Pathophysiology and Physicochemical Changes
Disruption of cytoplasmic protein metabolism affects both free enzymes and proteins of cell membrane lipoprotein complexes. The underlying mechanism involves altered physicochemical properties of protein molecules through denaturation, coagulation, or colliquation with polypeptide chain breakdown. This is accompanied by fluid and electrolyte imbalance, altered colloid-osmotic pressure, and cytoplasmic hydration.
To protect cells from injury caused by altered proteins, the ubiquitin-proteasome system is activated to degrade defective structures. If the load is excessive, persistent inclusions form, and protein aggregates evolve from fine granules into large droplets.
Granular Dystrophy (Cloudy Swelling)
This form of parenchymal dysproteinosis develops in the kidneys, liver, and myocardium under conditions of increased functional load. In the kidneys, the process is frequently associated with increased albumin reabsorption in the proximal tubules.
- Microscopy: the cell cytoplasm is covered with pronounced eosinophilic granularity, cells swell and become turbid, while nuclei typically remain intact.
- Macroscopic appearance: organs are enlarged, soft, and their cut surface acquires a dull, "boiled in water" appearance.
These changes are reversible if the underlying cause is promptly removed; however, disease progression can lead to more severe forms.
Hyaline-Droplet and Hydropic Dystrophies
If damaging factors persist, granular dystrophy is succeeded by severe damage to membrane structures.
- Hyaline-droplet dystrophy: characterized by the appearance of large, bright pink protein droplets within cells. In nephrocytes, it develops due to vacuolar-lysosomal apparatus failure during massive proteinuria and accompanies nephrotic syndrome. In hepatocytes during alcohol-induced injury, alcoholic hyaline (Mallory bodies) is formed.
- Hydropic (ballooning) dystrophy: associated with $Na^+/K^+$-ATPase pump failure and loss of ionic homeostasis. Cells become engorged with fluid, clear vacuoles form, and nuclei are displaced to the periphery, effectively representing focal colliquational necrosis.
Keratinizing Dystrophy and Hereditary Dysproteinoses
Pathological keratinization (keratinizing dystrophy) manifests as excessive production of keratin where it normally occurs (hyperkeratosis, ichthyosis) or its appearance on mucous membranes where it is normally absent (leukoplakia of the esophagus or oral cavity).
A distinct group comprises hereditary parenchymal dysproteinoses, caused by genetic defects in amino acid metabolism. These include cystinosis, tyrosinemia, and phenylketonuria, in which severe metabolic disturbances affect the liver, kidneys, central nervous system, and other organs.