Clinical Chem: Iron, Lead, Porphyrins

Is an essential nutrient that, among other functions, is needed in small quantities to help from normal RBCs.

Iron

__________ of the ________ of iron in the body is in hemoglobin

2.0-2.5g; 3-5g

T or F: The body can produce iron and absorb it from the foods we eat or from supplements.

false our body cannot produce iron

Multiple tests are ordered to evaluate iron in the body and they help do what?

diagnose and monitor patients with iron deficiency or iron overload

How is iron absorbed? (simplistic way) (4)

1) Ferric iron (Fe+3) is the common form consumed
2) Fe+3 is reduced to ferrous iron (Fe+2)
3) Fe+2 is absorbed and bound by ferritin for storage.
4) In ferritin Fe+2 is oxidized to Fe+3 and bound to transferrin for transport throughout the body.

What are some of the iron tests that are performed in the lab? (6)

- serum iron
- transferrin
- TIBC
- UIBC
- Transferrin saturation
- Serum ferritin

Measures the total serum iron concentration in circulation.

serum iron

When is serum iron measurement often requested? (3)

- when patients are symptomatic for iron deficiency
- there is evidence of an iron deficiency on a CBC
- when there is concern of iron overload

Serum iron measurement is often requested as an _____ or ___________ draw. It exhibits what?

- a.m. or fasting
- diurnal variation

What is the reference range for serum iron?

45-150 ug/dL

Directly measures the level of transferrin in the blood.

transferrin

What is transferrin?

protein that transports iron around the body, typically 1/3 saturated with iron

When is transferrin increased? When is it decreased?

- iron deficiency
- iron overload

What is the reference range for transferrin?

200-380 mg/dL

What does TIBC stand for?

total iron-binding capacity

Measures the total amount of iron that can be bound by proteins in the blood.

TIBC

TIBC is an indirect measurement of what? How?

- transferrin
- theoretical amount of iron that could be bound if transferrin and other proteins were saturated

What is TIBC increased? Decreased?

- iron deficiency
- iron overload

What is the reference range for TIBC?

250-400 ug/dL

What does UIBC stand for?

Unsaturated iron-binding capacity

Determines the reserve capacity of transferrin. The portion of transferrin that has not yet been saturated with iron.

UIBC

The sum of UIBC and serum iron= ?

TIBC

A calculation that reflects the percentage of transferrin that is saturated with iron.

Transferrin saturation

How is transferrin saturation calculated?

100 x (serum iron/TIBC)

When is transferrin saturation increased? Decreased?

- iron overload
- iron deficiency

What is the reference range for transferrin saturation?

20-50%

This reflects the amount of stored iron in the body.

serum ferritin

This is often decreased first in IDA due to the usage of available iron stores.

serum ferritin

What is ferritin?

a protein that contains iron and is the primary form of iron stored inside cells

Ferritin is released in small amounts in circulation. What is this a reflection of?

total amount of iron stored in the body

What is ferritin increased in? Decreased in?

- iron overload
- iron deficiency

What is the reference range for males in ferritin? Females?

- 24-336 ug/L
- 11-307 ug/L

What is iron depletion that occurs in iron deficiency? (2)

- diminished total body iron stores
- functional iron not effected

Advanced iron deficiency=

ANEMIA

What are the forms of anemia's with iron deficiency? (2)

- iron deficiency anemia (IDA)
- anemia of chronic disease (ACD)

Absolute iron deficiency.

Iron deficiency anemia

Functional iron deficiency.

anemia of chronic disease

Who is iron deficiency common in? (3)

- children
- young women/expectant women
- elderly

Decreased hemoglobin production due to decreased total body iron content.

Iron deficiency anemia

What are the causes of IDA? (4)

- increased demand
- increased loss
- nutritional deficiency
- malabsoprtion

What could cause increased demand of iron, which would result in IDA?

pregnancy

What could cause increased loss of iron, which would result in IDA? (2)

- menstruation
- GI bleed

What could cause malabsorption, which would result in IDA? (2)

- Crohn's or celiac disease
- intestinal parasites

What is stage 1 of IDA? What value is decreased? Is there anemia present?(4)

- iron DEPLETION
- decrease storage iron
- no anemia
- RBC morphology normal

What is stage 2 of IDA? What values are decreased? Increased? Is there anemia present? (5)

- Iron-deficiency erythroposies
- decreased in iron for erythropoiesis
- decrease ferritin, serum iron
- increased TIBC
- no anemia; slight microcytic

What is stage 3 of IDA? What values are decreased? Increased? Is anemia present? (5)

- Iron DEFICIENCY
- decrease in hgb, ferritin, serum iron, tissue oxygen delivery
- increase TIBC
- all lab tests abnormal
- microcytic, hypochromic anemia

What does the RBC morphology look like in IDA? (3)

- Microcytic hypochromic anemia
- Ansiocytosis
- poikilocytosis

What labs are increased in IDA? What labs are decreased? (2)

- TIBC
- Total iron
- Ferritin

This is when there is decreased hemoglobin production due to a decreased amount of free iron

Anemia of chronic disease

What is anemia of chronic disease also called?

Anemia of chronic inflammation

Anemia of chronic disease causes decreased bone marrow ________.

erythropoiesis

Decreased _______ is seen in anemia of chronic diseases which is why there is a decreased use of iron stores.

Hematopoiesis

What lab features are decreased in anemia of chronic disease? (2) What are increased?

- Iron
- TIBC
- Ferritin increased

What are the two types of iron overload?

- Hemochromatosis
- Hemosiderosis

What are the characteristics of hemochromatosis? (2)

- Effects on liver, heart, and endocrine glands
- Irreversible

Hemosiderin in hemochromatosis is deposited where?

Cells and interstitial fluid

This is a hereditary disorder of iron metabolism

Hemochromatosis

What are the characteristics of hemosiderosis? (2)

- No tissues damage
- reversible

Where is hemosiderin deposited in hemosiderosis?

In cells only

This is a secondary/acquired iron accumulation

Hemosiderosis

What lab results are increased in hemochromatosis? (2) What lab results are decreased?

- Total iron
- Percent saturation
- TIBC decreased

What symptom is seen with hemochromatosis?

Hyperpigmentation

Hemochromatosis causes excessive iron to deposit. Where in the body does it occur? (3)

- Organs
- Tissues
- Interstitial fluid

This is characterized by an increased rate of absorption of iron

Hemochromatosis

Given the following tests, state the results for acute liver disease.
- Serum iron
- Transferrin
- Ferritin
- % saturation

- Increased
- Variable
- Increased
- Increased

Given the following tests, state the results for chronic anemia.
- Serum iron
- Transferrin
- Ferritin
- % saturation

- Decreased
- normal/decreased
- normal/increased
- Decreased

Given the following tests, state the results for malnutrition.
- Serum iron
- Transferrin
- Ferritin
- % saturation

- Decreased
- Decreased
- Decreased
- Variable

Given the following tests, state the results for hemochromatosis.
- Serum iron
- Transferrin
- Ferritin
- % saturation

- Increased
- Slight decrease
- Increased
- Increased

Given the following tests, state the results for iron overdose.
- Serum iron
- Transferrin
- Ferritin
- % saturation

- Increased
- Decreased
- Increased
- Increased

Given the following tests, state the results for iron deficiency anemia.
- Serum iron
- Transferrin
- Ferritin
- % saturation

- Decreased
- Increased
- Decreased
- Decreased

This is used in the production of storage batteries, ammunition, solder, and foils

Lead

What did lead used to be present in? (2)

- Additive in gasoline
- Paints manufactured before 1970

Once lead is absorbed in the body, 99% of lead is taken up by what?

Erythrocytes lead to distribution in the body

What percentage of lead is excreted in urine? What percentage of lead is excreted in feces? What percentage of lead is excreted in hair, sweat, and nails?

1) 76%
2) 16%
3) 8%

What percentage of lead is inhaled? What percentage is absorbed in GI?

- 30-40%
- Variable

How do people get exposed to lead?

Respiratory and gastrointestinal

What are the toxicity effects of lead in children? (6)

- IQ declines
- Clumsiness
- Gait
- Headache
- Behavior changes/cognitive
- Seizures

What are the toxicity effects of lead in adults? (5)

- Peripheral neuropathies
- Motor weakness
- Chronic renal insufficiency
- Systolic hypertension
- Anemia

What are the health effects of lead? (2)

- nonessential / no function in human physiology
- toxic

When is lead testing recommended? (3)

- Childhood screening at 1-2 years of age
- When the occupation of a hobby exposes you/your family to lead
- Have symptoms or at risk for lead poisoning

What is the reference range for lead?

<10 ug/dL

At low levels of lead intoxication, irreversible damage can occur without causing what?

Physical symptoms

What are the symptoms of lead intoxication? (7)

- Weakness
- Anemia
- Nausea
- Weight loss
- fatigue/headaches
- Stomach pain
- Kidney, nervous system, reproductive dysfunction

Lead can be passed from mother to fetus and cause what? (2)

- Miscarriages
- Premature births

Children who have elevated blood lead levels should be tested for what?

Iron deficiency anemia

Lead can interfere with the adsorption of what?

Iron

What are porphyrins? (2)

- By-products of heme synthesis
- Present at low concentrations in blood and body fluids

The precursors that accumulate depend on which enzyme is deficient and they can exert what type of effects?

Toxic effects (AACC)

If there is a deficiency in the enzymes that synthesize heme, the process impedes porphyrins such as what ones? (3)

- Uroporphyrin
- Coproporphyrin
- Protoporphyrin

The impeded porphyrins that are due to deficient enzymes build up where in the body?

Body fluids and tissues

The synthesis of heme is a step-by-step process that requires the sequential action of _____ different enzymes.

Eight

What is the structure of heme? (3)

- Iron-containing pigment
- contains hemoglobin and other proteins
- Has organic portion of protoporphyrin bound to iron

What specimens can porphyrins and their precursors be measured in? (3)

Urine, blood, stool

What are the porphyrin precursors that can be measured in urine? (3)

- Porphobilinogen
- Delta-aminolevulinic acid (ALA)
- Porphyrins (uroporphyrin, coproporphyrin, protoporphyrin)

True or false. Laboratories don't offer direct testing of affected enzymes when evaluating porphyrias.

False, they sometimes offer direct testing of enzymes

Patients with this porphyria have a deficiency in the enzyme PBG-D

Acute intermittent porphyria

What enzymes is measured in the lab for porphyrias?

Porphobilinogen deaminase (PBG-D) in RBCs