Acute Inflammation Flashcards
What molecular event establishes the leukocyte (neutrophils/macrophages) adhesion?
TNF-alpha + IL-1 -> Stimulates I-CAM/V-CAM expression in the endothelium
C5a + LTB4 -> Stimulates INTEGRIN expression on leukocytes
I-CAM/V-CAM Bind INTEGRINS (of leukocytes) -> Leukocyte is “adhesed” to the endothelium of the BV
What is the inheritance pattern of LEUKOCYTE ADHESION DEFICIENCY? What is the most common mutation?
AUTOSOMAL RECESSIVE
Most common mutation = Defect in the CD18 subunit of the LEUKOCYTE INTEGRIN
Leukocyte integrin can no longer can bind the adhesion molecules (CAM) on the endothelium
What is the most common clinical feature of LEUKOCYTE ADHESION DEFICIENCY?
Delayed separation of the umbilical cord
Normally, after birth, the baby’s umbilical cord is no longer receiving blood supply -> Necrosis -> Acute inflammation -> Neutrophil-mediated response will facilitate umbilical cord separation.
LACKING NEUTROPHIL ADHESION = DELAYED SEPARATION
What lab finding is associated with LEUKOCYTE ADHESION DEFICIENCY (Hint: Neutrophils)?
INCREASED CIRCULATING NEUTROPHILS - Due to release of marginated neutrophils
Are pts with LEUKOCYTE ADHESION DEFICIENCY more likely to get bacterial infections?
YES, more recurrent bacterial infections that LACK PUS FORMATION
Pus = dead neutrophils sitting in fluid
What is the inheritance pattern of CHEDIAK-HIGASHI SYNDROME? What is the mutation?
Autosomal Recessive
Mutation in the lysosomal trafficking regulator protein -> Phagosome can NO LONGER traffick over to merge with the lysosome in the leukocyte (neutrophil) -> Can NOT form phagolysosome to neutralize the pathogen
What is the lab finding of CHEDIAK HIGASHI SYNDROME in terms of neutrophil count?
NEUTROPENIA - Ineffective division of the neutrophils inside the bone marrow with this defect (Microtubule-like, lysosome trafficking protein regulator deficiency)
Name 3 clinical Sx of CHEDIAK HIGASHI SYNDROME.
- Increased risk of pyrogenic infections
- Albinism
- Peripheral neuropathy
What happens to granule dispersal in platelets and leukocytes in CHEDIAK HIGASHI SYNDROME pts? What are those implications?
- Lack of Golgi-derived granule dispersal in leukocytes -> See GIANT GRANULES next to the golgi in leukocytes
- Lack of platelet dense granule dispersal -> Lack of vWF -> Defective primary hemostasis -> INCREASED bleeding time
What is the defect in CHRONIC GRANULOMATOUS DEFECT?
Defect in NADPH OXIDASE - Enz involved in oxidative burst that converts O2 -> O2- (pathway for the production of HOCl bleach by the phagolysosome for destroying phagocytosed microbes)
How is a pt with CHRONIC GRANULOMATOUS DISEASE more susceptible to infection by CATALASE + organisms?
CGD -> Defective NADPH oxidase -> Decreased O2- prodn -> Decreased H2O2
BUT, there is another means of H2O2 presence: Bacteria naturally can make H2O2 -> Can be converted into HOCl by MPO -> Neutralize phagocytosed microbe
BUT Catalase + Organisms reduce the H2O2 produced inherently by bacteria -> No longer generates HOCl at all to neutralize the microbe
What lab test can be used to SCREEN for CHRONIC GRANULOMATOUS DISEASE? How does it work?
NITROBLUE TETRAZOLIUM (NBT) TEST
NORMAL NBT TEST (NBT turns blue): If NADPH oxidase is functional and can reduce O2 to O2-
ABNORMAL NBT TEST (CGD, NBT will NOT turn blue): Defective NADPH oxidase -> Can NOT reduce O2 to O2-
Are vast majority of pts with MPO DEFICIENCY symptomatic or asymptomatic?
ASYMPTOMATIC
What infections are pts with MPO Deficiency more susceptible to attaining?
CANDIDA ALBICANS infections - “ORAL THRUSH, DIAPER RASH”
How do pts with CGD and MPO DEFICIENCY differ in terms of NITROBLUE TETRAZOLIUM TEST?
CGD: NADPH oxidase is NOT functional -> NBT does NOT turn blue (ABNORMAL NBT Test)
MPO DEFICIENCY: NADPH oxidase is STILL functional -> NBT can turn blue (NORMAL NBT Test)
