2 . Cell Flashcards
Types of cells in relation to miyotic cell division
Permanent neurons cardiac and skeletal
Stable - G0 state - Hepatocyte endothelial cells pct
Labile cells - stem cells
Epidermis mucosal lining bone marrow elements
Causes of cellular stress or injury
Physical
Chemical
Biological
Ischemic reperfusion injury because of
Free oxygen radicals
Ca influx but there is already ca build up in cell because of damage to SR
So state of hyper contraction in myocardium
Inflammation cytokines
Generation of ROS
Physiological - partial reduction of O2 during oxidative phosphorylation
Pathological
Ionizing radiation
Inflammation
Fenton reaction
Ratio of Reduced glutathione to oxidized is indicator of
Health when it’s high
Unfolded protein response and ER stress
When misfolded proteins accumulate in the ER they trigger the UPR
Response is
Increased production of chaperons which control the proper folding of proteins
Enhance proteosomal degradation of misfolded proteins
Slow protein translation
If UPR doesn’t work it cause apoptosis and is called ER stress
Intracellular accumulation of misfolded protein caused by
Increased misfolding
Viral infection mutation ph and redox state
Or
Decreased correction
Atp for foldase and aging
Cellular adaptation by
Hyperthrophy
Hyperplasia
Metaplasia
Atrophy
Protein degradation by
Ubiquitin proteasome system
Autophagy lysosome system
Ubiquitin proteasome system stimulated by and inhibited by
Stimulate -
Glucocorticoid
Thyroid
Cytokines
Inhibited -
Insulin
Physiologic hyperplasia 2 types
Hormonal hyperplasia uterus and breast
Compensatory hyperplasia regeneration of liver
Pathological hyperplasia
Hyperplasia of
Of CT in wound healing
Of epidermis in skin warts due to HPV infection
Of endometrial hyperplasia due to unopposed estrogen
Of prostatic nodes due to androgen
Mechanism of hypertrophy
•Due to increased synthesis of structural components
•Through gene activation, protein synthesis, and production of organelles
•Nuclei may have a higher DNA content probably because cell cycle arrest without mitosis
Physiologic hyperthrophy
Uterus
breast
Pathological hyperthrophy
Cardiac muscle hyperthrophy
Compensatory hyperthrophy hepatomegaly
Bladder trabiculation in BPH
Metaplasia
Reversible change in which one adult cell type is replaced by another adult cell type
Pathologic hyperplasia can progress to cancer and dysplasia except
BPH
Atrophy by decrease in cell size and cell number
Size
UPS and Autophagial lysosome system
Number
Apoptosis
Dysplasia
Dysplasia refers to abnormal changes in the size, shape, and organization of mature cells
Is Not a True Adaptive Change
Slowly developing ischemia (e.g., renal artery atherosclerosis) results in……… ; whereas, acute ischemia (e.g., renal artery embolus) results in …… (AKI).
atrophy
injury
2 types of cell injury
reversible cell injury plus hallmark
The structural and functional changes can revert to normal on removal of the an injurious stimulus
The hallmark of reversible injury are cellular swelling and fatty change
irreversible cell injury plus hallmark
The structural and functional changes cannot be reversed even after removal of the injurious stimulus
The hallmark of irreversible injury is membrane damage
cell death plus hallmark
The end result of irreversible injury
The morphologic hallmark of cell death is loss of the nucleus
types of cell death
necrosis and apoptosis
pyknosis
karyorrhexis
karyolysis
nuclear condensation (pyknosis), fragmentation (karyorrhexis), and/or dissolution (karyolysis).
necrosis
is localized death of cells, tissues, organs, or parts of the body in a living organism
Due to some underlying pathologic process; never physiologic
Cytoplasmic changes in necrosis
loss of RNA and denaturation of proteins(increased eosinophilia)
Glassy homogenous cytoplasm b/c of loss of glycogen
Swelling and vacuolation of the cytoplasm
Cell and organelle membranes rupture
Formation of myelin figures
Nuclear changes in necrosis
Nuclear shrinkage and increased basophilia (pyknosis)
Nuclear fragmentation (karyorrhexis)
Fading of basophilia due to DNase activity (karyolysis)
types of necrosis
Coagulative necrosis
Liquefactive necrosis
Caseous necrosis
Fat necrosis
Fibrinoid necrosis
coagulative type
tissue firm and pale and preserved
most common
because of ischemia or infraction except brain
ischemia leads to protein/enzyme denaturation
coagulative in order
reduced ph
denatured enzymes
no proteolysis
liquefactive necrosis or colliquative
Enzymatic breakdown»_space; protein denaturation
Usually associated with bacterial or fungal infections and form abcess or pus
Seen in organs that have a high-fat and low protein content -brain
high-enzymatic content (eg, the pancreas) or lack of a proper collagenous connective tissue framework
gangrene types
dry
wet
gas
dry and wet gangrene difference
caseous
Combination of coagulative and liquefactive necrosis.
Typically found in tuberculous and fungal granuloma.
On gross; it is soft and greasy, resembling cottage cheese.
fat necrosis
Fat necrosis: This type of necrosis occurs when there is damage to adipose tissue, resulting in the release of fatty acids, which can combine with calcium ions to form chalky white deposits. It is commonly seen in the breast and acute pancreatitis
chalk white deposit is soap so saponification
limited to small blood vessels.
No distinct macroscopic features.
This type of necrosis is characterized by the deposition of immune complexes and fibrin in the walls of blood vessels, which can lead to vessel damage and inflammation.
Characteristic of malignant hypertension and vasculitis. It may also be seen in rheumatic fever, rheumatoid arthritis, hepatitis B virus (HBV) infection, systemic lupus erythematosus (SLE), etc
Sequence of Morphological Changes in Apoptosis
Examples and causes of apoptosis
Physiologic
Involution following hormone withdrawal
Removal of cells during embryogenesis
Negative selection of thymocytes in thymus
Death of cells after fulfilling their function
Pathologic
CD8⁺ T cell-mediated killing of virally infected cells
DNA damage beyond repair
Atrophy of parotid, kidney, pancreas after duct obstruction
Sequence of Morphological Changes in Apoptosis
- Cell shrinkage (increased density of the cytoplasm with tightly packed organelles)
- Chromatin condensation under the nuclear membrane followed by nuclear fragmentation (karyorrhexis)
- Surface blebbing followed by fragmentation into membrane-bound apoptotic bodies
- Phagocytosis of apoptotic bodies (ingestion by macrophages followed by lysosomal degradation)
Sequence of Biochemical Events in Apoptosis
protein cleavage by proteolytic enzymes/caspases
protein cross link
DNA condensation and breakdown
recognition of dying cells by phagozytes
Mechanism of Apoptosis
- Initiation of apoptosis by activation of signalling pathways:
- Control and integration:
- Execution phase:
- Removal of dead cells:
intrinsic mitochondrial activation of apoptosis
This pathway is initiated by the release of cytochrome c from the mitochondria into the cytosol. Cytochrome c then binds to Apaf-1 (apoptotic protease activating factor-1), which leads to the activation of caspase-9 and the subsequent activation of downstream caspases.
all because of increase in permeability of mitochondial membrane
Release of these factors is regulated by Bcl family of proteins on mitochondrial membrane
extrinsic death receptor pathway
This pathway is initiated by the binding of ligands such as tumor necrosis factor (TNF) or Fas ligand (FasL) to death receptors such as TNF receptor-1 or Fas. This binding leads to the activation of caspase-8, which can then activate downstream caspases.
p53 pathway
This pathway is initiated by the binding of ligands such as tumor necrosis factor (TNF) or Fas ligand (FasL) to death receptors such as TNF receptor-1 or Fas. This binding leads to the activation of caspase-8, which can then activate downstream caspases.
other way of activation of apoptosis hint lymphocytes
Lymphocytes release perforins that punch a hole in the cell membrane of the target cell
Then, they release granzyme B into target cell that activates the caspases
Control and integration:
controlled by BCL2 family of proteins which include ‘antiapoptotic proteins’ (BCL2, BCL-XL and MCL1); ‘proapoptotic proteins’ (BAX and BAK); and ‘BCL2 sensor proteins’ (BAD, BIM, Puma, Noxa).
Execution phase:
Proteolytic cascade involving execution caspases (caspases 3 and 6).
Removal of dead cells:
by macrophages
Removal is aided by expression of phosphatidylserine, secretion of soluble factors like thrombospondin and coating of apoptotic cells by natural antibodies and of the complement proteins (opsonization)
Phosphatidylserine and thrombospondin for removal of death cells
Phosphatidylserine is normally located on the inner leaflet of the plasma membrane, but during apoptosis, it becomes exposed on the outer leaflet. This serves as a signal for phagocytic cells, such as macrophages, to recognize and engulf the apoptotic cell.
Soluble factors such as thrombospondin can also contribute to the recognition and removal of apoptotic cells. Thrombospondin can bind to receptors on phagocytic cells and promote the engulfment of apoptotic cells.
Disorders associated with decreased apoptosis
cancer and autoimmunity
Disorders associated with increased apoptosis:
Neurodegenerative diseases (Alzheimer, Huntington, Parkinson)
Ischemic injury in stroke and myocardial infarction
Death of virus-infected cells as in AIDS
Graft rejection
difference between necrosis and apoptosis
other types of cell death
necroptosis
ferroptosis
pyroptosis
necroptosis
hybrid
