Regulation of Calcium and Phosphate

Question 1

what is the biological form of Ca+

Answer 1

Free ionized Ca2+

Question 2

What happens with Hypocalcemia

Answer 2

decrease in plasma Ca concentration

hyperreflexia
spontaneous twitching
muscle cramp and tingling and numbness

Indicators: Chvostek sign: twitching of facial muscles after tapping on facial nerve

Trousseau sign: carpopedal spasm upon inflation of a blood pressure cuff

Question 3

What happens in hypercalcemia

Answer 3

increase in plasma Ca concentration

Decreased QT interval, constipation, lack of appetite, polyuria, polydipsia, muscle weakness, hyporeflexia, lethargy, coma

Question 4

How does calcium concentrations affect the membrane excitabillity

Answer 4

Hypocalcemia:

• reduces activation threshold for Na channels making it easier to evoke a AP
• increase in membrane exictabillity (more AP)
• production of tingling and numbness

Hypercalcemia:

• decrease in membrane excitabillity
• nervous system becomes depressed and reflex responses are slo

Question 5

How can Acid base abnormalities alter ionized Ca concentration

Answer 5

Albumin binds free calcium and H+

therefore the acidic the more H+ bound to ALbumin meaning more free floating Ca (increase concentration)

More basic the more Ca bound to albumin therefore a lower free floating Ca concentrations (hypocalcemia)

Question 6

What is the relationship between Calcium and phosphate

Answer 6

Extracellular concentration of P is inversely related to that of Ca

Extracellular concentration of P is regulated by the same hormones that regulate Ca concentration

Question 7

Where is PTH synthesized, how and secreted and what is its main function

Answer 7

chief cells of the Parathyroid gland synthesized on ribosomes as PreproPTH then cleaved to ProPTH and the finally cleaved in golgi to PTH and is packaged in secretory granules

used to regulate the concentration of Calcium and Phosphate in the plasma

Question 8

what is the stimuli for PTH secretion

Answer 8

a decrease in Plasma concentration

Question 9

What causes inhibition of PTH synthesis and secretion

Answer 9

hich concentration in Plasma Concentration

Question 10

WHat happens in chronic Hypercalcemia

Answer 10

decrease in synthesis and storage of PTH that leads to an increase breakdown of stored PTH and release of inactive PTH fragments into circulation

Question 11

what happens in chronic Hypocalcemia

Answer 11

AN increase in synthesis and storage of PTH that cases hyperplasia of the parathyroid gland (secondary hyperparathyroidism)

Question 12

WHat happens if an individual has hypomagnesemia

Answer 12

chronic Mg depletion as in alcoholism

inhibition of PTH synthesis storage and secretion

Question 13

How does PTH act on the bone, Kidney, and intestine

Answer 13

BOne: increase bone resorption

Kidney: increase Ca reabsorption, decrease Pi reabsorption
increase urinary cAMP

Intestine: Increase Ca absorption indirectly via vitamin D

all of these increase Plasma Ca concentrations

Question 14

What is Vitamin D

Answer 14

Cholecalciferol

is a prohormone
steroid hormone (in active form)
it is physiologically inactive
Must be hydoxylated to be active

regulated by negative feedback mechanisms

Question 15

what is the process of converting Vitamin D to active form

Answer 15

in liver Cholecalciferol converted to 25-OH-cholecalciferol then in the renal proximal tubule it is converted to 1,25-OH-Cholecalciferol

this is the active form and is done by CYP1a hydroxylase

Question 16

where are the PTH receptors located on bone and what is PTH short term and long term actions on bone
howw does Vitamin D compare

Answer 16

PTH receptors located on osteoblasts

short term actions: Bone formation

Long term action: increase bone resorption (indirect action on osteoclasts mediated by cytokines released from osteoblasts)

vitamin D acts simularly to PTH

Question 17

Summary of factors important in bone formation: M-CSF

Answer 17

Macrophage colony stimulating factor

induce stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts, and finally mature multinucleated osteoclasts

Question 18

Summary of factors important in bone formation: RANKL

Answer 18

receptor activator for NF-kB ligand

cell surface protein produced by osteoblasts, bone lining and apoptotic osteocytes
-primary mediator of osteoclast formation

Question 19

Summary of factors important in bone formation: RANK

Answer 19

Cell surface protein receptor on osteoclasts and osteoclast precursors

Question 20

Summary of factors important in bone formation:OPG

Answer 20

osteoprotegerin

soluable protein produced by osteoblasts that inhibits the RANKL/RANK interaction

Question 21

How does PTH and Vitamin D affect RANKL

Answer 21

increases RANKL and decreases OPG

Question 22

Summary of PTH actions on the kidney

Answer 22

Stimulates 1a hydroxylase to activate Vitamin D

stimulates Ca reabsorption by the thick ascending limb of heneles loop and the distal tubule

Inhibits P reabsorption by proximal nephrons (represses NPT2a expression)

Question 23

process of Vitamin D on intestinal calcium absorption

Answer 23

1,25 dihydroxy Vitamin D changes transcription to make TRPV6 channel to allow for Calcium to enter from the intestine

from their Calbindin binds and then uses 3 Na from the intersitial space to get Calcium into the blood stream

Question 24

Summary of how Vitamin interacts with Ca and P in the small intestine, bone, kidney and Parathyroid gland

Answer 24

Small intestine: increases Ca and P absorption

Bone: sensitizes osteoblasts to PTH
regulates osteoid production and calcification

Kidne: Promotes P reabsorption byy proximal nephrons (stimulates NPT2a)

Parathyroid gland:
Directly inhibits PTH gene expression
Directly stimulates CaSR gene expression

Question 25

WHat is the role of calcitonin

Answer 25

decrease Ca and P concentration does this by inhibiting bone resorption -decreases the activity and number of osteoclasts it does this if there is a high level of Calcium in the plasma

Question 26

How does thyroid tumors and thyroidectomy affect calcitonin

Answer 26

decrease in thyroidectomy increase in a thyroid gland overall no change in Ca from this though

Question 27

How does Estradiol 17B affect Ca levels

Answer 27

stimulates intestinal Ca absorption and renal tubular Ca reabsorption promotes the survival of osteoblasts and apoptosis of osteoclasts favoring bone formation over resorption

Question 28

How do adrenal glucocorticoids affect Ca

Answer 28

Cortisol promotes bone resorption and renal Ca wasting and inhibit intestinal Ca absorption patients treated with high levels of cortisol can induce osteoprosis

Question 29

Primary Hyperparathyroidism: PTH levels, Ca levels, P levels and Vitamin D, Treatment and characteristics

Answer 29

high PTH High Ca Low P High Vitamin D patients have hypercalciuria stones increase bone resorption constipation groans treat ment is parathyroidectomy

Question 30

Secondary Hyperparathyroidism: PTH levels, Ca levels, P levels and Vitamin D, Treatment and characteristics

Answer 30

Renal failure: high PTH low Ca high P low Vitamin D ``` Vitamin D deficiency: High PTH low Ca low P low vitamin D ```

Question 31

Hypoparathyroidism: PTH levels, Ca levels, P levels and Vitamin D, Treatment and characteristics

Answer 31

Low PTH Low Ca High P low Vitamin D causes are thyroid or parathyroid surgery autoimmune or congenital muscle cramping seizures poor teeth numbness in hands and mouth oral calcium and active form of vitamin D

Question 32

Pseudohypoparathyroidism type 1a PTH levels, Ca levels, P levels and Vitamin D, Treatment and characteristics

Answer 32

Albright hereditary osteodystrophy high PTH low Ca high P low Vitamin D inherited autosomal dominant where the Gs for PTH in bone and kidney is defective hypocalcemia and hyperphosphatemia develop short stature short neck obesity subcutaneous calcifications shortedned metatarslas and metacarpals

Question 33

Humoral hypercalcemia of malignancy PTH levels, Ca levels, P levels and Vitamin D, Treatment and characteristics

Answer 33

low PTH high Ca low P low Vitamin D PTHrelated peptide produced by tumor and this peptide will bind and activate same receptor as PTH high PTHrP levels increase urinary cMP, Pi, Ca

Question 34

Familial Hypocalciuric hypercalcemia PTH levels, Ca levels, P levels and Vitamin D, Treatment and characteristics

Answer 34

FHH ``` normal to high PTH High serum Ca low Urine Ca normal P normal Vitamin D ``` mutation that inactivates CaSR in the parathyroid glands and in the ascending limb of the kidney

Question 35

what does the CaSR gene do

Answer 35

activated by levels of vitamin D and Ca but will inhibit the release of PTH from the Parathyroid hormone

Question 36

What are the two types of congenital Rickets

Answer 36

Congenital disorders: -Pseudovitamin D deficient rickets or vitamin D dependant rickets type 1 (decrease in 1 alpha hydroxylase) -Pseudovitamin D deficient rickets or vitamin dependant rickets type II (decrease in viramin D receptor) lead to insufficient Ca and P and stunted growth and skeletal deformities

Question 37

Osteomalacia

Answer 37

Vitamin D deficiency in adults due to malnutrition, gastrointestinal disorder, inadequate sun exposure bone pain and muscle weakness bone tenderness fracture muscle spasms and positive chvosteks sign

Question 38

Treatment of osteoprosis

Answer 38

PTH Bisphosphonates estrogen Calcitonin RANKL inhibitors