Lecture 5 - Renal Transport Processes Flashcards
What is the primary regulatory process of kidney function?
Reabsorption
Flow and transport rate through the proximal tubule vs the rest of the nephron?
Proximal tubule: high flow and high transport rate
Rest: low flow and low transport rate
List the 11 substances reabsorbed in the proximal tubule and the % reabsorption.
- H2O (70%)
- Na+ (70%)
- K+ (80%)
- HCO3- (85%)
- HPO4– (70-80%)
- AAs (100%)
- Glucose (100%)
- Cl- (60%)
- Ca++ (60%)
- NH3
- SO4–
List the 4 substances reabsorbed in the distal tubule.
- Na+
- K+
- HCO3-
- Cl-
Where are the tight junctions between the cells in the proximal tubule located?
Near apical membrane (soda can plastic wrapper analogy)
4 types of solute active transports? Provide an example for each.
- Primary active transport: Na+/K+-ATPase
- Secondary active transport: SGLT-1/2 glucose transporter with Na+
- Tertiary active transport
- Endocytosis: macromolecules (e.g. large proteins) are engulfed by the plasma membrane
What is secondary active transport?
Transporter protein couples the movement of an ion down its electrochemical gradient, created using energy, to the uphill movement of another molecule or ion against a concentration/electrochemical gradient
3 types of passive solute transport? Common thread?
ALL DOWN CONCENTRATION GRADIENTS:
- Simple diffusion
- Facilitated diffusion (with carrier)
- Osmosis
List the pumps of the proximal tubule cells.
LUMENAL
- Na+/H+ lumenal exchanger
- SGLT-1/2 lumenal glucose transporter
- Na+/HPO4– lumenal co-transporter
- AA Na+ lumenal dependent transporter
- K+ active channel
BASOLATERAL:
- Basolateral Na+/K+-ATPase
- GLUT on basolateral membrane for glucose facilitated diffusion
- Anion exchangers on the basolateral membrane
- Facilitated diffusion transporters for AAs on the basolateral membrane
Concentration of plasma Na+?
140 mEq/L
Concentration of plasma K+?
4.5 mEq/L
Describe the transport of water in the proximal tubule.
With each solute transported transcellularly, water follows paracellularly
Does the transport of solutes in the proximal tubule occur entirely transcellularly?
NOPE, some paracellularly
4 important characteristics regarding the proximal tubule with regard to transport?
LEAKY
- It is highly permeable
- High transport rate
- Low concentration and electrical gradients between lumen and blood due to the fast transport
- Low resistance
4 important characteristics regarding the cortical collecting duct with regard to transport?
TIGHT
- It is not permeable (no paracellular transport, not even of water under normal conditions)
- Low transport rate, but very efficient
- High concentration and electrical gradients between lumen and blood due to the selective transport
- High resistance
List the pumps/channels of the cortical collecting duct cells. Common thread?
ALL HIGHLY REGULATED:
- Na+ channel
- K+ channel
- H+ ATP-ase to secrete
- Na+/K+-ATPase on basolateral membrane
- Cl-/HCO3- exchanger
How do the cells of the proximal tubule change from segments S1 to S3?
- Less mitochondria, because lower rate of transport
2. Deeper microvilli, because need for higher affinity to glucose since 80% of it has already been absorbed in S1 and S2
Na+ concentration in the peritubular capillaries?
10 mEq/L
Describe the transport of glucose in the proximal tubule.
At normal plasma glucose, the rate of glucose delivery is easily handled by transport capacity in the proximal tubule so that no glucose is excreted
BUT, past this point, which is the tubular maximum for glucose, Tmg, (375 mg of glucose/min) the reabsorption is maximal and cannot be increased, so that we start excreting glucose
Mechanism:
- SGLT-2 Na+ glucose symporter (1 Na+ for 1 glucose) takes up glucose in S1/S2 and SGLT-1 (2 Na+ for 1 glucose and HIGHER affinity and LOWER capacity)
- Glucose exits via a GLUT uniporter on the basolateral membrane
What is the Tmg dependent on?
Capacity of nephrons to transport glucose per unit time
What is the renal threshold for glucose?
Plasma glucose (in mg%) at which glucose first appears in the urine
How do we call the curves of excretion and reabsorption of glucose vs plasma glucose? Why?
Splay = space between the 2 curvolinear curves => refers to the difference between renal threshold and saturation, Tm
Splay occurs because different kidney nephrons (juxtamedullary vs outer cortical nephrons) do not all have the same tubular maximum for glucose (TmG), aka the same density of glucose transporters, therefore some nephrons may excrete before others
What do we call the point where the curves of excretion and reabsorption of glucose vs plasma glucose cross?
Maximal reabsorption capacity for glucose of the kidney
Normal fasting BGL? Far or close to Tmg?
70-90 mg%
FAR
Consequence of glucose being excreted in urine?
It acts as an osmotic agent and pulls water => diuresis
Normal Tmg?
375 mg/min
What substance has a fasting blood level close to its Tm? What does this mean?
Phosphate
You will excrete it as soon as you ingest it
Describe the relationship between plasma glucose and filtered glucose?
Directly proportional and linear since it passes readily through the glomerular pores
Normal renal threshold for glucose?
180-200 mg%
Where does most of the secretion of organic acids and bases occur?
S2 of the proximal tubule
What is the rate limiting step of secretion of organic molecules?
Active transport from the plasma to the cell of the nephron
What happens to the organic molecule to be secreted once it has been pumped into the nephron cell?
It passively diffuses down its concentration gradient into the nephron lumen
What is another substance similar to PAH? Implications?
Penicilin - cleared so quickly by the kidneys that you need to ingest a lot of it for enough to remain in plasma (used to strain it from urine), so physiologists developed an inhibitor for the penicilin transporter in the nephron
Does PAH also have a Tm? What does it mean?
Maximal rate of secretion of PAH after which some of it will remain in the renal vein
How does the fact that we lose nephrons as we age impact drug dosage for the elderly?
Should be lower, as the clearance will be lower and there will be risks of toxicity
LIST substances that are actively transported in the tubules.
TBD
DESCRIBE the renal handling of proteins and small peptides.
- Peptides and small proteins (e.g. angiotensinogen, growth hormone, insulin) are filtered in considerable quantities
- Small amount of large proteins is filtered (0.02% of plasma albumin)
=> 100% reabsorbed by being enzymatically cleaved into AAs:
LARGE PROTEINS:
- Binding to proximal tubule apical membrane receptors (requires energy)
- Endocytosis by apical membrane
- Pinched off intracellular vesicle merges with lysosome => degradation into AAs
- Exit via basolateral membrane via facilitated diffusion to enter peritubular capillaries
SMALL PEPTIDES:
- Catabolized into AAs, di and tripeptides in proximal tubule lumen by brush border peptidases
- Na+ co-transport into proximal tubule cell
- Exit via basolateral membrane via facilitated diffusion to enter peritubular capillaries
What does the rate of endocytosis of filtered proteins in the proximal tubule depend on? What to note?
Depends on concentration of proteins in glomerular filtrate, until a maximal rate of vesicle formation and Tm for protein uptake is reached => this process is easily saturated so a large increase in filtered proteins causes the excretion of large quantities of proteins
Normal excretion of proteins per day?
100 mg/day
Where are most organic solutes transported? What to note?
Proximal tubule
If they escape reabsorption or are secreted, then they are usually excreted AND urea is the exception
Describe the transport of small organic solutes in the proximal tubule.
- Na+/K+-ATPase on basolateral membrane exports Na+
2a. Neutral or negative organic solutes enter via Na+ symporters
2b. Positive organic solutes enter via uniporters driven by the negative membrane potential - Resulting intracellular accumulation of organic solute establishes favorable gradient for its efflux
- Exit basolateral membrane via many different pathways
Purpose of Na+/H+ lumenal exchanger? Net effect?
HCO3- reabsorption because HCO3- is impermeable intra and paracellularly in proximal tubule!
H+ is secreted and reacts with HCO3- to form H2O and CO2 by lumenal carbonic anhydrase, which diffuse into the proximal tubule cells. HCO3- in then reformed by carbonic anhydrase inside the cell and exits via the basolateral membrane via facilitated diffusion
NET EFFECT:
1 Na+ reabsorbed = 1 H+ pumped out = 1 HCO3- reabsorbed
Where is Ca++ reabsorbed in the nephron? Explain how.
In distal convoluted tubule, particularly under the effects of PTH
Does the collecting duct either secrete or reabsorb K+ and HCO3-?
Can do both
At which nephron site would penicilin be secreted?
PCT
