endothelium conference
TRANSCRIPT
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Endothelium conference
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FUNCTIONS:
COVER ORGANS, LINE VISCERA AND BLOOD VESSELS, SECRETORY CELLS OF GLANDS
DISTINGUISHING FEATURES AND DISTRIBUTION:
ALWAYS SIT ON A BASEMENT MEMBRANE, BUT COME IN A VARIETY OF CONFIGURATIONS: CLASSIFIED ON THE BASIS OF THE SHAPE OF THE SURFACE CELLS AND WHETHER ONE (SIMPLE) OR MORE (STRATIFIED) LAYERS OF CELLS ARE STACKED UPON EACH OTHER. THESE CELLS ARE ALWAYS ATTACHED TO THEIR NEIGHBORS BY DESMOSOMES, TIGHT JUNCTIONS, AND GAP JUNCTIONS.
Epithelium
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SIMPLE SQUAMOUS – SINGLE LAYERS OF FLAT
CELLS (BLOOD VESSELS, COVERING OF
ORGANS)
STRATIFIED SQUAMOUS – MULTIPLE LAYERS OF
CELLS WITH FLAT ONES AT THE SURFACE
(SKIN, GUMS)
SIMPLE CUBOIDAL – SINGLE LAYER OF SQUARE
CELLS (KIDNEY TUBULES, LIVER CELLS, MANY
OTHERS)
SIMPLE COLUMNAR – SINGLE LAYER OF TALL,
THIN CELLS (INTESTINAL EPITHELIUM)
Epithelium HISTOLOGICAL INDENTIFICATION
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ORIGIN AND DISTRIBUTION OF
EPITHELIUM
ECTODERM - EPIDERMIS OF SKIN AND EPITHELIUM OF CORNEA TOGETHER COVERS THE ENTIRE SURFACE OF THE BODY; SEBACEOUS AND MAMMARY GLANDS
ENDODERM - ALIMENTARY TRACT,
LIVER, PANCREAS, GASTRIC
GLANDS, INTESTINAL GLANDS – ENDOCRINE GLANDS - LOSE
CONNECTION WITH SURFACE
MESODERM – ENDOTHELIUM - LINING OF BLOOD VESSELS
– MESOTHELIUM - LINING SEROUS CAVITIES
ECTODERM
ENDODERM
MESODERM
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MESENCHYMAL
CELLS
Endothelial cells
Smooth muscle cells
Fibroblasts
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Terminal bars
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ZONULA OCCLUDENS - TIGHT JUNCTION (BELT)
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TRANSCYTOSIS TO GET ANTIBODIES INTO SECRETIONS
SURFACE SPECIALIZATIONS OF EPITHELIA
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EXTRACELLULAR MATRIX -
GROUND SUBSTANCE
FIBRONECTIN - BIOLOGICAL GLUE
– (GLYCOPROTEIN)
– BINDS CELLS TO EXTRACELLULAR
– MATRIX AND TO EACH OTHER (FIBRONECTOUS JUNCTIONS)
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EPITHELIA ARE SPECIALIZED
FOR FUNCTIONS ABSORPTION - INTESTINE
SECRETION - PANCREAS
TRANSPORT - EYE, ENDOTHELIUM IN VESSELS
EXCRETION - KIDNEY
PROTECTION – AGAINST
MECHANICAL
DAMAGE AND
DEHYDRATION
SENSORY RECEPTION –
PAIN TO AVOID
INJURY, TASTE BUDS,
OLFACTORY, ETC.
CONTRACTION –
MYOEPITHELIUM
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SURFACE SPECIALIZATIONS OF EPITHELIA
ENDOTHELIUM IN VESSELS
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SIMPLE SQUAMOUS
Blood vessels
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Which luminal surface would be
provide less turbulence to blood?
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EM 10a: Endothelial cells lining
capillary with pericyte in the vessel
wall.
1. Lumen
2. Endothelial cell
3. Tight junction
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CARDIOVASCULAR
SYSTEM COMPONENT FUNCTION
HEART - PRODUCE BLOOD
PRESSURE (SYSTOLE)
ELASTIC ARTERIES - CONDUCT BLOOD AND MAINTAIN PRESSURE DURING DIASTOLE
MUSCULAR ARTERIES - DISTRIBUTE BLOOD, MAINTAIN PRESSURE
ARTERIOLES - PERIPHERAL RESISTANCE AND DISTRIBUTE BLOOD
CAPILLARIES - EXCHANGE NUTRIENTS AND WASTE
VENULES - COLLECT BLOOD FROM CAPILLARIES
(EDEMA)
VEINS - TRANSMIT BLOOD TO LARGE VEINS,
RESERVOIR
LARGER VEINS - RECEIVE LYMPH AND RETURN BLOOD TO
HEART, BLOOD RESERVOIR
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CARDIOVASCULAR
SYSTEM
HEART PRODUCES BLOOD
PRESSURE (SYSTOLE)
Vessels are structurally adapted to physical and metabolic requirements.
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CARDIOVASCULAR
SYSTEM VEINS - TRANSMIT BLOOD TO LARGE
VEINS RESERVOIR
LARGER VEINS - RECEIVE LYMPH AND
RETURN BLOOD TO HEART, BLOOD
RESERVOIR
VOLUME:
5-6 L = 12-13
PINTS/PERSON
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METHODS OF TRANSPORT
THROUGH CAPILLARY WALLS
DIFFUSION
VESICLE
TRANSPORT
CHANNELS
BETWEEN
JUNCTIONS
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Typical
endothelial
tight junction
and marginal
fold
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ENDOTHELIUM - ACTIVE CELL
HAS ENZYMES AND RECEPTORS
TRANSPORT THROUGH THIN
CYTOPLASM WITHOUT MUCH
ENERGY REQUIRED
FLAT FOR LESS TURBULANCE
NEGATIVELY CHARGED
SURFACE
NOT WETABLE SURFACE
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SUMMARY Vessels are structurally adapted to physical and metabolic requirements.
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CELL
MEMBRANE
PLASMALEMMA - 8.5 - 10 nm
FUNCTION
• POSSESS RECEPTORS FOR HORMONES
• POSSESS MECHANISMS FOR GENERATING MESSENGER
MOLECULES THAT ACTIVTAE THE CELL’S
PHYSIOLOGICAL RESPONSES TO STIMULI
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LIGAND INTERACTIONS with receptors
SPECIFICITY
SATURABILITY
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SUMMARY continued:
MEMBRANES AND RECEPTORS
MEMBRANES ARE IMPORTANT IN CELLS
• COMPARTMENTALIZATION
• SEGREGATION OF PRODUCTS
(VECTORAL REACTIONS)
• DEVELOPMENT OF GRADIENTS
• RECEPTORS PROVIDE MECHANISMS
FOR CELL’S PHYSIOLOGICAL
RESPONSE TO EXTERNAL STIMULI
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Conference considerations
• Receptor-mediated transport model
• Transport chambers to measure crossing
• SDS gel electrophoresis for MW/degradation
• Transport chambers to measure direction
• Electron microscopy for cellular detail to trace
pathway through cell
• Patient’s problem due to
– Transferrin receptors
– Transport endosomes
– Other possible
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Insulin receptors do
not recycle
clathrin coated vesicle
(dots label clathrin coat)
uncoated vesicle
(no dots)
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CONFERENCE ON ENDOTHELIAL CELLS The following paragraph introduced a paper in Science: "The mechanism by
which macromolecules such as polypeptide hormones are transported across
non-fenestrated capillaries is not well understood. Endothelial cells probably
have an important role in this process, since they are connected by tight
junctions and thus form a major barrier for the rapid diffusion of hormones to
their target cells. The control of hormonal transport across the vascular barrier
may be a rate limiting and regulating step for the mediation of hormonal action
in many tissues.“
Because of the obvious potential clinical importance of endothelial cell transport
for hormone action, drug delivery, and pathology, you decide to study the
process in detail. Being clever, you have devised the following tissue culture
model system that will permit you to examine transport of molecules across
endothelial cells in the absence of all the other competing influences that would
occur in whole animals. You have two chambers separated by a dialysis
membrane of large pore size (it permits molecules of <100,000 MW to pass
freely). You wish to examine transport of transferrin, an 80,000 MW protein that
carries iron in the blood and delivers it to cells.
After you treat one surface of the dialysis membrane with fibronectin, you
discover that bovine endothelial cells will attach and grow on it. These cells also
have receptors for transferrin, so you are in a position where you can add
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transferrin or other molecules to one side of the chamber and measure the rate of
transport to the other side of the chamber.
1. Using your assay system, you now need to develop the methodology to
study transferrin transport.
a) How could you detect movement of transferrin from one chamber to the
other? How could you test if it was degraded during transfer?
b) How could you determine if transferrin transport was specific (i.e.,
receptor-mediated) or if nonspecific transport occurred (e.g., leakage of
transferrin through portions of the filter where the cells are non-confluent).
c) Transferrin transport could be unidirectional or bidirectional. How
would you test this? If transport were unidirectional, speculate on
reasons why cells are unable to transport transferrin in the reverse direction.
2. How could you trace the pathway of transport of transferrin across the cell
membrane and cytoplasm of a vascular (endothelial) cell?
3. Using endothelial cells isolated from patients who are unable to take up
transferrin into their tissues, how could you determine if their inability to use
transferrin is due to defective transferrin receptors, defective transport of
endosomes, or some other problem?