L5 Parathyroid Hormone Flashcards Preview

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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

Regulators of bone remodeling

- PTH and vitamin D: increase resorption
- Estrogen: reduce resorption
- Calcitonin (?): inhibits osteoclasts
- Glucocorticoids: inhibit intestinal Ca absorption
- GH (IGF,TGFbeta): stimulate bone formation
- Mechanical loading: locally promotes bone accrual and maintenance to keep stresses in moderate range