Cellular response to stress and toxic insults: adaptation, injury, and death Flashcards
(50 cards)
What is adaptation?
Adaptations are reversible functional and structural responses to changes in physiologic states and some pathologic stimuli, during which new but altered steady states are achieves, allowing cell to survive and continue to function. When the stress is eliminated the cell can recover to its original state.
What is hypertrophy? What types are there? What causes it?
An increase in the size of cells resulting in an increase in the size of the organ. It can be physiologic (enlargement of uterus during pregnancy) or pathologic (enlargement of cardiac muscle due to hypertension) and is caused either by increased functional demand (workload) or by growth factor or hormonal stimulation.
Name 3 transcription factors important in hypertrophy!
What are there function?
GATA4
NFAT
MEF2
Increase protein synthesis
What are the pathogenesis of hypertrophy?
Hypertrophy is the result of increased production of cellular proteins.
Three basic steps in the molecular pathogenesis of cardiac hypertrophy:
- The integrated actions of mechanical sensors (increased workload), growth factors (TGF-beta, IGF1, fibroblast growth factor) and vasoactive agents (alfa-adrenergic agonists, endothelin-1, and angiotensin II).
- These signals originating in the cell membrane activate a complex web of signal transduction pathways. Two such biochemical pathways involved in muscle hypertrophy are the phosphoinositide 3-kinase (PI3K)/ AKT pathway (important in physiologic, exercise-induced, hypertrophy) and signaling downstream of G-protein-coupled receptors (induced by many growth factors and vasoactive agents, important in pathologic hypertrophy).
- These signaling pathways activate a set of transcription factors such as GATA4, nuclear factors of activated T cells (NFAT), and myocytes enhancer factor 2 (MEF2). These transcription factors work coordinately to increase the synthesis of muscle protein that are responsible for hypertrophy.
List biochemical pathways involved in muscle hypertrophy!
The phosphoinositide 3-kinase (PI3K)/ AKT pathway (important in physiologic, exercise-induced, hypertrophy) and signaling downstream of G-protein-coupled receptors (induced by many growth factors and vasoactive agents, important in pathologic hypertrophy).
What is hyperplasia?
An increase in the number of cells due to the increased cell mitosis.
List the types of hyperplasia1
- Physiologic hyperplasia:
. Compensatory hyperplasia permits tissue and organ regeneration. Example: when part of a liver is resected.
. Hormonal hyperplasia occurs in organs that depend on oestrogen. Example: proliferation of the glandular epithelium of the female breast at puberty. - Pathologic hyperplasia is caused by excessive or inappropriate actions of hormone or growth factors acting on target cells. Patient with pathological hyperplasia are at a higher risk for developing endometrial cancer.
What is atrophy?
Is shrinkage in the size of cells by the loss of cell substance (autophagy). Atrophic cells may have diminished function, they are not dead.
what causes atrophy?
Causes: decrease workload, loss of innervation, diminished blood supply, inadequate nutrition, loss of endocrine stimulation, and aging.
Cellular atrophy results from a combination of decreased protein synthesis (due to reduced metabolic activity) and increased protein degradation (by ubiquitin ligases). It is accompanied by increased autophagy.
What is metaplasia?
Occur when a differentiated cell of a certain type is replaced by another cell type, which may be less differentiated but able to withstand the adverse environment.
The influences that induce metaplastic changes in an epithelium, if persistent, may predispose to malignant transformation in the metaplastic epithelium.
What are the mechanisms of metaplasia?
Metaplasia doesn’t result from a change in the phenotype of an already differentiated cell type; instead it is the result of a reprogramming of stem cells that are known to exist in normal tissues, or of undifferentiated mesenchymal cells. The differentiation of stem cells is brought about by signals generated by cytokines, growth factors, and extracellular matrix components in the cells’ environment.
Retinoic acid regulates gene transcription directly through nucleus retinoid receptor, which can influence the differentiation of progenitors derived from tissue stem cells.
what is dysplasia?
An abnormal change in cellular shape, size, and/or organization.
What are the morphology of necrosis?
Necrotic cells show increased eosinophilia in haematoxylin and eosin stains, attributable in part of the loss of cytoplasmic RNA and in part to denatured cytoplasmic proteins. Dead cells may be replaced by large, whorled phospholipid masses called myelin figures that are derived from damage cell membrane. These phospholipids are either phagocytosed or degraded into fatty acids; calcification of such fatty acid may result in calcium soaps. The dead cells may become calcified.
what are the nuclear changes pattern during necrosis?
Nuclear changes patterns:
- Karyolysis: a change that presumable reflects loss of DNA because of enzymatic degradation by endonucleases.
- Pyknosis - characterized by nuclear shrinkage and increased basophilia. Here the chromatin condenses into a solid, shrunken basophilic mass.
- Karyorrhexis: the pyknotic nucleus undergoes fragmentation and then totally disappear.
List the six pattern of necrosis!
Coagulation necrosis Liquefactive Necrosis Gangrenous necrosis Canceous necrosis Fat necrosis Fribrinoid necrosis
Talk about coagulation necrosis!
Coagulation necrosis is characteristic of infarcts in all solid organs except the brain. When the underlying tissue architecture is preserved for at least several days after death of cells in the tissue. The affected tissue takes on a firm texture. The injury denatures the
structural proteins and enzymes, thereby blocking the proteolysis of the dead cells; eosinophilic, anucleate cells may persists for days or weeks. Leukocytes are then recruited to digest by the action of lysosomal enzymes.
Talk about liquefactive necrosis!
Liquefactive necrosis is characterized by digestion of the dead cells, resulting in transformation of the tissue into a liquid viscous mass. Seen in focal bacterial or fungal infections because microbes stimulate the accumulation of leukocytes. Hypoxic death of cell within the central nervous system often manifests as liquefactive necrosis.
Talk about gangernous necrosis!
Gangrenous necrosis applied to a limb that has lost its blood supply and has undergone necrosis involving multiple tissue planes.
Talk about Fat necrosis!
Fat necrosis refers to focal areas of fat destruction, typically resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity. The pancreatic enzymes leak out of acinar cells and liquefy the membranes of fat cells in the peritoneum. The released lipases split the triglyceride esters contained within fat cells. The fatty acids combine with calcium to produce grossly visible chalky-white areas.
Talk about caseous necrosis
Caseous necrosis is encountered in foci of tuberculous infection. The necrotic area appears as a structureless collection of fragmented or lysed cells and amorphous granular debris enclosed within a distinctive inflammatory border.
Talk about fibrinoid necrosis!
Fibrinoid necrosis is usually seen in immune reactions involving blood vessels. This pattern of necrosis typically occurs when complexes of antigens and antibodies are deposited in the walls of arteries. These complexes and plasma protein produce a bright pink appearance.
What are the consequences of mitochondrial damage?
Mitochondrial damage
Mitochondria can be damaged by increases of cytosolic Ca2+, reactive oxygen species, and oxygen deprivation.
Consequences of mitochondrial damage:
- Mitochondrial damage results in formation of a high-conductance channel in the mitochondrial membrane, called the mitochondrial permeability transition pore. The opening of this conductance channels lead to loss of mitochondrial membrane potential, resulting in failure of oxidative phosphorylation and progressive depletion of ATP, cell necrosis. One of the components of the mitochondrial permeability transition pore is the protein cyclophilin D (target by the immunosuppressive drug).
- Abnormal oxidative phosphorylation that lead to the formation of reactive oxygen species.
- Mitochondria protein between the outer and inner membranes capable activating apoptotic pathways; these include cytochrome c.
What happens when calcium homeostasis is lost?
Calcium protects cells from injury induced by harmful stimuli. Ischemic cause an increase in cytosolic calcium concentration, because of release of calcium from intracellular store and increased influx across membrane.
Explain hydropic swelling during cellular damage!
Hydropic swelling is an increase in water content of the cytoplasm in the cell. This can be caused due to the failure of Na+/K+ pump. During ischemia (lack of adequate blood flow), tissues are deprived of oxygen, ATP can’t be produced by aerobic metabolism and is instead made inefficiently by anaerobic metabolism. This initiates a series of chemical and pH imbalances, which are accompanied by increase generation of injurious free radical.
