Pathophysiology of ischaemia + infarction

Question 1

Define ischaemia

Answer 1

Relative lack of blood supply to tissue/organ leading to inadequate O2 supply to meet needs of tissue/organ:

Question 2

What are the factors affecting oxygen supply

Answer 2

1. Inspired O2
2. Pulmonary function
3. Blood constituents
4. Blood flow
5. Integrity of vasculature
6. Tissue mechanisms

Question 3

What are the factor affecting oxygen demand

Answer 3

1. Tissue itself - different tissues have different requirements
2. Activity of tissue above baseline value

Question 4

What are examples of conditions that causes ischaemia

Answer 4

Hypoxia - Low oxygen
Anaemia - abnormal delivery
Stagnant - abnormal delivery
Cytotoxic - abnormal tissue

Question 5

What are the potential oxygen supply issues that can cause myocardial ischaemia

Answer 5

coronary artery atheroma, 
cardiac failure (flow),
 pulmonary function – other disease 
pulmonary oedema (LVF), 
anaemia, 
previous MI

Question 6

What are the potentially oxygen demand issue that can cause myocardial ischaemia

Answer 6

heart has high intrinsic demand, exertion/stress

Question 7

What is the clinical consequences of ischaemia due to atheroma

Answer 7

MI 
TIA - symptoms of a stroke that are resolved 
Cerebral infarction
Abdominal aortic aneurysm
Peripheral vascular disease
Cardiac failure
Stable/unstable angina

Question 8

How does atheroma cause ischaemia

Answer 8

Atheroma causes vessels radius to decrease, decreasing the flow of blood, decreasing oxygen delivery resulting in decreased supply of oxygen to an organ - ischaemia

Question 9

What is the biochemical effect of ischaemia

Answer 9

Decreased oxygen results in anaerobic respiration which promotes cell death

Question 10

What cells are more susceptible to ischaemia

Answer 10

Cells with a high metabolic rate

Question 11

What is the clinical effects of ischaemia

Answer 11

(a) Dysfunction - e.g. abnormal heart rhythms
(b) Pain

(c) Physical damage
Specialised cells

Question 12

What is the there possible outcomes of ischaemia

Answer 12

No clinical effect

Resolution versus therapeutic intervention

Infarction

Question 13

Define infarction

Answer 13

Ischaemic necrosis within a tissue/organ in living body produced by occlusion of either the arterial supply or venous drainage

cessation of blood flow

Question 14

What are examples of the aetiology of infarction

Answer 14

1. Thrombosis
2. Embolism
3. Strangulation e.g. gut
4. Trauma - cut/ruptured vessel

Question 15

What does the scale of damage in infarction depend upon

Answer 15

Time period
Tissue/organ
Pattern of blood supply
Previous disease

Question 16

What is the pathology of infarction

Answer 16

Anaerobic metabolism cell death liberation of enzymes breakdown of tissue

Question 17

What is the two types of necrosis

Answer 17

Coagulative necrosis e.g. heart, lung

Colliquitive necrosis e.g. brain

Question 18

How long does it take in myocardial ischaemia for anaerobic metabolism to occur/ ATP depletion

Answer 18

few seconds

Question 19

How long does it take in myocardial ischaemia for loss of myocardial contractility i.e. heart failure

Answer 19

< 2 minutes

Question 20

After a few minutes in a myocardial ischameia what ultrasound changes can be seen

Answer 20

myofibrillar relaxation,
glycogen depletion,
cell and mitochondrial swelling

Question 21

At what timing and stage does the affect of myocardial infarction become irreversible and why is this

Answer 21

Severe ischaemia 20-30 mins

As myocyte necrosis is occurring

Question 22

What occurs in myocyte necrosis

Answer 22

disruption of integrity of sarcolemmal membrane resulting in leakage of intracellular macromolecules

Question 23

What happens after one hour into a myocardial infarction

Answer 23

Injury to the microvasculature

Question 24

What is the appearance of infarcts in less than 24 hours

Answer 24

No change on visual inspection

A few hours to 12 hours post insult, see swollen mitochondria on Electron Microscopy

Question 25

What is the microscopic appearance if infarcts from 24-48 hours

Answer 25

acute inflammation initially at edge of infarct; loss of specialised cell features

Question 26

What is classified as pale infarct

Answer 26

Solid tissues | myocardium, spleen, kidney

Question 27

What is classified as red infarct

Answer 27

Loose tissue - previously congested | Lung, liver

Question 28

72 hours onwards into MI what is the appearance of pale and rd infarcts

Answer 28

Pale infarct - yellow/white and red periphery | Red infarct - little change

Question 29

72 hours onward into MI what can be seen microscopically

Answer 29

chronic inflammation; macrophages remove debris; granulation tissue; fibrosis

Question 30

What is Reperfusion injury

Answer 30

tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen

Question 31

What is the reparative process of MI and what is the end result

Answer 31

``` Cell death Acute inflammation Macrophage phagocytosis of dead cells Granulation tissue Collagen deposition (fibrosis) Scar formation As Scar replaces area of tissue damage ```

Question 32

What is two different type of MI

Answer 32

Subendocardial infarction | transmural infarction

Question 33

What is the affect of Subendocardial infarction

Answer 33

ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart

Question 34

What is the affect of transmural infarction

Answer 34

ischaemic necrosis affects full thickness of the myocardium

Question 35

What is the similarity and differences in reparative process in subendocardial and transmural

Answer 35

They have the same histological features but granulation tissue stage followed by fibrosis - in subendocardial infarct possibly slightly shortened compared to transmural infarct

Question 36

How is acute infarcts classified in investigation with ECG

Answer 36

according to whether there is elevation of the ST segment on the ECG

Question 37

What does it mean If no ST segment elevation but a significantly elevated serum troponin level:

Answer 37

non-STEMI

Question 38

What kind of infarct is is non STEMI thought to correlate with

Answer 38

a subendocardial infarct

Question 39

Why is it Difficult to carry out detailed studies to show link between ECG changes seen with an infarct and exact pathological features

Answer 39

because declining post mortem rates | people don't stick around long enough for us to see the pathology

Question 40

What is the complications of myocardial infarction

Answer 40

Sudden death; arrhythmias - abnormal heart rhythm angina; cardiac failure; cardiac rupture - ventricular wall, septum, papillary muscle; reinfarction - repeat infarction pericarditis; pulmonary embolism secondary to DVT; mural (bv/cavity) thrombosis; ventricular aneurysm; Dressler's syndrome