BED Revision Lecture

IC1 2013 Prof Mary Leader BED

1

Acute Inflammation
Definition response of tissue to cell damage

Professor Mary Leader Professor of Pathology Royal College of Surgeons Dublin and Bahrain

Causes of Acute Inflammation

Cell Necrosis What are the causes of cell necrosis?

Causes of Cell Necrosis

Ischaemia Micro-organisms Radiation Hypersensitivity Cold Heat Trauma Chemicals
4

Role of Inflammation
1. Contain and isolate injury 2. Destroy microorganisms 3. Inactivate Toxins

4. Prepare for tissue repair and healing

5

Inflammation

Acute - minutes to days

Immediate and early response to injury Characterized by fluid protein Polymorphonuclear cells (neutrophils)

Chronic - weeks to years

Cells (Lymphocytes and macrophages) Granulation tissue
Define Granulation tissue?
6

Acute inflammation Vascular & Cellular Response

Components of acute inflammation Vascular
Vasodilatation Increased endothelial permeability. This allows protein, fluid, polymorphs and monocytes into the area of tissue damage

Cellular
Extravasation of neutrophils and monocytes
7

Cellular response

Leucocyte Function
Opsonisation-coating a bacterium or a particle to facilitate its phagocytosis
Phagocytosis (to engulf and destroy cells and cell constituents) Release of leucocytes products/mediators with effects on surrounding tissue (tissue injury)

Vascular permeability- osmotic pressure

Exudate - Extravascular fluid with high protein concentration

Exudate is the characteristic fluid of acute inflammation

Transudate -Extravascular fluid with low protein concentration

Signals that attract leucocytes

Products of invading micro-organisms Endogenous Compounds
4 plasma systems eg Complement, Kinin, Clotting, Fibrinolytic

Vasoactive Compounds

10

Chemical mediators of inflammation

Vasoactive amines eg histamine & heparin Phospholipid-derived products
Arachnoid Acid metabolites Platelet activating factor

Cytokines Nitric oxide Lysosomal enzymes Oxygen derived free radicals

No need to know function of each, just know they are pro inflammatory 11

Plasma Proteases: These are 4 interrelated systems that are activated in inflammation

Complement system Kinin system Clotting system Fibrinolytic System What are the functions of complement and kinins? What activates complement?
12

The Complement System

Cascade of 20 proteins activated by 2 Pathways Classical Ag/Ab Complex

Alternate 1. Lipopolysaccharide from cell wall 2. Ig A 3. Ig E 4. Plasmin

13

Functions of Complement proteins

Chemotaxis Opsonization Phagocytosis Cell Lysis Vascular permeability Anaphalotoxins

14

The Kinin System

Function: Change the tone of the blood vessel wall Cascade commences with activation of Hageman Factor

15

Beneficial effects of inflammation

Contain and isolate injury Destroy microorganisms Dilute toxins Arrival of antibodies to the site of inflammation Drug transport Delivery of nutrients and oxygen Prepare for healing and repair
16

Outcome of Acute Inflammation

Complete Resolution Healing by Scarring

Abscess Formation
Progression to Chronic Inflammation

17

Chronic Inflammation
Definition: Inflammation of prolonged duration in which active inflammation, tissue destruction and attempts at repair are proceeding simultaneously.

18

Chronic Inflammation
Tissue infiltrated by: Lymphocytes

Plasma cells
Macrophages

Granulation tissue
19

What is granulation tissue?

Newly formed blood vessels and chronic inflammatory cells.

20

Causes of Chronic Inflammation

Progression from Acute Inflammation Following repeated bouts of Chronic Inflammation

Primary Chronic Inflammation

21

Macrophages
Central character in Chronic Inflammation.

Functions
Phagocytosis Secretion : oxygen metabolites, proteases, cytokines, chemotactic factors, growth factors.

22

Lymphocyte Macrophage Relationship

Lymphocytes are activated by antigen presented by macrophages.
Lymphocytes consequently produce lymphokines. Lymphokines stimulate macrophages to further stimulate macrophages to present antigen and secrete mediators
23

Granulomas
Localised collection of Histiocytes and macrophages. Causes of granuloma formation. o TB o Fungal infections o Sarcoidosis o Foreign material o Response to tumours o Type IV Hypersensitivity reactions.

24

Systematic Effects of Inflammation.

o Pyrexia polymorphs and macrophages produce pyrogens which act on the hypothalmus o Constitutional symptoms malaise, anorexia, nausea o Weight Loss o Reactive hyperplasia of mononuclear phagocytic system nodes o Haematological changes increased ESR, wcc, anaemia, amyloidosis.
25

Morphologic patterns in acute and chronic inflammation

Serous inflammation Fibrinous inflammation Suppurative inflammation Ulcers Sinus Fistula

26

Serous inflammation
Accumulation of thin fluid derived from the blood serum or secretion of mesothelial lining
Effusion
Peritoneal Pleural Pericardial

Skin blisters
Viral infection Burn

27

Fibrinous inflammation
Accumulation of fluid and fibrin Body cavities May be removed by fibrinolysis (resolution) Organisation

28

Suppurative inflammation
Characterised by large amounts of pus Can be seen in association with certain organisms (staphylococcus) May lead to abscess formation

29

Abscess
Localised collection of pus
Dead and degenerate leucocytes Dead and degenerate host tissue cells Oedema fluid Dead microorganisms

Empyema
Localised collection of pus in a cavity eg pleura, gallbladder
30

Ulcer
Local defect in an epithelial surface They are distinguished from erosions by the extent of tissue loss

31

Sinus
Is a tract lined by granulation tissue leading from a chronically inflamed cavity to a surface eg Sinuses associated with osteomyelitis Pilonidal sinus

32

Fistula
Is a track open at both ends, with abnormal communication between two surfaces Gastrointestinal fistula in Crhons disease

33

Wound healing
Types of wound healing
Primary intention Secondary intention

34

Primary intention
Wound with apposed edges Minimal loss of tissue Surgical incision or clean wound

35

Secondary intention
Large gaping wound Extensive loss of cells
Infarction Ulcer Abscess

36

Pathologic aspects of wound healing

Deficient scar formation
Wound rupture

Excessive scar formation

Keloid

Contracture deformity Malignant transformation (v. very rare)

37

Factors that influence healing

Local factors Systemic factors

38

Factors which impair bone healing

Movement Poor approximation Poor blood supply Infection Steroids Poor nutrition Interposition of soft tissue
39

Systemic factors
Age Nutrition (protein, Vit. C) Metabolic status (Diabetas Mellitus) Hormones (steroids) Malignancy Chemotherapy Radiotherapy
40

Steps in Repair
Formulation of new vessels, migration and proliferation of fibroblasts. Deposition of extra cellular matrix. Maturation and organisation of fibrous tissue.

41

Necrosis

42

Necrosis

Definition: cell death in living tissue

43

Atoptosis

Programmed cell death in living tissue

44

Causes of Necrosis
Ischaemia Microorganisms High or low temperature Chemicals Hypersensitivity Radiation Drugs
45

Inflammation is the bodys response to Necrosis

46

Types of Necrosis
Coagulative cell outlines visible Caseous no cell outlines Liquifactive brain

Fibrinoid associated with fibrin deposition

Fat Necrosis

Gangrenous (ischaemia and anaerobic organisms)

47

Microscopical Features of Necrosis

Nuclear
Karryohexis Karyyolysis Pyknosis

Cytoplasm - Eosinophilic

48

 Bodys response to Apoptosis no inflammation

49

Ischaemia Reperfusion Injury

Causes Oxygen radicals during reoxygenation damage the mitochondrial membrane Xss Oxygen radicals are toxic to the cell Cytokines from adjacent dead cells attract polymorphs

50

OEDEMA (EDEMA) Definition is an increase in interstitial water.

51

ECF l
3 litres Intravascular fluid (plasma high ) content)

m
9 litres of Interstitial fluid (low protein content)

52

ECF contains practically all body sodium, whereas intracellular fluid has a high potassium and magnesium concentration. Interstitial fluid has a low colloidal osmotic pressure.

53

Fluid collections in body cavities Hydrothorax Hydropericardium Hydroperitoneum (ascites) More commonly referred to as effusions

54

 Hydrostatic pressure pushes fluid out of vessel Oncotic pressure -due to high protein in vessel -pulls fluid into vessel. Lymphatics also play a role in removal of interstitial fluid.

55

Factors which cause oedema

Inflammation Increased Hydrostatic Pressure in Vessels
Local or generalised venous obstruction

Na & Water retention Lymphatic Obstruction Low intravascular protein levels

56

Reduced plasma osmotic pressure

Liver Failure Nephrotic Syndrome Protein losing enteropathy Starvation Malabsorption Burns

57