Cell injury (NECROSIS & APOPTOSIS)

Question 1

What is Necrosis ?

Answer 1

Death of a gp of cells or tissues within the living body, followed by their degradation by hydrolytic Enzymes.
Not Accompained w/ inflammation.

Question 2

the morphologic Appearance of the necrosis is due to :
…………….. & …………..

Answer 2

1. Enzymatic Digestion by hydrolytic enzymes from lysosomes, inflammatory cells, or from dead cells (autolysis)
2. Denaturation of proteins => Eosinophilia.

Question 3

Causes of necrosis changes during Necrosis ?

Answer 3

Breakdown of DNA & Chromatin : Pyknosis, Karyrrhexis, Karyolysis.

Question 4

Myocardial infarct requires necrosis to develop within
A. Hours
B. Immediate
While Necrosis requires …….. to develop.

Answer 4

Immediate

Hours

Question 5

The necrotic cells show increased eosinophilia. Explain.

Answer 5

1. Attachment on eosin on denatured Cytopl. proteins
2. Loss of basophilia imparted by the RNA in cytoplasm.

Question 6

What are the morphological features of the nectrotic cells due to the coagulative necrosis ?

Answer 6

Grossly At first, the necrotic area appears as pale, firm, slightly swollen then it becomes shrunken, softer, yellowish.
Microscopically The general architecture of the cell is maintained so that the cell type can be recognized. BUT, the cytoplasmic & Nuclear details are lost.
The necrotic cells are swollen & appear more eosinophilic due to denaturation of proteins.

Question 7

What are types of necrosis ?

Answer 7

1. Coagulative
2. Liquifactive
3. Fat
4. Fibrinoid
5. Caseous
6. Gangrenous

Question 8

What is the most common type of necrosis ? Where can it happen ? What causes it ?

Answer 8

• Coagulative necrosis
• In all solid organs except the brain
• Sudden cessation of blood flow causing ischemic necrosis or infarction.

Question 9

What are the causes of the liquifactive necrosis ? Its mechanism ?

Answer 9

1. Ischemic injury as in Brain infarction
2. Bacterial or protozoal infection as in Pyogenic abscess and amoebic abscess.

degradation of tissue by the action of hydrolytic enzymes from lysosomes, parasites or inflammatory cells.

Question 10

What are the morphological features of the nectrotic cells due to the Liquefactive necrosis ?

Answer 10

Grossly The affected area is soft w/ liquefied center containing necrotic debris, then a cyst is formed.
Microscopically The cyst space is filled w/ necrotic debris & macrophages w/ phagocytosed material.
The cyst wall is formed of proliferating cap. & inflammatory cells &
proliferating glial cells in case of Brain infarction
Proliferating Fibroblasts in case of abscess cavity.

Question 11

What are the morphological features of the nectrotic cells due to the coagulative necrosis ?

Answer 11

Grossly The eraly necrotic area is firm, pale, slightly swollen, then lately it becomes yellowish, soter & shrunken.
Microscopically General architecture & outlines are maintained. But cytoplasmic & nuclear details are lost.
Cell is swollen & eosinophilic than normal.
Nuclear changes.

Question 12

What is Caseous Necrosis ?

Answer 12

• Type of necrosis in between coagulative & liquiefactive (semiliquified).
• Occurs in the center of tuberculous granuloma.
• Term “Caseous” refers to its white cheesy gross appearrence of the central necrotic Area.
• Caused by : Type 4 delayed hypersen. Reaction => recruitment of modified macrophage (granuloma) => destruction of walls of mycobacteria => relrease of lipids.

Question 13

What are the morphological features of the nectrotic cells due to the Caseous necrosis ?

Answer 13

Grossly The foci of the necrotic Area resemble dry cheese, yellowish, granular, soft.
Microscopically The necrotic foci is composed of structurless, eosinophili, amorphous granular debris surrounded by granulomatous inflammation.
The general architecture is destroyed.

Question 14

What are types of Fat necrosis ? + Explaination ?

Answer 14

1. Enzymatic Fat necrosis (Acute Pancreas necrosis)
In Acute panceatic necrosis, there is a liberation of lipases from inflamed tissue => necrosis of pancreas & fat depots in peritoneal cavity and also may harm extra-abdominal Adipose tissue.
Lipase hydrolyses the neutral fat into FA & Glycerol. FA will combine w/ Ca => Calcium soaps (saponification)
2. Traumatic Fat necrosis (Breast) Trauma in subcutaneous Tissue of Breast => Rupture of fat cells => Breast lump fromation.

Question 15

What are the morphological features of the nectrotic cells due to the Fat necrosis ?

Answer 15

Grossly Fat necrosis appears as Yellowish-white firm deposits. Formation of Ca soaps gives the necrotic foci firm, whit & Chalky appearance.
Microscopically The Necrotic fat cells have shdowy outline surrounded by inflammatory Reaction. Ca soaps appear as amorphous, granular, basophilic material.

Question 16

What is fribrinoid necrosis ?

Answer 16

Necrosis associated w/ exudation & deposition of fibrin in wall of BV in case of immune complex vasculitis.

Question 17

What are the morphological features of the nectrotic cells due to the fibrinoid necrosis ?

Answer 17

Microscopically Fibrinoid necrosis appear as brigh eosinophilic hyaline like deposition in BV walls.

Question 18

What is Apoptosis ?

Answer 18

It’s a coordinated & internally programmed cell Death.

Question 19

Apoptosis is controlled & regulated by …………….

Answer 19

the rate of Cell division

Question 20

Apoptosis happens when ………

Answer 20

the cell is deprived from growth factors, or DNA damage or protein damage beyond repair.

Question 21

Apoptosis is not accompained w/ inflammation. Why ?

Answer 21

As it occurs w/ the fragmentation of nucleus w/O loss of memb intergrity and w/ rapid phagocytosis of apoptotic bodies.

Question 22

What are types of Apoptosis ? + EX ?

Answer 22

1. Physiologic
   - Involution of thymus in early Age.
   - Involution of hormone dependent tissue as : endometrium shedding, regression of lactating breast after withdrawel of Breast feeding.
   - Destruction of cells during embriogenesis to from organs (organogenesis) : fingers ….
   - Cells served their purpose
   - Self reactive Lymphocytes.
   - Proliferating Population
2. Pathologic
   - DNA damage due to hypoxia or radiation.
   - Graft rejection reaction by cytotoxic T cell.
   - Viral Hepatitis forming Councilman Apoptotic Bodies.
   - Pathological atrophy : Obstruction of duct => Pancreas Atrophy.
   Hormonal deprivation after orchiectomy => Prostatic atrophy.
   - Tumors exposed to Chemotherapy.

Question 23

What are pathological features of Apoptosis ?

Answer 23

1. Death of a single cell, or small cluseters of cells.
2. The apoptotic cell is round to oval w/ eosinophilic cytoplasm.
3. The nucleus is fragmented or condensed (pyknosis, karyorrhexis).
4. There may be formation of apoptotic bodies containing organelles around cell. and they are phagocytosed by macrophage.
5. No inflammation reaction.

Question 24

What is the BCL-2 gene family ?

Answer 24

IT’s a family of gene located in the outer mitochondrial memb possessing activators & inhibitors of Apoptosis.
It regulates the apoptotic process by binding to some related proteins :
Bax & BAK => enhancing Apoptosis
BCL-xl & BCL2 => inhibiting Apoptosis

Question 24

What are the mechanisms of Apoptosis ? Diff betw them ?

Answer 24

1. **Death Receptor extrinsic pathway** 2. **Mitochodrial intrinsic pathway.** 1- **Death** : Triggered by activation of FAS receptor (a member of TNF receptor) 2- **Mitochondrial** : triggered by DNA damage caused by : Hypoxia, Heat, Radiation, Withdrawal of cytokines, certain hormones, growth factors. 1- **Death** : When T Lymphocyte w/ FAS ligand recognizes FAS expressing targets => activate caspase 8 => activate caspase cascade => apoptosis. 2- **Mitochodrial** : - these factors activate Bcl-2 family => activate pro-apoptotic factors : BAX & BAK => these factors will increase the premeability of mitochodrial memb => realease of cytochrome C into cytosol of cell => activation of caspase 9 => activation of caspase cascade. - Also, The apoptotoc pathway may be induced by p53 molecule.

Question 25

What's meant by Autolysis ?

Answer 25

Disintegration of the cell by its own hydrolytic enzymes secrested by its lysosomes, this term is used for postmortem change.

Question 26

Diff Betw Apoptosis & Necrosis.

Answer 26

**DEF** *AP* : coordinated & internally programmed cell death. *NE* : death of a group of cells or part of tissue within the living body followed by its degradation by hydrolytic enzymes. **Causes** *AP: * Physiologic & Pathologic processes. *NE:* Pathological, Hypoxia, Toxins ... **Morphology** AP : 1- No inflammation. 2 - death of a single cell. 3 - Apoptotic bodies, 4 - Apoptotic cell is rounded to oval w/ eosinophilic cytoplasm. 5 - Nuclear condensation or fragmentation. 6 - Cell shrinkage 7 - Cytoplasmic blebs on memb. 8 - Apoptotic Bodies phagocytosed by macrophage. NE:1 - Inflammation 2 - Death of many adjacent cells 3- Damaged Organelles 4 - Incesed eosinophilia as binding of eosin to denaturated proteins & loss of basophilia due to imparted RNA. 5 - Nuclear changes due to breakdown of DNA & Chromatin. 6 - Cell swelling 7 - Memb disruption 8 - Phagocytosis of cell debris by Macrophage **Molecular Changes** *AP: * Lysosomes & Organelles are intact Controlled by Hormones & enzymes : FAS // BCL-2 // P53. *NE: * Lysosomal breakdown w/ liberation of hydrolytic enzymes . Cell death by ATP depletion, Memb damage, Free radical injury.

Question 27

DEF of gangrene

Answer 27

Necrosis (usually coagulative) of tissue w/ superadded putrefaction.

Question 28

What are types of Gangrene ?

Answer 28

1. Dry Gangrene 2. Wet (moist) gangrene 3. Gas gangrene

Question 29

Where can dry gangrene happens ? for what general cause ? due to what causes ?

Answer 29

Dry gangrene begins in the **distal part** of a limb due to **ischemia**. **Causes** : 1. **Atherosclerosis** (accumulation of fats, cholestrole or any other substances in Artery wall) 2. **Ergot poisening** (eating food contaminated by a fungus called C-purpurea. 3. **Thromboangitis Obliterans (Buerger's Disease)** (small BV inflamed & swollen then gets blocked) 4. **Trauma** 5. **Raynaud's Disease** (feeling numb in distal parts of limb due to cold T, or stress))

Question 30

How does dry Gangrene evolve ?

Answer 30

1. It begins at distal part of the limb w is the farthest from the Blood supply. 2. Then moves upwards until it reaches a part where the blood supply is adequate to keep the tissue viable. 3. A line of demarcation (zone of acute inflammation) is formed separatin the gangrenous part from the viable part. 4. Later on, it becomes a line of separation formed of inflammatory granulation tissue & fibrosis that falls off on its own if not surgically removed.

Question 31

Gross Appearance of Dry gangrene ?

Answer 31

The affected part is dry, shrunken, dark black, resembled the mummy. The dark black color is due liberation of Hb from haemolysed RBCs and it reaction w/ Hydrogen disulphide (H2S) produced by bacteria, producint black iron sulphide.

Question 33

What is the general cause of wet gangrene ?

Answer 33

1. Blockage of venous 2. Blockage of arterial blood flow due to thrombosis or embolism.

Question 34

Wet gangrene can occur in .....

Answer 34

1. Naturally moist tissues as mouth, lung, intestine, cervix, vulva. 2. Intestine commonly due to : - Strangulated hernia (loop of intestine is forced through an opening in Abdomen as inguinal opening) - Volvulus (loop of intestine twists around itself w/ the mesentry supplying it => bowel obstruction) - Intussusception (a part of inestint slides into antoher part of inestine) - Mesentry vascular occlusion (ischemia) due to thrombosis or embolism. 3. Diabetic food due to higher sugar content in nectrotic tissue favorable for bacterial growth. 4. Bed Sores occuring in bed ridden patient due to pressure on sites like sacrum, buttocks, heels.

Question 35

1. The affected part of wet gangrene is stuffed w/ ......... w favors ............ 2. the ....... products of bacteria are absorbed causing ......... & finally .........

Answer 35

1. Blood // bacterial growth. 2. toxic // profound toxemia // death.

Question 35

Gross Appearance of wet gangrene

Answer 35

Soft, swollen, no line of demarcation, black, putrified.

Question 36

Diff betw : Dry & Wet Gangrene

Answer 36

1. **Site** Dry : distal parts of limb Wet : bowel, lung, mouth, cervix, vulva .. 2. **Mechanisms** Dry : Arterial Occlusion Wet : More common venous occlusion than areterial one. 3. **Grossly** Dry : dry, dark black, shrunken Wet: soft, swollen, black, putrified. 4. **Putrefaction** Dry : limited due to very little blood supply Wet : Marked due to stuffing the affected oargan w/ blood. 5. **Line of demarcation** Dry : yes Wet : NO 6. **Bacteria** Dry : Bacteria fail to survive as no blood. Wet : Numerous 7. **Prognosis** Dry : better due to little toxemia Wet : poor due to profound toxemia

Question 36

DEF gas gangrene + Gross Appearance

Answer 36

Special type of wet gangrene caused by gas-froming bacteria Clostridia (gram +ve anerobic bacteria). Grossly, there are cripitations due to gas bubbles w/ foul smelling.