Physiology Block 3 Week 15 12 Calcium Flashcards Preview

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Flashcards in Physiology Block 3 Week 15 12 Calcium Deck (24)

Functions of Calcium Ion

-maintenance of normal ion product for mineralization
-cofactor for prothrombin factors
-maintenance of plasma membrane stability and permeability

-skeletal and cardiac muscle contraction
-cellular secretion
-neural excitation and light transmission
-regulation of membrane ion transport
-enzyme regulation (gluconeogenesis, glycogenolysis)
-cell growth and division


Calcium Absorption/Secretion

35% absorbed in small intestine

Calcitrol 1, 25 (OH) 2D of vitamin D pathway--stimulates calcium and phosphate absorption

25% of calcium intake is secreted into GI tract



Calcium Deposition/Resorption

1 kg Ca2+ stored in bone--metabolically active

Parathyroid Hormone (PTH) stimulates resorption--reclamation of calcium (and phosphate) from bone

Deposition--calcium and phosphorus stored in bone

Continual exchange (bone turnover) helps to maintain healthy bone

Resorption > Deposition = net loss of bone calcium and phosphorus = osteoporosis

Estrogen is anti-resorptive; at menopause, women have less estrogen and have a higher incidence of osteoporosis


Calcium Filtration/Reabsorption

99.9% calcium filtered in kidney

Parathyroid Hormone stimulates reabsorption--critical to minimize loss of calcium and phosphate ions at proximal tubule


How is calcium transported in the blood?

50% ionized (free, dissolved)--biologically active

Circulates bound to albumin

Small amount complexed to anions (CaCl2)

**Important in patients with hypoalbuminuria**


Negative Feedback of Parathyroid Hormone

Synthesized and Secreted by the chief cells from 4 parathyroid glands (glands behind thyroid)

-stimulates bone resorption of calcium and phosphate
-stimulates production of 1,25(OH)2D (converted from 25OHD3)-->increases calcium absorption in GI tract and REabsorption in kidneys

-inhibited by increases in extracellular Ca2+

**Decreases in calcium releases PTH from inhibition, allowing resorption (bone breakdown) to restore plasma calcium levels**


Negative Feedback of Calcitonin

No importance in humans

Secreted from P,arafolicular Cells of Thyroid

Used as anti-resorptive therapy
--if plasma calcium is VERY high, calcitonin is stimulated and inhibits bone resorption (bone break down)


Calcium Inhibition of Parathyroid Hormone Secretion

Calcium Receptor is a G-Protein coupled Receptor

If calcium is low, the receptor is unloaded, and PTH is secreted from the chief cells of the parathyroid gland


What happens to the feedback loop if plasma calcium is too high (hypercalcemia)?

If there is too much calcium, there will be an inhibition of PTH secretion from parathyroid cells

PTH stimulates bone resorption (bone breakdown)

During hypercalcemia, PTH is inhibited, preventing bone breakdown


Effect of plasma calcium concentration on PTH and Calcitonin

(Hypercalcemic) High Calcium:
-PTH inhibited
-high calcitonin

Low Calcium:
-PTH inhibition relieved = PTH released
-low calcitonin

Chronic Hypocalcemia:
-small changes in calcium concentration result in 100 inc in PTH concentration


What will happen to bone calcium content with long term decreases in calcium intake?

What is the hormonal mechanism involved?

100% increase in PTH

PTH increases bone resorption (bone breakdown)

Leads to osteoporosis


Role of Vitamin D in controlling plasma Calcium Concentration

D3 = cholecalciferol; D2 = ergocalciferol

Vitamin D intake (diet and supplementation)
--liberated from the skin (UV light)

Liver converts to 25OHD3
--reflection of Vit D intake and stores in body

PTH stimulates enzyme 1-hydroxylase to convert 25OHD3 to 1, 25(OH)2D3 = CALCITRIOL

Calcitriol stimulates calcium and phosphate absorption in small intestine
--increases plasma Ca2+ levels
--inhibits PTH when Ca2+ levels are high


Does 1-hydroxylase activity alter:
-plasma 1, 25(OH)2D3?
-plasma 25OHD concentration?

25OHD concentration 100-1000x > 1,25(OH)2D3

Only a small portion of 25OHD is actually activated to 1,25(OH)2D3

1-hydroxylase activity:
-can increase or decrease plasma 1,25(OH)2D
-does NOT alter plasma 25OHD because is in excess


Clinical Interpretation of serum 25OHD

Index of Vitamin D Stores (intake/absorption)
--not altered by changes in 1-hydroxylase activity


Clinical Interpretation of serum 1,25(OH)2D3

Index of renal 1-hydroxylase activity


Why must one take caution when taking Vitamin D?

Vitamin D is NOT a vitamin, but a STEROID HORMONE

Works via a nuclear receptor
--activates transcription and translation

Main function is to increase calcium and phosphate absorption in the small intestine


Parathyroid Hormone and Phosphate Balance

PTH stimulates:
-phosphate absorption in GI tract
-phosphate resorption from bone

PTH inhibits:
-phosphate reabsorption in proximal tubule of kidney
-although PTH increases phosphate entry into EC space from the gut and bone, kidney dumps phosphate into the urine
**prevents hyperphosphatemia



Response in:

-Parathyroid Glands

Parathyroid Glands:
Low calcium results in no binding of G-protein coupled receptor (Ca2+ sensing receptor)
--relieves PTH inhibition and its release

--PTH increases bone resorption (bone breakdown)
--results in Ca2+ efflux

-PTH stimulates renal enzyme 1-hydroxylase to convert 25OHD3 to 1,25(OH)D3 = calcitriol
-calcitriol increases Ca2+ GI absorption and kidney reabsorption
-PTH decreases phosphate reabsorption at proximal tubule (excreted in urine)

-PTH stimulates calcium and phosphate reabsorption


Primary Hyperparathyroidism

Caused by an increase in PTH secretion
--due to an adenoma

Results in:
--hypercalciuria (due to transport max reached)


Hypercalcemia of malignancy (by PTHrp)

PTH receptor peptide released from cancer cells

Results in:
--a suppression of PTH secretion


Primary Hypoparathyroidism

Caused by a deficiency in PTH secretion (familial or iatrogenic)

Results in:


Secondary Hyperparathyroidism

Caused by renal failure
--no 1-hydroxylase, so can't convert 25OHD3 to 1,25(OH)2D3 = calcitriol
--no synthesis of calcitriol results in hypocalcemia

Caused by malabsorption
--celiac sprue (destruction of villi in small intestine) results in inadequate Vitamin D intake (deficiency)
--results in hypocalcemia

Hypocalcemia results in an increase in PTH secretion
--brittle bones

Tx: Give 1,25(OH)2D3 Calcitriol directly
--not 25OHD because kidneys can't make 1-hydroxylase


Chronic hypercalcemia is an expected finding in which disease?

Vitamin D deficiency
Primary hyperparathyroidism
Chronic renal failure
Primary hypoparathyroidism

Primary hyperparathyroidism


Assume patient is HYPERCALCEMIC

What is the cause?
What labs would you measure?
What is affected?
What is treatment? What should you be aware of post-treatment?

Primary Hyperparathyroidism due to adenoma
--causes an increase in PTH
--suppresses parathyroid glands (atrophy)


What is affected?
-increased bone resorption (bone breakdown)
-increases calcium and phosphorous efflux from bone

GI and Vitamin D pathway:
-increases conversion of 25OHD3 to 1,25(OH)2D3 calcitriol
-increased calcitriol increases cut absorption of calcium and phosphorus

--increases calcium reabsorption
--increases phosphorous excretion in urine
--increased urinary excretion of calcium due to transport maximum exceeded from hypercalcemia

-inc plasma calcium
-inc/unchanged plasma phosphorus (due to absorption and excretion)
-inc urinary calcium
-inc DRAMATICALLY urinary phosphate
-inc 1,25(OH)2D3 calcitriol
-25OHD3 unchanged because 100-1000x more conc than 1,25(OH)2D3

Due to increased calcium and phosphate in urine, can result in kidney stone precipitation

Tx: Removal of parathyroid tumor.
The other parathyroid glands are suppressed and atrophied because the tumor was producing all the PTH
--the patient will become HYPOCALCEMIC post surgery