FOM 5.3.3

Question 1

What are the basic defects of volume regulation in reversible damage?

Answer 1

ATP depletion

Increased permeability to sodium

O2 free radical damage to the membrane of Na-K pump

Question 2

What is the basis of necrosis?

Answer 2

Loss of calcium homeostasis

Membrane defects

Mitochondrial damage.

Question 3

What is the effect of hydroxyl radicals on the membrane?

Answer 3

Hydroxyl radicals leads to lipid peroxidation, which can subsequently destroy the lipid membrane. The formation of one peroxy radical on one chain of the hydrophobic tail of the lipid bilayer puts that radical in close approximation to another lipid. An autocatalytic reaction ensues, destroying membranes, until it is terminated. It can also destroy the membranes of mitochondria, resulting in the release of pro-apoptotic molecules, shutting down ATP production.

Question 4

What is hydropic swelling and is it reversible or irreversible?

Answer 4

Cellular swelling or hydropic change is the first manifestation of almost all forms of injury to cells. It is a difficult morphologic change to appreciate with the light microscope; it may be more apparent at the level of the whole organ. When it affects many cells, it causes some pallor, increased turgor, and increase in weight of the organ. On microscopic examination, small clear vacuoles may be seen within the cytoplasm; these represent distended and pinched-off segments of the ER. This pattern of nonlethal injury is sometimes called hydropic change or vacuolar degeneration . Swelling of cells is reversible. Cells may also show increased eosinophilic staining, which becomes much more pronounced with progression to necrosis (described later).

Question 5

What is this an example of?

Answer 5

Hydropic swelling?

Question 6

What is this picture associated with and is it reversible or irreversible?

Answer 6

This is free ribosomes which is a reversible type of damage.

Question 7

What are the main ultrastructural changes of reversible cell damage?

Answer 7

1. Plasma membrane alterations, such as blebbing, blunting, and loss of microvilli
2. Mitochondrial changes, including swelling and the appearance of small amorphous densities
3. Dilation of the ER, with detachment of ribosomes; intracytoplasmic myelin figures may be present (see later)
4. Nuclear alterations, with disaggregation of granular and fibrillar elements

Question 8

What are the main morphology of irreversible cell injury?

Answer 8

Eosinophilia

Calcification

Pyknosis

Karyorrhexis

Karyolysis

Question 9

What is the increased eosinophilia due to in irreversible cell damage?

Answer 9

In H&E staining necrotic cells show increased eosinophilia due to loss of cytoplasmic RNA (binds the blue dye in hematoxylin) and denatured cytoplasmic proteins.

Question 10

What is karyolysis?

Answer 10

A nuclear change involved in the fading of the basophilia of the chromatin which reflects enzymatic degradation of DNA by endonucleases

Question 11

What is pyknosis?

Answer 11

A nuclear change characterized by nuclear shrinkage and increased basophilia. The chromatin condenses into a solid shrunken mass

Question 12

What is karyorrhexis?

Answer 12

This is when the pyknotic nucleus undergoes fragmentation, and with the passage of time the nucleus of the necrotic cell with completely disappear.

Question 13

The morphologic appearance of a necrotic cell is the result of what?

Answer 13

the result of denaturation of intracellular proteins and enzymatic digestion of the lethally injured cell

Question 14

What is this a slide of?

Answer 14

Karryohexis

Question 15

What is this a slide of?

Answer 15

Karyolysis

Question 16

What is coagulative necrosis?

Answer 16

Coagulative necrosis is a form of necrosis in which the architecture of dead tissues is preserved for a span of at least some days. The affected tissues exhibit a firm texture. Presumably, the injury denatures not only structural proteins, but also enzymes, and so blocks the proteolysis of the dead cells; as a result, eosinophilic, anucleate cells may persist for days or weeks. Ultimately the necrotic cells are removed by phagocytosis of the cellular debris by infiltrating leukocytes and by digestion of the dead cells by the action of lysosomal enzymes of the leukocytes.

Question 17

What is this a picture of?

Answer 17

Coagulative necrosis

Question 18

What type of necrosis is seen in this picture?

Answer 18

Coagulative

Question 19

What is gangrenous necrosis? And when can it be referred to as wet?

Answer 19

It is usually applied to a limb, generally the lower leg, that has lost its blood supply and has undergone necrosis (typically coagulative necrosis) involving multiple tissue planes. When bacterial infection is superimposed, there is more liquefactive necrosis because of the actions of degradative enzymes in the bacteria and the attracted leukocytes (giving rise to so-called wet gangrene ).

Question 20

What is liquefactive necrosis and what is it restricted to?

Answer 20

This occurs when the rate of cell destruction exceeds the rate of repair. Characterized by digestion of the dead cells, resulting in transformation of the tissue into a liquid, viscous (due to solubilized DNA) mass.

This is limited to pyogenic (pus-forming) abscesses and hypoxic necrosis of the brain

Question 21

What type of necrosis is this a picture of and do antibiotics tend to work against this?

Answer 21

Liquefactive necrosis.

Antibiotics do not work well in the case of an abscess, for 2 reasons: 1), they don’t penetrate well, because there are no blood vessels entering the abscess; and 2) the pH is low, and antibiotics will not work properly at low pH.

Question 22

What is caseous necrosis and what is it associated with?

Answer 22

Caseous necrosis is encountered most often in foci of tuberculous infection. The term “caseous” (cheese like) is derived from the friable white appearance of the area of necrosis.

the necrotic area appears as a structureless collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border

Question 23

What is this a picture of?

Answer 23

Caseous necrosis

Question 24

What is fat necrosis, what does it tend to be caused by, and does it lead to?

Answer 24

it refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity. This occurs in the calamitous abdominal emergency known as acute pancreatitis ( Chapter 19 ). In this disorder pancreatic enzymes leak out of acinar cells and liquefy the membranes of fat cells in the peritoneum. The released lipases split the triglyceride esters contained within fat cells. The fatty acids, so derived, combine with calcium to produce grossly visible chalky-white areas (fat saponification), which enable the surgeon and the pathologist to identify the lesions

Question 25

What is this a picture of?

Answer 25

Fat necrosis

Question 26

What is fibrinoid necrosis?

Answer 26

It is an indication of sever damage to the vessel wall, usually caused by inflammation. Thrombosis is often a result of this.

Question 27

What is this a picture of?

Answer 27

Fibrinoid necrosis

Question 28

What are the microscopic changes associated with an MI?

Answer 28

Less than 4 hours - None

4-24 hours - coagulative necrosis

1-3 days - neutrophils infiltration

4-7 days - Macrophage

1-3 weeks - Granulation tissue with plump fibroblasts, collagen, and blood vessels

Months - Fibrosis