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Inflammation acute and chronic
The document summarizes inflammation and its processes. It describes the sequence of events in acute inflammation, from vasodilation to resolution. It lists chemical mediators involved like histamine, cytokines, and eicosanoids. Acute inflammation can resolve completely, form scar tissue, or progress to chronic inflammation. Chronic inflammation involves lymphocytes, macrophages and plasma cells and can be caused by persistent infection, prolonged insult, or autoimmunity.
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Introduction to the concepts and objectives related to inflammation, focusing on understanding the sequence of events and roles of mediators.
Detailed progression of acute inflammation stages including vascular changes, cell recruitment, mediators, and morphologic patterns.
Examination of chronic inflammation, its causes, cellular participants, granuloma formation, and systemic effects.
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Inflammation acute and chronic
- 1.
- 2. CHAPTER 2 Inflammation(5 OBJECTIVES) 1) (Concept) Understand the chain, progression, or sequence of vascular and cellular events in the histologic evolution of acute inflammation
- 3. 2) (Rote?) Learnthe roles of various “chemical mediators” of acute inflammation 3) Know the three possible outcomes of acute inflammation 4) Visualize the three morphologic patterns of acute inflammation 5) Understand the causes, morphologic patterns, principle cells, minor cells, of chronic and granulomatous inflammation
- 4. SEQUENCE OF EVENTSNORMAL HISTOLOGY VASODILATATION INCREASED VASCULAR PERMEABILITY LEAKAGE OF EXUDATE MARGINATION, ROLLING, ADHESION TRANSMIGRATION (DIAPEDESIS) CHEMOTAXIS PMN ACTIVATION PHAGOCYTOSIS: Recognition, Attachment, Engulfment, Killing (degradation or digestion) TERMINATION 100% RESOLUTION , SCAR , or CHRONIC INFLAMMATION are the three possible outcomes
- 5. ACUTE INFLAMMATION “PROTECTIVE” RESPONSE NON -specific
- 6. ACUTE INFLAMMATION VASCULAR EVENTS CELLULAR EVENTS (PMN or P oly M orphonuclear N eutrophil, Leukocyte?, “POLY”, Neutrophil, Granulocyte, Neutrophilic Granulocyte “ MEDIATORS”
- 7. ACUTE INFLAMMATIONNeutrophil Polymorphonuclear Leukocyte, PMN, PML “ Leukocyte” Granulocyte, Neutrophilic granulocyte “ Poly-” Polymorph
- 8. Rubor Calor TumorDolor 5 th (functio laesa) HISTORICAL HIGHLIGHTS (Egypt, 3000 BC)
- 9. STIMULI foracute inflammation INFECTIOUS PHYSICAL CHEMICAL Tissue Necrosis Foreign Bodies (FBs) Immune “responses”, or “complexes”
- 10. Vascular Changes Changesin Vascular Flow and Caliber Increased Vascular Permeability
- 11. INCREASED PERMEABILITY DILATATIONEndothelial “gaps” Direct Injury Leukocyte Injury Transocytosis (endo/exo) New Vessels
- 12. LEAKAGE OF PROTEINACEOUSFLUID ( EXUDATE , NOT TRANSUDATE)
- 13. EXTRAVASATION of PMNsMARGINATION (PMN’s go toward wall) ROLLING (tumbling and HEAPING) ADHESION TRANSMIGRATION (DIAPEDESIS)
- 14. ADHESION MOLECULES (glycoproteins)affecting ADHESION and TRANSMIGRATION SECRETINS (from endothelial cells) INTEGRINS (from many cells)
- 15. CHEMOTAXIS PMNs goingto the site of “injury” AFTER transmigration
- 16. LEUKOCYTE “ACTIVATION” “triggered” by the offending stimuli for PMNs to: 1) Produce eicosanoids (arachidonic acid derivatives) Prostaglandin (and thromboxanes) Leukotrienes Lipoxins 2) Undergo DEGRANULATION 3) Secrete CYTOKINES
- 17. PHAGOCYTOSIS RECOGNITION ENGULFMENTKILLING (DEGRADATION/DIGESTION)
- 18. CHEMICAL MEDIATORS Fromplasma or cells Have “triggering” stimuli Usually have specific targets Can cause a “cascade” Are short lived
- 19. CLASSIC MEDIATORS HISTAMINESEROTONIN COMPLEMENT KININS CLOTTING FACTORS EICOSANOIDS NITRIC OXIDE PLATELET ACTIVATING FACTOR (PAF) CYTOKINES /CHEMOKINES LYSOSOME CONSTITUENTS FREE RADICALS NEUROPEPTIDES
- 20. HISTAMINE Mast Cells,basophils POWERFUL Vasodilator Vasoactive “amine” IgE on mast cell
- 21. SEROTONIN (5HT , 5 - H ydroxy- T ryptamine ) Platelets and EnteroChromaffin Cells Also vasodilatation, but more indirect Evokes N.O. synthetase (a ligase)
- 22. COMPLEMENT SYSTEM >20components, in circulating plasma Multiple sites of action, but LYSIS is the underlying theme
- 23. KININ SYSTEM BRADYKININis KEY component, 9 aa’s ALSO from circulating plasma ACTIONS Increased permeability Smooth muscle contraction, NON vascular PAIN
- 24. CLOTTING FACTORS Alsofrom circulating plasma Coagulation, i.e., production of fibrin Fibrinolysis
- 25.
- 26. EICOSANOIDS (ARACHIDONIC ACIDDERIVATIVES) Part of cell membranes 1) Prostaglandins (incl. Thromboxanes) 2) Leukotrienes 3) Lipoxins (new) MULTIPLE ACTIONS AT MANY LEVELS
- 27.
- 28. Prostaglandins (thromboxanes included)Pain Fever Clotting
- 29. Leukotrienes Chemotaxis VasoconstrictionIncreased Permeability
- 30. Lipoxins INHIBIT chemotaxisVasodilatation Counteract actions of leukotrienes
- 31. P latelet- Activating F actor (PAF) Phospholipid From MANY cells, like eicosanoids ACTIVATE PLATELETS, powerfully
- 32. CYTOKINES/CHEMOKINES CYTOKINES are PROTEINS produced by MANY cells, but usually LYMPHOCYTES and MACROPHAGES, numerous roles in acute and chronic inflammation TNF α , IL-1 , by macrophages CHEMOKINES are small proteins which are attractants for PMNs (>40)
- 33. N ITRIC O XIDE Potent vasodilator Produced from the action of nitric oxide synthetase from arginine
- 34. LYSOSOMAL CONSTITUENTS PRIMARYAlso called AZUROPHILIC, or NON-specific Myeloperoxidase Lysozyme (Bact.) Acid Hydrolases SECONDARY Also called SPECIFIC Lactoferrin Lysozyme Alkaline Phosphatase Collagenase
- 35. FREE RADICALS O2 – (SUPEROXIDE) H2O2 (PEROXIDE) OH - (HYDROXYL RADICAL) VERY VERY DESTRUCTIVE
- 36. NEUROPEPTIDES Produced inCNS (neurons) SUBSTANCE P NEUROKININ A
- 37. OUTCOMES OF ACUTEINFLAMMATION 1) 100% complete RESOLUTION 2) SCAR 3) CHRONIC inflammation
- 38. Morphologic PATTERNS ofAcute INFLAMMATION (EXUDATE) Serous (watery) Fibrinous (hemorrhagic, rich in FIBRIN) Suppurative (PUS) Ulcerative
- 39. BLISTER, “Watery”, i.e.,SEROUS
- 40.
- 41. PUS = PURULENT ABSCESS = POCKET OF PUS
- 42.
- 43.
- 44. SEQUENCE OF EVENTSNORMAL HISTOLOGY VASODILATATION INCREASED VASCULAR PERMEABILITY LEAKAGE OF EXUDATE MARGINATION, ROLLING, ADHESION TRANSMIGRATION (DIAPEDESIS) CHEMOTAXIS PMN ACTIVATION PHAGOCYTOSIS: Recognition, Attachment, Engulfment, Killing (degradation or digestion) TERMINATION 100% RESOLUTION, SCAR, or CHRONIC inflammation
- 45. CHRONIC INFLAMMATION (MONOS) LYMPHOCYTE MONOCYTE MACROPHAGE HISTIOCYTE
- 46. CAUSES of CHRONICINFLAMMATION 1) PERSISTENCE of Infection 2) PROLONGED EXPOSURE to insult 3) AUTO-IMMUNITY
- 47. Cellular Players LYMPHOCYTESMACROPHAGES (aka, HISTIOCYTES) PLASMA CELLS EOSINOPHILS MAST CELLS
- 48. MORPHOLOGY INFILTRATION TISSUEDESTRUCTION HEALING
- 49. GRANULOMAS GRANULOMATOUS INFLAMMATION4 COMPONENTS FIBROBLASTS LYMPHS HISTIOS “ GIANT” CELLS
- 50. GRANULOMAS GRANULOMATOUS INFLAMMATIONCASEATING (TB) NON-CASEATING
- 51. LYMPHATIC DRAINAGE SITE REGIONAL LYMPH NODES
- 52. SYSTEMIC MANIFESTATIONS (NON-SPECIFIC)FEVER, CHILLS C-Reactive Protein (CRP) “ Acute Phase” Reactants Erythrocyte Sedimentation Rate (ESR) increases Leukocytosis Pulse, Blood Pressure Cytokine Effects, e.g., TNF( α ), IL-1
- 53. NORMAL SPE SerumProtein Electrophoresis In ACUTE Inflammation Alpha-1 & alpha-2 are increased, i.e., “ acute phase” reactants.
Editor's Notes
- #3 Think of it as a Cecil B. DeMille epic movie!
- #6 The sequence of changes occurring in acute inflammation are NOT specific for the stimuli which cause them
- #7 These are the three “phases”, in order, of acute inflammation. Please NOTE they, in no way, are the independent of each other, and as you might suspect by now, quite the contrary, CRUCIALLY all wrapped up with each other!
- #8 Many names, same cell
- #9 The four “cardinal”, i.e., “classic” signs of inflammation, translated, literally, 1) redness, 2) heat, 3) swelling, 4) pain. Just like a fith Marx bother, Gummo, was often added, so was the term “functio laesa” or “loss of function”
- #10 The usual suspects, again. “Stimuli”, like “etiologic agents” is a very elusive term if you like to think in terms of ultimate causes.
- #11 Vascular changes occur BEFORE any infiltration of inflammatory cells arrive.
- #12 These are all events which either cause, or result, from the phenomenon of “increased permeability”
- #13 Transudate vs. Exudate. Transudates can be thought of as being fairly pure water. Transudates are water PLUS most serum proteins, fibrin, and many blood cells often.
- #14 The four things neutrophils do, in order, in acute inflammation.
- #15 Secretins and integrins are classes of substances to help neutrophils stick to vessel walls and migrate through the wall.
- #16 Chemokines
- #17 These three events are the results of leukocytes (i.e., neutrophils) being “activated”
- #18 The three phases of phagocytosis, in correct order.
- #19 These are the common features of ALL “chemical mediators” in acute inflammation.
- #21 How many of the 4 cardinal signs of inflammation can histamine cause, by virtue of its being a powerful vasodilator?
- #22 Serotonin is widely and primarily thought as being a neurotransmitter involved in the full spectrum of emotional responses, but its role in acute inflammation is just as powerful.
- #23 Complement fixation id the end stage of a cascade of multiple chemical events, similar to coagulation, which ultimately result in lysis of cell membranes, hopefully, bad cells.
- #24 Bradykinin is a potent endothelium -dependent vasodilator , causes contraction of non-vascular smooth muscle , increases vascular permeability and also is involved in the mechanism of pain .
- #25 Coagulation is also a cascade, like complement fixation.
- #26 Hypercoagulability is anything which accelerates the cascade, or inhibits its inhibitors
- #27 Three classic eicosanoids, new classes are also being discovered. ALL are derivatives from arachidonic acid.
- #28 Arachidonic acid
- #29 When you think of the three main things that ASPIRIN does, you can remember the three main properties of the prostaglandins.
- #31 Click back to the previous slide on LEOKITRIENES and realize that LIPOXINS generally do the OPPOSITE of what LEUKOTRIENES do.
- #32 It is produced in response to specific stimuli by a variety of cell types, including neutrophils , basophils , platelets , and endothelial cells .
- #33 There are gazillions of cytokines/chemokines. The two most classical and famous ones are TNF-alpha and Interleukin-1. TNF, also called tumor necrosis factor, or cachectin, is a substance that is destructive of human tissues, and is a key player in “cachexia”. Interleukin-1 was the first of many interleukins discovered and generally propagates the inflammatory response at many levels and also has a significant effect on T-cells.
- #34 Which drug INCREASES the effect of nitric oxide? Hint: you get spam ads for it 10 times a day in your spam, even if you are a female.
- #35 MPO produces Hypochlorous acid and tyrosyl radical are cytotoxic , so they are used by the neutrophil to kill bacteria and other pathogens . It is what makes pus look greenish yellow. Lactoferrin (LF), also known as lactotransferrin (LTF), is a globular multifunctional protein with antimicrobial activity ( bacteriocide , fungicide ) Lysozymes , also known as muramidase or N-acetylmuramide glycanhydrolase , are a family of enzymes ( EC 3.2.1.17 ) which damage bacterial cell walls by causing hydrolysis .
- #37 Substance P is an 11 amino acid polypeptide tied into many things including mood disorders, anxiety, stress, reinforcement, respiration rate, neurotoxicity, nausea, emesis, and pain. The Neurokinins are also peptide neurotransmitters involved in many things.
- #38 Three classic outcomes of acute inflammation
- #39 I must have said THREE patterns, but this looks like four to me. Who cares? Remember, they are only adjectives! (Onelook.com has 133 adjectives to the word “inflammation”)
- #41 FINRIN is the endpoint of coagulation and had a characteristic appearance both grossly and microscopically. Do you remember hearing the term fibrin-OID necrosis too?
- #43 It is EXTREMELY important to be able to recognize neutrophils (Polys) in H&E sections. The key tip is, OFTEN, they might NOT look multilobulated at first, but upon close examination, they are!
- #44 ULCERS (i.e., pathologic LOSS of mucosal or epithelial coverings, are both the CAUSE as well as a RESULT of acute inflammation. WHY? Identify the FOUT layers of the colon here, mucosa, submucosa, muscularis, and finally adventitia/serosa.
- #47 What does chronic inflammation look like? ANS: Infiltrates of lymphs and monos “peppering” normal histology.
- #48 Please note that the “cellular” players of chronic inflammation are NOT the baseball players who play in US Cellular Field in Chicago, i.e., the White Sox.
- #52 The drainage patters of acute or chronic inflammation follow the same general drainage patterns of tumor cells.
- #53 CRP is a member of the class of acute phase reactants as its levels rise dramatically during inflammatory processes occurring in the body. It is thought to assist in complement binding to foreign and damaged cells and affect the humoral response to disease. It is also believed to play an important role in innate immunity, as an early defense system against infections.
- #54 Which TWO of these 5 “hills” are significantly higher in nonspecific systemic acute inflammation? Answer: alpha-1 and alpha-2