A/1-5 NECROSIS, APOPTOSIS (Tamer) Flashcards
Definition Of Necrosis
Death of large group of cell (due to disease, injury or failure of blood supply) of a tissue/organ in a living person **followed by acute inflammation
-always pathologic**
Give at Least 5 causes of Necrosis
-
oxygen deprivation:
- hypoxia
- ischemia
-
chemical agents:
- glucose/salt in high concentration
- poisons
- drugs
-
infectious agents:
- viruses
- fungi
- bacteria
-
genetic defects
- deficiency of functional proteins
- accumulation of DNA or misfolded proteins
-
nutritional imbalance :
- deficiency of vitamins/proteins.
-
physical agents:
- temperature
- radiation
- atmospheric pressure
-
immunologic reactions:
- autoimmune/ allergic reactions
-
aging:
- -problem of the telomeres
Give at least 4 Morphological features of Necrosis
- *1.eosinophilia:**
- coagulation of denaturated enzymes/proteins
- *2.Glassy appearance:**
- glycogen decrease
- *3.vacculated** appearance of cytoplasm:
- due to enzymatic digestion
- *4.myelin figures**
- phospholipid masses
5.membrane fragmentation
6.nuclear changes
- pyknosis:
- karyolysis:
- karyorrhexis:
Give all Patterns of tissue necrosis
- *1.Coagulative necrosis**
- cell shape/organ structure are preserved
-nucleus dissapears
-all organs with ischemic infarction will exhibit
(except brain)
- *2.Liquefactive necrosis (** tissue becomes liquified )
- enzymatic lysis of the cells (by microglial cells)
e.g.
*brain infarction
*abscess
*pancreatitis
- *3.Gangrenous necrosis** (“mumified tissue”)
- ischemia of the lower limb (/extremities)
enzyme source:
- autolysis
- heterolysis (inflammatory cells )
**if tissue is infected –> Liquefactive necrosis –> wet gangrene
- *4.caseous necrosis**
- soft , friable necrotic tissue , “cottage-cheese like” appearance
-charechteristic for granulomatous inflammation due to TB/FUNGI
5.Fat necrosis
TRAUMA / LIPASE (from pancreatitis)–> FFA’S + CA+2
- chalky white appearance due to depostion of Ca+2
e. g. - stone in the common bile duct
- alcohol
6.fibrinoid necrosis
- necrotic damage to blood vessel wall
- leakage of proteins from b.stream to vessel wall
e.g.
- malignant hypertension
- vasculitis
name the mechanisms by which Necrosis occurs
1.ATP depletion
consequences :
- activity of Na+ pump decrease
- decrease in enzymatic activity
- decrease in protein synthesis
- Ca+2 influx
- *2.mitochondrial damage
- ** ATP depletion
-leakage of cytochrome C and other pro - apoptotic proteins –> apoptosis
- *3.Ca influx = point of no return**
- intracellular Ca+2 << extracellular Ca+2
- released from mitochondria , ER and ECM.
- Ca+2 activates enzymes: ATPase , Phospholipases/proteases, ,Endonucleases
4.ROS: reactive oxygen species
-Attack nucleic acids, proteins and lipids.
5.membrane damage
6.Damage to DNA and proteins:
severe damage –> the cell initiates the death program
Definition of Apoptosis
“cellular suicide” - programmed cell death
- energy dependent ,genetically programmed
- single cells / small groups of cells
e. g.
*endometrial shedding
*during embryogenesis
*mhc 1 mediated cytotoxic reaction
causes of apoptosis
physiologic situations
1.during embryogenesis
2.removal of hormone - dependent tissues during the hormone deprivation, for example: endometrial cells, regression of the lactating breast
3.death of inflammatory cells at the end of the immune response
- *4.death of proliferating cells** (as in mucus membrane) to maintain its constant number
In pathologic conditions
as in the cases of:
1.DNA damage
2.accumulation of misfolded proteins
3.inflammatory procedures: by viral infection because they integrate In the DNA and lead to cell cycle arrest
4.atrophy due to shortage of O2 and nutrients
Give the Morphological features of apoptosis
1. apoptotic bodies: formation of membrane blebs that separate from the cell . Might contain organelles.
2. cell shrinks , eosinophilic cytoplasm
- *3.nuclear changes**:
- condensation
- aggregation
- karyorrhexis
- Fragmentation of the DNA
4.phagocytosis of the apoptotic bodies.
No leakage of enzymes/no inflammatory response
What is The Key Mediator of Apoptosis
Caspases
IF CASPASES APPLIED FOR A JOB WHAT WOULD IT BE ?
- activate proteases- cytoskeleton breaks down
- activate endonucleases - breakdown DNA
How are Caspases activated
- intrinsic pathway
cytochrome-c
-extrinsic receptor-ligand pathway
fasL binds fas death receptor (CD95)
-Cytotoxic CD8+ T-cell pathway
perforins create pores in target membrane
granzymes enter pores –> caspases activated
molecular mechanisms of apoptosis
By activation of caspases
Mitochondrial (intrinsic) pathway
activation of Bcl - 2 sensors, effectors–> Bax-Bak insert into the mito–> formation of channels–>escape of cytochrome C –>active caspases
Bax and Bak are regulated by anti - apoptotic members of the Bcl - 2 family: Bcl-2 Bcl - Xα
Death receptor (extrinsic) pathway
- activation of adaptor molecule called FaDD->activation of caspase 8
- TNF and TNF - L also activate FaDD
features of Coagulative necrosis
- basic tissue architecture are preserved
- tissue is firm
- nucleus dissappears
organs with ischemic infarction will have coagulative necrosis
what’s an INFARCTION ? give 2 types of INFARCTION
Infarct : an area of ischemic necrosis caused by occlusion of the arterial supply or the venous drainage. The infarct is classified according to its color:
White infarct (anemic)
Occurs with arterial occlusions or in solid organs (heart, spleen, kidney) where the solidity of the organ limits the hemorhhage
Red Infarct (hemorrhagic)
- venous occlusion
- loose tissues
- tissues with dual circulation (lung, small intestine)
- reperfusion to a site that was occluded +necrotic
give examples of anemic coagulative necrosis
Kidney infarct
Spleen infarct
Gangrene sica
AMI (rare)
differencee between Necrosis and Apoptosis
