calcium

Question 2

• Total body calcium = 1kg (25mol)• __% of this is in bone as hydroxyapatiteo 990g in bone (hydroxyapatite)o __g as non-skeletal calcium

Answer 2

9910

Question 3

Intracellular calcium 0.1 – 1 μmol /LInterstitial fluid calcium 1.5 mmol /LSerum calcium __-__ mmol /L

Answer 3

2.2- 2.6

Question 4

__% bound to serum albumin__% complexed with citrate__% (~1.3 mmol /L) free Ca2+ ions

Answer 4

44947

Question 5

Ca intake: 25mmol__% filtered and reabsorbed so <__% excreted in urine

Answer 5

955

Question 6

in which organ are the following produced?__(caliciol)__(calcidiol)__(calcitriol)

Answer 6

Skin Liver Kidney

Question 7

Renal absorptionProximal tubule and Thick ascending limb: __t/p, not regulated by hormones TAL: transcellular transport: ↑ by_ ↓__Distal tubule: ____transport ↑ by___ and ___ ↓ by ___

Answer 7

paracellular PTH, Calcitonintranscellular PTH and calcitriolcalcitonin

Question 8

OsteoblastsDerived from fibroblast-like precursor cellsSynthesise ___(organic bone matrix)Involved in mineralisation of newly synthesised osteoidBecome surrounded by calcified bone –>

Answer 8

osteoid osteocytes

Question 9

OsteoclastsMultinucleate cells derived from ___Secrete lysosomal enzymes–>resorb bone

Answer 9

phagocytes

Question 10

Osteoblasts are stimulated by: (3)To produce factors that: ↑__differentiation ↑___activity

Answer 10

 parathyroid hormone calcitriol (PGE2)osteoclast

Question 11

Osteoclasts are inactivatedby _____

Answer 11

calcitonin

Question 12

Parathyroid hormoneHypercalcaemic action: ↑ bone resorption by stimulating osteoblasts to produce _________ ↑ renal tubule resorption of calcium ↑ phosphate excretion, lowering serum phosphate–> ↑serum calcium

Answer 12

osteoclast activating factors (but calcium excretion may increase because of the greater filtered load due to hypercalcaemia induced by PTH)

Question 13

Parathyroid hormone via cell surface __: on osteoblasts  on the antiluminal surface of the distal renal tubulesLinked to adenylate cyclase –> cAMP

Answer 13

receptors

Question 14

Parathyroid hormoneContinual secretion, rapid clearance (half-life ~5 min) chief cells have calcium receptor linked to PLC, –>___ and ___ Mg2+ is required for secretion

Answer 14

IP3 and DAG hypercalcaemia inhibits secretion hypocalcaemia stimulates secretion

Question 15

Primary hyperparathyroidism benign tumour of parathyroid glandsSecondary hyperparathyroidism compensation for long-standing____ poor Ca2+ intake / absorption response to low calcitriol in ____

Answer 15

hypocalcaemiachronic renal failureSub-periosteal bone resorption may –> cyst formation and bone pain

Question 16

HypoparathyroidismIatrogenic or Idiopathicsigns (3)Pseudohypoparathyroidism tissue ___to PTH action defect of bone +kidney PTH receptorssigns (3)

Answer 16

LOW circulating PTH, hypocalcaemia and hyperphosphataemiaresistance HIGH circulating PTH, hypocalcaemia and hyperphosphataemia

Question 17

in Hypoparathyroidism, injection of PTH –> ↑__Pseudohypoparathyroidism–> NO increase in__

Answer 17

cAMP

Question 18

Hypocalcaemia causes:↑ excitability of nerve tissue paraesthasia, tetany and sometimes __Treatment?

Answer 18

epilepsycalcium supplements and calcitriol

Question 19

Calcitonin: the hypocalcaemic hormoneparafollicular ‘C cells’ are embryologically distinct from thyroid cells–> they are derived from ___ ___

Answer 19

neural crest

Question 20

CalcitoninActs to lower serum calcium by inhibiting bone demineralisation___stimulates secretion

Answer 20

hypercalcaemia

Question 21

medullary thyroid cancer :tumour of the C cells may be assoc w/ tumour of ___cells of the adrenal medulla e.g. MEN II  have very __circulating calcitonin but ___serum calcium

Answer 21

chromaffin highnormal

Question 22

Skin: UV light7dehydrocholesterol–>preVitD–>_______

Answer 22

calciol (cholecalciferol)

Question 23

calciol-→ calcidiol by what enzyme?where does this reaction occur?

Answer 23

25-hydroxylaseliver

Question 24

calcidiol-→ calcitriol by what enzyme?where does this reaction occur?

Answer 24

1-hydroxylasekidney

Question 25

Calcitriol induces 24-hydroxylase and represses ____PTH stimulates _________suppresses 1-hydroxylase

Answer 25

1-hydroxylase1-hydroxylaseCalcitonin

Question 26

Hypercalcaemic actions of vitamin DStimulation of intestinal calcium absorption rapid action by __________ slow action by induction of calbindin-D Stimulation of reabsorption in distal tubuleStimulation of __to secrete __→___of bone mineral

Answer 26

recruitment of calcium transporters to cell surfaceosteoblasts , osteoclast stimulating factorsmobilisation

Question 27

Calcitriol synthesised only in the _____________After admin of radioactive calcitriol, accumulates only in the ______ – the site of its action on calcium reabsorption

Answer 27

proximal renal tubuledistal tubule (and collectingduct)

Question 28

nuclear actions of calcitriol circulates bound to Gc globulin binds to ___→ conformational changeactivated VDR forms heterodimer with RXR→ phosphorylation, permits binding of dimer to____

Answer 28

vitamin D receptor HRE on DNA

Question 29

interactions between Vit A and D__is required for binding calcitriol, thyroid hormone and PPAR receptors to DNA to act as __________absence of 9-cis-retinoic acid, heterodimers bind to DNA and act as_____

Answer 29

RXRtranscriptional activators repressorsFormation of RXR homodimers in high conc 9-cis-retinoic acid downregulates responses to calcitriol, etc as less RXR is available to form active heterodimers

Question 30

other actions of calcitriolInsulin secretion via ___Inhibition of cell proliferation and differentiation viaGPCRs linked to PLCPotentiation of apoptosis induced by vitamin __

Answer 30

calbindin induction in beta-cellsAVitamin A deficiency or excess impairs vitamin D function

Question 31

• APUD cells derived from the neural crest, are those that develop to form:

Answer 31

o C-cells of the thyroid glando Chromaffin cells of the adrenal medulla

Question 32

• APUD cells that are NOT derived from the neural crest are found in the

Answer 32

o Islet of Langerhanso Anterior pituitary gland o Gastro-intestinal glands

Question 33

• Defects in neural crest-derived APUD cells →__• Defects in APUD cells not derived from the neural crest → __.

Answer 33

MEN2MEN1

Question 34

The secretion of the PTH protein requires magnesium; deficiency can impair PTH secretion in premature→___. • Of the aa in PTH, only __residues at the N-terminus required for full activity.

Answer 34

hypocalcaemia34

Question 35

• Gene encoding calcitonin- subject to ___splicing.• In C-cells: first 4 exons translated →an N-terminal protein + calcitonin. • In the brain: 4th exon skipped→ “calcitonin gene-related peptide” (CGRP). a potent __,may also act as neurotransmitter.

Answer 35

alternative vasodilator

Question 36

symptoms of hypercalcaemia?

Answer 36

• Formation of renal calculi (kidney stones) in calyces• calcium-phosphate complexes may move down ureter:→ o Haematuria o Recurrent renal tract infections (pyelonephritis)↑ PTH/calcitriol ↑ subperiosteal bone reabsorption  cyst formation & bone pain.

Question 37

Why is hypercalcaemia common feature of malignant disease?

Answer 37

when malignant cells metastasise to bone, they secrete “OAFs” (PGs and interleukins) stimulating bone resorption, ↓serum calcium Common feature of cancerous cells (incl unmetastasised cells) : synthesis of parathyroid hormone related peptide (PTHRP): a hypercalcaemic hormone

Question 38

symptoms of hypocalcaemia?

Answer 38

o Tetanyo Myopathyo “Pins & needles” (paraesthesia)o extreme cases, epilepsy (due to↑ excitability of neurones)skeletal malformities