Lecture 5 Tubular reabsorption Flashcards
What are intraglomerular mesangial cells?
Smooth muscles that regulate intraglomerular capillary flow
How do intraglomerular mesangial cells regulate intraglomerular blood flow?
They contract and this contraction is coupled with contraction of capillary endothelium basement membrane which decreases surface area and GFR
What hormones do intraglomerular MC react to?
AtII
ANP
ADH
NO
Capillary stretch
What does the glomerulus filter out?
Molecules > 50 kDa
What does the breakdown of protein result in (in keto peeps)?
Ammonium which is a neurotoxin which gets degraded into urea
What happens in the tubules?
Tubular reabsorption which is highly selective and only excess amounts of required substances end up not getting reabsorbed.
Waste products do not get reabsorbed and are eliminated in the urine
What happens if you consume lots of salt?
The salt gets excreted immediately at the kidneys.
What happens to potassium?
it gets excreted very quickly
What happens to urea concentrations after excretion?
50% excreted and 50% retained
What happens to creatinine?
it is completely eliminated and not reabsorbed
What is the paracellular path of reabsorption?
Tight junctions between cells of the peritubular capillaries allow water to pass through them. This is based on concentration and osmotic gradients
What are the methods of bulk flow of fluid into the capillaries?
The paracellular path (between cells)
The transcellular path (within cells)
What is the transcellular path of reabsorption?
Goes through both cell membranes of the cell of tubules and this allows it to be more selective and active.
Sodium, for example, can move through the second membrane easily through active transport
What is active transport used for in the kidney?
Sodium is actively pumped through to maintain a concentration gradient of sodium in the peritubular capillary
H+
K+ (pumped into cell to maintain intracellular environment)
Ca2+
Mg2+
What is the difference between apical and basal membranes?
Basal membrane faces the capillaries whereas the apical membrance faces the lumen of the tubule
How is sodium active transport used?
When leaving the basal membrane it is used to power secondary active transport by counter current transport of potassium into the cell.
When entering the cell from the apical membrane it is used to power glucose concurrent transport into the cell.
It is also used to power concurrent amino acid entry into the cell from apical membrane
How are proteins picked up by the tubules?
Pinocytosis IT IS NOT SPECIFIC IT PICKS UP ALL PROTEINS
Why is glucose sometimes found in urine despite the capacity for 100% reabsorption?
When there is too much sugar the active transport capability is limited by saturation of active transporters
What is the maximum rate of glucose reabsorption?
375 mg/min
Which molecules are returned to circulation at tubules via passive transport?
Cl-, urea, HCO3, PO4, Na2+, Ca2+, Mg2+, K+, H2O
What is the rate of passive transport dictated by?
Electrochemical gradient
Permeability
Time
How is Cl- reabsorbed into circulation?
Anion drag - Na+ creates a passive electrochemical gradient that can be used by Cl-
How does urea get reabsorbed?
Resorption of everything else in the tubule creates a urea gradient. they move through urea channels
Can passive transport be saturated?
No
How does water move?
Regulated by tight junctions and aquaporins and it follows the osmotic gradient formed by sodium
How is sodium reabsorbed?
Approximately 2/3rds are absorbed at proximal convoluted tubule.
25% reabsorbed in ascending loop of henle
8% of sodium reabsorbtion that is controlled in the distal convoluted tubule which is under endocrine control
Where are amino acids, small proteins, and glucose reabsorbed?
Entirely in the proximal convoluted tubule
Where does water get reabsorbed?
65% obligatory at proximal tubule
15% reabsorbed at loop of henle obligatory
20% at loop of henle is under hormonal control (ADH is a big one)
How much of the salts in the filtrate is reabsorbed at the PCT?
65%
What are features of the PCT that make it good at reabsorption?
Extensive brush border with a huge surface area
Loaded with carriers such as
- Na+/K+-ATPase
- Na+ co/counter current flow
- Acid secretion
Is the PCT the same along its border?
No it is heterogeneous:
In the first half sodium is reabsorbed by cotransporters with glucose, amino acids, and proteins, etc
Second half there are little glucose and amino acids and instead sodium is reabsorbed with chlorine (lots of chlorine present)
What is secreted into urine at PCT?
NH3
Bile salts
Oxalate
Urate
Catecholamines
Penicillin
Salicylates
Creatinine
Why does osmolarity not change at the PCT?
Because you’re reabsorbing everything the relative constituents don’t change (remember that water is also getting reabsorbed)
Why does sodium concentration not change?
Because water gets absorbed with it
What can be said about the permeability of the descending loop of henle to water?
Descending loop of henle is very water permeable
What can be said about the ascending loop of henle’s permeability to water?
Ascending loop is impermeable to water and so water stays inside
Where does the osmotic gradient start to form?
At the ascending loop of henle where the water can’t get out and salts are being actively reabsorbed
What type of channels does the Thick Ascending Limb have?
Sodium is actively pumped out of the cell on the renal interstitial side of the cell by sodium potassium ATPase creating a higher potassium gradient and a lower sodium gradient.
On lumen side:
Contains Sodium Potassium 2 Chloride channels sodium drives transport of a potassium and 2 chlorides into the cell
Potassium in cell is now high and potassium channels open up on both sides and potassium leaks back out. Retaining sodium in the cell decreases potassium in the cell.
What happens overall at the TAL?
Salts are being actively reabsorbed
What happens when lots of sodium is retained in the Thick Ascendig Loop?
We lose a lot of potassium
What happens as fluid approaches the DCT?
It becomes very dilute
What happens at the DCT?
It is also a water impermeable salt resorber.
What cell types are present at the DCT?
Principle cells (sodium and potassium balance)
Intercalated cells (secrete H+ and reabsorb HCO3-)
What kind of transport is the Na+,2-Cl-,K+ transporter?
Secondary active transport
What is the DCT also known as?
The diluting segment
What does the DCT do?
Same as TAL it is a water impermeable salt resorber.
~5% NaCl load (Na+/K+ - ATPase drives Na+/Cl-co-transport
What controls DCT filtration?
JGA - feedback
What happens at the late DCT and corical DCT?
Principle Cells reabsorb sodium and secrete potassium
Na+/K+ - ATPase potassium leaks out of secreted channels
Intercalated cells secrete H+ through a H+ ATPase and reabsorb HCO3-
What happens at cortical CD?
Water permeability can be modified here.
H+ATPase secretes H+
H2O permeability is controlled by ADH
Impermeable to urea so all urea that enters these ducts ends up being excreted in urine
What hormone controls H2O permeability at collecting duct?
H2O permeability is controlled by ADH
What do the medullary collecting ducts do?
Control water in urine
How is urine concentrated and diluted?
increasing or decreasing ADH which opens and closes aquaporins on collecting ducts
How is a hyperosmotic interstitium maintained by collecting ducts?
Salts are actively pumped out
How is concentrated urine produced?
Aquaporins are opened
Leaky DCT/CT/CD must be present so that H2O can be resorped from impermeable tubule segments. This is done in response to to ADH production.
A hyperosmotic renal medullary interstitium provides the osmotic gradient for H2O resorption via countercurrent mechanism. Osmotic concentration is maintained via urea recirculation.
How concentrated can human urine be compared to blood plasma?
4 - 5x plasma (1200 - 1400 mOsm/L)
How does the LLoH countercurrent multiplier work?
Water is isoosmotic going through the loop of henle.
Salt pumped out creating higher concentration outside compared to inside.
Osmosis causes water to move towards the higher concentration gradient and active transport of salts is becoming harder and harder due to pushing against high osmolarity.
This results in concentrations becoming higher towards the bottom of the loop of henle and lower towards the top.
Why do we recycle half our urea?
We use it to create a concentration gradient
How does urea recirculation work?
Urea is initially reabsorbed like everything else. and then when much of the salts are removed at the loop of henle the urea is alone and has a huge concetration gradient at the collecting duct where it can diffuse through urea transporters towards the lower part of the nephron in the renal medulla.
Why don’t peritubular capillaries dilute the gradient?
Medullary blood flow is really low (<5% of renal blood flow)
Vasa recta countercurrent exchange
Blood equilibrates to osmotic gradient rather easily
What pathway does potassium use for reabsorption? the transcellular or paracellular path? why?
Paracellular pathway because it can’t be diffused into the cells due to high intracellular concentration of potassium in cells.
