06: Intracellular Accumulations

Types of intracellular acumulations

• Endogenous or exogenous

• Pigmented or non-pigmented

Causes of intracellular accumulations

• Increased production

• Metabolic disturbances (problems with enzymes)

• Genetic abnormalities

• Introduction of foreign materials

Condition of fat accumulation

Lipidosis

Common site of lipidosis

Liver

Common situation resulting in hepatic lipidosis

Excessive fat mobilization in over conditioned and anorexic animals

In what animal is hepatic lipidosis very detrimental

Feline

Where do most FAs in the blood come from

Triglyceride metabolism for energy access

How are TGs transported in the body

Conjugated with apoproteins to form a lipoprotein

How are lipoproteins moved out of the liver

Used ATP

Three mechanisms that cause lipidosis

1. Excessive FA uptake

2. Decreased ATP

3. Reduced protein synthesis

How does excessive FA uptake cause hepatic lipidosis

TGs are synthesized quicker than apoproteins can be synthesized and conjugated

How does decreased ATP cause hepatic lipidosis

Conjugating TGs with apoproteins and excreting the resulting lipoprotein are both energetic processes, and there will be TG and LP buildup without enough ATP

How does reduced protein synthesis cause hepatic lipidosis

Low protein means not enough AAs available to produce the apoproteins and enzymes required to metabolize FA and excrete TGs

Gross characteristics of hepatic lipidosis

• Yellow to pale

• Accentuated lobular pattern

• Friable

• Greasy

• Often floats in formalin/water

Gross marker of severe hepatic lipidosis

Capsular fracture → hemorrhage

Histologic features of hepatic lipidosis

Large lipid vacuoles that displace the hepatocyte nuclei

Condition of cholesterol accumulation in vessel walls

Atherosclerosis

Common veterinary causes of atherosclerosis

• Hypothyroidism

• Diabetes

• Hereditary hypercholesterolemia and hyperlipidemia

How does the cholesterol accumulate

Macrophages gorged on lipids sit in the fibrosing vessel wall beneath the endothelium

Gross characteristics of atherosclerosis

Thickened, pale vessels

How do horses abnormally accumulate cholesterol

Choroid plexus granuloma

Granuloma

Macrophage laden inflammatory mass

Common cause of protein accumulation

Kidney disease

How does kidney disease cause protein accumulation

Renal tubule cells are responsible for recycling protein, but the leaky glomeruli caused by kidney disease results in excess reabsorption, and it overwhelms the cellular processing mechanisms

Protein accumulation seen in kidney disease

Hyaline droplets

Histologic characteristics of hyaline droplet accumulation in kidneys

Lots of eosinophils in the cytoplasm

Protein accumulation seen with high immunoglobulins

Mott cells (constipated plasma cells)

Conditions that may result in mott cells

• High inflammation

• Strong immune stimulation

• Plasma cell tumors

Name for the globs of accumulated Igs in the mott cells

Russel bodies

Causes of acquired glycogen storage disease

• Diabetes mellitus

• High steroids

How do steroids cause glycogen storage disease

Stimulates excessive glycogen production and storage in hepatocytes

Histologic characteristics of excessive glycogen storage

Lacy/irregular, foamy clear globules

Pathogenesis of hereditary lysosomal storage diseases

An enzymatic defect interrupts a metabolic pathway, and there is a backup of intermediate products that are then stored in lysosomes to attempt breakdown, resulting in swollen cells

Common hereditary lysosomal storage disease

Equine polysaccharide storage myopathy

Equine PSSM pathogenesis

Lot of glycogen is stored in muscle, and when used quickly results in a lot of lactic acid that can cause exertional rhabdomyolysis and renal tubule necrosis

Hereditary lysosomal storage disease affecting angus cattle

Mannosidosis

Mannosidosis pathogenesis

Oligosaccharides high in mannose accumulate in neurons, causing CNS disease

What types of storage diseases usually affect the brain

Lipid storage diseases

Lipid storage disease example that affects the brain

Gangliosidoses

Complex lipid storage disease that doesn’t affect neurons but still results in CNS disease

Globoid cell leukodystrophy

Globoid cell leukodystrophy pathogenesis

Accumulation of glycolipids that damage myelin-producing support cells → decrease in myelin → uncontrolled neuronal activity

Colloquial name for globoid cell leukodystrophy

Krabbe’s disease