B6.050 Prework 1: Hyperparathyroidism Flashcards
how many parathyroid glands are there
85% of people have 4
origin of superior parathyroid glands
arise from 4th brachial pouch
more constant in location than inferior glands
location and blood supply of superior parathyroid glands
usually within 1 cm of where the recurrent laryngeal nerve pierces the cricothyroid membrane
perfused by inferior thyroid artery
origin of inferior parathyroid glands
arise from 3rd brachial pouch
location and blood supply of inferior parathyroid glands
typically within 1 cm of where inferior parathyroid artery enters the thyroid more often ectopic than superior glands -tracheoesophageal groove -paratracheal fat -thymus perfused by the inferior thyroid artery
common locations of ectopic parathyroid glands
15% within the thymus 1% intra thyroidal 3-5% within the posterior mediastinum or carotid sheath aortopulmonary window paraesophageal
primary cell of parathyroid
chief cells
properties vital to homeostatic function
function of chief cells
rapidly secrete stored PTH hormone in response to changes in blood calcium (seconds)
synthesize, process, and store large amounts of PTH in a regulated manner (hours)
replicate when chronically stimulated (days)
description of PTH production
synthesized as a larger precursor
pre-pro-PTH (115 AA)
transit across ER, pre sequence cleaved
in Golgi, pro sequence cleaved
biologically active form of PTH
intact PTH, 84 AA
function of PTH
peptide hormone that control the minute to minute level of serum ionized Ca2+
where are surface receptors for PTH located
bone and kidney
major physiological responses to PTH
bone resorption
renal reabsorption
increased renal synthesis of 1,25(OH)2D3
increased intestinal absorption of dietary calcium
how does PTH influence phosphate reabsorption in kidney
decreased reabsorption of phosphate
how does PTH influence phosphate absorption in intestines
increased absorption of phosphate
what receptor on the chief cell senses calcium levels in serum
CaSRs on cell surface
member of G protein coupled family of receptors
response to hypocalcemia
increased PTH secretion
response to hyperphosphatemia
VERY increase PTH secretion
action of calcitriol on PTH levels
inhibits PTH synthesis by interacting with vitamin D receptor
metabolism of PTH
half life = 4 min
metabolized by liver (70%) and kidney (20%)
impact of familial hypocalciuric hypercalemia on function of parathyroid
inactivating mutation
parathyroid glands less sensitive to calcium
at kidney increased reabsorption of Ca2+ and Mg
increased PTH, Ca2+, and Mg
decreased urine calcium
impact of familial hypoparathyroidism with hypercalciuria
activating mutation of the CaSR
decreased serum calcium and PTH
increased urine calcium
dietary forms of vit D
D3: cholecalciferol (animal products)
D2: ergocalciferol (plants)
+
7-dehydrocholesterol from UV light
liver metabolism of vit D
activated to calcidiol (25OH vit D)
circulating form
this form is measured for vit D status
2-3 week half life
kidney metabolism of vit D
activated to calcitriol (1,25(OH)2 vit D)
6-8 hour half life
exerts effects on body (increased intestinal Ca absorption, increased bone resorption, decreased renal Ca and phosphate excretion)
direct effects of 1,25(OH)2D3
active form
binds to vitamin D receptor
promotes enterocyte differentiation / intestinal absorption of Ca and PO4
direct suppression of PTH release
regulation of osteoblast function
permissively allows PTH induced osteoclast activation and bone resorption
mnemonic for signs and symptoms of primary HPTH
stones
bones
groans
psychiatric overtones
renal symptoms of HPTH
renal stones nephrocalcinosis polyuria polydipsia uremia
MSK symptoms of HPTH
osteitis fibrosa
radiologic osteoporosis
osteomalacia or rickets
arthritis
abdominal symptoms of HPTH
constipation
indigestion, nausea, vomiting
peptic ulcer
pancreatitis
psych symptoms of HPTH
lethargy, fatigue depression memory loss psychosis-paranoia personality change confusion, stupor, coma
Ca2+ correction equation
corrects serum calcium for albumin
(4-Alb)*0.8 + Ca
etiologies of hypercalcemia w/ elevated or mid to high normal PTH
pHPTH
FHH
differentiate by urine excretion (FHH is low, pHPTH is high)
etiologies of hypercalcemia w/ low PTH
non-PTH mediated
measure PTH related peptide (PTHrp) and vit D metabolites
PTHrp elevated
scan for malignancy
elevated 1,25D
chest x-ray for lymphoma, sarcoid
elevated 5D
check meds, vitamins, supplements
management of mild hypercalcemia
<12 mg/dL
no immediate treatment
management of severe hypercalcemia
> 14 mg/dL
volume expansion with isotonic saline
administer calcitonin
administer IV bisphosphonate
primary cause of pHPTH
parathyroid adenoma (89-95%)
single gland
mostly composed of chief cells
oxyphil cells to a lesser extent
other causes of pHPTH
parathyroid hyperplasia (6%) -four glands affected equally -chief cell hyperplasia parathyroid carcinoma (rare) -very increased PTH (hundreds) -Ca2+ > 14
epidemiology of pHPTH
women most commonly affected
1% of gen pop
2% elderly pop
diagnosis of pHPTH
increased serum chloride to phosphorus ratio >33:1
surgical indications for pHPTH
symptomatic disease (bones, stones, groans, psych overtones) asymptomatic disease - Ca over 1 mg/dL above upper limit -creatinine clearance <60 -osteoporosis -<50 years old
FHH description
benign, no ttx indicated autosomal dominant mild hypercalcemia with hypocalciuria normal to slightly elevated PTH high-normal to frankly elevated serum Mg level
secondary HPTH
seen in patients with renal failure
an appropriate increase in PTH responds to chronically low calcium
most DO NOT need surgery
treatment of secondary HPTH
dietary restrictions
phosphorus binding gels
calcium dialysate options
eventual fate of parathyroid glands in secondary HPTH
eventually become autonomous
-even with correction of serum calcium via renal transplant, PTH remains inappropriately elevated (TERTIARY HPTH)
surgery for secondary/tertiary HPTH
subtotal (3.5) / total parathyroidectomy with reimplantation
what is hypercalcemia of malignancy?
present in 20% of cancer patients (esp lung)
malignant cells elaborate humoral mediators of hypercalcemia (PTHrp)
rarely result from direct bony destruction by tumor ingrowth
endogenous PTH in hypercalcemia of malignancy
scarce or undetectable
requires suspicion of malignancy on part of physician
cortical bone
outer part
dense and compact
maintains structural function of bone
metabolic function of skeleton
storage for calcium, phosphorus, and carbonate
trabecular bone
inside long bones and vertebrae
maintains metabolic function of bone
T score
number of standard deviations from young adult mean density
Z score
number of standard deviations from age matched mean density
applies to pre-menopausal females and males <50
