Microcytic, Macrocytic And Aplastic Anemias Flashcards
How is iron transported in plasma?
By a glycoprotein called transferrin synthesized in the liver
- normally 1/3 saturated which makes average serum levels in men and women 120 and 100/dL respectively
Ferritin
Protein-iron complex that is found in spleen, bone marrow and skeletal muscles via macrophages
Due to macrophages breaking down RBCs
High levels of ferritin in serum implies RBC damage
How large is the normal zone of pallor in normal RBCs?
1/3 cell diameter
What are the 3 ways to classify anemia’s?
- amount of hematocrit in the blood (%)
- alterations in the RBC morphology/size
(Normocytic, microcytic and macrocytic) - degree of reflective color (normochromic or hypochromic)
What are the most useful measurements for red blood cells?
Mean cell volume (MCV)
- normal = 82-96
Mean Cell Hemoglobin (MCH)
- normal = 27-33
Mean cell hemoglobin concentration
- normal = 33-37
Microcytic hypochromic anemia’s
Caused by disorders of hemoglobin synthesis, usually due to iron deficiencies
Requires at least 1 of 3 components in sufficient amounts
- iron
- protoporphyrin
- globin
- decrease in any 3 causes microcytic anemia’s*
Most common form of anemia in hospitalized patients
Macrocytic anemia’s
Usually stem from abnormalities that impair Maturation of erythroid precursors in bone marrow
- usually folate or Vit B12 deficiencies
- both folate and Vit. B12 are required for DNA synthesis and hemopoiesis by enabling methionine and thymidylate synthase enzymes
Normochromic, normocytic anemia’s
Diverse etiologies and have a wide variety of specific abnormalities to the share of RBCs
Iron deficiency anemia
- Deficiency of iron is the most common deficiency in the Underdeveloped world and the most common reason for anemia*
- chronic blood loss it the most common cause of iron deficiency in the developed world*
- it is assumed, until proven otherwise, that if a patient in the developed world has iron deficiency, it must be attributed to GI blood*
Can be caused by 1 of 4 causes
- dietary lack
- impaired absorption
- increased requirement
- chronic blood loss
ALWAYS PRODUCES HYPOCHROMIC MICROCYTIC ANEMIA
What is the recommended daily iron requirement for men and women?
7-10 mg =. Men
7-20 mg = women
- these values are due to only 10-15% of ingested iron is absorbed properly
- at least 1 mg must be absorbed from the diet/day*
- increased requirement in premenopausal/ pregnant women, growing infants and children*
Organic vs inorganic iron
Red meat = organic form and is easily absorbed in diet (its in heme form)
Plant iron = inorganic form and is poorly absorbed in diet (in non heme form)
- populations that eat more plants than meat are at risk for anemia*
What are possible causes of impaired absorption of iron
Spure
Chronic diarrhea
Gastrectomy
Celiac disease
What is the most diagnostically significant finding for iron deficiency?
Disappearance of stainable iron in macrophages in the bone marrow
- RBCs being destroyed dont have iron so the macrophages wont stain either in iron deficiencies
Poikilocytosis
Small elongated red blood cells that are also called “pencil cells”
- seen in iron deficiencies and thalassemias
Clinical features of acute iron deficient anemia
Weakness
Malaise
Easily fatiguable
Dyspnea
- also present with symptoms based on the underlying causes of the anemia (i.e GI bleeds)*
Clinical features of chronic iron deficiency anemia
Koilonychia (brittle concaved looking nails)
Alopecia (paleness)
Atrophied changes in tongue and gastric mucosa
Intestinal malabsorption
Diagnostic criteria for iron deficiency anemias
Hypochromic and microcytic RBCs
Low MCV
Low serum ferritin
Low serum iron levels
Low transferrin saturation ( will lower before symptoms arise)
Elevated platelet count (not completely understood why)
responses to iron therapy
Anemia’s of chronic disease
Anemia’s that resemble iron deficiencies but are actually caused by suppression of erythropoiesis sue to systemic inflammation examples: - chronic microbial infections - chronic immune disorders - neoplasms
Stem from high levels of plasma hepcidin (blocks transfer of iron to erythroid precursors by down regulating ferroportin in macrophages)
- this is caused due to high IL-6 levels seen in inflammatory states
- Most common in hospitalized patients*
Clinical features of anemias of chronic disease
Serum iron levels are low
Plasma hepcidin are high
RBCs slightly hypochromic and microcytic
Storage levels of iron in bone marrow and ferritin are high, but overall decrease in measured iron-binding capacity
- treatment of anemia of chronic disease is commonly done via administration of erythropoietin, however the only way to reverse it is to cure the underlying cause*
Megaloblastic anemia
Type of macrocytic anemia caused by a deficiency in thmidylate synthatase enzymes which lowers the free amount of thymidine and thymidylate (building block of DNA)
- shows nuclear-cytoplasmic asynchrony disorder and causes premature apoptosis of RBCs in red bone marrow
(Ineffective hematopoiesis)
Clinical features of macrocytic anemias
Pancytopenia (low granulocyte and platelet precursors)
Hypercellular megaloblastic erythroid progenitors
RBCs appear ‘egg shaped”
Presence of hyper-segmented neutrophils in blood (5-6)
MCV = > 110 fL.
Folate deficiency anemia
Almost always results from Inadequate dietary intake
- most common in elderly, vegans, Pregnant women
Can results from absorption/ metabolism dysfunction
- high acidic foods in diets can causes an absorption disorder
- Drugs can as well such as methotrexate and phenytoin
- celiac disease and tropical sprue are the most common absorption issues
Function of folate
Converts dihydrofolate -> tetrahydrofolate via dihydrofolate reductase
Tetrahydrofolate acts and an acceptor and donor for synthesis of dTMP
-dTMP is required to synthesize hemoglobin and membrane proteins in RBCs as well as DNA replication
Clinical features of folate deficiency anemia
Insidious onset w/ weakness and easily fatigued
Often seen in alcoholics
GI symptoms (upset stomach, sore tongue/throat, diarrhea etc.)
- NO neurological abnormalities occur (unlike Vit. B12 deficiencies*
Only way to really make the diagnosis is blood smears showing megaloblastic cells and measuring serum folate/ B12 levels.
Vit B12 (cobalamin) deficiency anemia
Caused by Vit. B12 deficiencies usually via absorption/metabolic disorders
- almost never found in low dietary intake, except for vegans (avoiding milk and eggs)
Takes years form the beginning of onset to diagnose. (Due to very large stores of Vit B12 in the liver)
Pernicious anemia
Most common cause of vitamin B12 deficiency anemia
Caused by an autoimmune attack on gastric mucosa that suppresses intrinsic factor production. ( assumed to be T-cell initiated)
- histologically shows chronic atrophic gastritis and a loss of parietal cells and marked increases in lymphocytes in the mucosa
Antibodies in the serum block binding of Vit B12 to intrinsic factor/ cubilin
Vitamin B12 deficiency causes for malabsorption specifically
Gastrectomy
Ileal resection ( loss of intrinsic factor)
Chronic disease
Tropical sprue and whipped disease
Gastric atrophy
achlorhydria (low hydrochloride acid in the stomach)
Function of Vit B12 in blood
Recycles tetrahydrofolate
( form that is needed for DNA synthesis)
deficiencies can show demyelination and degeneration of the posterior/lateral columns of the spinal cord
Clinical features of Vit. B12 deficiencies
Pallor
Easy fatiguable
Dyspnea
red tongue
Symmetric numbness, tingling burning feet or hands
Unsteady gait/ loss of position of sense
4 laboratory findings of vitamin B12 deficiencies
1) low serum, Vit B12 levels
2) normal/ slightly elevated serum folate levels
3) moderate to serve macrocytic anemia
4) leukopenia with hypersegmented granulocytes
* show pernicious anemia with serum antibodies to intrinsic factor*
Normochromic/ normocytic anemia
Normal MCV
Increased reticulocyte counts for hemolytic anemia
Decrease reticulocyte counts for aplastic anemia
Aplastic anemia
Multipotent myeloid stem cells are suppressed which leads to bone marrow failure and pancytopenia
- bone marrow has high levels of fat and low red bone marrow
Most aplastic anemia is idiopathic but drug induced is common when exposed to cancer chemo/whole body irradiation,or hypersensitivity reactions
Viral hepatitis is a rare cause but possible as well
Specific inherited abnormalities that underlie aplastic aplasia
Fanconi anemia: rare autosomal disorder caused by defects in a multi-protein complex that is required for DNA repair
Marrow hypofunction: becomes evident early in life and is often seen via hypoplasia of kidney, spleen and bone marrow
Telomerase defects (always abnormally short telomeres in 510%)
Two mechanisms possibly invoked during aplastic anemia
Extrinsic immune-mediated suppression of marrow progenitors
- stem cells are first antigenically altered by drugs, infectious agents or environmental issues
- promotes cellular immune response (TH1) that promotes IFN-y and TNF that suppress and kill hematopoietic progenitors
- treated via immunosuppressive therapy against T cells
Intrinsic abnormality of stem cells with telomerase
- 5-10% of patients
- leads to premature senescence of hematopoietic stem cells
Neoantigens
Genetically altered stem cells via intrinsic pathway in aplastic anemia release neoantigens which attach T cells and cause them to release TNF and IFN-y
shows connection between intrinsic and extrinsic pathways
Clinical features of aplastic anemia
Can occur any age or any sex equally
- insidious onset
Pancytopenia and reticulocytopenia occurs with anemia induced weakness, pallor and dyspena
Thrombocytopenia induced petechiae and ecchymoses
Sudden random onset of chills and fevers
bone marrow biopsy is the only way to confirm
Prognosis and treatment of aplastic anemia
Prognosis varies however all treatment usually requires bone marrow transplantation (75% survival)
Older patients or no donor = immunosuppressive therapy but this doesn’t cure, only prevents further damage
Pure red cell aplasia
Only erythroid progenitors are completely absent from marrow
Often presents with cancers, autoimmune disorders and parvovirus B19 infections
- all of these will also produce autoimmune issues except parvovirus B19
Parvovirus B19 in pure red cell aplasia
Initially attacks red cell progenitors, resulting in pure red cell aplasia.
- usually clears up within 1-2 weeks and because of this is temporary
Moderate to severe hemolytic anemias sickle cell anemia and hereditary spherocytosis will produce aplastic crisis
- if compounded with autoimmunity, will produce chronic red cell aplasia
