12 - Disease of PTH gland and bone

Osteoblast vs osteoclast function

• Osteoblasts: Secrete osteoid to build the matrix

• Osteoclasts: Secrete acid to dissolve bone

Bone remodeling definition

Bone formation and resorption happening at the same site to “refresh” old bone with new one

Simple bone remodeling process

Osteoclasts precursors are recruited to a site → osteoclasts dissolve bone and leave a small pit → osteoblasts are recruited → lay down new osteoid

Bone mineralization

Hydroxyapatite(calcium and phosphate) crystals lay down on the collagen(osteoid) to create strong bones

Osteomalacia

• Is

• Version in children

• A mineralization defect, aka enough osteoid but no mineralization

• Rickets

Osteomalacia/Rickets in Thai

โรคกระดูกอ่อน

FGF23 function

Fibroblast growth factor 23 leads to phosphate excreting actions

Looser zone/pseudofracture

A band of unmineralized osteoid, looks like a fracture line but the bone isn’t broken

PTH

• Source(and cellular lvl too)

• Function(4 Actions)

• Parathyroid glands(From chief cells)

• Releases stored calcium by dissolving bone, increases calcium reabsorption, decreases phosphate reabsorption, activating vitamin D

Renal Osteodystrophy means ___, and what are the symptoms(3) and why?

Bone disorders that develop in patients with CKD

• Hyperphosphatemia: Kidney can’t excrete phosphate

• Reduced vitamin D activation: Kidney normally activates vit.D

• Secondary hyperparathyroidism: To compensate for the kidney’s inability to keep Ca2+ level normal

Osteoporosis

• Is, and distinction from osteomalacia

• Cause

• Thai name

• A reduction in bone mass with normally structured bone with normal mineral to matrix ratio

• Typically due to the body leaning more toward bone resorption > formation, such as aging

• โรคกระดูกพรุน

What are the 2 main types of calcium, and why does knowing the difference matter?

1. Free calcium, used by organs and all cellular processes

2. Bound calcium, to albumin

It matters because if albumin decreases, our total calcium seems lower, even if the one that actually matters, the free calcium, is still unaffected

How do we correct the calcium count?

Corrected calcium = Measured total calcium + 0.8 x (4 - Patient’s albumin)

What is free Ca2+ relationship with pH?

• If pH goes up: Less H+ to compete with Ca2+, Ca2+ can bind albumin → less free Ca2+

• If pH goes down: More H+ to compete with Ca2+, Ca2+ binds albumin less → more free Ca2+

Why does hemolysis cause elevated inorganic phosphate?

• Cells contain lots of organic phosphate, which when hemolysis happens, causes them to be released and turned into inorganic form

Why does K+ increase a lot when a sample isn’t heparinized?

Because platelets start to do clotting, releasing their intracellular contents, including potassium

What generation of PTH assay is the most popular, and what are these?

• 2nd gen.

• Basically parts of a PTH hormone that we can detect

What are the names of vitamin D obtained from sun vs plants?

• Cholecalciferol(vitamin D3) vs ergocalciferol(vitamin D2)

How is vitamin D activated after that?

1. Liver uses 25 hydroxylase to turn vitamin D to 25-hydroxyvitamin D(25OHD)

2. 25OHD is gets another hydroxyl group from 1 alpha hydroxylase which creates 1,25-dihydroxyvitamin D(1,25OH2D) called calcitriol, the active form

Which form do we use for vitamin D status and which one do we use for hyper/hypocalcemia?

1. Vitamin D status: 25 hydroxyvitamin D because it reflects total unregulated body supply and has a long HL

2. Hyper/hypocalcemia: 1,25 dihydroxyvitamin D because it has a short half life and represents how our body is currently regulating calcium

Upper normal limit of calcium

12 mg/dL

Hypercalcemia symptoms and why they happen

• Bones: Bone pain and increased fracture risk due to increased bone resorption

• Stones: Kidney stones due to calcium crystallizing

• Groans: GI symptoms due to impaired smooth m. contraction

• Psychiatric overtones: Altered mental status because of calcium’s usual nerve excitability role being impaired

Most common hypercalcemia cause

Primary hyperparathyroidism(Aka PTH secreting adenoma)

Hypercalcemia with

• Low P

• High P

• Low: PTH driven because PTH decreases P while increasing Ca2+

• High: Both ions released together like excess vitamin D activity

Thiazide impact on calcium

• Thiazides are a drug that inhibit the NCC, a cotransporter that reabsorbs both Na+ and Ca2+, allowing us to lose more fluid, but this means we have less sodium inside kidney cells, allowing for a better gradient for NCX to work better, pulling sodium from blood into cell, and calcium out to blood

What is the main causal agent in hypercalcemia of malignancy?

PTH-rP

PTH level in PTHrP malignancy vs primary parathyroidism

• Low(due to neg. feedback) vs high

Hypocalcemia value

<8.5 mg/dL

If there is high creatinine and hypocalcemia, what does that likely mean? And what other key value would we see with it?

• High chance of renal failure, since it means the kidney is failing(can’t clear creatinine). Kidney failure would then mean inability to turn vitamin D to it’s active form → less Ca2+ absorption

• High phosphate since kidneys can’t excrete it

If creatinine is normal in hypocalcemia, what are 2 causes we can look at?

• Hypoparathyroidism

• Vitamin D deficiency

Why does hypocalcemia cause:

• Fingertip tingling

• Muscle cramps and spasms(such as)

• Seizures

• Prolonged QT

• Tingling: Because Ca2+ usually keeps sodium channels stable; without calcium, nerves can fire spontaneously

• Muscle cramps: Same reason

  • Trousseau’s sign: A claw in the hand that happens after a cuff causes local ischemia in forearm nerves

  • Chvostek’s sign: Tapping a cheek causes it to twitch

• Seizures: Also same thing, spontaneous firing in the CNS

• Prolonged QT: Slows down plateau phase and slows repolarization

AHO Pseudohypoparathyroidism + symptoms

• Body makes enough PTH, but our tissues can’t respond to it due to genetic disorders of receptors

  • Short stature

  • Obesity

  • Mild intellectual disability

Osteoporosis primary diagnostic tool

• Dual X-Ray Absorptiometry

Bow legged medical term and cause

• Genu varum

• Failure of mineralization causes weaker bones to bend outward as it bears the weight of a growing child

Explain these secondary osteoporosis causes

1. Hyper PTH

2. Hyper thyroid

3. Glucocorticoid excess

1. PTH promotes bone resorption

2. Thyroid hormone speeds up bone remodeling while favoring resorption

3. Glucocorticoids suppress osteoblasts and increase RANKL