Cell injury. (Subject 2)

Содержание

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Conception of cell injury Cell Adaptation Pathological process Disease Pathological reaction Influences Stresses Cell Injury

Conception of cell injury

Cell
Adaptation

Pathological
process

Disease

Pathological
reaction

Influences
Stresses

Cell Injury

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The relationships among cell states (Hypertrophy) Myocardial fiber Hypertension Ischemia (short time) Ischemia (long time)

The relationships among cell states

(Hypertrophy)

Myocardial fiber

Hypertension

Ischemia (short time)

Ischemia (long time)

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Injury From Physical Agents Causes: Mechanical forces - trauma. Extremes of

Injury From Physical Agents

Causes:
Mechanical forces - trauma.
Extremes of temperature –

burns, heat stroke, freezing, frostbites.
Electrical injuries - disruption of nervous and cardiac impulses.
Ionizing radiation - radiation sickness, mutations, tumors.
Ultraviolet radiation- sunburn, ageing, skin cancers.
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Other causes of cell damage Chemicals – substances or their metabolites

Other causes of cell damage

Chemicals – substances or their metabolites
Hypoxia –

as a result of ischemia, cardiac failure or Hb abnormalities
Biological agents – from viruses to parasites
Nutritional imbalances – excesses and deficiencies
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Types of Cell Injury Acute (strong irritants) Chronic (moderate irritants) Reversible

Types of Cell Injury

Acute
(strong irritants)

Chronic
(moderate irritants)

Reversible
(angina pectoris)

Irreversible
(myocardial infarction)

Non-specific
(hypoxic injury)

Specific
(immune

hemolysis of RBC)
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Signs of Cell Injury Morphological Functional changes of shape and color

Signs of Cell Injury

Morphological

Functional

changes of shape and color
swelling or shrinking


the disturbance of contact between cells
damage of cell membrane
damage of cell organelles membranes
intracellular accumulation of substances

reduction of cell mobility
disturbance of cell division
change of cellular membrane permeability
intracellular enzymes presence in blood
appearance of new functions
changes of biochemical processes in injured cells

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General Principles of Cell Injury Factors, which determine cell response Kind,

General Principles of Cell Injury

Factors, which determine cell response
Kind, severity, and

duration of injury.
Type of affected cell, its prior state of health.
Major sensitive cell components:
integrity of cell membrane
aerobic respiration
protein synthesis
genetic integrity
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Major Processes of Cell Injury Decreased ATP production Injury by toxic

Major Processes of Cell Injury

Decreased ATP production
Injury by toxic oxygen radicals
Disturbances

of Ca regulation
Mitochondrial injury
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Example test Chose the example of specific cell injury from listed

Example test

Chose the example of specific cell injury from listed below:
myocardial

ischemia
intestinal epithelial injury due to bacterial toxins
immune hemolysis of RBC
liver cell injury due to chemicals
skin damage due to mechanical trauma
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Example test Which factors determine the type of cell’s response to

Example test

Which factors determine the type of cell’s response to injuring

stimuli?
kind of injuring factor
injuring factor severity and time of duration
prior state of the cell
type of the affected cell
all is correct
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Example test Patient was made blood biochemical test in order to

Example test

Patient was made blood biochemical test in order to confirm

hepatitis. Increased level of alanine transaminase (ALT) and aspartate transaminase (AST) was found. It has been defined as a functional sign of hepatic cells injury. Which from the listed may be the reason of it?
cell’s membrane damage
damage to plasma membrane sodium pump
depletion of ATP store in the cell
nonperoxidative mitochondrial injury
disturbance of cells aerobic respiration
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Major Types of Cell Injury Hypoxia Chemicals Free radicals

Major Types of Cell Injury

Hypoxia

Chemicals

Free radicals

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Reversible Hypoxic Injury Lack of oxygen Decreased ATP formation failure of

Reversible Hypoxic Injury

Lack of oxygen

Decreased ATP formation

failure of ATP
dependent Na/K

pumps
and Ca pump

Cell swelling

↓ mitochondrial
function

Disturbance
of energy metabolism

Ribosome's detachment
from ER

↓ proteins synthesis

↑ anaerobic glycolysis

↓ intracellular pH

↑ membranes
permeability

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Irreversible Hypoxic Injury ↑ membranes permeability Irreversible mytochondrial dysfunction ↓ intracellular

Irreversible Hypoxic Injury

↑ membranes
permeability

Irreversible
mytochondrial
dysfunction

↓ intracellular pH

loss of proteins,
essential

coenzymes,
and ribonucleic acids

Destruction
of lysosomes

Enzymes leakage

Auto-digestion
of cell components

Degradation
of cell organelles

Membranes
damage

CELL DEATH

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Mechanisms of membranes damage Progressive loss of membrane phospholipids Cytoskeletal abnormalities

Mechanisms of membranes damage

Progressive loss of membrane phospholipids
Cytoskeletal abnormalities


Toxic oxygen radicals
Lipid breakdown products
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Reperfusion injury Neutrophiles Calcium ions Blood stream Toxic oxygen radicals Cell

Reperfusion injury

Neutrophiles

Calcium ions

Blood stream

Toxic
oxygen radicals

Cell damage

Cytokines

Enzymes activation

Cell Death

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Example test Disturbance of which process is primary observed in hypoxic

Example test

Disturbance of which process is primary observed in hypoxic injury:
detachment

of ribosomes from EPR
reduction of intracellular pH
oxidative phosphorilation by mitochondria
sodium pump activity
activation of glycolysis
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Example test Which factor directly causes the decrease of intracellular pH

Example test

Which factor directly causes the decrease of intracellular pH in

the case of hypoxic injury?
detachment of ribosomes from EPR
decreased oxidative phosphorilation by mitochondria
failure of sodium pump
activation of anaerobic glycolysis
increased membranes permeability
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Example test Which process is initiated by calcium in hypoxic cell

Example test

Which process is initiated by calcium in hypoxic cell injury?
detachment

of ribosomes from EPR
disturbance of cells aerobic respiration
disturbance of sodium pump
activation of glycolysis
activation of intracellular enzymes
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Example test Which process determines irreversibility of hypoxic injury? inability to

Example test

Which process determines irreversibility of hypoxic injury?
inability to reverse mitochondrial

dysfunction
damage to plasma membrane sodium pump
inability to re-start protein synthesis
extremely low pH
depletion of ATP store in the cell
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Example test Which tissue cells are most sensitive to hypoxic injury?

Example test

Which tissue cells are most sensitive to hypoxic injury?
skeletal muscles
smooth

muscles
myocardial cells
brain cells
liver cells
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Sources of free radicals

Sources of free radicals

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Reactive oxygen species Superoxide O2- Hydroxyl radical OH- Hydrogen peroxide H2O2

Reactive oxygen species

Superoxide O2-

Hydroxyl radical OH-

Hydrogen peroxide
H2O2

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The effects of free radicals Positive: phagocytosis, energy production Negative: Lipid

The effects of free radicals

Positive: phagocytosis, energy production
Negative:
Lipid peroxidation of membranes
Nonperoxidative

mitochondrial injury
Lesions in DNA
Oxidation of proteins
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Antioxidative substances Enzymatic antioxidants Thioredoxin system Glutathione system Superoxide dismutase Catalase

Antioxidative substances

Enzymatic antioxidants
Thioredoxin system
Glutathione system
Superoxide dismutase
Catalase

Non-enzymatic

antioxidants
Vitamins A, C, E
Coenzyme Q10
Selenium
Zinc
Carotenoids
Bioflavonoids
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Example test Choose the effect which IS NOT directly caused by

Example test

Choose the effect which IS NOT directly caused by free

radicals:
lipid peroxidation of membranes
nonperoxidative mitochondrial injury
disturbance of cells aerobic respiration
DNA lesions
cross-linking of proteins
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Chemical injury mechanisms Direct cytotoxic effect mercury damages GIT and kidneys

Chemical injury mechanisms
Direct cytotoxic effect
mercury damages GIT and kidneys
cyanide breaks

oxidative phosphorilation.
Conversion to reactive toxic metabolites
free radicals
lipid peroxodation.
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Outcomes of cell injury

Outcomes of cell injury

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Cell death Necrosis - death of a cell due to external

Cell death

Necrosis - death of a cell due to external forces
Apoptosis

- programmed cell death
gene-related
energy dependent
initiated by external and internal influences)
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Physiological apoptosis Frog plants amphibia human

Physiological apoptosis

Frog

plants

amphibia

human

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Morphological signs of apoptosis Shrinkage of the cell. Condensation of chromatin

Morphological signs of apoptosis

Shrinkage of the cell.
Condensation of chromatin around

the nucleus.
Formation of apoptic bodies.
Phagocytosis of apoptic bodies by macrophages.
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Necrosis and apoptosis

Necrosis and apoptosis

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Example test Give the correct definition of apoptosis. Apoptosis is… a

Example test

Give the correct definition of apoptosis. Apoptosis is…
a process of

virus infected cells killing
a programmed cell death
a death of the cell after injuring factor influence
a cell’s death as a result of enzymes action
an irreversible cell injury
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Example test Which from the following is the most typical morphological

Example test

Which from the following is the most typical morphological sign

of cell death by apoptosis?
condensation of nucleus and cytoplasm
presence of inflammatory reaction
compensatory increase of DNA-synthesis
swelling of mitochondrions
increase of cell’s size
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Example test Every day, blood cells in our body become senescent

Example test

Every day, blood cells in our body become senescent and

die without producing signs of inflammation, and yet, massive injury or destruction of tissue, such as occurs with a heart attack, produces significant signs of inflammation. Why it happens?
due to necrosis of heart muscle
due to apoptosis of heart muscle
due to atrophy of heart muscle
due to swelling of heart muscle
due to disturbances in calcium metabolism
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Cell Adaptation to Injury compensation of energy metabolism disturbance protection of

Cell Adaptation to Injury

compensation of energy metabolism disturbance
protection of cells membranes
compensation

of water-ion disbalance
repair of cell genome
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Compensation of energy metabolism disturbance increased ATP formation, transport and effectiveness

Compensation of energy metabolism disturbance

increased ATP formation, transport and effectiveness of

ATP use
increase of enzymes activity taking part in reduction-oxidation reactions
decrease of cell’s functional activity and protein synthesis
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Protection of cells membranes activation of antioxidants action activation of cells

Protection of cells membranes

activation of antioxidants action
activation of cells buffer system
activation

of EPR enzymes
activation of cellular structures reparation
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Compensation of water-ion disbalance activation of ion “pumps” energy supply increase

Compensation of water-ion disbalance

activation of ion “pumps” energy supply
increase of ion-transporting

enzymes
activation of cell’s buffer system
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Mechanisms of cell genome repair revealing and elimination of damaged DNA

Mechanisms of cell genome repair

revealing and elimination of damaged DNA fragment
replacement

of damaged DNA fragments
elimination of DNA ruptures
normalization of DNA transcription and translation
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The types of cellular adaptations

The types of cellular adaptations

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Causes of atrophy decreased workload, loss of innervation, diminished blood supply,

Causes of atrophy

decreased workload,
loss of innervation,
diminished blood supply,
inadequate

nutrition,
loss of endocrine stimulation,
aging.

Muscle fibers atrophy

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Hypertrophy increase in the size of cells REASONS: increased functional demand

Hypertrophy

increase in the size of cells
REASONS:
increased functional demand
specific hormonal

stimulation
occurs under both physiologic and pathologic conditions

Left ventricle hypertrophy in hypertonic patient

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Hyperlasia increase in the number of cells It occurs in tissues

Hyperlasia

increase in the number of cells
It occurs in tissues where

cells are capable of mitotic division.

Hyperplasia of tonsills

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Metaplasia one adult cell type (epithelial or mesenchymal) is replaced by

Metaplasia

one adult cell type (epithelial or mesenchymal) is replaced by

another adult cell type

Squamous metaplasia in respiratory tract of the habitual cigarette smoker

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Dysplasia Deranged cell growth of a specific tissue that results in

Dysplasia

Deranged cell growth of a specific tissue that results in cells

that vary in size, shape, and organization.
Causes:
chronic irritation
chronic inflammation
pre-cancer state
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Example test Cells may adapt to external and internal stimuli by

Example test

Cells may adapt to external and internal stimuli by undergoing

changes in their size, number and type. What happens to other kidney when one is damaged? It undergoes…:
hypertrophy
atrophy
hyperplasia
metaplasia
dysplasia
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Example test Cells may adapt to external and internal stimuli by

Example test

Cells may adapt to external and internal stimuli by undergoing

changes in their size, number and type. What happens to muscles of extremities that have been encased in plaster casts? The muscles undergo…:
hypertrophy
atrophy
hyperplasia
metaplasia
dysplasia