Renal tubule function Flashcards
PCT reabsorbs what % of Na
65
PCT reabsorbs what % of water
65%
PCT reabsorbs what % of chloride
60%
PCT reabsorbs what % of amino acids
100%
PCT reabsorbs what % of glucose
100%
PCT reabsorbs what % pf urea
50-60%
PCT reabsorbs what % of K
55%
What intrinsic factors to the PCT anatomy/histology facilitate absorption
micorvilli
What factors limit reabsorption
Gradient limited - basolateral transit to capillaries and removal
Diffusion limited - ability to diffuse paracellualrly or transcelluarlly
- Tubular maximum/saturated transporters
Glucose reabsorption occurs where ? Via? What transporters are there? Where are each located?
ranscellular reabsorption (PCT) via SGLUT (sodium dependent glucose symporter) via secondary active transport. Two types of transporter
◦ Low affinity - high capacity - rapidly absorbs glucose but ineffective at low concentrations (early PCT) and reabsorbs 90% of filtered glucose
◦ High affinity low capacity - slowly reabsorbs, remains effective at low concentrations, late PCT (i.e. usually when most glucose has already been reabsorbed) and reabsorbs 10% of glucose filtered
Draw a graph outlining relationship between glucose concentration and plasma glucose indicating filtered and urine concentratinos
Glomerular tubular balance is?
As GFR increases the filtered load increases and can saturate transporters and reabsorption increasing excretion
What is the threshold of glycosuria or renal threshold for glucoe
11-12mmol/L
Why is glycosuria a problems
Osmotic diuretic - reduced Na reabsorption, increases solute load in filtrate and urinary flow rates –> reducing water and later electrolyte reabsorption due to higher flow rates. Increased K excretion due to increased Na/K exchange in DCT and aldosterone release
ADH release
Risk of urianry tract infection
How is the PCT implicated in glucose control
Reabsorption
Also in severe starvation can be responsible for 40% of gluconeogenesis
What is PAH and why does it matter?
PAH or paramino hippuric acid is a protein 90% protein bound, 10% free
But in the kidney 20% filtered and 80% secreted in PCT–> i.e. complete clearance
When PAH concentration is low all the plasma perfusing the kidney is being cleared
Effective renal blood flow = effective renal plasma flow / (1- haematocrit)
How do you use PAH to calculate renal blood flow
Effective renal blood flow = effective renal plasma flow / (1- haematocrit)
As renal clearance = 100%
Renal clearance = effective renal blood flow
So U x V/P = effectvie plasma flow /(1- haematocrit)
Normal urine protein content per day
100mg
What waste products are secreted by the kidney
Organ anions
- Urate, bile salts, fatty acids, PG, drugs
Organic cations
- Creatinine, ACh, catecholamines, histamine
Uncharged waste
- Urea
- Uric acid
- Bilirubin
What is glomerular tubular balance
Sodium reabsorption is adjusted to match filtration/GFR - so a constant FRACTION of sodium is reabsorbed in the PCT
◦ Increased filtered glucose and amino acids with elevated filtration –> increased sodium re-absorption
◦ Increased GFR increases the protein concentration in the glomerular cpiallary plasma which increases the oncotic pressure in the peritubular capillaries enhancing the movement of solutes and water into the capillary . Thus a constant fraction of sodium is reabsorbed of GFR
Freee water clearance refers to?
Any water present that is in excess of what is required to produce iso-osmotic water to the plasma
i.e. low osmolality = excess free water
High osmolality = negative free water
How would you calculate free water clearance
Urine volume, urine osmolality and plasma osmolality
Chloride intake per day
1.5mmol/kg
Chloride reabsorption via
Paracellular and transcellular tied to Na reabsroption
Collecting duct intercalated B cells exchange it with HCO2 dpeendent on basolateral H+ ATPase
What is the osmolality of glomerular filtrate
292mosmol/L
Which SGLT receptor is responsible for most glucose reabsorption
SGLT2 90%
How does glucose move across basolateral membranes in PCT
GLUT 2 faciliate diffusion –> later GLUT1 faciliated diffusion in late PCT
How to AT2 affect PCT
Increased Na/H countertransport
How to PTH act in the PCT
Decreased phosphate absorption
What is the osmolality at the end fo the PCT
300mosm/L
What % of water remains at the end of the LOH
25%
What is the osmolality of fluid n the lumen of the tubule at the end of the LOH
100mosm/L
How much water is reabsorbed in the descending loop of Henle
10-20%
What % of Na is reabsorbed in the ascending LOH
25%
What % of K is reabsorbed in the ascending loop of Henle
30%
What % of chloride is reabsorbed in the ascending LOH
25%
What is a leaky K channel called?
ROMK channel
What is the purpose of a ROMK channel in the ascending LOH?
“Leaky channels” allow K+ to move outside the cell —> create a luminal positive potential as K+ moves down its concentration gradient. Positively charged lumen repels diva lent cations pushing them paracellularly (PTH independent). Loop diuretics which interfere with luminal absorption and this gradient can reduce Ca and Mg reabsorption
25% Ca reabsorption
60% Mg absorption
What can take the place of an ion in the NaKCL2 transporter in the ascending LOH?
Ammonium can take the place of K
What produces the osmolality of the inner medulla?
Na , Cl 60% of osmolality
urea 40% of osmolality
What is the osmolality of the inner medulla of the kidney
1200mosm/L
Draw a DCT cell and explain the absorption of Ca and Na/Cl in this region
What effect do thiazides have on Calcium
◦ Reduce urinary calcium excretion as sodium concentration intracellularlyu drops with Na/Cl blockade meaning the Na/Ca exchanger ono the basolateral membrane becomes more active (chemical gradient) increasing calcium reabsorption.
◦ This effect is utilised with thiazide treatment in familial hypercalciuria
What % of Na reaches the DCT? What % is reabsorbed at this location?
10%
6% reasbrobed in th DCT leaving 4%
What does PTH do in the DCT?
GPCR –> adenylate cuclase –> cAMP increase –> protein kinase A –> increased Ca receptor activation and insertion for reabsorption at the basolateral membrane
What is the action of aldosterone
- Aldosterone —> binds to intracellular aldosterone receptors leading to mRNA production for Na and K+ channels luminally and increased Na/K ATPase. Increases Na and H20 reabsorption as well as K+ loss –> as loss of Na+ from the tubular fluid produces a negative charge + there is a concentration gradient
Where are aquaporins inserted?
Usually in basolateral membrane
Giving ADH causes insertion of aquaporin 2 into apical membrane
What does a principle cell do?
Regulated water excretion and reabsorption as well as K and Na
Aldosterone and ADH primary regulators at this point
Which is the most abundant cell in the colecting duct
Principal ell
Distal tubule osmoallity
100mosm/L
What secretion occurs in the collecting duct and DCT
K
H+
How low can the osmolality get inthe collecting duct
50mosm/L
What 2 things does ADH affect
Water reabsorption
Urea reabsorption
What is the volatile acid load of the body per dayu
13-20mol/day
Normal concentrations of CO2 in mmol/L and HCO3
◦ Normal concentration of CO2 is 1.2mmol/L (0.03 x 40mmHg) and normal HCO3 is 24mmol/L
What is the Henderson Hasselbach equation
pH = pKa + Log (HCO3-)/(CO2)
ForCO2 and HCO2= 7.4
Fixed non voltaile acid production per day includes what?> How much>
- Fixed e.g. lactate, sulphate, phosphate and ketones
◦ 10mmol/kg/day produced and eliminated by the kidney. AN exceedingly small amount of H+ is free in the blood and therefore a small amount is filtered and cannot comprise the required amount of acid to be excreted each day.. whereas loads of base is filtered and needs reabsorption
3 mechanisms of acid base control in the kidney
Reabsorbed bicarbonate
Ammonium
Buffers
What is the lowest the urine pH can get
4.4
Average urinary pH
6
Where is bicarbonate reabsorbed
90% PCT
Thick ascneding limb, DCT and CT for the final 10%
How is H+ secreted in the kidney 3
◦ Primary H+ ATPase in the PCT and DCT
◦ H+/Na+ anti porter in the PCT and ascending limp
◦ H+/K+ ATPase in the CT
How is ammonia produced in the kidney
From glutamine
Where does glutamine come from
Amino acid
Filtered and absorbed from circulation by PCT cells
What is glutamine metabolised to
NH4+ and HCO3