Week 6: Endocrine 4: calcium homeostasis and CKD

Question 1

What are the functions of calcium?

Answer 1

Muscle contraction
blood clotting
nerve conduction
Bone mineralisation
Hormonal communication

Question 2

What is the distribution of total body calcium?

Answer 2

99% is found in the bone
1% is found in body fluids

Question 3

What is the distribution of calcium in the body fluids?

Answer 3

50% is ionised or free
10% is bound to anions (phosphate)
40% if protein bound (of which 80% is bound to albumin and 20% to globin)

Question 4

What is the biologically active calcium?

Answer 4

Ionised or free calcium

Question 5

What is the normal levels of ionised calcium in adults?

Answer 5

4.64 to 5.28 mg/dL

Question 6

What is meant by adjusted calcium?

Answer 6

Aims to measure the amount of free or ionised calcium only - the active calcium in the body
This is useful when there are extremes in protein bound or anion bound calcium should as hypoalbuliminia that effect total calcium levels but may not effect the levels of active calcium.

Question 7

What hormones are responsible for the regulation of calcium levels in the blood?

Answer 7

parathyroid hormone
Calcitriol or vitamin D3
Calcitonin

Question 8

What are the main organs that are involved in the homeostasis of calcium?

Answer 8

Kideny
Bone
Intestines.

Question 9

What is the most potent regulator of calcium levels in the ECF?

Answer 9

Parathyroid hormone

Question 10

Where and under what conditions is parathyroid hormone produced?

Answer 10

Produced by parathyroid glands
Cheif cells in the gland

In response to low levels of Ca2+

Question 11

What is the suggested role of oxyphil cells in the parathyroid gland?

Answer 11

Hypothesised - not known
Suggested to be inacitvated chief cells - rather than undergoing apoptosis become inactive cells.

Question 12

What are the main mechanisms of parathyroid hormones effect on calcium levels?

Answer 12

Act directly on the kidney
Acts indirectly on the intestine by vitamin D
Acts indirectly on the bones

Question 13

What is the effect of parathyroid hormone on the kidney?

Answer 13

Directly - increase calcium reabsoprtion so decreased excretion in urine
- decrease phosphate reabsorption leadsing to increased secretion in urine
This leads to increased blood calcium and decreased blood phosphate

Indirectly - increased calcitriol formation - increases levels in the blood stream leading to increased calcium absorption from the small intestine - leading to higher levels of plasma calcium

Question 14

What are the effects of parathyroid hormone on the bone?

Answer 14

Acts indirectly
Binds to receptors on osteoblasts - causes to proliferate and release RANKL and M-CSF
RANKL and M-CSF binds to receptors on the surface of osteoclasts and activates the osteoclast
The osteoclast secretes acid and lysosomes fuse with the ruffled membrane to release enzymes to the bone.
Bone is reabsopbed (broken down) releasing phosphate and calcium into the blood.

Question 15

What is the process of vitamin D synthesis?

Answer 15

D3 ( 7-dehydrocholesterol) can be converted to cholecalciferol (D2) in the skin in the presence of UV light
Cholecaliferol can also be obtained. directly by diet

In the liver, 25-hydroxylase enzymes catalysed the first hydroxylation converting into calcidiol.

Travels to the kidney where 1-alpha hydroxylase catalysed the second hydroxylation converting into calcitriol (1,25 -(OH)2- cholecalciferol active vitamin D). This enzyme is promoted in low blood calcium.

Another pathway in the absence of 1-alpha hydroxylase in the kidney converts to an inactive form 24,25 (OH)2-cholecalciferol.

Question 16

What factors increase the levels of 1alpha hydroxylase enzyme in the kidney?

Answer 16

Decreased plasma Ca2+
Increased circulating levels of PTH
Decreased plasma phosphate concentration.

Question 17

What are the effects of active vitamin D?

Answer 17

Acts on the intestine to increase absorption of calcium and phosphorus

Act on the kidney to increase calcium retention

Acts on the bone to cause bone reabsorption to release calcium ions and phosphorus.

Question 18

What is meant by circulating Vitamin D?

Answer 18

Measure of nutritional Vitamin D status - calcidiol**

Question 19

Where and under what conditions causes the secretion of calcitonin?

Answer 19

Secreted by C cells or parafollicular cells int eh thyroid gland in response to hypercalcemia.
Is a PTH antagonist

Question 20

What is the action of calcitonin on the body?

Answer 20

Acts directly in the kidneys to decrease calcium reabsorption and decrease phosphate reabsorption - leads to increased urinary excretion of calcium and phosphate

Acts on the bones the inhibit osteoclasts hence decrease bone reasborption.

This leads to a decrease in plasma calcium and phosphate.

Question 21

What other hormones may contribute to the regulation of bone health?

Answer 21

Calcium-regulating hormones - PTH, calcitonin, calcitriol

Sex hormones - oestrogen, testosterone

Other hormones - growth hormone/insulin like growth factor, thyroid hormone and cortisol

Question 22

What are the effects of growth hormones on bone health?

Answer 22

Stimulates bone formation and stimulates longitudinal growth

Question 23

What are the effects of thyroid hormone of bone health?

Answer 23

Too much stimulates bone reabsorption
activates osteoclastic activity

Question 24

What are the effects of glucocorticoids on bone health?

Answer 24

Inhibits bone formation (inhibits osteoblasts)
Decreases calcium ion absoprtion from the intestines

Question 25

What is the effect of estrogen and testosterone on bone health?

Answer 25

Maintain bone density by inhibition osteoclasts
Stimulation of osteoblasts
Calcium absorption
Inhibit bone resorption.

Question 26

What lifestyle factors are important to maintaining bone health?

Answer 26

Calcium intake - especially in childhood, adolescence, pregnancy and lactation

Vitamin D - dietary supplements or sunshine

Regular exercise - muscle strengthening and weight bearing exercise

Avoid smoking and drinking to excess
Maintain a health body weight
Hormonal health

Question 27

What are the biological markers of primary hyperparathyroidism?

Answer 27

High PTH
High serum calcium
Low serum phosphate

Question 28

What are the common causes of primary hyperparathyroidism?

Answer 28

Parathyroid tumour
Ectopic parathyroid tissue

Question 29

What are the symptoms of primary hyperparathyroidism?

Answer 29

Renal stones
Bone bone
Abdominal pain and constipation
Depression

Question 30

What is the most common treatment for primary hyperparathyroidism?

Answer 30

Parathyroidectomy

Question 31

What are the key biochemical biomarkers of secondary hyperparathyroidism?

Answer 31

High levels of parathyroid hormone
Low levels of calcium ions
High levels of phosphate

(unable to excrete calcium and phosphate, calcium binds to phosphate decreasing free calcium levels)

Question 32

What are the common causes of secondary hyperparathyroidism?

Answer 32

Vitamin D deficiency or impaired renal function
End stage kidney disease

Question 33

What are the common presentations of secondary hyperparathyroidism?

Answer 33

Osteoporosis
Renal stones
Bone and joint pain

Question 34

What are the common treatments of secondary hyperparathyroidism?

Answer 34

Vitamin D3 supplements (cholecalciferol)
Treat underlying cause of kidney damage.

Question 35

How does vitamin D deficiency present in children?

Answer 35

Rickets

Demineralisation of bone - soft pliable bones
Characteristic bow leg deformity
Overgrowth of the costochondral junction - rachiatic rosary
Pigeon chest deformity
Frontal bossing - (as head growth preserved over other bone growth as calcium decreases)

Question 36

How does vitamin D deficiency present in adults?

Answer 36

Osteomalacia

Softening of bones - results in frequent fractures

Question 37

What biochemical markers are indicative of a vitamin D deficiency?

Answer 37

Hypocalcemia
Hypophosphatemia
Increased alkaline phosphatase

Question 38

What is renal osteodystrophy or CKD mineral disorder?

Answer 38

A complication of chronic kidney disease
Broad term that indicates biochemical and skeletal manifestations as a consequences of CKD or end stage renal disease.
These abnormalities are normally only seen in a GFR below 60mL/min.

Question 39

What are the key biochemical abnormalities seen in renal osteodystrophy or CKD mineral bone disorder?

Answer 39

1. Increased PTH
2. Decreased calcium
3. Increased phosphate.

Question 40

What are the two main physiological factors contributing to CKD mineral bone disorder or renal osteodystrophy?

Answer 40

1. Failure to synthesies active VD3 (calcitriol) - leads to hypocalcemia and no bone mineralisation (soft bone)
2. renal failure to excrete phosphate - hyperphosphatemia binds to remaining calcium ions resulting in decreased Ca2+, leads to elevated PTH

Question 41

What is the role of Fibroblast Growth Factor in Chronic Kidney disease?

Answer 41

Is produced in chronic kidney disease as a compensatory or safety mechanism.
Increased by 1000 fold

Increased urinary phosphate excretion (yay!!) and decreased vitamin D synthesis (bad) by suppresion of 1-alpha hydroxylase.

This leads to reduced calcium levels and elevated PTH - secondary hyperparathyroidism.

Question 42

What is osteoporosis and what are its symptoms?

Answer 42

Increased bone fragility as more porous - more suscpetibile to fracture particularly in the wrist, hip and spine.

Presents as painless fractures, height loss and curvature of the spine (due to compression fractures

More severe form of osteopenia

Question 43

What are the common causes of osteoporosis?

Answer 43

Hormonal related/postmenopausal
Long use of steroids (cushing syndrome)
Malabsoprtion disease
Drug related
Low BMI

Question 44

What are the indications for dual energy x-ray absorptiometry (DXA scanning or bone mineral density scan)?

Answer 44

For those with significant risk factors
When it is uncertain if bones are fragile
To decide whether drug treatment is necessary

Is NOT used for screening purposes

Question 45

What is the principle behind a bone mineral density scan?

Answer 45

It measures bone density and bone loss
Bone densities are often given as a T score
T score shows what a patients bone density is like in comparison to a young adult of the same gender with a peak bone mineral density.
Posititive values -0.1 and above indicate higher than normal density or normal density
Osteopenia is between -1.0 and -2.5
Osteoporosis is -2.5 or lower

Question 46

What is FRAX for assessing bone health?

Answer 46

WHO Fracture RIsk Assessment tool
Assesses the probability of a fracture occurring in the next ten years
This considered the age of the patient, sex, BMI, previous fractures, risks factors such as alcohol, smoking, glucocorticoids to give a percentage estimate of how likely a fracture is in the next ten years.