Acute and Chronic Inflammation Flashcards
List some possible causes of acute inflammation
Microbial infections
Foreign bodies (splinters, dirt, sutures) or trauma (blunt/penetrating)
Hypersensitivity reactions
Physical and chemical agents (thermal injury, irradiation)
Tissue necrosis
List the macroscopic features of acute inflammation
RUBOR - redness (erytherma) CALOR - heat TUMOUR - swelling (odema) DOLOR - pain Loss of function
Describe the changes that occur microscopically in acute inflammation.
- Vasodilation with increased blood flow
- Gaps form in the endothelium as endothelial cells swell and retract
- Exudation: vessels become leaky (to water salts and small proteins)
- Marination & emigration: neutrophils adhere to swollen endothelial cells the migrate through the vessel basement membrane
- Macrophages and lymphocytes migrate in a similar way
What is the action of neutrophils in acute inflammation?
Migrate through the basement membrane, travel to site of injury by chemotaxis.
Phagocytose microorganisms by making contact, recognising and internalising them. Phagosomes then fuse with lysosomes to destroy contents.
Activated neutrophils may also release toxic metabolites or enzymes, causing damage to the host tissue.
What chemical mediators cause vasodilation?
Histamine Prostaglandins C3a C5a Serotonin
What chemical mediators increase vascular permeability?
Histamine
Prostaglandins
Bradykinins
Serotonin
What chemical mediators cause emigration of leukocytes?
Leukotrienes
IL-8
C5a, C3a
What are the systemic consequences of acute inflammation?
Acute phase response = reduced appetite, increased heart rate, altered sleep patterns, changes in plasma concentration of acute phase proteins.
Spread of microorganisms and toxins lead to shock.
Fever produced by endogenous proteins IL-1, TNFa and prostaglandin.
Leukocytosis (high WBCs), IL-1, TNFa produce an accelerated release from bone marrow.
What an happen after an acute inflammation?
- Complete resolution
- Continued acute inflammation with chronic inflammation (abscess)
- Chronic inflammation with fibrous repair
- Death
Why does acute inflammation occur?
Acute inflammation is the response of living tissue to injury and is initiated to limit tissue damage.
How does resolution after acute inflammation occur?
All mediators have short half lives, can be inactivated by degradation/dilution/inhibition.
Gradually all changes reverse and vascular changes stop.
Exudate drains via lymphatics, fibrin degraded by plasmin, neutrophils die.
Damaged tissue may be able to regenerate but if tissue architecture is damaged complete resolution not possible.
Describe some possible complications of acute inflammation.
Swelling can lead to blockage of tubes eg. bile duct, intestine.
Exudate can lead to compression of structures eg. cardiac tamponade, or serositis (inflammation of serous membranes)
Loss of fluid leads to dehydration eg. in burns
Pain and loss of function
Give some clinical examples of acute inflammation
Skin blister
Pericarditis
Abscess
Describe the properties of a skin blister
Caused by heat, sunlight, chemicals.
Pain and profuse exudate (relatively few inflammatory cells so exudate is clear).
Collection of fluid strips off overlying epithelium.
Results in resolution or scarring.
Describe the properties of pericarditis
Inflammation of the serous cavity.
Pericardium becomes inflamed and increases pressure on the heart.
Describe the properties of an abscess
Occurs in solid tissues.
Inflammatory exudate forces tissue apart, liquefactive necrosis in the centre.
May cause high pressure, therefore pain, may cause tissue damage, squash adjacent structures.
What is Hereditary Angio-Odema and how is it treated?
Deficiency of C1 inhibitor which inhibits C1 (complement protein that cleaves C2 and C4 to form C3) and bradykinin.
Uninhibited bradykinin increases permeability of endothelia, causing odema.
Treat with C1 inhibitor infusion or fresh frozen plasma.
What is a1-antitrypsin Deficiency?
a1-antitrypsin inhibits elastase, without inhibition elastase breaks down lung/liver tissue causing emphysema and liver sclerosis.
What is Chronic Granulomatous disease?
Phagocytes can’t form reactive oxygen species so cannot kill some bacteria.
Granulomas are formed in attempt to contain the bacteria.
Recessive sex-linked
Give some examples of disorders of the acute inflammatory process
a1- antitrypsin deficiency
Inherited complement deficiencies eg. Hereditary Angio-Odema
Defects in neutrophil function/numbers
What are the different types of exudate?
- Pub/abscess: exudate is creamy white as it is rich in neutrophils, typical of infections by chemotactic bacteria.
- Haemorrhagic: contains more RBCs, indicates significant vascular damage, seen in destructive infections/infiltration by a tumour.
- Serous: exudate is clear, contains plasma proteins but few leukocytes suggesting no infection, typically seen in blisters.
- Fibrinous: significant deposition of fibrin, occur in pericardial/pleural spaces meaning the serous surfaces cannot slide smoothly, friction is heard as rubbing sound.
What is chronic inflammation?
A chronic response of living tissue to injury with associated fibrosis
How does chronic inflammation arise?
- May take over from acute inflammation if damage is too severe to be resolved.
- May arise de novo in autoimmune conditions/chronic infections/chronic low-level irritation
- May develop alongside acute inflammation, in severe/persistent/repeated irritation.
List the effects of chronic inflammation
Fibrosis eg. in chronic cholecystitis, chronic peptic ulcer, cirrhosis
Impaired function eg. in chronic inflammatory bowel disease (rarely causes increased function eg. in thyrotoxicosis, mucus secretion)
Atrophy eg. of gastric mucosa, adrenal glands
Stimulation of immune response, macrophage/lymphocyte interactions
List the cells involved in chronic inflammation
Macrophages Lymphocytes Eosinophils Fibroblasts/myofibroblasts Giant cells
What is the role of macrophages in chronic inflammation?
Phagocytose and destroy debris/bacteria
Presentation of antigen to the immune system
Synthesis of cytokines, complement components,clotting factors and proteases
Control other cells via cytokines release.
What is the role of lymphocytes in chronic inflammation?
Also called the ‘chronic inflammatory cells’, have immunological functions.
B-lymphocytes differentiate to produce antibodies
T-lymphocytes are involved in control & cytotoxic functions
What is the role of eosinophils in chronic inflammation?
Allergic reactions
Parasite reactions
Some tumours
How are fibroblasts/myofibroblasts involved in chronic inflammation?
They are recruited by macrophages, make collagen
What are giant cells?
Multinucleate cells made by fusion of macrophages, through the process of frustrated phagocytosis.
What are the three different types of giant cells and what do they indicate?
Langhans indicate tuberculosis (caseous necrosis in the centre)
Foreign Body Type indicate foreign body
Touton indicate fat necrosis
What is chronic cholecystitis and how is treated?
Repeated obstruction of the gall bladder with gallstones. Repeated acute inflammation leads to chronic inflammation and fibrosis of the gall bladder wall.
Treated with surgical removal of the gall bladder
What is gastric ulceration and how is treated?
Acute gastritis caused by alcohol/drugs, chronic gastritis caused by hello actor pylori.
Ulceration and fibrosis occurs because of an imbalance between acid production and mucosal defence.
Chronic is treated with a Proton Pump Inhibitor (omeprazole) & 2 antibiotics.
What are the symptoms of inflammatory bowel disease and what are 2 types?
Diarrhoea, rectal bleeding, abdominal pain
Ulcerative Colitis and Crohn’s Disease.
What is ulcerative colitis and how is treated?
Inflammation of the colon
Superficial
Increases risk of colon cancer
Treat with immunosuppression, surgical removal of large bowel.
What is Crohn’s disease and how is treated?
Inflammation of the GI tract lining
Transmural, cobblestone appearance, discontinuous distribution.
Causes strictures and fistulas (abnormal connections between 2 epithelia)
Treat with lifestyle modifications (diet/hydration) and immunosuppressants.
What is liver cirrhosis and how is treated?
Chronic inflammation with fibrosis leads to disorganisation of architecture and regeneration.
Common causes are alcohol, infection with HBV/HCV, immunological, fatty liver disease, drugs and toxins.
Cannot be reversed but treat with lifestyle changes to prevent further damage, transplant may be necessary.
What is thyrotoxicosis?
Graves’ disease, antibodies stimulate TSH receptors leading to hyperthyroidism.
What is granulomatous inflammation?
The formation of granulomas. Occurs when the immune system tries to fight off something that it is unable to eliminate
Eg. Irritant foreign material, infections (TB, leprosy, syphilis, some fungi), Crohn’s disease.
How can chronic inflammation and immune responses overlap?
Immune diseases can cause pathology by chronic inflammation and
Chronic inflammatory processes can stimulate immune responses.
What is Rheumatoid Arthritis?
An autoimmune disease that causes localised and systemic immune response.
Localised chronic inflammation leads to joint destruction by erosion of the articulating surfaces.
Systemic immune responses can affect other organs, can cause amyloidosis.
Give examples of diseases with granulomatous inflammation
TB Leprosy Sarcoidosis Syphilis Wegeners Granulomatosis Crohn's disease
What is TB and what are the possible outcomes?
Caused by mycobacterium, causes disease by persistence and induction of cell-mediated immunity (no toxins/lytic enzymes produced). Possible outcomes:
- Arrest, fibrosis and scarring
- Erosion into bronchus
- TB emphysema (collection of pus)
- Erosion into the blood stream
What is sarcoidosis?
A chronic idiopathic disease with abnormal collections of granulomas, they from nodules in organs eg lungs or lymph nodes.
Treat with steroids
What is leprosy?
Caused by mycobacterium leprechaun.
Causes vigorous cellular immune response, granulomas of nerves, respiratory tract, skin and eyes.
Leads to lack of ability to feel pain, loss of parts of extremities due to repeated injuries
What is Wegeners Granulomatosis?
An autoimmune disease with necrotising granulomatous inflammation (Granulomatosis with polyangitis).
Symptoms are fevers, night sweats, fatigue, lethargy, loss of appetite, weight loss.
What is syphilis?
An infection caused by Treponema Pallidum Bacteria, transmitted by sexual contact/from mother to foetus/blood transfusion.
Sores on genitals/mouth, skin rash & sore throat, can affect organs eg heart and brain.
