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Flashcards in MOD - Lecture 3 Deck (59):
1

Name 3 facts of acute inflammation

Evolves over hours or days
Innate
Stereotyped

2

How long does chronic inflammation take to evolve?

Weeks, months or years

3

What suffix is used to indicate inflammation of tissue or organ?

Itis e.g. Appendicitis

4

Describe acute inflammation

Rapid response that aims to deliver mediators of host defence
Most defensive agents circulate in the blood in active form
When needed, delivered and activated
Leave the blood at site of injury

5

Why is fluid delivered to site of injury before leucocytes?

Fluid - within seconds
Leuocytes - minutes

As leucocytes can't just pour out of vessels

6

What causes acute inflammation? (6)

Foreign bodies
Immune reactions
Infections
Tissue necrosis
Trauma
Physical/chemical agents e.g burns, irritation

7

What are the clinical signs of acute inflammation? (5)

Rubor = redness
Calor = heat
Tumour = swelling
Dollar = pain
Loss of function - enforces rest and reduces chance of further damage

8

When does pain occur in acute inflammation?

When the specialised nerve endings are stimulated by mediators especially bradykinin

9

Why does swelling occur in inflammation?

Fluid and leucocytes take up space within the tissue

10

What forces are involved in Starlings Law equilibrium?

Capillary pressure
Interstitial free fluid pressure
Plasma colloid osmotic pressure
Interstitial fluid colloid osmotic pressure

11

Where is histamine stored?

Granules for mast cells, basophils and platelets

Histamine and serotonin are available immediately from preformed supplies

12

What does histamine produce in acute inflammation?

Pain
Arteriolar dilation
Venular leakage

13

How does histamine cause fluid leakage?

Causes endothelial cells to contract and pull apart.
This creates gaps through which plasma proteins can pass

14

How can you reduce pain and swelling?

Describe the mechanism.

What drugs are taken?

Block the production of prostaglandins

By inhibiting the enzyme (cyclo-oxygenase) that produces prostaglandins from arachadonic acid.

Aspirin
NSAIDs

15

What is the effect of bradykinin?

Pain
Increased vascular permeability

16

How does serotonin differ from histamine?

Serotonin produces fibroblasts

17

In relation to Starlings law, what is the main force driving fluid out of the vessels?

and back into the blood?

Hydrostatic pressure of the blood

Colloidal osmotic pressure of plasma proteins

18

How does excess fluid drain from the tissues?

Lympathics - excess fluid drawings from the tissues taking with it microorganisms and antigens which are presented to the immune system in the lymph nodes.

Lymph nodes draining a focus of inflammation can themselves become inflamed, swollen and painful. (Lympahedenitis)

19

What are the three defensive proteins in the exudate?

How do they work?

Opsonins - coat foreign material and make them easy to phagocytose.

Complement - proteins assembled locally to produce bacteria-perforating structure

Antibodies - bind to surface of microorganisms, also act as opsonins.

20

What is the protein rich and protein poor tissue fluid that develops in inflammation called?

Exudate - protein rich
Transudate - protein poor

21

Name the chemical mediators that induce vascular leakage?

Histamine & Serotonin (mast cells and platelets)
Bradykinin (formed from plasma precursor)
Complement components - C3a, C4a, C5a (formed form plasma precursors)

22

What is the primary type of leucocyte found in acute inflammation?

Where are they normally found?

What does their presence in the tissue indicate?

What type of cell are they?

Neutrophil
Blood or bone marrow
Invasion by bacteria or some other parasite or tissue injury
End cell - cannot multiply

23

What is chemotaxis?

Directional movement towards a chemical attractant

E.g. Clotting blood (fresh blood isn't)
Activation of complement fragments C3a, C4a, C5a. All chemotactic - especially C5a.
Leukotriene produced by leucocytes

24

How does blood clot form? (3)

What enzyme breaks down a clot?

Plasma enzymes activate Thrombin
Thrombin acts on fibrinogen, converting it to fibrin (insoluble protein)
RBC become trapped in insoluble fibrin mesh which forms a clot.

Clots resolve when fibrin is broken down by proteolytic enzyme plasmin

25

What happens during activation?

Within 5 seconds of chemotaxis binding to cell surface receptors
Calcium and sodium ions rush into the cells
Cell swells
Reorganises its cytoskeleton
Activated cells are more sticky than normal cells

26

What is margination and what happens during margination?

What happens to the number of selectins and activation of integrins during inflammation?

Leucocytes assume marginal positions in the vessels
Leucocytes stick to the walls of venules
Roll along the wall and become trapped, stop and crawl out of the vessel.
They are trapped when their receptors bind to adhesion molecules

Increase by inflammatory mediators and chemotaxis

27

What is diapedesis and describe.

Leucocytes dig their way out of vessels as they don't use the endothelial gaps
Produce collagenase to digest basement membrane
Move towards their target by pulling along collagen fibres of other tissue structures.

28

What substances make it easier for phagocytes to recognise target?

Give two examples

Opsonins - plasma proteins

IgG antibody - not present when bacteria is encountered first time
C3b complement

29

What happens is opsonins are not present on the molecule to be phagocytosed?

Phagocyte will recognise microbial surface antigens

30

Describe phagocytosis

Phagocyte forms a crater shape around particle to be phagocytosed
Crater forms a cup shape around particle, edges of the cup come together, plasma membranes fuse.
Phagosome digests the particle

Degranulation can occur before particle is completely enclosed and cause some bactericidal enzymes to leak into surrounding tissue = local tissue injury.

31

What two mechanisms kill organisms that have been phagocytosed?

Oxygen dependent - using free radicals = oxidative burst

Oxygen independent - using enzymes e.g. Proteases, nucleases, phospholipases and lysozyme

32

What six steps does a neutrophil go through to kill bacteria?

Chemotaxis - summoned to place of injury
Activation - switch to higher metabolism
Margination - stick to endothelial lining
Diapedesis - crawl through endothelium
Recognition/attachment - recognise bacteria and attach
Phagocytosis - engulf bacterium

33

What is a chemical mediator?

Produced in a focus of inflammation and modulates the inflammatory response

34

What are the two most common responses to mediators?

Motion
Secretion

35

What must every mediator have to ensure the inflammatory response is not on-going?

Why is the duration of inflammation also limited?

Inhibitors

Mediators have short half lives

36

What are the seven groups of endogenous mediators?

Vasoactive amines - histamine and serotonin
Vasoactive peptides - bradykinin
Complement components - C3a, C5a, generated from complement forming into tube.
Clotting and Fibrinolytic cascades - generate inflammatory mediators
Mediators derived from phospholipids e.g. Prostaglandins. Leukotriene B4 very powerful chemotactic agent
Cytokines and chemokines - tumour necrosis factor
Exogenous mediators e.g. Endotoxin

37

What is the difference between a cytokine and chemokines?

Cytokines - polypeptides produced by many cells and act as messengers between cells
Chemokines - a group of cytokines involved in chemotaxis.

Both have local and systemic effects.

38

What are the five main roles of inflammatory mediators?

Vasoidlation - histamine and serotonin
Increased vascular permeability - histamine and serotonin get (mast cells and platelets) Prostaglandins
Chemotaxis - Leukotriene B4, C5a, C3a, Chemokines
Phagocytosis - C3b
Pain - bradykinin, prostaglandins

39

What are the local complications of acute inflammation? (4)

Damage to normal tissue - secondary to substances produced by neutrophils
Obstruction of tubes e.g. Fallopian or intestine and compression of vital structures e.g. Fluid accumulation in the brain
Fluid loss - fluid accumulates until a point where it prevents further exudate on. Can continuously leak from a surface wound e.g. Burns
Pain and loss of function

40

What are the four main systemic effects of acute inflammation?

Why do they occur?

Fever - thermostat of the body is switched higher. Aspirin inhibit cyclo-oxygenase reducing fever
Leucocytosis - Increase in no. Of circulation Leucocytes
Acute Phase Response - change in level of some plasma proteins. Some produced in small amounts e.g. Albumin and others in larger amounts fibrinogen. Sleepiness and lack of appetite are a result of APR
Shock - Blood stream inflammation can occur if bacteria or inflammatory mediators spread around body

Inflammatory mediators enter the blood stream in significant amounts. Effects seen within one day

41

What is shock?
Causes
Effects
Outcome

Inflammatory mediators spread around the body in the blood stream = inflammation throughout body
Dramatic drop in BP due to widespread vasodilation
Increase in vascular permeability - resultant fluid exudation

Often fatal.

42

What is resolution of acute inflammation?

Vascular permeability returns to normal
Neutrophils undergo apoptosis and phagocytosed
Exudate is reabsorbed into venules or drained away in lymphatics
Fibrin is degraded

43

What happens to tissue in resolution?

If damaged parenchymal cells can regenerate tissue will return to normal

If regeneration cannot occur an extensive fibrous scar will form

44

What are the four types of exudate?

Pus/abscess - exudate creamy white rich in neutrophils
Haemorrhagic - RBC's make it appear bloody to naked eye. Indicates as well as inflammation significant vascular damage has occurred
Serous - Plasma proteins but few leucocytes suggest there is no infection. Clear - seen in blisters
Fibrinous - Significant deposition of fibrin

45

How do serous exudates differ from transudates?

Serous - contain plasma proteins. Also differ from plasma as they don't contain fibrinogen

Transudates - don't contain plasma proteins

46

What are the clinical examples of inflammation?

Bacterial meningitis
Lobar pneumonia
Ascending colangitis
Liver abscess
Acute appendicitis

47

What are the three disorders of acute inflammation?

Hereditary angio-oedema
Alpha1-anti trypsin deficiency
Chronic granulomatous disease

48

Describe hereditary angio-oedema

Rare autosomal dominant disorder
Inherited deficiency of C1-esterase inhibitor
Patients have non itchy cutaneous angio-oedema. Recurrent abdo pain
Often a family history of sudden death

49

Describe alpha1-antitrypsin deficiency.

Autosomal recessive disorder with varying levels of severity
Low levels of alpha-1-antitrypsin = a protease inhibitor which deactivates enzymes released from neutrophils at site of inflammation
Develop emphysema - proteases released by neutrophils in the lungs act unchecked and destroy normal lung tissue
Liver disease - hepatocytes produce abnormal version of protein which is incorrectly folded. Polymerises cannot be exported from ER - hepatocyte damage and eventually cirrhosis

50

What is chronic granulomatous disease?

Genetic condition
Phagocytes unable to generate the free radical superoxide
Bacteria is phagocytosed but phagocytes cannot kill them as they cannot generate an oxygen burst
Results in formation of chronic infections in first year of life

51

What is a response to injury of living tissue?

What is its purpose?

Inflammation - deliver defensive materials
To protect body from infection
Clear damaged tissue
Initiate tissue repair

52

What type of respiration do neutrophils use?

Aerobic and anaerboic

53

How many nuclei do neutrophils have?

Single nuclei

54

What are all inflammatory cells derived from?

Bone marrow precursors

55

What do macrophages produce?

Interleukin - 1

56

What would happen to the CRP levels and plasma viscosity in acute inflammation?

CRP - Increase
CRP is an acute phase reactant
Plasma viscosity - increase in acute phase reaction

57

What are the causative organisms of:
1. Lobar pneumonia
2. Acute appendicitis
3. Bacterial meningitis
4. Ascending cholangitis/ Liver abscess

1. Pneumococci
2. Intestinal worms, foreign bodies trauma
3. Streptococcus. Young adults = Neisseriae meningitidis. Neonate a = Group B streptococci
4. Entercoli/Ecoli

58

What is ascending cholangitis?

Bacterial infection on an obstruction of the biliary tree commonly from a gall stone.
Organisms migrate backwards up the bile duct as a result of partial blockage
Symptoms - yellow discolouration of skin, fever, abdo pain
Can be life- threatening
Treatment - IV fluids and antibiotics

59

Why does acute inflammation occur?

To limit the tissue damage