Lecture 6 - Kapila - Infl Iii-morphology -10 Sep 2006

Inflammation III -Morphologic patterns Kusum Kapila September 2006

CLASSIFICATION OF INFLAMMATION Extent Mild Moderate Severe Duration Peracute Acute Subacute Chronic Chronic-active Distribution Focal Multifocal Coalescent Locally Extensive Diffuse

Exudate Suppurative Fibrinous Serofibrinous Fibrino-purulent Necrotizing Granulomatous, Anatomic Modifiers Interstitial Broncho-interstital Glomerulonephritis Submandibular Organ Nephritis Hepatitis Enteritis Etc

FOCAL Definition: Single abnormality or inflamed area within a tissue Size: Varies from 1 mm to several centimetres in diameter

MULTIFOCAL Definition: Arising from or pertaining to many foci (several foci separated from one another) Size: Variable. Note: Each focus of inflammation is separated from other inflamed foci by an intervening zone of relatively normal tissue.

LOCALLY EXTENSIVE Definition: Involvement of considerable area within an organ. Possible origin: 1. Severe local reactions that spread into adjacent tissue 2. Coalescence of foci in a multifocal reaction

DIFFUSE Involves all the tissue or organ in which the inflammation is present - Variations in severity may exist eg: Interstitial pneumonia. Diffuse lesions are often viral or toxic in etiology. Organ involved IMPORTANT

Morphologic Patterns in Acute and Chronic Inflammation 1- Serous Inflammation Marked by a thin fluid that derived from blood serum or mesothelial cells 2- Fibrinous Inflammation A fibrinous exudate develops with large vascular leak Characteristic of inflammation in body cavities (pericardium and pleura) 3- Suppurative or Purulent Inflammation Characterized by large amounts of purulent exudate (pus) Pus consists of neutrophils, necrotic cells, and edema 4- Ulcers A local defect or excavation of the surface of epithelial covering Sites: Skin, gastro-intestinal tract, urinary bladder, etc.

Morphologic Patterns – Serous Inflammation Definition: Inflammatory process characterized by accumulation of fluid relatively rich in protein on body surfaces with little cellular infiltrate. Time: Usually acute Causes: May be a dominant pattern of exudation for a wide variety of mild injuries. Example: Traumatic blisters, sunburn, within body cavities. Gross : Yellow, straw-like colour fluid, commonly seen in very early stages of many kinds of inflam responses.

Morphologic Patterns – fibrinous Inflammation 2-Fibrinous Inflam A fibrinous exudate develops with large vascular leak Characteristic of inflammation in body cavities Sites: a- pericardium b- pleura Example: Fibrinous pericarditis secondary to rheumatic fever (rheumatic pericarditis)

EXUDATE: The inflammatory process can be classified according to the predominant type of inflammatory cells, plasma protein content, and amount of fluid present. A transudate has a specific gravity of less than 1.012, a low protein content, and few if any cells. An exudate has a specific gravity of greater than 1.020, a high protein content, and usually contains leukocytes.

Morphologic Patterns – suppurative Inflammation 3- Suppurative or Purulent Inflammation Characterized by formation of a large amounts of purulent exudate (pus) Usually caused by pyogenic bacteria (pus-forming) PUS consists of: PMNLs, Necrotic cells, and Edema fluid -Appearance: yellow-white to gray-white and varies from watery to viscous

Suppuration - Abscess formation Abscess: A localized area of tissue loss leading to formation of a cavity filled with pus / purulent exudate

Morphologic Patterns in Acute and Chronic Inflammation Suppurative inflammation could take the form of: 2- Empyema: Suppurative exudate within a natural anatomic cavity e.g. Pleural/pericardial empyema of gallbladder etc

Spectrum of Inflammatory Responses to Infection

Suppurative ( Polymorphonuclear ) Inflammation - aetiology 1. Pneumococci 2. Staphylococci 3. Klebsiella

Acute lobar pneumonia Abscess formation Pneumonia

Name a pyogenic bacteria that causes Meningitis?

Morphologic Patterns in Acute and Chronic Inflammation 4- Ulcers A local defect or excavation of the surface of epithelial covering Sites: Skin Gastro-intestinal tract Urinary bladder Female genital tract Complications of ulcers include : Bleeding Perforation Fibrous scarring

Spectrum of Inflammatory Responses to Infection

Fibrinonecrotic Inflammation: Inflammation on a well-vascularized epithelial surface (eg: trachea, intestine, nasal passages), characterized by necrosis of the surface epithelium and presence of fibrin forming Pseudomembranes/ Diphtheritic Membranes. FIBRINOPURULENT EXUDATE: Term used to classify an inflammatory process in which neutrophils and fibrin are abundant.

Spectrum of Inflammatory Responses to Infection Haemorrhagic Inflammation: Haemorrhage predominates, occurs due to severe injury to blood vessel (acute pancreatitis) or depletion of coagulation factors (meningococcal septicaemia – DIC) Mucoid Exudate: Consists of mucus and pus (large numbers of neutrophils and neutrophil debris). Catarrhal inflammation - Synonym for mucopurulent inflammation eg. Common cold. Eosinophilic Inflammation: Eosinophils are the primary inflammatory cell type present Nonsuppurative Inflammation: This a microscopic diagnosis as mononuclear cells (lymphocytes and plasma cells) are present. Lymphocytic Inflammation: Lymphocytes are the predominant inflammatory cell type.

Spectrum of Inflammatory Responses to Infection

I- Acute Suppurative inflammation II- Mononuclear and Granulomatous Inflammation : Occur in response to: viruses intracellular bacteria spirochetes intracellular parasites helminthes

Granulomatous Inflammation Definition: Granulomatous response characterized by the presence of lymphocytes,macropha ges, and plasma cells .Macrophages can be clustered around the foreign matter and be as "epithelioid," or"multinucleated "

Spectrum of Inflammatory Responses to Infection III a. CytopathicInflammation : Viral-mediated damage to host cells in the absence of host inflammatory response Formation of viral inclusions within cells Examples Cytomegalovirus CMV Herpes Simplex

Spectrum of Inflammatory Responses to Infection

III b. Cytoproliferative Inflammation Human Papilloma Virus HPV Over 60 distinct types produces proliferative lesions of squamous epithelium condyloma accuminatum (6,10,11) common warts (1,2,4) flat warts

Condyloma acuminatum-HPV 6,10,11

Viral Inclusions

Molluscum contagiosum

Herpes simplex virus

CMV

Rabies – negri bodies

Spectrum of Inflammatory Responses to Infection IV NECROTIZING INFLAMMATION: Definition: Inflammation characterized primarily by necrosis variable amount of haemmorrhage, edema and inflammatory cells -Necrotizing inflammation is often associated with interruption of blood flow, such as in mycotic diseases of the gastrointestinal tract that result in arterial thrombosis – vascular obstruction. -It is also seen in association with toxin-producing bacteria - gangrenous infections. Histologically, there is only scant evidence of vascular or leucocytic contributions.

Spectrum of Inflammatory Responses to Infection IV. Necrotizing Inflammation : Clostridium perfringens Organisms secrete toxins causing rapid severe tissue damage and cell death. Few inflammatory cells are involved Lesions resemble ischemic necrosis Entamoeba histolytica Colonic ulcers and liver abscesses Extensive liquefactive necrosis Absence of a prominent inflammatory infiltrate viruses total destruction of temporal lobes of the brain by herpes virus the liver by HBV

Spectrum of Inflammatory Responses to Infection V. Chronic Inflammation and Scarring : Chronic inflammation may lead to extensive scarring eg. “Pipe-stem” fibrosis of the liver caused by schistosoma eggs (Bilharzial liver disease) Constrictive (fibrous) pericarditis secondary to tuberculous pericarditis

Resolution SuppurationAbscess formation Organisationscar formation regeneration Persistent inflammation (chronic inflammation)

INJURY

Outcome of Acute Inflammation

Resolution Mediators

Acute inflammation

Abscess formation Healing

Mediators

Chronic inflammation

Persistent infection Persistent toxins Autoimmune diseases

Regeneration Scarring

Resolution Means complete restoration of the tissues to normal Favouring factors Minimal cell death and tissue damage Occurrence in an organ or tissue which has regenerative capacity (eg the liver) rather than in one which cannot regenerate (eg. the central nervous system) Rapid destruction of the causal agent (eg. phagocytosis of bacteria) Rapid removal of fluid and debris by good local vascular drainage

Sequence of events leading to resolution of pneumonia Phagocytosis of bacteria (eg pneumococci) by neutrophils and intracellular killing Fibrinolysis Phagocytosis of debris, by macrophages and carriage to lymphatics and lymph nodes Disappearance of vascular dilatation

Abscess Formation 1- Abscess: A localized area of tissue loss leading to formation of a cavity filled with pus / purulent exudate

Organisation cavity Replacement by granulation tissue Increased fibrin which cannot be removed

Organisation - organ Substantial necrotic tissue not easily digested Exudate and debris cannot be removed or discharged

Outcome of Acute Inflammation:

Fibrosis – Repair by Connective Tissue Replacement’ a. Substantial tissue destruction b. Occurs when affected tissue can not degenerate c. Occurs when fibrin exudation is abundant as in effusions following pneumonias

Outcome of Acute Inflammation: Chronic Inflammation a. Persistent stimuli progression of inflammatory process b. Primary purpose is to contain and remove pathologic agents or processes.

ANATOMIC MODIFIERS: Terms used to describe a specific area within an organ that may be affected by inflammation or degenerative conditions. Example: Cardiac Inflammation Endocardium - Endocarditis valvular/mural Myocardium - Cardiomyopathy/myocarditis Pericardium - Pericardial effusion, pericarditis Pancarditis - Involves all layers

Effects of acute inflammation Beneficial Dilution of toxins Entry of antibodies Transport of drugs Fibrin formation Delivery of nutrients and oxygen Stimulation of immune response

Harmful Digestion of normal tissue Swelling Raised Intracranial pressure acute epiglottitis Allergic inflammatory response

Local Clinical Effects of Acute And Chronic Inflammation Mainly related to: 1.Loss of organ secretory / metabolic function function e.g. hepatitis, thyroiditis, pancreatitis, 2. Damage and Loss of vital functioning tissues causing organ failure e.g. acute / chronic pneumonitis, hepatitis, glomerulonephritis 3. Compression of vital organs : nerves, blood vessels, lymphatics

Local Clinical Effects of Acute And Chronic Inflammation 4. Interferences with normal mechanical function: a. post-burn scarring over joints b. scarring of articular joints in rheumatoid arthritis (RA) c. adhesions over peritoneal surface (?) and pericardial cavity 5.Hemorrhage: Ulcer Damaged blood vessels 6. Obstruction of vital organ passages: a- inflammatory exudate B- fibrous tissue formation (scarring) leading to stricture formation

Inflammation Systemic Manifestations

Fever - clinical hallmark of inflammation - Endogenous pyrogens: IL-2 ,TNF-α Constitutional symptoms - malaise, anorexia,nausea Weight loss - due to negative nitrogen balance Hyperplasia of reticuloendothelial system-LN, spleen Leukocytosis - may be neutrophils, eosinophils, or lymphocytes Anemia –blood loss,chronic due to toxic depression of bone marrow Acute Phase Reactants - non-specific elevation of many serum proteins ESR high-raised plasma proteins causing increased rouleaux formation of RBC Amyloidosis – longstanding chronic infection

Inflammation Systemic Manifestations Leukocytosis: most bacterial infection Lymphocytosis: Infectious mononucleosis, mumps, German measles Eosinophilia: bronchial asthma, hay fever, parasitic infestations Leukopenia: typhoid fever, infection with rickettsiae/protozoa