Cell Injury and Death Overview

Genetic defects can cause cell injury by leading to a deficiency of functional proteins like enzymes. This can happen in cases of "inborn errors of metabolism," where a genetic mutation disrupts the production of a crucial enzyme needed for a specific metabolic pathway. For example, a deficiency in the enzyme phenylalanine hydroxylase, caused by a genetic defect, leads to phenylketonuria, a metabolic disorder causing mental retardation due to the accumulation of phenylalanine.

Oxygen deprivation, or hypoxia, disrupts aerobic oxidative respiration, the primary energy source for cells. This leads to a decrease in ATP production, causing various cellular dysfunctions. Failure of energy-dependent pumps leads to cell swelling, and prolonged hypoxia ultimately causes cell death.

Reversible cell injury is characterized by cellular swelling and fatty change, both of which represent adaptations of the cell to stress. In reversible injury, the cellular structures are still intact. Irreversible cell injury culminates in cell death, typically manifested by necrosis. Here, the cell membrane loses integrity, leading to leakage of cellular contents, and degradation of cellular components. Morphological features of necrosis include increased eosinophilia (pink staining) and nuclear changes such as pyknosis, karyorrhexis, and karyolysis.

<p>Cellular senescence refers to the aging process of cells, leading to a decline in their ability to replicate and repair damage. Senescent cells accumulate with age, becoming more susceptible to injury, ultimately contributing to tissue dysfunction and overall aging.</p> Signup and view all the answers

<p>Understanding the causes of cell injury is foundational for diagnosing, treating, and preventing diseases. It provides insight into the pathogenesis of various disorders and informs the development of therapeutic strategies to protect cells, promote repair, or prevent further damage.</p> Signup and view all the answers

<p>The immune system, while crucial for defense against pathogens, can also contribute to cell injury. In autoimmune diseases or inappropriate immune responses, the immune system attacks the body's own tissues, leading to inflammation and cell damage. For example, in rheumatoid arthritis, the immune system targets the synovial membrane, resulting in joint inflammation and damage.</p> Signup and view all the answers

<p>The three nuclear changes observed in necrosis are: 1) Pyknosis: Nuclear shrinkage and increased density. 2) Karyorrhexis: Fragmentation of the pyknotic nucleus into small, dense masses. 3) Karyolysis: Dissolution of the nucleus, marked by fading of chromatin.</p> Signup and view all the answers

<p>Inflammation is a critical response to cell injury and death. Necrotic cells release their contents, triggering an inflammatory cascade. This inflammatory response involves recruitment of immune cells, release of inflammatory mediators, and tissue repair. The inflammatory process can be beneficial in clearing dead cells and initiating repair, but can also contribute to further tissue injury if uncontrolled.</p> Signup and view all the answers

<p>Reversible cell injury refers to cellular changes that, if the stress is removed, can be reversed. This includes changes like cellular swelling, fatty change, and accumulation of pigments. Two examples of cellular adaptations during this phase are</p> <ul> <li> <strong>Hypertrophy:</strong> Increase in cell size, often seen in response to increased workload, like in muscle cells during exercise.</li> <li> <strong>Atrophy:</strong> Decrease in cell size due to reduced workload or decreased nutrients.</li> </ul> <p>The transition to irreversible injury depends on factors like the nature and severity of the injury, the cell type, and the duration of the stress. Factors like depletion of ATP, membrane damage, and significant calcium influx can contribute to irreversible injury.</p> Signup and view all the answers

<p>Apoptosis and necrosis are distinct processes of cellular death, differing in their morphology, biochemical pathways, and roles.</p> <p>Apoptosis is a programmed, energy-dependent process characterized by cell shrinkage, nuclear fragmentation, and formation of apoptotic bodies. It is a highly regulated process involving caspases, a family of proteases. It plays a crucial role in development, tissue homeostasis, and removal of damaged or unwanted cells.</p> <p>Necrosis is a passive, uncontrolled process triggered by acute injury, leading to cell swelling, membrane rupture, and release of cellular contents. It is characterized by inflammation and tissue damage. Necrosis is often associated with pathological conditions, like ischemia or trauma.</p> Signup and view all the answers

<p>ROS are highly reactive molecules that can cause significant damage to cells. ROS are generated during normal cellular metabolism, but excessive production can overwhelm cellular defense mechanisms. They can damage DNA, proteins, and lipids through oxidation.</p> <p>The cellular defense mechanisms against ROS involve enzymes like superoxide dismutase (SOD), glutathione peroxidase, and catalase. These enzymes are crucial in converting ROS to less harmful products. Additionally, antioxidants like vitamins C and E can help neutralize ROS.</p> Signup and view all the answers

<p>Ischemia, a reduction of blood flow, leads to cell injury and death primarily through deprivation of oxygen and nutrients, leading to ATP depletion and accumulation of metabolic byproducts.</p> <p>Ischemia-reperfusion injury occurs when blood flow is restored to an ischemic tissue, but rather than immediate recovery, it triggers additional damage. This is due to the influx of oxygen radicals generated by the restored blood flow, further damaging already compromised cells. This phenomenon highlights the complexity of managing ischemic conditions and the challenges in restoring blood flow without inducing further injury.</p> Signup and view all the answers

<p>Calcium is a ubiquitous intracellular messenger, and its dysregulation plays a significant role in cell injury.</p> <p>Intracellular calcium levels increase during cell stress, triggering various damaging processes. Calcium acts as an activator for enzymes like phospholipases and proteases, which further damage cell membranes and proteins. It can also disrupt mitochondrial function, leading to ATP depletion and generation of ROS. Moreover, elevated calcium levels promote the activation of caspase enzymes, crucial for initiating apoptosis.</p> Signup and view all the answers

<p>During karyolysis, the nucleus fades and eventually disappears. This is thought to be caused by deoxyribonuclease (DNase) activity, which breaks down DNA.</p> Signup and view all the answers

<p>Pyknosis presents with a shrunken and intensely basophilic nucleus, while karyolysis shows a fading and eventually disappearing nucleus. Pyknosis involves nuclear condensation, whereas karyolysis signifies nuclear dissolution.</p> Signup and view all the answers

<p>Karyorrhexis, the fragmentation of the pyknotic nucleus, represents a crucial step in cellular demise. It further disrupts the crucial control center of the cell, leading to its complete breakdown.</p> Signup and view all the answers

<p>Coagulative necrosis maintains the basic tissue architecture, while liquefactive necrosis disrupts it. This difference is due to the breakdown of cellular debris by lysosomal enzymes in leukocytes in liquefactive necrosis.</p> Signup and view all the answers

<p>In coagulative necrosis, tissue architecture is preserved. Cells will appear ghost-like with their outlines intact, and the nuclei will exhibit pyknosis, karyorrhexis, or karyolysis.</p> Signup and view all the answers

<p>Leukocytes, particularly neutrophils, are crucial for liquefactive necrosis. They release lysosomal enzymes that digest the dead tissue, forming a viscous liquid mass.</p> Signup and view all the answers

<p>Granuloma formation in caseous necrosis is a hallmark of the body's immune response to the infectious agent, usually Mycobacterium tuberculosis.</p> Signup and view all the answers

<p>Caseous necrosis features a friable, yellowish-white appearance resembling cheese. This contrasts with the firm, coagulated tissue seen in coagulative necrosis, and the liquefied, viscous mass in liquefactive necrosis.</p> Signup and view all the answers

<p>Caseous necrosis is characterized by acellular pink areas of necrosis surrounded by inflammatory cells, giving a cheese-like appearance. In contrast, fat necrosis exhibits shadowy outlines of necrotic fat cells with basophilic calcium deposits. Caseous necrosis is a hallmark of tuberculosis infection, where Mycobacterium tuberculosis infects the lungs and spreads to lymph nodes, leading to the characteristic caseous necrosis in the hilar lymph nodes.</p> Signup and view all the answers

<p>Apoptosis is an active process where cells activate enzymes to degrade their own DNA and proteins, leading to fragmentation and formation of apoptotic bodies. Unlike necrosis, apoptosis doesn't cause inflammation. The term 'falling off' refers to the fragmented bodies detaching from the cell, giving a distinct appearance under microscopy.</p> Signup and view all the answers

<p>Apoptosis is vital in embryogenesis, ensuring the proper development of organs and tissues by eliminating unwanted cells. Hormone-dependent tissues undergo involution during hormone withdrawal, like the uterine lining in the menstrual cycle, through apoptosis. Finally, apoptosis eliminates neutrophils after their role in acute inflammation is complete, preventing excessive inflammatory response.</p> Signup and view all the answers

<p>DNA damage caused by radiation, cytotoxic anticancer drugs, or extreme temperature can activate apoptosis by triggering the intrinsic pathway, leading to cell death to prevent replication of damaged DNA. Certain viral infections can activate the apoptotic pathway, leading to viral clearance. Pathologic atrophy, such as in the pancreas after duct obstruction, can also induce apoptosis, where cells die due to lack of nutrients and oxygen.</p> Signup and view all the answers

<p>Apoptosis is a silent process, devoid of inflammatory response, which is crucial for preventing inflammation and tissue damage. When neutrophils, which mediate the acute inflammatory response, are no longer needed, they undergo apoptosis and are removed by phagocytes without triggering inflammation.</p> Signup and view all the answers

<p>Chalky white areas on the cut surface of the pancreas indicate fat necrosis, a characteristic feature of acute pancreatitis. The activated pancreatic lipases digest the fat in the pancreas, leading to the formation of fatty acids, which then combine with calcium to form chalky white deposits, visible on the surface.</p> Signup and view all the answers

<p>Normal fat cells have a peripheral nucleus and a clear, non-granular cytoplasm, whereas necrotic fat cells exhibit a loss of the peripheral nucleus, the cytoplasm becoming a pink amorphous mass of necrotic material. Moreover, necrotic fat cells often have calcium deposits, giving a chalky white appearance.</p> Signup and view all the answers

<p>Apoptosis is crucial for the efficient removal of unnecessary cells during involution, which is a process of organ shrinkage due to hormone withdrawal. The process is non-inflammatory, preventing tissue damage, and contributes to the proper physiological regression of the organ. For instance, during the menstrual cycle, the uterus undergoes involution, as the endometrial lining sheds, primarily through apoptosis, to prepare for a new cycle.</p> Signup and view all the answers