Pathophysiology of inflammation Flashcards
physiology
science of the function of living things
pathophysiology
study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury
pathology
scientific study of disease itself
disease
a condition where the presence of an abnormality is sufficient to cause a loss of normal health
causes of acute inflammation
Microbial infection e.g. bacteria, viruses
Allergy e.g. pollen, animals, dust
Physical agents e.g. trauma, ionising radiation, heat, cold
Chemicals e.g. corrosives, acids, alkali, smoke, bacterial toxins
Tissue necrosis e.g. ischaemia (not enough blood getting to tissue) , infarction (no blood getting to tissue)
disease depends on?
trigger and location
first 3 steps of inflammation
trigger, detection, signalling
inflammatory mediators explain
chemical messenger that convey info from one cell to another;operate in the immediate microenvironment (compared with hormones that are released from an endocrine gland & travel to distant targets in the circulation)
inflammatory mediators include:
histamines, prostaglandins and leukotrienes
- triggers a cascade that brings in defence forces against trigger, repel it & heal any damage
inflammatory mediators that are eicosanoids
prostanoids, leukotrienes, lipoxins, resolvins
inflammatory mediators that are peptides and proteins
cytokines, bradykinin
inflammatory mediators that are simple compounds (amines)
histamine, serotonin (5HT)
roles of interleukins
signal between wbc (and many other functions)
=pro-inflammatory e.g. TNF-a , IL-1
= anti-inflammatory e.g. TGF-beta, IL-4,10,13
Role of interferons (INF)
interfere with viral replication
e.g. INF-a, INF-b, INF-y
role of chemokines
control the migration of wbc e.g. neutrophils, IL-8, monocytes, eosinophils
role of colony stimulating factors
stimulate the formulation of maturing colonies of wbc
cytokines define
protein/ polypeptide mediators synthesised & released by cells of the immune system during inflammation; coordinate the inflammatory response
after signalling inflammation pathway leads to—
vascular response - and or fluid exudate /cellular exudate
during fluid exudate there are four proteolytic enzyme cascades involved:
coagulation cascade
fibrinloytic cascade
kinin cascade
complement cascade
cellular exudate is when?
chemokines attract circulating cells
-adhesion molecules (e.g.migration to tissues)
- neutrophils predominate
Drives clotting- stimulates the production of thrombin, which converts fibrinogen to fibrin ?
coagulation cascade
Breaks down clots – these systems are balanced
fibrinolytic cascade
kinin cascade:
maintains & amplifies the process
drives production of bradykinin which is a vasodilator but also mediates pain
complement cascade
releases histamines
is chemotactic (attracts cells)
opsonises (tags damages cells & microbes) & lyses bacteria
why is pus green?
as neutrophils die, they release myeloperoxidase which gives pus its green colour
harms of inflammatory
Digestion of normal tissues E.g. proteases released from lysis of neutrophils
Swelling E.g. of airway, in brain may be harmful
Inappropriate inflammatory response where stimulus is ‘harmless’
Hypersensitivity
example of antigen presenting cell (APC)
dendritic cell : detect pathogens , activate adaptive immunity
macrophages: engulf tissue debris, dead cells, microorganism
difference between macrophage (M1/M2)
M1- Pro-inflammatory
M2- tissue repair and healing
APC travel where?
in the lymphatic system to the lymphoid tissue, where they present the AT to the cell lymphocytes
what mature in the bone marrow, make antibodies?
B cells
what mature in the thymus, cell mediated immunity ?
T cells
Cytokine example
Interleukins, interferons (INF) , chemokines, colony stimulating factors (CSF)
What happens at vascular response stage(
Inflammatory mediators released
Vasodilation= increase blood flow (rubor calor)
Increased vascular leakiness (tumor)
What happens at vascular response stage?
Inflammatory mediators released
Vasodilation = increased good flow (rubor, calor)
Increased vascular leakiness (tumor)
- all lead to this and cellular exudate
3 types of examples of granulocytes
Basophil, eosinophil, neutrophil
3 types of example phagocytes
Neutrophil
Macrophage
Dendritic cell
What happens at cellular exudate?
Chemokines attract circulating cells
Adhesion molecules involved : can increase adherence to endothelial cells , allowing migration into tissues
Neutrophils predominate
Phagocyte process to APC
- Interaction between phagocyte and pathogen promoted by opsonisation
- Pathogen interacts with phagocyte receptors
- Phagocyte pathogen envelops: lysosomes contain proteolytic enzymes and hydrogen peroxide
- Pathogen digested
- Pathogen breaks down into proteins and other molecules
- Becomes APC
Benefits of inflammatory response
Delivery of: antibodies, nutrients and oxygen, drugs e.g. Antibiotics
Dilution of toxins
Fibrin formation: trapping bacteria, forming matrix of granulation tissue
Stimulates adaptive immunity
Example of pro-inflammatory
M1
Role of M2.
Tissue repair and healing
Macrophage role
Engulf tissue debris, dead cells, microorganism
Then antigen present
Dendritic cell role
Detect pathogens
Antigen present-activate adaptive immunity
How is an antigen presented?
Processed by cell and presented with major histocompatibility complex
Proteins found on surfaces of cell help the immune system recognise foreign substances
APC travel where to present the antigen?
Travel in the lymphatic system to the lymphoid tissue
Difference between B and T cell
B cells: mature in the bone marrow, make antibodies
T clue: mature in the thymus, cell mediated immunity
Memory antibody
IgG
Acute antibody
IgM
Allergic antibody
IgE
Antibody in body fluids e.g. Saliva, snot
IgA
Adaptive immunity involves
Humoral immunity: B cell make antibodies
Effective in intracellular fluid
Cell mediated immunity: Cytotoxic T cells kill intracellular microorganisms
Activate macrophages
Systemic effects of inflammation
Constitutional symptoms e.g. Fatigue
Lymph node enlargement
Increased circulating WBC
Liver-release acute phase response proteins (C-reactive protein)
Hypothalamus-pyrogens from leukocytes e.g.IL2 cause fever
Inflammation
Suppuration
Continuos fight between the bacteria and the immune system- abscess or collection of pus
Different classes of MHC
MHC 1
MHC 2
Trigger different pathways
Drugs to treat inflammation
Non steroidal anti-inflammatory drugs e.g. Aspirin, ibuprofen
Corticosteroids eg prednisolone
Role of NSAIDs
Inhibit synthesis of the prostaglandin mediators, therefore prevent activation of the inflammatory pathway
What can be used for acute or subacute inflammation?
Corticosteroids
But in the long term, have severe side effects which limit their use for chronic inflammation
If trigger persists in the inflammation response it can lead to?
Chronic inflammation and tissue destruction
Autoimmune disease
A process where we have abnormal detection of self; fail to recognise self, therefore antibodies/ cytotoxic cell against self— can lead to chronic inflammation and tissue destruction
Example of autoimmune disease: thyroid
Graves’ disease
Example of autoimmune disease: bones
Rheumatoid arthritis
Example of autoimmune disease: muscles.
Muscular dystrophy
Example of autoimmune disease: skin
Eczema
Vitiligo
Example of autoimmune disease: lung
Fibromyalgia
Example of autoimmune disease: nerves
Peripheral and diabetic neuropathy
Example of autoimmune disease: gi tract
Crohn’s disease
Celiacs disease
Diabetes type 1
Example of autoimmune disease: blood
Leukaemia
Example of autoimmune disease: brain
Autism
Multiple sclerosis
When treating autoimmune disease, the aim of treatment is to?
Reduce symptoms- anti-inflammatory drugs
Prevent long term tissue damage- disease modifying drugs
Maintain function: physiotherapy
Why is treatment for auto- immune disease targeted at inflammation? And not cause
Cause is largely unknown
DMARDs
Disease modifying anti-rheumatic drugs
Biologics
Subset of DMARDs
Synthetic antibodies that can be antibodies against a specific protein
Hypersensitivity
An excessive and potentially harmful immune reaction t0 a foreign substance not otherwise considered to be noxious ( harmful or injurious to health)
Role of DMARDs
Immunosuppressants that damp down the immune system to stop it from attacking the joints
How many types of hypersensitivity are there?
4
Immediate/anaphylactic hypersensitivity
Type 1
One key difference between hypersensitivity and acute inflammation is?
That mediating cell is called an eosinophil in cellular exudate
Stains red with certain stain under microscope
Laryngeal edema LE
Vocal cords in the larynx are incredibly swollen
Adrenaline is what agonist?
Adrenoceptor agonist
Effect of adrenaline on alpha and beta receptors
Vasoconstriction = alpha receptors
Vasodilation = beta receptors
How to treat anaphylaxis
Anti-histamine
Corticosteroids
Adrenaline injection -> alpha- constriction b/c of hypertension
B adrenoceptor agonist = vasodilation, increases in bp, reduce swollen airways and breathe
How to treat chronic type I hypersensitivity
Prevention: Maintain immune suppression so there isn’t inflammation via desensitisation / corticosteroids
Treatment: control flares/attacks asap with corticosteroids eg eczema topical steroid cream
Type 2 hypersensitivity is known as
Antibody-dependent cytotoxic hypersensitivity
What happens in type 2 hypersensitivity
Antibody-dependent reaction
Antibodies (IgG or IgM) attach to cellular antigen
E.g. rbc from transfusion
Happen- cell protein combined with drug
Opsonise cells, activate complement, own cells are phagocytes
Type 3 hypersensitivity also known as?
Complex-mediated hypersensitivity
What happens in type 3 hypersensitivity?
IgM or IgG antibodies form complexes with soluble antigen e.g in foreign serum
Complexes become deposited in tissues where they activate inflammation, causing tissue damage
Eg. Occurs in blood vessels, kidney, joints
Type 4 hypersensitivity also known as
Cell - mediated or delayed hypersensitivity
What happens in type 4 hypersensitivity
Pathological reactions to environmental chemicals or persistent microbes (eg tuberculosis)
How to treat hypersensitivity?
Anti-histamines
Leukofriene receptor antagonists
Monoclonal antibodies
Corticosteroids have multiple actions
Benefits of treating hypersensitivity
Relieve symptoms of inflammation : pain, swelling
Reduce tissue damage due to chronic inflammation
Adverse effects of treating hypersensitivity
Anti-inflammatories may prevent healing by: impairing resolution of inflammation
Allowing activity by suppressing pain
Immunosuppressants suppress other inflammatory responses e.g. Infection may be more severe
