Inflammation 3

Question 1

What is another name for a heart attack?

Answer 1

Myocardial infarction = Heart attack
Myo-muscle
Cardial - Heart
Infarction - death of tissue after loss of oxygen

Question 2

How does the heart normally work?

Answer 2

The heart is a muscle (cardiac myocytes).
Muscles need energy to contract.
Require ATP.
ATP is generated through respiration and the use of O2.

Question 3

What is the definition of Infarction?

Answer 3

Cell death after loss of O2

Question 4

Hoe does Hypoxic Injury and then cell death occur?

Answer 4

Hypoxia causes cell injury and then acute inflammation because
No oxygen = No ATP
and therefore the cell cannot undergo metabolism.

Question 5

What happens in the cell when there are no ATP available?

Answer 5

Na/K ATPase fails - increased K, swelling.
Calcium pump fails - increased intracellular calcium.
Increased calcium stimulates
- ATPase (makes things worse)
- Phospholipase (membrane damage)
- Proteases (membrane and cytoskeleton damage)
- Endonuclease (DNA damage and breakdown)
- Mitochondrial permeability (release pro death factors)

Question 6

What is Reversible Injury?

Answer 6

Reversible injury occurs If mild and short lived damage to cells doesn’t always result in cell death.

Question 7

Within the first 20 minute window what can or cannot be seen on the heart?

Answer 7

Nothing to see
See changes on an ECG
At autopsy - no macroscopic changes (naked eye changes)
Under the microscope - still no changes

Question 8

After the heart’s 20 minute window is over, what happens next, what are the 1st signs and what happens over the 1st 24 hours?

Answer 8

Cell death.
Cells die through 2 methods - apoptosis or necrosis.
Hypoxic injury - pathological and results in necrosis.
1st signs,
- Cells shrink (pyknotic)
- Become red
- Nucleus shrinks and becomes dark
- Marginal contraction bands appear.
1st 24 hours
- Revision
- Cell contents leaked
- Complement cascade initiated
- Acute inflammation

Question 9

what vascular changes occur with inflammation?

Answer 9

Vasodilation.
Slowing of flow.
White cell margination.
Rolling.
Pavementing (leukocytes adhere to the linings of capillaries).
Diapedesis(the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation).
Chemotaxis (movement of a motile cell or organism, or part of one, in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance.).
Phagocytosis.
Gross changes occur because of vascular changes.

Question 10

What is the role of neutrophils?

Answer 10

Phagocytic properties.
Cytokine production.
Neutrophils are associated with acute inflammation
(They essentially gobble everything up as do not differentiate between cells).

Question 11

What is Necrosis, and what are the different types of necrosis?

Answer 11

The cells are dead and neutrophils mop them up.
Types of necrosis
- Caseous
- Liquefactive
- Coagulative - cell death with some structure of cells left as “ghost outline” before complete phagocytosis of material.

Question 12

What are the Clinical Implications of inflammation to the heart?

Answer 12

At this point the wall of the heart is the weakest.
Necrosis and neutrophils may be all that is holding together if the full thickness is affected.
Implication - risk of cardiac rupture. Greatest at 3-7 days.

Question 13

What 4 processes could possibly follow Acute Inflammation?

Answer 13

Resolution
Restitution
Suppuration
Chronic inflammation

Question 14

What is restitution and what happens during restitution?

Answer 14

Gradual process.
Progressive scarring.
Macrophages fade away and are replaced by fibroblasts.

Question 15

What is the role of fibroblasts, how long does it take them to complete this task and once they have finished what consequence does this have?

Answer 15

Gradually lay down collagen.
Occurs progressively after 2 weeks after injury.
Complete at 6 weeks.
So if an MI occurred more than 6 weeks ago

Question 16

Whether scarring occurs depends on what, and what is the problem with scarring?

Answer 16

Whether scarring occurs depends on the amount of damage.
If scar tissue has replaced an area of muscle, the muscle can’t pump as well.
Results in a weak heart and the picture of heart failure.
The pumping of the heart is controlled by a sophisticated pacemaker. Nerve like bundles through the heart that relay the correct pace.
When an area is damaged and the pacemaker isn’t heard properly.
(There’s no nerves, hairs or sweat glands and an electrical signal causes the heart to pump and it is a coordinated contraction. If you’ve disrupted that network it wont pump vey well).

Question 17

What is the window of reversible injury in the heart, and what can be done within this window?

Answer 17

Myocardium - 20 minute window (Important number).
History - has it lasted longer than 20 mins?
After 30 mins there is no point in using clot busting drugs. The cells are going to die anyway.
(After a certain length of time the clot busting drugs are not going to work because after a certain window the cells are going to be dead).

Question 18

At what point can definite changes be seen at autopsy and what can be seen down the microscope?

Answer 18

As time progresses, neutrophils fade away and are gradually replaced by macrophages.
At this point definite changes can be seen at autopsy. The presence of macrophages imparts a yellow appearance.
Down the microscope - macrophages.

Question 19

What process(es) normally occur following chronic inflammation?

Answer 19

No suppuration - no persistence of injury (if there is then death usually occurs).
So resolution or restitution.

Question 20

When does resolution occur?

Answer 20

Only if short duration of injury and if injury is mild and blood supply is good.
MI - blood supply is almost by definition poor.
Generally, once cell death has occurred then resolution is unlikely in the heart.
Remember different tissues heal better than others e.g. liver, skin vs. brain.

Question 21

What can myocardial inflammation result in?

Answer 21

Hypoxia - small vessels
Tissue damage - acute inflammation and cell death
Time period - determines what happens
Chronic inflammation then restitution.