Hypocalcemia

Question 1

Identify the condition described

Cardiac defects - Truncus arteriosus, Tetralogy of Fallot
Abnormal facies
Thymic hypoplasia–> T cell deficiency–> recurrent viral/ fungal infections
Cleft palate
Hypocalcemia secondary to parathyroid aplasia
22q11 microdeletion

Answer 1

DiGeorge Syndrome

Question 2

Embryologic defect in DiGeorge syndrome that leads to hypocalcemia

Answer 2

failure to develop 3rd and 4th branchial (pharyngeal) pouches–> absent thymus and parathyroid glands

Question 3

Components of Autoimmune polyendocrine failure syndrome-1(APS-1)

Answer 3

chronic mucocutaneous candidiasis+ primary adrenal insufficiency+ hypoparathyroidism

Question 4

Cause for Autoimmune polyendocrine failure syndrome 1(APS-1).

Answer 4

mutations in the autoimmune regulator (AIRE) gene

Question 5

most common cause of hypocalcemia in a hospital setting

Answer 5

Hypomagnesemia

Question 6

Underlying mechanism of autosomal-dominant hypoparathyroidism

Answer 6

gain-of-function mutations in the calcium-sensing receptor (CASR) gene

Question 7

Why are alkaline phosphatase levels elevated in Vitamin D deficiency?

Answer 7

Vitamin D deficiency –> impaired intestinal absorption of calcium—>PTH elevated–> increased bone turnover–> ALP elevated

Question 8

How does hypophosphatemia occur in Vitamin D deficiency?

Answer 8

Vitamin D deficiency –> impaired intestinal absorption of calcium—>PTH elevated–> promotes renal phosphate excretion–>hypophosphatemia

Question 9

How does Vitamin D deficiency occur in chronic renal failure?

Answer 9

CRF–>impaired kidney function–>hampers the final conversion of 25-hydroxychalecalciferol to active 1,25-dihydroxycholecalciferol via 1-alpha hydroxylase

Question 10

How does hypocalcemia occur in chronic renal failure?

Answer 10

1. Failing kidneys—>poor calcium reabsorption
2. deficiency of active vitamin D –> decreased intestinal absorption of calcium

Question 11

Mechanism of renal osteodystrophy in chronic renal failure

Answer 11

Hyperphosphatemia & hypocalcemia –>upregulation of PTH–> increases bony turnover to raise serum calcium and promotes renal excretion of phosphate. Unregulated, this process results in renal osteodystrophy,

Question 12

alternating dense-lucent-dense appearance in untreated chronic hyperparathyroidism

Answer 12

Rugger jersey spine

Question 13

1.

Two radiologic features of long standing hyperparathyroidism

Answer 13

1.Rugger jersey spine
2.Pepper pot skull

Question 14

What’s the cause of this appearnce?

Answer 14

Salt and pepper signorpepper pot skullrefers to multiple tiny well-defined lucencies in the calvaria caused by resorption of trabecular bone inhyperparathyroidism

Question 15

Morphologic hallmark of osteomalacia on bone biopsy

Answer 15

Thickening of osteoid seams

Question 16

Mechanism of Vitamin D–dependent rickets type I

Answer 16

mutations in the gene encoding 25(OH)D-1α-hydroxylase

Question 17

Mechanism of Vitamin D–dependent rickets type II

Answer 17

mutations in the gene encoding the** vitamin D receptor**–>end-organ resistance to the active metabolite 1,25(OH)2D

Question 18

Reason why plasma levels of 1,25(OH)2D are elevated in Vitamin D–dependent rickets type II

Answer 18

1. of increased production due to stimulation of 1α-hydroxylase activity as a consequence of secondary hyperparathyroidism
2. impaired inactivation since induction of the 24-hydroxylase by 1,25(OH)2D requires an intact vitamin D receptor

Question 19

Underlying basis of pseudohypoparathyroidism

Answer 19

loss-of-function mutations in GNAS1–> inactivation of adenylate cyclase when PTH binds to its receptor creating–> end -organ resistance (kidney and bone) to PTH.

Question 20

Phenotype of Albright hereditaty osteodystrophy

Answer 20

short stature, obesity, round facies, Mental retardation, basal ganglia calcification, short fourth and fifth metacarpals

Question 21

Pseudopseudohypoparathyroidism

Answer 21

paternally transmitted mutations (imprinted GNAS gene) but without end-organ resistance to PTH due to normal maternal allele maintaining renal responsiveness to PTH.

Question 22

What is a positive Chvostek sign?

Answer 22

Twitching of the ipsilateral facial muscles on tapping on the facial nerve anterior to the ear

Question 23

What is a positive Trousseau sign?

Answer 23

inflating the sphygmomanometer with the cuff around the arm 20mmHg above the systolic blood pressure for 3 min–>painful carpal muscle contractions and spasms

Question 24

Why do paresthesias develop in hypocalcemia?

Answer 24

neuromuscular irritability

Question 25

What is tetany?

Answer 25

spontaneous tonic muscular contractions, manifested by painful carpal spasms and laryngeal stridor, in individuals with hypocalcemia