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17 Cards in this Set

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  • Back
List the causes of Primary HyperPTH and their incidences
Parathyroid Adenomas 80%
MEN 15%
Double Adeonomas 3%
Parathyroid Carcinomas less than 1-2%
Familial hyperPTH
Describe the major cause of secondary HyperPTH, and the pathogenesis in terms of serum phosphate concentration, serum calcium concentration, and PTH concentration
Increased secretion of PTH that is an inappropriate response to hypocalcemia, usually due to metabolic condition causing low serum calcium. The most common cause is Chronic renal disease. May also occur in secondary VitD deficiency, intestinal malabsorption syndromes, and pseudohypoPTH
List the causes of HyopPTH
Surgically induced
Congenital Absence of all glands
Familial HypoPTH
Idiopathic HypoPTH
Define PseudoHypoPTH and describe the differences between the 2 types
PseudoHypoPTH includes adequate levels of PTH, but the ability of the target tissues to respond to the hormone is subnormal.
Type1: Mutation on the maternal allelle. Associated with multihormone resistance, TSH, PTH, LH/FSH. Associated with Albright Hereditary Osteodystrophy(AHO). Short, fat, short metacarpal/tarsal bones, mental deficits
Type2: Mutation in Paternal Allele, AHO without accompanying multihormonal Resistance. Sercum Calcium, phosphate and PTH are all normal
Describe the role of MG in the regulation of PTH secretion
Hypomagnesia can result in hypocalcemia. MG is required for PTH to play its part in maintaining plasma calcium levels. any dx that results in lowered plasma MG levels may also cause hypocalcemia. MG has parallel effects on PTH secretion. HypoMG stimulates PTH secretion. SEVERE MG loss inhibits PTH synthesis, storage, secretion.
Describe PTHrP and its clinical significance
PTHR1 is expressed in bone osteoblasts, kidney, where PTH binds and PTHrP. PTHrP differs from PTH in structure, sharing only 13AA's in common with PTH, and is a product of a seperate gene. It mimics PTH. PTHrP binds to PTHR1, resulting in increased Ca, therefor, PTHR1 mediates the effects of PTh, but also plays an important role in the pathological effects of PTHrP.
Describe the effects of PTH on bicarb clearance and urinary cAMP
PTH inhibits PCT reabsorption of Na, H2O, HCO3, via inhibition of the apical Na/H exchanger. this inhibition results in increased excretion of bicarb. PTh exercises its calcium retaining properties by increasing the expression of calcium channels. B/c this expression os a cAMP dependent pathway, there is increases excretion of cAMP as an indirect result. this makes urinary cAMP a good marker of hyperPTH.
Describe the 2 phases of PTH action on bone
Initially, PTH causes an increase in bone formation by direct action on osteoblasts.
In a long acting action on osteoclasts, PTH causes an increase in bone resorption. this is mediated by cytokines released from osteoblasts to osteoclasts
Describe why null mutations in the gene for stimulatory G protein can cause pseudoHypoPTh
this is Hereditary Albright's osteodystrophy. this is an inheretide autosomal dominant disorder in which the Gs protein for PTH in the kidney and bone is defective. as a result, when PTH binds, it does not activate adenylyl cyclase or produce its usual actions.
Discern between failure to thrive and short stature
Failure to thrive: an abnormal weight for height pattern that usually involves the head
Short Stature: normal or excessive weight gain with normal height for weight pattern, just below the growth curve
Discuss organic vs non-pathologic causes for short stature
Non pathologic causes: familial short stature, consititutional growth delay.
Pathologic: Growth hormone deficiency. characterized by decreased growth velocity, delay in skeletal muscle maturation, absence of other explanations for poor growth, lab tests indicating subnormal GH secretion.
Small for gestational age/intrauterine growth restriction: birth weights less than the 10th percentile for the population's birth weight/gestational age relationship.
Disproportionate short stature: Skeletal dysplasias are disorders that result in disproportionate short stature
Short stature associated with syndromes: Turners, Down, Prader-willi
Explain the following:
Growth Hormone releasing hormones
Somatotropin: Growth hormone, increases linear growth via IGF1. Increases protein synthesis and uses fat as a fuel source by enhancing the release of fatty acids from adipose tissue
Somatostatin: Found in hypothalamus, D cells of pancreas, and GI mucosa, and C cells of thyroid. Inhibits GH, TSH, insulin, Glucagons,
For GH, describe its structure, 3 main activities, tissues affected, and cell types that secrete GH
GH is a 191AA polypeptide hormone
Increases linear growth, protein synthsis, and enhances fatty acid utilization
affects adipose, liver, muscle, bone, kidney, heart, pancreas, spleen, intestines
Secreted by somatotrophs in the anterior pituitary. account for 50% of the cells in the anterior pituitary
for the GHR, describe its structure, stoichiometry, name one hormone induced by the GH/GHR interaction, and intacellular signaling pathway
structure: 620AA protein consisting of of an extracellular ligand-binding domain, a single transmembrane domain, and a cytoplasmic component
Stoichiometry: 1GH/2GHR
Releases Insulin, IGF1
GH complexes with the 2GHR, causing JAK2 tyrosine kinase,activation, phosphorylation of intracellular signaling molecules, including STAT proteins which translocate to the nucleus, they elicit GH specific gene expression by binding to nuclear DNA.
Distinguish between somatotropin and somatomedin
Somatomedin: indirectly mediates the actions of GH. IGF1 is most important.
Somatotropin: a protein hormone of the anterior lobe of the pituitary produced by acidophiles, that promotes body growth, fat mobilization, and inhibition of glucose utilization.
Compare and contrast growth hormone insensitivity and growth hormone deficiency
Insensitivity: caused by defects in the GH receptor structure or signaling. Homozygous or heterozygous mutations of the GH receptor are associated w/GH insensitivity and growth failure (laron's syndrome). The Dx os based on normal or hight GH levels, with decrease in circulating GHBP, and low IGF1 levels
GH deficiency: decreased release in GH due to decrease in GHRH. defect in anterior pituitary gland can lead to GH deficiency as well. Failure to generate IGF1 can also cause GH deficiency
Discuss the TX of short stature
Medical care: recombinant growth hormone
Surgical care: brain tumor removal, limb lengthening procedures
Activity: do not restrict activity
Medical care: tx directed at cause of growth failure, whether it be hypothyroidism, GH deficiency, etc