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Renal I > Test 2 (Tubular Transport: Basic Principles, Organic Solute Transport) > Flashcards

Test 2 (Tubular Transport: Basic Principles, Organic Solute Transport) Flashcards

1
Q

“Logic” of Renal Handling of Substances

A
  • Bulk filtration of all small molecules into Bowman’s Capsule
  • Selective retention of useful materials by Tubular Reabsorption
  • Unwanted material pass into urine
  • Some transport processes are Physiologically regulated to CONTROL AMOUNTS of SUBSTANCES in Body Fluids
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2
Q

Renal Handling of Water, Sodium, Glucose, and Urea

A

1) Water:
a) Amount filtered per day:
- 180 g

b) Amount Excreted:
- 1.8 g
c) Percent Reabsorbed:
- 99%

2) Sodium:
a) Amount filtered per day:
- 630 g

b) Amount Excreted:
- 3.2 g

c) Percent Reabsorbed:
- 99.5%

3) Glucose:
a) Amount filtered per day:
- 180 g

b) Amount Excreted:
- 0 g

c) Percent Reabsorbed:
- 100%

4) Urea:
a) Amount filtered per day:
- 56 g

b) Amount Excreted:
- 28 g

c) Percent Reabsorbed:
- 50%

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3
Q

Structure of Tubular Epithelium

A
  • Basement Membrane
  • Basolateral Membrane
  • Interstitial Fluid
  • Tight Junction
  • Luminal Membrane
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4
Q

Transcellular vs Paracellular Movement

A

Transcellular:
- Movement of Solute and Water THROUGH the CELL

Paracellular:
- Movement of Solute and Water THROUGH the TIGHT JUNCTION

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5
Q

Basic Mechanisms for Transcellular Solute Movement

PASSIVE (“Downhill”) TRANSPORT

A

PASSIVE (“Downhill”) TRANSPORT:

1) Simple Diffusion:
- “Down” electrochemical gradient via LIPID BILAYER or Aqueous Channels

2) Facilitated Diffusion:
- “Down” electrochemical gradient; SPECIFIC CARRIERS REQUIRED

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6
Q

Basic Mechanisms for Transcellular Solute Movement

ENERGY–DEPENDENT (“Uphill”) PROCESSES

A

ENERGY–DEPENDENT (“Uphill”) PROCESSES:

1) Primary Active Transport:
- AGAINST Electrochemical Gradient; ATP HYDROLYSIS provides Energy

2) Secondary Active Transport:
- “Downhill” movement of one substance provides ENERGY for “Uphill” movement of another substance

  • Cotransport, Countertransport

3) Pinocytosis:
- Protein Reabsorption

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7
Q

Proximal Tubular Transport

A
  • Proximal Tubule Reabsorbs most of FILTERED Water, Na+, K+, Cl-, Bicarbonate, Ca2+, Phosphate
  • Normally, reabsorbs ALL the FILTERED Glucose, Amino Acids
  • Several Organic Anions and Cations (Including Drugs, Dug Metabolites, Creatinine, Urate) are secreted in PROXIMAL TUBULE
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8
Q

TF/ Plasma Concentration Ratios Provide information on Tubular Handling of Substances

A
  • What fraction of filtered water is reabsorbed in Proximal Tubule?

(HINT: Look at INULIN Concentration Ratio)

  • Na+ Concentration DOESNT CHANGE- does this mean Na+ isn’t Reabsorbed???
  • Concentration fo Urea and Cl- INCREASE Somewhat, are these compounds secreted by Proximal Tubule? What about PAH?
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9
Q

TF/ P Ration in Proximal Tubular Lumen: INULIN

A

TF/ P = 3!!!!!

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10
Q

TF/ P Ration in Proximal Tubular Lumen: GLUCOSE

A

TF/ P = 0!!!!!

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11
Q

TF/ P Ration in Proximal Tubular Lumen: PAH

A

TF/ P = 10!!!!

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12
Q

Proximal Tubular Na+ Reabsorption

A
  • Provides driving force for Reabsorption of Water, other solutes
  • Polarity of Epithelial Cell membranes facilitates net UNIDIRECTIONAL TRANSPORT
  • Ultimately powers by Na+, K+, ATPase in Basolateral membrane
  • Na+ Reabsorption usually coupled to Transport of/ Exchange for another solute
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13
Q

Sodium Reabsorption is linked to Transcellular Transport of other substances

A

LUMEN:
1) Na+ and Glucose (Same direction)

2) Na+ and H+ (Opposite)
3) Na+, K+, Cl- (Same Direction but move 2 Cl-)

INTERSTITIUM:

1) Na+ and K+ (Opposite)
- Na+, K+, ATPase

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14
Q

Water Reabsorption follows Na+ Reabsorption

A
  • In Proximal Convoluted Tubule, BULK FLOW!!!!
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15
Q

Paracellular Reabsorption of Cl- and Urea in Early PCT

A
  • Not ACTIVE process, but ultimately DEPENDENT on Na+ and Water Reabsorption
  • As Na+ and Water are Reabsorbed, Cl- and Urea become more concentrated in Luminal Fluid
  • Modest concentration Gradient between Lumen and Peritubular Interstitial provides driving force for PARACELLULAR REABSORPTION
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16
Q

TF/P Concentration Ratios

A
  • Note modest INCREASE in UREA and CL- Concentrations in Tubular Lumen
17
Q

Factors Promoting Fluid Movement into Peritubular Capillaries

A

1) HIGH PLASMA COLLOID OSMOTIC PRESSURE in the Peritubular Capillary Blood (Due to Filtration of Fluid in Glomerulus)
2) LOW HYDROSTATIC PRESSURE in these Capillaries
3) CONSEQUENCE: Almost as much Fluid is Reabsorbed as was initially Filtered into Bowman’s Capsule

18
Q

Impact of Organic Nutrient Handling

A
  • Large amount of Nutrients (Glucose, Amino Acids) filtered each day; must be RETAINED
    a) Small molecules: free filtered

b) Completely reabsorbed by Proxima Tubule
c) Mo reabsorption in more Distal Segments
- Kidneys DONT regulate PLASMA CONCENTRATION of Glucose and Amino acids, Liver and Endocrine systems do!!!

19
Q

Basic Mechanism of Tubular Reabsorption of Glucose and Amino Acids

A
  • Secondary ACTIVE TRANSPORT; Transcellular only
  • Uptake accrois Luminal Membrane:
    a) Against Concentration Gradient

b) Coupled to Na+ entry down its Electrochemical Gradient
c) Ultimately dependent on Na+, K+, ATPase
- Exits Cells through BASOLATERAL MEMBRANE by FACILITATED DIFFUSION

20
Q

Mechanisms of Glucose Reabsorption

A

Luminal Membrane:
1) Na-Glucose COTRANSPORT

Basolateral Membrane:
1) Facilitated Diffusion

21
Q

Glucose reabsorption is Saturable

A
  • Limited number of Na+, Glucose Cotransproters in Luminal Membrane
  • If filtered amount (load) of Glucose (=GFR x Pglucose) EXCEEDS a CERTAIN RATE:
    a) Capacity of Nephrons to Reabsorb all the Filtered Glucose is exceeded

b) Glucose appears in the Urine (GLUCOSURIA)
- Identify a disease in which saturation occurs
- Same principles apply to Amino Acid Transport

22
Q

Glucose Reabsorption is Saturable

A
  • TmG= Tubular Glucose Maximum

Ex: Maximum rate of Glucose Reabsorption by all the Nephrons COMBINED

23
Q

Questions for Discussion

A
  • Would the Filtered Load of Glucose change if GFR INCREASED by Plasma Glucose Concentration remained Constant? How would this affect the Threshold Value?
  • Would an inhibitor of the Renal Tubular Na+, K+ ATPase affect Reabsorption of Glucose? Why?
  • Urine Output increases in Diabetes. Why?
  • Why would a Diabetic patient by thirsty?
24
Q

Consequences of Osmotic Diuretics

A
  • INCREASED Water Excretion

- INCREASED Sodium Excretion (Why?)

25
Q

Secretion of Organic Anions (PAH, Bile Salts, Uric Acid, Creatinine, etc) in PCT

A
  • TERTIARY Active Transport

- Also drugs such as Penicillin, Salicylates, some Antiviral Drugs

26
Q

PAH Secretion

A
  • PAH Secretion is Saturable so that the Secretion can reach its threshold and therefore the Excreted PAH will not increase with such a steep slope
27
Q

Secretion of Organic Cations in PCT

A
  • Catecholamines, Acetylcholine, Dopamine
28
Q

Passive Diffusion of Organic Acids and Bases

A
  • Organic anions and Cations are ionized forms of Weak Acids and Bases, respectively
  • CHARGED FORMS: Highly Polar compounds CANNOT READILY DIFFUSE through Lipid Bilayer
  • UNCHARGED MOLECULES: Less polar, more lipid-soluble and therefore MEMBRANE-PERMEABLE
29
Q

Biochemistry of Weak Acids and Bases

A
  • Weak ACIDS are Neutral when PROTONATED:
    A- + H+ = HA
  • Weak BASES are Neutral when DEPROTONATED:
    B + H+ = BH+
  • ACIDS SOLUTIONS generate Neutral forms of WEAK ACIDS
  • BASIC SOLUTIONS generate Neural forms of WEAK BASES
30
Q

Tubular Handling of Organic Acids and Bases is affected by pH of Luminal Fluid

A
  • H+ in the Tubular Lumen FAVORS REABSORPTION of Organic Acids, but TRAPS Organic Bases in the Lumen
31
Q

Effects of Luminal pH on Tubular handling of Organic Acids and Bases

A
  • LUMINAL ACIDIFICATION favors REABSORPTION of Organic Acids, EXCRETION of BASES
  • Many drugs are Weak Acids or Bases
  • If your patient Overdoses on ASPIRIN (Acetylsalicylic Acid, an Organic Acid), how can you promote Urinary Excretion of Aspirin to help eliminate it from his body???
    ~~~~~MAKE URINE ALKALINE!!!!!
32
Q

Summary: Basic Tubular Processes

A
  • Large amounts of Small Molecules filtered each day; most Reabsorbed, especially in PROXIMAL TUBULE
  • Two routes: TRANSCELLULAR, PARACELLULAR
  • Na+ Reabsorption provides driving force for Solute and Water Transport in PROXIMAL TUBULE
  • Reabsorbed materials enter PERITUBULAR CAPILLARIES by BULK FLOW!!!!!!!
  • Osmotic Diuretics INCREASE H2O, Na+ EXCRETION
33
Q

Summary: Proximal Tubular Handling of Organic Compounds

A
  • Organic Nutrients: Reabsorbed by SECONDARY ACTIVE TRANSPORT, linked to Na+ Reabsorption
  • Glucose Reabsorption is Saturable; Glycosuria occurs when Filtered Load exceeds Reabsorptive Capacity of PROXIMAL TUBULAR EPITHELIUM
  • Organic anions, Cations SECRETED by Tertiary Active Transport
  • H+ secretions FAVORS REABSORPTION of Organic ACIDS, EXCRETION of Organic BASES

Renal I (14 decks)

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