Microcytic Anemia Flashcards
What causes red cells to be microcytic
When there is a problem producing hemoglobin. So when red cells come out of the bone marrow with decreased hemoglobin in each cell that usually leads to small red cells and therefore a microcytic anemia
Usually due to low hemoglobin in red cells
Usually associated with low MCH and MCHC
Low hemoglobin show hypo-chromic RBCs on smear
Low hemoglobin leads to low reticulocyte production (because reticulocytes contain hemoglobin)
What type of anemia could this be
Microcytic anemia
How do hypochromic red cells look like on blood smear
Small in size and have a a lot of paleness at their center
Loss of which components could lead to a microcytic anemia
Loss of iron
Loss of heme (lead, sideroblastic anemia)
Loss of globin chains (thalassemia)
What is the intracellular storage form of iron called
Ferritin
Where is iron stored in the body
Macrophages of liver and bone
The amount of transferrin goes up when the the iron stores in the body are low. Why
The body is producing more transferrin so it can be available to transport whatever iron is around to the places where it’s needed
What is the transport protein of iron
Transferrin
When the body is depleted of iron, ferritin stores are
Low
What are some iron measurements
Serum iron (iron level in the serum)
Total iron binding capacity (amount of transferrin in serum)
Serum ferrritin (amount of storage iron found in the serum)
% saturation (amount of transferrin bound to Fe - iron level/total iron binding capacity)
Explain what occurs in the body in the setting of iron loss
Ferritin decreases followed by an increase in transferrin (TIBC)(body seeks more iron to respond to low iron stores). Then serum iron decreases leading to a low % saturation of iron (low iron levels/high TIBC)
Normal distribution of red cell distribution is
Relatively narrow
Gets wider with iron deficiency anemia
Why is the red cell distribution width wider with iron deficiency anemia
Sometimes the bone marrow is able to to find enough iron to make cells of normal size and other times it can’t find enough so it makes small cells. So as a result you get a wider distribution of cell sizes
When there is a microcytic anemia with a normal red cell distribution width (RDW), what condition could be considered
Thalassemia
What spectrum is useful in distinguishing iron deficiency anemia from thalassemia
Red cell distribution width (RDW)
What are the most common causes of microcytic anemia
Iron deficiency and thalassemia
Spectrum of RBC size
Often increase in iron deficiency
Normal RDW makes iron deficiency unlikely
What could this be
Red cell distribution width
Low RBC/Hgb/Hct
Low MCV (small cells)
Hypochromic (low hemoglobin)
Low MCV/MCH/MCHC
Initially may be normocytic
Low reticulocyte count
What condition might this be
Iron deficiency anemia
Which type of iron in the body is poorly absorbed
Fe3+
Which type of iron in the body is easily absorbed
Heme iron (as part of a heme molecule)
Fe2+
What vitamin helps in converting Fe3+ to Fe2+ to make it easier to absorb iron that’s not in heme
Vitamin C
What are the underlying mechanisms of iron deficiency
Lack of iron uptake by the gut
Loss of iron (usually due to chronic blood loss)
Loss of acid production in the stomach could lead to iron deficiency. How
Loss of acid production in the stomach causes dietary iron to convert to the Fe3+ which the gut finds a hard time absorbing
What conditions could subject patients to loss of production of acid
Proton pump inhibitors
Celiac disease
Status post gastrectomy
What could cause chronic blood loss
Menstruation
Peptic ulcers
Colon cancer
GI blood loss
Negative iron balance (demand for iron exceeds the amount they take in in the diet) due to expansion in the mother’s hemoglobin mass and an increased demand in fetal growth
Prenatal vitamins often contain folate and iron
What could this be
Pregnancy as a cause of iron deficiency
What are the clinical features of IDA
Fatigue, pallor, dyspnoea (common symptoms in all anemia)
Pica (craving for non-food substances, clay or dirt - geophagia, craving for ice - pagophagia)
Restless legs syndrome
How is iron deficiency anemia treated
RBC transfusion if anemia is severe and highly symptomatic (when there is a severely reduced hematocrit or symptoms like a myocardial ischemia)
Oral iron (GI side effects very common - black, green or tarry stools)
IV iron (used when GI side effects prohibit oral replacement or patients with malabsorption or pregnancy (because pregnancy more rapidly repletes iron))
Anemia in association with inflammation
Common in rheumatoid arthritis, lymphoma or other conditions
Usually a mild anemia (Hgb > 10g/dL)
Symptoms from anemia is rare
Normocytic in 75% of cases
Microcytic in 25% of cases
Which condition could this be
Anemia of chronic disease
What is the mechanism of anemia of chronic disease
Triggered by cytokines which increases liver production of hepcidin (acute phase reactant produced by the liver and inhibits iron transport). Thus, iron is trapped in cells as ferritin. Thus, ferritin is usually increased which contrasts with iron deficiency anemia
What could be very helpful for distinguishing iron deficiency from anemia of chronic disease
Ferritin levels
Ferritin levels increased in anemia of chronic disease but reduced in iron deficiency anemia
How is anemia of chronic disease diagnosed
Serum iron is low (thought to be protective - bacteria can use iron for growth and metabolism so hepcidin leads to iron being trapped in a storage form and it makes the serum iron low so that the bacteria can’t use it)
Ferritin not low (normal or increased)
Transferrin (TIBC) is usually low
% saturation is usually low
Low reticulocyte count (low Hgb)
What is the first line therapy for anemia of chronic disease
Treat underlying disease
NSAIDs
Glucocorticoids
Chemotherapy
Usually normocytic and normochronic
Microcytic/hypochromic in about 25% of cases
Does not respond to iron treatment
What condition may this be
Anemia of chronic disease
Nucleated red cell precursors
Iron-loaded mitochondria seen with Prussian blue stain
Perinuclear ring of blue granules
What could this be
Ring sideroblasts
What is the cause of sideroblastic anemia
Failure to make protoporphyrin
Iron cannot bind protorporphyrin to form heme
Iron accumulation in mitochondria
What toxins could often cause sideroblastic anemia (occurs in adults)
Alcohol (mitochondrial poison)
Vitamin B6 deficiency (isoniazid)
Deficiency of what enzyme causes x-linked sideroblastic anemia
ALA synthase
What supplementation is often used as treatment in x-linked sideroblastic anemia
B6 supplementation
ALA synthase requires vitamin B6
How is sideroblastic anemia diagnosed
Microcytic, hypochromic
Iron studies often show iron overload (high serum iron, high ferritin)
Bone marrow biopsy (ringed sideroblasts)
Often clues from history (isoniazid treatment)
What enzymes does lead inhibit
Delta-aminolevulinic acid dehydratase
Ferrochatase
Inhibits heme synthesis
Decreases heme synthesis (microcytic, hypochromic anemia)
Adults: inhalation from industrial work (battery factory)
Children: eating lead-paint or contaminated water
What cause of microcytic anemia could this be
Lead poisoning
What are some clinical features of lead poisoning
Affects many organ systems
GI: abdominal pain, constipation, anorexia
Neurologic: behavioral changes, poor concentration
How is lead poisoning diagnosed
Serum lead level > or = 5mcg/dL (elevated blood lead level)
How is lead poison treated
Remove lead exposure
Chelation therapies (calcium disoriented EDTA (ethylenediaminetetraacetate) and DMSA (succimer) )
