Cellular Fatty Change

Introduction

NB This term does not refer to the fat stores within the body!
- Fatty substances accumulate or increase within the cytoplasm 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

Fat appears as clear colourless vacuoles of varying sizes in the cell 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 vacuoles 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 III, Sudan IV, and Oil Red O.
  - Stain fat varying shades of orange to red.
- The strong solvents used in paraffin embedding dissolve the fat out of the cell.
  - Sections must therefore be prepared differently to the routine paraffin embedding (used e.g. in H&E staining).
  - 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 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

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).

Cardiac

Deposition of fatty globules within an organ or tissue, indicative of myocardial hypoxia or toxicity. Seen therefore with myocardial ischaemia, anaemia and poisons such as chloroform, phosphorous and tetrachloride. Heart is grossly pale, soft, greasy and friable.

Cellular fatty change is an important intracellular abnormality where fatty substances accumulate or increase within the cytoplasm of specific cells. Principally this pathology affects the intracellular fat in hepatocytes, but the kidney and the heart can also be involved in cellular fatty changes. These organs are susceptible as they are involved in the metabolism of fat, or are dependant upon lipids as an energy source. In some instances, the fat stores may be involved in the transfer of fat to these specific cells. Fatty change can be readily recognised at post-mortem.