13) Bone and mineral Flashcards
hydroxyapatite
Crystal lattice composed of calcium, phosphorus, and hydroxide
forms of Ca in blood
iCa — free or ionized – active form (50%)
Complexes with anions (10%)
Bound to protein (40%)
anions that bind Ca
Bicarbonate
Lactate
Phosphate
Citrate
The —– affects how well serum proteins bind free calcium.
How?
pH
Alkalosis: increased negative charges = increased binding of free calcium= ↓iCa
Acidosis: decreased negative charge = decreased binding of free calcium= ↑iCa
For each —– unit change in pH, there is a —- mg/dL inverse change in serum free calcium.
0.1
0.2
Distribution of Ca bound to proteins
80% to albumin
20% to globulins
Low proteins = low total ——-
calcium
Pseudohypocalcemia
——- is independent of protein levels, where ——- is dependent
iCa
total Ca
corrected total Ca for when albumin is not in normal range
Corrected Total Ca = Total Ca + [(normal albumin – patient albumin)0.8]
Cannot apply this in states of acidosis or alkalosis
total Ca RR
8.6-10.0 mg/dL
PTH effect on Ca levels
↑serum iCa, ↓ Phos
Mg needed
1,25-dihydroxycholecalciferol/Vitamin D3 effect on Ca levels
↑serum iCa, ↓ Phos
functions of Ca
Nerve impulse transmission
Cofactor in certain enzymes
Coagulation of blood
Skeletal mineralization
Preservation of cell membrane integrity and permeability
PTH acts on the…
kidney (Ca reabsorption, P secretion)
intestine (Ca absorption)
bone (resorption)
why is iCa the best measure of Ca status?
- Biologically active.
- Tightly regulated by parathyroid hormone (PTH) and vitamin D.
- Measured in blood using ion-selective electrodes.
——- iCa values can cause seizures or cardiac arrest.
Low
—— iCa can cause nausea, constipation, and kidney failure if calcium salts are precipitated in the kidneys.
High
iCa concentration in plasma or serum is sensitive to both….
sample handling?
pH and temperature
Analyze within 30 mins, or within 4 hours on ice.
Analyzed immediately after uncapping the specimen.
pH should be measure with iCa. iCa and pH have an inverse relationship.
iCa RR
4.64 – 5.28 mg/dL
Increased urinary calcium concentration may be associated with an increase in….
osteoclastic bone resorption
urine Ca sample handling
24-hour urine specimens should be acidified with 5.0 mL of 6M HCL; solubilizes Ca crystals.
3 methods used to measure Ca
Colorimetric analysis
Atomic absorption
Indirect potentiometry
Approximately —% of extracellular phosphate occurs in inorganic form as hydroxyapatite crystals.
In plasma, most phosphate exists in the ——- form as mono- or dihydrogen phosphate ions.
85
inorganic
P RR
2.5-4.5 mg/dL
effects on intestinal and renal absorption of P
- absorption ↑ when there is a ↓ in dietary Ca
- Vit D ↑ absorption/reabsorption
- GH ↓ renal reabsorption
- PTH inhibits renal reabsorption
Reaction of ——– ion with ammonium molybdate to form a phosphomolybdate complex
phosphate
3 forms of circulating Mg
Free or ionized (55%)
Bound to proteins (30%)
Forming complexes with phosphate, citrate, and other ions (15%)
Since little Mg is found in plasma, what is recommended for measuring?
Suggested to measure in RBCs, mononuclear blood cells, or muscle biopsies.
Mg functions
- Serves as a cofactor for more than 300 enzymes.
- Cellular energy metabolism and membrane stabilization
- Nerve conduction
- Ion transport
- Ca2+ channel activity
improves Mg absorption in small intestine
calcitriol
majority of Mg reabsorption occurs in the…
thick ascending loop of Henle (60%)
urine Mg sample handling
Samples collected in metal free tubes without preservatives (No EDTA, fluoride, or oxalate)
pH adjusted to 1 prior to running the assay
Gold standard for determining body magnesium status
Determines Mg deficiency
parenteral magnesium loading test (MLT)
Excretion of <70% of infused Mg = Mg deficiency
pH relationship to Mg
↑ pH = iMg ↓
↓ pH = ↑ iMg
Ortho-cresolphthalein complexone (CPC or OCPC) and arsenazo III
total Ca indicators
calmagite, methylthymol blue, formazan dye, mango or xylidyl blue, chlorophosphonazo III, and arsenazo
total Mg indicators
Secreted as an intact hormone, but breaks up into fragments in circulation
PTH
relationship of Ca to PTH
↑ calcium concentration = ↓ PTH
↓ calcium concentration = ↑ PTH
PTH 3 effects on kidneys
- ↑ Ca reabsorption
- ↑ P excretion
- ↑ conversion of 1,25(OH)2 to Vit D3
promotes meal-related intestinal absorption of Ca
activated vit D3
Vitamin —– comes from food/supplements ingested (body can’t produce)
D2
Vitamin —–, or ————, is a prohormone that can be transformed into physiologically active compounds by irradiation with ultraviolet light.
D3
cholecalciferol
Pre-vitamin D is either ingested or synthesized in the skin from ————– through exposure to sunlight.
7-dehydrocholesterol
inert Vit D3 is transported to the —— and converted to ———
liver
D25
In the kidney, vit D25 undergoes further hydroxylation to become…
vit D1,25 (most active form)
vitamin D deficiencies
- Causes rickets among children
- Precipitates and exacerbates osteoporosis among adults
- Causes the painful bone disease osteomalacia.
optimal D25 RR
20-50 ng/mL
Calcitonin is synthesized and secreted by the parafollicular cells of the ———–.
thyroid gland
Major calcium-regulating hormone because it tends to lower calcium and phosphorus
calcitonin
Calcitonin tends to be increased in…
medullary thyroid carcinoma
Used therapeutically for treatment of osteoporosis and Paget’s Disease
calcitonin
2 principle causes of hypercalcemia
Malignancy (low PTH)
Primary hyperparathyroidism (high PTH)
2 types of hypercalcemic malignancies
Local osteolytic hypercalcemia
Humeral hypercalcemia of malignancy (HHM)
More serious symptoms are laryngeal spasm, convulsion, respiratory arrest, and tetany
hypocalcemia
Characterized by excessive secretion of PTH in the absence of an appropriate physiological stimulus.
Primary Hyperparathyroidism (PHPT)
> 60% of PHPT patients are ….
postmenopausal women
better diagnostic measure for PHPT
iCa better than total Ca
preferred sample for intraoperative management of parahyperthyroidism
K3-EDTA
Chronic kidney disease compromises how the kidney functions
Fail to reabsorb Ca back into the blood (↑ urine Ca, ↓ serum Ca)
Fail to excrete phosphorus (↓ urinary phos, ↑ serum phos)
Fail to convert Vit D 25 to Vit D 1,25
secondary hyperparathyroidism
secondary HPT tx
vitamin D
tertiary hyperparathyroidism found in 1/3 of…
renal transplant patients
1-3% of patients require parathyroidectomy
Tertiary Hyperparathyroidism
hypoparathyroidism most commonly caused by…
parathyroid gland destruction during neck surgery (90%)
PTH, Ca, and P all increased
tertiary HPT
If phosphate levels remain elevated for a period of time, ———— may occur.
ectopic calcification
levels decrease to about ½ the lower limit of normal
Respiratory failure
Impairment of cardiac contractility
hypophosphatemia
present with significantly elevated blood levels of magnesium
pregnant patients given magnesium supplements to treat preeclampsia or eclampsia
bone collagen structural feature
triple helix
formation of collagen fibrils
Fibrillogenesis
Collagen ——– represents the major component of bone.
Collagen ——– is the main component of cartilage.
type I
type II
functions of bone
- Providing mechanical protection for internal organs
- Allowing the direction of motion
- Facilitating the locomotion process
- Providing a protective housing for blood-forming marrow
- Serving as a reservoir for mineral ions
composition of bone
~60% minerals
~35% organic matrix
~ 5% cells, and water
Refers to the ordered deposition of apatite on a type I collagen matrix.
bone mineralization
Formation of bone on sites where it has not been before.
bone modelling
Formation of bone on surfaces previously containing bone.
bone remodelling
Refers to the amount of bone renewed during the bone remodeling process.
bone turnover
2 major types of bone
cortical
trabecular
Occur as a layer of contiguous cells that in their active state are cuboidal.
osteoblasts
Represent the most abundant cell in the skeleton
osteocytes
Major stimulator of both the differentiation of preosteoclasts to osteoclasts and the activity of the mature osteoclast.
Receptor activator of nuclear factor kappa B-ligand (RANK-L)
Protects the bone from osteoclastic activity by binding RANK ligand
Osteoprotegerin
ideal bone biomarker
- Structural protein released into the blood in a rate proportional to its incorporation into bone.
- Fraction released should be unchanged by disease.
- Should have a well-characterized function and should not be released unaltered during bone resorption.
- Metabolic pathway and serum half-life should be known.
- A bone marker should be a degradation product of a matrix component not found in any other tissue.
- Serum levels of bone resorption markers should not be under separate endocrine control.
- The marker should not be reused in new bone formation.
gold standard bone techniques
- Isotope bone scan
- Bone biopsy (histomorphometry)
- Whole body calcium kinetic studies.
osteoporosis
A progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fractures.
most common type of primary osteoporosis
menopausal
Side effect following transplant of kidney, heart, liver, lung, and bone marrow
pathogenesis not understood
secondary osteoporosis
———— significantly enhance the loss of bone and increase the incidence of bone fractures
immunosuppressant drugs
osteoporosis r/f
Caucasian race
Older age
Postmenopausal
Decreased dietary calcium
Decreased vitamin D
Physical inactivity
Tobacco use
Excess alcohol intake
Exposure to medications (e.g., loop diuretics, glucocorticoids, and anticoagulants)
Leads to widening of the epiphyseal plate, skeletal abnormalities, and possible growth retardation
rickets
Chronic, localized disease characterized by increased bone remodeling, bone hypertrophy, and abnormal bone structure
Paget’s disease
