Pathology - Inflammation Flashcards
What are the four inflammatory responses to injury?
Vascular Changes
Cellular Changes
Chemical Mediators
Morphological Patterns
What vascular changes occur in response to injury?
Changes in flow and vessel calibre
Vasodilatation
First involves arterioles then capillary beds
What mediates vascular changes?
Histamine and nitric oxide
What is the result of vascular changes?
Increased heat (calor) Redness/erythema (rubor)
What cellular changes occur in response to injury?
Stasis White cell margination Rolling Adhesions Migration
What is white cell margination?
With vascular dilatation, blood flow slows down
Allows cells, especially large white cells, to move peripherally
What are selectins?
Expressed on endothelial cell surface
What are integrins?
Bind to vessels walls, cell matrix and other cells
Over 30 types
Why does rolling occur?
Integrin/selectin interaction with their ligands is of low affinity and binding on and off are fast
Which mediators increase selectin expression?
Histamine and thrombin from inflammatory cells
What mediators increase endothelial cell expression of VCAM and ICAM?
Tumour necrosis factor
Interleukin-1
What are VCAM and ICAM?
Vascular cell adhesion molecule
Intercellular adhesion molecule
What increases the affinity of VCAMs and ICAMs for integrins?
Proteoglycans on endothelial cell surface (only when bound to chemokines from site of injury)
What changes occur to vascular permeability?
Leaky vessels = loss of proteins
Change in osmotic pressure
Water follows protein = swelling (tumour)
Why do vessels become so leaky?
Endothelial contraction - Histamine, bradykinin, substance P, leukotrienes
Direct injury - toxins, burns
White cells - attack vessel wall (self harm)
Transcytosis - VEGF mediated
New verse formation - VEGF makes new vessels and increases leakiness
What is chemotaxis and which components act as “chemotaxis molecules”?
Cells follow a chemical gradient and move along it Bacteria components Complement Leukotrienes Cytokines - interleukins
What are the three stages of phagocytosis?
Recognition and attachment
Engulfment
Killing and degradation
How does recognition and attachment occur?
Mannose receptors
Bacteria contain terminal mannose residues; mammalian cells do not
Scavenger receptors
Opsonins
Coated with proteins, including compliment cascade components and IgG
How does engulfment occur?
Pseudopods
Vesicle formation - phagosome
Joins with lysosome - phagolysosome
How does killing and degradation occur?
Reactive oxygen species
NADPH oxidase
Reactive nitrogen species
Nitric oxide synthase
What are the clinical features of acute inflmmation?
Rubor Calor Tumor Dolor Loss of function
What causes rubor?
Redness
Increased perfusion, slow flow, increased vessel permeability
What causes calor?
Heat
Increased perfusion, slow flow rate, increased vessel permeability
What causes tumor?
Swelling
Vascular changes
What causes dolor?
Pain
Mediated by prostaglandins and bradykinin
What is the microscopic appearance of the neutrophil?
Moly lobed nucleus (polmorph)
Granulocyte
Phagocytic and cytotoxic abilities
What is the main cell of acute inflammation?
Neutrophil
What are the potential outcomes of acute inflammation?
Resolution
Suppuration
Repair, organisation and fibrosis
Chronic inflammation
What factors can influence the outcome of acute inflammation?
Site of injury
Type of injury
Duration of injury
What is resolution?
Complete restoration of the tissue to normal after removal of inflammatory components
What factors are needed for resolution to occur?
Minimal cell death
Tissue has capacity to repair
Good vascular supply
Injurious agent easily removed
What is suppuration?
Formation of pus
What is pus?
Contains living, dying and dead cells
Neutrophils, bacteria and inflammatory debris
Why is an abscess difficult to get rid of?
No blood supply reaches the middle, and so antibodies cannot get in
What is an empyema?
Walled off space filled with pus
What factors might result in organisation?
Injury with lots of necrosis
Injury with lots of fibrin which isn’t easily cleared
Poor blood supply
Tissue type
Mucosa where damage goes beyond the basement membrane
What is organisation?
Scarring
What is an ulcer?
Erosion beyond the basement membrane
What is granulation tissue?
Aids healing
Defect is slowly infiltrated by capillaries and then myofibroblasts
Deposit collagen and smooth muscle cells
Looks very red
Acts as a stop gap
What is the main problem with scarring and fibrosis?
Loss of function
e.g. heart muscle that won’t contract, or tight skin
When might chronic inflammation be favoured?
Suppuration, empyema, scarring
Persistence of injury - foreign material
Infectious agent - virus, persistent (mycobacterium)
Type fo injury - autoimmune, transplant injury
What cells characterise chronic inflammation?
Lymphocytes and macrophages
What might cause granuloma formation?
Foreign bodies = Endogenous (e.g. keratin) or exogenous (e.g. asbestos) Specific infections Parasites Worms, eggs Syphilis Mycobacterium
What is a granuloma?
Aggregate of epthelioid histiocytes
What granuloma is seen in TB?
Caseous necrosis
