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Anatomical Pathology Cell Injury - Coggle Diagram
Anatomical Pathology Cell Injury
Describe the concept of a "steady state" in cell physiology ?
The normal cell is in a "steady state" when it is able to cope with normal physiological demands.
It must produce energy.
It must be functionally.
It must create a barrier between it's external and internal environment.
List the requirements for a "steady state"
Intact Genome: Preservation of normal DNA templates.
Intact membrane and transmembrane proteins.
Integrity of metabolic pathways - normal enzyme content.
Adequate metabolites - adequate supply of subtrates and oxygen.
Mechanisms of Cellular Injury
List the types of Injurious Agents
Hypoxia/Anoxia
Re-oxygenation/reperfusion injury due to free radical formation.
Physical Agents: mechanical trauma, thermal injury, electric shock.
Immunological reactions
Infections agents and their products
Nutritional imbalance
Drugs, chemicals and poisons
Congenital: inborn errors of metabolism, chromosomal defects
List the target sites of Injurious Agents
Cell membrane:
Transport and Receptor defects
Membrane damage due to free radicals.
Mechanical disruption due to damage to ion pumps and alteration in membrane lipids.
Nucleus:
Free radicals
Cytotoxic agents
Irradiation
Inherited or congenital abnormalities
Metabolic pathways:
Respiratory toxins/poisons
Disruption of protein synthesis (antibiotics)
Essential metabolites:
Glucose deprivation
Oxygen deficiency
Hormones
Cellular Responses to Injury
When injurious agents apply "stress" to a cell.
The stress can lead to increased/decreased functional demands being placed on the cell.
The cell has a variety of mechanisms available to it which may help it cope with the stress.
These are Cellular Adaptations regarded as Reversible Changes. One or more of these will be tried before cell death or apoptosis occurs.
Describe the various Cellular Adaptations:
Hypertrophy is the increase in the size of cells (=increase in organ/tissue size).
Hyperplasia is the increase in the number of cells (=enlargement of an organ/tissue). Is a result of cell division and replication.
Atrophy is the acquired diminution in the size of the organ or tissue due to the decrease in size, number and function of cells.
Metaplasia is the reversible change where an adult differentiated cell type (epithelia or mesenchymal) changes to another adult differentiated cell type.
eg: chronic exposure to certain respiratory irritants
Cellular Responses to Injury
If the cell continues to be stressed, past the capacity of adaptation, then injury will take
place. Initially, the injury will be Reversible.
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What are the types of reversible injuries detected on a light microscope ?
Intracellular Accumulation
Water
Fat - Triglycerides
Fat - Cholesterol & Cholesterol esters
Proteins
Glycogen
Hydropic/Vacuolar Degeneration occurs due to damage to the Sodium-Potassium pump resulting in the accumulation of Water and Sodium.
Initially detected as a mild, cloudy swelling of the cytoplasm. - Minor degree
Eventually, due to an increase in fluid, small clear cytoplasmic vacuoles will form. - Indicates irreversible change.
Eg: Hypokalemia in Renal Tubular epithelium. Hepatitis (enlargement of Hepatocytes and cytoplasm is pale) in the liver.
Fatty change ( Steatosis) is the abnormal accumulation of fat (triglycerides) in the Parenchymal Cells.
It is the most common form of degeneration, and is found in different organs.
It is commonly found in the liver, and also in the
heart and kidneys.
Steatosis in the liver is caused by: Alcoholism, Protein Calorie Malnutrition, Obesity, Diabetes mellitus, Drugs, Hepatotoxins and Inborn errors of metabolism.
Pathology of a Liver with Steatosis:
Microscopy: The liver is enlarged. It is soft and yellow. And it has a greasy cut surface.
Microscopy 2 types: Small droplet micro-vesicular steatosis. Large droplet macro-vesicular steatosis.
Lipoid Degeneration is the INTRACELLULAR accumulations of cholesterol and cholesterol esters in histocytes. (macrophages packed with cholesterol) Eg: Strawberry gallbladder.
The accumulation of proteins (immunoglobulins) in hypersecretory cells within the cytoplasm are known as Russel Bodies.
The accumulation of Glycogen/Carbohydrate typically seen in lysosomal storage disorders such as Gaucher disease.
Accumulations may be seen in the liver and heart muscles.
Results in Diabetes mellitus or Glycogen storage disease.
But after the stress persists and surpasses a threshold the injury will be Irreversible.
Or is the injurious agent is severe either in intensity and duration the threshold may be crossed whereby the cell can no longer recover from injury.
This is known as Irreversible Cell Injury
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What are the types of irreversible cell injuries that can be detected by a light microscope ?
Necrosis
Apoptosis
What is Necrosis ?
Necrosis is the death of cells in living organisms caused by the denaturation of cellular proteins and/or enzymatic digestion of cell.
How do we recognise Necrosis ?
The features of necrosis which are identifiable under a light microscope can be grouped as Nuclear changes and Cytoplasmic changes.
Nuclear:
Nuclear pyknosis - small dense, wrinkled mass of tightly packed chromatin.
Karyorrhexis - fragmentation of chromatin network.
Karyolysis - progressive dissolution by DNAases
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All result in nuclear dissolution and a Anuclear (without a nucleus) necrotic cell.
Cytoplasmic Changes:
Increasing Eosinophilia
Loss of RNA
Glassy appearance
Loss of glycogen
Other
Hyaline Degeneration
Myxoid Degeneration
Fatty Loading (Infiltration)
Hyaline degeneration is any alteration within cells or extracellular spaces which results in a translucent, homogenous, structureless, glassy pink appearances on routine H&E stain.
Myxoid degeneration is the accumulation of MUCOPOLYSACCHARIDES in the extracellular space.
eg: Connective tissue/ Mesenchymal tumors
Fatty loading (Infiltration) is the accumulation of adipocytes in tissues that they are not normally associated with them. Eg: Mycocardium
If the injurious agents causing the "stress" are removed, the cell can return back to its "normal" state.
NOTE: Whether the injury is reversible or irreversible is possibly dependent on:
Type of injurious agent
Duration and severity of injury
Number and type of cells involved
Regenerative potential of cell
List the most injured components of a cell:
Lysosomes
Smooth Endoplasmic Reticulum
Abnormalities of cytoskeleton, contractile proteins, and membrane skeletons.