Tissue Reactions To Infection

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Pathology

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Interested in morphology of disease

-Pathology

1) look at specimen grossly and under microscope - determine infection

2) Correlate with clinical presentation

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White Blood Cells- 2 Categories

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1. Granulocytes

2. M'Mononuclear' cells- nucleus is round and there no granules (but note, all WBCs are really mononuclear)

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Granulocytes

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Neutrophils (polymorphonuclear), Eosinophils (bilobed nucleus), Basophils

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'Mononuclear' Cells

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Lymphocytes, monocytes, plasma cells

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Infection- Definition

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-"Invasion by & multiplication of pathogenic microorganisms in a bodily part or tissue, which may reproduce subsequent tissue injury & progress to overt disease thru a variety of cellular or toxic mechanisms"

-Clinically - when microbes cause disease in humans

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6 Tissue Rxns to Infection

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1) Acute/Suppurative inflammation

2) Mononuclear & granulomatous inflammation

3) Chronic Inflammation & scarring

4) Inflammation w/ eosinophilia

5) Cytopathic/cytoproliferative changes

6) Tissue necrosis

*Bold - inflammation

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Inflammation

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-protective process that brings cells & other molecules of host defense system from blood to injury sites to get rid of infecting organisms & prepare tissue for repair. It is the general response of VASCULARIZED tissue to injury

-"-itis" = inflammation due to any cause

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Inflammation- Causes

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Many! not just microbial infections

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Factors that influence type of tissue rxn

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Many! location of microbe, type of microbe, host immune response to microbe, etc

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Location- one of factors that influence Tissue Rxn Type

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Extracellular organism:

-acute inflammation/supparative

-immune rxn involves neutrophils & macrophages

Intracellular organism:

-immune rxn involves mononuclear cell infiltrate: lymphocytes, plasma, cells, and macrophages

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Purulent/Suppurative Inflammation

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common subtype of acute inflammation- used interchangeably

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Pyogenic vs purulent

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pyogenic produces pus, purulent contains it

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Exudate

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fluid discharged or leaked into surrounding tissue due to tissue injury

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pus

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viable & dying WBC (neutrophils), liquefied necrotic tissue, cellular debris, & protein rich fluid

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Infectious causes of suppurative inflammation

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neutrophils react against extracellular organisms

-most bacteria (most gram+ cocci & gram-- rods)

-some fungi

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Features of Suppurative Inflammation

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-General Features of acute inflammation:

rubor, tumor, calor, dolor

-purulent exudate

-Diagnosis:

• gram stain for bacteria
• grocott stain for fungi

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Outcomes of Suppurative Inflammation

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-Normal Healing - usual outcome!

-Tissue Destruction

• often associated w/ abscess formation

-Chronic inflammation & scarring

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Abscess

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focal lesion where acute inflammatory response resulted in central area of tissue necrosis & neutrophil

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Summary of acute/supparative inflammation

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-Pt presents w/ acute illness/acute infection due to extracellular bacteria or some fungi will show acute/suppurative inflammation

-pus contains: neutrophlils, macrophages, protein rich fluid, cellular debris

-Inflammatory response may lead heal (usually), lead to tissue destruction (abscess), progress to chronic infection

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Mononuclear Inflammation

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-will see infiltrate of mononuclear cells in response to tissue infection

*No pus - bc intracellular organisms are handled differently by immune system

-most common organisms that elicit response are intracellular organisms & spirochetes

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Mononuclear inflammation- associated w/ Acute vs associated w/ Chronic Infection

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Acute infection - in response to intracellular organism (e.g. VIRUS)

Chronic infection - could be intra or extracellular organism

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Granulomatous Inflammation

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-Special subtype of mononuclear inflammation

-hallmark: "epitheloid histiocyte" - activated macrophage w/ abundant pink cytoplasm, that also secretes many mediators of inflammatory process

-can have infectious or noninfectious etiology

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Granuloma

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-nodules of activated macrophages, usually surrounded by rim of lymphocytes & plasma cells

-Pathogenesis: interaction of certain organisms w/ immune system results in recruitment and activation of macrophages to infection site ---> become activated macrophages aka eptheloid histiocytes --> these group together to form granuloma

--within a granuloma, macrophages may fuse to form giant cell that enhances their ability to kill organisms

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Giant cell

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-within a granuloma, macrophages may fuse to form giant cell that enhances their ability to kill organisms

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Granulomatous Inflammation- Clinical Presentation

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-Granulamotous inflammations due to microorganisms present as chronic infection

-tissues may or may not have central necrosis w/ lymphocytes & plasma cells around periphery

• caseous necrosis: type of necrosis, most often associated w/ granulomas, w/ cheesy-like appearance

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Granuloma Causes

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-can be caused by immune (infectious) or non-immune (noninfectious) mechanisms

-When due to infections, granulomas are due to immune-mediated mechanisms against a poorly degradable intracellular microbe

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Organisms that Elicit Granulomatous Inflammation

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-Limited # of organisms

-Intracellular

-Poorly digestible, poorly soluble

-resistant to eradication

Examples:

• Most Important: Mycobacteria (*TB)
• some fungi & some worms

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Caseous Necrosis

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-in central portion of lesion

-cheesy-like appearance

-characteristic of TB infection

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Lung Granuloma Histology - Lo Power View

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Lung Granuloma Histology - Hi Power View

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Histology: Abscess vs Granulomatous Inflammation w/ Caseous Necrosis

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-look similar, w/ necrotic tissue in center

-microscopic view tells them apart

• Abscess: purple center, indicating necrotic tissue & cells w/ nuclei (=purple) and pinker rim;
• hi power view (not shown here): shows neutrophils in various stages of degeneration
• Granuloma w/ caseous necrosis: pink, acellular necrosis in center

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Cultures: Abscess vs Granulomatous Inflammation w/ Caseous Necrosis

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Abscess:

-(UR) e.g. Staph on blood agar plate

-(BR) gram stain

Granulomatous Inflammation:

-(UL) M Tb doesn't grow on blood agar, needs special media tubes on upper right

-(LL) M Tb doesn't stain w/ gram stains but w/ special stains

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Summary: Mononculear & Granulomatous Inflammation

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Mononuclear:

-Presentation: Acute or chronic infection

-Organisms: intracellular, spirochetes, eradicate bacteria

-Pathology: ('Mononuclear cells' ) lymphocytes, plasma cells, macrophages

Granulomatous:

-Presentation: Chronic

-Organism: ****TB (other mycobacteria, fungi, parasites)

-Pathology: granulomas, epitheloid macrophages, giant cells, w/ or w/o caseous necrosis, rim of lymphocytes & plasma cells

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Chronic Inflammation & Scarring- Definition

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delayed-onset & protracted duration response of host to tissue injuries & certain foreign injurious agents that may persist for an indefinite period of time

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Chronic Inflammation- Clinical Presentation

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-can have infectious & noninfectious causes

-when due to microorganisms, presentation is a chronic infection

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Chronic Inflammation & Scarring - Causes

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-Intracelluar

-Hard-to-eradicate extracellular

-long-standing infection due to any type of organism

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Chronic Inflammation & Scarring - Tissue Rxn

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-mediated by many chemical mediators

-involves any or all of mononuclear cell infiltrate (lymphocytes, plasma cells, & macrophages) & mast cells

-When causes significant tissue damage --> scarring

*Note: no abscess

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Chronic Inflammation - Histology

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-Lymphocytes: small, scant cytoplasm, & round nuclei

-T/B cells: can't be told apart

-Cant tell type of organism by just looking at types of cells in tissue run - even though there are diff combinations of mononuclear cells in response to diff types of organisms

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Scarring aka fibrosis

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-one way to repair damaged tissue, caused by after prolonged or repeated bouts of chronic inflammation involves many cells and release of mediators

-fibroblasts move into area where damaged tissue was removed & lay down collagen

-permanent change in tissue structure

-possible permanent change in tissue function

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Hepatitis B

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-virus that infects hepatocytes of liver

-tissue run is chronic inflammation

-may result in cirrhosis - formation bumpy nodules on liver due to fibrosis

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Hepatitis B- Histology

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-Normal: homogenous

-Abnormal: many pink nodules (of hepatocytes), varying sizes, separated by bands of purple cells (area of fibrosis & chronic inflammation of mononuclear cells)

• other stain will stain blue in bands - collagen

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Cirrhosis Consequences

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Altered liver structure - increased pressure in portal system can cause

-Varices: abnormal, enlarged veins in distal esophagus --> risk of severe bleeding

-Ascites: fluid in peritoneal cavity --> risk of infection

Impaired liver function

-Inability to make clotting factors, protein

-Jaundice: inability to handle bile

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Summary: Chronic Inflammation & Scarring

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-Clinical Presentation: Chronic infection

-Organisms: Intracellular, hard-to-eradicate extracellular, longstanding infection due to any organism

-Tissue Rxn: Mononuclear cell infiltrate & Tissue Damage/Fibrosis w/ long duration

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Inflammation with Eosinophila

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-Clinical Presentation- Acute or chronic

-Organisms: helminths

-Tissue Rxn: abundance of eosinophils, mononuclear cell infiltrate, sometimes granulomas

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Eosinophils - Histology

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Eosinophils - bright orange-red granules & bilobed nucleus

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Eosinophils - Function

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Defend against helminthic infections

-parasites are too large to be ingested

-IgE Antibodies bind to helminths

-FcR on eosinophil recognizes Fc

-eosinophilic granules: secrete MBP, which is toxic for helminths but also causes extensive host tissue damage

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Worm Infections

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Cause eosinophilic response & can also cause granulomatous response

-their eggs are seen as a foreign object and granulomas form as a response

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Cytopathic Changes

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-Definition: Structural changes in cells due to infection by certain viruses

-diff changes --> diff viruses

Features:

• nuclear inclusions (viral aggregates)
• cytoplasmic inclusions (viral aggregates)
• multinucleated cells (cell fusion)
• features that suggest type of virus
• Variable amount of inflammation

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Cytomegalovirus (CMV)

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-inclusions made of viral aggregates & altered host cell structures

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Herpes Simplex Virus

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-different than CMV- causes multinucleated cells!

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HPV

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enlarged nucleus, binucleated, perinuclear halo

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Adenovirus

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Intranuclear inclusion

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Cytoproliferative Changes

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-increase in cell #

-Organisms: some viruses

-Viral infection w/ proliferation: usually associated w/ cytopathic features

-Viral infection, proliferation, & transformation to cancer: very uncommon & need viral infection & other factors to cause cellular changes for cancer

E.g HPV

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HPV

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-Some subtypes lead to proliferation and cytopathic changes

-infects squamous cells of cervix, inserting viral DNA into host DNA

-alone cannot cause development of cancer - needs co-factors!

-*

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Tissue Necrosis - Tissue Rxn

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-sometimes can be widespread necrosis w/ no inflammation

-This is most often seen w/ toxin-mediated injury

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Gas gangrene

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-bacterium secretes toxin that causes rapid death of mscl tissue & also produces gas

-Results in in necrotic mscl tissue, masses of bacteria, & no inflammatory infiltrate

-Example: Clostridium perfringens

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Chart: Diff Tissues Cause Diff Types of Tissue Rxns

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