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Degenerations and Infiltrations - Pathology (view source)
Revision as of 20:53, 13 August 2009
, 20:53, 13 August 2009New page: {{review}} {{toplink |linkpage =General Pathology |linktext =General Pathology |maplink = General Pathology (Content Map) |pagetype =Pathology }} <br> ==Introduction== * Degenerations a...
{{review}}
{{toplink
|linkpage =General Pathology
|linktext =General Pathology
|maplink = General Pathology (Content Map)
|pagetype =Pathology
}}
<br>
==Introduction==
* Degenerations and infiltrations are the morphological manifestation of an altered metabolism within the cell.
** A particular kind of change within a cell or tissue may suggest that a specific type of alteration has occurred.
* Degenerations and infiltrations are types of structural changes.
** These are best considered at a cellular level.
** These structural changes are deviations from the cell's normal structure and function.
*** Parameters are outside the normal physiological range for the cell.
* '''Degeneration'''
** The tissue cell shows some change in itself.
* '''Infiltration'''
** Something accumulates in the cell or tissue.
==Cellular Swelling==
* Cellular swelling is
** The earliest detectable degenerative change.
** The mildest form of cellular degeneration.
** The first stage in injury to a cell.
** Caused by a variety of insults, e.g.
*** Lack of oxygen (anoxia) to a tissue.
*** Toxic influences.
* Is due to the impairment of the integrity of the cell membrane.
* Cellular swelling is characterised by a moderate swelling of the individual cells.
** Due to an influx of water into the cell.
===Gross Appearance===
* Organs diffusely affected with cloudy swelling grossly appear pale.
** This may be partly due to the swollen cells impeding the tissue's blood supply.
* Without cutting into an organ, it may be difficult to appreciate a gross enlargement of it.
** Each individual cell is increased in size, meaning the entire volume of the organ is also increased.
** E.g. on cutting the [[Liver - Anatomy & Physiology|liver]] or kidney capsule, the underlying swollen parenchyma bulges outwards, making the cut ends of the capsule retract.
* The degree of gross swelling is not great.
** Could be easily confused with early post-mortem changes in the organ.
===Histological Appearance===
* Individual cells appear somewhat swollen.
* The cytoplasm appears more red in colour in hematoxylin and eosin (H&E) stained sections.
* The nucleus of the cell remains normal.
* Cellular swelling is best histologically appreciated in the [[Liver - Anatomy & Physiology|liver]] and kidney in damage caused by circulating toxins that are not powerful enough to actually kill the cells.
===Significance of Cellular Swelling===
* Cellular swelling is an important stage in degeneration.
** Not commonly observed on its own without more serious changes
*** Not easy to identify at post-mortem unless the examination is performed very soon after the animal's death.
**** Early post-mortem (autolytic) change in dead tissue looks rather similar.
*** Cellular swelling is also reversible.
**** When the toxin is no longer exerting its effect, the tissue returns to normal.
*** Cellular swelling may be a transient stage in the more serious forms of degenerations which follow.
==Hydropic Degeneration==
* Hydropic degeneration often indicates severe cellular damage due to viruses.
** Is a more severe or advanced form of cellular swelling.
* There are two types of hydropic degeneration, in which:
*# The cells may swell up like a balloon prior to their destruction.
*#* '''Ballooning Degeneration'''
*# There is a discrete bleb (vacuole) of fluid within the cytoplasm.
*#* '''Vacuolar Degeneration'''
===Ballooning Degeneration===
* May occur in a variety of conditions.
** Is particularly seen in viral conditions of epithelial tissue.
* [[Cavity & Gingiva - Pathology#Foot and Mouth disease|Foot and Mouth Disease]] is the best example.
** Foot and Mouth virus attacks the stratum spinosum of the epithelium of the [[Oral Cavity - Tongue - Anatomy & Physiology|tongue]] and feet.
** Affected cells balloon up with water containing the replicating virus, swelling until they burst.
*** The fluid contained in the cells then forms microvesicles (blisters) in the stratum spinosum.
**** Blisters may later burst, shedding vast quantities of the virus.
** On bursting, the edges of the erosions look ragged.
*** Within weeks, the germinal epithelium at the base of the erosion regenerates the epithelium, leaving no trace of a scar.
===Vacuolar Degeneration===
* In vacuolar degeneration, excess water is transferred to the endoplasmic reticulum (ER).
* The ER swells and eventually fragments.
** A fluid vacuole remains in the cytoplasm.
* Commonly occurs in cells that are very metabolically active and have well developed pumping mechanisms.
** E.g. as the hepatocyte, renal tubular epithelium and pancreatic acinar cell.
==Cellular Fatty Change==
* 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).
==Mucoid Degeneration==
* Mucoid degeneration is also known as mucinous or myomatous degeneration.
* Mucoid degeneration involves changes in epithelial tissue or the extracellular matrix/ ground substance.
* An extracellular phenomenon of some specific cells.
** Tend to show a bluish tinge in H&E stained sections.
===Epithelium===
* The specific cells involved in mucoid degeneration in the eptihelium are:
** The goblet cells of wet mucous membranes.
** The mucous glands themselves.
* This is not really a degeneration, but an increased production of mucin.
** It is a beneficial reaction; the product
*** Is important as a lubricant.
*** Soothes inflamed surfaces.
*** Traps and dilutes harmful agents.
*** Carries specific antibodies against infectious agents.
*** Provides a means for removal of infectious agents.
===Connective tissue===
* Here, the mucin forms part of the ground substance between the fibroblasts that produce it.
* A disturbance in the metabolism of the fibroblasts under some circumstances,means the ground substance takes on a bluish hue in H&E sections.
* Mucoid degeneration in the heart valves of middle-aged and older dogs is a common example.
** Causes '''endocardiosis'''.
*** A condition specific to the dog.
===Endocardiosis===
* Tends to affects middle-aged and older dogs.
* Primarily occurs in the mitral valve.
* Results in slowly developing heart failure
* The valves become swollen and misshapen
** The heart cannot pump blood effectively to the circulation from the left ventricle.
*** Blood passes back into the left atrium, compromising the filling from the pulmonary vein.
**** Leads to back pressure on the pulmonary capillaries.
***** [[Oedema - Pathology|Oedema]] forms in the lungs, and can be heard as moist sounds on auscultation.
***** Reduces the oxygenation of blood leading to exercise intolerance.
*** Failure of the left side eventually compromises the function of the right side.
**** There is pooling of blood in the venous system i.e. in the [[Liver - Anatomy & Physiology|liver]].
==Hyaline Degeneration==
* The term "hyaline degeneration" is applied to several types of degeneration or infiltration.
** "Hyaline" is a descriptive term meaning "glassy".
*** Used in pathology when structureless material appears in section, and stains red with eosin
**** Describes a variety of conditions in which structureless materials are present.
* Is applied to both extra- and intra-cellular degenerations/ infiltrations. ** '''Extracellular'''
*** Protein hyaline casts in the renal tubules.
**** From excessive protein passing through glomerulus.
**** When fresh urine is examined under the microscope, casts may be seen as elongated glassy tubes.
*** Hyaline membranes
**** Proteinaceous effusions into pulmonary alveoli
**** Prevent gaseous exchange. ** '''Intracellular'''
*** Hyaline degeneration of skeletal muscle.
**** In vitamin E/ selenium deficiency.
* There are two forms of hyaline degeneration that deserve their own mention.
** Fibrinoid degeneration.
** Amyloid infiltration.
===Fibrinoid Degeneration===
* Fibrinoid degeneration features a material which is fibrin-like.
* Is essentially a focal death of cells in the walls of small blood vessels (usually arterioles).
** Parts of the vessel wall become replaced by a granular material.
*** Pinkish-red (i.e. eosin-staining).
*** Has some of the appearance and staining properties of fibrin.
*** Consists partly of degenerated muscle and elastic fibres, and partly of an increased amount of protein ground substance around the degenerated fibres.
*** Looks like a red smudge in the vessel wall when viewed histologically.
* The presence of the fibrin-like material may suggest
** A local hypersensitivity reaction
** Hypertension
===Amyloidosis===
* Also known as amyloid infiltration
* Deposition of a proteinaceous hyaline substance in extracellular sites.
** Sites of deposition vary with species.
* The kidney is a common site of deposition.
** Amyloid is deposited under the capillary endothelium and progressively increases in volume.
* There are various categories of amyloid.
** Is essentially an abnormal protein produced in the body
** In most cases, it is produced in response to sustained antigenic stimulation caused by a chronic suppurative process.
*** E.g. a foot abscess, mastitis.
* Amyloid is a relatively inert substance.
** When it accumulates, it is not easily removed.
==Glycogen Infiltration==
* Glycogen is normally present in substantial amounts in the [[Liver - Anatomy & Physiology|liver]] and muscle.
** Is a readily utilisable source of energy.
* Moderate glycogen infiltration in the [[Liver - Anatomy & Physiology|liver]]:
** Grossly - doesn't have much effect.
** Histologically - shows up as foamy cytoplasmic vacuoles, similar to that of fat.
* Some conditions may result in an increase in glycogen deposits.
** [[DM|'''Diabetes mellitus''']]
*** Gives an increase in hepatic glycogen stores.
*** May be overshadowed by the increased fat in the hepatocytes, and therefore difficult to see.
**** Renal tubular deposits are more easily observed.
** '''Excessive glucocorticoids'''
*** Could be due to:
**** Hyperadrenocortism
**** Animals being maintained on glucocorticoid therapy over a long period of time.
***** Has more dramatic effect.
*** Huge amounts of glycogen infiltration.
**** [[Liver - Anatomy & Physiology|Liver]] appears larger and paler.
**** Vacuoles may be so extensive that the rest of the cytoplasm appear as pink strands passing from the nucleus to the plasma membrane.
***** A "feathery appearance" or "web-like effect".
** '''Glycogen storage diseases'''
*** Due to an inherited deficiency of an enzyme required for the breakdown of glycogen to glucose.
**** Cells continuously accumulate glycogen.
*** Seen in all tissues of the body but exerts its major effect in the CNS.
* Selective staining must be employed to distinguish glycogen vacuoles from fatty vacuoles in the [[Liver - Anatomy & Physiology|liver]].
** Alcohol fixation is preferred.
** Best's Carmine is the commonly used stain.
*** Stains the intracellular glycogen red.
==Cellular Inclusions==
===[[Viruses|Viruses]]===
* Either in the nucleus or cytoplasm.
===Storage Products===
* Due to '''hereditary storage diseases''' in which there is a missing or defective cellular enzyme. There are many types known in domestic animals.
** Break down/ build up of intracellular substances is halted.
*** The intermediate substance accumulates in the lysosomes.
** Affects all tissues
*** The central nervous system is particularly vulnerable.
* Due to '''age'''
** Lysosomes will accumulate non-degradable products
*** E.g. lipofuscin - the 'ageing' or 'wear and tear pigment'.
**** Commonly seen in middle-aged cats in the hepatocytes nearest the centrilobular veins.
===Intracellular Bacteria===
* For example, [[Mycobacteria spp.|''Mycobacterium tuberculosis'']] in macrophages.
===Protein Accumulation===
* In the renal tubular epithelium.
* Occurs when there is leakage of protein out through a damaged glomerulus.
{{toplink
|linkpage =General Pathology
|linktext =General Pathology
|maplink = General Pathology (Content Map)
|pagetype =Pathology
}}
<br>
==Introduction==
* Degenerations and infiltrations are the morphological manifestation of an altered metabolism within the cell.
** A particular kind of change within a cell or tissue may suggest that a specific type of alteration has occurred.
* Degenerations and infiltrations are types of structural changes.
** These are best considered at a cellular level.
** These structural changes are deviations from the cell's normal structure and function.
*** Parameters are outside the normal physiological range for the cell.
* '''Degeneration'''
** The tissue cell shows some change in itself.
* '''Infiltration'''
** Something accumulates in the cell or tissue.
==Cellular Swelling==
* Cellular swelling is
** The earliest detectable degenerative change.
** The mildest form of cellular degeneration.
** The first stage in injury to a cell.
** Caused by a variety of insults, e.g.
*** Lack of oxygen (anoxia) to a tissue.
*** Toxic influences.
* Is due to the impairment of the integrity of the cell membrane.
* Cellular swelling is characterised by a moderate swelling of the individual cells.
** Due to an influx of water into the cell.
===Gross Appearance===
* Organs diffusely affected with cloudy swelling grossly appear pale.
** This may be partly due to the swollen cells impeding the tissue's blood supply.
* Without cutting into an organ, it may be difficult to appreciate a gross enlargement of it.
** Each individual cell is increased in size, meaning the entire volume of the organ is also increased.
** E.g. on cutting the [[Liver - Anatomy & Physiology|liver]] or kidney capsule, the underlying swollen parenchyma bulges outwards, making the cut ends of the capsule retract.
* The degree of gross swelling is not great.
** Could be easily confused with early post-mortem changes in the organ.
===Histological Appearance===
* Individual cells appear somewhat swollen.
* The cytoplasm appears more red in colour in hematoxylin and eosin (H&E) stained sections.
* The nucleus of the cell remains normal.
* Cellular swelling is best histologically appreciated in the [[Liver - Anatomy & Physiology|liver]] and kidney in damage caused by circulating toxins that are not powerful enough to actually kill the cells.
===Significance of Cellular Swelling===
* Cellular swelling is an important stage in degeneration.
** Not commonly observed on its own without more serious changes
*** Not easy to identify at post-mortem unless the examination is performed very soon after the animal's death.
**** Early post-mortem (autolytic) change in dead tissue looks rather similar.
*** Cellular swelling is also reversible.
**** When the toxin is no longer exerting its effect, the tissue returns to normal.
*** Cellular swelling may be a transient stage in the more serious forms of degenerations which follow.
==Hydropic Degeneration==
* Hydropic degeneration often indicates severe cellular damage due to viruses.
** Is a more severe or advanced form of cellular swelling.
* There are two types of hydropic degeneration, in which:
*# The cells may swell up like a balloon prior to their destruction.
*#* '''Ballooning Degeneration'''
*# There is a discrete bleb (vacuole) of fluid within the cytoplasm.
*#* '''Vacuolar Degeneration'''
===Ballooning Degeneration===
* May occur in a variety of conditions.
** Is particularly seen in viral conditions of epithelial tissue.
* [[Cavity & Gingiva - Pathology#Foot and Mouth disease|Foot and Mouth Disease]] is the best example.
** Foot and Mouth virus attacks the stratum spinosum of the epithelium of the [[Oral Cavity - Tongue - Anatomy & Physiology|tongue]] and feet.
** Affected cells balloon up with water containing the replicating virus, swelling until they burst.
*** The fluid contained in the cells then forms microvesicles (blisters) in the stratum spinosum.
**** Blisters may later burst, shedding vast quantities of the virus.
** On bursting, the edges of the erosions look ragged.
*** Within weeks, the germinal epithelium at the base of the erosion regenerates the epithelium, leaving no trace of a scar.
===Vacuolar Degeneration===
* In vacuolar degeneration, excess water is transferred to the endoplasmic reticulum (ER).
* The ER swells and eventually fragments.
** A fluid vacuole remains in the cytoplasm.
* Commonly occurs in cells that are very metabolically active and have well developed pumping mechanisms.
** E.g. as the hepatocyte, renal tubular epithelium and pancreatic acinar cell.
==Cellular Fatty Change==
* 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).
==Mucoid Degeneration==
* Mucoid degeneration is also known as mucinous or myomatous degeneration.
* Mucoid degeneration involves changes in epithelial tissue or the extracellular matrix/ ground substance.
* An extracellular phenomenon of some specific cells.
** Tend to show a bluish tinge in H&E stained sections.
===Epithelium===
* The specific cells involved in mucoid degeneration in the eptihelium are:
** The goblet cells of wet mucous membranes.
** The mucous glands themselves.
* This is not really a degeneration, but an increased production of mucin.
** It is a beneficial reaction; the product
*** Is important as a lubricant.
*** Soothes inflamed surfaces.
*** Traps and dilutes harmful agents.
*** Carries specific antibodies against infectious agents.
*** Provides a means for removal of infectious agents.
===Connective tissue===
* Here, the mucin forms part of the ground substance between the fibroblasts that produce it.
* A disturbance in the metabolism of the fibroblasts under some circumstances,means the ground substance takes on a bluish hue in H&E sections.
* Mucoid degeneration in the heart valves of middle-aged and older dogs is a common example.
** Causes '''endocardiosis'''.
*** A condition specific to the dog.
===Endocardiosis===
* Tends to affects middle-aged and older dogs.
* Primarily occurs in the mitral valve.
* Results in slowly developing heart failure
* The valves become swollen and misshapen
** The heart cannot pump blood effectively to the circulation from the left ventricle.
*** Blood passes back into the left atrium, compromising the filling from the pulmonary vein.
**** Leads to back pressure on the pulmonary capillaries.
***** [[Oedema - Pathology|Oedema]] forms in the lungs, and can be heard as moist sounds on auscultation.
***** Reduces the oxygenation of blood leading to exercise intolerance.
*** Failure of the left side eventually compromises the function of the right side.
**** There is pooling of blood in the venous system i.e. in the [[Liver - Anatomy & Physiology|liver]].
==Hyaline Degeneration==
* The term "hyaline degeneration" is applied to several types of degeneration or infiltration.
** "Hyaline" is a descriptive term meaning "glassy".
*** Used in pathology when structureless material appears in section, and stains red with eosin
**** Describes a variety of conditions in which structureless materials are present.
* Is applied to both extra- and intra-cellular degenerations/ infiltrations. ** '''Extracellular'''
*** Protein hyaline casts in the renal tubules.
**** From excessive protein passing through glomerulus.
**** When fresh urine is examined under the microscope, casts may be seen as elongated glassy tubes.
*** Hyaline membranes
**** Proteinaceous effusions into pulmonary alveoli
**** Prevent gaseous exchange. ** '''Intracellular'''
*** Hyaline degeneration of skeletal muscle.
**** In vitamin E/ selenium deficiency.
* There are two forms of hyaline degeneration that deserve their own mention.
** Fibrinoid degeneration.
** Amyloid infiltration.
===Fibrinoid Degeneration===
* Fibrinoid degeneration features a material which is fibrin-like.
* Is essentially a focal death of cells in the walls of small blood vessels (usually arterioles).
** Parts of the vessel wall become replaced by a granular material.
*** Pinkish-red (i.e. eosin-staining).
*** Has some of the appearance and staining properties of fibrin.
*** Consists partly of degenerated muscle and elastic fibres, and partly of an increased amount of protein ground substance around the degenerated fibres.
*** Looks like a red smudge in the vessel wall when viewed histologically.
* The presence of the fibrin-like material may suggest
** A local hypersensitivity reaction
** Hypertension
===Amyloidosis===
* Also known as amyloid infiltration
* Deposition of a proteinaceous hyaline substance in extracellular sites.
** Sites of deposition vary with species.
* The kidney is a common site of deposition.
** Amyloid is deposited under the capillary endothelium and progressively increases in volume.
* There are various categories of amyloid.
** Is essentially an abnormal protein produced in the body
** In most cases, it is produced in response to sustained antigenic stimulation caused by a chronic suppurative process.
*** E.g. a foot abscess, mastitis.
* Amyloid is a relatively inert substance.
** When it accumulates, it is not easily removed.
==Glycogen Infiltration==
* Glycogen is normally present in substantial amounts in the [[Liver - Anatomy & Physiology|liver]] and muscle.
** Is a readily utilisable source of energy.
* Moderate glycogen infiltration in the [[Liver - Anatomy & Physiology|liver]]:
** Grossly - doesn't have much effect.
** Histologically - shows up as foamy cytoplasmic vacuoles, similar to that of fat.
* Some conditions may result in an increase in glycogen deposits.
** [[DM|'''Diabetes mellitus''']]
*** Gives an increase in hepatic glycogen stores.
*** May be overshadowed by the increased fat in the hepatocytes, and therefore difficult to see.
**** Renal tubular deposits are more easily observed.
** '''Excessive glucocorticoids'''
*** Could be due to:
**** Hyperadrenocortism
**** Animals being maintained on glucocorticoid therapy over a long period of time.
***** Has more dramatic effect.
*** Huge amounts of glycogen infiltration.
**** [[Liver - Anatomy & Physiology|Liver]] appears larger and paler.
**** Vacuoles may be so extensive that the rest of the cytoplasm appear as pink strands passing from the nucleus to the plasma membrane.
***** A "feathery appearance" or "web-like effect".
** '''Glycogen storage diseases'''
*** Due to an inherited deficiency of an enzyme required for the breakdown of glycogen to glucose.
**** Cells continuously accumulate glycogen.
*** Seen in all tissues of the body but exerts its major effect in the CNS.
* Selective staining must be employed to distinguish glycogen vacuoles from fatty vacuoles in the [[Liver - Anatomy & Physiology|liver]].
** Alcohol fixation is preferred.
** Best's Carmine is the commonly used stain.
*** Stains the intracellular glycogen red.
==Cellular Inclusions==
===[[Viruses|Viruses]]===
* Either in the nucleus or cytoplasm.
===Storage Products===
* Due to '''hereditary storage diseases''' in which there is a missing or defective cellular enzyme. There are many types known in domestic animals.
** Break down/ build up of intracellular substances is halted.
*** The intermediate substance accumulates in the lysosomes.
** Affects all tissues
*** The central nervous system is particularly vulnerable.
* Due to '''age'''
** Lysosomes will accumulate non-degradable products
*** E.g. lipofuscin - the 'ageing' or 'wear and tear pigment'.
**** Commonly seen in middle-aged cats in the hepatocytes nearest the centrilobular veins.
===Intracellular Bacteria===
* For example, [[Mycobacteria spp.|''Mycobacterium tuberculosis'']] in macrophages.
===Protein Accumulation===
* In the renal tubular epithelium.
* Occurs when there is leakage of protein out through a damaged glomerulus.