Intracellular accumulations

Parenchymal cells may accumulate normal (water, proteins, etc) or abnormal (mutated proteins, infectious agents, etc) substances in their nuclei or cytoplams (typically in phagolysosomes). These substances can be produced by the cell (endogenous) or elsewhere but stored in the cell (exogenous). This can be harmless for the cell or toxic. Here are some examples of accumulations.

• Fatty Change or Steatosis
• Cholesterol & Cholesteryl esters
• Proteins
• Glycogen
• Pigments

These can accumulate in the cell via 4 main pathways:

1. Abnormal metabolism (can't remove endogenous substance) - e.g. fatty change in liver and heart
   
2. Abnormal folding, transport, or degradation of endogenous proteins - e.g. α1-antitrypsin in liver cells
3. Storage diseases: Defect in enzymes that metabolize lipids and carbs -> accumulation of endogenous lipids and carbohydrates in usually lysozymes
4. Ingestion of indigestible materials - cell takes in exogenous substances that it can't metabolize or transport elsewhere

If the accumulation is harmful to the cell and isn't reversed it can lead to cell death. There are 5 categories of substance that may accumulate in the cell:

1. Lipids - triglycerides, cholesterol, phospholipids
   
2. Proteins
3. Hyaline Change
4. Glycogen
5. Pigments

LIPIDS
Fatty Change - in parenchymal cells of mainly the liver and heart, but also Kidney and muscle
Most common causes of fatty liver in the west: alcohol, obesity, diabetes mellitus. Other causes: protein malnutrition, anoxia, and toxins.
To understand what may cause excess triglycerides in hepatocytes, we need to look at what happens to fatty acids (FAs) [that are ingested, come from adipose tissue or are synthesized from acetate] once they reach the liver. In hepatocytes FAs become: triglycerides, cholesterol, phospholipids, and ketones. So lets look at the causes:
1) alcohol - reduces apoprotein thus lipoprotein synthesis (so can't transport triglycerides out into blood). Alcohol is also a toxin = hepatotoxin
2) obesity - increases triglyceride in blood -> increased FAs in livere
3) diabetes mellitus (type2) - here insulin resistance increases insulin levels which by a complex mechanism increase triglyceride levels in the blood which leads to accumulation of FAs in liver
4) hypoxia / anoxia - reduced ATP so can't oxidize fatty acids
5) protein malnutrition - again problem making lipoproteins

Examples of Fatty change (steatosis)
Fatty liver - image above is of non-alcoholic fatty liver disease (NAFLD), see here for more info. There is also alcoholic liver disease (ALD) - for more info see here.
Cardiac steatosis -