solute handling 2 of 2

Question 1

describe the mechanism in response to hyperkalemia

Answer 1

high K= stimulate

1. release of
   
   1. Insulin + Epinaphrine +aldosterone
2. these all stimulate NKATPase
   
   1. this pump increases the movement of Na into the interstitum and K into the cell
3. sequestering the K from the intracellular - breif?

Question 2

Describe the movment of K in the early and late PT

Answer 2

PT is involved in paracellular K+ uptake

1. early PT
   
   1. Na+ transcellular reabsorption ->H2O reabsoprtion-> K reabsorption via solvent drag
2. latePT
   
   1. electrochemical drive

Question 3

describe the movement of K in the TAL. how much is taken up by each method and how much is left in the lumen at the end of the TAL

Answer 3

1. paracellular
   
   1. 50% of K reabsorption
   2. two favorable factors
      
      1. electrochemical drive- lumen is +
      2. K concentration
2. transcellular
   
   1. apical
      
      1. NKCC2
   2. Basolateral
      
      1. passive leakage
3. End of TAL 10% of filtered load remains

Question 4

three locations for K reabsorption. explain them and the significance for the last of the three

Answer 4

1. early/late PT
   
   1. absorbs 80%
2. TAL
   
   1. absorbs 10%
3. ICT/CCT/MCD-initial collecting tubule/corticol collecting duct/inner medullary collecting duct
   
   1. low dietary intake
      
      1. ICT and CCT reabsorb
         
         1. reabsorbes- 2%
      2. MCD
         
         1. reabsorbs 6%
   2. normal /high dietary intake
      
      1. ICT and CCT
         
         1. secrete K
         2. degree ranges from 20-180%

Question 5

How can the nephron lead to an excretion of 150% K?

Answer 5

same load reaches DCT, difference in handeling at the ICT and CCT

1. high load, lumen [K] in MCD because of secretion at the ICT
   
   1. paracellular pathway is conductive to K+

Question 6

what cells in the ICT and CCT are responsible for K secretion absorption?

Answer 6

1. secretion
   
   1. principal cells
2. absorption
   
   1. alpha incercalated cells

Question 7

How do principal cells transport K into lumen?

Answer 7

1. in the ICT and CCT,
   
   1. principal cells
      
      1. upregulate the NKATPase in basolateral side
         
         1. take K from the interstitum and moves it intracellularly
2. kaluresis and naturesis
   
   1. the flow is high and K cannot move back across the channelEnac cannot reabsob Na
   2. increase K channels in apical side

Question 8

describe what happens in a diet rich with K+.

1. hours, days

Answer 8

• steps
  
  • increase K load
  • increase K plasma
  • increase NKATPase
  • increase K intracellularly
  • increase K exiting via apical channels
  • increase kaluresis
• steps
  
  • increase K load
  • increase plasma
  • depolarization of adrenal ZG
  • aldosterone affects K secretion in principal cells of the CCCT in 3 ways
    
    1. stimulates NKATPase
       
       1. over DAYS
    2. increases ENaC
       
       1. over HOURS
       2. increasing conductance
          
          1. increasing electrochemical force for kaluresis
    3. increases apical K channel activity

Question 9

describe the sensitivity of aldosterone and potassium release

Answer 9

1. adrenal cortex- Zona glomerulosa cells have a high density of K+ channels
2. increasing pasma K ->changes in conductance and charge of adrenal ZG cells. The cells depolarize quickly
3. increase in K and Ca results in cell swelling

this sensor is incredibly sensitive

Question 10

describe the cells involved in low potassium levels

1. cell
2. location and item used
3. function

Answer 10

1. alpha intercalated cells in the cct
2. H/K antiporter on apical side
3. initially low [K] plasma counteracts the factor icreasing secretion in the principal cells by reducign Na/K pump and aldosterond release

Question 11

what are the three types of calcium in the human body? Which, if any are reabsorbed?

Answer 11

1. ionized
   
   1. free Ca++
   2. this is the only form reabsorbed
2. diffusable
   
   1. complexed with small anions
   2. low pH in the nephron leads to these forms being ionized and frees the calcium for reabsorption
3. nondiffusable
   
   1. bound to proteins
   2. NOT FILTERED in healthy kidneys

Question 12

2/3 of the Ca++ is reabsorbed here

Answer 12

1. PT
   
   1. 2/3 reabsorbed
   2. mostly unregulated
   3. paracellular
      
      1. 80%
      2. electrochemical gradient
      3. solvent drag
   4. transcellular
      
      1. apical side
         
         1. Ca++ channel on the
      2. basolateral
         
         1. 3N/Ca exchanger-secondary
         2. Ca/H pump- active

Question 13

where can Ca reabsorption be regulated?

Answer 13

TAL

1. paracellular route
   
   1. 25% reabsobed this route
   2. high Ca decreases the activity of NKCC, which in turn makes the lumen less +, allowing less Ca to be reabsorbed by decreasing the elctrostatic drive of Ca++

DCT -the regulation site for Ca++

1. paracellular
   
   1. none in the location
2. trancellular
   
   1. apical
      
      1. PTH and calcitonin
         
         1. regulate Ca via calcium channel
         2. increasing its reabsorption
         3. Ca binds to calmodulin, keeping the interstitial Ca++ low
   2. basolateral-same as PT
      
      1. 3N/Ca exchanger-secondary
      2. Ca/H pump- active

Question 14

Where does Pi reabsorption occur?

Answer 14

most reabsoption occurs in PT via, secondary transportt system to generate an apical transporter: NAPi

1. high PTH
   
   1. more intracellular vesicles and increase in phophouresis
2. low PTH
   
   1. low vesicles reinserted

regulation

1. PTH
2. Acid base

Question 15

Where and what is the majority of Mg++ reabosrption?

Answer 15

along the paracellular route GREATEST in the TAL

two conditions

1. high Mg++concentration
   
   1. paracellular
   2. mediated by the same mechanism as Ca++ binds to NKCC2 decreasing activity, making the lumen less + and decreases the electrostatic drive to drag Mg++ in with Ca++
2. low Mg++ concentration
   
   1. transcellular and paracellular

Question 16

what is normal fasting glucose?

Answer 16

70-100mg/dL

Question 17

Describe the SGLT and GLUT receptors with respect to the kidney for a Type 1 diabetic.

Answer 17

freely filtered in the glomerulus

The receptors are fine, the problem is the kidney threshold is overwhelmed

PT reabsorption

1. early-98%
   
   1. apical
      
      1. SGLT2
         
         1. high cap
         2. low aff
         3. secondary active transport
   2. basolateral
      
      1. GLUT2
         
         1. Na+ independent
         2. low aff
         3. high cap
2. late-2%
   
   1. SGLT1
      
      1. low cap
      2. high aff
   2. basolateral
      
      1. GLUT1
         
         1. Na+ independent
         2. high affinity
         3. low cap

Question 18

Describe the glucose transport in the early PT

Answer 18

freely filtered in the glomerulus

PT reabsorption

1. early-98%
   
   1. apical
      
      1. SGLT2
         
         1. high cap
         2. low aff
         3. secondary active transport
   2. basolateral
      
      1. GLUT2
         
         1. Na+ independent
         2. low aff
         3. high cap
2. late-2%
   
   1. SGLT1
      
      1. low cap
      2. high aff
   2. basolateral
      
      1. GLUT1
         
         1. Na+ independent
         2. high affinity
         3. low cap

Question 19

Describe the glucose transport in the late PT

Answer 19

freely filtered in the glomerulus

PT reabsorption

1. early-98%
   
   1. apical
      
      1. SGLT2
         
         1. high cap
         2. low aff
         3. secondary active transport
   2. basolateral
      
      1. GLUT2
         
         1. Na+ independent
         2. low aff
         3. high cap
2. late-2%
   
   1. SGLT1
      
      1. low cap
      2. high aff
   2. basolateral
      
      1. GLUT1
         
         1. Na+ independent
         2. high affinity
         3. low cap

Question 20

A patient has a nonsense mutation in the SGLT2 gene. What is the outcome for this patient?

Answer 20

This is a deleterious mutation, as it will cause glucosuria. which decrease the trasnsport maximum

PT reabsorption

1. early-98%
   
   1. apical
      
      1. SGLT2
         
         1. high cap
         2. low aff
         3. secondary active transport
   2. basolateral
      
      1. GLUT2
         
         1. Na+ independent
         2. low aff
         3. high cap
2. late-2%
   
   1. SGLT1
      
      1. low cap
      2. high aff
   2. basolateral
      
      1. GLUT1
         
         1. Na+ independent
         2. high affinity
         3. low cap

Question 21

A patient has a nonsense mutation in the SGLT1 gene. What is the outcome for this patient?

Answer 21

Mild glucosuria, and susceptibility to fungal infections. This decreases the transportation maximum in the lumen.

PT reabsorption

1. early-98%
   
   1. apical
      
      1. SGLT2
         
         1. high cap
         2. low aff
         3. secondary active transport
   2. basolateral
      
      1. GLUT2
         
         1. Na+ independent
         2. low aff
         3. high cap
2. late-2%
   
   1. SGLT1
      
      1. low cap
      2. high aff
   2. basolateral
      
      1. GLUT1
         
         1. Na+ independent
         2. high affinity
         3. low cap

Question 22

describe the movement of glucose through the renal system

Answer 22

freely filtered in the glomerulus

PT reabsorption

1. early-98%
   
   1. apical
      
      1. SGLT2
         
         1. high cap
         2. low aff
         3. secondary active transport
   2. basolateral
      
      1. GLUT2
         
         1. Na+ independent
         2. low aff
         3. high cap
2. late-2%
   
   1. SGLT1
      
      1. low cap
      2. high aff
   2. basolateral
      
      1. GLUT1
         
         1. Na+ independent
         2. high affinity
         3. low cap

Question 23

What happens to the transporters when too much glucose is filtered?

Answer 23

SGLT transporters are saturable

kidney threshold

• transport rate at which carriers are completely saturated (across all nephrons)
• glucose Tm ~400mg/min but plasma = 350mg/dL
  
  • splay =
    
    • area between threshold and Tm
    • different transport capacity of different nephrons

Question 24

area between threshold and Tm of glucose

Answer 24

Splay

1. area between threshold and Transport maximum (Tm)
2. different transport capacity of different nephrons

Question 25

What location are proteins handled and how?

Answer 25

• specific transporters for anionic, cationic and neutral amino acids
  
  • cell transport
    
    • anionic + some neutral
  • H exchanger
    
    • neutral
  • gradient charged cationic exchanger in LATE PT
    
    • electrochemical drive
• oligo peptides
  
  • two transcellular pathways
    
    • hydrolyed by enzymes on brush border into amino acid
    • transporter of oligopeptides
• peptides
  
  • transported transcellularly by endocytosis and intracellular hydrolysis to free amino acids

Question 26

Describe what happens to oligopeptides and peptides that make it through the filter

Answer 26

• specific transporters for anionic, cationic and neutral amino acids
  
  • cell transport
    
    • anionic + some neutral
  • H exchanger
    
    • neutral
  • gradient charged cationic exchanger in LATE PT
    
    • electrochemical drive
• oligo peptides
  
  • two transcellular pathways
    
    • hydrolyed by enzymes on brush border into amino acid
    • transporter of oligopeptides
• peptides
  
  • transported transcellularly by endocytosis and intracellular hydrolysis to free amino acids

Question 27

where does amino acid reabsorption occur?

Answer 27

• specific transporters for anionic, cationic and neutral amino acids
  
  • cell transport
    
    • anionic + some neutral
  • H exchanger
    
    • neutral
  • gradient charged cationic exchanger in LATE PT
    
    • electrochemical drive
• oligo peptides
  
  • two transcellular pathways
    
    • hydrolyed by enzymes on brush border into amino acid
    • transporter of oligopeptides
• peptides
  
  • transported transcellularly by endocytosis and intracellular hydrolysis to free amino acids

Question 28

end product of amino acid catabolism. how does it affect the kidneys?

Answer 28

urea is a nitrogenous end product of amino acid catabolism occurring in the liver

1. freely filtered
   
   1. 20-40% of filtered load is excreted
2. secreted in loop of henle
   
   1. tDLH and tALH 60%
3. reabsorbed
   
   1. IMCD-70%
   2. PT-50%
      
      1. paracellular-concentration gradient and solvent drag

Question 29

What is used to confirm hypovolemia? why?

Answer 29

[BUN]/creatinine ratio. urea excretion decreases with a greater filtration rate.

Urea reabsorption is dependent on concentration gradient

• high flow in tubule->decrease water reabsorption-> decrease [urea] gradient = decrease urea reabsorption
• low flow in tubule ->increase water reabsorption-> increase [urea] gradient =increase urea reabosorption
• if the ratio increases above normal value ~10, hypovolemia is confirmed- b/c the person will be absorbing more urea.

Question 30

what is urea reabsorption dependent on?

Answer 30

urea reabsorption is dependent on concentration gradient

• high flow in tubule->decrease water reabsorption-> decrease [urea] gradient = decrease urea reabsorption
• low flow in tubule ->increase water reabsorption-> increase [urea] gradient =increase urea reabosorption

Question 31

discuss the variety of organic solutes that are manipulated in the kidneys

Answer 31