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, 13:56, 23 June 2010
* DOES NOT REFER TO THE THE FAT STORES OF THE BODY!
** Fatty substances accumulate or increase within the cytoplams of specific cells.
** In some instances, the fat stores may be involved in the transfer of fat to these specific cells.
* Cellular fatty change is an important intracellular abnormality.
** Principally concerns the intracellular fat in hepatocytes.
* Fatty change is commonly seen in three organs of the body.
** Principally in the [[Liver - Anatomy & Physiology|liver]].
** Also in the '''kidney''' and the '''heart'''.
** This is because these organs are either:
*** Involved in the metabolism of fat, or
*** Dependant upon lipids as an energy source.
* Fatty change can be readily recognised at post-mortem.
=== Gross Appearance of Fatty Change===
* [[Liver - Anatomy & Physiology|Liver]]
** This is the main organ involved in fatty change.
** May be greatly increased in size.
** Is tan to yellowish in colour.
*** Is normally reddish brown.
** Very prone to rupture with slight pressure (friable).
** Parenchyma bulges outwards on being freed from the constraint of the capsule when cut.
** Parenchyma is dull, yellowish and greasy.
* '''Kidney'''
** The cortex appears paler.
***N.B. This is normal in e.g. the cat!
*** Diffuse paleness is not the prominent feature, unlike in the liver.
* '''Heart'''
** Anoxia, as a result of anaemia, causes fatty change.
** The heart is flabby.
** Fatty change may occur as streaks in the papillary muscles.
*** I.e. those muscles furthest away from the blood supply.
** Contractile ability is reduced, and blood is therefore not pumped efficiently.
===Histological Appearance of Fatty Change===
* The fat either appears as globules or is contained in varying sizes of vacuoles in the cytoplasm.
** In the heart, fat appears as groups of tiny vacuoles dispersed along the myofibrils.
** In the [[Liver - Anatomy & Physiology|liver]] and kidney, vacuoles tend to coalesce to form larger ones.
*** One or more large globules may fill the cytoplasm.
**** The nucleus is displaced to the periphery of the cell.
* The nucleus remains normal.
** Nuclear changes are only seen if the degree of fatty change becomes incompatible with the continued existence of the cell.
* In hepatocytes, it is necessary to stain for fat in order to ellucidate if a vacuole in the cytoplasm is fat-containing.
** Two further conditions may produce vacuoles in hepatocytes.
*** [[Degenerations and Infiltrations - Pathology#Vacuolar Degeneration|Vacuolar hydropic degeneration]]
*** Glycogen accumulation
** Stains commonly used include Sudan 111, Sudan 1V, and Oil Red O.
*** Stain fat varying shades of orange to red.
** Sections must be prepared differently to the routine paraffin embedding (used e.g. in H&E staining).
*** The strong solvents used in paraffin embedding dissolve the fat out of the cell.
*** When staining for fat, the tissue to be examined is frozen and sectioned in a cryostat before being stained.
**** These sections are more than twice as thick as those attained by sectioning paraffin blocks
***** There may be some overlap of cells on the section.
***** Individual cells are less clear.
===Causes of Fatty Change===
====Dietary and Metabolic====
# '''Starvation'''
#* A reduction in dietary intake necessitates the increased mobilisation of fat from body fat stores to meet energy needs.
#* Fat from stores is transported in the blood as fatty acids.
#** The [[Liver - Anatomy & Physiology|liver]] cannot cope with them all properly.
#*** The fatty acids are stored in the [[Liver - Anatomy & Physiology|liver]] as neutral fats.
# '''Overeating'''
#* When the dietary intake is greater than the energy expenditure, the fat is temporarily stored prior to movement to the body fat stores.
#** Also occurs in fat-rich diets.
# '''Lipotrope Derangement'''
#* Lipotropes are substances which hasten the removal of fat from the [[Liver - Anatomy & Physiology|liver]] cells.
#* Lipotropes include the amino acids that allow conjugation of fat with proteins to form the lipoprotein that is excreted from cells.
#** E.g. choline, methionine.
#** Dietary deficiency of these leads to fatty change within the cells.
#* Some poisons also prevent stages of lipoprotein formation.
#** E.g. CCl4, phosphorus and alcohol
====Metabolic diseases====
* Certain metabolic diseases may result in deranged carbohydrate metabolism.
* Glucose is not made available for uptake into the tissues.
** The cells still require energy, and so alternative pathways are resorted to.
*** This leads to fatty change.
* Examples:
** [[DM|Diabetes mellitus]] in dogs
*** Deficiency of the hormone insulin required for cellular glucose utilisation.
** Ketosis in ruminants
*** The body is exhorted to find another source of energy following drainage of the glucose reserves.
**** Fat reserves are mobilised and transported to the [[Liver - Anatomy & Physiology|liver]].
*** E.g.
**** Twin lambs in sheep
***** The condition is known as Pregnancy Toxaemia
**** Milk producion in high-yielding dairy cattle shortly after parturition.
***** Acetonemia
====Anoxia====
* Any condition that reduces the oxygen supply to the tissues will cause fatty change in the
[[Liver - Anatomy & Physiology|liver]].
* Examples:
** Anaemia
*** Reduced numbers of red blood cells circulating in the blood
*** Caused by sustained loss of erythrocytes from the vessels by
**** Chronic haemorrhage
**** Excessive destruction of erythrocytes (haemolysis).
** Circulatory disorders
*** [[Ischaemia and Infarction - Pathology#Ischaemia|Ischaemia]]
**** Reduced blood supply to a tissue
*** Chronic [[Venous Congestion and Hyperaemia- Pathology|venous congestion]]
**** Slowing of blood flow through the vasculature e.g. due to a failing heart.
====Toxins====
* Many toxins will cause fatty change in the [[Liver - Anatomy & Physiology|Liver]].
** In these cases fatty change may be considered to be a more severe form of [[General Pathology#Cellular Swelling|cellular swelling]].
* Examples:
** Bacterial and fungal toxins
*** May be:
**** Produced in the bloodstream by circulating bacteria (septicaemia/bacteraemia)
**** Produced elsewhere and absorbed into the bloodstream.
** Chemical toxins
*** For example, CCl4, phosphorus, arsenic and lead.
** Plant toxins
*** Some plant toxins will cause fatty change in the very early stages of poisoning.
===Distribution of Fatty Change in the Liver===
* Fatty change in the [[Liver - Anatomy & Physiology|liver]] tends to be throughout the whole lobule.
* Occasionally there is a preferential localisation - this may give some clue as to the inciting cause.
** E.g. in chronic venous congestion
*** Due to a failing heart (a cause of anoxia).
*** Blood pools in the centrilobular area (due to ineffective blood flow back to the heart), as well as fatty change being induced.
**** Gives a striking gross appearance - areas of yellow interspersed with red.
***** Described as a 'nutmeg' [[Liver - Anatomy & Physiology|liver]].
*** When found post-mortem examination, indicated the heart should be examined for the cause.
===Significance of fatty change===
* Fatty change is '''reversible''', provided that the underlying cause is brought under control.
* '''Necrosis'''
** 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.
*** In toxic effects, the fatty change can be considered as a more serious form of cellular swelling.
**** There may be evidence of necrosis.
*** If a metabolic defect is prolonged, cellular function may be impaired by the substantial amount of fat.
**** [[Necrosis - Pathology|Necrosis]] may also result in this instance.
* '''Wallerian Degeneration'''
** A special form of fatty change in the nervous system.
** Damage to myelinated nerves results in the degeneration of the myelin that ensheaths them.
* '''Extracellular accumulation of lipids'''
** [[Necrosis - Pathology|Necrosis]] of cells containing lipid may release lipid into the extracellular space.
*** [[Haemorrhage - Pathology|Haemorrhage]] or tissue damage may result in cholesterol being released from cells or pooled from lipoproteins in crystalline form (cholesterol clefts).[[Category:Myocardial_Pathology]][[Category:General Pathology]]