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Blwyddyn 1; Tymor 3 > 137; Calcium Homeostasis > Flashcards

137; Calcium Homeostasis Flashcards

1
Q

Why is VitD considered a hormone?

A

It is produced intrinsically and acts as different sites within the body

(Other vitamins acquired through diet)

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2
Q

What VitD derived from?

A

7-dehydrocholesterol

(A sterol)

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3
Q

What is the first step in VitD activation? Where does this occur?

A

7-dehydrocholesterol

–>

*UVlight @ skin*

–>

VitaminD3

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4
Q

What is the next step in VitD activation following formation of VitD3?

Where does this occur?

A

VitD3

–>

*25-hydroxylase, liver*

–>

25(OH)VitD3

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5
Q

What regulates the activity of 25-hydroxylase?

A

Nothing, it is active regardless of PTH/Ca levels

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6
Q

What is the next step in VitD activation following formation of 25(OH)VitD3?

Where does this occur?

A

25(OH)VitD3

–>

*renal 1-a-hydroxylase, kidneys*

–>

1,25(OH)VitD3

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7
Q

What regulates the activity of renal 1-a-hydroxylase?

A

PTH is stimulatory

Ca stimulates to a lesser extent

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8
Q

What is the best screening test for VitD adequacy?

A

25(OH)VitD3 blood test

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9
Q

Diagram fo VitD synthesis

A
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10
Q

Rocaltrol, Calcijex, Decostriol, Biowoz, Vectical… are market names for what?

A

VitaminD

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11
Q

On what type of receptor does VitD act?

A

Transmembrane GPCR

They exist internally and on cell surfaces (evolutionary similarities with steroid receptors)

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12
Q

What is the role of VitD in the gut?

A

Small intestine- stimulates trans-epithelial movement of Ca and PO4

This increases serum Ca levels

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13
Q

What is the role of VitD in bones?

A

Stimulate terminal differentiation of OsteoClasts (directly, and via OsteoBlasts), which resorb bone

…Increases serum Ca

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14
Q

What is the role of VitD on the Parathyroid glands?

A

Decreases transcription of the PTH gene;

PTH increases VitD production through its stimulatory action on renal 1-a-hydroxylase

Negative feedback

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15
Q

Where is PTH produced?

A

Parathyroid glands

It is an 84aa peptide hormone

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16
Q

On what organs within the body does VitD act?

A

GIT

Bones

Parathyroids

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17
Q

List 5 majorfunctions of PTH

A
  1. Maintain normal Ca and PO4 levels
  2. Activates VitD (VitD -ve feedback on PTH)
  3. Stimulates bone resorption
  4. Stimulates renal tubular reabsorption of Ca
  5. Stimulates activity of renal 1-a-hydroxylase (indirectly causing Ca absorption in gut)
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18
Q

What stimulates PTH secretion?

A

Falling Ca levels

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19
Q

What supresses PTH secretion?

A

VitD

Rising Ca levels

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20
Q

On what type of receptor does PTH act?

A

GPCR

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21
Q

The PTH receptor binds to PTH with the same affinity as which other protein?

A

PTHrP

ParaThyroid Hormone related Protein

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22
Q

What effect does PTH have on tubular reabsorption of minerals?

A

PTH promotes Ca reabsorption

PTH internalises and degrades Phosphate receptors leading to reduced reabsorption

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23
Q

How are Ca levels detected in various organs?

A

Via Ca-sensing receptors

…on the kidneys and parathyroids

24
Q

Where is Calcitonin produced and secreted?

A

Parafollicular cells of the thyroid glands

(C-cells)

25
How is Calcitonin regulated?
Directly by Calcium S T I M U L A T O R Y
26
What is the role of Calcitonin?
Inhibits OsteoClast function; thus reducing resorption At high Ca levels, calcitonin decreases bone resorption It has no role in daily maintenance of Ca homeostasis
27
What is Hypercalcaemia?
Blood Ca level above **2.1 - 2.5 mmol/l**
28
What are the signs and symptoms of Hypercalcaemia?
**Stones**; renal- diuresis, dehydration and kidney (&biliary) stones **Bones**; bone resorption, bone pain, inc. fractures **Groans**; nausea, vomiting, anorexia, abdominal pain **Thrones**; constipation, polyuria **Phsychiatric Overtones**; depression, anxiety, decreased alertness, coma, confusion CV risks; cause/exacerbate hypertension, shorten QT interval
29
What are the hormonal causes for Hypercalcaemia?
1. Primary hyperParathyroidism (eg Parathyroid tumour) 2. Hypervitaminosis D 3. Praneoplastic; PTHrP, cytokines...
30
What are the non-hormonal causes of Hypercalcaemia?
1. Milk-alkali syndrome 2. Renal failure 3. Medications; Thiazide diuretics, Lithium
31
What is Hypocalcaemia? How is it measured?
Blood Ca level below 2.1mmol/l Measured through ionised Ca; cannot be accurately measured without knowing serum albumin levels
32
What are the signs and symptoms of Hypocalcaemia?
Lowers depolarisation threshold; associated with increased activity 1. Perioral tingling and parasthesia 2. Tetany 3. Facial spasms 4. Hyper-reflexia 5. Laryngospasm 6. Cardiac arrhythmias
33
What are the hormonal causes of Hypocalcaemia?
Hypoparathyroidism ee. Surgical removal Autoimmune Pseudo hypoparathyroidism (PTH receptor dysfunction) Idiopathic
34
What are the non-hormonal causes of Hypocalcaemia?
**HypovitaminosisD**; diet, rickets, osteomalacia **Organ dysfunction**; GI mamabsorption, renal loss **Genetic**; Ca-sensing receptor dysfunction Or an endocrine response to a non-hypoparathyroid hypocalcaemia, causing secondary hyperparathyroidism?
35
What is Rickets?
VitD deficiency in children
36
What are the signs and symptoms of rickets?
Bowed legs Abnormal amounts of unmineralised osteoid Soft bones; easily fractured, loss of rigidity
37
What is Osteomalacia?
VitD deficiency in adults
38
What are the signs and symptoms of Osteomalacia?
Increased amounts of unmineralised osteoid Reduced bone strength, easily fractured Adults with VitD deficiency do not have bowed legs because epiphyses are fused, bone growth complete
39
What does Ca-sensing receptor dysfunction cause?
Hypocalcuric-Hypercalcaemia (familial) ## Footnote An inactivating mutation desensitises the receptor for Ca; higher Ca levels required to supress PTH Mild in Hetero-, lethal in Homo- children due to extreme Hypercalcaemia Also causes reduced Ca loss from urine
40
What does PTH receptor dysfunction cause?
Pseudo-Hypoparathyroidism Hypocalcaemia PTH levels are **high** but receptors are resistant. Caused by mutation i one of G subunits
41
What 2 major factors are required for Ca absorption?
VitD Sunlight
42
Give examples of GI dysfunctions that reduce Ca absorption
Short bowel Malabsorptive disorders IBS
43
Why might a high phosphate diet compromise Ca absorption?
Phosphate binds with high affinity for Ca; With high PO4 less Ca is available for absorption
44
Give examples of Renal dysfunctions that cause Hypocalcaemia
Abnormal response to PTH; * 1-a-hydroxyl activation * Ca reabsorption in tubules Insufficiency of 1,25(OH)D3 Genetic tubular Ca leak; * hypercalciuria * secondary hyperparathyroidism
45
What is the main cause of Hypercalcaemia?
Primary hyperparathyroidism; Adenoma or hyperplasia of parathyroids
46
What are the clinical features of primary hyperparathyroidism?
Hypercalcaemia High PTH Hypercalciuria Increased fractures Increased risk of kidney stones
47
Renal failure-associated hypercalcaemia...
Renal failure can cause hyper- and hypo- calcaemia. Hypercalcaemia due to; Reduced tubular Ca clearance Increased resorption from bones (high PTH) Renal failure causes: PTH elevation Low endogenous 1,25(OH)D3 Abolished Ca and PO4 clearance (dialysis filters these poorly also)
48
What are the causes of hypervitaminosis D?
Excess dietary intake; through supplements Excess intrinsic production; Extra-renal 1-a-hydroxylase activity Granulomas (MO) or lymphomas 1-a-OH not regulated by PTH or Ca
49
What are the clinical features of Hypervitaminosis D?
HypoPTH Hypercalcaemia
50
Study this diagram of Ca homeostasis
51
Study this diagram of VitD synthesis
52
Name a population at risk of VitD deficiency
Finnish Anyone with lack of sunlight
53
What are the problems with using VitD and PTH as medications?
They are peptides; Will be digested if taken orally
54
Ca, PTH & VitD feedback loops:
55
Detailed Ca homeostasis diagram

Blwyddyn 1; Tymor 3 (13 decks)

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