Renal Physio.docx

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University of Manitoba
Biochem. and Medical Genetics
BGEN 3020
Jason Leboe- Mcgowan

Renal Physio ECF/ICF ECF (1/3) = extracellular fluid of two compartments – vascular (1/3) and interstitial (2/3) ICF (2/3) = intracellular fluid compartment Example: how many liters of isotonic saline do you have to infuse to get 1 liter into the plasma? 3 Liters (2/3:1/3 relationship); 2 liters in interstial space, and 1 L would go to the vascular space; it equilibrates with interstial/vascular compartments. Osmolality = measure of solutes in a fluid; due to three things: Na, glucose, and blood urea nitrogen (BUN) – urea cycle is located in the liver, partly in the cytosol and partly in the mitochondria; usually multiply Na times 2 (b/c one Na and one Cl). Audio file 6: Fluid and hemodyn 2 Normal Na is 135-140 range, times that by 2 that 280. For glucose, normal is 100 divide that by 18, let’s say it’s roughly 5, so that’s not contributing much. BUN: located in the liver, part of the cycle is in the cytosol and part of it is in mitochondria. The urea comes from ammonia, that’s ammonia is gotten rid of, by urea. B/c the end product of the urea cycle is urea. The normal is about 12; divide that by 3, so we have 4. Therefore, in a normal person Na is controlling the plasma osmolality. To measure serum osmolality: double the serum Na and add 10. Osmosis 2 of these 3 are limited to the ECF compartment; one can equilibrate between ECF and ICF across the cell membranes – urea; therefore, with an increased urea, it can equilibrate equally on both sides to it will be equal on both sides; this is due to osmosis. B/c Na and glucose are limited to the ECF compartment, then changes in its concentration will result in the movement of WATER from low to high concentration (opposite of diffusion – ie in lungs, 100 mmHg in alveoli of O , 2nd returning from the tissue is 40 mmHg pO ; 100 vs. 40, which is bigger, 100 is bigger, so via diffusion, O moves 2 2 through the interspace into the plasma to increase O to 2bout 95mmHb). Therefore, in diffusion, it goes from high to low, while in osmosis, it goes from low to high concentration. 1. Example: In the case with hyponatremia – water goes from ECF into the ICF, b/c the lower part is in the ECF (hence HYPOnatremia); water goes into the ICF, and therefore is expanded by osmosis. Now make believe that the brain is a single cell, what will we see? cerebral edema and mental status abnormalities via law of osmosis (the intracellular compartment of all the cells in the brain would be expanded) 2. Example: hypernatremia – water goes out of the ICF into the ECF, therefore the ICF will be contracted. So in the brain, it will lead to contracted cells, therefore mental status abnormalities; therefore, with hypo and hypernatremia, will get mental status abnormalities of the brain. 3. Example: DKA – have (1000mg) large amount blood sugar. Remember that both Na and glucose are limited to the ECF compartment. You would think that glucose is in the ICF but it’s not. You think that since glycolysis occurs in the cytosol therefore glucose in the ICF (again its not) b/c to order to get into the cell (intracellular), glucose must bind to phosphorus, generating G6P, which is metabolized (it’s the same with fructose and galactose, which are also metabolized immediately, therefore, there is no glucose, fructose, or galactose, per se, intracellularly). So, with hyperglycemia, there is high glucose in the ECF, so water will move from ICF to ECF. Therefore, the serum Na concentration will go down – this is called dilutional hyponatremia (which is what happens to the serum sodium with hyperglycemia). Therefore the two things that control water in the ECF are Na and glucose; but a normal situation, Na controls. Urea does not control water movements b/c its permeable, and can get through both compartments to have equal concentrations on both sides. Tonicity – isotonic state, hypotonic state, and hypertonic state We have all different types of saline: Isotonic saline, hypotonic saline (1/2 normal saline, ¼ normal saline, 5% dextrose in water), and hypertonic saline (3%, 5%); normal saline is 0.9%. We are referring to normal tonicity of the plasma, which is controlled by the serum Na. These are the three types of tonicity (iso, hypo, and hyper). Serum Na is a reflection of total body Na divided by total body H 2. For example: hypernatremia is not just caused by increased total body Na; it can also be caused by decreasing total body water with a normal total body Na, therefore there is an increase in serum Na concentration. It is really a ratio of total body Na to total body H 2. To determine serum Na, just look at serum levels. With different fluid abnormalities, can lose or gain a certain tonicity of fluid. 1. Isotonic loss of fluid – look at ratio of total body Na and water; in this case, you are losing equal amounts of water and Na, hence ISOtonic. This fluid is mainly lost from the ECF. The serum Na concentration is normal when losing isotonic fluid. ECF would look contracted. There would be no osmotic gradient moving into or out of the ECF. Clinical conditions where there is an isotonic loss of fluid: hemorrhage, diarrhea. If we have an isotonic gain, we have in equal increase in salt and water; ie someone getting too much isotonic saline; normal serum Na, excess isotonic Na would be in the ECF, and there would be no osmotic gradient for water movement. 2. Hypotonic solutions – by definition, it means hyponatremia. Hypoglycemia will not produce a hypotonic condition. MCC of low osmolality in plasma is hyponatremia. How? Lose more salt than water, therefore, serum Na would be decreased. If losing more salt than water, kidney is probably the location of where/why it is happening. Main place to deal with sodium (either to get rid of it or to get it back) is in kidney, esp when dealing with diuretics (furosemides and HCTZ). The tonicity of solution you lose in your urine is HYPERtonic, so that’s how you end up with hyponatremia with a hypotonic condition. ECF concentration is low with hyponatremia, therefore the water will move into the ICF compartment. (Osmosis-remember low to high) Example: If you gained pure water, and no salt, you have really lowered your serum Na: MCC = SIADH – in small cell carcinoma of the lung; you gain pure water b/c ADH renders the distal and the collecting tubule permeable to free water. With ADH present, will be reabsorbing water back into the ECF compartment, diluting the serum Na, and the ECF and ICF will be expanded. The ECF is expanded due to water reabsorption, and the ICF is expanded b/c it has a high concentration levels (its levels are not diluted). This can lead to mental status abnormalities. Therefore, the more water you drink, the lower your serum Na levels would be. The treatment is by restricting water. Don’t want to restrict Na b/c the Na levels are normal. When ADH is present, you will CONCENTRATE your urine b/c taking free water out of urine; with absent ADH, lose free water and the urine is diluted. Therefore, for with SIADH, water stays in the body, goes into the ECF compartment, and then move into the ICF compartment via osmosis. The lowest serum sodium will be in SIADH. On the boards, when serum Na is less than 120, the answer is always SIADH. Example: pt with SIADH, not a smoker (therefore not a small cell carcinoma), therefore, look at drugs – she was on chlorpropramide, oral sulfylureas produce SIADH. Example: Gain both water and salt, but more water than salt, leading to hyponatremia – these are the pitting edema states – ie RHF, cirrhosis of the liver. When total body Na is increased, it always produces pitting edema. What compartment is the total body Na in? ECF What is the biggest ECF compartment? Interstial compartment. Therefore, increase in total body Na will lead to expansion of interstial compartment of the ECF, water will follow the Na, therefore you get expansion via transudate and pitting edema; seen in right HF and cirrhosis. Example: hypertonic loss of salt (from diuretic) leads to hyponatremia Example: SIADH (gaining a lot of water) leads to hyponatremia
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