Other Alterations in Granulocytes and Monocytes Flashcards Preview

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Flashcards in Other Alterations in Granulocytes and Monocytes Deck (52)
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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
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

1. three different mutations each resulting in a different defect in the leukocyte adhesion process
2. Patient has marked leukocytosis
3. 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

1. 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)

1. Hepatomegaly and/or splenomegaly
2. Slow physical and/or mental development
3. 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

1. Enzyme replacement therapy
2. Bone marrow transplant


Name 4 lysosomal storage disorders

- Mucopolysaccharidoses (MPS) (aka: Alder-Reilly Anomaly)
- Gaucher Disease
- Niemann-Pick Disease
- Tay-Sachs Disease


Gaucher Disease
- Deficiency in what?

Deficiency of the enzyme Beta-glucocerebroside


Gaucher Disease
- What increases?

increase in glucocerebroside


Gaucher Disease
- General pathogenesis of all types of the disease

- Spleen and liver enlargement
- Anemia
- Thrombocytopenia
- Growth Retardation
- May have effects on skeletal system and nervous system


- Most common form of Gaucher Disease
- Reduced levels of glucocerebrosidase
- Involves liver, spleen, lymph nodes, BM
- may have skeletal effects
- slight decrease in life expectancy

Gaucher Disease
- Type 1


- More severe form of Gaucher Disease
- Acute neuronopathic
- Undetectable levels of glucocerebrosidase
- Involves ALL tissues, including brain
- Mortality in early childhood

Gaucher Disease
- Type 2