6. Abnormal accumulation of substances in the cell. Mechanisms. Accumulation of protein (hyaline-drop degeneration, Lewy and Mallory bodies; Russel bodies) and carbohydrates. Methods of proof.

Introduction

This topic covers how substances abnormally accumulate inside cells, the four mechanisms behind it, and the accumulations of protein (hyaline, hyaline-drop degeneration, Mallory, Russell and Lewy bodies) and of carbohydrates (glycogen, mucopolysaccharides, glycoproteins), with the methods used to prove them.

Morphogenesis of abnormal accumulation

1. Infiltration - import from outside, pathological reabsorption by cells.
2. Decomposition - disintegration of membranous structures of cells and of the extracellular matrix.
3. Pathological synthesis - of amyloid, of glycogen in the loop of Henle in diabetes, of alcoholic hyaline.
4. Transformation - into other kinds of chemical substances than the usual ones.

Protein accumulation

Hyaline and hyaline casts

Hyaline is an acellular, proteinaceous substance that looks glassy and pink with haematoxylin and eosin (e.g. hyaline cartilage, the transparent, glossy cartilage of joints).

Hyaline casts are acellular casts made of a protein matrix. An occasional cast is normal, but they increase in renal disease.

Hyaline-drop degeneration (dystrophy)

• Occurs in the kidneys, liver and myocardium; characterised by aggregation of small protein granules (pink) in the cytoplasm of cells.
• Organs with hyaline degeneration have no specific macroscopic changes.
• Hyaline is seen as eosinophilic deposits in the cytoplasm of epithelial cells of the proximal renal tubules (tubular epithelium effects lead to proteinuria). It can occur in diseases with proteinuria: glomerulonephritis, amyloidosis of the kidney, diabetic nephropathy.
• Causes: alcoholic hepatitis, viral hepatitis; alpha-1 antitrypsin deficiency (alpha-1 antitrypsin normally breaks down proteases) is another cause of protein granule accumulation in the cytoplasm of hepatocytes.

Specific intracellular protein accumulations

These are named according to their organ location.

Mallory bodies

• Found in hepatocytes when there is hyaline degeneration.
• Believed to represent degeneration of the cytoskeleton of damaged hepatocytes in alcoholic and viral hepatitis.
• Outcome is poor: focal or total coagulative necrosis occurs.

Lewy bodies

• Divided into brainstem and cortical types. Brainstem Lewy bodies are seen in brainstem nuclei and the diencephalon; cortical ones in the cerebral limbic cortex and amygdala.
• Brainstem Lewy bodies are spherical intraneuronal cytoplasmic inclusions with hyaline eosinophilic cores, concentric lamellar bands and narrow pale halos; cortical Lewy bodies lack a halo.