Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology > Cell Injury > Flashcards

Cell Injury Flashcards

1
Q

Cell injury

A

Disruption of cell homeostasis or steady state
Injury may come from outside the cell, or inside
Injury effects one or more of important cellular structures
Response of cell to injury: adaptation, degeneration, death of cell
Can be: reversible-with eventual healing; irreversible- progression from degeneration to death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Morphology of cell injury

A

What the injury looks like is variable and depends on:

  • what caused the injury
  • extent of injury
  • duration of injury
  • cell type affected
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Causes of cell injury

A

Oxygen deficiency
Infectious agents common/important
Immunological dysfunction
Workload imbalance: atrophy, hyperplasia, hypertrophy, metaplasia
Physical agents: heat, cold, crush, friction, UV radiation, electrocution
Nutritional imbalances: calorie deficiency/excess, vit/mineral deficiency (and excess)
Genetic derangement: especially selective breeding
Toxins
aging

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Oxygen deficiency

A

Hypoxia: partial reduction in O2 delivery to a tissue
Anoxia: no O2 delivery to a tissue
What causes hypoxia/anoxia
-inadequate oxygenation of blood (heart/respiratory failure)
-reduced transport of O2 in blood (anemia, CO toxicosis)
-reduction in blood supply=ischemia (thrombosis)
-blockage of cell respiratory enzymes (cyanide toxicosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Infectious agents: viruses

A

Obligate intracellular parasites -> use host cell enzyme systems
Cell survival depends on method viruses leave the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Infectious agents: bacteria

A

Toxins

Overwhelming and uncontrolled replication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Infectious agents: fungal (mycosis)

A

Progressive, chronic inflammatory disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Infectious agents: protozoan

A

Replicate in specific host cells -> cell destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Infectious agents: metazoan parasites

A

Inflammation, tissue distortion, utilization of host nutrients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Immune dysfunction-fails to respond

A 
Congenital defects: severe combined immunodeficiency (SCIDS)-> antigen receptors (lymphocytes)
-acquired defects
-may be transient (but not always)
results from damage to lymphoid tissue
viral infections, chemicals, drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Immune dysfunction- over-responds

A

Autoimmune diseases
Hypersensitivity reactions
-anaphylaxis, flea allergy dermatitis, feline asthma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Workload imbalance

A

Often leads to cell adaptation
Some cells can compensate:
-increased workload- hypertrophy, hyperplasia
-decreased workload- atrophy, some forms on oncosis
Some cells cannot compensate:
-degeneration and possible death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mechanisms of cell injury: depletion of ATP

A

ATP produced through aerobic (Krebs) and anaerobic (glycolysis) pathways
Both require glucose
ATP is required for almost all synthetic and degradative processes within the cell
Depletion of ATP is fundamental cause of necrotic cell injury
Depletion of 5-10%=bad
Na/K ATPase pulp failure= cell swelling, ER swelling, plasma membrane damage
Altered cell metabolism= anaerobic glycolysis- depletion of glycogen stores, increased lactic acid, decrease pH, loss of enzyme function
Ribosome detachment=decreased protein synthesis

Culminates in irreversible mitochondrial and lysosomal membrane damage-> cell necrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mechanisms of cell injury: Mitochondrial damage

A

3 Consequences
Formation of the mitochondrial permeability transition pore (MPTP)
Increased production of reactive oxygen species (ROS)
Activation of apoptotic pathways

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mitochondrial damage: Formation of the mitochondrial permeability transition pore (MPTP)

A

High conductance channel in the mitochondrial membrane
When opened, leads to loss of membrane potential
-Failure of oxidative phosphorylation
-progressive depletion of ATP
-cell necrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mitochondrial damage: Activation of apoptotic pathways

A

Proteins that activate the apoptosis pathway are sequestered in the mitochondria
Leakage of apoptosis activating proteins into the cytosol and leads to cell death

17
Q

Mechanisms of cell injury: Loss of Ca homeostasis

A 
Accumulation of Ca2+
3 sources:
1. Extrinsic (cell damage)
2. Intrinsic released from SER
3. Intrinsic released from mitochondiron
Sets off a cascade of event
1. Opening of MPTP-> decreased ATP
2. Enzyme activation
- phospholipases: membrane damage
- Proteases: membrane and cytoskeletal proteins
- Endonucleases: DNA and chromatin fragmentation
-ATPases: break down ATP, accelerates ATP depletion
18
Q

Mechanisms of cell injury: Loss of Ca homeostasis- forms of damage

A

Membrane damage
Nuclear damage
ATP depletion

19
Q

Mechanisms of cell injury: Reactive oxygen species

A

Derived from oxygen
Normally produced during cellular respiration by mitochondria
Molecules or atoms with unpaired electrons- reactive free radical
Cellular quenching/scavenging systems neutralize normally
Excess ROS or decreased scavenging capacity= oxidative stress

20
Q

Mechanisms of cell injury: Reactive oxygen species- normal metabolic processes

A

Reduction-oxygenation reactions (o2+2h2=2 h2o)
Transfer 4 electrons in this reaction
Small amounts of partially reduced intermediated produced
-superoxide anion
-hydrogen peroxide
-Hydroxyl ions

21
Q

Pathological sources of ROS: inflammation

A

Rapid bursts of ROS produced by activated WBCs (esp neutrophils)
-generates superoxide anion

22
Q

Pathological sources of ROS: Transition metals

A

Copper, Iron
Frequently donate or accept free elections
Catalyze free radical formation

23
Q

Pathological sources of ROS: Nitric oxide

A

Important chemical mediator
Generated by endothelial cells, macrophages, neurons, and others
Can act as a free radical
Can be converted into peroxynitrate anion ONOO-, or NO2 or NO3

24
Q

Pathological sources of ROS: Absorption of radiant energy

A

H2O and ionizing radiation = OH + H

25
Q

Pathological sources of ROS

A 
Oxidative stress
Implicated in a variety of pathologic processes
-cell injury
-cancer
-aging
-degenerative diseases
26
Q

Neutralization of ROS

A

Removal of Free radicals
Spontaneous decay: O2+H2O->O2 + H2O2
Enzymes: Catalase, superoxide dismutase, glutathione peroxidase– breakdown H2O2 and O2*; located near sites where oxidants are formed
Storage and transport proteins: transferrin, ferritin, ceruloplasmin– bind reactive metals: Fe, Cu
Antioxidants- Vitamin E, Vit A, glutathione– block initiation, inactivate

27
Q

Pathological effects: ROS Lipid peroxidation in membranes

A

Lipid peroxidation in membranes -> extensive membrane damage
Formation of peroxides -> autocatalytic reaction (propagation)
-Decreased phopholipid synthesis
-increased phospholipid breakdown
-cytoskeletal abnormalities
Activation of proteases -> damaged cytoskeleton
Cells stretch and rupture

28
Q

Pathological effects: ROS- Oxidative modification of proteins

A

Oxidative modification of proteins-> damage active sites, change conformation, enhance degradation
-Generated by monamine oxidase (MOA) in outer mitochondrial membrane
Oxidation of amino acid side chains, formation of protein cross-linkages (disulfide bonds), oxidation of protein backbone
Mitochondrial membrane damage
Plasma membrane damage: loss of osmotic balance -> influx of fluids and ions; loss of cell contents and metabolites
Injury to lysosomal membranes: leakage of enzymes into the cytoplasm- RNases, DNases, proteases, phosphatases, glucosidases; enzymatic digestion of RNA, DNA, proteins, etc

29
Q

Pathological effects: ROS- Lesions in DNA

A

Lesions in DNA-> cell aging, malignant transformation

-MOA: single or double stranded breaks, cross-linking of DNA strands, formation of adducts

30
Q

Mechanisms of cell injury: membrane damage

A

Numerous mechanisms for damaging the PM
ROS
Decreased phospholipid synthesis: secondary to defective mitochondrial function and/or hypoxia
-decreased production of ATP -> decreased phospholipid synthesis
-Affects all cellular membranes (PM, mitochondria etc)
Increased phospholipid breakdown
-activation of Ca-dependent phopholipases
-accumulation of lipid breakdown products: detergent effect on membranes; may insert into membranes; changed in permeability and electrophysiologic alterations

31
Q

Mechanisms of cell injury: membrane damage- cytoskeletal abnormalities

A

Increased cytosolic Ca
activation of proteases-> damage to cytoskeleton
In presence of swelling, plasma membrane can detach from the cytoskeleton -> susceptible to stretching and rupture

32
Q

Mechanisms of cell injury: membrane damage- summary

A

Mechanisms of membrane damage in cell
Decreased O2 and increased cytosolic Ca2+ are typically seen in ischemia but may accompany other forms of cell injusry.
ROS, which are often produced on reperfusion of ischemic tissues, also cause membrane damage (not shown)

33
Q

Consequences of Membrane damage

A

Mitochondrial membrane damage
-open the MPTP -> leakage of pro-apoptotic protiens
- decrease ATP
Plasma membrane damage
- loss of osmotic balance -> influx of fluids and ions
-loss of cell contents and metabolites
Injury to lysosomal membranes
-leakage of enzymes into the cytoplasm: RNases, DNases, proteases, phosphatases, glucosidases
-Enzymatic digestion of RNA, DNA, proteins, etc

34
Q

Clinical pathology correlation: membrane damage

A

Chemistry panel- analytes used to determine hepatocellular injury: alanine aminotransferase (ALT)
-located in the cytoplasm of hepatocytes
-converts alanine to pyruvate
-pyruvate used for gluconeogenesis or krebs cycle
When hepatocytes undergo cell injury, ALT released
1) cell necrosis (ruptures and releases ALT)
2) membrane blebs that contain ALT

35
Q

Mechanisms of cell injury: Protein damage

A

Accumulation of misfolded proteins
-genetic mutations
-free radical damage
Cells have repair mechanisms for misfolded proteins
When overwhelmed -> proteins accumulated in the ER -> ER stress -> initiates apoptosis

36
Q

DNA damage: repair, apoptosis, senescence, cancer

A

Radiation, cytotoxic anticancer drugs, hypoxia
-direct damage
-free radical damage
Cells have repair mechanisms when overwhelmed -> initiates apoptosis

Pathology (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions