Cell Injury and Cellular adaptations, Wound healing - Robbins Pathology - Chapter 1
Dr.G Bhanu Prakash Animated Medical Videos・135 minutes read
Cell injury can be reversible or irreversible, leading to adaptations or death, with different types of cell death like necrosis and apoptosis discussed. Understanding cellular adaptations, such as hypertrophy and hyperplasia, is crucial for comprehending how cells respond to stress and stimuli to maintain functionality and health.
Insights
- Cell injury is a crucial starting point in general pathology, focusing on reversible and irreversible damage distinctions.
- Mitochondrial dysfunction and sodium-potassium ATPase failure are key initial changes in reversible cell injury.
- Visible morphological changes in reversible cell injury include hydropic swelling and loss of microvilli.
- Irreversible cell injury involves severe membrane damage, leading to calcium influx and nuclear changes.
- Different types of necrosis, such as coagulative, liquefactive, and caseous, have distinct characteristics and locations in the body.
- Cell death pathways like apoptosis, necroptosis, and pyroptosis involve intricate molecular mechanisms that lead to programmed or pathological cell demise.
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Recent questions
What is reversible cell injury?
Reversible cell injury allows cells to return to normal function if damage is minimal. It initiates with a decrease in ATP levels, leading to sodium-potassium ATPase failure and cellular swelling. Visible morphological changes include hydropic swelling, loss of microvilli, and formation of cytoplasmic blebs. Electron microscopic features like myelin figures show laminated appearances due to membrane damage in swollen organelles. Membranous walls are mainly composed of phospholipids, with phosphore being the primary component, along with calcium.
What is necrosis?
Necrosis is like a murder, where cells are stressed from outside leading to cell death. Coagulative necrosis is the most common type, preserving cell architecture even after death. It is seen in heart, kidneys, spleen, and most solid organs due to infarction. Denaturation of proteins in coagulative necrosis preserves cell architecture. Brain and pancreas show liquefactive necrosis due to high hydrolytic enzymes. Cheesy appearance in lung tissue indicates caseous necrosis, a combo of coagulative and liquefactive necrosis. Fat necrosis in areas with high fat content like breasts and buttocks leads to chalky white appearance due to saponification.
What is apoptosis?
Apoptosis is a programmed cell death that can be both physiological and pathological. Examples include embryogenesis, endometrial shedding, and deletion of self-reactive T cells. Tumor cells undergo death through apoptosis, which is a programmed cell death. Anti-cancer drugs induce cell death in cancerous cells through apoptosis. Physiological examples of apoptosis include embryogenesis and endometrium shedding during menstruation. The extrinsic pathway involves an external signal binding to the death receptor CD95, while the intrinsic pathway involves stress sensors activating pro-apoptotic factors.
What is hypertrophy?
Hypertrophy is a cellular adaptation characterized by an increase in cell size due to elevated protein synthesis and transcription factors like GATA4 and NFAT. Examples include muscle growth from exercise, organ enlargement due to outflow tract obstruction, and breast and uterine tissue growth during puberty and pregnancy.
What is metaplasia?
Metaplasia is the change of one cell type into another due to stress, involving stem cell reprogramming. Vitamin A deficiency can lead to metaplasia, seen in conditions like Barrett's esophagus where squamous epithelium is replaced by columnar epithelium and goblet cells due to acid reflux. Goblet cells are not typically found in the esophagus, but in cases of gastroesophageal reflux disease (GERD), they can appear due to acid regurgitation. The presence of goblet cells in the esophagus leads to the production of mucus, contributing to the symptoms of GERD.
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Summary
00:00
Understanding Cell Injury and Adaptation in Pathology
- The class begins with an introduction to general pathology, focusing on cell injury as the starting point.
- Emphasis is placed on covering essential exam topics and clinical examples throughout the class.
- The chapter delves into the concept of cell injury, distinguishing between reversible and irreversible cell injury.
- Two types of cell death are discussed: necrosis and apoptosis.
- Stress on cells leads to adaptation, but if adaptation fails, cell injury occurs.
- Reversible cell injury allows cells to return to normal function if damage is minimal.
- Mitochondrial dysfunction is the initial cellular change in reversible cell injury due to hypoxia.
- Sodium-potassium ATPase failure results in sodium accumulation and cellular swelling.
- Visible morphological changes in reversible cell injury include hydropic swelling, loss of microvilli, and formation of cytoplasmic blebs.
- Electron microscopic features like myelin figures show laminated appearances due to membrane damage in swollen organelles.
16:56
Cell Injury: Reversible and Irreversible Mechanisms
- Membranous walls are laminated aggregates of phospholipids derived from damaged membranes of mitochondria, endoplasmic reticulum, or cell membrane.
- These walls are mainly composed of phospholipids, with phosphore being the primary component, along with calcium.
- Reversible cell injury initiates with a decrease in ATP levels, leading to sodium-potassium ATPase failure and cellular swelling.
- Morphological changes in reversible cell injury include endoplasmic reticulum swelling, loss of microvilli, cytoplasmic blebs, and myelin figure formation from phospholipids.
- Hypoxia due to ATP depletion shifts respiration to anaerobic pathways, producing lactic acid and causing acidosis.
- Nuclear changes in reversible cell injury involve clumping of chromatin, while ribosomal detachment leads to decreased protein synthesis.
- Irreversible cell injury is marked by severe membrane damage, preventing cell repair and leading to irreversible damage.
- Calcium influx into damaged cells activates phospholipases, proteases, and nucleases, causing cell membrane, protein, and nuclear breakdown.
- Calcium deposits in mitochondria, termed large amorphous flocculent densities, signify irreversible cell injury.
- Nuclear changes in irreversible cell injury include nuclear condensation (hypnosis), fragmentation (carrier axis), and dissolution (carriolysis), indicating irreversible damage.
33:20
Types of Necrosis in Human Tissues
- Necrosis is like a murder, where cells are stressed from outside leading to cell death.
- Coagulative necrosis is the most common type, preserving cell architecture even after death.
- It is seen in heart, kidneys, spleen, and most solid organs due to infarction.
- Denaturation of proteins in coagulative necrosis preserves cell architecture.
- Ghost cells, empty cells without a nucleus, are seen in coagulative necrosis.
- Brain and pancreas show liquefactive necrosis due to high hydrolytic enzymes.
- Cheesy appearance in lung tissue indicates caseous necrosis, a combo of coagulative and liquefactive necrosis.
- Associated with infections like TB, histoplasmosis, and coccidioidomycosis.
- Fat necrosis in areas with high fat content like breasts and buttocks leads to chalky white appearance due to saponification.
- Fibrinoid necrosis, with pink fibrin-like material, is seen in vasculitis conditions like polyarteritis nodosa and rheumatic heart disease.
50:01
Types and Characteristics of Gangrene Syndromes
- Dry gangrene is commonly seen in the limbs, both upper and lower, while wet gangrene is more prevalent in the bowels or intestines.
- Vertical gangrene is primarily due to arterial occlusion, leading to hypoxemia, hypoxia, reversible cell injury, and irreversible cell injury.
- Wet gangrene is often caused by venous blockage, resulting in venous congestion and tissue death, with infections commonly developing.
- Dry gangrene is characterized by a mummified appearance and coagulative necrosis, with no bacterial growth, while wet gangrene shows liquefactive necrosis with infections.
- A clear demarcated line and a mummified appearance indicate dry gangrene, while the absence of a clear line of demarcation suggests wet gangrene.
- Bacteria do not thrive in dry gangrene but can cause liquefactive necrosis and infections in wet gangrene.
- Zenger's degeneration, also known as hyaline necrosis, occurs in skeletal muscles during acute infectious conditions, such as typhoid fever.
- Zenger's degeneration is a form of coagulative necrosis, affecting muscles like the rectus abdominis.
- Apoptosis, a programmed cell death, can be both physiological and pathological, with examples including embryogenesis, endometrial shedding, and deletion of self-reactive T cells.
- Councilman bodies are dying hepatocytes infected with the hepatitis virus, undergoing apoptosis to prevent viral replication and spread to healthy tissues.
01:06:06
Understanding Apoptosis: Cell Death in Cancer
- Tumor cells undergo death through a process called apoptosis, which is a programmed cell death.
- Anti-cancer drugs induce cell death in cancerous cells through apoptosis.
- Physiological examples of apoptosis include embryogenesis and endometrium shedding during menstruation.
- The extrinsic pathway of apoptosis involves an external signal binding to the death receptor CD95, leading to cell death.
- In the intrinsic pathway of apoptosis, stress sensors within cells activate pro-apoptotic factors, leading to cell death.
- In the intrinsic pathway, stress sensors inhibit anti-apoptotic factors, allowing cytochrome C to leak into the cell and trigger cell death.
- Cytochrome C binds with Apaf-1 to form an apoptosome, activating caspase-9 and leading to cell death.
- Caspase-8 and caspase-10 are activated in the extrinsic pathway, while caspase-9 is activated in the intrinsic pathway, initiating cell death.
- Executionary caspases, including caspase-3, -6, and -7, are activated to cause cell death by damaging cell membranes, cytoskeleton, and DNA fragmentation.
- Caspases contain 16 amino acids and cleave proteins at aspartate residues, leading to cell death.
01:22:36
Cell Death Mechanisms and Processes Explained
- Cysteine aspartacus caspasis contain 16 amino acids and break protein at aspartate residues.
- Endonucleases cut DNA at every 200 base pairs.
- Apoptosis occurs due to activation of caspases, leading to cell fragmentation.
- Apoptotic bodies contain cell organelles and cytoplasm.
- Phosphatidyl serine and thrombosponding act as "eat me" signals on apoptotic bodies.
- Macrophages clear apoptotic bodies due to the "eat me" signal.
- Differentiation between apoptosis and necrosis can be done through DNA gel electrophoresis.
- Tunnel stain is positive in apoptosis and negative in necrosis.
- Brain infarction due to atrial fibrillation leads to liquefactive necrosis.
- Necroptosis is a combination of necrosis and apoptosis, caspase-independent, active, and can be both physiological and pathological.
01:37:40
Understanding Necroptosis and Pyroptosis Pathways in Cell Death
- Apoptosis is a programmed active process that occurs both physiologically and pathologically.
- Physiological examples of necroptosis include cells undergoing necroptosis during growth plate formation in bones.
- Pathological examples of necroptosis are seen in conditions like pancreatitis, fatty liver, cytomegaloviral infection, Parkinsonism, and Alzheimer's.
- Necroptosis is a combination of necrosis and apoptosis, involving a specific pathway.
- The pathway of necroptosis starts with tumor necrosis factor binding to its receptor, activating RIP kinases.
- RIP kinases phosphorylate MLKL, leading to cell membrane damage and cell death resembling necrosis.
- In necroptosis, cell membrane damage triggers inflammation and cellular swelling.
- Pyroptosis is a type of cell death involving the release of interleukin-1 as a pyrogen, causing fever.
- Pyroptosis is a combination of pyrogen and apoptosis, with a pathway involving bacterial antigens binding to toll-like receptors.
- In pyroptosis, toll-like receptors activate pro-caspases 11, 4, and 5, leading to the activation of gasdermin and cell membrane damage.
01:52:28
Cellular Adaptations: Hypertrophy, Hyperplasia, and More
- Pro caspase number one and Pro caspase number 11 are crucial enzymes that can lead to cell death.
- Caspase number one converts into active caspase number one, which activates gasdermin, causing cell membrane damage and cell death.
- Caspase number one also converts inactive interleukin 1 and interleukin 18 into active forms, contributing to the production of interleukins.
- Two pathways for gasdermin production involve antigen binding with toll-like receptors and bacterial antigens recognized by nod-like receptors, leading to inflammasome activation.
- Caspase number 11 can directly activate the inflammasome, contributing to the inflammatory response.
- Hypertrophy is a cellular adaptation characterized by an increase in cell size due to elevated protein synthesis and transcription factors like GATA4 and NFAT.
- Examples of hypertrophy include muscle growth from exercise, organ enlargement due to outflow tract obstruction, and breast and uterine tissue growth during puberty and pregnancy.
- Hyperplasia is a cellular adaptation involving cell division, leading to an increase in cell number through mitosis.
- Certain types of hyperplasia can increase the risk of cancer, such as post-menopausal females developing ovarian tumors.
- Understanding cellular adaptations like hypertrophy and hyperplasia is essential for comprehending how cells respond to stress and stimuli, adapting to maintain functionality and health.
02:07:33
Hormonal Tumors and Cell Changes in Atrophy
- Ovarian tumor named granulosa cell tumor produces excessive estrogen due to granulosa cells, leading to endometrial hyperplasia in females.
- Endometrial hyperplasia from granulosa cell tumor can increase the risk of endometrial cancer in postmenopausal females.
- Benign prostatic hyperplasia in males does not increase the risk of cancer, unlike other hyperplasias.
- Estrogens stimulate endometrium growth, while dihydrotestosterone stimulates prostate growth in males.
- Inhibiting 5 Alpha reductase enzyme can decrease dihydrotestosterone levels in benign prostatic hyperplasia, controlled by drugs like finasteride and dutasteride.
- Atrophy is a decrease in tissue size due to reduced cell number and size, activated by ubiquitin proteasome degradation pathway.
- Examples of atrophy include wasting atrophy from muscle disuse, malnutrition atrophy, ischemic atrophy from decreased blood supply, and denervation atrophy from nerve damage.
- Endometrial atrophy can lead to type 2 endometrial carcinoma, while endometrial hyperplasia can lead to type 1 endometrial carcinoma.
- Metaplasia is the change of one cell type into another due to stress, involving stem cell reprogramming.
- Vitamin A deficiency can lead to metaplasia, seen in conditions like Barrett's esophagus where squamous epithelium is replaced by columnar epithelium and goblet cells due to acid reflux.
02:22:23
Cellular Adaptations and Metaplasia in Disease Processes
- Goblet cells are not typically found in the esophagus, but in cases of gastroesophageal reflux disease (GERD), they can appear due to acid regurgitation.
- The presence of goblet cells in the esophagus leads to the production of mucus, contributing to the symptoms of GERD.
- Barrett's esophagus, a condition associated with GERD, involves the replacement of squamous epithelium with goblet cells, leading to mucus production.
- Metaplasia examples include Barrett's esophagus, myositis ossificans, smoker's lung, and small airways disease in smoking females.
- Metaplasia involves the transformation of one cell type into another, such as muscle tissue turning into bone tissue in myositis ossificans.
- Squamous metaplasia in the lungs occurs due to continuous smoking, converting ciliated columnar epithelium into squamous epithelium.
- Dysplasia is characterized by disorganized cell growth, loss of differentiation, and irreversibility, often indicating a pre-cancerous stage.
- All cellular adaptations, except dysplasia, are reversible when the stressor is removed.
- Melanin accumulation in the skin and substantia nigra is a normal occurrence, but in Parkinson's disease, the loss of dopaminergic neurons leads to a pale substantia nigra.
- Intracellular accumulations like iron in hemochromatosis, copper in Wilson disease, and glycogen, calcium, and other substances in various conditions can be identified through specific stains like Prussian Blue for iron and rubionic acid for copper.
02:38:24
Intracellular Pigments and Stains in Cells
- Homogenesic acid is an acid that accumulates intracellularly, causing blackish discoloration known as acronosis in alcaptonuria.
- Lipofusion or lipochrome is a pigment that accumulates in cells as individuals age due to free radical damage, leading to lipid peroxidation.
- Lipofusion is a wear and tear pigment seen in brown atrophy of the heart, accumulating around the nucleus due to free radical injury.
- Oil Red O is the stain used to identify lipofusion, while other stains like Sudan Black B, Sudan 4, and osmium tetroxide are used for lipids.
- Fatty liver is a common condition where excess fats accumulate in hepatocytes, while cholesterolosis in the gallbladder results in cholesterol deposits, known as strawberry gallbladder.
- Glycogen deposition occurs in conditions like diabetes mellitus, where glucose is stored as glycogen in proximal convoluted tubule epithelial cells, known as Armani Epstein cells.
- Periodic acid-Schiff stain is used to identify glycogen, which appears pink, and diastase enzyme can dissolve glycogen, making it diastase-sensitive.
