Acute Inflammation Flashcards
What are the 2 differences between acute and chronic inflammation?
Time course and cell types involved
Why is inflammation both good and bad?
Beneficial effects - destruction of invading microorganisms
Walling off an abscess cavity thus preventing spread of infection
Destructive - abscess in brain acts as a SOL compressing vital surrounding structures
Chronic inflammation causing fibrosis distorting and permanently altering tissue function
What is the basic definition of acute inflammation?
Response of a living, vascularised tissue to injury, initiated to limit tissue damage (protective response)
What are the defining characteristics of an acute inflammatory response?
Innate, protecting us right from birth
Immediate and stereotyped I.e. Same every time regardless of cause
Short duration - lasts usually for minutes or hours, couple of days max.
What is acute inflammation a combination of?
Vascular and cellular reactions involving accumulation of fluid exudate and neutrophils in tissues
What are 5 main causes of acute inflammation?
What is important to keep in mind?
Microbial infection e.g. Pyogenic bacteria
Hypersensitivity reactions e.g. Parasites,
Physical agents e.g. Trauma, ionising radiation, heat and cold
Chemical agents e.g. Corrosives, acids, bacterial toxins etc.
Tissue necrosis e.g. Ischaemic infarction
Reaction to any of these will be the same so we cannot tell cause from response
How can microbial infections cause acute inflammation?
Viruses lead to death of individual cells by intracellular multiplication
Bacteria can release specific exotoxins that initiate inflammation
Some organisms cause immunologically mediated inflammation via hypersensitivity
How can tissue necrosis be a cause of acute inflammation?
Death of tissues from lack of oxygen or nutrients is a potent inflammatory stimulus.
Edge of a recent infarct often shows an acute inflammatory response presumably due to peptides released from the dead tissue
What are the 3 key changes caused by acute inflammation in tissues?
Changes in blood flow
Exudation of fluid into tissues
Infiltration of inflammatory cells particularly neutrophil polymorphs
Name the 5 keg macroscopic features of acute inflammation and briefly explain them
Rubor - dilation of small blood vessels within the damaged area
Tumour - oedema due to accumulation of fluid in the extravascular space as part of the fluid exudate, and from physical mass of inflammatory cells migrating into the area. As inflammation continues, formation of new connective tissue actually contributes to swelling
Calor - vascular dilation increasing blood flow to the area
Dolor - partly from stretching and distortion of tissues due to the oedema and pus under pressure in an abscess cavity. Some chemical mediators such as bradykinin and prostaglandins are also known to induce pain
Loss of function - movement consciously and reflexly inhibited by pain while swelling physically immobilises tissues
What is meant by serous inflammation?
Abundant protein rich fluid exudate with a relatively low cellular content
Can occur in serous cavities and also in synovial joints
Vascular dilation may be visible macroscopically (like in blood shot eyes)
What is meant by catarrhal inflammation?
When mucus hyper secretion accompanies acute inflammation of a mucous membrane
The common cold is an example
What is meant by fibrinous inflammation?
When inflammatory exudate contains lots of fibrinogen, which polymerises into a thick fibrin coating
Seen in acute pericarditis giving parietal and visceral pericardium a “bread and butter” appearance
What is meant by haemorrhagic inflammation?
Indication of severe vascular injury or depletion of coagulation factors
Acute pancreatitis - due to proteolytic destruction of vascular walls
Septicaemia - disseminated intravascular coagulation
What is meant by suppurative inflammation?
Refers to production of pus - consists of dying and degenerate neutrophils, infective organisms and liquefied tissues.
Pus may be walled off by granulation tissue to produce an abscess
If a hollow viscus fills with pus this is called an EMPYEMA (common in the gall bladder and appendix)
What is meant by membranous inflammation?
Epithelium coated with fibrin, desquamated epithelial cells and inflammatory cells
Seen in pharyngitis and laryngitis
What is meant by pseudo membranous inflammation?
Superficial mucosal ulceration with an overlying slough of disrupted mucosa, fibrin, mucus and inflammatory cells
Seen in pseudo membranous colitis due to clostridium difficile colonising bowel
Gangrenous inflammation?
High tissue pressure due to oedema may lead to vascular occlusion and thrombosis may result in septic necrosis of organ
Necrosis + bacterial putrefaction is gangrene
Gangrenous appendicitis
What are the 5 microscopic features of acute inflammation?
1) vasodilation of small blood vessels adjacent to the site
2) gaps form in the endothelium as cells swell and retract
3) vessels become leaky and water, salts and small plasma proteins can leak out to form an exudate
4) margination and emigration - circulating neutrophils adhere to swollen endothelial cells and then migrate through the vessel BM
5) macrophages and lymphocytes migrate just as the neutrophils did
What happens in the early stages of inflammation?
Oedema fluid, fibrin and neutrophils accumulate in extracellular spaces of the damaged tissue
Presence of cellular component is essential for a histological diagnosis of acute inflammation
What is the basic definition of general inflammation?
The sum of a host’s defences to infectious or noxious stimuli
What are the 5 possible mechanisms by which vascular leakage can occur?
Endothelial contraction - gaps forming between cells of wall caused by histamine and leukotrienes
Cytoskeleton reorganisation due to cytokines IL-1 and TNF
Direct injury
Leukocyte-dependent injury - fee radicals and enzymes
Increased transcytosis triggered by VEGF
What are the key cellular players in acute inflammation?
Neutrophil polymorphs (granulocytes) Easily identified by multi-lobed nuclei
What are the 4 steps needed for successful infiltration of neutrophils into the damaged tissue?
Stasis of blood causes cells to line up at edge of endothelium rather than staying in axial stream in central vessel lumen (MARGINATION)
Neutrophils then roll along the endothelium, sticking to it intermittently (ROLLING)
Cells stick more avidly to vessel walls via adhesion molecules (ADHESION)
Neutrophils emigrate through leaky walls
What is leukocyte surface adhesion increased by?
Complement component C5a
Leukotriene B4
TNF
What is movement of leukocytes like?
Movement of RBCs?
Active ameboid movement through walls of venues and small veins (not capillaries)
Insert Pseudopodia between endothelial cells
For RBCs the process is passive and depends on hydrostatic pressure - this is DIAPEDESIS
Overall, what do all chemical mediators involved cause?
Vasodilation Emigration of neutrophils Chemotaxis Increased vascular permeability Itching and pain
What are 3 important proteases to mention?
1) Kinins - bradykinin which mediates pain
2) complement system C3a and C5a. This is a cascade of enzymes activated in situations such as tissue necrosis when enzymes that activate complement are released from dying cells. C5a is a chemo tactic for neutrophils, increases vascular permeability and releases histamine from mast cells.
3) coagulation/fibrinolytic system
What are the prostaglandins and leukotrienes?
Metabolites of arachidonic acid
Some prostaglandins increase vascular permeability and some potentials platelet aggregation
Leukotrienes have vasoactive properties
What is the main function of cytokines and chemokines?
Chemo taxis - chemokines bind to extracellular matrix components and set up a gradient of chemo tactic molecules fixed to ECM
Summarise the 3 phases and the mediators responsible for them
Vasodilation - histamine mainly, prostaglandins, complement
Vascular permeability - histamine mainly, prostaglandins and Kinins
Leukocyte emigration - leukotrienes, IL-8 and C5a
How does Exudation of fluid combat injury?
Delivers plasma proteins to site of injury e.g. Immunoglobulins, inflammatory mediators and fibrinogen
Fluid also dilutes toxins
Increased lymphatic drainage - delivers MOs to phagocytes and antigens to the adaptive immune system
How can cellular infiltration and vasodilation combat injury?
Cells remove pathogenic organisms and necrotic debris by phagocytosis
Vasodilation increases cell delivery to the area and increases temperature thus reducing movement and possibility of further damage
What are the 4 steps involved in neutrophil movement by chemotaxis?
Chemotaxins such as C5a and LTB4 released from site of injury to which neutrophils have receptors
Receptor-ligand binding onto neutrophil
Rearrangement of cytoskeleton
Production of Pseudopodia which allow amoebic movement by contracting
What are the 2 types of killing mechanisms used by neutrophils?
Oxygen dependent - superoxide and hydrogen peroxide
Oxygen independent - in ischaemic tissue enzymes such as lysozyme and hydrolases
What are 4 local effects of acute inflammation?
Swelling - can cause blockage of tubes
Exudate - compression e.g. Cardiac tamponade
Loss of fluid
Pain and loss of function
What are the 7 systemic effects? Briefly explain them
Fever/pyrexia - endogenous pyrogens such as IL-1 and TNF which cause vasodilation and act on hypothalamus to set higher temp.
Leukocytosis - increase in WBC count
Acute phase response - decrease appetite, raised pulse, changed concentrations of acute phase proteins such as alpha 1 antitrypsin.
Weight loss - negative nitrogen balance
Reactive hyperplasia of reticulo-endothelial system
Haematological changes e.g. Anaemia due to blood loss in exudate, haemolytic due to bacterial toxins
Amyloidosis
What are the 4 possible outcomes following acute inflammation?
Complete resolution
Continued acute with some chronic (Abscess)
Chronic inflamm and fibrous repair
Death due to shock
What happens in bacterial meningitis?
Acute inflammation of meninges commonly between arachnoid and pia mater where blood vessels abundant
Vascular thrombosis - leads to reduced cerebral perfusion
Pressure on brain due to fluid accumulation, reducing resp rate and eventually leading to death
What happens in lobar pneumonia?
Caused by streptococcus pneumonia
Alveoli filled with acute inflammatory exudate containing fibrin, bacteria and neutrophils
If treated in good time it can easily resolve completely
What happens in an abscess?
Inflammatory exudate in solid tissue forces tissues apart
Liquefactive necrosis centrally which causes high pressure and pain
Need to remove the liquefactive region to relieve pressure.
What is hereditary angio-oedema?
Deficiency of complement 1 inhibitor
C1 cleaves C2 and 4 to form C3 (one of the important ones)
C1 inhibitor also inhibits bradykinin
Uninhibited bradykinin increases permeability causing oedema
What happens in alpha 1 Anti-trypsin deficiency?
Elastase uninhibited so breaks down lung and liver tissue causing emphysema and liver sclerosis
What are 4 more examples of disorders of acute inflammation?
Inherited complement deficiency
Chronic granulomatous disease - sex linked recessive, immune phagocytes can’t form ROS so can’t kill some bacteria, granulomas form to try to contain the bacteria
Defects in neutrophil function
Defects in neutrophil number
