Lecture 9: Transport of AA's/glucose/urea/sulphates & refeeding syndrome

Question 1

Where does the reabsorption of AA’s/glucose/urea/sulpahtes take place predominantly?

Answer 1

Proximal convoluted tubule

Question 2

What is your normal plasma glucose concentration?

Answer 2

2.5-5.5 mmol/L

Question 3

What is the filtration rate of glucose?

Answer 3

0. 2-0.5 mmol of glucose if filtered per minute

- virtually all glucose that is filtered is reabsorbed in the PCT

Question 4

How is glucose reabsorbed?

Answer 4

Via secondary active transport, driven by the energy from transport of Na+ down its conc gradient

• on basolateral membrane of PCV cells, there is a Na/K ATPase pumping sodium out of the cell and potassium in, lower Na+ conc in the cell forming a diffusion gradient
• Na+ now passively diffuses down gradient via a sodium/glucose transporter
• on basolateral membrane there is a glucose channel so glucose can diffuse out to blood (passively)

Question 5

What are the 2 types of sodium/glucose transporter in the kidney?

Answer 5

1st part of PCT: SGLT2 (couples one sodium with one glucose and brings it into the cell)

2nd part of PCT: SGLT1 (couples two sodiums for every glucose)

Question 6

What is the Tm?

Answer 6

The maximum tubular resorptive capacity for a solute

Question 7

Is absorption of glucose limited?

Answer 7

• limited number of Na/glucose carriers, so glucose reabsorption is Tm limited
• if plasma glucose rises above 10mmol/L glycosuria will develop

Question 8

Why is glycosuria common in pregnancy?

Answer 8

The Tm for glucose falls and therefore glucose is excreted in urine

Question 9

How do you screen for glucosuria?

Answer 9

Urine dipstick

Question 10

What is the plasma concentration of AA’s?

Answer 10

2. 5-3.5 mmol/L

- filter easily through the glomerulus

Question 11

Where are AA’s reabsorbed?

Answer 11

In PCT by secondary active transport

• same mechanism as with glucose
• Tm limited process

Question 12

What is the plasma concentration of urea?

Answer 12

2.6-7.5 mmol/L

Question 13

How does urea concentration increase in the filtrate?

Answer 13

Urea concentration increases in the filtrate as a result of Na+ and Cl- and water reabsorption (becomes more concentrated as less volume for urea to be dissolved in)
-this means there is a higher concentration of urea in filtrate than blood, so it allows for passive reabsorption (40-50%) down conc gradient into blood

Question 14

What parts of the nephron are impermeable to urea?

Answer 14

• distal tubule

- collecting ducts as they move into the outer medulla

Question 15

What is the plasma concentration of sulphate?

Answer 15

1-1.5 mmol/L

-Tm limited absorption

Question 16

What happens during early starvation?

Answer 16

• glucose levels decline and insulin levels decrease
• glucagon level rises
• glucagon stimulates glycogenolysis in the liver and lipolysis of triacetylglycerol in fat reserves producing fatty acids and glycerol
• these are used by tissues for energy and converted to ketone bodies in liver
• as glycogen reserves become depleted, gluconeogenesis is stimulated in the liver, using AA’s, lactate and glycerol to synthesise glucose for the brain

Question 17

Why do you get whole body deficits of potassium, phosphate and magnesium during starvation?

Answer 17

The body reduces all energy consuming metabolic pathways (including action of cellular pumps), allowing electrolytes to leak across cell membranes
-this means they move into the plasma and are excreted by the kidneys causing whole body deficits (but the plasma level stays consistent but in the cells there is deficit)

Question 18

Why do cardiac, intestinal and renal functions become imparied during starvation?

Answer 18

Sodium and fluid leak into cells resulting in an increase in intracellular sodium and water
-causes cardiac, intestinal and renal functions to become impaired leading to reduced ability to excrete excess sodium and water

Question 19

What are some metabolic changes to reintroduction of nutrition?

Answer 19

• increased insulin production
• increased cellular uptake of glucose, phosphate, potassium causing a big fall in serum levels
• decreased glucagon secretion
• reactivation of Na+/K+ pump leading to increased K+ inside cells and increased Na+ and fluid loss, out of cells
• Na+/K+ pump utilies magnesium as a co-factors reducing its availability
• decreased renal function and decreased ability to excrete sodium and fluid resulting in a fluid overload
• increased demand for thiamine as part of carbohydrate metabolism
• increased glucose levels may occur as a consequence of excessive glucose introductionto a starved system adapted to fat metabolism
• stimulation of protein synthesis leading to an increased anabolic tissue growth which in turn leads to increased cellular demand for phosphate, potassium, glucose and water

Question 20

What is the main outcome of the re-introduction of nutrition in those with refeeding syndrome?

Answer 20

Return to carbohydrate metabolism and increased uptake of electrolytes intracellularly resulting in low serum levels
Resulting in:
-hypokalaemia
-hypomagnesaemia
-hypophosphataemia
-thiamine deficiency
-salt and water retention= oedema

Question 21

What factors do you consider to determine if a patient is at high risk of refeeding syndrome?

Answer 21

• dietary intake (very little/no food for >5 days)
• low BMI (<18.5kg/m2)
• large % weight loss in last 3-6 months
• electrolyte levels are low
• alcohol abuse/use of insulin/chemotherapy/antacids/diuretics
• malabsorption e.g. chronic vomiting/diarrhoea

Question 22

What are the main biochemical markers to assess and monitor in a patient at risk of refeeding syndrome?

Answer 22

• potassium
• phosphate
• magnesium

Question 23

How do you feed a patient at risk of refeeding syndrome?

Answer 23

Refer a dietitian

• starting on max of 10 kcal/kg/day increasing levels slowly to meet or exceed full needs by 4-7 days
• using only 5 kcal/kg/day in extreme cases and monitoring cardiac rhythm

Question 24

What else do you need to consider alongside feeding?

Answer 24

• provide full dose of IV vitamin B daily
• balanced multivitamin supplement daily
• provide electrolyte replacement as per guidelines
• monitor cardiac rhythm
• restore circulatory volume
• monitor fluid balance