Flashcards in Pathology of Parathyroid and Metabolic Bone Disease Deck (70)
What is the key cell within the parathyroid gland and its role?
- chief cell= regulates serum FREE (ionized) calcium via PTH secretion.
*** 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).
**** What is PRIMARY HYPERparathyroidism?
- excess PTH due to disorder of the parathyroid gland.
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
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.
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.
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).
How do you treat parathyroid adenoma (primary hyperparathyroidism)?
- surgical removal of the affected gland.
**** What is SECONDARY HYPERparathyroidism?
- excess production of PTH due to disease process EXTRINSIC to the parathyroid gland.
*** What is the most common cause of secondary hyperparathyroidism?
- CHRONIC RENAL FAILURE
*** 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).
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).
**** 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)
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)
What labs will you see with HYPOparathyroidism?
- decreased PTH
- decreased serum calcium
**** What is PSEUDOHYPOparathyroidism?
- signs and symptoms of hypoparathyroidism, but due to END-ORGAN RESISTANCE (due to Gs protein) to PTH.
What will you see with pseudohypoparathyroidism?
- HYPOcalcemia with INCREASED PTH.
With what is the autosomal dominant form of pseudohypoparathyroidism associated?
- SHORT stature
- SHORT 4th and 5th DIGITS
*** 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
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.
*** What are the clinical features of achondroplasia?
- SHORT EXTREMITIES with normal-sized head and chest, due to poor ENDOCHONDRAL BONE formation.
Is intramembranous bone formation affected in achondroplasia?
- NO, just endochondral.
What is endochondral bone formation?
- formation of a CARTILAGE MATRIX, which is then REPLACED by BONE.
*how LONG BONES form.
What is intramembranous bone formation?
- formation of bone without a preexisting cartilage matrix.
- how FLAT BONES (skull and ribcage) develop.
Will mental function, life span, and fertility be affected in achondroplasia?
- NO :)
**** 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.
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.
**** 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
*** 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.