1.1 about 16 minDeep Learning viewL1 p.3–8

How cells respond to stress

A cell under stress either adapts, is injured and recovers, or dies. This section sets out that spectrum, the causes that push cells along it, and the organelles that decide which way they go.

Four lenses on one disease

L1 p.1, 4–5Ref. · Robbins ch. 1

Pathology describes every disease through four questions. Etiology asks what caused it. Pathogenesis asks how the cause produces the damage, step by step. Morphology asks what the damage looks like to the naked eye and under the microscope. Clinical consequences ask what the patient experiences and what tests show. One example carries all four through this chapter.

Myocardial infarction through the four lenses

  • Etiology

    Question it answers
    What caused it?
    Myocardial infarction
    A thrombus on a ruptured atherosclerotic plaque blocks a coronary artery.

  • Pathogenesis

    Question it answers
    How does the cause do damage?
    Myocardial infarction
    Ischemia → ATP depletion → pump failure and swelling → calcium overload → membrane and mitochondrial failure → myocyte death (1.3–1.4).

  • Morphology

    Question it answers
    What does it look like?
    Myocardial infarction
    Coagulative necrosis: ghost outlines of myocytes without nuclei, then neutrophils, macrophages and finally a scar (1.6).

  • Clinical consequences

    Question it answers
    What does it do to the patient?
    Myocardial infarction
    Chest pain, troponin in the blood from ruptured myocytes, arrhythmias, heart failure.

From normal to death

L1 p.4–7

Concept map

  1. Normal cell

    Homeostasis: steady state within a narrow range

  2. Adaptation

    Stress or demand: hypertrophy, hyperplasia, atrophy, metaplasia

  3. Reversible injury

    Cannot adapt: swelling, blebs, ribosome loss; recovers if the stress ends

  4. Irreversible injury

    Mitochondria cannot restore ATP; membranes badly damaged

  5. Cell death

    Necrosis (always pathologic) or apoptosis (can be physiologic)

Dashed line: the point of irreversibility. Restoring the cell's conditions before it allows recovery; after it, death follows.

A cell moves along this spectrum depending on the strength and duration of the stress and on its own capacity to cope.L1 p.5, 7

A normal cell keeps its internal state within a narrow range (homeostasis). Moderate, sustained stress or increased demand leads to adaptation: a new steady state with bigger, more, smaller or different cells (1.2). When the stress exceeds the cell's ability to adapt, or the cell is damaged directly, cell injury follows.

Injury is reversible while mitochondria can still restore ATP and membranes remain intact. Remove the stress and the cell repairs itself. If the stress is severe or persists, the cell crosses a point of irreversibility and dies, either by necrosis, which is always pathologic, or by apoptosis, which can also be a normal, programmed event.

What makes recovery possible, and what changes when it is lost

Recovery still possible

  • Mitochondria can resume oxidative phosphorylation
  • Plasma and lysosomal membranes intact
  • Destructive enzymes not yet activated
  • Changes are mostly water and ion shifts

Past the point of no return

  • Mitochondria cannot restore ATP even if oxygen returns
  • Plasma and lysosomal membranes severely damaged
  • Calcium-activated enzymes digest the cell
  • Nucleus condenses, fragments or fades
L1 p.4, 18

Causes of cell injury

L1 p.8–9

The lecture groups the causes of cell injury into ten families. Many different causes funnel into a few shared mechanisms: loss of ATP, membrane damage, calcium overload, free radicals and DNA or protein damage.

Ten causes, one example eachL1 p.8

  • Hypoxia and anoxia

    Example
    Ischemia, cardiac arrest, CO poisoning
    Main way it injures
    Too little oxygen for ATP production (1.3)

  • Physical agents

    Example
    Trauma, burns, ionizing radiation
    Main way it injures
    Direct mechanical or thermal damage; radiation splits water into free radicals

  • Chemicals and drugs

    Example
    Acetaminophen overdose, carbon tetrachloride
    Main way it injures
    Reactive metabolites made by liver P450 enzymes (1.5)

  • Microbes

    Example
    Viruses, bacteria, fungi, parasites
    Main way it injures
    Direct lysis, toxins, and the immune response they provoke

  • Immune reactions and inflammation

    Example
    Autoimmune disease, hypersensitivity
    Main way it injures
    Antibodies, complement and immune cells injure host cells

  • Genetic and metabolic disorders

    Example
    Storage diseases, misfolded proteins
    Main way it injures
    Missing enzymes or abnormal proteins that accumulate or trigger apoptosis

  • Nutritional deficiencies

    Example
    Vitamin deficiencies; protein–calorie malnutrition
    Main way it injures
    Missing substrates for normal structure and repair

  • Intracellular accumulations

    Example
    Lipids, proteins, pigments
    Main way it injures
    Substances that crowd or poison the cell (1.8)

  • Aging

    Example
    Cumulative cellular damage
    Main way it injures
    Accumulated free-radical and DNA damage with reduced repair

  • Free radicals

    Example
    Reperfusion, radiation, inflammation
    Main way it injures
    A common final pathway for many of the causes above (1.5)

Organelles in the story

L1 p.2, 17–22

Each organelle plays a part in the chapter. Select one to see its normal job, what happens to it in injury, and where it returns.

Interactive map

Mitochondria

Normal job

Make most ATP by oxidative phosphorylation; hold cytochrome c.

Role in injury

First to fail in hypoxia; leak electrons as superoxide; calcium opens their permeability pore; cytochrome c release starts intrinsic apoptosis.

Returns in sections 1.3, 1.4, 1.5, 1.7

Organelles and their roles across the chapter.L1 p.2

The organelle inherited from your mother

L1 p.3

The lecture opens with a question: which organelle do we inherit only from our mother? The answer is the mitochondrion. The egg contributes hundreds of thousands of mitochondria; the few in the sperm's midpiece are marked and destroyed after fertilization. Mitochondria carry their own small circular DNA (mtDNA), which encodes thirteen proteins of the electron transport chain along with mitochondrial RNAs.

A mother with an mtDNA mutation can pass it to all of her children; an affected father passes it to none. Because each cell holds many mitochondria, mutant and normal mtDNA can coexist (heteroplasmy), and the proportion varies between tissues and between siblings, which is why severity varies so much.

Knowledge check · 1.1

Answer, read why, and try again whenever you like. Answers are kept in both study modes.

0 of 4 correct
  1. Q1Etiology, pathogenesis, morphology, consequencesL1 p.33

    A report describes “a pale, wedge-shaped area of coagulative necrosis in the renal cortex.” Which of the four lenses does this sentence describe?

  2. Q2Reversible versus irreversibleL1 p.4, 17–18

    Which feature most clearly means that a cell injured by brief ischemia can still recover?

  3. Q3Maternal mitochondrial inheritanceL1 p.3

    A woman has a disorder caused by a mutation in mitochondrial DNA. Her husband is unaffected. What is true of their children?

  4. Q4Organelles in injuryL1 p.20

    Which organelle's enzymes convert acetaminophen and carbon tetrachloride into reactive, injurious products?

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