Q2: parathyroid

Question 1

whats the % allocation of calcium in the body

Answer 1

.1% ECF
(45% as free ionized calcium 9ca), 45% bound to serum proteins - albunmn, 10% bound to low molecular weight organic anions -citrate and oxalate

.9% Soft tissues

99% crystalline form (bone and teeth)

Question 2

which calcium regulates PTH

Answer 2

the only body calcium that regulates PTH is free calcium which is the only active calcium. (45% of ecf which is .1% of body calcium)

Question 3

where is most cellular calcium found

Answer 3

Endoplasmic reticulum

Question 4

how does calcium enter the body/what are its possible routes once inside (absorption/reabsorption/excretion and secretion)

phosphate?

Answer 4

-through diet. can either be absorbed or excreted into feces from the GI system. if absorbed, calcium is now in the ecf and can either form into bone or get filtered by kidneys and excreted into urine. Calcium can also be SECRETED from the ecf into GI for feces excretion, or reabsorbed by the kidneys back into the ecf!! also through bone resorption it goes back into the ecf

phosphate follows the EXACT same route options

-regulated by same hormones (PTH, vitamin D, calcitonin, and both part of hydroxyapatite)

Question 5

whats composition of hydroxyapatite

Answer 5

ca10(po4)6(oh)2

-precipitate around collagen fibers in the matrix of bone

Question 6

whats the purpose of bone remodeling

Answer 6

formation/resorption occurs concurrently and the purpose is:

• growth
• repair and reshape in response to stress
• helps maintain the plasma calcium level

Question 7

what are the following bone cells and where do they differentiate from : osteoprogenitor, osteoblast, osteoclast, osteocytes

Answer 7

osteopronitor: from mesenchymal cells , they differentiate into osteoblasts! so osteoblasts come frm mesenchymal too
osteoblast: secrete extracell organic matrix
osteocyte: differentiated osteoblasts! trapped in bony wall
osteoclats :resorb bone in their vacinity, dervied from macrophages, they secrete HCl to dissolve calcium phosphate crystals and enzymes to break down the organic matrix

Question 8

describe process from macrophage to osteocytes

Answer 8

macrophages (or PRE osteoclasts) and mononuclear cells undergo osteoclastogenesis to form osteoclasts! these adhere to bone and secrete acid/enzymes to dissolve minerals and organic matter (collagen and proteins).
bone resorption ends up killing the osteoclast. osteoprogenitor cells then inhabit the area and differentiate into osteoblasts. the osteoblasts secrete organic matrix for mineralization and become trapped within the matrix. at this point they are now osteocytes!!!!!

(role of mononuclear?)

Question 9

What isthe role of the RANK ligand . what secretes it?

Answer 9

aka RANKL : rankl binds to RANK (receptor activator of NF-kappab) which is a protein receptor on MACROPHAGE surfaces. this induces macrophages to differentiate into osteoclasts!!
-this interaction also supressess osteoclast apoptosis!

• promotes resorption
• gets secreted by OSTEOBLASTS and their precursors!!

dot forget that osteoblasts/precursosr also secrete osteoprotegerin- when this binds to RANKL, blocking RANK, it stops , so now differetnation of macropphages wont occur and bone resorption is reduced!!!
opg/rankl ratios are important for what occurs

Question 10

what is the role of osteoprotegerin (OPG) and what secretes it

Answer 10

secreted by osteoblasts and their precursors…

• osteoprotegerin supresses osteoclast activity . it binds to RANKL and inhibits it from binding to RANK!
• this reduces bone resorption!

Question 11

what are the functions of free calcium ion

Answer 11

• muscle contraction (skeletal, heart); binds troponin to release tropomyosin
• release of excretory product by exocytosis; neurotransmitter, hormone and saliva secretion
• nociception ?
• pacemaker potential
• synthesis of protein or molecules; NO by endothelial cels
• clotting of blood; cofactor in clot formation
• cellcell adhesion (cadherin function!)

Question 12

what occurs with hypocalcemia

Answer 12

low BLOOD calcium-
increases probability that a stimuli will bring the membrane potential to threshold. ( difference))
-skeletal muscle discharge and contract–goes into spasm spontaneously (absence of normal stimulation..)
-spastic contraction of the respiratory muscles can result in death by asphyxiation

(low levels of calcium causes increased Na permeability, higher inflx of sodium)
-muscle stim is based on calcium from ER not ecf really

Question 13

what occurs with hypercalcemia

Answer 13

high BLOOD calcium -
decreasess probability of a membrane threshold . can cause cardiac arrhythmias, generalized depression of neuromuscular excitability

high blood calcium , sodium permeability decreases and lowers restng membrane potential (more negative) a stronger stimuli is needed to reach threshold

Question 14

whats the main mechanism to maintain calcium homeostasis? how else is it achieved

Answer 14

MAIN is rapid ; ca exchange between bone and ecf!

-also theres immediate adjustment of ca to make sure theres a constant concentration of calcium in ecf

Question 15

how is calcium BALANCE maintained

Answer 15

slow adjustments to maintain a constant total amount of calcium in the body. ensures calcium intake =calcium excretion!

-maintained by adjusting intestinal calcium absorption and urinary calcium excretion

Question 16

how do the 3 hormones involved in calcium metabolism regulate it

Answer 16

parathyroid hormone : principle regulator, regulates urinary excretion of calcium, ca exchange between ecf and bone, and absorption of calcium from digestive tract.

Vitamin D: enhances calcium absorption from gi tract

calcitonin: counters effects of PTH; backup functions ONLY during times of extreme hypercalcemia

Question 17

what is parathyroid hormone made of? what does it do? what are the major epithelial cells of it?

Answer 17

peptide hormone , major epithelial cells involved are chief and oxyphil cells.

• it INCREASES plasma calcium concentration
• DECREASES plasma phosphate concentration

normal conditions: low levels of calcium triggers PTH, which increases calcium levels. high calcium levels have neg feedback to lower pth again.

Question 18

how does lack of PTH cause death

Answer 18

asphyxiation due to hypocalcemic spasms of respiratory muscles!

Question 19

how does primary hyperparathyroidism impact calcium levels

Answer 19

too much PTH means calcium is too high. the parathyroid gland gets insensitive to the calcium levels and continues to secret PTH even when the levels of serum calcium is high.

Question 20

how does hyperparathyroidism of malignancy impact calcium levels

Answer 20

calcium levels are high and pth are low, but calcium stays high even if PTH levels are low.

tumor that produces a parathyorid related protein, not PTH but similar enough that it induces the same effects in target cells.

confiused

Question 21

what is the ACTIOn of PTH on bone (acute)

Answer 21

rapid ca transfer from bone to plasma. source is BONE FLUID!

bone fluid: fluid within the space of bones. ca is replenished w calcium from partly mineralized bone along adjacent bone surface. bone mass is not decreased since mineralized bone is not resorbed. usually this suffices for the need of calcium..

-bone fluid concentrations vary themselves based on osteoblast activity etc.

Question 22

what is the chronic impact of PTH on the bones

Answer 22

promotes localized dissolution of bone to release calcium into plasma. bone resorption.
this is a slower process than just from bone fluid..
-stimulates osteoblast to secrete RANKL - which increases differentiation of macrophages and osteoclast activity
(osteoclasts have no pth receptor!!!!)

Question 23

what is osteoporosis?

list treatments

Answer 23

prolonged pth activity leads to reduced calcium levels= osteoporosis
treatments:
-biphosphonates (inhibits osteoclast activity)
-HRT and raloxifene (evista) inhibits differentiation of osteoclast and induces apoptosis
-Teriparatide (forteo) - recombinant PTH
-denosumab (prolia) - antibody against RANKL (acts like osteoprotegerin; stops rankl from binding to rank and reduces bone resorption)

Question 24

what is pth action on phosphate

Answer 24

promotes phosphate elimination!

Question 25

how does PTH impact the kidneys

Answer 25

kidneys reabsorb more filtered calcium, less calcium loss in the urine.
-decreased phosphate reabsorption!! more phosphate is excreted in the urine. removing of phosphate prevents precipitation of calcium….

-PTH enhances activation of vitamin D by the kidneys. (vitamin D-> 1,25-dihydroxycholecalciferol (1,25-DHCC 1,25-DHCC, 1,25-dihydroxyvitamin d3, calcitriol)

Question 26

what are the actions of vitamin D

Answer 26

increases concentration of calcium in blood

• GI absorption of ca
• kidneys ca reabsorption
• increases bone mineralization

Question 27

what are the 3 forms of vitamin d

Answer 27

D2: from diet (veggies)
D3: synthesized by skin
1,25 DHCC (1,25 dihydroxyvitamin D, calcitriol)= active form

Question 28

what is the vitamin d deficiency disease called in children/adults? what occurs

Answer 28

rickets in kids
osteomalacia in adults

impaired intestinal absorption of calcium!!

• reduced calcium uptake; ca levels maintained by PTH at expense of bone density
• bone matrix is not properly mineralized.
• calcium salts are not available for depoisiton.
• bones are soft and deformed.

Question 29

what is the role of calcitonin

Answer 29

made by C cells in thyroid gland

• function: inhibits osteoclast mediated bone resorption. decreases plasma calcium levels.
• no significant role in normal calcium metabolism….

Question 30

how does a thyroidectomy impact ca concentration in the plasma? c cell tumor?

Answer 30

thyroidectomy: no effect on plasma calcium concentration.. even tho calcitonin inhibits osteoclast resorption and decreases calcium levels, the function only occurs when blood calcium levels are very high. under normal calcium metabolism the effects of calcitonin are minimal…

if someone gets a thyroidectomy but no parathyroid issue, no observable effect on plasma calcium concentration.

C cell tumor: increases concentration of calcitonin. no effect on plasma calcium concentration. so physio function of calcitonin when PTH is normal is unclear?

Question 31

describe how low calcium levels impacts calcitonin levels

-

Answer 31

low calcium levels stimulate parathyroid to release pth, and inhibit thyroid cells from releasing calcitonin

Question 32

describe how high calcium impacts calcitonin levels

Answer 32

inhibits parathyroids from releasing pth

stimulates thyroid c cells to release calcitonin