Pathophysiology: Cellular Injury, Cellular Aging, and Cell Death
Systemic pathologic processes are the result of alterations in cellular function. Cellular response to environmental changes or injury occurs in three general ways:
- Mild or short change: the cell withstands and returns to normal; this is a reversible cell injury
- Persistent, but sublethal injury: the cell changes its structure or function – generally also reversible
- Injury that is too severe or prolonged: cell death – irreversible (Banasik & Copstead, 2018)
DISCLAIMER: Yes, I am a nursing student. Yes, I am a scuba diver. No, I am not yet a licensed nurse nor have I graduated as of the date of this publication. This information is derived from my nursing school notes and should not be seen as medical advice. Resources are provided whenever possible regarding both nursing information and scuba diving. You should consult with your physician before scuba diving, especially if you have a condition which may limit your scuba diving fitness.
Reversible Cell Injury
These changes reflect the cell’s inability to do NORMAL METABOLIC functions due to reduced ATP or dysfunction of associated metabolic enzymes. Examples include hydropic swelling (where water accumulates in the cells; this is often the first sign of a reversible injury and it can lead to organ enlargement “-megaly”), intracellular accumulations (e.g., toxins; sometimes these are not the cause of injury, but rather, an indicator of injury), increased glycogen storage (usually because of good old diabetes mellitus; glucose WNL is 70-110 mg/dL), protein accumulation in renal tubules, and calcification (dead or dying tissues show up as dense areas on an X-ray, like the lung damage you would see in TB) (Banasik & Copstead, 2018).
“Adaptation” implies a change for the better, but sometimes it isn’t. Common adaptations are potentially reversible when stress is relieved:
Atrophy (reduced cell SIZE); cells shrink and reduce their differentiated functions in response to both normal and injurious factors. General causes include disuse (the result of decreased functional demand, such as in immobilization by bed rest/casting of extremity where skeletal muscles shrink), denervation, ischemia (inadequate blood supply to a tissue), nutrient starvation, interruption of endocrine signals, and persistent cell injury.
Hypertrophy (increased cell SIZE) is an increase in cell mass with altered functional capacity due to increased physiologic or pathophysiologic demands. It subsides when the increased demand is removed, but may not entirely return to normal. Cellular enlargement may occur due to increased protein. Hypertrophic adaptation is important for cells that don’t undergo mitosis (like muscle cells). For example, with repeated exercise you’ll see hypertrophy of individual muscle cells, leading to increased skeletal muscle mass and strength. Organ enlargement may be due to both increased cell SIZE and NUMBER (hypertrophy AND hyperplasia). For example, liver enlargement due to toxins and cardiac enlargement due to increased blood pressure.
Hyperplasia (increased cell NUMBER) – cells that DO mitotically divide can increase functional capacity by hyperplasia & hypertrophy. Hyperplasia may be caused by increased physiologic demands, hormonal stimulation, or persistent cell injury. For example, increased RBC count at high altitude or liver enlargement due to drug detox. Chronic irritation of epithelial cells leads to hyperplasia. For example, calluses and corns due to chronic frictional injury to the skin.
Metaplasia (CONVERSION of one cell type to another) is often due to persistent injury – the injured cell is replaced with a cell type that can better tolerate the stimulus. It is (generally) fully reversible when the stimulus is removed. For example, cigarette smoke causing chronic irritation of bronchial mucosa converts ciliated columnar epithelium to stratified squamous epithelium. Metaplastic cells generally stay well-differentiated and of the same tissue type – however, sometimes cancer happens (lung/cervix/stomach/bladder).
Dysplasia (disorderly growth) – the disorganized appearance of cells because of abnormal variations in size/shape/arrangement – high potential for cancerous cells or “preneoplastic lesions” (severe and entire thickness of epithelial – “carcinoma in situ”) (Banasik & Copstead, 2018).
Physically demanding activity and increased environmental pressure associated with scuba diving cause a lot of cardiovascular and oxidative stress. In a healthy individual, this stress can cause reversible cell injury and increase cardiovascular adaptation – it can make your body strong and better able to withstand subsequent similar stressors (Perovic, Unic, & Dumic, 2014).
Irreversible Cell Injury
“Cell death” is injury that is too severe or prolonged for cellular adaptation/repair. There are two different processes of cell death: necrosis, caused by EXTERNAL injury (a pathological process), and apoptosis, which is triggered by signaling cascades (this is normal).
Necrosis is caused by ischemia or toxic injury, usually characterized by cell RUPTURE, the spilling of contents into extracellular fluid) and inflammation. Several manifestations indicate that the system is responding to cell injury and death, such as a general inflammatory response, general malaise, fever, increased heart rate, increased WBC count, and decreased appetite.
When necrotic cells die, intracellular contents are released into the bloodstream and may be detected in laboratory studies (e.g., serum amylase as seen in pancreatic damage, or increased creatine kinase/troponin levels in myocardial infarction). The location of the pain helps diagnose cell death.
The four types of tissue necrosis differ in the types of tissue affected: coagulative, liquefactive, fat, & caseous. Coagulative is the most common; liquefactive may be due to a bacterial infection as WBCs eat dead cells and form liquid debris, and may also be seen in the brain; fat necrosis is usually due to trauma or pancreatitis; and caseous is observed in TB damage. Gangrene is a type of cell death involving a large area of tissue. It may be dry, wet, or gas gangrene; gas and wet may be rapidly fatal).
Apoptosis is cellular suicide. It triggers cellular cascades that activate a cellular suicide response. The cell doesn’t rupture; instead, it is ingested by neighboring cells with minimal tissue disruption. So, it’s tidy and not usually associated with systemic manifestations of inflammation (Banasik & Copstead, 2018).
Etiology of Cellular Injury
Common causes are hypoxic injury, chemical injury, and physical/mechanical injury. Ischemia and hypoxic injury occur because the cell needs continuous oxygen to make ATP. Tissue hypoxia usually results from ischemia, but other things like heart failure and blood disorders can also cause it. ISCHEMIA is the most common cause of cell injury and injures cells faster than hypoxia alone because ischemia disrupts O2 supply and also allows wastes to accumulate.
Most cell damage occurs after blood supply is restored; this is called “reperfusion injury”. This is when free radicals (reactive O2) are formed, causing inflammation (Banasik & Copstead, 2018).
Other forms of injury include nutritional injury, infections, immunologic injury, chemical injury, electrical injury (e.g., radiation; note that most irradiated cells are thought to die because of APOPTOSIS and NOT the effects of radiation), and physical and mechanical injury. One form of physical injury is associated with changes in atmospheric pressure – such as deep-sea diving. Changes in pressure may interfere with gas exchange in the lungs, cause emboli in the bloodstream, collapse the thorax, and rupture internal organs (Banasik & Copstead, 2018).
Recreational scuba diving (down to 40 meters) can affect your health through the effects of oxidative stress related to which may be caused by increased physical activity, increased oxygen intake, and exposure to cold. Other factors that can affect cardiovascular function are the formation of intravascular bubbles and the effects of being immersed in a high pressure environment (Perovic, Unic, & Dumic, 2014).
Cellular Aging – the result of accumulated DNA damage, reduced proliferative capacity of stem cells, and accumulated metabolic damage. Cells may age faster when DNA repair mechanisms are faulty and with increased metabolic damage (reduced antioxidant activity).
Any type of exercise can have both positive and negative effects on oxidative status depending on the exercise load and type as well as an individual’s physical fitness. Whether scuba diving, specifically, is helpful or harmful regarding oxidative stress and how it compares to other activities is still unclear. Oxidative stress is known to contribute to the effects of aging and disease – as we grow older, our ability to deal with oxidative stress goes down while free radicals continue to pile up. However, oxidative stress associated with exercise helps train our bodies to adapt to this stress more effectively while increasing our production of mitochondria and cause hypertrophy of skeletal muscle (Perovic, Unic, & Dumic, 2014).
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Banasik, J.L. & Copstead, L.C. (2018). Pathophysiology (6th ed.). St. Louis, MO: Elsevier.
Perovic, A., Unic, A., & Dumic, J. (2014). Recreational scuba diving: negative or positive effects of oxidative and cardiovascular stress?. Biochemia medica, 24(2), 235–247. https://doi.org/10.11613/BM.2014.026