Flashcards in L5 Parathyroid Hormone Deck (20):
1
What is considered high [Ca]? What are the symptoms?
High [Ca] > 12mg/dl
EXCEPTION: people with familial hypercalcemic hypocalcuria normally have high [Ca] w/o symptoms
- General: fatigue, apathy, anorexia, delirium, coma
- Neuro: headache, intracranial pressure, muscle weakness
- Cardiac: bradycardia short Q-T interval
- Renal: Polydipsia (thirst), polyuria (excessive urine), hypertension, calculi (stones)
2
What is considered low [Ca]? What are the symptoms?
Low [Ca] < 7 mg/dl
- General: learning retardation, apnea (children)
- Neuro: tetany (spasms, seizures, numbness, muscle cramps), reduced membrane pol. and increased hypersensitivity
- Cardiac: long Q-T interval, CO reduced
- Skeletal: Ca/PO4 deficiency --> weak bone development (rickets of osteomalacia)
3
Where is calcium regulated in the body?
IRS (where our taxes are regulated)
- Intestine (80% of intake excreted in feces)
- Renal tubules (filters 10x daily intake, excretes 175mg)
- Skeleton (formation/resorption if ~280mg/day)
4
What effect does PTH have on the kidney?
PTH output is HIGH when [Ca] is LOW
Target 1: kidney (rapid)
- increases [Ca] by increasing reabsorption in distal tubule
- decreases PO4 by reducing reabsorption in proximal tubule
- increase active vitamin D synthesis
5
What does PTH target?
Kidney and Bone cells
6
What effect does PTH have on bone cells?
PTH output is HIGH when [Ca] is LOW
Target 2: bone cells (slow)
- Increase osteoclastic resorption via receptors on osteoblasts, which releases more Ca and PO4 into blood
- "osteocytic osteolysis"
7
How is PTH secreted?
- PTH is released by chief cells on the parathyroid gland
- Stimulated by a reduction in plasma [Ca]
8
What is familial hypercalcemic hypocalcuria (FHH)?
- Ca sensing receptor is defective
- Serum Ca is naturally high
- No symptoms
- Urine calcium excretion is low
9
How does vitamin D aid in calcium reabsorption in the kidney?
- Vitamin D increases calbindin/Ca transport and efflux at the basal side
- This helps PTH facilitate Ca reabsorption
10
What are the 2 targets of vitamin D?
Target 1: Intestine (increase Ca and PO4 absorption)
Target 2: Bone (binds receptors on osteoblasts that signal to promote maturation/activation of osteoclasts - increases Ca and PO4)
- Also, vitamin D reduces the production of PTH (negative feedback, acts as buffer)
11
What causes the active form of vitamin D to increase?
- Drop in plasma calcium
- Vitamin D production is stimulated by increases plasma PTH
12
Synthesis of vitamin D
UV converts cholesterol --> cholicalciferol (vitamin D3) --> travels in blood to liver --> converted to 25-hydroxy-vitamin D3 --> 1-alpha-hydroxylase in kidney converts to 1-25 dihydroxy vitamin D3 (calcitriol)
* Activity of 1-alpha-hydroxylase is enhanced by circulating PTH (low [Ca] leads to more conversion of vit D to active form)
13
How does active vitamin D (calcitriol) act in the intestine?
- Increases active and passive transport of Ca and PO4 into the blood by increasing the synthesis of the transporter (calbindin)
14
Rickets
- Causes by a chronic deficiency in vitamin D and/or dietary deficiency of Ca or PO4 during early development
- Results in poor mineralization, weakened and bowed long bones, large growth plates
- Osteomalacia is a similar problem with mineralization seen in adults
15
Primary hyperparathyroidism
- Results in high PTH, which causes the kidneys to increase Ca reabsoprtion and bones to release Ca (seen by high alk phos - marker for bone turnover) --> increases serum Ca
- Urinary Ca excretion is high
- Tx is surgical removal of offending parathyroid nodule (adenoma)
16
Humoral hypercalcemia of malignancy
- Low PTH but high serum Ca --> cancer cells releasing PTH-relate peptide (PTH-rp), which activates same receptors as PTH
- Actual PTH low from being inhibited by the high serum Ca
17
What are the two types of bone cells and what do they do?
OsteoBlasts - Build bone
Osteoclasts - degrade bone by secreting acid molecules that dissolve mineral and proteases that digest collagen
18
What triggers osteoclast maturation?
Endocrine factors (PTH, vit D, growth hormones) stimulate RANK-L (cytokine) to be released from osteoblasts --> binds RANK on osteoclasts --> osteoclast maturation and activation
19
What is the function of osteoprotegerin (OPG)?
In response to stimuli, osteoblasts can produce OPG that binds RANK and competitively inhibits osteoclast activation
- Results in decreased bone resorption
- Rate of bone remodeling controlled by OPG/RANK-L ratio
20