How Does the Cell Respond To Injury Flashcards
5 Cardinal Signs of Inflammation
Calor (heat)
Dolor (pain)
Rubor (redness)
Tumour (swelling)
Functio laesa (loss of function)
What is inflammation?
A complex biological response of body tissues to harmful stimuli (e.g. pathogens, cell damage, irritants, …) which involves immune cells, blood vessels and molecular mediators.
Function of inflammation
It’s function is to eliminate the initial cause of injury, clear out damaged tissues (by the insult and the inflammatory response) and initiate tissue repair.
Compare Acute and Chronic Inflammation
Acute: Short duration but usually severe
- Acutus = sharp (latin)
- Classically neutrophil granulocytes/polymorphs
Chronic: Long duration, varies from mild to severe
- Chronos = time (greek)
- Classically other white blood cells (lymphocytes, histiocytes)
What causes inflammation?
- Infections (bacterial, fungal, viral, parasitic)
- Tissue necrosis (ischaemia, trauma, physical or chemical injury)
- Foreign bodies (dirt, sutures, splinters, …)
- Immune reactions (hypersensitivity/allergy, autoimmune reactions)
The five Rs of the inflammatory process:
Recognition (of the injurous agent)
Recruitment (of leukocytes)
Removal (of the injurous agent)
Regulation (of the inflammatory response)
Resolution (or repair)
Characteristics of Acute inflammation
Rapid onset in minutes
Short duration of hours to days
Exudation of plasma fluid and proteins
Emigration of leukocytes, predominantly neutrophil polymorphs
UC Acute meningitis
Myocardial infarction
UC Myocardial infarction
Acute Bronchopneumonia
Vascular dilatation (vasodilatation)
Increased vascular permeability and extravasation of fluid
Emigration of leukocytes, primarily neutrophil polymorphs
to maximise movement of plasma proteins and leukocytes out of the circulation and into the site of the insult
Explain vascular microcirculation
Vascular wall is semi-permeable which acts as a filter.
high arterial hydrostatic pressure leads to extravasation of fluid. the large molecules cannot pass through and remain in the vessels creating strong osmotic pressure.
this high osmotic pressure is countered by the low hydrostatic pressure in the veins.
Vasodilatation effects
vascular smooth muscle relaxes rapidly mediated by histamine and NO
increased volume of blood into the region but also a slower flow which accumulates pressure and the stasis of blood.
as a result it causes swelling, redness and heat.
Vascular permeability in swelling
- Histamine and nitric oxide also activate endothelial cells and cause them to contract
- Often, there is also damage to the endothelium by leukocytes or the insulting stimulus (cause)
- The venule walls becomes more permeable to large proteins which leak into the tissues
- The osmotic pressure in the tissue increases and water follows
- More fluid leaves the blood vessels than returns to them
What is exudate and transudate and what is its clinical significance?
This escape of protein rich fluid out of the vascular compartment is called exudation and it results in oedema (tumour)
The escape of protein poor fluid (just by increased hydrostatic pressure) is called transudation and it also results in oedema
The lymphatic system is also involved in regulating the amount of extravascular fluids by draining tissues through lymph nodes and back into the venous system (thoracic duct)
what are the three steps a neutrophil takes to leave the blood vessel?
- Margination and rolling along the vessel wall
Leukocytes are displaced peripherally by a central axial column of erythrocytes. In stasis, more leukocytes assume a peripheral position next to the endothelium (margination). Transient connections occur between the leukocytes and the endothelial cells (rolling). Proteins involved: Selectins which may be upregulated by Tumour necrosis factor TNF and Interleukin 1 IL-1.
- Adhesion to the activated endothelium
Mediated by integrins (VCAM-1, ICAM-1) which are also upregulated by TNF and IL-1.
- Emigration through the vessel wall into the surrounding tissues
Mediated by CD31/PECAM-1
How is complement involved in extravasation?
complement is involved in the process of margination (extravasation in this context) as well as the immune function it already has.
how does a leukocyte move around?
Contractile cytoplasmic microtubules and changes in cyto- plasmic fluidity result in amoeboid movement
Movement occurs towards high concentrations of chemical mediators = chemotaxis
Explain the process of phagocytosis of a bacteria
opsonised by Ab or by C3b.
this is recognised and internalised by macrophage
now the pathogen is in the phagosome
phagosome fuses with lysosome to become phagolysosome where the free radicals are generated.
these as well as the lysosomal enzymes kill the microbe
List the mediators in Acute Inflammation
Vasodilatation - Histamine, NO, prostaglandins
Increased vascular permeability - Histamine, Complement C3a and C5a, bradykinin, leukotrienes
Chemotaxis and leukocyte recruitment - TNF, IL-1, Complement C3a and C5a
Fever - TNF, IL-1, prostaglandins
Pain - Prostaglandins, bradykinin
Tissue and cell damage - Lysosomal enzymes from leukocytes, ROS, NO
Beneficial and harmful effects of inflammation
Beneficial
- Degradation of bacteria and toxins | Fever (pyrexia) via hypothalamus thermoregulation
- Stimulation of immune response | Haematological changes (leukocytosis, anaemia)
- Facilitation of transport of drugs
- Fibrin formation
- Delivery of nutrients and oxygen
- Initiating healing
Harmful
- Digestion of normal tissues | Constitutional symptoms (malaise, nausea, anorexia)
- Swelling | Weight loss
- Inappropriate inflammatory response | Fever
Effects of acute inflammation
Serous inflammation of cell poor transudation/effusion
Fibrinous inflammation
Purulent inflammation and abscess formation
Ulcer
What are the different outcomes of acute inflammation?
Features of chronic inflammation
If acute inflammation fails to clear the aetiologic agent it may progress to a chronic phase
May also be insidious in onset (primary)
Lasts longer
Involves leukocytes other than neutrophil polymorphs: Lymphocytes
- Plasma cells
- Eosinophil
- Macrophages / histiocytes
What are causes of chronic inflammation?
Persistent infections (e.g. some viral or fungal infections)
Inability to heal (e.g. chronic peptic ulcer of the stomach)
Immune mediated inflammatory diseases (e.g. Crohn’s disease)
Prolonged exposure to toxic agents (e.g. silicosis of the lung)
What cells are involved in chronic inflammation?
- Lymphocytes
T-lymphocytes (CD3 positive)
B-lymphocytes (CD20 positive)
- Plasma cells
- Macrophages
- Eosinophil polymorphs
- Fibroblasts
- Few neutrophil polymorphs
- Little fluid exudation
Granulomatous inflammation features
- A distinctive pattern of chronic inflammation
- Characteristic of some infections (e.g. mycobacterial infection)
- Characteristic of some non-infectious conditions (e.g. sarcoidosis, foreign body granulomas)
- May be caused by drugs
- May be idiopathic (aetiology unkown)
- A granuloma is an area of activated epithelioid (epithelium-like) macrophages they may form giant cells*
- It may be surrounded by lymphocytes or not (naked granulomas seen in sarcoidosis)*
- It may show central necrosis (= caseating granuloma) or not (= non-caseating gran.)*
