Editing Fluids lecture notes

*started here on 03/31/10.
*on monday we start Hypertension; read the 1 paper.

==Fluid electrolyte homeostasis==
 I would suggest that she give us an outline or at least spend a longer time on the outline-like slides.

===Body fluid compartments===
*Human body is a lot of water.
**There is a large variablitiy; because fat is pro water and muscle is antiwater.
*Most of the water is in the intracellular space; 20% in extracellular fluid.
**Blood plasma is a minor part of the extracellular fluid; most of it is the fluid that is outside the cells that bathes the organs.

===Control of water movement===
*Intracellular fluid is very different than extracellular fluid (ion composition, protein comnposition).
*These are separated by just the cellular plasma membrane.
*Transprot across the membrane (particularly osmolytes) is what maintains the difference.
*Most osmolytes are ions; they are called electrolytes just becuase they have a charge.
*The transporters recognize each ion separately and specifically (Na separate from Cl).
*Book sucks at explaining electrolytes and balance.
*Valance is the number of charges: 2 for Ca++, 1 for Na+.
*Equivalents are the number of chargers per liter (or per kg water).
*Osmolar is the number of particles.
*Examples:
**1mM glucose = 1 mOsmolar, no charge so no equivalents.
**1mM NaCl = 2 mOs = 2 mEq
**1mM CaCl2 = 3 mOs = 4 mEq.
*When we talk about water movement we talk about it in terms of osmolar (that is, number of particles).
*When we talk about water movement we only talk about osmotic driving forces, not electron or concentration forces as we've discussed when we talked about Na or Cl movement.
*'''Fluid moves acording to number of molecules, not charge!'''

===Maintenance of electrolyte compositions===
*The biggest thing for maintaining these differences is NaKatpase.
**Almost every cell has atpase.
**In nonpolar cells it is found wherever; in polarized it is found on the side that faces the blood.
*If the solutes of the ECF (blood) become more concentrated, water will leave the cells.
*If the solutes of the ECF (Blood) become less concentrated, water will enter the cells.
*How can we manipulate these concepts
**If you add water, it first increases water in the ECF.  Then ECF volume goes up.  As it increases the osmolarity decreases.  This causes the water to move into cells until the osmolarity equilizes.
**If you add isotonic fluid, the ECF volume will go up.  There will be no force moving water into the cells because there is no difference in osmolarity between ECF and ICF.
**If you add NaCl to the ECF.  The osmolarity of the ECF goes up.  Water is sucked out of cells.  ECF volume will ultimately increase and osmolarity of ICF will increase, too, because of decreased water volume.

===Regulation of fluid and electrolytes===
*We regulate this routinely by eating and drinking.
*We have receptors that can monitor the ICF and ECF.
*We have sensors that sense changes in ECF volume.
*We have sensors detect osmotic concentration and/or plasma volume.
*Remember that water follows salt.
*In homeostasis:
**water in = water out,
**electrolytes in = electrolytes out

====Water balance====
*Maintianed by two mechanisms, one conscious one unconscious: thirst and kidney.
**Unconscious is hormonally controlled renal water retention via ADH.

=====Thirst=====
*Need for water sensed in hypothalamus.
*Two mechanisms that signal for this feeling, one for cellular dehydration one for extracellular dehydration.

======Cellular dehydration======
*If osmotic pressure of the plasma changes, water moves.  this happens even in sensory cells in the hypothalamus.
*They can sense a change of 1-2% osmolarity in themselves.
*Then they trigger the cerebral cortex and generate the feeling of thirst.

=====Extracellular dehydration======
*Singaling goes to the hypothalamus.
*Can be triggered by:
**acute changesis blood volume, blood pressure, or ECF.
*Examples: loss of flbood, diarrhea, vomiting, congestive heart failure (the body just thiks you have dehydration in CHF).
*Sensed by baroreceptors.
**In the corotid sinus and the aoritc arch (so big vessels directly from heart).
**They sense a decrease in blood pressure.
*Stretch receptors
**In cardiac atria and great veins.
**These are similar to baroreceptors, but are not identical.
**This is the return system, note.
*Send signals to the hypothalamus.

====Thirst and regulation of fluid intake====
*As soon as water equilibrates, the two systems are in concert.
*The systems are working against each other in congestive heart failure, however:
**baroreceptors sense a "decrease in bp" that is actually a difficulting in pumping the blood.

=====Hormonal control of water balance=====
*Cellular dehydration: There are osmoregulatory cells in the hypothalamus (different cells than from thirst cells) that send signal to release ADH from pit.
*Extracellular dehydration:
**baroreceptors sense a decrease in blood pressure and stimulate adh release.
**stretch receptors sense an increase in blood pressure and inhibit the ADH release.
*ADH is made in the hypo, released from the pit.
**ADH causes the insertion of water channels in membrane of kidney to cause water retention.

======Congestive heart failure======
*If baroreceptors are firing to sitmulate thirst and secretion of ADH, the body will retain water.  This is bad, though, if you have congestive heart failure!
*These patients will be on high levels of diuretics.

===Regulation of electrolyte balance===
*Water and electrolytes are moved separately.
*There are conscious and unconscious cravings for electrolytes just as for water.
**We don't know the mechanism for this, though.
*We know craving occurs because there are some disease stagtes that are hormone deficient and the patients crave salty food.
*Why crave stuff?  How does the body know?  Especially for non-food products?

====Hormonal controlled movement of Na+====
*Major electrolyte moved in Na+.
*We have lots of excess of Na+ in our diet.
**This can become an issue in salt-sensitive individuals to increase blood pressure.
**We'll talk about this in the hypertension lectures.
*How do we regulate?


=====Glomerular Filtration Rate=====
*Recall that this system is poised...?
*You can change GFR, but not through direct effect on the afferent vessel., it uses '''pressure naturesis'''.
*Muscles in the heart, neck, and thorax signal to the hypothalamus.
*Then the afferent vessel dilates.  This increases GFR.  This increases the filtration of water and Na+.
**this leads to increased excretion of water and Na+.
*There must be some other mechanism, though, because we would expect water and Na+ to be equally secreted but Na+ is more highly excreted than water.
**We don't know the other mechanism.
*Increase in Blood Volume = increase in BP = increase in GFR = increase in Na secretion.

=====Aldosterone - renin = angiotensin=====
*Aldosterone is the major player in regulating electrolytes.
*It is released after renin is released from the juxtaglomerular apparataus because:
***of decreased bp at afferent arteriole
**of increased activity of renal sympathetic nevers that innervate granular cells
**decrease in NaCl to macular densa cells
*Missed a slide of the juxtamerlul apparatus.
*Target of aldosterone is the distal tubule and the collecitng duct.  It causes the insertion of sodium channels.
*Extra reabsorption of Na causes water to follow and yields increased blood volume and pressure.
*There is an alternative method for releasing aldosterone: increases in plamsa potassium.
*Aldosterone works on the na channel on the apical membrane (filtrate side).

=====Peritubular capillaries=====
*These are the ones that go around the tubules and that take up the things being reabsorbed.
*There are several ways to decrease fluid uptake by these vessels:
**increased hydrostatic pressure,
**decreases in colloidal osmotic pressure.
*This is unusual.

=====Renal sympathetic nerve activity=====
*We are not talking about the release of renin.
*We are talking about sympathatic innervation of the smooth muscle cells.
*In flight or flight reaction, there is vasoconstriction in the kidney.
**This results in a lowering of the GFR and Na+ exceretion.

=====Atrial natiureti peptidec=====
*This is exactly opposite of aldosterone.
*Get specifics from Omar.
*This reduces blood pressure.

=====Miscellaneous=====
*These can be important.
*Glucocorticoids:
**Can bind the aldosterone (a mineralocorticoid) receptor.  Doesn't usually happen because in cells with a mineralcorticoid receptor also ahve an enzyme that digests glucocorticoids.  When the enzyme is over run, though, they bind.  This can happen in pts getting lots of glucocorticoids.  This can increase blood pressure.
*Estrogen
**Distracted
*Insulin
**If salt is limited, then if you stimulate insulin release because you just ate something, you'd want to conserve everthing: sugar, salt, fat, etc.
**but if there is plenty of sugar, the insulin goes up (hyperinsulinemia) such that sodium gets absorbed too much.  This increases blood pressure (a hallmark of hyperinsulinemia from insensitivity).
*Poorly absorbed ions

====Potassium regulation====
*Importance of regulating K:
**It plays a role in electrial excitability in all tissues.
**It is necessary for repolarization of action potentials.
**It is involved in pH regulation because there are lots of K/H antitransporters.
*Major player is NaKatpase.
*You can inhibit this pump with digitalis but be careful.
*Acid-base balance and insulin can also help maintain K.
*Tissue trauma and breakdown can also control K.
*How is K regulated?
**Mostly by secreting it into the filtrate.
**This happens mostly in the distal tubule.
**Two factors that control this: plasma K concentrations and aldosterone.
***Remember that we said increases in K can cause aldosterone release.  This happens because ... ?

====Calcium regulation====
*We release from the bones or collect in the bones.
*We used PTH and calcitonin to do this.

====Transport of anions====
*Cl is the main anion in the fluid.
*There are at least 4 families of transproters.
*Some can be regulated by hormones, but this is just fluid balance in an individual organ system, not systemically.
**Think CFTR and epinephrine.
**She's using epi to study CFTR in the lung.
*Bicarbonate is second main anion.
**Controlled through acid-base reactions.
**Cover it more during hypertension in next lectures.

*next we'll cover hypertension.
**We'll look at hormonal control and water balance more in this light, too.

*stopped here on 03/31/10.