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** E.g. as the hepatocyte, renal tubular epithelium and pancreatic acinar cell.
 
** E.g. as the hepatocyte, renal tubular epithelium and pancreatic acinar cell.
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==Cellular Fatty Change==
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==[[Cellular Fatty Change]]==
 
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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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** Principally in the [[Liver - Anatomy & Physiology|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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=== Gross Appearance of Fatty Change===
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* [[Liver - Anatomy & Physiology|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 pumped efficiently.
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===Histological Appearance of Fatty Change===
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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 - Anatomy & Physiology|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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*** [[Degenerations and Infiltrations - 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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===Causes of Fatty Change===
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====Dietary and Metabolic====
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# '''Starvation'''
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#*  A reduction in dietary intake necessitates 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 - Anatomy & Physiology|liver]] cannot cope with them all properly.
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#*** The fatty acids are stored in the [[Liver - Anatomy & Physiology|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 - Anatomy & Physiology|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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====Metabolic diseases====
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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 cells 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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** [[DM|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 - Anatomy & Physiology|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 after parturition.
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***** Acetonemia
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====Anoxia====
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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 - Anatomy & Physiology|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 and Infarction - Pathology#Ischaemia|Ischaemia]]
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**** Reduced blood supply to a tissue
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*** Chronic [[Venous Congestion and Hyperaemia- Pathology|venous congestion]]
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**** Slowing of blood flow through the vasculature e.g. due to a failing heart.
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====Toxins====
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* Many toxins will cause fatty change in the [[Liver - Anatomy & Physiology|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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===Distribution of Fatty Change in the Liver===
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* Fatty change in the [[Liver - Anatomy & Physiology|liver]] tends to be throughout the whole lobule.
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* Occasionally there is a preferential localisation -  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 - Anatomy & Physiology|liver]].
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*** When found post-mortem examination, indicated the heart should be examined for the cause.
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===Significance of fatty change===
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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 - Pathology|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 - Pathology|Necrosis]] of cells containing lipid may release lipid into the extracellular space. 
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*** [[Haemorrhage - Pathology|Haemorrhage]] or tissue damage may result in cholesterol being released from cells or pooled from lipoproteins in crystalline form (cholesterol clefts).
      
==Mucoid Degeneration==
 
==Mucoid Degeneration==
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