Session 4 Flashcards
How may chronic inflammation arise?
- May take over from acute inflammation if damage is too severe to be resolved within a few days.
- May arise de novo (no preceding acute inflammation phase)
- May develop alongside acute inflammation in severe persistent or repeated episodes of irritation e.g. In chronic colitis/ulcerative colitis. In the abscess that forms, the centre is pus (inflammation) and the periphery is scarring (result of chronic inflammation)
What is Chronic Inflammation?
“Chronic response to injury with associated fibrosis”
Less is known compared to acute inflammation.
There is an overlap with host immunity - including immunological reactions
Certain specific insults cause chronic inflammation with acute phase first.
When may chronic inflammation arise de novo?
In response to specific stimuli e,g. Some autoimmune conditions (e.g. Rheumatoid arthritis), some chronic infections (e.g. Viral hepatitis) and “chronic low level irritation” e.g. Foreign body in tissue space
e.g. Gravel in wound which could lead eventually to scarring.
What does Chronic Inflammation look like?
Not stereotyped - very heterogenous
Most important characteristic is the type of cell present.
Characterised by microscopic appearances which are much more variable than in acute inflammation
List the cells principally involved in chronic inflammation
Macrophages
Lymphocytes
Plasma cells
Eosinophils
Fibroblasts/myoblasts
Giant cells
Describe the role of macrophages in chronic inflammation
Derived from blood monocytes: large granular cytoplasm, bean-shaped nuclei
Important in acute and chronic inflammation
Various levels of activation - normally activated upon receiving inflammatory stimuli.
Functions:
- Phagocytosis (including opsonisation) and destruction of debris and bacteria.
- Processing and presenting of antigens (they become APCs) to the immune system
- Synthesis of cytokines, complement components, blood clotting factors and proteases
- Control of other cells via cytokine release (communication function)
Describe the role of lymphocytes in chronic inflammation
Very large nuclei, stains dark blue (almost no cytoplasm visible)
Sometimes called chronic inflammatory cells
Link between immune system and chronic inflammation
Functions: Complex, mainly immunological
- B lymphocytes mature (become Plasma cells) and differentiate to produce antibodies.
- T lymphocytes mature in the thymus and are involved in control of response (T helper cells - CD4) and some cytotoxic functions (T killer cells - CD8)
Describe the role of plasma cells (mature B lymphocytes) in chronic inflammation
Clock face nucleus - lumpy bumpy chromatin which is often at the periphery of membrane.
Crescent-shaped pale pink component surrounding plasma cells are Golgi apparatus.
They are differentiated mature B lymphocytes that synthesis and secrete antibodies and usually imply considerable chronicity.
Describe the role of eosinophils in chronic inflammation
Bi-lobed dark nucleus
Important in allergic reactions, parasite infestations and some tumours
Describe the role of fibroblasts/myoblasts in chronic inflammation
Recruited by macrophages
Make collagen
Important in wound contraction
What are Giant Cells?
Multinucleate cells made by fusion of macrophages.
Due to frustrated phagocytosis (debris/bacteria cannot be easily phagocytosed by single macrophages)
Several types recognised:
- Langhans –> Tuberculosis
- Foreign Body Type –> commonly found during joint replacement
- Touton –> Fat Necrosis
Describe the characteristics of Langhans Type, Foreign Body Type and Touton Giant Cells
Langhans: very structured horseshoe arrangement of nuclei arranged around the periphery of the cytoplasm
Foreign Body Type: disorganised arrangement of multiple nuclei
Touton: nicely organised parallel nuclei, foamy cytoplasm
Morphology of some chronic inflammatory reactions is non-specific BUT proportions of each cell type might vary in different conditions. E.g:
Rheumatoid Arthritis: mainly plasma cells
Chronic gastritis (cause is usually bacterial): mainly lymphocytes
Leishmaniasis (a protozoan infection - intracellular parasite): mainly macrophages
Giant cell type might be a help to diagnose (maybe specific)
List the effects of Chronic Inflammation and give some examples
Fibrosis (predominant pathological process); e.g. Gall bladder (chronic cholecystitis), chronic peptic ulcers, cirrhosis
Impaired Function; e.g. Chronic inflammatory bowel disease. Rarely, increased function can occur e.g. Mucus secretion, hyperthyroidism
Atrophy; e.g. Gastric mucosa, adrenal glands
Stimulation of immune response; macrophage-lymphocyte interactions
Describe Chronic Cholecystitis (Chronic inflammation of the gallbladder)
Gallstone disease is very common
Repeated obstruction of the gall bladder, obstructing bile flow with gallstones.
Repeated attacks of acute inflammation caused by gallstones cause damage of mucosa and leads to ischaemia and chronic inflammation –> fibrosis of gall bladder wall.
May be symptomatic or asymptomatic
Treated with the surgical removal of the gallbladder.
Describe Gastric Ulceration (Fibrosis)
Acute gastritis (alcohol, drugs)
Chronic gastritis (helicobacter pylori)
Ulceration occurs because of an imbalance of acid production and mucosal defence (in most cases mucosal defence is compromised by inflammation)
H. Pylori triple treatment: Proton Pump inhibitor e.g. Omeprazole 2 antibiotics: e.g. Clarithromycin/amoxicillin
Describe Inflammatory Bowel Disease (Impaired Function)
Chronic inflammation is always seen
Cobblestone ulcer Idiopathic (unknown cause) inflammatory disease affecting large and small bowel.
Patients present with a spectrum of symptoms including diarrhoea and rectal bleeding.
IBD is mainly used to describe two diseases: Ulcerative colitis and Crohn’s Disease
What are the differences between Ulcerative colitis and Crohn’s disease?
Ulcerative colitis: superficial, diarrhoea and bleeding can occur, treat with immunosuppression, surgical removal of the large bowel (colectomy)
Crohn’s disease is transmural (across the entire wall) so as well as diarrhoea and bleeding, structures (narrowing) and fistulae (abnormal connections between epithelium lined organs) also occur. Treat with lifestyle modifications, diet/hydration, immunosuppression.
Both result in severe impaired function of the bowel
Describe Liver Cirrhosis (fibrosis and impaired function)
Chronic inflammation with fibrosis; multiple nodules of normal tissue on the liver- liver is so extensively destroyed, there is disorganisation of architecture and attempted regeneration –> cirrhosis
Common causes: alcohol, infection with HBV or HCV, immunological, fatty liver disease, drugs and toxins
Liver cirrhosis is irreversible so treatment involves lifestyle changes to prevent further damage, and transplantation of a new liver if necessary.
Describe Atrophy of the Gastric Mucosa
Parietal cells are all destroyed leading to gastritis
Impaired function Inhibits acid secretion
Describe Rheumatoid Arthritis (Chronic Inflammation)
Autoimmune disease
Affects small joints, usually symmetrical
Localised and systemic immune responses.
Localised chronic inflammation leads to joint destruction.
Systemic immune response - can affect other organs and cause amyloidosis.
What is meant by Chronic Inflammation and Immune Response?
Chronic inflammation and immune responses overlap. Immune diseases cause pathology by chronic inflammation C
hronic inflammatory processes can stimulate immune responses
What is Granulomatous Inflammation?
Chronic inflammation with granulomas
What are Granulomas?
A granuloma is a mass of 2 types of cells: macrophages (modified, immobile - known as epithelioid histiocytes) and lymphocytes.
Granulomas form when the immune system walls off something that it is unable to eliminate for example bacteria, fungi and other foreign material.
Granulomas arise with persistent, low-grade antigenic stimulation and hypersensitivity.
