Calcium metabolism

Regarding calcium metabolism and physiology:

Organs involved:

Parathyroid glands

Kidney

Bone

Hormones involved:

PTH hormone

Vit D

Calcitonin

Calcium balance in adult:

Dietary Calcium 1000mg

Absorption 400 mg

Daily loss 300 mg in stool

Daily loss 100 mg in urine

In steady state Net gain 0 mg

Conceptualise role of PTH and calcitonin

Conceptualise Vit D biochemistry

HYPERCALCAEMIA

Common (90%) of causes:

Other (10%) of causes:

{{c2::Increased calcitriol production Sarcoidosis tuberculosis and lymphoma}}

{{c2::Adrenal crisis}}Hypercalcemia of malignancy:

{{c1::Production of PTHrp}} 80%

{{c1::Osteolytic metastasis}}20 %

{{c2::Excessive production of calcitriol}} >1%

What is the prognosis like?

{{c1::

}}What are the causes of hyperparathyroidism?

{{c2::

Adenoma 90%

Diffuse hyperplasia 5- 7 %

Carcinoma < 2 %

}}

{{c3::

2ry to hypocalcemia most often resulting from renal insufficiency

Other causes: Chronic pancreatitis, Malabsorption

}}

{{c1::

Tertiary hyperparathyroidism

}}

{{c4::The parathyroid gland become autonomous after prolonged stimulation}}What is Osteitis Fibrosa Cystica (OFC)

´Prolonged {{c1::hyperparathyroidism}}

´Intense {{c1::osteoclastic}} activity

´Osteoclastic bone {{c1::resorption}}

´Reduced {{c1::calcification}} of bone matrix

´Replacement by of bone matrix by {{c1::fibrous tissue}}

´{{c1::Cystic}} lesions in bone

Clinical features of hypercalcaemia? They are mainly due to {{c2::hyperparathyroidism}}

{{c1::

Psychiatric moans

}}{{c3::

´mild neuropsychiatric disturbances

´anxiety, depression, and cognitive dysfunction

´ lethargy, confusion, stupor, and coma

}}

{{c3::

´gastrointestinal abnormalities :

´ constipation, anorexia, and nausea

´Peptic ulcer disease, Pancreatitis

}}

{{c3::

´Renal manifestations

´Nephrogenic diabetes insipidus – polyuria - dehydration

´Nephrolithiasis

´Renal tubular acidosis type 1 /distal RTA /Normal anion gap acidosis

´Renal failure

}}

{{c3::

´Bone pain

´skeletal deformities

´pathological fractures

´osteitis fibrosa cystica (OFC)

}}

{{c3::

´Shortened QT interval

´Deposition of Ca in Heart valves

}}

In diagnostic evaluation of serum calcium must correct for {{c1::hypoalbuminaemia}}

What are the investigations for diagnosis of hypercalcaemia? Work up?

{{c1::Serum Calcium}}

{{c1::Serum PTH}}

{{c1::Urinary excretion of Calcium}}

{{c1::Vitamin D ( 25 OH Cholecalciferol level )}}

Normocalcaemic Hyperparathyroidism - think of coexisting vit. D Deficiency

This is done by:

{{c2::

´Calcium corrected = Ca mg/dl(measured) +

0.8 (4 - albumin g/l )

}}

Regarding hypercalcaemia:

Physical signs:

{{c1::´There are usually no specific physical signs of hypercalcemia other than those that might be related to an underlying disease such as malignancy and nonspecific findings related to dehydration}}

ECG findings (must correct for {{c2::heart rate}})

{{c2::

}}Regarding management of hypercalcaemia:

{{c1::Correct volume deficit N. Saline infusion until euvolemic}}

{{c1::After volume status restored iv frusemide – prevents resorption of Calcium in distal tubule}}

{{c1::

Bisphosphonates

Pamidronate iv infusion- adverse effect osteonecrosis of jaw

Zoledronic acid – iv infusion over 15 min

}}{{c1::Calcitonin inhibits osteoclasts administer IM or Sc}}{{c1::Steroids- Hypercalcemia due to ectopic production of calcitriol granulomatous disease and lymphoma}}{{c1::Gallium nitrate- 5 day infusion - risk of nephrotoxicity}}{{c1::}}HYPOCALCAEMIACauses of hypocalcaemia:Dietary deficiency of calciumDeficiency of Vit DHypoparathyroidismMiscellaneous-Osteoblastic bone metastasis-Pancreatitis-Multiple transfusions-Acute respiratory alkalosis-hyperphosphataemiaCauses of hypoparathyroidism:-Thyroidectomy or irradiation to neck-Autoimmune parathyroid disease as a component of autoimmune polyglandular syndrome Type 1-adrenal insufficiency and mucocutaneous candidiasis-Infiltration of the parathyroids---Haemochromatosis----Metastatic cancer-Hypomagnesemia-PTH resistanceCauses of Vit D defiency includeInadequate exposure to sunlightInadequate intake of vitamin DReduced absorption of vitamin DAbnormal metabolism of vitamin D and phosphate-Vit D dependent rickets (defective conversion )-Familial hypophosphataemic ricketsResistance to the effects of vitamin D-Vit D resistant rickets ( Vit D dependent rickets type II ) Non functional receptorExcessive catabolism of calcitriol by induction of Cy p 450 by anti epileptic medication carbamazepine Calcipaenic rickets-Nutritional rickets-Vitamin D-dependent rickets type I – pseudovitamin D deficiency because its clinical manifestations mimic those of vitamin D deficiency.´ defect in the vitamin D 1-alpha hydroxylase enzyme that converts 25OHD into the active metabolite 1,25(OH) 2 vitamin D. Serum levels of 25OHD are normal and 1,25(OH) 2 D levels are low.-Hereditary vitamin D-resistant rickets – (vitamin D-dependent rickets type II) mutation in the gene that encodes the vitamin D receptor, leading to vitamin D resistance. 25(OH)D levels are normal and 1,25(OH) 2 D levels are high or very high. Regarding hypocalcaemia:Physcal signs:-Perioral paresthesia-Muscle stiffness, cramps, Tetany-Shortness of breath (spasms of diaphragm)-Sweating-Chvostek’s sign-Trousseau’s sign-Seizures-Hypotension-PsychosisWhat is the management of hypoparathyroidism?>> Oral CalciumCa Carbonate, Ca Citrate>> IV calcium Ca gluconate, Ca chlorideindications-seizuresprolonged QT interval