Inflammation Flashcards
Inflammation is an end product of the activation of the immune system. It is a physiological response to what 3 things? Give some examples of when it is a pathologic response.
- Infection, wound healing, malignancy
- autoimmunity, autoinflammation, hypersensitivity, ineffectual inflammation
What are the 4 cardinal signs of inflammation and what is sometimes included as the 5th sign?
- swelling (tumor)
- Redness (rubor)
- Heat (calor)
- Pain (dolor)
- Loss of function (functio laesa)
Briefly explain the pathophysiology of the signs of inflammation
- inflammation leads to the expansion and “leakiness” of blood vessels that allow the humoral and cellular components of the immune system to reach the tissues
- important for this to be localized to avoid shock and death
List 3 mediators of inflammation
- Kallikrein-Bradykinin system
- Histamine
- Complement
What happens in the Kallikrein-bradykinin system?
- at site of inflammation, kallikrein causes cleavage of kininogen into bradykinin
- bradykinin receptors on endothelium get activated and allow for plasma and cellular exudation
- this occurs in both the tissue and blood vessels since their is plasmaKK and tissue KK which allows for a reinforcement of the vasodilation in a local manner!
Role of histamine in inflammation
- one of many factors released upon tissue injury
- H1 histamine R on endothelium become activated and dilate and increase permeability
Role of complement in inflammation
- C5a receptor and C3a receptors on various cell types lead to increase in blood vessel permeability when activated
- local activation of the complement cascade will therefore lead to dilation of local vessels and inflammation
2 ways to categorize inflammatory response
- Quantitative: systemic vs. local
2. Qualitative: cytokines and type of cells
Systemic vs. local inflammation examples
- Systemic: bacteremia, metastatic cancer, systemic autoimmune disease
- Local: local infection, primary tumor, organ specific autoimmune disease
Qualitative categorization of inflammation and examples
- cytokines: Th1 vs. Th2; TNFa vs. IFNy vs. IL-1B
- Types of cells: neutrophils vs. eosinophils; T cells vs. B cells
Describe what is seen in acute vs. chronic inflammation
Acute: granulocytes predominant, usually neutrophils; followed by macrophages; phagocytic response to clean up and kill the acute insult
-Edema, neutrophils, then macrophages
Chronic: macrophage and lymphocyte predominant (lymphohistiocytic infiltrate); attempt to deal with inadequate clearance on insult by the acute response
4 patterns of acute inflammation
- Fibrinous
- Purulent
- Serous
- Ulcerative
Fibrinous Inflammation and example of where it occurs
- inflammation resulting in a large increase in vascular permeability allows fibrin to pass through the blood vessels
- fibrinous pericarditis
Purulent inflammation
- inflammation resulting in large amount of pus, which consists of neutrophils, dead cells, and fluid
- Infection by pyogenic bacteria such as staph is characteristic of this kind of inflammation
- abscesses
What is an abscess?
- large, localized collections of pus enclosed by surrounding tissues
- purulent inflammation
Serous inflammation and common example
- characterized by copious effusion of non-viscous serous fluid, commonly produced by mesothelial cells of serous membranes, but may be derived from blood plasma
- skin blisters are example
Describe the histology of a skin blister
- serous inflammation
- epidermis has separated from dermis due to serous effusion
Ulcerative inflammation
-inflammation occurring near an epithelium
Ulcerative inflammation
- inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface, exposing lower layers
- the subsequent excavation in the epithelium is known as an ulcer
3 histologic characteristics of chronic inflammation
- collection of chronic inflammatory cells: lymphocytes
- destruction of parenchyma
- replacement of tissue by connect tissue–fibrosis** why tissues will not return back to full capacity
Granulomatous inflammation
- special pattern of chronic tissue inflammation
- characterized by formation of granulomas, which are the result of a limited but diverse number of diseases, which include among others TB, leprosy, sarcoidosis, and syphilis
- maintained by TNFa
- giant cells common: large, multi-nucleated marcophages in horse-shoe shaped pattern
Granulomas are often maintained by what cytokine?
-TNFa
Sarcoid vs TB granulomas
- sarcoid: non-caseating
- TB: caseating
Outcomes of acute inflammation
- healthy resolution
- progression to abscess and fibrosis (scarring)
- Fibrosis right away
- progress to chronic inflammation and then fibrosis
What are acute phase reactants?
- proteins made usually by the liver in response to systemic inflammation
- provide useful clinical marker for inflammation
Acute phase reactants can be indirectly measured by __________. What is this? What is the main agent of this phenomenon?
- Erythrocyte Sedimentation Rate (ESR)
- red blood cells form aggregates (rouleaux) in the presence of acute phase reactants (particularly fibrinogen)
- rouleaux fall faster under gravity compared to free standing RBCs
- if sedimentation rate is >20, probably have some inflammation
What causes an ESR fakeout?
- a patient has severe inflammation, due to cytokine storm, and part of the pathophysiologic response to this is the consumption of fibrinogen
- don’t see rouleaux formation
- can be helpful do determine infection type though, some are associated with this
What is an amyloid and what is it caused by? How can one see them?
- prolonged exposure to acute phase reactants (specifically serum amyloid A—chronic inflammation) can cause large globs of protein to deposit in tissues
- these disrupt function of tissues and can ultimately lead to organ failure
- seen microscopically by looking for “apple-green birefringence” on a Congo Red stain
2 types of immune therapy
- immunosuppressives (need less inflammation)
- immune boosters (where increased inflammation can resolve injury)
4 types of immunosuppressives
- Glucocorticoids: alter nuclear transcription and reduces leukocyte number and function (multiple, potentially severe side effects)
- Cyclosporin A: inhibits calcineurin signaling, effectively blocking IL-2 and T-cell functions
- Cytotoxics: giving chemotherapy to kill immune cells
- Biologics: recombinant proteins or antibodies against specific cytokines, ligands, or receptors
4 kinds of immune boosters
- Imiquimod: TLR7 ligand useful for tx of certain epithelial cancer and viral warts (TLR agonist)
- IFNa/IFNy: used to tx chronic viral infections and for certain immunodeficiencies
- IVIG: passive immunization with other’s antibodies
- Vaccines: stimulate adaptive immune response against an antigen (infections, cancer)