Lecture 24: Ischemia and Infarction

Question 1

What is ischemia vs hypoxia vs anoxia?

Answer 1

Ischemia = Inadequate blood supply
Hypoxia = Deficiency in oxygen causing injury
Anoxia = Complete lack of oxygen

Question 2

In addition to hypoxia what else does ischemia cause?

Answer 2

Ischemia also causes reduced transfer of metabolic substances (i.e glucose) into tissues and catabolites (i.e H+) out of tissues.

Question 3

What are the possible causes of ischemia?

Answer 3

• External occlusion i.e tumour
• Internal occlusion i.e atherosclerosis
• Spasm i.e frost bite
• Capillary blockage i.e sickle cell
• Shock i.e heamorrhage
• Increased demand i.e hypertrophy + exercise
• Venous obstruction

Question 4

Are all cells equally sensitive to oxygen deprivation?

Answer 4

No, neurons are extremely sensitive, myocardium is halfway in continuum and neutrophils work best in absence of oxygen

Question 5

Whats the impact of ischemia at the cellular level?

Answer 5

• Long duration that does kill cell will change cell biology
• Reduced ATP availability
• Rapid build up of anaerobic catabolites
• Activation of signalling cascades

Question 6

What are the effects of ischemia at a tissue level?

Answer 6

[Less damage]
- No effect
- Functional defects due to sub-optimal tissue performance i.e myocardial dysrhythmia, renal insufficiency
- Adaptation i.e fatty change, atrophy and shut down
- Apoptosis of isolated cells
- Infarction = necrosis of most/all cells in a tissue due to overwhelming ischeamic injury
[Most damage]

Question 7

What are some other factors that can influence the outcomes for tissues of vessel occlusion?

Answer 7

- Anatomy of the blood supply to organ;
 \+ End organs 
 \+ Organs with collateral circulation
- Size of the occluded vessel
- Speed of onset
- Duration of occlusion
- Reperfusion
- Metabolic demands of the tissue at the time
- Adequacy of circulatory system i.e HF and anaemia

Question 8

What is infarction?

Answer 8

Infarction is necrosis (non-programmed cell death) of a tissue due to ischeamia

Question 9

What do infarctions result from?

Answer 9

Infarctions result from thrombosis or embolism, spasm, torsion or extrinsic compression of vessels

Question 10

Whats a red heamorrhage? and white?

Answer 10

Infarcts that occur from:

• TIssues with dual blood supply i.e lungs
• Tissues where blood supply is reestablished after infarct

White infarct is where the blood supply is not re-established

Question 11

What can ischemic heart disease lead to?

Answer 11

IHD = Narrowing of coronary art.

Leads to;

• Angina pectoris (transient ischemia, no necrosis)
• Chronic ischeamic HD with HF
• MI (transmural, subendocardial infarct)
• Cerebral ischeamic injury

Question 12

Describe the timing and events of a typical infarction:

Answer 12

• Within 24hr acute inflam (neutrophils) devepps from the viable margins
• 1-3days macrophages and lymphocytes appear
• Fibroblasts and endothelial cells are then recruited (Organisation of injury) to form granulation tissue
• Over 6-8 weeks the infract is organised (Replaced by a non-functional fibrous scar)
• Some tissues i.e liver may attempt regeneration

Question 13

How can MI be treated?

Answer 13

• Thromobolitic agents (i.e streptokinase or tissue type plasminogen activator)
• Mechanical re-expansion of the occluded vessel (Angioplasty + Stenting) or CABG
• Further issues due to reperfusion injury

Question 14

What are the complications of MI?

Answer 14

• Mural thrombosis leading to embolism via aorta to brain, gut, spleen etc
• Dysrhythmias
• HF
• Reperfusion injury

Question 15

What are the effects of reperfusion following ischaemia;

Answer 15

Short periods of ischemia followed by reperfusion may result in complete reversal of ischeamic cell injury

Long periods of ischeamia followed by reperfusion may cause additional damage to cells

Question 16

Describe how reperfusion can result in injury?

Answer 16

Reperfusion brings oxygenated blood back to the tissue and after long periods of ischeamia the aerobic mechansims are offline thus oxygenation results in the formation of ROS, if sufficient causing oxidative stress when the protective mechanisms cant cope.

Question 17

What damage can ROS cause?

Answer 17

• Oxidation of thymine residues
• Oxidation of AA side chains, enzyme damage
• Oxidation of UFA double bonds, lipid peroxidation

Autocatalytic reactions propagate a chain of damage.

Question 18

Describe the flow diagram of atherosclerosis in an artery;

Answer 18

Atherosclerosis in an artery-> turbulence and EC damage
\+
Vulnerable plaque becomes damaged
\+
Thrombosis
\+
Downstream ischemia and infarction
\+
Reperfusion

i.e consider synergistic risk factors, virchows triangle, ischemia ATP depletion etc, Reperfusion ROS

Question 19

Describe the flow diagram of atherosclerosis in an vein:

Answer 19

Venous stasis, EC injury and systemic factors
+
Deep vein thrombosis
+
Emolisation and/or fibrinolysis and recanalisation
+
Distant ischemia and infarction

Question 20

Following ischemia and infarction what are the flow on effects?

Answer 20

Cell injury
Inflammation
Healing and repair