Cell Death and Perfusion Disorders 2

Question 1

Define hypoxia

Answer 1

Inadequate oxygenation of the blood.

Question 2

Define anemia

Answer 2

Inadequate oxygen carrying capacity of the blood.

Question 3

Define ischemia

Answer 3

Inadequate delivery of blood to tissue (decreased blood flow).

Question 4

What are the four causes of ischemia?

Answer 4

• vascular occlusion
• vasospasm
• shock
• Infarct

Question 5

What causes a vascular occlusion?

Answer 5

Thrombus or foreign body

Question 6

What occurs in hypovolemic shock?

Answer 6

A large amount of blood is lost in a small amount of time, decreases forward blood flow.

Question 7

Define infarct

Answer 7

Area of ischemic necrosis where all tissue elements are dead. Necrosis of all cell types.

Question 8

What are the cellular events that can lead to necrosis in hypoxia/ischemia?

Answer 8

draw diagram…see notes

Question 9

What are the 5 factors influencing the significance of ischemia?

Answer 9

• pre existing collateral circulation
• rapidity of development of ischemia
• type of tissue/degree of metabolic activity
• whether ischemia is due to defect in arterial or venous perfusion
• whether or not there is reperfusion injury (less common in vet med)

Question 10

How does pre-existing collateral circulation relate to the significance of ischemia?

Answer 10

With only one blood supply, a disruption means there is likely greater risk since no other blood supply to tissue with lack of collateral circulation.

Question 11

Define thrombus

Answer 11

Clot of blood attached to wall that occludes flow.

Question 12

Define thromboembolism

Answer 12

Thrombus throw off bits that quickly block vessel.

Question 13

Why is it important to consider the type of tissue and degree of metabolic activity in ischemia?

Answer 13

Brain starts to undergo necrosis after 4 minutes in ice.

Consider skeletal vs muscle vs brain or cells within a tissue, ie renal stroma vs tubular epithelium.

Question 14

What is a saddle thrombus in cats?

Answer 14

Thrombosis of the distal feline aorta -> ischemia of the hindlimb. This if lifethreating as the thromboembolism quickly disrupts flow.
-sudden onset, no femoral pulses, limbs cold, paralyzed, due to hypertrophic cardiomyopathy
Heart enlarged, blood pools in atria, disruptive event releases clot to bifurcation of femoral artery.

Question 15

What is an anoxic cellular injury?

Answer 15

Inadequate oxygenation of blood (hypoxia).

Can be from anemia (lack of RBCs) or pneumonia (lack of aeration of red cells).

Question 16

Which zone of liver cells are most susceptible to hypoxia?

Answer 16

Zone 3, the cells in the centre of the lobule.

Question 17

What is the difference between arterial and venous impairment of blood flow (ischemia)?

Answer 17

Arterial: initially pale, area of affected artery has been blocked.
Venous: deep red-black congested as accumulation of blood in vessels. Congestion and lack of outlflow in blood.

Question 18

Why are tissues supplied by end arteries more susceptible to infarction?

Answer 18

Examples such as areas served by interlobar or arcuate arteries in the kidney lack collateral circulation, so infarct is much more severe in these areas, may see a triangular appearance in kidneys.

Question 19

What is the shape of renal arterial infarcts dictated by?

Answer 19

End-arterial circulation.

Question 20

What causes the pallor in arterial infarcts?

Answer 20

Loss of blood supply with swelling of necrotic cells and lack of RBC in the dead tissue. There may be an increased zone of redness surrounding necrosis as necrosis stimulates inflammation.

Question 21

When does hemoglobin start to break down and what colour does it start as?

Answer 21

Starts to break down and show green colour around 3 days.

Question 22

How long does it take in a peripheral hemorrhage for red cells to seep into infarcted tissue?

Answer 22

~24-36 hours

Question 23

What are the three colours of hemoglobin breakdown?

Answer 23

Biliverdin - green
Bilirubin - olive/yellow
Hemosiderin - brown

Question 24

What are infarcts replaced by in time?

Answer 24

In a few weeks, infarcts will be replaced by scars. The dead tissue is derided by macrophages and replaced by fibrous tissue.
Only regeneration and wound healing if cells regenerate.

Question 25

What happens to scar tissue as it matures?

Answer 25

Contracts, so will see a depression in the surface of the organ.

Question 26

What kind of infarcts are intestinal infarcts most commonly?

Answer 26

Venous infarcts due to torsion or volvulus. Twist in intestine preventing outflow of blood, lack of oxygen.

Question 27

When do venous infarcts occur?

Answer 27

Whenever the venous return from a tissue field is compressed before the arterial supply is obstructed.

Question 28

Is venous infarction of the intestine well-demarcated?

Answer 28

Yes, the intestine has a segmental vascular supply and drainage, so the lesion appears segmental. When the displacement or twist is reduced, a sharp margin usually is visible between the deeply congested infarcted gut and adjacent more normal intestine.

Question 29

How can reperfusion injury damage ischemic tissue more?

Answer 29

- reflow of blood into area of moderate hypoxia results in additional damage to sub lethally injured cells and may tip cells to necrosis - reflow increases free radical generation and inflammation - often necrosis has already occurred in animals once ischemia has started to be treated

Question 30

What is a watershed zone?

Answer 30

Reduced arterial blood flow may cause ischemia in regions between two arterial supplies where collateral circulation is poorest. Eg pelvic flexure and tip of cecum.

Question 31

What is renal papillary necrosis due to?

Answer 31

reduced perfusion of the medulla/papilla associated with NSAIDS blocking prostaglandin production in horses

Question 32

What is the cause of gangrene in peripheral tissues?

Answer 32

Frostbite - gangrene is necrosis in peripheral tissues. Can be a complication of diabetes. Cold -> vasoconstriction -> ischemia coupled with direct freezing injury to cells.

Question 33

What is the type of necrotic lesion influenced by?

Answer 33

- distribution of the noxious insult (blood borne or inhaled) - relative susceptibility of the cells or tissue (cell metabolism-zone 3 hepatocytes vs zone 1; renal tubules vs interstitial) - blood supply (end artery or collateral circulation)

Question 34

What necrosis pattern does a randomly distributed lesion suggest in the liver?

Answer 34

A multifocal random distribution of areas of necrosis suggests a blood borne infectious agent. Lots of pin point foci of necrosis.

Question 35

What necrosis pattern do non-random lesions indicate in the liver?

Answer 35

The disease process is targeting specific anatomic zones of the tissue. Some toxins and metabolic disorders produce such lesions.

Question 36

In the lung, when necrosis is localized to the anterior-ventral regions, what was the necrosis pattern of injury?

Answer 36

Inhaled

Question 37

What do the distribution of lung lesions tell us?

Answer 37

Whether the injurious stimulus was inhaled or blood borne.

Question 38

In the lung, when there are random white foci, what was the necrosis pattern of injury?

Answer 38

Blood-borne injury

Question 39

What are the characteristics of coagulation necrosis?

Answer 39

- basic tissue architecture still intact - pale - swollen - friable

Question 40

What does necrosis of fat look like macroscopically?

Answer 40

Mineralized and chalky. White firm foci.

Question 41

What does necrosis of fat look like microscopically?

Answer 41

Basophilic areas of mineralization in necrotic adipocytes. Precipitation of calcium.

Question 42

What happens if necrotic tissue on a surface sloughs off?

Answer 42

It can cause ulcers.

Question 43

How does severe necrosis heal?

Answer 43

By scarring (if epithelium unable to grow over).

Question 44

What is the significance of necrosis related to?

Answer 44

Its location, size, rate of development and sequelae.

Question 45

Define sequestrum

Answer 45

A focus of coagulation necrosis that fails to undergo liquefaction snd debridement, usually because blood flow is completely cut off, inhibiting the immigration of neutrophils and macrophages.

Question 46

Where do circulating bacteria settle in young animals?

Answer 46

In growth plates. The bone will continue to grow towards the lesion, deformation towards the lesion.

Question 47

Is bone a common site for sequestrum?

Answer 47

Yes, mainly due to poor vascular infiltration of the necrotic region. Tissue hard to digest,