Parathyroid

Question 1

Where is calcium stored?

Answer 1

Mitochondria and ER

Question 2

What is “pump-leak” transport?

Answer 2

Ca2+ leaks into cytosolic compartment and is pumped into storage sites in organelles

Question 3

How is calcium stored in serum?

Answer 3

• Ionized (50%)
• Protein-bound (40%) - 9/10 of this is bound to albumin, rest to globulins
• Complexed to serum constituents (10%) - like citrate and phosphate

Question 4

Why are patients with acute respiratory alkalosis prone to seizures?

Answer 4

Low ionized calcium in ECF (increased binding to proteins) and therefore increased permeability to sodium ions

Question 5

Normal calcium range in plasma:

Answer 5

8.5-10 mg/dL

Question 6

Where does Vitamin D3 synthesis occur?

Answer 6

Keratinocytes in skin (stimulated by PTH)

The active metabolite is 1,25-dihydroxy-D

Skin/diet –> liver –> kidney –> bone/intestine

Question 7

What is the point of regulation in Vitamin D synthesis?

Answer 7

1alpha-hydroxylase (mitochondrial P450 enzyme in kidney)

PTH stimulates this

Question 8

Order of best calcium absorption (and phosphate)?

Answer 8

Duodenum > jejunum > ileum

Dependent on vitamin D

Question 9

What type of activation regulates PTH?

Answer 9

G-protein (phospholipase C and IP3); decrease in cAMP

Question 10

Overall action of PTH:

Answer 10

Increase plasma Ca2+, decrease plasma phosphate

• bone resorption
• kidney reabsorption (distal tubule)
• inhibit phosphate reabsorption
• stimulate 1,25-(OH)2-D synthesis (Vitamin D activity)

Question 11

Normal plasma phosphate?

Answer 11

3-4.5 mg/dL

Question 12

Parathyroid chief cells have a…

Answer 12

Calcium sensing receptor (CaSR)

Regulate ionized calcium via PTH secretion (low levels will stimulate PTH)

Question 13

What produces calcitonin?

Answer 13

Parafollicular cells of thyroid (NEURAL CREST DERIVED - rest of thyroid is endoderm)

• Inhibit osteoclast resorption and promote renal excretion of calcium

Question 14

Calcitonin acts via ______

Answer 14

Increased cAMP concentrations in bone and kidney (inhibit osteoclast; also inhibit urinary excretion of calcium/phosphate)

• Probably not necessary for survival, but can be used to treat hypercalcemia

Question 15

List some bone formation stimulants:

Answer 15

• GH
• Insulin-like GF
• Insulin
• Estrogen
• Androgens
• Vitamin D
• Calcitonin

** Inhibitor is cortisol

Question 16

Bone reabsorption stimulators:

Answer 16

• PTH
• Cortisol
• Thyroid hormone
• Prostaglandins
• IL-1, IL-6, TNF-alpha and beta

Question 17

Bone reabsorption inhibitors:

Answer 17

• Estrogen, androgen
• Calcitonin
• gamma-interferon
• NO
• Transforming GF beta

Question 18

What is a cause of Pseudohypoparathyroidism?

Answer 18

End organ PTH resistance (PTH high, but no response, so calcium is low)

• Classic sign is “knuckle knuckle dimple dimple” on metacarpals
• Short, obese, variable mental retardation, Elfin faces, enamel hypoplasia

Question 19

What is an important cause of hypercalcemia of malignancy?

Answer 19

Parathyroid hormone related protein (PTHrP)

• Can activate PTH receptor
• May be important in lactation
• Associated with a few cancers (can be secreted by them)

Question 20

What does vitamin D deficiency lead to in children?

Answer 20

Rickets (prior to closure of growth plates)

Sufficient osteoid, poor mineralization
- Osteomalacia occurs at any age

Question 21

Consequences of primary hyperparathyroidism? Treatment?

Caused by adenoma, hyperplasia, carcinoma

Answer 21

• Nephrolithiasis / nephrocalcinosis
• CNS disturbances (depression, seizures)
• Constipation, peptic ulcer disease, acute pancreatitis
• Osteitis fibrosa cystica

Surgical excision or Cinacalcet (Sensipar)

Question 22

Primary hyperparathyroidism labs…

PTH, calcium, phosphate, urinary cyclic AMP, alkaline phosphatase

Answer 22

Increased PTH
Increased calcium
Decreased phosphate
Increased urinary cyclic AMP
Increased alkaline phosphatase

Question 23

What is secondary hyperparathyroidism?

Answer 23

Excess PTH in response to problem outside of glands - chronic renal failure or after gastric bypass surgery

Question 24

Describe the process of secondary hyperparathyroidism in RENAL INSUFFICIENCY

Answer 24

• Decreased kidney phosphate excretion
• Increased phosphate binds calcium
• PTH released (free calcium lower)
• More bone resorption

Question 25

Labs for secondary hyperparathyroidism…

Answer 25

Inc PTH
Dec serum calcium
Inc phosphate
Inc alkaline phosphatase

Question 26

DiGeorge syndrome has hypoparathyroidism with hypocalcemia

Answer 26

Don’t forget, now!

Question 27

Trosseau’s sign? (in hypoparathyroidism)

Answer 27

indication of latent tetany in which carpal spasm occurs when the upper arm is compressed

Question 28

Chvostek’s sign? (in hypoparathyroidism)

Answer 28

twitching of the facial muscles in response to tapping over the area of the facial nerve

Question 29

Hypoparathyroidism treatment?

Answer 29

Calcitriol and calcium supplements / NatPara

Question 30

Causes of Rickets / Osteomalacia:

Answer 30

• Nutritional deficiency (Vitamin D, calcium chelators, antacids)
• GI absorption defects
• Renal tubular defects / osteodystrophy

Question 31

What is Paget’s Disease?

Answer 31

Disease of bone remodeling; accelerated resorption and formation

• Increased vascularity and fibrosis
• Cause unknown (virus?)

Question 32

What is osteogenesis imperfecta?

Answer 32

Brittle Bone Disease; heritable disorder of connective tissue

• Bone fragility, tendency to fracture
• BLUE SCLERA (rare)