Lecture 3 Acute & chronic inflam Flashcards
What does inflammation do?
Remove/contain cause. Initiate repair. Reinstate useful function. Stops when agent is eliminated
5 reasons for inflammation?
Foreign body, infection, ischaemia/infarction, physical/chemical injury, immune reactions
Define acute inflammation?
Rapid host response triggering vascular and cellular reaction
What induces vasodilation?
Histamine and nitric acid
Result of increased permeability?
Fluid leaking into extravascular tissues -> oedema
Define blood stasis?
Pooling the blood at inflammation site
What triggers endothelial cells of vessel wall to contract? (4)
Histamine, bradykinin, leukotriens, substance P.
Define immediate transient response
Endothelial cells of vessel wall triggered to contact-> ^ interendothelial spaces
What does endothelial injury lead to?
endothelial cell death -> vessel wall damaged -> immediate extravascular leakage
Define transcytosis
^ transport of fluids/proteins through cell channels.
Define VEGF
Vascular endothelial growth factor (new blood vessels)
Define transcytosis
through the cell in and out
Main aim of inflammation is to recruit…
leucocytes to area of damage
What do neutrophils and macrophages do?
Ingest and kill bacteria and necrotic cells AND promote repair
What are 5 steps of cellular reaction?
Margination. Rolling. Adhesion. Transmigration. Chemotaxis
Define margination
Red blood cells flow in centre, WBC flow peripherally. In stasis more WBC fall to peripheral flow
Define rolling
Increased amount of leucocytes roll along edge of damaged endothelium (mediated by selectins)
Define adhesion
Leucocytes stop and adhere to endothelium.
What encourages the adhesion of leucocytes?
Cytokines from injured cells
Define transmigration
Leucocyte encouraged to pass through endothelium to extravascular space.
What is PECAM-1?
Platelet endothelial cell adhesion molecule
Define chemotaxis
Exogenous (bacteria) and endogenous (cytokines/complement) substances attract leucocytes
When do neutrophils appear?
6-24 hours
When do monocytes appear?
24-48 hours
Are neutrophils or monocytes more common in circulating blood and respond to chemokines?
Neutrophils
What do leucocytes do?
Recognise foreign microbes
What receptors do leucocytes have?
Toll like, G-protein coupled receptors and, opsonin receptors and cytokine receptors
What do toll like receptors do?
Attach to bacteria products
What do G-protein coupled receptors recognise?
N-formymethionyl of bacteria & chemokine breakdown
What do opsonin receptors recognise?
microbes that have been coated with proteins (antibodies/compliment) or opsonins. (opsonisation). Targets them for phagocytosis
What do cytokine receptors do?
respond to cytokines.
After substantial tissue destruction, X regeneration, what replaces damaged area?
Connective tissue
Chronic inflammation is caused by?
Persistent infection (parasite), immune mediated, prolonged exposure to toxic agent (asbestos, lipids).
With chronic inflammation what is normally seen?
Show infiltration of mononuclear cells (macrophages), Tissue destruction following prolonged inflam, signs of attempts at healing.
Define granulomas
Cellular attempt to contain offending agent that it cannot remove. Macrophages &T-lymphocutes cause injury. (Tuberculosis.
Damaged tissues release…
histamine that ^ blood flow to area
What do histamines do?
cause capillaries to leak releasing phagocytes & clotting factors.
What can cause acute inflam?
infarction, bacterial infection, trauma, burn
What can cause chronic inflam?
virus, autoimmune
What can acute inflam result in?
resolution, abscess, fibrosis
What can chronic inflam result in?
Fibrosis
Clinical cardinal signs of inflam
Redness (rubor), heat (calor), swelling (tumor), pain (dolor) and loss of function
Signs and symptoms of inflam?
fever, tachy, hypotension, ^ WCC, ^CRP.
Weight loss, malaise, sepsis -> CV failure (septic shock)
Numbers for CRP
> 10 means inflam. Not worried about 15 but will in 100’s
Examples of exagerated or inappropriate inflam response?
Allergies, hypersensitivity & autoimmune diseases
What can we do for inflam?
NSAIDs, antihistamines, steroids, targeted biologics (anti TNF)
What happens if there is no inflam response?
^ chance of infection, delayed wound healing, tissue damage
Acute appendicitis notes
10-30 years old. Pain localised to right iliac fossa. Worse on movement. N/V. Pyrexia. Tachy. ^WCC. ^CRP.
Management of acute appendicitis?
Appendicectomy
Complications of appendicitis?
Performation leading to peritonitis & abscess formation
Septic arthritis notes
Red, hot, swollen joints, unable to move. Pyrexia, tachy, ^WCC, ^CRP.
Risk factors for septic arthritis?
prosthetic joint, recent surgery/trauma. age. RA.
Treatment of septic arthritis?
Joint aspirate. IV antibiotics. Sepsis 6.
Minor injury inflam response
has no benefit. Rest prevents further injury.
RA notes
Chronic autoimmune inflam. Warm, swollen, stiff and painful joints. Immune sees host as foreign -> healthy joint destroyed.
Complications with RA.
Vessels can become involved- vasculitis -> circulatory problems
Treatment of RA
Steroids, DMARDS, biologics
Peptic ulcers notes
Acute inflam response (hpylori/excess acid). Necrotic inflamed mucose falls away. Does not repair.
Complications of peptic ulcers
developing bleed/perforation
Treatment of peptic ulcers
PPIs/ histamine receptor agonist/ antibiotics.
