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PH-FD11

Intracellular accumulations

Why cells fill with water, fat, protein or glycogen: the four routes to an accumulation, what fatty change and storage diseases look like, and when a build-up is harmless, reversible or the start of lasting damage.

By the end, you can

  • Explain how failure of the sodium–potassium pump produces hydropic (vacuolar) change, and why it is reversible.
  • Describe the four routes by which a substance accumulates inside cells, with an example of each.
  • Explain how a liver cell normally handles fatty acids and how each cause of fatty liver upsets it.
  • Relate protein and glycogen accumulations, including alpha-1 antitrypsin globules and storage diseases, to their effects.
  • Describe the gross and microscopic appearance of hydropic and fatty change.
  • Recognise the classic accumulations under the microscope and the stains that identify them, and explain how removing the cause, enzyme replacement and substrate reduction act on them.

What it is

An intracellular accumulation is an abnormal amount of a substance inside cells: water (hydropic change), lipid (fatty change, or steatosis, and cholesterol), protein, glycogen, complex lipids and carbohydrates in storage diseases, or pigment. It may be a normal substance made or delivered faster than the cell can use it, an abnormal substance the cell cannot fold or export, a substance it cannot break down for lack of an enzyme, or foreign material it cannot digest. Many accumulations are reversible; some injure or kill the cell.

4 types to tell apart
Hydropic (vacuolar) change
Water and sodium enter when the sodium–potassium pump fails; the earliest light-microscopic sign of reversible injury.
Lipid accumulation
Triglyceride in parenchymal cells (fatty change, mainly in the liver) or cholesterol esters in macrophages and smooth muscle cells (foam cells, xanthomas).
Protein and glycogen accumulation
Reabsorbed or retained proteins, misfolded proteins held in the endoplasmic reticulum, and glycogen in diabetes or inherited glycogen storage diseases.
Lysosomal storage diseases
Inherited lack of a lysosomal enzyme, so its substrate builds up in lysosomes, as in Gaucher and Tay–Sachs disease.

Normal function

A cell keeps its contents in balance

A cell holds its volume steady by spending ATP: the sodium–potassium pump in the pushes sodium out, and water follows sodium, so little water enters. If the pump slows, water comes in.

Every substance a cell handles has a way in, a use and a way out. Proteins are folded in the and packaged by the ; misfolded ones are destroyed. The makes lipids, burn fatty acids, and liver and muscle store glucose as glycogen.

Enzymes in the break down worn-out organelles and engulfed material. A substance accumulates whenever its arrival outpaces its use, export or breakdown.

Point to it on the model