Acute and Chronic Inflammation Flashcards
What causes acute inflammation?
- Tissue death (e.g. ischaemia, trauma, toxins)
- Infection (especially bacterial)
What does pyogenic mean?
Involving the production of pus.
What is suppuration?
The formation of pus.
Acute inflammation; what happens in cells can regrow?
Healing by regeneration.
Acute inflammation; what happens if cells cannot regrow?
Healing by repair.
Acute inflammation; what happens if the damaging agent persists?
Suppuration»_space; more acute inflammation»_space; chronic inflammation.
What is the purpose of acute inflammation?
- Clear away dead tissue
- Locally protect from infection
- Allow access of immune system components
What are the 4 Celsus ‘cardinal signs’ of inflammation?
- Calor (heat)
- Rubor (redness)
- Dolor (pain)
- Tumor (swelling)
What does ‘functio laesa’ (Virchow) mean?
Disturbance of function.
What are the main types of acute inflammation? (4)
- Serous
- Fibrinous
- Purulent (pus)
- Pseudomembranous
What is serous inflammation?
Release of serous fluid, usually by mesothelial cells.
-e.g. skin blisters
What is fibrinous inflammation?
Increased vascular permeability allows fibrin to enter blood vessels.
-e.g. intestinal inflammation
What is purulent inflammation?
Pus formation»_space; abscess formation.
-e.g. bacterial infection
What are the main components of acute inflammation? (3)
- Vascular reaction
- Exudative reaction
- Cellular reaction
What vascular reactions are associated with acute inflammation?
- Dilation (rubor)
- Changes in flow (initially decreases then increases)
- Increased permeability
What 2 processes control the vascular reaction?
Active control process;
MEDIATED - histamine, bradykinin, etc
NON-MEDIATED - damage e.g. toxins
What exudative reaction is associated with acute inflammation?
Formation of inflammatory exudate»_space; swelling.
What is the composition of acute inflammatory exudate?
Protein rich (~50g/L).
- immunoglobulins
- fibrinogen
What is the purpose of fibrinous mesh formation as part of the exudative reaction?
Collects debris/bacteria.
What change occurs on the heart during pericarditis due to acute exudative reaction?
Outer surface changes from being shiny»_space; rough.
-precipitated fibrin from exudate
What cellular reaction is associated with acute inflammation?
Migration of inflammatory cells out of vessels.
- neutrophils accumulate in extracellular space
- can form pus
What are systemic effects of inflammation?
- Pyrexia
- Acute phase reaction
What is pyrexia?
Raised body temperature, fever.
What is acute phase reaction?
Changes in the synthesis of certain proteins during inflammation.
» non-specific protection
What tests are done to measure acute phase reaction?
- C-reactive protein
- Erythrocyte sedimentation rate (ESR)
What are the commonest white blood cells?
Neutrophils.
Where are neutrophils produced?
Bone marrow.
What is amoeboid movement?
Crawling-like movement due to protrusion of cytoplasm»_space; temporary projection.
One feature of neutrophils is directional chemotaxis. What is this?
The movement of an organism in response to a chemical stimulus.
What is the lifespan of neutrophils?
Short - hours in tissues.
Where do neutrophils normally flow?
In the axial stream - don’t interact much with the endothelium.
What happens to neutrophils when there’s an infection?
They interact with receptors on endothelial cells which are activated.
» MARGINATION and PAVEMENTING
What is margination?
Process of free-flowing leukocytes leaving axial flow and initiating leukocyte-endothelial cell interactions.
What is pavementing?
Leucocytes adhering to the linings of capillaries during inflammation.
What are the 2 types of mediator that control inflammation?
- Cell derived
- Plasma derived
What half life do mediators of acute inflammation have?
Short half lives.
What is a STORED cell-derived mediator of acute inflammation?
Histamine.
Give examples of SYNTHESISED cell-derived mediators of acute inflammation. (6)
Prostaglandins Leukotrienes PAF Cytokines NO Chemokines
Give examples of plasma derived mediators of acute inflammation. (4)
-cascades
Kinin system
Clotting pathway
Thombolytic pathway
Complement pathway
Which processes of acute inflammation do mediators act on? (4)
- Vascular dilation
- Increased permeability
- Neutrophil adhesion
- Neutrophil chemotaxis
Give examples of anti-inflammatory drugs that interfere with the action of mediators.
- Glucocorticooid steroids
- NSAIDs
- Leukotriene receptor anatagonists
How do glucocorticoid steroids interfere with inflammatory mediators?
Bind to glucocorticoid receptors and up-regulate the expression of anti-inflammatory proteins in the nucleus.
How do NSAIDs interfere with inflammatory mediators?
COX inhibitors.
-decreased formation of prostaglandins and thromboxane
How do leukotriene receptor antagonists interfere with inflammatory mediators?
Leukotrienes are inflammatory mediators.
-prevents their production/action
What components of a FBC can be used to assess inflammation?
- Haemoglobin (increase with lung disease)
- WBC (increase with infection)
- Platelets (increase with inflammation)
How is erythrocyte sedimentation rate (ESR) used to assess inflammation?
ESR increases with inflammation.
-high proportion of fibrinogen in the blood
Give an example of an acute phase protein.
C-reactive protein.
How can C-reactive protein be used as a marker of inflammation?
Protein produced by the liver, which increases when there is inflammation anywhere in the body.
What are the main processes that trigger endothelial activation? (2)
- Tissue damage
- Neutrophil activation
What does resolution mean?
Reduction of inflammation and the removal of waste products.
List 5 conditions in which the inflammatory pathway has gone wrong.
- Systemic inflammatory response syndrome (SIRS)
- Acute adult respiratory distress sydrome
- Chronic granulomatous disease of childhood
- Hereditary angio-oedema
- Amyloidosis
What is systemic inflammatory response syndrome(SIRS)?
Non-specific systemic inflammation caused by ischaemia/trauma/infection.
What is acute respiratory distress syndrome(ARDS)?
Severe inflammation of the lungs due to infection/injury»_space; difficulty breathing.
What is hereditary angio-oedema?
Autosomal dominant disorder»_space; episodic swelling in airways/face/extremities/genitals.
-can be life-threatening
What is amyloidosis?
Accumulation of amyloid in the body, often in kidney and heart.
What bacteria is the main cause of pneumonia?
Streptococcus pneumoniae.
How do the lungs become inflamed with pneumonia?
WBCs try to fight the infection»_space; inflammation in the alveoli.
What are the main differences between acute and chronic inflammation? (4)
ACUTE
- fast onset (mins-hours)
- neutrophils
- mild and self-limiting
- prominent signs
CHRONIC
- slow onset (days)
- macrophages/lymphocytes/plasma cells
- severe and progressive
- subtle signs
What is the difference between cells types involved with acute and chronic inflammation?
ACUTE - mainly neutrophils
CHRONIC - mainly macrophages, plasma cells and lymphocytes
What is the basic process of acute inflammation?
Vessels dilate and become leaky»_space; protein rich exudate.
What are the main outcomes of acute inflammation? (4)
- Resolution
- Suppuration (abscess)
- Organisation
- Chronic inflammation
Is chronic inflammation normally primary or secondary?
Usually primary.
-but can be sequential from acute
Is granulation and scar tissue more abundant in acute or chronic inflammation?
Chronic inflammation.
What are the main primary causes of chronic inflammation? (5)
- Infection
- Endogenous material
- Exogenous material
- Autoimmune
- Primary granulomatous diseases
Give an example of an infection that causes chronic inflammation.
TB
Leprosy
What is the difference between endogenous and exogenous material?
ENDOGENOUS has internal origin within the body.
EXOGENOUS has external origin outside the body.
Give an example of endogenous material that causes chronic inflammation.
Necrotic adipose tissue
Uric acid crystals
Give an example of exogenous material that causes chronic inflammation.
Asbestos
Sutures
Implanted prostheses
Give an example of an autoimmune condition that causes chronic inflammation.
Arthritis
SLE
Pernicious anaemia
Give an example of a primary granulomatous disease that causes chronic inflammation.
Crohn’s
Sarcoidosis
What is the most common type of acute inflammation to turn into chronic inflammation?
Suppurative (pus forming) inflammation.
How does acute suppurative inflammation lead to chronic inflammation?
Pus can form an abscess
» walls thicken
» granulation and fibrous tissue
» recurrent acute can lead to chronic
Give an example of acute suppurative inflammation becoming chronic inflammation.
Cholecystitis.
-gall bladder inflammation due to stones can become chronic
How does chronic inflammation lead to fibrosis?
Infiltration by mononuclear cells
» tissue destruction
» healing by fibrosis
What is fibrosis?
The thickening and scarring of connective tissue during repair of injured tissue.
Which mononuclear cells are involved in chronic inflammation?
Macrophages
Lymphocytes
Plasma cells
What are the main macroscopic appearances of chronic inflammation? (4)
- Ulcer
- Granulomatous
- Chronic abscess cavity
- Fibrosis
What cells are present in connective tissue during inflammation? (3)
Macrophages
Plasma cells
Mast cells
What is the function of mast cells?
Release mediators (e.g. histamine). >> increased vessel permeability to WBCs and proteins
What is the main function of macrophages during inflammation?
Engulf and digest cellular debris and microbes.
What are the main polymorphonuclear leukocytes (granulocytes)?
Neutrophils
Basophils
Eosinophils
Mast cells
Where are granulocytes produced?
Bone marrow.
What is the most abundant phagocyte?
Neutrophils.
What is the main function of eosionophils during inflammation?
Antigen presenting cells.
-don’t phagocytose
What are the main functions of basophils during inflammation?
- Produce histamine
- Release prostglandins when injured
What is the main function of prostaglandins in inflammation?
Vasodilation.
-increase blood flow to the site of injury
What is the main function of macrophages in chronic inflammation?
- Increase inflammation (phagocytose bacteria)
- Release cytokines to signal monocytes
- Fibrosis
What stimulates macrophages to produce factors that induce angiogenesis?
Low oxygen content.
What happens when macrophages release cytokines to signal monocytes to the site of injury?
Monocytes enter damaged tissue from blood (RECRUITMENT).
» macrophages PROLIFERATE locally in damaged tissue
» IMMOBILISATION of macrophages in tissue
What is granulation tissue?
New connective tissue and blood vessels that form on the surface of a wound during healing. Grows up from the base of the wound.
What structures does granulation tissue contain?
- New blood vessels (angiogenesis)
- Fibroblasts (deposit collagen)
- Inflammatory cells
What is the aim of granulation tissue?
To repair and replace injured tissues with fibrous tissues.
What is the appearance of granulation tissue?
Light red/dark pink.
-due to capillaries
What is angiogenesis?
The formation of new blood vessels.
What is a fibroma?
A benign fibrous tumour of connective tissue.
-arises from 1* cell line
What type of cell induces fibrosis?
Macrophages.
What is a granuloma?
An aggregate/nodule of epithelioid histiocytes and other cells (lymphocytes, histiocytic giant cells).
What can macrophages be known as when in tissues?
Histiocytes.
What are the main structural features of epitheloid histiocytes?
- Large vesicular nuclei
- Eosinophilic cytoplasm
What enzyme do epitheloid histiocytes secrete?
Angiotensin converting enzyme.
What are histiocytic giant cells and where do they form?
Multinucleated giant cells that form where material is indigestible to macrophages.
-e.g. tubercle bacilli with cell walls resistant to macrophages
What is a giant cell?
Mass formed from the union of several cells (usually macrophages), often forming a granuloma.
Give an example of a giant cell seen in TB.
Langerhans giant cells.
- nuclei form peripheral horseshoe arrangement
- found at the centre of granulomas
Are solitary giant cells called granulomas?
No, not in the absence of epitheloid histiocytes.
Give 2 examples of bacterial granulomatous diseases.
- TB (lungs)
- LEPROSY (nerves, airways, skin, eyes)
Give an example of a parasitic granulomatous disease.
Schistosomiasis.
-urinary tract and intestines
Give an example of a fungal granulomatous disease.
Cryptococcus.
Give an example of a granulomatous disease caused by synthetic materials.
Silicosis.
-inhaling silica dust
»scarring and granulomas in upper lobes of lungs
Give 2 examples of granulomatous disease of unknown causes.
- Sarcoidosis
- Crohn’s
What is the general mechanism of granuloma formation in TB?
- Alveolar macrophages release cytokines»_space; recruit more macrophages.
- Dendritic cells present antigens to T cells»_space; T cell respeonse.
> > granuloma formation
What type of granuloma forms in TB?
CASEOUS GRANULOMA.
-macrophages, epitheloid cells and Langherans cells surrounded by T cells
