Editing Chapter 19 notes (Cardiovascular system)

*started here on 01/11/10.

*Essay tests!
*More articles.
*In general, what is presented in class is what is important.
*She'll be doing 90% of the lecturing.
*There is a snow day.
*There are four equally weighted exams. "Final" is not cumulative.
*The last exam will be of normal exam length.

*stopped here on 01/11/10.
*started here on 01/13/10.

=Blood=

==Extracellular fluids==
*Includes blood plasma, lymph, and interstitial fluid.
*Lungs are a good model of interstitial fluid because the whole organ is bathed in a fluid that is critical for function but is outside of all the cells.

===Extra versus intra cellular fluids===
*Protein levels are different.
*Difference is maintained by plasma membrane.
*Sodium is high outside the cells, potassium is high inside.
*Na+ and K+ are the molecules and gradients used to move things quickly across the membrane to equilibriate.

===Extracellular fluid===
*Blood, lymph, and interstitial fluid are all similar in electrolytes.
*They are not similar in the amount of blood cells, proteins, and lipids.
*But the difference is less than between extra and intra- cellular.

===Functions of blood===
*Transport, regulation of heat, ph, and fluid balance, and defense.

====Transport====
*Moves nutrients (sugars, aas, fatty acids, electrolytes, and water), gasses (O2 and CO2), wastes (urea, uric acid, water, CO2), and hormones.
*Blood can move things that are not very soluble in water.

====Regulation====
*Heat: talked about it last semester.
*pH:
**metabolism produces pH changes but the blood has buffers to deal with this.
**blood carries acids and bases to organs of excretion.
**blood pH is slightly alkaline: 7.35-7.45.
*Fluid balance:
**Osmotic balance is normal even though osmolytes are different.

====Defense====
*Phagocytic cells:
**Part of the innate immune system.
**Ingest microorganisms.
*Antibody producing cells, T cells,
**Part of the specific immune system.
*Chemicals to regulate blood flow and clotting.

===Blood as a tissue===
*Blood is more viscous than water.
**This is because of proteins, cells, etc.
**Changing levels or proteins or cells can change viscocity which can mean it takes more work to pump it around.
**If the blood volume is elevated, the resulting elevated blood pressure can damage vessels and strain the heart.

==Blood - detail of components==
*After centrifugation, you get the plasma (55%), the buffy coat (the leukocytes), and the erythrocytes (RBCs, 45%).
*The erythrocyte fraction is called the hematocrit.
*Anemia is not making enough RBCs and therefore presents with too low hematocrit.
*Polycythemia is making too many RBCs and therefore presents with too high hematocrit.
*Hydration can also change hematocrit, too.
*Plasma and serum are different.  Serum results from allowing RBCs to clot and then spinning out.  If you put in anticoagulant in, then spin, you generate plasma.  So the difference is that plasma has clotting factors and serum doesn't.
*95% of plasma proteins are albumins and globulins.
*Fibrinogen makes up 4% of the plasma protein levels.

===Plasma proteins===
*Albumin:
**Made by the liver.
**Most abundant protein in plasma.
**Transports lipid-soluble components.
**Add an osmotic force to the plasma.
***Inside and outside of cells must be osmotically balanced and proteins can help with this.  So the albumins are blancing all the protein (like Hb) in blood cells.
*Globulins:
**alpha, beta, and gamma globulins are called that because that's the way they came off the chromatography.  So alphas are heaviest (carrying the heaviest stuff), then beta, then gammas are the lightest.
**One globulin of interest is transferrin.  It carries Fe around in the body.  It keeps Fe from wandering around and messing stuff up.  Transferrin allows the liver to store Fe.
**The gamma globulin fraction of blood serum will have the antibodies needed after a snake bite.
**Inside and outside of cells must be osmotically balanced and proteins can help with this.  So the globulins are blancing all the protein (like Hb) in blood cells.

===Plasma protein function===
*Carriers as we've mentioned.
*Act as buffers because they have lots of positive and negative side chains.
*They are part of the clotting cascade.
*They contribute from the osmotic pressure.  We call the choloital osmotic pressure to speak specifically of the effect of proteins on osmotic balance.
*Proteins can be broken down into amino acids for energy (starvation).

==Osmotic pressure - tonicity==
*Isotonic means it has the same osmotic pressure of the plasma.  Isotonic saline (0.85% NaCl) can be used to increase blood volume.
*Hypertonic means that the tonicity of the plasma is higher than normal.  This can be because you have too much protein or because you have too little water.  This means water will move out of the cells.
*Hypotonic means the tonicity of the plasma is lower than normal.  This could occur because of liver disease (albumin can't be made).  This decreases the choloital osmotic pressure.  This causes adema because the cells will take up water to balance osmotic pressure.

==Formed elements==
*We call them formed elements because most of them are not cells.
*Platelets nor RBCs are cells; RBCs have no nuclei and platelets are just chunks of cells.
*We don't have to memorize the intermediate states of the cells (myelocytes, band cells, etc.).
*''Blast'' means not fully differentiated.
*HSCs are committed to the hematopoietic line.
*Factors that stimulate HSC development:
**EPO -> RBCs
**Thromopoietin -> platelets
**Colony stimulating factor -> WBCs
**Cytokines -> WBCs
***Released by WBCs themselves.
*You can stimulate how long it takes to generate a cell but only by a day or two.
*RBCs live for only a couple of weeks.
*WBCs (particularly those for...) can live for years.

===Erythrocytes===
*Fully mature has no nucleus or organelles.
*It is a biconcaved disc for increased surface area to volume ratio and flexibility.
*We can make about 2 million RBCs / second!  That's 230 billion / day.
*You can make RBCs in the spleen and liver, but this is only under extreme conditions.
*RBCs die after 4 months because they have no nucleus so they cannot repair themselves.
*They are broken down by macrophages in the spleen, liver, and marrow.
*Hemocytoblasts -> myeloid stem cells -> proerythroblast -> bone marrow -> erythroblasts (basophilic, polychromatophilic, normoblast) -> start generating lots of Hb and turning red -> loss of nucleus -> reticulocyte (still has some small organelle) -> enter circulation -> finish up making Hb -> mature red blood cell.

====Stuff required for erythropoiesis====
*2/3 of the body's iron is in RBCs.
*We don't want to waste Fe, so we use ferritin and transferrin to store (in the liver) and transfer iron.
 Why is copper required?
*B12 is required so you can make erythrocyte maturation factor and thus mature your RBCs.
*Pyridoxine and folic acid are required for DNA synthesis since we're making lots of protein.

====Hormonal control of RBC production====
*EPO
**Causes HSCs to go down RBC lineage.
**Increases speed of differentiation.
**Comes from kidney in response to hypoxia.
*The stimulus is low blood oxygen, not necessarily low numbers of RBCs.  So it could be:
**reduced numbers of RBCs which means there is less oxygen getting carried around,
**reduced O2 in the RBCs because of high altitude,
***This is altitude sickness: can't catch breath, heart is going a mile a minute, etc.  Gets better because you make more RBCs.
**increased tissue demand for O2 because of aerobic exercise.
*EPO extends the life of patients on dialysis.  It used to be that they handed out EPO to the most needy dialysis patients.  Now that we have a purified form, it is abused by athletes.
**EPO increases RBCs which increases O2 carrying ability which leads to increased stamina.  However, more RBCs also means increased viscocity and makes the heart work harder.

===Article about EPO abuse===
*There have been 18 deaths among top cyclists because of EPO.
*Hard to measure abuse of EPO because it is natural.
*So we try to measure the hematocrit (RBCs) but this can be counter-acted with saline injection.  Well, this leads to increased volume and harder work on the heart and death.
*Doping is when you take some blood out before the event and inject them back in before the event.
*So, this is hard to catch, too, because hematocrit levels are quite variable based on temperature, work load, etc.
*So this article suggests that we measure via transferrin receptor : ferritin ratio.
*Transferring receptors are released by the RBC precursor cells so Transferrin receptor will go up whenever RBC production is up.
*Ferritin gets broken down if it doesn't have Fe bound.
*If you're making lots of RBCs, then Ferritin isn't storing any Fe, so it is going down.
*So the ratio will be very sensitive because one factor (transferrin receptor) is going up and the other (ferritin) is going down.

===More regulation of RBC production===
*Intrinsic factor is required for absorbing B12 from diet.
*B12 + IF bind to form erythrocyte maturation factor which is required for the last steps of RBC maturation.
*If you don't have this, your RBCs will not be carrying as much oxygen and a form of anemia will occur.

*stopped here on 01/13/10.

==Hemoglobin==

==Blood - ?==