Obstructive Jaundice and Related Disorders

Intracellular Accumulations

• Cells can accumulate abnormal amounts of substances, which can be harmless or cause injury.
• Substances can accumulate in the cytoplasm, organelles (like lysosomes), or the nucleus.
• Three pathways can lead to abnormal accumulation:
  • A normal substance is produced at a normal or increased rate, but the metabolic rate to remove it is inadequate. An example is fatty change in the liver.
  • A normal or abnormal endogenous substance accumulates due to a genetic or acquired defect in metabolism, transport, or secretion. An example is lysosomal storage diseases.
  • An abnormal exogenous substance may accumulate because the cell lacks the enzymes to degrade the substance or the ability to transport it elsewhere. Examples include carbon (anthracosis) or silica (silicosis) deposits in the lungs.

Fatty Change

• Abnormal accumulation of neutral fat within parenchymal cells.
• It is a reversible change, but if the cause isn't removed, it can lead to cell death.
• Most commonly seen in the liver, which is the major organ involved in fat metabolism.
• Can also be seen in the heart and kidneys.
• Various irritants, including hepatotoxins (both organic and inorganic), bacterial toxins, plant toxins, and chemical toxins (including alcohol), can cause fatty change.

Metabolic Diseases

• Diseases like diabetes mellitus can lead to intracellular accumulations.
• Deficiency of lipotropic factors (like choline, which is needed for transforming neutral fat into phospholipids) can reduce the transformation of neutral fats and cause their accumulation in body tissues.
• Methionine is a choline precursor and is a lipotropic factor.
• Obesity can also be a factor.

Pathogenesis of Fatty Liver

• Abnormal accumulation of triglycerides or neutral fats in the liver.
• Accumulation can result from defects in these different events:
  • Excessive entry of fatty acids into the cell.
  • Enhanced fatty acid synthesis.
  • Increased esterification of fatty acids to triglycerides.
  • Decreased apoprotein synthesis. Apoproteins are needed for converting triglycerides to lipoproteins for excretion from the cells.
  • Impaired lipoprotein secretion from the cell.

Macroscopic Appearance of Fatty Liver

• The liver is most commonly affected.
• The liver appears yellow, but the color depends on the animal species' natural fat color.
• In cats, it's white; in cattle, yellow; and in horses, orange.
• The liver's borders become rounded as it enlarges.
• The liver's consistency becomes soft and greasy.
• The liver is easily ruptured, and its cut surface bulges outwards with a greasy appearance.

Microscopic Appearance of Fatty Liver

• Small, clear vacuoles of varying sizes are seen in the cytoplasm.
• The vacuoles can combine to form larger ones, indicating severe or chronic injury.
• Water and glycogen can also be seen as clear vacuoles.
• Specific stains (Oil Red-O or Sudan IV) help identify fat.
• Periodic Acid-Schiff (PAS) reaction is used to identify glycogen.

Pigmentation

• Pigments are colored substances found in cells.
• Some are normal, like melanin, which gives skin color.
• Pigments can be endogenous (synthesized within the body) or exogenous (from outside).
  • Endogenous pigments include melanin, lipofuscin, and hemoglobin derivatives.

Melanin

• Melanin is a brown to black pigment made in melanocytes.
• Tyrosinase enzyme oxidizes tyrosine amino acid to produce melanin.
• Melanocytes are in the epidermis' basal layer.
• Melanin is stored in granules within the epithelial cells of the stratum germinativum.
• Melanin's color (black, brown, or red) depends on its concentration and distribution in the skin.
• Melanin protects against harmful ultraviolet rays.
• Cells storing melanin are called melanophores.
• Melanosis can occur in various internal organs, including intestines, lungs, and heart, during early development. This condition can cause blindness in certain dog breeds.
  • Excessive melanin can be seen in some tumors (melanomas/melanocarcinomas).
  • Acanthosis nigricans is an increased amount of melanin in the skin.
  • Albinism is the complete absence of melanin due to inherited deficiency in the tyrosinase enzyme.
  • Other conditions exist such as vitiligo or leukoderma, where specific areas lack pigment in the skin

Derivatives of Hemoglobin

• Erythrocytes (red blood cells) live about 120 days.
• They break down in the spleen, liver, and bone marrow (mononuclear phagocytic cells).
• Hemoglobin breaks down into globin (recycled), iron (stored as ferritin or hemosiderin), and heme.
• Iron is stored as ferritin. When iron levels are high, it forms hemosiderin granules.

Hemosiderin

• Golden yellow to brown pigment derived from hemoglobin.
• Local accumulation occurs from local hemorrhages (like bruises).
• Systemic accumulation is known as hemosiderosis.
• It can be related to increased iron intake or decreased iron utilization (e.g., hemolytic anemia).

Bilirubin

• A pigment derived from hemoglobin that lacks iron.

• The major pigment in bile.

• About 70% of bilirubin originates from the destruction of red blood cells (RBCs) in the liver, spleen, and bone marrow.

• Remaining 30% comes from other heme proteins (hemoproteins).

• Hemoglobin is broken down into biliverdin, which is converted to bilirubin.

• Bilirubin is transported in the blood, bound to albumin, to the liver.

• In the liver, bilirubin is conjugated to glucuronic acid and secreted into bile.

• In the intestine, bacteria convert bilirubin to urobilinogen and stercobilin.

• Some urobilinogen is reabsorbed into the bloodstream, returned to the liver, and re-excreted in the bile.

• Remaining urobilinogen is converted to urobilin, which is excreted in urine (giving it color).

• Also, some urobilinogen and stercobilin are excreted in the feces (giving it color).

Jaundice

• Jaundice is the yellowing of the skin and sclera due to elevated bilirubin levels in the blood (hyperbilirubinemia).
• Bile pigments may also be excreted in the urine.
• There are three types of jaundice: prehepatic (hemolytic), hepatic (toxic), and posthepatic (obstructive).
  • Prehepatic jaundice occurs from increased destruction of red blood cells.
  • Hepatic jaundice arises from impaired liver function.
  • Posthepatic jaundice occurs from obstruction of bile flow.

Exogenous Pigments

• Pigments originating from outside the body.
• Lungs and their lymph nodes hold various dust particles.
• Lung disorders from dust inhalation are called pneumoconiosis (often occupation-related).
  • Anthracosis: Carbon (coal dust) accumulation in the lungs.
    • Siderosis: Iron accumulation in the lungs.
    • Silicosis: Silicon or stone dust accumulation in the lungs, which can cause severe fibrosis and a predisposition to tuberculosis.

Mineral Deposits

• Pathological calcification occurs when minerals (especially calcium) deposit in tissues.
• Dystrophic calcification – abnormal areas; in degenerating or necrotic tissue.
• Metastatic calcification – secondary to some primary condition, such as hyperparathyroidism or abnormal vitamin D function.

Renal disease, high vitamin D intake, may also contribute.

Gout

• Gout is a metabolic disorder characterized by elevated uric acid levels in the blood.
• The body forms uric acid from purine metabolism.
• Excess uric acid can crystallize in joints and tissues (like synovium).
• This formation of crystals triggers inflammation, pain, and joint damage.
• Crystal formation initiates inflammation, resulting in joint injury.
• Macrophages then release enzymes and other mediators that exacerbate the inflammatory response and contribute to joint damage.