|
|
| (20 intermediate revisions by 2 users not shown) |
| Line 1: |
Line 1: |
| − | {{review}}
| + | #REDIRECT[[:Category:Degenerations and Infiltrations]] |
| − | | |
| − | {{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, [[:Category:Mycobacterium species|''Mycobacterium tuberculosis'']] in macrophages.
| |
| − | | |
| − | ===Protein Accumulation===
| |
| − | | |
| − | * In the renal tubular epithelium.
| |
| − | * Occurs when there is leakage of protein out through a damaged glomerulus.
| |