Lecture 11 - Inflammation and repair Flashcards
What is inflammation/
Response of living tissue to injury. It is a well organised of cascade of fluid and cellular changes in tissue
What causes inflammation?
Aetiologic agents such as viruses, bacteria, fungi, and parasites
Hypersensitivity
Physical and Chemical agents (trauma, sunburn, and acid)
Necrosis (anoxia, trauma)
What is hypersensitivity?
Body reacts against itself
What is good about inflammation?
It opens up the site for influx of drugs, antibodies, mediators
Fibrin and fibrosis can wall it off
What is bad about inflammation?
Persistent swelling and cytokines make you feel sick
What are the five principle effects of inflammation?
Redness (due to influx of blood)
Swelling (due to accumulation of fluid)
Heat (Increase in temperature due to increased blood flow to area)
Pain (due to stretching of skin)
Loss of function Movement inhibited by pain and welling. (this principle was added later
What are the general characteristics of inflammation?
Redundant and complex due to many mediators
Continuous over long periods of time (per-acute, sub-acute, and chronic desvribe different stages)
Caused by a stimulus and removal of stimulus should resolve it
Blood is the primary delivery system for inflammatory components
Inflammation is on a continuum with healing process
What are the causes of inflammation?
Microbial infection
Allergens
Autoimmunity
Trauma
What the local effects of inflammation?
Destruction of invading microorganisms
At other times appear to serve no effect
What are the beneficial effects of inflammation?
Dilution of toxins
Entry of antibodies
Fibrin formation
Delivery of nutrients and oxygen
Stimulation of immune response
What are the harmful effects of inflammation?
Persistent cytokine release
Destruction of normal tissues
Swelling
Inappropriate inflammatory response
How is inflammation grouped based on time course?
per acute - minutes or hours
Acute - a few hours to a few days
Sub-acute - period between acute and chronic
Chronic - weeks to months
How is inflammation grouped based on type of exudate?
Purulent
Serous
Haemorrhagic
Catarrhal
Mixed
Fibrinous
How is inflammation grouped based on severity?
Mild
Moderate
Severe
How is inflammation grouped based on distribution of lesion?
Focal (just one small part of an organ is affected)
Multifocal (several small parts affected)
Diffuse (whole organ is affected)
Focally extensive (diffuse but just in one part of organ)
What does pus mean?
heavy neutrophil response which means bacteria
What is the suffix related to inflammation?
“itis”
What are the categories of acute inflammation?
Cellular events
Vacular events
What are the vascular events of acute inflammation?
Changes in blood vessel calibre and blood flow
Increased vascular permeability
Formation of fluid exudate
What are the cellular events of acute inflammation?
Cells move out of vessels into area of inflammation via chemotaxis.
Inflammatory cells become activated and can phagocytose offending pathogens
How do macrophages that are activated by bacterial ingestion respond to inflammation?
They release cytokines and chemokines then release pain causing inflammatory mediators and vasodilators for other WBCs to join
What are the major chemical signals of inflammation?
Histamine (causes vasodilation and increased permeability)
Kinins (released from damaged tissue, chemotactic factors)
Prostaglandins (intensify effects of histamine)
Leukotrines (Promote adherence of phagocytic cells and increase vascular permeability)
Also delivers clotting elements which can wall off affected area to prevent spread of infection
Where are Complement proteins, kinins, and factor XII (hageman factor) produced/activated?
In the liver
Where are newly synthesized mediators produced?
In WBCs
What is an exudate?
Fluid that filters from circulation into lesions or areas of inflammation
Which cytokines are preformed and stored in secretory granules?
Histamine
Serotonin
Which mediatos are newly synthesized in WBCs during inflammatin?
Prostaglandins
Leukotrienes
Platelet-activating factor
Reactive Oxygen Species
Nitric oxide
Cytokines
Neuropeptides
What is a transudate?
Fluid pushed through capillaries due to high pressure within capillarie
What are mixed exudates?
More common than simple exudates because of inflammatory process which frequently persists long enough to evoke exudation of more than one type of exudate
What is serous exudate?
Outpouring of translucent, thin fluid that can accumulate on mucosal surface, skin, or in perioneal and pericardial cavities
When is serous exudate commonly seen?
Acute inflammation which indicates that insult is mild and transient. If it doesn’t worsen the fluid is reabsorbed and inflammation is resolved
What is purulent/suppurative exudate?
PUS which is an accumulation of dead neutrophils.
Almost all cases due to bacterial infection
Pyogenic bacteria promote production of pus
Neutrophils have enzymes that can liquefy surrounding tissues
What is pus?
an accumulation of dead neutrophils
What causes variation in colour and consistency of pus?
Hostm stimulus, and the duration
What is a pus filled lump with a fibrous wall or capsule called?
An abscess
What can happen to localized pus?
It can break loose and spread resulting in septicaemia
What happens if pyogenic bacteria is close to body surface?
discharges purulent exudate to the outside surface
What would happen if pus is reabsorbed?
Ill effects such as fever and general illness
What are the types of exudate?
Serous (mild)
Pyogenic (pus field can be mild or severe)
Catarrhal (can be mild or severe)
Haemorrhagic (Severe most of the time often fatal)
Fibrinous exudate (severe but can resolve without any sequelae)
What is catarrhal exudate?
Heavy mucous production and ofte associated with mucosal surfaces like intestinal, repiratory, and reproductive tracts
Appears as thin grey-yellow
What surfaces are associated with catarrgal exudate?
Mucosal surfaces such as GI tract Resp tract and Repro tract
What is haemorrhagic exudate?
Blood vessel holes causing blood cells to leave in large numbers.
What do haemorrhagic exudates consist of?
RBCs, fibrin, serum, and leukocytes
What is fibrous exudate?
Occurs in more severe conditions with escape of larger fibrinogen molecules from vascular system. What hapens is fibrinogen reaches tissue and is converted to fibrin .
Where can fibrinous exudate be found?
Chiefly on mucous and serous membranes (respiratory tract, digestive tract, pleura, peritoneum, and pericardium)
How does fibrinous exudate look?
Slightly roughened appearance, slightly dull and granular
What happens as fibrin deposition increases?
Gets thick and yellow strands can be peeled off and if insult is repeated it can cause fibrin carpet
How is inflammation resolved?
It is resolved by complex cascade of steps and mediated by complex resolvin molecules.
Exudate is produced and influx of neutrophils and destroy residual debris
Apoptosis of neutrophils
What are the differences between acute and chronic responses?
Time: Chronic inflammation is acute inflammation that has not been resolved. Acute inflammation is exudative chronic inflammation which is productive and proliferative.
Best indicator of chronic inflammation is deposition of fibrinogen
What are the characteristics of chronic inflammation?
Not usually red or hot
Do not ooze
Productive or proliferative
Often present in infections with higher order organisms such as mycobacteria, fungo, and metazoan parasites and many autoimmune diseases.
How does chronic inflammation look histologically?
Primarily mononuclear cells involved
Fibroblasts and new blood vessels. Together called granulation tissue
What is granulomateous inflammation?
Always chronic
Composed predominantly of macrophages but may have multinucleate giant cells
What causes chronic inflammation?
Infection by organisms resistant to killing
Repeated bouts of acute inflammation
Prolonged exposure
Autoimmune disease
What is granulomatous inflammation?
Inflammatory response consisting mostly of macrophages that try to phagocytose and then differentiate to become epitheloid macrophages and giant cells (fusion of several macrophages)
Ring of lymphocytes around main site
What happens when mycobacteria resist macrophage activation effects?
A granuloma develops
Chronic activation of macrophages by TH1 cells forming granulomas to contain intracellular pathogens that cannot be cleared
What happens during chronic inflammation of liver?
Fibroblasts migrate in and generate new fibrous connective tissue
When does repair and wound healing take place?
Repair starts soon after inflammation and continues during and beyond inflammatory phase.
When is perfect restoration of function expected?
Depends on regeneration of lost cells by similar cells
What happens if cells cant be replaced by their own kind?
if ordinary cells cannot be replaced by their own kind they are replaced by other cell types (often scar tissue.)
If necrosis is extensive even tissues capable of regenerating are replaced by scar tissue
Which tissue have unique ways of repair?
Bone
Nervous tissue (cannot repair)
Heart myofibers
What are the cell types based on ability to regenerate?
Permanent cells that almost never double (nerve cells)
Stable cells which divide if stimulated (eg smooth muscle)
Jabile cells (such as epithelial cells of surfaces or linings of ducts)
What are the systemic effects of inflammation?
Leukocytosis which is an abnormally high circulation number of WBCs
Fever which is an elevation of body temperature regulated by hypothalamus and involves a wide range of factors
What infections are associated with higher neutrophil count?
Bacterial infections
What infections are associated with high lymphocyte count?
Viral infections
Why does fever occur?
Thought to improve leukocyte killing efficiency and impairs replication of many organisms
