Kidney Basics

Question 1

What are the various segments of the renal tubule?

Answer 1

• Proximal convoluted tubule
• Descending limb of loop
• Loop of Henle / Thin ascending limb
• Thick ascending limb
• Distal convoluted tubule
• Collecting duct
• Medullary collecting duct

Question 2

Where does tubular reabsorption/secretion occur (from and to, cell-location wise)? Why is this important?

Answer 2

• Reabsorption is from the tubular lumen (tubule) -> peritubular plasma (capillar)
• Likewise, secretion is from the peritubular plasma -> the tubular lumen
• This clears unwanted substances by excretion into urine
• And returns wanted substances by reabsorption into blood

Question 3

What is active transfer (primary active transport)?

Answer 3

• moving molecule/ion against conc gradient (low to high)
• operates against electrochemical gradient
• requires energy - driven by ATP

Question 4

What is passive transfer?

Answer 4

• Passive movement down conc gradient
• Active removal of one component -> concentrates other components ie. passive transfer can be a consequence of active transport

Question 5

Describe secondary active transport or co-transport

Answer 5

• Movement of one substance down its conc gradient -> generates energy
• -> allows transport of another substance against its conc gradient
• Requires carrier protein
• 2 types: symport and antiport

Question 6

How does the structure of the proximal convoluted tubule amplify its function?

Answer 6

• Directly adjacent to Bowman’s capsule
• Highly metabolic, numerous mitochondria for active transport
• Extensive brush border on luminal side -> large SA for rapid exchange

Question 7

What are the functions of the PCT?

Answer 7

• Major site of reabsorption
• 65-70% of filtered load reabsorbed here
  
  • 100% of glucose and amino acids are reabsorbed
  • Much of bicarbonate reabsorbed
  • Cl^- and Na⁺ reabsorbed

Question 8

What is Fanconi’s syndrome?

Answer 8

• All PCT reabsorptive mechanisms are defective
• Glucose, AA, Na, K etc all found in urine

Question 9

What are the 3 functionally distinct segments of the Loop of Henle? What is their structure?

Answer 9

• Thin descending
• Thin ascending
• Thick ascending

Both thin parts have thin epithelial cells, no brush border, few mitochondria and low metabolic activity.

Thick ascending part has thick epithelial cells, extensive lateral intercellular folding, few microvilli, many mitochondria -> resulting in high metabolic activity.

Question 10

What are the functions of the the Loop of Henle?

Answer 10

• Critical role in concentrating/diluting urine by adjusting rate of water secretion/absorption
• Thin descending loop: very permeable to water
• Thin ascending loop: virtually impermeable to water
• Thick ascending loop: virtually impermeable to water, actively reabsorbs Na

LoH creates osmolality gradient in medullary interstitium, has countercurrent multiplication - vasa recta.

Question 11

Where do loop diuretics act?

Answer 11

Block sodium transport* out of LoH at thick ascending loop, cause 20% of filtered sodium to be excreted. Eg. furosemide

*Inhibit Na:K:2Cl transporter (symporter)

Question 12

What are the functions of the distal convoluted tubule?

Answer 12

• Solute reabsorption continues, w/out H₂O reabsorption
• High Na⁺K⁺-ATPase activity in basolateral membrane
• Very low H₂O permeability
• Further dilution of tubular fluid
• Anti-diuretic hormone (ADH) can exert actions
• Role to play in acid-base balance via secretion of NH₃

Question 13

What are the 2 types of cells in the collecting ducts, what are the functions?

Answer 13

• Intercalated cells: involved in acidification of urine + acid-base balance
• Principal cells: role to play in Na balance and ECF volume regulation
• Final site for processing urine
• Made very permeable to H₂O by ADH*
• Also permeable to urea*

*contribute to counter-current mechanism

Question 14

Describe countercurrent multiplication by the Loop of Henle

Answer 14

• LoH has 2 parallel limbs arranged so that tubular fluid flows into descending limb into medulla and out of medulla through the ascending limb (ie flow of fluid is in opposite directions)
• Fluid entering descending limb from prox tubule has osmotic conc approx to that of plasma (300mosm/kg). The ascending limb is impermeable to water, but reabsorbs solutes (NaCl).
• As tubular fluid travels up ascending limb, it becomes more dilute - whilst the solute (NaCl) accumulating in the interstitial fluid around loop, raising its osmolality
• On other hand, descending limb is freely perm to water, thus the hyperosmotic ISF causes water to leave descending limb. This creates an osmotic gradient.
• This effect is multiplied by the entry of new fluid into the descending limb which pushes fluid from around the loop to the ascending limb. Thus a continuous osmolality gradient is created the top of the loop

Question 15

How are the thin and thick ascending limbs different in terms of solute reabsorption?

Answer 15

Thin ascending limb permeable to Na & Cl, but thick ascending limb actively pumps Na & Cl out of tubular fluid

Question 16

What does the vasa recta do?

Answer 16

• Delivers O₂ and nutrients to cells of LoH
• Permeable to both H₂O and salts
• Acts as counter-current multiplier system as well
• As it descends into renal medulla, water diffuses out into the surrounding fluids, and salts diffuse in.
• When the VR ascends, reverse occurs -> conc of salts is always about the same in VR and salt gradient established by LoH remains in place.
• Water is removed by VR
• Medullary blood flow in VR is slow -> sufficient to supply metabolic needs of the tissue, but minimise solute loss from medullary interstitium

Question 17

Where is ADH made and stored?

Answer 17

• Produced in hypothalamus
• Stored in pituitary gland

Question 18

What does ADH/Vasopressin do?

• Aim of ADH?
• Most important variable?
• Where is it sensed?
• Regulated by?

Answer 18

• Triggers kidney tubules to reabsorb water back into bloodstream rather than excreting water into urine
• Aim of ADH: conserve body water by reducing water lost in urine
• Most important variable regulating ADH secretion = plasma osmolarity (or conc of solutes in blood)
• Osmolarity is sensed in hypothalamus by osmoreceptors
• If plasma osmolarity inc above threshold -> osmoreceptors activate -> stimulate ADH release
• ADH secretion also regulated by volume receptors + arterial baroreceptors

Question 19

Describe what happens at a cellular level upon action of ADH/Vasopressin

Answer 19

• Vasopressin is secreted by hypothalamus
• AVP (vasopressin/ADH) binds to V2 receptors (on principal cells of CD)
• Stimulates synthesis of aquaporin-2 water channel proteins
• Also promotes cAMP-dependent trafficking of aquaporin-2 water channels to luminal membrane of principal cells allowing back diffusion of water down its conc gradient
• Vasopressin via V2 receptors also activates urea transporters in distal nephron to facilitate urea reabsorption and urea recycling, whcih allows maximisation of sodium reabsorption in the thick ascending limb, supporting the axial hyperosmotic gradient drawing water from distal nephron

Question 20

Urea is a waste product formed in the liver during metabolic breakdown of proteins. How is urea excreted?

Answer 20

• Would imagine most urea is excreted from body via urine - it isn’t!
• Urea filters freely through glomerulus and passes down tubule
• Unlike cortical collecting tubule, the medullary collecting duct is permeable to urea
• As water is reabsorbed from CD (say in presence of ADH), urea is concentrated so that it moves out of the CD and is absorbed into the surrounding capillaries
• Also absorbed into the interstitium of medulla
• Contributes to osmotic gradient around LoH
• Urea reabsorption enhanced in pre-renal failure
• Dehydration -> inc urea reabsorption