Hypoca Flashcards
Calcium is the most abundant mineral (cation) in the human body. • 99% of calcium are in the skeleton in the form of calcium phosphate salts. • The plasma total calcium concentration is in the range of 2.1-2.6 mmol/L
(8.5-10.5 mg/dL). • Normal ionized calcium is 1.3-1.5 mmol/L (4.5-5.6 mg/dL), almost 50%. • Between 35-50% of the calcium in plasma is protein-bound, and 5-10% is
in the form of complexes with organic acids and phosphates . • Plasma Calcium level is regulated by Calcium Homeostasis.
Calcium homeostasis is maintained through tight
regulation with various hormones, most notably
parathyroid hormone (PTH), 1,25(OH)2D (the
active form of vitamin D), and Fibroblast growth
factor 23 .
Calcium homeostasis
Calcium homeostasis
• Blood calcium is tightly regulated by: 1. Principle organ systems : • Intestine • Bone
• Kidney
2. Hormones : • Parathyroid hormone • Vitamin D • Calcitonin • Fibroblast growth factor 23 FGF23 (bone cells). Suppress activation of
Vitamin D 3. Calcium-sensing receptor (CaSR) G-protein coupled receptor
Calcium-sensing receptor (CaSR)
Calcium-sensing receptor (CaSR) It senses extracellular level of calcium
( in parathyroid gland and renal tubules)
• The CaSR regulates calcium level in blood by
influencing parathyroid hormone secretion,
urinary Ca2+ excretion.
Hypocalcemia
In children, hypocalcemia is defined as a total serum calcium concentration less than 2.1 mmol/L (8.5 mg/dL).
Hypocalcemia Etiology and differential diagnoses:
Hypocalcemia Etiology and differential diagnoses:
• Vitamin D disorders : dietary deficiency, lack of sunlight,
malabsorption. • Vitamin D synthesis or receptor defect • Hypoparathyroidism: familial, DiGeorge syndrome,
idiopathic, postsurgical, autoimmune polyglandular syndrome
type 1. • Other: chronic kidney disease, acute pancreatitis,
magnesium deficiency. • Neonatal hypocalcemia ( early Vs late)
Sangad sakati syndrome
Congenial hypo parathyroid
Late opneonatal hypoca
Clinical Presentation of hypocalcemia
Clinical Presentation of hypocalcemia
Nonspecific symptom of weakness
Neurologic symptoms and signs
perioral numbness, paresthesia, carpal-pedal spasms, tetany, seizures, positive Chvostek’s sign, and positive Trousseau’s sign
Rickets (skeletal) signs if hypocalcemia is chronic
hypocalcemia
Laboratory evaluation should include: Calcium , Phosphorus, Magnesium, creatinine PTH 25-OH vitamin D level, 1,25-OH vitamin D level, Urine calcium/urine creatinine
Albumin should always be assessed: For every 1 g/dL that the serum albumin is below normal, 0.8 mg/dL should be added to the serum calcium Corrected Ca = S.Ca + 0.8 (4 – S. Albumin)
Ionized calcium is often a more reliable estimate of serum calcium level
Treatment hypocalcemia
Treatment
• Treat the underlying cause. • If severe hypocalcemia (e.g., ECG changes showing prolonged QT interval) and/or
symptomatic hypocalcemia, administer IV calcium gluconate ( 1-2 ml/kg of 10%
calcium gluconate diluted in NS) • Consider ECG monitoring because there is a risk of cardiac arrest if calcium
infusion is too rapid. • If the patient is stable and/or hypocalcemia is chronic , oral calcium should be
initiated (50 mg/kg/day of elemental ca). • Start cholecalciferol or calcitriol if Vit D deficiency or hypoparathyroidism,
respectively . • Replete with magnesium if the patient is hypomagnesemic • Long-term monitoring is needed to avoid hypercalcemia , which may have
negative consequences (e.g., nephrocalcinosis, pancreatitis)
Hypoparathyroidism Etiology
Hypoparathyroidism Etiology
• Congenital : isolated or syndromic (DiGeorge
Syndrome, Sanjad-Sakati Syndrome ) • Iatrogenic— neck surgery
• Component of autoimmune polyglandular
diseases.
• Resistance to parathyroid hormone receptor
(Pseudohypoparathyroidism)
Congenital Hypoparathyroidism
Congenital Hypoparathyroidism
• Several familial forms exist with autosomal recessive, autosomal
dominant, or X-linked recessive inheritances • Other inherited syndromes: Barakat syndrome (hypoparathyroidism-deafness-
renal dysplasia [HDR]) Sanjad-Sakati syndrome (hypoparathyroidism-
mental retardation-dysmorphism [HRD])
Acquired Hypoparathyroidism
Acquired Hypoparathyroidism
• Autoimmune forms often exist as part of autoimmune
polyendocrinopathy syndrome type 1 • Infiltrative conditions such as hemochromatosis, iron
overload, Wilson disease • Idiopathic hypoparathyroidism: diagnosis of exclusion • Iatrogenic: Usually secondary to anterior neck surgery
such as thyroidectomy (look for neck scar)
Type 1a is the most common type of pseudohypoparathyroidism
Albright’s hereditary osteodystrophy
Albright’s hereditary osteodystrophy • Resistance to thyroid-stimulating hormone, gonadotropins, and
growth hormone-releasing hormone. • Short stature, cognitive impairment, skeletal abnormalities. • Brachydactyly of the third, fourth, and fifth metacarpals • Round face with low nasal bridge • Subcutaneous calcifications
Hypocalcemia Manifestations:
Hypocalcemia Manifestations:
• Irritability • Seizures • Jitteriness • Carpopedal spasm • Chvostek’s sign and Trousseau’s sign.
Hypoparathyroidism
Hypoparathyroidism)
• Low calcium and high phosphate. • Low PTH in primary hypoparathyroidism. • High PTH with low calcium in
(psoudohypoparathyroidism) due to receptor defect. • One-alfa hydroxylation defect of vitamin D. Low 1,25
vit D • High urine Ca /creatinine ratio
Treatment of hypoparathyroidism
• Calcium supplements • Calcium infusion if symptomatic • Calcitriol (active form of vit D) • Frequent follow-up for growth and calcium levels . • Adjusting the dose to maintain the plasma calcium concentration
just below the normal range . • Hypercalciuria should be avoided as it may cause
nephrocalcinosis, so urinary calcium level should be monitored.
Recombinant human PTH analogs not
recommended in children due to high risk of
osteosarcoma
The recommended intake of vitamin D to prevent deficiency
in normal infants and young children is 400 - 600 units/day.
Phosphopenic rickets usually is caused by renal phosphate
wasting.
• FGF23 is the major phosphate regulator that stimulates
phosphaturia (renal phosphate wasting) it get increased in
phosphopenic rickets e.g. ( X-linked hypophosphatemic
ricket).
Alkaline phosphatase levels are usually high in
calcipenic rickets. • Whereas they are marginally elevated in
phosphopenic rickets. • PTH is the most important biochemical
investigation which is elevated in calcipenic rickets
but usually normal in phosphopenic rickets.
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Vitamin D deficiency
Vitamin D deficiency
• Nutritional vitamin D deficiency (commonest
type). • Vitamin D deficiency also can be secondary to: Malabsorption Anti-epileptic drug therapy Chronic renal failure Liver failure
Clinical assessment of rickets
Clinical assessment of rickets
• Clinical history plays an important role in delineating
the cause of rickets. • Dietary and sun exposure history. • Consanguinity • Family history of rickets • History suggestive of chronic renal, liver disease, and
malabsorption.
In the older child
In the older child
• Waddling gait • Harrison sulcus • rachitic rosary • Genu-valgum • Genu-varum • Seizures • Bone pain • Short stature
Radiological investigation • X- rays of wrist and knee
Wide od distal end of ulna and radios
Cupping and fraing of metaphysical part
Vitamin D deficiency
Vitamin D deficiency
• Diagnosis: • Low 25-OH vitamin D (but 1,25-[OH]2 vitamin D
may still be normal) • PTH will be elevated • Alkaline phosphatase will be elevated because of
increased bone turnover
Managements
• If symptomatic Hypocalcaemia consider calcium iv infusion . ( 1-2
ml/kg of 10% calcium gluconate diluted in NS) (acute treatment) • Calcium supplements.(50 mg/kg/day of elemental calcium). • Vit D replacement therapy 2000-4000 IU daily for 4-6 weeks then
follow up with vit D level and x-ray if improved continue
maintenance therapy 400-600 U daily. • If malabsorption, liver disease or compliance is an issue, a single
oral or intramuscular dose of vitamin D 150-300,000 units can be
given every 3 months.
Vitamin D “Dependent” Rickets
Vitamin D “Dependent” Rickets
Genetic defect of vitamin D synthesis or receptors:
• 25 hydroxylase deficiency in liver (rare). • 1-hydroxylase deficiency in kidney. (Vitamin D-
dependent type I rickets VDDR 1) • Vitamin D receptor resistant rickets. (Vitamin D-
dependent type II rickets VDDR 2)
Vitamin D receptor resistant rickets ( vitamin D-dependent rickets type II)
Vitamin D receptor resistant rickets ( vitamin D-dependent rickets type II)
• Very rare inherited autosomal recessive disorder , usually caused by
mutations in the gene encoding the vitamin D receptor , leading to end-
organ resistance to vitamin D • Normal at birth, develops rickets within first 2 years of life. • Associated with alopecia • Diagnosis: elevated 25-OH vitamin D and 1,25-(OH) 2 vitamin D levels • Treatment: high-dose calcitriol and calcium supplementation; depending
on severity, may not respond to oral treatment and could require
IV calcium infusions
Hypophosphatemic Rickets Vitamin D-resistant rickets
Vitamin D-resistant rickets
• Low phosphorous intake . • Prematurity/ Total parenteral nutrition. • Renal phosphate wasting . • Excessive Fibroblast growth factor-23 (FGF-23) is a hormone secreted by osteoblasts, osteoclasts, and osteocytes that decreases phosphate reuptake in the kidney.
X-linked hypophosphatemic rickets (XLH)
X-linked hypophosphatemic rickets (XLH)
• The most common cause of inherited rickets
• XLH is caused by mutations in the phosphate regulating
endopeptidase on the X chromosome (PHEX) gene , which
leads to elevated levels of FGF23 and hypophosphatemia • FGF23 inhibits 1-alpha-hydroxylase, which leads to a net
decrease in intestinal phosphate absorption.
• FGF23 decreases renal phosphate absorption , leading to
renal phosphate wasting
Clinical presentation
• Is similar to vitamin D deficiency rickets, with
a propensity toward dental abscesses,
craniosynostosis, lower limb deformity
• Bone pain is also characteristic • Family history of rickets is typical, although
some cases are caused by sporadic PHEX
mutations
Burosumab, human monoclonal antibody against
FGF23, has been approved for treatment of XLH
