I.

Introduction
• Pathology 병리학 is the study of the structural and functional causes of human
disease.

• Patho = suffering
Disease (pathophysiology) <-> Homeostasis (physiology)

• The four aspects of a disease process that form the core of pathology are:
Chapter 2. Cellular Responses to Stress and
Toxic Insults: Adaptation, Injury, and Death - Etiology 병인론: the cause of a disease

- Pathogenesis 발병기전: the mechanism(s) of disease development

- Morphologic change 형태학적 변화: the structural alterations induced in cells

and tissues by the disease

- Clinical significance 임상소견: The functional consequences of the

morphologic changes

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II. Overview: cellular responses to stress and noxious stimuli

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 III. Adaptations of Cellular Growth and Differentiation
• Adaptation 적응 occurs when physiologic or pathologic stressors induce a new
state that changes the cell but otherwise preserves its viability in the face of
the exogenous stimuli.

• These changes include:

1. Hypertrophy 비대 (increased cell mass)

2. Hyperplasia 증식 (increased cell number)

3. Atrophy 위축 (decreased cell mass)

4. Metaplasia 화생 (change from one mature cell

type to another)

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III. Adaptations of Cellular Growth and Differentiation III. Adaptations of Cellular Growth and Differentiation

III-1. Hypertrophy 비대 III-2. Hyperplasia 과다증식

• Hypertrophy refers to an increase in the size of cells, that results • Hyperplasia is defined as an increase in the number of cells in an
in an increase in the size of the affected organ. organ or tissue in response to a stimulus.
- Physiologic hyperplasia: due to the action of hormones or growth factors occurs.
- Pathologic hyperplasia: caused by excessive or inappropriate actions of hormones or
growth factors.

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 III. Adaptations of Cellular Growth and Differentiation III. Adaptations of Cellular Growth and Differentiation

III-3. Atrophy 위축 III-4. Metaplasia 화생

• Atrophy is defined as a reduction in the size of an organ or tissue due to • Metaplasia is a reversible change in which one differentiated cell type
a decrease in cell size and number. (epithelial or mesenchymal) is replaced by another cell type.

9 10

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 IV. Overview of Cell Injury and Cell Death
• Cell Injury 세포손상
- Reversible injury: pathologic cell changes that can be restored normally if the stimulus “point of no return”

is removed or the cause is mild.

- Irreversible injury: occurs when stressors exceed the capacity of the cell to adapt
(beyond a point of no return) and permanent pathologic changes that cause cell death.

‣ Cell death 세포사 occurs primarily through two morphologic and mechanistic patterns
: necrosis 괴사 and apoptosis 세포자멸사.

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세포손상에 따른 형태적 변화
V. Causes of Cell Injury 세포손상 원인 VI. Morphologic Alterations in Cell Injury
• Oxygen deprivation 산소결핍: Hypoxia 저산소증 affects aerobic respiration and therefore - All stresses and noxious influences exert their effects first at the molecular or
ability to generate adenosine triphosphate (ATP). This extremely important and common biochemical level.
cause of cell injury and death occurs as a result of: - There is a time lag between the stress and the morphologic changes of cell injury or
- Ischemia 허혈 (loss of blood supply) death.
- Inadequate oxygenation (e.g., cardiorespiratory failure)
“point of no return”
- Loss of oxygen-carrying capacity of the blood (e.g., anemia, carbon monoxide poisoning)

• Physical agents 물리적 요인: trauma, heat, cold, radiation, and electric shock (Ch. 9)

• Chemical agents and drugs 화학적 요인과 약물: therapeutic drugs, poisons…

• Infectious agents 감염원: viruses, bacteria, fungi, and parasites (Ch. 8)

• Immunologic reactions 면역반응: including autoimmune diseases (Ch. 6) and cell

injury following responses to infection (Ch. 2)

• Genetic derangements 유전적 장애: chromosomal alterations and specific gene

mutations (Ch. 5)

• Nutritional imbalances 영양불균형: including protein–calorie deficiency or lack of

specific vitamins, as well as nutritional excesses (Ch. 9)

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 VI. Morphologic Alterations in Cell Injury VI. Morphologic Alterations in Cell Injury

1. Reversible Injury 가역적 손상 - The ultrastructural changes of reversible cell injury

- Two changes of reversible cell injury recognized under the light microscope.
1. Plasma membrane alterations 원형질막의 변화

‣ Cellular swelling 세포종창 appears whenever cells cannot maintain ionic and : such as blebbing, blunting, and loss of microvilli
fluid homeostasis. 2. Mitochondrial changes 미토콘드리아의 변화

‣ Fatty change 지방변화 is manifested by cytoplasmic lipid vacuoles 지방공포, : including swelling and the appearance of small amorphous densities
principally encountered in cells involved in or dependent on fat metabolism 3. Dilation of the ER 소포체의 팽창
(e.g., hepatocytes and myocardial cells). : with detachment of polysomes; intracytoplasmic myelin figures 미엘린상 may be present
4. Nuclear alterations 핵의 변화
: with disaggregation of granular and fibrillar elements

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VI. Morphologic Alterations in Cell Injury VI. Morphologic Alterations in Cell Injury

2. Necrosis 괴사: Cell death resulted from irreversible Injury 비가역적 손상

- The morphologic appearance of necrosis is the result of denaturation of

intracellular proteins 세포내 단백질 변성 and enzymatic digestion of the lethally
injured cell.

- Distinctive features of necrotic cells

‣ Necrotic cells are more eosinophilic (pink) 호산성의 증가 than viable cells by
standard hematoxylin and eosin (H&E) staining

‣ Large, whorled phospholipid masses called myelin figures 미엘린상 that

are derived from damaged cell membranes → phagocytosed by other
cells or further degraded into fatty acids → Calcification

‣ Nuclear changes

• pyknosis 핵농축 (small, dense nucleus)

• karyolysis 핵융해 (faint, dissolved nucleus)

• karyorrhexis 핵붕괴 (fragmented nucleus)

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 VI. Morphologic Alterations in Cell Injury VI. Morphologic Alterations in Cell Injury

Nuclear changes of necrotic cells

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VI. Morphologic Alterations in Cell Injury VI. Morphologic Alterations in Cell Injury

2-A. Coagulative necrosis 응고괴사 Patterns of Tissue Necrosis 조직괴사의 유형 2-B. Liquefactive necrosis 액화괴사 Patterns of Tissue Necrosis 조직괴사의 유형

• A form of necrosis in which the architecture of dead tissues is preserved for - Characterized by digestion of the dead cells, resulting in transformation of the tissue into
a liquid viscous mass 액상의 점액덩어리.
some days
- Seen in focal bacterial or, occasionally, fungal infections, because microbes stimulate the
- Presumably, the injury denatures not only structural proteins but also enzymes accumulation of leukocytes and the liberation of enzymes from these cells.
→ blocks the proteolysis of the dead cells
- The necrotic material is frequently
- As a result, eosinophilic, anucleate cells may persist for days or weeks. creamy yellow because of the
presence of dead leukocytes and is
• A localized area of coagulative necrosis is called an infarct 경색. called pus 고름.
- For unknown reasons, hypoxic death of
cells within the central nervous system
(brain) often manifests as liquefactive
necrosis.

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 VI. Morphologic Alterations in Cell Injury VI. Morphologic Alterations in Cell Injury

3. Gangrenous necrosis 괴저괴사 Patterns of Tissue Necrosis 조직괴사의 유형 4. Caseous necrosis 건락괴사 Patterns of Tissue Necrosis 조직괴사의 유형

- Not a specific pattern of cell death, but the term is commonly used in clinical practice. - Encountered most often in foci of tuberculous 결핵 infection

- The term “caseous” (cheese-like) is derived from the friable white appearance of the
- Usually in the lower leg, that has lost its blood supply and has undergone necrosis
area of necrosis
(typically coagulative necrosis) involving multiple tissue planes.

- When bacterial infection is superimposed, there is more liquefactive necrosis

→ Wet gangrene 습성괴저

Gangrene of the 1st to 4th toes of the right foot in

person with diabetes.

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VI. Morphologic Alterations in Cell Injury VI. Morphologic Alterations in Cell Injury

5. Fat necrosis 지방괴사 Patterns of Tissue Necrosis 조직괴사의 유형 6. Fibrinoid necrosis 섬유소성괴사 Patterns of Tissue Necrosis 조직괴사의 유형

- Fat destruction, typically resulting from release of activated pancreatic - A special form of necrosis usually seen in immune reactions in blood vessels
lipases into the pancreas and the peritoneal cavity. - Fibrinoid necrosis typically occurs when complexes of antigens and antibodies are
deposited in the walls of arteries.
- The released lipases split the triglyceride esters in fat cells → The fatty acids
combine with calcium to produce grossly visible chalky-white areas (fat - Deposits of these “immune complexes,” together with fibrin that has leaked out of
vessels, result in a bright pink and amorphous appearance in H&E stains, called
saponification 지방비누화)
“fibrinoid” (fibrin-like)

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 VII. Mechanisms of Cell Injury 세포손상 기전

• Several principles to cell injury

- The cellular response to injurious stimuli depends on the nature of the injury, its
duration, and its severity.

- The consequences of cell injury depend on the type, state, and adaptability of the
injured cell.

- Cell injury results from different biochemical mechanisms acting on several essential
cellular components.

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VII. Mechanisms of Cell Injury VII. Mechanisms of Cell Injury

1. Depletion of ATP (ATP 고갈)

• Reduction in ATP levels is fundamental cause of necrotic cell death.

• The major causes of ATP depletion are reduced supply of oxygen and nutrients,
mitochondrial damage, and the actions of some toxins (e.g., cyanide)

• Depletion of ATP to 5% to 10% of normal levels has widespread effects on many critical
cellular systems:

- The activity of the plasma membrane energy-dependent sodium pump (ouabain-

sensitive Na+/K+-ATPase) is reduced.

- Cellular energy metabolism is altered.

- Failure of the Ca2+ pump leads to influx of Ca2+, with damaging effects on numerous
cellular components.

- Reduction in protein synthesis.

- In cells deprived of oxygen or glucose, proteins may become misfolded, and

accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers“the
unfolded protein response” that may culminate in cell injury and even death

- Ultimately, if there is irreversible damage to mitochondrial and lysosomal membranes,

and the cell undergoes necrosis.

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 VII. Mechanisms of Cell Injury VII. Mechanisms of Cell Injury

2. Mitochondrial damage (미토콘드리아 손상)

• Mitochondria are critical players in cell injury and cell death

• Three major consequences of mitochondrial damage.

- Mitochondrial damage results in the formation of a high-conductance

channel in the mitochondrial membrane, called the mitochondrial
permeability transition pore 미토콘드리아 투과성 전이공 (MPTP).

- Abnormal oxidative phosphorylation also leads to the formation of

reactive oxygen species 활성산소종 (ROS).

- The mitochondria isolate several proteins that are capable of activating

apoptotic pathways between their outer and inner membranes
→ these proteins include cytochrome c and caspases (apoptosis-
inducing enzymes) → increased permeability of the outer mitochondrial
membrane may result in leakage of these proteins into the cytosol and
death by apoptosis.

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VII. Mechanisms of Cell Injury VII. Mechanisms of Cell Injury

3. Influx of Calcium and Loss of Calcium Homeostasis (칼슘 유입과 칼슘 항상성의 소실)

• Cytosolic free calcium is normally maintained at very low concentrations

(~0.1 μmol) compared with extracellular levels of 1.3 mmol, and most
intracellular calcium is sequestered in mitochondria and the ER.

• Increased intracellular calcium causes cell injury by several mechanisms.

- The accumulation of calcium in mitochondria results in opening of the

mitochondrial permeability transition pore (MPTP)→ as described earlier,
failure of ATP generation.

- Increased cytosolic calcium activates a number of enzymes with

potentially deleterious effects on cells
: phospholipases, proteases, endonucleases, ATPases

- Increased intracellular calcium levels also result in the induction of

apoptosis, by direct activation of caspases and by increasing
mitochondrial permeability.

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 VII. Mechanisms of Cell Injury
산소유래 자유라디칼의 축적(산화성 스트레스)
4. Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress)

• Reactive oxygen species 활성산소종 (ROS) are a type of oxygen-derived free

radical whose role in cell injury is well established.

• Generation of free radicals

- The reduction-oxidation reactions that occur during normal metabolic

processes.

- Absorption of radiant energy (e.g., ultraviolet light, x-rays).

- ROS are produced in activated leukocytes during inflammation.

- Enzymatic metabolism of exogenous chemicals or drugs can generate

free radicals that are not ROS but have similar effects
(e.g., CCl4 can generate •CCl3)

- Transition metals (e.g. iron and copper) can catalyze free radical formation

- Nitric oxide (NO) can act directly as a free radical or be converted to other
highly reactive forms

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VII. Mechanisms of Cell Injury VII. Mechanisms of Cell Injury

4. Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) 5. Defects in Membrane Permeability 막 투과성 손상

• Removal of Free Radicals • Early loss of selective membrane permeability, leading ultimately to membrane damage, is
a consistent feature of most forms of cell injury (except apoptosis).
- Free radicals are inherently unstable and generally decay spontaneously.
‣ O2•- , for example, is unstable and decays (dismutates) spontaneously to O2 and • Mechanisms of Membrane Damage
H2O2 in the presence of water.
: Several biochemical mechanisms may
- Antioxidant contribute to membrane damage

- Superoxide dismutase (SOD) - Reactive oxygen species: by lipid

peroxidation
- Glutathione peroxidase, catalase…
- Decreased phospholipid synthesis
• Pathologic Effects of Free Radicals ‣ The production of phospholipids may be
reduced by defective mitochondrial
- Lipid peroxidation in membranes 막지질의 과산화
function or hypoxia, both of which
‣ Membrane lipids are attacked particularly by •OH → damage to membrane decrease the production of ATP and thus
affect energy-dependent biosynthetic
- Oxidative modification of proteins 단백질의 산화적 변화 pathways.

- Lesions in DNA DNA 손상 - Increased phospholipid breakdown

‣ Free radicals are capable of causing single- and double-strand breaks in DNA,
- Cytoskeletal abnormalities
cross-linking of DNA strands, and formation of adducts.

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 VII. Mechanisms of Cell Injury VII. Mechanisms of Cell Injury

5. Defects in Membrane Permeability 막 투과성 손상 6. Damage to DNA and Protein (DNA와 단백질 손상)

• Consequences of Membrane Damage • Cells have mechanisms that repair damage to DNA

- Mitochondrial membrane damage - but if DNA damage is too severe (e.g., after exposure to DNA damaging drugs,
radiation, or oxidative stress), the cell initiates a suicide program, apoptosis.
- Plasma membrane damage
• Reversible vs Irreversible Injury
‣ loss of osmotic balance and influx of fluids and ions
Q: When reversible injury becomes irreversible and progresses to cell death?
‣ loss of cellular contents A: The “point of no return,” at which the damage becomes irreversible, is still largely
undefined, and there are no reliable morphologic or biochemical correlates of
- Injury to lysosomal membranes results in leakage of their enzymes
irreversibility
(RNases, DNases, proteases…) into the cytoplasm
• Two phenomena consistently characterize irreversibility
- The inability to reverse mitochondrial dysfunction

- Profound disturbances in membrane function.

• Leakage of intracellular proteins through the damaged cell membrane and

ultimately into the circulation provides a means of detecting tissue-specific
cellular injury necrosis using blood serum samples → Biomarkers

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VIII. Clinicopathologic Correlations: Selected Examples of Cell Injury and Necrosis

임상병리학적 관계: 세포손상과 괴사의 예

• Ischemic and Hypoxic Injury 허혈과 저산소성 손상

- Ischemia 허혈 is the most common type of cell injury in clinical medicine

- Ischemia results from hypoxia 저산소증 induced by reduced blood flow, most commonly
due to a mechanical arterial obstruction.

• Ischemia-Reperfusion Injury 허혈-재관류 손상

- Restoration of blood flow to ischemic tissues can promote recovery of cells if they are
reversibly injured, but can also paradoxically exacerbate the injury and cause cell death.

• Chemical (Toxic) Injury 화학적(독소에 의한) 손상

- Chemical injury remains a frequent problem in clinical medicine and is a major limitation
to drug therapy.

‣ Direct toxicity
e.g. cyanide 청산가리 poisons mitochondrial cytochrome oxidase and thus inhibits
oxidative phosphorylation.

‣ Conversion to toxic metabolites

e.g. CCl4: converted by cytochrome P-450 to •CCl3
Acetaminophen: converted to a toxic product during detoxification in the liver

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 IX. Apoptosis 세포자멸사
IX. Apoptosis 세포자멸사 1. Causes of Apoptosis 세포자멸사의 원인

• Apoptosis is a pathway of cell death that is induced by a tightly regulated • Apoptosis in Physiologic Situations
suicide program in which cells activate intrinsic enzymes that degrade the - Programmed destruction of cells during embryogenesis

cells’ own nuclear DNA and nuclear and cytoplasmic proteins. - Involution 퇴화 of hormone-dependent tissues upon hormone withdrawal
‣ e.g. endometrial cell breakdown during the menstrual cycle, ovarian follicular atresia in menopause, the regression
- Apoptotic cells break up into fragments, called of the lactating breast after weaning, and prostatic atrophy after castration.

apoptotic bodies 세포자멸소체 - Cell loss in proliferating cell populations (to maintain a constant number)

- The dead cell and its fragments are rapidly devoured,

- Elimination of potentially harmful self-reactive lymphocytes

before the contents have leaked out. - Death of host cells that have served their useful purpose
‣ e.g. neutrophils in an acute inflammatory response, and lymphocytes at the end of an immune response.

- Therefore, cell death by this pathway does not elicit • Apoptosis in Pathologic Conditions
- DNA damage: radiation, cytotoxic anticancer drugs, and hypoxia
an inflammatory reaction in the host.
- Accumulation of misfolded proteins

- Because it is genetically regulated, apoptosis is sometimes ‣ Excessive accumulation of these proteins in the ER leads to a condition called “ER stress”, which leads to
apoptotic cell death.
referred to as programmed cell death.
- Cell death in certain infections
‣ Particularly viral infections, in which loss of infected cells is largely due to apoptosis

- Pathologic atrophy in parenchymal organs after duct obstruction

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IX. Apoptosis 세포자멸사 IX. Apoptosis 세포자멸사

2. Morphologic and Biochemical Changes in Apoptosis 세포자멸사에서 일어나는 형태학적, 생화화적 변화

• Cell shrinkage 세포수축

- The cell is smaller in size, the cytoplasm is dense, and the organelles, although
relatively normal, are more tightly packed.

• Chromatin condensation 염색질 응축

- The most characteristic feature of apoptosis.

- The chromatin aggregates peripherally, under the nuclear membrane, into dense
masses of various shapes and sizes

• Formation of cytoplasmic blebs and apoptotic bodies 세포질 수포와 세포자멸소체 형성

- The apoptotic cell first shows extensive surface blebbing, then undergoes
fragmentation into membrane-bound apoptotic bodies

• Phagocytosis of apoptotic cells or cell bodies, usually by macrophages

대식세포에 의한 세포자멸사세포 혹은 세포자멸소체의 포식작용

- The apoptotic bodies are rapidly ingested by phagocytes and degraded by the
phagocyte’s lysosomal enzymes.

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 IX. Apoptosis 세포자멸사

3. Mechanisms of Apoptosis 세포자멸사의 기전

• Apoptosis results from the activation of enzymes called caspases 카스파제

(so named because they are cysteine proteases that cleave proteins after
aspartic residues)

• Two distinct pathways converge on caspase activation

- The mitochondrial (intrinsic) pathway

- The death receptor (extrinsic) pathway

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IX. Apoptosis 세포자멸사 IX. Apoptosis 세포자멸사

3-1. The Intrinsic (Mitochondrial) Pathway of Apoptosis 3-2. The Extrinsic (Death Receptor-initiated) Pathway of Apoptosis

• Mitochondrial permeability is regulated by

• This pathway is initiated by engagement of
more than 20 proteins of the Bcl family. plasma membrane death receptors.
- Anti-apoptotic: BCL2, BCL-XL, and MCL1
• When FasL binds to Fas, three or more
- Pro-apoptotic
molecules of Fas are brought together, and
‣ BAX and BAK
their cytoplasmic death domains form a
‣ They form a channel in the outer mitochondrial
binding site for an adaptor protein FADD
membrane, allowing leakage of cytochrome c
from the intermembranous space.
(Fas-associated death domain).

• Released cytochrome c binds to apoptosis • FADD that is attached to the death receptors
activating factor-1 (Apaf-1) to form a large in turn binds an inactive form of caspase-8
multimeric apoptosome complex that triggers (and, in humans, caspase-10), again via a
caspase-9 activation. death domain.

• The essence of the intrinsic pathway is a • Multiple pro-caspase-8 molecules are thus
balance between proapoptotic and brought into proximity, and they cleave one
antiapoptotic molecules that regulate another to generate active caspase-8.
mitochondrial permeability.

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 IX. Apoptosis 세포자멸사

3-3. The Execution Phase of Apoptosis 세포자멸사 실행기

• The two initiating pathways converge to a cascade of caspase activation,

which mediates the final phase of apoptosis.

- The mitochondrial pathway leads to activation of the initiator caspase-9, and the death
receptor pathway to the initiator caspases-8 and -10.

• After an initiator caspase is cleaved to generate its active form, the enzymatic
death program is set in motion by rapid and sequential activation of the
executioner caspases.

• Executioner caspases, such as caspase-3 and -6, act on many cellular

components.

- For instance, these caspases, once activated, cleave an inhibitor of a cytoplasmic

DNase and thus make the DNase enzymatically active; this enzyme induces cleavage of
DNA.

• Caspases also degrade structural components of the nuclear matrix and thus
promote fragmentation of nuclei.

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IX. Apoptosis 세포자멸사

3-4. Necroptosis 세포자멸괴사 X. Autophagy 자가포식

• Autophagy is a process in which a cell eats its own contents
• This form of cell death is a hybrid that shares aspects of (Greek: auto, self; phagy, eating).
both necrosis and apoptosis.
• It is a survival mechanisms whereby, in states of nutrient deprivation, the starved cell lives
by cannibalizing itself and recycling the digested contents.
• Morphologically, and to some extent biochemically, it
resembles necrosis • Several steps

- Loss of ATP, swelling of the cell and organelles, generation of - Formation of an isolation membrane 격리막, also called phagophore 자가소화포, and its
ROS, release of lysosomal enzymes and ultimately rupture of the nucleation 핵형성; the isolation membrane is believed to be derived from the ER
plasma membrane. - Elongation of the vesicle

• Mechanistically, it is triggered by genetically programmed - Maturation of the autophagosome, its fusion with lysosomes, and eventual degradation
of the contents
signal transduction events that results in cell death.
microtubule-associated
→ In this respect it resembles apoptosis. protein light chain 3 (LC3)

• Necroptosis is sometimes called programmed necrosis to

distinguish it from the more usual forms of necrosis.

• In sharp contrast to apoptosis, necroptosis does not result

in caspase activation and hence it is also sometimes
referred to as “caspase-independent” programmed cell
death.

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 XI. Intracellular Accumulations 세포내 축적
XI. Intracellular Accumulations 세포내 축적
• Lipids
• There are four main pathways of abnormal
intracellular accumulations - Steatosis 지방증 (fatty change)

1. Inadequate removal of a normal substance secondary to - Cholesterol deposition

defects in mechanisms of packaging and transport
• Proteins
e.g. fatty change (steatosis) in the liver (Chapter 18)

2. Accumulation of an abnormal endogenous substance

• Hyaline Change 유리질 변화
as a result of genetic or acquired defects in its folding, - Any deposit that imparts a
packaging, transport, or secretion homogeneous, glassy pink
e.g. certain mutated forms of α1-antitrypsin (Chapter 15) appearance in H&E staining

3. Failure to degrade a metabolite due to inherited enzyme • Glycogen

deficiencies.
e.g. storage diseases (Chapter 5).
• Pigments

4. Deposition and accumulation of an abnormal - Exogenous: carbon, coal

exogenous substance when the cell has neither the - Endogenous: lipofuscin, melanin,
enzymatic machinery to degrade the substance nor the ability hemosiderin
to transport it to other sites.
e.g. accumulation of carbon or silica particles (Chapter 15).

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Melanin Carbon

Lipid Cholesterol

Iron

α1-antitrypsin Lipofuscin

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 XII. Pathologic Calcification 병적 석회화
• Pathologic calcification is the abnormal tissue deposition of
calcium salts, together with smaller amounts of iron, magnesium,
and other mineral salts.

- Dystrophic calcification 비정상조직석회화: encountered in areas of necrosis

‣ May occur at any serum calcium level

‣ Usually occurs in previously injured tissue

- Metastatic calcification 전이성석회화: may occur in normal tissues

whenever there is hypercalcemia

‣ Occurs at high serum calcium levels

‣ Often related to bone metastases, but can occur in any organ, even in normal
tissue, during periods of hypercalcemia (from whatever cause)

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XIII. Cellular Aging 세포노화

• Cellular aging is the result of a progressive decline in
cellular function and viability caused by genetic abnormalities
and the accumulation of cellular and molecular damage due to the effects of
exposure to exogenous influences.

- Telomere attrition 텔로미어 마모: One mechanism of replicative senescence involves

progressive shortening of telomeres, which ultimately results in cell cycle arrest.

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 Life According to Sam
http://www.youtube.com/watch?v=Z5hm44x7ICA&list=PLio7GaXoQ3Sj-Md9k6VWQp7RsxsdZjjm6&index=2

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