Chronic Inflammation Flashcards
Define chronic inflammation
- When inflammation persists and lacks resolution
- If it persists for weeks/months/years with ongoing tissue damage,
- when tissue is infiltrated by lymphocytes, plasma cells and macrophages.
- It can be the initial response to certain viral/fungal infections
What are the cells involved in chronic inflammation
- Macrophages,
- Plasma cells
- Lymphocytes
(cells of acute is neutrophil polymorphs)
Describe the appearence of plasma cells on a histology slide
- Round/oval shape
- Dark cytoplasm
- Clock-face pattern nucleus (lots of spots) which is dark
- Can be di/trinuclear
Describe the appearence of a lymphocyte
- Dark purple. Have a very large dark nuclei and little cytoplasm
Describe the appearence of a neutrophil, basophil and eosinophil and platelets
Neutrophil - segmented nucleus of 2-5 lobes and a pale blue nucleus.
Basophil - Bilobed or S shape dark blue nucleus with a pale blue nucleus.
Eosinophil - Bilobed nucleus with pale pink granular cytoplasm
Platelets - Very small, no nucleus and purple
Describe the appearence of a macrophage
Oval in shape, abundant pale blue nucleus. Called monocytes in blood
What is the function of macrophage products?
They can be involved in tissue destruction by activating proteases, arachidonic acid metabolites, nitric oxide and coagulation factors or fibrosis by activating growth factors, fibrogenic cytokines, angiogenesis factors and remodelling collagenases.
What is granulomatous inflammation?
It is a distinctive pattern of chronic inflammatory reactions.
- Predominant cell types are epithelioid macrophages (Activated macrophages with a modified appearence) and giant cells (fused epithelioid macrophages). These cells form granulomas
Granulomas within lung tissue without necrosis suggests?
Pulmonary sarcoidosis (not TB due to lack of necrosis that accompanies granulomas)
Chronic granulomatous inflammation can be due to?
- Infectious agents: TB, leprosy or toxoplasmosis,
- Foreign material,
- Sarcoidosis or crohn’s disease,
- Response to a tumour (Hodgkin’s lymphoma)
What cells are involved in chronic granulomatous inflammation?
- Epithelioid macrophages (Mainly have a secretory role, giant cells form where material is hard to digest)
- Lymphocytes (CD4 which produces interferon gamma which can activate more macrophages and CD8)
- Formation of granulomas can be a manifestation of T cell mediated immune reactions
What is healing by primary and secondary intention?
Primary - Healing of a simple wound were the edges are closely opposed. Minimal granulation tissue is needed to close gap.
Secondary - Healing of the wound with a larger surface defect in the edges or one that is dirty/infected. Abundant granulation tissue is needed.
What are the phases of healing a tissue wound?
- Formation of blood clot,
- Formation of granulation tissue (new connective tissue),
- Cell proliferation and collagen deposition,
- Scar formation,
- Wound contraction,
- CT remodelling,
- Recovery of tensile strength
Describe the basic overview of fracture healing
Inflammatory
Repair
Remodeling
Describe the inflammatory stage of fracture healing
- Haematoma forms at the site of fracture,
- Prostaglandins recruit neutrophil polymorphs, macrophages, lymphocytes and fibroblasts to injury.
- Granulation tissue, ingrowth of new vessels and migration of mesenchymal cells occurs.
- Nutrients and oxygen are supplied by the exposed bone and muscle.
Describe the repair stage of fracture healing
- Fibroblasts lay down stroma to support ingrowing vessels,
- Collagen matrix is laid down,
- Osteoid (bone tissue) is secreted and mineralised leading to soft callus formation.
- Callus ossifies after 4-6 weeks by forming bridge of woven bone between fracture fragments.
Describe the remodelling phase of fracture healing
- Occurs slowly over months and years
- Returns bone to its original shape, structure and mechanical strength
- Facilitated by mechanical stress
What are factors that facilitate wound healing?
Local factors - Type, size, location, movement within wound, infection, presence of foreign bodies, irritation and poor blood supply.
Systemic - Age, nutrition, systemic diseases, drugs and smoking
Name and describe a chronic inflammatory disease
- Rheumatoid Arthritis. There is destruction of articular cartilage leading to infiltration of inflammatory cells causing increased vascularity, aggregation of fibrin and pannus formation leading to erosion of cartilage and bone.
Describe the role of inflammation in atherosclerosis
- Macrophages play a key role as they ingest LDL and become foam cells.
- Lymphocytes release chemical mediators
Describe features of chronic granulomatous diseases
- X-linked defect in NADPH oxidase system within phagocytes.
- Inability to kill intracellular organisms so patients have repeated infections and develop granulomata of the lymph nodes, skin, lungs, liver and GI tract.
What is hypereosinophilia syndrome?
A genetic mutation which drives excess production of clone eosinophils. This driver inflammatory processes within the myocardium which damages myocytes in a subendocardial distribution.
Fibrosis ensues and patient presents with clinically with restrictive cardiomyopathy
How does syphilis present histologically?
With plasma cell rich infiltrate
What is systemic mastocytosis?
- Excessive mast cells. Results in lots of histamine release. The mast cells can infiltrate the bone marrow, spleen, liver and lymph nodes which can supress their normal function. It is a CD117 mutation which can be treated with imatinib
