Degenerations and Infiltrations - Pathology

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.

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 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.

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 and muscle.
  • Is a readily utilisable source of energy.
• Moderate glycogen infiltration in the 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.
  • 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 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.
  • Alcohol fixation is preferred.
  • Best's Carmine is the commonly used stain.
    • Stains the intracellular glycogen red.

Cellular Inclusions

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, Mycobacterium tuberculosis in macrophages.

Protein Accumulation

• In the renal tubular epithelium.
• Occurs when there is leakage of protein out through a damaged glomerulus.