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Flashcards in MOD 2 Deck (85):
1

What are 5 major causes of acute inflammation?

1. Infections (bacterial, viral, parasitic) and microbial toxins
2. Acute phase hypersensitivity reactions
3. Physical agents (thermal, irradiation)
4. Chemicals
5. Tissue necrosis (any cause)
6. Foreign bodies (splinters, dirt, sutures)

2

What are the 5 cardinal signs of tissue necrosis?

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

3

How are changes to vascular flow brought about in acute inflammation?

Vasodilators (such as histamine) cause arterioles to dilate, increasing flow to the capillaries and capillary pressure. Venules become more leaky

4

How does a fluid exudate form in acute inflammation? Use Starling's Law in your explanation.

1. Semi-permeable capillary and venule membrane becomes more leaky
2. Capillary pressure increases (main driving force for fluid out of the vessels)
3. Plasma proteins escape into tissue spaces, increasing the interstitial oncotic pressure, so it roughly equals blood oncotic pressure

5

How does neutrophil emigration occur in acute inflammation?

a

6

What tissues changes cause rubor?

Vasodilation of arterioles in the damaged area.

7

What tissue changes cause tumour?

After the vasodilation of arterioles, venules become leaky and plasma can escape through tiny gaps between endothelial cells. The decrease in viscosity of the blood (increased haematocrit) within the venules, increases the resistance to blood flow in the venules, hampering the outflow of blood from the area of injury and increasing blood pressure upstream.This greater pressure increases the outflow of fluid and plasma proteins into the space within the tissues and so the inflamed area swells.

8

What tissue changes cause calor?

Vasodilation of arterioles by vasodilators such as histamine increases the flow and therefore the capillary pressure rises. Capillaries that are normally empty fill.

Temperature increase during inflammation only occurs at the skin, as internal organs are already the same temperature as blood.

9

What tissue changes cause dolor?

Pain occurs when specialised nerve endings are stimulated by mediators, especially bradykinin.

10

What tissue changes cause loss of function?

Reduced movement due to swelling and pain?

11

What are the benefits to the tissue changes seen in acute inflammation?

1. Delivery of:nutrients, oxygen, cells, plasma proteins (such as antibodies), inflammatory mediators, fibrinogen.
2. Dilution of toxins - excess fluid drains into lymph vessels and is presented to immune system in nodes
3. Maintenance of temperature
4. Stimulation of immune response
5. Destruction and removal of dead or foreign material
6. Pain and loss of function -> enforcing rest.

12

How do neutrophils undergo margination?

The stick to the blood vessel walls as they heed the chemotactic signal and roll along the wall until they adhere. They roll along by binding to receptors on the blood vessel surface called selectins and adhere finally using integrins (such as ICAM-1). Chemotaxins and inflammatory mediators increase the concentration of selectins and activate integrins.

13

How do neutrophils phagocytose material?

They engulf it -> phagosome creation. The cell's bacteriocidal granules then move toward the phagosome and fuse with it injecting their bacteriocidal substance into it (degranulation). These granules fuse with the phagosome before it is completely enclosed, therefore bacteriocidal substances leak out into the surrounding tissue interstitium, causing local tissue damage. Neutrophils can also phagocytose local necrotic tissue debris.

14

What are the two main mechanisms that neutrophils kill phagocytosed microbes?

oxygen dependent and oxygen independent methods

15

List four important chemical mediators in acute inflammation?

Histamine
Bradykinin
Prostaglandin
Complement system

16

What produces histamine? What is its role in acute inflammation?

Histamine is a vasoactive amine (these tend to be the first mediators to appear during inflammation) that is stored in granules in basophils, mast cells and platelets. It is released in response to many stimuli (e.g. physical damage, immune reactions and complement components) and causes myoepithelial cells to contract causing gaps to form between endothelial cells allowing plasma proteins to pass. It also causes pain, increases venule leakage and vasodilation of arterioles.

17

What produces bradykinin? What is its role in acute inflammation?

It is produced from circulating plasma precursors. It stimulates specialised nerve endings causing pain and increases vascular permeability.

18

What produces prostaglandin? What is its role in acute inflammation?

Prostaglandins are produced from membrane phospholipids. They cause vasodilation, make the skin more sensitive to pain and cause fever.

19

What produces proteins of the complement system? What is their role in acute inflammation?

They circulate in blood as a number of disassembled proteins. In acute inflammation they assemble into a tube which can punch holes in and kill bacteria. Assembly of this tube produces by products which are powerful inflammatory mediators e.g. C3a and C5a (chemotaxins) and C3b (opsonin).

20

List the local complications of acute inflammation:

1. Damage to normal tissue
2. Obstruction of tubes, compression of vital structures
3. Loss of fluid
4. Pain and loss of function

21

What are the systemic consequences of acute inflammation?

1. Fever
2. Leucocytosis
3. Acute phase response
4. Shock

22

How does resolution of acute inflammation occur?

1. Mediators have short half-lives and are degraded after release
2. As triggers of inflammation are removed the normal vascular permeability returns and there's cessation of neutrophil emigration
3. Exudate is reabsorbed into venules or flows away through lymph vessels
4. Fibrin is degraded
5. Neutrophils undergo apoptosis and are phaogcytosed along with necrotic debris by the macrophages
6. If damaged parenchymal cells can regenerate or if unable to regenerate they can form a fibrous scar.

23

In acute appendicitis what is the causative organisms and its affects?

Appendicitis is caused by a blockage of the hollow portion of the appendix,most commonly by a calcified "stone" made of feces. However, inflamed lymphoid tissue from a viral infection, parasites, gallstone, or tumors may also cause the blockage. This blockage leads to increased pressures within the appendix, decreased blood flow to the tissues of the appendix, and anaerobic bacterial growth inside the appendix causing inflammation. Necrosis can lead to rupture of appendix and release of contents into peritoneum.

24

In bacterial meningitis what is the causative organisms and its affects?

In:
Children - Group B streptococcus, E coli, Listeria monocytogenes and Streptococcus pneumoniae
Adults - Streptococcus pneumoniae and Neissaria meningitidis
It causes inflammation of the brain and therefore a rise in intracranial pressure which can lead to neurone damage , occlusion of blood vessels leading to ischaemia and optic nerve damage, causing vision problems.

25

In ascending cholangitis and liver abscess what is the causative organisms and its affects?

This is an infection of the bile duct, usually caused by bacteria ascending from its junction with the duodenum. It tends to occur if the bile duct is already partially obstructed by a gallstone. It's caused mainly by gram-negative bacteris which live in the intestinal tract e.g. enterobacterus, E.coli etc...

26

What is the inherited disorder, hereditary angio-oedema?

A rare autosomal dominant condition in which sufferers have an inherited deficiency of C1-esterase inhibitor (a component of the complement system). Patients have attacks of non-itchy cutaneous angio-odemea (rapid oedema of the dermis, subcutaneous tissue, mucosa and submucosal tissues). They also experience recurrent abdominal pain which is due to intestinal oedema. There is often a family history of sudden death which is due to laryngeal involvement.

27

What is the inherited disorder, alpha-1 antitryspin deficiency?

A autsomal recessive disorder with varying levels of severity in which there are low levels of alpha-1 antitrypsin, a protease inhibitor which deactivates enzymes released by neutrophils at the site of inflammation. Patients with the disorder develop emphysema as proteases released from neutrophils within the lung act unchecked and destroy normal parenchymal tissue. Liver diease also occurs as the hepatocytes produce an abnormal version of the protein which is incorrectly folded. It polymerises and cannot be exported from the endoplasmic reticulum. This causes hepatocyte damage and eventually cirrhosis.

28

What is the inherited disorder, chronic granulomatous disease?

A genetic condition in which phagocytes are unable to generate the free radical superoxide, due to a genetic defect in NADPH oxidase. Therefore bacteria are phagocytosed but are unable to be killed as they are incapable of producing a respiratory burst. This results in the formation of chronic infections in the first years of life. Numerous granulomas and abscesses affecting the skin, ;lymph nodes an sometimes the lung, liver and bones occur, however they are ineffective at eminiating the infectious agent.

29

What is inflammation?

It is the response to injury of vascularised living tissue. It's purpose is to deliver defensive materials to a site of injury, to protect the body against infection (particularly bacterial), to clear damaged tissue and to initiate tissue repair.

30

What is the time scale of acute inflammation as compared to chronic inflammation?

Acute: hours or days
Chronic: months or even years

31

What is the order that defensive materials are supplied to the damaged tissue?

1. Fluid within seconds
2. Leucocytes take minutes

32

The passage of fluid and leucocytes out of blood vessels is a complex process which is controlled by what group of molecules (chemical messages)?

Chemical mediators of inflammation

33

Vasoactive amines are usually the first mediators to appear during inflammation. List two examples:

Histamine
Serotonin

34

What role does serotonin (5-HT) have in acute inflammation?

It has similar vascular effects to histamine. It, unlike histamine, is also able to stimulate fibroblasts.

35

How does aspirin and NSAIDs reduce pain and swelling?

They inhibit the enzyme cyclo-oxygenase (COX) which produces prostaglandins form arachadonic acid. Inhibition of prostaglandin synthesis reduces pain and swelling.

36

What is lymphadenitis?

Inflammation of the lymph nodes

37

List the three main types of defensive proteins in the exudate found in acute inflammation?

1. Opsonins
2. Complement
3. Antibodies

38

What are opsonins?

Defensive proteins which coat foreign materials and make them easier to phagocytose.

39

What are complement proteins?

A group of defensive proteins which assemble together to form a bacteria-perforating structure.

40

What are antibodies?

Defensive proteins which coat microbes, like opsonins, making them easier to phagocytose.

41

What is the difference between an exudate and a transudate?

An exudate is formed during inflammation and is protein-rich. A transudate is protein-poor and is an ultrafiltrate of non-leaky vessels that occurs in situations such as heart failure where there is an increased hydrostatic capillary pressure.

42

What chemical mediators induce vascular leakage?

Histamine and serotonin (from mast cells and platelets), bradykinin (plasma precursor) and the complement components C3a, C4a and C5a (also from plasma precursors).

43

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

Neutrophil

44

Where are neutrophils normally found?

They are normally found in bone marrow and blood, therefore their presence in a tissue invasion by bacteria or some other parasite and/ or tissue injury.

45

What is the lifespan of a neutrophil?

12-20 hours. They are an end cell therefore cannot multiply/

46

What are the 6 steps that a neutrophil must undergo in order to kill a bacterium in tissue space?

1. Chemotaxis - summoned to the area of injury
2. Activation - switch to a higher metabolic level
3. Margination - stick to the endothelial surface
4. diapedisis - crawl through the endothelium
5. Recognition-attachment - recognise the bacterium and attach to it
6. Phagocytosis - engulf the bacterium

47

Define chemotaxis

Chemotaxis is the directional movement towards a chemical attractant (chemotaxin).

48

How fast do neutrophils move up the chemotactic gradient?

30 micrometres/minute = approximately 2mm/ hour

49

List some chemotaxins for neutrophils

1. Bacterial products (e.g. endotoxins (a lipopolysaccharide from the outer membrane of gram negative bacteria)
2. Injured tissues
3. Substances produced by leucocytes - e.g. leukotriene B4 which is the most powerful.
4. Clotting blood (thrombin and fibrin degradation products (FDPs) are chemotaxins)

50

Why is the activation of complement chemotactic?

Activated complement releases fragments on C3, C4 and C5 (C3a, C4a and C5a) which are chemotactic - especially C5a.

51

How do neutrophils become activated?

Chemtaxins bind to their cell surface receptors and within 5 seconds Ca2+ and Na+ flood in causing cellular swelling and reorganisation of its cytoskeleton so it is roughly triangular and points in the direction of the chemotactic stimulus. Within 5-10 seconds the cell produces pseudopodia. Activated neutrophils are stickier than normal neutrophils.

52

How do neutrophils undergo diapedesis?

Neutrophils do not go between endothelial cells like fluid does, but use collegenase to digest their way through the basement membrane. This takes 3-9 minutes. Once in extravascular space they pull themselves along other cell's collagen fibres in order to move closer to their target.

53

How do neutrophils recognise bacteria?

They recognise the opsonins bound to the bacteria. The most important of which is Ig-G (this won't be present the first time the bacteria is encountered) and C3b (a complement protein which is released when complement is activated). If opsonins are not present the neutrophil recognises the microbial's cell surface antigens.

54

What is the oxygen-dependent method of microbe killing of phagosomes by neutrophils?

Oxygen or respiratory burst - release of oxygen-derived free radicals (superoxide, hydroxyl and H2O2) into the phagosome.

55

What is the oxygen-independent method of microbe killing of phagosomes by neutrophils?

Uses enzymes such as proteases, phospholipases nucleases and lysozyme.

56

What are mediators of inflammation?

Any molecule that is produced in the focus of inflammation and modulates the inflammatory response in some way.

57

List some common responses to mediators:

1. Movement (Relaxation or contraction of vascular smooth muscle cells, Contraction of venule endothelial cells, Movement along a chemotactic gradient, Phagocytosis by neutrophils)
2. Secretion

58

What limits the duration of inflammation?

1. Short half-lives of mediators (seconds-minutes)
2. Short effector response duration of mediators (minutes to hours)
3. Every mediator has inhibitors

59

How is a prolonged acute inflammation response sustained?

By continous production of mediators

60

What is the difference between cytokines and chemokines?

Cytokines are polypeptides that are produced by many cells and act as messengers between cells. Chemokines (short for chemotactic cytokines) are a group of cytokines involved in chemotaxis.

61

What type of cell produces many cytokines?

Macrophages - start to produce cytokines in the hours after injury

62

What are the main inflammatory mediators of vasodilation?

1. Histamine and serotonin (from mast cells and platelets)
2. Prostaglandins (from many cells)

63

What are the main inflammatory mediators of increased vascular permeability?

1. Histamine and serotonin (from mast cells and platelets)
2. Bradykinin (from plasma precursor kininogen)

64

What are the main inflammatory mediators of chemotaxis?

1. Leukotriene B4 (from leucocytes)
2. C5a and C3a (from complement plasma precursors)
3. Chemokines (from leucocytes and other cells)
4. Bacterial products (from bacterial metabolism)

65

What are the main inflammatory mediators of phagocytosis?

C3b (from complement plasma precursor)

66

What are the main inflammatory mediators of pain?

1. Bradykinin (from the plasma precursor kininogen)
2. Prostaglandins (from many cells)

67

How does acute inflammation result in the local complication of damage to normal tissue?

It occurs secondary to substances produced by neutrophils and released during the process of phagocytosis.

68

How does acute inflammation result in the local complication of obstruction of tubes e.g. intestine or fallopian tubes, and compression of vital structures?

This occurs secondary to the swelling produced by the inflammatory exudate.

69

Why can there be very serious consequences of fluid accumulation in an enclosed space?

The resultant increase in pressure can compress vital structures e.g.
1. Cardiac tamponade - fluid accumulation within pericardial sac reduced ventricular filling
2. Swelling of the brain -> compression of neurons, nerve tracts and coronal arteries

70

How does acute inflammation result in the local complication of loss of fluid?

Fluid accumulation in tissue spaces increases tissue pressure until no more exudation can occur. However this pressure increase does not happen in surface wounds, therefore fluid can continuously leak out and result in very large amount of fluid loss.

71

How does acute inflammation result in the systemic effect of fever?

1. Macrophages stimulated by exogenous (bacterial) pyrogens (particularly endotoxin) produce pyrogenic cytokines, e.g. TNF, Interleukin-1.
2. These cytokines cause an increase in synthesis of prostaglandin E2 within the anterior hypothalamus
3. This switches the thermostat of the body (situated in the anterior hypothalamus) to a higher setting.

72

Why can fever be a useful response to acute inflammation?

Some bacteria can't survive at high temperatures (40-41 degrees) and inflammation has been demonstrated to be more effective at higher temperatures.

73

By what mechanism does aspirin reduce fever?

It inhibits cyclo-oxygenase (COX) - the enzyme which produces prostaglandins, therefore the prostaglandin E2 increase, which triggers higher temperatures in the anterior hypothalamus, does not occur.

74

What is leucocytosis? How does acute inflammation result in the systemic effect of leucocytosis?

Leucocytosis is an increase in the number of circulating leucocytes. This occurs during acute inflammation as macrophages and endothelial cells produce colonoy stimulating factors which stimulate bone marrow to produce more neutrophils.

75

What is the acute phase response? How does acute inflammation result in the systemic effect of the acute phase response?

The acute phase response is a change in the levels of some plasma proteins that is seen because the liver changes its pattern of protein synthesis. It occurs within hours of injury produced by cytokines released during inflammation.

76

What changes in plasma proteins are observed in the acute phase response?

1. Decrease in albumin
2. Increase in fibrinogen - needed for blood clotting
3. Ceruloplasmin - free radical scavenger
4. C3 - protein of the complement system
5. Alpha-1 antitrypsin - protease inhibitor
6. C-reactive protein (CRP) - an opsonin

77

In serious injuries, what are the symptoms observed due to the acute phase response?

Sleepiness and lack of appetite.

78

How does acute inflammation result in the systemic effect of shock?

If bacterial products or inflammatory mediators spread around the body in the blood stream, inflammation can occur throughout the body. This results in shock. Shock is a dramatic drop in blood pressure due to widespread vasodilation and increase in vascular permeability with resultant fluid exudation. It is often fatal.

79

List four types of exudate

1. Pus/abscess
2. Haemorrhagic exudate
3. Serous exudate
4. Fibrinous exudate

80

What is pus/abscess exudate and when does it occur?

It occurs in an abscess and is creamy/white as it is rich in neutrophils. This type of exudate is typical of infections caused by chemotactic bacteria.

81

What is haemorrhagic exudate and when does it occur?

It is an exudate that contains enough red blood cells to appear bloody to the naked eye. It indicates that as well as inflammation significant vascular damage has occurred. It is seen in destructive infections or where exudate is a result of infiltration by a malignant tumour.

82

What is serous exudate and when does it occur?

Serous exudate contains plasma proteins but few leucocytes suggesting that there is no infection by microbes. They are clear and typically seen in blisters. e.g. after a mild burn.

83

What is the difference between serous exudate, plasma and transudate?

Unlike transudates, serous exudate contains plasma proteins, and plasma unlike serous exudate contains fibrinogen.

84

What is a seroma?

A tissue space filled with a clear, sterile fluid that occurs as a post-operative complication.

85

What is fibrinous exudate and when does it occur?

An exudate where there is a significant deposition of fibrin (i.e. a blood clot without the red blood cells). When fibrinous exudates occur in the pericaridal or pleural spaces the fibrin that is deposited means that the serosal surfaces no longer slide smoothly over each other. This results in friction between the serosal surfaces which can be heard as a rubbing sound/