Reabsorption and Secretion

Question 1

Which molecules are reabsorbed via passive carrier mediated transport?

Answer 1

• Glucose
• Amino Acids
• organic acids
• Sulphate
• phosphate ions

Question 2

What determines the maximum amount of substrate that can be reabsorbed during carrier mediated reabsorption?

Answer 2

Tm: maximum transport capacity of carriers, due to saturation of all carriers

Question 3

What occurs if Tm (maximum transport capacity) is met during carrier mediated reabsorption?

Answer 3

• The excess substrate enters the urine

Question 4

What is the renal threshold of the kidneys?

Answer 4

The plasma [substrate] at which Tm (max. transport capacity) occurs in carrier mediated reabsorption

Question 5

The renal threshold for glucose is 10mmol/L. What will happen in a person with a plasma glucose of 15mmol/L during renal filtration?

Answer 5

• Since glucose is freely filtered, plasma [glucose] will equal filtrate [glucose], therefore filtrate glucose 15mmol/L
• Beyond the renal threshold the excess is excreted so: 10mmol/L of filtrate [glucose] will be reabsorbed, and 5mmol/L will be excreted in urine

Question 6

Why is the renal threshold for glucose and amino acids set significantly higher than the normal physiological concentration?

Answer 6

• To prevent the unnecessary excretion of valuable nutrients
• The concentration of glucose and AA’s is controlled by insulin and other counter regulatory hormones

Question 7

What are some molecules that are regulated by their renal threshold?

Answer 7

• Sulphate and Phosphate ions

- The normal plasma concentration of these ions is close to their Tm

Question 8

Where does most Na reabsorption occur?

Answer 8

The proximal tubule (65-75%)

Question 9

Via which mechanism is Na reabsorbed? Why?

Answer 9

• Active transport

- To establish a gradient of Na across the tubule wall

Question 10

How does the Na gradient across the tubule wall encourage reabsorption of Na?

Answer 10

• The ATP/Na pump is on the basolateral surface of the tubule epithelium, pumps Na to interstitial fluid creating low epithelium [Na]
• Concentration gradient then drives Na from [high] in the tubule lumen across the luminal membrane into the tubule epithelium

Question 11

How does Na move passively across the luminal wall into the epithelium, as it is not permeable at cell membranes?

Answer 11

• because the luminal brush border has higher Na permeability due to the microvilli and the large amount of Na ion channels

Question 12

Which molecules does Na reabsorption facilitate the reabsorption of? how?

Answer 12

• Cl ions and water
• negative Cl follows the electrical gradient established by Na
• the movement of Na & Cl out of the lumen creates an oncotic force that draws water out of the tubules

Question 13

How does the reabsorption of Na lead to the reabsorption of other substrates in addition to Cl and water?

Answer 13

Water following Na and Cl out of the lumen causes fluid concentration of other substrates in the tubules to increase - creating outgoing concentration gradients

Question 14

What is the rate of reabsorption for non-actively reabsorbed substrates determined by? Examples of these substrates?

Answer 14

Determined by:

• Amount of water that has been reabsorbed (determines substrate concentration)
• Permeability of the membrane
• K, urea, Ca

Question 15

Why is only about 50% of urea reabsorbed despite a concentration gradient being established? Why is there no reabsorption of substances like inulin and mannitol?

Answer 15

• Urea: because the lumen membrane is only partially soluble towards urea, resulting in 50% excretion
• Inulin / mannitol: lumen membrane is not permeable to these

Question 16

How does the active transport of Na also mediate the reabsorption of carrier transported molecules such as glucose, AA’s, etc.?

Answer 16

These molecules are often symported across the luminal membrane along with Na by the same carriers

• Therefore if the gradient bringing Na into cells that is created by active transport is large, there will be more of these other substrates reabsorbed with Na

Question 17

What is the effect of high [Na] in the tubule on the reabsorption of other substrates such as glucose?

Answer 17

• High tubule [Na] facilitates transport across the membranes
• therefore high [Na] = high reabsorption

Question 18

What is the symporter that moves glucose and Na across the luminal membrane? What protein facilitates glucose movement across the basolateral membrane?

Answer 18

SGLT - sodium-dependant glucose transporter

GLUT

Question 19

Do the molecules that get excreted only enter the tubule via filtration at the corpuscle?

Answer 19

• No, secretory mechanisms also transport substances from the peritubular capillaries into the tubule lumen, providing a second route into the tubule

Question 20

What substances need to enter the tubule via secretory mechanisms, as filtration is very restricted?

Answer 20

• Protein bound substrates

Question 21

How is much of the secretion from peritubular capillaries managed? What does this mean for the rate of excretion?

Answer 21

• Via carrier mediated transport

- Means there is a Tm for secretion as well as reabsorption

Question 22

What are some molecules that can be secreted through the same carriers due to the relative non-specific nature of secretory carrier proteins?

Answer 22

• The organic acid mechanism, which secretes lactic and uric acid can also be used for substances such as penicillin, aspirin and PAH
• The organic base mechanism for choline, creatinine etc, can be used for morphine and atropine

(seems to transport based on charge not shape??)

Question 23

Where does most secretion occur?

Answer 23

Proximal tubule

Question 24

What is the normal blood concentration of K? What concentration constitutes hypokalaemia / hyperkalaemia?

Answer 24

Normal [K]: 4mmol/L

Hyperkalaemia: >5.5mmol/L
Hypokalaemia: <3.5mmol/L

Question 25

What are some consequences of hyperkalaemia? Of hypokalaemia? Why does K have this regulatory role?

Answer 25

• Hyper: decreased resting membrane potential, depolarization of cells: eventually VF
• Hypo: increases resting membrane potential, hyperpolarizes cells: cardiac arrhythmias
• Because K is the major cation in cells

Question 26

how is plasma [K] mediated by the kidneys?

Answer 26

• Reabsorption of filtered K occurs mostly in the proximal tubule
• k excretion is determined by K secretion in the distal tubule, increases in tubule epithelium [K] due to ingestion stimulate K secretion. Decreases in epithelial [K] cause decreased secretion

Question 27

Other than the renal secretion / reabsorption loop, what regulates K plasma concentration? How?

Answer 27

Aldosterone

• Increases in plasma K stimulate the release of aldosterone from the adrenal cortex, causes K to be excreted and Na to be reabsorbed