PMD 604 APP II Lecture 15 Parathyroid, Calcitonin, and Bone

when bones build up, what happens to the blood calcium levels?

they reduce

what does calcitonin do?

it helps build the bones

What are three major compounds that control calcium metabolism?

- parathyroid hormone

- calcitonin

- vitamin D

parathyroid hormone is secreted from which cells?

chief cells

What does parathyroid hormone do?

- increases the number and activity of osteoclasts thereby releasing calcium and HPO3-4 into the blood and promoting bone resorption

How does parathyroid hormone affect kidney function?

kidney slows the rate at which calcium and magnesium are lost from the blood into the urine

parathyroid hormone promotes the formation of which hormone?

calcitriol (an active form of vitamin D)

calcitonin is secreted from which cells?

parafollicular cells

How does calcitonin build bones?

- it decreases the level of calcium in the blood by preventing action of osteoclasts

- when its blood levels are high, calcitonin inhibits bone resorption

calcitonin derived from ______________________ is used to treat osteoporosis.

salmon

which form of vitamin D is formed in the skin?

vitamin D3

another name for vitamin D3 is ________________________.

cholecalciferol

active vitamin D increases the rate of absorption of Ca2+ from GI tract into the blood. Another name for active vitamin D is _____________________________.

calcitriol

besides calcium, which 2 other molecules/electrolytes are absorbed from GI tract into the blood?

HPO2-4 and MG++

blood calcium levels directly control the secretion of _____________________ and __________________________ via negative feedback loops that DO NOT involve the pituitary gland.

parathyroid hormone, calcitonin

parathyroid also stimulates kidneys to release _____________________ to increase calcium absorption from foods, which increases blood calcium level.

calcitriol

total calcium in the blood is equal to....

BOTH protein bound calcium and free calcium

Ionized calcium is equal to....

only free calcium

How does acidemia influence calcium levels?

- more ionized calcium ions

- fewer protein bound calcium

How does alkalemia influence calcium levels?

- increased protein bound calcium

- decreased ionized calcium

What are the outcomes of hypocalcemia?

- easy initiation of action potential (i.e. NS excitement)

- spontaneous discharge (i.e. tetany)

- reduced calcium, increased permeability to Na+

what are the outcomes of hypercalcemia?

- sluggish CNS

- reduced QT interval of the heart

- constipation (reduced contractility of the GI muscle)

Describe the steps in the correct order for bone remodeling.

resting stage --> osteoclast recruitment + activation --> bone resorption --> osteoblast recruitment + activation/ osteoclast removal --> transition --> matrix synthesis --> bone formation

PTH binds to receptors on osteoblasts causing them to secrete _______________________, which will bind to pre-osteoclasts, causing them to differentiate into their mature counterparts.

RANKL

osteoclasts develop a ruffled border and release acids and enzymes (from lysosomes) to promote bone resorption (T/F).

TRUE

What is the mechanism of osteoclast formation?

- RANK receptors are expressed pre-osteoclasts and osteoclasts

- RANK ligands (RANKL) is expressed in osteoblasts

- RANKL binds to RANK, activating the NFkB, which activates gene expression to promote osteoclast formation

What compound can block and prevent osteoclast differentiation?

OPG

In addition to OPG that can block and prevent osteoclast differentiation, how could you design a drug that can interfere with the process regulated by OPG?

- use another ligand that mimics the other ligand and can block the receptor

- form a molecule with similar properties as OPG and bind to ligand to prevent ligand-receptor interaction

- make a ligand that mimics a specific step in the process

osteoprotegerin (OPG) production is stimulated in vivo by which hormone?

estrogen

What is the name of the drug that stimulates the production of OPG?

strontium ranelate

which drug mimics OPG and is a decoy for RANKL?

denosumab

Under parathyroid hormone actions, kidney increases calcium reabsorption and ____________________________. Kidney also decreases ____________________ and _____________________ reabsorption (weak effect).

D3, phosphate, sodium

What are the cellular actions of parathyroid hormone in the thick ascending loop and distal tubule?

- increases calcium reabsorption in two ways:

1. calcium is reabsorbed and Na+ is filtered through a protein channel

2. calcium is reabsorbed on its own BUT requires ATP to be reabsorbed through a protein channel (active transport)

What is the cellular action of parathyroid hormone in the proximal tubule?

kidney decreases phosphate reabsorption

What is the relationship between calcium levels in the plasma and PTH secretion?

- as total plasma calcium levels decrease, PTH secretion (and calcitonin) increases

- as total plasma calcium levels increase, PTH secretion (and calcitonin) decreases

How does calcitonin influence osteoclasts?

calcitonin decreases the activity and number of osteoclasts

calcitonin plays ________________ role in acute regulation of plasma calcium ions AND _______________ role in chronic regulation of plasma calcium ions.

minor, no

where does vitamin D3 (cholecalciferol) come from?

- diet

- skin via sunlight

Where does calcitriol (1,25-(OH)2-cholecalciferol) come from?

1alpha-hydroxylase AND PTH

How does vitamin D influence intestine?

it helps to increase the absorption of calcium and phosphate

vitamin D increases calcium and phosphate reabsorption in which organ?

intestine

What are the two forms of rickets-osteomalacia?

rickets type I (decrease in 1a-OHase)

rickets type II (decrease in 1,25-(OH)2-receptor)

List four forms of treatment of rickets-osteomalacia.

•Vitamin D2 (ergocalciferol) or D3 (cholecalciferol)

•

• Calcium

•

• Sunlight

•

• 1,25-(OH)2- D3 (calcitriol)

Hyperparathyroidism is more prevalent in ___________________.

women than men

What happens in patients with hyperparathyroidism?

- extreme osteoclastic activity in the bones leads to high calcium resorption and low concentration of phosphate ions (due to high renal excretion of phosphate)

- osteoblastic activity increases more to compensate

How can you diagnose hyperparathyroidism?

osteoblastic activity increases to compensate. As a result, large quantities of alkaline phosphatase are secreted. -- diagnostic

osteoporosis is a prevalent __________________ disorder in adults that is more prevalent in ____________________.

endocrine, women than men

Generally, what happens in patients with osteoporosis?

- inhibited osteoblasts and increased osteoclasts

List three factors associated with osteoporosis?

- aging

- increases glucocorticoids

- immobilization

in patients with osteoporosis, what are three hormones that decrease with age?

- estrogen

- testosterone

- GH

How does aging contribute to osteoporosis?

- decreases osteoblast activity

- decreased replication of osteoprogenitor cells

- reduced physical activity

How does menopause contribute to osteoporosis?

- decreased serum estrogen

- increased expression of RANK, RANKL

- increased osteoclast activity

What are two categories of treatment for osteoporosis?

- anabolic therapy

- antiresorptive therapy

one form of anabolic therapy for osteoporosis is ____________________.

PTH

Name four methods of antiresorptive therapy for osteoporosis?

- bisphosphonates

- estrogen

- SERMs (raloxifene, tamoxifen)

- calcitonin

_____________________________ is a disease of bone demineralization, in CONTRAST to _________________________ which is a degenerative disease caused by wear and tear of the joints.

osteoporosis, osteoarthritis