Cellular Fatty Change

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  • 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.
    • 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).