Chronic inflammation Flashcards
Chronic Inflammation Comparison with Acute Inflammation
Prolonged duration (weeks/months – years)
- Inflammatory cells mainly mononuclear: – Lymphocytes, plasma cells, macrophages
- Tissue destruction
- Healing (angiogenesis and fibrosis)
Chronic Inflammation - Causes
1. Progression from acute inflammation
- Repeated episodes of acute inflammation (e.g. chronic cholecystitis, peptic ulcer)
- Persistence of injurious agent with failure of resolution – Formation of abscess with lack of drainage ( e.g. osteomyelitis, empyema )
2. Primary chronic inflammation
• Micro-organisms associated with intracellular infection
– Viral agents (e.g. hepatitis B and C)
– Bacteria resistant to phagocytosis e.g, Mycobacterium TB, leprosy
• Foreign body reactions
– Exogenous materials eg silica, asbestos fibres, suture materials.
– Endogenous substances e.g. lipid material in atherosclerosis
• Autoimmune diseases
– Organ specific e.g Hashimoto’s thyroiditis,
– Non-organ specific eg rheumatoid arthritis.
• Unknown aetiology
– Chronic inflammatory bowel disease , sarcoidosis
Chronic Inflammation Progression from Acute Inflammation (Repeated Episodes)
Examples?
Examples:
- Chronic cholecystitis
- Chronic peptic ulceration
Both are associated with damage to deeper layers of the wall
• Damaged smooth muscle cannot heal by regeneration • Healing by repair results in fibrous scarring
What does this person have?
It may be asymptomatic or present with ongoing RUQ or epigastric pain with associated nausea and vomiting. it is ongoing
what complications may occur?
Chronic cholecystitis with gallstones
- Gallstones predispose to acute inflammation of the gallbladder
- Tendency to develop repeated episodes (may be associated with mild/no clinical symptoms)
- Fibrous scarring of the wall results in loss of normal gall bladder function
Complication:
Inflammation of the gallbladder (typically if recurrent or silent) can cause a fistula to form between the gallbladder wall and the duodenum, allowing gallstones to pass into the small bowel. As a consequence, bowel obstruction can occur:
Bouveret’s Syndrome – stone impacts to cause duodenal obstruction
Gallstone Ileus*– stone impacts to cause an obstruction at the terminal ileum (the narrowest part of the adult bowel)
Other complications include obstructive jaundice, ascending cholangitis, and acute pancreatitis.
*The term ileus is misleading, as it is actually a bowel obstructio
This can happen to someone who takes too many NSAIDs or H-pylori infection(unclean water or food)?
chronic peptic ulcer
label what is missing
What are the consequence of chronic cholecystitis?
What are the consequences of chronic peptic ulcer
Gall bladder (chronic cholecystitis)
- Non-contractile
- Fatty food intolerance
- Right upper quadrant pain
Stomach (chronic peptic ulcer)
• Fibrous scarring of muscle still present after mucosa has healed
may be visible at endoscopy
• Fibrous scarring contributes to important complications
Pyloric stenosis
Gastric haemorrhage
What are the roles of CD4, CD8 and B lymphocytes?
T lymphocytes (cell-mediated immune responses)
• CD4+ T cells (“helper” T cells)
– Secrete cytokines in response to antigen presentation
- Activation of effector cells (CD8+ cells, macrophages)
- Co-operate with B cells in humoral response
- CD8+ T cells (“cytotoxic “ T cells)
– Involved as effector cells
- Direct cell killing by apoptosis (receptor specific)
- Production of cytotoxic cytokines (non-specific)
B lymphocytes (humoral immune responses)
- Respond to stimulation by differentiating into plasma cells
- Plasma cells secrete immunoglobulin
What type of cell is this?
what is it’s role?
What type of cell is this?
What is it’s role?
Plasma cells
Produce antibodies -> humoural response
a patient that is asymptomatic presents with elevated alanine aminotransferase level (ALT). They have chronic hepatitis B. What has not shown to become the problem. anti smooth muscle is positive
AUTOIMMUNE HEPATITIS Portal/periportal lymphocytes and plasma cells
AIH subtypes depend on autoantibody serology:
Type 1: positive for antinuclear antibody (ANA) or anti smooth muscle antibody (SMA); 10% have other autoimmune disorders
Type 2: positive for anti liver kidney microsomal (LKM) antibody or anti liver cytosol type 1 (LC1) antibody positive; often presents with acute or fulminant hepatitis; 17% have other autoimmune disorders
A person gets a needle stick injury but does not have symptoms. 20 years later life gets hard and they start drinking more alcohol and started noticing themselves getting jaundiced. Going to the doctor the person gets tested and find they are positive for HCV RNA.
what do they have?
CHRONIC HEPATITIS C INFECTION
Chronic Inflammatory Cells are what ?
Macrophages
- Derived from circulating monocytes and are transformed in the tissues
- Normal resident population in many tissues ( e.g Kupffer cells – liver, alveolar macrophages – lung). Involved with: − phagocytosis (e.g. inhaled particles, senescent red blood cells) − immune surveillance (e.g. antigen processing and presentation)
- May become activated by cytokines and other inflammatory mediators
- Activated macrophages increase in size, mobility and phagocytic activity and produce a range of substances promoting tissue injury, angiogenesis and fibrosis.
- Often seen in the late stages of acute inflammation, where they may be involved in removing dead tissue and initiating repair processes
What are the biological effects of each or in what situations are they released?
what is granuloma?
A granuloma is an aggregate of macrophages (INF-gamma)
- May have an epithelioid morphology (resemble epithelial cells) - large vesicular nuclei, eosinophilic cytoplasm.
- Little phagocytic activity
- May fuse to form giant cells – eg Langhans’, foreign body and Touton(Touton giant cells are a type of multinucleated giant cell seen in lesions with high lipid content such as fat necrosis, xanthoma, and xanthelasma and xanthogranulomas.They are also found in dermatofibroma.[1])
this is a type of cell seen in chronic inflammation?
Foreign body giant cell
Rectal biopsy - 35 year old man with abdominal pain and diarrhoea
You see this what do you suspect this person has?
Crohn’s disease
- This is a non -caseating granuloma
Tuberculosis - Pathological Features
Primary infection in lung
- Subpleural location (Ghon focus)
- Centre undergoes caseation necrosis (TNF-mediated)
- Bacilli carried to regional lymph nodes (Ghon complex)
This person has just come back from India and has been coughing out blood and has rigors. A histology specimen shows this. what is it?
TB granuloma
What sort of necrosis is seen with TB patients?
Caseation necrosis and Langhans’ giant cell
What is this been shown? This person has a remanant of TB
Old calcified Ghon focus in elderly male
How does miliary TB occur?
What does the picture shows?
- Full thickness (transmural) inflammation of bowel wall
- Damage to smooth muscle – heals by fibrosis
- Stenosis may lead to bowel obstruction
What does this person have?
- chronic inflammation with ulceration
- mucosa heals by regeneration
- repeated cycles of ulceration/regeneration induce pre-malignant changes (dysplasia)
- may progress to invasive carcinoma (20-25% risk after 30 years)
What are the differences between UC and Crohns
