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.

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.

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.

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.
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 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

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

Any condition that reduces the oxygen supply to the tissues will cause fatty change in the

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.

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).