Week 6 Flashcards
Zygote
The cell formed by the fusion of two gametes
Morula
More than 32 cells, undifferentiated, still in ball form
Where do the first few cell divisions occur?
In the oviduct
What is the significance of the inner and outer cells in the morula?
Inner cells form the embryo, outer cells form the placenta
What is compaction?
Tight junctions and gap junctions form between adjacent blastomeres, and the cells flatten together to form a tight ball in a process called compaction. Cadherins appear to play important roles in compaction, because interfering with cadherins prevents this process. During compaction, the cells also become polarized, with a well- defined apical and basal surface. A fluid-filled space, the blastocoel, appears in the embryo, which is now called a blastocyst.
When and where does implantation usually occur?
What happens to the zona pellucida prior to implantation?
At 6 to 7 days after fertilization, the blastocyst reaches the uterus and implants. Before the embryo can attach to the uterine epithelium, however, it must get rid of the zona pellucida, which still envelopes the embryo. Hydrolytic enzymes are released by the embryo that degrade the wall of the zona, allowing the blastocyst to squeeze out, or “hatch” out of the zona. It is thought that the presence of the zona prior to hatching helps prevent ectopic implantation.
What is placenta previa?
Implantation close to the mouth of the cervix results in the placenta partially covering the cervical canal, a condition known as placenta previa. Placenta previa can cause hemorrhage during pregnancy and can threaten the survival of the fetus and mother.
How does the bilaminar disc form?
On about day 7 after fertilization, at about the time of implantation, a number of changes occur at the animal pole (the inner cell mass) of the embryo. A fluid space appears between the inner cell mass and the adjacent trophectoderm cells; this space will become the amniotic cavity. This process, called delamination, isolates the inner cell mass as a separate entity from the trophoblast. The inner cell mass flattens and forms a roughly circular disc, composed of two layers of cells. The cells closest to the forming amniotic cavity are tall columnar cells, and collectively are called the epiblast. The underlying cells are more cuboidal and form the hypoblast. The epiblast will eventually give rise to the embryo, as well as some extraembryonic structures, while the hypoblast will form extraembryonic structures only. The formation of epiblast and hypoblast is sometimes referred to as the delamination of the inner cell mass. The epiblast side of the disc identifies the dorsal direction. By about day 9, cells of the hypoblast have proliferated and extend below the embryonic disc to enclose a space called the primary yolk sac. A number of these cells break free from the wall of the primary yolk sac to fill the space between the yolk sac and the trophoblast and are subsequently called extraembryonic mesoderm cells. A dense cluster of extraembryonic mesoderm cells connect the bilaminar disc to the trophoblast; this connection will become the umbilical cord. Meanwhile, a distinct cellular layer, apparently derived from the cytotrophoblast, begins to form a roof (the amniotic membrane) over the amniotic cavity.
What are the epiblast and hypoblast? From what layer does the embryo proper arise?
The cells closest to the forming amniotic cavity are tall columnar cells, and collectively are called the epiblast. The underlying cells are more cuboidal and form the hypoblast. The epiblast will eventually give rise to the embryo, as well as some extraembryonic structures, while the hypoblast will form extraembryonic structures only. The formation of epiblast and hypoblast is sometimes referred to as the delamination of the inner cell mass.
When does gastrulation occur?
Gastrulation takes place after cleavage and the formation of the blastula and primitive streak.
What is the primitive streak?
The first sign of gastrulation is a
migration of epiblast cells toward the midline of the
embryonic disc. The thickening formed is called the primitive streak, and serves to demarcate the anterior-postior and left-right axes of the embryo
Primitive node (Hensen’s node)?
As epiblast cells continue migrating, the streak extends in a rostral direction along the disc, and a thickening - Hensen’s node (or the primitive node) - appears at the rostral end of the streak. Then, the streak turns into a groove, through which other epiblast cells migrate.
What three germ layers arise from the process of gastrulation?
Epiblast cells migrate ventrally through the primitive streak to give rise to mesoderm and endoderm. The ventrally-most migrating cells displace hypoblast cells and form embryonic endoderm. Cells that come to reside between the epiblast and endoderm become mesoderm. The cells remaining in the epiblast become ectoderm.
What major body structures are eventually formed from each germ layer?
ECTODERM: Epidermis, hair, nails, cutaneous and mammary glands; central and peripheral nervous system
MESODERM: Paraxial: Muscles of head, trunk, limbs, axial skeleton, dermis, connective tissue; Intermediate: Urogenital system, including gonads; Lateral: Serous membranes of pleura, pericardium, and peritoneum, connective tissue and muscle of viscera, heart, blood cells
ENDODERM: Epithelium of lung, bladder and gastrointestinal tract; glands associated with G.I. tract, including liver and pancreas.
How does the trophoblast become transformed into chorion and placenta?
Magic, or, in certain cases, witchcraft.
What is the notochord, and what two of its main functions?
The rostral-most epiblast cells that migrate toward and through the primitive streak are channeled through the anterior swelling of the streak - Hensen’s node. Many cells which migrate through Hensen’s node and descend into the mesoderm subsequently migrate rostrally and form a thick cord of cells called the notochord. Toward the end of gastrulation, the primitive streak regresses, and as it regresses, the notochord lengthens. The notochord is an immensely important structure in the early embryo: it lends longitudinal mechanical support to the embryo, but - most importantly - is serves as a powerful inductive force on the subsequent differentiation of many cell types. Notably, it is the prime inducer of nervous system development. Eventually, the vertebral column forms around the notochord.
What is the neural plate?
The first stage of nervous system formation occurs when epiblast (ectoderm) cells directly overlying the notochord are induced by the notochord to proliferate and to form a thickening called the neural plate. By about the 18th day, the neural plate begins to buckle, forming neural folds.
What are somites?
The paraxial mesoderm gives rise to somites, which are periodic thickenings that occur along the length of the paraxial mesoderm. They begin to form at about the time of neurulation (the third week). They form in pairs, one on each side of the notochord, and eventually 42 to 44 pairs are formed by the end of the fifth week. The
somites give rise to most of the axial skeleton and associated musculature, and the adjacent dermis of the skin.
Neural folds?
By about the 18th day, the neural plate begins to buckle, forming neural folds. The neural folds at the cranial end of the embryo enlarge, and will ultimately form the brain. By the end of the 3rd week, the neural folds have curved around and fused to form a tube, called the neural tube.
Neural tube?
neural folds have fused
ectoderm fully enclosed
end of the third week
How does the neural crest and its derivatives form, and what structures do they give rise to?
At the time the neural tube is forming, a population of cells, the neural crest cells, detach from the lateral border of the folds, and actively begin to migrate within the embryo. The neural crest cells eventually give rise to a number of structures, including the spinal and autonomic ganglia, Schwann cells, the meninges, the adrenal medulla, and melanocytes. Because of this, they are sometimes referred to as the “fourth germ layer.”
What are epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions?
gastrulation and neural crest cell migration. Both instances involve an epithelial-to-mesenchymal transition (MET).
Snail (a transcription factor) represses cadherin, claudin and occludin expression, which results in loss of adherens and tight junctions.
Matrix metalloproteinase and vimentin expression is increased. These promote the detachment of cells from an epithelium and convert them into mesenchymal-like cells able to invade the extracellular matrix.
Specific Binding
Specific binding is a criteria for both strength of interaction and selectivity. Different biological systems depend on different binding stringencies. Antibodies must precisely identify pathogens while ignoring self material.
Tell A from B
Affinity
very tight interaction at one small region. How well you hold it
Avidity
several interactions that resemble a zipper Cooperative interactions
The sum of many tiny binding sites yield very high binding strength.
PAMP
Pathogen Associated Molecular Patterns
imunogen
Molecular moieties (i.e. parts) that are absolutely required for pathogen survival
Recognition system has co-evolved with the appearance of the PAMP
Examples Endotoxin Flaggelin dsRNA CpG DNA Peptidoglycan Terminal mannose
DAMP
Damage Associated Molecular Patterns imunogen Occult and obscured from the defense mechanisms Danger signal Damage signal Recognized by the Innate immune system Examples Proteins Heat Shock proteins Non-Proteins Uric acid crystals ATP DNA Heparin sulfate Hyaluronan fragments S100 molecules
Toll-like Receptor
Toll Like receptors are surface molecules with recognition sites for PAMPs, DAMPs and other soluble factors that bind PAMPS (i.e. MD-2/CD14/LBP)). Nine different TLRs have been identified. Three are found in the endosomal compartments of phagocytic cells (e.g. Neutrophils, Macrophage, Dendritic Cells and B-cells). Six are expressed on the cell surface as dimers (homodimers or heterodimers). The TLRs initiate danger signals using the transcription factors NF-κB (Inflammation) and IRF3 (Viral response, increase MHC class I expression)
Natural Immunization
Artificial Immunization
Passive Immunization
Active Immunization
know ‘em
T-cell receptors
T cells express surface receptors that weakly recognize peptides
Peptides must be displayed for detection
T cells screen mDCs for Ag
A match results in T cell activation
Positive Selection
In order to be positively-selected, thymocytes will have to interact with several cell surface molecules, MHC, to ensure reactivity and specificity.[3] Positive selection selects cells with a T cell receptor able to bind MHC class I or II molecules with at least a weak affinity. This eliminates (by a process called "death by neglect") those T cells which would be non-functional due to an inability to bind MHC.
Negative Selection
Negative selection is the active induction of apoptosis in thymocytes with a high affinity for self peptides or MHC. This eliminates cells which would direct immune responses towards self-proteins in the periphery. Negative selection is not 100% effective, some autoreactive T cells escape thymic censorship, and are released into the circulation.
What is the difference between mosaic and regulative development?
In regulative development, blastomeres initially have similar developmental potencies, each capable of giving rise to a complete embryo. The process of differentiation is responsive to environmental signals, which allows the developmental program to respond and adjust to various types of perturbations.
In mosaic development, cell fate is already assigned during cleavage, and a strict developmental plan is in place, whereby removal of one or more cells results in an incomplete embryo. Cell fate is usually determined by the differential inheritance of specific factors among daughter cells during cell divisions, in a process called asymmetric cell division.
What is the mechanism by which identical (monozygotic) twins are produced?
Occasionally, the cells of early embryos fail to adhere together normally, and can fall apart into two (or more) masses. Each mass is able to give rise to an entire individual if it occurs early enough
Splitting can occur as early as the 2-cell stage, and as late as the blastocyst stage. The later splitting occurs, the greater the chance it will not be complete, and the twins will be conjoined (not completely separated).
Define totipotent
can give rise to all embryonic and extra-embryonic cell types and structures
Define pluripotent
can give rise to all embryonic cell types and structures
Define multipotent
can give rise to multiple (but not all) cell types
Define unipotent
can give rise to just one type of cell
What is induction?
the ability of one cell (or some type of environmental signal) to influence the development of another cell. Cells are not ‘born different,’ but instead become different by receiving distinct environmental signals. This leads to a regulative pattern of development, where not only does removal of cells from an early embryo not result in missing body parts (because cell fates take longer to be instructed), but a single cell from an early embryo is able to give rise to an entire organism. This process is most obvious in higher animals, including humans.
What are morphogens
Induction: the process where one cell or group of cells changes the developmental fate of another group
Signals that alter cell fate are called morphogens
Cells producing signals are the inducers
Cells receiving the signals must be competent to respond to the signal
Instructive: cell “a” gives signal, causing specification and differentiation of cell “b”
Permissive: cell “b” already specified, but a signal from “a” allows differentiation to proceed- extracellular matrix interactions are commonly of this type
Compare paracrine, juxtacrine, and autocrine signaling
Paracrine: involves diffusable molecules
Juxtacrine: Involves cell-cell contact
Autocrine: Cells stimulate themselves
Compare the different patterns of gradient, antagonist, cascade, and combinatorial signaling
gradient: signa decreases over distance
antagonist: one morphogen on one side, competing morphogen on the other side
cascade: morphogen hits cell, causes it to produce more morphogens to pass on the signal
combinatorial: two morphogens, working together in proportions
How are trophoblast vs. inner cell mass fates determined?
Signals from the polarized outer cells (including plasma membrane and cytoskeleton) inhibit Mst1/2 phosphorylation of Yap, allowing active Yap to translocate into the nucleus and activate Tead4 transcription factors, which activate genes associated with proliferation, differentiation, and development, stimulating trophoblast formation. These genes include Cdx2, which is a transcription factor that appears to drive trophoblast formation. The hippo pathway remains active in the unpolarized inner cells, maintaining Yap and Tead4 inhibition.
How does epiblast and hypoblast formation progress?
Initially, all blastomeres express Oct4 and Nanog, transcription factors associated with pluripotency and stem cell function.
Cdx2 becomes expressed solely in trophoblast cells via inhibition of Hippo signaling.
Cells of the inner cell mass maintain Hippo signaling and express Oct4, Nanog, and Gata.
Oct4/Nanog and Cdx2/Gata inhibit each other’s expression, creating a double-negative feedback loop.
Because of the reciprocal inhibition of Oct4/Nanog and Cdx2/Gata, inner cells end up expressing EITHER Oct 4 and Nanog, OR Gata – but not both.
By an incompletely understood mechanism, Gata-positive cells segregate out to form the hypoblast.
How are sonic hedgehog, nodal, lefty, and homeobox genes involved in these processes? (Axes determination)
sonic: secreted by notochord in dorsal/ventral
nodal/lefty: The exact mechanism is still being worked out, but leftward fluid flow from the node increases the expression of the signaling molecule Nodal on the left side of the embryo.
Nodal stimulates the production of itself and another signaling molecule called Lefty, which is antagonistic to nodal (nodal and lefty both belong to the TGF-b family). Not enough lefty is produced to inhibit nodal on the left side, but it is enough to inhibit the lesser amounts of nodal expressed on the right side.
Nodal stimulates the production of Pitx2, a transcription factor that modulates gene expression patterns associated with l-r asymmetry.
homeobox: Arranged in the same general order on chromosome as ant-post axis
How are signaling pathways related to the the regulation of gene expression?
Secreted signaling molecules play central roles in mediating inductive events – for example, FGF (fibroblast growth factor) in eye formation, and Shh (sonic hedgehog) and BMP (bone morphogenetic protein) in neuronal differentiation.
A common mechanism of action is that secreted paracrine factors induce target cells to produce different sets of transcription factors, which then specify cell fates.
What are the ‘big five’ signaling pathways involved in morphogenesis, and what are their basic features?
TGF pathway (transforming growth factor; includes TGF and BMP proteins)
Hedgehog pathway (sonic hedgehog is the protein mammals express)
FGF pathway (fibroblast growth factor; includes a number of FGFs)
Wnt pathway
Notch pathway
How is cell migration and cell adhesion involved in morphogenesis?
know this
How do cadherins function in this process? (morphogenesis)
Selective cell-cell adhesion is mediated by cadherins that are expressed in tissue-specific patterns
How is the metastatic spread of cancer like the cell movements that occur in embryogenesis?
know this
What is chemotaxis?
movement according to certain chemicals in the environment
Asymmetric cell division
unequal partitioning of specific factors among daughter cells during cell division. Essentially, daughter cells are ‘born different,’ resulting in the assignment of different fates as daughter cells are produced. This process is very obvious in lower animals.
Brief Summary of Early Developmental Events
Trophoblast/inner cell mass formation (induced by peripheral and cytoskeletal signals via Hippo pathway)
Formation of a epiblast and hypoblast (accompanied by differential expression of Oct4, Nanog, and Gata transcription factors)
Formation of ectoderm, mesoderm and endoderm via gastrulation
Formation of specific tissues and organ rudiments from cells of the different germ layers, which achieve their adult organization through embryo rolling and folding.
These events reflect two fundamental processes:
A progressive restriction of cell fate
Extensive cell motility and migration events
Potencies of trophoblasts and epiblasts
Trophoblast cells can only give rise to extraembryonic tissues, and only epiblast cells give rise to all of the cells of the fetus; thus, these cells are associated with different potencies.
Dorsal-ventral axis formation
Initially, the neural tube resembles a homogeneous collection of cells which are committed to a neural fate, but not yet specified to a particular type of neural cell. This changes when the notochord induces the ventral floor plate to secrete sonic hedgehog (Shh), and when the overlying ectoderm induces the dorsal roof plate to secrete BMP. The apposing gradients formed instruct the cells in between to express particular transcription factors (like Pax6, Pax7, and NKx6.1), and adopt specific fates. As with eye development, there are additional positional signals that come into play. Another fundamentally important family of transcription factors that is involved in instructing positional identity along the anterior-posterior axis are the Homeobox (or Hox) genes. This gene family has been shown to be responsible for body patterning in organisms as diverse as fruit flies and humans.
Left-right axis formation
A surprising clue to l-r axis determination was the discovery that dynein mutants/knock-outs exhibit random placement of asymmetric organs.
It was then discovered that ciliary cells of the primitive node establish directional fluid flow from right-to-left (by all beating in the same direction).
The exact mechanism is still being worked out, but leftward fluid flow from the node increases the expression of the signaling molecule Nodal on the left side of the embryo.
Nodal stimulates the production of itself and another signaling molecule called Lefty, which is antagonistic to nodal (nodal and lefty both belong to the TGF-b family). Not enough lefty is produced to inhibit nodal on the left side, but it is enough to inhibit the lesser amounts of nodal expressed on the right side.
Nodal stimulates the production of Pitx2, a transcription factor that modulates gene expression patterns associated with l-r asymmetry.
Anterior-posterior axis formation
Hox genes – Homeobox genes Involved in anterior-posterior axis formation
Organized in a gene complex of 13 genes (repeated 4 times on different chromosomes; HoxA, B, C and D)
Encode transcription factors that contain homeodomains: a DNA-binding sequence of 60 amino acids
Arranged in the same general order on chromosome as ant-post axis
RA appears to be involved in regulating Hox expression; Exogenous retinoic acid (RA) can disrupt normal patterns of Hox gene expression
RA found in the primitive node; the longer cells are reside in the node (exposed to RA), the more posterior fate they adopt.
List and explain the adaptive responses to physiologic stimuli and injurious stimuli
hypertrophy, hyperplasia, atrophy, and metaplasia
Describe the gross patterns and microscopic findings of tissue necrosis
Morphologic appearance of necrosis is due to denaturation of intracellular proteins and enzymatic digestion of lethally injured cells
Microscopic changes of individual cell necrosis: Increased cytoplasmic eosinophilia in tissue stains (hematoxylin and eosin) Myelin figures (dead cell replaced by mass of damaged cell membranes) Nuclear changes: karyolysis (nucleus fades away), pyknosis (shrunken nucleus, can also be seen in apoptosis), karyorrhexis (pyknotic nucleus undergoes fragmentation)
Key point: necrotic cells are unable to maintain membrane integrity and their cell contents can leak out; cell specific proteins and enzymes can be detected in the blood, and this is the rationale for using diagnostic tests to detect the presence of organ specific tissue necrosis (e.g. myocardial infarct, liver damage)
List the causes and describe the mechanisms of cell injury
Depletion of ATP
Mitochondrial damage
Influx of calcium and loss of calcium homeostasis
Accumulation of oxygen-derived free radicals
Defects in membrane permeability
Damage to DNA and proteins
Define apoptosis, and describe the typical microscopic findings. Which enzyme pathway is typically activated in apoptosis?
Apoptotic cells demonstrate:
Activation of caspases (cysteine proteases)
DNA and protein breakdown
Membrane alterations with enhanced recognition by phagocytes
Morphologic features of apoptotic cells include:
Cell shrinkage
Condensation of nuclear chromatin
Formation of blebs and fragments (apoptotic bodies)
Phagocytosis, usually by macrophages
In tissue sections, apoptotic cells are typically shrunken, and appear as a round or oval mass of eosinophilic cytoplasm with fragments of condensed, often fragmented nuclear chromatin
Key point: apoptosis and necrosis often appear together
Describe the four mechanisms of intracellular accumulations, and list some examples discussed in class.
abnormal metabolism
defect in protein folding/transport
lack of enzyme
ingestion of indigestible materials
Some examples:
Fatty change of the liver, associated with alcohol abuse or nonalcoholic fatty liver disease
Cholesterol or cholesterol esters, associated with atherosclerotic vascular disease; patients can get accumulation of cholesterol within dermal macrophages (xanthomas)
Proteins can accumulate in a variety of conditions:
Reabsorption droplets in proximal renal tubules seen in renal diseases with protein loss
Excessive protein production, such as Russell bodies in plasma cells
Defective secretion of proteins, such as alpha-1-antitrypsin deficiency
Accumulation of cytoskeletal proteins, such as Mallory bodies in the liver in fatty liver disease
Aggregation of abnormal proteins, such as amyloidosis
Hyaline change is a microscopic descriptive term for eosinophilic glassy protein which can be seen in a variety of conditions
Glycogen can accumulate in various cells in patients with diabetes; patients with glycogen storage diseases (genetic enzymatic defects of glycogen metabolism) can have massive accumulations of glycogen.
Exogenous pigments (anthracosis, tattoo)
Endogenous pigments:
Lipofuscin (brown lipid), results from free radical injury and lipid peroxidation of subcellular membranes – seen in liver and heart as part of aging process, malnutrition, cancer cachexia
Melanin (skin)
Hemosiderin granules, which are aggregates of ferritin, a protein iron complex. The common bruise is an example of localized hemosiderosis. Systemic hemosiderosis can occur in disorders resulting in systemic overload of iron
Describe the two types of pathologic calcification.
Dystrophic calcifications (normal serum calcium level):
Can occur in areas of necrosis with deposition of crystalline calcium phosphate; can get heterotopic bone formation
Often seen in association with atherosclerosis, damaged heart valves, fat necrosis, tuberculosis
Metastatic calcification:
Due to hypercalcemia secondary to disordered calcium metabolism (elevated serum calcium)
Calcium phosphate is deposited in normal tissues (lung, kidney (nephrocalcinosis), gastric mucosa, systemic arteries, pulmonary veins); can get heterotopic bone formation
Four principal causes of hypercalcemia are:
-Increased parathyroid hormone production (PTH)
-Destruction of bone tissue
-Renal failure (phosphate retention, secondary hyperparathyroidism)
-Vitamin D related disorders
In your own words, describe cellular aging.
Commen da ne talomares ca nepho melandra ca.
Cellular aging is the result of a progressive decline in cellular function and viability caused by genetic abnormalities and the accumulation of sub lethal cellular and molecular damage due to effects of exposure to exogenous influences
Aging is a regulated process, controlled by a limited number of genes
Changes which contribute to aging include:
Decreased cellular replication: after a fixed number of divisions all somatic cells become arrested in a terminally non-dividing state known as senescence. Telomere shortening may play a role.
Accumulation of metabolic and genetic damage
The causes of aging, as well as strategies for reducing aging, are very active areas of research
Using examples discussed in class, explain the rationale for measuring biomarkers of cellular necrosis.
AST (aspartate aminotransferase):
Present in the liver as well as heart, skeletal muscle, brain, and kidneys.
Elevation is not specific for the liver.
ALT (alanine aminotransferase):
Only small amounts are found in tissues other than the liver, so ALT is a more specific indicator of hepatocyte injury than AST.
Tests that establish the presence of bile duct damage:
Alkaline phosphatase (ALP):
Consists of various isoenzymes found in bone, liver, placenta, intestine, and leukocytes. Increase is usually due to bone or liver disease. Measurement of gamma-glutamyl transferase (GGT, associated with biliary epithelium) can assist in determining if ALP rise is due to bone or liver.
Comprehensive metabolic profile (a group of laboratory tests) typically includes AST, ALT, and alkaline phosphatase.
Elevation of cardiac troponin I typically reflects damage to cardiac muscle:
Hypertrophy
Increase in the size of cells, resulting in increase in the size of the organ.
Can be physiologic or pathologic.
Results from increased production of cellular proteins.
Selective hypertrophy can occur at the level of the subcellular organelle (e.g. smooth endoplasmic reticulum).
Hyperplasia
Increase in the number of cells, resulting in an increase in the size of the organ.
Occurs if the cells of the organ can divide.
Can be physiologic (hormonal or compensatory) or pathologic (excesses of hormones or growth factors); new cells may arise from mature cells or tissue stem cells.
Atrophy
Decrease in cell size and number, resulting in reduced size of a tissue or organ.
Can be physiologic or pathologic.
Common causes of pathologic atrophy are:
Decreased workload
Loss of innervation (denervation atrophy)
Diminished blood supply
Inadequate nutrition
Loss of endocrine stimulation
Pressure
Results from decreased protein synthesis and increased protein degradation within the cells; increased autophagy may also be involved (“self-eating” – autophagic vacuole fuses with a lysosomal vacuole, thereby digesting cellular components with the formation of residual bodies (such as lipofuscin granules)
Metaplasia
Reversible change in which one differentiated type of cell is replaced by another cell type.
Results from the reprogramming of stem cells present in normal tissue or reprogramming of undifferentiated mesenchymal cells.
External stimuli promote expression of genes that lead to a specific differentiation pathway.
Many examples exist:
Columnar to squamous (squamous metaplasia)
Squamous to columnar (Barrett esophagus)
Connective tissue metaplasia
Key point: influences that predispose to metaplasia, if persistent, may lead to malignant transformation (e.g. Barrett esophagus leading to adenocarcinoma).
types of necrosis
Coagulative necrosis:
Architecture of dead tissue is preserved (infarct)
Liquefactive necrosis:
Digestion of the dead tissue results in liquid viscous mass; typically seen in focal bacterial or occasionally fungal infections, the microbes stimulate the accumulation of neutrophils which liberate tissue destroying enzymes, resulting in creamy necrotic material filled with neutrophils (pus)
Gangenous necrosis:
Clinical term, not specific pattern, usually applied to necrosis of a limb undergoing coagulative ischemic necrosis
Caseous necrosis:
Cheeselike necrosis associated with necrotizing granulomas, seen with tuberculosis and fungal infections
Fat necrosis:
Refers to focal areas of fat destruction
Fibrinoid necrosis:
Pattern of necrosis seen in immune reactions involving vessels
Depletion of ATP
ATP is required for virtually all synthetic and degradative processes in the cell (e.g. membrane transport, protein synthesis)
Major causes of ATP depletion are reduced blood supply of oxygen and nutrients, mitochondrial damage, exposure to certain toxins (e.g. cyanide) Depletion of ATP to 5-10% of normal levels has widespread effects on the cell. These effects include: -Failure of plasma membrane energy-dependant sodium pump (cell swelling) -Altered energy metabolism (reduced oxidative phosphorylation, increased anaerobic glycolysis, increase in lactic acid – lab test!) -Calcium pump failure -Disruption of ribosomes with reduced protein synthesis; also get misfolded proteins (unfolded protein response) -Eventually get irreversible damage and cell death
