Calcium and phosphate homeostasis and hyperparathyroidism

Calcium and phosphate homeostasis and hyperparathyroidism

Charles Hand

vitamin D2

(diet)

1,25(OH)2D3

calcitriol

Synthesis of active vitamin D

10%,

90%,Bile Salts

Tightly regulated

25-hydroxylase

1a-hydroxylase

calcidiol

Ca2+

BONEKIDNEY

Ca2+ reabsorption

PO4 reabsorption

GUT 25(OH)D3

1,25(OH)2D3

bone resorption Ca2+

release

Ca2+ & PO4 absorption

low Ca2+

PARATHYROIDS

High Ca2+

thyroid gland/calcitonin

PTHbone resorption

Ca2+release

1a-OHase

Calcium (PO4) homeostasis

FGF23

PO4

BONE

KIDNEY

PO4 reabsorption

GUTcalcidiol

calcitriol

↑ PO4 release

↑ PO4 absorption

Phosphate homeostasis

low PO4+

feedback-

PARATHYROIDS

PTH

- -

Klotho

1a-OHase FGF23-

Hyperparathyroidism What is it?

Over activity of parathyroid gland causing excess parathyroid hormone (PTH) production

What are the consequences? Damage to bone

What are the types? Primary Secondary Tertiary

Primary What is it?

Over activity of the parathyroid glands themselves. Causes?

Adenoma Hyperplasia Carcinoma (rare)

Secondary What is it?

Normal response to low calcium levels Causes?

Vit D deficiency main cause Chronic renal failure

Consequences? Renal osteodystrophy

Tertiary What is it?

Seen in chronic 2ndary hyperparathyroidism Hyperplasia of parathyroid glands Become unresponsive to changes in Ca2+ Gets stuck on high production mode

Who gets it? Patients with chronic renal failure

Exam Q (ESA 3 2011)Question 8

A 54 year woman presents to A&E complaining of severe back pain that radiates into the groin. You suspect she has a kidney stone.

A. Give THREE pieces if information that you could obtain from taking a clinical history of a patient that would indicate why a kidney stone had formed.

Exam technique Make sure with each new question you highlight the key

points and any traps you are likely to fall into: Patient demographics, age, sex. This gives you potentially a big clue Describe, list, explain. Make sure you do what it asks Clinical history etc. If it says clinical history, you can’t give information

you would gain from an examination Give THREE. If it says three, make sure you give three! Never leave a question blank. If you don’t know keep reading ahead,

often you will find a clue later in the question. If you still don’t know, just guess! Everyone else may have found that question hard and the marks be brought down, so don’t despair!

A. Answers Dehydration Gout, IBD (Crohn’s) High protein diet Recurrent infections Familial

B. Blood tests show that this patient has hypercalcaemia.

(i) Why is she likely to have developed a kidney stone?

(ii) Name TWO types of stone that are likely to be visible on a plain X-ray film. The stone is located in the abdominal ureter. iii) Where would you expect to see it on a plain X-ray film?

B. Answers i)

As calcium increases, amount of oxalate in bloodstream for absorption increases. Oxalate then excreted more into the urine. Causes calcium oxalate precipitation. Most common type.

ii) Calcium phosphate Calcium oxalate

iii) PUJ VUJ Pelvic brim

C. Further tests demonstrate high parathyroid hormone levels and a single enlarged parathyroid gland. She has primary hyperparathyroidism.

(i) Apart from parathyroid hormone name ONE other hormone which you would expect to be elevated in this patient.

(ii) Explain why she has hypercalcaemia.

C. Answers i) Calcitriol. Calcitonin?

ii) I’ll this one to you to work out from the diagrams/ text at the beginning of this presentation.

D. Her parathyroid gland is enlarged due to hyperplasia. How does hyperplasia differ from hypertrophy?

D. Answers Hypertrophy: Enlargement of organ or tissue due to increase

in cell size

Hyperplasia: Enlargement of an organ or tissue due to an increase in number of cells

E. Cell division is involved in hyperplasia. Describe the cell cycle, including the four stages of cell division, and indicate where the two checkpoints are located. A diagram may be used.

E. Answers