13) Bone and mineral Flashcards by Samantha Boyer

hydroxyapatite

Crystal lattice composed of calcium, phosphorus, and hydroxide

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forms of Ca in blood

iCa — free or ionized – active form (50%)
Complexes with anions (10%)
Bound to protein (40%)

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anions that bind Ca

Bicarbonate
Lactate
Phosphate
Citrate

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The —– affects how well serum proteins bind free calcium.

How?

Alkalosis: increased negative charges = increased binding of free calcium= ↓iCa
Acidosis: decreased negative charge = decreased binding of free calcium= ↑iCa

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For each —– unit change in pH, there is a —- mg/dL inverse change in serum free calcium.

0.1
0.2

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Distribution of Ca bound to proteins

80% to albumin
20% to globulins

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Low proteins = low total ——-

calcium

Pseudohypocalcemia

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——- is independent of protein levels, where ——- is dependent

iCa
total Ca

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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

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total Ca RR

8.6-10.0 mg/dL

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PTH effect on Ca levels

↑serum iCa, ↓ Phos

Mg needed

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1,25-dihydroxycholecalciferol/Vitamin D3 effect on Ca levels

↑serum iCa, ↓ Phos

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functions of Ca

Nerve impulse transmission
Cofactor in certain enzymes
Coagulation of blood
Skeletal mineralization
Preservation of cell membrane integrity and permeability

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PTH acts on the…

kidney (Ca reabsorption, P secretion)
intestine (Ca absorption)
bone (resorption)

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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.

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——- iCa values can cause seizures or cardiac arrest.

Low

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—— iCa can cause nausea, constipation, and kidney failure if calcium salts are precipitated in the kidneys.

High

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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.

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iCa RR

4.64 – 5.28 mg/dL

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Increased urinary calcium concentration may be associated with an increase in….

osteoclastic bone resorption

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urine Ca sample handling

24-hour urine specimens should be acidified with 5.0 mL of 6M HCL; solubilizes Ca crystals.

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3 methods used to measure Ca

Colorimetric analysis
Atomic absorption
Indirect potentiometry

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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.

inorganic

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P RR

2.5-4.5 mg/dL

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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)

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

13) Bone and mineral Flashcards

(90 cards)