1. Endothelium conference

2. Epithelium FUNCTIONS: DISTINGUISHING FEATURES AND DISTRIBUTION:
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.

3. Epithelium HISTOLOGICAL INDENTIFICATION
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)

4. 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
MESODERM
ENDODERM

5. MESENCHYMAL
CELLS
Endothelial cells
Smooth muscle cells
Fibroblasts

6. Terminal bars

8. ZONULA OCCLUDENS - TIGHT JUNCTION (BELT)

10. TRANSCYTOSIS TO GET ANTIBODIES INTO SECRETIONS
SURFACE SPECIALIZATIONS OF EPITHELIA
TRANSCYTOSIS
TO GET ANTIBODIES
INTO SECRETIONS

12. EXTRACELLULAR MATRIX - GROUND SUBSTANCE
FIBRONECTIN - BIOLOGICAL GLUE
(GLYCOPROTEIN)
BINDS CELLS TO EXTRACELLULAR
MATRIX AND TO EACH OTHER (FIBRONECTOUS JUNCTIONS)

13. 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

14. SURFACE SPECIALIZATIONS OF EPITHELIA
ENDOTHELIUM IN VESSELS

15. Blood vessels
SIMPLE SQUAMOUS

16. Which luminal surface would be provide less turbulence to blood?

17. EM 10a: Endothelial cells lining capillary with pericyte in the vessel wall.
Lumen
Endothelial cell
Tight junction

18. 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

19. CARDIOVASCULAR SYSTEM
HEART PRODUCES BLOOD PRESSURE (SYSTOLE)
Vessels are
structurally
adapted to
physical
and metabolic
requirements.

20. CARDIOVASCULAR SYSTEM
VEINS - TRANSMIT BLOOD TO LARGE VEINS RESERVOIR
LARGER VEINS - RECEIVE LYMPH AND RETURN BLOOD TO HEART, BLOOD RESERVOIR
VOLUME:
5-6 L = PINTS/PERSON

22. METHODS OF TRANSPORT THROUGH CAPILLARY WALLS
DIFFUSION
VESICLE TRANSPORT
CHANNELS
BETWEEN JUNCTIONS

23. Typical endothelial tight junction and marginal fold

24. 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

25. SUMMARY Vessels are structurally
adapted to physical and metabolic requirements.

26. 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

27. LIGAND INTERACTIONS with receptors
SPECIFICITY
SATURABILITY

28. 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

29. 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

30. Insulin receptors do
not recycle
clathrin coated vesicle
(dots label clathrin coat)
uncoated vesicle
(no dots)

32. CONFERENCE ON ENDOTHELIAL CELLS
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

33. 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?