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Structure of a Nephron-Bowmans capsule
- Surrounds glomeruli capillaries
- Continuous with first portion of nephron
- Blood is ultrafiltered through this space
- First step in urine formation
What remains of nephron has specialized cells that serve for reabsorption and secretion.
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Functional unit of kidney
- Nephron
- Each kidney contains approximately 1 million nephrons.
- Consists of glomeruli and renal tubule
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First step in urine formation happens where
Bowmans capsule
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Nephron comprised of 5 segments
- 1. Proximal convoluted tubules
- 2. Proximal straight tubule
- 3. Loop of Henle (thin descending, thin ascending, thick ascending)
- 4. Distal convoluted tubule
- 5. Collecting ducts
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2 types of nephrons
- 1. Superficial cortical nephrons
- 2. Juxtamedullary nephrons
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Superficial cortical nephrons
- glomeruli in outer cortex
- short loops of Henle
- descend only into outer medulla
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Juxtamedullary nephrons
- glomeruli near the coritocomedullary border
- Larger
- Higher flow rates
- Long loops of Henle
- Descend deep into inner medulla and papilla- essential for formation of concentration of urine.
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Afferent arterioles
- Deliver blood to the glomeruli capillaries.
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- BLOOD TO!!
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Efferent arterioles
Blood leaves the glomeruli capillaries
blood then delivered to secondary capillary network.
BLOOD AWAY!!!
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Renal Cortex
Outer region of kidney located just under renal capsule
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Renal Medulla
A central region , divided into outer and inner medulla
Outer medulla has outer stripe and inner medulla has inner stripe
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Papilla
The innermost tip of the inner medulla and empties into pouches called minor and major calyces, which are extensions of ureter.
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Water is how much of body weight?
50-70%
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Relationship between water content and body weight is clinically important
Example:
3 Kg weight loss = 3 liters loss of total body water.
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Plasma = what percentage of blood volume
What makes up other portion of blood volume?
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Plasma proteins constitute _____ % of plasma by volume?
7%
The other 93% of plasma volume is plasma water.
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Mannitol as a marker for volume
- In the ECF
- Cannot cross cell membrane
*choose marker based on where it will go. Mannitol will not cross cell membrane so it stays in the ECF.
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Innulin as a marker for volume
- Innulin is same as mannitol, it cannot cross cell membrane.
- It is found in ECF not in the ICF
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Volume in a compartment depends on the _________?
Solute it contains.
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Normal value for osmolarity of the body fluids is__________?
290 mOsm/L
simplicity=300
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Isosmotic volume contraction
Example Diarrhea, sunburn
ECF=
ICF=
Osmolarity=
Hematocrit=
Plasma protein=
- ECF= goes down
- ICF= N.C
- Osmolarity=N.C
- Hematocrit= goes up
- Plasma Protein= goes up
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Hyperosmotic volume contraction
Example: sweating, fever, diabetes
ECF=
ICF=
Osmolarity=
Hematocrit=
Plasma protein=
- ECF= goes down
- ICF=goes down
- Osmolarity= goes up
- Hematocrit= no change
- Plasma Protein= goes up
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Hyposmotic volume contraction
Example: Adrenal insufficieny
ECF=
ICF=
Osmolarity=
Hematocrit=
Plasma Protein=
- ECF=goes down
- ICF=goes up
- Osmolarity=goes down
- Hematocrit=goes up
- Plasma Protein=goes up
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Isosmotic volume expansion
Example: Infusion of isotonic NaCl
Ecf=
Icf=
osmolarity=
hematocrit=
plasma protein
- ecf= goes up
- icf=no change
- osmolarity= no change
- hematocrit= goes down
- plasma protein= goes down
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Hyperosmotic volume expansion
Example: High NaCl intake
ECF=
ICF=
Osmolarity=
Hematocrit=
Plasma Protein=
- ECF= goes up
- ICF= goes down
- Osmolarity= goes up
- Hematocrit= goes down
- Plasma Protein= goes down
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Hyposmotic volume expansion
Example: SIADH
ECF=
ICF=
Osmolarity=
Hematocrit=
Plasma Protein=
- ECF= goes up
- ICF= goes up
- Osmolarity= goes down
- Hematocrit= No change
- Plasma protein= goes down
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Renal clearance equation
C=U x V/P
- C= clearance (ml/min)
- [U]x= urine concentration (mg/ml)
- V= urine flow per minute (ml/min)
- [P]x=plasma concentration (mg/ml)
Renal clearance is a ration of urinary excretion to plasma concentration.
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Solve for renal clearance
Urine concentration=100 mg/ml
Plasma concentration = 2 mg/ml
Urine flow= 1 ml/min
- C=U x v/p
- C= 100 x 1/2= 50 ml/min
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What substance clearance is equal to its GFR?
Inulin
Unique properties
Glomerular Marker
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Kidneys receive about ______% of cardiac output?
L/min ?
25%
1.25 L/min
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Renal blood flow and sympathetic stimulation
Vasoconstriction for activation of alpha 1 receptors
Because there are far more alpha receptors on afferent arterioles (taking blood to capillaries) and this increases sympathetic nerve activity- this causes decreased GFR and RBF (renal blood flow) *attempts to raise BP at the expense of kidneys.
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Renal blood flow =
RBF=
RPF( renal plasma flow)
RBF= RPF/1-HCT
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Ficks Principle
The amount of a substance entering the kidney via the artery equals the amount leaving via the vein.
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[RA]pah=
[PAH] in renal blood flow
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[RV]pah=
- [PAH] in renal vein
- PAH- substance used to measure RPF with Ficks principle
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Measuring effective Renal Plasma Flow
RFP
Effective RPH=
effective RPF= [U]pah X V/[P]pah=Cpah
- [U]pah= urine concentration of pah (mg/ml)
- V= urine flow rate (ml/min)
- [P]pah= plasma concentration of PAH (mg/ml)
- Cpah= clearance of PAH (ml/min)
- IN SIMPLIFIED FORM
- EFFECTIVE RPF=CLEARANCE OF PAH
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LOOK AT EXAMPLE IN CONSTANZA BOOK FOR CALCULATION RBF AND RPF
PAGE 250-251
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GFR of inulin- measurement of GFR by clearance of glomeruli marker
Use Renal clearance equation or GFR (which is same)
Urine concentration=150 mg/ml
Plasma concentration= 1 mg/ml
Urine Flow= 1 mg/min
- C= (Urine concentration) [U]x X (urine flow) V/( plasma concentration) [p]x
- or
- GFR= [U]inulin x V/[P]inulin=C inulin
- 150 x 1/1=
- GFR= 150ml /min
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Filter load
- Use renal clearance equation
- GFR x plasma concentration
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GFR is the first step in ________?
Happens where________?
- Urine formation
- Bowmans capsule
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Excretion=
Formula
Amount of substance excreted per unit of time
- V x U
- urine flow rate x urine concentration of X
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Reabsorption or secretion
Filter load - excretion rate
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Starling Forces
4 pressures
- two hydrostatic pressure- one in capillary blood, and one in interstitial fluid
- two oncotic pressures= one in capillary blood, and one in interstitial fluid
- Oncotic pressure in Bowman's capsule is 0
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Starling forces
GFR=Kf=
Kf= filtration coefficient
GFR=Kf= (Pgc-Pbs) - (pie symbol not in parenthesis)gc
- Pgc-Pbs= hydrostatic pressure of glomeruli capsule - hydrostatic pressure of Bowman's capsule
- (Pie)gc= oncotic pressure in glomeruli capsule
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Changes in GFR are cause by changes in the __________?
Starling Pressures
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Effects of Changes in Starling Pressure
Constriction of afferent arterioles
RPF=
GFR=
Pgc=
FF=
- RPF=Decreased
- GFR=Decreased
- Pgc=decreased b/c of decreased blood flow
- FF (GFR/RPF)= No change
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Effects of Changes in Starling Pressure
Constriction of efferent arterioles
RPF=
GFR=
Pgc=
FF=
- RPF= decreased
- GFR- increased (opposite of afferent end)
- Pgc- increases
- Filtration fraction (GFR/RFP)= increased
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Effects on changes in Starling Pressure
Increased Plasma protein concentration
RPF=
GFR=
FF (GFR/RPF)=
- RPF= N.C.
- GFR= Decreases
- FF=Decreases
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Effects on changes in Starling Pressure
Decreased plasma protein concentration
RPF=
GFR=
FF=
- RPF= N.C
- GFR= increase
- FF= increase
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Effects on changes in Starling Pressure
Constriction of Ureter
RPF=
GFR=
FF=
- RPF= N.C.
- GFR= decreased
- FF= decrease
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Can use ______ (besides inulin) for calculation of GFR.
Use same calcuation
Creatinine
Slightly overestimates GFR
GFR= [U]creatinine x V/[P] creatinine = C of creatinine
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Renal blood flow and Angiotensin II simulation
- Vasoconstrictor at both sides- afferent and efferent
- Efferent more sensitive
- Low levels increase GFR (constrict efferent)
- High levels decrease GFR (constrict afferent and efferent)
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Renal blood flow and Prostoglandins stimulation
What effect does NSAIDS have?
- Produced in kidneys, causes vasodilation of both
- Protective of RBF (long term vasoconstriction after hemorrhage can cause renal failure)
- Modulated constriction caused by SNS and release of angiotensin II
- NSAIDS- inhibit this synthesis of prostaglandins and therefore interfere with protective effects of prostaglandins on renal function following hemorrhage
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Filtration
amount of substance filtered into Bowman's space per unit of time = filtered load
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Reabsorption
water and many solutes are reabsorbed from the glomerular filtrate into the peritubular capillary blood
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Secretion
- Few substances are secreted from peritubular capillaries
- Organic acids, organic bases, and potassium
- Mechanism for excreting substances in the urine
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Filtered Fraction
GFR/RPF
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Cellular Mechanism for Glucose reabsorption
(carrier mediated)
- In proximal tubule
- 2 steps
- 1.Sodium glucose co-transport- sodium and glucose released into ICF, and potassium moved out -
- 2.facilitated glucose transport across peritubular membrane (no energy required).
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Tmax of reabsorption=
Tmax of renal reabsorption=
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Reabsorption of glucose tmax less than 200
all filtered glucose is reabsorbed
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Reabsorption of glucose tmax more than 200
All filtered glucose is not reabsorbed.
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Reabsorption of glucose tmax above 300
All carriers are saturated, no reabsorption will take place
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Causes of glycosuria (spilling of glucose into the urine)
Normal plasma glucose is 70-100 and all is reabsorbed, some conditions can alter this level causing glycosuria:
- Uncontrolled DM
- Pregnancy
- congenital abnormalities in sodium glucose transport
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Urea
Reabsorbed-
By what-
- Most segments of nephron reabsorb urea
- Urea reabsorbed by simple diffusion and is freely filtered.
- Urea follows the same pattern as water. As water reabsorption increases so does urea reabsorption.
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PAH as a marker for volume
para-aminohippuric acid- the substance used to measure RPF (renal plasma flow) in Ficks principle
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PAH secretion
PAH- (para-aminohippuric acid) used as a marker for RPF
filtered across capillary and secreted from peritubular capillary blood into tubular fluid
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Most important function of the kidney
- maintaining a normal sodium balance
- sodium excretion should equal sodium intake
- Na freely filtered across glomerular capillaries and reabsorbed throughout nephron.
- Excreted 1%
- Reabsorbed 99%
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99 % of Na in Kidney reabsorbed where at?
- 67%- Proximal convoluted tubule
- 25%-thick ascending loop of henle
- 8% distal convoluted tubule and collection ducts
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If 67% of sodium reabsorbed, how much water is reabsorbed?
- 67%
- Where sodium goes, water follows
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Sodium reabsorption in proximal convoluted tubule
What type of transport
Exchanger?
- 67%
- Co-transport with bicarb, organic solutes, amino acids, and glucose
- 100 % of glucose and amino acids reabsorbed
- Na-H exchanger- causes net absorption of bicarb
- 85% bicarb reabsorbed here.
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What part of nephron does Lasix work on
Thick ascending limb of Henle
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Thick ascending loop of Henle
Reabsorbs by what mechanism?
What kind of transport takes place here?
- Reabsorbs a significant amount of sodium by an active mechanismNa-K-2Cl co-transporter= three ion co-transport, energy from sodium gradient, maintained by sodium potassium pump
- Site for loop diuretics, lasix
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What part of nephron does thiazide diuretics work on
Early distal convoluted tubule
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Distal Tubule and reabsorption
percent of Na
Dependent on ?
what type of transport takes place here
What diuretics work here?
- 8% of Na reabsorption
- Load dependent= the more you bring to it the more will be absorbed.
- Na-Cl co-transport
- Site for thiazide diuretics
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Late distal tubule and collecting ducts
What type of cells?
What type of regulation?
- Principle and alpha cells
- Hormonal regulation: aldosterone, water, reabsorption
- Aldosterone-increase Na reabsorption in principle cells
- Water- without water permeability is low.
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Potassium balance
- 98% ICF
- 2% ECF
- Freely filtered
- Excretion of potassium must be equal to the intake.
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How does insulin affect internal potassium balance?
Stimulates potassium uptake in cells.
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How does H-K exchanger affect internal potassium balance?
- alkaline= hydrogen decrease, hydrogen leaves and potassium enters
- academia= k leaves and hydrogen enters
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How do beta 2 agonists affect internal potassium balance
Increase the sodium potassium pump causing a shift of potassium into the cells.
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How does alpha agonists affect internal potassium balance?
shift of potassium out of cell
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How do alpha antagonists affect internal potassium balance
take potassium into the cells.
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How does hyperosmolarity affect internal potassium balance?
shifts potassium out of the cell
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How does lysis of cells affect internal potassium balance?
Large amount of potassium is released from ICF
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What percent of Potassium is reabsorbed in the proximal convoluted tubule?
what percent in thick ascending limb of henle?
Distal convoluted tubule and collecting ducts?
- 67%
- 20%-diffuses to blood
- Fine adjustments of potassium excretion, varies with diet
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Alpha intercalated cells in distal tubule and collecting ducts do what with low potassium diet?
reabsorb potassium
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Principle cells in the distal tubule and collecting ducts do what with high potassium diet?
Excrete potassium
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What increases Secretion of potassium
- High potassium diet
- Increase in aldosterone
- Alkalosis
- loop and thiazide diuretics
- presence of large anions in lumen
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Spirolactone
potassium sparing diuretic
- inhibits actions of aldosterone (increases potassium excretion)
- inhibits potassium excretion
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Renal handling of Calcium
______% to plasma proteins?
______% reabsorbed proximal convoluted tubule?
______% reabsorbed at thick ascending loop of henle
______% reabsorbed in distal tubule?
- 40% bound to plasma proteins
- 67% reabsorbed at proximal convoluted tubule
- 25%
- 8% reabsorbed in distal tubule
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Reabsorption of Phosphate
_____% proximal convoluted tubule
_____% proximal straight tubule
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Magnesium
____% bound to plasma protein
____% reabsorbed in proximal tubule
____% reabsorbed in thick ascending loop of henle
Loop diuretics inhibit magnesium reabsorption strongly.
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Regulation of body fluid osmolarity
Response to water deprivation
6 steps
- 1. water is lost from body (if not replaced increase osmolarity of plasma)
- 2. Increased osmolarity
- 3. stimulation of receptors (stimulates thirst and ADH)
- 4. ADH- increases permeability
- 5. Increased water reabsorption in late distal tubules
- 6. more water returned to body, osmolarity decreases
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Corticopapillary osmotic gradient
Two processes
1. countercurrent multiplication
2 steps
- function of the loop of henle
- deposits NaCl deep into regions of the kidney
- 1st step- single effect
- thick ascending limb, no water is reabsorbed but NaCl
- 2nd step-descending limb reabsorbs water
- equilibrates with interstitial spaces
- THE TWO BASIC STEPS REPEAT UNTIL FULL GRAIDIENT IS ESTABLISHED. SIZE OF GRADIENT DEPENDS ON LENGHT OF LOOP OF HENLE.
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Corticopapillary osmotic gradient
Two processes
2nd- Urea recycling
Urea is recycled instead of thrown away in the urine.
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Countercurrent exchange
- maintains the corticopapillary osmotic gradient.
- passive
- slow flowing blood
- vasa recta
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3 actions of ADH on renal tubules
- 1. increases water permeability in the distal tubules and collecting ducts.
- 2. Increases activity of na-k-2cl cotransporter in thick ascending limb
- 3. increases urea permeability in the inner medullary collecting ducts (enhances urea recycling).
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Production of hyperosmotic urine
- NaCl reabsorbed in thick ascending loop of henle- water reabsorption can not happen here.
- Nacl reabsorbed by NaCl transporter in early distal tubule.
- Principle cells become permeable to water in the presence of ADH
- Urine is produced and osmolarity 1200 mOsm
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Production of hypoosmotic urine
- Low circulating ADH
- Tubular fluid diluted
- Dilution continues
- (most dramatic if ADH low or absent)
- final urine does not equilibriate with interstitial fluid.
- Final osmolarity= 75 mOsm/L
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Change in Pgc (hydrostatic pressure of glomeruli capsule) are produced by what?
Changes in Pcg are produced by changes in resistance to afferent and efferent arterioles
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What type of transport takes place in thick ascending loop?
Active transport
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Na-K-2Cl cotransporter
All three ions are transported into the cell on the co-transporter
Energy from sodium potassium pump
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Where is NaCl co-transport system located
early distal convoluted tubule
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Were is Na-K-2Cl co-transporter located at
Thick ascending limb
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Where is Na-glucose co-transporter located at?
Proximal convoluted tubule
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What two things contribute to the establishment of the corticopapillary osmotic gradient?
- Countercurrent multiplication
- Urea Recycling
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