Flashcards in LMP301 Lecture 11: Calcium, Vit D, Parathyroid Deck (90)
Where is calcium excreted?
- intestines (poop)
Which hormones regulate calcium homeostatsis?
- parathyroid hormone
- 1,25 (OH)2 vit D
What stimulates PTH release?
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?
How do we get to the active form of 1,25 (OH)2 vit D?
1. pro-vitamin D --(UV)--> vit D
2. vit D --(25-OH'ase)--> 25-(OH)D3
3. 25-(OH)D3 --(1a-OH'ase)--> 1,25-(OH)2D3
Where can 25-OH'ase be found?
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...
25 OH vit D can be converted into ____ by ____ (not the reaction to make 1,25-(OH)2D3)
Sources of vit D3
- sunlight on skin
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?
- 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
effect of 1,25-(OH)2D3 on parathyroid gland
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...
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
hypercalcemia may cause ___ because of hypercalciuria and Ca buildup in the kidney
causes of hypocalcemia
- magnesium deficiency
- renal failure
- vit D deficiency
parathyroid can't produce PTH
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
- 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
1. intestine absorption
2. bone reabsorption
3. renal reabsorption
Causes of hypercalcemia
- problem at parathyroid gland
- milk-alkali syndrome
- increased 1-OH'ase activity
familial hypocalciuric hypercalcemia
- mutations of calcium sensing receptor in parathyroid gland
- autosomal dominant
- not severe, asymptomatic
FHH can be mistakenly diagnosed as...
Some cancers that may cause hypercalcemia may secrete...
PTHrP (related protein)
take too much antacid
- increase bicarb / Ca++
- metabolic alkalosis
Example of a disease with increased 1-OH'ase activity
> 60% of patients with primary hyperparathyrodism are...
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?
Mimic PTH effects
Is PTHrP common? Where can high concentrations of it usually be found?
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
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?
Markers for bone resorption
collagen degradation product
markers for bone formation
- alkaline phosphatase
bone specific isoenzyme
produced by osteoblasts
defects of bone & cartilage mineralization in children
What are the two bone diseases present in adults/children?
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
- defective 1-OH'ase
- can't make 1,25(OH)2D3
Treatment for vit D dependent type I
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
- 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
relationship between calcitonin and osteoclasts
calcitonin can stop osteoclast activity
Who is more affected by osteoporosis? This is called...
- primary osteoporosis
cause of primary osteoporosis?
cause of secondary osteoporosis?
Increased cortisol -> increased osteoclast activity
To maintain proper bone health, what 2 requirements must be met?
2. weight bearing (gravity, standing)
What are the 3 major forms of vit D supplements?
1. native vit D
vit D deficiency caused by malnutrition / lack of sun / only breastfed baby should be treated by which form of vit D?
(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?
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?
vit D deficiency caused by vit D dependent rickets type I should be treated by which form of vit D?