ACUTE&CHRONIC INFLAMMATION, TISSUE REPAIR AND WOUND HEALING Flashcards
INTRO
Inflammation is a protective attempt of the body to remove the injurious stimuli and initiate the healing process
Considered as a mechanism of innate immunity
4 CARDINAL SIGNS OF INFLAMMATION + 1
Calor(heat)
Rubor(Redness)
Dolor(Pain)
Tumor(Swelling)
Functio - laesa(Loss of function)
COMPONENTS OF ACUTE INFLAMMATION
Acute inflammation is a rapid host response that serves to deliver leukocytes and plasma proteins such as antibodies to sites of infection or tissue injury
Vascular events;
-Vascular Dilation(due to several mediators namely histamine and NO)
-Increased Vascular Permeability (leading to protein and cell rich exudation of fluid)
-Vascular stasis.
Cellular Events; 7 (Mr pdp.cc)
1 Margination
2 Rolling
3 Pavementing
4 Diapedesis/Emmigration
These First 4, all made possible by cell adhesion molecules(Integrins, Sialy-lewis protein, immunoglobulin superfamily and selectins)
5 Chemotaxis(migration of cells towards attractant chemicals or away from repellants)
Examples; C5a, Leucotriene B4, bacterial products, breakdown products of PML
6 Phagocytosis— Opsinins are extracellular proteins which binds to substances or cells and induces phagocytes to phagocytose(acts as a tag for the cells or substances to be phagocytosesd)
Examples; IgG, C3b, fibronectin and fibrinogen.
Neutrophils carry out phagocytosis
7 Cellular Killing
Killing and Degradation is by 2 mechanisms
I. Oxygen dependent mechanisms
II. Oxygen independent mechanisms
Effected by— Lactoferrin, Lysozyme, Cationic proteins, MBP(major basic proteins), BPI(Bactericidal permeability increasing factor)
MECHANISM OF INCREASED VASCULAR PERMEABILITY
(FC-IDDLL)
Formation of endothelial gaps in venules
Cytoskeletal reorganization
Increased transcytosis across endothelial cytoplasm
Direct endothelial injury
Delayed prolonged leakage
Leucocyte mediated epithelial injury
Leakage from new blood vessels
EXUDATE AND TRANSUDATE
- Exudate is an inflammatory extra vascular fluid
Transudate is an ultrafiltrate of blood plasma resulting from hydrostatic imbalance between the arteriolar and venus end - Exudate has high protein concentration
Transudate has low protein concentration - Exudate has much cellular debris, Transudate doesnt
- Exudate with specific gravity of 1.020
Transudate with specific gravity of 1.012
PROPERTIES OF CHEMICAL MEDIATORS OF INFLAMMATION
Cells or Plasma Derived
Produced in response to various stimuli
One mediator stimulates the release of all others
They all have a short half life
CELL DERIVED MEDIATORS (VAP.CNN)
1.Vasoactive amines / Histamine
2.Arachidonic acid metabolites(Prostaglandins, Prostacyclin, Thromboxane, Leukotrienes, Lipoxin)
3.PAF
4.Cytokines and Chemokines
5.NO
6.Neuropeptides e.g substance P
PLASMA DERIVED MEDIATORS
1.Complement Proteins (several cleavage products cause increased vascular permeability, chemotaxis and opsonization)
2.Kinin system
3.Clotting system
ROLE OF MEDIATORS IN DIFFERENT REACTIONS OF INFLAMMATION
- VASODILATION: Prostaglandins, Nitric Oxide, Histamine
- INCREASED VASCULAR PERMEABILITY: Histamine, C3a & C5a(complement proteins), leukotrienes, PAF, Substance P
- CHEMOTAXIS: Leukotriene B4, C3a & C5a, Chemokines
- FEVER: IL-1, TNF, Prostaglandins
- PAIN: Prostaglandins, Bradykinin
- TISSUE DAMAGE: Lysozyme, Nitric oxide
MORPHOLOGICAL PATTERNS, OUTCOMES AND SYSTEMIC EFFECTS OF ACUTE INFLAMMATION
MORPHOLOGICAL PATTERNS (FUSS)
1. Serous inflammation
2. Fibrinous inflammation
3. Suppurative inflammation or abscess
4. Ulcer
OUTCOMES
1. Resolution
2. Healing by Fibrosis
3. Progression to Chronic inflammation
SYSTEMIC EFFECTS
1.Leukocytosis
2. Fever
CHRONIC INFLAMMATION
Definition, causes, morphological features
Defined as an inflammation of prolonged duration(weeks or months) in which active inflammation, tissue destruction and attempts at repair are proceeding simultaneously
It is the cause of tissue damage in some of the most common and disabling human diseases such as
-Rheumatoid arthritis
-Artherosclerosis
-Tuberculosis
-Pulmonary fibrosis
Also progression of cancer and Alzheimers
CAUSES OF CHRONIC INFLAMMATION
1. Persistent infections
-Tubercle bacilli
-Trepenoma pallidum
-certain viruses, fungi and parasites
- Non biodegradable substances
-Toxic agents either exogenous or endogenous e.g Silica - Autoimmune conditions
MORPHOLOGICAL FEATURES
1. Infiltration with mononuclear cells(Macrophages, lymphocytes and plasma cells)
2.Tissue destruction
3. Attempts at healing by CT replacement of damaged tissue, accomplished by angiogenesis and fibrosis
CELLS, TYPES OF CHRONIC INFLAMMATION
Granuloma, types of giant cells
CELLS
1. Macrophage (predominant cell)
2. Lymphocytes
3. Plasma cells
4. Eosinophils
5. Mast cells
TYPES
1.Non specific chronic inflammation
2. Specific granulomatous chronic inflammation
What is a granuloma?
A granuloma is a FOCUS of chronic inflammation characterized by microscopic aggregation of MACROPHAGES transformed into epithelium-like cells, surrounded by a collar of MONONUCLEAR LEUKOCYTES, principally lymphocytes but occasionally plasma cells with or without giant cells
TYPES OF GIANT CELLS
1.PHYSIOLOGICAL
Syncitiotrophoblasts and megakaryocytes
2. PATHOLOGICAL
—Inflammatory (Langhans, touton)
—Neoplastic(Reed sternberg, floret cell, popcorn cell, Rhadomyoblast)
PATHOGENESIS OR MECHANISM OF GRANULOMA FORMATION
Examples of diseases with granulomatous inflammation
- Injury
- Inability to digest inciting agent
- Failure of acute inflammatory responses
- Persistence of injurious agent
- Cell mediated immune response and Sequestration
- Recruitment of Macrophages with epitheloid and giant cell formation
EXAMPLES OF DISEASES WITH GRANULOMATOUS INFLAMMATION
1. Tuberculosis
2. Sarcoidosis
3. Brucellosis
4. Syphilis
5. Mycotic infections and Berryliosis
6. Leprosy
TISSUE RENEWAL AND REPAIR
Entails 3 things
1. Regeneration- growth of cells and tissues to replace the lost ones
2. Healing - consist if regeneration and laying down of fibrous tissue or scar formation
3. Fibrosis- laying down of collagen or fibrous tissue in the site of injury
Tissue Cells of the body divided into 3 groups based on their Proliferative Activity;
1.. LABILE CELLS—
Continuosly dividing cells of the bone marrow and hematopoietic tissues
These tissues include;
— stratified squamous surfaces of the skin, oral cavity, vagina and cervix
— the lining mucosa of all excretory ducts e.g salivary glands, pancreas and biliary tracts
2..QUIESCENT (or stable) TISSUES
Normally have a low level of replication however they can undergo rapid division in response to stimuli and thus capable of reconstituting the tissue of origin
E.g
— Liver, Kidney and Pancreas
— Mesenchymal cells such as Fibroblasts and Smooth muscle
— Vascular endothelial cells and resting lymphocytes and other leukocytes
3..NON DIVIDING (PERMANENT) TISSUES
Contains cells that have left the cell cycle and cannot undergo mitotic division in post natal life
— Neurons, Skeletal and Cardiac muscle cells
CUTANEOUS WOUND HEALING
Divided into 3 phases
1. Inflammation (early and late)
2. Granulation tissue formation and reepithelialization
3. Wound contraction, ECM deposition and Remodeling
Skin wounds classically described to heal by PRIMARY or SECONDARY INTENTION
Based on nature of the wound rather than the healing process
HEALING BY PRIMARY INTENTION
—Healing of a clean, uninfected surgical incision approximated by surgical sutures
—The narrow incisional space immediately fills with clotted blood containing fibrin and blood cells; dehydration of the surface clot forms the well known scab that covers the wound
HEALING BY SECONDARY INTENTION
—Regeneration of parenchymal cells cannot completely restore the original architecture and hence abundant granulation tissue grows in from the margin to complete the repair
FACTORS AFFECTING WOUND HEALING
COMPLICATIONS IN CUTANEOUS WOUND HEALING
Local factors
-blood supply, mechanical stress, denervation, necrotic tissue, local infection, dressings, foreign body, hematoma, type of tissue
Systemic factors
Age, malnutrition, anemia, obesity, drugs(steroids), systemic infection, temperature, trauma, genetic disorders
COMPLICATIONS IN CUTANEOUS WOUND HEALING
3 general categories
1. Deficient scar formation(Ulcer, Wound Dehiscence, Contracture)
2. Excessive formation of repair components(Keloid, Hypertrophic scar, Desmoids, Exuberant granulations)
3. Formation of contractures
