Pathology - inflammation

Question 1

What are some vascular changes that occur in response to injury?

Answer 1

• Changes in flow and vessel caliber and vasodilation
• These first involve arterioles and then capillary beds

Question 2

What chemicals mediate vasodilation and what is the result of vasodilation?

Answer 2

Mediated by histamine and nitric oxide and results in increased heat (calor) and redness/erythema (rubor)

Question 3

What are some cellular changes that occur in response to injury?

Answer 3

Stasis, white cell margination, rolling, adhesions, migration

Question 4

How is white cell margination able to occur after injury?

Answer 4

Vasodilatation occurs which slows the rate of blood flow making cells able to move peripherally - especially larger white cells

Question 5

Name some chemical mediators that are expressed after injury

Answer 5

• Selectins - expressed on endothelial cell surface
• Integrins - bind to vessel walls, cell matrix and other cells
• Vascular cell adhesion molecule (VCAM)
• Intercellular adhesion molecule (ICAM)

Question 6

What chemicals cause release of inflammatory mediators in cells?

Answer 6

• Histamine and thrombin increase selectin expression
• TNF and IL-1 increase endothelial expression of VCAM and ICAM

Question 7

What substance increaes the affinity of VCAMs and ICAMs for integrins?

Answer 7

• Chemokines from the site of injury bind to proteoglycans on endothelial cell surface.
• These proteoglycans then increase the affinity of VCAMs and ICAMs for integrins

Question 8

What happens as a result of vascular permeability in response to injury?

Answer 8

• Leaky blood vessels - loss of proteins
• Change in osmotic pressure - water follows protein - swelling

Question 9

What happens in chemotaxis?

Answer 9

Cells follow a chemical gradient and move along it

Question 10

What are the 3 phases of phagocytosis?

Answer 10

1. Recognition and attachment
2. Engulfment
3. Killing and degradation

Question 11

What is involved in the recognition and attachment stage of phagocytosis?

Answer 11

• Mannose receptors
  
  • Bacterial surface glycoproteins and glycolipids contain terminal mannose residues.
  • Mammalian glycoproteins and glycolipids do not
• Scavenger receptors - similar to mechanism that phagocytes recognise low density lipoprotein
• Opsonins - bacteria etc are coated with proteins making them stand out, include components of the complement cascade as well as Ig

Question 12

What is involved in the engulfment stage of phagocytosis?

Answer 12

• Pseudopods
• Vesicle formation - phagosome
• Joins with lysosome - phagolysosome

Question 13

What is involved in the killing and degradation stage of phagocytosis?

Answer 13

• Reactive oxygen species
  
  • NADPH oxidase - oxygen gains an electron from NADPH and becomes superoxide
• Reactive nitrogen species
  
  • Nitric oxide synthase - combines NO with superoxide and produces ONOO

Question 14

What are the clinical features of inflammation according to Celsus?

Answer 14

Rubor (erythema), calor (heat), tumor (swelling), dolor (pain) and loss of function

Question 15

What mediates the pain/dolor part of the inflammatory response?

Answer 15

Prostaglandins and bradykinin

Question 16

What is the main cell of acute inflammation?

Answer 16

Neutrophil

Question 17

What is the resolution stage of inflammation?

Answer 17

Complete restoration of the tissue to normal after removal of inflammatory components

Question 18

What is needed for effective resolution?

Answer 18

• Minimal cell death
• Tissue has capacity to repair (e.g. GI tract frequently replaces epithelium)
• Good vascular supply
• Injurious agent easily removed

Question 19

What is suppuration?

Answer 19

• Pus - contains living, dying and dead cells, neutrophils, bacteria and inflammatory debris (fibrin)
• May be termed an abscess

Question 20

When a space is filled by pus and walled off what is it called?

Answer 20

An empyema

Question 21

When does organisation occur as part of the inflammatory process?

Answer 21

Mucosa where damage goes beyond the basement membrane favours healing by organisation and repair, not resolution

Question 22

When can resolution occur as part of the inflammatory healing process?

Answer 22

• Erosions and abrasions describe injury with basement membrane intact.
• These heal rapidly with complete resolution

Question 23

How is granulation tissue formed?

Answer 23

• Defect is slowly infiltrated by capillaries and then by myofibroblasts
• Deposit collagen and smooth muscle cells
• Given constituents it looks very red

Question 24

What happens when there is too much scarring and fibrosis of the liver?

Answer 24

• Cirrhosis occurs - results in liver failure
• The liver has some regenerative capacity but can be overwhelmed

Question 25

What happens as a result of liver cirrhosis?

Answer 25

* Liver failure - loss of liver function, can't remove toxins and can't make any proteins * Plus, large volume of blood flows throughout the liver so can result in vascular disturbances

Question 26

What factors favour chronic inflammation?

Answer 26

* Suppuration * Persistence of injury * Infectious agent e.g. virus * Type of injury - autoimmune, transplant rejection

Question 27

What is a granuloma?

Answer 27

Aggregate of epitheloid histiocytes

Question 28

What can cause granuloma formation?

Answer 28

* Foreign bodies: * Endogenous - keratin, bone, crystals * Exogenous - talc, asbestos, suture material, oil * Specific infection, parasites, syphilis * Mycobacterium - TB

Question 29

What is the characteristic feature of a granuloma caused by TB?

Answer 29

Caseous necrosis - cheesy necrosis

Question 30

How does hypoxia cause cell injury and then acute inflammation?

Answer 30

* No oxygen = No ATP * No ATP: * Na/K ATPase fails -\> increased K + swelling * Ca pump fails -\> increased intracellular Ca * increased Ca stimulates; ATPase, phospholipase (membrane damage), proteases (membrane and cytoskeleton damage), endonuclease (DNA damage and breakdown) and mitochondrial permeability (release pro death factors)

Question 31

What are the first signs in cells after an MI?

Answer 31

* Cells shrink, become red, nucleus shrinks and becomes dark * Marginal contraction bands appear

Question 32

What happens in the first 24 hours following an MI?

Answer 32

Cell contents leaked, complement cascade initiated and acute inflammation

Question 33

At what point is the heart most susceptible to cardiac rupture post-MI?

Answer 33

* 3-7 days post-MI * Necrosis and neutrophils may be all that is holding it together if the full thickness is affected

Question 34

What happens after the acute inflammation response to an MI (48 hours)?

Answer 34

* Resolution, restitution and chronic inflammation * As time progresses, neutrophils fade and are replaced by macrophages * At this point definite changes can be seen at autopsy - presence of macrophages causes a yellow appearance

Question 35

Would resolution ever occur after an MI?

Answer 35

* Only if it was short lived and if the injury was mild and blood supply was good * MI - blood supply is by definition poor, generally once cell death has occurred **resolution is unlikely**

Question 36

Describe the process of restitution after an MI

Answer 36

Progressive scarring - macrophages fade and are replaces by fibroblasts

Question 37

How long after an MI do fibroblasts start to work?

Answer 37

Occurs progressively after **2 weeks** and is **complete at 6 weeks,** so if an MI occurred more than 6 weeks ago it is impossible to date it i.e. could be 7 weeks or 7 years

Question 38

What is the issue with scarring of the heart post-MI?

Answer 38

* Scar tissue has replaced an area of muscle so the muscle can't function as well which results in a weaker heart -\> **heart failure** * Scar tissue can also damage the nerves innervating the heart causing **ineffective pace making**