Cell Injury and Adaptation
Learning Objectives
By the end of this page, you should be able to:
- Distinguish reversible from irreversible cell injury using morphological and biochemical criteria
- Explain the sequence of events from a cellular stimulus to necrosis or apoptosis
- Differentiate the major morphological patterns of necrosis (coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous) and identify the tissue/disease each is classically associated with
- Describe the mechanism of apoptosis via the intrinsic and extrinsic pathways and contrast it with necrosis
- Identify the four cellular adaptations (hypertrophy, hyperplasia, atrophy, metaplasia), give a physiologic and pathologic example of each, and explain why metaplasia is a red flag
- Apply these concepts to identify the correct type of cell death or adaptation in a clinical vignette
Quick Answer
Cell injury and adaptation describe how cells cope with stress before something breaks permanently. When a stimulus (hypoxia, toxins, free radicals, infection) is mild or brief, cells adapt — they shrink (atrophy), grow (hypertrophy), multiply (hyperplasia), or switch cell type (metaplasia) — or they undergo reversible injury and recover once the stress is removed. Push past a critical threshold — usually mitochondrial failure and membrane damage — and injury becomes irreversible, ending in one of two deaths: necrosis (messy, unregulated, triggers inflammation) or apoptosis (clean, programmed, no inflammation). This distinction matters because it explains why a myocardial infarction causes pain and scarring while normal tissue turnover doesn't, and it's one of the most heavily tested concepts in pathology.
Overview
Every cell lives within a narrow window of conditions it can tolerate — enough oxygen, stable pH, controlled calcium, functioning membranes. Pathology as a discipline essentially begins with the question: what happens when that window is exceeded?
The answer unfolds as a spectrum, not a switch. A cell exposed to a mild, transient stressor will first try to adapt — changing its size, number, or differentiation state to survive under the new conditions. If the stress is removed at this stage, the cell returns to normal. Push the stress further and the cell crosses into injury: initially reversible (swelling, fatty change, loss of ATP), then, if the insult persists or is severe enough, irreversible — the point of no return. From there, the cell dies by one of two fundamentally different routes: necrosis, an uncontrolled, energy-independent death that spills cellular contents and provokes inflammation, or apoptosis, a tightly regulated, energy-dependent suicide program that clears cells quietly without disturbing neighbors.
Nearly every disease you will study in medicine is a variation on this theme — ischemic heart disease, stroke, viral hepatitis, tuberculosis, and cancer all involve some combination of injury, cell death, and adaptation. Getting comfortable with the vocabulary and mechanisms here pays off across the entire curriculum.
The Cell Injury Pathway: Stimulus to Outcome
The key branch point is mitochondrial and membrane integrity. As long as the cell can still make ATP and keep its plasma membrane sealed, it can recover. Once calcium floods in uncontrollably and mitochondrial permeability transition pores open, the cell is committed to death — the only question left is which pathway it takes.
Reversible vs. Irreversible Cell Injury
Definition
Reversible injury is cell damage that resolves completely once the causative stress is removed, because the cell's structural and biochemical integrity — especially membrane function — is still intact. Irreversible injury has crossed a threshold (usually severe mitochondrial dysfunction and membrane damage) beyond which the cell cannot recover even if the stress stops.
Explanation
The earliest and most sensitive change in almost any injury is reduced ATP production, typically from hypoxia or mitochondrial toxins. Low ATP shuts down the Na+/K+-ATPase pump, so sodium and water accumulate inside the cell — this is cellular swelling (hydropic change), the first light-microscopic sign of injury, seen as pallor and increased turgor of the organ. Anaerobic glycolysis kicks in to compensate, generating lactic acid and dropping intracellular pH, which clumps nuclear chromatin. Ribosomes detach from the rough ER, reducing protein synthesis, and lipid deposits may accumulate (fatty change), especially in the liver, heart, and kidney.
All of this is reversible if oxygen or the missing substrate is restored in time. But if the insult continues, intracellular calcium — normally kept extremely low in the cytosol — starts leaking in from the extracellular space and from damaged ER/mitochondria. Calcium activates a set of destructive enzymes: phospholipases (degrade membranes), proteases (break down cytoskeleton), endonucleases (fragment DNA), and ATPases (accelerate ATP depletion further). This is the point where amorphous densities appear in mitochondria, membrane blebs form and can rupture, and lysosomal enzymes leak out. Once membrane integrity is lost this way, the injury is irreversible.
Example
A hepatocyte briefly deprived of oxygen during a hypotensive episode swells, loses glycogen, and develops fatty change — but recovers fully once blood pressure normalizes.
Real-World Example
In an evolving myocardial infarction, the "golden hour" concept exists precisely because of this reversible-to-irreversible window: myocytes are reversibly injured for roughly the first 20-30 minutes of complete coronary occlusion. Reperfusion (PCI or thrombolysis) within that window can salvage muscle; beyond it, an expanding wavefront of irreversible necrosis occurs, which is why "time is muscle."
Why It Matters
This concept is the biological basis for every emergency reperfusion protocol in medicine — stroke thrombolysis windows, cardiac catheterization lab activation, and even organ preservation during transplant all hinge on how long tissue can sit in the reversible zone.
Common Misunderstanding
Students often think a single named change (e.g., "cell swelling") always means reversible and any necrosis-type description means irreversible. In reality, the reversible/irreversible line is defined functionally (can the membrane and mitochondria still recover?), and early necrotic features like membrane blebbing can appear before the process is fully irreversible — the exact cutoff is a continuum, not a single microscopic finding.
Necrosis: Patterns and Their Clinical Correlates
Definition
Necrosis is the morphologic pattern of cell death that occurs in living tissue following irreversible injury, characterized by enzymatic digestion of cellular components and denaturation of proteins, always followed by an inflammatory reaction because cell contents spill into the extracellular space.
Explanation
There isn't just one kind of necrosis — the pattern depends on the tissue involved and the type of insult, and pathologists use these patterns diagnostically.
- Coagulative necrosis: The classic pattern of ischemic death in solid organs (heart, kidney, spleen) except the brain. Protein denaturation outpaces enzymatic digestion, so the basic architecture of the dead tissue is preserved for days — you can still see a "ghost outline" of cells under the microscope, just without nuclei. Classic example: myocardial infarction.
- Liquefactive necrosis: Enzymatic digestion dominates and the dead tissue turns into a liquid, viscous mass. Seen in brain infarcts (the brain is lipid-rich and has few structural proteins, so it liquefies rather than coagulates) and in bacterial/fungal abscesses (neutrophil enzymes digest the tissue, producing pus).
- Caseous necrosis: A "cheese-like" combination pattern — friable, white, and structureless (neither fully coagulative nor liquefactive) — pathognomonic for tuberculosis granulomas, though also seen in some fungal infections.
- Fat necrosis: Enzymatic destruction of fat, classically from lipases released in acute pancreatitis (autodigestion of peripancreatic fat) or from direct trauma to fatty tissue (e.g., the breast). Calcium binds the released free fatty acids to form chalky white deposits (saponification), which is why serum calcium can drop in severe pancreatitis.
- Fibrinoid necrosis: Immune complexes deposit in vessel walls along with fibrin, giving a bright pink, amorphous appearance on H&E. Seen in malignant hypertension and vasculitis (e.g., polyarteritis nodosa).
- Gangrenous necrosis: Not a distinct microscopic pattern but a clinical term for coagulative necrosis of an extremity due to ischemia (dry gangrene); if superimposed bacterial infection causes enzymatic digestion on top of that, it becomes wet gangrene (essentially coagulative necrosis + liquefactive necrosis from infection).
Example
A patient's leg artery is occluded by an embolus; the distal tissue undergoes coagulative necrosis first (dry gangrene), and if bacteria invade the dead tissue, liquefactive change is added (wet gangrene).
Real-World Example
On a head CT a week after an ischemic stroke, the infarcted brain tissue appears as a hypodense, softened area — the imaging correlate of liquefactive necrosis — very different from the firm, architecturally preserved pale infarct you'd find on autopsy in a kidney or heart.
Why It Matters
Recognizing the necrosis pattern on histology or imaging often tells you the organ and the mechanism simultaneously — this is a favorite pathology exam trick where a single micrograph is expected to yield the diagnosis.
Common Misunderstanding
Many students assume "necrosis" is one uniform process. It isn't — the pattern is a clue, not just a description. Also, a very common error is forgetting that brain infarction is liquefactive (not coagulative) despite being caused by the same ischemic mechanism as a myocardial infarction — the tissue's own composition (lipid-rich, protease-poor) determines the pattern, not just the cause.
Apoptosis: Programmed Cell Death
Definition
Apoptosis is a regulated, energy-dependent form of cell death in which a cell activates its own internal death program to eliminate itself in an orderly way, without releasing its contents or provoking inflammation.
Explanation
Apoptosis proceeds through two converging pathways, both ending in activation of caspases (a family of proteases that dismantle the cell from within).
- Intrinsic (mitochondrial) pathway: Triggered by DNA damage, growth factor withdrawal, or cellular stress. The tumor suppressor p53 senses irreparable DNA damage and tips the balance of BCL-2 family proteins — decreasing anti-apoptotic BCL-2/BCL-XL and increasing pro-apoptotic BAX/BAK. This increases mitochondrial outer membrane permeability, releasing cytochrome c into the cytoplasm, where it activates caspase-9, which then activates the executioner caspases (caspase-3, -6, -7).
- Extrinsic (death receptor) pathway: Triggered by ligand binding to death receptors on the cell surface — Fas (CD95) binding FasL, or TNF binding its receptor. This recruits adaptor proteins that activate caspase-8, which again converges on the executioner caspases.
Once executioner caspases are active, the cell shrinks, chromatin condenses at the nuclear periphery (pyknosis), DNA is cleaved into regular fragments by endonucleases, and the cell breaks into membrane-bound apoptotic bodies. Phosphatidylserine flips to the outer membrane leaflet as an "eat me" signal, so macrophages phagocytose the fragments quickly and quietly — no membrane rupture, no content spillage, no inflammation.
Example
Thymocytes that fail positive or negative selection during T-cell development undergo apoptosis — this happens constantly and generates no inflammatory response, which is why the thymus doesn't look inflamed despite constant cell death within it.
Real-World Example
Cytotoxic T lymphocytes killing a virus-infected cell use both perforin/granzyme (granzyme B directly activates caspases) and Fas-FasL engagement — the immune system deliberately chooses apoptosis over necrosis so that killing an infected cell doesn't trigger collateral inflammatory damage to surrounding healthy tissue.
Why It Matters
Apoptosis dysregulation underlies major disease categories: too little apoptosis (cancer, where BCL-2 overexpression in follicular lymphoma prevents cell death; or autoimmune disease, where self-reactive lymphocytes fail to be deleted) and too much apoptosis (neurodegenerative diseases, HIV-related CD4+ T-cell depletion, ischemic neuronal death).
Common Misunderstanding
Students frequently think apoptosis "doesn't need energy" because it's often described as a passive process — the opposite is true: apoptosis is an active, ATP-requiring program. A dying cell with no ATP left can only necrose, it cannot execute the apoptotic machinery. Another common error is assuming apoptosis never causes any immune response at all — while it doesn't trigger acute inflammation, defective clearance of apoptotic bodies can still contribute to autoimmunity (e.g., proposed mechanism in SLE).
Cellular Adaptations
Definition
Cellular adaptations are reversible functional and structural responses that cells make to sustained physiologic or pathologic stress, allowing them to survive and maintain function under new steady-state conditions — as opposed to progressing straight to injury.
Explanation
There are four classic adaptations, and each answers a different kind of demand:
- Hypertrophy — increase in the size of individual cells (not number), which increases overall organ size. Occurs in cells with limited ability to divide (cardiac and skeletal muscle). Driven by increased functional demand or growth factor/hormonal stimulation, mediated by activation of signaling pathways that boost synthesis of cellular proteins and organelles.
- Hyperplasia — increase in the number of cells in an organ, occurring only in tissues whose cells can still divide (epithelium, liver, bone marrow, endometrium). Can be physiologic (hormonal, e.g., breast/uterine hyperplasia in pregnancy; compensatory, e.g., liver regrowth after partial hepatectomy) or pathologic (excessive hormonal or growth factor stimulation, e.g., endometrial hyperplasia from unopposed estrogen, benign prostatic hyperplasia).
- Atrophy — a decrease in cell size and/or number, shrinking the tissue, due to reduced workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of hormonal stimulation, or aging. Mechanistically driven by decreased protein synthesis and increased protein degradation via the ubiquitin-proteasome pathway, along with increased autophagy.
- Metaplasia — a reversible change in which one differentiated cell type is replaced by another differentiated cell type, usually one better suited to withstand the new stress. This occurs through reprogramming of stem cells, not transdifferentiation of mature cells. Classic examples: squamous metaplasia of the bronchial respiratory epithelium in chronic smokers (columnar ciliated cells replaced by tougher stratified squamous cells, at the cost of losing mucociliary clearance) and Barrett esophagus (squamous esophageal epithelium replaced by columnar, intestinal-type epithelium in response to chronic acid reflux).
Example
A weightlifter's cardiac and skeletal muscle cells enlarge (physiologic hypertrophy) in response to sustained increased workload; a cast-immobilized limb's muscle cells shrink (atrophy of disuse) within weeks.
Real-World Example
A patient with long-standing gastroesophageal reflux disease develops Barrett esophagus on endoscopy and biopsy — a textbook case of metaplasia that clinicians monitor closely because it is a recognized precursor to esophageal adenocarcinoma.
Why It Matters
Adaptations are what keep organs functioning under chronic stress rather than failing outright, but several of them (pathologic hyperplasia, and especially metaplasia) sit right at the border of neoplasia and require surveillance — this is exactly why understanding adaptation is inseparable from understanding cancer risk.
Common Misunderstanding
The most common exam trap is confusing hypertrophy and hyperplasia — remember hypertrophy is bigger cells, hyperplasia is more cells, and they can occur together (e.g., the pregnant uterus undergoes both). Another frequent error is calling metaplasia a step toward cancer that is itself malignant — it is not malignant and it is reversible if the stimulus is removed; it simply increases the risk that dysplasia (truly abnormal, potentially preneoplastic growth) will develop if the irritant persists.
Key Terms
| Term | Definition |
|---|---|
| Reversible injury | Cell damage (swelling, fatty change) that resolves fully once the causative stress is removed |
| Irreversible injury | Damage beyond the point of no return, typically marked by mitochondrial failure and plasma membrane rupture, that leads to cell death |
| Necrosis | Unregulated, enzyme-driven cell death in living tissue that spills cell contents and triggers inflammation |
| Apoptosis | Programmed, caspase-mediated cell death that occurs without inflammation |
| Coagulative necrosis | Necrosis pattern preserving tissue architecture (protein denaturation dominant); classic in ischemic solid organs except brain |
| Liquefactive necrosis | Necrosis pattern where enzymatic digestion dominates, turning tissue into liquid; seen in brain infarcts and abscesses |
| Caseous necrosis | Cheese-like, structureless necrosis combining coagulative and liquefactive features; hallmark of tuberculosis |
| Fat necrosis | Enzymatic (lipase-driven) destruction of fat with calcium saponification; classic in acute pancreatitis |
| Fibrinoid necrosis | Bright pink, amorphous necrosis of vessel walls from immune complex/fibrin deposition; seen in vasculitis and malignant hypertension |
| Caspases | Family of proteases that execute apoptosis by dismantling cellular structures in an ordered sequence |
| Intrinsic pathway | Mitochondrial apoptotic pathway triggered by DNA damage/cell stress, regulated by the BCL-2 family and p53 |
| Extrinsic pathway | Death-receptor apoptotic pathway triggered by Fas-FasL or TNF binding, activating caspase-8 |
| Hypertrophy | Increase in the size of individual cells, increasing organ size, without new cell formation |
| Hyperplasia | Increase in the number of cells in a tissue capable of mitotic division |
| Atrophy | Decrease in cell size and/or number due to reduced workload, nutrients, innervation, or hormonal stimulation |
| Metaplasia | Reversible replacement of one differentiated cell type by another, better-adapted type, in response to chronic stress |
| Dysplasia | Disordered, atypical cellular growth that is a precursor lesion to neoplasia, distinct from and beyond simple metaplasia |
Common Mistakes
Misconception 1: "Necrosis and apoptosis are basically the same thing, just different speeds." Why it's wrong: This ignores that they are mechanistically and clinically opposite processes — one is a passive, energy-independent failure and the other is an active, energy-dependent program. Correct explanation: Necrosis is unregulated, does not require ATP, causes cell/organelle swelling and membrane rupture, spills contents, and always triggers inflammation. Apoptosis is tightly regulated, requires ATP to run the caspase cascade, causes cell shrinkage and chromatin condensation, keeps the membrane intact until phagocytosis, and produces no inflammation.
Misconception 2: "All infarcts undergo coagulative necrosis." Why it's wrong: Students overgeneralize the "ischemia = coagulative necrosis" rule learned for heart, kidney, and spleen without accounting for tissue-specific composition. Correct explanation: Brain infarcts undergo liquefactive necrosis because the brain's high lipid content and minimal structural protein/collagen framework mean enzymatic digestion outpaces protein denaturation. The mechanism of injury (ischemia) is the same; the tissue's biochemistry determines the morphologic outcome.
Misconception 3: "Metaplasia is already a form of cancer / is irreversible." Why it's wrong: The word looks alarming and is often mentioned alongside cancer risk, so students conflate it with malignant or premalignant change itself. Correct explanation: Metaplasia is a benign, reversible adaptation — if the chronic irritant (acid reflux, cigarette smoke) is removed, the tissue can revert to its original cell type. It only becomes a concern because persistent metaplasia raises the risk that true dysplasia (and eventually carcinoma) will develop on top of it; metaplasia itself is not malignant.
Comparison and Connections
| Feature | Necrosis | Apoptosis |
|---|---|---|
| Trigger | Ischemia, toxins, severe trauma | DNA damage, growth factor withdrawal, immune signaling |
| Energy (ATP) requirement | Not required (often occurs because ATP is depleted) | Required — active process |
| Cell size | Swells | Shrinks |
| Membrane integrity | Ruptures early | Intact until phagocytosis |
| Nuclear change | Karyolysis, karyorrhexis, pyknosis (random) | Pyknosis with organized fragmentation |
| Inflammation | Present (contents spill, immune cells recruited) | Absent |
| Extent | Usually affects groups of contiguous cells | Usually affects single, scattered cells |
| Physiologic or pathologic | Always pathologic | Both — physiologic (development, homeostasis) and pathologic (disease) |
| Adaptation | Change | Cell division needed? | Reversible? |
|---|---|---|---|
| Hypertrophy | Cell size increases | No | Yes |
| Hyperplasia | Cell number increases | Yes (only in mitotically active tissue) | Yes |
| Atrophy | Cell size/number decreases | No | Yes |
| Metaplasia | Cell type changes | Yes (via stem cell reprogramming) | Yes |
Practice Questions
Recall 1: Name the four classic cellular adaptations. Answer guidance: Hypertrophy, hyperplasia, atrophy, and metaplasia.
Recall 2: Which necrosis pattern is pathognomonic for tuberculosis, and what does it look like grossly? Answer guidance: Caseous necrosis — a friable, white, "cheese-like" structureless area, combining features of coagulative and liquefactive necrosis.
Understanding 1: Explain why brain infarction produces liquefactive necrosis while a myocardial infarction produces coagulative necrosis, even though both are caused by ischemia. Answer guidance: The mechanism (loss of blood supply/hypoxia) is identical, but the outcome depends on tissue composition. The brain is lipid-rich with minimal structural protein scaffolding, so enzymatic digestion by released hydrolases dominates and liquefies the tissue. The heart has a dense structural protein framework, so protein denaturation dominates, preserving the tissue's architecture ("ghost" cell outlines) for several days.
Understanding 2: Why doesn't apoptosis cause inflammation, while necrosis does? Answer guidance: In apoptosis, the plasma membrane stays intact throughout the process — the cell buds off membrane-bound apoptotic bodies that display "eat-me" signals (e.g., externalized phosphatidylserine) and are rapidly phagocytosed by macrophages before any contents leak out. In necrosis, the membrane ruptures early, releasing intracellular contents (enzymes, DAMPs) into the extracellular space, which recruits and activates the inflammatory response.
Application 1: A 55-year-old with acute severe abdominal pain and elevated lipase is found on CT to have chalky white deposits around the pancreas. What process explains this finding, and why is it accompanied by hypocalcemia in severe cases? Answer guidance: This is fat necrosis due to acute pancreatitis — released pancreatic lipases digest peripancreatic and mesenteric fat, and the liberated free fatty acids bind circulating calcium to form insoluble calcium soaps (saponification), which is why severe cases can cause clinically significant hypocalcemia.
Application 2: A long-term smoker's bronchial biopsy shows replacement of normal ciliated columnar epithelium with stratified squamous epithelium. What is this process, and what is the functional cost? Answer guidance: This is squamous metaplasia, an adaptive response of the airway epithelium to chronic irritation from smoke. The trade-off is loss of mucociliary clearance (cilia and mucus-secreting cells are gone), which impairs the airway's ability to clear debris and pathogens — and if the irritant persists, the tissue is at increased risk of progressing to dysplasia and squamous cell carcinoma.
Analysis 1: A patient's tissue biopsy shows a mix of cells undergoing hydropic swelling and others with karyolysis and total loss of architecture, surrounded by neutrophilic infiltrate. Is this reversible or irreversible injury, and how do you know? Answer guidance: This is irreversible injury progressing to necrosis. Hydropic swelling alone would suggest reversible injury, but karyolysis (nuclear dissolution), loss of architecture, and a surrounding neutrophilic/inflammatory infiltrate indicate the membrane has ruptured and contents have spilled — features only seen once the cell has died, past the point of recovery.
Analysis 2: Compare and contrast physiologic hyperplasia in pregnancy with pathologic hyperplasia in benign prostatic hyperplasia (BPH) in terms of mechanism and clinical significance. Answer guidance: Both involve hormone-driven increases in cell number in tissues capable of mitosis. In pregnancy, estrogen and prolactin drive physiologic hyperplasia of breast and uterine glandular tissue to prepare for lactation/childbirth — it is expected, self-limited, and reverses postpartum. In BPH, excess dihydrotestosterone signaling drives pathologic hyperplasia of prostatic stromal and glandular cells, which is not part of a normal physiologic cycle, does not spontaneously reverse, and causes clinical problems (urinary obstruction) purely from unchecked growth — illustrating that the same adaptive mechanism can be appropriate or maladaptive depending on context.
FAQ
Is cell injury always visible under a light microscope? No. Some of the earliest biochemical changes — falling ATP, early calcium influx, initial mitochondrial swelling — occur before light-microscopic changes appear. Electron microscopy can catch subtler ultrastructural changes (like mitochondrial swelling or ribosome detachment) earlier than a standard H&E slide.
Can a cell go from apoptosis to necrosis, or vice versa? Not exactly a "switch," but the two pathways interact — severe ATP depletion can prevent a cell that started down the apoptotic pathway from completing it, causing it to die by necrosis instead (sometimes called "secondary necrosis" when apoptotic bodies aren't cleared in time). This is why ATP availability is considered a key determinant of which death pathway a stressed cell ultimately uses.
Why doesn't the heart regenerate the way the liver does after damage? Cardiac myocytes are terminally differentiated with very limited capacity to re-enter the cell cycle, so the heart can only respond to increased demand through hypertrophy (bigger cells), not hyperplasia. The liver retains a robust population of cells capable of division, so it can regenerate through true hyperplasia, as seen after partial hepatectomy.
Is dysplasia the same as metaplasia? No, and this distinction is tested often. Metaplasia is an orderly, reversible replacement of one normal differentiated cell type with another. Dysplasia is disordered, atypical growth with loss of normal maturation and architecture — it is not a simple adaptation, and it is considered a preneoplastic lesion that can progress to carcinoma in situ and invasive cancer if unchecked.
Why is free radical injury emphasized so much in pathology courses? Because reactive oxygen species (superoxide, hydroxyl radical, hydrogen peroxide) are a final common pathway of injury in many different insults — ischemia-reperfusion, radiation, chemical toxicity, and inflammation all generate free radicals that damage membrane lipids (lipid peroxidation), proteins, and DNA. Understanding this one mechanism explains injury across a huge range of clinical scenarios.
Quick Revision
- Sequence: stimulus → adaptation (if mild) OR injury → reversible injury (if stress removed) → irreversible injury (point of no return) → necrosis or apoptosis.
- The point of no return is defined by mitochondrial failure and loss of plasma membrane integrity, usually via calcium-activated enzymes.
- Cellular swelling (hydropic change) is the earliest light-microscopic sign of reversible injury.
- Necrosis = unregulated, ATP-independent, causes inflammation. Apoptosis = programmed, ATP-dependent, no inflammation.
- Coagulative necrosis: architecture preserved; classic in heart, kidney, spleen (ischemia) — NOT brain.
- Liquefactive necrosis: tissue turns to liquid; classic in brain infarcts and abscesses.
- Caseous necrosis: cheese-like, structureless; hallmark of TB.
- Fat necrosis: lipase-driven, with calcium saponification; classic in acute pancreatitis.
- Fibrinoid necrosis: pink, amorphous, in vessel walls; seen in vasculitis and malignant HTN.
- Apoptosis intrinsic pathway: p53 senses DNA damage → shifts BAX/BAK vs BCL-2 balance → cytochrome c release → caspase-9 → executioner caspases.
- Apoptosis extrinsic pathway: Fas-FasL or TNF binding → caspase-8 → executioner caspases.
- Adaptations: hypertrophy (bigger cells), hyperplasia (more cells, needs mitotic capacity), atrophy (smaller/fewer cells), metaplasia (cell type switch — reversible, not malignant, but raises risk of dysplasia).
Related Topics
Prerequisites: Normal cell structure and organelle function, basic cell membrane physiology, an introduction to ATP/mitochondrial metabolism
Related Topics: Inflammation (acute and chronic), free radical injury and oxidative stress, ischemia-reperfusion injury, intracellular accumulations (fatty change, hyaline change)
Next Topics: Neoplasia and carcinogenesis, wound healing and tissue repair, genetic disorders and their cellular basis