Module 2: Alterations in Cells and Tissues Flashcards
1
Q
Atrophy
A
- Cell size decreases or shrinks
- Normal example: thymus
- Pathological ex: loss of blood circulation, hormones, aging = loss of brain cells
- Mechanism: decrease in protein synthesis
- upregulation of proteasome activity
- autophagy by lysosomes
- cellular debris breaks down
- Visible Changes: smaller cell size
2
Q
Hypertrophy
A
- Cell size increases
- Normal ex: increased demand by hormones or growth factors
- i.e. construction worker with hypertrophied upper body
- Pathological Ex: chornic hemodynamic overload
- leads to cardiomegaly
- Mechanism: Increased protein synthesis
- increased DNA synthesis
- does NOT occur due to swelling caused by fluid
- Visible Changes: increase total cell size
- increased number of organelles
3
Q
Hyperplasia
A
- the number of cells increases due to increased cell divison
- Physiological Ex:
- compensatory hyperplasia: hepatocytes of the liver regenerate and replicate in the liver after they are damaged by alcohol
-
hormonal hyperplasia: hormone dependent organs experience replication of cells when exposed to certain hormones
- i.e. endometrium of uterus grows with increased hormone production
- Pathological Ex: abnormal proliferation of cells
- i.e. cancer/tumors
- Mechanism: hormonal and growth facotrs increase
- failure of normal growth regulation
- Visible changes:
- excess cells
- enlarged nucleus with enlarged nucleoli
4
Q
Metaplasia
A
- a type of cell is replaced with another type of cell, often becoming more homogenous (less differentiated)
- New cell type may be more suitable for new environment–> prolonged exposure can lead to neoplasia
- Mechanism: cytokines and growth factors related to inflammation and injury cause precursor cells to reprogram
- Visible changes: cells look more homogenous (less differentiated)
- abnormal cells that are not typical of surrounding cells are present
5
Q
Dysplasia
A
- mature cells end up with abnormal shapes, size, and organization
- aka atypical hyperplasia
- caused by persistent cell injury or irritation
- NOT a good adaptive change
- can be classified as low or high grade; or mild, moderate, or severe
- can be associated with neoplastic growths in the cervix, respiratory tracts, or breast cancer
- Mechanism: increased cell division
- visible changes: increased number of cells, abnormal shape, and organization
- Enlarged nucleus as inm hyperplasia and hypertrophy
6
Q
Cellular Injury
A
a change occurs that can result in death
7
Q
cellular adaptation
A
changes that occur in the cell as a result of changes in the environment
8
Q
Causes of cellular injury (8)
A
- hypoxia
- free radicals
- chemical agents
- infectious agents
- physical or mechanical stress
- immune reactions
- genetic factors
- nutritional imbalance
9
Q
Early Reversible Stages of Cellular Injury
A
- Trigger is low oxygen
- mitochondria reduce ATP production (only glycolysis can occur)
- results in loss of Na/K pump acitvity
- Na builds up intracellularly
- water no longer block by Na in the ECF and enters the cell
- K build up in the ECF
- Na builds up intracellularly
- Results in loss of Na/Ca exchanger
- intracellular build up of Ca in the ICF
- Water enters the cell
- causes cellular swelling, endoplasmic reticulum dilation, detached ribosomes, decreased protein synthesis, and lipid deposition
- anaerobic glycolysys occurs
- increased production of lactic acid leads to a decrease in pH in the cell which causes the nuclear chromatin to clump
- results in loss of Na/K pump acitvity
- mitochondria reduce ATP production (only glycolysis can occur)
10
Q
Prolonged Hypoxic Cellular Injury
A
- swelling continues which causes vacuolation: the formation of cavities within the cell; and blebs to occur
- swelling of lysosomes:
- becuase they are digesting cytoplasm and nuclear components
- swelling of mitochondria
- Ca2+ activates intracellular enzymes
- proteases, phospholipases, and endonucleases
- cell membrane damage occurs
- influx of Ca2+
- Further loss of proteins, degradation of nucleic acids, loss of ATP
- Becomes irreversible–>cell death
11
Q
Hypoxic Cellular Injury Causes
A
***Most common type of cellular injury*** Caused by lack of O2
- loss of local blood supply
- low oxygen in the air
- loss or alteration of hemoglobin
- decreased number of red blood cells ie anemia
- damage to oxidation enzymes (Cytochromes)
- insufficient systemic respiration
- insufficient system circulation
12
Q
Ischemia
A
- reduced blood supply
- but if it is gradual then adaptations can occur
- ex. thrombus that is growing and reducing blood supply
- can adapt by creating new vessels that circumvent the thrombus
- ex. thrombus that is growing and reducing blood supply
13
Q
Anoxia
A
- total lack of oxygen–> not tolerated by most tissues
- ex. an embolus that gets stuck in a vessel
14
Q
Oxidative Stress
A
- Caused by reactive oxygen species(ROS)
- ROSs causes cell, membrane, and organelle damage by:
- peroxidation of lipids–> breakdown of unsaturated fatty acids
- alteration of proteins
- DNA damage
- MITOCHONDRIA are very important in this oxidative stress
- they produce and are damaged by ROS
- they generate them during the electron transport chain
- if ROS levels are high they can overhwlem the peroxisomes which carry antioxidant enzymes
- they produce and are damaged by ROS
- Lipids, proteins, and mtDNA are all affected by ROS
15
Q
Free Radicals
A
- Definition: they are uncharged atoms with unpaired electrons that are unstable and often damage other molecules
- Formed by: neutrophils and other inflammatory cells
- endothelial cells, vascular smooth muscle, fibroblasts
- they are possible in all cell types to different degrees
- Formed due to:
- energy sources that hve excess energy: UV and other radiation
- redox reactions
- enzymatic breakdown of exogenous molecules or drugs
- They cause:
- peroxidation of lipids–> breakdown of unsaturated fatty acids
- alteration of proteins
- DNA damage
16
Q
Chemical Injury
A
- Examples of chemicals that cause injury
- carbon tetrachloride (CCl4)
- lead
- carbon monoxide
- ethanol/alcohol
- mercury
- drugs
- exposure via inhalation, ingestion, and absorption
- Common mechanisms:
- direct toxicity to the cell, membrane or organelles
- production of free radicals
- cellular enzymes or proteins may be altered
- blocked synthesis of molecules
- blocked cellular functions
17
Q
Reperfusion Injury
A
- Reperfusion can lead to apoptosis of cells
- calls accumulate xanthine and hypoxanthine during ischemia
- these two molecules combine with oxygen to form the ROS superoxide and hydrogen peroxide
- causes cell membrane damage
- mitochondrial Ca2+ overload
- mitochondrial permability transition pore (MPTP)
- results in loss of ATP and loss of solutes
- mitochondrial permability transition pore (MPTP)
- Apoptosis–> activation of cell death by activation of Caspases
- caspases are activated by the release of cytochrome C from the mitochondria
- calls accumulate xanthine and hypoxanthine during ischemia
18
Q
Caspases
A
- pro-apoptotic enzyme
- lead to a cascade that breaks down DNA \
- can be activated by the release of Cytochrome C from the mitochondria