Cell Injury and cell death

Question 1

What are the 3 situations when you get reversible cell injury?

Answer 1

1. decreased oxidative phosphorylation
2. decreased ATP production
3. decreased cell integrity resulting in cell swelling

Question 2

Describe how a normal cell and a hypoxic cell differ with cell swelling

Answer 2

• in a normal cell, there is ATP used to work the Na/K pump, which pumps 3Na out of the cell and 2 K into the cell. If there was an unbalance in this, then water would follow the concentration gradient
• in a hypoxic cell, there is a decreased amount of o2 so there is less oxidative phosphorylation that will occur. With less O2 the cell has to depend on anaerobic glycolytic pathway to produce energy. This produces less ATP then oxidative phosphorylation and it also uses up all of the glycogen stores and results in excess lactic acid production. Since there is less ATP production, then there is a decreased ability to make the Na/K pump function normally so the 3 Na stays in the cell and the 2 K stays outside the cell. Since there are more molecules inside the cell, water moves into the cell, causing cell swelling. Additionally, there will be damage to the cell membranes, resulting in the destruction of the selectively permeable barrier, which will allow the product of cell metabolism to enter the cell.

Question 3

What is another name for acute cell swelling? describe it

Answer 3

• Hydropic degeneration.
• when there is an increased in cell size and volume because there is an increased amount of water within the cell. this results in the modification and degeneration of organelles and the break down of cell membranes

Question 4

What are the gross changes in a swollen cell? Microscopic?

Answer 4

• swollen, heavier and more pale than normal
• may have cloudy swelling, hydropic degeneration or ballooning degeneration (cells greatly enlarged and clear) and lipidosis (accumulation of excessive intracellular lipid filled vacuoles

Question 5

What are some ultrastructural changes to a reversible cell injury?

Answer 5

• plasma membrane alterations like blabbing, loosening of intercellular attachments
• mitochondrial swelling
• dilation of ER

Question 6

What are some clinical examples of reversible cell damage?

Answer 6

• pox virus causing epidermal injury
• ruminal acidosis
• hepatic lipidosis
• steroid hepatopathy

Question 7

describe pox virus causing epidermal injury

Answer 7

the virus affects the epidermal cells and causes degradation of the cytoplasmic proteins and a net flux of water into the cytoplasm. This causes cell swelling, which progresses to ballooning degeneration, forming blisters from the lysing of individual epidermal cells

Question 8

describe ruminal acidosis

Answer 8

ruminant consumes carbohydrate rich feed, which alters the bacterial composition within the rumen to gram positive bacteria. This causes a decrease in pH, killing the normal microflora in the gut. Then water from the blood moves into the rumen to try and dilute out the feed, and this causes dehydration of the animal. If the animal survives, it will have stellate stars in its rumen - or the animal will die

Question 9

describe hepatic lipidosis

what does the liver look like?

Answer 9

• this occurs with obese animals or animal that have good body condition but are unable to eat for a prolonged period of time
• the body runs out of protein to use for energy so the body starts mobilizing its free fatty acids, which move into the blood to travel to the liver. Since there is a lack of energy in the animal’s system, there isn’t energy to catabolize the ffa into TAGs. Additionally, there is no way to remove the triglyercides that are in the liver because there is a lack of apoproteins which are needed. therefore, the ffa and the TAGs are trapped in the liver. this makes the liver develop a diffuse yellow colour, makes it friable, greasy and able to float if it was put in formalin.

Question 10

describe steroid hepatopathy

what does the liver look like

Answer 10

-this happens when there is long term administration of corticosteroids. The steroids cause glycogen to accumulate in the hepatocytes.
it will appear bronze colour, will not be friable or greasy and will not float if it is placed in formalin

Question 11

what are the two types of irreversible cell injury?

Answer 11

1. necrosis

2. apoptosis

Question 12

What is necrosis?

Answer 12

it is the death of cells within a living animal. it is alway pathological.
it causes severe damage to the cell membrane when lysosomal enzymes enter the cytoplasm, digest the cell and allow its organelles to leak out.
the leaking of intracellular enzyme causes damage to the surrounding tissue and initiates an inflammatory response

Question 13

what two enzymes leak out of the cytoplasm of the cell and can be detected in blood?

Answer 13

-creatinine kinase (from muscle) and ALT (from liver)

Question 14

With necrosis, what does the influx of Ca do?

Answer 14

1. activated phospholipase A which breaks down the phosphlipids in the mitochondria
2. generates arachidonic acids, which initiates inflammation
3. activates proteases, which damages the cytoskeleton and membrane, making the membrane more damaged

Question 15

how do necrotic cells appear

Answer 15

grossly: pale, firm, swollen or shrunken
micro: nucleus is pushed to the side and it will be pyknotic, karyolytic or karyohexic

Question 16

What are the 5 types of necrosis?

Answer 16

1. coagulation necrosis
2. liquidative necrosis
3. caseous necrosis
4. gangrenous necrosis
5. fat necrosis

Question 17

Describe coagulation necrosis

Answer 17

• most commonly occurs because of hypoxia to the cells, but it may also be due to toxins.
• tissue has its original structure but is pale, swollen, firm and more friable than normal tissue
• nucleus normally lysis

Question 18

describe liquifactive necrosis

Answer 18

• typical type of necrosis that occurs in the brain - malacia
• in other tissues it is a pyogenic bacterial infection that results in the release of enzymes from the neutrophils that have accumulated, the lysing of the tissue and the formation of pus.
• if the pus if not removed, it is walled off by a fibrous capsule and is then called an abscess. If this abscess persists then the interior part becomes more caseous and there are multiple layers of fibrous capsule and this makes an “onion ring”

Question 19

describe caseous necrosis

Answer 19

-introduction of a specific bacteria or a fungus and macrophages are used to try and remove it.
-conversion of nuclear and cytoplasmic debris in the dead tissue into granular friable mass and if it is surrounded by fibrous capsule it is called a granuloma
it is a more chronic lesion

Question 20

What are the different types of gangrene? describe them

Answer 20

• Dry gangrene: coagulation necrosis of distal extremities followed by mummification. It can be caused by ingesting toxins (ergot - causes vasoconstriction), frost bite (decreased vascular flow) or septicaemia
• Wet gangrene: dry gangrene with secondary bacterial infection.
• gas gangrene: infecting bacteria are within the necrotic tissue and start producing gas bubbles (ex black leg - bacteria are introduced via intestines but they migrate to the muscle and wait for trauma or necrosis to occur and then they produce anaerobic conditions and form gas bubbles)

Question 21

describe fat necrosis

Answer 21

necrosis within body fat stores. result in the formation of white/ chalky areas surrounded by inflammatory cells

Question 22

What is the purpose of necrosis?

what happens if it doesn’t work

Answer 22

the goal is to digest and liquify the necrotic tissue so that it can be removed and replaced with new, functional tissue.
-if necrosis isn’t removed than it may become dystrophic calcification

Question 23

Name the various types of postmortem changes one can see

Answer 23

1. rigor mortis -ATP and glycogen are depleted so unable to reverse the contraction of muscle
2. liver mortis - red discolouration of dependent areas. blood settling with gravity.
3. postmortem clotting - clot will not be attached to the vessel but will be a replica of the inside of the vessel. the clot will divide with the RBC settling to the bottom and the serum staying closer to the top - chicken fat clot
4. hemoglobin imbibition - red staining of tissue from blood cells
5. bile imbibition -bile seeping out of the gall bladder and staining the surrounding tissue green
6. Pseudomelanosis -blue-green discolouration from iron sulphide
7. bloating - post mortem gas production from bacteria in the rumen
8. postmortem emphysema - gas production of bacteria from GIT shortly before death
9. mucosal sloughing - in rumen a few hours before death

Question 24

Describe apoptosis

Answer 24

• physiological or pathological cell death on an individual level.
• the cells that are destined to die activate enzymes that will degrade the cells own nuclear DNA and cytoplasmic proteins. This alters the cells structure making it a target for apoptosis - without any inflammatory response

Question 25

Explain an example of a physiological and pathological apoptosis

Answer 25

• physiological apoptosis is the process of forming fingers during embryogensis (programmed cell death for the cells that are no longer needed)
• pathological apoptosis is with cytotoxic T cells fighting against a virus or tumor by eliminating the virus infected cells or hydronephrosis - when there is a blockage in the urinary tract down stream of the kidneys then the renal pelvis dilates

Question 26

How do apoptotic cells appear?

Answer 26

• cells shrink, organelles are more tightly packed in the cytoplasm, nucleus becomes small and dark and begins to break into fragments.
• the cells begins to form blabbing and then apoptotic bodies

Question 27

Describe the two phases in the mechanism of apoptosis

Answer 27

1. initiation phase: starts the process off by either the intrinsic or extrinsic pathways which activate their certain caspase
2. execution phase: the enzymes act to cause cell death by activation the execution caspase 3 and 6. This causes cleavage of cytoskeleton and nuclear matrix and activation of endonucleases so the cell forms apoptotic bodies. These have markers on them to initiate phagocytosis

Question 28

Describe the intrinsic pathway in apoptosis

Answer 28

• growth factors stimulate anti-apoptotic Bcl-2 proteins in the mitochondria normally.
• if there is a stressed or a decreased survival signal then anti-apoptotic proteins are lost in the mitochondrial membrane and are replaced by pro-apoptotic proteins of Bcl-2 family. These increase the mitochondria’s permeability causing leakage of cytochrome c into to the cytosol. The cytochrome C activates factor 1 and triggers the activation of caspase 9, triggering the execution phase.

Question 29

Describe the extrinsic pathway in apoptosis

Answer 29

Fas protein binds to its ligand Fas L which initiates the activation of caspase 8, which triggers the activation of the execution phase

Question 30

name and describe 3 examples of apoptosis

Answer 30

1. deprivation of growth factors: the there is no anti-apoptotic proteins so there will be excess amount of apoptosis
2. DNA damage-mediates apoptosis: cells that are exposed to radiation or DNA damage have p53 gene. This gene accumulates with DNA damage and the cell will try to repair it but if it is unable to then the p53 triggers apoptosis by stimulating Bcl family. If there is a mutation and this gene is not present then there is a lack of apoptosis
3. Cytotoxic T lymphocytes express Fas L ligands so it binds to Fas via extrinsic pathway