vitamin D dependant type II (Vit D resistant)

Hypophosphataemic
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Medications
Antacids
Anticonvulsants
Corticosteroids
Loop diuretics
Malignancy
Prematurity
 Skeletal deformities
 Features of hypocalcaemia ( eg. Apathatic,
poor feeding, tetany and seizures)
 Hypotonia and delayed motor development
Bone profile
 calcium
 Phosphate
 Alkaline phosphatase
 Parathyroid hormone
 Vitamin D (25 OH VitD +/- 1,25 (OH)2 Vit D)
 Urinary calcium and phospherus
X- rays
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Low or normal serum Ca
Low phosphorus
High alkaline phosphatase
X rays of ends of long bones at knees or
wrists: Widening, fraying, cupping of the
distal ends of the shaft.
Vit D level low
Parathyroid hormone high

Inadequate growth plate mineralization.

Defective calcification in the interstitial
regions

Increase in thickness of growth plate.

The columns of cartilage cells are
disorganized.
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Bowing or widening of physis
Costochondral beading (rachitic rosary)
Craniotabes
Delayed closure of anterior fontanel
Dental abnormalities
Flaring of ribs at diaphragm level (Harrison’s
groove)
Flaring of wrists
Fraying and cupping


Vitamin D supplement or
Vitamin D analogues (one alpha, calcitriol)
Dose and type depends on the underline
cause of Rickets

Calcium

Phosphate
Before
After
Hyperparathyroidism
Vitamin D toxicity (excessive intake)
William syndrome
Familial hypocalcuric hypercalcemia
Malignant disease

Calcium metabolism

Calcium disorders (↓Ca, ↑Ca)
• Parathyroid disorders
• Vitamin D disorders

Rickets