Serum Iron Flashcards
What are protein that serve as chemical messengers (primarily interleukin (IL) and tumor-necrosis factor (TNF))?
cytokines
What promotes interactions and communication between cells and causes actions that can increase inflammation or reduce it?
cytokines
Cytokines can be made by multiple cells, including what?
- T-helper cells
- macrophages
- neutrophils
- basophils
- eosinophils
What work in coordination with the immune system to rid the body of infectious invaders?
cytokines
What are also known as acute phase proteins and are not the same as cytokines but often are affected by cytokine release?
acute phase reactants
What are produced in the liver during times of stress, inflammation, or infection or chronic illness?
acute phase reactants
- An increase in acute phase reactants is known as what?
- A decrease in acute phase reactants is known as what?
- positive acute phase reactant
- negative acute phase reactant
The release of cytokines and activation of APRs causes many symptoms that we associate with illness like what?
- fever
- fatigue
- myalgias
The concentration of many plasma proteins increase during inflammatory states, largely in response to (…)
inflammation-associated cytokines
APPs are commonly defined as plasma proteins that increase, (…), by at least (…) during inflammatory states. In addition, a number of (…), whose concentration decrease significantly under these circumstances, have been recognized. All of these changes largely reflect altered production by (…)
- positive acute phase proteins
- 25%
- negative acute phase proteins
- hepatocytes
What are inflammatory/stress conditions that can cause changes to acute phase reactants?
- infections
- tissue ischemia
- malnutrition
- autoimmune disease
- cancer
What can cause tissue ischemia?
- severe trauma
- ischemic stroke
- myocardial infarction
What are some examples of autoimmune diseases that can cause changes to the acute phase reactants?
- lupus
- rheumatoid arthritis
- crohn’s disease
Ferritin is an APR that (…) in response to system stress
increases
Some APRs decrease in response to stress, such as?
- albumin
- transferrin
What are the steps in cytokine release/APR release after inflammatory stimuli?
- Inflammatory stimuli (tissue injury, heat stress, muscle breakdown)
- activation of monocytes and macrophages
- release of cytokines
- increase/decrease of acute phase proteins
- systemic response
When a CBC reveals possibility of anemia (low H&H), we need to perform further investigation using (…)
- generally, if patient has normal CBC, this test will be less useful unless early case of anemia is suspected
serum iron studies
Iron-deficiency anemia represents (…) of all anemias
- what will you need to evaluate for?
- 50%
evaluate for: - possibility of blood loss
- poor intake of iron
What is the first step in evaluation of anemia, after taking a great history?
check iron studies
What labs are ordered independently of the CBC?
- serum iron
- serum ferritin
- TIBC
- transferrin saturation
In some cases, CBC and iron studied are drawn simultaneously. Which cases are these?
- history or iron-deficiency anemia (only if you have already investigated the cause)
- history of a procedure that we know causes low iron (gastric bypass - poor absorption of multiple vitamins and iron)
- 70% of the body’s iron is found in what?
- hemoglobin = (…)
- each of the two alpha and two beta hemoglobin changes have what?
- hemoglobin of the RBCs
- great oxygen delivery system
- a heme unit
What are the structural characteristics of heme?
- composed of a porphyrin ring with iron in the center
- the center iron in the heme ring binds to oxygen
- each hemoglobin can then bind to four O2
What happens in iron-deficient states?
- less oxygen binding occurring
- reduced oxygen transport to tissues
- results in fatigued patient
What is not always accurate to diagnose iron abnormalities and should be used in conjunction with other iron studies to determine information about anemia?
a single iron measurement
Iron is “…” and varies throughout the day, how is iron affected throughout the day?
- fickle
- iron level typically higher in the morning
- some recent studies have shown enough variation to recommend testing at a specific time
With testing serum iron, what can elevate iron reading levels? What can reduce iron levels?
- elevate: medications such as oral contraceptives that contain iron and multivitamin with iron
- reduce: stress
What type of serum iron level is less common to see in practice?
What type of serum iron level is more common to see in practice?
- increased serum iron level
- decreased serum iron level
What causes increased serum iron levels and what are the mechanisms of each?
alcoholic cirrhosis/viral hepatitis
- ferritin, storage form in iron, is stored in liver so when liver is damaged, iron is released into circulation
high iron intake
- diet (high intake of foods with iron such as red meat, spinach, beans, quinoa, almonds)
hereditary hemochromatosis
- HFE gene is impaired iron detection and regulation
What causes decreased serum iron levels and what are the mechanisms of each?
increases iron loss
- GI tract (colon cancer, peptic ulcer)
- nose w/ severe epistaxis
- menstrual losses/loss in urine
- trauma
- phlebotomy
renal disease
- inadequate EPO production
inadequate absorption
- celiac disease
- IBS
- gastric bypass
- bowel resection
increased demand
pregnancy
decreased intake
- poor dietary intake
- What serves as the storage unit for iron?
- Where is this stored in the body?
- ferritin
- liver, spleen, skeletal muscles, and bone marrow
What % of the body’s iron is stored within ferritin?
15-20%
What is shaped like a hollow sphere with iron stored inside; the iron is stored as Fe (III) and is oxidized to Fe(II) which allows its release through channels of the sphere when demand occurs?
ferritin
When excess dietary iron is absorbed, the body responds by producing more (…) to facilitate iron storage
ferritin
What is one of the more important tests used in the diagnosis of anemia, especially iron-deficiency anemia?
serum ferritin
What is the gold standard for diagnosis of iron deficiency anemia?
serum ferritin
What is a test that all others are compared against and represents the highest validity and reliability?
gold standard
Ferritin is a (…) acute phase reactant
positive
Ferritin is a positive acute phase reactant and increases in cases of what?
- chronic disease
- cancer
- systemic infection
- inflammation or pronounced system stress
What refers to the general state of any anemia in which iron levels are low AND can occur with other forms of anemia, such as anemia of chronic disease?
iron-deficiency anemia
What are the diseases that can lead to anemia of chronic disease (ACD)?
- kidney failure
- cancer
- chronic infectious diseases
- autoimmune disease with widespread systemic inflammation (rheumatoid arthritis/lupus)
ACD has (…) EPO production and (…) hepcidin
- decreased EPO production
- increased hepcidin
What is the master regulator of iron?
hepcidin
When hepcidin is high, it blocks the absorption of iron, resulting in (…) erythropoiesis; when low, it (…) erythropoiesis
- reduced
- favors
What is a true iron deficiency due to increased blood loss and hepcidin-mediated decrease in intestinal iron absorption?
anemia of chronic disease (ACD)
ACD has suppression of erythropoiesis by (…) and has a (…) erythrocyte lifespan
- inflammatory cytokines
- shortened
What are indications for serum ferritin testing?
- to help identify all causes for anemia
- helps to differentiate a pure IDA from ACD+/-IDA
- iron deficiency anemia: ferritin < 10 ng/mL
- anemia of chronic disease: ferritin > 10 ng/mL
- to monitor patients taking replacement iron therapy
- What will ferritin levels be in IDA pts?
- What will ferritin levels be in ACD pts?
- ferritin < 10 ng/mL (low)
- ferritin > 10 ng/mL (high)
When you have a chronic disease, cytokines are increased, which increases acute phase reactants, so there will be a (…) ferritin level
higher
If ferritin is high in anemia, what should you do?
evaluate if the anemia pt has an underlying chronic disease like kidney disease, cancer, or autoimmune
What should be monitored at 4-week intervals until stabilized to check progress with replacement therapy?
serum ferritin
- Increased serum ferritin levels is from what?
- Decreased serum ferritin levels is from what?
- same as increased serum iron; elevated in ACD
- same as decreased serum iron; decreased in pure IDA with ACD as underlying contributor
- What type of molecule is transferrin
- What is transferrin responsible for?
- Were is transferrin synthesized in the body?
- Synthesis of transferrin increases in states of what?
- Synthesis of transferrin decreases when?
- glycoprotein
- iron transport in the body
- in the liver
- in states of iron deficiency
- during bacterial infections
What is thought to prevent transport of iron to bacteria for use?
transferrin
Transferrin can bind to (…) iron molecules and transport to tissues?
two
Instead of measuring transferrin, what will we use?
the TIBC (total iron binding capacity)
Normally, (…)% of the two transferring binding sites are filled by iron
33%
In what condition might more than 33% of the transferrin binding sites be filled?
hemochromatosis
What is useful in the evaluation of anemia and is combined with information of CBC, serum iron, and serum ferritin?
total iron binding capacity
What measures total iron binding sites and is mostly reflective of transferrin levels?
total iron binding capacity
What represents how much iron could be potentially bound to transferrin if all sites (seats) on transferrin were filled?
total iron binding capacity
Total iron binding capacity is also used in evaluation or diagnosis of what?
- anemia of chronic disease
- thalassemia
- hemochromatosis and/or iron toxicity
What are the steps with how total iron binding capacity is performed?
- radioactive iron is incubated with human serum containing transferring & amount of radioactive iron taken up by transferring is serum is measures
- the radioactive iron can only bind to iron-binding sites on transferring that are unoccupied (empty seats) - normally 66%
- In iron deficient states there is less iron in the body, so there are (…) sites for the radioactive iron to bind to, so this (…) TIBC
- In iron overload states, there is too much iron in body, so there are (…) sites for the radioactive iron to bind to, so this (…) TIBC
- more sites, increases TIBC
- fewer sites, decreases TIBC
What causes increased TIBC (open seats without iron in them)?
- iron deficiency anemia of any cause
- pregnancy (due to increased demand/use of iron)
What causes decreased TIBC (lots of iron in their seats)?
- hemochromatosis
- anemia of chronic disease
How does hemochromatosis affect TIBC?
- HFE gene mutation
- increased serum iron & less seats to choose from
- decreases TIBC
How does anemia of chronic disease affect TIBC?
- in chronic disease states, body reduces transferrin level overall (originally to keep iron away from bacteria)
- results in a decrease in total seats available and a reduction in TIBC
What is the normal level of transferrin saturation?
33%
What is the measurement of percentage of transferrin binding sites that are actually bound by iron?
transferrin saturation
- An increase in transferrin saturation represents what?
- A decrease in transferrin saturation results from what?
- increase in iron absorption (higher in iron overdose and hemochromatosis)
- decreased iron absorption (lower in deficiency anemia)
How can you calculate percent saturation (transferrin saturation)?
serum iron/TIBC
If you find low hemoglobin/hematocrit or indices in your patient, what can you draw?
- CBC
- serum iron
- serum ferritin
- TIBC
transferrin saturation is not always ordered because TIBC is the same value but stated differently
What is the cause of iron-deficiency anemia (not related to chronic disease)?
- blood loss
- poor vitamin intake
- poor absorption of iron in small intestine
In iron-deficiency anemia (not related to chronic disease) the body attempts to make more (…) to compensate, resulting in more (…) seats
- transferrin
- empty
What will your lab results be with iron-deficiency anemia (not related to chronic disease)?
- MCV: decreased
- serum iron: decreased
- serum ferritin: decreased
- TIBC: increased (more empty seats)
What is the cause of anemia of chronic disease?
- cancer
- kidney disease
- severe autoimmune diseases
- decreased EPO production in kidneys & production of cytokines during disease
In anemia of chronic disease, the body produces less (…) to keep iron away from infections that cause it?
transferrin
What will the lab results be with anemia of chronic disease?
- MCV: normal in beginning and becomes decreased over time
- serum iron: decreased
- serum ferritin: normal or increased
- TIBC: normal or decreased (less transferrin produced)
Ferritin is a (…) that increased when people are sick
acute phase reactant
