42) Structure and Function of the Renal Tubule

Question 1

What is glomerular filtrate?

Answer 1

• The material/fluid that is made after filtration by the glomerulus

Question 2

What is the composition of the glomerular filtrate?

Answer 2

• It has the same composition as the plasma except for the fact that it has no cells and very little proteins

Question 3

What are tubular capillaries?

Answer 3

• Capillaries run along/around the tubules

Question 4

Describe the movement of material within the kidneys

Answer 4

• Blood travels from afferent arterioles into glomerular capillaries where filtration occurs. This is where substances pass out of the blood into tubules at the glomerulus (glomerular filtrate)
• However some of the material in the tubules can pass back into the blood and they do this by reabsorption into tubular capillaries which are adjacent to the tubules
• Finally we have a final process of secretion of material from the tubular capillaries into the tubule

Question 5

What are the different ways in which material moves into and out of the tubules?

Answer 5

• Active transfer: Movement of a molecule/ion against its concentration gradient which operates against an electrochemical gradient. It requires energy in the form of ATP
• Passive transfer (flux): Passive movement of molecules/ions down their concentration gradient which requires a suitable route. The removal of one component concentrates the other component
• Co-transport: Movement of one substance down its concentration gradient generates energy that allows a second substance to move against its concentration gradient. It requires a carrier protein and utilises two types of transporters (symports and anti-ports)

Question 6

What are the different types of transporters?

Answer 6

• Uniporter: Transport of one substance only in one direction
• Symports: Transport of two substances in the same direction
• Anti-ports: Transport of two substances in opposite directions

Question 7

What are the different types of techniques used to investigate tubular function?

Answer 7

• Clearance studies (applies to humans as it is non-invasive and observational)
• Micropuncture and isolated perfusion tubule (applied to animals as it is more invasive and are mechanistic or they allow us to reach under and see what is going on)
• Electrophysiological analysis (applied to animals as it is more invasive and are mechanistic or they allow us to reach under and see what is going on)

Question 8

How do we carry out micropuncture?

Answer 8

• First a tubule is punctured with a pipette and a viscous oil is injected using the pipette
• This injection is follow up with a second injection of fluid which we want to study
• In doing so the viscous oil prevents the fluid that we inserted from mixing with other liquids located within the tubule
• After a period of time the sample is taken out and analysed to record any changes

Question 9

How do we carry out electrical potential electrophysiological experiments within the microtubules?

Answer 9

• First we use a microelectrode to measure the potential across a membrane
• We can combine this with microperfusion techniques to alter the membrane potential
• This will allows us to judge whether or not ions are moving with or against their electrochemical gradient

Question 10

How do we carry out patch clamping electrophysiological experiments within the microtubules?

Answer 10

• A pipette is docked on the membrane in a way that it does not puncture the cell but can hold a single transporter within it
• We can measure the ion flow through the single channel
• We can also measure the electrical resistance across this part of the membrane and also look to see what happens when ion channels open and close
• It is useful for studying drugs and hormones that affect transporters

Question 11

What are the different types of nephrons within the kidneys?

Answer 11

• Juxta-medullary nephron: A rarer type of nephron which has longer loops of Henle. They reach deep in the medulla. Their capillaries run next to the loops of Henle and forms a vascular structure (called the Vasa Recta). These nephrons facilitate the uptake of water
• Cortical nephron: A more common type of nephron which has shorter loops of Henle. They do not reach very far into the medulla. Their capillaries run next to the distal and proximal convoluted tubules. These nephrons facilitate the secretion and reabsorption of substances such as ions and amino acids

Question 12

What is the structure and function of proximal microtubules?

Answer 12

• They are located adjacent to the glomerulus and is involved in reabsorption (of Na+, Cl-, HCO3-, K+, H2O, glucose and amino acids) and in secretion (of H+, organic acids and bases)
• They have a high capacity of absorption.
• They are highly metabolic with numerous mitochondria that allow for active transport. Furthermore they have extensive microvilli on the luminal side creating a larger surface area which allows for rapid exchange

Question 13

How is protein uptake in the convoluted tubules take place?

Answer 13

• They are first engulfed by a endocytic/pinocytic vesicle
• It is then taken into the cell and degraded by lysosomes into its amino acids and sugars
• These products are released into the capillary via passive diffusion

Question 14

What is the function of the loop of Henle?

Answer 14

• Determines the concentration of urine by adjusting the rate of absorption/secretion of water

Question 15

Which part of the loop of Henle is most permeable to water?

Answer 15

• The descending arm

Question 16

Which part of the loop of Henle are impermeable to water?

Answer 16

• The thin ascending and the thick ascending arm of the loop of Henle

Question 17

Where does the active reabsorption of Na take place?

Answer 17

• In the thick ascending arm of the loop of Henle
• This is the site of action for some drugs (called loop diuretics) which blocks the Na symporter causing some of the Na to be excreted
• This causes an increased rate of urine formation

Question 18

Describe the movement of ions in the thick loop of Henle.

Answer 18

• Na+, K+ and Cl- travel from the tubular lumen into the epithelial cells via symporters
• On the other side 3 Na+ leave the epithelial cell into the peritubular capillary and 2K+ move into the epithelial cell via the Na+/K+ ATPase (the sodium-potassium pump)
• On the same side K+ and Cl- move via uniporters from the epithelial cell into the peritubular capillaries via passive flux

Question 19

What creates the osmolality gradient within the medulla?

Answer 19

• The combination of removal of water and urea in the thin descending arm along with removal of salt (Na+ in particular) within the ascending arms creates an osmolality gradient within the medulla

Question 20

How is the osmolality gradient created in the medulla?

Answer 20

• In the ascending arm Na+ and Cl- pass out of the Loop of Henle which increases the osmolality within the interstitial fluid and decreases osmolality of the glomerular filtrate
• Due to the increase in osmolality throughout the ascending arm water is able to pass out of the descending arm through osmosis
• This osmosis carries on throughout the arm as it constantly comes into contact with an increasing osmolality gradient
• It is only at the bottom of the loop of Henle where the osmolality within the loop matches that of the interstitial fluid

Question 21

How is the osmolality gradient maintained in the medulal?

Answer 21

• The flow of blood within the vasa recta is in the opposite direction around the loop of Henle
• Hence there is a counter current system between the filtrate (in the loop of Henle) and blood (in the vasa recta)
• Since the vasa recta is freely permeable to H2O and other solutes it acts as a counter current exchange system
• As the blood descends water is drawn out of the vasa recta and diffuses into the thick ascending arm of the loop of Henle whilst the Na+ and Cl- are drawn into the blood
• As the blood ascends water it taken back into the vasa recta and Na+ and Cl- are drawn back into the loop of Henle

Question 22

How can altering blood flow within the vasa recta cause problems?

Answer 22

• It can affect and change the gradient in the loop of Henle and hence it can affect the functioning of the kidneys

Question 23

What are the different parts of the distal convoluted tubule?

Answer 23

• Earl distal convoluted tubule: The first part of the convoluted tubule located next to the juxtaglomerular apparatus. It is relatively straight
• Late distal convoluted tubule: It is the second part of the convoluted tubule which is relatively convoluted. It has a high Na+/K+-ATPase activity in the basolateral membrane and a very low permeability to water
• Collecting/connecting convoluted tubule: Located in the outer cortex and joins the distal convoluted tubule with the collecting duct. It is relatively straight in shape

Question 23

What is the function of the early distal convoluted tubule?

Answer 23

• It provides a feedback control of blood pressure
• It regulates the rate of glomerular filtration
• It controls the flow of fluid through the tubule in the same nephron
• It is involved in the reabsorption of ions

Question 24

What is the function of the late distal convoluted tubule?

Answer 24

• It is involved in solute reabsorption without water reabsorption.
• It is involved with further dilution of tubular fluid.
• Anti-diuretic hormone (ADH) can act on it.
• Finally it has a role to play in maintaining acid base balanced by secreting NH3

Question 25

What is the function of the collecting/connecting convoluted tubule?

Answer 25

• Its function is to connect the distal convoluted tubule to the collecting duct

Question 26

What is the collecting duct?

Answer 26

• Formed by the joining of collecting tubules
• Their cells/epithelia are cuboidal-to-columnar with low mitochondria
• There are made of two types of epithelial cells: intercalated cells and principle cells
• It is the final site of urine processing where it can be made very permeable to H2O and urea by ADH
• It contributes to the counter-current mechanism

Question 27

What are the functions of the different types of epithelial cells within the collecting ducts?

Answer 27

• Intercalated cells: Involved in the acidification of urine and acid-base balance
• Principle cells: Involved in Na+ balance and regulating extracellular fluid volume

Question 28

What is ADH?

Answer 28

• ADH (also called vasopressin) is secreted by the posterior pituitary where it enters the blood supply and induces changes in plasma osmolality
• It travels in the peritubular capillaries and acts on epithelial cells surrounding the collecting duct
• It triggers water to be released from the tubules causing the urine to be more concentrated

Question 29

What is the mechanism of ADH action?

Answer 29

• ADP binds to its receptor (Vasopressin receptor 2) on the plasma membrane of the principle cell
• This triggers a G-protein signalling cascade through the activation of cAMP and protein Kinase A
• This triggers the synthesis of AQP (Aquaporin 2) and also causes AQP to be transported to the plasma membrane.
• The AQP acts as a pore in the membrane for water
• There is a separate pore for urea called urea channels

Question 30

What happens when urea is excreted out of the collecting duct?

Answer 30

• It contributes to the medullary interstitial gradient

Question 31

How is urea levels measured?

Answer 31

• A Blood Urea Nitrogen (BUN) test

Question 32

What happens when we are water deprived?

Answer 32

• There will be a low osmolarity in the fluid entering the collecting duct
• As the fluid passes down the Na+, Cl- and urea are transported out of the collecting duct
• In this case (due to water deprivation) ADH will be released and will act on principle cells to create AQP
• These AQP creates pores in the membrane allowing more water to be passed out into the blood
• The effect of this is higher water retention and a very small amount of highly concentrated urine

Question 33

What happens when we are in water excess?

Answer 33

• The fluid will enter the collecting duct at a low osmolarity.
• As the fluid passes down the duct Na+, Cl- and some urea will all pass out of the tubule
• However there will be no ADH secreted
• As a result there will be no AQP being synthesised and hence less pores for water to enter into the blood stream
• The result of this is a large volume of heavily diluted urine