Week 1: Cellular Response to Stress Flashcards
What kind of tissue is depicted here?
Liver/hepatocyte (normal)
What is etiology?
Etiology is the cause or set of causes for a given disease. Etiology can be genetic or acquired, and most diseases have multifactorial causes.
What is pathogenesis?
The mechanism of disease–cell, biochemical, or molecular events that follow the exposure of a cell to injurious stimuli
What are morphological changes? Why do we assess them?
Morphologic changes are structural alterations in cells or tissues characteristic of a disease. These are assessed in order to determine clinical manifestations of a disease.
What are the main ways cells respond to stress?
Cells can adapt to stress, or if the stress is overwhelming, the cell can become injured. Some injuries are mild and reversible, while others are irreversible and lead to cell death (necrosis or apoptosis)
What are the general categories of physiologic stress and toxic stimuli that cells might encounter?
Increased demand
Decreased nutrients
Increased or decreased stimulation
Chronic irritation
Reduced oxygen supply (hypoxia, reduced blood supp. = ischemia)
Microbial infection
Metabolic alterations
What are the types and definitions of cellular adaptations? Are they reversible?
Cell adaptations are somewhat reversible until a certain point. Reversible changes in cell size, number, type, activity or function can all occur in response to the environment. These include:
Hypertrophy = enlargement of an organ or tissue from increase in cell size
Atrophy = decrease in organ/tissue size from a decrease in cell size
Hyperplasia = enlargement of an organ caused by an increase in cell reproduction rate and, thus, cell number (i.e. in cancer)
Metaplasia = the transformation of a differentiated cell type into another differentiated cell type
What is hypertrophy and why does it occur?
Increase in cell size, resulting in increased organ size, usually due to increase in synthesis
Etiology: Increased workload and/or stimulation
Mechanisms: Induction of select genes, and subsequent protein synthesis
Ex: lifting weights increases muscle cell size
What stimuli can induce cells to behave differently?
Mechanical stretch (increased workload, as in muscles), agonists like (a-adrenergic hormones, angiotensin) and growth factors (i.e. IGF1)
This helps reduce the workload of a cell by increasing mechanical performance
What organ is depicted here? What kind of tissue is mostly present? What is the difference between right and left sides?
This is uterine smooth muscle tissue–it has hypertrophied (R side, cell size increase) compared to its normal state (L side)
What is hyperplasia and why does it occur? What is it’s etiology? What are it’s mechanisms?
Hyperplasia is an increase in the number of cells. It can occur concurrently with hypertrophy and lead to an increase in the size of an organ.
Etiology: physiologic–hormonal/compensatory, and pathologic–excessive stimulation (hormonal)
Mechanisms: Growth factors, increased receptor #, stem cell activation
What is the difference between the left and right images shown here? What tissue is this, and what structures are shown?
The left side shows normal tissue, whereas the right side displays hyperplasia. This is prostate tissue showing glands and a mesenchymal framework (fibroblasts and smooth muscle cells as well).
What is atrophy and why does it occur? When is it frequent (and normal)? What is its etiology and what are its mechanisms? What cellular changes are observed?
Decrease in cell size, accompanied by a decrease in organ size. Can be physiologic or pathologic. Physiologic atrophy is normal and common during development.
Etiology: Decreased workload, denervation, decreased blood supply, decreased endocrine stimulation
Mechanisms: increased protein degradation, lysosomal breakdown, ubiquitin/proteosome pathway
Cell changes include an increase in autophagic vacuoles and lipofuscin granules
What tissue type is shown here, and what is occurring within it? How can you tell?
This is atrophy of the prostate gland displaying prostate cancer On the LH side, the cells lining the glands are very thin and stretched, and become filled with proteinaceous material
What is metaplasia? What is its etiology and what are its mechanisms?
Metaplasia is the replacement of one differentiated cell type with another. This results from external stress, and often involves epithelial tissues. This originates at the stem cell level, and involves reprogramming.
Etiology: irritation or persistent stress
Mechanisms: reprogramming of stem cells, signaling from specific cytokines and growth factors
What tissue type and cellular response is being shown here?
This is metaplasia of respiratory tract cells due to smoking, in which normal, ciliated columnar epithelium is transitioning to squamous epithelial cells, which can “deal” with smoke better. However, these cells cannot clear mucus and infections as effectively, so this is an overall detriment to the person’s health.
What is the etiology of cell injury?
Hypoxia/ischemia, infection, physical/chemical injury, immunologic response, genetic, and nutritional
The type of injury depends on the cell type, and the degree to which the cell can react.
What ae the two forms of cell death and how do they arise?
Necrosis - can occur due to decreased ATP or increased ROS in mitochondria, or from damage to lysosomal/plasma membranes
Apoptosis - usually occurs do to DNA mutations, which activate caspases and lead to apoptosis
What is the difference between necrosis and apoptosis?
Necrosis is accidental/unregulated cell death from membrane damage and loss of ion homeostasis
Apoptosis is programmed cell death, often secondary to DNA damage
How is necrosis identified in tissue? Why does it usually occur?
Cytoplasmic changes: increased eosinophils, nuclear shrinkage/distortion, and calcification in late stages
What is pyknosis?
Nuclear shrinkage in necrotic cells
What is karyolysis?
Fading of the color of the nucleus
What is karyorrhexis?
Fragmentation of the nucleus
What are the general patterns of necrosis?
Cobras Like Cats Fat and Full
Coagulative (most common)
Liquefactive
Caseous
Fat necrosis
Fibrinoid necrosis
What is coagulative necrosis?
Usually due to hypoxia/ischemia. Cells become eosinophilic (pink), outlines become blurred, nucleus breaks down, neutrophils come in during late stage and remove debris. Macrophages are present to “clean up” in final stages.
Kidney shown has necrosis in yellowed areas, with necrotic tissue shown in green circle
What is liquefactive necrosis and where does it occur? What role do neutrophils play in the process?
Occurs in the brain due to ischemia and in the kidneys. Occurs due to enzymatic digestion of brain/kidney tissues.
Neutrophils break down tissue and “liquefy” it, often producing pus. Thus, neutrophils are a sign of necrotic tissue.
What is caseous necrosis and where does it often occur?
Caseous necrosis occurs in granulomatous inflammation, a coagulative necrosis in the center of a granuloma. Specialized inflammatory cells surround/encase necrotic dissue and attempt to destroy it. The border between necrotic (pink) and healthy tissue is shown in the lower righthand photo.
What is fat necrosis and where does it occur?
Necrosis within adipose tissue, which becomes blurry when ischemia or other injury occurs. This is often due to enzymatic release from the pancreas, and subsequent breakdown of fat.
What is fibrinoid necrosis and where does it usually occur?
Occurs in vessels, an example being vasculitis or the inflammation of blood vessels
What areas is necrosis commonly seen? What kinds of necrosis is occuring?
ITTI:
Ischemic areas - MI + stroke, coagulative and liquefactive
Tumors - malignant and aggressive, coagulative
Trauma - peripheral tissues and pancreatitis, fat necrosis
Infection - TB, classic caseous
What is the etiology of common forms of apoptosis in healthy, active cells?
Embryogenesis, hormone-dependent involution, cell deletion, elimination of lymphocytes, and cytotoxic T cell signaling to virally infected cells
What are caspases? When and how are they activated?
Proteases activated in the cell, which activate enzymes that cause the nucleus of a cell to fragment. Leads to formation of apoptotic bodies. They are activated by intrinsic mitochondrial pathways (BCL2 sensors/effectors, cytochrome c from mitochondria) as well as extrinsic death receptor pathways (Fas and TNF receptor-ligand interaction)
What morphological changes are seen in apoptosis?
Cell shrinkage, chromatin condensation, cytoplasmic blebs, and phagocytosis
What are the ways things can accumulate in cells?
1) Inadequate removal of substance
2) Accumulation of normal endogenous substance due to defects in folding/packaging/transport/secretion
3) Failure to degrade metabolites
4) Deposition and accumulation of abnormal exogenous substances, when cells can’t degrade or expel the substance
What does excess alcohol do to liver tissue?
Alcohol-damaged liver tissue can take up FAs normally, but cannot properly incorporate them into lipoproteins for export. This is called steatosis.
What kinds of pigments can accumulate in cells?
Endogenous: lipofuscin, melanin, hemosiderin (breakdown of RBCs, mostly iron)
Exogenous: carbon (smoke), tattoo ink
How does calcification generally occur? How do we recognize it in a stain?
We recognize calcified tissue as having a deep purple color (see photo). It occurs dystrophically, either via:
Normal systemic calcium metabolism
or
From abnormal tissues, like tumors, which might recruit and/or secrete increased calcium levels
Also occurs metastatically via systemic hypercalcemia in normal tissues.
