Lecture 25

• Know where most of it is reabsorbed and the percentages that are excreted. Don't memorize the handout, just know what Prof. D says.
  
• Proximal Tubule is really the only thing that has permeability to urea.
  
• Loosing 45% of the Urea to the Proximal Tubule and then we have 10% reabsorption coming in through the Inner Medullary Collecting duct and that varies up and down depending on ADH
  
  • When the urea gets into the inner medulla it goes into the vasa recta. The vasa recta picks it up, as it goes up it lies very tightly next to a thin descending loop of Henley of a corticle nephron. The urea gets passed to the cortical nephron and is reabsorbed.
    
• In the Late Distal Tubule and the Collecting duct we have 14% of our water reabsorption, and that is where the regulation of water reabsorption by ADH is happening (we only regulate 14% of our water reabsorption and that is a hell of a lot of water to regulate)
  
• There is only a 3% loss of that in Na
  
• When you drink beer, the alcohol blocks the action of the ADH and that increases your urine output when you go to the bar
  
• We lost a lot of K, we lost 15 % of our K (remember how much K comes in, in the first place, K is high in cell it is not high outside of the cells or plasma, so we are filtering very little K to begin with and if we are only losing 15% of that very little number then we are retaining our K pretty well)
  
• (KNOW ALL THE ONES THAT REABSORB 100%)
  
• Essentially 100% of all the Bicarbonate is reabsorbed mainly in the Thick Loop of Henle and the Proximal Tubule
  
• 100% of Protein, Amino acids, and Glucose are reabsorbed in the Proximal Tubule.
  

 
 

 
 

 
 

Micturition: Lots of different names – basically urination (Voiding is another term)

• The collecting ducts empty via the Renal Papilla via the Minor Calyces, and the Minor Calyces empty into the Major Calyces, which empty into Renal Pelvis.
  
  • In the human the end of the Collecting Duct is the end of any reabsorption.  In some animals that live in the desert they send their Loop of Henle down into the Ureter so that it can reabsorb more water. 
    
• When the Renal Pelvis starts to fill, the distention at the top of the ureter will cause a Peristaltic wave.  This wave starts in the minor calyces and works its way to the renal pelvis.
  
• Peristaltic wave pushes urine into Ureter and then a peristaltic wave carries it through the Ureter to the Bladder.
  
• The Ureter enters the Bladder at the bottom at the oblique, there is no valve, the oblique type of entry more or less functions as a valve (to prevent urine from going back up to the ureter), and it regulates the pressure. The wave should have enough pressure to push open the oblique and into the bladder. 
  
• In the wall of the bladder (in the smooth muscle of the bladder – the Detrusor Muscle) there are Mechanical Receptors that function as Stretch Receptors during the filling of the bladder.  They function for telling when the bladder is contracting and they function for telling when the bladder is expanding.
  
  • They are unique – if they are expanded or contracted they increase their firing rate. They always increase the firing rate.
    
  • They are excitatory in both cases and send a reflex arc to the spinal cord, which sends a stimulation of EPSP's to the muscle so it will contract.
    
  • If we do a Pressure (on the Y axis) Volume (on the X axis) curve on the bladder itself, for the first 300ml to 400ml of urine coming into the bladder there is very little change in pressure, there is a slow rise in pressure. Then at the 300ml-400ml mark, the change in pressure starts to rise at a rapid rate. As the pressure builds (and we have an increased firing rate of the Mechanical Receptors), Micturition Pressure Spikes occur. This is because of the reflexive action of the stretch receptors of the detrusor muscle of the bladder. The spikes go away because the brain resets the receptor, another spike occurs, and the brain resets it again (this is under Parasympathetic control).  These pressure spikes generate the sensation of needing to pee, but they can be overcome.
    
  • The neck of the bladder is initially closed to the urethra, but when receptors in the neck of the bladder are hit, IPSP's will be sent to the muscle holding the urine in, and urine will fill into the external sphincter urethra. These can get reset too but you have to mentally think about it at this point, because this is first time you get the sensation of having to go to the bathroom. Each time you reset the IPSP's the IPSP's get more and more demanding until you cannot fight it anymore.
    
  • Pudendal Nerve
    
  • On the walls of the urethra we have a second reflex action, and this is going to go back to the spinal cord, and it comes back to tell the smooth muscle urethra to relax. This gets the message of the IPSP's, and that says to relax.
    
  • During the second part of the Micturition reflex to overcome this message from the IPSP's you tighten up the relaxation of the urethra. Every time you reset the IPSP message, the stimulus from the IPSP's comes back stronger the next time, and stronger the time after that, until you can't fight the urge anymore.  It is a Positive Feedback System.
    
  • When you are peeing (we think of it as relaxing) and as soon as urine is started to be released, the bladder is being contracted and it does not get reset until it empties completely.  
    
  • All you are doing is you are not fighting the relaxation reflex anymore.  The Detrusor muscle stretch receptors increase their firing rate and the contraction of the bladder occurs until it is empty.
    
  • You are relaxing the attempt to keep the sphincter constricted.
    
  • Voluntary urination is usually initiated by abdominal compression of the bladder, and relaxation of the pelvic floor muscles.  It increases the pressure of the bladder and forces the urine into the neck of the bladder.
    

 
 

Water Balance: You must keep the amount of water in your body balanced.

• There are three main fluid compartments of the human body.
  
  • Intracellular fluid – this accounts for 25 to 28 liters in the body – fluid within cells.
    
  • Interstitial fluid – this accounts for 10.5 to 12 liters in the body.
    
  • Plasma – this accounts for 3 to 3.5 liters in the body.
    
    • Extracellular fluid is combining Interstitial fluid and Plasma.
      
  • DON'T HAVE TO KNOW LITERS
    
• Total Body Water (TBW) is stated as a percentage of total body weight.
  
  • A human's TBW is 60%
    
    • Plasma – 5% of your body weight, Interstitial – 15% of your body weight, Intracellular – 40% of your body weight  this all adds to 60% like it is supposed to.
      
• Fluids are composed of water and solutes.
  
• The amount of any one fluid in any one compartment and the flow of fluid between compartment are due to Starling Forces (Hydrostatic Pressure and Osmotic Gradient (mmHg – the pressure that was needed to offset the gradient))
  
• 1 Osmole = Avogadro's # = 6.02 x 10²³
  
  • Particles per liter or per kilogram.
    
  • If it is per liter it is Osmolarity
    
  • It if is per kilogram it is Osmolality
    
• At Standard Temperature and Pressure (STP) 1kg = 1L, but humans are not STP so we prefer to use Osmolality
  
  • As the blood flows around the osmolality changes but the osmolarity does not, this has to do with the idea that the temperature of the blood changes as you move through the body (ex. your hands are cooler than the core). Water can expand and contract as you are heating it, but a kilogram of water is always the same. This means that Osmolarity changes but Osmolality does not.
    
• Osmoles has to do with the number of particles. If you put 1 mole of Sodium chloride (NaCl) into 1 kg of solution, you would have 2 osmoles because it is the combination of two ions.  But if you put 1 mole of Glucose into 1 kg of solution, this would only creates 1 osmole because it only has 1 particle.
  
• Your Basilar Water Intake – assuming you do very little exercise (couch potato for day) and that you are at a constant temperature of 70F
  
  • 1.) Drinking Fluids consists of 1200ml per day
    
  • 2.) Eat moist foods consists of 1000ml per day
    
  • 3.) You are creating metabolic water that consists of 300ml per day (you are going to be creating water, and you are actually burning Hydrogen – and the water forms from oxidative phosphorylation in the ETC)
    
    • Total of all of these above 3 is about 2500ml per day.
      
• If we are going to get rid of this fluid you have to get rid of the 2500 ml.  We are still assuming basal level (with little exercise and you are at a constant temp of 70F).  You get rid of the fluid through:
  
  • 1.) Urine excretes about 1500ml per day
    
  • 2.) Feces excretes about 200ml per day
    
  • 3.) Sweat excretes about 100ml per day
    
  • 4.) Insensible water loss (through Skin and Lungs) – you excrete a certain amount of water from your Skin that is not perceived and you excrete about 350mL; and in the Lungs this also happens and you excrete about 350ml
    
    • All of these excretions equal about 2500mL.
      
  • If we increase the temperature in the environment (hot weather): Urine = 1200ml, Feces about 200ml, this is questionable b/c you are anorexic (if you eat less you poop less). Sweat goes up to about 1400ml. The skin stays about 350ml, but the lungs go down to about 250ml – when you get into a hot environment you are doing less work/exercise (you are dropping the amount of respirations you do) and since you don't move very much you lose less water.  And you lose a total of about 3400 ml. All of this extra comes from drinking fluids (if we have less feces). Only drinking fluid fixes this, versus during heavy exercise we drink, have increased food intake, increased breathing, etc.
    
  • If we are doing Heavy exercise – Urine drops to 500ml, Feces stays about 200ml (this is questionable, because you increase food intake), 5000ml sweat, 350ml from skin, and lungs go to 650ml because we are increasing breathing rate. This is a total of 6700ml. This comes from increased metabolic rate (metabolic water increases also), we eat more food, drinking more fluids, and lungs (more breathing).
    
  • We have poor control over our water loss.
    
    • Sweat and fecal losses can be curtailed by not eating and trying to stay cool.
      
    • Insensible can be changed by keeping activity to a minimum.
      
    • Under best of conditions you loose about 500mL a day.
      
  • Water balance is controlled by (at the intake end) the thirst feeling and ADH
    

  Basal Water Intake:
  

  • Basal = Means constant temperature of 70 degrees with little or no exercise
    

Drink Fluids	1200 ml per day
Eat Moist Foods	1000 ml per day
Metabolic Water (burn hydrogen  H2O)	300 ml per day
Total	2500 ml per day

• If you have 2500 ml coming in then you have to have 2500 ml going out
  

 
 

Basal Output

 
 

Urine	1500 ml out
Feces	200 ml out
Sweat	100 ml out
Insensible Loss             Skin             Lungs	350 ml out 350 ml out
Total	2500 ml out

Hot Weather

Urine	1200 ml out
Feces	200(??) ml out
Sweat	1400 ml out
Insensible Loss                Skin                Lungs	350 ml out 250 ml out
Total	3400

• Lungs insensible drops because in hot weather we reduce our activity and become quite so respirations are not increasing for the work we would usually be doing
  
• Because the total is 3400 we need more water
  
  • In hot weather you become anorexia, therefore you are not going to eat more
    
  • Become docile therefore lower metabolic rate
    
  • In hot weather 100% of excess comes from drinking excess fluid
    

 
 

Heavy Exercise

Urine	500 ml out
Feces	200(??) ml out
Sweat	5000 ml out
Insensible Loss                Skin                Lungs	350 ml out 650 ml out
Total	6700

• Where does the excess water come from when doing heavy work
  
  • Drink more water
    
  • Eat more moist foods
    
  • Increase metabolic rate
    
    • They all increase in heavy exercise
      
• The question marks are there because you are eating less but outputting the same amount of water in fecal matter
  

 
 

Control of water loss

• Poor control of water loss
  
• Go with out food and water die due to lack of water
  
• Sweat and Fecal loss can be curtailed by not eating and stay cool
  
• Insensible water loss can be decreased by not exercising a lot
  
• Even under extreme dehydrating condition still loss about 500 ml of water a day.
  
• Water is regulated by intake
  
  • ADH
    
  • Thirst
    

 
 

Electrolyte Balance

• What are they
  
  • Ion that can conduct electrical current in solution
    
  • Cations – Na⁺, K⁺, Ca²⁺, Mg²⁺
    
  • Anions – Cl^-, HCO₃^-, HPO₄^-, SO₄^-
    
• Na+ Balance
  
  • Single most abundant cation in the extracellular fluid
    
    • 90-95 percent of ECF is NaCl or NaHCO3
      
  • It is responsible for the osmotic gradient due to cations
    
  • It is ideal for regulating intracellular volume
    
    • Add Na+ for more volume
      
    • Take Na+ out for less volume
      
  • Na+ Intake
    
    • We don't have any Na+ receptors in our body
      
    • Regulation is monitored indirectly by osmotic receptors
      
  • Eat a low sodium diet
    
    • When you eat a super salty potato chip will not think that it is overly salty
      
    • Keep on a low Na+ diet long enough then you will adjust and think the chip is too salty
      
    • Unsure of the mechanism
      
  • Na+ Excretion
    
    • Controlled by Aldosterone
      
    • Angiotensin II
      
    • Sympathetic
      
    • Increase reabsorption of fluid increase the reabsorption of Na+ at the same time
      
    • When BP increase Na+ is excreted
      
• K+ Balance
  
  • Mainly in the intracellular fluids
    
    • Diets high in cellular basis have a lot of potassium (not in liver)
      
  • K+ is readily absorbed
    
  • Cell up take is stimulated by insulin and epinephrine
    
  • Excess K+ levels is a function of transport maximum
    
  • Getting rid of K+ is easy
    
  • K+ Defiencies are not uncommon
    
• Ca2+ balance
  
  • Parathyroid Hormone regulated blood Ca level
    
  • PTH incresase uptake of Ca2+ via vitamin D
    
  • Excretion of Ca2+
    
    • Low PTH levels decrease levels of absorption of Ca2+ in the kidney
      
• Mg2+ balance
  
  • Closely regulated but mechanism is unknown
    
  • Some transport mechanisms are shared with Ca2+
    
  • Have come paracellular Mg absorption
    
• Cl- Balance
  
  • Follows Na+ around like a little dog
    
    • Except in the proximal tubule when HCO3- is brought in
      
  • Mainly found in ECF due to intracellular protein and phosphate anions that push the Cl- out
    
• PO4--
  
  • In intracellular fluid
    
  • Therefore in the cellular Diet
    
  • Readily Absorbed
    
  • More PO4 is excreted with PTH
    
  • Absorbtion and excretion is regulated by Transport Maximium
    
• SO4-
  
  • Regulated by Transport Maximum
    

 
 

Hydrogen Ion and the Acid Base Balance of the Body

 
 

Blood	7.4
Interstitial Fluid	7.35
Cell	7.0

• So when we have a blood ph of 7.4 that represent the 7.0 or neutral pH of the cell
  
  • The blood is easier to monitor
    
• Blood pH drops to less than 7.4  Acidosis
  
  • Might be 7.3 because it represents a drop of pH in the cells and the cells would be acidic
    
• Blood pH increases more than 7.4  Alkalosis
  
• From 7.0-7.4 this is physiological acidosis
  
  • A blood pH of 6.9 – Lethal
    
  • Extreme Acidosis is 7.0
    
• Metabolic Acidosis
  
  • Based upon the HCO3- levels of your blood
    
    • <22 milliequivelents/liter of HCO3-   Acidosis
      
    • >28 milliequivelents/liter of HCO3-  Alkalosis
      
• Respiratory Acidosis
  
  • Based on the partial pressure of Carbon Dioxide
    
    • > 45 mmHg of pp CO2  Acidosis
      
    • < 35 mmHg of pp CO2  Alkalosis