Transcript Trace Elements

Trace Elements
Reed A Berger MD
Visiting Clinical Professor in
Nutrition
Trace Elements
-a naturally occurring, homogeneous,
inorganic substance required in humans
in amounts less than 100 mg/day
Copper
-found in the liver, brain, heart, kidneys,
and muscle
-about 90% of copper in the plasma is in
the form of ceruloplasmin
-the rest is bound to albumin,
transcuprein, and AA’s
Functions
-component of many enzymes
-oxidation of Fe prior to transport in the
plasma
-cross-linking of collagen
-mitochondrial energy production,
protection from oxidants, etc…
Absorption, Transport,
Excretion
-some absorption from the stomach, but
most in the small intestine
-absorption varies—it decreases with
increased intake
Metabolism
-for short term transport to the liver
copper is carried primarily by albumin
-copper-albumin complex acts as a
temporary storage site for copper
-in the liver, metallothionein is the
storage site
-ceruloplasmin is the storage site in the
plasma and cells
-secreted from the liver as a component of
bile
-once in the GI tract, it becomes part of the
body’s pool and is reabsorbed or excreted
depending on the body’s need
-biliary excretion increases in response to
copper overload
-small amts of copper are present in the
urine, sweat, and menstrual blood
-can be conserved by the kidney for
reabsorption
-unabsorbed copper is in the feces
-in high levels, zinc can induce copper
deficiency by stimulating intestinal cells
to produce more metallothionein which
binds copper more avidly than zinc and
then is exfoliated with the intestinal cells
-fiber and phytate do not adversely
effect copper absorption
RDA and Sources
-see handout
Deficiency
-decrease in serum copper and ceruloplasmin
levels are seen
-neutropenia, leukopenia,bone
demineralization
-subperiosteal hemorrhages, hair and skin
depigmentation, defective elastin formation
-failure of erythropoiesis, cerebral and
cerebellar degeneration>>>death
-neutropenia, leukopenia are the best
early indicators in children
-because it is stored in the liver,
deficiency takes a long time to develop
-bone changes such as osteoporosis,
soft tissue calcification can occur with
prolonged TPN
Menke’s disease
-sex-linked recessive defect that results in
copper malabsorption, increased urinary loss,
and abnormal intracellular copper distribution
-affected infants: retarded growth, defective
keratinization and pigmentation of hair,
hypothermia, degenerative changes of the
aorta, mental deterioration, abnormalities of
the metaphyses of long bones
-all of the above is due to interference with
collagen and elastin cross-linking
Menke’s cont’d
-there is accumulation of copper in the
intestinal mucosa even though copper
and ceruloplasmin levels are very low
-transient improvement with parenteral
copper
-***decreased plasma copper levels are
also seen in malabsorptive diseases,
celiac sprue, tropical sprue, proteinlosing enteropathies, and nephrotic
syndrome
Toxicity
-increased copper levels seen during
pregnancy and in women on OCP’s, those
with acute and chronic infections, pts with
liver disease
-***any liver disease that interferes with bile
excretion (primary biliary cirrhosis) and
mechanical obstruction causes increases in
liver copper
-***Wilson’s disease: accumulation of
excessive copper in the body tissue as the
result of a genetic deficiency in the liver
synthesis of ceruloplasmin
Iodine
-body normally has 20-30 mg of iodine
and more than 75% is in the thyroid
gland
-the rest is in the mammary gland,
gastric mucosa, and blood
-it’s only function is related to thyroid
hormone
Absorption and
Excretion
-iodine is absorbed in the form of iodide
-occurs both as free and protein-bound iodine
in circulation
-iodine is stored in the thyroid where it is used
for the synthesis of T3 and T4
-the hormone is degraded in target cells and
in the liver and the iodine is conserved if
needed
-excretion is primarily via urine
-small amts from bile are excreted in the
feces
Deficiency
-goiter—enlargement of the thyroid
gland
-deficiency may be absolute—in areas
of deficiency, or relative—adolescence,
pregnancy, lactation
-goiters are more prevalent in women
and with increased age
-goitrogens occurring naturally in foods can
cause goiter by blocking absorption or
utilization of iodine (cabbage, turnips,
peanuts, soybeans)
-***severe deficiency during gestation and
early postnatal growth: cretinism—mental
deficiency, spastic diplegia, quadriplegia, deaf
mutism, dysarthria, shuffling gait, short
stature, hypothyroidism
Toxicity
-iodine has wide margin of safety
-goiter usually occurs with excess
intake>need
Chromium--Functions
-required for normal lipid and CHO
metabolism and for the fxn of insulin
-?can supplementation raise HDL
Absorption and
Excretion
-10-25% absorption in its trivalent form
-amount absorbed remains constant at
dietary intakes >40 ug (micrograms) at which
point excretion in urine is proportional to
intake
-increased intake of simple sugar, strenuous
exercise, or physical trauma also increase
urinary excretion
-both chromium and Fe are carried by Tf,
however albumin can also assume this role
Deficiency
-altered CHO metabolism, impaired glucose
tolerance, glycosuria, fasting hyperglycemia,
increased insulin levels and decreased insulin
binding
-impaired growth, peripheral neuropathy,
negative nitrogen balance
-increased chromium losses in stress
-hyperglycemia and wt loss reverse with IV
supplementation in TPN
Cobalt
-most stored with vitamin B12
-component of B12—cobalamin
-essential for maturation of RBC’s and
normal function of all cells
Absorption and
Excretion
-shared with Fe
-absorption is increased in pts with
deficient Fe intake, portal cirrhosis with
Fe overload, and hemochromatosis
-excretion is mainly thru the urine
-small amts in feces, hair, sweat
Sources and Intakes
-microorganisms are able to synthesize
B12
-***humans must obtain B12 and cobalt
from animal foods such as organ and
muscle meat
-***takes a long time to become
deficient—happens in vegetarians
Deficiency
-related to vit B12 deficiency
-**macrocytic anemia
-genetic defect: pernicious anemia
-tx: massive doses
-more in the vitamin lecture
Toxicity
-polycythemia
-hyperplasia of BM
-reticulocytosis
-increased blood volume
Selenium
-glutathione peroxidase
-acts with other antioxidants and free
radical scavengers
-overlaps with vit E for antioxidant
effects
-fxn with vit E to protect cell and
organelle membranes from oxidative
damage
Absorption and
Excretion
-upper segment of the small intestine
-increased absorption with deficiency
-status is measured by measuring
selenium or glutathione peroxidase in
plasma, platelets, and RBC’s or
selenium levels in whole blood or urine
-RBC selenium is an indicator of longterm status
Deficiency
-rare
-Keshan Dz or Kashin-Beck Dz
-long term TPN, cancer, CF
Molybendum
-relationship with copper and sulfate
-cofactor of many enzymes involved in
the catabolism of sulfur AA, purines and
pyridines
-Toxicity: gout-like syndrome,
reproductive SE’s
-Deficiency: increased risk with coexisting copper deficiency, TPN
Silicon, Vanadium,
Arsenic, Boron
-see handouts
-will not be on the exam!!!