Trace Elements and other Electrolytes Flashcards
What are the toxic trace elements?
-aluminum
-Arsenic
-Cadmium
-Lead
-Mercury
What are the essential trace elements tested in the lab?
-chromium
-copper
-Fluorine
-Iodine
-Manganese
-Molybdenum
-Selenium
-Zinc
increased copper absorption is facilitated by binding to ____________
amino acids
-can be used as treatment to increase levels
Copper source dietary (~___% of intake is absorbed)
50
Copper is Excreted mainly in ______, with some excretion via urine
around ______ug/day
bile, <40
Copper is important for enzymatic activity and is a ___________.
cofactors
examples of copper cofactors
Ceruloplasmin***, cytochrome oxidase, dopamine β-hydroxylase, tyrosinase, and many
others.
Fe2+ —-> Fe3+
copper carrier that is important for iron
Ceruloplasmin***
(ferroxidase?)
Copper:
In plasma, _____% bound to ceruloplasmin (ferroxidase, an enzyme important in
Fe2+ oxidation prior to “transferrin” binding)
95
-small amount associated with albumin (not strong binding)
Copper induces ____________ synthesis (complexes with Cd2+, Cu2+, and Zn2+)
Metallothionein
What is the function of Cysteine (-SH) rich low MW protein?
unclear
Research indicate that protection against metal toxicity
against oxidative stress (similar to how transferrin prevents damage from iron)
Glutathione is reduced from _____ oxidized from GS.
2GSH/GSSG ratio
What does an increased ratio mean? a decreased?
GSH
-can handle more oxidative stress
-increased in cells, could have damage by oxidative stress
diet contains about ____ mg/d of copper
1.2
During the last 3 months of
pregnancy, liver development
occurs. A premature baby has less ______ storage in the liver.
copper
-also abnormal hematological characters and abnormal bone formation
Typically in male infant
@ 2-3 month
X-linked genetic defect
Menke’s Kinky Hair Syndrome
- Impaired Cu2+ intestinal absorption
- Severe cerebellar & cerebral degeneration, failure to thrive, osteoporosis,
motor delay, and death within the first decade of life (about 3 year)
Menke’s Kinky Hair Syndrome:
how is Menke’s Kinky Hair Syndrome treated?
Cu-histidine if caught ealry
causes of copper deficiency?
Decreased dietary intake
▪ ↓ Activities of various Enzymes
- Microcytic-hypochromic anemia, neutropenia, heart disease, bone & joint
osteoarthritis, hypothermia, hypercholesterolemia.
- decreased antioxidant protection and metabolic activity
What levels are considered copper deficiency for plasma and ceruloplasmin?
< 10μM (70mg/dl) : [Cu++]
plasma
< 220mg/L: ceruloplasmin
Copper excess Can be detected with
* ____ Liver function
* “ [Cu2+] in urine (> _______)
decreased, 500μg/L
copper excess is associated with _____________ disease
Wilson’s
↑ copper accumulation in
liver, brain, kidney, & cornea of the eye (rings of Cooper-Kayser-Fleisher rings).
* No copper found in serum due to a decrease in “ceruloplasmin”
-with increased non-ceruloplasmin bound Cu2+
Wilson’s disease
What is the treatment for Wilson’s disease?
chelating agents, .V administration, e.g. Penicillamine
increased copper causes….
________ Vit. C
________ Zinc
_________Vit. A
decrased
decreased
increased
◆Factors that increase serum [Cu2+]
oral contraceptives, pregnancy, infections.
Increased serum Cu, __________ hepatic synthesis of ceruloplasmin.
increased
With Wilson’s disease, is copper increased in tissue or serum?
increased in tissues to toxic levels
What is it called when there is a copper ring in the eyes associated with Wilson’s disease
Cooper-Kayser-Fleisher rings
Copper levels in ________ is not a reliable indicator of copper status.
serum
- Measurement of [Cu2+]serum is ______ indicative of copper status
NOT
What is a more accurate indicator of copper levels?
Examination of decreased cytochrome oxidase activity in
leukocytes****
Three ways copper can be measured?
- Flame Atomic Absorption spectrophotometry (serum plasma or urine)
- Colorimetric spectrophotometry using chromagen;
1) cuppizone or 2) bathocupoine - Immunoassay: Ceruloplasmin
TRACE ELEMENTS: COPPER METHODOLOGY
[Cu2+]serum is not reliable indicator of Cu2+ status
* In the case of Cu2+ depletion: “ free ceruloplasmi
In the case of Cu2+ depletion: ________ free ceruloplasmin
increased
What are the two chromagens that can be used with Colorimetric spectrophotometry?
1) cuppizone or 2) bathocupoine
_______ is 2nd most abundant trace element in body (~2g in adult)
(first is iron)
Zinc
Zinc: ______% found in muscle, _____% in bone, _____% in blood.
50-60,
28,
0.5 (RBCs are 75-88%)
Zinc:
In serum, ________% bound to albumin, ________% to α2-macroglobulin & transferrin
60-70, 30-40
*small fraction in free from
Zinc is an essential __________ for many enzymes. examples?
Cofactor
carbonic anhydrase, alcohol dehydrogenase, RNA/DNA polymerase
Zinc is necessary for cell _________________ and organ ________________.
Reproduction, development
copper binds to protein more firmly than ____ does.
➢ Unabsorbable (zinc?) complex in GI tract —-> Decrease Cu++ absorption
zinc
zinc fingers are formed from…
cysteine and histadine
about ___ mg/d of zinc in diet
10
- Required for the activity of enzyme that are critical for nucleic acid replication &
protein synthesis
-Necessary component for cell replication
zinc
most common cause of zinc deficiency
Malabsorption & dietary deficiency
(causes increased susceptibility to disease)
effects of zinc deficiency
infections, trauma, sickle cell anemia, renal disease,
and alcohol abuse
* skin lesions (extremities and orifices), diarrhea, hair loss,
growth retardation, and decreased immune system function.
CLINICAL CASES OF Zn DEFICIENCY:
-IV feeding after surgery
-delayed wound healing, dermatitis,
mental depression, diarrhea
Experimental evidences for Zinc deficiency
- Fetal abnormalities…
Impaired embryogenesis
* Impaired brain development
* Impaired vision
symptoms of zinc toxicity
Abdominal pain
* Diarrhea
* Nausea
* Vomiting
What is the major source of circulating ammonia?
action of Bacterial 1) proteases, 2) Urease, 3) Amine oxidase acting on GI tract content
NH3 is absorbed into ________ circulation
portal
ammonia is removed by the _______, urea synthesis, and eliminated in ________
liver, urine
cirrhosis or severe hepatitis, or decreased liver function = _________
increased ammonia due to inability to convert to urea
________ function determines the NH3
liver
small amounts of ammonia are produced by _____________.
exercise
Renal tubules produce their own NH3 from…
deamination of glutamine
-NH3 diffuses from renal cells into tubule
Does the kidney contribute to blood NH4?
NO**
NH3 in urine binds to H+ to form…
NH4
False elevation [NH3]: correction of sources of preanalytical error include…
1) Contamination
2) Collection process: prolonged tourniquet use
3) Delayed analysis
causes of increased ammonia?
-infants (liver is still developing)
-liver disease (acute viral hepatitis and “Reyes syndrome”
-Chronic cirrhosis
is a form of hepatic destruction following recovery from viral infection
REYES SYNDROME
what can increased ammonia cause?
Causes neurological abnormalities because NH3 can cross BBB (coma, seizures)
In pH of 9-9.6, Lactate dehydrogenase ______ —> _______ by NAD+ to NADH + H+
L-Lactate —–> Pyruvate
In pH of 7.5, Lactate dehydrogenase ______—> _______ by NADH + H to NAD+
Pyruvate —–> L-lactate
_______ in blood, is a sensitive indicator of oxygen deprivation.
Who should be monitored for this?
lactate
critically ill patients
Increased lactate may be caused by…
Decrease in 1) tissue blood perfusion which could decrease tissue oxygenation (coronary
ischemia)
* Defective carbohydrate metabolism
* Respiratory disease
what are the therapeutic levels of lithium?
toxic levels?
-1-1.2 mEq/L
->1.5 mEq/L)
How does lithium affect the CNS?
inhibiting effects of norepinephrine (NE) and serotonin release and increasing reuptake of NE.
Toxicity of Lithium is associated with…
vomiting, ataxia, muscular rigidity, and EEG changes.
