11. Parathyoid Hormone Flashcards
Which important processes does calcium play a role in?
- Neuromuscular excitability
- Coagulation
- Synaptic transmission
- Exocytosis
- Intracellular second messenger
- Regulation of gene transcription
- Bone formation
What important roles does phosphate play?
Part of ATP - cellular energy metabolism
Activation and de-activation of enzymes
Is phosphate concentration regulated tightly?
No, levels fluctuate during the day, particularly after meals.
Where is the bodies largest store of calcium, how is it stored?
Skeleton bones - as hydroxyapatite crystals (contain phosphate and calcium)
Which 3 hormones are involved in regulating calcium and phosphate levels?
- Parathyroid hormone (PTH)
- Calcitriol
- Calcitonin (less important)
Which 3 organ systems do these hormones act on?
Bone
Kidneys
GI tract
What 3 forms does calcium exist in within the plasma?
- Free ionised
- Protein- bound (albumin)
- Complexed with organic ions (citrate, oxalate)
What is the total concentration of all 3 calcium forms in the plasma?
2.2-2.7 mmol/L
Which form is the most important in terms of regulating PTH secretion?
Free ionised form - physiologically active
What symptoms are associated with hypocalcaemia?
Hyper-excitability of the NS - parasethesia of mouth and fingers, tetany, paralysis, convulsions
What symptoms are associated with hypercalcaemia?
Groans - constipation
Stones - kidney stones
Moans - depression, tiredness and dehydration
Bones - bone and muscle aches
What is calcitriol?
Active form of vitamin D
How do the effects of PTH and calitrol compare?
Both raise serum calcium, but via different mechanisms and over different time scales.
PTH = short term
Calcitriol = longer term
What are the 2 forms of Vitamin D?
D2 = ergocalciferol D3 = cholecalciferol
What reactions must inert Vitamin D2/D3 undergo in order to become activated?
2 hydroxylation reactions in the liver and kidney
How can vitamin D obtained within the body?
D3 Synthesis in skin when sun exposure and dairy
D2 - yeast, fungi, margarines
How can tumour influence calcium metabolism?
Some tumours produce parathyroid hormone related peptide (PTHrP) which is a PTH analogue and causes hypercalcaemia.
Which cancers commonly produce PTHrP?
Breast, prostate and occasionally myeloma.
How do the effects of PTHrP differ to PTH itself?
Does not increase renal C-1 hydroxylase activity so does not increase calcitriol concentration like PTH.
How does PTHrP cause hypercalcaemia?
Shares actions of PTH leading to increased calcium release from bone, reduced renal excretion and reduce phosphate reabsorption.
What are the actions of PTH?
Stimulates osteoclasts and bone resorption, increased calcium release.
Stimulates renal calcium reabsorption
Stimulates excretion of phosphate
Stimulates C-1 hydroxylase activity which activates VitD to calcitriol.
What is the effect of calcitonin?
Counteract PTH - decrease calcium levels
Where is calcitonin released from?
Thyroid gland - parafollicular C cells
Where are the parathyroid glands, how many do most people have?
Posterior thyroid
Usually 4
What are the 2 cell typespresent in the parathyroid gland?
Chief cells - secrete PTH
Oxyphil cells
What type of hormone is PTH?
polypeptide hormone, water-soluble, no binding protein.
What stimulus up-regulates PTH synthesis?
low serum Ca2+
What is the T1/2 of PTH?
4 minutes - short term
How do serum calcium levels alter PTH synthesis?
When plasma calcium is high, Ca2+ binds to GPCR alpha q coupled receptor.
IP3 second messenger reduces PTH synthesis inhibits PTH secretion.
Why is it important that phosphate excretion is increased when calcium is released?
Precent formation of hydroxyapatite crystals within the body
What does calcitriol do?
Increased calcium uptake in the GI tract.
Increases kidney reabsorption of calcium
How does the half life of Vitamin D3 and calcitriol differ to PTH?
Longer half life, hence longer term regulation of calcium levels.
What protein is vitamin D3 bound to in the plasma?
Transcalciferin
What role does calcium play in the clotting cascade?
Factor IV
What is EDTA used for?
Calcium chelator used to prevent blood samples clotting
Which patients are likely to need IV calcium?
Patients given >5 units of blood
What are the most common causes of hypercalcaemia in the hospital setting?
- Malignant osteolytic bone metastases
- Multiple myeloma
Which common cancers metastasise to bone causing LYTIC lesions and hypercalcaemia?
Breast
Kidney
Thyroid
Lung
Prostate cancer metastasises to bone but doesn’t cause hypercalcaemia, why?
Osteoblastic effect rather than lytic.
What are the most common sites for bone metastases?
Vertebrae Pelvis Ribs Skull Proximal humerus and femur
What causes primary hyperparathyroidism?
PTH secreting- adenoma of one of the parathyroid gland
What would you expect serum calcium and phosphate levels to be in a patient with primary hyperthyroidism?
Raised calcium
Low phophate
What is secondary hyperparathyroidism usually due to?
Vitamin D deficiency
What can cause vitamin D deficiency?
- Dietary deficiency
- Chronic renal failure - cannot hydroxylate and activate
What would you expect serum calcium and PTH levels to be in patients with secondary hyperparathyroidism?
Raised PTH (negative feedback) Low calcium
What condition affecting the bone is often the presenting cause of Vitamin D deficiency?
Osteomalacia - patients experience bone pain due to renal osteodystrophy
How does calcium affect neuronal activity?
Raises the threshold for membrane depolarisation
What effect does hypercalcaemia have on neuronal activity?
Suppresses neuronal activity - lethargy, confusion, coma
What effect does hypocalcaemia have on neuronal activity?
tingling, tetany, convulsions.
Can kill due to laryngeal muscle tetany.
What is the difference between osteoporosis and osteomalacia?
Osteoporosis - decreased bone density but normal ratio of mineral to matrix. (normal bone, just less of it)
Osteomalacia - decreased ratio of mineral to matrix
What condition is a result of osteomalacia in children?
Rickets
What are risk factors for osteoporosis?
Post-menopausal women low BMI Long term steroid used Prolonged inactivity Heavy drinking
What is high alkaline phosphatase an indicator of?
Enzyme on osteoblasts, marker of bone turnover. Increased in hyperparathyroidism.
Which 2 ways can malignancy lead to hypercalcaemia?
- Bone metastases produce
local factors that act in a paracrine manner to activate osteoclasts (osteolytic) - Produce PTHrP that acts on PTH receptors
Parathyroid hormone has direct actions on the gastrointestinal tract to increase the rate of clacium and phosphate absorption from food. True or False?
False - indirect through promoting formation of calcitriol
What type of hormone is calcitonin?
Peptide
7-dehydrocholesterol is converted to vitamin D3 by?
Sunlight
