Inflammation Flashcards
What is acute inflammation?
A stereotyped, immediate response of a living, vascular tissue to injury in order to limit the tissue damage
What are the cardinal signs of inflammation?
- Heat (calor)
- Swelling (tumor)
- Redness (rubor)
- Pain (dolor)
- Loss of function
What are the features of acute inflammation?
- innate
- immediate and early
- stereotyped (always the same regardless of cause)
- short in duration
What are the main causes of acute inflammation?
infections hypersensitivity reactions trauma physical and chemical agents/ damage tissue necrosis
Outline the 2 key stages of acute inflammation
change in blood flow + exudate formation (vascular phase)
infiltration of inflammatory cells/delivery of neutrophils (cellular phase)
Why cant you get inflammation in cartilage or the lens of the eye?
No/ little blood supply
What changes occur to blood flow in acute inflammation and how? (vascular phase)
- after a few seconds the blood vessels vasoconstrict (not sure why)
- then they dilate to increase blood flow to the area (redness and heat)
- they then become more permeable (so fluid escapes and exudate forms)
what 2 chemical mediators cause increased blood flow and dilation, where are they released from?
histamine and prostaglandins (from mast cells, basophils ect)
What 2 chemical mediators causes increased capillary permeability?
histamine and leukotrienes, bradykinin, c3b and c5a
How does the exudate form?
Increased hydrostatic pressure due to vasodilation means more fluid leaves. Increased permeability means proteins from blood can enter the interstitial fluid which increases its oncotic pressure so less fluid moves back into blood at venous end- leading to swelling
(increased hydrostatic + decreased oncotic pressure)
What are the differences between exudate and transudate? (3)
- transudate has low protein concentration, exudate is protein rich
- increased vascular permeability in exudate, unchanged in transudate
- Exudate occurs in inflammation, transudate in HF/hepatic failure/renal failure
What is the result of water and proteins leaving the blood?
stasis (reduced flow through vessel) - blood becomes more viscous
How are blood vessels made more permeable? (3)
1) histamine makes endothelial cells contract to create gaps by cytoskeletal reorganisation
2) direct injuries (burns) - cause damage to vessel wall
3) leukocyte dependant injury (by toxic o2 species and enzymes released by inflammatory cells)
Outline the steps in infiltration of neutrophils into exudate (cellular phase) - 4 steps
- stasis causes RBCS to aggregate in middle and neutrophils on outline (margination)
- Neutrophils roll along endothelium and stick to it intermediately (rolling)
- IL1 and TNF causes increased expression of adhesion molecules which help it adhere to endothelium (adhesion)
- they relax the cell junctions, digest the basement membrane and then move into interstitial space (emigration)
Give examples of chemoattractants - what do they allow for?
C5a, bacterial peptides - allow neutrophils to move through interstitial towards site of injury via increasing concentration of chemokines.
What mediators cause pain?
bradykinin, substance P, prostaglandins
What local complications can be caused by acute inflammation?
- swelling (via compression of tubes) - e.g.: bile duct
- exudate can compress organs - e.g. cardiac tamponade
- loss of fluid (severe burns)
- pain and loss of function
- shock due to wide spread vasodilation
What are the systemic complications of acute inflammation? (4)
- fever due to pyrogens such as prostaglandins
- leukocytosis (increased production of white cells)- TNF, IL-1, macrophage and endothelial cells stimulate leukocyte release from bone marrow
- acute phase response (reduced appetite, increased pulse, sleep pattern changes, tiredness)
- Septic shock, huge release of chemical mediators leading to widespread hypotension, tachycardia and multi-organ failure
What are possible outcomes to inflammation? (3)
1) Complete resolution - exudate drained by lymphatics, mediators short t1/2, neutrophils undergo apoptosis, tissue undergoes regeneration.
2) Repair w/connective tissue (fibrosis) - if theres been substantial tissue destruction.
3) Progression to chronic inflammation - prolonged inflammation with repair
What is lobar pneumonia
- exudate in alveolar sacs due in strep. pneumoniae infections
- characterised by fever, dry cough, dysopnea
only effects a single lobe- bronchopneumonia effects multiple lobes supplied by same bronchus
What is most common cause of appendicitis?
- obstruction/blockage of lumen
- appendix invaded by gut flora/bacteria
- Increased pressure + perforation
What is seen in autopsy of brain with meningitis?
purlent exudate in sulci
Name 2 causative organims of meningitis
neisseria meningitidis,
strep pneumonia
group b streptococcus
Give possible complications of meningitis
seizures walking difficulty, cognitive impairment, inconenance, deafness amputations sepsis abcesses thrombosis
how does an abcess form?
- exudate from acute inflammation forces tissue apart due to pressure and often damages tissue around it
- liquifactive necrosis of this tissue occurs
What is a serous exudate
- a clear one seen in blisters ect w/ no infection present
- exudate pours into serous cavities
What is chronic inflammation?
chronic response to injury with associated fibrosis, macrophages and lymphocytes. Less is known and it is more variable than acute inflammation
When does chronic inflammation occur? (3)
1) after acute inflammation if it doesn’t resolve in a few days
2) de novo (without preceding acute inflammation) with some auto immune conditions or chronic infections like TB
3) alongside acute inflammation in severe or repeated irritation
What cells are involved in chronic inflammation?
- macrophages
- b and t lymphocytes
- eosinophiles
- fibroblasts and myofibroblasts
- giant cells
What is a giant cell why do they occur?
multinucleated cells from fusion of macrophages when they cant phagocytose something they just surround it (frustrated phagocytosis)
When are langerhans, forgein body type and touton cells (giant cells) found and what do they look like?
- langhans- horseshoe of nuclei around organism- TB infections
- Forgein body type- disorganised nuclei around foreign body
- touton giant- organised nuclei in cirlce, with foamy cytopalsm- usually found in fat necrosis
What are the effects of chronic inflammation? (4)
- fibrosis - deposition of collagen
- impaired function
- atrophy
- stimulation of immune response - antigen presentation
What is granulomatous inflammation?
Groups of macrophages and lymphocytes that stick together in lumps called epithiliod histocytes as a result of chronic inflammation due to difficult to eliminate microorganisms and particles (chronic inflammation + granuloma) - a specific type of chronic infection.
When does granulomatous inflammation occur?
- mildly irritant forgein material like from artificial joint breakdown
- infections such as TB, leprosy, fungi
- sarcoidosis, crohns, wengers granulomatosis
How do ulcerative colitis and crohns present?
UC- affects large bowel only, bloody diahorrea (rectal bleeding), continous inflammation, no granulomata
Crohns- affects all GI tract, causes skip lesions (discontinuous patches of inflammation), can sometimes find granulomata, less likely to have rectal bleeding.
What are the key differences between crohns and ulcerative colitis?
- crohns is discontinous in distribution
- ulcerative colitis is usually only the distal colon
- crohns has a cobblestone appearance to bowel mucosa
- ulcerative colitis is generally superficial and limited to mucosa and submucosa
- crohns has granulomas on microcopic appearance
What are the complications of ulcerative colitis?
- bowel cancer more common (colonectomy often performed)
- cirrhosis and hepatitis
- other auto immune conditions common- RA, eyritis, skin conditions
What is cirrhosis?
irreversible fiborsis in liver leading to loss of function
caused by hep B and C, alcohol and fatty liver disease - fibrosis and attempted regeneration
How does mycobacterium tuberculosis cause disease?
Doesn’t produce toxins or lytic enzymes but resides in granulomas and causes caseous necrosis of the lung tissue. When immunosupressed the latent TB will become activated and spread throughout lungs and lymph nodes
How does TB appear under microscope?
Granulomas, casesous necrosis, usually langhans giant cells
What stain is needed to see TB? (acid fast bacteria)
zeihl- neelsen stain
What is a mantoux test?
injecting some TB proteins, if pt has been exposed to TB there will be an immune response and youll get inflammation, if no TB nothing will happen
What is a ghon focus and ghon complex?
The primary legion caused by the TB.
If lymphnodes are involved its called a ghon complex
What is secondary TB?
when latent TB becomes activated
What is sarcoidosis?
A chronic granulomatous inflammatory condition of unknown cause effecting pts in mid 20s-40s, usually effecting lungs then skin, eyes and liver but it can effect any system.
How are TB and sarcoidosis differnt microscopically?
Sarcoidosis is non caseous and TB is caseous
Other than biopsy how else can you differentiate between TB and sarcoidosis?
Mantoux test- positive for TB only
Risk factors- sarcoidosis effects everyone (mainly young women though), TB generally only in poor living conditions
ACE is high in 60% sarcoidosis but not TB
How can you differentiate between acute and chronic inflammation on a microscope slide?
Acute has macrophages
Chronic has lymphocytes (big round nuclei)
