MoD session 3: chronic inflammation Flashcards
Define chronic inflammation
A chronic response to injury with associated fibrosis. Overlaps with host immunity, can last years
Characteristics of chronic inflammation?
Swelling
Pain
Fibrosis
In what situations could chronic inflammation arise?
- AI damage too severe to be resolved in a few days so takes over, e.g. in burn infections most common
- Begins without AI: in chronic infections (e.g. TB), autoimmune conditions (e.g. rheumatoid arthritis) or chronic low-level irritation (e.g. reaction to foreign material)
- Develops alongside AI, e.g. prolonged exposure to toxic agents
Role of macrophages in CI?
Monocytes in blood, enter tissue become macrophages. Main cell type in CI, can replicate (unlike neutrophils), take over from neutrophils
Functions:
- phagocytosis
- secretion of cytokines
- synthesise complement components and clotting factors
- present antigen to immune system
- stimulate angiogensis
- induce fibrosis
- induce fever, acute phase reaction and cachexia
How do macrophages/monocytes appear microscopically?
Similar to lymphocytes
Largest WBC
Kidney bean-shaped nucleus
Larger amount of cytoplasm compared to nucleus than lymphocytes
“Ground glass” appearance of granules. Not granulocytes
Role of lymphocytes in CI?
If present, the areas without lymphocytes usually indicate some antigenic material is there.
Functions:
-processing antigens
-B lymphocytes–>plasma cells that secrete antibodies
-secrete cytokines
-natural cytotoxic killer cells kill cells
-T lymphocytes control some cytotoxic functions
Microscopic appearance of lymphocytes?
Vary
Usually plasma cells have a clock-face nucleus: clumps of chromatin at periphery of nucleus, often an eccentric pink cytoplasm with lots of ER
Role of eosinophils in CI?
Normally present but concentration increases in CI
Function:
-attack large parasites, e.g. worms
-allergic reactions and immune response (IgE relation)
-in some tumours e.g. Hodgkin’s lymphoma
Microscopic appearance of eosinophils?
“Tomato wearing sunglasses”
Granules in cytoplasm stain bright red as acidophilic
Bilobed nucleus
Which inflammatory cells are granulocytes?
Neutrophils
Eosinophils
Basophils (very blue staining granules)
Role of fibroblasts and myofibroblasts in CI?
Fibroblasts respond to chemotactic stimuli and move to sites needed, where they produce collagen, elastin and GAGs.
Can differentiate into myofibroblasts which can contract to help healing
How are giant cells formed?
Macrophages can fuse with each other due to the presence of foreign bodies or bacteria which cause frustrated phagocytosis
Langhans type giant cell?
Horseshoe of nuclei around periphery, foamy cytoplasm
E.g. in TB
Foreign body type giant cell?
Nuclei arranged randomly
Often when hard to digest the foreign body: giant cell sticks to its surface
Touton’s type giant cell?
Nuclei in a ring towards centre, form in lesions with a high lipid concentration, and lesions will also contain foam cells (macrophages with foamy cytoplasm)
E.g. fat necrosis, xanthomas
What are some complications of CI?
- Fibrosis: fibroblasts stimulated by cytokines, excess collagen deposition, impairs organ function, if has myofibroblasts can contract and cause more problems (e.g. contraction of cirrhotic liver will impair portal blood flow, causing ascites)
- Impaired function: e.g. chronic inflammatory bowel disease
- Atrophy: loss of functional tissues. E.g. gastric mucosa loss causes increased lamina propria and lymphocytes
- Inappropriate immune response: can attack innoculous targets or the body’s normal tissues.
What is a granuloma?
A mass of macrophages that often form giant cells; the result of a particle that is poorly soluble or difficult to eliminate: a foreign body (e.g. a thorn) or “tough” bacteria (e.g. mycobacterium tuberculosis). Usually 0.5-1mm diameter. Also in leprosy and syphilis
Granuloma forms around the free or phagocytosed particle, or for unknown reason such as in Crohn’s disease
Foreign body granuloma?
Contains macrophages and foreign body giant cells, epithelioid cells, fibroblasts at the periphery
Few or no lymphocytes
Develop around non-antigenic material such as surgical thread
Hypersensitivity/immune granuloma?
Contain macrophages, giant cells (Langhans), more epithelioid cells than in FBG, some fibroblasts at periphery, lymphocytes
Develop around insoluble antigenic particles that cause cell-mediated immunity, can be harmful as occupy parenchymal space within organ
Can undergo central necrosis (e.g. in TB)
Sarcoidosis?
Non-caseous granulomas form throughout the body, especially in the lymph nodes and lungs
Often affects young adult women, idiopathic
Chronic cholecystitis?
Inflammation and ulceration of the gallbladder mucosa
Causes gall stones, fibrotic wall, repeat attacks of AI
If untreated CI will persist due to repeated obstruction by gallstones
Gastritis?
Acute-alcohol, drugs
Chronic-helicobacter pylori
Both can cause CI and ulceration due to imbalance of acid production and loss of mucosal defence
Inflammatory bowel disease?
Idiopathic, describes CD and UC.
- Crohn’s disease: transmural. Causes strictures, fistulae, and patchy full-thickness inflammation throughout the bowel. Can affect entire digestive system: from mouth to anus. Symptoms commonly include diarrhoea, abdo pain, fatigue, weight loss, blood in faeces
- Ulcerative colitis: superficial, only affects colon. Causes diarrhoea, abdo pain.
Cirrhosis?
Common causes: alcohol, infection (HBC, HCV), immunological diseases, fatty liver, drug abuse
Causes fibrosis and impaired function
Rheumatoid arthritis?
Autoimmune condition:
-localised effects- CI joint destruction
-systemic effects-can cause amyloidoses in organs
CI can stimulate immune response as well as CI causing pathology itself
Wegeners granulomatosis?
Unknown cause but causes granulomas
Now called Granulomatosis with Polyangiitis
Commonly affects kidneys and lungs
Tuberculosis-how bacteria cause disease and possible outcomes
Bacteria produce no toxins or lytic enzymes, but cause disease by persistence and induction of cell-mediated immunity. Tends to have granulomas with necrosis (caseous)
Outcomes:
1. Arrest, fibrosis, scarring
2. Erosion into bronchus: bronchopneumonia, TB in gastrointestinal tract
3. TB empyema (TB in pleura)
4. Erosion into blood stream –> miliary TB (TB in multiple organs)
Features of Crohn’s disease?
Discontinuous distribution
Affects any part of the GI system
Classically a “cobbelstone” appearance to bowel mucosa
Granulomas often present
Common-anal lesions and bowel fistulae (as deeper inflammation)
Features of ulcerative colitis?
Inflammation only in mucosa and submucosa
Commonly has crypt abscesses and distorted crypt architecture
Significant increased risk of colon cancer
Often most severe in distal colon
Colectomy often indicated
May develop complications in other organs e.g. bile ducts (Sclerosing cholangitis), liver (cirrhosis), spine (ankylosing spondylitis), skin ulcers, arthritis
Microscopic features of rheumatoid arthritis?
Pus in joints
Hypertrophy
Immune cells
Damaged articular cartilage
Define ulcer
A break in the skin or mucous membrane with loss of surface tissue, disintegration and necrosis of epithelial tissue
How does H. pylori cause gastritis and what are the microscopic features?
Colonises gastric pits in mucosa, damages epithelial cells by release of enzymes, imbalance of acid leads to loss of mucosal defence so inflammation results
Microscopically: loss of mucous membrane, lamina propria has lymphocytes, plasma cells and neutrophils
Describe what happens when a person inhales M. tuberculosis
- AI-vascular dilation, exudate leaks into tissues
- Neutrophils emigrate and begin phagocytosis
- CI after a few days: macrophages take over, release cytokines and complement components. Lymphocytes-plasma cells-for immune response
- Caseous necrosis
- Frustrated phagocytosis of macrophages–>giant cells (Langhans)
6, Persistent hypersensitivity leads to granuloma
Acid fast stain?
Stain for mycobacteria
As they are not sensitive to Gram staining
Mantoux test?
Synthetic tuberculin protein injected underneath skin, site checked 48-72 hours later, reaction indicates exposure to TB (active or latent disease, BCG vaccine or natural immunity)
Primary complex and Ghon focus and complex in reference to TB?
Primary complex-local lung area in which the bacteria reside
Ghon focus-primary lesion that is usually asymptomatic
Ghon complex-lesion in lung due to TB, calcified focus of infection and associated lymph node
Ranke complex?
An area seen in “healed” TB
Define miliary TB, Pott’s disease and scrofula
Miliary TB: numerous small granulomas in many organs showing a wide TB distribution
Pott’s disease: TB in the vertebrae
Scrofula: TB infection of lymph nodes causing neck lymphadenopathy
