Cell Death Adaptation Lecture 2 Opt

7/21/2019 Cell Death Adaptation Lecture 2 Opt

http://slidepdf.com/reader/full/cell-death-adaptation-lecture-2-opt 1/8

9/21/20

Cell Death & Adaptations

Types of Cell Death

• Necrosis – Pathologic cell death

• Apoptosis

– Programmed cell death (physiologic or

some times pathologic)

Types of Necrosis

• Coagulative Necrosis (protein denaturation)

• Liquefactive Necrosis (enzymatic catabolism)

• Caseous Necrosis

• Fat Necrosis

• Gangrenous Necrosis

• Fibrinoid Necrosis

Coagulative Necrosis

• Cell’s basic outline is preserved

(presumably due to denaturation of both

structural & enzymatic proteins)

• Appearance-- Glassy homogeneous (loss ofglycogen granules),eosinophilic (loss of

cytoplasmic RNA) & opaque

• Nuclear changes- pyknosis, karyorrhexis,

karyolysis or

• Usually seen in hypoxic injury of solid organ

like spleen, heart & kidney

Renal infarct -- gross Splenic infarcts -- gross



9/21/20

Myocardium photomicLiquefactive Necrosis

• Usually due to enzymatic dissolution of

necrotic cells (usually due to release ofproteolytic enzymes from neutrophils in

bacterial or fungal infections)

• Necrotic area undergoes softening and

are filled with pigmented or turbid fluid

• Complete loss of structure

• Most often seen in CNS and in

abscesses

Liquefactive necrosis -- grossLiquefactive necrosis of brain

-- micro

Liquefactivenecrosis of brain

Liver abscess -- micro

Liver abscess

Caseous Necrosis

• Gross: Creamy-cheese appearance,slightly greasy to touch

• Micro: Amorphous, granular eosinophilcmaterial surrounded by a rim ofinflammatory cells – No visible cell outlines – tissue architecture

is obliterated

• Commonly seen in tuberculosis



9/21/20

Caseous necrosis -- grossExtensive caseous necrosis

-- gross

Caseous necrosis -- microEnzymatic Fat Necrosis

• Results from hydrolytic action of lipaseson fat

• Most often seen in and around thepancreas due to escape of pancreaticenzymes hydrolyzing triglyceride esters

• Fatty acids released via hydrolysis reactwith calcium to form chalky white areas“saponification”

• Can also be seen in other fatty areas ofthe body, usually due to trauma

• Shadowy cell outlines(without nucleus & with insoluble soap deposits)

Enzymatic fat necrosis of

pancreas -- grossFat necrosis -- micro



9/21/20

Gangrenous Necrosis

• A complication of necrosis most often seen

on extremities, usually due to trauma or

physical injury e.g. diabetic foot• Necrotic tissue invaded by putrefactive

organisms & looks green or black

• “Dry” gangrene – no bacterial superinfection;

tissue appears dry---Coagulative necrosis

• “Wet” gangrene – bacterial superinfection;tissue swells & looks wet---Coagulative

necrosis progressing to liquefactive one

Gangrene -- gross

Wet gangrene -- gross Gangrenous necrosis -- micro

Fibrinoid Necrosis

• Usually seen in the walls of blood vessels

(e.g., in vasculitis)

• Glassy, eosinophilic fibrin-like material isdeposited within the vascular walls

Apoptosis

• Involved in many processes, somephysiologic, some pathologic – Cell death during embryogenesis (organ

development & modeling)

– Hormone-dependent involution or atrophy oforgans in the adult e.g. uterus, breast, prostate

– Deletion of autoreactive T cells in thymus

– Cell deletion in proliferating cell populations(intestinal crypt epithelium)

– Cell death in tumors

– Mild injurious stimuli causing irreparable DNAdamage-p53



9/21/20

Apoptosis – Morphologic Features

• Cell shrinkage with increased

cytoplasmic density

• Chromatin condensation

• Formation of cytoplasmic blebs and

apoptotic bodies

• Phagocytosis of apoptotic cells by

adjacent healthy cells

Mechanism of Apoptosis

• Four separable but overlappingcomponents

-signaling

-control & integration

-execution

-removal of dead cells

Events in apoptosis

1Intrinsic

embryogenic

signals

Phagocytosis by

Macrophages or

adjacent epithelial cells

Cyt. c

Apaf-1

Transglutaminases

activationCross-linking

Comparison b/w Necrosis & Apoptosis• Necrosis

– Not a programmed cell death

– Always pathologic – result of irreversible injury (detrimental or fatal)

– Large number of cells die at a time (homicide) i.e. death of tissue or organ

– Cells or tissue remain part of the body (often need surgical removal)

– Mechanisms involved → ATP depletion, free radical damage, membrane

injury etc.

– DNA break down-Random

– Inflammation

• Apoptosis – Programmed cell death

– Mostly physiologic & beneficial (seldom pathologic)

– Involved death of single cells or cluster of cells (suicide)

– Dead Cells remain no more part of the body

– Mechanism involved →gene activation, endonucleases, proteases

– l DNA break down-Internucleosomal

– No inflammation

Apoptosis Diagram Cellular Adaptations

Hypertrophy

Hyperplasia

Atrophy

Metaplasia



9/21/20

Slide – Adaptation diagramHypertrophy

• Increase in the size of cells leading toan increase in the size of the organ(often seen in tissues made up ofterminally differentiated cells – they canno longer divide, their only responseto the stress is to enlarge)

• End result is that the amount ofincreased work that each individual cellmust perform is limited

• Can be either physiologic or pathologic

Hypertrophy (cont’d)

• Physiologic

– Due to hormonal stimulation (e.g.,

hypertrophy of uterine smooth muscle

during pregnancy)

• Pathologic

– Due to chronic stressors on the cells (e.g.,

left ventricular hypertrophy due to long-

standing increased afterload such as HTN,

stenotic valves)

Physiologic hypertrophy

Myocyte adaptation

Chronic Hypertrophy

• Chronic cardiac volume overload-neonatal

genes activated-contractile proteins shift

• High DNA content due to cell cycle arrest

• If the stress that triggered hypertrophy does

not abate, the organ will most likely proceedto failure – e.g. heart failure due to

persistently elevated HTN

• Hypertrophied tissue is also at increased risk

for development of ischemia, as its

metabolic demands may outstrip its blood

supply



9/21/20

Hyperplasia

• Increase in the number of cells in anorgan or tissue

• May or may not be seen together with

hypertrophy


Physiologic Hyperplasia

• Hormonal – Hyperplasia of uterine muscle during

pregnancy or glandular epithelium of breastat puberty and during pregnancy

• Compensatory – Hyperplasia in an organ after partial

resection (e.g. liver) or wound healing

• Mechanisms include increased DNAsynthesis-increased GF

• Growth inhibitors will halt hyperplasiaafter sufficient growth has occurred

Pathologic Hyperplasia

• Due to excessive hormonal stimulation – Endometrial proliferation due to increased

absolute or relative amount of estrogen

• Due to excessive growth factor stimulation – Warts arising from papillomaviruses-TF

• Not in itself neoplastic or preneoplastic –but the underlying trigger may put thepatient at increased risk for developingsequelae (e.g., dysplasia or carcinoma)

Atrophy

• Shrinkage in the size of the cell due to

loss of cell substance (with or without

accompanying shrinkage of the organ or

tissue)

• Atrophied cells are smaller than normal

but they are still viable – they do not

necessarily undergo apoptosis or

necrosis


Atrophy (cont’d)

• Physiologic

– Tissues / structures present in embryo or in

childhood (e.g., thymus) may undergo atrophy as

growth and development progress

• Pathologic – Decreased workload

– Loss of innervation

– Decreased blood supply

– Inadequate nutrition

– Decreased hormonal stimulation

– Aging

– Physical stresses (e.g., pressure)

Physiologic atrophy82 yrs old man 25 yrs old man



9/21/20

Metaplasia

• A reversible change in which one

mature/adult cell type (epithelial ormesenchymal) is replaced by another

mature cell type

– If injury or stress abates, the metaplastic

tissue may revert to its original type

• A protective mechanism rather than a

premalignant change

Metaplasia (cont’d)

• Bronchial (pseudostratified, ciliated

columnar) to squamous epithelium – E.g., respiratory tract of smokers

• Endocervical (columnar) to squamousepithelium – E.g., chronic cervicitis

• Esophageal (squamous) to gastric orintestinal epithelium – E.g., Barrett esophagus

Squamous metaplasiaGastric metaplasia in

esophagus -- micro

Metaplasia -- Mechanism

• Reprogramming of epithelial stem cells

(reserve cells) from one type of epithelium

to another

• Reprogramming of undifferentiated

mesenchymal (pluripotent) stem cells to

differentiate along a differentmesenchymal pathway

Documents

Cell Death Adaptation Lecture 2 Opt