1. Clinical Chemistry of Parathyroid disorders

3. BONE 88% 12% H2O Inorganic Ca-hydroxyapatite
Organic (osteoid)
osteocalcin
osteonectin
osteopontin
collagen
(type I)
Ca x (H3O+)2x(PO4 3-)6(OH-)2
H2O
Proteoglycans
lipids
12%
88%

4. CELLS IN BONE 1. Osteoblast - production of organic matrix (osteoid)
- potentiate and control mineralisation
- potentiate production of alkaline phosphatase
2. Osteocyte
- connection with extracellular fluid
- regulation of Ca and Pi movement between bone and extracellular fluid
3. Osteoclast
- polynuclear specific macrophages
- bone resorption

5. PROTEIN
(albumin)
Ca 2+
Anion - - - - - - - - - - - - - - -
Anions
HCO3-
H2PO4-
HPO4-2
Citrate
Lactate - - -
Protein bound calcium
46%
Free calcium
47%
Complexed calcium 7%
Total calcium ( mmol/l)

7. Hormones regulating plasma calcium concentration
Parathyroid hormone (PTH)
parathyroid glands
Calcitriol DHCC (active vitamin D)
Formed after hydroxylation! (liver, renal)
Calcitonin (thyreoidea C cells)
Its physiological function is not well characterized

8. A parathyroid hormone (PTH)
Polypeptide (84 amino acids)
Product of chief cells of parathyroid glands
N-terminal 34 AA fragment and intact PTH
are biologically active
increase of serum Ca2+
decrease of serum phosphate

9. Half life:
3-4 min
Half life:
2-3 hours

10. Target organs for PTH Bone: Ca and Pi resorption by osteoclasts Kidney
tubular Ca reabsorption
tubular Mg reabsorption
tubular P reabsorption
tubular HCO3 reabsorption
Intestine
1-25 DHCC production in kidneys

11. PTH regulation and mechanism of action
Stimulatory effects:
Se Ca 2+
Mild hypomagnesaemia
Inhibition:
Se Ca 2+
Severe hypomagnesaemia
Calcitriol
PTH release
PTH binding to the target cell receptors (Mg dependent)
Adenylate cyclase
cAMP
Ca 2+ cellular influx to the target cells

12. Abnormal functions of parathyroid glands
Hyperparathyroidism
Primary
Secondary (PTH increase is physiological response)
Tertiary (autonome PTH secretion)
Hypoparathyroidism
Congenital/acquired
Pseudohypoparathyroidism

13. Secondary hyperparathyreoidism
A/ With osteomalacia or rickets
a. Decrease of Ca and vitamin D uptake or absorption Ca, vitamin D deficient diet, Steatorrhoea or malabsorption
b. Defect in production of active vitamin D
Chronic renal failure
Chronic hepatopathia
lack of alpha hydroxylation
c. Increased inactivation of vitamin D
anticonvulsive therapy
d. Lack of 25 HCC transport protein
e. D vitamin receptor defect
B/ Without osteomalacia and rickets
a. acute pancreatitis
b. neonatal hypocalcaemia

14. Typical biochemical features of
hyperparathyroidism
Se Ca2+
Phosphate
Alkaline
phosphatase
PTH
Primary
Secondary
Tertiary
or N or or
N or
N or

15. Parathyroid hormone-related peptide
It is elevated in 50-90% of patients with
hypercalcemia associated with malignancy
Its gene on chr 12 (PTH gene on chr 11)
3 isoforms
N terminal end shows homology to PTH
Can bind to PTH receptors and mimic its
biological action

16. Serum calcium
Normal or decreased
Increased
PTH
PTH
Increased
Increased
Normal
Decreased
Secondary HPT
Primary
HPT
Tumor
hypercalcemia
Creatinine
Other
causes of
Hyper-
calcemia
Increased
Normal
Other
causes of
secondary
HPT
Renal
disease

17. Hypoparathyreoidism Congenital Acquired
e.g. DiGeorge synd. (immunodeficiency + thymic aplasia)
- Pseudohypoparathyroidism
Acquired
1/ Operation
a. total or partial thyroidectomy
b. laryngectomy
c. parathyroidectomy
2/ Autoimmune disorder
3/ Haemochromatosis
4/ infiltrative states

18. Pseudohypoparathyroidism
Hereditary disorders, plasma PTH are elevated, but superficially resembles hypoparathyroidism
Type 1
Activation of adenyl cyclase is defective and cyclic AMP is not formed
Rounded face and skeletal abnormalities, learning difficulties
Type 2
cAMP is formed, but the responses to it are blocked
Differentiation:
Urinary cAMP after PTH: elevated in type 2

19. Typical biochemical features of hypoparathyroidism
True
Pseudo
Se Ca2+
Phosphate
Alkaline
phosphatase
PTH N

20. Calcitriol Derived from Vitamin D by successive hydroxylation UV
7-dehydrocholesterol
Cholecalciferol
Liver
25-(OH)-Cholecalciferol (Calcidiol)
Kidney
1,25-(OH)2-
Cholecalciferol
(Calcitriol)
24,25-(OH)2-
Cholecalciferol

21. Regulation of hydroxylation in the kidney
Synthesis of a Ca2+-binding
protein (calbindin D)
Longer term stimulatory effect: GH, prolactin, estrogen

22. Calcitriol Effects: Ca and P absorption from intestine
Ca and P resorption from bones by osteoclasts
Receptors of calcitriol in other tissues
Cellular differentiation (normal and malignant cells)
Immunomodulatory effect :
Stimulation of production of cytokines

23. Calcitonin Polypeptide hormone Thyreoid C cells
Its physiological function is unknown / under investigation
after total thyreoidectomy no clinical symptoms!
calcium homeostasis is normal
Its level is elevated
pregnancy
lactation
Has been detected
gut
CNS (neurotransmitter)
Experimentally
inhibit osteoclast activity, thus bone resorption
Clinical significance
medullary carcinoma, small cell cc