Title: The Fate of the Cell: Injury, Adaptation, and Death

Authors: highered-h5paccount (Author); Jina Kum (Author)
Licence: CC BY-NC-SA 4.0

Cell Injury, Adaptation, and Death

The Fate of the Cell:

CELL INJURY, ADAPTATION, & DEATH

Funded by the Government of Ontario.
The views expressed in this publication are the views of the author(s) and do not necessarily reflect those of the Government of Ontario or the Ontario Online Learning Consortium.

Overview

Click on the audio button for narration.

OVERVIEW

- Cell Adaptation & Injury
- Cell Adaptation Mechanisms
- Reversible Cell Injury
- Irreversible Cell Injury & Cell Death
- Types of Necrosis
- Apoptosis: Programmed Cell Death
- Case Study: Maya Anderson

Cell Adaptation & Injury

- The body must maintain a narrow physiological range, known as homeostasis.​
- Cells are constantly adapting to extracellular stresses (e.g., environmental changes) to maintain homeostasis​.
- If environmental changes overwhelm the cell’s capacity to maintain homeostasis, cell injury results​.
- Cells can adapt to injury; however, disease results when adaptive mechanisms fail or the adaptive mechanism itself becomes detrimental​.

Cell Adaptation Mechanisms

Note: These mechanisms can be part of both physiological (normal) and pathologic (disease-related) processes.​

CELL ADAPTATION MECHANISMS

Click on the icons to learn more about the following cellular adaptation mechanisms.​

Metaplasia is when a cell changes into a different cell type. For example, in people who smoke, the lining of the bronchi changes from ciliated columnar (tall and rectangular) epithelial cells to squamous (flat) epithelial cells. This process may result in decreased function or increased chance of malignancy.

Atrophy is a decrease in tissue mass resulting from a decrease in cell size. This could be due to a decrease in blood supply, workload (e.g., immobilization of a limb), nutrients, or trophic (growth) factors. Atrophy of muscle can occur naturally due to aging

Autophagy occurs when the cell breaks down its own components to destroy or reuse them. The cell is constantly building up and breaking down material.

Hyperplasia is an increase in cell number (i.e., increased cell division).

Hypertrophy is an increase in the size of existing cells and involves the synthesis of new organelles and proteins. It is the opposite of atrophy. Hypertrophy and hyperplasia often occur together in response to increased demand or hormonal stimulation. However, some cells are unable to divide, such as cardiomyocytes, and thus only undergo hypertrophy (e.g., cardiomegaly).

Reversible Cell Injury

- Results from an acute or mild stressor
- Reversible if the stressor is eliminated
- Key features: ↓ Oxidative phosphorylation, ATP depletion, & cellular swelling

Hydropic swelling occurs when there is an increase in cell volume due to impaired processes regulating ion concentration within the cell. Injurious agents can inhibit mitochondrial function and thus, the production of ATP. Consequently, the ATP-dependent sodium-potassium pump (Na+/K+) pump on the plasma membrane stops functioning, leading to sodium accumulation in the cell. Water follows sodium into the cell by osmosis, resulting in swelling and diluting the cytoplasm.

Note: Cells that have undergone hydropic swelling differ from hypertrophic cells, which look like normal cells but are simply bigger (new organelles and proteins are synthesized, so cytoplasm retains its typical colour).

Irreversible Cell Injury & Cell Death

- Cell death is a response to acute, severe stress or prolonged, unrelieved stress.
- It has two features: 1) Inability to reverse mitochondrial dysfunction, and 2) Severe disruption to membrane integrity/function (i.e., leaking of cellular contents).
- If an overwhelming injury occurs or happens at a rate at which the cell cannot adapt, necrosis will result & an inflammatory response will ensue.

Necrosis refers to the death of body tissue due to disease, injury, or failure of the blood supply. It is energy-independent and not regulated.

Types of Necrosis - Coagulative Necrosis

Types of Necrosis

Click on the icons to learn about the histological features of
coagulative necrosis.

Histology is the microscopic study of tissues and organs. It involves sectioning, staining, and examining biological tissues under a microscope.

COAGULATIVE NECROSIS

- Most common type of necrosis
- Often results from ischemia (injury due to lack of blood flow)
- Firm texture (tissue architecture is preserved)
- Seen in all solid organs (e.g., heart and kidney) except the brain (see Liquefactive Necrosis)

Dead myocardial fibres that have undergone necrosis.

Note: the loss of nuclei (due to processes of pyknosis, karyorrhexis, and karyolysis) and darker pink cytoplasm (increased eosinophilia compared to viable fibres). Eosin is an acidic dye, thus staining is increased upon exposure to the basic amino groups on denatured proteins of necrotic cells.

Viable myocardial fibres with paler pink cytoplasm and visible blue nuclei.

Figure 1: Myocardium from a 65-year-old male who suffered an acute myocardial infarction (i.e., heart attack; necrosis due to inadequate blood supply).
Image from the University of Leeds, https://www.virtualpathology.leeds.ac.uk/.

Types of Necrosis - Liquefactive Necrosis

Types of Necrosis

LIQUEFACTIVE NECROSIS

- Rapid loss of tissue architecture (tissue becomes "liquefied") & digestion of dead cells
- Most often seen in the central nervous system (especially the brain) or lungs
- Typical of bacterial damage

Necrotic areas are soft and mushy, hence the name “liquefactive”.

Figure 2: Liquefactive necrosis in the brain after infarction (loss of blood supply).
Courtesy of Javier Redding-Ochoa, M.D. and PathologyOutlines.com, see URL.

Types of Necrosis - Fat Necrosis

Types of Necrosis

FAT NECROSIS

- Specific to adipose (fat) tissue
- Enzymes leak out of necrotic cells and digest fat cells
- Digested fat combines with calcium to form chalky white deposits
- Associated with acute pancreatitis and breast tissue damage

Chalky, yellow discolouration within adipose tissue.

Figure 3: Fat necrosis within a lumpectomy specimen (surgical removal of a lump of cancerous or abnormal breast tissue).
Courtesy of Elizabeth Abels, M.D. and PathologyOutlines.com, see URL.

Types of Necrosis - Caseous Necrosis

Types of Necrosis

CASEOUS NECROSIS

- “Cheese-like” gross appearance
- Soft and friable (easily crumbled) texture
- Most often seen in the lungs
- Typical of tuberculosis

Necrotic areas have a yellow-white, crumbly, and cheesy appearance/texture.

Figure 4: Lungs from a 65-year-old male chronic smoker who had suffered from tuberculosis.
Courtesy of Sajna V.M. Kutty, M.D. and PathologyOutlines.com, see URL.

Types of Necrosis - Gangrenous Necrosis

Types of Necrosis

GANGRENOUS NECROSIS

- Coagulative necrosis, typically of a limb, after a loss of blood supply
- When there is a superimposed bacterial infection, necrotic tissue takes on a liquefactive appearance (also known as "wet gangrene").
- If the necrotic tissue dries out, it turns black and mummified (called "dry gangrene").

Figure 5: Dry gangrene of the toes in a patient with diabetes.
Courtesy of James Heilman, M.D. and Wikipedia.org, see URL.

Apoptosis

APOPTOSIS: Programmed Cell Death

- Controlled, energy-dependent process designed to eliminate unneeded or damaged cells
- Can occur under physiologic or pathologic conditions
  - Note: Necrosis is always pathologic!
- Membrane integrity preserved & no inflammatory response

Case Study - Patient profile

CASE STUDY

PATIENT PROFILE

- Name: Maya Anderson
- Age: 65
- Sex: Female
- Occupation: Retired teacher
- Medical History: Hypertension, Type 2 Diabetes

Photo by Marcus Aurelius (Pexels, a Canva Germany GmbH). See URL.

Case Study - Patient symptoms

Patient Symptoms

Mrs. Anderson visits her primary care physician with complaints of persistent chest pain and shortness of breath upon exertion. She reports a gradual decrease in her physical activity tolerance over the past year.

Mrs. Anderson and her husband exercise together twice a week. This is when her symptoms tend to flare up.

Photo by Marcus Aurelius (Pexels, a Canva Germany GmbH). See URL.

Case Study - Signs and symptoms of disease

Signs and Symptoms of Disease

During the examination, Mrs. Anderson appears fatigued, and her blood pressure is elevated. The physician notes a decreased intensity in heart sounds on auscultation (listening to the heart using a stethoscope) and orders a series of diagnostic tests, including an electrocardiogram (ECG) and echocardiogram.

Photo by Pavel Danilyuk (Pexels, a Canva Germany GmbH). See URL.

Photo by Pavel Danilyuk (Pexels, a Canva Germany GmbH). See URL.

Knowledge Check

Drag and match the descriptions to the correct diagnostic finding.

- These changes reflect the denaturation of cytoplasmic proteins and degradation of the nuclear DNA.
- The ECG indicates signs of myocardial ischemia, and subsequent cardiac catheterization reveals severe coronary artery disease.
- This energy-dependent process contributes to overall loss of functional myocardial cells, especially in areas affected by ischemia.
- Histological examination shows intense eosinophilia of the cytoplasm and pyknosis, karyorrhexis, and karyolysis of the nucleus.
- Key features: cell shrinkage, chromatin condensation, and the formation of apoptotic bodies
- Microscopic examination of myocardial cells shows hydropic swelling, also known as vacuolar degeneration.
- The echocardiogram reveals evidence of concentric cardiac hypertrophy, indicating the heart muscle's adaptation to increased workload associated with chronic hypertension.
Q: REVERSIBLE CELL INJURY
A: Microscopic examination of myocardial cells shows hydropic swelling, also known …; The echocardiogram reveals evidence of concentric cardiac hypertrophy, …
Q: NECROSIS
A: These changes reflect the denaturation of cytoplasmic proteins and degradation …; The ECG indicates signs of myocardial ischemia, and subsequent cardiac …; Histological examination shows intense eosinophilia of the cytoplasm and …
Q: APOPTOSIS
A: This energy-dependent process contributes to overall loss of functional …; Key features: cell shrinkage, chromatin condensation, and the formation of …

Case Study - Conclusion

Conclusion

Mrs. Anderson's myocardium shows evidence of both hypertrophy and atrophy.

Hypertrophy is evident in response to chronic hypertension (demands a compensatory increased workload on the heart), whereas adjacent areas affected by ischemia exhibit atrophy due to a decreased blood supply.

Photo by Marcus Aurelius (Pexels, a Canva Germany GmbH). See URL.

Check Your Understanding

Consider the following question. Once you have an answer, click the "Turn" button below to check your understanding.

Hypertrophy Understanding Question

Q: 1. How might hypertension have contributed to the hypertrophy of Mrs. Anderson’s myocardium, and why did hyperplasia not occur?
A: Hypertension increased the workload on the heart and, to compensate having to work harder, the myocardial cells grew bigger to increase force of contraction. Hyperplasia was not observed because cardiomyocytes are permanent cells; and therefore, cannot divide to form more cells in response to an increased workload on the heart.

Knowledge Check

Cellular Adaptation MCQ

Q: Which of the following is a pathological example of cellular adaptation?
- A. When Mrs. Anderson broke her leg last year, she had to wear a cast for six months. When she removed the cast, she noticed her calf muscles were visibly smaller than those of her unbroken leg.
- B. When Mrs. Anderson was younger, she had very large biceps. However, with age, they seem to have shrunken despite no major changes in her activity level.
- C. The muscular wall of Mrs. Anderson’s left ventricle has thickened over time to compensate for her hypertension. (correct) (The correct answer is C because her cardiac muscles are undergoing hypertrophy in response to increased workload as a result of her hypertension. This pathological process is known as cardiomegaly.) (if not chosen: The correct answer is C because her cardiac muscles are undergoing hypertrophy in response to increased workload as a result of her hypertension. This pathological process is known as cardiomegaly.)
- D. After Mrs. Anderson underwent a partial liver resection, her remaining hepatocytes proliferated to restore her liver to normal mass.

Knowledge Check

Necrosis MCQ

Q: If ischemia had been prolonged in Mrs. Anderson's heart, which type of necrosis would her myocardium have displayed?
- A. Coagulative (correct) (The correct answer is A because coagulative necrosis is typically seen in the heart due to its susceptibility to ischemic injury. Liquefactive necrosis is typically specific to the central nervous system and fat necrosis is specific to adipose tissue (the heart is mostly muscle tissue). Caseous necrosis is commonly caused by tuberculosis infection and thus typical of the lungs.) (if not chosen: The correct answer is A because coagulative necrosis is typically seen in the heart due to its susceptibility to ischemic injury. Liquefactive necrosis is typically specific to the central nervous system and fat necrosis is specific to adipose tissue (the heart is mostly muscle tissue). Caseous necrosis is commonly caused by tuberculosis infection and thus typical of the lungs.)
- B. Liquefactive
- C. Fat
- D. Caseous
- E. Gangrenous

Knowledge Check

Cellular Adaptation Mechanisms Summary

Drag the words into the correct boxes to complete the following summary.

Q: Cell size is decreased in [...] and increased in [...]. The number of cells is increased in [...]. Atrophy, hypertrophy, hyperplasia, and metaplasia are all potentially [...] if the cause is addressed. Cellular function is increased in [...] and hyperplasia, but decreased in [...]. Cellular function may become abnormal in [...].
A: atrophy; hypertrophy; hyperplasia; reversible; hypertrophy; atrophy; metaplasia