Week 10: Minerals

99% of calcium is found in the ________, while 1% is found in _________

bone, plasma

calcium in the bone is bound to phosphate to form what?

hydroxyapatite

_____ of plasma calcium is protein-bound

40%

_____ of plasma calcium is free (“ionized”)

50%

_____ of plasma calcium is complexed to anions

10%

what anions can calcium be complexed to in plasma?

• PO4

• HCO3-

• citrate

• lactate

decreased pH causes _________ bound calcium and __________ free calcium

decreased, increased

pH changes do not cause changes in _________ calcium levels

total

total calcium levels depend on total _________

protein

decreased total protein causes ____________ total calcium

decreased

decreased total protein does not cause a change in _______ calcium

free

total calcium equation

albumin adjusted total calcium = calcium - albumin + 4.0

use the total calcium equation carefully for the _____________

critically ill

the critically ill have ________ blood protein, pH, and anion changes

rapid

_______ calcium is biologically active and is a superior indicator over total calcium

free

functions of ionized (free) calcium

• neuromuscular excitation

• bone mineralization

low ionized calcium causes ___________ neuromuscular excitability

increased

increased ionized calcium causes ___________ excitability

decreased

tetany is associated with ______ ionized calcium

low

coma is associated with _______ ionized calcium

high

__________ phosphate is found in bone, ___________ phoshpate is found in serum

organic, inorganic

inorganic phosphate

• measured by lab

• regulated by kidneys

functions of phosphate

• bone mineralization

• ATP, nucleic acids, phospholipids

• buffering

  • renal

  • plasma

  • RBCs

calcium and phosphate tend to have a ___________ relationship

reciprocal

hormones that regulate calcium/phosphate balance

• PTH

• vitamin D

• calcitonin

target organs of hormones that regulate calcium/phosphate balance

• bone

• kidney

• intestine

the parathyroid gland senses low serum __________ and secretes PTH

calcium

PTH acts upon the kidneys to increase __________ formation and decrease excretion of ___________

calcitriol, calcium

PTH acts upon the bone to release ___________ and ___________

calcium, phosphorus

vitamin D acts upon the _________ to release calcidiol

liver

calcidiol acts upon the ___________

kidneys

calcitriol from the kidneys acts upon the ________ and _____________

bone, small intestine

calcitriol causes the small intestine to increase ___________ absorption

calcium

PTH works to increase serum ____________ and decrease serum __________

calcium, phosphate

PTH has a __________________ mechanism

negative feedback

osteoclastic activity

• breaking down and resorbing bone tissue

• releases calcium and phosphate into blood

PTH triggers bone ____________ activity

osteoclastic

how does PTH affect the kidneys?

• increased calcium reabsorption

• increased phosphate excretion

• increased active vitamin D production

what tissues synthesize vitamin D?

• skin

• liver

• kidneys

methods for vitamin D

• radioimmunoassay (RIA)

• HPLC and LC-MS

what can cause increased vitamin D?

• sunlight exposure

• high in diet

what can cause decreased vitamin D levels?

• chronic renal insufficiency

• lack of sunlight

• lack in diet

• malabsorption

• medication

vitamin D is also called what?

cholecalciferol

how does vitamin D affect calcium levels?

increases absorption

how does vitamin D affect the kidneys and intestine?

increased calcium and phosphate reabsorption

how does vitamin D affect the bone?

it enhances PTH effects → increased osteoclastic activity

vitamin D has a much _________ regulatory effect on calcium balance than PTH

slower

active vitamin D production

1. inactive from diet or UV

2. liver converts inactive vitamin D3 or D2 → inactive 25-OH-D3

3. kidney converts 25-OH-D3 → active 1,25-(OH)2-D3

4. steps 2 and 3 are hydroxylation steps

__________ is the main source of vitamin D

sunlight

what is 25-OH-D3 (25-hydroxyvitamin D) called?

calcidiol

what is 1,25-(OH)2-D3 (1,25-dihydroxyvitamin D) called?

calcitriol

calcitriol is the ____________ form of vitamin D

activated

calcitonin __________ free calcium

decreases

calcitonin is released by _______________

thyroid C cells

calcitonin inhibits ________ and ______________ action on kidney and bone

PTH, vitamin D

when is calcitonin secreted?

hypercalcemia

endogenous sources of phosphate

• bone

• intracellular

what functions do kidneys serve to regulate phosphate balance?

• hormones: PTH, vitamin D

• acid-base balance

symptoms of hypercalcemia

• neuromuscular symptoms

• fatigue

• weakness

• nausea

• CNS hypofunction

• coma

primary hyperparathyroidism causes ___________ calcium levels

elevated

what causes primary hyperparathyroidism?

parathyroid tumor that increases PTH secretion

primary hyperparathyroidism increases ___________ and decreases _____________

calcium, phosphate

what are general causes for hypercalcemia?

• primary hyperparathyroidism

• malignancy

• overdosing calcium and vitamin D

• medications

how can certain cancers raise blood calcium levels?

• bone metastasis → direct bone destruction

• some secrete PTHrP (parathyroid hormone-related protein)

what effect does PTHrP have?

• increased calcium

• low or normal phosphate

• low or normal PTH

what effect does vitamin D toxicity have?

• increased calcium

• variable phosphate

• low or normal PTH

symptoms of hypocalcemia

• tetany

• seizures

what can cause hypocalcemia?

• hypoalbuminemia = most common

• chronic renal failure

• hypoparathyroidism

• alkalosis

• vitamin D deficiency

what occurs with chronic renal failure and calcium/phosphate balance?

• increased phosphate

• decreased calcium

• decreased vitamin D production

what occurs with hypoparathyroidism?

• decreased PTH

• decreased calcium

• increased phosphate

hypoalbuminemia causes decreased __________ calcium and normal __________ calcium

total, ionized

alkalosis causes __________ total calcium and ___________ ionized calcium

normal, decreased

hypoalbuminemia is _______________ while alkalosis is ______________

asymptomatic, symptomatic

vitamin D deficiency causes PTH to ___________

increase

decreased bone mineralization with hypocalcium can cause what?

• rickets in children

• osteomalacia in adults

some pre-term neonates can develop neonatal ________ due to hypocalcemia (sometimes with hypomagnesemia)

tetany

hypoparathyroidism causes ___________ phosphate levels

increased

hyperparathyroidism causes ___________ phosphate levels

decreased

what can cause hyperphosphatemia?

• hypoparathyroidism

• renal insufficiency

  • reduced excretion

what can cause hypophosphatemia?

• primary hyperparathyroidism

• vitamin D deficiency → increases PTH secretion

normal range for total calcium

8.5-10.5 mg/dL

normal range for inorganic phoshpate

2.8-4.0 mg/dL

normal range for magnesium

1.6-2.6 mg/dL

specimen for calcium methods

• serum

• heparinized whole blood/plasma

• urine

total calcium methods

• cresolphthalein complexone (o-CPC)

• arsenazo III dye

• AAS

cresolphthalein complexone (o-CPC) principle

• calcium + o-CPC → red colored complex

• alkaline medium

• avoid cation (Mg) interference

  • hemolysis

  • icterus

free “ionized” calcium methods

potentiometric with ion selective electrode

specimen for free “ionized” calcium

• whole blood, plasma, serum

• keep tightly stoppered

• analyze ASAP

interferences with free “ionized” calcium method (potentiometric)

• pH changes in vitro

• low pH → falsely elevated (delayed analysis)

• high pH → falsely decreased (unstoppered tube)

inorganic phosphate method

• fiske and subbarow (phosphomolybdate)

• phosphate + ammonium molybdate → complex

• 340 nm

interferences with fiske and subbarow (inorganic phosphate) method

• non fasting → falsely low

• intracellular phosphate → falsely high

  • avoid hemolysis

  • separate cells ASAP

magnesium methods

• dye binding

  • calmagite

  • methylthymol blue

• AAS (reference lab)

interferences with magnesium methods

• calcium chelator (EDTA) → falsely low

• hemolysis → falsely elevated