11. Transport of Organic Solutes, K, and Acids & Bases

Question 1

What are the 3 solutes that are present at low concentrations in the body that the kidney controls plasma levels of?

Answer 1

1. Glucose
2. Amino acids
3. Inorganic ions (K, Ca, etc)

Question 2

What is the transport of glucose in the kidney?

Answer 2

Proximal convoluted tubule reabsorbs nearly all filtrated glucose (near zero glucose concentrations in fluid emerging from the proximal tubule)

Glucose transport is transcellular- cross apical membrane by Na/glucose cotransporter (SGLT1 & 2), across basolateral membrane CoA facilitated diffusion

Glucose excretion in the urine only occurs when the plasma concentration exceeds a threshold

Slides 11-14 Nov 26

Question 3

What is the difference between SGLT1 and SGLT2 Na/glucose cotransporters?

Answer 3

SGLT1- 2Na:1glucose
Has high affinity for glucose
Late proximal tubule
Glucose concentration low in distal segments

SGLT2- 1Na:1glucose
Reabsorbs 90% of glucose (first one third of the PCV)
High capacity, low affinity
Early proximal tubule

Slides 12-13 Nov 26

Question 4

How are amino acids transported in the kidney?

Answer 4

Glomerulus freely filter amino acids
Proximal tubule reabsorbs >98% -> transcellular route

Wide variety of amino acid transporters:
Apical membrane AA transport is Na, H, or AA linked
Basolateral membrane AA exit via exchangers and facilitated diffusion

Slide 15 Nov 26

Question 5

How are oligopeptides transported in the kidney?

Answer 5

H driven cotransporter takes up oligopeptides across the apical membrane
Proximal tubule reabsorbs ~99% of filtered oligopeptides
Peptidases are present on the brush-border of proximal-tubule cells, these brush border enzymes hydrolyze many peptides including angiotensin II
This releases free amino acids and oligopeptides that are reabsorbed through apical H/oligo cotransporters (PepT1)
Oligopeptides broken down in cell

Slide 16 Nov 26

Question 6

How are proteins transported in the kidney?

Answer 6

Glomerular barrier prevents filtration of large amounts of protein, this restriction is incomplete tho
Proximal tubule reabsorbs small proteins
Proximal tubule cells use receptor mediated endocytosis to reabsorb proteins and polypeptides

Slide 17 nov 26

Question 7

How is potassium (K) transported in the kidney?

Answer 7

K homeostasis involved external K balance between environment and body, and internal K balance between intracellular and extracellular compartments

External balance- relationship between dietary intake and excretion determines this
During steady state they are equal
Excretion adjusts to intake

Internal balance- appropriate distribution of K mostly inside cells
Release or uptake from cell may have large effect on ECF concentration

Slides 19-26 Nov 26

Question 8

What are the differences in Na and K that make distribution much different?

Answer 8

Na is largely extracellular
K is largely intracellular

High K inside cells and mitochondria is essential for maintenance of cell volume, regulation of intracellular pH, and control of cell enzyme function
Low K outside cells is essential for maintaining the steep K gradient across cell membranes that is largely responsible for the membrane potential of excitable and nonexcitable cells

Slide 19 nov 26

Question 9

What are the mechanisms by which potassium (K) is excreted?

Answer 9

Ingested K moved transiently into cells for storage before excretion by the kidney
The kidney excretes K by a combination of filtration, reabsorption and secretion

Low K intake = 2% excretion
Normal K intake = 10% excretion
Chronic high K intake = 150% excretion

Proximal tubule reabsorbs most of filtered K whereas distal nephron reabsorbs or secreted K

Slides 21-24 Nov 26

Question 10

What 3 things promote K transfer from ECF into the cells?

Answer 10

Insulin, epinephrine, and aldosterone promote the transfer from ECF into the cells
via the Na/K ATPase

Aldosterone increases K secretion by ICT and CCT
Increase in Na reabsorption and K secretion by principal cells

Slide 22 Nov 26
Slide 26 Nov 26

Question 11

How does the proximal tubule reabsorb potassium (K)?

Answer 11

Passive reabsorption- paracellular pathway
Electrochemical gradient and solvent drag

Thick ascending limb- mostly transcellular mediated NKCC2
Distal tubule- DCT, CNT, ICT, CCT

Principal cells K secretion transcellular

α and β intercalated cells involved in K reabsorption

Slide 25 Nov 26

Question 12

What does an increase in luminal flow mean?

Answer 12

Increase luminal flow=increase K secretion
Low flow allows K in lumen to increase, opposing more K flow to line
Higher flows sweeps K, resulting in lower K in lumen, steeper gradient

Slide 26 Nov 26

Question 13

How are acids and bases transported in the kidney?

Answer 13

Lungs & kidneys regulate blood acid-base balance by independently controlling 2 major components of the body’s major buffering system:
CO2 (lungs) & HCO3- (kidney)
pH buffer: a substance that reversibly consumes or releases H+ (minimizes size of pH changes)

Lungs excrete CO2 and nonvolatile acids and bases from metabolism
Kidney must reabsorb virtually all filtered HCO3 and excrete non volatile acids from metabolism and food and bases from metabolism

Slides 44-53 Nov 26

Question 14

What are nonvolatile acids?

What are nonvolatile bases?

Answer 14

Nonvolatile acids- sulfuric acids, phosphoric acids, various organic acids that the lungs can not handle

Nonvolatile bases- end up as HCO3

Slide 47 Nov 26

Question 15

Study the interactions between CO2 and HCO3 on slide 45 Nov 26

Answer 15

The most important physiological buffer pair is CO2 and HCO3

Question 16

What is respiratory acidosis?

What is respiratory alkalosis?

Answer 16

Respiratory acidosis- increase in PCO2, decrease alveolar ventilation, decrease lung diffusing capacity (pulmonary edema)
Ventilation-perfusion mismatch
⬇️pH⬆️HCO3⬆️PCO2

Respiratory alkalosis- decrease in PCO2, increase in alveolar ventilation caused by:
Hypoxia, anxiety, aspirin intoxication
⬆️pH⬇️HCO3⬇️PCO2

Slide 46 Nov 26

Question 17

What is acidosis compared to alkalosis?

Answer 17

Acidosis- blood has an excess of H causing the pH to fall below 7.35, this requires removal of H & reabsorption of HCO3 to buffer H & increase the pH to normal

Alkalosis- deficit of H, resulting in a more basic blood pH of above 7.45, this requires the reabsorption if H as well as the excretion of HCO3, to return free H to the blood & decrease the pH to normal levels

Majority of HCO3 reabsorption occurs in proximal tubule

Question 19

What is metabolic acidosis?

What is metabolic alkalosis?

Answer 19

Metabolic acidosis- addition of acids other than CO2 or H2CO3, removal of alkali (fixed PCO2)
Decrease urinary secretion of H (renal failure), ketoacidosis (diabetes mellitus), lactic acidosis (shock), HCO3 loss (sever diarrhea)
⬇️pH⬇️HCO3 (no change)PCO2

Metabolic alkalosis- removal of acids other than CO2 or H2CO3 (fixed PCO2), addition of alkali 
HCO3 load (NaHCO3 therapy), loss of H (severe vomiting)
⬆️pH⬆️HCO3 (no change)PCO2

Slide 46 nov 26

Question 20

What are the 2 major non-HCO3 buffers in the kidneys?

Answer 20

1. Divalent phosphate (HPO4)- buffers H to create a monovalent phosphate (H2PO4) which is not readily absorbed & is excreted in urine
2. Ammonia (NH3)- buffers H to create ammonium (NH4), which is also excreted in urine

Slide 50 nov 26

Question 21

What do α and β intercalated cells do during acidosis and alkalosis?

Answer 21

α intercalated cells- function during acidosis, excrete H & reabsorb HCO3

β intercalated cells- function during alkalosis, resulting in the reabsorption of H & excretion of HCO3

Slide 53 Nov 26
Slide 21 Dec 3

Question 22

What are the 3 steps in which the body deals with the 70mmol/day acid challenge?

Answer 22

1. Extracellular bicarbonate neutralizes most of the H load (also non-bicarbonate buffers)
2. Lungs excrete the CO2 formed in the process
3. The kidneys regenerate the bicarbonate (and non-bicarbonate) buffers in the ECF by creating new bicarbonate at a rate that is equal to the rate of H production

During alkaline challenge (vomiting->loss of HCl) kidneys decrease H excretion, reduce bicarbonate production