Lecture 12 - Endocrine control of calcium metabolism Flashcards

1
Q

What are the roles of calcium?

A

Control of NEUROMUSCULAR EXCITABILITY Muscle contraction Strength in bones Intracellular second messenger/co-enzyme Hormone/NT stimulus secretion coupling Blood coagulation (factor IV)

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2
Q

Where is most calcium found in the body?

A

Bone (99%) - as complex hydrated Ca salt Blood - present as Ca2+, some bound to protein and a little left as soluble salts

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3
Q

How is most calcium present in the body?

A

Calcium salts

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4
Q

What happens to glucose when it enters the body?

A

MOST absorbed by GI tract into blood (and some secreted back into GI) Can then pass to kidneys which regulates content of blood and returns most of the Ca back into blood, though some excreted Hydroxyapatite crystals in bone can be broken down to increase BCaL Hair, nails, dead cells also loose tiny amounts of Ca

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5
Q

How much Ca is taken up and how much is excreted every day?

A

1000mg/24h intake 850mg/24h lost as faeces 150mg/24h excreted by kidneys

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6
Q

What is the total value of Ca2+ in blood?

A

~2.5mM

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7
Q

How is Ca2+ in blood found?

A

50% - unbound (ionised) 45% - bound to plasma proteins 5% as diffusible salts

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8
Q

What hormones is Ca controlled by?

A

^ by PARATHYROID HORMONE and 1,25 dihydroxycholecalciferol OR calcitriol Decreased by Calcitonin

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9
Q

What are the parathyroid glands?

A

Usually 4 Encapsulated glands Source of PTH Made up by follicles with parafollicluar cells inbetween Parafollicular cells produce calcitonin

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10
Q

What is Parathyroid hormone?

A

Protein, so synthesised as Pre-proPTH PTH polypeptide of 84 aa

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11
Q

Where does PTH bind?

A

To transmembrane G-protein linked receptors Activate adenyl cyclase and phospholipase C as 2nd messenger

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12
Q

What does PTH do to the kidneys?

A

^ Ca2+ reabsorption ^ PO4^3- excretion ^ Calcitriol production (by ^ 1alpha OHase activity) causes in small intestine ^ Ca2+ and PO4^3- absorption

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13
Q

What does PTH do to the bones?

A

OsteoClasts stimulated OsteoBlasts inhibited Hence: ^ BONE RESORPTION

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14
Q

What is the equilibrium between Ca and PO4?

A

3Ca+2PO4 Ca3(PO4)2

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15
Q

What is an important enzymes in the kidneys?

A

1 alpha hydroxylase - involved in the synthesis of calcitriol

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16
Q

How does PTH increase BCaL?

A
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17
Q

What are the 3 main organs with respect to Ca2+?

A

Gut - where most absorbed Kidneys - where most excreted Bone - where most stored

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18
Q

How does PTH act on the bone?

A

PTH acts on the receptor present on the OSTEOBLAST, inhibiting various activities and stimulating production of Osteoclast activating factors OAFs move to osteoClasts and stimulate the breakdown of bone matrix to release Ca2+

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19
Q

Name an OAFs and describe its function

A

RANKL links PTH via osteoblasts but has an inderect effect on osteoclasts

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20
Q

How is PTH regulated?

A

Decreased plasma Ca and catecholamines (via beta receptor) stimulate parathyroid glands PTH produces calcitriol which inhibits PTH production PTH increases plasma [Ca2+], which causes negative feedback

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21
Q

What receptors are present on parathyroid glands that secrete PTH?

A

Beta receptors which can be stimulated by catecholamines to secrete PTH

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22
Q

How is calcitriol synthesised?

A

7-dehydrocholesterol in skin (+UV) and from diet form Vit D3 or cholecalciferol Then 25 (OH) D3 is synthesised in the liver and stored 1aOHase stimulated by PTH forms 1,25 (OH)2 D3, in the kidneys

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23
Q

What are the 2 main sources of cholecalciferol?

A

Diet - different vit D from diet Sunlight - UV B works on skin converting 7-dehydrocholesterol to cholecalciferol

24
Q

What type of molecule is Vit D3?

A

Steroid, circulates around body and taken up by liver

25
Q

What are the actions of calcitriol in the body?

A
26
Q

What do osteoblasts do?

A

They store the calcium in the bone matrix

27
Q

What does RANKL stand for?

A

Receptor activator of nuclear factor kappa-B ligand

28
Q

How does phosphate reabsorption work?

A

On apical membrane there are Na+/PO4^3- cotransporters PTH inhibits transporter so phosphate not reabsorbed and excreted in urine Through FGF23, calcitriol can block the transporter

29
Q

What is FGF23?

A

Fibroblast growth factor 23

30
Q

What is calcitonin?

A

32 aa polypeptide

31
Q

How is it synthesised?

A

Pre-procalcitonin

32
Q

How does calcitonin act?

A

Via transmembrane G-protein linked receptors, activating adenyl cyclase or PLC as 2nd messenger

33
Q

What does Calcitonin act upon?

A

Works on bone, INHIBITS osteoBlast activity - decreases release of Ca into blood Affects kidneys - ^ excretion of Na+ -> Ca and PO4 ions

34
Q

How long do the effects of calcitonin last?

A

Short-lived effects

35
Q

What are the physiological benefits of clacitonin?

A

BCaL ^ during pregnancy, so calcitonin protects the mother’s bones from being broken down when BCaL are low

36
Q

How is calcitonin regulated?

A

^ BCaL and gastrin stimulate parafollicular cells to release calcitonin Acts on bone and kidney and overall decreases BCaL concentration for a short time

37
Q

What is hypocalcaemia?

A

Decreased levels of Ca in blood

38
Q

What are some of the causes of hypocalcaemia?

A

Hypoparathyroidism (insufficient PTH) Pseudohypoparathyroidism (PTH resistance) Vit D deficiency

39
Q

How can hypocalcaemia present?

A

Trousseau’s Sign (main d’accoucheur) Chvostek’s Sign

40
Q

What is Trousseau’s sign?

A

When slight pressure placed on arm, the hand goes into contraction

41
Q

What is Chvostek’s sign?

A

When facial nerve at angle of jaw is tapped, muscles contract

42
Q

What is tetany?

A

Constant contraction due to lack of Ca, allowing Na+ into cell causing constant depolarisation

43
Q

What are the causes of hypoparathyroidism?

A

Idiopathic Hypomagnesaemia (as Mg/Ca share channels)

Suppression by raised BCaL Tumour in parathyroid glands

44
Q

What is pseudohypoparathyroidism?

A

AKA: Allbright Hereditary osteodystrophy Target organ resistance to PTH - due to defective G-protein

45
Q

What are the features of PHoPTism?

A

Short stature, round face Low IQ Subcutaneous calcification and bone abnormalities (shortening of metacarpals) Endo disorders - hypothyroidism, hypogonadism

46
Q

What is the difference between Idiopathic, surgical and pseudo-hypoparathyroidism?

A

Idiopathic and surgical still have sensitive target cells to PTH PHoPTism has target cell resistance to PTH

47
Q

What happens if you are given PTH?

A

Normal: ^ in urinary excretion of cAMP - same for idiopathic and surgical PHoPT: no change occurs as resistant to PTH

48
Q

What is the differential diagnosis of hypo- (1),pseudohypo-(2) parathyroidism and vit D deficiency (3)

A

Plasma Ca - 1, 2 and 3: decrease Plasma PO4 - 1 and 2: ^, 3 decrease PTH: 1: decreases, 2 and 3: ^

49
Q

What diseases are caused by vitamin D deficiency?

A

Rickets in children, Osteomalacia in adults

50
Q

What are the clinical features of vit D deficiency?

A

Decreased calcification of bone matrix - softening of bone Bowing of bone (kids), fractures in adults

51
Q

What are the endocrine causes of hypERcalcaemia?

A

1ry hyperparathyroidism 3ry hyperparathyroidism Vit D toxicosis

52
Q

How common is Vit D toxicosis?

A

Relatively uncommon, but are people who take too much vit D

53
Q

What happens to the kidneys when there is an excess of PTH?

A

^ Ca2+ reabsorption, PO4 excretion and Calcitriol synthesis Polyuria, Renal stones (Ca deposited as stones), Nephrocalcinosis

54
Q

What happens to the GIT and bone when excess PTH?

A

GIT: Gastric acid and duodenal ulcers Bone: lesions, rarefraction and fractures occur

55
Q

What are some features of 1ry HerPTism?

A

Clubbing of fingers Marked periosteal bone erosion in terminal phalanges

56
Q

What is the difference between primary, secondary and tertiary hyperparathyroidism?

A
57
Q

What are the actions of PTH?

A