Other Alterations in Granulocytes and Monocytes Flashcards
Chronic Granulomatous Disease (CGD)
- What defect is
Genetic mutation where phagocytes are unable to produce superoxide and reactive oxygen species
Chronic Granulomatous Disease (CGD)
- inheritance (2 most common)
- Sex-Linked (x linked recessive more common in males)
- Autosomal recessive
Chronic Granulomatous Disease (CGD)
- prognosis
Death usually around 5-7 years due to bacterial infection
Chronic Granulomatous Disease (CGD)
- Manifestations
- Defective or absent respiratory burst
- Reduced membrane NADH or NADPH
- Absence of superoxide anion and H202
Chronic Granulomatous Disease (CGD)
- Physical manifestations
- Chronic pyogenic infections of all systems
- Abscess formation
- Lymphadenophathy
- Hepatosplenomegaly
- Anemia of chronic inflammation
Chronic Granulomatous Disease (CGD)
- Differential findings
Toxic granulation Hypogranulation Vacuolization Doelhe bodies Immature granulocytes
Chronic Granulomatous Disease (CGD)
- Good test to run
Nitroblue tetrazolium reduction or NBT test
In NBT test the dye is reduced by NADPH oxidase to form black formazan deposits. What happens in a cell with CGD?
There is no dye reduction in CGD, and no color change because NADPH oxidase is not functional
Leukocyte Adhesion Deficiency (LAD)
- What is wrong in this disease?
- It results in the inability of neutrophils and monocytes to exit the blood vessel and enter the tissue
- Results in repeated infections despite leukocytosis
Leukocyte Adhesion Deficiency (LAD)
- Inheritance
Rare autosomal recessive
Mutation resulting in reduced or defective beta2 integrin subunits (CD18) which are found on the leukocytes
Type 1 Leukocyte Adhesion Deficiency (LAD)
Mutation resulting in faulty selectins (CD62E) which are found on the endothelial cells
Type 2 Leukocyte Adhesion Deficiency (LAD)
Mutation resulting in a faulty binding mechanism between the b2 intern subunits and the selections on the endothelial cells
Type 3 Leukocyte Adhesion Deficiency (LAD)
Leukocyte Adhesion Deficiency (LAD)
- Hallmarks of the disease
- three different mutations each resulting in a different defect in the leukocyte adhesion process
- Patient has marked leukocytosis
- Recurrent infections
Leukocyte Adhesion Deficiency (LAD)
- Cure
Bone marrow or stem cell transplantation
Lysosomal Storage Disorders
- Cause
Caused by inborn errors of metabolism in which specific enzyme deficiencies allow the accumulation of products of cellular metabolism with lysosomes
Lysosomal Storage Disorders (LSD)
- Two broad Categories
- Mucopolysaccharide Storage Disorders
2. Lipid Storage Disease
Membrane bound structures present in cytoplasm of most cells. They contain hydrolytic enzymes that usually digest complex macromolecules that are normal products of cell metabolism.
Definition of a lysosome
What cells are rich in lysosomes?
Cells of Monocyte/Macrophage system
Lysosomal Storage Disorders (LSD)
- Pathogenesis (whats going on?)
- Enzyme deficiency leads to accumulation of cell metabolism and disrupts normal architecture
- Spleen and liver are often enlarged
- BM may be replace by macrophages
- Pancytopenia
- Vacuolated lymphocytes
- CNS may be involved
Lysosomal Storage Disorders (LSD)
- inheritance
autosomal recessive
Lysosomal Storage Disorders (LSD)
- Broad diagnosis (3)
- Hepatomegaly and/or splenomegaly
- Slow physical and/or mental development
- If CNS involved, seizures or blindness my occur
This may be seen in many of lysosomal storage diseases but most characteristic in Taysachs (eye)
Cherry-red spot on back of the eye
Lysosomal Storage Disorders (LSD)
- Treatment
- Enzyme replacement therapy
2. Bone marrow transplant
