Ischaemia and Infarction

Question 1

Ischaemia is

Answer 1

inadequate local blood supply to a tissue.

-Causes hypoxia and reduced transfer of metabolic substances (eg glucose and catabolites)

Question 2

Hypoxia is

Answer 2

deficiency of O2 which causes cell injury

Question 3

ANoxia is

Answer 3

COmplete lack of O2

Question 4

Infarction. Results from?

Answer 4

necrosis of a tissue due to ischaemia.

thrombosis/embolism, spasm, extrinsic compression of vessel

Question 5

Possible causes of Ischaemia

Answer 5

Ext/int occlusion of vessels (bed sores or atherosclerosis)

Spasm of vessel
capillary block (sickle cell anaemia)
shock (low arterial BP)
Increased Demand (inc tissue mass, workload)
venous obstruction

Question 6

Sensitivity of different cell types to Ischaemia from least to most

Answer 6

Fibroblasts & macrophages
Skeletal muscle
Myocardium
Renal proximal tubular epithelium
Neurons

Question 7

Neutrophils sensitivity to ischaemia?

Answer 7

Right OFF the scale, and actually do better with ischaemia!!
Their resistance to apoptosis and necrosis is enhance by hypoxia!
A number of genes are turned on at the transcriptional level, which turn on many enzymes required for survival.

Question 8

Main Transcription factor turned on by hypoxic neutrophils?

Answer 8

HIF which leads to survival.

Question 9

Why is is the Neutrophils are enhanced in hypoxic environments?

Answer 9

The role of neutrophils is often required in hostile, damaged environments, therefore it makes sense that their survival is enhanced.

Question 10

Effect of ischaemia on cells, If not severe or of long enough duration

Answer 10

still changes cell biology.

Reduced ATP availability (all energy mechanisms crippled).

More activation of signalling cascades> protect and repair

Question 11

How does ischaemia cause lowered ATP?

Answer 11

Increased anaerobic glycolysis
low glycogen
lower pH
nuclear chromatin clumping

Decr Na+ pumps
influx of calcium, water and Na+
ER swelling, cell Swelling, loss of micro villi.

Protein breakdown

Question 12

Do ischaemic cells usually die by apoptosis or necrosis?

Answer 12

Necrosis, due to the lowered ATP levels there’s not enough energy to allow the process of apoptosis to occur

Question 13

Levels of ischaemic effect?

Answer 13

No effect
Functional defects (due to sub-optimal tissue perfusion)
Adaptation, atrophy and shut down
Apoptosis 
Infarction/necrosis

A LARGE RANGE, functional parenchyma more at risk

Question 14

Other factors that influence the outcome for tissues of vessel occlusion

Answer 14

Anatomy, size of occlusion, speed of onset, repurfusion, metabolic demands, adequency

Question 15

Red (haemorrhagic) infarcts may occur in?

Answer 15

• tissue with dual blood supply (lung)
• Tissues where blood flow is re-established after arterial occlusion

(pumping blood into dead tissue)

Question 16

White (anaemic) infarcts occur in

Answer 16

-solid tissues supplied by a single artery, often wedge shaped.
(bc usually artery supplies wedge tissue)

Question 17

Coagulative necrosis

Answer 17

usual pattern after infarction in solid organs

Question 18

how to get ischaemia in ARTERY

Answer 18

1) artherosclerosis (turbulence and EC injury)
2) Vulnerable plaque gets damaged
3) thrombosis
4) Downstream ischaemia and infarction
5) repurfusion

Question 19

how to get ischaemia in VEIN

Answer 19

1) Venous stasis, EC injury and systemic factors
2) deep vein thrombosis forms
3) embolisation
4) distant ischaemia and infarction

Question 20

Ischaemia effect if coronary arteries were occluded

Answer 20

Angina
Chronic ischaemic heart disease with heart failure
MI > transmural or subendocardial infarction
Cerebral ischaemic injury

Question 21

Timing of a typical infarction

Answer 21

1) 24hr acute inflammation develops from viable margins
2) 1-3 days, macrophages and lymphocytes appear
3) Fibroblasts and endothelial cells then recruited > granulation tissue “organisation”
4) 6-8wks infarct organised > fibrous scar

** some tissues (liver) may attempt regeneration

Question 22

How to treat infarcts

Answer 22

Thrombolitic agents

Mechanical re-expansion

have to be done quickly before irreversible molecular events

Question 23

Complications of MI

Answer 23

mural thrombus (in heart)
Dysrhythmias
heart failure
Repurfusion injury

Question 24

Repurfusion injury

Answer 24

Short period ischaemia then repurfused : back to normal

Long period ischaemia then repurfused : additional damage due to accumulation of ROS in cells producing oxidative stress

Question 25

How exactly due free radicals damage cells in repurfusion

Answer 25

• attack double bonds
• oxidise sude chains > enzyme damage
• DNA damage

autocatalytic chain of damage