Cell Death and Perfusion Disorders 2 Flashcards
Define hypoxia
Inadequate oxygenation of the blood.
Define anemia
Inadequate oxygen carrying capacity of the blood.
Define ischemia
Inadequate delivery of blood to tissue (decreased blood flow).
What are the four causes of ischemia?
- vascular occlusion
- vasospasm
- shock
- Infarct
What causes a vascular occlusion?
Thrombus or foreign body
What occurs in hypovolemic shock?
A large amount of blood is lost in a small amount of time, decreases forward blood flow.
Define infarct
Area of ischemic necrosis where all tissue elements are dead. Necrosis of all cell types.
What are the cellular events that can lead to necrosis in hypoxia/ischemia?
draw diagram…see notes
What are the 5 factors influencing the significance of ischemia?
- 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)
How does pre-existing collateral circulation relate to the significance of ischemia?
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.
Define thrombus
Clot of blood attached to wall that occludes flow.
Define thromboembolism
Thrombus throw off bits that quickly block vessel.
Why is it important to consider the type of tissue and degree of metabolic activity in ischemia?
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.
What is a saddle thrombus in cats?
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.
What is an anoxic cellular injury?
Inadequate oxygenation of blood (hypoxia).
Can be from anemia (lack of RBCs) or pneumonia (lack of aeration of red cells).
Which zone of liver cells are most susceptible to hypoxia?
Zone 3, the cells in the centre of the lobule.
What is the difference between arterial and venous impairment of blood flow (ischemia)?
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.
Why are tissues supplied by end arteries more susceptible to infarction?
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.
What is the shape of renal arterial infarcts dictated by?
End-arterial circulation.
What causes the pallor in arterial infarcts?
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.
When does hemoglobin start to break down and what colour does it start as?
Starts to break down and show green colour around 3 days.
How long does it take in a peripheral hemorrhage for red cells to seep into infarcted tissue?
~24-36 hours
What are the three colours of hemoglobin breakdown?
Biliverdin - green
Bilirubin - olive/yellow
Hemosiderin - brown
What are infarcts replaced by in time?
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.
What happens to scar tissue as it matures?
Contracts, so will see a depression in the surface of the organ.
What kind of infarcts are intestinal infarcts most commonly?
Venous infarcts due to torsion or volvulus. Twist in intestine preventing outflow of blood, lack of oxygen.
When do venous infarcts occur?
Whenever the venous return from a tissue field is compressed before the arterial supply is obstructed.
Is venous infarction of the intestine well-demarcated?
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.
How can reperfusion injury damage ischemic tissue more?
- 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
What is a watershed zone?
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.
What is renal papillary necrosis due to?
reduced perfusion of the medulla/papilla associated with NSAIDS blocking prostaglandin production in horses
What is the cause of gangrene in peripheral tissues?
Frostbite - gangrene is necrosis in peripheral tissues. Can be a complication of diabetes.
Cold -> vasoconstriction -> ischemia coupled with direct freezing injury to cells.
What is the type of necrotic lesion influenced by?
- 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)
What necrosis pattern does a randomly distributed lesion suggest in the liver?
A multifocal random distribution of areas of necrosis suggests a blood borne infectious agent. Lots of pin point foci of necrosis.
What necrosis pattern do non-random lesions indicate in the liver?
The disease process is targeting specific anatomic zones of the tissue. Some toxins and metabolic disorders produce such lesions.
In the lung, when necrosis is localized to the anterior-ventral regions, what was the necrosis pattern of injury?
Inhaled
What do the distribution of lung lesions tell us?
Whether the injurious stimulus was inhaled or blood borne.
In the lung, when there are random white foci, what was the necrosis pattern of injury?
Blood-borne injury
What are the characteristics of coagulation necrosis?
- basic tissue architecture still intact
- pale
- swollen
- friable
What does necrosis of fat look like macroscopically?
Mineralized and chalky. White firm foci.
What does necrosis of fat look like microscopically?
Basophilic areas of mineralization in necrotic adipocytes. Precipitation of calcium.
What happens if necrotic tissue on a surface sloughs off?
It can cause ulcers.
How does severe necrosis heal?
By scarring (if epithelium unable to grow over).
What is the significance of necrosis related to?
Its location, size, rate of development and sequelae.
Define sequestrum
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.
Where do circulating bacteria settle in young animals?
In growth plates. The bone will continue to grow towards the lesion, deformation towards the lesion.
Is bone a common site for sequestrum?
Yes, mainly due to poor vascular infiltration of the necrotic region. Tissue hard to digest,
