GP 09 - Chronic Inflammation Flashcards
What are the key features of chronic inflammation?
- Infiltration with mononuclear cells
- Tissue destruction
- Attempted healing with new vessel formation and fibrosis
What are the cells of chronic inflammation?
- Macrophages
- Lymphocytes
- Others
- eosinophils
- mast cells
- some neutrophils
What are the different forms of macrophages found during chronic inflammation? What term is used to describe all of these forms?
- Monocytes
- Resident tissue macrophages
- Free macrophages
- Epithelioid cells
- Gian cells
All together, these compromise the mononuclear phagocytic system.
Briefly describe the formation and differentiation of macrophages.
- Myeloid progenitor in the bone marrow becomes a monoblast
- Monoblast becomes monocyte as it enters the blood
- Once in the tissues, a monocyte becomes a macrophage
- Microglia (CNS)
- Kupffer Cell (liver)
- Alveolar Macrophage (lung)
- Osteoclast (bone)
What is this? Where is this?
Monocyte in the blood
What is an epithelioid cell? How do you spot it on a micrograph? What is its function?
- It is a form of activated macrophage
- They have abundant cytoplasm and resemble epithelial cells
- They have some phagocytic activity but function primarily as secretory cells
Epithelioid cells
What are giant cells?
Activated macrophages that have fused together. They are multinculeated cells and are named based on the arrangement of their nuclei:
- Langhans Giant Cells have a U-shaped nucleus
- Foreign Body Giant Cells have randomly arranged nuclei
Langhans Giant Cells
Foreign Body Giant Cells
What are the basic roles of macrophages in chronic inflammation?
Contribute in inflammatory reactions by secreting cytokines and growth factors which:
- Destroy foreign invaders with collateral tissue damage
- Activate other inflammatory cells
- Promote angiogenesis by activating fibroblasts and stimulating collagen synthesis
Describe the classically activated macrophage pathway.
- Macrophage becomes activated by microbe products or interferon gamma (IFN-γ). This is called M1 activation
- Macrophage phagosytoses and destroys microbes/dead tissues utilizing ROS, NO, and lysosomal enzymes
- Macrophage releases IL-1, IL-12, IL-23, and chemokines to promote inflammation
Describe the alternatively activated macrophage pathway.
- Macrophage is activated by IL-13 and IL-4. This is called M2 activation
- Macrophage releases growth factors, most notably transforming growth factor beta, TGF-ß, to promote tissue repair and fibrosis
- Macrophage releases IL-10 and TGF-ß which will have anti-inflammatory effects
What is happening in this tissue? What is each arrow pointing to?
Chronic Inflammation
Red Arrow - Foreign Body Giant Cell
Blue Arrow - Lymphocytes
Green Arrow - Neutrophil
Orange Arrow - Epithelioid Cells
Yellow Arrow - Plasma Cells
List the lymphocytes important to chronic inflammation. What are their key roles in chronic inflammation?
- Helper T Cells
- THI1 cells produce IFN-γ which cause M1 activation
- TH2 cells produce IL-4, IL-5, and IL-13 which recruit eosinophils and cause M2 activation
- TH17 cells produce IL-17 which recruits neutrophils
- Cytotoxic T cells, when activated, release perforins and granzymes that will initiate cell death in microbes
- Plasma Cells - antibody secretion
Why do eosinophils stain red? For what types of infections are these cells most important?
They contain major basic protein in their granules which bind eosin strongly
They play an important role in parasitic infections and allergic reaction.
Eosinophil
Describe why mast cells can be important to chronic inflammation.
They have IgE surface receptors that, when bound, can cause the cell to release hitamine and prostaglandins
They play a role in allergic reactions to food, insect venom, and drugs
What is granulomatous inflammation?
A form of chronic inflammation where the cells are attempting to contain an offending agent that is difficult to eradicate. The cell types presents are:
- Activated Macrophages
- Epithelioid cells
- Giant Cells
- T-lymphocytes
Sometimes central necrosis is present
What is this?
A granuloma
What is this?
A Granuloma
What are the most common causes of granulomatous inflammation that we need to know?
- Tuberculosis (mycobacterium tuberculosis)
- Leprosy (mycobacterium leprae)
- Syphilis (treponema pallidum)
- Cat scratch disease (bartonella sp.)
- Indigestible Material (talcosis and berylliosis)
- Idiopathic (sarcoidosis, Crohn’s disease)
What is this?
A Caseous Granuloma
What are the most common morphological features of chronic inflammation?
- Fistula Formation (connection between two epithelial sufaces)
- Sinus Formation (connection between a granulomatous cavity and an epithelial surface)
- Chronic Ulcer (abnormal discontinuity or break in a biological membrane)
- Chronic Abscess
- Thickening of a hollow viscus
- Stricture formation (wall thickening that narrows a lumen)
What are the systemic effects of inflammation and what causes them?
- Fever - increased body temp by 1-4 C. Caused by pyrogens but mechanism is unknown
- Leukocytosis - increased WBC count up to 15000-20000 cells/mL. Sometimes a leukemoid reaction (40000-100000 cells/mL) can occur. Caused by increased [cytokine]
- Acute phase response - decerase in liver synthesis of albumin and an increase in synthesis of acute phase proteins - CRP, serum amyloid A (SAA), fibrinogen. Caused by increased release of IL-1, IL-8, and TNF
- Other Manifestation - increasted HR & BP, chills, rigor, decreased or increased sweating, lethargy, sepsis, and/or septic shock
What are the primary outcomes of chronic inflammation?
- Healing by fibrosis
- Fibroblast proliferation and activation leads to increased ECM production which occupies the space where parenchyma once was
- Lack of resolution with persistence of inflammatory process
- Metaplasia to Dysplasia to Neoplasm
- Amyloidosis from prolonged production of SAAs
- Loss of function
- ECM changes normal mix of ECF proteins
- Fibrosis alters the function of the area
List the cardinal signs of inflammation and give their pathogeneses.
- Redness & Hotness - vasodilation
- Swelling - edema nd cell infiltrates
- Pain - direct stimulation of nociceptors by K+, bradykinin, PGs, and Substance P
- Tenderness - decreased nociceptor threshold caused by IL-1, IL-6, IL-8, & TNFα, and increased tension (from swelling, abscess, etc.)
- Loss of function - lack of resolution in chronic inflammation
