Parathyroid Hormone Flashcards
1
Q
calcium in plasma
A
- total 9-10.6 mg/dl, typically measured (false high if albumin is high)
- ionized 4.5-5.2- tightly regulated portion
- acidosis blocks Ca binding to albumin and increases free ionized
- total broken into bound (40%) and ultrafilterable (60%)
- ultrafilterable is 50% ionized and 10% complexed to anions
2
Q
calcium in body
A
- 1 kg, 99% in skeleton
- 1 % in ECF and muscles
3
Q
high calcium
A
- greater than 12 mg/dl
- fatigue, apathy, anorexia, delirium, coma
- headache, inctracranial pressure, muscle weakness
- increases membrane polarization and reduces neural responses
- bradycardia, short QT interval
- polydipsia, polyuria, hypertension, calculi
4
Q
low calcium
A
- due to poor diet/malabsorption, lactation
- learning retardation, apnea
- tetany, reduces membrane polarization and increases hypersensitivity (more excitable)
- long QT interval, cardiac output reduced
- Ca/PO4 deficiency, weak bone development- rickets or osteomalacia
5
Q
normal balance of calcium
A
- gut, ECF, bone, kidney
- over 80% of ingested daily calcium is excreted in the feces
- kidneys filter 10x average daily intake and recapture all by 175 mg or so
- bone is an active repository and buffer of calcium with daily turnover of 280 mg
- if dietary intake is low, kidneys can compensate by increasing reabsorption of filtered Ca, in long run bone reservoir will bear brunt by increasing resportion, loss of bone mass and density
- PTH and vitamin D
- phosphate
6
Q
calcitonin
A
- thyroid gland
- stronger role in early development
- potent inhibitor of bone resporption
- used to be used as treatment (from salmon)
- role in adult unclear
7
Q
PTH
A
- peptide hormone
- high when Ca low
- target 1-kidney- increases absorption in distal tubule decreases re absorption of P in proximal tubule, and increases second step syn of Vit D
- target 2 is bone cells
8
Q
target 2
A
- bone cells
- osteoclastic resorption via receptors on osteoblasts (RankL)
- increases Ca and Po in ECF and plasma
- increases osteocytic osteolysis
- (pulse PTH can enhance bone formation)
9
Q
PTH secretion
A
- parathyroid chief cells
- secrete more PTH when Ca is below set point
- sensor is G protein coupled with signaling cascade that involves Ca binding/releasing to ER that controls PTH
- when calcium drops, PTH increases fast
10
Q
familial hypercalcemic hypocaluria (FHH)
A
- curve shifted right, urine Ca is low
- ppl are symptom free even though they have high calcium
- genetic defect in Ca sensors
- increased Ca reabsorption
11
Q
Ca transport in kidney
A
- increase in PTH causes increased Ca reabsorption in the distal tubule
- reduces P re-absorption in proximal tubule (increases P in urine)
- 60% of daily calcium reabsorption occurs in proximal tubule (active transport) and 9% in distal (active transport, what is controlled)
12
Q
Ca transport in kidney 2
A
- PTH increases reabsorption in distal tubule
- Vit D helps by increasing amount of calbindin to increase Ca transport and efflux at the basal side
13
Q
vitamin D
A
- target 1- intestine- increases Ca and P absorption
- bone is second target- increases osteoclastic resorption by receptors on osteoblasts
- parathyroid gland suppresses PTH in negative feedback
- kidney distal tubule- aids in increased Ca and P transport
14
Q
vitamin D 2
A
-synthesized from cholecalciferol to 25-OH-D3 in liver, then 1,25-diOH-D3 in kidney
-cacidiol can be stored and released slowly
-25-hydroxylase and 1a-hydroxylase
-PTH increases 1a-hydroxylase
-
15
Q
calcium in the intestine
A
-Vitamin D increases passive and active transport of Ca and P int o the blood by increasing synthesis of calbindin
16
Q
rickets
A
- chronic deficiency in Vitamin D and/or deficiency of dietary calcium or phosphorous
- disturbance of developing bone formation
- poor mineralization due to lack of Ca
- weakened and mechanically distorted long bones
- large and abnormal growth plates
- adults get osteolamacia-poor quality bone formed during remodeling
17
Q
primary hyperparathyroidism
A
- high calcium
- high serum PTH
- low P
- alkaline P and urinary C elevated
- would expect high PTH when calcium is low
- adenoma on parathyroid releasing PTH
- bone resportion releasing Ca into ECF increased alkaline phosphatase
- urine high in Ca because chronically high serum will eventually increase Ca excretion despite PTH
- surgical removal of offending nodule, leaving 3 normal
- adenoma
18
Q
humoral hpercalcemia of malignancy
A
- serum Ca high, P low, PTH low, alkaline P very elevated
- serum Ca high due to release of PTH-related peptide from lung tumor
- activates same actions as PTH, caused Ca to increase by increasing reabsorption, absorption in kidney, resorption of bone, decreasing reabsorption of P
- PTH was decreased because the negative feedback was still working
- normal albumin- high total not due to Ca bound to excess, really due to ionized
19
Q
secondary hyperparathyroidism
A
- hypocalcemia is primary, causes the excess PTH
- low D, renal failure, diet
20
Q
hypoparathyroidism
A
- hypocalcemia
- surgical damage to gland or genetic
21
Q
pseudohypoparathyroidism
A
- hypocalcemia
- genetic defect in G protein in PTH receptor in kidney
22
Q
phosphorous
A
- plasma 2.5-2.5 mg/dl
- inorganic portion
- 10-20% Pi is protein bound
- Pi not rigidly maintained, plus/minus 30% per diurnal variations
- PTH influences reabsorption in proximal tubule
- PTH increases P absorption form small intestine, but decreases reabsorption from proximal tubule and excretes more
23
Q
chronic kidney failure
A
-P excretion is reduced and hyperphosphatemia results
24
Q
collagen matrix synthesis and mineralization
A
-pre collagen triple helix molecules are synthesized by osteoblast and then polymerized extracellularly, forming fibrils and osteoid matrix that eventually mineralizes
25
Q
osteoblasts
A
- line the bone surfaces
- become rounder and contain extra ER
- precursors synthesized here then exported by telopeptides
- osteoid is b/n osteoblasts and matrix
- do most of the signaling-osteoblasts
- osteocyte also important
- osteoblasts have receptors for Vitamin D, PTH, estrogen, paracrine and GFs
26
Q
bone mineralization
A
- microcrystalline HA mineral deposition in collagen matrix
- seeding on collagen-via phosphoproteins starts in gaps and then keeps going
- bone mineral is 65% of weigh
- rest is collagen (22%), fluid (10%) and 1-2% non collagenous proteins and cells
27
Q
microcrystalline hydroxylapatite
A
- bone mineral
- Ca10(OH)2(PO4)6 with Mg, Co3 and other trace constituents
- once seeded, crystals coalesce and accumulate within and around the collagen fibrils until the area is fully mineralized with 65% by weight of mineral
28
Q
bone remodeling
A
- rate can accelerate or decline in response to plasma calcium, injury, immobilization and metabolic and hormonal changes
- varies by location and age
- spinal vertebrae and other trabecular areas can rapidly lose or gain bone, cortex in tibia more stable
- SA:V much bigger in trabecular bone
- osteoclast, secretes acidic molecules to dissolve mineral, and proteases to digest and phagocytize the collagen matrix
- mature osteoclasts do not divide but must develop from mono-nuclear precursors
- they don’t last longer than a few days
29
Q
bone remodeling 2
A
- RANKL (RANKL/OPG system) from osteoblasts activates osteoclasts and precursors, increases osteoclast number and bone resorption and turnover
- RANKL release from blasts stimulated by endocrine factors, PTH, calcitriol, other systemic hormones and GFs
- osteoblastic cells can also produce OPG, which binds to RANKL-sites and inhibits binding of RANKL and production and activation of osteoclasts -slows resorption
30
Q
estrogen
A
- reduces resorption (receptors on blasts)
- mode of action unclear
31
Q
calcitonin
A
-transient inhibitor of clasts
32
Q
glucocorticoids
A
-primarily inhibits intestinal Ca absorption
33
Q
GH
A
-stimulate bone formation
34
Q
mechanical loading
A
-locally promotes bone accrual and maintenance
35
Q
mechanical loading
A
- osteocyte and canaliculae network are highly sensitive to fluid shear
- express Sclerostin- inhibits bone formation, increased with subnormal loading (not enough mechanical force, bone doesn’t form)
- increased loading stimulates bone formation and repair
36
Q
osteoporosis
A
- loss of bone mass associated with fracture
- trabecular and cortical sites (and/or)
- can be local or systemic
- related to disease or aging (idiopathic)
- inappropriate or excess remodeling
- trabecular first/more common, walls become thinner and less numerous
- cortical bone thinner and more porous
- excess resorption- lack of Ca, D, or excess PTH
- immobilization and lack of suitable loading
- poor kidney function, long term glucocorticoids
- slight annual loss with aging
- treatment-replacing nutrients, loading exercise, drugs to stop clasts or stimulate blasts
