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)

 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 (Ca 2+ ); mmol/l (total)  Phosphate (HPO 4 2- ); mmol/l  Magnesium (Mg 2+ ); mmol/l  Organ systems that play an import role in Ca 2+ metabolism  Skeleton  GI tract  Kidney  Calcitropic Hormones  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 Ca 2+.  Secretion of PTH is inversely related to [Ca 2+ ].

 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

 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 Non parathyroidPTH Resistance PostoperativeVitamin D deficiency Pseudo- hypoparathyroidism IdiopathicMalabsorptionhypomagnesaemia Post radiationLiver disease CongenitalKidney 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 G  s 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  Vitamin D dependant type II (Vit D resistant)  Hypophosphataemic

 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

 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.

 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