Chapter 5 Flashcards
Symptoms of Anemia
Weakness, fatigue, dyspnea
Pale conjunctiva and skin
headache and lightheadedness
Angina, especially with preexisting CAD
Definition of anemia
Hb <13.5 in males
Microcytic anemia (four general causes)
- Iron deficiency
- ACI
- Sideroblastic anemia (decreased production of protoporphyrin)
- Thalassemia
Iron absorption in the GUT
Absorbed in the duodenum (acidic environment favors Fe2+, better for absorption)
DMT1 brings it into enterocytes, ferroportin takes it into blood. Stored in liver and bone marrow macrophages.
Why is gastrectomy linked to Iron deficiency?
Decreased acid production –> more iron in Fe3+ state, poorer absorption.
Four Stages of Iron Deficiency anemia
- Storage depletion
- Serum iron depletion
- Normocytic anemia
- Microcytic, hypochromic anemia
Clinical findings with Iron deficient microcytic anemia
Anemia, koilonychia (spoon shaped nails), and PICA!
Lab findings of iron deficient anemia
- Microcytic, hypochromic anemia with increased RDW
- Decreased ferritin, increased TIBC, decreased serum iron and % sat.
- Increased free erythrocyte protoporphyrin
Plummer Vinson syndrome
Iron Deficiency Anemia + Esophageal web (dysphagia) + Glossitis
Lab findings with Anemia of Chronic Inflammation
Increased ferritin, decreased TIBC, decreased serum Fe and %sat.
Protoporphyrin synthesis key steps (3)
- Succinyl CoA –> Aminolevulinic Acid (ALA) by ALA synthetase. B6 required cofactor (RATE LIMITING STEP)
- ALA –> Porphobilinogen by ALA dehydrogenase.
- Protoporphyrin + iron –> heme by ferrochelatase. IN MITOCHONDRIA
In protoporphyrin deficient sideroblastic anemias, where is the iron located???
In MITOCHONDRIA surrounding the nucleus.
Most common cause of congenital sideroblastic anemia
Defects in ALAS (aminolevulinic acid synthetase)
Acquired causes of sideroblastic anemia (3)
- Alcoholism (damage mitochondrias)
- Lead poisoning (denatures ferrochetalase and ALAD)
- Vit. B6 deficiency (often due to ISONIAZID)
Lab findings with Sideroblastic anemia
IRON OVERLOAD:
Increased ferritin, decreased TIBC, increased serum iron and %sat.
Evolutionary advantage of Thalassemia
Protection against P. falciparum
HbF
alpha2gamma2
HbA
alpha2beta2
HbA2
alpha2delta2
Cause of a-Thalassemia
gene deletion of one or more copies of alpha gene (4 total) on Chromosome 16
HbH
beta chain tetramers seen in a-Thalassemia (3 deletions)
Hb Barts
gamma chain tetramers formed in utero in fetuses with 4 gene deletion a-Thalassemia. This is lethal in utero (hydrops fetalis)
Cause of b-Thalassemia
Mutations resulting in absent or diminished b globin production on chromosome 11
Findings with b-Thalassemia minor on electrophoresis
Decreased HbA, increased HbA2, increased HbF
Symptoms of b-Thalassemia major
- Ineffective erythropoiesis (due to excess a globin aggregations) and extravascular hemolysis –> severe anemia
- Erythroid hyperplasia (crewcut appearance, chipmunk facies) and hepatosplenomegaly due to extramedullary hematopoiesis.
- Risk of aplastic crisis w/ Parvo B19
Parvovirus B19 effect on RBCs…
Infects erythroid progenitor cells, shuts them down for ~1-2 weeks.
Findings with b-Thalassemia major on electrophoresis
Little/no HbA, increased HbA2, increased HbF.
Overall anemia due to Thalassemia
Microcytic, hypochromic anemia
Folate/B12 pathway
Folate-M –> B12-M –> Converts homocysteine to methionine. M = methyl group. Folate-M inactive.
Other causes of macrocytic anemia aside from megaloblastic (3)
- Alcoholism
- Liver disease
- Drugs (ex. 5-FU)
Where is folate absorbed???
Jejunum
Mechanism of methotrexate???
Inhibitor of Dihydrofolate reductase. Thus can lead to megaloblastic anemia
Clinical/lab findings with folate deficiency
- Macrocytic RBCs and hypersegmented polys
- Glossitis
- Decreased serum folate
- Increased serum homocysteine
- Normal methylmalonic acid
Source of Vit. B12
Animal derived products
Absorption of B12
Liberated from complexe with animal products via salivary enzymes, binds to R-binder (from salivary gland). Pancreatic proteases detach B12 from R-binding in duodenum, binds to IF from parietal cells. Absorbed in the ILEUM.
Most common cause of Vit. B12 deficiency
Pernicious Anemia
Other causes of Vit B12 deficiency
Pancreatic insufficiency, damage to the terminal ileum (Crohn’s, Diphyllobothrium latum). Dietary deficiency rare except in vegans.
Clinical/lab findings with Vit. B12 deficiency
- Macrocytic RBCs and hypersegmented polys
- Glossitis
- Subacute degeneration of spinal cord (due to buildup of methylmalonic acid which impairs myelenation)
- Decreased serum B12
- Increased Homocystein
- Increased methylmalonic acid.
What do Reticulocytes looks like?
Larger cells with bluish cytoplasm due to residual RNA
How to correct the reticulocyte count?
Reticulocytes x Hct/45
Lab findings of intravascular hemolysis
- Hemoglobinemia
- Hemoglobinuria (when haptoglobin saturated)
- Hemosiderinuria (from iron laden renal tubular cells that die a few days later)
- Decreased haptoglobin
Most common defects leading to hereditary spherocytosis
Spectrin, Ankyrin, or Band 3.1
Clinical and lab findings with hereditary spherocytosis
- Spherocytes
- Increased RDW and MCHC
- Splenomegaly, jaundice, and gallstones
- Increased risk for aplastic crisis (Parvo B19)
How to diagnose hereditary spherocytosis
Osmotic Fragility Test
What are Howell-Jolly bodies
fragments of nuclear material in RBCs that persist due to splenectomy!
What increases the risk of sickling in HbS
Hypoxia, dehydration, and acidosis
Treatment for HbS
Hydroxyurea (increases HbF levels, decreases sickling)
Symptoms of Sickle Cell Anemia
- Extravascular hemolysis
- Intravascular hemolysis
- Massive erythroid hyperplasia (in both BM and extramedullary)
- Increased risk of Aplastic crisis
- Dactylitis in kids
- Autosplenectomy
- ACS
- Pain crisis
- Renal papillary necrosis
With sickle cell trait, do you see sickling?
Yes, but only in the renal medulla. With the trait, have <50% HbS. This normally prevents sickling, except in extreme hypoxic and hypertonic environment of renal medulla
In HbC, what is mutated?
Glutamic acid is replaced by Lysine (instead of valine, seen in HbS)
Cause of Paroxysmal Nocturnal Hemoglobinuria
Acquired defect in myeloid stem cells resulting in absent GPI –> cannot bind to Decay Accelerating Factor –> increased complement fixation leading to intravascular hemolysis, particularly at night (respiratory acidosis)
Main cause of death in PNH
Thromosis of the hepatic, portal, or cerebral veins. This is because not only RBCs, but also WBC and platelets are destroyed. Factors released from platelets induce thrombosis.
Complications of PNH
Anemia (iron deficiency)
AML (in 10% of patients)
Cause of G6PD Deficiency
X linked recessive disorder resulting in reduced half life of G6PD. This decreases glutathione production, leading to early death of RBCs.
Causes of RBC oxidative stress (in G6PD Deficiency)
- Infections
- Drugs (primaquine, sulfa drugs, and dapsone)
- Fava beans!
Histology of G6PD deficiency
Heinz bodies (precipitated Hemeglobin) and bite cells
How to confirm G6PD Deficiency ?
Do enzyme studies to detect low levels, but must do weeks after last hemolytic episode (otherwise all cells lacking the enzyme dead)
What conditions are known to precipitate IgM (cold) immune hemolytic anemia
Mycoplasma pneumoniae AND mononucleosis…
Histological finding of Microangiopathic Hemolytic Anemia
Schistocytes! (helmet cells)
Type of hemolysis seen with Malaria?
Intravascular primarily (RBCs rupture as part of Plasmodium life cycle…)
Etiologies of aplastic anemia
- Drugs
- Viral infections
- Autoimmune damage
What is myelophthisis???
Pathologic process (eg. metastatic cancer) that replaces bone marrow.
