Acute Inflammation

Question 1

What is acute inflammation?

Answer 1

The response of living tissue to injury, initiated to limit tissue damage - innate, immediate and of short duration.

Question 2

Vascular and cellular reactions lead to the accumulation of what in tissues? How is it controlled?

Answer 2

Fluid exudate and neutrophils.

Controlled by chemical mediators from cells/plasma.

Question 3

What are the causes of acute inflammation?

Answer 3

Microbial infections (e.g. Pyogenic/pis-causing organisms), hypersensitivity reactions, physical agents, chemicals and tissue necrosis.

Question 4

What are the clinical features of acute inflammation?

Answer 4

Rubor, tumor, calor, dolor and loss of function

Question 5

Which changes lead to rubor and calor?

Answer 5

Transient vasoconstriction of arterioles happen first, then vasodilation of arterioles followed by capillaries, which increases blood flow to an area, making it redder and more hot.

Question 6

What affect does the increased permeability of blood vessels have?

Answer 6

Exudation of protein-rich fluid into tissues and slowing of circulation - swelling.
Stasis is concentration of RBCs in small vessels and increased blood viscosity.

Question 7

Which chemical mediators acts immediately/as part of the early response in the 1st half an hour, and what does it do?

Answer 7

Histamine is released from mast cells, basophils and platelets in response to many stimuli including compliment components and factors from neutrophils and platelets. It causes vascular dilation, a transient increase in vascular permeability and pain.

Question 8

Which chemical mediators are part of the persistent response?

Answer 8

Leukotrienes and bradykinin - many and varied with interlinked and varying importance.

Question 9

How may oedema arise in acute inflammation?

Answer 9

Starling’s Law - hydrostatic and colloid osmotic pressure balance. Increased blood flow leads to increased hydrostatic pressure in vessels and increased colloid osmotic pressure in interstitium from exudate, so there’s increased fluid flow out of the vessel.
Oedema caused by arteriolar dilation and increased blood vessel permeability.

Question 10

What are the 2 types of oedema and why is it employed in acute inflammation?

Answer 10

Oedema (increased fluid in interstitium), can be transudate, e.g. From cardiac failure or venous outflow obstruction, where the fluid in the interstitium has the same protein content as the plasma, or exudate, where it has a higher plasma concentration. It’s useful in acute inflammation, as it leads to increased lymphatic drainage, potentially leading pathogens to dendritic cells in lymph nodes.

Question 11

What are the mechanisms of vascular leakage? Why is it helpful?

Answer 11

Endothelial contractions creating gaps, cytoskeleton reorganisation creating gaps, direct injury, leukocyte dependent injury and increased transcytosis - channels across endothelial cytoplasm.
Used to deliver plasma proteins to the site of injury, e.g. Fibrin, so meshwork can localise, which is important at serous cavities.

Question 12

What is a neutrophil/polymorph?

Answer 12

The primary type of WBC involved in acute inflammation, a type of granulocyte, with multilobed nuclei. Make up pus.

Question 13

Outline the steps of neutrophil infiltration.

Answer 13

Margination - stasis causes neutrophils to line up at the edges of blood vessels, along the endothelium.
Rolling - along endothelium, sticking intermittently.
Adhesion - neutrophils then stick more avidly.
Emigration - neutrophils go through blood vessel wall.
Neutrophils escape the vessels by relaxation of interendothelial cell junctions, digestion of vascular basement membrane and movement.

Question 14

Explain the importance of chemotaxins.

Answer 14

When neutrophils infiltrate the tissue, they move along concentration gradients of chemoattractants.
Chemotaxins: C5a, LTB4, bacterial peptides. Receptor-ligand binding induces rearrangement of cytoskeleton and production of pseudopod.

Question 15

Neutrophils phagocytise, how?

Answer 15

Contact, recognition, internalisation. Facilitated by opsonins, cytoskeleton changes, phagosome + lysosome = phagolysosome/secondary lysosome. The kill is either oxygen dependent - produces superoxide and hydrogen peroxide, myeloperoxidase-halide system produces HOCl to manage cause of inflammation, or oxygen independent - lysozyme and hydrolases, bactericidial permeability increase protein (BPI) and cationic proteins -‘defensins’.

Question 16

What is a downside of oxygen dependent killing of pathogens by neutrophils?

Answer 16

Activated neutrophils may release toxic metabolites and enzymes, causing damage to the host tissue.

Question 17

Name and mention the origins of 4 types of chemical mediators in acute inflammation.

Answer 17

Proteases-plasma proteins produced in liver.
Kinins-complement system, coagulation/fibrinolytic system.
Prostaglandins/Leukotrienes-metabolites of archidonic acid.
Cytokines/chemokines are produced by white blood cells - many and varied including interleukins and tissue necrosis factor alpha.

Question 18

Some functions of chemical mediators include to increase blood flow, to stimulate vascular permeability, induce neutrophil chemotaxis and phagocytosis, which do which?

Answer 18

Blood flow - histamine and prostaglandins.
Vascular permeability - histamine and leukotrienes.
Neutrophils chemotaxis - C5a, LTB4, bacterial peptides.
Phagocytosis - C3b.

Question 19

What are the 2 hallmarks of inflammation?

Answer 19

1. Exudate of fluid (oedema).

2. Infiltrate of inflammatory cells.

Question 20

How is injury combated by exudation of fluid?

Answer 20

Delivers plasma proteins to area of injury (immunoglobulins, fibrinogen, inflammatory mediators), dilutes toxins and increases lympathic drainage, so microorganisms are delivered to phagocytes and antigens go to the immune system.

Question 21

How is injury combated by infiltration of cells?

Answer 21

Removes pathogenic organisms and necrotic debris by phagocytosis.

Question 22

How is injury combated by vasodilation?

Answer 22

Increased delivery of inflammatory substances by the blood and an increase in temperature.

Question 23

How is injury combated by pain and loss of function?

Answer 23

Enforces rest, reduces the chance of further traumatic damage.

Question 24

State 4 local complications of acute inflammation.

Answer 24

1. Swelling causing blockage of tubes.
2. Exudate - compression e.g. Cardiac tamponade, serositis.
3. Loss of fluid e.g. Burns.
4. Pain and loss of function are unhelpful if prolonged.

Question 25

Fever is a systemic effect of acute inflammation, what is it caused by?

Answer 25

Release of endogenous pyrogens - IL1 and TNF-alpha and prostaglandins - so aspirin reduces fever.

Question 26

What occurs in leukocytosis?

Answer 26

IL1 and TNF-a cause accelerated release from marrow, macrophage as T cells produce colony stimulating factor, bacterial infections = neutrophils or virus = lymphocytes - useful clinically.

Question 27

What is the result of the acute phase response?

Answer 27

Decreased appetite, raised pulse, altered sleep patterns and changes in plasma concentrations of acute phase proteins: CRP, alpha1-antitrypsin, haptoglobin, fibrinogen, serum amyloid A proteins.

Question 28

There may be spread of microorganisms and toxins resulting in a clinical syndrome of circulatory failure known as what?

Answer 28

Shock.

Question 29

What are the various sequelae of acute inflammation?

Answer 29

Complete resolution, continued actuate inflammation with chronic inflammation –> abscess, chronic inflammation and fibrous repair, probably with tissue regeneration or death.

Question 30

What is the resolution morphology of acute inflammation?

Answer 30

Changes gradually reverse and vascular changes stop - neutrophils no longer marginate, vessel permeability and calibre will be normal. Exudate drains to lymphatics, fibrin degraded by plasmin and other proteases, neutrophils die and break up (carried away/phagocytosed), damaged tissue might regenerate - if tissue architecture destroyed, complete resolution impossible.

Question 31

Which mechanisms cause cessation and localisation of the effect of chemical mediators in acute inflammation?

Answer 31

All mediators have a short half life, they may be inactivated by degradation (e.g. Heparinase), inhibitors may bind, they may be unstable, they may become dilute in the exudate or there might be specific inhibitors of acute inflammatory changes.

Question 32

What may be the detrimental effects of acute inflammation in Bacterial meningitis?

Answer 32

May cause vascular thrombosis and reduce cerebral perfusion.

Question 33

What are the consequences of acute inflammation in lobar pneumonia?

Answer 33

Exudate in alveoli caused by Streptococcus pmeumoniae with worsening fever, prostration (weakness), hypoxaemia, dry cough and breathlessness. Treatment can resolve it completely.

Question 34

Describe the process of acute inflammation in relation to a skin blister.

Answer 34

Cause by heat, sunlight, chemicals - pain and profuse exudate - collection of fluid strips off overlying epithelium - relatively few inflammatory cells, so exudate clear unless bacterial infection develops. Resolution or scarring.

Question 35

What is going on when there is an abscess?

Answer 35

Usually of a solid tissue - exudate forces tissue apart with liquefactive necrosis in centre - may cause high pressure, so pain, may cause tissue damage and squash adjacent structures.

Question 36

What is the result of acute inflammation on the serous cavities?

Answer 36

Ascites (fluid accumulation in peritoneal cavity), pleural or pericardial effusion, respiratory/cardiac impairment, localised fibrin disposition. Pericarditis (‘bread and butter’), exudate in pericardium.

Question 37

Disorders in acute inflammation are rare, what may they involve?

Answer 37

Defects in neutrophil number or function or inherited complement deficiencies.