Physiology of Proximal Tubule and Loop of Henle Flashcards
What is the normal GFR in the kidneys?
125 ml/min (180 l/day)
How many times is plasma filtered in a day?
65 times a day
What substances are reabsorbed by the kidneys?
99% of fluid, 99% of salt, 100% of glucose, 100% of amino acids, 50% urea, 0% of creatine
How is reabsorption different from filtration?
Reabsorption is specific
What is the glomerular filtrate?
Modified filtrate of blood
How much fluid is reabsorbed in the proximal tubule?
About 80 ml/min
What property does the fluid reabsorbed from the proximal tubule have?
Iso-osmotic with the filtrate
What substances are reabsorbed in the proximal tubule?
Sugars, amino acids, phosphate, sulphate and lactate
What substances are secreted from the proximal tubule?
H+, hippurates, neurotransmitters, bile pigments, uric acid, drugs and toxins
What is the flow of transcellular reabsorption in the proximal tubule?
Tubular lumen - tubular epithelial cell - lateral space - interstitial fluid - peritubular capillary
Where does paracellular reabsorption of the proximal tubule occur?
Between tubular epithelial cells
What are some forms of carrier-mediated transport?
Primary active transport, secondary active transport, facilitated diffusion
What occurs in primary active transport?
Energy is directly required to operate the carrier and move the substrate against its concentration gradient
What occurs in secondary active transport?
Carrier molecule is transported coupled to the concentration gradient of an ion (usually Na+)
What occurs in facilitated transport?
Passive carrier-mediated transport of a substance down its concentration gradient
What is essential for Na+ reabsorption in the proximal tubule?
An energy dependent Na+/K+-ATPase transport mechanism at the basolateral membrane
How is iso-osmotic fluid reabsorbed in the proximal tubule?
Reabsorbed across the leaky epithelium = due to standing osmotic gradient and oncotic pressure gradient
How is water reabsorbed in the proximal tubule?
Passively down the NaCl osmotic gradient
What kind of drag exists in the peritubular plasma of the proximal tubule?
Oncotic drag
What ion is Na+ exchanged for in the proximal tubule?
H+ by co-transport
How much glucose is reabsorbed from the filtrate in the proximal tubule?
100% = by co-transport with Na+ and facilitated diffusion
What is the transport maximum (Tm)?
Point at which increases in concentration of a substance don’t result in an increase in movement of a substance across a cell membrane
How is the Tm of glucose expressed?
By the maximum transporting capacity of the SGLT transport system
How is the excretion of PAH calculated?
Excretion = filtration + secretion
What do the protein channels in the proximal tubule do?
Either reabsorb glucose or secrete PAH
What is the maximum reabsorption of glucose in healthy people?
About 375 mg/min
How is glucose excretion calculated?
Excretion = filtration - reabsorption
What direction is PAH transport in the proximal tubule?
From the peritubular capillaries to the lumen = opposite direction from glucose
What happens to clearance once Tm is reached?
Clearance of reabsorbed/secreted substance isn’t constant
How is high [PAH] obtained?
By infusion or injection
What does Na+ reabsorption in the proximal tubule drive?
Cl- reabsorption through the paracellular pathway
What property does the tubular fluid have once it leaves the proximal tubule?
It is iso-osmotic
What is the function of the loop of Henle?
Generates a cortico-medullary solute concentration gradient, enabling the formation of hypertonic urine
How does fluid flow occur in the loop of Henle?
Opposing flow in the two limbs = countercurrent flow
Entire loop functions as a countercurrent multiplier
What do the vasa recta and loop of Henle establish collectively?
A hyperosmotic medullary interstitial fluid
What are some features of the ascending limb of the loop of Henle?
Na+ and Cl- are reabsorbed along entire length
Relatively impermeable to water = little/no water reabsorbed
What are some features of the descending limb of the loop of Henle?
Doesn’t reabsorb NaCl and is highly permeable to water
How is NaCl absorbed in the ascending loop of Henle?
Thick (upper) ascending limb absorbs NaCl by active transport
Thin (lower) ascending loop does this passively
What do the selective permeabilities of the ascending and descending limbs of the loop of Henle enable?
The establishment of an osmotic gradient in the medulla
What is the function of the TALH triple co-transporter in the loop of Henle?
Pumps ions out of the lumen = moves Na+, Cl- ad K+ out
K+ recycling means that NaCl is absorbed into the interstitial fluid
What drug class block the triple co-transporter in the loop of Henle?
Loop diuretics
What occurs when the triple co-transporter pumps solute from the thick ascending limb?
Solute removed from lumen of ascending limb = water can’t follow
Tubular fluid is diluted and osmolality of interstitial fluid is raised
Interstitial solute can’t enter the descending limb
How does water leave the descending limb of the loop of Henle?
By osmosis
What property does the fluid in the descending limb of the loop of Henle have?
It is concentrated
What happens once fluid enters the descending limb of the loop of Henle?
Is concentrated and moves into the ascending limb
Hypotonic fluid then moves into the distal tubule from the ascending limb
How does pumping occur in the loop of Henle?
Solute pumped out of the ascending limb
Osmolality of the interstitial fluid rises
Passive water efflux from descending limb
Flow occurs, moving everything on as before
What does countercurrent multiplication allow?
A steady state to be reached = horizontal gradient has been multiplied into a large vertical gradient due to countercurrent flow
What property does the fluid entering and leaving the loop of Henle have?
Iso-osmotic fluid leaves the proximal tubule and enters the loop of Henle, hypo-osmotic fluid leaves the loop to enter the distal tubule
What contributes to half of the medullary osmolality?
The urea cycle
How do the kidneys interact with urea?
Distal tubule not permeable to urea
Collecting duct absorbs 50% of urea
Urea adds solute to the interstitium
Urea diffuses passively into the loop
What promotes the absorption of urea from the collecting ducts?
ADH
What mechanism concentrates the medullary interstitial fluid?
Countercurrent multiplication
How does countercurrent multiplication concentrate the medullary interstitial fluid?
Enables the kidneys to produce urine of a different volume and concentration according to the amounts of circulating ADH
Where do the vasa recta run?
Run alongside the long loop of Henle to juxtamedullary nephrons
What does capillary blood equilibrate with across the leaky endothelium of the vasa recta?
Interstitial fluid
What happens to blood osmolality as it dips down into the medulla?
It rises = water is lost, solute is gained
What happens to blood osmolality as it rises back up into the cortex?
It falls = water is gained, solute is lost
What forms the countercurrent system?
The loop of Henle and the vasa recta
What effect does essential blood flow through the medulla have on solutes?
Tends to wash away NaCl and urea
How is the removal of NaCl and urea from the medulla by blood overcome?
Vasa recta capillaries follow hairpin loops
Vasa recta capillaries freely permeable to NaCl and H2O
Blood flow to vasa recta is low
Why is the blood flow to the vasa recta low?
There are few juxtamedullary nephrons
What preserves the medullary gradient?
Passive exchange across the endothelium = blood equilibrates at each layer to ensure solute isn’t washed away
What creates the medullary osmotic gradient?
Countercurrent multiplier and the urea cycle
What preserves the medullary osmotic gradient?
The countercurrent exchanger
What does high medullary osmolality allow?
The production of hypertonic urine in the presence of ADH
What is the only part of the nephron that doesn’t absorb sodium?
Descending limb of the loop of Henle