Cell Injury and Adaptations

I'm going to cover a few more pathology lectures. Since I didn't do much pathology in undergrad, I feel like I need to make myself more familiar with the foundations.

Understand the possible causes of cell/tissue injury.

The main causes of cell/tissue injury include the following:

• Oxygen deficiency- Cells need oxygen to carry out aerobic respiration. Without the ability to perform aerobic respiration, many metabolically-active cells would die. Oxygen deprivation can occur when there is ischaemia (a lack of blood flow), or hypoxia (normal blood flow but there is less oxygen than normal in the blood).
• Physical agents- Cells can be injured by trauma, heat, cold, pressure, and so on.
• Chemical agents- Various drugs and toxins can injure cells. For instance, paracetamol can damage your liver if you take too much of it.
• Infectious agents- Bacteria, viruses, etc. can all cause damage to cells.
• Immunologic reactions- Autoimmunity (where the body attacks its own tissues) and uncontrolled inflammation can be damaging to cells.
• Genetic mutations- Certain mutations can cause cells to become more easily damaged. For instance, sickle cell anaemia, in which the cells are misformed and more prone to damage, is caused by a simple genetic mutation.
• Nutritional imbalances- Too much or too little food, or too much or too little of certain nutrients, can all affect the way that cells behave.

When cells are subjected to one or more of the causes of cellular injury listed above, various organelles within the cell can become damaged, leading to further downstream effects. For instance, if mitochondria are damaged, this can adversely affect the production of ATP and increase the production of damaging reactive oxygen species. If the plasma membrane is affected, calcium can rush in, causing over-activation of many downstream signalling pathways. DNA may be damaged and proteins may be misfolded, causing activation of pro-apoptotic proteins and eventual death of the cell.

Describe the possible outcomes for a cell subjected to stress or injury

In a nutshell, an injured cell might be able to revert back to normal (if the injury is reversible) or undergo various forms of cell death (if the injury is irreversible). In cases of more long-term stress, cells may undergo adaptation, but if they are unable to adapt, they become injured and either recover or die.

Describe the changes in cellular appearance and function resulting from cell injury

As a result of cell injury, cells may have increased permeability (probably due to membrane damage etc.) and/or altered cellular metabolism. Increased permeability can lead to cell swelling, which may manifest as an increase in the number of vacuoles (pinched-off segments of the endoplasmic reticulum) and eosinophilia (pink staining from the eosin dye) in cells. Altered cellular metabolism can lead to fatty change (an increase in lipid vacuoles). These changes can be reversible, though sometimes accumulated by-products of altered metabolism might remain.

Describe how tissues react to cell injury

As I mentioned earlier, cells respond to injury by healing, adapting, or dying. Healing will be covered in a later post, so let's focus on adaptation and death for now.

Adaptation

The main methods of adaptation are hypertrophy, hyperplasia, atrophy, and metaplasia. Sometimes multiple methods of adaptation can occur together (e.g. hypertrophy and hyperplasia are often found together).

Hypertrophy is an increase in the size of cells (while keeping the number of cells constant). This is most likely to occur when cells are unable to or have limited capacity to divide, and can be due to either pathological causes or normal physiological causes. For instance, cardiac muscle that is placed under a lot of stress might get thicker due to the size of the cells increasing. Also, if you work out, your skeletal muscle cells will grow in size, but you won't gain any more muscle cells.

Hyperplasia is an increase in the number of cells (while keeping the number of cells more or less constant). Hyperplasia, just like hypertrophy, can occur due to normal physiological processes of the body or due to some kind of pathological cause. For instance, there is an increase in cells during breastfeeding (physiological cause), and an increase in cells in benign prostatic hyperplasia (pathological cause).

Atrophy is the opposite of both hypertrophy and hyperplasia. It can refer to a decrease in the size of cells or a decrease in the number of cells. It is due to either decreased protein synthesis or increased protein degradation. Once again, atrophy can be due to a normal physiological process (if you stop working out, your muscles get smaller), or due to some kind of pathological cause (e.g. hormonal abnormalities).

Metaplasia is when one adult cell type is induced to become a different adult cell type. Metaplasia can be physiological or pathological. Pathological metaplasia is often due to some kind of chronic irritation that requires special adaptations from the cells in order to survive. For instance, smokers may get squamous metaplasia of the upper respiratory tract. Metaplasia can increase the risk of further cellular alterations and dysplasia (abnormal cells within a tissue).

Death

There are two main ways in which cells can die: necrosis and apoptosis.

Necrosis is unregulated cell death that is the end result of severe damage. As such, it is always pathological. Cells undergoing necrosis may experience several changes that are visible under a microscope, such as increased eosinophilia and a "glassy" cytoplasm due to the loss of organelles. The nucleus will also change: during pyknosis the nucleus becomes dark, during karyorrhexis the nucleus begins to break up, and in karyolysis the nucleus begins to disappear altogether due to digestion of DNA. Necrotic cells may hang around for a while or be digested (presumably by phagocytic cells like macrophages?).

There are several different types of necrosis. The main types of necrosis are coagulative and liquefactive. In coagulative necrosis, cells lose their nuclei but retain their shape. Since they retain their shape and scaffolding is still present, coagulative necrosis forms a defined area (often wedge-shaped) that heals by scar formation. In contrast, no damaged tissue or scaffolding remain in liquefactive necrosis, so a cavity forms. Liquefactive necrosis is more common in the central nervous system.

Aside from coagulative and liquefactive necrosis, there are other types of necrosis. Caseous necrosis, which is a mixture of coagulative and liquefactive necrosis, is pretty much exclusive to tuberculosis. Fat necrosis involves the presence of "foamy" macrophages and calcification due to lipid accumulation. Fibrinoid necrosis is immunologic injury to vascular smooth muscle, resulting in an injury that looks like fibrin in the walls of blood vessels. Finally, gangrene is a type of coagulative necrosis where tissue turns black, rather than white, as necrosis tends to be. Gangrene can be further subdivided into dry gangrene (dry tissue caused by chronic ischaemia), wet gangrene (an infarcted region- i.e. area that died due to lack of oxygen- that becomes infected), and gas gangrene (infection of dead tissue by gas-forming organisms).

Apoptosis, in contrast to necrosis, is a regulated mechanism of cell death. It is often just a physiological process that is important both during development and throughout life, but can be pathologic following cell injury. The two main apoptotic pathways are mitochondrial/intrinsic (triggered by loss of survival signals, DNA damage, or other internal signals) and death receptor/extrinsic (triggered by engagement of death receptors by ligands on adjacent cells). Cells that have undergone apoptosis are rapidly cleared by phagocytes before inflammation is triggered, so apoptosis is not generally associated with inflammation (in contrast with necrosis, which is frequently associated with inflammation).

Autophagy

Autophagy is an interesting kind of survival mechanism that can progress to apoptosis. When a cell detects nutrient deprivation, intracellular organelles and portions of the cytosol are digested in autophagolysosomes. The idea is that the cell basically "eats itself" in order to maintain enough nutrition to survive. Over time, cells may become atrophied or undergo apoptosis.

Define the terms hyperplasia, hypertrophy, atrophy, metaplasia, necrosis, apoptosis, autophagy

• Hyperplasia- Increase in the number of cells.
• Hypertrophy- Increase in the size of cells.
• Atrophy- Decrease in the size of cells.
• Metaplasia- Transition from one mature adult cell type to another mature adult cell type.
• Necrosis- Uncontrolled cell death that is always associated with some kind of pathogenic process.
• Apoptosis- Controlled cell death that may or may not be due to a pathogenic cause.
• Autophagy- This term literally means "eating oneself." It refers to cells breaking down organelles in order to keep themselves nourished during times of extreme nutrient deprivation.