Chp. 1 Cell Death Flashcards
What is the morphological hallmark of cell death?
LOSS OF THE NUCLEUS!!
Loss of the nucleus occurs three ways:
Pyknosis - Nuclear condensation (ink dot)
Karyorrhexis - Fragmentation
Karyolysis - Dissolution of the nucleus
So basically it shrinks down fragments, then dissolves
What are the two mechanisms of cell death?
Necrosis and apoptosis
What is necrosis always followed by?
ACUTE INFLAMMATION!!
Necrosis is death of a LARGE NUMBER OF CELLS followed by acute inflammation, its always due to some pathological issue. NECROSIS IS NOT NORMAL
Divided into several types based on morphological features
What are the 6 types of necrosis?
- Coagulative
- Liquefactive
- Gangrenous
- Caseous
- Fat
- Fibrinoid
What is coag necrosis? What is it characteristic of? What is red infarction?
Coag necrosis is when necrotic tissue keeps its shape and organ structure BUT LOSES ITS NUCLEUS (remember necrosis means to lose the nucleus)
It is characteristic of infarction of every organ EXCEPT THE BRAIN. The brain undergoes liquefactive necrosis. The area of infarcted tissue is usu wedge shaped and pale.
Red infarction is when blood re-enters previously infarcted loose or spongy tissue (i.e. testicles or lung)
What is liquefactive necrosis and what is it characteristic of?
It is necrotic tissue that becomes liquefied; cells and proteins become lysed due to hydrolytic enzymes.
This is characteristic of BRAIN INFARCTION. Proteolytic enzymes from the microglial cells (brain macrophages with lytic enzymes) liquefy the brain.
Also characteristic of Abscesses where proteolytic enzymes from neutrophils liquefy tissue
Also seen in Pancreatitis where lytic pancreatic enzymes liquefy the pancreatic parenchyma
What is gangrenous necrosis and what is it characteristic of?
It is COAG NECROSIS that resembles mummified tissue (dry gangrene).
It is characteristic of infarction of the lower limb and GI Tract.
Should an infection occur on top of gangrenous necrosis, then the gangrenous necrosis turns into liquefactive necrosis. This is now called WET GANGRENE
…and its on humm
What is caseous necrosis and what is it characteristic of?
It is soft and friable necrotic tissue with cottage cheese like appearance that is a COMBO OF COAG AND LIQUEFACTIVE NECROSIS.
Characteristic of granulomatous inflammation due to TB or fungal infection
What is fat necrosis? What is it characteristic of? What does the fatty acids or lipase join with? What is that process called?
Fat necrosis necrotic tissue with a chalky white appearance due to Ca2+ deposition.
It is characteristic of trauma to fat i.e. breast, and peripancreatic fat. Trauma to breast causes fatty acids to leak out, and when peripancreatic fat is damaged lipase’s leak out. Both fatty acids and lipases join with CALCIUM in a process called SAPONIFICATION.
What is dystrophic Ca2+’ification? What is metastatic Ca2+’ion?
Dystrophic Calcification (saponification is an ex of this) where Ca deposits on DEAD TISSUE. The necrotic tissue acts as a NIDUS for which Ca to stick to. This is with NORMAL Ca AND PO4 LEVELS!!
An example would be psammoma bodies. This is where tumor cells outgrow their blood supply and die, then Ca2+ deposits onto them in laminated round patterns. So remember, Psammoma bodies are an ex of DYSTROPHIC Ca2+’ion!!!!
Metatstatic Ca2+’ion occurs when there is HIGH SERUM CALCIUM OR PO4 LEVELS that lead to deposition of Ca in HEALTHY TISSUES. An ex is hyperPTH where PTH takes Ca out of the bones to put into the bloodstream.
Even tho it says metastatic, its not a cancerous process. Metastatic here just means it can occur anywhere in the body
What is fibrinoid necrosis and what is it characteristic of?
It is necrosis of a BLOOD VESSEL WALL and is characteristic of malignant HTN and VASCULITIS
Necrotic damage to the blood vessel wall causes proteins (even fibrin) to leak out into the interior vessel wall. These leaked proteins are seen as bright pink staining of the wall microscopically
What is apoptosis?
It is an energy dependent (ATP) genetically programmed cell death of one or a few small groups of cells. Ex are:
Endometrial shedding during menstruation
Removal of cells during embryogenesis
CD8+ killing of infected cells (usu infected by a virus)
What is the process of apoptosis? What happens to the nucleus?
The dying cell shrinks, so the cytoplasm becomes way more concentrated or eosinophilic (basically a deeper pink color).
The nucleus condenses and fragments in an organized manner
Then the cell begins to fragment and “apoptotic bodies” fall away and are eaten by macrophages. NOT NEUTROPHILS, THEREFORE THERE IS NO ACUTE INFLAMMATION FOLLOWING APOPTOSIS
What enzyme mediates apoptosis? What do they activate and how are they activated?
Caspases
Activate proteases (break down cytoskeleton) and endonucleases (break down DNA)
Activated in multiple pathways:
1. Intrinsic Mitochondrial Pathway where Bcl2 is inactivated. Inactivation leads to Cyto C leaking out of mitochondria into cytosol and activating caspases.
Bcl2 is a proto-oncogene that is implicated in B Cell Lymphoma (BCL). It competes with apoptotic proteins ie Bax which is a pro-apoptotic protein activated by p53 when it senses cell damage. When activated it combines with Bak which releases Cyto C.
Cyto C then activates Apaf-1 which activates caspases. Bcl2 can also bind Apaf-1, blocking it from activating cytosolic caspases.
So in cancer formation, its the Bcl2 that doesn’t let Cyto C out so that the cell cannot undergo apoptosis but instead stays around multiplying itself…—>cancer. Excessive Bcl2 formation seen in follicular lymphoma
- Extrinsic receptor ligand pathwy
Fas/FasLigand…Fas ligand binds FAS death receptor (CD95) on the target cell. This binding activates caspases. This exact thing happens in Neg selection of thymocytes in the Thymus. - Cytotoxic CD8+ pthwy
CD8+ secrete performs that punch holes into the target cell. Granzyme enter the holes and activate caspases.
