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→Cellular Fatty Change
===Cellular Fatty Change===
===Cellular Fatty Change===
Cellular fatty change - an important intracellular abnormality, and concerns
principally intracellular fat in liver cells.
This is the accumulation or increase of fatty substances within the cytoplasm of specific
cells and does not refer to the fat stores of the body, although in some cases they may be
involved in the transfer of fat to these specific cells.
Fatty change is commonly seen in three organs of the body, i.e. principally in the liver but
also the kidney and heart; mainly because these organs are either involved in the metabolism
of fat or dependant upon lipids as an energy source.
It is an important condition, because it is something that can readily be recognised at postmortem
examination.
Appearance of fatty change
Liver: this is the predominant organ
involved in fatty change.
Grossly, the liver may be greatly
increased in size;
it is tan to yellowish in colour in
contrast to the normal reddish brown;
it is very prone to rupture with slight
pressure (friable);
on cutting through the surface the underlying
parenchyma bulges outwards having been freed
from the constraint of the capsule;
and this parenchyma is dull in appearance,
yellowish and greasy.
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Kidney: where not normal as in the cat, the cortex appears somewhat paler, but diffuse
paleness is not the prominent feature as it is in the liver.
Heart: fatty change is found in anaemia in animals and is the result of anoxia ;
the heart is flabby and the fatty change may occur as streaks in the papillary
muscles (those furthest away from the blood supply).
Overall it has reduced contractile ability, and does not pump blood efficiently.
Microscopically, the fat
appears as globules or
vacuoles of varying size
in the cytoplasm of the
cells. In the heart, it
appears as tiny groups of
vacuoles dispersed along
the myofibrils
throughout the whole
cell. In the liver and
kidney, these vacuoles
tend to, but not always,
coalesce (come together;
fuse with one another )
to form larger ones, and
you may see one or
more large globules
filling the cytoplasm
with displacement of the nucleus to the periphery of the cell. The nucleus remains normal
unless the degree of fatty change becomes incompatible with the continued existence of the
cell.
To decide whether or not a vacuole in the cytoplasm of a hepatocyte is fat ( because there are
two further conditions which may produce vacuoles in hepatocytes, namely the vacuolar
hydropic degeneration mentioned before and also the accumulation of glycogen ), it is
necessary to stain for the fat present. There are a variety of stains and common ones are
Sudan 111, Sudan 1V, and Oil Red O which stain fat varying shades of orange to red.
It is necessary to prepare the sections differently to the routine paraffin embedding as per
H&E. This is because in paraffin embedding, the fat is dissolved out of the cell by the strong
solvents employed. To get over this problem, the block of tissue to be examined is frozen
and sectioned in a cryostat (a cabinet containing a microtome and kept at - 20 0 C), before
being stained.
These sections are over twice as thick as those attained by sectioning paraffin blocks, and so
there may be some overlap of cells on the section, and less clarity of the individual cells.
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Causes of 'fatty change'
1. Dietary and Metabolic
a. Starvation - this is an increased mobilisation of fat from the body fat stores in response to
energy needs occasioned by a reduction in dietary intake. These are transported in the blood
as fatty acids, the liver is unable to cope with them all properly, and so they are stored here as
neutral fats.
b. Overeating - obesity where the dietary intake is greater than the energy expenditure and
the fat is temporarily stored prior to movement to the body fat stores. It also occurs on a diet
rich in fat.
c. Lipotrope derangement - lipotropes are substances which hasten the removal of fat from
the liver cells. Some are the amino acids that facilitate conjugation of the fat with proteins to
form the lipoprotein that is excreted from the cell, and deficiency of these e.g. choline and
methionine in the diet, lead to fatty change within the cells.
Some poisons e.g. CCl4, phosphorus and alcohol also prevent stages leading to the
formations of lipoproteins.
2. Metabolic diseases - those accompanying a deranged carbohydrate metabolism in which
glucose is not made available for uptake into the tissues. Alternative pathways are resorted to
for the production of energy needed by the cells, and this leads to fatty change.
Examples are Diabetes mellitus in dogs where there is a deficiency of the hormone insulin
which is required for cellular glucose utilisation, and Ketosis in ruminants where the drain on
glucose reserves in sheep caused by twin lambs ( condition is called Pregnancy Toxaemia) or
in the milk of high-yielding dairy cows shortly after parturition (Acetonemia), exhorts the
body to find another source of energy, with consequent mobilisation of fat reserves and their
transportation to the liver.
3. Anoxia - an inadequate supply of oxygen to the tissues
Any condition that reduces the oxygen supply to the tissues will cause fatty change in the
liver. Anaemia ( a reduced numbers of red blood cells circulating in the blood ) caused by
sustained loss of erythrocytes from the vessels as in chronic haemorrhage or the excessive
destruction of erythrocytes within the vessels ( haemolysis ) are examples as are the various
circulatory disorders such as ischaemia ( reduced blood supply to a tissue ) and chronic
venous congestion ( slowing of blood flow through the vasculature ) due to a failing heart.
4. Toxins. A large number of toxins will cause fatty change in the liver. In these cases,
consider the fatty change to be a more severe form of cellular swelling. Among these are;
a. bacterial and fungal toxins- either produced in the bloodstream from circulating bacteria
(septicaemia/bacteraemia) or produced elsewhere and absorbed into the bloodstream.
b. chemical toxins such as CCl4, phosphorus, arsenic and lead.
c. some plant and fungal toxins, will cause fatty change in the very early stages of
poisoning.
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Distribution of fatty change in the liver.
The distribution of fatty change in the liver lobule tends to be throughout the whole lobule
but occasionally there is a preferential localisation which may give some clue to inciting
cause.
Chronic venous congestion in the liver due to a failing heart ( a cause of anoxia ) will also
produce fatty change. In conjunction with the fatty change the pooling of the blood in the
centrilobular area due to ineffective flow back to the heart, gives a striking gross appearance
of areas of yellow interspersed with red, and this has been described as a 'nutmeg liver'.
The practical implication of this when found at post-mortem examination, is to examine the
heart for the cause.
Significance of fatty change
It is important to remember that fatty change is reversible, provided that the underlying cause
is brought under control. It may be difficult to decide whether the fatty change is due to a
toxic effect or metabolic defect, from the distribution of the fat within the cell.
In the former, fatty change can be considered as a more serious form of cellular swelling and
you may see evidence of a further change in the cells, which is death of the cell (necrosis).
But if the metabolic defect is prolonged for any period, the impairment of cellular function
occasioned by the substantial amount of cytoplasmic fat, may also result in death of the cell.
Wallerian Degeneration. This is a special form of fatty change in the nervous system, where
damage to myelinated nerves results in the degeneration of the myelin that ensheaths them. It
can be selectively stained and will be discussed further in the CNS lectures in Systematic
Pathology.
Extracellular accumulation of lipids
Lipid may be present outside the cell in some conditions. Necrosis of cells containing lipid
may release lipid into the extracellular space where they are visible. Cholesterol is released
from cells or pooled from lipoproteins in crystalline form( cholesterol clefts )as a result of
haemorrhage or tissue damage.
4. Mucoid ( mucinous, myxomatous ) degeneration - changes in epithelial tissue
or ground substance (matrix) produced by fibroblasts in connective tissue..
This is an extracellular phenomenon of some specific cells. They tend to show a bluish tinge
in H&E stained sections.
a. Epithelium - specifically the goblet cells of wet mucous membranes and the mucous
glands themselves. It is a beneficial reaction and is not really degeneration, but an increased
production of mucin. Their secretions are important as lubricants and protective substances
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soothing inflamed surfaces, entrapping and diluting harmful agents, carrying specific
antibodies against infectious agents, and providing a means for their removal.
b. Connective tissue - the mucin here forms part of the ground substance between the cells
( fibroblasts ) producing it. In some circumstances, there appears to be a disturbance in the
metabolism of the fibroblasts which produce the mucin and the ground substance takes on a
bluish hue in H&E sections.
The common example is the
mucoid ( myxomatous, myxoid )
degeneration that occurs in the
heart valves of middle-aged and
older dogs. It occurs primarily in the
mitral valve and is responsible for a
condition specific for this species
called endocardiosis.
It is important and results in slowly
developing heart failure due to the
inability of a heart with swollen
misshapen valves to effectively pump
blood from the left ventricle out into
the systemic circulation. A substantial
portion of the blood passes back into
the left
atrium and compromises the filling of the atrium from the pulmonary vein. This leads to
back pressure on the pulmonary capillaries with oedema formation in the lungs. This
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reduces the oxygenation of blood leading to exercise intolerance and may be heard as moist
sounds on auscultation of the lungs. Eventually, this failure of the left side compromises the
function of the right side and there is also pooling of blood in the venous system i.e. in the liver.
===Mucoid Degeneration===
===Mucoid Degeneration===
===Hyaline Degeneration===
===Hyaline Degeneration===