Biochemistry

Question 1

List the biochemical features of primary hyperparathyroidism

Answer 1

High calcium
High PTH

High or NORMAL alkaline phosphatase

LOW phosphate

Question 2

List the biochemical features of secondary hyperparathyroidism

Answer 2

High PTH

Low calcium
Low or normal phosphate

Question 3

List the biochemical features of Paget’s disease

Answer 3

High alkaline phosphatase

NORMAL calcium
NORMAL phosphate

Question 4

List the biochemical features of osteomalacia

Answer 4

Low vitamin D
Low phosphate

Low or normal calcium

HIGH PTH
High alkaline phosphatase

Question 5

List the biochemical features of osteoporosis

Answer 5

Normal calcium
Normal phosphate
Normal alkaline phosphatase

Question 6

List the biochemical features of bone metastases

Answer 6

High calcium
High phosphate
High alkaline phosphatase

Question 7

What actions does PTH have on the kidney? State how it has its effects on phosphate and where it has its effects on calcium.

Answer 7

Calcitriol formation
Calcium resorption in distal tubule
Phosphate excretion (blocks the sodium phosphate transporter)

Question 8

How many amino acids does PTH contain?

Answer 8

84 amino acids

Question 9

PTH is dependent upon which ion and who is this particularly bad for?

Answer 9

Dependent upon Mg

Bad for alcoholics

Question 10

What’s the half life of PTH?

Answer 10

8 minutes!

Question 11

What else activates the PTH receptor and when is it released?

Answer 11

PTHrP
(parathyroid hormone related peptide)

Released in pregnancy to supply calcium to the milk

Question 12

How does the parathyroid hormone monitor levels of calcium?

Answer 12

Via the calcium sensing receptor

Question 13

What effect does PTH have on bone?

Answer 13

Increased cortical bone resorption due to:

PTH binds to receptors on osteoblasts and stimulates RANKL production.

This increases osteoclast stimulation and resorption.

Question 14

Primary HPT is more common in males or females and at what age?

Answer 14

Females (3:1)

Aged 50, after menopause

Question 15

List four causes of primary hyperparathyroidism

Answer 15

Parathyroid adenoma
Parathyroid hyperplasia
Parathyroid cancer
Familial syndromes

Question 16

List three familial syndromes causing primary hyperparathyroidism

Answer 16

MEN 1
MEN 2A
HPT-IT

Question 17

What are the symptoms of primary hyperparathyroidism?

Answer 17

High calcium

Therefore:
Stones - renal colic, nephrocalcinosis, chronic renal failure
Moans - pancreatitis, dyspepsia, constipation, nausea, anorexia
Groans - depression, impaired concentration, drowsiness, coma

Also:
Thirst
polyuria 
Tiredness
Fatigue
Muscle weakness

Question 18

Why does primary HPT cause polyuria?

Answer 18

High serum calcium stops potassium, recycling in the loop of Henle, which in turns prevents the Na/Cl/K cotransporter from working, thus leading to diuresis.

Question 19

What are the downstream effects of calcitriol in the intestine?

Answer 19

Increased calcium and phosphate absorption

via TRPV6 and calbindin

Question 20

Where in the gut is calcium mostly absorbed, and through what type of transport?

Answer 20

Duodenum/jejunum
Colon

Passive paracellular linear transport (60%)
Active transport (40%)

Question 21

What is the effect of vitamin D on bone?

Answer 21

Maintains calcium in bone (increases osteoblast differentiation and bone formation)

(also works with PTH to increase calcium and phosphate release from bone if needed via RANKL and osteoclasts)

Question 22

What is the effect of Vitamin D on the kidney?

Answer 22

Increased calcium reabsorption from distal tubule via TRPV5, calbindin

Question 23

Vitamin D causes the production of what from the bone? Name the type of cell which produces this.

Answer 23

FGF-23 from osteoblasts in long bones

Question 24

What are the effects of FGF-23?

Answer 24

Inhibits sodium phosphate transporter in the proximal convoluted tubule
Also provides negative feedback to decrease calcitriol synthesis

Question 25

What are the symptoms of rickets?

Answer 25

Bone pain and tenderness (axial) Muscle weakness Lack of play

Question 26

What are the signs of rickets?

Answer 26

Myopathy Hypotonia Short stature Tenderness on percussion

Question 27

What are the causes of vitamin D deficiency?

Answer 27

Small bowel malabsorption Pancreatic insufficiency Liver/kidney problem Drugs e.g. phenytoin/phenobarbitone

Question 28

What are the rare hereditary causes of rickets?

Answer 28

Type 1 - 1 alpha hydroxylase deficiency | Type 2 - Defective vitamin D receptor

Question 29

Name three causes of rickets which cause chronically high levels of fibroblast growth factor

Answer 29

X-linked hypophosphatemic rickets (XLHR) Autosomal dominant hypophosphatemic rickets (ADHR) Oncogenic osteomalacia (mesenchymal tumours)

Question 30

What is X-linked hypophosphatemic rickets caused by?

Answer 30

Mutations in PHEX (phosphate-regulating endopeptidase)

Question 31

How does X-linked hypophosphatemic rickets present?

Answer 31

``` In toddlers, with: Hypophosphatemia Leg deformity Enthesopathy Dentin anomalies ```

Question 32

Explain the problem in autosomal dominant hypophosphatemic rickets

Answer 32

Cleavage site of FGF-23 is mutated, therefore you get high levels of FGF-23

Question 33

When does ADHR present?

Answer 33

Age of onset is variable

Question 34

Explain oncogenic osteomalacia

Answer 34

Mesenchymal tumours produce FGF-23 which stops 1 alpha hydroxylase and causes phosphaturia Therefore you get low phosphate and calcium, causing decreased mineralisation and osteomalacia

Question 35

What is the most common cause of damage to the proximal convulted tubule?

Answer 35

Fanconi syndrome

Question 36

What are the causes of Fanconi syndrome?

Answer 36

Multiple myeloma Heavy metal poisoning Drugs Congenital diseases

Question 37

What drugs can cause Fanconi syndrome?

Answer 37

Tenofovir | Gentamycin

Question 38

What congenital diseases cause Fanconi syndrome?

Answer 38

Wilsons disease | Glycogen storage diseases

Question 39

What is Wilson's disease?

Answer 39

A genetic disorder where excess copper builds up in the body