Cell injury

Reversible cell injury:

indicates that the cellular changes will regress and disappear when the injurious agent is removed; the cell will return to normal both morphologically and functionally e.g.
1- Cloudy swelling (Hydropic changes, Hydropic degeneration)
this is an early changes in reversible cell injury. The extra-fluid may be seen by light microscope as an increase in the size of the cell with pallor of the cytoplasm (cloudy swelling), with further water accumulation, clear vacuoles are created within the cytoplasm (vacular degeneration).
2- fatty changes

Fatty changes

abnormal accumulation of fat within parenchymal cells. (Fatty degeneration, fatty infiltration).
occurs in the liver, myocardium, and the kidney.
The liver plays an important role in the metabolism of fat because it is largely responsible for the conversion of free fatty acids into a lipoprotein which is more readily utilizable by other cells
causes of fatty liver: alcohol, anoxia, obesity, diabetes mellitus, protein malnutrition, and hepatotoxins.

  SHAPE \* MERGEFORMAT 


The significance of fatty change depends on the cause and severity of the accumulation. When mild, it may have no effect on cellular function. More severe fatty change may impair cellular function, typically when some vital intracellular process is also impaired (e.g., in CCl4 poisoning). In the severe form, fatty change may precede cell death, and may be an early lesion in a serious liver disease called nonalcoholic steatohepatitis.

Morphology:

Gross features : In the liver mild fatty changes may not affect the gross appearance, but with further accumulation the organ enlarges & become increasingly yellow, soft & greasy .
Microscopically : In the early stages there are small fat vacuoles around the nucleus. As the process progresses, the vacuoles coalesce, creating cleared spaces that displace the nucleus to the periphery of the cell.


Irreversible injury:
occurs when stressors exceed the capacity of the cell to adapt (beyond a point of no return) and denotes permanent pathologic changes that cause cell death. The two pathologic patterns of cell death are necrosis and apoptosis .

Necrosis

Necrosis is cell death in living tissue or organs. It is characterized by severe cell swelling, denaturation and coagulation of proteins, breakdown of cellular organelles, and cell rupture. Usually, a large number of cells in the adjoining tissue are affected.

Morphology:

Necrotic cells are more eosinophilic(pink) than viable cells by standard hematoxylin and eosin (H&E) staining. They appear "glassy" owing to glycogen loss and may be vacuolated; cell membranes are fragmented.
Nuclear changes include: - Pyknosis small and dense nuclei
- Karyolysis complete lysis of the nuclei
- Karyorrhexis fragmented nuclei
Types:
Coagulative necrosis
is the most common form of necrosis in cells without large numbers of lysosomes. The cells converted into a homogeneous, eosinophilic mass with the loss of nucleus but preservation of cellular outline. Coagulative necrosis typically occurs after sudden ischemia, or toxin injury. The heart is the most common site, but can also occur in kidney and spleen.
Liquefactive necrosis
results from cellular destruction by hydrolytic enzymes. Typically, liquefactive necrosis occurs in brain infarcts. Liquefaction by leukocytic enzymes is called suppuration, and the resultant fluid is called pus.
Caseous necrosis
is a combination of coagulation and liquefaction necrosis, which produces tissue that is grossly soft, friable, and "cheese-like." Histological staining shows an amorphous eosinophilic area stippled by haematoxyphilic nuclear debris. Caseous necrosis is characteristic of tuberculosis, some granulomas and fungal infections, and the center of certain malignancies.
Fat necrosis
Enzymatic necrosis of fat: destruction of fat in the abdominal cavity especially around pancreas due to leakage of activated pancreatic lipases from injured pancreas. Lipases split the triglyceride of adipocytes to fatty acids which combine with calcium to form chalky white areas white saponification.
Traumatic fat necrosis: seen where adipose tissue is crushed as e.g., in female breast
Gangrenous necrosis
Gangrene is necrosis with the putrefaction of the tissues, sometimes as the result of the action of certain bacteria (e.g. clostridia). The affected tissues appear black due to the deposition of iron sulphide from degraded hemoglobin.
'dry' gangrene sterile; 'wet' gangrene - with bacterial putrefaction.
Sequelae of Necrosis (outcome)
Surrounding inflammatory reaction with hyperemia and phagocytes .
Digestion and liquefaction of necrotic debris by enzymes, autolytic and
heterolytic. Absorption of liquid debris by lymphatics and removal of solid
debris by macrophages
Fibrosis and scarring.
Regeneration of parenchyma if appropriate cell types and stromal retention
Calcification of debris slow to be removed (dystrophic calcification)


Apoptosis:
The term is from the Greek meaning dropping away as the leaves from a tree.
Apoptosis (apoptotic necrosis) a type of programmed cell death with initiation of a
self-induced cell death process (cell suicide)


Causes of Apoptosis
Normal occurrence in many situations, physiologic and pathologic
Eliminates unwanted, potentially harmful, useless, damaged cells.
DNA damage of many types is a cause, e.g. due to failure of DNA repair
Physiologic Apoptosis
Programmed cell destruction during embryogenesis.
Hormone dependent involution in adults. E.g. endometrial and uterine involution
Cell deletion in proliferating cell populations. Skin, gut
Death of inflammatory and immune cells
Elimination of self-reactive lymphocytes
Cell death by cytotoxic T cells. Defense mechanism against viruses, tumors,
Pathologic Apoptosis
Cell death produced by injurious stimuli.
Radiation, anticancer drugs that damage DNA, heat, hypoxia (if mild), ER stress
induced by unfolded proteins
Cell injury in some viral diseases.
Pathologic atrophy as in the prostate after castration & in parenchymal organs
after duct obstruction.
Cell death in tumors.

Mechanisms of Apoptosis

A variety of stimuli result in self-programmed, genetically determined, energy-
dependent sequences of molecular events involving
initiation by cell signaling,
control and integration by regulatory molecules,
a common execution phase by caspase family genes, and
dead cell removal
A- Signals that initiate the process
(1) Binding of tumor necrosis factor TNF to its receptor
(2) Injurious agents: viruses, radiation, free radicals that damage DNA.
(3) Withdrawal of growth factors or hormones.
B- Modulators that control cell response to the signal
(1) P53 suppressor gene: temporarily arrest the cell cycle to repair DNA
damage (abort apoptosis) or promote apoptosis if DNA damage is too
great by activating the BAX apoptosis gene.
(2) BCL2 gene family: manufactures gene products that inhibit apoptosis
by preventing mitochondrial leakage of cytochrome c in to the cytosol.
C- Enzymatic cell death ( Execution) beginning with activation of the caspases
(group of cysteine proteases)
(1) Activation of endonuclease leads to nuclear pyknosis ( "ink dot"
appearance) and fragmentation.
(2) Activation of protease leads to break down of the cytoskeleton.
D- removal of dead cells.
(1) Formation of cytoplasmic buds on the cell membrane, which contain
nuclear fragments, mitochondria, and condensed protein fragments.
(2) Formation of apoptotic bodies by the breaking off of the cytoplasmic
buds.
(3) Phagocytosis of apoptotic bodies by neighboring cells or macrophages.












PAGE 

PAGE \* MERGEFORMAT7

10 -10-2018

1. Excessive entry of lipids into the liver ( DM, Starvation)
2. Enhanced fatty acid synthesis by hepatocytes
3. Decreased oxidation of fatty acids by mitochondria (Alcohol,Anoxia)
4. Increased esterification of fatty acids to triglycerides
5. Decreased apoprotein synthesis (CCl4 and protein malnutrition)
6. Impaired lipoprotein excretion