Anemia Flashcards
Hypochromic, Microcytic Anemia
Small RBC
Low Hemoglobin
- Caused by chronic blood lose causing iron deficiency
Megaloblastic Anemia
Large RBC
RBC are few in number
- Caused by Vit 12 / Folic Acid Deficiency
Pernicious Anemia
Normal RBC
RBC are fewer in number
Normal Hemoglobin
- Lack of intrinsic factor, can not absorb Vit B12
= Vitamin B12 Deficiency
Other Blood Cell Deficiencies (Anemia)
Erythrocytes
Neutrophils
Platelets
Causes of Anemia
Deficiency of Nutrients
- Iron
- Folic Acids and Vitamin B12
- B6 and Vitamin C
Bone Marrow Depression
- Less surface for RBC production
Caused by
- Drug toxicity (Clozapine)
- Exposure to radiation
- Bone Marrow Disease
- Reduced production of erythropoietin
Excessive Destruction of RBC
Drug Classes for Anemia Treatment
Hematinic Agent
Hematopoietic Growth Factors
Iron (Anemia)
- MOA
Iron is recycled through the body
Used for RBC production and is mostly contained as Hemoglobin
In 1 day about 0.8% of RBCs are broken down and iron is recycled
Senescent (Old) RBCS are taken up by the reticular system (Spleen and Macrophages) where they are relived of their iron
Iron (Anemia)
- Where?
Most iron is found in hemoglobin (65%)
Half of the rest is found as ferritin in the liver, spleen, and bone marrow
Iron (Anemia)
- Requirements
Men:
- 5 mg
Growing Child and Menstruating Women:
- 15 mg
Pregnant Women
- 2 to 10 times 5mg
Iron can be collected from meat usually present as heme iron (20-40%) for absorption
Iron (Anemia)
- Absorption Process
- Given as Ferric Sulfate (Fe3+)
- Ferric Reductase Enzyme converts it into Ferrous Iron (Fe2+) (GI Tract)
- Transported into plasma and stored intracellularly as ferritin (Duodenum and Jejunum)
- Any iron needed is transported by transferrin
- Transported to liver for storage
- Transported to bone marrow for further hemoglobin and RBC production
Iron (Anemia)
- Absorption Considerations
Iron should be taken on an empty stomach as some foods inhibit iron absorption
Ascorbic Acid (Vitamin C) enhances absorption of Iron
Iron (Anemia)
- Animal Foods vs Vegetarian Foods
Iron from animals is Ferrous
- Larger percent is available for absorption
Iron from vegetarian foods is Ferric
- Smaller percent is available for absorption
Iron (Anemia)
- Highest Sources of Iron
Dry Iron (Desiccated Iron) contains the most. Ex:
- Ferrous Sulfate contains the highest elemental iron
- Ferrous Fumarate contains the 2nd highest elemental iron
Iron (Anemia)
- Clinical Uses
Iron Deficiencies caused by:
- Chronic Blood Loss
- Increased Demand (Pregnant and Early Infancy)
- Inadequate Diet
- Inadequate Absorption (Celiac Disease, After Gastrectomy)
Iron (Anemia)
- Side Effects
Gastrointestinal Disturbances
If large amounts ingested can cause toxic effects (People with Thalassaemia are especially sensitive)
Folic Acid
- MOA
Folic Acid is reduced by Dihydrofolate Reductase
- Yields FH2 and FH4
–> These co-factors transfer methyl groups in several important metabolic pathways
–> FH 4 is essential for DNA synthesis
Vitamin B12
- MOA
Converts Methyl-FH4 to FH 4
Converts Homocysteine to Methionine
FH 4 is essential for DNA synthesis
Vitamin B12
- Indications
Megaloblastic and Macrocytic Anemia
- Caused by Vitamin B12 and Folic Acid deficiency
Pernicious Anemia
- Caused by Vitamin B12 deficiency
Folic Acid
- Indications
Megaloblastic and Macrocytic Anemia
- Caused by Vitamin B12 and Folic Acid deficiency
Pernicious Anemia (Combine with B12)
- Caused by Vitamin B12 deficiency
Prevent Methotrexate Toxicity
Erythropoietin
- MOA
Epoetin Alfa
Stimulates the production of RBC
- Synthesized in kidneys with small amount coming out of liver
- Released in response to hypoxia
- Is released by liver
- Binds to receptor on committed erythroid progenitor cells in bone marrow
- Binding to receptor on bone marrow induces intracellular effects through tyrosine kinase
- Inhibition of Apoptosis of RBC
- Also promotes proliferation through Janus Protein Kinase-2 Pathways (JAK2)
Result:
- Inhibits Apoptosis of RBC
- Promotes proliferation of RBC
Erythropoietin
- Anemia
Renal Failure can cause Erythropoietin to become low which will result in anemia
Erythropoietin
- Indication
Anemia
Renal Failure
Chemotherapy and AIDS
Erythropoietin
- Adverse Effects
Iron Deficiency: Iron stores can not keep up with RBC production
Thrombosis: Patients on dialysis are at risk
Hypertension: Erythropoietin interacts with Angiotensin II which is vasoactive
Seizures: Patients on dialysis receiving epoetin Alfa are at risk
Granulocyte Colony Stimulating Factors
- MOA
Filgrastim
- Bind to receptors on myeloid progenitor cells in Bone Marrow
- Affecting production of RBCs, Platelets, Granulocytes, and Monocytes
- Mediated by Janus Protein Kinase/Signal Transducers and Activators of Transcription Pathway (JAK/STAT)
G-CSF:
- Stimulates proliferation and differentiation of progenitors that become neutrophils
Granulocyte-Monocyte Colony Stimulating Factors
- MOA
Sargramostim
- Bind to receptors on myeloid progenitor cells in Bone Marrow
- Affecting production of RBCs, Platelets, Granulocytes, and Monocytes
- Mediated by Janus Protein Kinase/Signal Transducers and Activators of Transcription Pathway (JAK/STAT)
M-CSF
- Stimulates production of neutrophils and monocytes
- Stimulates the actions of neutrophils, monocytes, and eosinophils
–> Actions: Phagocytosis, Superoxide production, and cell-mediated toxicity
Granulocyte-Monocyte Colony Stimulating Factors
- Controls what actions?
- Phagocytosis
- Superoxide production
- Cell-mediated toxicity
Colony Stimulating Factors
- Indications
Given with Myelosuppressive Chemotherapy
Severe Chronic Neutropenia
Prevention and Treatment of Neutropenia in HIV Infection
Colony Stimulating Factors
- Side Effects
Bone Loss: G-CSF increases Osteoclast activity
Joint Pain: G-CSF stimulate cytokine release
Renal Dysfunction: G-CSF cause renal impairment through clumping of leukocytes in kidney
Acute Respiratory Distress: G-CSF can lead to accumulation and activation of neutrophils in lung
Splenomegaly or Splenic Rupture: G-CSF can cause splenic ruptures
Sickle Cell Crises: Fatal in patients with Sickle Cell disorders as their Hemoglobin can not carry oxygen
Megakaryocyte (Thrombopoietic) Growth Factors
- MOA
Oprelvekin (IL-11)
- Stimulate growth of megakaryocytic progenitors
- Increase number of peripheral platelets
Megakaryocyte (Thrombopoietic) Growth Factors
- Indication
Treats thrombocytopenia after cancer chemotherapy
