Renal Tubular Transport Flashcards
1
Q
‘Logic’ of renal handling of substances
-What happens to the small molecules?
A
Bulk filtration of all small molecules into Bowman’s capsule
2
Q
‘Logic’ of renal handling of substances
-What happens to useful materials?
A
Selective retention of useful materials by tubular reabsorption
3
Q
‘Logic’ of renal handling of substances
-What happens to unwanted materials?
A
Unwanted materials pass into urine
4
Q
Pathways for movements of solute and water across epithelium
-Transcellular?
A
Goes from the tubular lumen through the epithelial cell and into the peritubular interstitium
5
Q
Pathways for movements of solute and water across epithelium
-Paracellular?
A
Movement from the tubular lumen through a tight junction and into the peritubular interstitium
6
Q
Basic mechanisms for transcellular solute movement
-Passive (‘downhill’) transport:
A
- Simple diffusion
- Facilitated diffusion
7
Q
Basic mechanisms for transcellular solute movement
-Simple diffusion?
A
‘down’ electrochemical gradient via lipid bilayer or aqueous channels
8
Q
Basic mechanisms for transcellular solute movement
-Facilitated diffusion?
A
- ‘down’ electrochemical gradient
- specific carriers required
9
Q
Basic mechanisms for transcellular solute movement
-Energy-dependent (‘uphill’) processes?
A
- Primary active transport
- Secondary active transport
- Pinocytosis
10
Q
Basic mechanisms for transcellular solute movement
-Primary active transport?
A
- Against electrochemical gradient
- ATP hydrolysis provides energy
11
Q
Basic mechanisms for transcellular solute movement
-Secondary active transport?
A
- ‘downhill’ movement of one substance provides energy for ‘uphill’ movement of another substance
- cotransport, countertransport
12
Q
Basic mechanisms for transcellular solute movement
-Pinocytosis
A
protein reabsorption
13
Q
Proximal tubular transport
- What does it reabsorb (normally):
- most of?
- all of?
A
- Reabsorbs most of the filtered water, Na, K, Cl, bicarbonate, Ca, and phosphate
- Reabsorbs all of the filtered glucose and aas
14
Q
Proximal tubular transport
-What is secreted in the proximal tubule?
A
Several organic anions and cations (including drugs, drug metabolites, creatinine, and urate)
15
Q
Changes in solute concentrations along proximal tubule (graph)
- Which substance is at the top? Why?
- Which substances are at the bottom? Why?
A
- PAH and inulin at the top-freely filtered (neither secreted/reabsorbed)-stays in tubule and as water is reabsorbed inulin the TF/P ratio increases
- Amino acids and glucose at the bottom (fully reabsorbed)-concentration going down as you move down the PCT
16
Q
Tubular fluid (TF)/plasma concentration ratios provide information on? -What fraction of filtered water is reabsorbed in proximal tubule?
A
- TF/plasma concentration ratios provide information on tubular handling of substances
- About 2/3
17
Q
- TF/plasma concentration ratios provide information on tubular handling of substances
- What fraction of filtered water is reabsorbed in proximal tubule:
- Hint: look at?
- What fraction of filtered water is reabsorbed in proximal tubule:
A
Inulin concentration ratio
18
Q
TF/P ratio in proximal tubular lumen:
-Inulin-If the TF/P of a water/inulin solution is 1?
A
2/3 of water is reabsorbed and inulin is not reabsorbed/secreted–>TF/P=3
19
Q
Glucose-Starts out at TF/P ratio of 1
-What happens as you go along the proximal tubular lumen?
A
In the proximal tubular lumen 2/3 of the water is reabsorbed but all of the glucose is reabsorbed as well so TF/P ratio becomes 0
20
Q
Proximal tubular Na reabsorption
-Provides driving force for?
A
-Provides driving force for reabsorption of water other solutes
21
Q
Proximal tubular Na reabsorption
-Polarity of epithelial cell membranes facilitates?
A
Net unidirectional transport
22
Q
Proximal tubular Na reabsorption
-Ultimately powered by what in the basolateral membrane?
A
NaK ATPase
23
Q
Proximal tubular Na reabsorption
-Na reabsorption usually coupled to?
A
Transport of/exchange for another solute
24
Q
Figure of different Na transporters (slide 19)
- 3 on apical membrane?
- where are they located in the nephron?
A
- Na-glucose cotransporter and Na-H exchanger are found in the PCT
- Na, K, 2Cl is found in the loop of henle
25
Bulk flow?
| -Slide 20?
Water reabsorption follows Na reabsorption in PCT
26
Paracellular reabsorption of Cl- and urea in what part of the nephron?
Early PCT
27
Paracellular reabsorption of Cl- and urea in early PCT
- Not active processes, but ultimately dependent on Na and water reabsorption
- As Na and water are reabsorbed, Cl- and urea become more concentrated in luminal fluid causes Cl and urea to be reabsorbed
28
Paracellular reabsorption of Cl- and urea in early PCT
- Modest concentration gradient between?
- Provides driving force for?
- How is this expressed on the graph (slide 22)?
- Lumen and peritubular interstitium
- Provides driving force for paracellular reabsorption
- This is expressed on the graph by modest increases in urea and Cl- concentrations in tubular lumen
29
Factors promoting fluid movement into peritubular capillaries?
- High plasma colloid osmotic pressure in peritubular capillary blood (due to filtration of fluid in glomerulus)
- Low hydrostatic pressure in these capillaries
30
Factors promoting fluid movement into peritubular capillaries
-Consequence of these factors?
Almost as much fluid is reabsorbed as was initially filtered into Bowman's capsule
31
Impact of organic nutrient handling?
- Large amounts of nutrients (glucose, aas) filtered each day; must be retained
- Small molecules: freely filtered
- Completely reabsorbed by proximal tubule
- No reabsorption in more distal segments
32
Organ and system that regulate plasma concentrations of glucose and aas?
Liver and endocrine system regulate plasma concentrations of glucose and aas
33
Basic mechanism of tubular reabsorption of glucose and aas?
- Secondary active transport
| - Transcellular only
34
Basic mechanism of tubular reabsorption of glucose and aas
- Uptake across luminal membrane (into cell)
- Which way is it going relative to the concentration gradient?
- Coupled to?
- Ultimately dependent on?
- Against concentration gradient
- Coupled to Na entry down its electrochemical gradient
- Ultimately dependent on NaK ATPase
35
Basic mechanism of tubular reabsorption of glucose and aas
| -Exits cell through? By what mechanism?
Exits cell through basolateral membrane by facilitated diffusion
36
Mechanism of glucose reabsorption figure
Slide 27
37
Glucose reabsorption is saturable (applies to aa transport also)
-Limited number of Na, glucose cotransporters in luminal membrane
38
Glucose reabsorption is saturable (applies to aa transport also)
- If filtered amount (load) of glucose (= GFR x Pglucose) exceeds a certain rate?
- How does this apply to aas?
- Capacity of nephrons to reabsorb all the filtered glucose is exceeded
- Glucose appears in the urine (glucosuria)
- Same principles apply to aas
39
Glucose reabsorption is saturable-graph on slide 29
| -Tmg?
tubular glucose maximum i.e. maximum rate of glucose reabsorption by all the nephrons combined
As the plasma glucose increases (up to about 200 mg/dl) the glucose filtered equals the amount reabsorbed but once the glucose gets too high the reabsorption levels off and the glucose excreted starts to increase
40
Questions for discussion
-Would the filtered load of glucose change if GFR increased but plasma glucose concentration remained constant? How would this affect the threshold value?
Yes it would increase
| -Threshold value would not change because the number of transporters stays the same no matter what
41
Questions for discussion
| -Would an inhibitor of the renal tubular NaK ATPase affect reabsorption of glucose? Why?
Yes it would change the concentration gradient for sodium
-If we are not pumping sodium out of the cell and creating the gradient for sodium to move from the luminal space into the cell, glucose will not be reabsorbed
42
Questions for discussion
| -Urine output increases in diabetes. Why?
If the glucose is higher in the tubular fluid, filtered load has increased, at Tm for reabsorptive capacity->glucose goes into tubular fluid->higher glucose conc in tubular fluid->water is pulled into the tubular lumen (pulling water out of cells-why diabetics are thirsty)
43
Case presentation
- A 10 y/o girl is found unconscious in her bedroom and is rushed to the ER. The attending physician learns from her parents that the patient has appeared lethargic and sometimes disoriented for the previous 2-3 weeks, and often complained of thirst despite drinking unusually large amounts of water and Dr. Pepper. She has been urinating frequently and bedwetting which her parents ascribe to her excessive fluid intake. A urine specimen is obtained and dipstick reveals 4+ glucosuria; plasma glucose is 700 mg/dL
- Explain the patient's polyuria. Why is she thirsty?
Because the glucose is pulling the water from her cells
44
Mechanism of osmotic diuretics (pictures on slide 33)
| -Under normal conditions, what happens to Na?
-Under normal conditions (iso-osmolar tubular fluid), Na is reabsorbed into the peritubular capillary
45
Mechanism of osmotic diuretics (pictures on slide 33)
| -When an osmotically active agent is filtered?
- They prevent water reabsorption, thus diluting the Na that is present in the tubule
- Under these conditions, Na will move from the peritubular capillary to the tubular lumen
46
Consequences of osmotic diuretics?
- Increased water excretion
| - Increased sodium excretion
47
Consequences of osmotic diuretics
| -Increased sodium excretion-why?
Lose water and sodium to maintain osmolar gradient
48
Secretion of organic ions (e.g. PAH, bile salts, uric acid, creatinine, etc.) and also drugs (penicillin, salicylates, some antiviral drugs) in PCT (figure slide 35)
-Type of transport?
-Tertiary active transport
49
PAH secretion is saturable-graph
As the amount excreted increases there is a secretion max as the amount filtered increases
At the secretion max all of the transporters that secrete PAH back into the tubular lumen have been saturated
50
Clearances of inulin, glucose, PAH vs plasma concentrations graph
RPF always stays the same
- As plasma conc of PAH increases, PAH clearance decreases because transporters get saturated
- Inulin clearance doesn't change (GFR)
- Glucose clearance increases (never goes over GFR-transporters get saturated and glucose gets excreted)
51
Secretion of organic cations (catecholamines, acetylcholine, dopamine, etc.) in PCT
-Gradient initiated by?
Na-K ATPase
52
Passive diffusion of organic acids and bases
| -Organic anions
Charged forms of acids
53
Passive diffusion of organic acids and bases
| -Organic cations
Charged forms of bases
54
Passive diffusion of organic acids and bases
| -Charged forms?
Highly polar compounds, cannot readily diffuse through lipid bilayer
55
Passive diffusion of organic acids and bases
| -Uncharged molecules?
Less polar, more lipid-soluble and therefore membrane-permeable
56
When protonated, weak acids are?
neutral (when deprotonated, weak bases are neutral)
57
Acidic solutions generate?
neutral forms of weak acids (basic solutions generate neutral forms of weak bases)
58
Tubular handling of organic acids and bases is affected by?
pH of luminal fluid
59
Tubular handling of organic acids and bases is affected by pH of luminal fluid
-H+ in the tubular lumen favors?
H+ in the tubular lumen favors reabsorption of organic acids, but traps organic bases in the lumen
60
Effects of luminal pH on tubular handling of organic acids and bases
-Luminal acidification favors?
- Luminal acidification favors reabsorption of organic acids, excretion of bases
- Many drugs are weak acids or bases
61
Effects of luminal pH on tubular handling of organic acids and bases
-If a patient overdoses on aspirin (acetylsalicylic acid, an organic acid), how can you promote urinary excretion of aspirin to help eliminate it from his body?
Inject bicarbonate into patient to alkalinize the urine to help them excrete the overdose of aspirin
-opposite would happen with a weak base overdose
62
Changes in solute concentrations along proximal tubule (graph slide 13)
-TF/P ratio of 1 can mean what 2 things?
- Sodium and water are reabsorbed in equal proportions
| - No secretion/reabsorption
63
Why doesn't the osmolarity change (graph slide 13)?
Because sodium is the major osmole
64
```
Tubular fluid (TF)/plasma concentration ratios provide information on-refers to graph on slide 13
-Na concentration doesn't change-does this mean Na isn't reabsorbed?
```
No just means it is reabsorbed in the same proportion as water
65
```
Tubular fluid (TF)/plasma concentration ratios provide information on-refers to graph on slide 13
-Concentrations of urea and Cl- increase somewhat-are these compounds secreted by proximal tubule? What about PAH?
```
- No urea and Cl are not secreted but are not reabsorbed in the same amount as water either-concentrating in tubular lumen
- PAH TF/P ratio is higher so we know it is being secreted
66
TF/P ratio in proximal tubular lumen-PAH
2/3 of water is reabsorbed and secreting PAH into tubular lumen-->TF/P ratio of 10
67
Figure of different Na transporters (slide 19)
| -1 found on basolateral membrane?
Na-K ATPase
