SBM: Pharmacology & therapeutics - Calcium Metabolism & Therapeutics

Question 1

How much calcium is there in the body?

Answer 1

1000g

Question 2

what is our avg daily intake?

Answer 2

1000mg

Question 3

How is our daily intake broken down?

Answer 3

lost in lumen of GI (200mg)
Absorbed from bowel (200-400)
in stool (800-1000mg)

Question 4

How is net Ca balance maintained?

Answer 4

Renal Ca excretion averaging 200mg/day

Question 5

There are 3 areas where extracellular Ca can be found. list them

Answer 5

ionised 50%
protein bound 40% (90% with albumin)
Calcum/Phosphate/Citrate complexs 10%

Question 6

What level is Serum Ca maintained at?

Answer 6

2.2-2.6mM

Question 7

What is the clinical importance of ionised Ca?

Answer 7

cofactor in coagulation cascade (Factor 7,9,PT)

Question 8

Where are the intracellular Ca found?

Answer 8

Mitochondria and microsomes.

Question 9

How is calcium excreted?

Answer 9

Complex and ionised are filtered by glomerulus.

Question 10

How much Ca is reabsorbed and where?

Answer 10

98% - Kidney

70% in the PROXIMAL, 20% in loop, 18% in distal convoluted tubule.

Question 11

PLEASE TRY AND UNDERSTAND THIS…

sLIDE 10/54

Answer 11

↑ glomerular filtration
Hypercalcaemia
 ↓glomerular filtration
Hypocalcaemia
Renal impairment
 ↑ tubular reabsorption
Metabolic alkalosis
Thiazide diuretics (use in renal stones)
Parathyroid hormone
 ↓ tubular reabsorption
Metabolic acidosis
Loop diuretics
↑ extracellular fluid volume

Question 12

What is PTH

Answer 12

parathyroid hormone

Question 13

where is PTH secreted

Answer 13

chief cells in parathyroid

Question 14

what effect does PTH have?

Answer 14

Increase bone resorption, increase Ca reabsoption in DISTAL. Increase Active VIT D production

Question 15

what is Vit D

Answer 15

a secosteroid made in the skin by sun

Question 16

What make it activate?

Answer 16

2 hydoxylations: in liver and kidney

Question 17

What is the active form called?

Answer 17

1,5 (OH)2 D

Question 18

Where can you get vit D?

Answer 18

Vit D2 - yeast/plants

Vit D3 - Fatty fish/cod liver oil

Question 19

What effect does Vita D have?

Answer 19

intestine - increase ca absorption. Bone - mobilisation of calcium stores and mineralisation of bone matrix. And decreases PTH secretion

Question 20

What effect does PTH have on Vit D? And what does Vit D do for PTH?

Answer 20

PTH stimulates increase in active Vit D production. Vit D inversely reduces PTH.

Question 21

What stimulates PTH secretion?

Answer 21

hypocalcaemia

Question 22

factors that affect vit d production?

Answer 22

increase Melanin.
Age .
Lattitude, day, time, season, .
Clothing .

Question 23

What are 2 parts of bone?

Answer 23

Cortical and spongy (trabecular)

Question 24

Describe cortical bone

Answer 24

85% of bone. dense, and compact

Question 25

describe trabecullar bone

Answer 25

15% of bone. Spongy, There is fracture risk here.

Question 26

Describe the bone remodelling cycle.

Answer 26

-

Question 27

What are osteoblasts?

Answer 27

help with bone formation

Question 28

What are osteoclasts?

Answer 28

break down bone

Question 29

What are the clincal symptoms of HYPERcalcaemia?

Answer 29

Poor concentration, confusion, depresion, coma, anorexia, POLYURIA, POLYDIPSIA, NEPHROLITHIASIS, dehydration, SHORT QT interval

Question 30

What differential would flag in your mind for HYPERcalcaemia?

Answer 30

Malignancy (90% cases). Primary HyperParathryoidism. Thyroxicosis. Drug induced (Vit D toxication, Thiazide diuretics, lithium).

Question 31

How would you investigate Hypercalcaemia?

Answer 31

CXR, bloods (renal, PSA, PTH, Vit D). Isotope bone scan

Question 32

how would you treat Mr Smith presenting with Ca levels between 2.6 to 2.8mM? (mild hypercalcaemia)

Answer 32

may not need treatment. Treat symptoms.

Question 33

Severe hypercalcaemia is classified at what stage?

Answer 33

>3mM.

Question 34

how would you treat Mr Smith presenting with Ca levels greater than 3mM?

Answer 34

Rehydrate (0.9% saline), Bisphosphonates (IV pamidronate) , Loop diuretics

Question 35

Define osteoporosis?

Answer 35

Systemic skeletal disease that involves deterioration of bone tissue, leading to bone fragility and increase fracture risk

Question 36

Men or women are more at risk?

Answer 36

Woman 1in2, men = 1in5

Question 37

Risk factors for osteoporosis?

Answer 37

Early menopause, low BMI, low testosterone, glucocorticoid use, malignancy, GI diease, inflammatory disease, FH, smoking/alcohol

Question 38

How would you diagnose osteroporosis?

Answer 38

history. X Ray of thoracolumbar spine. DEXA.

Question 39

What is DEXA?

Answer 39

Bone density scan.

Question 40

A patient with a DEXA score of 0 to -0.1 should be diagnosed with what?

Answer 40

Nothing - normal

Question 41

A patient with a DEXA score of less than -2.5 should be diagnosed with what?

Answer 41

Osteoporosis

Question 42

What are the drugs you can give to treat osteoporosis? (6)

Answer 42

``` Vit D/Calcium. Bisphosphonates. . Strontium Ranelate . Teriparatide . Raloxifene . Densoumab ```

Question 43

How could you maximise Ca/Vit D intake?

Answer 43

Give ca and vit d. | Adcal D3

Question 44

What are bisphosphonates?

Answer 44

Inhibits osteoclastic bone resorption

Question 45

What bisphosphonates are licensed for use?

Answer 45

Alendronate | Risedronate

Question 46

What is Strontium Ranelate?

Answer 46

drug that stimulates bone formation and reduces resorption.

Question 47

What is Teriparatide

Answer 47

A form of of PTH. Severe cases only.

Question 48

How does Densoumab work?

Answer 48

Monoclonal antibodies against the RANK Ligand. The RANK ligand on osteoblasts bind to RANK on osteoclasts to activate the resorption. Therefore antibody blocks this.

Question 49

What is osteomalacia?

Answer 49

Rickets

Question 50

Define rickets?

Answer 50

Defect of bone matrix mineralisation occuring after skeletal growth is COMPLETE.

Question 51

What can cause osteomalacia? And how will it present?

Answer 51

Poor sunlight, bowel disease, elderly. ---- Bone pain, and waddling gait.

Question 52

How do you treat rickets?

Answer 52

Vit D and Ca. Adcal?

Question 53

What investigation for Rickets?

Answer 53

Ca and phosphate. (Low ca and high phosphatase). Serum 1,25 (OH)2D. Pelvic X ray looking for Loose's Zone.