Physiology (Urinary) Flashcards
What determines the amount of water in each body compartment
- Amount of solute in each compartment
- Amount of water is each compartment depends on the number of solute partciles in the compartment (Called Colligative property)
- How permeable the compartment is to water
Types of pressure
- Osmotic Pressure
- Hydrostastic Pressure
BOTh affect the amount of water in each body compartment
Osmotoc pressire
Membrane is permeable to water NOT other solutes
IF you add solute to compartment A = creates an osmitic pressure (compartment A has more solute than B) –> Water will move towards comparment A to normilize the solute concentraton
END - chnage the volume of the compartments so that the solute concentration will be normilized
Hydrostatic Pressure
Hydrostatic pressure = physical force pressure
Example -
1. Water coming out of the end of a harden hose = hydrostatic pressure
2. Bloop pressure
When add hydrostatic pressure it forces water through the semipermeable memebrane
- Hydrostatic pressure occurs when the kidney filters blood (hydrostatic force pushes things through the memembrane)
What does hydrostatic pressure create
Hydrostatic pressure creates osmotic pressure because it leads to differences in concetration of solutes in different compartments
Hydrostatic and osmotic pressure oppse each other
What detremermines the total amount of salts in the intracellular compartments
Osmotic pressure is driven by the number of solute artciles in each compartmemt BUT the active trasnporters determine the amount of these salts in the intracellular compartment
- Uses ATP driven pumpes
Need active trasnport otherwise everyhing would leak out and equilibrilate (would lose all gradietnts)
In order to miantain gradients = need ATP moving ions through active trasnport
Active Transport
Example - Na/K ATPase pump –> creates needed gradients
Important in creating grdaient where you have more K in intracellular and more Na in extracellular
What determines the amount of salts in teh EXTRAcellular compartment
Total amount of salts AND the composition of salts in the extracellular copartment is determined by balancing input via GI tract vs. several outflows
Ionic content of the Extra cellular Fliud is regulated by balcing outflow and intake
- Example - When you eat more salt THEN you will pee out more salt
- Extrete the same maount that you take in = maintain homeostasis
Function of the kidney
Overall - Kidney is trying to mainatin homoestasis
- Regulation of volume and composition of bodily fluids
- Regulates ECF Volume + Blood Pressure - Miantin balance/homoestasis
- Hormone Production
- Snethsis of Important compounds
- Toxin Extretion
Function o Kidney (Regulation of volume)
Kindey = regulates volume and composition of bodily fluids
- regulates EC volume and Bloop pressure
- Afefcts water and NaCl extretion or retention
Because kidneys can regulate ECF olume = regulates BP (How much volume is in the sytem affects how much pressure is in the system)
- Does this by controling water and salt
- Genes that affect BP are all expressed in the collecting duct of the kidney (all monogenic disaes causing hypotension of hypertension rsult from mutaion in renal protein)
Function of Kidney (Homoestasis)
Kidney maintains balance/homeostasis
- balnaces intake with outake for many substances (Example Acid base balance, Na, K, Cl, Phosphate, Amino Acds)
- Kidney determines if you have to much or too little based on activity or oral intake and miantains homoestaisis
- K = needs t be around 5mM - if halved or doubles = die
Function of Kidney (Hormones)
Kidneys makes homrones
includes:
1. Rennin - affects BP
2. Angiogenstin 2 - affects BP
3. Erthropeotin - affects RBCs
4. Activated for of vitamen D
Function of Kidney (synthesis)
Kidney synthesized important compounds
Example - Ammonium and Bicarbinate - important for acid base regulation
Homeostasis
The life of every organism depends upon the preservaton of constant internal envrinment
Steady State
Want everything in the body to be in steady stat (the parameter is not changing over time) BUT you want it to be at steady state at teh SET POINT
Animal is in steady state when total body water and composition are constant
Set point
Optimum conditions exist that allow the organsim to preform normal bodily functions
Example - If you have a gfeevr for 5 days you are in the steady state BUT you are not at the set point –> still feel ill
- Shows you want the steady state at the set point
How do you know you are at the set point
You have sensors to know what the set point is and how to correct to get back to the set point
Sensorys + Mediators + Efefctors = exist in order to maintain a ste pont
- To maintain set point you need sensory mechanisms to evaluate the magnitude of the components in the internal envirnment
Kidney sensorrs
There are many renal senors in the kidney + have many extra-renal sensors that will send information back to the kidney
Example - Kidney has pressure receptors (baroreceptors) + mechnanoreceptors (BOTH IN juxtagolerular aparatus)
- Allows the kidney to sense chnages in human dynamics and sense chnages in composition of fluid
- Also has renal tubules for interstitial pressire + Glemerular fluid rate)
Kidney gets infomration rom within and outside the kidney –> kidney can make decison about what to do
Kidney regulation
Kidney is the key regulator of many things
- regulation of kidney can be seen by phenotype of pateint in renal failre
In renal failure –> all things go wrong
- Kidney is a primary system = when teh kidney is not working there is not enough gain in other systems to compensate = all things are disturbed
Chart - shows kidney function + disoerder that occurrs when kidney fails
Extrection of substances equation
Extreton of a substance = intial filtration - amount Reabsorption + amount Secretion
Extrection - amont in final urine
Left = see the kidney
- Outer part is teh cortext
- Inner part = medula
Right side of image (Big grey part)
- Top part (ligtest grey)= corext ; middle great = middle meudlar (outter medula)
- Shows the nephron + greneular (bundle) + see the loop of henle + distal tube + collecting ducts
Normal kidney filtration
Kidney filters 180 L per day BUT you do not pee 180 L per day –> means a LOT of reabsorbed
A LOT of what is intially filters is reabsorbed by the kidney ONLY some will be extreted
- Primary urine is absorbed back into the body by various nephron segemnts
Glenerular
Bundle pf capilaries that atke sblood and filters it into filtrate –> Filtrate will become urine
Filtrate goes to the proximal tube (proximal to the Glamerilar) –> goes to the Loop of henle –> distal tube (goes to the collecting tube/ducts
CHECK ORDER
Functional Unit of the Kidney
Nephron
Reabsorbtion
The various nephron segments reabsorb most of the ultrafiltrate back into the blood
- Process is the result of specific transport mechanisms located in the cell membranes of each individual nephron segment.
Secretion
Some substances enter the final urine by moving across the nephron directly from the blood stream into the tubule lumen
- The final amount of these particular substances which appears in the final urine is a combination of the amount filtered at the glomerulus and that secreted into the urine.
Function of the Nephron
Glomerals (Bowmans capsul capillary Tufts) - Completes the intial filtration of urine
Proximal tubes – forst segment that urin encounters
- Function - reabsorbes 65% of total filtrate (Includes all glucose and Amio acids_
- Secretion of organic solutes
- Important in Acid/Base balance
Loop of henele - Reabsorbes 25% of filtrate
- Concentrating mechanism
Distal Tubes - rabsorbes 5% of filtrate + secretes
Collecting ducts - Reabsorbs 5% of filtrate
- Acid/base balance
- Controls Na+ and water extretion
Diatel Tubes and Collecting ducts
Can secrete or absorb the rest of the filtrate
Reabsorption
Chart - shows how much each parameter has in total ECF
Kidney filters all ECF 12-13X per day
- Amount extreted per day is lower than the amount filtered per day – BECAUSE absorb 99% of it per day (rebsorb what you are filtering
- If you were not able to reabsorb what you are filteing = you would dehdyraye very fast
How much is extreted in the final Urine
Balance of Filtratiion + reabsoprtion + secretion = affects how much is extreted in the final urine
Based on equation - Extretion = Filtration-reabsorption+secretion
Increasing hydrostatic Pressure
When you apply hyrdostatic pressure (shove piston in on one side) = leads he pressure to shove water through the memebrane –> movement of water will cerate oppsoing osmotic pressure that favors water going back to the original comparent
- Hydrosatic prssure pushing water from A to B will lead to osmotic pressure moving water from B to A
Balance of the two pressures = determines how much filtration will happen
GFR
GFR = glomerular fltration rate
Equation for GFR –> hydrostatic pressure diference that fvors filtration (PGc - PBs) ; subract from oncotic prssure differece that is oppsing filtratiion (Pic - Pibs)
- Kf is the ultrafultration constant
Use GFR to determine kidney function
- GFR is dteermined by the balance of the two forces
Kidney filtration in Glemerular
Glamerular - capilariers that will filter –> filtrate will then go to tubule and evetually will be come urine
Image
NOTE - Numbers = hydrostatic pressures and oncotic (osmotic) pressure
Hydrostatic pressure is high in on both sides of the the glamerular capilaries –> have filtering pressure from the hydrostatic pressure in capilaries themselces (hydrostatic pressure favors filteration)
Oncotic pressure is high on the right side of the capilary BUT NOT at the bottom of the capilary
MIGHT expect water to go back into the glameuli at the end of the capialry BUT based on hydrostatc pressure the water is able to go to the proximal tube
What does hydrostatic pressure
Hydrostatic pressure favors filtration
Why is there no oncotic pressre in the capilary itself (no oncotic pressure in the bottom of the capilary)
No oncotic pressure i the bottom of the glamerili because in a helathy person there is no proetin in the filtrate going through the glomerular = no protein in the glamerular capilaries
BUT have high oncotic pressure at the end of the caplaries because proteins have been maimatined and the fluid is lost
- At the end of the capilaries you have oncotic presure that is oposing the filtration (oppsoning hydrostatic pressure)
Organization of the vessels in the glameruli/kidney
Organization of renal vaculature is unique
Have artial + capilary bed THEN anotehr arterial + capilary bed
This sturcture is the reason filtration can happen at the glamerular (because this organization allows the hydrostatic pressure to stay high on both sides)
- IF had a vein on the other side = hydrostic pressure would drop
- Kidney is able to filter because of the organization keeping this hydrstatic pressure high
Peritubular capilaries
Hydrstatic pressure drps because have vein on one side
Have arty + capilary bed + vein –> presnece of the vein causes the hdyrostatic pressure to drop
Why is Pibs included if there is no protein in filtrate
PiBS (osmotic pressure (protein ressure) within the gameular) - should equal 0
BUT the term is still included in the equation becaue the value is equal to zero in health BUT not in disease
Chnages in pressure in glamerular capilaries + peritubular capilaries
Glamerular capilary has arterial on both sides = keeps hydrostatic pressure high (Pc stays high) = drives fltration despite the fcat that osmotic preessire rises at the end of the glomerular capilary (Pic gets higher at the eend of the capilary)
- have low GFR
In peritubrlar capilaries - hydrostatic pressure is low and oncotic pressire is high (low Pc and High PiC) = allsows for reabsorption
Sturcture of the filtration barrier
There is no protein in the filtrate going through the glameular because of the structure of the filtration barrier
Stucture includes obstacles that things ahve to go through to go from the capialry lumen to bowmans space (first part of tube)
- Na and water can go through freely BUT larger things get stuck in the capilary lumen
- Structure acts like a collender –> water goes through BUT bigger things get stuck (plasma proteins and larger molceules get stuck and can’t go through)
Crossing the Filtration barrier
Chart - shows the weight + radius + Concetration ratio
- Concentration ratio = filtrate/blood
Value:
1.0 = no barier to being filters (goes from one side to another)
- Example - urea and glucose are freely filtered - can pass through the barrier
Larger mo;ecular weight OR large radius = the molecule would be exluded from urine and the concetration ratio decreases
Estimating GFR
I think she skipped but her notes:
Inulin 90-120 ml/min
Sinistrin also
NOT creatinine
Chart of substances that are absrobed or secreted
Chart:
X-Axis - Different segemnts of the nephrone
Y Axis - ratio of amounts (hard to know concetration because the water is always changing)
Each line on the graph = different substance –> can see how the substance is handled in the nephron
IF the line goes down = the substance is reabsorbed into the blood
IF the line goes up = the substance is secreted into urine
IN chart = see that a lot of reabsorption occurs in the proximal tube
Insulin
Substance that is filtered BUT NOT screted and NOT reabsorbed = used for GFR
- Has straight line in graph
- Can easily know filtration rate
Creatine
Used in the clinic to measure renal function
Creatin = secreted a little by the proximal tubule (see line goes up) –> thsi complicates things
- The amount scereted by the proximal tubule chnages in disease = it is not a perfect substance BUT it is easily measure –> it can give a genral idea of the glamaeular filtration rate (know the idea of if the genral glameular filtration rate is correct)
Issue = creatine can’t pick up mid defects in kdiney function
Secretion and absorption of different dubstances
IF the line goes down = the substance is reabsorbed into the blood
- Glucose + AA + Porteins, Na are reabsorbed in the proximal tube
IF the line goes up = the substance is secreted into urine
- Urea is secreted in the Loop of henele
LOOK at chart to see where secreted and where absorbed
What do you NOT want to pee out
Things that the body spent ATP to make you do NOT want to pee out
- 99% of what is filtered is reabsorbed
Example - Glucose + Amino Acids + Protein should NOT be in final urine
Diabetes = have glucose in urine
Movment of Urea in Nephron
Morvment of Urea is imoortant for how kidneys concetrated Urine
Urea (or urine?) is cycling through the nephron by being reabsorbed –> secreted –> reabsrobed
- Cycling is required for concetrating
Na and water in the moving through the nephron
Chart - Na line and water line overlap until the distal tube –> after the distal tube they become seperate
- In the proximal tube and the Loop of Henle the Na and water are reabsored together (Na and water are isoosmotic)
- Na and water have to be seprated in later part of nephrone
- Na and water are reabsorbed together earyy BUT then have fine tubed conrtol that the kidney needs to have in toder to maintain homoestasis so you seperate the handling of Na and water later in the nephron
Important part of Na absorption
Most important part for Na = last part of absorption
BECAUSE the 65% and 25% in teh promxinal tube and Loop of henle won’t change (always the same amount) BUT the last segemnt is about fine tubing how much to reabsorbe (will make small adjustments)
- Regulation happens in teh distal fine tuning (last segment does the fine tuning in repsonse to hormones coming for otehr parts of the body to tell the nephron how much Na and water is needed)
- 65% and 25% = values for males ; females rely less on the proximal tubule and more on the loop (differnces in how salt and water are hanlded in males and females)
The kdiney filters all blood 12-13X per day = small adjustments make a bog difference in Extracellular fluid
Absorption of water
Start of nephron - water is reabsorbed isomoticly with Na THEN have seperation
- Seperation can occur in different places
How much water you absorb is different based on how much water you drink
- How concetrated urine is = based on how much you drink (diference in final osmolarity in urine is based on how much as been reabsprbed)
- At the end of the nephron water is either reabsorbed more or not depending on how much water you drink
Water T/P ratio
T/P - osmoalrity of the forming urine/osmolarity of the plasma - line going up be reabsorption
T/P doesn’t chnage in the proximal tubule because Na and water are isomatic –> ratio is indifferent
In loop of henle = urine is initially conetarted
- Different lines in chart show different hydration status = have different urine concetration
- High water or low water = affects the final omolarity of the urine
Potasium reabsorpbtion in nephron (overall)
Postasum = reabsorbed in the proximal tubule ; Fine tuning occurs in the dstal part of the nephron
Chart - have 2 lines depending on the amount of K in the body (amount of K in body affects how K is handled in the nephron)
- Kidney can reabsorb K if you need more or can extrete K to get rid of it
Healthy K = 4 Milimolar (if have wrong concetraton then you can die so it is regulated well)
Potasium reabsorpbtion in nephron (Values)
Proximal Tubule = reabsorbe 80% of K
- Always 80% in proximal tubuls no matter if have high dietray K or low K
- Reabsorpton in the oop is similar in both high and low K
- Males - 70% ; females 55% in PT
Distal part of nephron = can absorbe 2% and then 6% OR you can extrete more K to protect plasma K levels
Urine secretes more or less K to make sure the blood vlume K stayes steady
How do epithelial cells more ions (overall)
Epithelial cells trasnport salts and water into or out of a compartment
- Have polar/direction vectroial transport
Need to localize proteins in certain parts of the cell (basal or apical) –> cell needs to idetofy basolateral protein –> traffic them –> keep them there using tight junction/oculins)
Vectoral transport
Vectroral transport requires structural polarity –> have structrial polarity on the apical and basalateral sides = localize proteins differentley = can transprt in tandmen
Can transport in tansem - one transprt of substance in teh basalateral side and then pass to apical side trasnprter and transprort on the apical side
- Need to know if apical or basal to traffic proepry
Functional properies of epthlieal cells
Distrubutions of ion trasnprt proteins determines the functional properties of epithelial cells
- Can have the same transporters but build TWO diffreent types of epithlium
Example (BOTH use the same trasnporters but orented diferentley):
1. Absorptive epithelium - have all Na/K ATPase on the basolateral side ; have cotraspoerter in the apical side to move fluids in + for K recycing
- Na goes out to ECF ; K goes out in lumen
- Na and K can be reabsorbed by oritenting trasnprters this way
2. Lung epithlum - Cl is in the apical memebran ; co-trasnpter on the basal memebrane with K recycling chabel –> allows for secretion of K
Cells know what the cell type is and what job to do = an have the transporters in the right place
Epithelial surface
Epithelial surface specilization facilitate transprt
Proximal tubule = has a brush boarder (microvill) –> Increases the SA of linear distance = can pack in trasnprters
- Proximal tubule needs to reabsorb a lot = need a lot of SA = have microvill
Basal side = has invaginations to pack in all of teh Na/K ATPase pumps that drive transprt
Proximal tubule brush boarder
Image - looking down at Proximal tubule –> see brush boarder as ring all around the tubule
Shows need a lot of SA for the transport to happen
Absoption of NaCl
Water follows Na
Distal nephron = absorbe Na and Secrete K
In Distal nephron (NaCl is reabpsrbed ; K is secreed) - Have Na/K pump on basal side ; have Na chanel and K chanel on apical side – Na will goe down the concetration gradient into the cell AND K goes down the concetration gradinet out of the cell
- Basal side maintains the concetration gradient (using Na/K pump)
- K is secreted to apical side
- Cl transprt is para cellulaer (goe sto basal) ; Na goes to basal
Thick ascedning limb (NaCl reabsprtion) - Use Na/K/2Cl trasnprters on the apical side –> drive the reabsprtion of Na and Cl
- K is reccyling through recycling chalen
- na gets reabsprbed by the Na/K ATPase on basal side (Na goes out to basal side)
- Cl exits through chael on basal side (Cl goes out to basal side)
Water pemeable epithelium
When Na is rebasorbed in the proximal tubule –> water will follow (have isosmotic reabsrtion)
- In proximal Tubule = when Na + Glucose + AA are reabsorbed = water follows
NOTE - in proximal tubule)
Proximal tubule iso-osmotic absorbtion
Because when salt move water follows –> valie of compartments chnage BUT the concetrayion is not chnaging ONLY the volume is chnaging
- Compartmnet A gets small BUT teh concetratino stays the same = iso-osmotic absortion
Do you have to absorb salt and water together
After the Proximal tubule you can reabsorbe na and water sepreatly BUT they are absorbed tgether in the Proximal Tubule
- Can absorb salt and leave water in the lumen by not putting water chanels in the memebrane
Hyperosmotic reabsprtion can happen
- Take out water chanel = membrane is imermeale to water = water can’t follow = get hyper-osmotic reabsorption
- Volume of the compartment stays the same BUT concentration chnages
End function of the nephron
Have a big concentraton for Na to be absorbed
Kidneys se secodary active trasnprt to absorb other things
- Example - Na/Glucose –> use the concetration of Na to rebasorb glucose
- Can do the same for reabsrbing AA
If you have good Na pump activity = Take advantage of the Na Gradinet = can use secondary transport for the absorption of Glucose + AA + phosphate
- Have antiporters that ise secondary active trasnprt (coupled to the secreyion of H+ ions)
If absorb Na = use Na going down the gradinet to move other things
NOTE - occurs in the proximal porton of the nephone
Secondary transprt
Occurs in the priximal part of the nephron
Proximal tube uses na reabsprotion going down concetration gradeint on the appical side = drive reabsoprtion of other molecules
Need faciliateted duffusion on basolateral side to get glucose out
- Put a lot of pumps and mitocondria to keeo sodium low
Exmaple - Protein receptor mediate endocytosis (magalin) , degrdaed in the lysosomes, trasnported acros BL with AA trasnorters
Why do you need high Na in Lumen
Need to keep sodium concetration high in the lumen because you can use this concetration to reaborb lots of other things
- High Na in the lumen dirves many substances into the cell
- Solute coupled water movment
Promixal part of nephroen (end)
Division of the prosximal protion
Proximal portion of the nephron is heterogenous
Proximal tubule = divided into different segments
1. S1 - does most of the transprt
- Has bursh boader + more mitocondria + taller –> absorbs larger amounts in terms of total amount
- Does more bulk transport
2/3. S2 and S3 are important for clean up
- S3 - has high affinity trasnprters to get the last molecule of glucose = makes sure you don’t lose molecules
Ratio of concetraions in proximal tubule
Chart - shows that mos of the reabsprtion (in terms of amount) occyrs before 50% mark BUT you need the last bit (100% length) to get the line to zero
Secreted compounds
Proximal Tubule is important for secreting compounds the body wants to get rid of
Image - shows the anions and cations the proximal tubules secretes
Example - Penecilin anion is secreted by the proximal tubule
- Created an issue in WW2 because had very little Pencilin and a lot was sceretd out = need more of it for it to work
- made proveset = secreted by the same transprter as pencilin = competivley inhibits for teh same secretion machiner = can maintain higher pencilin levels
Loop of Henle
Loop of Henle = middle portion of the nephron
Loop = has different reabsprotion of water vs. naCl to concetrate the urine
Function of Loop = concetrate the Urine
