gene models and nephron Flashcards
what does filtration permit and restrict
-permits H2O and small molecules
-restricts blood cells and proteins
what does ultra filtrate consist of
-protein free plasma
-low K+, high Na+
-1% protein filtered- very little protein ends up in the nephron
what’s filtrate modification
-tubular reabsorption and secretion
-afferent arteriole-> glomerular capillaries -> efferent arteriole -> peritubular capillaries -> venous blood
-where glomerular capillaries are, glomerular filtration occurs, in which the filtrate travels through the renal tubules, the proximal tubule, loop of Henle, distal tubule and the collecting duct, and eventually excreted out by urine
-lots of things taken out as filtrate passes down the nephron
-tubular reabsorption occurs at the beginning of the peritubular capillaries, and tubular secretion at the end (venous end)
what’s tubular transport
-renal tubules are epithelium allowing net transport across epithelium
-nephron is a tubular structure, where the lumen is is where the filtrate goes
-on the other side (basolateral membrane) we have interstitial fluid and peritubular capillaries
-apical membrane sits next to the filtrate (near lumen)
-rebabsorption is the movement from tubular lumen to the peritubular capillary
-secretion moving from peritubular capillary to the lumen across the epithelium
-two types of transport: transcellular and paracellular
-transcellular reabsorption is across the cell from lumen to the peritubular capillary
-transcellular secretion is from peritubular capillary to the lumen
-paracellular transport is transport that occurs between the cells- tight junctions- water and solutes can be let through
-trabnsport membranes on apical membrane and basolateral membrane- different types of proteins
what gets reabsorbed in the proximal tubules
-bulk reabsorption is 70% filtrate
-70% H2O and Na+
-100% glucose and AA are reabsorbed
-90% of HCO3- reabsorbed
what occurs in the proximal tubule: transportation
-different transport proteins on AM and BM allow net transport
-NaK ATPase- primary active transport protein- hydrolyses ATP to give it energy to transport Na and K, 3 Na out, 2 K in. needs ATP because extracellular level of sodium is high and intracellular is low but we want Na+ into high conc of Na+
-K+ coming in recycles across BM via basolateral potassium channel
-ATPase and K channels set driving force for transport at apical membrane
-ATPase = low intracellular Na, K channels = negative membrane potential- means a big driving force for Na influx on AM- large electrochemical driving force for Na uptake
-AM has a sodium glucose transport protein- in which both move into cell, Na+ leaves by ATPase, glucose leaves BM by another facilitated diffusion protein
-Na amino acid transport protein- in which both move in, both leave the same way as glucose Na transport protein
-Na phosphate co-transporter called NapiIIa- leave the same way as before
-sodium gradient is needed otherwise no transport is going to happen
-reabsorption of sodium, glucose, AA and phosphates also drives water reabsorption (paracellular) can be transcellular is water reabsorption is through aquaporins
NaPiIIa knockout mouse research
-took mice and deleted both copies of gene that codes for NaPiIIa -can’t make sodium phosphate co-transport protein so normal amount of phosphate reabsorption to right
-significant different between normal mouse and NaPiIIa phosphate level
-more calcification in knockout mouse and m ore intraluminal stones - kidney stones therefore damaging kidneys
what is bicarbonate reabsorption like in the proximal tubule
-BM contains NaK ATPase again
-sodium hydrogen exchange protein 3 (NHE3) on AM in which it uses the driving force of sodium in the ATPase in exchange for H+ ion- so the Na+ enters and H+ leaves via AM- + moving against electrochemical gradient- secondary AT
-H+ ion which moves back into the body fluid, binds with HCO3- to form H2CO3- this dissociates to CO2 and H2O under carbonic anhydrase (on AM)
-CO2 freely permeable down AM
-water moves into cell by aquaporins on AM
-inside cell, CO2 and H2o form H2CO3 using carbonic anhydrase found in the cell -equilibrium system , then it breaks down again to a H+ and HCO3- therefore H+ recycled
-sodium bicarbonate co-transport protein on BM used to move both Na+ and HCO3- out of cell
what happens if there is a loss of NHE3
-inhibition of H+ secretion
-inhibiton of a+ and HCO3- transport
-fall fluid reabsorption
-drop in plasma HCO3-
-pH falls due to HCO3- compensation
what does splay mean
-not all nephrons are working at the same amount so a ‘leak’ starts to occur
what’s transport maximum
-substances reabsorbed via membrane carriers e.g. glucose, AA via Na+ co-transporters
-consequence of limited number of carriers in the cell membrane
-all working at maximum rate therefore maximum transport
-the more glucose there is, the more filtration
what are the 2 systems of secretion via the proximal tubule
-organic cations
-organic anions
why is the loop of Henle important
-controls concentration of urine
-controls reabsorption of Na+, Cl-, and H2O
-controls reabsorption of Ca2+ and Mg2+
-is the site of action of loop diuretics
what’s the structure for the loop of Henle
-thin descending limb- high water permeability, not permeable to Na+ and Cl-
-thick ascending limb- water impermeable , permeable to Na+ and Cl-
transportation in the thick ascending limb
-NaK ATPase on BM
-K+ channel on BM
- both of these set a negative membrane potential- during force for sodium uptake on AM
-AM contains Na+K+2Cl- co transport protein, these 4 ions bind to the protein, when they bind they undergo conformational change , then it releases 4 ions into the intracellular fluid
-protein called NKCC2- exclusive expressed here
-only works on the sodium gradient
-Na leaves cell by the NaK ATPase
-Cl- accumulates in cell and leaves via a chloride channel on BM called CLCK
-barttin= protein that is classed as a beta subunit- not an ion channel but it regulates ion channels and regulates CLCK
-K+ recycles - invia NKCC2, leaves via apical potassium channel called Kir1.1 or ROMK (same thing)
-Kir1.1 recycles the potassium- need this because without recycling there isn’t enough potassium for NKCC2 to work
-paracellular transport : Ca2+ and Mg2+ driven by Na+ reabsorption
