Biochemistry : part 2

Question 1

Describe the relationship between PTH level and calcium in vivo.

Answer 1

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 2

What are the causes of primary hyperparathyroidism?

Answer 2

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

Question 3

What biochemical results are diagnostic of primary hyperparathyroidism?

Answer 3

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 4

What are the clinical features of primary hyperparathyroidism?

Answer 4

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)

Question 5

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

Answer 5

Small intestine – increases calcium and phosphate absorption

Question 6

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

Answer 6

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

Question 7

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

Answer 7

TRPV6
Calbindin

Question 8

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

Answer 8

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

Question 9

What is Rickets?

Answer 9

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

Question 10

State some signs and symptoms of Rickets.

Answer 10

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

Question 11

State some Vitamin D related causes of Rickets/Osteomalacia.

Answer 11

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

Question 12

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 12

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 13

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

Answer 13

FGF23

Question 14

What effect does this factor have that is unlike PTH?

Answer 14

It inhibits 1 alpha-hydroxylase, thus inhibiting calcitriol production

Question 15

Which cells produce this factor?

Answer 15

Osteoblast lineage cells

Question 16

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

Answer 16

Phosphate deficiency

Question 17

State some phosphate-related conditions that cause Rickets/Osteomalacia.

Answer 17

X-linked Hypophosphataemic Rickets (mutation in Phex (this cleaves FGF23))
Autosomal Dominant Hypophosphataemia Rickets
Oncogenic Osteomalacia (mesenchymal tumours can produce FGF23)

Question 18

What can cause osteoporosis due to increased bone resorption and decreased bone formation?

Answer 18

Glucocorticoids