Pathology of Inflammation Lecture Notes PDF

Pathology of INFLAMMATION CH 2: Lecture III Al-Quds University Faculty of Medicine Pathology Department 1  Chronic Inflammation Chronic - weeks to months or years – Fibrosis – Scarring. – Lymphocytes and macrophages Def...

Pathology of INFLAMMATION CH 2: Lecture III Al-Quds University Faculty of Medicine Pathology Department 1  Chronic Inflammation Chronic - weeks to months or years – Fibrosis – Scarring. – Lymphocytes and macrophages Definition: Inflammation of prolonged duration in which active inflammation, tissue injury and healing proceed simultaneously 2 Characteristics of chronic inflammation  Persistence or recurrence of injurious agent  Prolonged inflammation  Tissue destruction by the inflammatory cells  Healing/repair: involving new vessel formation (angiogenesis) and fibrosis.  Infiltration by mononuclear cells (macrophages, lymphocytes, and plasma cells) 3 Chronic inflammation arises in the following settings: 1. unresolved acute inflammation example: chronic abscess 2. repeated acute inflammation example: chronic pancreatitis 4 Chronic inflammation arises in the following settings: 3. delayed hypersensitivity reaction intracellular infectious agents example: brucellosis, viral infections Fungi, parasite repeated contact sensitivity example: contact dermatitis 5 6 Chronic inflammation arises in the following settings: 4. foreign body reaction endogenous material example: fat, uric acid crystals in gout exogenous material example: suture material, asbestos, silica 7 Chronic inflammation arises in the following settings: 5. ❑ auto-immune disease example: Hashimoto's disease 6. ❑ unknown example: inflammatory bowel disease sarcoidosis 8  White Blood Cells Band Eosinophil Neutrophil segmented neutrophil Lymphocyte Basophil Monocyte 9 Chronic inflammatory cells: Macrophages 10 Chronic inflammatory cells: Macrophages The main cells in chronic inflammation. Called: – Kupffer cells in the liver – sinus histiocytes in the lymph nodes & spleen – alveolar macrophages in the lungs – microglial cells in the CNS – Osteoclasts in the bone 11 Chronic inflammatory cells: Macrophages Derived from blood monocytes, where they begin to emigrate within the first 24-48 hrs after the onset on acute inflammation. They are transformed into big cells which are capable of phagocytosis (macrophages). Macrophages may also become activated, resulting in increased cell size and lysosomal enzymes, more active metabolism, & greater ability to kill ingested organisms.12  The effect of macrophages in inflammation phagocytosis chemotaxis multinucleated lysis of ECM giant cells increase tissue injury endothelial cells fibroblasts increase angiogenesis increase fibrosis 13 14  The effect of macrophages in inflammation After activation, macrophages secrete a wide variety of biologically active products, that can result in the tissue injury and fibrosis. These products include: 1) Tissue injury: – Proteases & plasminogen activator. – Complement component and coagulation factors. – Reactive oxygen species and NO – Arachidonic acid metabolites – Cytokines 15  The effect of macrophages in inflammation 2) Fibrosis: growth factors: influence the proliferation of smooth muscle cells and fibroblasts and the production of extracellular matrix cytokines angiogenesis factors collagenase 16 Macrophages in chronic inflammation IMMUNE ACTIVATION 17 Macrophages in acute inflammtion: Macrophages can engulf excess fluid, apoptotic neutrophils and debris resulting from acute inflammation, thus participating in resolution of acute inflammation 18 Chronic inflammatory cells: Macrophages under the influence of INF-γ, endotoxins, ECM like fibronectin and other products, they are activated; they increase in size, with eosinophilic cytoplasm, assume an epithelial-like appearance so they are called “epithelioid macrophages”. under the influence of IL-4 or INF-γ, several cells may fuse to give “multinucleated giant cells”. 19  20 multinucleated giant cells, chronic glomerulonephritis Chronic inflammatory cells: Lymphocytes They are mobilized in any specific stimulus (infection), or in non-immune stimulus like in infarction or tissue trauma. T-lymphocytes: have a reciprocal relation with the number of macrophages involved in the chronic inflammation. B-lymphocytes: responsible for the production of antibodies through the differentiation into plasma cells. 21 Chronic inflammatory cells: Lymphocytes T-lymphocytes:  cellular immunity  macrophage interaction lymphocyte B-lymphocytes: antibody-mediated immunity transform to plasma cells 22 plasma cells T-Lymphocytes–macrophages interaction Lymphocytes are initially activated by interaction with macrophages presenting antigen fragments on their cell surface The activated lymphocytes then produce a variety of mediators, including IFN-γ to activate macrophages. Activated macrophages in turn release cytokines, including IL-1 & TNF, that further activate lymphocytes and other cell types The end result is an inflammatory focus where macrophages and T cells can persistently stimulate one another until the triggering antigen is removed, or some modulating process occurs. 23 24 T-Lymphocytes – macrophages interaction: 25 Chronic inflammatory cells: Eosinophils found in inflammation induced by parasitic infections or in allergic reactions involving IgE, Type I hypersensitivity reactions. Eotaxin is a specific chemokine for eaosinophils. major basic protein (MBP) is a protein found in the granules of eosinophils. It is toxic to parasites and causes tissue damage. 26  Chronic inflammatory cells: Mast cells widely distributed in tissues, especially around blood vessels. Has IgE receptors, and so it is important in allergic reactions and in anaphylactic shock. They are the primary source of histamine, mediating acute inflammation, and cytokines like TNF, so participating in chronic inflammation. 27 Chronic inflammation: morphological types 1. non specific: general features of inflammation example: chronic cholecystitis, chronic pyelonephritis 2. Granulomatous: histological pattern (granulomas) example:leprosy, sarcoidosis, syphilis 28  Chronic inflammation 1. non specific: ❑ Characterized by granulation tissue  formation of new blood vessels  inflammatory cells  fibroblasts  collagen ❑ aim: repair by replacement of injured tissue by fibrous tissue 29  Chronic inflammation 1. non specific type - morphology increased 30 vascularity  Chronic inflammation 1. non specific type - morphology increased numbers of 31 lymphocytes and plasma cells (a) (b) Formation of the acute inflammatory exudate: (a) Early vascular changes (b) Migration of neutrophils (c) Acute inflammation 32 (c) Early formation of exudate  Chronic inflammation 2. Granulomatous type Defined as aggregates of activated macrophages that assume an epithelial or squamoid-like appearance (epithelioid macrophages). Seen in few pathological conditions, so once identified, the differential diagnosis is limited. Important defense mechanism aiming at either eradication of the causative microorganism, or “walling off” of the particles that are resistant to killing and degradation, thus preventing their spread. 33 34 35 Infectious Non- infectious 36 37  Chronic inflammation 2. Granulomatous type 38 Infectious Non-infectious Granulomatous inflammation 39 Granulomatous disease: Here are numerous granulomas in upper lung fields in a case of active pulmonary tuberculosis 40  Chronic inflammation granulomatous type - morphology ❑ Langhans giant cell ❑ caseous necrosis ❑epitheloid macrophages miliary tuberculosis 41 These are epithelioid cells around the center of a granuloma. They get their name from the fact that they have lots of pink cytoplasm similar to squamous epithelial cells. Their nuclei tend to be long 42 Here is a foreign body giant type cell at the upper left of center adjacent to a segment of vegetable material aspirated into the lung. 43 44 Inflammation: The other defense lines The lymphatics, lymph nodes & mononuclear phagocyte system form the secondary defense lines. During inflammation, lymphatics help in draining edema fluid together with leukocytes, debris and micro-organisms into the lymph nodes, resulting in lymphangitis and lymphadenitis. 45 Inflammation: The other defense lines Bacteremia develops if the micro-organisms failed to be contained within the lymph nodes and gain access into the blood stream. Failure of containment of the micro-organism leads to seeding of distant sites. Heart valves “endocarditis”, meninges “meningitis”, kidney “renal abscesses”, and joints “septic arthritis” are the favored sites. The phagocytic cells in the liver, spleen and bone marrow constitute the next defense line. 46  Systemic Effects of Inflammation Called the acute phase response that is characterized by: – Fever – Malaise: a feeling of general discomfort – Anorexia: loss of appetite – Somnolence: tendency to sleep – Wasting: accelerated degeneration of skeletal muscles – Hypotension – Alteration in the circulating leukocytes – hepatic synthesis of plasma proteins 47 48 49  Systemic Effects of Inflammation Cytokines IL-1, IL-6, and TNF are the most important mediators of the acute phase reaction These cytokines are produced by leukocytes and other cells in response to infection, immune and toxic injury TNF induces the production of IL-1, which in turn stimulates the production of IL-6 TNF and IL-1 act on the thermoregulatory center to cause fever by the production of prostaglandins 50  Systemic Effects of Inflammation IL-6 stimulates hepatic synthesis of plasma proteins, mainly fibrinogen IL-1 and TNF cause increased production of leukocytes by the bone marrow Some infections cause a selective increase in the leukocyte count: – Bacteria: PMNs – Parasites with allergy: eosinophils – Viruses: lymphocytes 51  1 2 4 3 Chronic inflammation- outcome 52  Chronic Inflammation outcome - prolonged exposure to toxic agents Liver cirrhosis 53  Chronic Inflammation outcome - prolonged exposure to toxic agents normal lung interstitial fibrosis asbestos 54 body  Chronic Inflammation outcome - persistent infection ❑ chronic ulcer of the stomach with perforation 55  Acute versus Chronic Inflammation: Acute Chronic Long (weeks to Duration Short (days) months) Onset Acute Insidious Lymphocytes, Inflammatory Neutrophils, plasma cells, cells macrophages macrophages, fibroblasts New vessel Vascular Active vasodilatation, formation changes increased permeability (granulation tissue) Fluid exudation & + – edema 56 Cardinal signs + –  Acute versus Chronic Inflammation: Acute Chronic Tissue – (Usually) + (ongoing) necrosis Fibrosis – (Usually) + Systemic Fever, often high Low–grade fever, manifestations weight loss, anemia Changes in Neutrophil Frequently none; peripheral leukocytosis; variable leukocyte blood lymphocytosis (in changes, increased viral infections) plasma IG 57 58