L5 Parathyroid Hormone Flashcards

(20 cards)

1
Q

What is considered high [Ca]? What are the symptoms?

A

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)

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2
Q

What is considered low [Ca]? What are the symptoms?

A

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)
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3
Q

Where is calcium regulated in the body?

A

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)
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4
Q

What effect does PTH have on the kidney?

A

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

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5
Q

What does PTH target?

A

Kidney and Bone cells

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6
Q

What effect does PTH have on bone cells?

A

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”

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7
Q

How is PTH secreted?

A
  • PTH is released by chief cells on the parathyroid gland

- Stimulated by a reduction in plasma [Ca]

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8
Q

What is familial hypercalcemic hypocalcuria (FHH)?

A
  • Ca sensing receptor is defective
  • Serum Ca is naturally high
  • No symptoms
  • Urine calcium excretion is low
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9
Q

How does vitamin D aid in calcium reabsorption in the kidney?

A
  • Vitamin D increases calbindin/Ca transport and efflux at the basal side
  • This helps PTH facilitate Ca reabsorption
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10
Q

What are the 2 targets of vitamin D?

A

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)

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11
Q

What causes the active form of vitamin D to increase?

A
  • Drop in plasma calcium

- Vitamin D production is stimulated by increases plasma PTH

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12
Q

Synthesis of vitamin D

A

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)

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13
Q

How does active vitamin D (calcitriol) act in the intestine?

A
  • Increases active and passive transport of Ca and PO4 into the blood by increasing the synthesis of the transporter (calbindin)
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14
Q

Rickets

A
  • 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
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15
Q

Primary hyperparathyroidism

A
  • 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)
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16
Q

Humoral hypercalcemia of malignancy

A
  • 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
Q

What are the two types of bone cells and what do they do?

A

OsteoBlasts - Build bone

Osteoclasts - degrade bone by secreting acid molecules that dissolve mineral and proteases that digest collagen

18
Q

What triggers osteoclast maturation?

A

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
Q

What is the function of osteoprotegerin (OPG)?

A

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
Q

Regulators of bone remodeling

A
  • 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