Cell death Flashcards
What is the morphological hall mark of cell death?
Loss of nucleus
What are the three ways which can cause a loss of nucleus?
- Pyknosis - condensation
- Karyorrhexia - fragmentation
- Karyolysis - dissolution
What is the mechanism of ‘Pyknosis’?
- Irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis
- Followed by Karyorrhexia ie. fragmentation of the nucleus.
What is the mechanism of Karyorrhexia?
Karyorrhexis is the destructive fragmentation of the nucleus of a dying cell.
Chromatin is distributed irregularly throughout the cytoplasm
What is the mechanism of Karyolysis?
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
What are the two mechanism of cell death?
- Necrosis
- Apoptosis
What is the definition of necrosis?
- Death of large groups of cells followed by acute inflammation
- Always due to pathological process, never physiologic
- Divided into several types based of gross features.
Describe the process of coagulative necrosis?
- Coagulative necrosis is a type of accidental cell death typically caused by ischemia or infarction.
- In coagulative necrosis, the architectures of dead tissue are preserved for at least a couple of days.
- This is as the injury denatures structural proteins as well as lysosomal enzymes, thus blocking the proteolysis of the damaged cells.
- 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 - Like most types of necrosis, if enough viable cells are present around the affected area, regeneration will usually occur.
- Different diseases are associated with coagulative necrosis, including acute tubular necrosis and acute myocardial infarction
In which organs does coagulative necrosis occur in?
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.
What is the gross appearance of coagulative necrosis?
- a pale segment may be seen in contrast to surrounding healthy tissues
What is the microscopic appearance of coagulative necrosis?
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.
What is the definition of ‘Liquefactive necrosis’
Necrotic tissues that becomes liquified, enzymatic lysis of cells and protein results in liquefaction.
Which organs are affected by ‘Liquefactive necrosis’
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
What is the mechanism behind ‘Liquefactive necrosis’
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.
What is the macroscopic appearance of liquefactive necrosis?
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.
What is the microscopic appearance of ‘Liquefactive necrosis’
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.
What is the definition of gangrenous necrosis?
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.
What is the gross appearance of gangrenous necrosis?
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.
What is the microscopic appearance of gangrenous necrosis?
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.
What is the defintion of ‘Caseous necrosis’
- Soft and friable necrotic tissue with ‘ cottage cheese-like’ appearance
- Combination of coagulative and liquefactive necrosis
- Characteristic of granulamatous inflammation due to tuberculosis or fungal infection.
What is the mechanism behind ‘Caseous necrosis’
What is the gross appearance of caseous necrosis?
a yellow-white soft cheesy sphere that is enclosed by a distinct border
What is the microscopic appearance of caseous necrosis?
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.
