Renal Tubular Function 1 Flashcards
How is the proximal tubule divided?
Where it is located?
The proximal convoluted tubule and the proximal straight tubule.
It is present in the renal cortex.
How is the inner-surface of the proximal tubule adapted?
The surface area of the proximal tubule is greatly enhanced by the presence of microvilli forming a brush border
Describe the difference between primary and secondary active transport in the proximal convoluted tubule.
The selective distribution of ion channels, exchangers and cotransporters = secondary active transport. NO ATP DIRECTLY , other forms of energy e.g cotransport
Pumps on the apical and basolateral membranes = primary active transport USES ATP
In the proximal convoluted tubule substances can move transcellularly and paracellularly. What does this mean?
Transcellular - through cells
Paraceullar - between cells
How does water move through the proximal convoluted tubule?
The movement of Na+ creates an osmotic gradient for the movement of water between and through cells (AQP1).
This segment of the tubule is quite water permeable, implying that the filtrate is (almost) isotonic with the interstitial space, which in the cortex means that it is effectively isotonic with plasma. By the end of the tubule, about 70% of the water is reabsorbed.
What flows through the paracellular route because of the net outward hydrostatic and osmotic forces
How are substances such as glucose and amino acids reabsorbed in the proximal convoluted tubule?
Uses the electrochemical gradient of Na+ into epithelial cells to drive the movement of other substances.
Uses Na+/K+ATPase to move Na+ out of the cell on the basolateral membrane
Are the following molecules absorbed along the proximal tubule? What is their conc at the end of the tubule?
- inulin/creatinine
- urea
- chloride
- Na+/ K+
- HCO3-
- Amino Acids
- Glucose
- inulin/creatinine = NO, higher
- urea = WEAKLY, higher
- chloride = WEAKLY, higher
- Na+/ K+ = YES, same (proportional to water)
- HCO3- = YES, lower (absorbed faster than water)
- Amino Acids = STRONGLY, much lower
- Glucose = STRONGLY, much lower
How is glucose absorbed early and late in the proximal tubules?
Early
- conc of glucose is high, absorbed by SGLT2 cotransport with 1 x Na+
- leaves cell via GLUT2 on basolateral membrane
Late
- conc of glucose is lower, SGLT1 cotransport with 2 xNa+
- leaves cell via GLUT1 on basolateral membrane
What is the tubular maximum tranport with regards to glucose?
Tm = 2.1mmol/min. This is the maxims tubular load of glucose. If this is exceeded, there will be glucose present in the urine
When is SGLT2 inhibition useful?
Recently been proposed for the use as treatment of diabetes
E.g canagliflozin, dapagliflozin
The concept is that by inhibiting the transporters, you cause glucosuria. However this may increase risk of UTI
What is the plasma amino acid concentration?
How are amino acids reabsorbed in the proximal tubule?
Is the transport Tm limited?
2.5-3.5mM
Due to diversity of AA’s, many different tranporters are used. Most are cotransporters with Na+
Transport is rate limited
How is bicarbonate (HCO3-) absorbed in the proximal tubule?
25mM is present in the filtrate
The main mechanism is by reaction with H+, entering through Na+/H+ exchanger.
The rate at which the equilibrium is achieved is increased by carbonic anhydrase.
- HCO3- reacts with H+ to form carbonic acid
- This dissociates in to H20 and CO2
- They diffuse into the cell via aquaporins
- In the cell with form carbonic acid which dissociates into HCO3- and H+.
- bicarbonate leaves via Na+/3HCO3- coo transporter using gradient of HCO3- (Na+ is going against its conc grad!)
What is the mechanism of action of acetazolamide?
- acts in the proximal tubule
- inhibits CA, to stop cycle so Na+ stays in tubule and therefore so does water
- acts as a weak diuretic (lots more tubule to come which can compensate)
- used in glaucoma, mountain sickness prophylaxis
- urine become alkaline, metabolic acidosis
Describe Cl- movement in the proximal tubule.
Active:
- Cl-/anion transporter
- methanoate equilibrium
- Given the absorption of HCO3, with the difference balanced by Na+ absorption, less Cl- is moved than Na+ in the early proximal tubule.
- Given than water is reabsorbed with Na+ and HCO3-, this means that Cl- concentration modestly increases along the proximal tubule
Passive:
- As Cl- concentration increases towards the end of the proximal tubule, it drives paraceullar Cl- movement down its concentration gradient
Describe the movement of albumin in the proximal tubule
Very little albumin enters the filtrate, but that which does binds to the plasma membrane of the tubule cells, is endocytose, then catabolised to its amino acids for subsequent recycling in the body.
