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Anatomical Pathology: Cell Death, image - Coggle Diagram
Anatomical Pathology: Cell Death
Necrosis
What is Necrosis ?
Necrosis is the death of cells of a living organism due to the denaturation of cellular proteins and/or enzymatic digestion of the cell.
How do we recognise Necrosis ?
There are two ways in which we recognize Necrosis.
Cytoplasmic Changes:
Swelling of cytoplasm
Increased eosinophilia due to loss of RNA and increased binding of eosin to denatured proteins.
Glassy appearance due to loss of glycogen.
Loss of striations.
Nuclear Changes:
Nuclear Pyknosis is the shrinkage of a small, dense, wrinkled mass of tightly packed chromatin.
Karyorrhexis is the fragmentation of the chromatin network.
Karyolysis is the progressive dissolution by DNAases
Describe the causes of Necrosis
Ischemia, which cause a type of necrosis called infarction.
Toxins e.g. snake venom and bacterial toxins.
Infections e.g. virus(hepatitis) and bacteria (typhoid)
Hypersensitivity reactions e.g. caseative necrosis in TB
Chemical poisons e.g. Acids char, Alkalis liquify, Phenol coagulate
Physical factors: Irradiation (blocks Mitosis), Freezing (ice crystals and vasospasms), Heat greater than 450 degrees Celsius kills cells.
List the types of necrosis
Describe their respective features, with examples of where in the body they occur
There are 4 types of Necrosis:
Coagulative Necrosis
Liquifactive Necrosis
Caseative Necrosis
Fat Necrosis
Coagulative Necrosis
It is the most common type of necrosis.
Microscopic Features of Coagulative necrosis include
Preservation of basic cell shape
Loss of nucleus
Eosinophilic (pink) opaque cytoplasm
This is due to protein denaturation of structural or enzymatic (no proteolysis of cell) proteins.
It is seen in all tissue except brain tissue.
Liquifactive (Colliquative) Necrosis
This type of necrosis results in the liquefaction of tissues.
Due to lytic enzymes
It is characteristic of the infarction of the brain and also in abcess.
Liquifactive necrosis is seen due to water content in bran.
Microscopic Features: Compound granular corpuscles.
Caseative Necrosis
Caseative necrosis is a combination of Coagulative and Liquifactive Necrosis.
Macroscopic: It has a SOFT friable, yellow-white debris similar to cheese appearance.
It is seen due to hypersensitivity reaction in TB
Location: Lung tissue
Microscopic Features of this necrosis:
Caseative necrosis in center
Epithelioid histocytes forming a granuloma
Fragmented granular cellular debris
Fat Necrosis
Fat necrosis is caused by:
Enzymatic activity
Trauma to fatty tissue
Infections
Enzymatic Fat Necrosis is seen in Acute Pancreatitis
Acute Pancreatitis is caused by Alcohol, Bile reflux/Regurgitation
The enzymatic fat necrosis seen in acute pancreatitis is caused by a Pancreatic Enzyme
The Pancreatic enzyme:
Liquifies the cell membrane
Lipases catalyse triglycerides forming free fatty acids which complex with Calcium -- forming calcium soaps (Saponification)
This results in focal necrosis in pancreas & abdominal fat.
Enzymatic fat Necrosis Macroscopy:
Chalky white deposits on pancreas are indicative of enzymatic fat necrosis.
Enzymatic Fat Necrosis Microscopy in Acute Pancreatitis context:
Shadowy outlines of necrotic fat cells.
Amorphous granular basophilic deposits.
Variable inflammatory reaction
Traumatic Fat Necrosis
Occurs due to trauma inflicted on fatty tissue such as injection.
Site of trauma: Breasts and Buttocks
Traumatic Fat Necrosis Macroscopy: Firm to hard mass.
Traumatic Fat Necrosis Microscopy: Foamy Histocytes, Granulation tissues
Describe the two types of lysis which fall under Necrosis.
Autolysis is the cellular enzymatic degradation by a catalytic enzyme derived from lysosomes of dead tissues.
Heterolysis is the cellular enzymatic degradation by a catalytic enzyme derived from immigrant leucocytes and other living cells. (neutrophils and macrophages)
*Lysis differ only by type enzyme derivation.
Gangrene
What is Gangrene ?
Gangrene is necrosis with putrefaction of a number of tissues in a body part.
Describe the Classification of Gangrene
Gangrene can be classified as Primary or Secondary Gangrene.
Primary Gangrene is due to infections with pathogenic bacteria which kills tissues and then invade and digest dead tissue.
Secondary Gangrene is necrosis due to another cause such as Ischemia.
Primary Gangrene
An example of primary gangrene is gas gangrene.
Caused by anaerobic gram positive sporulating bacilli. For example Clostridium perfringens, an intestinal commensal.
Spores of this bacteria are found in the soil.
In an anaerobic environment - exotoxins - kill adjacent tissues which are in turn invaded - process spreads rapidly.
Bacteria ferment sugar, producing Water and Carbon Dioxide bubbles in the tissues. (crepitant on palpitation)
Secondary / Ischemic Gangrene
This type of gangrene can be either Dry or Wet.
Cause of Secondary Gangrene are: Vascular Disease, Embolism, Trauma, Frostbite, Chemicals.
Dry Ischemic Gangrene - shrivelled and dry
Black appearance is due to presence of Iron Sulphide Fe2S3
Healing above the line may lead to spontaneous amputation.
Sharp line of demarcation and usually starts in the toes.
Wet Ischemic Gangrene:
Putrid, foul smelling.
Rapid Proximal Spreading
No clear or sharp line of demarcation.
Apoptosis
What is Apoptosis ?
Apoptosis is a pathway of cell death induced by regulated intracellular programmes in which the targeted cells activate enzymes that destroy the DNA and other cellular proteins.
It is programmed cell death.
it is associated with energy dependent fragmentation of DNA by endogenous endonucleases.
Apoptosis results in individual cells deletion of unwanted/defective cells induced by physiological or pathological stimuli.
NOTE: Apoptosis may occur as pathological or physiological process.
What are the Functions of Apoptosis ?
Apoptosis has several functions or roles.
Apoptosis may be part of a physiological process such as:
Embryogenesis
Hormone dependent involution
Cell deletion in proliferating tissues - intestine.
Preventing genome instability.
Apoptosis may also be part of pathological processes such as:
Cell death in tumors
Death of immune cells ( B and T lymphocytes)
Atrophy of hormone dependent organs
Cell Injury by viruses.
Describe in detail the morphological Features of Apoptosis
The cell shrinks and the nuclear material condenses.
The cell membrane "blebs" form. this can only be detected by an electron microscopy)
The membrane blebbing continues. And the cell Nucleus collapses further.
The cell fragments into Apoptotic (seperate pieces) bodies.
This is then mopped up and digested by phagocytes.
Microscopy shows a cell that is smaller and is with a condensed nucleus.
Apoptosis has specific disease association
Reduced Apoptosis results in cell accumulation. For example: Neoplasia where P53 and bcl-2 play a role.
Increased Apoptosis results in excess cell loss. For example: Atrophy, AIDS and Neurodegenerative disorders
