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| | ===[[General Pathology - Degenerations and Infiltrations|Degenerations and Infiltrations]]=== | | ===[[General Pathology - Degenerations and Infiltrations|Degenerations and Infiltrations]]=== |
| | | | |
| − | ==Degenerations and Infiltrations==
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| | | | |
| − | * Degenerations and infiltrations are the morphological manifestation of an altered metabolism within the cell.
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| − | ** A particular kind of change within a cell or tissue may suggest that a specific type of alteration has occurred.
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| − | * Degenerations and infiltrations are types of structural changes.
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| − | ** These are best considered at a cellular level.
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| − | ** These structural changes are deviations from the cell's normal structure and function.
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| − | *** Parameters are outside the normal physiological range for the cell.
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| − | * '''Degeneration'''
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| − | ** The tissue cell shows some change in itself.
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| − | * '''Infiltration'''
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| − | ** Something accumulates in the cell or tissue.
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| − |
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| − | ===Cellular Swelling===
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| − |
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| − | * Cellular swelling is
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| − | ** The earliest detectable degenerative change.
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| − | ** The mildest from of cellular degeneration.
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| − | ** The first stage in injury to a cell.
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| − | ** Caused by a variety of insults, e.g.
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| − | *** Lack of oxygen (anoxia) to a tissue.
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| − | *** Toxic influences.
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| − | * Is due to the impairment of the integrity of the cell membrane.
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| − | * Cellular swelling is characterised by a moderate swelling of the individual cells.
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| − | ** Due to an influx of water into the cell.
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| − |
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| − | ====Gross Appearance====
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| − |
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| − | * Organs diffusely affected with cloudy swelling grossly appear pale.
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| − | ** This may be partly due to the swollen cells impeding the tissue's blood supply.
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| − | * Without cutting into an organ, it may be difficult to appreciate a gross enlargement of it.
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| − | ** Each individual cell is increased in size, meaning the entire volume of the organ is also increased.
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| − | ** E.g. on cutting the liver or kidney capsule, the underlying swollen parenchyma bulges outwards, making the cut ends of the capsule retract.
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| − | * The degree of gross swelling is not great.
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| − | ** Could be easily confused with early post-mortem changes in the organ.
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| − |
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| − | ====Histological Appearance====
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| − |
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| − | * Individual cells appear somewhat swollen.
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| − | * The cytoplasm appears more red in colour in hematoxylin and eosin (H&E) stained sections.
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| − | * The nucleus of the cell remains normal.
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| − | * Cellular swelling is best histologically appreciated in the liver and kidney in damage caused by circulating toxins that are not powerful enough to actually kill the cells.
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| − |
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| − | ====Significance of Cellular Swelling====
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| − |
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| − | * Cellular swelling is an important stage in degeneration.
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| − | ** Not commonly observed on its own without more serious changes
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| − | *** Not easy to identify at post-mortem unless the examination os perfomred very soon after the animal's death.
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| − | **** Early post-mortem (autolytic) change in dead tissue looks rather similar.
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| − | *** Cellular swelling is also reversible.
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| − | **** When the toxin is no longer exerting its effect, the tissue returns to normal.
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| − | *** Cellular swelling may be a transient stage in the more serious forms of degenerations which follow.
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| − |
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| − | ===Hydropic Degeneration===
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| − |
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| − | * Hydropic degeneration often indicates severe cellular damage due to viruses.
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| − | ** Is a more severe or advanced form of cellular swelling.
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| − | * There are two types of hydropic degeneration, in which:
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| − | *# The cells may swell up like a balloon prior to their destruction.
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| − | *#* '''Balloning Degeneration'''
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| − | *# There is a discrete bleb (vacuole) of fluid within the cytoplasm.
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| − | *#* '''Vacuolar Degeneration'''
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| − |
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| − | ====Ballooning Degeneration====
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| − |
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| − | * May occur in a variety of conditions.
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| − | ** Is particularly seen in viral conditions of epithelial tissue.
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| − | * [[Oral Cavity - Cavity & Gingiva#Foot and Mouth disease|Foot and Mouth Disease]] is the best example.
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| − | ** Foot and Mouth virus attacks the stratum spinosum of the epithelium of the tongue and feet.
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| − | ** Affected cells balloon up with water containing the replicating virus, swelling until they burst.
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| − | *** The fluid contained in the cells then forms microvesicles (blisters) in the stratum spinosum.
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| − | **** Blisters may later burst, shedding vast quantities of the virus.
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| − | ** On bursting, the edges of the erosions look ragged.
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| − | *** Within weeks, the germinal epithelium at the base of the erosion regenerates the epithelium, leaving no trace of a scar.
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| − |
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| − | ====Vacuolar Degeneration====
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| − |
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| − | * In vacuolar degeneration, excess water is transferred to the endoplasmic reticulum (ER).
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| − | * The ER swells and eventually fragments.
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| − | ** A fluid vacuole remains in the cytoplasm.
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| − | * Commonly occurs in cells that are very metabolically active and have well developed pumping mechanisms.
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| − | ** E.g. as the hepatocyte, renal tubular epithelium and pancreatic acinar cell.
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| − |
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| − | ===Cellular Fatty Change===
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| − |
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| − | * DOES NOT REFER TO THE THE FAT STORES OF THE BODY!
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| − | ** Fatty substances accumulate or increase within the cytoplams of specific cells.
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| − | ** In some instances, the fat stores may be involved in the transfer of fat to these specific cells.
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| − | * Cellular fatty change is an important intracellular abnormality.
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| − | ** Principally concerns the intracellular fat in hepatocytes.
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| − | * Fatty change is commonly seen in three organs of the body.
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| − | ** Prinicpally in the '''liver'''.
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| − | ** Also in the '''kidney''' and the '''heart'''.
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| − | ** This is because these organs are either:
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| − | *** Involved in the metabolism of fat, or
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| − | *** Dependant upon lipids as an energy source.
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| − | * Fatty change can be readily recognised at post-mortem.
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| − |
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| − | ==== Gross Appearance of Fatty Change====
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| − |
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| − | * '''Liver'''
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| − | ** This is the main organ involved in fatty change.
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| − | ** May be greatly increased in size.
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| − | ** Is tan to yellowish in colour.
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| − | *** Is normally reddish brown.
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| − | ** Very prone to rupture with slight pressure (friable).
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| − | ** Parenchyma bulges outwards on being freed from the constraint of the capsule when cut.
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| − | ** Parenchyma is dull, yellowish and greasy.
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| − | * '''Kidney'''
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| − | ** The cortex appears paler.
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| − | ***N.B. This is normal in e.g. the cat!
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| − | *** Diffuse paleness is not the prominent feature, unlike in the liver.
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| − | * '''Heart'''
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| − | ** Anoxia, as a result of anaemia, causes fatty change.
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| − | ** The heart is flabby.
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| − | ** Fatty change may occur as streaks in the papillary muscles.
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| − | *** I.e. those muscles furthest away from the blood supply.
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| − | ** Contractile ability is reduced, and blood is therefore not umped efficiently.
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| − |
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| − | ====Histological Appearance of Fatty Change====
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| − |
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| − | * The fat either appears as globules or is contained in varying sizes of vacuoles in the cytoplasm.
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| − | ** In the heart, fat appears as groups of tiny vacuoles dispersed along the myofibrils.
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| − | ** In the liver and kidney, vacuoles tend to coalesce to form larger ones.
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| − | *** One or more large globules may fill the cytoplasm.
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| − | **** The nucleus is displaced to the periphery of the cell.
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| − | * The nucleus remains normal.
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| − | ** Nuclear changes are only seen if the degree of fatty change becomes incompatible with the continued existence of the cell.
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| − | * In hepatocytes, it is necessary to stain for fat in order to ellucidate if a vacuole in the cytoplasm is fat-containing.
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| − | ** Two further conditions may produce vacuoles in hepatocytes.
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| − | *** [[General Pathology#Vacuolar Degeneration|Vacuolar hydropic degeneration]]
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| − | *** Glycogen accumulation
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| − | ** Stains commonly used include Sudan 111, Sudan 1V, and Oil Red O.
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| − | *** Stain fat varying shades of orange to red.
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| − | ** Sections must be prepared differently to the routine paraffin embedding (used e.g. in H&E staining).
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| − | *** The strong solvents used in paraffin embedding dissolve the fat out of the cell.
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| − | *** When staining for fat, the tissue to be examined is frozen and sectioned in a cryostat before being stained.
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| − | **** These sections are more than twice as thick as those attained by sectioning paraffin blocks
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| − | ***** There may be some overlap of cells on the section.
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| − | ***** Individual cells are less clear.
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| − |
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| − | ====Causes of Fatty Change====
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| − |
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| − | =====Dietary and Metabolic=====
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| − |
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| − | # '''Starvation'''
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| − | #* A reduction in dietary intake neccessitates the increased mobilisation of fat from body fat stores to meet energy needs.
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| − | #* Fat from stores is transported in the blood as fatty acids.
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| − | #** The liver cannot cope with them all properly.
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| − | #*** The fatty acids are stored in the liver as neutral fats.
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| − | # '''Overeating'''
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| − | #* When the dietary intake is greater than the energy expenditure, the fat is temporarily stored prior to movement to the body fat stores.
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| − | #** Also occurs in fat-rich diets.
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| − | # '''Lipotrope Derangement'''
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| − | #* Lipotropes are substances which hasten the removal of fat from the liver cells.
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| − | #* Lipotropes include the amino acids that allow conjugation of fat with proteins to form the lipoprotein that is excreted from cells.
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| − | #** E.g. choline, methionine.
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| − | #** Dietary deficiency of these leads to fatty change within the cells.
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| − | #* Some poisons also prevent stages of lipoprotein formation.
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| − | #** E.g. CCl4, phosphorus and alcohol
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| − |
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| − | =====Metabolic diseases=====
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| − |
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| − | * Certain metabolic diseases may result in deranged carbohydrate metabolism.
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| − | * Glucose is not made available for uptake into the tissues.
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| − | ** The celles still require energy, and so alternative pathways are resorted to.
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| − | *** This leads to fatty change.
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| − | * Examples:
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| − | ** Diabetes mellitus in dogs
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| − | *** Deficiency of the hormone insulin required for cellular glucose utilisation.
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| − | ** Ketosis in ruminants
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| − | *** The body is exhorted to find another source of energy following drainage of the glucose reserves.
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| − | **** Fat reserves are mobilised and transported to the liver.
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| − | *** E.g.
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| − | **** Twin lambs in sheep
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| − | ***** The condition is known as Pregnancy Toxaemia
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| − | **** Milk producion in high-yielding dairy cattle shortly afer parturiton.
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| − | ***** Acetonemia
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| − |
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| − | =====Anoxia=====
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| − |
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| − | * Any condition that reduces the oxygen supply to the tissues will cause fatty change in the
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| − | liver.
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| − | * Examples:
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| − | ** Anaemia
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| − | *** Reduced numbers of red blood cells circulating in the blood
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| − | *** Caused by sustained loss of erythrocytes from the vessels by
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| − | **** Chronic haemorrhage
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| − | **** Excessive destruction of erythrocytes (haemolysis).
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| − | ** Circulatory disorders
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| − | *** Ischaemia
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| − | **** Reduced blood supply to a tissue
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| − | *** Chronic venous congestion
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| − | **** Slowing of blood flow through the vasculature e.g. due to a failing heart.
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| − |
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| − | =====Toxins=====
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| − |
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| − | * Many toxins will cause fatty change in the liver.
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| − | ** In these cases fatty change may be considered to be a more severe form of [[General Pathology#Cellular Swelling|cellular swelling]].
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| − | * Examples:
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| − | ** Bacterial and fungal toxins
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| − | *** May be:
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| − | **** Produced in the bloodstream by circulating bacteria (septicaemia/bacteraemia)
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| − | **** Produced elsewhere and absorbed into the bloodstream.
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| − | ** Chemical toxins
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| − | *** For example, CCl4, phosphorus, arsenic and lead.
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| − | ** Plant toxins
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| − | *** Some plant toxins will cause fatty change in the very early stages of poisoning.
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| − |
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| − | ====Distribution of Fatty Change in the Liver====
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| − |
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| − | * Fatty change in the liver tends to be throughout the whole lobule.
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| − | * Occasionally there is a preferential localiasation - this may give some clue as to the inciting cause.
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| − | ** E.g. in chronic venous congestion
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| − | *** Due to a failing heart (a cause of anoxia).
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| − | *** Blood pools in the centrilobular area (due to ineffective blood flow back to the heart), as well as fatty change being induced.
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| − | **** Gives a striking gross appearance - areas of yellow interspersed with red.
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| − | ***** Described as a 'nutmeg liver'.
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| − | *** When found post-mortem examination, indicated the heart should be examined for the cause.
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| − |
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| − | ====Significance of fatty change====
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| − |
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| − | * Fatty change is '''reversible''', provided that the underlying cause is brought under control.
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| − | * '''Necrosis'''
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| − | ** From the distribution of fat in a cell, it may be difficult to decide whether the fatty change is due to a toxic or metabolic defect.
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| − | *** In toxic effects, the fatty change can be considered as a more serious form of cellular swelling.
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| − | **** There may be evidence of necrosis.
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| − | *** If a metabolic defect is prolonged, cellular function may be impaired by the substantial amount of fat.
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| − | **** Necrosis may also result in this instance.
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| − | * '''Wallerian Degeneration'''
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| − | ** A special form of fatty change in the nervous system.
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| − | ** Damage to myelinated nerves results in the degeneration of the myelin that ensheaths them.
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| − | * '''Extracellular accumulation of lipids'''
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| − | ** Necrosis of cells containing lipid may release lipid into the extracellular space.
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| − | *** Haemorrhage or tissue damage may result in cholesterol being released from cells or pooled from lipoproteins in crystalline form (cholesterol clefts).
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| − |
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| − | ===Mucoid Degeneration===
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| − |
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| − | * Mucoid degeneration is also known as mucinous or myomatous degeneration.
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| − | * Mucoid degeneration involves chanages in epithelial tissue or the extracellular matrix/ ground substance.
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| − | * An extracellular phenomenon of some specific cells.
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| − | ** Tend to show a bluish tinge in H&E stained sections.
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| − |
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| − | ====Epithelium====
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| − |
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| − | * The specific cells involved in mucoid degeneration in the eptihelium are:
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| − | ** The goblet cells of wet mucous membranes.
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| − | ** The mucous glands themselves.
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| − | * This is not really a degeneration, but an increased production of mucin.
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| − | ** It is a beneficial reaction; the product
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| − | *** Is important as a lubricant.
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| − | *** Soothes inflamed surfaces.
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| − | *** Traps and dilutes harmful agents.
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| − | *** Carried specific antibodues against infectious agents.
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| − | *** Provides a means for removal of infectious agents.
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| − |
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| − | ====Connective tissue====
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| − |
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| − | * Here, the mucin forms part of the ground substance between the fibroblasts that produce it.
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| − | * A disturbance in the metabolism of the fibroblasts under some circumstances,means the ground substance takes on a bluish hue in H&E sections.
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| − | * Mucoid degenration in the heart valves of middle-aged and older dogs is a common example.
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| − | ** Causes '''endocardiosis'''.
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| − | *** A condition specific to the dog.
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| − |
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| − | ====Endocardiosis====
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| − |
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| − | * Tends to affects middle-aged and older dogs.
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| − | * Primarily occurs in the mitral valve.
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| − | * Results in slowly developing heart failure
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| − | * The valves become swollen and misshapen
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| − | ** The heart cannot pump blood effectively to the circulation from the left ventricle.
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| − | *** Blood passes back into the left atrium, compromising the filling from the pulmonary vein.
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| − | **** Leads to back pressure on the pulmonary capillaries.
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| − | ***** Oedema forms in the lungs, and can be heard as moist sounds on ausculatation.
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| − | ***** Reduces the oxygenation of blood leading to exercise intolerance.
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| − | *** Failure of the left side eventually compromises the function of the right side.
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| − | **** There is pooling of blood in the venous system i.e. in the liver.
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| − |
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| − | ===Hyaline Degeneration===
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| − |
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| − | * The term "hyaline degeneration" is applied to several types of degeneration or infiltration.
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| − | ** "Hyaline" is a descriptive term meaning "glassy".
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| − | *** Used in pathology when structureless material appears in section, and stains red with eosin
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| − | **** Describes a variety of conditions in which structureless materials are present.
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| − | * Is applied to both extra- and intra-cellular degenrations/ infiltrations.
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| − | ** '''Extracellular'''
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| − | *** Protein hyaline casts in the renal tubules.
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| − | **** From excessive protein passing through glomerulus.
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| − | **** When fresh urine is examined under the microscope, casts may be seen as elongated glassy tubes.
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| − | *** Hyaline membranes
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| − | **** Proteinaceous effusions into pulmonary alveoli
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| − | **** Prevent gaseous exchange.
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| − | ** '''Intracellular'''
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| − | *** Hyaline degeneration of skeletal muscle.
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| − | **** In vitamin E/ selenium deficiency.
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| − | * There are two forms of hyaline degeneration that deserve their own mention.
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| − | ** Fibrinoid degeneration.
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| − | ** Amyloid infiltration.
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| − |
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| − | ====Fibrinoid Degeneration====
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| − |
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| − | * Fibrinoid degeneration features a material which is fibrin-like.
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| − | * Is essentially a focal death of cells in the walls of small blood vessels (usually arterioles).
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| − | ** Parts of the vessel wall become replaced by a granular material.
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| − | *** Pinkish-red (i.e. eosin-staining).
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| − | *** Has some of the appearance and staining properties of fibrin.
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| − | *** Consists partly of degenerated muscle and elastic fibres, and partly of an increased amount of protein ground substance around the degenerated fibres.
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| − | *** Looks like a red smudge in the vessel wall when viewed histologically.
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| − | * The presence of the fibrin-like material may suggest
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| − | ** A local hypersensitivity reaction
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| − | ** Hypertension
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| − |
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| − | ====Amyloidosis====
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| − |
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| − | * Also known as amyloid infiltration
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| − | * Deposition of a proteinaceous hyaline substance in extracellular sites.
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| − | ** Sites of deposition vary with species.
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| − | * The kidney is a common site of deposition.
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| − | ** Amyloid is deposited under the capillary endothelium and progressively increases in volume.
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| − | * There are various categories of amyloid.
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| − | ** Is essentially an abnormal protein produced in the body
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| − | ** In most cases, it is produced in response to sustained antigenic stimulation caused by a chronic suppurative process.
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| − | *** E.g. a foot abscess, mastitis.
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| − | * Amyloid is a relatively inert substance.
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| − | ** When it accumulates, it is not easily removed.
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| − |
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| − | ===Glycogen Infiltration===
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| − |
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| − | * Glycogen is normally present in substantial amounts in the liver and muscle.
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| − | ** Is a readily utilisable source of energy.
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| − | * Moderate glycogen infiltration in the liver:
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| − | ** Grossly - doesn't have much effect.
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| − | ** Histologically - shows up as foamy cytoplasmic vacuoles, similar to that of fat.
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| − | * Some conditions may result in an increase in glycogen deposits.
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| − | ** '''Diabetes mellitus'''
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| − | *** Gives an increase in hepatic glycogen stores.
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| − | *** May be overshadowed by the increased fat in the hepatocytes, and therefore difficult to see.
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| − | **** Renal tubular deposits are more easily observed.
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| − | ** '''Excessive glucocorticoids'''
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| − | *** Could be due to:
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| − | **** Hyperadrenocortism
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| − | **** Animals being maintained on glucocorticoid therapy over a long period of time.
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| − | ***** Has more dramatic effect.
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| − | *** Huge amounts of glycogen infiltration.
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| − | **** Liver appears larger and paler.
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| − | **** Vacuoles may be so extensive that the rest of the cytoplasm appear as pink strands passing from the nucleus to the plasma membrane.
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| − | ***** A "feathery appearance" or "web-like effect".
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| − | ** '''Glycogen storage diseases'''
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| − | *** Due to an inherited deficiency of an enzyme required for the breakdown of glycogen to glucose.
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| − | **** Cells continuously accumulate glycogen.
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| − | *** Seen in all tissues of the body but exerts its major effect in the CNS.
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| − | * Selective staining must be employed to distinguish glycogen vacuoles from fatty vacuoles in the liver.
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| − | ** Alcohol fixation is preferred.
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| − | ** Best's Carmine is the commonly used stain.
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| − | *** Stains the intracellular glycogen red.
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| − |
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| − | ===Cellular Inclusions===
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| − |
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| − | ====Viruses====
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| − |
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| − | * Either in the nucleus or cytoplasm.
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| − |
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| − | ====Storage Products====
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| − |
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| − | * Due to '''hereditary storage diseases''' in which there is a missing or defectivecellular enzyme. There are many types known in domestic animals.
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| − | ** Break down/ build up of intracellular substances is halted.
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| − | *** The intermediate substance accumulates in the lysosomes.
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| − | ** Affects all tissues
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| − | *** The central nervous system is particularly vulnerable.
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| − | * Due to '''age'''
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| − | ** Lysosomes will accumulate non-degradable products
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| − | *** E.g. lipofuscin - the 'ageing' or 'wear and tear pigment'.
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| − | **** Cmmonly seen in middle-aged cats in the hepatocytes nearest the centrilobular veins.
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| − |
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| − | ====Intracellular Bacteria====
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| − |
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| − | * For example, [[Mycobacteria spp.|''Mycobacterium tuberculosis'']] in macrophages.
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| − |
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| − | ====Protein Accumulation====
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| − |
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| − | * In the renal tubular epithelium.
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| − | * Occurs when there is leakage of protein out through a damaged glomerulus.
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| | | | |
| | ==Necrosis== | | ==Necrosis== |