31. Pathophysiology of trace elements.

Trace elements
A trace element is an element that is present in our bodies in very minute quantities.



Usually, mineral and trace elements deficiency manifestations occurs during
developmental and growth phases, and thus, more of these factors are needed, and
since they are present in low quantities, deficiency is easy to occur.

Trace elements:

I. Iron

• Iron is obtained from 2 sources - meat and seafood - the best way to obtain iron due
to the fact that in these sources, iron present is in the heme-iron form (has better
bioavailability);

In non-heme iron present in fortified cereals, beans, dark chocolate and nuts, not as
much iron is readily absorbed - good sources for vegetarians.

• Iron supplements can also be taken - especially if diagnosed with hypothermic

anemia;

Most supplements recommended for women, which are at high risk of iron deficiency
due to menstruation, take supplements with the recommended dose of 18 mg of iron.

1. Deficiency

• Epidemiology: 

- Children (during growth)

- Young females (after menarche and before menopause), especially if they suffer
from menorrhagia 

- Pregnant women (producing blood for 2)

- Note: Lactating women are not at risk due to the fact that they are not menstruating,
thus, they do not lose the iron by menstruation. 

- Malabsorptive states

- Frequent blood don ors

- Patients with cancer/heart failure

- Vitamin C deficiency - acidifies the body - increases iron absorption

• Manifestations - Consistent with anemia (sideropenic) - fatigue, pallor, weakness,

tachycardia, dyspnea, brittle nails;

In iron deficiency anemia - pica - craving of adults for chewing ice; in children - try to
eat dirt.

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 • Restless leg syndrome - difficulty sleeping, uncomfortable legs unless they are
moving; associated with iron deficiency.

• Labs:

- Low Hb

- Low hematocrit

- Low MCV (macrocytic)

- Low serum iron, low ferritin, high transferrin

• Etilogy:

- Chronic bleeding

- Low iron intake

- Celiac disease

2. Excess

a) Acute iron poisoning

• Used to be common 25 years ago;it was one of the main causes of poisoning in
children;

• Not from food sources, because the amount one has to take to present acute
symptoms of acute iron poisoning are too big - can only be obtain by ingesting iron
capsules - children usually; if adults - suicide, possibly.

• Symptoms - abdominal pain, nausea, vomits, diarrhea, some hematemesis (<6 hh)
-> latent period ->liver problems - coagulopathy, shock, fever, metabolic acidosis ->
cirrhosis - jaundice, coagulopathy, hypoglycemia

b) Hemochromatosis

• Chronic disease

• Autosomal recessive hereditary disease but with variable penetrance

• Abnormal accumulation of iron in parenchymal organs leading to organ toxicity

• Adult-onset disorder that represents an error of iron metabolism characterized by

inappropriate high absorption of iron by GIT resulting in a progressive iron overload.
Organs involved - liver, heart, pancreas, pituitary, joints and skin.

• Excess iron is hazardous because it produces free radical formation and its presence
in biological systems can lead to a rapid formation of damaging ROS metabolites
which can induce DNA cleavage, impaired protein synthesis and impairment of cell
integrity and proliferation -> cell injury and fibrosis.




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 • For this disease, it is important to be aware of the iron route of excretion. An adult
man loses around 1 mg of iron daily, most by desquamated epithelium and
secretions from the gut and skin.



During childbearing age, women lose an average of and additional milligram of iron
daily from menstrual bleeding (40 mL blood loss) and around 500 mg with each
pregnancy.



In hemochromatosis, dysregulation of intestinal iron absorption occurs - iron
continues to be absorbed even in the face of substantial elevation of body iron
stores. Since the body also doesn’t have a clear pathway for iron elimination, it starts
to build up in our body with many toxic effects.



Most common cause of death: liver cirrhosis and high risk of hepatocellular
carcinoma.

II. Iodine

Sources: iodized salt; baked potatoes, milk, seafood, cranberries

A. Deficiency

• Iodine deficiency is nowadays mainly a problem of the developing countries and in

parts of Eastern Europe.

• Nowadays, in developed countries, is very unlike to get iodine deficiency due to

iodized table salt - half a spoon of table salt is enough to fulfill the daily requirements
of iodine.

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 • Iodine is a component of the thyroid hormone, so deficiency leads to goiter or
myxedema in severe cases.

• Chronic deficiency in the mother during pregnancy, result in poor growth and CNS
development of the baby = Cretinism

B. Excess - quite uncommon and when it occurs, it rarely affects the thyroid function.
Rarely may lead to hyperthyroidism.

Excess may occur via iodine supplements in patients who must take them to
counteract iodine deficiency, or it may occur in countries where people consume too
much seafood.

III. Magnesium

• Sources: nuts (almonds), spinach, soy milk, peanut butter

• Used for enzymatic processes and is found in any kind of tissues since it is used for
metabolism

• Associated with derangements of other other ions, particularly hypokalemia and

hypocalcemia - because ATPase pumps work with the help of magnesium; so
problems of potassium or calcium in the presence of a magnesium derangement can
occur - patient who presents hypokalemia or hypocalcemia, magnesium should be
checked. If it is decrease, the hypokalemia/calcemia will be corrected once
magnesium is corrected

• Magnesium is also a vaso/bronchodilator - this is why magnesium sulfate to women

with preeclampsia

• Deficiency - can result in tachycardia, long QT, Vfib because Mg is necessary for the
heart myocytes Na/K pump.

• People at risk for magnesium deficiency:

- Alcoholics (especially those in withdrawal), B1 deficiency
- Diuretics - number 1 cause of iatrogenic hypomagnesemia
- Malabsorptive states
- Renal disease
• Excess - leads to Manganism - psychiatric and motor disorders occurring due to
magnesium poisoning - reduced response speed, irritability, mood changes, and
compulsive behaviors.

IV. Zinc

• One of the strongest antioxidants (stronger than Vit. C)

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• Critical component of various membrane proteins; it is also required for immunity and
testosterone production.

• Growing prevalence of Zinc deficiency due to more processed food; higher intake of
white bread instead of wheat bread.

• Deficiency - diverse and non-specific

- ↓ Immune function and wound healing
- Oral ulceration = canker sores
- Angular cheilits
- Stomatitis
- Dermatitis
- Leukonychia (white spots on the nails)- zinc deficiency highly associated with it;
may mean subclinical zinc deficiency (non-specific)

• Population at risk of zinc deficiency:

- Pregnant women
- Growing children
- Alchoholis
- Malabsorptive syndrome
- Patients with copper excess (Wilson’s) - copper and zinc compete with each other


V. Copper

• Plays essential role in development of heme - cofactor of ALA synthase (first step in
heme synthesis)

• Important for proper collagen development and nerve functioning.

• Deficiency
- quite rare in developed countries; if severe enough, it will look a lot like iron
deficiency since heme is not being produced - hypochromic macrocytic anemia
- Other manifestations - weakness neuropathy and osteoporosis
- People at risk: malabsorption, people with too much zinc, premature infants or
Menkes Disease (AR)

• Excess

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 - Wilson’s disease - AR disorder characterized by excessive deposition of copper in
organs such as liver, brain.

It is fatal if not recognized and treated when recognized.



Around 50-75% of intestinal copper is absorbed and then transported to the
hepatocytes. This pathway is intact in Wilson disease. After copper reaches the
hepatocyte, it is incorporated into copper-containing enzymes and copper-binding
proteins (CBPs), including ceruloplasmin, a serum ferroxidase.



In Wilson disease, the processes of incorporation of copper into ceruloplasmin and
excretion of excess copper into bile are impaired.