Overview of inflammation
Survival all organisms requires eliminate foreign invaders e.g. infectious pathogens and damage tissue These functions are mediated by a complex host response called : INFLAMMATION
Inflammation is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult Inflammation accomplishes its protective mission by diluting, destroying, or neutralizing harmful agents (microbes and toxins)
INFLAMMATION
Local response to injury in a living tissue Fundamentally a vascular phenomenon it is is added to base to state condition: myositis, arthritis, tendinitis, synovitis etc 4 ancient cardinal sign: - tumor swelling - rubor redness - calor warmth - dolor pain + functiolaesaimpair of function
Causes
Burns
Chemical irritants Frostbite Toxins Infection by pathogens Physical injury, blunt or penetrating Immune reactions due to hypersensitivity Ionizing radiation Foreign bodies, including splinters, dirt and debris
Cardinal sign
English Redness Swelling Heat Pain
Loss of function
Celsus -- Aulus (Aurelius) Cornelius, a Roman physician and medical writer, who lived from about 30 B.C. to 45 A.D.
The classic signs and symptoms of acute inflammation: Latin Rubor* Tumor/Turgor* Calor* Dolor* Functio laesa** ow
Virch
The first four (classical signs) were described by Celsus (ca 30 BC38 AD), while loss of function was added later by Galen[6] even though the attribution is disputed and the origination of the fifth sign has also been ascribed to Thomas Sydenham[7] and Virchow.[4][5]
Redness and heat are due to increased blood flow at body core temperature to the inflamed site; swelling is caused by accumulation of fluid; pain is due to release of chemicals that stimulate nerve endings. Loss of function has multiple causes.
These five signs appear when acute inflammation occurs on the body's surface, whereas acute inflammation of internal organs may not result in the full set. Pain only happens where the appropriate sensory nerve endings exist in the inflamed area e.g., acute inflammation of the lung (pneumonia) does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings.
All the above signs may be observed in specific instances, but no single sign must, as a matter of course, be present. These are the original, so called, "cardinal signs" of inflammation.*
Functio laesa is a bit of an apocryphal notion, as it is not really unique to inflammation and is a characteristic of many disease states.**
ABSCES
INCOMPLETE REPAIR/FIBROSIS
Vascular Leakage
(20-60 m)
15-30 minutes immediate transient response Cytokines (IL-2, TNF, IFN-) also increase vascular permeabilityby inducing a structural reorganization of cytoskeleton endothelium retract from one another
Vascular Leakage
All levels of of the microcirculation are affected, including venules, capillaries, and arterioles
DELAYED Sunburn
Vascular Leakage
Vascular Leakage
Vesiculovacuolar organelle
Vascular Leakage
Acute Inflammation
is the immediate and early response to an injurious agent. Vascular phenomena play a major role : Alterations in vascular caliber that lead to
an increase blood flow
The major local manifestations of acute inflammation, compared to normal. (1) Vascular dilation and increased blood flow (causing erythema and warmth); (2) extravasation and extravascular deposition of plasma fluid and proteins (edema);
Extravasation of leukocyte
3.
4.
Endothelial Mol. Leukocyte Rec. Major role P-Selectin Sialyl-Lewis X Rolling PSGL-1 E-Selectin Sialyl-Lewis X Rolling, adhesion ESL-1,PSGL-1 ICAM-1 CD11/CD18(integrin) Adh,arrest,transm (LFA-1,Mac-1) VCAM-1 alphaB1(VLA4) adhesion (integrin) alpha B7(LPAM-1) GlyCam-1 L-selectin Lymphocyte homing CD34 to high end.venules
Neutrophils phagocytize a foreign material e.g.bacteria, and then attempt to oxidize and digest it through oxidase and protease. To be seen particularly in acute phase Eosinophils also phagocytic and posess many enzymes of the neutrophil, also can dispense antihistamine in an area of histamine release, and these cells is associated with allergic responses. It is seen in both acute and chronic inflammation
Simple-appearing cells with varied and complex functions Briefly, some lymphocytes are in the T-cell system and produce various types of lymphokine, which have local effect Immunoglobulins or antibodies can also be produced by this cells as a B cells Characterizes chronic inflammation, antibody production is the function of the plasma cells, a specialized B cell. It is particularly prominent in chronic inflammation involving mucosal surfaces
Cells in the inflammatory process . .cont Macrophag phagocytosis of foreign material and antigen processing Communicates with immune system as a part of antigen processing Enzymes also present in the macrophage to digest foreign material Appear in late stages of acute inflammation and are present during chronic inflammation
Mechanism of phagocytosis
Cells of inflammation
CELL
NEUTROPHIL EOSINOPHIL MACROPHAG
ACTIVITY
PROTEASES, OXIDASES ANTIHISTAMINE ANTIGEN PROCESSING, DIGESTION
PHAGOCYTOSIS INFLAMMATION
+ + + ACUTE ACUTE, CHRONIC LATE ACUTE, CHRONIC
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LYMPHOCYTE LYMPHOKINES
CHRONIC
CHRONIC
ACUTE immediate; short duration; exudative; - Systemically may be accompanied by fever, leucocytosis especially neutrophil.
TYPES OF INFLAMMATION
- Locally, it is vascular response to injury arteriolar vasocontriction, followed by vasodilatation and > vascular permeabilities
CONDITION
CONTENT
EXUDATE
ACUTE INFLAMMATION
HIGH PROTEIN
> 1.O20
PUS
ACUTE INFLAMMATION
> 1.020
Chemical Mediators
Chemical Mediators
Mediators originate either from plasma and from cells Mediators perform their biologic activity by binding to specific receptors on target cells. But some have direct enzymatic activity or mediate oxidative damage A chemical mediator can stimulate the release of mediators by target cells themselves Mediators can act on one or few target cell types Once activated and released from the cell, most of these mediators are short-lived Most mediators have the potential to cause harmful effects
Chemical Mediator
LYSOSOMAL PROTEASES
++
----------------------------------------------------------------------------------------------Migration inhibition Aggregation of Activated T Factor (MIF) macrophages at lymphocytes site of injury Macrophage Increased Activated T Activation factor phagocytosis by lymphocytes (MAF) macrophages Complement 5a Chemotactic for Complement macrophages system Eosinophil chemo- Chemotactic for Mast cells and Tactic factor of eosinophils in basophils Anaphylaxis(ECF-A) metazoan infections
Vascular phenomena Dilatation of arteriolar and capillary beds - increased bloodflow to the injured area Increased vascular permeability Exudate
Leukocyte activity adhesion molecule, transmigrate, migrate to the site of injury; phagocytosis of the offending agents During chemotaxis and phagocytosis activated leukocyte may released toxic metabolites and proteases extracellulary, potentially causing tissue damage.
Chronic inflammation
Collection of inflammatory cells (monocyte) lymphocytes , plasma cells Tissue destruction Replacement by connective tissue accomplished by angiogenesis & fibrosis
Activated lymphocytes and macrophages influence each other and also release inflammatory mediators that affect other cells
Granulomatous Inflammation
is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume an epitheloid appearance. Ex. : - TBC - Leprosy - Syphillis - Cat scratch disease - Sarcoidosis If granuloma develop in response to foreign bodies (suture or splinter), forming Foreign bodies granuloma
SUMMARY
Features of Chronic Inflammation
Prolonged host response to persistent stimulus Caused by microbes that resist elimination, immune responses against self and environmental antigens, and some toxic substances (e.g. silica) Characterized by coexisting inflammation, tissue injury, attempted repair by scarring, and immune response Cellular infiltrate consists of macrophages, lymphocytes, plasma cells, fibrosis is often prominent Mediated by cytokines produced by macrophages and T cell lymphocytes tend to amplify and prolong inflammatory reaction
Nature of leukocyte infiltrates in inflammatory reactions. The photomicrographs are representative of - the early (neutrophilic) (A) and - later (mononuclear) cellular infiltrates (B) seen in an inflammatory reaction in the myocardium following ischemic necrosis (infarction). - The kinetics of edema and cellular infiltration (C) are approximations.
Serous inflammation
Low power view of a cross section of a skin- blister showing the epidermis separated from the dermis by a focal collection of serous effusion
Fibrinous Pericarditis
A, Deposits of fibrin on the pericardium. B, a pink meshwork of fibrin exudate (F) overlies the pericardial surface (P)
Suppurative Inflammation
A, a subcutaneous bacterial abscess with collection of pus. B, the abscess contains neutrophils, edema fluid, and cellular debris
A, chronic duodenal ulcer. B, low-power cross-section of duodenal ulcer crater with an acute inflammatory excudate in the base.
TISSUE REPAIR
TISSUE REPAIR
Restoration of normal structure - occurs when the connective tissue infrastructure remains relatively intact - requires that the surviving affected parenchymal cells have the capacity to regenerate
REPAIR
Two distinct processes: Regeneration Replacement of injured cells by cells of the same type Fibroplasia / fibrosis Replacement of injured cells by connective tissue
cell migration cell proliferation & differentiation cell-matrix interaction
repair
Cell-matrix interaction
Intimate contact with ECM cells grow, move, and differentiate 3 groups of macromolecules ECM 1. fibrous structural proteins: collagens & elastins 2. diverse group of adhesive glycoprotein: fibronectin, laminin 3. gel of proteoglycans and hyaluronan
MINI TEST
1. Histamin akan memberi tipe endothelial leaking apa ? 2. Seorang laki2 44 th dengan gingivitis Tuberkulosa, bila di biopsi, bagaimana gambaran mikroskopiknya ? 3. Periodontitis supurativa, eksudatny apa dan bagaimana gambaran mikroskopiknya ? 4. Beda eksudat dan transudat ? 5. Apa saja tanda kardinal radang, berikan gambaran klinik nya dan mekanisme nya.
Formation of new blood vessels (angiogenesis) Migration and proliferation of fibroblast Deposition of ECM Maturation and organization of the fibrous tissue remodeling
Angiogenesis
Granulation tissue
WOUND HEALING
Wound Healing:
a complex but orderly phenomenon involving a number of processes
Induction of an acute inflammatory process by the initial injury Regeneration of parenchymal cells Migration and proliferation of both parenchymal and connective tissue cells Synthesis of ECM proteins Remodeling of connective tissue and parenchymal components Collagenization and acquisition of wound strength
Wound Healing
Penyembuhan primer
Contoh : Insisi bedah yang bersih dan tidak terinfeksi di sekitar jahitan bedah 24 jam neutrofil pd tepi insisi, migrasi menuju bekuan fibrin, sel basal pada tepi irisan epidermis mulai mitosis 24 48 jam sel epitel kedua tepi irisan migrasi dan proliferasi sepanjang dermis dan mendepositkan MB. Sel tsb bertemu di garis tengah dibawah keropeng permukaan menghasilkan lapisan epitel tipis yg tidak putus Hari ke 3 neutrofil digantikan makrofag , jar. Granulasi terbentuk kolagen muncul vertikal, proliferasi epitel berlanjut Hari ke 5 Neovaskularisasi, jar. Granulasi mengisi ruang insisi Serabut kolagen berlimpah menjembatani ruang insisi Epidermis mengembalikan ketebalan normal dg deferensiasi Minggu ke 2 penumpukan kolagen dan proliferasi fibroblas berlanjut infiltrasi lekosit dan vaskularisasi telah amat berkurang. deposisi kolagen dan regresi pembuluh darah Akhir bulan pertama Jaringa parut td. Jaringan ikat tanpa sel radang ditutupi epidermis normal
Penyembuhan Sekunder
o o
Jika luka luas, destruksi jaringan banyak, proses penyembuhan menjadi lebih kompleks Regenerasi parenkhim saja tidak dapat mengembalikan arsitektur asal. Akibatnya : terjadi pertumbuhan jaringan granulasi luas ke arah dalam dari tepi luka, diikuti penumpukan ECM serta pembentukan jaringan parut. Bentuk ini disebut sebagai penyatuan sekunder, atau penyembuhan sekunder. Secara intrinsik, kerusakan jaringan luas membuat debris nekrotik, eksudat, dan fibrin yang lebih banyak yang harus disingkirkan Jaringan granulasi akan terbentuk lebih luas, lebih besar Penyembuhan sekunder menimbulkan fenomena kontraksi luka dlm 6 mgg kerusakan kulit luas dapat berkurang 5-10% ukuran semula, terutama melalui kontraksi oleh karena adanya miofibroblas
Kekuatan Luka
Luka yang dijahit cermat 70% kekuatan semula Jika jahitan dilepas (1 mgg ) kekuatan luka menjadi 10% dari kekuatan kulit yang tidak terluka, tetapi kekuatan ini meningkat cepat dalam waktu 4 mgg berikutnya Pemulihan kekuatan regangan diakibatkan sintesis kolagen yang melebihi degradasinya selama 2 bln pertama dan oleh perubahan struktural kolagen ketika sintesisnya berkurang di saat selanjutnya. Kekuatan luka mencapai + 70-80% dari normal pada bulan ke-3, tetapi biasanya tidak akan meningkat melebihi angka tersebut
BONE HEALING
Mechanical
Deficient scar formation - wound dehiscence - ulceration Excessive formation of the repair components - hypertrophic scar - exuberant granulation - desmoid (aggressive fibromatosis) Formation of contractures deformities of the wound and surrounding tissue
REFERENCES
Pathologic basis of disease, Robbins and Cotran, 8th ed. 2010 General and systemic Pathology, Underwood, 5th ed. 2009 Pathology, Rubbin, 2006 Pathology illustrated, Reids/Robert, 6th ed. 2005
Thank you