LMP301 Lecture 11: Calcium, Vit D, Parathyroid Flashcards
Calcium, Vit D, parathyroid
Where is calcium excreted?
- intestines (poop)
- kidneys
Which hormones regulate calcium homeostatsis?
- parathyroid hormone
- 1,25 (OH)2 vit D
- calcitonin
What stimulates PTH release?
low Ca++
effect of PTH on bone
reabsorption (break down)
effect of PTH on kidney
- Ca++ reabsorption
- P secretion
- incr. 1-OH’ase
- incr. 1,25 (OH)2 vit D
Where does PTH act on?
- bones
- kidneys
How do we get to the active form of 1,25 (OH)2 vit D?
- pro-vitamin D –(UV)–> vit D
- vit D –(25-OH’ase)–> 25-(OH)D3
- 25-(OH)D3 –(1a-OH’ase)–> 1,25-(OH)2D3
Where can 25-OH’ase be found?
liver
where can 1a-OH’ase be found?
many tissues, including kidneys, pancreas, colon, prostate, breasts…
The active 1,25 (OH)2 vit D can be converted into the inactive…
1,24,25-(OH)3D3
25 OH vit D can be converted into ____ by ____ (not the reaction to make 1,25-(OH)2D3)
24,25-(OH)2D3
24-OH’ase
Sources of vit D3
- supplement
- sunlight on skin
- milk
- salmon
function of 1,25-(OH)2D3 at pancreas, colon, prostate, breasts…
regulate cell growth (prevent cancer)
Prevent autoimmune diseases
function of 1,25-(OH)2D3 at kidneys
prevent autoimmune diseases
maintain calcium homoeostasis (muscle & bone health)
Where does 1,25-(OH)2D3 act on?
- intestines
- bones
- parathyroid gland
effect of 1,25-(OH)2D3 on intestines
- increase Ca absorption
- incr P absorption
Overall effect of 1,25-(OH)2D3
raise blood Ca++ levels
effect of 1,25-(OH)2D3 on bone
increase reabsoprtion
effect of 1,25-(OH)2D3 on parathyroid gland
decrease PTH
Feedback of 1,25-(OH)2D3
- inhibit its own synthesis
- promotes its own breakdown
1,25-(OH)2D3 is bound to ___ when in circulation
vit D binding protein
receptor for 1,25-(OH)2D3
nuclear vit D receptor
calcitonin is secreted by…
parafollicular / C cells of thyroid gland
Secretion of calcitonin is stimulated by…
- high Ca
- GI hormones
Effect of calcitonin
- lower serum CA
- lower serum P
- stops bone reabsorption
Calcitonin is used as treatment for which bone diseases?
- post-menopausal osteoporosis
- Paget’s disease
Calcitonin is a tumour marker for…
medullary thyroid carcinoma (tumor of the C cells in thyroid gland)
Tetany is a symptom of…
hypocalcemia
Tetany
flexed wrist & ankle joint, muscle twitching, cramps
Hypocalcemia is usually present with…
neuromuscular hyperexcitability (tetany, Trousseau’s sign)
Hypercalcemia is usually present with…
reduced neuromuscular excitability (fatigue, weakness, depression)
Hypercalcemia may induce…
ADH resistance = nephrogenic diabetes
- thirst
- polydipsia
- polyuria
hypercalcemia may cause ___ because of hypercalciuria and Ca buildup in the kidney
kidney stones
causes of hypocalcemia
- hypoparathyroidism
- pseudohypoparathyroidism
- magnesium deficiency
- renal failure
- vit D deficiency
hypoparathyroidism
parathyroid can’t produce PTH
pseudohypoparathyroidism
high PTH
low Ca++
PTH resistance
magnesium deficiency contributing to hypocalcemia
Mg affects secretion of PTH
high Mg = more PTH secretion
Why might renal failure cause hypocalcemia
- Retain P, so Ca++ is secreted
- 1,25-(OH)2D3 deficiency
causes of vit D deficiency
- diet
- lack of sun
- can’t absorb
- chronic liver disease
- chronic renal disease
- vit D dependent rickets
what are the Ca and PTH levels in renal failure and vit D deficiency?
- low Ca
- (in response) high PTH
This is secondary hypoparathyrodism
What are the causes of secondary hyperpaarathyrodism?
- renal failure
- vit D deficiency
3 ways which hypercalcemia may happen
- intestine absorption
- bone reabsorption
- renal reabsorption
Causes of hypercalcemia
- problem at parathyroid gland
- malignancies
- milk-alkali syndrome
- increased 1-OH’ase activity
- FHH
FHH
familial hypocalciuric hypercalcemia
- mutations of calcium sensing receptor in parathyroid gland
- autosomal dominant
- not severe, asymptomatic
FHH can be mistakenly diagnosed as…
hyperparathyroidism
Some cancers that may cause hypercalcemia may secrete…
PTHrP (related protein)
milk-alkali syndrome
take too much antacid
- increase bicarb / Ca++
- metabolic alkalosis
Example of a disease with increased 1-OH’ase activity
Sarcoidosis
> 60% of patients with primary hyperparathyrodism are…
post-menopausal women
Biochemical profile of primary hyperparathyrodism
- high PTH
- high Ca
- low P
- high / normal 1,25-(OH)2D3
Difference between PTH and PTHrP
PTH on chrom 11
PTHrP on chrom 12
Similarities between PTH and PTHrP
first 8 AA on N term shows close homology
Where does PTHrP bind, and what effects does it have?
PTH receptor
Mimic PTH effects
Is PTHrP common? Where can high concentrations of it usually be found?
Very common
Breast milk
biochemical differences of PTH and PTHrP
PTH cause slight increase of 1,25-(OH)2D3
PTHrP cause slight decrease of 1,25-(OH)2D3
PTHrP is produced in…
some tumours that cause humoral hypercalcemia of malignancy (HHM)
Common bone disorders
- osteomalacia & rickets
- paget’s disease
- osteoporosis
is Ca++ a marker of bone disease?
Not necessarily; bone disease can occur even when Ca++ is normal
What is responsible for bone resorption? formation?
osteoclasts
osteoblasts
Markers for bone resorption
deoxypyridinoline
deoxypyridinoline
collagen degradation product
markers for bone formation
- alkaline phosphatase
- osteocalcin
alkaline phosphatase
bone specific isoenzyme
osteocalcin
produced by osteoblasts
Rickets
defects of bone & cartilage mineralization in children
What are the two bone diseases present in adults/children?
Osteomalacia
Rickets
Osteomalacia
defective bone mineralization in adults
difference between Osteomalacia and Rickets
- adult vs. child
- cartilage also impacted in children
- same disease but different names for diff age
causes of rickets
vit D deficiency
Rickets is divided into…
- vit D dependent type I
- vit D dependent type II
vit D dependent type I
- hereditory
- defective 1-OH’ase
- can’t make 1,25(OH)2D3
Treatment for vit D dependent type I
give 1,25(OH)2D3
biochemical profile of vit D dependent type I
- high PTH
- low Ca++
- low 1,25(OH)2D
biochemical profile of vit D dependent type II
- high 1,25(OH)2D
vit D dependent type II rickets
vit D receptor defect
Paget’s disease
- increased osteoclast activity
- increased osteoblast activity, but new bone is not formed properly
clincal presentation of paget’s diease
severe bone pain
- loss of hearing (bones in ear)
biochemical profile of Paget’s disease
- normal Ca
- increased alkaline phosphatase activity
treatment of Paget’s disease
- bisphosphate drug
- calcitonin
relationship between calcitonin and osteoclasts
calcitonin can stop osteoclast activity
Who is more affected by osteoporosis? This is called…
post-menopausal women
- primary osteoporosis
cause of primary osteoporosis?
unknown
cause of secondary osteoporosis?
Increased cortisol -> increased osteoclast activity
To maintain proper bone health, what 2 requirements must be met?
- exercise
2. weight bearing (gravity, standing)
What are the 3 major forms of vit D supplements?
- native vit D
- 25(OH)D
- 1,25(OH)2D
vit D deficiency caused by malnutrition / lack of sun / only breastfed baby should be treated by which form of vit D?
native
Ca++ metabolites can be used if more severe
vit D deficiency caused by chronic liver disease should be treated by which form of vit D?
25(OH)D
1,25(OH)2D can also be used if severe
vit D deficiency caused by chronic renal disease should be treated by which form of vit D?
1,25(OH)2D
vit D deficiency caused by vit D dependent rickets type I should be treated by which form of vit D?
1,25(OH)2D
vit D deficiency caused by vit D dependent rickets type II should be treated by which form of vit D?
Nothing; insensitivity to vit D
