Lecture 3.1: Chronic Inflammation Flashcards
What is Chronic Inflammation associated with?
Chronic response to injury usually with associated fibrosis
How Does Chronic Inflammation Arise? (3)
1) May ‘take over’ from acute inflammation (if
damage is too severe)
2) May arise de novo (from start, in autoimmune
conditions/chronic disease)
3) May develop along with acute inflammation
What does Chronic Inflammation look like?
Characterised by the microscopic appearances which are much more variable than acute inflammation
Most important characteristic is the type of cell present
Granulation Tissue
Typical Features of Chronic Inflammation Include…? (6)
• Macrophages
• Lymphocytes
• Plasma Cells
• Absence of Polymorphs
• Angiogenesis
• Proliferation of fibroblasts with collagen production leading to fibrosis
Macrophages and Chronic Inflammation
• Derived from blood monocytes
• Important in acute and chronic inflammation
• “Masterminds” of chronic inflammation
Functions of Macrophages (5)
• Phagocytosis and destruction of debris & bacteria
• Processing and presentation of antigen to immune system
• Synthesis of cytokines.- IL, TNF
• Control of other cells by releasing: EGF, FGF, PDGF
• Fibrosis and Angiogenesis
How are B-Lymphocytes able to create a large variety of antibodies?
B-lymphocytes “shuffle” the DNA encoding their immunoglobulins to create a repertoire of antibodies able to recognise a variety of antigens
When and how do B-Lymphocytes produce antibodies?
If a B-cell is presented to a foreign antigen that it “recognises”, it will proliferate (under the control of T-helper cells)
Then a a population of plasma cells that produce antibodies specific for that antigen are formed
Where do T-Lymphocytes originate and mature?
• T-lymphocytes originate in the bone marrow
• They mature in the thymus (or spleen in adults)
• Undergo rearrangement of their T-cell receptor
genes
T-Lymphocytes: T-Helper Cells/ CD4+
These cells induce proliferation and differentiation of T&B cells, and activate macrophages
T-Lymphocytes: T-Cytotoxic Cells/ CD8+
These cells induce apoptosis in cells that present foreign antigens in the correct MHC context by punching holes in the plasma membrane and injecting granzyme
What is the role of Natural Killer Cells?
• NK cells recognise “stressed” cells, such as in a
viral infection/ tumour cells
• Mechanism of killing similar to cytotoxic T-cells
• They do not have the requirement for MHC
presentation
Plasma Cells
• Differentiated antibody-producing B lymphocytes
• Usually implies considerable chronicity.
Eosinophils
• Allergic reactions, parasite infestations, some
tumours
Fibroblasts / Myofibroblasts
• Recruited by macrophages; make collagen
What are ‘Giant’ Cells?
Multinucleate cells made by fusion of macrophages
What do ‘Giant’ Cells do?
Frustrated phagocytosis
When does frustrated phagocytosis occur?
Occurs when phagocytic cells are exposed to an opsonised surface and spread as if trying to engulf it
Types of ‘Giant’ Cells?
• Langhans giant cell in tuberculosis
• Foreign Body Type
• Touton type giant cell
What cells are most common in Chronic Inflammation in Rheumatoid Arthritis?
Mainly plasma cells
What cells are most common in Chronic Inflammation in Chronic Gastritis?
Mainly Lymphocytes and Plasma Cells
What cells are most common in Chronic Inflammation in Leishmaniasis (protozoal infection)?
Mainly macrophages
Effects of Chronic Inflammation (4)
• Fibrosis (e.g. cirrhosis)
• Impaired Function (e.g, chronic IBS)
• Atrophy (e.g. automatically gastritis)
• Stimulation of (inappropriate) immune response
What is Fibrosis?
The development of fibrous connective tissue as a reparative response to injury or damage
What is Chronic Cholecystitis?
• It is swelling and irritation of the gallbladder that
continues over time
• Very common disease
• Can affect both sexes any age
• Attacks of acute cholecystitis cause the walls of the gallbladder to thicken
• Fibrosis
• The gallbladder begins to shrink/atrophy
Who is ‘typically’ affected by Chronic Cholecystitis?
“Typically” female, fair, fat, fertile, forty
What causes Chronic Cholecystitis?
Gall Stones
Chronic Cholecystitis Treatment
Elective laparoscopic cholecystectomy
What is Chronic Peptic Ulcer (Gastric Ulcer)?
• Ulceration due to imbalance of acid and pepsin attack and mucosal defence
• Fibrosis (narrowing or pyloric stenosis)
• Aka Peptic Ulcer Disease (PUD)
What parts of the body are affected in Peptic Ulcer Disease (PUD)?
• Antrum
• First part of duodenum
What causes Peptic Ulcer Disease (PUD)?
Helicobacter pylori (HP gastritis), hyperacidity
Causes of Peptic Ulcer Disease (PUD)
• NSAID Use
• Genetic
• Alcohol
• Cigarettes
• Steroids
Peptic Ulcer Disease (PUD) Treatments
• Antibiotic medications to kill H. pylori
• Proton Pump Inhibitors (medications that block acid production)
• Acid blockers (reduce amount of stomach acid released into digestive tract)
• Antacids (neutralise stomach acid)
• Cytoprotective Agents (protect the lining of your stomach and small intestine)
Liver Cirrhosis
• Cirrhosis is scarring of the liver caused by long-
term liver damage
• Inflammation with destruction of hepatocytes
• Fibrosis and Impaired Function
• The scar tissue prevents the liver working
properly
Causes of Liver Cirrhosis
• Alcohol
• Fatty Liver Disease
• Infection with HBV, HCV
• Immunological- PBC (Primary Biliary
Cholangitis)
Common Complication Liver Cirrhosis
• Portal Hypertension
• Liver Failure
• HCC (Hepatocellular Carcinoma)
What is Inflammatory Bowel Disease (IBD)?
• Idiopathic inflammatory disease affecting large
and small bowel
• Impaired Function
Symptoms of IBD (7)
• Diarrhoea
• Constipation
• Rectal Bleeding
• Cramping
• Abdominal Pain
• Bloating
• Gas
IBD: What is Crohn’s Disease? What parts are affected?
• Crohn’s disease is a long-term condition where
the gut becomes inflamed
• Small bowel and large bowel but 50% rectum
spared
IBD: Symptoms/ Characteristics of Crohn’s Disease
• Skip lesions
• Granulomas
• Transmural Inflammation
• Fibrosis (can cause shortening)
• Obstruction/Strictures
• Fistula Formation,
• Anal Lesions in 75%
IBD: What is Ulcerative Colitis (UC)? What parts are affected?
• IBD that causes inflammation and ulcers (sores)
in your digestive tract
• Large Bowel (90% rectum)
IBD: Symptoms/ Characteristics of Ulcerative Colitis [UC] (6)
• Continuous mucosal inflammation
• No granulomas
• Malignant change
• Urgency to defecate.
• Inability to defecate despite urgency.
• Weight Loss
Increased Function Thyrotoxicosis (Grave’s Disease)
• Autoimmune Disease
• Exophthalmos, thyrotoxic signs (palpitation, tremor etc.), enlarged thyroid
• Auto Ab - LATS (TSI – thyroid stimulating immunoglobulin)
• Ab acts on TSH surface receptor on thyroid epithelium and it mimics TSH
• Increased T4 and T3 and reduced TSH
Chronic Inflammation: Rheumatoid Arthritis
• Autoimmune disease- Rheumatoid factor.
• 3 female : 1 male
• Common, systemic disease, invariably affects
joints
• Localised chronic inflammation leads to joint
destruction - small joints
• Systemic immune response – rheumatoid
nodule, splenomegaly, amyloid
What is a Granuloma?
Organised collection of epithelioid cells (modified macrophages)
What is Granulomatous Inflammation?
Chronic Inflammation with Granulomas
Foreign Body Granulomas
Deal with particles which are poorly soluble (foreign bodies) or organisms which are difficult to eliminate (mycobacterium tuberculosis or mycobacterium leprae)
Immune Granulomas
Form when the immune system responds to a causative agent, eventually leading macrophage transformation to epithelioid cells, which may bind tightly together, forming the granuloma
Innate Immunity
Main Causes of Granulomatous Inflammation: Irritant Material
• Suture Material
Main Causes of Granulomatous Inflammation: Infections
• Tuberculosis
• Leprosy
• Other infections e.g. some fungi
Main Causes of Granulomatous Inflammation: Unknown Causes
• Sarcoidosis
• Granulomatosis with polyangiitis GPA (akla
Wegener’s granulomatosis)
• Crohn’s disease
What causes Tuberculosis?
• Caused by Mycobacteria
• Especially M. tuberculosis
• Difficult & Slow to Culture
How does M. tuberculosis cause Tuberculosis?
• Produces no toxins or lytic enzymes
• Causes disease by persistence and induction of
cell-mediated immunity
Outcomes of Granulomas in Tuberculosis (4)
1) Arrest (stop progression), fibrosis, scarring
2) Erosion into bronchus
– Tuberculous bronchopneumonia
– T.B. in gastro-intestinal tract
3) Tuberculous empyema
4) Erosion into blood stream
What are some other Granulomatous Infections?
• Leprosy
• Syphilis
• Chronic Fungal Infections
• ‘Cat-scratch’ Disease
Acid-Fast Test [for TB] (6 Steps)
1) Bacterial smear stained with carbol fuchsin
2) Stain solubilises lipoidal material present in the
Mycobacterial cell wall
3) By the application of heat, carbol fuchsin
further penetrates through lipoidal wall and
enters cytoplasm
4) Then after all cell appears red
5) Then the smear is decolourised with
decolourising agent (alcohol)
6) But the acid fast cells are resistant due to the
presence of large amount of lipoidal material in
their cell wall, thus remain red
Mantoux Test [aka the Tuberculin Test or PPD test]
1) Inject a 0.1 mL of liquid containing 5 TU
(tuberculin units) PPD (purified protein
derivative) into the top layers of skin of the
forearm
2) Doctors should read skin tests 48-72 hours
after the injection
3) The basis of the reading of the skin test is the
presence or absence and the amount of
induration (localised swelling)
For which age range is the Mantoux Test most preferred?
The skin test is the preferred test in children under 5 years of age
Important things to remember about the Mantoux Test (2)
A negative test does not always mean that a person is free of tuberculosis
A person who received a BCG vaccine (administered in some countries but not the U.S.) against tuberculosis may also have a positive skin reaction to the TB test
Categories of the Mantoux Test: Category 1
5-9mm positive
Categories of the Mantoux Test: Category 2
10-14mm positive
Categories of the Mantoux Test: Category 3
> 15mm positive
Primary Complex/Ghon Focus/Ghon Complex [TB]
A primary (Ghon) complex is formed, consisting of a granuloma, typically in the middle or lower zones of the lung (primary or Ghon focus)
It is a Primary Lesion
Can be seen on a X-Ray/ CT Scan
What is often associated with a Primary Complex [TB]
• Activates the innate immune system and
induces changes in the pattern of histone
modifications of specific genes in innate immune
cells
• Activates the innate immune system and
induces changes in the pattern of histone
modifications of specific genes in innate immune
cells
• Paratracheal Lymphadenopathy (paratracheal
lymph nodes become swollen)
• Some overlying Pleural Reaction (i.e. unusual
amount of fluid around the lung)
TB Blood Test
• Aka the Interferon Gamma Release Assay or
IGRA
• Finds out if you have TB germs in your body
• The TB blood test can be done instead of a TB
skin test (Mantoux)
BCG Vaccination [TB]
• Bacillus Calmette–Guérin Vaccine
• Vaccine primarily used against tuberculosis
• Activates the innate immune system
• Induces changes in the pattern of histone
modifications of specific genes in innate immune
cells
What is a Ranke Complex?
It consists of two components:
• A Ghon lesion that has undergone calcification
• An ipsilateral calcified mediastinal node
Seen in ‘healed’ primary pulmonary tuberculosis and is a later manifestation of the Ghon complex
What is Miliary Tuberculosis?
• A potentially life-threatening type of tuberculosis
• Occurs when a large number of TB bacteria
travel through the bloodstream
• Thus the TB can spread throughout the body
and grow in many organs
What is Single Organ Tuberculosis?
When the TB infection is contained to one organ and not spread throughout the body via the blood stream
E.g. Pulmonary TB, TB Meningitis
What is Potts Disease
• Aka tuberculosis spondylitis
• A rare infectious disease of the spine
• Typically caused by an extra-spinal infection
• Potts Disease is a combination of osteomyelitis
and arthritis which involves multiple vertebrae
What is Osteomyelitis?
• Inflammation or swelling that occurs in the bone
due to infection
• Infection somewhere else in the body that has
spread to the bone
• Or it can start in the bone, often as a result of an
injury
What is Scrofula?
• TB of the throat
• Aka cervical tuberculous lymphadenitis
