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.
  • 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
  • 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 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.
    • 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

1. 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 cannot cope with them all properly.
       • The fatty acids are stored in the liver as neutral fats.
2. 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.
3. Lipotrope Derangement
   • Lipotropes are substances which hasten the removal of fat from the 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:
  • 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.
    • 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.

• 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
      • Reduced blood supply to a tissue
    • Chronic 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.
  • In these cases fatty change may be considered to be a more severe form of 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 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.
    • 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 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 of cells containing lipid may release lipid into the extracellular space.
    • Haemorrhage or tissue damage may result in cholesterol being released from cells or pooled from lipoproteins in crystalline form (cholesterol clefts).