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Kidneys and Renal functions > Structure & Function of Renal Tubule > Flashcards

Structure & Function of Renal Tubule Flashcards

1
Q

What occurs in the Bowman’s Capsule and glomerulus?

A

Filters large amounts of plasma

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2
Q

What occurs in the segments of the renal tubule?

A

Filtered fluid is converted to urine

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3
Q

Explain the composition of GF compared to plasma

A

GF = same composition as plasma except has no cells and v. little protein
BUT composition of urine ≠ plasma (and GF)

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4
Q

What rate is GF formed at?

A

GF formed at 120 ml/min

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5
Q

When does urine formation begin?

A

when large amounts of fluid (virtually protein free) is filtered from the glomerular capillaries → Bowman’s capsule

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6
Q

What is GF?

A

GF is an ultrafiltrate of plasma

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7
Q

What happens to the filtrate as it travels along the tubule?

A

There is selective modification of filtrate as it passes through tubule

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8
Q

How is the filtrate modified along the tubule?

A

Modified by process of reabsorption and secretion of water / various solutes
Modification done by tubular transport of solutes and water into and out of tubule

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9
Q

What is Polycystic Kidney Disease (PKD)?

A

Genetic disorder characterised by the growth of numerous cysts in the kidney

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10
Q

What are the diseases of the glomerulus?

A

Usually called glomerulonephritis (GN)
Inflammation of glomeruli of some or all of million nephrons in kidney
Can be primary or secondary to systemic disease like diabetes mellitus
Inherited diseases of the glomerular basement membrane

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11
Q

Describe the diseases of the tubules

A

obstruction (reducing GFR)

Impairment of transport functions (reducing water & solute reabsorption) eg. Fanconi’s syndrome

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12
Q

How does hypertension affect the kidneys

A

Kidneys regulate ECF volume; influence BP ⇒ compensatory mechanisms responding to high BP can lead to chronic kidney damage

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13
Q

How does congenitive cardiac failure affect the kidneys?

A

Fall in CO ⇒ renal hypoperfusion ⇒ registered as hypovolaemia, compensation results in pulmonary oedema

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14
Q

What is diabetic nephropathy?

A

As a consequence of diabetes, filtering system of kidneys gets destroyed over time

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15
Q

How does lithium treatment affect the kidneys?

A

Lithium treatment results in acquired nephrogenic diabetes insipidus due to reduction of AQP2 expression

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16
Q

Explain what is meant by reabsorption in the kidneys

A

Fluid movement from

Tubular lumen → peritubular capillary = reabsorption

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17
Q

Describe the movement of fluid during secretion in the kidneys

A

peritubular plasma→ tubular lumen = secretion

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18
Q

What is the purpose of creating a glomerulur filtrate?

A

Clearing unwanted substances by excretion into urine & Returning wanted substances by reabsorption into blood

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19
Q

What is active transfer/transport ?

A

Moving molecule/ion against conc gradient (low→high)
Operates against electrochemical gradient
Requires energy - driven by ATP

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20
Q

What is passive transfer?

A

Passive movement down concentration gradient (requires suitable route)

Active removal of one component concentrates other components
* can generate energy -> co-transport

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21
Q

What is co-transport (secondary active transport)?

A

Movement of one substance down its [ ] gradient generates energy
Allows transport of another substance against its [ ] gradient
Requires carrier protein

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22
Q

What are the 2 types of Co-transport?

A

symport and antiport

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23
Q

What is a symport?

A

Symport = transported species move in same direction e.g. Na+-glucose

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24
Q

What is an antiport?

A

Antiport = transported species move in opposite directions e.g Na+-H- antiport

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25
Q

What type of transport occurs in tubules?

A

Combination of active & passive mechanisms ⇒

transcellular transport over luminal & basolateral membranes (either direction)

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26
Q

Explain how movement in tubules occurs?

A
  1. High [Na] in tubule (140mEq/L)
  2. low [Na] (12mEq/L) inside cell
  3. ∴ Na moves down conc gradient at luminal membrane aided by greater intracellular negative potential (-70mv)
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27
Q

How is glucose transported into cells through tubules?

A

As Na diffuses down electrochemical gradient, energy is released driving glucose against its concentration gradient across luminal membrane → cells
(Na-glucose symport via a specific carrier protein)

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28
Q

Where is energy generates from to allow glucose transport?

A

Energy generated from Na moving into cell is generated by primary active transport of Na out of the cell at the basolateral membrane

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29
Q

What is the role of the Na/K/ATPase pump?

A

Na-K-ATPase keeps the cytoplasmic [Na] lower than tubular [Na] and maintains electrochemical gradient for passive Na transport across luminal membrane

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30
Q

How does glucose leave the cells into the bloodstream?

A

Glucose exits out at basolateral membrane via SGLT2 (sodium-glucose cotransporter) by facilitated diffusion driven by high [glucose] in the cell

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31
Q

What is familial renal glycosuria?

A

genetic defect in SGLT2 protein: just like similar defect in intestinal protein SGLT1 – glucose-galactose malabsorption

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32
Q

What other substances are co-transported with Na?

A

Cl- and aa (symport) and H+ (antiport)

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33
Q

What techniques can we use to investigate tubular function?

A
  1. Clearance studies ✔
  2. Micropuncture & Isolated Perfused Tubule
  3. Electrophysiological Analysis
    • Potential measurement
    • Patch clamping

(1 = applied to man, 2 & 3 = applied to lab animals)

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34
Q

Explain how micropuncture is carried out

A

only applied to lab animals

  1. Puncture
  2. Inject Viscous oil
  3. Inject fluid for study
  4. Sample and analyse
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35
Q

How is the electric potential used to determine tubular function?

A

Electrodes (micropipettes of very small diameter <0.5μm) inserted into cell and the Potential difference measured across whole cell epithelium

Combine with microperfusion to alter potential difference (PD)

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36
Q

What does the electric potential method measure?

A

Measure whether ion moving with/against electrochemical gradient
Actively transported?

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37
Q

Compare patch clamping to electric potential method

A

Rather than insert a microelectrode through membrane, a blunt-tip pipette (opening ~0.5-1 µm) is pressed against the cell membrane until a seal forms between electrode tip and membrane surface.
Plasma membrane can be pulled away from the cell and placed in a test solution of desired composition

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38
Q

Explain how patch clamping works

A

Current flow through individual ion channel measured
Measure electrical resistance
- Across patch of cell membrane
- Changes when channels open/close
Types of channels & response to drugs & hormones

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39
Q

Describe the cellular structure of tubules

A

Throughout its length the nephron is comprised of a single layer of epithelial cells resting on a basement membrane. There are characteristic differences in the structure of the cells which reflect their different functions.

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40
Q

What are the 2 types of nephron?

A
  • Cortical nephron

- Juxtamedullary nephron

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41
Q

Outline the features of the Cortical nephrons

A

Cortical nephron

  • 85%
  • Don’t extend into medulla
  • Short Loop of Henle (LoH)
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42
Q

Describe the juxtamedullary nephrons features

A

Juxtamedullary nephron

  • 15%
  • Penetrate deep into medulla
  • Long Loop of Henle (LoH)
43
Q

What is the major difference between the 2 types of nephron?

A

The major anatomic difference between the Cortical nephrons & Juxtamedullary nephrons is the length of the loops of Henle

The Vascular system is also different.

44
Q

What is the role of the juxtamedullary nephrons?

A

Juxtamedullary nephrons have long-reach loops that penetrate deep into the medulla. These play a crucial role in concentrating and diluting urine.

45
Q

Where is the Proximal Convoluted Tubule (PCT) located?

A

Directly adjacent to Bowman’s capsule

46
Q

How is the PCT got such high capacity for reabsorption?

A

special cellular characteristics:
- highly metabolic, numerous mitochondria for active
transport
- extensive brush border on luminal side ⇒ large surface
area for rapid exchange

47
Q

How much filtrate is reabsorbed at the PCT?

A

Major site of reabsorption

~65-70% of filtered load reabsorbed here

48
Q

How does reabsorption occur in the PCT?

A

Driven by the Na/K ATPase pump as Na moves down its conc. Gradient, taking all the glucose and a.a with it back into blood

49
Q

How is water reabsorbed from the PCT?

A

Water is also reabsorbed by osmosis

50
Q

Describe the protein content in GFR

A

Glomerular filtrate is protein free but some small proteins (<60kD) get through

51
Q

What is the fate of proteins found in the GFR?

A

Any small protein that may escape into the filtration system are taken up by lysosomes via endocytosis and degraded → a.a + sugars to be reabsorbed into blood

52
Q

What is the consequence of Fanconi’s Syndrome?

A

where all PCT reabsorptive mechanisms are defective so all the solutes are present in urine rather than begin reabsorbed

53
Q

What are the 3 functionally distinct segments of the loop of henle?

A
  • thin descending
  • thin ascending
  • thick ascending
54
Q

Describe the structure of the thin ascending limb

A

Thin epithelial cells, no brush border, few mitochondria & low metabolic activity
Can travel variable distance into medulla

55
Q

Describe the cellular structure of the thick ascending limb

A

thick epithelial cells, extensive lateral intercellular folding, few microvilli, many mitochondria ⇒ high metabolic activity
Extends back into cortex

56
Q

What is the role of the loop of henle?

A

LoH critical role in concentrating/diluting urine

» adjusting rate of water secretion/absorption

57
Q

How is water reabsorbed from the descending limb?

A

An osmolality gradient is created in the LoH tissue in the medulla, pulling water out of LoH back into blood by osmosis

58
Q

Describe the loop of Henle’s permeability to water

A

Only the descending limb is permeable to water

Both thin/thick ascending limb are impermeable to water but actively reabsorbs Na

59
Q

Where on the loop of Henle do loop diuretics cause their effect?

A

Ascending limb is site of action for Loop diuretics, causing 20% of filtered Na to be excreted, by blocking Na-transport out of LoH e.g. Furosemide
Usually due to CVS pathologies

60
Q

What is the medullary interstitium?

A

The tissue surrounding the loop of Henle in the renal medulla

61
Q

What causes an osmotic gradient in the medulla?

A

Solutes accumulate in the renal medullary interstitium, maintained by a balanced inflow and outflow of solutes and water in the medulla

62
Q

How is the medullary osmotic gradient maintained?

A

A high [solute] (high osmotic pressure) is generated and maintained in medullary interstitium and tubule fluid becomes hypotonic

63
Q

What is counter-current flow?

A

Flow of fluid is in opposite directions

64
Q

Describe the osmolality of the fluid present in the descending limb

A

Fluid entering descending limb from proximal tubule has approx. equal osmolarity to that of plasma = 300 mosm/kg

65
Q

What occurs in the ascending limb?

A

The ascending limb is impermeable to water but has lots of NaCl transporters∴reabsorbs NaCl

66
Q

Explain how the osmotic gradient is kept high in and around the LoH

A

as tubular fluid travels up ascending limb it becomes more dilute – solute accumulates in the interstitial fluid around the loop (in the medullary tissue space) raising it’s osmolality (increasing osmotic gradient)

67
Q

What is the effect of the osmotic gradient created in the LoH?

A

Gradient created causes water to be drawn out by osmosis in the descending limb

68
Q

What ensures the osmotic gradient between the ascending and descending limb is maintained?

A

Descending limb is freely permeable to water; hyperosmotic ISF causes water to leave descending limb.
→ leads to osmotic gradient between ascending and descending limb of 200 mOsm/kg.

69
Q

Compare the osmolality of fluid entering and leaving LoH

A

Fluid that leaves the LoH is hypo-osmotic with ref to plasma (~100 mOsm/kg)

70
Q

Describe the osmolality of the fluid travelling through the loop of henle

A

High osmolality as filtrate moves through descending limb as water is drawn out
Low osmolality as filtrate move sup through ascending limb as ions moved out

71
Q

How much of the filtered Na is reabsorbed in the thick ascending LoH?

A

The thick ascending LoH reabsorbs approx 25% of filtered Na

- can compensate partially for any failure by PCT to reabsorb Na.

72
Q

How does Na enter tunular cells?

A

Na enters cell via Na:K:2Cl symporter due to electrochemical difference favoring entry of Na into the cell (along with Cl and K)

73
Q

How is Na transported to the peritubular capillaries from the cells?

A

Na is transported actively out via Na-K-ATPase, while K & Cl cross into the peritubular fluid passively creating medullary conc. Gradient

74
Q

What effect do loop diuretics have on the Na:K:2Cl cotransporter?

A

e.g. furosemide; inhibit Na:K:2Cl cotransporter → in inhibition of net NaCl reabsorption & increased excretion of these ions along with water.

75
Q

What is the vasa recta?

A

Capillary delivering O₂ and nutrients to cells of the loop of Henle

76
Q

Explain the movement of substances through the vasa recta

A

VR freely permeable to solutes & H20
Descending into medulla H20 diffuses out & salts diffuse in
Reverse occurs as it ascends

77
Q

How does the vasa recta help maintain an osmotic gradient with the LoH?

A

Blood flow in VR countercurrent to fluid flow in LoH, allowing movement of substances in and out of VR maintaining gradient

78
Q

Describe the flow of blood through the vasa recta

A

Blood flow in VR is low ~5% of renal blood flow » minimizes solute loss from interstitium & maintains medullary interstitial gradient
Alteration of blood flow in VR can change gradient

79
Q

Describe the first part of the DCT

A 
1st part (macula densa) linked to juxtaglomerular complex
Provides TGF feedback control of GFR &amp; tubular fluid flow in the same nephron
80
Q

What is the structure of the second part of the DCT?

A

2nd part very convoluted

81
Q

What are the functions of the collecting duct?

A

Connects end of DCT to collecting duct – mainly in outer cortex
Overlap in functional characteristics with 2nd part of DCT

82
Q

What occurs in the DCT?

A

Solute reabsorption continues in the absence of water reabsorption and the tubular fluid is further diluted in its passage through the distal convoluted tubule

83
Q

Outline the functions of the DCT

A
  • Solute reabsorption continues, w/out H2O reabsorption
  • High Na+/K+/ATPase activity in basolateral membrane
  • V. low H2O permeability
  • Further dilution of tubular fluid
  • ADH exert actions
  • Acid-base balance via secretion of NH3
84
Q

How is the collecting duct formed?

A

Collecting ducts formed by joining of collecting tubules

cuboidal epithelia, very few mitochondria

85
Q

What are the 2 cell types in the collecting ducts?

A
  • intercalated cells

- principal cells

86
Q

What is the role of the intercalated cells in the collecting duct?

A

Involved in acidification of urine and acid-base balance

87
Q

What do the principal cells of the collecting duct do?

A

Role to play in Na balance & ECF volume regulation

88
Q

What factors of the collecting duct contribute to the counter-current mechanism?

A
  • Final site for processing urine
  • Made very permeable to H2O by ADH
  • Also permeable to Urea
89
Q

How is ADH secretion initiated?

A

ADH secretion triggered by changes in plasma osmolality

90
Q

How is osmolarity sensed?

A

Osmolarity is sensed in the hypothalamus by osmoreceptors, which simulate secretion from the posterior pituitary to produce ADH - makes CD permeable to water

91
Q

How does ADH produce a more concentrated volume of urine?

A

ADH concentrates urine by triggering the kidney tubules to reabsorb water back into bloodstream rather than excreting water into urine

92
Q

What is the role of ADH?

A

ADH conserves body water by reducing the loss of water in urine - regulated by plasma osmolarity, or [solutes] in blood

93
Q

How is ADH secretion regulated?

A

ADH secretion can also be regulated by volume receptors and arterial baroreceptors

94
Q

Outline the mechanism of ADH at a cellular level

A
  1. AVP binds to V2-receptors
  2. Stimulates aquaporin-2 water channel synthesis &
    promotes cAMP-dependent insertion of aquaporin 2
    water channels to luminal membrane of principal cells
  3. This allows back diffusion of water down its [ ] gradient
  4. Vasopressin via V2 receptors activates urea
    transporters in distal nephron to facilitate urea
    reabsorption and urea recycling
  5. Enables maximization of Na reabsorption in thick
    ascending limb, supporting the axial hyperosmotic
    gradient drawing water from the distal nephron
95
Q

What is urea?

A

Urea is a waste product formed in the liver during metabolic breakdown of proteins

96
Q

How does urea pass through the kidneys?

A

Urea filters freely through glomerulus and passes down the tubule

97
Q

How does urea in the collecting duct contributes to the osmotic gradient?

A

As water is reabsorbed from CD (e.g. in ADH presence) the urea = concentrated ∴ some urea moves out of CD into surrounding capillaries and medulla interstitium contributing to the osmotic gradient around LoH

98
Q

How can urea in the kidneys allow detection of renal failure?

A

Increasing levels of urea in kidney is a sign of pre-renal failure because reabsorption is enhanced.
Monitored using blood urea nitrogen test (BUN). Can see that urea reabsorption would increase during dehydration.

99
Q

Describe the osmotic pressure of the tubular fluid entering the CD

A

The tubular fluid entering the CD system is always hypo-osmotic

100
Q

What does the [tubular fluid] in the CD depend upon?

A

concentration depends on the water permeability of the duct, which is determined by ADH action

101
Q

How does ADH affect water permeability to the collecting duct?

A

In the presence of ADH water permeability is increased.
Water reabsorption increases the CD [urea]
ADH increases duct permeability to urea ∴ reabsorption is ↑

102
Q

How is medullary hyperosmolarity maintained by the CD?

A

Other solutes, esp. Na+ and Cl-, continue to be reabsorbed in the CD to maintain medullary hyperosmolarity → facilitates reabsorption of water in the presence of ADH

103
Q

What is the effect of ADH absence?

A

CD becomes impermeable to H₂O + urea
Na reabsorption continues in CD = tubular fluid becomes more dilute along the duct
Large volume of urine excreted

104
Q

What are the major factors contributing to [solute] build up in renal medulla?

A
  1. Active transport of Na+, co-transport of K+ & Cl- out of
    thick ascending limb→medullary interstitium
  2. Active transport of ions from CD→medullary interstitium
  3. Facilitated diffusion of large amounts of urea from CD→
    medullary interstitium
  4. V. little diffusion of H₂O from ascending limbs of tubules
    → medullary interstitium

Kidneys and Renal functions (14 decks)

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