L10 - Inflammation

Question 1

Cardinal signs of acute inflammation

Answer 1

1. Redness (rubor)
   – Acutely inflamed tissue appears red due to dilatation of local small blood vessels
2. Heat (calor)
   – Increase in blood flow to area
   – Chemical mediators contribute
3. Swelling (tumor)
   – Accumulation of extracellular fluid due increase in permeability of vessels (oedema)
4. Pain (dolor)
   – Distortion of tissues from oedema, pus formation causing pressure
   – Chemical mediators contribute
5. Loss of function
   – Loss of flexibility by pain and swelling
   – Joints

Question 2

Chronic inflammation

Answer 2

• Chronic: over a long time
• If causative agent not removed during acute inflammation
• Often chronic inflammation is the primary event (does not follow acute)

• Cellular exudate changes:
– Lymphocytes, plasma cells, macrophages
– Giant multinucleated cells
– Replace neutrophils (if following acute inflammation)

• Often with systemic effects

Question 3

Acute inflammation

Answer 3

• Early stage
– Oedema fluid
– Neutrophil/polymorph infiltration
– Fibrin formation

• This is driven by:
– Vasodilation
– Increase in permeability of blood vessels (formation of fluid exudate) – Migration of polymorphs (Formation of cellular exudate)

Question 4

Types of Injury

Answer 4

• Microbes: infection (bacteria, viruses)
• Hypersensitivity: parasites, proteins
• Physical: trauma, heat, cold, radiation
• Chemical: corrosive agents, acids, alkalis, toxins
• Necrosis: tissue death (ischaemic infarct)

Question 5

Large blood vessels

Answer 5

– Blood flowing continuously

– Cells flow in centre of vessel (plasma near walls)

– Pre-capillary sphincters control flow in capillaries

Question 6

Capillaries

Answer 6

– Most are closed (empty)

– Open and close due to physiological response

– Acute inflammation
• Sphincters are open causing blood to flow
• Become permeable (plasma and fluid leaks out) – this is exudation (fluid exudate)

Question 7

Types of exudate

Answer 7

• Serous exudate (very watery)
• Fibrous exudate (with fibrin deposits)
• Purulent exudate (lots of pus)

Question 8

What does exudate contain?

Answer 8

– Water

– Salts

– Proteins
• Immunoglobulin, Coagulation factors, Fibrinogen

– Cells
• Neutrophils/monocytes/macrophages/lymphocytes
• Pus (mainly neutrophils but other cells as well)

Question 9

Chemical mediators of Acute Inflammation

Answer 9

• Vasodialation
– Histamine, prostaglandins, nitric oxide

• Vascular permeability
– histamine, bradykinin, nitric oxide, C5a

• Adhesion of cells
– IL-1, IL-8, C5a, TNFα

• Neutrophil chemotaxis – IL-8, IL-17

Question 10

Signs and symptoms of acute inflammation

Answer 10

– Malaise, Fever (pyrexia),Pain, Rapid pulse, Anorexia, Nausea, Weight loss, Lymphadenopathy (swollen lymph nodes)

– Severe cases: generalise vasodilation, Platelet aggregation, Organ dysfunction, Cytokine storm

Question 11

Lab findings of acute inflammation

Answer 11

– Raised Erythrocyte Sedimentation Rate (ESR)
• Reduced viscosity of plasma

– Anaemia (blood loss)

– Raised neutrophil count (granulation & left shift)

– Increase in acute phase proteins
• C-reactive protein (CRP) - binds to bacteria, activates complement

Question 12

Role of neutrophils in acute inflammation

Answer 12

• Attracted to site of inflammation by chemokines

• Phagocytosis: engulf and destroy foreign objects (microbes) 
– Attach 
– Engulf 
– within phagosome 
– Phagosome fuses with lysosome 
– Digest 
– Release debris 

• Release chemotactic agents

• 1 – 3 day life, die (apoptosis), removed by lymphatics
24

Question 13

Later Stages of Acute Inflammation

Answer 13

• Neutrophils first cells at site
– Attracted by endogenous chemical mediators

• Next: chemical mediators from cells
– Lysosomal proteins from neutrophils together with C3a/C5a cause mast cells to release histamine

• More neutrophils attracted
• Other cells types attracted to site

Question 14

Other Cells of Acute Inflammation

Answer 14

• Mast cells

* Macrophages

Question 15

Mast cells

Answer 15

– Already in tissue (at site)

– Stimulated by C3a/C5a

– Major source of histamine

– Release of heparin: anticoagulant

Question 16

Macrophages

Answer 16

– Derived from blood monocytes

– Secrete a large number of chemical mediators
• IL-1 and TNFα - stimulates endothelial cells and other immune cells , chemotactic (more cells),induces fever
• IL-8 and E-selectin: chemotactic agents and activate neutrophils

– Phagocytic
• Cleans wound of debris
• Antigen presenting Cell
• Wound healing

– Arrive latter (24 – 48 hr) but increase numbers over time

Question 17

Beneficial effects of acute inflammation

Answer 17

– Dilution of toxins 
– Allow entry of antibodies 
– Fibrin formation 
– Delivery of nutrients 
– Stimulate immune response

Overall: Removal of harmful material (microbes), healing

Question 18

Harmful effects of acute inflammation

Answer 18

– Digestion of normal tissue

– Swelling (obstruction, intracranial pressure)

– Inappropriate inflammation (allergic reaction to food)

Overall: Inadvertent unwanted damage, self harm

Question 19

Histamine and IL-8 are chemical mediators of acute inflammation. What do they do?

Answer 19

Histamine: vascular permeability

IL-8: adhesion of cells

Question 20

Organisation

Answer 20

Replacement of normal tissue with granulation tissue

Question 21

Granulation

Answer 21

is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process (a scab)

Question 22

Fibrous repair

Answer 22

The replacement of functional tissue

by scar tissue

Question 23

Collagenous scar

Answer 23

A scar where collagen replaces normal tissue after an inflammatory response

Question 24

How a gastric ulcer is formed

Answer 24

– Epithelium damage (Gastric acid)

– Breakdown of epithelium and stroma

– Acute inflammation (exudate)

– Organisation&raquo_space; granulation&raquo_space; scar

– Damage removed&raquo_space; fibrous scar&raquo_space; healing

If stimulus is not removed:

Damage stimulus remains&raquo_space; balance between repair and damage&raquo_space; Chronic Ulcer

Question 25

Acute abscess formation

Answer 25

– Mass of necrotic tissue

– includes dead neutrophils

– enzymes break down surrounding tissue

– surrounded by exudate

Question 26

Chronic abscess formation

Answer 26

– Bacteria survive

– more necrosis

– abscess enlarges

– wall replaced by granulation and scar tissue

Question 27

What is an abscess?

Answer 27

Pyogenic bacterial infection