Cell death

Question 1

What is the morphological hall mark of cell death?

Answer 1

Loss of nucleus

Question 2

What are the three ways which can cause a loss of nucleus?

Answer 2

1. Pyknosis - condensation
2. Karyorrhexia - fragmentation
3. Karyolysis - dissolution

Question 3

What is the mechanism of ‘Pyknosis’?

Answer 3

1. Irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis
2. Followed by Karyorrhexia ie. fragmentation of the nucleus.

Question 4

What is the mechanism of Karyorrhexia?

Answer 4

Karyorrhexis is the destructive fragmentation of the nucleus of a dying cell.

Chromatin is distributed irregularly throughout the cytoplasm

Question 5

What is the mechanism of Karyolysis?

Answer 5

Karyolysis is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases.

It is usually associated with karyorrhexis and occurs mainly as a result of necrosis, while in apoptosis after karyorrhexis the nucleus usually dissolves into apoptotic bodies

Question 6

What are the two mechanism of cell death?

Answer 6

1. Necrosis
2. Apoptosis

Question 7

What is the definition of necrosis?

Answer 7

1. Death of large groups of cells followed by acute inflammation
2. Always due to pathological process, never physiologic
3. Divided into several types based of gross features.

Question 8

Describe the process of coagulative necrosis?

Answer 8

1. Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction.
2. In coagulative necrosis, the architectures of dead tissue are preserved for at least a couple of days.
3. This is as the injury denatures structural proteins as well as lysosomal enzymes, thus blocking the proteolysis of the damaged cells.
4. The lack of lysosomal enzymes allows it to maintain a “coagulated” morphology for some time.
   - cell shape and organ structure are maintained but nucleus disappears
5. Like most types of necrosis, if enough viable cells are present around the affected area, regeneration will usually occur.
6. Different diseases are associated with coagulative necrosis, including acute tubular necrosis and acute myocardial infarction

Question 9

In which organs does coagulative necrosis occur in?

Answer 9

Coagulative necrosis occurs in most bodily organs, excluding the brain.
In the central nervous system ischemia causes liquefactive necrosis, as there is very little structural framework in neural tissue.

Question 10

What is the gross appearance of coagulative necrosis?

Answer 10

1. a pale segment may be seen in contrast to surrounding healthy tissues

Question 11

What is the microscopic appearance of coagulative necrosis?

Answer 11

The green star shows healthy cells that are less pink and have nuclei present.

The blue star is a Bowman’s capsule.

The yellow star indicates the necrotic portion. Notice that the architectural structure of the cell is still present, but no nuclei can be seen. You could almost draw a line between damaged and non-damaged cells.

Question 12

What is the definition of ‘Liquefactive necrosis’

Answer 12

Necrotic tissues that becomes liquified, enzymatic lysis of cells and protein results in liquefaction.

Question 13

Which organs are affected by ‘Liquefactive necrosis’

Answer 13

Liquefactive necrosis can be associated from bacterial, viruses, parasites or fungal infections. Unlike coagulative necrosis, liquefactive necrosis forms a viscous liquid mass as the dead cells are being digested.

• Brain infarction - proteolytic enzymes from microglial cells liquefy the brain
• Abscess - proteolytic enzymes from neutrophils liquefy tissue
• Pancreatitis - proteolytic ezymes from pancreas liquefy parenchyma

Question 15

What is the mechanism behind ‘Liquefactive necrosis’

Answer 15

Unlike coagulative necrosis, liquefactive necrosis forms a viscous liquid mass as the dead cells are being digested.

The micro-organisms can release enzymes to degrade cells and initiate an immune and inflammatory response.

Cellular dissolution and digestion of dying cells may also release further enzymes, which speeds up the liquefying process.

The micro-organisms stimulate the leukocyte to home-in on the necrotic area and release powerful hydrolytic enzymes (such as lysozymes) which causes local damage and cells to be lysed, causing a fluid phase.

The enzymes responsible for liquefaction are derived from either bacterial hydrolytic enzymes or lysosomal hydrolytic enzymes. These are proteases (collagenases, elastases), DNases and lysosomal enzymes.

Question 16

What is the macroscopic appearance of liquefactive necrosis?

Answer 16

Liquid-like layer can be seen; pus should be present. Yellowing, softening or swelling of the tissue should be seen. Malacia (softening, or loss of consistency) should be present.

A cystic space should be present for tissue resolution.

Question 17

What is the microscopic appearance of ‘Liquefactive necrosis’

Answer 17

Macrophages and neutrophils, both dead and alive, should be present.

Debris and lysed cells should be seen with inflammation. Partial space should be filled with lipids and debris.

There is a loss of neurons and glial cells, with the formation of clear space

Demonstrates the histology slide of liquefactive necrosis. Notice the middle where it is pinker with more space and fewer neurons. On high power, macrophages should be present with lipids and debris.

Question 18

What is the definition of gangrenous necrosis?

Answer 18

Gangrenous necrosis generally describes the damage that has occurred to the extremities (especially lower) where there is severe ischaemia.

These extremities lack in blood supply and oxygen and typically cause coagulative necrosis at different tissue planes (this is also called dry gangrene).

Severe frostbite injuries can lead to dry gangrene.

If bacterial infection occurred, liquefactive necrosis could also be occurring due to the degrading enzymes and the involvement of the leukocytes. When liquefactive necrosis is present, the term ‘wet’ gangrene is used.

Question 19

What is the gross appearance of gangrenous necrosis?

Answer 19

black skin is generally seen with a degree of putrefaction (the process of decay or rotting in a body or other organic matter).

The tissues may look ‘mummified’, be sure to ascertain if this is dry or wet gangrene. Smelling may give a clue if there is an infection.

Question 20

What is the microscopic appearance of gangrenous necrosis?

Answer 20

due to the ischaemia which would suggest dry gangrene, coagulative necrosis histological traits should be seen.

If there is a bacterial infection which would suggest wet gangrene, liquefactive necrosis histological traits should be

Gangrenous necrosis involves the tissues of a body part.

The inflammation seen here is extending beneath the skin of a toe to include soft tissue (fat and connective tissue at the right) and bone (at the left). Because multiple tissues are non-viable, amputation of such areas is necessary.

Question 21

What is the defintion of ‘Caseous necrosis’

Answer 21

1. Soft and friable necrotic tissue with ‘ cottage cheese-like’ appearance
2. Combination of coagulative and liquefactive necrosis
3. Characteristic of granulamatous inflammation due to tuberculosis or fungal infection.

Question 22

What is the mechanism behind ‘Caseous necrosis’

Question 23

What is the gross appearance of caseous necrosis?

Answer 23

a yellow-white soft cheesy sphere that is enclosed by a distinct border

Question 24

What is the microscopic appearance of caseous necrosis?

Answer 24

a granuloma should be present. The core is necrotic and uniformly eosinophilic, which is surrounded by a border of activated macrophages and lymphocytes.

The core is structureless and should have debris and lysed cells. Langhans giant cells may be seen, and inflammation should also be noticed and present.

There is a fibrous case surrounding and enclosing the core; hence fibroblasts should also be seen.

Question 25

What is the defintion of ‘Fat necrosis’

Answer 25

Characteristic of trauma to fat e.g. breast and pancreatitis-mediated damage of peripancreatic fat

Question 26

What is the mechanism behind ‘Fat necrosis’

Answer 26

Fat necrosis does not denote a type of necrosis pattern but instead is used to describe the destruction of fat due to pancreatic lipases that have been released into the surrounding tissues.

The pancreas itself is at risk along with the peritoneal cavity.

Acute pancreatitis causes the pancreatic enzymes to leak out from the acinar cells.

Once the enzymes come into contact with fat cells, their plasma membrane is liquefied, releasing the fats/triglycerides.

The fatty acids combine with calcium through a process called saponification.

An insoluble salt is created and gives the appearance of a chalky-white area.

Saponification is an example for dystrophic calcification in which calcium deposits on dead tissue.

In dystrophic calcification, the necrotic tissue acts as nest for calcification in the setting of normal serium calcium and phosphate.

In metastatic calcification - as opposed to dystrophic calcification occurs when high serum calcium/phosphate leads to calcium deposition.

Infections, viruses, trauma, ischaemia and toxins could be responsible for the pancreas to be damaged and release its enzymes. Breast tissues can also have fat necrosis to which is triggered from trauma.

Question 27

Dystropic vs metastatic calcification

Answer 27

In dystrophic calcification, the necrotic tissue acts as nest for calcification in the setting of normal serium calcium and phosphate.

In metastatic calcification - as opposed to dystrophic calcification occurs when high serum calcium/phosphate leads to calcium deposition.

Question 28

What is the gross appearance of fat necrosis?

Answer 28

Soft chalky-white area should be seen on the pancreas

Question 29

What is the microscopic appearance of Fat necrosis?

Answer 29

basophilic (bluish) calcium deposits are present. Anucleated adipocytes with a cytoplasm that is more pink and contains amorphous mass of necrotic material. Inflammation would be present.

Answer 30

Question 31

What ia the definition of ‘Fribrinoid necrosis’

Answer 31

1. Necrotic damage of blood vessel wall
2. Leaking of proteins (incl fibrin) into the vessel wall results in bright pink staining of the wall
3. Characteristic of malignant hypertension and vasculitis

Question 32

What is the mechanism of ‘Fibrinoid necrosis’?

Answer 32

Fibrinoid necrosis is associated with vascular damage (caused mainly by autoimmunity, immune-complex deposition, infections) and the exudation of plasma proteins (such as fibrin).

This pattern typically occurs due to a type 3 hypersensitivity, where an immune complex is formed between an antigen (Ag) with an antibody (Ab).

The Ag-Ab complex may be deposited in the vascular walls causing inflammation, complement being activated, and phagocytic cells are recruited, which could be releasing oxidants and other enzymes causing further damage and inflammation.

Fibrin, a non-globular protein involved in the clotting of blood, is leaked out of the vessels

Question 33

What is the microscopic appearance of ‘Fibrinoid necrosis’

Answer 33

an amorphous appearance that is bright pink in an H&E stain. The deposition of fibrinoid are surrounding the blood vessels. Inflammation should be present.

Question 34

What is the definition of ‘Apoptosis’

Answer 34

ATP dependant, genetically programmed cell death involving single or small groups of cells

Question 35

What is the morphology of apoptosis?

Answer 35

1. Dying cell shrinks, leading cytoplasm to become even more eisonophilic

2, Nucleus condenses and fragments in an organised manner

3. Apoptotic vodies fall from the cell and are removed by macrophages apoptosis is not followed by inflammation

Question 36

How is Apoptosis mediated?

Answer 36

1. Proteases breakdwon the cytoskeleton
2. Endonucleases break down DNA

Question 37

Capsase activation pathway - Intrinsic mitochondiral pathway

Answer 37

1. Cellular injury, DNA damage or decreased hormonal stimulation leads to inactivation of Bcl2 (protein that determines apoptosis)
2. Lack of Bcl2 allows cytochrome c to leak from the inner mitochondrial matrix into the cytoplasm and activate caspases (family of proteases that are involved in cell death)

Question 38

Capsase activation pathway - Extrinsic receptor lingand pathway

Answer 38

Fas ligand (FasL) is a type II membrane protein that belongs to the TNF superfamily. It is found in the eye and can induce apoptotic cell death in cells that express Fas.

Fas ligand binds to FAS death receptor (CD95) on target cell activating caspases

Question 39

Capsase activation pathway - Cytotoxic CD8+T cell mediated pathway

Answer 39

1. Perforins secreted by CD8+ T cell create pores in the membrane of target celll
2. Granxyme from CD8+T enter pores and activate caspases
3. CD8+ T cell killing of virally infected cells is an examle