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Endocrinology > Pathology of Parathyroid and Metabolic Bone Disease > Flashcards

Pathology of Parathyroid and Metabolic Bone Disease Flashcards

1
Q

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

A
  • chief cell= regulates serum FREE (ionized) calcium via PTH secretion.
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2
Q

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

A
  • 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).
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3
Q

** What is PRIMARY HYPERparathyroidism?

A
  • excess PTH due to disorder of the parathyroid gland.
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4
Q

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

A
  1. parathyroid adenoma (MOST COMMON)
  2. sporadic parathyroid hyperplasia
  3. parathyroid carcinoma
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5
Q

What is parathyroid adenoma (primary hyperparathyroidism)?

A
  • benign neoplasm (usually involving one gland).

- results in ASYMPTOMATIC HYPERcalcemia, however it can present with consequences of increased PTH and hypercalcemia.

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6
Q

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

A
  • 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.
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7
Q

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

A
  • 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).
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8
Q

How do you treat parathyroid adenoma (primary hyperparathyroidism)?

A
  • surgical removal of the affected gland.
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9
Q

** What is SECONDARY HYPERparathyroidism?

A
  • excess production of PTH due to disease process EXTRINSIC to the parathyroid gland.
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10
Q

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

A
  • CHRONIC RENAL FAILURE
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11
Q

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

A
  • 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).
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12
Q

What lab findings will you see with secondary hyperparathyroidism?

A
  • increased PTH
  • decreased serum calcium
  • increased serum phosphate
  • increased alk phos (again bc PTH is stimulating the osteoBLASTS to increase alk phos).
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13
Q

** What is HYPOparathyroidism?

A
  • 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)
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14
Q

How does HYPOparathyroidism present?

A

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)
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15
Q

What labs will you see with HYPOparathyroidism?

A
  • decreased PTH

- decreased serum calcium

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16
Q

** What is PSEUDOHYPOparathyroidism?

A
  • signs and symptoms of hypoparathyroidism, but due to END-ORGAN RESISTANCE (due to Gs protein) to PTH.
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17
Q

What will you see with pseudohypoparathyroidism?

A
  • HYPOcalcemia with INCREASED PTH.
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18
Q

With what is the autosomal dominant form of pseudohypoparathyroidism associated?

A
  • SHORT stature

- SHORT 4th and 5th DIGITS

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19
Q

*** What is Achondroplasia? (PICMONIC)

A
  • AUTOSOMAL DOMINANT ACTIVATING mutation in fibroblast growth factor 3 (FGFR-3) leading to impaired cartilage proliferation in the growth plate
  • common cause of DWARFISM
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20
Q

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

A
  • inhibition of cartilage growth.

* most mutations are sporadic and related to increased paternal age.

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21
Q

*** What are the clinical features of achondroplasia?

A
  • SHORT EXTREMITIES with normal-sized head and chest, due to poor ENDOCHONDRAL BONE formation.
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22
Q

Is intramembranous bone formation affected in achondroplasia?

A
  • NO, just endochondral.
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23
Q

What is endochondral bone formation?

A
  • formation of a CARTILAGE MATRIX, which is then REPLACED by BONE.
  • how LONG BONES form.
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24
Q

What is intramembranous bone formation?

A
  • formation of bone without a preexisting cartilage matrix.

- how FLAT BONES (skull and ribcage) develop.

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25
Q

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

A
  • NO :)
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26
Q

** What is Osteogenesis Imperfecta? (PICMONIC)

A
  • 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.
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27
Q

What are the clinical features of Osteogenesis Imperfecta?

A
  • 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.
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28
Q

** What is Osteopetrosis?

A
  • inherited defect of bone RESORPTION resulting in abnormally THICK, HEAVY BONE that FRACTURES easily.
  • due to poor osteoCLAST function.
  • multiple genetic variants exist
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29
Q

*** What mutation is most common in osteopetrosis?

A
  • 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
Q

*** What are the clinical features of osteopetrosis?

A
  • 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.
31
Q

*** How do you treat osteopetrosis?

A
  • BONE MARROW TRANSPLANT bc osteoclasts are derived from monocytes.
32
Q

** What is Rickets/Osteomalacia?

A
  • defective mineralization of osteoid due to LOW levels of VITAMIN D, which results in low serum calcium and phosphate.
  • osteoblasts normally produce osteoid, which is then mineralized with calcium and phosphate to form bone
33
Q

How can vitamin D deficiency occur?

A
  • decreased sun exposure (vitamin D is normally derived from the skin upon exposure to sunlight; 85% and from the diet; 15%).
  • poor diet
  • malabsorption
  • liver failure and renal failure
34
Q

How is vitamin D activated?

A
  • via 25-hydroxylation by the liver followed by 1-alpha-hydroxylation by the proximal tubule cells of the kidney.
35
Q

How does active vitamin D raise serum calcium and phosphate?

A

by acting on:

  • intestine= increases absorption of calcium and phosphate.
  • kidney= increases reabsorption of calcium and phosphate.
  • bone= increases resorption of calcium and phosphate.
36
Q

*** What is Rickets?

A
  • LOW vitamin D in CHILDREN (usually less than 1 y/o), resulting in abnormal bone mineralization.
37
Q

How does Rickets present?

A
  • PIGEON-BREAST deformity
  • FRONTAL BOSSING (enlarged forehead) due to osteoid deposition on the skull.
  • RACHITIC ROSARY due to osteoid deposition at the costochondral junction.
  • BOWING of the LEGS in ambulating children.
38
Q

*** What is Osteomalacia?

A
  • LOW vitamin D in ADULTS.
  • inadequate mineralization (aka osteoid being laid down, but no calcium and phosphate to mineralize it) results in weak bone with an increased risk for fracture.
39
Q

What lab findings will you see with Osteomalacia?

A
  • decreased serum calcium
  • decreased serum phosphate
  • increased PTH
  • increased ALK PHOS
  • remember, whenever osteoBLASTS are activated, you will see an increase in alk phos (bc an alkaline environment is needed to mineralize bone).
40
Q

** What is osteoporosis?

A
  • REDUCTION in TRABECULAR BONE mass.

- results in POROUS bone with an increased risk for fracture.

41
Q

*** On what is risk for osteoporosis based?

A
  • PEAK BONE MASS (attained at early adulthood) and RATE of BONE LOSS that follows thereafter.
42
Q

When is your peak bone mass reached, and on what is it based?

A
  • by 30 years of age
  • based on genetics (vitamin D receptor variants), diet, and exercise.
  • thereafter slightly less than 1% of bone mass is lost each year.
43
Q

What would cause bone mass to be lost more quickly, leading to osteoporosis?

A
  • lack of weight-bearing exercise (e.g. space travel)
  • poor diet
  • decreased estrogen (e.g. menopause).
44
Q

What are the 2 most common forms of osteoporosis?

A
  1. senile

2. postmenopausal

45
Q

What are the clinical features of osteoporosis?

A
  • bone pain and fractures in weight-bearing areas such as the vertebrae (leads to loss of height and kyphosis), hip, and distal radius.
46
Q

How is bone density measured?

A
  • DEXA scan
47
Q

What will labs show with osteoporosis?

A
  • serum calcium, phosphate, PTH, and ALK PHOS are NORMAL.

* labs help to exclude osteoMALACIA, which has a similar clinical presentation.

48
Q

How do we treat osteoporosis?

A
  • exercise, vitamin D, and calcium to limit bone loss.
  • BISPHOSPHONATES= induce apoptosis of osteoCLASTS.
  • estrogen replacement therapy is debated.
49
Q

Are glucocorticoids contraindicated for use in osteoporosis?

A
  • YES bc they worsen it.
50
Q

** What is Paget Disease of bone?

A
  • imbalance between osteoCLAST and osteoBLAST function.
  • usually seen in late adulthood (over age 60).
  • remember: the osteoclast cannot work, without the permission of the osteoBLAST (which receives its signals from PTH).
51
Q

What causes Paget Disease of bone?

A
  • unknown, but possibly viral.
52
Q

Does Paget disease involve the entire skeleton?

A
  • NO! It is localized to one or more bones.
53
Q

** What are the 3 distinct stage of Paget disease?

A
  1. osteoCLASTIC (goes crazy)
  2. MIXED osteoBLASTIC-osteoCLASTIC (until osteoclasts burn out).
  3. osteoBLASTIC (lays down as much bone as possible).
    * end result is thick sclerotic bone that fractures easily.
54
Q

What will a biopsy of bone reveal in Paget disease?

A
  • MOSAIC pattern of lamellar bone.

* looks like a puzzle piece.

55
Q

*** What are the clinical features of Paget disease?

A
  • bone pain (due to microfractures).
  • increasing hat size (skull is commonly affected).
  • hearing loss (impingement on cranial nerve).
  • lion-like facies (involvement of craniofacial bones).
  • isolated ELEVATED ALK PHOS (most common cause of isolated elevated alk phos in patients over 40).
56
Q

How do we treat Paget disease of bone?

A
  • CALCITONIN= inhibits osteoCLAST function.

- BISPHOSPHONATES= induces apoptosis of osteoCLASTS.

57
Q

** What are the complications of Paget disease?

A
  • high-output cardiac failure= due to formation of AV shunts in bone.
  • osteosarcoma (malignant tumor of osteoBLASTS).
58
Q

** What is Osteomyelitis?

A
  • infection of marrow and bone, usually in CHILDREN.
59
Q

What is the most common cause of osteomyelitis?

A
  • bacterial infection arising due to hematogenous spread.
60
Q

How does seeding of Osteomyelitis differ between CHILDREN and ADULTS?

A
  • CHILDREN= seeds METAPHYSIS.

- ADULTS= seeds EPIPHYSIS

61
Q

*** What bacteria most often cause Osteomyelitis?

A
  • Staph aureus (MOST COMMON)
  • Neisseria gonorrhoeae= sexually active young adults.
  • Salmonella= sickle cell disease
  • Pseudomonas= diabetics or IV drug abusers.
  • Pasteurella= associated with cat or dog bites/scratches.
  • Mycobacterium tuberculosis= usually involves the VERTEBRAE (POTT DISEASE).
62
Q

*** What are the clinical features of osteomyelitis?

A
  • BONE PAIN with systemic signs of infection (fever and leukocytosis).
  • lytic focus (abscess) surrounded by sclerosis of bone on x-ray; lytic focus is called SEQUESTRUM, and sclerosis is called INVOLUCRUM.
63
Q

How do you make the diagnosis of Osteomyelitis?

A
  • blood culture
64
Q

What is Avascular (aseptic) necrosis?

A
  • ischemic necrosis of bone and bone marrow.
65
Q

What causes Avascular (aseptic) necrosis of bone?

A
  • trauma or fracture (MOST COMMON)
  • steroids
  • sickle cell anemia
  • Caisson disease= development of gas emboli (nitrogen) which can precipitate out of the blood and lodge in the blood.
66
Q

What are the major complications of avascular (aseptic) necrosis?

A
  • osteoarthritis (wear and tear) and fracture
67
Q

What is osteoprotegrin?

A
  • a decoy receptor of RANKL which removes excess ligand and prevents unbalanced bone resorption.
68
Q

What causes familial primary hyperparathyroidism?

A
  • inactivated MEN-1 gene on chromosome 11q13, which occurs in parathyroid adenomas and parathyroid hyperplasia.
  • MEN-2 syndrome caused by activating mutation in the tyrosine kinase receptor RET; associated with parathyroid hyperplasia.
69
Q

What is parathyroid carcinoma?

A
  • rare circumscribed tumor affecting one parathyroid with an irregular mass, which is larger than 10 gm.
70
Q

Can nonparathyroid tumors secrete PTHrP?

A
  • YES, which inhibits osteoprotegerin (a decoy RANKL receptor) secretion by osteoblastic cells, altering the RANKL/osteoprotegerin ratio to favor osteoCLASTOGENESIS.

Endocrinology (18 decks)

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