THE MORPHOLOGICAL APPROACH 69 



A. Cell Surfaces 



Although probably one of the commonest and earliest reactions to injury 

 is the formation of multiple thin extrusions of various lengths and thick- 

 nesses, this formation has not been purposefully studied in detail. These ex- 

 trusions may simply represent an immediate hyperplasia of the intercellular 

 processes or extensions of the normal microvilli which occur commonly on 

 epithelium. Extensive bubbling of the cell surface is seen in the last stages of 

 "pyknosis" (Bessis, 1956), but is also a common accompaniment of the last 

 stages of mitosis (Hughes, 1952b) except in hemopoietic cells (Rondanelli et 

 al., 1956). It is likely that the numerous bits of ballooned cytoplasm seen so 

 typically in the electron microscope (Murphy and Bang, 1952) rise from cells 

 degenerating in this manner. 



B. Osmotic Imbalance 



The accumulation of fluid droplets within the cell under both physiological 

 and pathological conditions has been observed frequently (Lewis and Lewis, 

 1924). In a tissue culture study of the effect of hypotonic and hypertonic 

 solutions on chick fibroblasts, Hogue (1919) described and illustrated the 

 changes with drawings. In hypotonic solutions, the colonies increased in size, 

 but the cells accumulated fluid in cytoplasmic vacuoles and died early. A 

 large vacuole situated next to the nucleus was frequently found. The neutral 

 red vacuoles and granules lost their color. The mitochondria were not affected 

 at first, but as the cell died vesicles formed at the extremities and persisted 

 after the mitochondria disappeared. It is likely that the newer understanding 

 of the detailed series of lamellae and minute intracellular channels within the 

 cell will allow an explanation of the accumulation of fluid in between these 

 "spaces" within the cell when osmotic imbalance occurs. This would be the 

 simplest explanation for the distended "endoplasmic reticulum" seen in a 

 destructive cell lesion such as influenza in the ferret nasal epithelium. Fluid 

 under these conditions may remain accumulated in large vesicles, forcing a 

 separation of the nuclear and cytoplasmic portions of the so-called double 

 nuclear membrane (Hotz and Bang, 1957). 



Hogue (1919) further found that cells grown in hypertonic media usually 

 contracted; the thin processes became long and threadlike and were later 

 drawn in. Neutral red staining showed that channels formed in the cell, and 

 the cytoplasm became alveolar in the terminal stages. Little droplets are 

 shown to form at the cell edge and often attach to the cell by fibrils. Again, 

 the mitochondria were not affected significantly. 



It would be of great interest to measure the density of fluid within these 

 droplets by Barer's recent interference microscope methods (Barer and 

 Joseph, 1955), particularly since it is possible to follow the change in density 



