Cell Injury

Pathology Dr. KHALID W. ABDULATTAH Lecturer in pathology department/Mousel Medical college Cell Injury, Cell Death, and Adaptations Lecture 1

Cellular Responses to Stress and Toxic Insults:

- Cellular adaptations Atrophy, hypertrophy, hyperplasia, metaplasia - Cell injury *Reversible injury *Irreversible injury (Cell death) 1-Necrosis 2-Apoptosis - Intracellular accumulations - Pathologic calcification

Stages of the cellular response to stress and injurious stimuli

According to capacity of cell to division it divided into
High capacity (labile cell) Nil capacity (permanent cell) Epidermis Neurons Gastrointestinal epithelium Cardiac muscle Respiratory epithelium Bone marrow Low capacity (stable cell) Hepatocytes Pancreas Kidney Smooth muscle Bone cartilage

Cellular adaptations: 1-Atrophy:- Shrinkage in the size of the cell by the loss of cell substance resulting in decrease in the size of the organ. causes: 1-Decrease in the workload 2-Denervation: e.g. paralysis of limb due to nerve injury or poliomyelitis. 3-Under nutrition as in starvation 4-Loss of endocrine stimulation e.g. atrophy of the gonads in hypopituitarism. 5-Aging 6-Diminish blood supply

On the left is a normal testis. On the right is a testis that has undergone atrophy

left ventricular hypertrophy.

Hypertrophic cardiomyopathy is an example of pathological hypertrophy due to increase demand, this ultimately results in increase in the size of the organ



3-Hyperplasia:- increase in the number of cells resulting in increase in the size of the organ.-usually associated with hypertrophy.- occurs in tissues whose cells are able to divide (labile & stable cells), could be:Physiological:  hormonal: proliferation of the breast glandular epithelium of female at puberty, or during pregnancy.  compensatory: hyperplasia of the cell when part of the tissue is removed e.g. when part of the liver is resected. Pathological: Extensive hormonal stimulation e.g. endometrial hyperplasia.

Endometrial hyperplasia is an example of hormone-induced hyperplasia due to hyperestrogenism.


This is an endometrial hyperplasia in which the amount of endometrium is abnormally increased.

4-Metaplasia: this refers to replacement of one mature cell type by an other mature cell type. It is a reversible process It may represents an adaptation (replacement) of cells more sensitive to stress by others that are more resistant to the adverse environment, e.g: Squamous metaplasia of the laryngeal and bronchial respiratory epithelium due to habitual smoking. Columnar metaplasia of esophageal squamous epithelium. as a result of prolonged reflux esophagitis.

Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus

Barrett esophagus: Metaplastic transformation (arrow) of the normal esophageal stratified squamous epithelium (Lt) to mature columnar epithelium

Squamous metaplasia of bronchial epithelium

If the adaptation capacity is exceeded or if the cell cannot undergo adaptation the cell injury will occur & up to certain limit these changes are reversible and then cell can return to normal if the causative agent is removed. however if the stress is severe or persistent this lead to irreversible cell injury.

Cell Injury

General Principles related to cell injury: Cellular response to injurious stimuli depend on type of injury , its duration & its severity . Consequences of an injurious depend on type , status & genetic make up of the cell. Four intracellular systems are vulnerable to injury include : mitochondria (ATP) , protein synthesis , integrity of genetic apparatus & cell membrane.


Free radical induced cell injury: Free radical species: are chemical substances with an unpaired electron in the outer orbit, these substances are unstable so it reacts with any organic or inorganic substances to be stable . Examples of free radicals: superoxideanion (O2–) and hydroxyl radical (OH·)Free radical causes cell injury by: DNA fragmentation which lead to cell death & neoplasia Membrane damage through the process of lipid peroxidationCross link of proteins which enhance loss of enzyme activity or cause fragmentation of protein.Normally, there are several enzymatic and nonenzymatic systems to inactivate free radicals:glutathione peroxidase and superoxide dismutase.Endogenous or exogenous antioxidants (e.g. vitamin E, A & C & β carotene)

Stages of the cellular response to stress and injurious stimuli

Causes of cell injury:1-HypoxiaIschemiaCardiac & respiratory diseasesLow O2 carrying capacity ( anemia)2-Physical injury (temp, radiation, electrical shock, trauma, change in atmospheric pressure)3-Chemical agents & drugs4-Microbial agents (virus, bacterial, …..etc)5-Immunologic reactions (hypersensitivity reaction , anaphylactic shock & autoimmune diseases) 6-Genetic derangement (Down’s syndrome & sickle cell anemia)7-Nutritional imbalance (vitamin deficiency, protein deficiency, increase fat, alcoholism)8-Aging

Reversible cell injury :

It is a common type of cell injury usually due to ischemia (hypoxia) in this type of injury the cellular changes will regress and disappear when the injurious agent is removed; the cell will return to normal both morphologically and functionally Morphology of reversible cell injury: The two main morphologic correlates of reversible cell injury are cellular swelling and fatty change.

2-Fatty changes (steatosis): Is abnormal accumulation of fat of triglyceride type within parenchymal cells rather than adipocytes. It is an example of reversible cell injury, Seen often in the liver in which fat centrally metabolized & to less extent in the heart & kidney

Fat Droplets

Irreversible cell injury: occurs when the injury persist or when it is severe from the start. Here the cell reaches the point of no return and progression to cell death is inevitable. It is of 2 types: 1) Necrosis 2)Apoptosis Necrosis: it is a sequence of morphologic changes that follow cell death in the living tissue or organs due to action of degradative enzymes or protein denaturation on irreversibly injured cells.


NecrosisIt is a passive processAssociated with inflammationRandomly occurs Involve a group of cells Always pathologicCauses : ischemia, chemical injury or infarction( cell death due to cut of blood supply), nutritional….etcMechanisms of necrosis:Denaturation of proteinsEnzymatic digestion of the cell: either by its own enzymes (autolysis) or the cell digested by proteolytic enzymes secreted from invading inflammatory cells, this is called (heterolysis)

Liver cell necrosis: Nuclear changes

normal
pyknosis
karyorrhexis
karyolysis

Types (Patterns) of necrosis

coagulation necrosis liquifactive necrosis fat necrosis caseous necrosis fibrinoid necrosis gangrene

Coagulative necrosis: The most common type of necrosis. Occurs Any where in the body except C.N.S Usually due to hypoxia Grossly: Whitish-gray or red-hemorrhagic firm wedge shape area of infarction,(the occluded vessel at the apex and the periphery of the organ forming the base). Histology: Preservation of the tissue architecture & cellular outline. loss of internal details including nuclei. It Results from denaturation of proteins

Coagulative necrosis(infarction)-Spleen

infarction
It is an ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage. Coagulative necrosis is characteristic of infarcts (areas of ischemic necrosis) in all of the solid organs except the brain.

Coagulative necrosis(infarction)-kidney

Myocardial infraction, the cells become more eosinophilic , loss of striation, absence of nucleus & their outline are preserved

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