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General Pathology

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Basic Principles of Cellular and Organ Pathology Inflammation - I Jaroslava Du kov Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz ... – PowerPoint PPT presentation

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Title: General Pathology


1
General Pathology
  • Basic Principles of Cellular and Organ Pathology
  • Inflammation - I

Jaroslava Dušková Inst. Pathol. ,1st Med.
Faculty, Charles Univ. Prague http//www1.lf1.cuni
.cz/jdusk/
2
Inflammation
  • Definition
  • complex reaction
  • of organism to damage
  • (aim homeostasis maintenance)

3
Inflammation
  • Sense
  • defensive agent elimination
  • reparative damage reparation

4
Inflammation - Classification
  • Time view
  • acute (days)
  • subacute (weeks)
  • chronic (months-years)

5
Inflammation - Classification
  • Causes
  • nonliving
  • physical
  • chemical
  • living
  • viral
  • bacterial
  • mycotic
  • parasitic
  • AUTOIMMUNE

6
Inflammation Celsus features
  • rubor
  • tumor
  • calor
  • dolor
  • functio laesa

7
Phases of Inflammatory Response
  • alteration
  • exsudation
  • proliferation

8
Phases of Inflammatory Response

Alteration
Proliferation
Exsudation
9
Phases of Inflammatory Response
Proliferation

Alteration
Exsudation
10
Vascular Changes in Inflammation
  • Flux hyperemia - axonal reflex
  • Peristatic hyperemia
  • Stasis
  • Increased permeability - exsudation
  • Inflammatory edema

11
Active Hyperemia
  • vasodilatation
  • slowing of the circulation
  • increased microvasculature permeability
    leakage
  • ----------
  • leucocyte emigration

12
Active Hyperemia
  • vasodilatation
  • leakage
  • Chemical mediators
  • Cells histamine , serotonin, catecholamins,
    lysosomal enzymes
  • Plasma complement, kinin system,
    coagulation/fibrinolysis system

13
Mast Cell ruling the process
  • Degranulation (immediate response)
  • histamin-vasodilation-permeability-exsudation
  • neutrofil chemotactic factor (micro)fagocytosis
  • eosinophil chemotactic factor -modulation of the
    vascular effect
  • Synthesis (long-term response)
  • leukotriens (SRS-A) vasodilation-permeability-exs
    udation
  • prostaglandins - vasodilation-permeability-exsudat
    ion- PAIN

14
Active Hyperemia
  • vasodilatation
  • slowing of the circulation
  • increased microvasculature permeability -
    leakage
  • leucocyte emigration
  • chemotaxis
  • soluble bact. products
  • complement components esp. C5a
  • products of lipoxygenase pathway of arachidonic
    acid (esp.leukotriene B4)

15
Main Inflammatory Mediators
  • Vasodilation prostaglandins, NO
  • Permeability vasoactive amins, C3,C5,
    bradykinin
  • Chemotaxis C5a, bacterial products, leucotriens,
    cytokins
  • Fever interleukin 1,6, TNF, prostaglandins
  • Pain prostaglandins, bradykinin
  • Tissue damage lysosomal enzymes

16
Mechanisms and Morphological Features of Immune
Reaction

17
Mechanisms of Immune Response
  • nonspecific
  • antigen specific
  • humoral
  • cellular

18
Mechanisms of Immune Response
  • nonspecific
  • PHAGOCYTOSIS
  • bactericid substances (lysozym)
  • complement
  • interferon
  • proteins distinguishing general microbial
    structures

19
Cytokines
  • Def.
  • polypeptides and proteins - regulatory molecules
    participating by autocrine, paracrine
    endocrine function in homeostasis maintenance

20
Cytokines
  • Types
  • growth fcs.
  • colony stim. fcs.
  • chemokins (interleukins)
  • TNFa, TNF ß LT
  • interferons
  • Source
  • macrophages
  • APC
  • T- lympho

21
Bradley JR.TNF-mediated inflammatory disease.
  • TNF was originally described (1975) as a
    circulating factor that can cause necrosis of
    tumours, but has since been identified as a key
    regulator of the inflammatory response.
  • TNF interacts with two different receptors,
    designated TNFR1 and TNFR2,
  • TNF stimulation leads to a range of cellular
    responses, which include cell death, survival,
    differentiation, proliferation and migration.
  • Vascular endothelial cells increase leukocyte
    adhesion, transendothelial migration and vascular
    leak and promote thrombosis.
  • J Pathol. 2008 Jan214(2)149-60

22
Zhang X, Mosser DM.Macrophage activation by
endogenous danger signals.
  • Most microbes have Pathogen Associated Molecular
    Patterns (PAMPS) that are recognized by
    macrophages and trigger this activation response.
  • J Pathol. 2008 Jan214(2)161-78.

23
Interleukin 4
  • Th2 stimulation antibody mediated immune
    response
  • Th1 interferon ? suppresion
  • inhibition of the T-lymphocytes proliferation
  • inhibition of TNF a Il6 secretion

24
Mechanisms of Immune Response
  • antigen specific
  • humoral B lymphocytes
  • cellular T lymphocytes
  • INTERACTION
  • B-lymphoTh affinity maturation plasmocyte

25
Inflammatory cells
  • neutrophile granulocytes
  • eosinophil granulocytes
  • basophil granulocytes heparinocytes
  • lymphocytes plasmocytes
  • monocytes macrophages
  • erythrocytes
  • platelets

26
Mechanisms of Immune Response
  • antigen specific
  • cellular T lymphocytes
  • APC CD8 precursors Th,Tc

27
Heparinocytes
  • IgE receptors
  • mediators production (heparin, histamin,
    serototnin, catecholamins)
  • cytokin production IL4, TNF a
  • chemotactic factors for neutrophils
    eosinophils

28
Neutrophilic granulocytes
  • pavementing (selectins, integrins)
  • emigration (chemotactic factors from bacteria,
    complement 3a, 5a, kinins, histamin.)
  • fagocytosis (both non specific without
    opsonisation and specific IgG compl.)

29
NG disorders 1.
  • migration chemotaxis
  • lazy leucocytes syndrome
  • diabetes (locomotion)
  • Chédiak- Higashi syndrome (bacteria killing, lack
    of elastase, locomotion)
  • ß2-integrin defect (adhaesion)
  • locomotion
  • serum changes
  • corticoids
  • phenylbutazone

30
NG disorders 2.
  • phagocytosis
  • opsonins IgG in sickle cell anaemia
  • morphin abusers
  • lyzosom fusion (corticoids, antimalaric drugs,
    CH-H sy
  • bactericid effect
  • chronic granulomatosis in children
  • cytochrom oxidase H2O2 defects
  • recidives of staphylococcus and aspergillus
    infection

31
Eosinophilic Granulocytes
  • alergic response
  • IgA receptors
  • anti parasites defence
  • peroxidase, histaminase, acid phophatase,
    cytokins

32
Macrophages - Function
  • phagocytosis
  • bacteria killing
  • mediators production
  • antigen processing presentation
  • modulation of fibroblast proliferation IL-1
  • modulation of endothelia proliferation TNFa

33
Macrophages - secretion
  • acid neutral proteases
  • cytokins IL-1 , TNF
  • O2, NO
  • complement components

34
Thrombocytes
  • mediators production
  • vasoactive substances, thrombosis, mesenchymal
    cell proliferation
  • granules serotonin, ADP, acid phophatase,
    thromboxan, Ca cationic protein

35
Systemic Inflammatory Response
  • lymphatic tissue activation
  • fever IL 1, prostaglandins
  • leucocytosis
  • lymfocytosis in viral infections
  • eosinophilia in parasitic diseases

36
Inflammation Development
  Complete resolution - ad integrum vessel
permeability normalized migration
stopped necrosis resorption tissue
regeneration Healing with a defect - per
defectum regeneration impossible extensive
necrosis granulation tissue scar Progression
towards a chronic inflammation
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