US Lecture 4 - Tubular function

Question 1

What is the function of the kidney?

Answer 1

Central regulator of homeostasis - consume more salt and water than needed so we need to lose this and other waste products

Question 2

What is osmolarity?

Answer 2

Measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane - each ion is counted seperately

Question 3

Fill in the blanks of the kidney nephron during filtration

Answer 3

Question 4

What does the renal tubular wall look like diagramatically?

Answer 4

Question 5

Through which pathways does reabsorption and secretion take place?

Answer 5

Paracellular and transcellular from/to peritubular capillary to/from tubular fluid

Question 6

What are the types of transport that can occur in the tubules?

Answer 6

Osmosis, Active transport, Co-transport, movement down electrical gradient and passive transport

Question 7

What are the 2 types of passive protein transport?

Answer 7

Protein INdependent (lipophilic molecules) and dependent (hydrophilic molecules) transport

Question 8

How do the graphs of conc vs time appear with protein IN/dependent transport?

Answer 8

Question 9

How does active movement occur?

Answer 9

Directly coupled to ATP hydrolysis or in directly coupled

Question 10

What is the graph of conc vs rate with active movement?

Answer 10

Question 11

How does water transport occur?

Answer 11

By osmosis - through tight junctions or aquaporins

Question 12

How is a passive uptake system regulated?

Answer 12

By reducing the number of channel proteins in the membrane, so the molecule only has one output, leading to regulation

Question 13

How are proteins reabsorbed?

Answer 13

Protein attaches to membrane receptor, which is then endocytosed, and the protein and membrane receptor break apart

Question 14

How does transport maxima vary?

Answer 14

Depending on circumstances and applies to whole individual

Question 15

What does secretion do in the nephron?

Answer 15

Moves substances from peritubular capillaries into tubular lumen - constitutes of a pathway into the tubule, either by diffusion/transcellular mediated transport Active secretion from blood side into tubular cell and then into lumen

Question 16

What are the most important substances secreted?

Answer 16

H+ and K+ Choline, creatinine, penicillin and other drugs are also secreted NB: creatinine secretion levels are so low that they aren’t very relevant, hence can be used as clearance

Question 17

How uniform is reabsorption at the proximal convoluted tubule, distal convoluted tubule, collecting duct and loop of henle?

Answer 17

Question 18

What is the structure of each of the cells lining the PCT, LoH, DCT and collecting duct?

Answer 18

Question 19

What substances are reabsorbed in the proximal convoluted tubule?

Answer 19

Question 20

What do the Na/K pumps in the basolateral membrane of PCT do?

Answer 20

Na/K pump keeps intracellular [Na] low and [K] high Large conc. and electrical gradients favour Na movement into the cell (occurs in most nephron segments)

Question 21

What does Na help to occur in reabsorption in the early proximal tubule?

Answer 21

Na+ entry down a large electrochemical gradient can bring about the “uphill” entry of glucose and a-a’s and exit of H+

Question 22

What is the function of carbonic anhydrase in the early proximal tubule?

Answer 22

Leads to Na reabsorption and increased urinary activity

Question 23

What is passively and actively reabsorbed in the PCT?

Answer 23

Passive: urea and water Active: Glucose, a.a., Na, K, Ca, Vit C, Uric acid Reabsorption of all solutes/water is sensitive to metabolic poisons

Question 24

Is there any secretion in the proximal tubule and why is this important?

Answer 24

Net secretion of some substances from plasma into proximal tubular fluid, important because some drugs and other substances are excreted in this way and some drugs enter the tubular fluid and act further down the nephron

Question 25

What is reabsorbed in the descending limb of loop of henle?

Answer 25

Water passively reabsorbed through squamous epithelium Na and K drawn in

Question 26

What is reabsorbed in the ascending limb of loop of henle?

Answer 26

Cl actively reabsorbed, Na passively reabsorbed with it Bicarbonate reabsorbed Impermeable to water - cuboidal epithelium, few microvilli - high energy requirement so prominent mitochondria

Question 27

What osmolarity is the tubular fluid leaving the loop of Henle?

Answer 27

Hypo-osmolar with respect to plasma

Question 28

How are the substances reabsorbed in the loop of henle?

Answer 28

Question 29

What can loop diuretics do?

Answer 29

Block the Na/K/Cl co-transporter in the ascending loop of Henle

Question 30

What is the proximal part of the DCT’s structure?

Answer 30

Cuboidal epithelium, with few microvilli Complex lateral membrane interdigitations with Na pumps Numerous large mitochondria

Question 31

What is reabsorbed in the proximal part of the DCT?

Answer 31

Na and Cl co-transporter linked to Ca reabsorption - higher amount of calcium being reabsorbed Na and chloride are reabsorbed by channel sensitive to thiazides

Question 32

What is a specialisation that occurs at the macula densa?

Answer 32

Detects changes in [Na+] of filtrate

Question 33

What happens at the distal part of DCT and the collecting duct?

Answer 33

DCT and CD - Na reabsorbed (dependent on aldosterone) CD - Adjustment of Na/K/H/NH4 Water reabsorbed under control of ADH Distal part of nephron is impermeable to water without ADH

Question 34

How does reabsorption work in the distal DCT and CD?

Answer 34

Prinicpal cell - important in Na, K and H2O balance (Na/K ATP pump) Intercalated cell - important in acid-base balance (H-ATP pump)

Question 35

What is an adaption of the cells in the cortical CD to regulate water transport?

Answer 35

Very ‘tight’ epithelium, so little paracellular transport Can regulate by changing number of aquaporin channels

Question 36

Which single gene defects affect tubular function?

Answer 36

Renal tubule acidosis Bartter syndrome Fanconi syndrome

Question 37

What is renal tubular acidosis?

Answer 37

Hyperchloremic metabolic acidosis, leads to impaired growth and hypokalaemia (can cause temporary paralysis)

Question 38

Which mechanisms underlie the main types of defects in Bartter’s syndrome?

Answer 38

Question 39

What is Bartter syndrome?

Answer 39

Excessive electrolyte secretion - antenatal BS leads to premature birth, polyhydramnios, severe salt loss, moderate metabolic alkalosis, hypokalaemia, renin and aldosterone hypersecretion

Question 40

Which mechanisms underlie the main types of defects in Renal Tubular Acidosis?

Answer 40

Leak of protons back into the blood, so cannot reabsorbed the bicarbonate, leading to metabolic acidosis

Question 41

What is Fanconi syndrome?

Answer 41

Increased excretion of uric acid, glucose, phosphate, bicarbonate, increased excretion of low MW protiens, disease of PCT associated with renal tubular acidosis

Question 42

Which mechanisms underlie the main types of defects in Fanconi syndrome?

Answer 42

Lose transporters, so pump protons into the endosome, so one Na leaves and 2 Cl are brought in, so suppresses the transport maxima

Question 43

What is normal plasma and urine osmolarity?

Answer 43

Plasma: 285-295 mosmol/L Urine: 50-1200 mosmol/L

Question 44

Which of transcellular and Paracellular are more easily regulated?

Answer 44

Transcellular

Question 45

What is transport maxima?

Answer 45

The highest amount of the substance they can absorb

Question 46

What is a good example of transport maxima?

Answer 46

Glucose: when too much glucose is in the filtrate, then reabsorption occurs, but if there is too much glucose, their is a limit to reabsorption (transport maxima) so the rest is excreted