Exam 3: Chronic Inflammation and Repair Flashcards
What are the characteristics of chronic inflammation?
Predominance of mononuclear cells –> mainly macrophages, lymphocytes, and plasma cells
Vascular changes are minimal
Increased connective tissue (fibrosis)
Alteration in tissue architecture
Why does chronic inflammation occur?
Neutrophils are short lived
Neutrophils signal macrophages
Macrophages are longer lived –> can proliferate in tissues
Persistence of antigen
Some stimuli signal chronic inflammatory cells directly
When does an abscess develop?
When acute inflammation fails to eliminate stimulus
What is an abscess?
Liquefaction due to neutrophil enzymes
What does the color of exudate in an abscess depend on?
Pigment produced by inciting stimulus
What happens around exudate to form an abscess?
Fibroblasts produce collagen and form a thin connective tissue, which can mature into a fibrous capsule which eventually walls off
What is the inner wall of an abscess?
Granulation tissue: “pyogenic membrane”
Full of vessels that allow continual recruitment of neutrophils
Describe NAG
Grossly abscess and granulomas can be very similar in appearance. Sometimes abscesses can have thicker capsules but it depends on duration
Neoplasms can also be similar grossly
Differentials are Neoplasia, Abscess, and Granuloma (NAG)
Describe macrophages
Have abundant cytoplasm, can be foamy
Large, round nucleus that is sometimes indented
What does granulomatous mean?
Macrophages
What is granulomatous inflammation dependent upon?
Presence of indigestible organisms/particles
Presence of cell mediated immunity to inciting agent
What is seen grossly with granulomatous inflammation?
DIffuse: tissue appears thickened
Nodules: firm nodules of various sizes
What is seen microscopically with granulomatous inflammation?
Numerous macrophages present
Often accompanied by variable numbers of lymphocytes and plasma cells and connective tissue
What is the effect of granulomatous inflammation?
Chronic infection which the body cannot eliminate
Interfere with organ function
What are causes of granulomatous inflammation?
Bacteria
Fungi
Parasitic disease
Foreign bodes
What are bacteria and fungi resistant to that allows them to cause granulomatous inflammation?
Phagocytosis
What does the look of macrophages depend on?
Differentiation status
What are epithelioid macrophages?
Abundant eosinophilic cytoplasm and large pale nuclei
More secretory and less phagocytic than typical macrophages
What are giant cells?
Large, multinucleated cells that arise from the fusion of macrophages
What is a granuloma?
Macrophages that are in aggregates
Describe classic granulomas
Central core of caseous necrosis
Zone of epithelioid macrophages and giant cells
Zone of lymphocytes
An outer zone of fibroblasts and fibrosis
How can you differentiate between diffuse and nodular granulomatous inflammation?
Morphologic forms based on immunologic response
Th2–> diffuse granulomatous inflammation
Th1–> nodular granulomas
What is a stage 1 granuloma?
Days after infection
The lesion site is infiltrated by neutrophils, monocytes, macrophages, and lymphocytes. Epithelioid macrophages form
What is a stage 2 granuloma?
From roughly 48 hours to multiple days and weeks
Lesions contain macrophages, epithelioid macrophages, thin rims of fibrous connective tissue, variable numbers of lymphocytes, MGCs can also form
What is a stage 3 granuloma?
From weeks to 1 month
The central area can caseate or become dense with macrophages and mineralize
Lymphocytes, plasma cells, a zone of fibroblasts, and a fibrous connective tissue capsule surround this core
What is a stage 4 granuloma?
From several weeks to months
The lesion can be walled off by a dense capsule
Regions within the lesion can become mineralized and overtake the surrounding tissue
What is a good example of diffuse granulomatous inflammation?
Johne’s in cattle
How can you identify that there is diffuse granulomatous inflammation?
There are no well defined modules
There is a diffuse accumulation of epithelioid macrophages
What is lymphocytic inflammation?
Accumulation of lymphocytes
What is seen grossly with lymphocytic inflammation?
Difficult to determine grossly
If infiltrates are extensive, the tissue may have a tan/white color
What is seen microscopically with lymphocytic inflammation?
Lymphocytes present
Can be mixed with plasma cells
What are causes of lymphocytic inflammation?
Certain viral infections (rabies, WNV, EEE
Certain bacterial infections (listeria)
Some parasitic infections (Toxoplasma gondii)
What are effects of lymphocytic inflammation?
Indicates the immune response is occurring against an agent
Many cases involving the nervous system are fatal
Describe lymphocytes
Small cells, with very little cytoplasm
Lymphocytes entered unresolved areas of acute inflammation within 24-48 hours
In some organs (brain), will have a perivascular pattern
What are B cells?
- Lymphocytes take up and present antigen
2. Differentiate into plasma cells- secrete immunoglobulins
When do plasma cells predominate?
Certain chronic inflammatory conditions
Describe eosinophilic granulomas
Recruited into and stimulated to proliferate- IL-5 and eotaxin
Dense infiltrate of eosinophils with macrophages, varying numbers of lymphocytes and plasma cells
What does fibrosis stimulate?
Fibroblasts
What do fibroblasts contribute to?
Structural integrity of tissue
What are fibroblasts responsible for?
Synthesis of collagen and extracellular matrix proteins
Produce cytokines and chemokines that regulate the extracellular environment
What do fibroblastic growth factors signal?
Proliferation
What is fibrous connective tissue?
Dense accumulation of fibroblasts and collagen
With time, connective tissue becomes more dense and fewer inflammatory cells
What are the 4 phases of wound healing?
Hemostasis
Inflammation
Proliferation
Remodeling
What is the hemostasis phase of wound healing?
Platelet plug, angiogenesis
What is the inflammation phase of wound healing?
Cardinal signs of inflammation
Clean up cell debris from tissue injury
How does excessive inflammation effect wound healing?
It inhibits it
What is the proliferation phase of wound healing?
New endothelium, epithelium, and connective tissue to restore normal function
What is the remodeling phase of wound healing?
Remodeling of granulation tissue and conversion to mature connective tissue
What does wound repair require?
Extracellular matrix and it must be resynthesized
What is granulation tissue?
Fibroblasts and endothelial cells proliferate to fill in tissue defects
How do fibroblasts grow?
Parallel to the wound surface and perpendicular to the proliferating capillaries
What can excessive granulation tissue lead to?
A hypertrophic scar
How is healing affected if the basement membranes are damaged?
Healing will take longer
What happens if healing is delayed?
Altered healing can occur leading to extensive fibrosis
What is 1st intention healing?
Primary intention healing
When edges are directly apposed
Heals rapidly with little trace of wound
What is 2nd intention healing?
Gaping wound or infected wound
Connective tissue disorganized
What is epithelialization?
Epithelial cells at periphery proliferate
Very rapid in 1st intention healing
What must epithelialization move along?
A basement membrane
Describe bone healing
Hematoma
Fibroblast proliferation and mesenchymal proliferation
Callus formed (primary)
Secondary callus formed
What inhibits fracture repair?
Malnutrition Infection Instability Necrotic bone fragments Movement at site Inadequate blood supply
