Biochemistry:part 2

Question 1

What else can the PTH receptor be activated by other than PTH?

Answer 1

PTHrP (PTH related protein)
This is produced by some tumours

Question 2

What does the parathyroid gland use to monitor serum calcium?

Answer 2

Calcium-sensing receptors

Question 3

Describe the relationship between PTH level and calcium in vivo.

Answer 3

Steep inverse sigmoid function
NOTE: there is a minimum level of PTH release (it can’t get below this even in the case of hypercalcaemia)

Question 4

What are the causes of primary hyperparathyroidism?

Answer 4

Parathyroid adenoma (80%)
Parathyroid hyperplasia (20%)
Parathyroid cancer
Familial syndromes

50s, female 3:1 male

2% post menopausal develop

Question 5

What biochemical results are diagnostic of primary hyperparathyroidism?

Answer 5

Elevated total/ionised calcium
With PTH levels frankly elevated or in the upper half of the normal range (negative feedback should drop PTH if there is hypercalcaemia)

Question 6

What are the clinical features of primary hyperparathyroidism?

Answer 6

Stones, Bones, Abdominal Groans and Psychic Moans
Stones – renal colic, nephrocalcinosis
Bones – osteitis fibrosa cystica
Abdominal moans – dyspepsia, pancreatitis, constipation
Psychic groans – depression, impaired concentration
NOTE: patients may also suffer fractures secondary to the bone resorption
IMPORTANT NOTE: hypercalcaemia also causes diuresis (polyuria and polydipsia,Tiredness, fatigue, muscle weakness

)

Question 7

What is the main site of action of calcitriol and what effect does it have?

Answer 7

Small intestine – increases calcium and phosphate absorption

Question 8

Describe the effects of calcitriol on bone and in the kidneys.

Answer 8

Facilitates PTH effect on the DCT in the kidneys (increased calcium reabsorption)
Synergises with PTH in the bone to increase osteoclast activation/maturation

Question 9

Which receptors/proteins are involved in mediating the effects of calcitriol on the intestines?

Answer 9

TRPV6
Calbindin

Question 10

What parameter is used to determine whether a patient is vitamin D deficient?

Answer 10

Deficient < 20 ng/M (50 nmol/L)
Normal > 30 ng/M (75 nmol/L)

Question 11

What is Rickets?

Answer 11

Inadequate vitamin D activity leads to defective mineralisation of the cartilaginous growth plate (before a low calcium)

Question 12

State some signs and symptoms of Rickets.

Answer 12

Symptoms:
 Lack of play
 Bone pain and tenderness (axial)
 Muscle weakness (proximal)
Sign:
 Age dependent deformity
 Myopathy
 Hypotonia
 Short stature
 Tenderness on percussion

Question 13

State some Vitamin D related causes of Rickets/Osteomalacia.

Answer 13

Dietary deficiency
Malabsorptoin
Drugs – e.g. enzyme inducers such as phenytoin
Chronic renal failure
Rare hereditary

Question 14

For each of the following state whether it would be high, low ornormal in the serum of a Rickets patient:

a. Calcium
b. Phosphate
c. Alkaline Phosphatase
d. 25-OH cholecalciferol
e. PTH
f. URINE phosphate

Answer 14

a. Calcium
Normal or Low
b. Phosphate
Normal or Low
c. Alkaline Phosphatase
High
d.25-OH cholecalciferol
Low
e. PTH
High
f. URINE phosphate
High

Question 15

Other than PTH, what else can cause increased phosphate excretion?

Answer 15

FGF23

Question 16

What effect does this factor have that is unlike PTH?

Answer 16

It inhibits 1 alpha-hydroxylase, thus inhibiting calcitriol production

Question 17

Which cells produce this factor?

Answer 17

Osteoblast lineage cells

Question 18

Other than Vitamin D deficiency, what else can cause Rickets/Osteomalacia?

Answer 18

Phosphate deficiency