Anemia Flashcards
Porphyria
disorder of heme synthesis due to abnormal accumulation of porphyrin precursors or porphyrins in the bone marrow/liver
Thalassemia
reduced/absent synthesis of globin chains
Structural hemoglobinopathy
synthesis of abnormal globin chains
Fe deficiency anemia pathophys
Extracorporeal blood loss most common reason
Poor iron uptake/poor nutrition less common
women - 1 mg/day during menstruation, 1000 mg/pregnancy
Infancy: primary dietary cause
Pernicious anemia pathophys
Gastric parietal cells damaged by autoimmune processes, leading to:
- loss of gastric acid (required for release from food)
- loss of IF (required for binding + effective absorption from terminal ileum)
- major antigen appears to be H/K ATPase
- many also have antibodies against IF, or IF-cobalamin complex
- slower DNA synthesis but accumulation of protein –> megaloblastic
- also affects other rapidly dividing cells; e.g. glossitis
Pernicious anemia age of onset
may be as late as 30’s
Folate deficiency anemia pathophys
Folate reserves limited - deficiency develops rapidly (takes 6-8wks for reserve to completely diminish)
Supplemented in foods - def rarely seen in Canada
Cannot synthesize enough thymine
Accumulation of protein products without DNA synthesis - megaloblastic anemia
Lead poisoning anemia pathophys
Interferes with synthesis of heme
Seen more commonly in children (small, growing)
Thalassemia pathophys
Imbalance of globin production
Accumulation of normal globin - hemolysis
Increased synthesis due to erythropoietin, but they hemolyze
manifest at around 6 months of age
Beta thalassemia pathophys
Intramedullary destruction of RBC precursors
Hemolysis of mature RBCs with alpha globin inclusions
Hypochromic, microcytic cells due to overall reduction of heme production
degradation products of free alpha also plays a role in destruction
Increase in HbF to compensate
Alpha thalassemia pathophys
Similar to beta
No increase in HbF because alpha is a component of HbF
Excess gamma/beta chains are soluble - do not see severely ineffective erythropoiesis
BUT beta4 tetramers precipitate as red cells age - see reduced RBC life span due to inclusions in adulthood
Anemia of chronic disease pathophys
- increased erythrocyte destruction due to activation of host factors (e.g. macrophages)
- some cytokines exert a suppressive effect on erythrocyte colony formation
- less EPO than other types of anemia
- inflammation could lead to EPO resistance?
- IL6 induces hepcidin, iron unavailable for developing RBCs
- During inflammation release of iron from macrophages and the liver is markedly inhibited
Aplastic anemia pathophys
Injury to/abnormal expression of the hematopoietic stem cell due to pharmacologics, toxins, radiation, chemotherapy, etc
Bone marrow becomes hypoplastic - leading to anemia or pancytopenia
Most commonly: T-cell mediated autoimmunity
SLE - IgG against stem cell
Hereditary spherocytosis pathophys
Most common disorder of the RBC membrane (spectrin, ankyrin, paladin, Rh-associated glycoprotein)
Autosomal dominant
Decreased membrane elasticity - blebs removed in the spleen - RBCs lose biconcave shape, becomes more spherical
Eventually, spherical RBCs detained and phagocytosed in the narrow fenestrations of the spleen
Sickle cell anemia pathophys
Glu-Val substitution in the sixth aa of beta globin gene
Conformational change in Hb tetramer - polymerizes under acidic/deoxygenated conditions
Adhesion to endothelial receptors + physical rigidity/distortion leads to occlusion of microvasculature
Leads to tissue hypoperfusion
Some sickling is reversible, but past a certain point they hemolyze
Warm AIHA pathophys
RBCs coated with IgG autoantibodies with or without complement proteins
Trapped in spleen or Kupffer cells (liver)
Macrophages “nibble” leading to spherocytosis, or if the antibody amount is high the whole cell is phagocytosed
Most damage done to RBC in extravascular compartment
Cold AIHA pathophys
Cold agglutinins only ppt above 30C - most are not clinically significant
Depends on the ability of the cold agglutinins to bind RBCs and activate complement at body temperature = complement fixation
Leads to 1) direct lysis and 2)opsonization for hepatic and splenic macrophages
G6PD deficiency pathophys
X-linked recessive
Enzyme involved in pentose phosphate pathway
Maintains NADPH - maintains a high ratio of reduced to oxidized glutathione
Patients at risk of hemolytic anemia during times of oxidative stress (infection, fava beans)
Damaged RBCs phagocytosed and sequestered in the spleen
Rarely see RBC disintegration in circulation - do not see hemoglobinuria except in severe cases
Causes of microcytic anemia
Thalassemia Anemia of chronic disease Iron deficiency Lead poisoning Sideroblastic anemia
Fe def anemia histo
microcytic
hypochromic
poikilocytosis - elliptocytes
Anemia of chronic disease histo
Microcytic or normocytic
no elliptocytes
microcytosis/hypochromia not as severe
Hereditary spherocytosis histo
Normocytic (borderline macrocytic due to increased reticulocytes)
Spherocytes
Occasional schitocytes (fragmented RBCs)
Polychromasia
AIHA histo
Normocytic (borderline macrocytic due to increased reticulocytes)
Spherocytes
Occasional schitocytes (fragmented RBCs)
Polychromasia
Differentiating microcytic anemia
Ferritin
- low in Fe def
- high in anemia of chronic disease (iron store normal, but ferritin increases as an acute phase reactant)
Differnetiating normocytic anemia
DAT test
- positive in AIHA
Pernicious anemia/folate deficiency histo
Macrocytic megaloblastic
oval macrocytes
neutrophil nuclear hypersegmentation
Sickle cell anemia histo
Normocytic
Howell-Jolly body: blue dot-like RBC inclusion, representing DNA
- inclusions normally removed by splenic macrophages
(patients with SCA usually are hyposplenic due to childhood splenic infarctions - see peripheral signs of hyposplenism)
Lead poisoning anemia histo
microcytic usually presents with iron deficiency, therefore see microcytic RBCs Basophilic stippling (punctuate basophilia)
