Calcium metabolism and vitamin d deficiency
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Transcript of Calcium metabolism and vitamin d deficiency
CALCIUM METABOLISM AND VITAMIN D DEFICIENCY
CALCIUM METABOLISM ANDVITAMIN D DEFICIENCYPRESENTED BY : KUMAR AMIT
MODERATED BY : DR.K.C.PATRAHOD AND PROFDEPT.OF PEDIATRICS
CALCIUM METABOLISM
INTRODUCTIONCALCIUM IS THE FIFTH MOST ABUNDANT ELEMENT IN THE EARTHS CRUST.
CALCIUM DERIVES ITS NAME FROM CALCIS MEANING LIME
IN HUMAN BODY NINETY NINE PERCENT OF CALCIUM FOUND IN SKELETON AND ABOUT ONE PERCENT IS IN ECF FOR PHYSIOLOGICAL FUNCTIONS.
FUNCTION OF CALCIUM FORMATION OF SKELETONBLOOD COAGULATIONCELLULAR COMMUNICATIONEXOCYTOSIS AND ENDOCYTOSISMUSCULAR CONTRACTION AND RELAXATIONNEUROMUSCULAR COMMUNICATION
PHYSIOLOGYIN BLOOD,
TOTAL CALCIUM CONCENTRATION IS NORMALLY - 8.5-10.5mg/dl
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BECAUSE CALCIUM BINDS TO ALBUMIN AND ONLY THE UNBOUND CALCIUM IS BIOLOGICALLY ACTIVE ,THE SERUM LEVEL MUST BE ADJUSTED AS FOLLOWS
CORRECTED Ca2 = [4-plasma albumin in g/dl]*0.8 + measured serum calcium
Factors affecting calcium concentration1) Changes in plasma protein concentrationIncreased [protein] Increased total [Ca2+]
2) Changes in anion concentrationIncreased [anion] increased fraction of Ca2+ that is complexed decrease ionized [Ca2+]
3)Acid base abnormality
Acid Base Abnormality
Calcium HomeostasisBlood calcium is tightly regulated by:
1) Principle organ systems: IntestineBoneKidney
2) Hormones: Parathyroid hormone (PTH)Vitamin DCalcitonin
Parathyroid GlandHuman beings have four parathyroid glands, which are situated on the posterior surface of upper and lower poles of thyroid gland.
Parathyroid glands are very small in size, measuring about 6 mm long, 3 mm wide and 2 mm thick, with dark brown color.
HistologyMade up of chief cells and oxyphil cells. Chief cells:Secrete parathormone.
Oxyphil cells Degenerated chief cells and their function is unknown. May secrete parathormone during pathological condition called parathyroid adenoma.
ParathormoneSecreted by parathyroid gland
Essential for the maintenance of blood calcium level within a very narrow critical level.
Maintenance of blood calcium level is necessary because calcium is an important inorganic ion for many physiological functions.
CHEMISTRY
Parathormone is protein in nature, having 84 amino acids.
Its molecular weight is 9500.
Half-life and Plasma LevelParathormone has a half-life of 10 minutes.
Normal plasma level of PTH is about 1.5 to 5.5 ng/dL.
SynthesisSynthesized from the precursor called pre-pro-PTH containing 115 amino acids.
First, the pre-pro-PTH enters the endoplasmic reticulum of chief cells of parathyroid glands.
There it is converted into a prohormone called pro-PTH, which contains 96 amino acids.
Pro-PTH enters the Golgi apparatus, where it is converted into PTH.
Metabolism
60 70 % of PTH is degraded by Kupffer cells of liver, by means of proteolysis.
Degradation of about 20% to 30% PTH occurs in kidneys and to a lesser extent in other organs.
Actions Of Parathormone On Blood Calcium Level
Primary action of PTH is to maintain the blood calcium level within the critical range of 9 to 11 mg/dL.
PTH maintains blood calcium level by:Resorption of Ca from BonesReabsorption Ca from the renal tubules (Kidney)Absorption of Ca from Gastrointestinal tract.
On Bones
Parathormone enhances the resorption of calcium from the bones by acting on osteoblasts and osteoclasts of the bone.
Resorption of calcium from bones occurs in two phases:Rapid phaseSlow phase.
PTH calcium and phosphate absorption from the bone Second phaseFirst phaseslowrapidDays-weeksMinutes-hoursProliferation of osteoclastsActivation of already existing osteocytes /osteoblastsActivated osteocytes/osteoblasts send secondary signals to osteoclastsReceptor protiens on octeocytes/osteoblasts that bind PTH and activate calcium pumpOsteoclastic absorption of bone itselfPromote calcium and phosphate absorption
On Kidney
PTH increases the reabsorption of calcium from the renal tubules along with magnesium ions an hydrogen ions.
It increases calcium reabsorption mainly from distal convoluted tubule and proximal part of collecting duct.
PTH also increases the formation of 1,25- di-hydroxycholecalciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys.
On Gastrointestinal Tract
PTH increases the absorption of calcium ions from the GI tract indirectly.
It increases the formation of 1,25- dihydroxycholecalciferol in the kidneys. This vitamin, in turn increases the absorption of calcium from GI tract.
Thus, the activated vitamin D is very essential for the absorption of calcium from the GI tract & PTH is essential for the formation of activated vitamin D.
Parathyroid Hormone (PTH)
CALCITONIN
Calcitonin secreted by parafollicular cells of thyroid gland.
It is a calcium-lowering hormone.
It reduces the blood calcium level mainly by decreasing bone resorption.
Effects of Other HormonesGrowth hormone
Growth hormone increases the blood calcium level by increasing the intestinal calcium absorption. It is also suggested that it increases the urinary excretion of calcium.
However, this action is only transient.
Glucocorticoids
Decrease blood calcium by inhibiting intestinal absorption and increasing the renal excretion of calcium
INTRODUCTIONElmer McCollum in 1922 noticed that vitamin A deficient cod liver oil cured rickets in dogs. He named it Vitamin D because it was the fourth vitamin to be named.
It is a fat soluble vitamin requires in the body for the maintenance of calcium and phosphorus to support different metabolic functions.
ANTI-MYCOBACTERIAL EFFECTVitamin D stimulates the synthesis of cathelicidin, an anti-microbial peptide that is particularly active against Mycobacterium Tuberculosis.
METABOLISM
OVERVIEW OF CALCIUM METABOLISM
VITAMIN D DEFICIENCY
Rickets is an entity in which mineralization is decreased at the level of
the growth plates, resulting in growth retardation and delayed skeletal
development.
Osteomalacia is found within the same spectrum, affects trabecular
bone, and results in undermineralization of osteoid bone
RICKETS
INTRODUCTION
The term rickets is said to have derived from the ancient English word wricken, which means "to bend.
In several European countries, rickets is also called English disease, a term that appears to stem from the fact that at the turn of the 19th century, rickets was endemic in larger British cities.
Disease of growing bone due to unmineralized matrix
at the growth plates and occurs in children only before fusion of epiphyses
CAUSES OF RICKETS:
1. VITAMIN D DISORDERS2. CALCIUM DEFICIENCY3. PHOSPHORUS DEFICIENCY4. RENAL LOSSES5. DISTAL RTA
EtiologyVITAMIN D DISORDERS - Nutritional vitamin D deficiency- Congenital vitamin D deficiency- Secondary vitamin D deficiencyMalabsorption- Increased degradation- Decreased liver 25-hydroxylase
- Vitamin Ddependentricketstype 1- Vitamin Ddependentricketstype 2- Chronic renal failure
CALCIUM DEFICIENCY Low intake DietPremature infants (ricketsof prematurity)
MalabsorptionPrimary disease- Dietary inhibitors of calcium absorption
RENAL LOSSES X-linked hypophosphatemicrickets Autosomal dominant hypophosphatemicrickets Autosomal recessive hypophosphatemicrickets Hereditary hypophosphatemicricketswith hypercalciuriaOverproduction of phosphatonin Tumor-inducedricketsMcCune-Albright syndromeEpidermal nevus syndrome Neurofibromatosis Fanconi syndromeDent diseaseDistal renal tubular acidosis
PHOSPHORUS DEFICIENCYInadequate intakePremature infants (ricketsof prematurity)Aluminum-containing antacids
PATHOPHYSIOLOGYOvergrowth of epiphyseal cartilage due to inadequate calcification and maturation
Persistence of distorted irregular masses of cartilage which project into marrow cavity.
Deposition of osteoid matrix on inadequately mineralised cartilagenous remnants.
PATHOPHYSIOLOGY Disruption of the orderly replacement of cartilage by osteoid matrix with enlargement and lateral expansion of osteochondral junction
Abnormal growth of capillaries and fibrobkast in the disorganised zone.
Deformation of the skeleton due to loss of structural rigidity of the developing bones.
CLINICAL FEATURESPeak incidence 6 months 2 yearsIrritability profuse sweating while asleephypotonia frequent respiratory infections.Failure to thriveProtruding abdomen. Delay in walking,delayed dentitionTetany.
HEAD Craniotabes Frontal bossing Delayed fontanelle closure Delayed dentition; caries Craniosynostosis
CHEST Rachitic rosary Harrison groove Respiratory infections and atelectasis
BACK Scoliosis Kyphosis Lordosis
EXTREMITIES Enlargement of wrists and ankles
Valgus or varus deformities
Anterior bowing of the tibia and femur
Coxa vara
Leg pain
EXTREMITIES Enlargement of wrists and ankles
Valgus or varus deformities
Anterior bowing of the tibia and femur
Coxa vara
Leg pain
EXTREMITIES Enlargement of wrists and ankles
Valgus or varus deformities
Anterior bowing of the tibia and femur
Coxa vara
Leg pain
EXTREMITIES Enlargement of wrists and ankles
Valgus or varus deformities
Anterior bowing of the tibia and femur
Coxa vara
Leg pain
HYPOCALCEMIC SYMPTOMS:
Tetany
Seizures
Stridor due to laryngeal spasm
Rachitic Rosary:
Craniotabes:
Softening of cranial bones.
KYPHOSIS
Harrison groove:Horizontal depression along lower anterior chest.Due to pulling of softened ribs by diaphragm during inspiration. Softening of ribs impairs air movement & predisposes to atelectasis. Risk of pneumonia high in children with rickets
RADIOLOGY:
Decreased calcification Thickening of growth plate.
FRAYING: Edge of metaphysis loses its sharp border.
CUPPING: Edge of metaphysis changes from convex or flat to concave surface. Most easily seen at distal ends of radius, ulna, fibula.
Widening of distal end of metaphysis Clinically causes thickened wrists and ankles, and rachitic rosary.
RADIOLOGY:
Especially on PA view of wrist. Also in other growth plates.
Other radiologic features: - Coarse trabeculation of diaphysis - Generalized rarefaction.
FrayingCupping
Widening ofGrowth plateAfter treatment
Clinical Evaluation. HISTORY REGARDING:1.Diet intake of Vit D, Calcium2.Sun exposure3.Maternal risk factors for vit D deficiency.4.Child's medication history.5.History of liver or intestinal disease malabsorption of vit D6.History of Renal disease7.Family history of bone disease, short stature, unexplained sibling death.8.History of dental caries, poor growth, delayed walking, waddling gait, pneumonia, and hypocalcemic symptoms.
TreatmentStoss therapy 300000 600000 IU Vitamin D oral or IM, 2-4 doses over one dayAlternatively high dose vit D, 2000-5000 IU/day over 4-6 wkFollowed by oral Vit D : < 1 year of age - 400IU > 1 years of age- 600IUSymptomatic hypocalcemia IV calcium gluconate 100 mg/kg followed by oral calcium or calcitrol -0.05mcg/kg/day
NUTRITIONAL VIT D DEFICIENCY:Prognosis. Most: Excellent response to treatment.Radiologic healing within 4 weeks.Laboratory tests normalize rapidly. Many of the bone malformations improve dramatically, but children with severe disease may have permanent deformities. Short stature does not resolve in some children. Prevention. Universal administration of daily multivitamin containing 200400 IU of vitamin D to children who are breast-fed. For other children, diet should have sources of vitamin D.
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PREVENTIONTo prevent rickets, health experts recommend a child should be breast-fed weaned and put on to cow's milk and other foods rich in vitamin D and calcium, like eggs and dairy products such as butter and leafy vegetables.Fish
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