Apoptosis and Necrosis Flashcards

1
Q

Two types of Neoplasms

A
  • BENIGN- slow growth, localized,encapsulated,resembles cell of origin, few mitosis, normal or slight increase in ratio of nucleus to cytoplasm. Cells are uniform throughout the tumor,resembles cells of origin (well differentiated).
  • MALIGNANT-rapid growth/proliferation,may spread. Abnormal growth tissue,cancer cell unregulated,cells and nuclei vary in shape and size, high nuclear to cytoplasmic ration, many mitosis, NOT ENCAPSULATED.
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2
Q

Carcinoma

A

Malignant tumor growing from Epithelial tissue cancer

-glands

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3
Q

Sarcoma

A

Malignant tumor growing from Connective tissue cancer

  • bones
  • blood
  • cartilage
  • fat
  • muscle
  • tendons
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4
Q

Metastasis

A
Distant spread of the tumor cells into other tissues of the body.
MODES
-Vascular-veins
-Lymphatic-lymphatic vessels
-Transcoelomic-across coelomic spaces
Ex. Peritoneal and pleural cavities
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5
Q

Tumor formation (two theories)

A
  • Clonal evolution-develops through repeated rounds of mutation and proliferation
  • cells acquire selective growth advantage over neighbor cells
  • Stem cell evolution
  • Tumors contain cancer stem cells
  • Indefinite proliferative potential
  • Linked initially to Leukemia’s
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6
Q

Two major mechanisms of Cell death

A
  • NECROSIS
  • Ischemia
  • toxins
  • infections
  • trauma
  • APOPTOSIS
  • Regulated cell death
  • Occurs throughout adulthood and development
  • Physiological (development, tissue homeostasis) and some pathological conditions such as DNA damage, misfolded proteins, some viral infections
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7
Q

Necrosis (PACCLCSI)

A
  • Pathological
  • Acute cell injury
  • Cell swelling
  • Cell unable to maintain homeostasis
  • Loss of tissue membrane integrity ( damage to plasma membrane)-Random DNA degradation
  • Cell contents released
  • Surrounding tissue damage
  • Inflammation
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8
Q

APOPTOSIS

A
  • Physiological
  • Genetic
  • Programmed cell death
  • Cell shrinking
  • Maintains plasma membrane integrity
  • PLASMA MEMBRANE BLEBBING
  • DNA aggregation-Aggregation of chromatin
  • Fragmentation of oligonucleosomal DNA/Nucleus
  • Capsase cascade activation
  • No surrounding tissue damage
  • No inflammation
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9
Q

ASSESMENT OF NECROSIS

A

MORPHOLOGICAL

  • Propidium Iodide (PI) staining
  • PI positive-leaky/discontinuous plasma membrane-necrosis
  • H&E staining
  • increased eosinophilia
  • variable nuclei staining
  • TEM
  • Discontinuous plasma and organelle membranes

BIOCHEMICAL
-Random DNA degradation- increased levels of LDH-Lactate dehydrogenase

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10
Q

CYTOKINES MACROPHAGE RELEASES TO INHIBIT INFLAMMATION

A

** ILB-10

** TGF-BETA

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11
Q

CYTOCHROME C

A

Released from the mitochondria for apoptosis

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12
Q

WEBBING OF HUMAN TOES

A

Interruption of Apoptosis

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13
Q

Mechanisms of Apoptosis

-TWO PATHWAYS

A
  • Intrinsic
  • Death signal received
  • Pro-apoptotic proteins unregulated
  • Release of cytochrome c from mitochondria
  • Apoptosome formation (Apache-1,cytochrome c, procaspace 9)
  • Caspase cascade-activation of initiator Caspace 9 and effector Caspace 3
  • Extrinsic
  • Binding of ligand to death receptor
  • Fas ligand
  • Recruitment of death adaptor proteins
  • FADD
  • TRADD
  • Formation of death inducing signaling complex (DISC)
  • Capsase cascade:
  • Activation of initiator Capsase 8
  • Activation of effector or “executioner” caspases ex. Caspase 3
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14
Q

CASPACE FAMILY

A

Family of protease enzymes

  • Cysteine dependent, aspartame-directed protease
  • synthesized as inactive precursors-procaspaces
  • activated by proteolytic cleavage
  • target cytoplasmic and nuclear proteins and Caspace-active DNAse
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15
Q

CASPASE 1

A

Cytokines maturation

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16
Q

CYTOKINES 2,8,9,10

A

INITIATOR CASPACES

17
Q

CASPASES 3,6,7

A

Effector/Executioner Caspases

18
Q

CASPASES 4,5

A

INFLAMMATION

19
Q

CASPASE 14

A

Skin development

20
Q

Bcl-2 protein family

*Intracellular regulators of apoptosis

Two classes:

A

Pro-apoptotic/pro-death

  • [Bak
  • [Bax
  • *both of the above : permeabilization/ entering of mitochondrial outer membrane
  • Bid-links extrinsic and intrinsic pathways

Anti-apoptotic/anti-death

  • Bcl-2
  • Bcl-xL
21
Q

ASSESSMENT OF APOPTOSIS

***CAD E T

A

C- Capsase activity

A- Annexin 5- this protein binds to phosphatidylserine when exposed on the outer leaflet of plasma membrane

D- DNA Laddering: DNAse cleaves internucleocomal DNA, 180-200bp fragments

T-TUNEL-this assay detects DNA fragmentation
Terminal Uridine deoxynucleotidyl transferase nick end labeling. Tagged or labeled deoxynucleotides to 3’ DNA ends