Endocrinology Session 4

Question 1

What cellular processes is calcium involved in?

Answer 1

• Hormone secretion
• Muscle contraction
• Nerve conduction
• Exocytosis
• Intracellular second messenger

Question 2

How is the calcium sequestrated in bone?

Answer 2

Hydroxyapatite crystals (within collagen fibres)

Question 3

What is the function of phosphate?

Answer 3

• Cellular energy metabolism (ATP)

- Levels fluctuate

Question 4

How are calcium and phosphate regulated?

Answer 4

• Parathyroid hormone
• 1,25-dihydroxyvitamin D / calcitriol
• Calcitonin (less)

Question 5

What is the function of the skeleton?

Answer 5

• Providing structural support
• Major reserve of calcium
• Buffering serum levels
• Releasing calcium phosphate into interstitium
• Taking up calcium phosphate

Question 6

What do the 3 hormones ac on?

Answer 6

Bone, kidneys, GI tract

Question 7

How much calcium does the adult human have?*

Answer 7

1000g

Question 8

What are the main dietary sources of calcium?

Answer 8

Dairy

Question 9

What is protein bound calcium used for?

Answer 9

• Not easily moved across cell membranes
• Not biologically active
• Serves as a reserve

Question 10

How much calcium is reabsorbed in the kidneys?

Answer 10

About 98%

Question 11

What three physiochemical forms of calcium in plasma?

Answer 11

1) Free ionised species (45%)
2) Bound to anionic sites on serum proteins (albumins) 45%
3) Complexed with low-molecular weight organic ions (10%)

Question 12

What is the total concentration of all three forms of calcium in plasma?

Answer 12

2.2-2.7 mmol/L

Question 13

Which plasma calcium is measured and which one is physiologically active?

Answer 13

• Free ionised is physiologically active

- Total calcium is commonly measured and then levels are corrected

Question 14

What is hypocalcaemia and what does it result in?

Answer 14

Low calcium concentration

• Hyperexcitability of the nervous system (+ NMJ)
• Paraesthesia
• Tetany, paralysis, convulsions

Question 15

What is chronic hypercalcaemia and what does it result in?

Answer 15

Elevated calcium levels over a longer period of time

• Kidney stones
• Constipations
• Dehydration
• Kidney damage
• Tiredness
• Depression

Question 16

What is responsible for the short and long term control of serum calcium concentration?

Answer 16

• Short: parathyroid hormone

- Long: calcitriol

Question 17

How is PTH synthesised?

Answer 17

• Pro-pre-hormone cleaved
• Regulated at the transcriptional and post transcriptional levels, so:

Low serum calcium = upregulated gene transcription, prolonged mRNA survival
High serum calcium = downregulated gene transcription

Question 18

What is the half life of PTH and why?

Answer 18

4 1/2 minutes - means that the hormone is responding quickly

Question 19

What is the function of chief cells?

Answer 19

Degradation and synthesis of PTH (cleavage initiated by high serum calcium levels)

Question 20

What are the target organs and the physiological effects of PTH?

Answer 20

• Bone: increased osteoclast activation to release calcium and phosphate into blood
• Intestine: activated vit. D and increases transcellular uptake
• Kidney: decreases loss to urine (more reabsorption)

Question 21

What is the relationship between calcium and phosphate?

Answer 21

If more phosphate is excreted, more calcium is reabsorbed which reduces the likelihood of crystal formation

Question 22

How is bone deposited?

Answer 22

Osteoblasts producing collagen matrix mineralised by hydroxyapatite

Question 23

How is bone reabsorbed?

Answer 23

Osteoclasts producing an acid micro-environment to dissolve hydroxyapatite

Question 24

How does PTH act on the bone?

Answer 24

• Stimulated osteolysis
• Inducing osteoblastic cells to synthesise and secrete cytokines on cell surface
• Decreased osteoblast activity exposes bony surface to osteoclasts

Question 25

What is the feedback regulation of serum calcium?*

Answer 25

- Increase = lower PTH secretion - Less Ca2+ reabsorbed from gut - Less vit D and less Ca2+ from gut - More bone building = Lower plasma Ca2+

Question 26

What are the symptoms of chronic hypercalcaemia?

Answer 26

- Renal calculi - Kidney damage - Constipation - Tiredness - Depression Stones, moans, groand

Question 27

When do symptoms of severe hypercalcaemia appear?

Answer 27

- When serum calcium raises above 3.0 mmol/L - Lethargy - Weakness - Confusion - Coma - Renal failure

Question 28

How do you treat hypercalcaemia?

Answer 28

Rehydration

Question 29

What is the aetiology of hypercalcaemia?

Answer 29

- Malignant osteolytic bone mets (big bone patches missing) - Multiple myeloma - Cancers that metastasise to bone (breast, lung, renal, thyroid)

Question 30

Why would prostate cancer mets not cause hypercalcaemia?

Answer 30

Rather than osteolytic mets, it causes osteoblastic mets and no calcium will be liberated so it would not cause hypercalcaemia

Question 31

What are the common sites for bone metastases?*

Answer 31

- Vertebra - Pelvis - Proximal femur - Ribs - Proximal humerus - Skull

Question 32

What is primary hyperparathyroidism?

Answer 32

A condition where one of the four parathyroid glands develops an adenoma which secretes excess PTH - Causes serum calcium rises and phosphate falls

Question 33

What is secondary hyperparathyroidism?

Answer 33

A condition where all 4 parathyroid glands become hyperplastic

Question 34

What causes secondary hyperparathyroidism?

Answer 34

- Vitamin D deficiency | - Low serum calcium absorption so low calcium and therefore high PTH

Question 35

What are the symptoms of primary hyperparathyroidism?

Answer 35

- Stones (kidney) - Moans (tiredness, depression) - Groans (constipation) - Bones (+ muscle aches)

Question 36

Why does hypercalcaemia lead to suppression of neuronal activity?

Answer 36

More is needed to fire the action potential, and therefore not as many will fire

Question 37

Why does hypocalcaemia lead to excitabe nerves?

Answer 37

Less contribution to RMP so less needed to reach threshold and more will fire

Question 38

When is symptomatic hypocalcaemia seen?

Answer 38

- When serum calcium falls below 2.1 mmol/l - Most common in post-total thyroidectomy - Can start within 6 hours of thyroidectomy

Question 39

What are the symptoms of hypocalcaemia?*

Answer 39

- Tingling in mouth and fingers - Tetany of muscles - Carpopedal spasm

Question 40

What is the difference between osteoporosis and osteomalacia?

Answer 40

- Osteomalacia: normal bone structure that is under mineralised - Osteoporosis: structurally degraded bone that is fully mineralised

Question 41

What is the cause of osteomalacia?

Answer 41

- Vitamin D deficiency - Rickets in children - Can be due to diet or renal disease

Question 42

What are the symptoms of osteomalacia?*

Answer 42

- Bone pain - Muscle weakness - Deformity

Question 43

How is vitamin D obtained?

Answer 43

Sun exposure, food, supplements

Question 44

How is inert vitamin D converted into 1,25-dihydroxycalficerol?

Answer 44

By undergoing two hydroxylation reactions

Question 45

What is parathyroid hormone related peptide?

Answer 45

A peptide that is produced by tumours and mimics the action of PTH without increasing calcitriol concentration Causes humeral hypercalcaemia of malignancy (HMM)

Question 46

What does PTHrP cause?

Answer 46

- Increased calcium release from bone - Reduced renal calcium excretion - Reduced renal phosphate reabsorption = Hypercalcaemia

Question 47

Why des PTHrP not increase calcitriol concentration?

Answer 47

- Does not increase renal C-1 hydroxylase activity that catalyses the hydroxylation of calcifediol to calcitriol - Therefore cannot make calcitriol - So no increase in concentration