Obligatory reabsorption and secretion in the proximal convoluted tubule Flashcards
Define blood urea nitrogen. What is the effect of GFR increase on BUN ? Identify a treatment option for increased BUN.
Blood urea nitrogen (BUN) = Measures nitrogen in the blood as urea (waste product of amino acid catabolism). If GFR decreases (as in renal disease) BUN increases. Increased BUN can be treated with a reduced protein diet (decreased amino acids). Normal range 7-18 mg/dL or 1.2 – 3 mM.
Define oncotic P.
Osmotic pressure for large molecules (e.g. proteins). These attract H2O, but number of particles per kg is low.
Define osmolarity.
Number of solute particles per litre (mOsm/L)
Define osmolality.
Number of solute particles per kg solute (mOsm/kg H2O). NOT temperature dependent and therefore correct term for biology.
Define osmosis.
Movement of H2O across cell membranes. Driving force is osmotic
pressure difference.
Define osmotic P.
Determined by number of solute particles in solution. Not affected by size of particle, charge or mass. Generally expressed in terms of osmolarity or osmolality.
What is the formula for specific gravity ? Based on this, what is the specific gravity of distilled water ?
Weight of a set volume of solution / Weight of same volume of pure water
Distilled water is therefore 1.000
What is the specific gravity of normal urine ?
1.007 due to presence of solutes.
What is the osmolality of 1 mmol/L solution of CaCl2 ? of glucose ? of NaCl ?
mmol/L solution of CaCl2 has an osmolality of 3 mOsm/kg H2O, since CaCl2 is comprised of Ca2+ and 2Cl-.
1 mmol/L solution of glucose has osmolality of 1 mOsm/kg H2O.
1 mmol/L solution of NaCl has an osmolality of 2 mOsm/kg H2O, since NaCl is comprised of Na+ and Cl-.
What is the main site for obligatory reabsorption ?
Proximal Tubule
Is obligatory reabsorption regulated ? What is the one factor that does regulate the amount of obligatory reabsorption that takes place ?
No
Only thing that
regulates reabsorption of solutes is the amount of solutes filtered in first place from glomerulus (i.e. no intrinsic factor other than availability of ions/metabolites)
Identify the main solutes/metabolites which are reabsorbed in the PT.
Glucose AAs Magnesium Calcium Sodium Potassium H20 Phosphate Urea
What are the main functions of the PT ?
1) Most of the recovery of water, glucose, Na+ etc.
2) Actively secretes a number of compounds for excretion with urine (e.g. antibiotics, waste products of metabolism), and metabolises some of the amino acids
Are proteins filtered by the glomerulus ? Why or why not ?
Almost all proteins not filtered by glomerulus because of negatively charged BM (so stay in blood) but small amount of proteins do come through.
There are proteases on PT cell surface that break those proteins down into AAs, which then get reabsorbed.
There are also some proteins that come through that are smaller, and are taken up by
endocytosis (into cell).
Identify the possible pathways taken by molecules and ions across the tubule epithelium in reabsorption.
- Transcellular route (through the apical surface into the cell body, into the interstitial fluid, then into bloodstream)
- Paracellular route (through the leaky tight junctions between cell bodies, into the bloodstream)
Identify the main forces involved in the obligatory reabsorption from the PT.
- Ion gradients across the basolateral membrane– active transport 3 Na out 2K in
- This sets up an electrochemical gradient (pumping more positive charge out than in) of about -3mV (tubule lumen negative compared to interstitial fluid; causes paracellular efflux of cations)
- Osmotic gradient set up by pumping Na out of the cell in to the interstitial space
- Water moving along the paracellular path due to osmotic pressure drags solutes along with it (especially negative electrolytes, because transluminal negative potential in PT means cations tend to fight solvent drag). Known as solvent drag
- Chemical concentration of solutes left behind when water leaves the tubule facilitates a chemical gradient (can then use transcellular route to diffuse down their concentration gradient)
Is the lumen negative relative to the interstitial fluid along the entirety of the tubules ?
No, lumen negative in PT and distal tubule and collecting ducts, BUT lumen positive relative to interstitial fluid in loop of Henle and TAL.
Where does a cotransporter with sodium move substances ?
Co-transport with sodium moves substances into the cell
Where does an exchanger with sodium move substances ?
Counter transport (exchange) with sodium moves them out
Give an example of secondary active transport.
Sodium pump (actuve transport) sets up Na+ concentration gradient. This gradient is then used by cell to transport other substances.
Identify the main reabsorption pathways in the PT (i.e. which molecules in/out, using which transport systems etc.).
APICAL SURFACE (out means into tubular fluid, in means into cell)
1) Na+ H+ exchanger (1 Na+ in, 1 H+ out), using Na+ gradient. In the tubular fluid, H+ combine with filtered bicarbonate to form carbonic acid. Extracellular carbonic anhydrase then catalyses dissociation of carbonic acid into water and CO2, still in tubular fluid. CO2 diffuses back into cell (freely permeable to lipid membrane) whereas H2O enters cell through aquaporins. Intracellular carbonic anhydrase converts H2O and CO2 back into carbonic acid, which dissociates into H+ and bicarbonate. H+ is used in the Na+ H+ exchanger (into tubule lumen), whilst the the bicarbonate is excreted/secreted from basolateral membrane.
2) Ion channels for divalent cations (e.g. Ca++ channel)
3) Na+ glucose/AA cotransport (uses Na+ gradient to transport metabolites into cell)
BASOLATERAL SURFACE (out means into isf then blood, in means into the cell) 1) Na+ K+ ATPase (3 Na+ out, 2K+ in)
2) HCO3- Cl- exchanger (HCO3- out, Cl- in), or HCO3- Na+ cotransport (HCO3- out, Na+ out) to secrete HCO3- obtained from apical surface.
3) K+ Cl- cotransport (both out, uses K+ gradient to reasborb Cl-)
Overall, bicarbonate, chloride and potassium all leave down their concentration gradients.
4) Na+ Ca++ exchanger (Na+ in, Ca++ out, uses Na+ gradient to reabsorb Ca++ against its concentration gradient)
5) Glucose/AA transport (out of cell)
ALSO
Increased concentrations of Cl- and K+ in isf due to secondary active transport (K+ diffuses down concentration gradient into isf, Cl- follows). Because of increase in osmolarity, water will follow through paracellular route, into isf. Solutes dissolved in this water (e.g. Cl-) will follow (not cations, because because transluminal negative potential in PT means cations tend to fight solvent drag, so net flow of anions into isf whereas in other parts of tubule, where lumen is positive, net intake of cations into isf) through solvent drag, through paracellular route
ALSO
Entry of other solutes: coupled to Na+ entry on apical membrane; facilitated diffusion on the basolateral membrane. Other solutes have their own channels through which they diffuse, this is facilitated by the process of concentration (water loss) and Na + entry.
ALSO
Organic ions transporters on both apical and basolateral membranes to reabsorb wanted ones (e.g. nucleotides) from tubular fluid, or to secrete ones (e.g. antibiotics, absorbed pesticides) from blood
Why is it possible to segregate between proteins (i.e. transporters) of basolateral membrane and those of the apical membrane ?
Because of tight junctions (proteins cannot diffuse across these)
Define Tmax, in reabsorption. What are the units for it ? Are there any circumstances in which Tmax can be exceeded ?
Tmax is “the point at which increases in concentration of a substance do not result in an increase in movement of a substance across a cell membrane” – transport maximum.
Measured in mg/min or mmol/min (rate).
If blood conc. is high, Tmax can be exceeded (e.g. high blood concentration of glucose in diabetes mellitus: normally, almost 100% of
glucose can be reabsorbed by PT. In diabetes, blood glucose higher, exceeds
Tmax of PT for glucose, so glucose appears in urine)
Graph amount of glucose filtered versus plasma glucose concentration.
Refer to slide 3 on page 5 of lecture.
Normally, plasma glucose concentration should be 100-120 mg/100 mL. Up to 120 mg/100 mL, that amount can be reabsorbed. Once above 180 (range for diabetes), Tmax for glucose is exceeded, so more filter but can only reabsorb this maximum right here. Hence, concentration of plasma glucose increases even more. Amount reabsorbed is saturated, so amount excreted increases.
