How Does the Cell Respond To Injury

Question 1

5 Cardinal Signs of Inflammation

Answer 1

Calor (heat)

Dolor (pain)

Rubor (redness)

Tumour (swelling)

Functio laesa (loss of function)

Question 2

What is inflammation?

Answer 2

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.

Question 3

Function of inflammation

Answer 3

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.

Question 4

Compare Acute and Chronic Inflammation

Answer 4

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)

Question 5

What causes inflammation?

Answer 5

• Infections (bacterial, fungal, viral, parasitic)
• Tissue necrosis (ischaemia, trauma, physical or chemical injury)
• Foreign bodies (dirt, sutures, splinters, …)
• Immune reactions (hypersensitivity/allergy, autoimmune reactions)

Question 6

The five Rs of the inflammatory process:

Answer 6

Recognition (of the injurous agent)

Recruitment (of leukocytes)

Removal (of the injurous agent)

Regulation (of the inflammatory response)

Resolution (or repair)

Question 7

Characteristics of Acute inflammation

Answer 7

Rapid onset in minutes

Short duration of hours to days

Exudation of plasma fluid and proteins

Emigration of leukocytes, predominantly neutrophil polymorphs

Question 8

UC Acute meningitis

Question 9

Myocardial infarction

Question 10

UC Myocardial infarction

Question 11

Acute Bronchopneumonia

Answer 11

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

Question 12

Explain vascular microcirculation

Answer 12

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.

Question 13

Vasodilatation effects

Answer 13

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.

Question 14

Vascular permeability in swelling

Answer 14

1. Histamine and nitric oxide also activate endothelial cells and cause them to contract
2. Often, there is also damage to the endothelium by leukocytes or the insulting stimulus (cause)
3. The venule walls becomes more permeable to large proteins which leak into the tissues
4. The osmotic pressure in the tissue increases and water follows
5. More fluid leaves the blood vessels than returns to them

Question 15

What is exudate and transudate and what is its clinical significance?

Answer 15

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)

Question 16

what are the three steps a neutrophil takes to leave the blood vessel?

Answer 16

• 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}

Question 17

How is complement involved in extravasation?

Answer 17

complement is involved in the process of margination (extravasation in this context) as well as the immune function it already has.

Question 18

how does a leukocyte move around?

Answer 18

Contractile cytoplasmic microtubules and changes in cyto- plasmic fluidity result in amoeboid movement

Movement occurs towards high concentrations of chemical mediators = chemotaxis

Question 19

Explain the process of phagocytosis of a bacteria

Answer 19

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

Question 20

List the mediators in Acute Inflammation

Answer 20

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

Question 21

Beneficial and harmful effects of inflammation

Answer 21

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

Question 22

Effects of acute inflammation

Answer 22

Serous inflammation of cell poor transudation/effusion

Fibrinous inflammation

Purulent inflammation and abscess formation

Ulcer

Question 23

What are the different outcomes of acute inflammation?

Answer 23

Question 24

Features of chronic inflammation

Answer 24

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

Question 25

What are causes of chronic inflammation?

Answer 25

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)

Question 26

What cells are involved in chronic inflammation?

Answer 26

• Lymphocytes

T-lymphocytes (CD3 positive)

B-lymphocytes (CD20 positive)

• Plasma cells
• Macrophages
• Eosinophil polymorphs
• Fibroblasts
• Few neutrophil polymorphs
• Little fluid exudation

Question 27

Granulomatous inflammation features

Answer 27

• 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.)*