Pathology of Parathyroid and Metabolic Bone Disease Flashcards Preview

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Flashcards in Pathology of Parathyroid and Metabolic Bone Disease Deck (70)
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1

What is the key cell within the parathyroid gland and its role?

- chief cell= regulates serum FREE (ionized) calcium via PTH secretion.

2

*** What does PTH do in response to low FREE (ionized) calcium in the blood?

- increases bone osteoCLAST activity (by activating the osteoBLAST which uses RANKL to activate the osteoCLAST), increasing calcium and phosphate.
- increases small bowel absorption of calcium and phosphate (indirectly by activating vitamin D).
- increases renal calcium reabsorption (distal convoluted tubule) and decreases phosphate reabsorption (proximal convoluted tubule; important bc this is what allows the increase in FREE calcium, unbound to phosphate).

3

**** What is PRIMARY HYPERparathyroidism?

- excess PTH due to disorder of the parathyroid gland.

4

What are the 3 possible ways by which you can get PRIMARY HYPERparathyroidism?

1. parathyroid adenoma (MOST COMMON)
2. sporadic parathyroid hyperplasia
3. parathyroid carcinoma

5

What is parathyroid adenoma (primary hyperparathyroidism)?

- benign neoplasm (usually involving one gland).
- results in ASYMPTOMATIC HYPERcalcemia, however it can present with consequences of increased PTH and hypercalcemia.

6

Even though parathyroid adenoma (primary hyperparathyroidism) is most often asymptomatic, what are some consequences that can occur due to increased PTH and hypercalcemia?

- NEPHROLITHIASIS (calcium oxalate stones)
- NEPHROCALCINOSIS= metastatic calcification of renal tubules, leading to renal insufficiency and polyuria.
- CNS disturbances (depression and seizures)
- CONSTIPATION, PUD, and ACUTE PANCREATITIS (bc calcium can activate pancreatic enzymes).
- OSTEITIS FIBROSA CYSTICA= resorption of bone leading to fibrosis and cystic spaces.

7

What lab findings will you see with parathyroid adenoma (primary hyperparathyroidism)?

- increased serum PTH
- increased serum calcium
- decreased serum phosphate
- increased urinary cAMP
- increased serum ALK phos (bc remember PTH receptors are actually on the osteoBLAST, causing it to increase alk phos).

8

How do you treat parathyroid adenoma (primary hyperparathyroidism)?

- surgical removal of the affected gland.

9

**** What is SECONDARY HYPERparathyroidism?

- excess production of PTH due to disease process EXTRINSIC to the parathyroid gland.

10

*** What is the most common cause of secondary hyperparathyroidism?

- CHRONIC RENAL FAILURE

11

*** Why does chronic renal failure lead to secondary hyperparathyroidism?

- renal insufficiency leads to decreased phosphate excretion.
- increased serum phosphate then binds FREE calcium in the blood.
- decreased FREE calcium stimulates all 4 parathyroid glands.
- increased PTH leads to bone resorption (contributing to renal osteodystrophy).

12

What lab findings will you see with secondary hyperparathyroidism?

- increased PTH
- decreased serum calcium
- increased serum phosphate
- increased alk phos (again bc PTH is stimulating the osteoBLASTS to increase alk phos).

13

**** What is HYPOparathyroidism?

- LOW PTH caused by autoimmune damage, surgical excision, or DIGEORGE syndrome (failure to develop 3rd and 4th pharyngeal pouches bc the parathyroid is a derivative of these)

14

How does HYPOparathyroidism present?

symptoms of low serum calcium:
- numbness and tingling (perioral)
- muscle spasms (tetany)= elicited by filling of blood pressure cuff (TROUSSEAU sign) or tapping on the facial nerve (CHVOSTEK sign)

15

What labs will you see with HYPOparathyroidism?

- decreased PTH
- decreased serum calcium

16

**** What is PSEUDOHYPOparathyroidism?

- signs and symptoms of hypoparathyroidism, but due to END-ORGAN RESISTANCE (due to Gs protein) to PTH.

17

What will you see with pseudohypoparathyroidism?

- HYPOcalcemia with INCREASED PTH.

18

With what is the autosomal dominant form of pseudohypoparathyroidism associated?

- SHORT stature
- SHORT 4th and 5th DIGITS

19

*** What is Achondroplasia? (PICMONIC)

- AUTOSOMAL DOMINANT ACTIVATING mutation in fibroblast growth factor 3 (FGFR-3) leading to impaired cartilage proliferation in the growth plate
*common cause of DWARFISM

20

What does over-expression of FGFR-3 lead to in achondroplasia?

- inhibition of cartilage growth.
*most mutations are sporadic and related to increased paternal age.

21

*** What are the clinical features of achondroplasia?

- SHORT EXTREMITIES with normal-sized head and chest, due to poor ENDOCHONDRAL BONE formation.

22

Is intramembranous bone formation affected in achondroplasia?

- NO, just endochondral.

23

What is endochondral bone formation?

- formation of a CARTILAGE MATRIX, which is then REPLACED by BONE.
*how LONG BONES form.

24

What is intramembranous bone formation?

- formation of bone without a preexisting cartilage matrix.
- how FLAT BONES (skull and ribcage) develop.

25

Will mental function, life span, and fertility be affected in achondroplasia?

- NO :)

26

**** What is Osteogenesis Imperfecta? (PICMONIC)

- congenital defect of bone formation resulting in WEAK BONE.
- most commonly due to AUTOSOMAL DOMINANT defect in COLLAGEN TYPE I synthesis.
*remember bONE has the word ONE in it for type 1 collagen.

27

What are the clinical features of Osteogenesis Imperfecta?

- MULTIPLE FRACTURES (can mimic child abuse, but bruising is absent).
- BLUE SCLERA= thinning of scleral collagen reveals underlying CHOROIDAL VEINS.
- hearing loss= bones of the middle ear easily fracture.

28

**** What is Osteopetrosis?

- inherited defect of bone RESORPTION resulting in abnormally THICK, HEAVY BONE that FRACTURES easily.
- due to poor osteoCLAST function.
*multiple genetic variants exist

29

*** What mutation is most common in osteopetrosis?

- CARBONIC ANHYDRASE II mutation, which leads to LOSS of the ACIDIC microenvironment required for bone resorption.
*think of carbonic anhydrase like dumping a can of coke down calcified water pipes to clear them.

30

*** What are the clinical features of osteopetrosis?

- bone fractures
- anemia, thrombocytopenia, and leukopenia with extramedullary hematopoiesis due to bony replacement of the marrow (myelophthisic process).
- vision and hearing impairment (due to impingement on cranial nerves).
- hydrocephalus (due to narrowing of the foramen magnum).
- renal tubular acidosis (seen with carbonic anhydrase II mutation= lack of carbonic anhydrase results in decreased tubular reabsorption of HCO3-, leading to metabolic acidosis.