MoD Session 2: acute inflammation

Question 1

Causes of acute inflammation?

Answer 1

Foreign bodies
Microbial infection
Hypersensitivity
Tissue necrosis
Trauma
Physical agents (thermal injury, irradiation)
Chemicals

Question 2

Hallmarks of acute inflammation?

Answer 2

Rubor (redness)     [vasodilation]
Tumor (swelling)  [fluid and leukocytes]
Calor (heat)   [vasodilation]
Dolor (pain)  [nerve endings stimulated by mediators]
Loss of function

Question 3

Vascular phase of acute inflammation?

Answer 3

1. Transient vasoconstriction of arterioles (A few seconds, least important)
2. Vasodilation of arterioles then capillaries (rubor + calor)
3. Increased permeability of blood vessels (exudation of protein-rich fluid into tissues, slowing of circulation, increased resistance)
4. Stasis of blood flow

Question 4

Role of histamine in vascular phase of acute inflammation?

Answer 4

Vasoactive amine released from mast cells, basophils and platelets due to trauma, immune reactions, complement proteins, IL-1…
Causes endothelial cells to contract and pull apart, gaps appear, plasma protein can pass through causing fluid leakage

Question 5

How does a fluid exudate form?

Answer 5

Arteriole and capillary dilation causes increased hydrostatic pressure
Increased permeability of vessel walls causes loss of protein, so the interstitium has a higher colloid osmotic pressure
Both of these factors cause net flow out of the vessel (so more fluid in tissue spaces–> oedema). Fluid can be transudate or exudate

Question 6

What is a transudate?

Answer 6

Due to increased hydrostatic pressure
Low protein
Occurs in cardiac failure or venous outflow

Question 7

What is an exudate?

Answer 7

Occurs in acute inflammation
High protein content
Leads to increased lymphatic drainage, taking microbes and antigens to lymph nodes, can get lymphadenitis

Question 8

Mechanisms of vascular leakage?

Answer 8

Endothelial contraction-gaps (histamine, leukotrienes)
Cytoskeletal reorganisation-gaps (cytokines IL-1 & TNF)
Direct injury: toxic burns, chemicals
Leukocyte-dependent injury: toxic oxidative species and enzymes from leukocytes
Increased transcytosis (VEGF)

Question 9

Role of fibrin in fluid exudate?

Answer 9

Is rich in exudate
Activated in inflammation, mesh–>clot
Localised area around injured tissue

Question 10

Defensive forces of the exudate?

Answer 10

Opsonins: coat foreign matrials and make them easy to phagocytose
Complement: produce a bacteria-perforating structure locally
Antibodies: also act as opsonins

Question 11

The four stages in the infiltration of neutrophils?

Answer 11

1. Margination (line up at edge of blood vessels along endothelium due to stasis: usually flow down middle when laminar flow)
2. Rolling (roll along endothelium and loosely stick to it)
3. Adhesion (stick more tightly)
4. Emigration (through blood vessel wall)

Question 12

How do neutrophils move?

Answer 12

Chemotaxis

Move along the concentration gradients of chemoattractants e.g. C5a, receptor-ligand binding

Question 13

Neutrophil activation?

Answer 13

Switched to a higher metabolic level

Ca2+ and Na+ move in, cell swells and reorganises cytoskeleton, stickier cells

Question 14

Neutrophil other names?

Answer 14

Neutrophil leucocyte
Main WBC of acute inflammation
A type of granulocyte
Also called polymorphs (old terminology)

Question 15

Diapedesis of neutrophils?

Answer 15

Produce collagenase-digests basement membrane

Move by pulling themselves along collagen fibres towards target

Question 16

What are opsonins?

Answer 16

Substances that make it easier for phagocytes to recognise targets. If there are no opsonins then the phagocyte can recognise surface antigens
They are plasma proteins
E.g. complement protein C3b, IgG antibody

Question 17

What is phagocytosis?

Answer 17

Phagocyte membrane forms crater shape around target particle
Plasma membrane fuses with phagocyte surrounding it making a phagosome
Granules move towards phagosome aand fuse
Inject their bactericidal substances causing degranulation and removal of necrotic cell debris

Question 18

How do neutrophils kill bacteria?

Answer 18

1. Oxygen-dependent: use free radicals in respiratory burst

2. Oxygen-independent: use enzymes e.g. proteases, nucleases

Question 19

Name the main chemical mediators of acute inflammation

Answer 19

Proteases (e.g. complement)
Prostaglandins (cause vasodilation, increase flow, fever, pain. Blocked by aspirin and NSAIDs to reduce pain and fever)
Leukotrienes (increase permeability)
Histamine (increase blood flow and permeability)
Cytokines and chemokines (from WBCs. E.g. IL, TNFa)
Bradykinin (permeability, vasodilation, pain)
Complement components (form a hole in bacteria)
Exogenous mediators (e.g. endotoxin made by gram negative bacteria)

Question 20

List the main roles of inflammatory mediators

Answer 20

Vasodilation (histamine and serotonin)
Increased vascular permeability (hisamine, serotonin, bradykinin)
Chemotaxis (leukotrienes, complement proteins)
Phagocytosis (C3b)
Pain (bradykinin)

Question 21

How do inflammatory mediators constitute an effective response to injury?

Answer 21

1. Fluid exudation (so move lymph drainage and more proteins to site and dilutes toxin)
2. Infiltration of cells
3. Vasodilation
4. Pain and loss of function (enforces rest)

Question 22

Local complications of acute inflammation?

Answer 22

Swelling
Exudate (can compress e.g. cardiac tamponade)
Damage of normal tissue
Fluid loss (e.g. in burns as fluid can leak continually from a surface wound)
Pain and loss of function

Question 23

Systemic effects of actue inflammation: can be seen within one day

Answer 23

1. FEVER-endogenous pyrogens (IL-1, TNFa) increase prostaglandin synthesis. Can be useful at killing bacteria. Aspirin inhibits cyclooxygenase to reduce prostaglandin made so reduce fever
2. LEUKOCYTOSIS-increased no. circulating leucocytes
3. ACUTE PHASE RESPONSE-within hours change in pattern of protein synthesis so change in levels of plasma proteins (e.g. CRP-an opsonin). Causes symptoms of decreased appetite, fatigue and increased heart rate)
4. SHOCK-dramatic fall in blood pressure due to vasodilation and increased permeability causing fluid exudation. Often fatal. As bacterial products or inflammatory mediators spread around body

Question 24

Sequeale of unresolved acute inflammation?

Answer 24

Abscess (AI + CI)
Chronic inflammation and fibrous repair
Death

Question 25

Morphological changes in AI resolution?

Answer 25

Neutrophils stop marginating Vessel permeability to normal Vessel calibre back to normal

Question 26

Effects of AI resolution?

Answer 26

Exudate drains to lymphatics Fibrin degraded by proteases Neutrophils apoptosise and are phagocytosed Damaged tissue may be able to regenerate If tissue architecture destroyed and complete resolution not possible, fibrous scar tissue will form

Question 27

Describe the four types of exudate

Answer 27

Pus/abscess: creamy/white, rich in neutrophils, often bacterial Haemorrhagic: RBCs so appears red, indicates significant vascular damage, seen in destructive infections and malignancy Serous: plasma proteins but few leucocytes, clear, e.g. in blisters. Not transdudate as has proteins Fibrinous: a blood clot without the RBCs, in pericardial/pleural spaces

Question 28

Describe hereditary angio-oedema

Answer 28

Autosomal dominant, rare, potentially life threatening Deficiency in a complement enzyme (C1-esterase inhibitor) Symptoms: episodic swelling attacks in hands/face/airway etc, recurrent abdo pain (intestinal oedema)

Question 29

Describe alpha 1-antitrypsin deficiency?

Answer 29

Autosomal recessive condition Low levels of this protease inhibitor which deactivates enzymes released by neutrophils Develop emphysema as proteases act unchecked to destroy tissue, and cirrhosis as hepatocytes produce incorrectly-folded protein so damages them

Question 30

What is chronic granulomatous disease?

Answer 30

Phagocytes can't generate superoxide radical Bacteria are phagocytosed but not killed as can't generate oxygen burst Leads to chronic infections: numerous granulomas and abscesses

Question 31

Brief overview of lobar pneumonia?

Answer 31

Acute, exudative inflammation of a pulmonary lobe. Alveoli have exudate Cause gram +ve diplococci -Streptococcus pneumoniae Can be resolved completely if treated

Question 32

Brief overview of acute appendicitis?

Answer 32

Appendix lumen obstructed by faecolith or generalised AI If not removed: gangrene +perforation = peritonitis Presentation: vague abdo pain localised to R iliac fossa,nausea etc. ESR and CRP bloods Complications: paralytic ileus, peritonitis-septicaemia-multi organ failure

Question 33

Brief overview of bacterial meningitis?

Answer 33

Sudden onset, many symptoms AI of meninges: congested with neutrophils, pus forms, causes adhesions, cranial nerve palsies and hydrocephalus result, vascular thrombosis-reduced cerebral perfusion. Exudate in a small space-cerebral oedema Viscous grey-green exudate

Question 34

Brief overview of ascending cholangitis?

Answer 34

Infection of bile duct High morbidity and mortality. Need IV antibiotics and bile duct drainage Jaundice, lethargy, abdo pain, hypotension Severe cases result in liver abscess