Acute Inflammation Flashcards
Endogenous Chemoattractants (3)
Leukotrine B4
C5a
IL-8
Hallmark of Acute Inflammation (4)
Vasodilation
Increased vascular permeabilty
Exudate formation
Entry of neutrophils to the site of injury
Vascular Events (3)
Vasodilation of arterioles
Increased permeability of venules
Slowing of blood flow
Cardinal Signs
Rubor (histamine mediated vasodilation )
Calor (histamine mediated vasodilation)
Tumor (histamine dependent)
Dolor (PGE2 and Bradykinin, PGE2 has stronger)
Loss of function
Cellular Events
Leukocyte extravasation
Phagocytosis
Important opsonins
C3b
IgG
Bruton’s Agammaglobulinemia (recognition and attachment for
Defective IgG receptor, so reduced IgG
Chediak-Higashi Syndrome (engulfment)
A defect in membrane fusion prevents phagolysosome formation
Microbial Killing: O2 dependent patway
H2O2-MPO-halide system
Killing of bacteria by ROS and
NAPDH Oxidase, etc. (refer to nt
Microbial Killing: O2-INDEPENDENT pathway enzymes (4)
Lactoferrin
Major Basic Protein (eosinophil cytotoxic to helminths)
Lysozyme
Bacterial Permeability Increasing Protein (BPI)
Neutrophil (PMN): Primary (Azurophilic) Granules
Myeloperoxidase
Lysozyme
Neutrophil (PMN): Secondary (specific) Granules
Lactoferrin Leukocyte Alkaline Phosphatase (LAP) Seen in normal PMNS Benign process: high LAP Malignant: Low LAP
Defects in Neutrophil (PMNs, 4)
CGD of Childhood
Myeloperoxidase Deficiency
Chediak-Higashi Syndrome
LAD 1 and 2
Defects in Neutrophil: CGD of Childhood
Phagocytic cells INGEST BUT DON’T KILL
Catalase + organisms (staph aureus): they produce catalase that destroys the bacterial H202 (because PMN doesn’t produce H202)
NBT Test –> NEGATIVE
Defects in Neutrophil: Myeloperoxidase Deficiency
Infections with candida
NBT TEST IS POSTIVE (normal)
Defects in Neutrophil: Chediak-Higashi Syndrome
A defect in membrane fusion prevents phagolysosome formation (engulfment)
NeutroPENIA
Albinism
Cranial & Peripheral Neuropathy
Abnormal microtubule formation (functional mark)
Large cytoplasmic granules representing abnormal lysosomes (morphological mark)
Defects in Neutrophil: LAD Type 1
Defect in CD 11/18/ (beta 2 integrain), LFA-1, Mac-1
Example: delayed separation of umbilical cord, increased neutrophils, recurrent bacterial infections that lack pus formation
Defects in Neutrophil: LAD Type 2
Absence of Sialyl-Lews on neutrophils
Plasma Derived Chemical Mediators (3)
Kinin System
Clotting System
Complement System
Cell Derived Chemical Mediators (4)
Vasoactive amines - (Histamine and Serotonin)
AA metabolites
Cytokines
Other
Cell Derived Chemical Mediators - Vasoactive Amines
Histamine
Serotonin
Caricinoid syndrome
Plasma Derived Chemical Mediators - Bradykinin effects (under Kinin system, 4)
Pain (dolor)
Increases vascular permeability
Vasodilation
Bronchoconstrictor
Plasma Derived Chemical Mediators - The Kinin System
Intiated by ACTIVATED Hageman factor 12
Factor 12 initiates
Kinin system, coagulation, and the plasminogen complement systems
Other Mediators of Acute Inflammation: PAF
Derived from basophils, mast cells, and enthothelial cells
Actions: Activates and aggregates platelets, activates arachidonic acid metabolism
Other Mediators of Acute Inflammation: Nitric Oxide
Produced by endothelial cells
Stimulates relaxation of smooth muscles (vasodilation), this inhibiting platelet aggreggation
Important in endotoxic shock
Other Mediators of Acute Inflammation: Chemokines
Activate and attract leukocytes
IL-8
MCP-1
Eotaxin
Other Mediators of Acute Inflammation: Lysosomal Constituents
In granules of neutrophils and monocytes
2 types: Acid proteases (in phagolysosomes) and neutral proteases (active in extracellular matrix, for tissue injury)
Proteases controlled by: alpha 2 macroglobulin and alpha 1 anti-trypsin (panlobar emphysema)
Other Mediators of Acute Inflammation: O2-derived free radicals
From NADPH oxidase pathway
Include: superoxide, hydroxyl, H2O2
Small dose amplification of inflammatory response
Tissue injury: large doses (neutralize alpha-2 macroglobulin and A1-AT (from lysosomal protease constituents))
Protection: antioxidant mechanisms (catalase, superoxide dismutase, and glutathione)
Exogenous chemotactants
Bacterial products (e.g. N-formyl methionine)
Complete System Pathology Diseases (2)
Paroxysmal Nocturnal Hemoglobinuria
Hereditary Angioedema
Paroxysmal Nocturnal Hemoglobinuria
complement mediated lysis of RBCs
Defect/lack of DAF and CD59
Hereditary Angioedema
Deficiency of C1 inhibitor
Overall Outcome of Acute Inflammation (3) 1
- Complete resolution
- Healing by Fibrosis
- Abscess
- Progression to chronic inflammation
Overall Outcome of Acute Inflammation: Complete Resolution
Regeneration of damaged epithelium WITHOUT SCAR TISSUE FORMATION
Restores structure and fxn of tissue
Overall Outcome of Acute Inflammation: Healing by Fibrosis
Organization and repair WITH SCAR TISSUE FORMATION
Scar tissue laid down by FIBROBLASTS (distorts structure and fxn)
Overall Outcome of Acute Inflammation: Abscess
Tissue destruction and persistent acute inflammation
Pus from pyogenic bacteria
Overall Outcome of Acute Inflammation: Progression to Chronic Inflammation
When acute inflammation can’t remove noxious agents
Marked by:
Replacement of PMNS by macrophages, lymphocytes, and plasma cells
Angiogenesis
Healing by fibrosis
Serous Inflammation
Outpourig of thin protein poor water fluid
Skin blister Body cavities (effusions)
Fibrinous inflammation
Protein rich fluid (fibronogen) that has bread and butter appearance
Fibrinous pericarditis (shaggy, fibrinous exudate)
Suppurative (purulent) Inflammation
Production of pus
Staphylococcus
Abscess
Suppurative conjunctivitis
Suppurative meningitis
Lung abscess
White and milky on surface it adheres to like eye or brain
Catarrahal Inflammation
Excessive mucus secretion
Runny nose from rhinoviral infection
Cellulitis
Thin, watery exudate that spreads throughout subcutaneous tissues (usually from STREPTOCOCCUS which has hyaluronidase)
Erysipelas and Impetigo
Pseudomembranous Inflammation
Toxin induced –> resulting in necrotic membrane formation
E.g. psedomembrane of diphtheria (thick, gray coating on BACK OF THROAT)
Pseudomembranous colitis from C. Difficile
Ulcers
Agend prudicing defect in the epithelial lining of skin or mucosa
Ulcer is a loss of continuity of skin or mucosa due to sloughing of inflammatory necrotic tissue
Peptic ulcer from H. Pylori induced cytokine damage
Exceptions to Acute Inflammatory by PMNS: Acute Inflammation from Viruses (viral hepatitis)
Principal cells: lymphocytes
Exceptions to Acute Inflammatory by PMNS: Allergic rxns and parasitic infections
Eosinophils dominate from start to finish
Exceptions to Acute Inflammatory by PMNS: Acute dermatitis
Lymphocytes predominate
Exceptions to Acute Inflammatory by PMNS: Whooping Cough (Bordetella pertussis)
Lymphocytes prodominate
Exceptions to Acute Inflammatory by PMNS: Gas gangrene (Clostridium)
Little to no PMNS
