Path Pro Flashcards
What are the stages of acute inflammation
- Stimulus
2.Vascular stage - slowing the circulation and forming exudate at the site of inflammation - Cellular stage - the migration of neutrophils to the site
- Resolution or persistance (develops into chronic inflammation)
Describe vascular phase of acute inflammation
vasoconstriction for a few seconds
then vasodilation=>
-↑ blood flow to affected area
-↑ permeability=allows fluid, cells and proteins to exit
-↑ viscosity of blood due to less fluid
how is vascular phase regulated?
For the first 30 mins, main mediator is histamine (released by mast cells, basophils, platelets). As the inflammatory response continues, it is mediated by leukotrienes, bradykinins
What is the purpose of exudate?
-deliver proteins (fibrin, immunoglobulins, and inflammatory mediators)
-dilutes toxins to reduce damage
-increases lymphatic drainage
How is exudate formed?
-↑ hydrostatic pressure in the vessel (the pressure exerted by a fluid which forces fluid out)
-↑ oncotic pressure in the interstitium (osmotic pressure exerted by proteins which draws fluid in).
-endothelial contraction
What causes vascular leakage?
-Retraction of endothelial cells (mediated by histamine, nitric oxide, leukotrienes)
-direct injury (burns, toxins, etc.)
-leucocyte dependent injury (ROS, enzymes from leukocytes)
Types of exudate
-Pus- neutrophil rich, infections of pyogenic bacteria
-Haemorrhage- presence of RBC’s, significant vascular damage
-Serous- clear fluid with leukocytes, blisters and burns
-Fibrinous- deposition of fibrin, friction betwen serosal surfaces, seen in pericarditis
What does the presence of neutrophils indicate? Identifying feature?
Indicates pathogenic organism or injury
trilobed nucleus
What happens in the cellular phase of acute inflammation
Neutrophils are attracted to affected area
Removal of pathogens and necrotic tissue
Release of inflammatory mediators
How do circulating neutrophils infiltrate site of injury?
-Margination- due to increased viscosity, blood contents including neutrophils move to the walls of the vessel
-Rolling- roll along the endothelial wall forming weak bonds
-Adhesion- neutrophils form strong bonds with the endothelial cells; mediated by adhesion molecules
-Diapedesis/Emigration- neutrophils exit directly through the endothelial cells or between them
Adhesion Molecules (neutrophils, AI)
-Selectins- expressed on endothelial cell, form weak bonds (Rolling)
-Integrins- expressed on neutrophil surface, can change from low affinity to high affinity, tight bonds (Adhesion)
How do neutrophils reach site of injury (AI)
Chemotaxis- Neutrophils are attracted to chemoattractants (bacterial peptides, inflammatory mediators) that are released at site of injury
How do neutrophils destroy pathogens?
Phagocytosis
Engulf→ phagosome→ phagolysosome→ digestion→ release of debris
How do neutrophils recognize what to phagocytose?
Pathogens are recognised by opsonisation
Opsonins=cell tags that flag it for phagocytosis, ex- Fc, C3b
Where are inflammatory mediators released from?
Activated inflammatory cells
platelets
endothelial cells
toxins
Inflammatory mediators that cause vasodilation
Histamine
Serotonin
Prostaglandins
Nitric Oxide
Inflammatory mediators that cause vascular permeability
Histamine
Bradykinin
Leukotrienes
C3a, C5a
Inflammatory mediators that cause chemotaxis
C5a
TNF-a
IL-1
bacterial peptides
Inflammatory mediators that cause pyrexia
Prostaglandins
IL-1, IL-6
TNF-a
Inflammatory mediators that cause pain
Bradykinin
Substance P
Prostaglandins
Local complications of AI
-Swelling- compression of tubes (airways, bile ducts, etc.)
-Exudate- compression of organs (cardiac tamponade)
-Loss of fluids- dehydration (burns)
-Pain- Muscular atrophy, psycho-social complications
Systemic complications of AI
-Fever
-Leucocytosis (inc. prodn. of WBC’s)
-Acute Phase Response (malaise, red. appetite, altered sleep)
What causes Acute Phase Response
Acute Phase Proteins, ex- C-reactive Protein, Fibrinogen, α1 antitrypsin
How do NSAIDS work
Non-Steroidal Anti-Inflammatory Drugs (ex-aspirin, ibuprofen) block cyclo-oxygenase enzymes which are involved in production of prostaglandins
How does chronic inflammation arise?
-Takes over from acute inflammation (if resolution is not possible from AI alone)
-Develops alongside AI (severe/persistent insult)
-De novo chronic inflammation (ex- autoimmune diseases)
Macrophages- identifying histology features
large foamy cytoplasm (full of lysosomes)
sometimes indented nucleus
Role of macrophages?
-phagocytosis
-antigen presentation to immune system
-synthesis and release of inflammatory mediators
lymphocyte histology appearance
small cells, large round nucleus, small cytoplasm
Role of Lymphocytes
-Helper T cell: assist other inflammatory cells
-Cytotoxic T cells: directly destroy pathogens
-B cells: mature into plasma cells which produce antibodies
Plasma cell histology appearance
large cells
acentric nucleus with clockface pattern
peri-nuclear clearing (dues to prominent golgi bodies)
Eosinophil histology appearance
similar size to lymphocyte, bilobed nucleus, granular red staining cytoplasm
‘tomato wearing sunglasses)
Eosinophil function
release of a variety of mediators
especially during hypersensitivity reactions and parasitic infections
how are giant cells formed?
formed by fusion of multiple macrophages (frustrated phagocytosis)
Types of giant cells
-Foreign body GC (in response to a foreign body, scattered nuclei)
-Langhans GC (Nuclei arranged as a ring or horseshoe shape at the cell border; seen in TB)
-Touton GC (ring of nuclei in the middle; seen in fat necrosis)
Which is the main cell type in CI?
generally non-specific but sometimes can indicate a diagnosis
Rheumatoid arthritis- plasma cells
Chronic gastritis- lymphocytes
Whipples disease (bacterial)- macrophages
Parasitic- eosinophils
Effects of Chronic inflammation
-Fibrosis (deposition of collagen)
-Impaired function
-Atrophy
-Stimulation of immune response (antigen presentation)
-rarely, increased function (ex-graves disease)
Crohns disease
-affects entire GI tract
-discontinuous patches of inflammation
-affects full thickness of bowel wall (transmural)
-can sometimes cause granulomata
-rectal bleeding rare
Ulcerative Colitis
-affects large bowel only
-continuous inflammation
-affects only superficial layers (mucosa and submucosa)
-no granulomata
-prone to rectal bleeding
Causes of cirrhosis
-alcohol
-drugs/toxins
-fatty liver disease
-hepatitis
Granulomatous inflammation
chronic inflammation + granuloma
What is a granuloma
a collection of epithelioid histiocytes (macrophages) with surrounding lymphocytes
Difference btwn giant cell and granuloma
both are made of macrophages but in giant cells the macrophages are fused into one multi-nucleated cell, in granuloma the individual cells are still distinct
Types of granuloma
-Foreign body granuloma
=few surrounding lymphocytes)
-Immune mediated granuloma
=destruction/ removal of pathogens (bacteria/fungi)
=can undergo central (caseous) necrosis
=many surrounding lymphocytes
Examples of infections characterized by granulomatous inflammation
Myobacterium infections
-myobacterium tuberculosis (TB)
-myobacterium leprae (leprosy)
Examples of idiopathic granulomatous inflammation
-Sarcoidosis (in lymph nodes, skin, lungs, etc.)
-Crohns disease (in GI tract)
(non-necrotising)
Define atherosclerosis
Disease Process
Accumulation of intra and extracellular lipid in the intima and media of large and medium sized arteries
Define atheroma
Necrotic core of the atherosclerotic plaque causing thickening and hardening of arterial walls
what is the blood supply of blood vessels called
Vaso vasorum
Risk factors for chronic endothelial damage
Raised levels of LDL
Hypertension
Smoking-toxins
Haemodynamic stessors
How are foam cells formed?
Chronic endothelial damage→ endothelial dysfunction
smooth muscle cell proliferation and migration
Lipids (LDL and Ch) cross into intima
Macrophages engulf lipids in the intima
Macrophages+sm cells=foam cells
What do foam cells do
secrete cytokines which leads to
-further smooth muscle cell stimulation
-recruitment of other inflammatory mediators
How are the necrotic center and fibrous cap of atherosclerotic plaque formed?
-Lipid debris secreted by macrophages in the center forms the necrotic contents
-Covered by a fibrous cap (sm cells produce collagen, elastin and other proteins)
Components of atherosclerotic plaque
Cells: endothelial cells, platelets, neutrophils, macrophages, leucocytes, sm cells
Lipid: intracellular(foam cells) and extracellular (pools)
Extracellular Matrix: collagen, elastin, proteoglycans
Complications of unstable atherosclerotic plaque
unstable plaque→ can rupture → can allow platelet aggregation (thrombus formation)→ pressure atrophy of underlying media, weakening of elastic lamina
Complications of Atherosclerotic plaque
-Ulceration
-Thrombosis (further stenosis or occlusion)
-Vasospasm (local vasoconstrictor release)
-Embolisation
-Calcification (cholesterol cleft deposition)
-Haemorrhage
-Aneurysm formation
-Rupture
Atherosclerosis in brain
-Transient Ischaemic Attacks (resolve within 24hrs)
-Cerebral Infarction
-vascular dementia
-cerebral haemorrhage (stroke)
Atherosclerosis in heart
-sudden death
-MI
-angina pectoris
-Arrythmias
-Cardiac failure
Atherosclerosis in GI tract
acute- intestinal infarction
chronic- ischaemic colitis, malabsorption
Atherosclerosis in peripheral arteries
-acute limb ischaemia
-Ischaemic pain
-Intermittent claudication
-Gangrene
Risk factors for atherosclerosis
-Age
-Gender (post-menopausal)
-Hyperlipidaemia (including defects in lipid metabolism)
-Smoking
-Hypertension
-Diabetes mellitus, obesity
-Infection (chlamydia pneumoniae, helicobacter pylori, CMV)
-Lack of exercise
-Stress
Prevent/reduce atherosclerosis
-decrease Cholestrol and LDL in diet
-Lipid lowering drugs (statins)
-Low fat, high fibre diet
-Aspirin
(*small amounts of alcohol may be protective)
