1st lecture (cell death)

Question 1

define death?

Answer 1

when the living bodies coordinated function is suspended and is irreversible; breathing, circulation, brain function is irreversibly stopped.

Question 2

define Clinical death?

Answer 2

when the breathing, circulation and brain function is reversibly and temporary suspended.

Question 3

Brain death definition?

Answer 3

when the function of the brain is irreversibly suspended.

Question 4

2 types of postmortal changes?

Answer 4

early postmortal changes

late postmortal changes

Question 5

Early postmortal changes?

Answer 5

• Palor mortis: paling of the body. (sedimentation of blood do the gravity)
• algor mortis: chilling of the body/or heating depending on the environmental temperature. 7-8 hours
• Rigor mortis: rigidity of the body do the muscles. Deficit of ATP causes rigidity. 2-4 hours later the body relaxes due to loss of muscle structure
• livor mortis: HYPOSTATIC: sedimentation of blood (opposite of palor mortis) do to gravity. INHIBITION: (happens later) the hemolysis of the RBC causes liberated Hb penetrating the surrounding tissue causing a pink-blue coloration around vessels, if you press on it, it will dissapear.
• Crusta mortis: coagulation of blood occurs hours after death (4 hours later) POST-mortal clot.

Question 6

Nysten law?

Answer 6

muscle relaxation after death does not start in all the bodies muscle simultaneously. Starts in the face, and continues to the legs. (can be used to determine the time of death.)

Question 7

compare the post-mortal-clot (PMC) with a thrombus?

Answer 7

SURFACE: PMC=shiny Thrombus=opaque
CONSISTENCY: PMC=rubbery Thrombus: Fragile
RELATION to vessels: PMC=slips easily out of vessels/no adhesion. Thrombus=will stick to the wall of vessels.

Question 8

LATE postmortal changes?

Answer 8

• Exicatio postmortalis: loss of water; drying/shrinking
• Maceiatio: desqumation of cells from fluid containing structures like the bladder.
• gastromalacia: stomach and GI digests itself.
• Pseudomelanosis: blue discoloration
• Mumification: lack of fermintation of the bacteria means that there is a lack of bacteria destruction of the body
• adipocera: typical for bodies floating in water.

Question 9

Pseudomelanosis definition?

Answer 9

GI flora bacteria make SH2 which reacts with hemoglobin making sulfur-hemoglobin with a blue color, resulting a blue discoloration around the large intestine.

Question 10

adipocera definition?

Answer 10

characteristic of bodies who drowned in water and their bodies were floating in water for an extended period of time. their fatty acids bind the Na and K of the water making a waxy cover of the body.

Question 11

after death there is a loss of water, what is this called?

Answer 11

Exicatio postmortalis

Question 12

after death there is a desqumation of cells lining the structures such as the bladder, what is this called?

Answer 12

maceiatio

Question 13

what is it called when the GI tract digests itself after death?

Answer 13

gastromalacia

Question 14

Define necrosis?

dissociation of cell, autolysis, heterolysis (another cell digests its)

Answer 14

dead cells/tissues/organs in a living body. the cells digestive enzymes are activated and released digesting itself as mitochondria and golgi membranes break down releasing enzymes.
inflammatory cells: macrophages and polymorphonuclei go to the area and release digestive enzymes, and phagocytose the necrotic cell.

Question 15

causes of necrosis?

Answer 15

1. Oxygen deprivation, hypoxia: drop in oxygen levels in the blood or anemia. Ischemia occlusion of the vessel.
2. Chemicals; acids, alkaline
3. inflammation; immune competent cells kill injured cells.
4. nutritional imbalance: too much, too little nutrition.
5. physical agents: chemical, heat, radiation.

Question 16

Morphology; how to recognize a necrotic cell.

Answer 16

acidophillic/eosinophilic cytoplasm due to:

• pH dropping
• decrease in protein synthesis which is normally basophilic (lack of blue)
• vacules in cytoplasm; dilated golgi and ribosomes and mitochondria, which are dilated due to lack of energy to keep their shape. (myelin figure, membrane disintegrated, the fatty acids uptake water.)
• Nuclear fragmentation: (karyorrhexis)
• chondensation of chromatin (picnosis)
• kardiolysis: shadow of former nucleus (karyolysis)

Question 17

define karyorrhexis:

Answer 17

fragmentation of the nucleus of the cell

Question 18

fate of necrotic cells?

Answer 18

• could stay here
• generate a inflammatory response
• regeneration of new cell in the area

Question 19

calcification of necrotic cells?

Answer 19

necrotic cells can pick up calcium.

Question 20

events of necrosis? (in order that they occur)

Answer 20

1. hypoxia/ischemia (which then causes:)
2. Ca2+ influx (which then causes:)
3. Reperfusion injury (which then causes:)
4. ER stress
5. toxins can also play a role

Question 21

during Necrosis the hypoxia/ischemia causes what?

Answer 21

DECREASE of oxidative phosphorylation causes ATP drop. The affected Na+ pump shuts down and water influx causes swelling.
ANAEROBIC GLYCOLYSIS = drop in glycogen = Ph drop
DETACHMENT of ribosomes, DROP in protein synthesis as structural elements of cells are lost.

Question 22

during Necrosis the Ca2+ influx

Answer 22

there is a 10,000x difference between intracellular and extracellular Ca concentration. the ATP dependent Ca2+ pump shuts down. Ca2+ influx from mitochondria and SER. the high Ca2+ activates enzymes; protease, lipases, DNase.
THIS IS THE POINT OF NO RETURN.

Question 23

During necrosis describe Reprefusion injury?

Answer 23

O2 levels are low —-> Cells make ROS —-> H2O2, O-. (these are normally neutralized by mitochondria enzymes, but lack of blood flow kills the mitochondria 1st) —-> ROS cause;
Lipid peroxidation, DNA fragmentation, protein crosslinking.
since the mitochondria is already destroyed reperfusion causes and increase in oxygen supply, resulting in more ROS do to the lack of enzymes to neutralize them.
— polymorphic cells may detect damaged cells and release ROS to kill the cell and activate complement system.

Question 24

during necrosis what is Endoplasmic reticulum stress?

Answer 24

The ER produced protein which have to be properly folded by chaperons. Chaperons may be suspended due ER stress resulting in misfolded proteins accumulation.

Question 25

Cell injury by toxins during necrosis? Name the 2 types of toxins.

Answer 25

2 types of toxins:

• 1: direct acting proteins —> substances that kill the cell/organ directly
• 2Latent toxins —> metabolites of the toxin will be toxic in itself as P450 can modify the toxin making it toxic.

Question 26

Name the 6 morphological aspects of necrosis?

Answer 26

1. Coagulative necrosis
2. Liquefactive necrosis
3. Gangranna humida?
4. Cascouse necrosis (cheesry necrosis)
5. Fat hermis
6. fibrinoid necrosis

Question 27

describe coagulative necrosis?

Answer 27

the outline/shape of cells are preserved. They show granularity, due to the digestive enzymes are coagulated. The enzymes that could cause cell lysis are inactivated do to the coagulation, so the cell remains.

Question 28

Describe liqufactive necrosis?

Answer 28

cells are dissolved, so outline is lost and the NO coagulation of enzymes meaning the enzymes that cause lysis are activated and the cell is dissolved.
the dead cells are soft and can be washed off.
liqufactive necrosis can occur in coagulative necrosis because inflammatory cells can migrate to the area and release digestive enzymes.

Question 29

2 ways in which liquefactive necrosis can occur?

Answer 29

1. via the cells own activated enzymes
2. heterolysis via inflammatory cell enzymes.
   SEE-SAW analogy;
   inactivation enzymes = coagulative necrosis
   activation of enzymes = liquefactive necrosis

Question 30

Gangrene definition?

Answer 30

affecting the extremities mostly, related to reduced blood supply of the lower extremities.
Gangrene cica: (dry gangrene) coagulative necrosis as the tip of fingers are shrinking
Gangrene humida: bacteria superimpose the necrosis (bactera in shoes) liquefaction necrosis.

Question 31

caseous necrosis description?

Answer 31

Cheesy-necrosis, related tuberculosis due to TB causes necrosis of tissue, combining coagulative, liquefactive necrosis.

Question 32

Fat necrosis description?

Answer 32

related to pancreatitis, the inflammation of pancreas due to activation/liberation of lipases, which splits lipids to TAG and FA. the fatty acids combine Ca2+ which makes salt.

Question 33

Fibrinoid necrosis description?

Answer 33

Not a form a necrosis, we just call it as necrosis.
related to autoimmunity reaction, where you have a vessel and due to the inflammatory procedure causing endothelium to leak, plasma proteins complement immune precipitates in the wall of the vessel.
results in the accumulation of the plasma in the leaky endothel of vessels.