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195 Cards in this Set
- Front
- Back
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Microcytic anemias: Definition
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Mean Corpuscular Volume less than 80 cubic micrometers
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Macrocytic anemias: Definition
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Mean Corpuscular Volume more than 100 cubic micrometers
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Normocytic anemias: Definition
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Mean Corpuscular Volume between 80 and 100 cubic micrometers
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Corrected reticulocyte count less than 3%: Bone marrow status
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Ineffective erythropoiesis
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Corrected reticulocyte count greater than or equal to 3%: Bone marrow status
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Effective erythropoiesis
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Regular hematocrit level
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45%
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Stimuli for erythropoietin
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-hypoxemia
-left-shifted oxygen binding curve -high altitude |
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Where is erythropoietin made?
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Endothelial cells of peritubular capillaries
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Corrected reticulocyte count: Definition
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(Actual hematocrit/45) * reticulocyte count
If polychromasia, divide by 2. |
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Reticulocyte count: What does it measure?
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-Effective erythropoiesis
-Must be corrected for degree of anemia |
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How long does it take for reticulocyte count to increase after blood loss?
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5-7 days.
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Microcytic (less than 80 cubic micrometers) anemias: List
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-Iron deficiency
-Anemia of chronic disease -Thalassemia (alpha and beta) -Sideroblastic anemia |
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Sideroblastic anemias: List
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-Chronic alcoholism (most common)
-Pyridoxine (B6) deficiency -Lead poisoning |
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Anemias of chronic disease: List
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-Chronic inflammation (eg rheumatoid arthritis, TB)
-Alcoholism -Malignancy |
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Type of anemia: Iron deficiency
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Early-stage: Normocytic with a low reticulocyte count.
Later-stage: Microcytic |
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Type of anemia: Anemia of chronic disease
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Early-stage: Normocytic with a low reticulocyte count.
Later-stage: Microcytic |
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Type of anemia: Thalassemia
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Microcytic
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Sign: Dark blue iron granules around the nucleus of developing normoblasts
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Ringed sideroblasts, indicating sideroblastic anemia
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Type of anemia: Sideroblastic
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Microcytic
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Type of anemia: Pyridoxine deficiency
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Sideroblastic, so Microcytic
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Type of anemia: Lead poisoning
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Sideroblastic, so microcytic
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Type of anemia: Alcoholism
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Either sideroblastic, or anemia of chronic disease. Either way, microcytic.
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Type of anemia: Rheumatoid arthritis
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Chronic inflammation, so anemia of chronic disease, so microcytic
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Type of anemia: TB
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Chronic inflammation, so anemia of chronic disease, so:
Early: Normocytic with low reticulocyte count Later: Microcytic |
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Type of anemia: Malignancy
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Anemia of chronic disease, so microcytic
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Type of anemia: Vitamin B12 deficiency
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B12 deficiency or metabolism defect means megaloblastic macrocytic
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Type of anemia: Vitamin B12 metabolism defect
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B12 deficiency or metabolism defect means megaloblastic macrocytic
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Type of anemia: Folate deficiency
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Folate deficiency or metabolism defect means megaloblastic macrocytic
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Type of anemia: Folate metabolism defect
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Folate deficiency or metabolism defect means megaloblastic macrocytic
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Type of anemia: DNA synthesis defect
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Macrocytic megaloblastic
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Type of anemia: Liver disease
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non-megaloblastic macrocytic
or normocytic with a normal reticulocyte count and an extrinsic RBC defect |
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Type of anemia: Cytotoxic drugs
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Macrocytic non-megaloblastic
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Type of anemia: Hypothyroidism
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Macrocytic non-megaloblastic
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Type of anemia: Stress erythropoiesis
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Macrocytic non-megaloblastic
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Type of anemia: Blood loss
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Normocytic
Reticulocyte count -Less than one week: low -More than one week: normal |
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Type of anemia: Aplastic anemia
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Normocytic with a low reticulocyte count
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Type of anemia: Renal disease
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Normocytic
Reticulocyte count -low -normal: extrinsic defect hemolytic anemia |
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Type of anemia: Absence of erythropoietin
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Normocytic with a low reticulocyte count
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Type of anemia: Replacement of bone marrow
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Normocytic with a low reticulocyte count
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Type of anemia: Hereditary spherocytosis
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Membrane defect, so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Hereditary elliptocytosis
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Membrane defect, so:
Normocytic with normal reticulocyte count |
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Type of anemia: South-East Asian Ovalocytosis
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Membrane defect, so:
Normocytic with normal reticulocyte count |
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Type of anemia: Paroxysmal Nocturnal Hemoglobinuria
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Membrane defect, so:
Normocytic with normal reticulocyte count |
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Type of anemia: G6PD deficiency
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Metabolism defect so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Glutathione deficiency
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Metabolism defect so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Pyruvate kinase deficiency
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Metabolism defect so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Sickle cell disease
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Hemoglobin defect so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Drugs
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Normocytic hemolytic anemia with normal reticulocyte count
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Type of anemia: Chemical/Physical agents
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Normocytic hemolytic anemia with normal reticulocyte count
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Type of anemia: Snake bite venom
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Toxin so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Clostridial toxin
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Toxin so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Burns
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Injury so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Fresh water drowning
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Injury so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Hypersplenism
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Normocytic hemolytic anemia with normal reticulocyte count
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Type of anemia: Cold antibody type
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Autoimmune so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Warm antibody type
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Autoimmune so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Alloimmune
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Immune so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Drug induced immune hemolytic anemia
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Drug-induced and/or immune so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Vasculitis
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Red cell fragmentation syndrome so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Mechanical devices
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Red cell fragmentation syndrome so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Microangiopathic hemolytic anemia
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Red cell fragmentation syndrome so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: Macroangiopathic hemolytic anemia
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Red cell fragmentation syndrome so:
Normocytic hemolytic anemia with normal reticulocyte count |
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Type of anemia: March hemoglobinuria
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Normocytic hemolytic anemia with normal reticulocyte count
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How do you identify a reticulocyte?
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-Supravital stain (new methylene blue)
-RNA filaments |
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How do you get hemoglobin from hematocrit?
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hb = (1/3)hct
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For every unit of packed red blood cells, you increase:
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hemoblobin by 1
hematocrit by 3 |
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Most common cause of anemia in the world
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iron deficiency
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Most common cause of iron deficiency
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GI bleed
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RDW: Definition
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RBC Distribution Width
Checks uniformity of size. |
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Low MCV with Increased RDW
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-Increases variation in size: Mixture of normocytic and microcytic RBCs
-Iron deficiency |
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Spherocyte: membrane defect
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Too little membrane
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Target cell: membrane defect
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Too much membrane so more hemoglobin can collect in the middle
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Target cell: markers for what?
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-Alcoholism
-Hemoglobinopathy |
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How to identify a microcytic cell
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Too much central pallor
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How to identify a spherocyte
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-No central pallor
-Small and red |
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Spoon nails: Sign of?
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Iron deficiency
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Cheilosis: Sign of?
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-Iron deficiency
-Riboflavin deficiency |
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Pale conjunctiva: Sign of?
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Low hemoglobin
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No red in palmar creases: Sign of?
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Iron deficiency
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Discoloration of gum margin: Sign of?
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Known as "lead lines". A sign of lead poisoning.
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Normal serum iron
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About a 100 (like the alveolar oxygen)
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Serum ferritin: what is it?
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Soluble circulating form of iron storage
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Serum ferritin: what does it represent?
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Amount of iron in bone marrow
-Best overall screening test |
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Carrying protein for iron
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Transferrin (Carries iron)
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TIBC: What does it measure?
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Transferrin
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What does increased TIBC indicate?
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Increased transferrin synthesis by liver, so decreased iron stores in the bone marrow.
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What does decreased TIBC indicate?
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Decreased transferrin synthesis by liver, so increased iron stores in the bone marrow.
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Define: % iron saturation
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Serum iron/TIBC
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Normal TIBC
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300
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Normal % iron saturation
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33%
=normal serum iron/ normal TIBC = 100/300 |
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Hemoglobin type: 2 alpha chains and 2 beta chains
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HbA
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Hemoglobin type: 2 alpha chains and 2 delta chains
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HbA2
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Hemoglobin type: 2 alpha chains and 2 gamma chains
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HbF
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Mechanism of pathogenesis in Anemia of Chronic Disease
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Bugs increase reproduction with iron, so body assumes there is a bacterial infection, and keeps iron away from bacteria.
Iron is normally stored in macrophages in bone marrow. It's kept away from RBCs. |
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Where does Hemoglobin synthesis begin?
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Mitochondria of RBC
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First reaction of Hemoglobin synthesis
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Succinyl CoA + Glycine (catalyzed by ALA synthetase) yields delta-ALA
all in the mitochondria |
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What kind of neurotransmitter: Glycine
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Inhibitor of muscle.
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What toxin blocks glycine?
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Tetanus
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Rate limiting step in Heme synthesis
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delta-ALA synthesis
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What enzyme does heme inhibit?
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ALA synthase
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Why does alcoholism cause sideroblastic anemia?
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Alcohol is a mitochondrial toxin.
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What are sideroblasts?
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Overloaded mitochondria
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Why does B6 deficiency cause sideroblastic anemia?
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Can't form CoA, so can't form succinyl CoA, so can't do first reaction of heme synthesis.
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Mechanism of lead poisoning
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Lead denatures ferrochelatase --> Can't form heme
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Test for lead poisoning
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Blood lead levels
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What are the main groups that we see alpha-thalassemia?
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-Southeast asians
-Black Americans |
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What are the main populations we see beta-thalassemia in?
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-black Americans
-Greeks -Italians |
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% of Hb that is: HbA
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95%
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% of Hb that is: HbA2
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2%
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% of Hb that is: HbF
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1%
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alpha-thalassemia: mode of inheritance
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Autosomal recessive
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alpha-thalassemia: pathogenesis
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problem making alpha chains
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alpha-thalassemia: electropheresis results
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all normal proportions (all Hbs decreased)
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alpha-thalassemia: one gene deletion
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Silent carrier
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alpha-thalassemia: two gene deletions
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alpha-thalassemia minor
-mild anemia (microcytic because globin is decreased) |
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alpha-thalassemia: three gene deletions
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Four beta chains form making HbH. Found in electropheresis.
Called HbH disease |
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alpha-thalassemia: four gene deletions
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Four gamma chains form making Hb Bart. Found in electropheresis. Called hydrops fetalis.
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Why is choriocarcinoma increased in far east?
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1. Increased alpha thalassemia rates
2. Increased spontaneous abortions due to Hb Bart 3. Increased choriocarcinoma |
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alpha-thalassemia: treatment
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None
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beta-thalassemia: permutations of problems
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beta by itself: normal number of beta chains
beta with a + sign: not making enough, but are making beta with a 0: not making it at all |
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beta-thalassemia: mode of inheritance
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autosomal recessive
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beta-thalassemia: what is the genetic association with severe anemia?
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Nonsense mutation with formation of a stop codon
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beta-thalassemia: what hemoglobin will decrease
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HbA
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beta-thalassemia: what hemoglobins will increase
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HbA2 and HbF
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beta-thalassemia: electropheresis results
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Will show increased HbA2 and HbF with decreased HbA
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beta-thalassemia: treatment
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none
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Cooley's anemia: disease type
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Not making any beta chains (beta 0)
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Cooley's anemia: Prognosis
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Will not live past 30
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Main way to tell Anemia of chronic disease from Iron deficiency
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Ferritin levels
Low: Iron deficiency High: Anemia of chronic disease |
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Stain used to find Ringed Sideroblasts
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Prussian Blue
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Histologic sign associated with Lead poisoning
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Coarse basophilic stippling
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Where does stippling come from?
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Inability to break down ribosomes.
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Classic presentation of lead poisoning in children
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-Severe abdominal colic
-Cerebral edema (convulsions, etc) -Severe microcytic anemia -Failure to thrive |
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What is seen on a flat plate?
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-Iron (if kid took iron tablets)
-Lead (from intestine) -Mercury |
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Mechanism of lead poisoning
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Buildup of delta-ALA, leading to neuronal toxicity
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Presentation of lead poisoning in adults
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-Workers from automobile factory or moonshine makers or pottery painters
-Abdominal colic -Diarrhea -Neuropathy (slapping gait, drops (radial, ulnar palsies), claw hand |
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What is the disease: Serum Iron (low), TIBC (high), % iron saturation (low), Serum ferritin (low)
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Iron deficiency
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What is the disease: Serum Iron (low), TIBC (low), % iron saturation (low), Serum ferritin (high)
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Anemia of Chronic Disease
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What is the disease: Serum Iron (normal), TIBC (normal), % iron saturation (normal), Serum ferritin (normal)
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Thalassemia
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Sideroblastic anemias: Iron status
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Iron overload
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Hemochromatosis: Iron status
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Iron overload
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Hemosiderosis: Iron status
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Iron overload
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What is the disease: Serum Iron (high), TIBC (low), % iron saturation (high), Serum ferritin (high)
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Iron overload (Sideroblastic anemia, hemochromatosis, hemosiderosis)
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What do B12 and folate deficiencies most immediately not allow production of?
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dTMP (using Thymidylate synthase) leading to lack of DNA production
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What is the size of immature nuclei?
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Nucleus gets smaller and more condensed due to increased DNA?
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What are cells called with immature nuclei?
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Megaloblasts
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Why is B12 called Cobalamin?
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It has cobalt in it.
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What is the circulating form of Folate?
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N5-methyl-Tetrahydrofolate
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What does B12 do in folate metabolism?
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B12 removes methyl group from N5-methyl-THF to make THF
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What happens when you add a methyl group to homocysteine?
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Methionine
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Which amino acid is used for one-carbon transfers?
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Methionine
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What are serum homocysteine levels in B12 or THF deficiency?
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High
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Why do high homocysteine levels produce thromboses?
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It damages endothelial cells predisposing them to thrombosis.
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What is the most common cause of high homocysteine levels?
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Folate deficiency
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Drugs which inhibit folate metabolism
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5-fluorouracil (which inhibits thymidylate synthase),
Methotrexate and TMP-SMX (which both inhibit DHF reductase), Phenytoin (which inhibits intestinal conjugase), Oral contraceptives and alcohol (which both inhibit of uptake of monoglutamate in jejunum, but alcohol also inhibits the release of folate from the liver) |
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What happens if B12 is missing to Methylmalonyl-CoA?
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It builds up, because it cannot form succinyl-coA
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Sensitive test for B12 deficiency
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Methylmalonic acid
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What is methylmalonic acid level a test for?
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B12 deficiency
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What is the mechanism of B12 deficiency leading to neurologic deficiencies?
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Propionyl CoA builds up, and myelin production is deficient.
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What are the neurologic effects of B12 deficiency?
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Dementia, demyelination of posterior columns (proprioception and vibratory sensation) and lateral corticospinal tract (upper motor neuron problems)
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Serum levels to order in dementia
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TSH to rule out hypothyroidism and B12 to rule out B12 deficiency
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Where is B12 gotten from?
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Animal products
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What is the first factor B12 binds to?
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R factor
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What does R factor do?
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It protects B12 from being destroyed?
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Where does intrinsic factor come from?
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Parietal cells in the gastric body and fundus.
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Where is vitamin B12 absorbed?
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Terminal ileum
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What deficiencies are found in Crohn's disease?
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Bile salts and vitamin B12 (both due to reabsorption problems in terminal ileum)
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Most common cause of B12 deficiency
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Pernicious anemia
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What is the mechanism in pernicious anemia?
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Autoimmune destruction of parietal cells and intrinsic factor
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What is achlorhydria?
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Atrophic gastritis of the body and fundus leading to :
lack of acid which leads to gastric adenocarcinoma AND bacterial overgrowth from stasis |
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Causes for achlorhydria
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Tapeworms, pernicious anemia, folate deficiency
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Eaten form of folate
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Polyglutamate
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What converts polyglutamate to monoglutamate?
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Intestinal conjugase
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What drug blocks intestinal conjugase?
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Phenytoin
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What is the mechanism of Phenytoin?
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Blocks intestinal conjugase
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What blocks absorption of monoglutamate from jejunum?
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Alcohol and oral contraceptives
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What are hypersegmented neutrophils with neurologic deficiency diagnostic for?
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Vitamin B12 deficiency
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What are hypersegmented neutrophils without neurologic deficiency diagnostic for?
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Folate deficiency
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What is a characteristic CBC finding in macrocytic anemia?
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Pancytopenia
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Schilling's test
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1. Give radioactive B12 by mouth
2. 24 hour urine collection 3. If nothing comes out, can't reabsorb B12. 4. Then give radioactive B12 and intrinsic factor together by mouth. 5. 24 hour urine collection. If something comes out, it's pernicious anemia. If not, go to step 6. 6. Give broad-spectrum anti-biotic. If you see B12 in the urine, you have bacterial overgrowth. If not, go to step 7. 7. Take pancreatic extract with radioactive B12. If you get B12 in the urine, they have chronic pancreatitis. If not, it could be Crohn's disease, a worm, or some other cause. |
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Stages of iron deficiency
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1. Ferritin goes down
2. Iron decreases, TIBC increases, % iron sat decreases 3. Mild normocytic anemia 4. Microcytic anemia |
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What test must be ordered to confirm aplastic anemia?
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Bone marrow study
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Most common cause of aplastic anemia
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Idiopathic
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Most common known cause of aplastic anemia
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Drugs (Indomethacin, Phenylbutazone, Thyroid-related drugs, Chloramphenicol)
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Second most common known cause of aplastic anemia
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Hepatitis C
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Most common infective cause of pure RBC aplasia
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Parvovirus
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Mechanisms of hemolysis
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1) Intravascular hemolysis
2) Extravascular hemolysis which is more common |
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What is the mechanism of extravascular hemolysis?
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Macrophages kill them at the Cords of Bilroth
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What are some causes of RBCs being phagocytosed at the cords of Bilroth?
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IgG or c3b on the surface,
or Howell-Jolly bodies inside, or an abnormal shape (such as spherical or sickle cell) |
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End product of phagocytosing an RBC
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Unconjugated bilirubin
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Clinical finding in extravascular hemolysis
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Jaundice, which is due to unconjugated bilirubin due to macrophages phagocytosing red blood cells.
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Causes of intravascular hemolysis
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1) Congenital bicuspid aortic valve.
2) IgM binding to surface and activating complement system |
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End product of intravascular hemolysis
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Hemoglobin
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Name of protein which binds free hemoglobin in blood
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Haptoglobin
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Clinical findings in intravascular hemolysis
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1) Hemoglobinuria
2) Low haptoglobin levels |
