Mechanism of urine formationMechanism of urine formationIt means the way by which the urine is formed.It means the way by which the urine is formed.

This occur by three main processThis occur by three main process1-Glomerular filtration.1-Glomerular filtration.2- tubular reabsorbtion.2- tubular reabsorbtion.

3- tubular secretion.3- tubular secretion.

Glomerular filtrationGlomerular filtration . .20%of the blood passed in the glomerular 20%of the blood passed in the glomerular

capillaries is filtrated into the bowman capillaries is filtrated into the bowman capsule ,this filtrate is formed of all plasma capsule ,this filtrate is formed of all plasma constituent except colloid (plasma protein), constituent except colloid (plasma protein),

this filtrate flow into the renal tubule , it this filtrate flow into the renal tubule , it can be measure by inulin clearance and can be measure by inulin clearance and less accurately by creatinin clearanceless accurately by creatinin clearance

The glomerular membraneThe glomerular membraneIt It is semipermiable membrane.it allow filtration of substance of is semipermiable membrane.it allow filtration of substance of small molecular weight (nasmall molecular weight (na++,, Glucose, amino acids, Glucose, amino acids, creatinin) does not filtrate substance of large molecular creatinin) does not filtrate substance of large molecular weight( proteins)weight( proteins)

It is composed of three layersIt is composed of three layers: : 11 - -Endothelial layerEndothelial layer..

22--basement membranebasement membrane..33--Layer of epithelial cellsLayer of epithelial cells..

Endothelial cell lining the glomerulus are perforated by Endothelial cell lining the glomerulus are perforated by thousands of small holes (fenestrate)thousands of small holes (fenestrate). .

Basement membraneBasement membrane

It is protein it appear por-less but it contain fenestrate through It is protein it appear por-less but it contain fenestrate through which fluids can filtratewhich fluids can filtrate

Epithelial cellEpithelial cell.. It is formed of numerous cytoplasmic It is formed of numerous cytoplasmic process this cell is called podocyteprocess this cell is called podocyte..

Functionally the glomerular membrane permits the free the glomerular membrane permits the free passage of substance up to 4nm in diameter, does not allow passage of substance up to 4nm in diameter, does not allow

passage of substance with diameter greater than 8nmpassage of substance with diameter greater than 8nm..

Factor favoring glomerular Factor favoring glomerular filtrationfiltration

11 - -The high pressure in the glomerular capillaries The high pressure in the glomerular capillaries (60 mmhg) because of the narrow efferent (60 mmhg) because of the narrow efferent arteriolearteriole. .

22--The large surface area in the glomerular The large surface area in the glomerular capillarycapillary. .

33 - -The high permeability of the glomerular The high permeability of the glomerular membranemembrane..

Glomerular capillary blood pressureGlomerular capillary blood pressure: : It is 50 mmhg but part is antagonized by osmotic It is 50 mmhg but part is antagonized by osmotic

pressure of plasma protein 25mmhg , and by pressure of plasma protein 25mmhg , and by intrcapsular pressure 10 mmhg .so the effective intrcapsular pressure 10 mmhg .so the effective

pressure50-(25+10)= 15 mmhgpressure50-(25+10)= 15 mmhg. .

Glomerular filtration rateGlomerular filtration rate It is the quantity of glomerular filtrate formed each minute in all It is the quantity of glomerular filtrate formed each minute in all

nepherons of both kidney 125ml/ minutes . The glomerular nepherons of both kidney 125ml/ minutes . The glomerular capillary blood pressure is 50mmhg ,in other capillary of the body capillary blood pressure is 50mmhg ,in other capillary of the body it is 30 only ,it is 50 not 30it is 30 only ,it is 50 not 30 because:because: renal arteries is wide and renal arteries is wide and

short and arises directly from aortashort and arises directly from aorta. . Afferent arteriole is wider than the efferentAfferent arteriole is wider than the efferent. .

Factor affecting glomerular filteration rateFactor affecting glomerular filteration rate; ; 11 - -renal blood flowrenal blood flow ; ↑ R BF →↑ G.F.R ; ↑ R BF →↑ G.F.R

22--Systemic blood pressureSystemic blood pressure ;↓S.B.P→↓G.F. R. at blood pressure 60 ;↓S.B.P→↓G.F. R. at blood pressure 60 mmhg→stop G.F.Rmmhg→stop G.F.R..

33--Constricton of afferent arterioleConstricton of afferent arteriole →↓blood pressure in the →↓blood pressure in the glomerulus →↓filtrationglomerulus →↓filtration Dilatation→↑pressure & filtrationDilatation→↑pressure & filtration

Mild constrictionMild constriction of efferent arteriole always increase filtration at of efferent arteriole always increase filtration at the beginning the beginning while strong constrictionwhile strong constriction always increase always increase

filtration at the beginning later the osmotic pressure of plasma filtration at the beginning later the osmotic pressure of plasma protein will increase and this decrease filtrationprotein will increase and this decrease filtration . .

44 - -Sympathetic stimulationSympathetic stimulation constrict both afferent & efferent arteriole constrict both afferent & efferent arteriole so decrease blood flow & decrease filtration ( During a state of so decrease blood flow & decrease filtration ( During a state of emergency ). But sympathetic supply under normal condition has emergency ). But sympathetic supply under normal condition has

no function on filtration rateno function on filtration rate . .

55 - -Intra capsular pressureIntra capsular pressure It is the pressure influenced on the bowman capsule on It is the pressure influenced on the bowman capsule on

the glomerular capillariesthe glomerular capillaries If this pressure ↑→↑G F.RIf this pressure ↑→↑G F.R This pressure increased in case of 1- uretric obstructionThis pressure increased in case of 1- uretric obstruction

22 - -edema of the kidneyedema of the kidney. .

66 - -Concentration of plasma proteinConcentration of plasma protein ; ↑Plasma ; ↑Plasma protein concentration (occur in dehydration )↑Colloidal protein concentration (occur in dehydration )↑Colloidal osmotic pressure →↓G .F.Rosmotic pressure →↓G .F.R

↓↓PP con in hypoprotonemia ↓colloidal osmotic pressure PP con in hypoprotonemia ↓colloidal osmotic pressure →↑G .F R→↑G .F R

77 - -Glomerular capillary permeabilityGlomerular capillary permeabilityIt is increased in case of nephritis ,fever, hypoxia leads to It is increased in case of nephritis ,fever, hypoxia leads to

increased G F Rincreased G F R

Filtration fraction (F.F) (F.F)It is the ratio of glomerular filtration rate to renal plasma It is the ratio of glomerular filtration rate to renal plasma

flow (0.16-0.2)flow (0.16-0.2)It is an indication efficiency of filter bedIt is an indication efficiency of filter bed . .

Function of the renal tubulesFunction of the renal tubules Tubular reabsorptionTubular reabsorption

It is the transport of substances from the lumen of the tubules to the blood It is the transport of substances from the lumen of the tubules to the blood streamstream

This process may be active or passiveThis process may be active or passive..

Passive reabsorptionPassive reabsorption This occurs by simple or facilitated diffusion requiring no energy ,down a This occurs by simple or facilitated diffusion requiring no energy ,down a

concentration gradient ,electrical or osmotic gradientconcentration gradient ,electrical or osmotic gradient. .

Active reabsorptionActive reabsorption::This requires energy because it occurs against one or more of the This requires energy because it occurs against one or more of the above gradients which utilizes enzymatic activity, specific carriers above gradients which utilizes enzymatic activity, specific carriers and it is either primary or secondary most of glomerular filtration is and it is either primary or secondary most of glomerular filtration is reabsorped again by the renal tubules, this reabsorption may need reabsorped again by the renal tubules, this reabsorption may need energy active or may not need energy (passive)energy active or may not need energy (passive)..

Active reabsorption Active reabsorption (Primary ,secondary)(Primary ,secondary) eg of eg of active reabsorption active reabsorption (na(na++ ,glucose ,amino acids, ,glucose ,amino acids, creatinin ,vitamin uric acids ,vit B12.)creatinin ,vitamin uric acids ,vit B12.)

Eg , of passive reabsorption as (water, urea )Eg , of passive reabsorption as (water, urea )

Load of a substanceLoad of a substance; ; The load is the amount of substance which is applied to the renal The load is the amount of substance which is applied to the renal

tubules in one minutestubules in one minutes Load =plasma level of substance X rate of glomerular filtrationLoad =plasma level of substance X rate of glomerular filtration. .

((Tubular or transfer maximum TmTubular or transfer maximum Tm))Maximum amount of substance in mgs which can be reabsorped or Maximum amount of substance in mgs which can be reabsorped or

secreted by renal tubules in one minutesecreted by renal tubules in one minute,,

TMTMGG It is the maximum capacity of the renal tubules to reabsorb It is the maximum capacity of the renal tubules to reabsorb glucose/min=375mg/min in man ,305 mg/min in womanglucose/min=375mg/min in man ,305 mg/min in woman It is the process of glucose reabsorption it is need carrier, the carrier It is the process of glucose reabsorption it is need carrier, the carrier leave the glucose molecule inside cell and come back to outside to leave the glucose molecule inside cell and come back to outside to

bring another molecule and so onbring another molecule and so on . . The amount of glucose reabsorption is limited ,the limitation of the The amount of glucose reabsorption is limited ,the limitation of the capacity of the tubule cell to reabsorb glucose is called capacity of the tubule cell to reabsorb glucose is called (Tubular (Tubular maxima for glucose )maxima for glucose ) at the blood glucose level at the blood glucose level 80-180 mg80-180 mg the glucose filtered is completely reabsorped by the the glucose filtered is completely reabsorped by the renal renal tubules ,when the blood glucose level exceed the threshold tubules ,when the blood glucose level exceed the threshold valuevalue 180mg %180mg % .it start to appear in urine .it start to appear in urine (glucosuria)(glucosuria) because the absorptive power of some tubule become saturatedbecause the absorptive power of some tubule become saturated..With gradual increase in the blood glucose above the threshold value With gradual increase in the blood glucose above the threshold value more renal tubules become saturated until the blood glucose level more renal tubules become saturated until the blood glucose level reach 300mg% all the tubules become saturated, at higher blood reach 300mg% all the tubules become saturated, at higher blood

glucose level ,no increase in glucose reabsorption occur, the glucose level ,no increase in glucose reabsorption occur, the excess glucose filtered is excreted in the urine as the tubules excess glucose filtered is excreted in the urine as the tubules

reach the maximum absorptive capacity it is reach the maximum absorptive capacity it is 375mg % in 375mg % in males and 305 in femalesmales and 305 in females. .

Phlorizine glucosuriaPhlorizine glucosuria;;It block reabsorption of glucoseIt block reabsorption of glucose..

So this type of glucosureia is called renal So this type of glucosureia is called renal glucosuria because it is renal in origin but glucosuria because it is renal in origin but

not due to hyperglycemianot due to hyperglycemia. .

Alloxan glucosuriaAlloxan glucosuria; ; Alloxan destroy beta cells of islands of Alloxan destroy beta cells of islands of

langerhans present in pancreas ,so there langerhans present in pancreas ,so there is no secretion of insulin .this leads to is no secretion of insulin .this leads to hyperglycemia followed by glucosureiahyperglycemia followed by glucosureia. .

Glucose transport mechanismGlucose transport mechanismIt is transport by a special carrierIt is transport by a special carrier . .

It can also transport mannose ,galactose ,xylose.& arbinose ,insulin can It can also transport mannose ,galactose ,xylose.& arbinose ,insulin can increase rate of facilitated diffusion of glucose up to 20 foldincrease rate of facilitated diffusion of glucose up to 20 fold. .

Also amino acids are transported across cell membrane by facilitated Also amino acids are transported across cell membrane by facilitated diffusiondiffusion . .

Sodium reabsorptionSodium reabsorption 85%85% of na+ is reabsorped in the proximal convoluted tubules , sodium is of na+ is reabsorped in the proximal convoluted tubules , sodium is

carried from the cells into the interstitial place by sodium pump ,The carried from the cells into the interstitial place by sodium pump ,The rapid diffusion of sodium into the cells is due to ; high sodium rapid diffusion of sodium into the cells is due to ; high sodium

permeability. A carrier protein that increase permeability it transport by permeability. A carrier protein that increase permeability it transport by facilitated diffusionfacilitated diffusion..

It is need energy obtained by ATP breakdownIt is need energy obtained by ATP breakdown. . Na+ take water with it also sodium is positive and take negative ion with it Na+ take water with it also sodium is positive and take negative ion with it

as (Cl & hco3-) ,CL Ion are more absorbed because they are more as (Cl & hco3-) ,CL Ion are more absorbed because they are more diffusible ,so water & CL are reabsorped secondary to na+ Reabsorption diffusible ,so water & CL are reabsorped secondary to na+ Reabsorption so water & cl are passively reabsorped from proximal convoluted tubule so water & cl are passively reabsorped from proximal convoluted tubule

secondary to active sodium reabsorption ,so it is known secondary to active sodium reabsorption ,so it is known as( as( obligatory H2o reabsorption)obligatory H2o reabsorption) . .

In distal convoluted tubul, collecting tubules ,H2o reabsorption , in not In distal convoluted tubul, collecting tubules ,H2o reabsorption , in not secondary to sodium reabsorption .so it may occur or not so secondary to sodium reabsorption .so it may occur or not so it is known as it is known as facultative water reabsorptionfacultative water reabsorption ,This is ,This is

under the effect of Antiduretic hormone (ADH)under the effect of Antiduretic hormone (ADH) When ADH Is high in amount ,the DCT& CT become highly permeable to When ADH Is high in amount ,the DCT& CT become highly permeable to

waterwater . .

Potassium reabsorptionPotassium reabsorption Potassium reabsorption is an active process. Potassium reabsorption is an active process.

100% of potassium reabsorbed from the renal 100% of potassium reabsorbed from the renal tubules ,65% by the proximal convoluted tubules ,65% by the proximal convoluted

tubules ,27%by thick portion of the loop of tubules ,27%by thick portion of the loop of henele,8% by distal tubules & collecting ductshenele,8% by distal tubules & collecting ducts..

Urea reabsorptionUrea reabsorptionUrea is passively reabsorped. As water is Urea is passively reabsorped. As water is

reabsorped from the renal tubules.half of the reabsorped from the renal tubules.half of the urea filtered is passively reabsorped ,while the urea filtered is passively reabsorped ,while the

other half passes into the urineother half passes into the urine..Creatinin reabsorptionCreatinin reabsorption

Not reabsorped & excreted in the urineNot reabsorped & excreted in the urine,,Protein reabsorptionProtein reabsorption

It is reabsorped in the proximal convoluted It is reabsorped in the proximal convoluted tubules by facilitated diffusiontubules by facilitated diffusion..

Tubular secretionTubular secretion;;It means formation of substance in the tubular cell It means formation of substance in the tubular cell wall, and transfer it to the tubular fluids inside wall, and transfer it to the tubular fluids inside tubules as amonia & tubules as amonia & hydrogenhydrogen..

PAHA,Diodrast& CreatininPAHA,Diodrast& Creatinin;;This substances are completely secreted by the This substances are completely secreted by the renal tubules when their plasma level don’t renal tubules when their plasma level don’t exceed 2mg%,creatinin are secreted by the exceed 2mg%,creatinin are secreted by the proximal tubulesproximal tubules..

Potassium ionsPotassium ionsDistal tubules& collecting tubules secrete large Distal tubules& collecting tubules secrete large

quantity of potassium in the tubular lumen .and it quantity of potassium in the tubular lumen .and it is depend on na/K ATP ase pump which pump na+ is depend on na/K ATP ase pump which pump na+

out of the cell at the same time k+ to inside the out of the cell at the same time k+ to inside the cellcell..

HydrogenHydrogen::Proximal tubule ,thick segment of the loop of henel Proximal tubule ,thick segment of the loop of henel

& distal tubule secrete H+ into tubular fluid& distal tubule secrete H+ into tubular fluid . .

Water excretionWater excretion Normally Normally 180 l180 l of fluids are filtered through the glomeruli , of fluids are filtered through the glomeruli ,urine volume urine volume

is about 1 is about 1 liter/day,99%liter/day,99% of filtrated water is reabsorbed, of filtrated water is reabsorbed, the rest is the rest is treated according to the body needtreated according to the body need

The kidney can excrete either watery or concentrated urine.The kidney can excrete either watery or concentrated urine. Proximal convoluted tubulesProximal convoluted tubules:: Water is passively reabsorbed as a result of active na+ reabsorption ,this Water is passively reabsorbed as a result of active na+ reabsorption ,this

known as known as obligatory obligatory waterwater reabsorptionn reabsorptionn Water reabsorption is not affected by ADHWater reabsorption is not affected by ADH THE osmotic pressure remain isotonicTHE osmotic pressure remain isotonic

Descending limb of the loop of henelDescending limb of the loop of henelPermeable to waterPermeable to water . .

Impermeable to sodiumImpermeable to sodium..

Ascending limbAscending limb;;Thinner partThinner part

Impermeable to waterImpermeable to waterUpper thick partUpper thick part

Impermeable to waterImpermeable to water Active reabsorption of cl ,passive reabsorption of sodiumActive reabsorption of cl ,passive reabsorption of sodium

Distal convoluted tubule ,collecting tubulesDistal convoluted tubule ,collecting tubulesIncrease ADH, →↑Permeability to H2O & ureaIncrease ADH, →↑Permeability to H2O & urea..

Counter current mechanismCounter current mechanismThis is a mechanism by which the urine is concentrated in the kidney. This is a mechanism by which the urine is concentrated in the kidney.

It is depend on the production & maintenances of the state of It is depend on the production & maintenances of the state of hyperosmolality or hypertoncity in the renal medullary hyperosmolality or hypertoncity in the renal medullary

interstitium by the action & structure which pass in the medulla. interstitium by the action & structure which pass in the medulla. The osmolality of the medullary interstitium gradually increase The osmolality of the medullary interstitium gradually increase from 300 ml osmol in the renal cortex to 1200-1400 ml osmol / from 300 ml osmol in the renal cortex to 1200-1400 ml osmol /

Liter at the renal papillaeLiter at the renal papillae..

The vasa rectaThe vasa recta Help to keep osmotic gradient in the medulla. Vasa recta is a special Help to keep osmotic gradient in the medulla. Vasa recta is a special blood supply to loop of henelblood supply to loop of henel..

Because any usual blood supply will remove excess na+ in the Because any usual blood supply will remove excess na+ in the hypertonic interstitial fluids' and make it loss of hypertoncityhypertonic interstitial fluids' and make it loss of hypertoncity..

But in vasa recta does not occur because vasa recta is formed of 2 But in vasa recta does not occur because vasa recta is formed of 2 limbs ascending & descending both close to each otherlimbs ascending & descending both close to each other. .

So na+ absorbed from the hypertonic solution cross from ascending So na+ absorbed from the hypertonic solution cross from ascending to descending limb also excess H2o reabsorbed from descending to descending limb also excess H2o reabsorbed from descending

limb of the loop of henel & collecting tubules pass to ascending limb of the loop of henel & collecting tubules pass to ascending and vasa rectaand vasa recta. .

So the main function of vasa rectaSo the main function of vasa recta ::

Maintain the medullary interstitum hyperosmolality ,this is achieved Maintain the medullary interstitum hyperosmolality ,this is achieved by operating as counter current exchanger system ( system that by operating as counter current exchanger system ( system that

can rapidly exchange of material between its two limb thuscan rapidly exchange of material between its two limb thus; ; 11 - -provide trapping or holding mechanism for nacl & urea in M.Iprovide trapping or holding mechanism for nacl & urea in M.I..

22 - -Remove excess water from M.IRemove excess water from M.I..

In descending limbIn descending limb; ; The solutes diffuse from M.I into the blood ., While H2o diffuse from The solutes diffuse from M.I into the blood ., While H2o diffuse from blood to M.I so the blood osmolality riseblood to M.I so the blood osmolality rise. .

In In ascending limbsascending limbs;;The solutes diffuse from the blood into M.I, while H2o diffuse from M.I The solutes diffuse from the blood into M.I, while H2o diffuse from M.I

to the blood so the blood osmolality fallsto the blood so the blood osmolality falls. . In this way, the solutes are trapped in the M.I by continues In this way, the solutes are trapped in the M.I by continues

recirculation while excess water is removed from it and both recirculation while excess water is removed from it and both effects help to maintain of M.I hyperosmolalityeffects help to maintain of M.I hyperosmolality

NoteNote;;The excess water come from two sourcesThe excess water come from two sources

Water that diffuse from descending limb of both V.R & Loop of henelWater that diffuse from descending limb of both V.R & Loop of henel Water that is reabsorbed from the collecting ductsWater that is reabsorbed from the collecting ducts. .

Increase urea promotes osmosis of Increase urea promotes osmosis of water out of the descending thin water out of the descending thin limb of loop of henel,therfore limb of loop of henel,therfore concentration of na+cl rise twice concentration of na+cl rise twice normal, so na+cl diffuse normal, so na+cl diffuse passively out of the thin segment passively out of the thin segment into MIinto MI

The counter current exchanger The counter current exchanger function of vasa recta is helped function of vasa recta is helped

byby;;11 - -They are highly permeable to both They are highly permeable to both

solutes & H2osolutes & H2o. .

22 - -They constitute the low pressure system They constitute the low pressure system of capillary at which the blood flow is of capillary at which the blood flow is small & sluggishsmall & sluggish. . Such properties allow maximal diffusion of Such properties allow maximal diffusion of solutes from ascending limb of V .R into solutes from ascending limb of V .R into

M.I and the water in the opposite M.I and the water in the opposite direction and minimize the loss of solutes direction and minimize the loss of solutes

into the blood leaving the renal medullainto the blood leaving the renal medulla. .

The vasa rectaThe vasa rectaHelp to keep osmotic gradient in the medullaHelp to keep osmotic gradient in the medulla..

Vasa recta Vasa recta is a special blood supplyis a special blood supply to the loop of henelto the loop of henel..Because any usual bllod supply will remove Because any usual bllod supply will remove excess sodium in the hypertonic solution and excess sodium in the hypertonic solution and make it loss to hypertonicitymake it loss to hypertonicity. .

But in vasa recta does not occur because But in vasa recta does not occur because vasa recta is formed of two limb ascending vasa recta is formed of two limb ascending

and dscending both close to each otherand dscending both close to each other. . So sodium absorbed from the hypertonic So sodium absorbed from the hypertonic

solution cross from ascending to dscending solution cross from ascending to dscending limblimb..Also excess water reabsorbed from descending Also excess water reabsorbed from descending limb of loop of henel , collecting tubules pass limb of loop of henel , collecting tubules pass to ascending vasa rectato ascending vasa recta..