Enzyme Deficiencies Flashcards
G6PD Deficiencies
Important enzyme in the hexose monophosphate shunt: Deficiency leads to defective HMP, Oxidized heme accumulates, Precipitation of hemoglobin, Poor oxygen carrying capacity, Heinz bodies cause membrane damage (Extravascular hemolysis during splenic pitting
Intravascular hemolysis in severe deficiency)
G6PD Deficiencies- exacerbation of anemia
Hemolysis can be worsened by exposure to oxidants: Chemicals, Certain antibiotics, Severe infections, Fava beans (Rich in an oxidizing compound, The historical name of G6PD deficiency is “favism”)
G6PD Deficiencies- Clinical Presentation
Most are asymptomatic
Severe cases: Extravascular and intravascular hemolysis, Neonatal jaundice, Kernicterus (Prolonged, severe neonatal hyperbilirubinemia- Brain damage), Renal failure
G6PD Deficiency- Lab Findings
Heinz bodies, Bite cells (RBCs with a chunk missing, A result of Heinz body pitting), Reticulocytosis, Decreased haptoglobin (Indicates intravascular hemolysis)
Pyruvate Kinase Deficiency
Important enzyme in anaerobic glycolysis
Deficiency causes poor ATP production: Ion pumps are impaired, Cellular dehydration (Echinocytes, Extravascular hemolysis)
Increased 2,3 BPG production (Glycolytic pathway backs up into the Rapoport-Leubering shunt, Increases O2 dissociation from hgb)
Pyruvate Kinase Deficiency- Clinical Manifestations
Dependent upon degree of deficiency, Extravascular hemolysis, Neonatal jaundice
Hemoglobinopathy
(The type of hemoglobin) Based on the exact amino acid sequence of the globin chains, Abnormalities may result in a hemoglobinopathy
Two types of hemoglobinopathies: Quantitative (Thalassemia), Qualitative (Globin quality is affected not the quantity, Usually due to an amino acid deletion or substitution)
Pyruvate Kinase Deficiency- Lab Findings
Reticulocytosis
Various poikilocytes
Howell-Jolly bodies
Enzyme Deficiencies- Hemolytic Anemia
(Pathophysiology) Several enzymes are important for: Energy production, Membrane viability, Protection from oxidations
Two deficiencies resulting in hemolysis: G6PD, Pyruvate kinase
Sickle Cell Anemia
Caused by homozygous inheritance of βs gene, A qualitative hemoglobinopathy- Production of Hgb S: Valine is substituted for glutamic acid at the 6th position of the β-chain, Tetrametric α2βs2, Deoxygenated hgb S allows polymerization of surrounding hgb S molecules
Sickle Cell Anemia- Pathophysiology
Polymerization of Hgb S
Deoxygenated Hgb S molecules stick together: Causes sickled appearance, The extent of sickling is dependent upon the amount of Hgb S present in the cell, Hgb S denatures and precipitates (Heinz bodies)
Compensation: Production of non-β hemoglobins (Hgb F), Increased cardiac output, BM hyperplasia (Increased hematopoiesis, May develop Fe or folate deficiency, Cortical thinning (bone pain))
Sickle Cell Anemia- Sickling
Occurs in hypoxic areas (spleen, kidney, etc), Begins when O2 saturation falls below 85% (Hypoxic tissues, High altitude, Respiratory disease), Reversible upon reoxygenation (Polymerization resists reoxygenation, Repeated sickling becomes irreversible- Irreversibly sickled cells are dehydrated, MCHC >36%)
Erythrocyte destruction: Primarily extravascular hemolysis, Moderate to severe anemia
Sickle Cell Anemia- Vaso-occlusive crisis
Most frequent cause of hospitalization
Causes: Hypoxic tissues, High altitude, Respiratory disease, Sickled cells aggregate in microcirculation
Blockage worsens hypoxia and sickling: Organ failure (Autosplenectomy, others), Thrombosis, Pain, fever, Swelling of hands and feet
Sickle Cell Anemia- Lab Findings
Moderate to severe NC/NC anemia
Variable anisopoikilocytosis: Polychromasia, Drepanocytes (usually only apparent in crisis), Target cells, Inclusions indicate spleen dysfunction (HJ bodies, Basophilic stippling, Heinz bodies)
Falsely increased microhematocrit- poikilocytes increases trapped plasma
