Inflammation Flashcards
List 6 causes of acute inflammation.
- Micro-organisms
- Mechanical
- Chemical
- Physical
- Dead tissue
- Hypersensitivity
What are the benefits of acute inflammation?
- Rapid response
- Cardinal signs and loss of function
- resolution and return to normal
What is the function of neutrophils?
Destroy organisms and denature antigens for macrophages.
What is the function of neutrophils?
Destroy organisms and denature antigens for macrophages.
What is the function of plasma proteins in acute inflammation?
Localise process.
Describe the three main steps in the sequence of microvascular change.
- Change in vessel radius and blood flow
- Increase permeability of vessel wall.
- Movement of neutrophils from the vessel to the extracellular compartment.
What changes occur with the vessel radius and blood flow during inflammation>
- Transient arteriolar constriction and local arteriolar dilatation.
- relaxation of smooth muscle
- increase blood flow to local tissues
What causes endothelial leak?
Released during the localised vascular response when the permeability of the cell wall is increased.
What are the effects of endothelial leak?
Net movement of plasma from capillaries to extravascular space (exhudation) causes OEDEMA, PAIN and REDUCES FUNCTION.
Describe the main three steps regarding the movement of neutrophils.
- Margination (move to endothelial aspects of lumen)
- Pavementing (neutrophils adhere to endothelial aspects)
- Emigration (neutrophils squeeze between endothelial cells to extravascular tissues)
What is exudate composed of?
Protein, plasma, immunoglobulins and fibrinogen.
What is the result on blood after fluid loss?
Increased viscosity and slows rate of flow.
What are the local effects of acute inflammation?
Redness and heat, swelling, door (pain) and loss of function.
List the immediate systemic effects of acute inflammation.
Pyrexia, feel unwell (malaise, anorexia, nausea, abdominal pain and vomiting in children) and neutrophilic (increased WBC)
List the longer term systemic side effects of acute inflammation.
Weight loss, lymphadenopathy, anaemia.
Describe complications of acute inflammation.
Dissemination i.e septic shock.
Describe dissemination.
Inflammation spread to bloodstream (bacteraemia in blood, toxaemia with toxic products in blood or septicaemia with growth in blood). Shock prevents perfusion of tissues, causing vasodilatation.
What are the signs of shock.
Increase HR, decrease BP, increase temperature, rash
What is the cause of dissemination.
Chemical release mediators from cells to plasma
What chemical mediators are released by bacterial endotoxins?
IL-1
What is the result of compensation failure?
Septic shock (unable to perfuse tissues)
Summarise the cell-surface mediators of acute inflammation?
ICAM-1 and P-selectin
Summarise the mediators released from cells.
Histamine, 5-hydroxytryptamine, prostaglandins, leukotrienes, omega-3 polyunsaturated fats, platelet-activating factor, cytokines and chemokine, NO, oxygen free radicals.
Name three process of acute inflammation that can be altered to the detriment of patients.
Suppuration (pus formation), Organisation (granulation tissue - fibrous and scar), Dissemination (spread to bloodstream)
List the cell types involved in chronic inflammation.
Lymphocytes, plasma cells, macrophages, fibroblasts, NK cells, T cells.
What are the major causes of chronic inflammation?§
- From acute inflammation
2. Arising as a primary lesion
Describe the effects of chronic inflammation.
Long term, tissue or organ damage, no specific “for bit”, malaise and weight loss, loss of function.
Describe organisation.
Granulation tissue, healing and repair, fibrosis and scar.
What is the function of fibroblasts?
Produce collagens to form matrix and replace exudate to form a scar.
Describe adverse effects of tissue scarring.
Structural and functional deterioration.
E.g peptic ulcer, cholecystitis, osteomyelitis, pain or numbness, hair follicles don’t grow back, loss of muscle power (after MI).
List factors involved in promoting healing and repair.
- cleanliness
- apposition of edges
- sound nutrition
- metabolic stability
- normal inflammatory and coagulation mechanisms.
Describe the role of angiogenesis in healing and repair.
New vessels form (capillary beds), VEGF released by hypoxic cells stimulates proliferation, enzyme secretion aids progression, enabled blood supply to enter damaged tissue.
Describe instances where angiogenesis occur.
- In thrombosis to reinstate flow
- In malignant tumours as tumour grows
- In atherosclerosis for fibrosis and scarring
Name factors that impair healing.
Dirty, gaping wound, large haematome, poorly nourished, abnormal CHO metabolism, diabetes, corticosteroid therapy, inhibition of angiogenesis.
What is the role of histamine?
Relaxes vascular smooth muscle in acute inflammation.
what does hypoxia impede?
Wound healing.
What cells are a major component of the acute inflammatory response?
Neutrophil polymorphs.
What hypersensitivity reaction requires immune complex formation?
Type III.
What hypersensitivity reaction requires local IgG or IgM production?
Type II.
What hypersensitivity reaction is the basis of allergy and requires inappropriate IgE synthesis?
Type I
What hypersensitivity reaction is not antibody mediated?
Type IV
What hypersensitivity reaction is mediated by the inappropriate action of Th1 cells and cytokine products?
Type IV
What cells are responsible for the inappropriate synthesis of IgE in type I hypersensitivity reactions?
Mast cells.
What hypersensitivity reaction causes complement activation?
Type II
What hypersensitivity reaction is caused by the abnormal deposition of fomed Ag-Ab complexes?
Type III
What hypersensitivity reaction results in Antibody dependent cellular cytotoxicity (ADCC)?
Type II
Give two examples of type III hypersensitivity reactions.
Serum sickness (systemic) or Arthus (local)
What reaction involves the binding of hapten and a carrier host protein to produce antigenic stimuli?
Type IV.
what hypersensitivity reaction has a 48-72 hour delay?
Type IV.
Describe the pathophysiology of early phase allergic reactions.
Occurs in minutes and involves preformed mast cell mediators.
Describe the pathophysiology of late phase allergic reactions.
Occurs in hours and involves newly synthesised mediators e.g Th2 cytokines and eosinophil mediators.
Define atopy.
A genetic tendency to produce IgE to normally innocuous, common environmental allergens.
Define allergy.
Clinical expression of atopic tendency with inappropriate production of IgE.
What is used in type IV hypersensitivity to direct immune response?
Haptens
What is the purpose of carrier proteins in type IV hypersensitivity reactions?
Produce sufficient antigenic bulk.
Define the two mechanisms of immunological tolerance.
- Central tolerance (deletion of auto reactive b and T cells during maturation)
- Peripheral tolerance ( inhibit activity of autoreactive cells which escape central tolerance processes)
What results in the breakdown of tolerance?
Autoimmune disease.
Define autoimmune disease.
Large group of clinical disorders which are characterised by tissue or organ damage mediated through aberrant immunological mechanisms which are directed against autoantigens.
What 5 factors are involved in the aetiology of autoimmune disease.
- Genetic factors (e.g inheritance of particular HLA genes)
- Immune regulatory factors
- Hormonal factors
- Environmental factors
- ‘Other’ factors
What are the pathogenetic mechanisms involved in autoimmune disease?
- Genetic Background & environmental factors (e.g infection)
- Effector mechanisms = cellular or antibody mediated, autoAb activation of complement-mediated inflammation, immune complex formation, recruitment of innate immune components.
Can organ specific and non-organ specific autoimmune diseases overlap in one patient?
No. Overlap of different ends rarely found however, overlap of disorders found at same side of spectrum can be found e.g thyroid and gastric organ specific disorders in one patient.
What imaging techniques are used in inflammatory disorders?
PET, CT, SPECT
Outline the scientific basis of a PET scan.
Use nucleotides that decay by positron emission (proton to neutron + positron)
What is the main isotope used for PET?
18F with a half-life of 110mins.
State the properties of an ideal isotope for labelling.
- Half-life similar to length of examination.
- Radionuclides should be readily available at hospital.
- Easily bound to pharmaceutical component.
- Radiopharmaceutical should be easy to repair.
What type of radiation is used in PET scanning.
Gamma emitter.
Explain detection of gamma radiation and production if digital image by digital camera, PET, SPECT.
Occurs due to radioactive decay of unstable isotopes.
Put these steps in order. Light electromagnetic energy, electrical energy, nuclear energy and gamma electromagnetic energy.
- Nuclear Energy
- Gamma electromagnetic energy
- Light electromagnetic energy
- Electrical energy.
What is the function of the gamma camera?
Rotates around the patient for 25 minutes and detects gamma radiation being admitted.
What is SPECT?
Single Photon Emission Computed Tomography (Ct version of nuclear medicine).
List typical effective doses.
4mSV = bone scan, 10mSV = CT abdomen/ pelvis), 18mSV = myocardial perfusion
What is the UK average for natural background radiation.
2.2mSV/year.
Explain the role of diagnostic imaging in the diagnosis, monitoring and treatment of inflammatory/infectious conditions.
- Need to know normal distribution of tracers to determine abnormal distribution.
- Identifies tissue type
- Show anatomical changes therefore, late/chronic stages.
- Detect biological and biochemical changes in earliest phase of disease (increase specificity and diagnostic accuracy)
What does a high neutrophil count indicate?
Acute inflammation.
What does a high amylase suggest?
Pancreatitis (caused by alcohol, gall stones or idiopathic).
Is acute inflammation specific?
No.
What hypersensitivity reaction is interleukin-4 associated with?
Type II
What are type IV hypersensitivity reactions also known as?
Delayed-type hypersensitivity.
What hypersensitivity reaction is associated with the production of gamma-interferon?
Type IV (delayed type)
What does rubber mean?
Redness
What does dollar mean?
Pain