Renal Physiology

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					PHYSIOLOGY DEC12,2011                                                               The blood in glomerular capillaries is separated from the fluid in bowman’s
Dr. Paguirigan                                                                      space by a filtration barrier that has 3 layers:
                                                                                       1.Single-celled capillary endothelium
RENAL PHYSIOLOGY                                                                       2.single-celled layer of Epithelial lining in bowman’s capsule
                                                                                       3.Glans cellular layer of basement membrane -between endothelium &
FUNCTIONS OF THE KIDNEY                                                                   epithelium
-regulate water& inorganic ion balance
-removal of metabolic waste products from blood, excreted in urine                  TUBULES
-Removal of foreign chemicals in the blood then excreted in urine                     -extending out from bowman’s capsule are the nephrotubules-lumen are
-Secretion of hormones                                                              continuous in bowman’s space; throughtout the course of tubules, composed
        Erythropoietin- controls erythrocyte production                             of single-celled layer of epithelial cell that rest on the basement membrane.
        Rennin-controls formation of angiotensin                                      As you go along the length of tubule, the epithelial cells differ in function &
                *angiotensin-influences blood pressure & sodium balance             structure.
        Dihydroxy-vitamin B3 (1,25-dihydroxy-vit.B3)-influences Ca balance          4 major divisions recognized in the tubules:
                                                                                    Proximal tubule- segment of tubule that drains directlythet bowman’s capsule
STRUCTURE OF THE KIDNEYS                                                            Loop of henle- sharp hairpin-like loop consisting of descending limb from
-Each kidney is composed of approx. 1million nephron (functional unit)                proximal tubule & ascending limb leads to the next segment of the tubule
Nephron-consist of glomerulus, tubule, collecting ducts                             Distal tubule - completely separates from its neighbors but several distal
Glomerulus- initial component of nephron                                              tubules from adjacent nephrons join to form the Collecting duct.
         -forms protein-free filtrate of blood that passes into it                    Distal tubules of other nephron should drain into the collecting duct that is
Tubules- process is filtrate as it flows through it, processing is done before it     formed from the union of the ducts towards the central cavity of the kidney.
reach the kidney as urine                                                           Then Collecting ducts unite to form renal pelvis
Glomerulus is formed from systemic arterial blood enters each kidney through
  renal artery which progressively divides into smaller branches.                   IMPORTANT REGIONAL DIFFERENCES IN THE KIDNEY
Each smaller arteries give off a series of arterioles called afferent arterioles.   Renal cortex-outer portion
  Each of these arterioles will conduct blood into a compact part that produce      -contains all glomeruli, proximal and distal tubules, outer portion of the loop of
  a balloon-like hallow capsule called bowman’s capsule                             henle and collecting ducts
The combination of glomerular capillaries &bowman’s capsule constitutes the         -Loop of henle extends from cortex bound into the inner portion (renal
  glomerulus.                                                                       medulla) to which also courses the collecting ducts on their way to the renal
The capillaries in the glomerulus invaginate into the bowman’s capsule.             pelvis
The part of the bowman’s capsule that is in contact with the glomerullar            Renal pelvis-continuous with ureter
  capillary are pushed inward but not actually in contact with opposite side of             *ureter- a tube that passes to the kidney going to urinary bladder
  the capsule. There is a fluid filled space between themBowman's space            where urine is temporarily stored until eliminated during urination via the
  which exists within the bowman s capsule.                                         urethra

                                                                                    To return the kidney blood vessels, Glomerular capillaries, instead of leading to
the veins, recombines to form another arteriole efferent arteriole                      movement of protein (protein is a high molecular weight substance)
*Efferent arteriole-blood leaves the glomerulus                                    -The urine that eventually enters the renal pelvis is quite different from
-divides into 2nd set of capillary peritubular capillaries which branch very      glomerular filtrate ‘coz as the filtrate flows from the bowman’s capsule,
profusely to form a network around the tubule and then eventually rejoins to       through the tubules, to the loop of henle, the composition is altered. The
form the veins in which the blood will leave the kidney                            alteration or exchange occurs by two general processes called tubular
                                                                                   reabsorption and tubular secretion.
                                                                                       *The tubule is in intimate association with the peritubular capillary
JUXTAGLOMERULAR APPARATUS (JGA)                                                        network. This relationship permits the transfer of materials betweenn
before the ascending limb of the lood of Henle becomes the distal tubule, it           peritubular blood and the lumen of the tubules.
  passes between the arterioles that supply the glomerulus                             -When the direction of transfer is from tubular lumen to peritubular
macula densa-short segment of the tubule                                               capillary plasma, it is called tubular reabsorbtion or simply reabsobtion
Wall of the afferent arteriole of the macula densa contains secretory                  -When the movement of substance in the opposite direction from the
  cellsgranular cells                                                                 peritubular plasma going to the tubular lumen, it is called tubular
 Combination of macula densa & granular cells is the JUXTAGLOMERULAR                   secretion or simply secretion
  APPARATUS                                                                            *that is a two way process; the substance is either reabsorbed or secreted
                                                                                       in the urine
JGA FUNCTIONS:                                                                     Tubular reabsorbtion and tubular secretion denotes only the direction of the
Granular cell-secretes rennin which is involved in blood pressure regulation       transfer mechanism but actually it’s a diffusion for some substances and it is a
  and sodium balance                                                               mediated transport for others
Macula densa- sensor of tubular fluid flow,                                        When in a mediated transport, the transport process are in the plasma
               - it also senses the fluid composition in the local hemeostatic     membrane of the tubular epithelial cell
  responses that regulates both the secretion of rennin and the weight of fluid
  secretion by the glomeruli
                                                                                   COMPOSITION OF GLOMERULAR FILTRATE
                                                                                   - Essentially low in weight
FUNDAMENTAL/BASIC RENAL PROCESSES                                                  -Contains all other substance in the plasma
URINE FORMATION                                                                    -Same concentration as blood plasma
-begins with the glomerular filtration-> it makes a backflow of the protein free       *Exceptions:
  plasma from glomerular capillaries to the glomerular membrane, capillary             --Certain low molecular weight substances that are filterable but are bound
  epithelium, basement membrane, and ends in the epithelium of the                     to plasma protein so they cannot be filtered
  bowman’s capsule                                                                     Example—half of plasma calcium & all fatty acids in the plasma are bound
-Capsule fluid filtrated in the bowman’s capsule is called glomerular fitrate          to plasma protein and not filtered
    *GLOMERULAR FILTRATE-contains all the substances that is present in the        -The glomerular fitrate as essentially protein free is not entirely true; in reality
      plasma except protein                                                        there is very small amount of protein in the filtrate since the glomerular
    -concentration is the same as blood plasma                                     membranes are not perfect barriers for protein.
    -normally does not contain protein ‘coz glomerular membrane restricts the      Normally, these filtered proteins are completely removed from the tubule so
there will be no protein that will appear in the final urine.                           -Since the glomerular capillaries are very much more permeable to fluid than
-If the kidneys are diseased, the glomerular membrane may become much                   the capillaries in the muscle or the capillaries in the skin. The net filtration
more permeable to protein even the tubules may lose their ability to remove it          pressure of 10mmHg can already cause massive filtration. So a 70kg person,
from the tubules. In either case, protein will appear in the urine                      the average volume that is filtered into the bowman’s capsule is about
                                                                                        180L/day compared to a net filtration of all the capillaries in the body is only
FORCES THAT ARE INVOLVED IN FILTRATION                                                  4L/day.
  -Glomerular filtration, like filtration across any capillary is the bulk flow
process. These capillary filtration is determined by opposing forces.                   SEVERAL INDICATIONS THAT IS REMARKABLE IN FILTRATION RATE:
  -Hydrostatic pressure difference across the capillary wall favors filtration.           To form a huge volume of filtrate. To do this, the kidney must receive a large
While protein concentration across/between the protein concentration                    share of cardiac output. Each moment the kidney receives about 25% of blood
differences across a wall and osmotic force opposes filtration. These opposing          pumped by the left ventricle. The two kidneys’ combined weight is about 1% of
forces also applies to glomerular capillaries.                                          the body weight but it receives 25% of cardiac output. Since the total volume
  -The pressure of the blood in the glomerular capillary averages about                 of the plasma in the cardiovascular system is approximately 3Liters, it follows
25mmHg. It is higher than other capillaries in the body because the afferent            then that the entire plasma volume is filtered by the kidneys about 30x/day.
arteriole of the nephron has relatively large diameters so they are less resistant      These opportunity of the kidneys to process such volume of plasma, enables
than most arterioles so more of the arterial pressure is transmitted to the             the kidneys to regulate the constitution of internal environment and excrete
capillaries. These glomerular capillary hydrostatic pressure favors filtration.         large quantities of water-waste products.
  -The fluid in the bowman’s capsule exerts a hydrostatic pressure of about
50mmHg and this is the one that also opposes filtration into the capsule.                 If you want to calculate the amount of tubular reabsorption, you can subtract
  -Another force that tends to oppose the filtration is the force that results in       the filtered load less the GFR times the plasma concentration of the substance
the presence of protein in the glomerular capillary plasma. Its absence would           and you can get the tubular reabsorption of a certain substance. Water, for
be bowman’s capsule. This unequal distribution of proteins causes the water             example, the amount of water that is filtered by the kidneys per day is 180L
concentration of the plasma to be less than that of the fluid in the bowman’s           and amount excreted per day is 1.8L. so the percent of reabsorption is 99%.
capsule so it is another opposing factor. This difference in the water                       Water:
concentration will favor osmotic flow of the fluid.                                          filtered -180L
  -For water and all low molecular weight solutes from the bowman’s capsule                  excreted-1.8L
goes to glomerular capillaries. and these flow is equivalent to what is produced             percent of reabsorbtion-99%
to a pressure difference of about 30mmHg. So the net glomerular filtation                    Sodium:
pressure will have an algebraic sum from 3 chemical forces that we have                      filtered -630g
mentioned is about 10mmHg. This pressure will initiate urine formation by                    excreted-3.2g
forcing and essentially protein-free filtration of the plasma through the                    percent of reabsorbtion-99.5%
glomerular membrane into the bowman’s capsule, then down into the tubules                    Glucose:
and into the renal pelvis. The glomerular membrane serves only as filtration                 filtered -180g
barrier and they have no energy-requiring function. It is just like a passive filter.        excreted- normally 0
  -The volume of fluid that is filtered from the glomerular capillaries into the             percent of reabsorbtion-100%
bowman’s capsule per unit of time is the glomerular filtration rate (GFR).                   Urea:
    filtered -54g                                                                     load becomes very high. The glucose will appear in the urine because the
    excreted-30g                                                                      tubules cannot reabsorb the entire filtered load.
    percent of reabsorbtion-44%                                                          Example of a passive reabsorption by means of diffusion is the reabsorption
                                                                                      of urea. Urea reabsorption is a passive process that is dependent upon the
  In tubular reabsorbtion, there is little bulk flow across epithelial cells of the   reabsorption of water. This process causes reabsorption of about 50% of the
tubules; from the lumen to interstitial fluid. So the reabsobtion is not by mass      filtered urea. Reabsorption by diffusion is of considerable importance in many
movement rather reabsobtion of some substances by diffusion and others                foreign chemicals. If you try to remember the plasma membranes, like that of
requires, more or less, mediated transport system. Except for substances that         tubular epithelium, are primarily lipid. So lipid-soluble substances can
can diffuse across tight junction between cells, tubular reabsobtion requires         penetrate through them readily. One of the major determinants of lipid
the movement of substances across several membrane.                                   solubility is the polarity of the molecule. Less polar, more lipid soluble.

                                                                                        Many drugs and environmental pollutants that are nonpolar and highly lipid
DEFINITION OF TERMS IN PLASMA MEMBRANE OF TUBULAR EPITHELIAL CELL                     soluble. So they are filtered and excreted in the urine. They are filtered in the
  luminar membrane-The portion of the plasma membrane facing the lumen                glomerulus but reabsorption by diffusion, like in water absorption, causes
of the tubules                                                                        intraluminal concentration to increase. To make it more excretable, the liver
  basolateral membrane -Beginning at the tight junctions and constituting the         transforms them into more polar metabolites. And it reduces their lipid
plasma membrane of the sides/base of the cell                                         solubility so they diffuse across the tubular wall fully and they can be excreted
  *To be reabsorbed through the cell, the substance must first cross the              more readily. Without the liver, the metabolites cannot be excreted readily.
luminal membrane then diffuses through the cytosol of the cell and finally
cross the basolateral membrane into the interstitial fluid.                             Tubular secretion- another process by which substances move from
  *Membrane then the pertitubular capillary epithelium then entry to the              peritubular capillaries into the tubular lumen
capillaries.                                                                            Hydrogen ion & potassium-most important substances that is secreted by the
  active process -If the movement across either the luminal membrane or the           tubules. The kidney is also able to secrete a large number of organic ions. Some
basolateral membrane active then the entire process is termed                         of which are normally occurring metabolites like choline and creatinine. While
  passive process-If the movement across the basement membrane into the               others are foreign chemicals like for example antibiotic, penicillin. These
capillary epithelium into the peritubuilar capillaries, by a combination of           substances diffuse from a peritubular capillaries into the interstitial fluid that is
diffusion and backflow                                                                outside the basolateral membranes of the tubular epithealial cells. They are
  transport maximum (TM) – the limit of many of the active-reabsorbtive               then actively transported across the basolateeral membrane into the cell
system in the renal tubule                                                            followed by an exit across the luminal membrane and into the tubular lumen.
         -the limit of amount of the material that they can transport per unit of
time because the membrane protein that is responsible for the transport can             The fourth function/process of the kidney,as we have mentioned,is
become saturated.                                                                     METABOLISM. The cells of renal tubules are able to systhesize certain
                                                                                      substances notably ammonia which is then added into the luminal fluid then
  Example of the active transport process for glucose. Normal persons do not          excreted. The cells are also capable in catabolizing certain organic substances.
secrete glucose in their urine because all filtered glucose is reabsorbed             Peptides,for example, is taken up from the tubular lumen or peritubular
however if the plasma glucose concentration is high and therefore the filtered        capillaries & eliminated from the body,as if excreted in the urine.
PROCESS OF MICTURATION/URINATION                                                     and the parasympathetic will not fire nerve impulses but as the bladder is filled
-The composition of urine is not significantly altered after it already reached      with urine, become distended and the stretch receptors is stimulated, reflexly
the collecting ducts, the tubules and the loop of henle where the alteration         stimulated, stimulation of the parasympathetic neurons so there's contractions
takes place.                                                                         of the bladder. So anytime anywhere the infant will just urinate by spinal reflex.
-The composition of the urine once it has reached the collecting ducts and the       The contraction will just pull the bladder outlet the pressure required the urine
renal pelvis, is not altered anymore.                                                to flow through the urethra.

                   Urine from collecting ducts & renal pelvis                          The voluntary control of micturition is learned during childhood and involves
                                       ↓                                             the skeletal muscles of the pelvic diaphragm, forms the floor of pelvis and
                             goes to the ureters                                     helps support the lower part of the UrinaryBladder.
                                                                                       Voluntary relaxation of the pelvic diaphragm will allow the neck of the
                                         by pumping process; continuously            bladder to move downwards, opens the bladder outlet while simultaneously
                                         propelled by contractions of the            stretching the wall of the bladder and eliciting a reflex bladder contraction via
                                         smooth muscles of the urethral wall         parasympathetic nerves.
                                                                                       If the increase pressure resulting from the contractions of the bladder wall is
                              to the urinary bladder                                 insufficient to force the urine into the urethra, the pressure can further
                                        ↓                                            increase by voluntary contraction of the abdominal muscles and the respiratory
             intermittently ejected during urination or micturition                  diaphragm can even increase the intra-abdominal pressure so these can
                                                                                     increase the pressure acting on the bladder so you can expel the urine.
  The urinary bladder is a balloon-like chamber that its walls are made up of          The voluntary control is now in the pelvic diaphragm, which we learn from
smooth muscles.                                                                      childhood to control it, not like the infants that they cannot control urination
  The smooth muscle at the neck of the urinary bladder is the one that act as        ‘coz they it’s just the basic spinal reflex.
the sphincter and we call it the internal urethral sphincter.
  This is not a distinct muscle from the muscle of the UrinaryBladder which is          Micturition can also be stopped voluntarily, just simply by contracting the
only a last portion of the bladder and first portion of the urethra.                 pelvic diaphragm. Halimbawa Umiihi ka bigla kang nakakita ng ahas, edi
  When the bladder is relaxed, the outlet of the bladder is closed. When the         gagawin mo, tumayo kaagad.
urinary bladder is either actively contracts or passively distended, the outlet is   The last drop of urine is expelled by different muscles…
full open by changes in the bladder's shape. It open so you can urinate, but this    In the female, the urinary bladder wall that expels the last drop of urine
can be controlled by several factors.                                                In male, I think it's the flexor digitorum (lol) . So if I ask that in the examination,
  In an infant, the micturition is basically a local spinal reflex and the time,     it would be a subjective answer. It depends if you’re a male or female (lol).
even the place, when they urinate is dependent entirely on the volume of
urine in the bladder active to this spinal reflex only.
  The bladder wall stretch receptors afferent fibers enter the spinal cord and
this stimulates the Parasympathetic nerves smooth muscle to the bladder. If
they are stimulated, there's bladder contraction and the bladder they contain
only small amount of urine but the internal pressure is low so little stimulus
PROCESSES THAT INVOLVE VOLUNTARY CONTROL OF MICTURITION                                voluntary control, mawawala na un, so just purely spinal reflex.
                        Brain: conscious desire to urinate                               Another situation associated in bladder control and bladder emptying is fear.
                                          ↓                                            The sudden fear, mapapaihi ka, hindi mo na makontrol yung pag-ihi mo.
                          goes to descending pathways,                                 Or others, strong emotions, which acts via descending pathway into bladder
                                          ↓                                            innervation.
              inhibition of efferent nerves to the pelvic diaphragm
                                          ↓                                            Maganda pala maglecture kapag may microphone, hindi ka na mapapagod.
                          then pelvic diaphragm relaxes                                Wahahahahaha
                             bladder neck moves down                                   REGULATION OF SODIUM(Na) & WATER(H20) BALANCE
                                          ↓                                            -The other function of the kidney
                                bladder outlet opens                                   -The total body balance and the internal distribution of sodium and water.
                                          ↓                                              If we try to look at the amounts that we take in and is excreted, parang
                                  the wall stretches                                   ganito..
                                          ↓                                              WATER INTAKE from:
                       wall stretch receptors are stimulated                                > we normally drink - usually 1200ml or 1.2L
                                          ↓                                                 > contents in the food we take in - 1000ml or about 1L
 stimulation of the parasympathetic to the bladder smooth muscle is activated               > those that are metabolically produced - 350ml
                                          ↓                                                 TOTAL WATER INTAKE: usually 255Oml
                                  bladder contracts                                      WATER OUTPUT:
                                          ↓                                                 > insensible water loss (what we lose in the skin and the lungs)-900ml
                                 urine is micturated                                        > sweat - 50ml (in not very warm, in the normal temperature)
                                                                                            > feces - about 100ml unless You have diarhhrea
  When you were young, esp in the males, meron tayong palayuan ng ihi which                 > urine - 1500ml
we call the parabolic curve. Malayo ang mararating ng ihi mo ‘pag bata ka.                  TOTAL OUTPUT: 2550ml
Palayuan nga! Contest yun! But as you grow old, this parabolic curve decreases         In normal condition, normally functioning kidney, and normal system of the
esp. when you are above 50y/o which will drasctically decrease bec. of the             body, the water intake is equal to the water output.
enlargement of the prostate gland. So there's diminution or even absence of              Being a low molecular weight and not bound to plasma protein, Na and H20
parabolic curve. So there are individuals that when they urinate, wala na yung         are both freely filtered by the glomerulus, they both undergo considerable
parabolic curve, they just dribble. It’s just dribbling of the urine. Sabi nga nila,   reabsorption normally as we saw it is 99% and there is no secretion of these
kapag matanda ka na, naiihian na yung paa mo. That is also because of the              two. Na reabsorbtion is primarily an active process and water reabsorbtion is
decrease in the force of contraction in the UrinaryBladder.                            by osmosis. And water reabsorbtion is also dependent upon Na
  In adults, if they have damage in the CNS that interrupts the descending             reabsorbtion…That is very important!
pathways mediating the voluntary control of pelvic diaphragm, micturition will           The primary active transport of Na is via the Na-K ATPase pump that is
again go back, will come again as purely spinal reflex, like in infancy. So if         located in the epithelial cell basolateral membrane. Na is taken up to this
there's a damage in descending pathway coming from the brain controlling the           system, it goes out of the cell into the interstitial fluid. This active transport
keeps the intracellular concentration of Na very low and the cell inferior            fluid leaving the proximal tubule like the fluid entering it from the bowman’s
becomes electrically negative with respect to the outside. Therefore, there           capsule is therefore isotonic to plasma which is about 300milliosmol/L.
exist a chemical difference and also an electrical difference to move the Na out         But water permeability of the segments of the nephron beyond the proximal
of the lumen into the luminal epithelial cells.                                       tubules vary considerably. The water permeability of the distal tubule and
   This movement across the luminal membrane is either by diffusion through           collecting ducts can be high or low because it is subject to physiological
Na channels or by carrier-mediated transport. The specific mechanism varying          control.
from segment to segment of the tubule, depends upon which protein channel                The major determinant of water permeabiIity in this segment is a peptide
or transporters present on their luminal membranes. When Na moves through             hormone that is secreted by the posterior pituitary hormone that is known as
the channels, it moves along. But if it is the carrier mediated pathway , it          ADH or vasopressin. The ADH stimulates production of cyclicAMP in the
cotransports or countertransports a large number of substances together with          epithelial cells of the distal tubules and collecting ducts leading to the
Na. These substances undergo secondary active reabsorbtion or secretion. So           appearance in the luminal membrane in these segments, a protein that
for this people Na reabsorbtion is critical not only for retention of Na itself but   functions as a water channel.
for the renal processes of many other solutes.                                           In the presence of high plasma concentration of ADH, the water permeability
For example:                                                                          in the distal tubule and the collecting duct is much very high, water
-the countertransport of glucose and Na into the proximal tubular epithelial          reabsorbtion is maximal, final urine volume becomes small that can reach less
cells,                                                                                than 1% of filtered water.
-the cotransport of amino acid and lactate with Na in the proximal tubule,               In the absence of the ADH, H20 permeability of this segments is very low,
-the cotransport of Na and Cl in the ascending limb of loop of henle, this            little water is reabsorbed and therefore there is large volume of urine is
system even cotransports potassium. We call this, Na-K-Cl cotransporter.              secreted. The urine secreted is hyperosmotic that is it has an osmolality much
-hydrogen ion, these are countertransported with Na in the proximal tubules.          lower than that of the plasma. This increase urine secretion resulting from a
they are transported from the cells to lumen as Na moves in the lumen to cells.       very low ADH is termed as water diuresis.
It’s not Na alone that moves but it cotransports or countertransports other              In the disease which we know as diabetes insipidus, illustrates what happens
substances as well.                                                                   when the ADH system is destructed. Persons with this dse have lost the ability
   The movement of Na from the tubular lumen into the interstitium across the         to produce ADH. Usually as a result of the damage of the hypothalamus. DI is
epithelial cells will lower the osmolality. So the lower osmolality because it        characterized by constant H20 diuresis as much as 25L/day.
raises the concentration of the luminal fluid. When it does this, it also                The urinary concentration or the concentration of the urine takes place as
simultaneously raises the osmolality that is it lowers the water concentration        tubular fluid flows through the collecting ducts forcing to the medulla to the
of the interstitial fluid that is adjacent to the epithelial cells.                   renal pelvis. InterstitialFluid surrounding these ducts are hyperosmolar.
   The difference in water concentration between the lumen and the interstitia
causes a net osmosis of water from the lumen across the tubular cells, plasma                                     In the presence of ADH
membrane, and the tight junction of the interstitial. From there, water, Na, and                                             ↓
everything else in the interstitial fluid moves together by bulk flow into the                    water diffuses out of the ducts into the InterstitialFluid
peritubular capillaries as the final step in reabsorbtion.                                                                   ↓
   Normally, the water permeability of the proximal tubule is always very high.                       goes back to the BloodVessels in the medulla
Water molecules are reabsorbed almost as rapidly as Na ions. As a result, the
proximale tubule always reabsorb Na and water in the same proportion. The
HOW DOES MEDULLARY INTERSTITIAL FLUID BECOME HYPEROSMOTIC?                           countercurrent multiplier system → concentrated descending limb fluid
  Process is… this a complex process that sets up this interstitial                                                            ↓
hyperosmolarity, collectively called the countercurrent multiplier system                                           immediately rediluted
which takes place in the loop of henle. This loop, like the collecting duct,                                                   ↓
extends to medulla of the kidney. The fluid first flow in one direction down to                 Enters distal tubule (which is more dilute than the plasma)
the descending limb, and then to the opposite direction up to the ascending                                                    ↓ ←presence of ADH
limb. The fluid entering the descending limb from the proximal tubule is about                        water movement across the tubular epithelium
300milliosmol (osmotic like the plasma).                                                                                       ↓
  The ascending limb actively cotransports Na and Cl and is relatively                   fluid in the distal tubule will reequilibrate with the peritubular plasma by
impermeable to water. So little water follows the salt. The pumps in the                   using water until it becomes isotonic to plasma that is present in the
ascending limb do not transport Na and Cl into the descending limb but rather                      peritubular capillaries, until it becomes 300millioslol/L
in the InterstialFluids that surrounds the limbs.                                                                              ↓
  In contrast, the descending limb does not pump Na -Cl and highly permeable                              enters and flows along the collecting ducts.
to water. Therefore, the net diffusion of water out of the descending limb out                                                 ↓
into the more concentrated InterstitialFluid until the osmolality inside limb and      Under the influence of ADH, the collecting ducts become more permeable to
interstitial fluid becomes equal. The interstitial osmolality is maintained at                                               water
400milliosmol/L during this equilibrium because the ascending limb continues                                                   ↓
to pump Na-Cl to maintain the 200milliosmol/L difference between it and the            water diffuses from the collecting duct into the interstitial fluid as a result of
interstitium.                                                                               the high osmolality by the loop counter current multiplier system.
  The osmolality of the descending limb and the InterstialFluid becomes equal                                                  ↓
and both are 200milliosmol higher than that of the ascending limb. This is the                               Water enters the medullary capillaries
essence of the countercurrent system.                                                                                          ↓
  The loop countercurrent multiplier causes the interstitial fluid of the medulla                         carried out of the kidneys by venous blood
to become concentrated. It is its hyperosmolality that will draw water out of
the collecting ducts and concentrate the urine. If this system is not functioning,
then you will have water dieresis. The urine that your patient will be excreting       This water reabsorption occurs all along the length of the collecting duct.
will be not concentrated.                                                            Fluid along the collecting ducts is essentially the same osmolality with the
  However, it must be emphasized at this point that the active Na-Cl transport       interstitial fluid surrounding the loop of henle that is in the bottom of the
mechanism in the ascending limb is the essential component of this entire            medulla. So final urine becomes hyperosmotic.
system. If there is a defect in the Na-Cl transport, then the ascending limb and       Now if the plasma ADH concentration is low, the opposite will happen, distal
the whole system will be disrupted.                                                  tubules and collecting ducts become relatively permeable to water. As a result,
                                                                                     a large volume of hypoosmotic urine will be excreted.
  If we try to analyze the processes that we mentioned, you we will see that
countercurrent multiplier system concentrated the descending limb fluid but it
then immediately rediluted it so that it can entering the distal tubule that is
actually more dilute than the plasma.

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