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Renal and Endocrine Biology > REB 21. Renal Tubule Function and Physiology > Flashcards

REB 21. Renal Tubule Function and Physiology Flashcards

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1
Q

What are some of the substances that are reabsorbed from the tubules?

A
  • electrolytes
  • glucose
  • proteins
  • amino acids
  • urea
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2
Q

Solute absorption occurs through 2 processes which are:

A

[1] passive diffusion
- solutes are absorbed through epithelial cells along concentration gradients

[2] active transport
- establishes concentration gradients using energy derived from Na+/K+ ATPase pumps

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3
Q

What are the 3 main changes of filtrate osmolarity that happens throughout the nephron?

A

[1] Proximal Convoluted Tubule

  • 300 mOsm/L
  • same as plasma

[2] Descending Loop of Henle

  • 1200 mOsm/L as water is reabsorbed
  • becomes very concentrated

[3] Distal Convoluted Tubule + Collecting Duct
- variable and largely dependent on water permeability

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4
Q

What are some of the substances that are secreted into the tubules?

A
  • K+
  • H+
  • NH4+
  • Creatinine
  • Urea
  • Some Hormones
  • Some Drugs
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5
Q

Why is secretion of urea into the tubular fluid important?

A

important in FORMATION OF URINE

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6
Q

Why is secretion of H+ and NH4 into the tubular fluid important?

A

important for MAINTAINING BLOOD pH

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7
Q

What are the 2 mechanisms by which tubular secretion occurs through?

A

[1] Passive Secretion
- diffusion of molecules from the interstitium to the filtrate/urine along osmotic or chemical gradients

[2] Active Secretion
- the movement of molecules inot the filtrate against osmotic and chemical gradients via energy dependent ATPase pumps

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8
Q

What type of cells make up the proximal convoluted tubules?

A
  • cuboidal epithelium
  • – microvilli increase surface area for reabsorption
  • – mitochondria ensures that energy is available for active transport needed for efficient reabsorption
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9
Q

What type of cell makes up the thin limb of the Loop of Henle? (thin ascending and thin descending)

A

squamous cells

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10
Q

What type of cell makes up the thick limb of the Loop of Henle?

A

cuboidal cells

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11
Q

What are the 2 common properties of tubular epithelial cells that allow them to carry out their absorptive and secretory functions?

A

[1] Tight Junctions

  • point of contact between neighbouring cells
  • consists of transmembrane proteins that form homotypic bonds w/ neighbouring cells
  • are permeable to (a) water and (b) ions/small molecules
  • — forms paracellular pathway
  • — structural components = occludins, claudins, junctional adhesion molecule (JAM)
  • closely associated with intracellular signalling and cytoskeletal proteins that control permeability

[2] Functional Polarity

  • ability of epithelial cells to express different transport proteins on their apical and basolateral sides
  • — enables vectorial transport of solutes (allows for directional transport)
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12
Q

What are the 3 main proteins that make up the tight junctions?

A

[1] Occludins
[2] Claudins
[3] Junctional Adhesion Molecule (JAM)

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13
Q

What are epithelial transport proteins? What are the functions of these proteins?

A

Epithelial Transport Proteins: specialized proteins embedded into epithelial cell membranes

Function:
- to form transport pathways that enable water soluble molecules to traverse hydrophobic cell membranes

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14
Q

What are the 3 main types of epithelial transport protein?

A 
[1] ATPase Pumps
[2] Channels
[3] Carriers
(a) Co-Transporters
(b) Exchangers
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15
Q

What are the 2 sub-types of the Carrier type of epithelial transport proteins?

A

[1] Co-Transporters
- symporters

[2] Exchangers
- antiporters

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16
Q

What is the main mechanism that drives transepithelial solute transport?

A

Na+/K+ ATPase pump

- it creates the electrochemical gradient

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17
Q

How does the Na+/K+ ATPase pump work?

A
  • 3 Na+ out of cell

- 2 K+ into the cell

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18
Q

Explain the structure of ion channels.

A
  • act as pores selective for certain ions
  • normally closed
  • channels are gated and open in response to specific stimuli
  • transport occurs PASSIVELY along the electrochemical gradients established by ATPase pumps
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19
Q

Water crosses the cell membranes by 2 routes which are:

A

[1] through Tight Junctions and Paracellular Space

[2] Aquaporins - water channels

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20
Q

Where are aquaporins located in the renal tubules? What passes through these channels?

A
  • expressed along the length of the tubules
  • transports solute-free water across cell membranes
  • transport is bidirectional in accordance with osmotic gradients established by active solute transport
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21
Q

Different aquaporins are expressed in different regions of the tubules, what aquaporin channels are located in the:

Proximal Tubule + Descending Thin Limb

What is the function of this aquaporin?

A

Aquaporin 1

- mediates constitutive H2O resorption

22
Q

Different aquaporins are expressed in different regions of the tubules, what aquaporin channels are located in the:

Distal Convoluted Ducts + Collecting Ducts

What is the function of these aquaporins?

A

Aquaporins 2, 3 and 4

- important in regulation of water reabsorption by antiduiretic hormone (ADH
e. g. vasopressin)

23
Q

What solutes are reabsorbed in the early proximal convoluted tubules?

A 
- NaCl
(70% of Na reabsorbed) 
- other ions
(K+ - 70%) 
(bicarbonate - 90%)
- Glucose (100% reabsorbed)
- Amino Acids (100% reabsorbed) 
- Phosphate (85%)
- Lactate 
- Citrate
- Urea (50%)
24
Q

What types of channels does most of the uptake that occurs in the proximal convoluted tubule occur through?

A

Na+/Nutrient Cotransporters:

  • Na+/Glucose CT
  • Na+/Pi CT
  • Na+/Amino Acid CT
  • Na+/Lactate CT
25
Q

How is water reabsorbed in the proximal convoluted tubule?

A

reasborbed passively by osmosis

26
Q

In the early proximal tubule, how is Na+ reabsorbed? What gets reabsorbed along with the Na+

A

Na+ enteres via:
[1] apical Na+/solute co-transporters

[2] Na+/H+ exchangers (NHE’s)

  • HCO3- gets reabsorbed with the Cl-
27
Q

What is the PCT impermeable to for reabsorption?

A

Cl- cannot be reabsorbed by the proximal convoluted tubule

  • late PCT is permeable to Cl- and Cl- is reabsorbed passively through the paracellular pathway
28
Q

What is the maximum rate for the transporter for glucose to be reabsorbed? (numerical value)

A

Tmg = 2 mmol/min

29
Q

Explain the process by which glucose is reabsorbed from the proximal convoluted tubules?

A
  • glucose uptake occurs by a secondary active transport process
    — dependent on energy from basolateral Na+/K+ ATPase activity
    — entry from the lumen occurs through a Na+/Nutrient cotransporer
    (primarily the sodium/glucose co-transporter, SGLT2)
30
Q

What are the steps involved in glucose reabsorption in the proximal convoluted tubule (PCT)?

A

[1] Na+ gradient is created from the Na+/K+ ATPase

[2] Na+ and glucose crosses the apical membrane through SGLT2 (symporter)

[3] Na+ exits into the interstitium via the Na+/K+ ATPase pump

[4] Glucose enters the interstitium through the GLUT2 transporter

31
Q

What is SGLT2 a drug target for? What does it do?

A

it is a target for Gliglozins (e.g. dapagliflozin)

- it helps lower blood glucose in diabetes

32
Q

In glycosuria, what is the Tmg values?

A

Tmg values are around 3x higher than the normal filtered load
- increases in filtered load may lead to some glucose being excreted in the urine

33
Q

What are the causes of glycosuria?

A

[1] Hyperglycaemia

  • plasma glucose > 11 mmol/L
  • both type I and type II are characterized by persistently high blood glucose levels
  • glomerular filtered load exceeds Tmg

[2] Normoglycaemia

  • plasma glucose < 7.8 mmol/L
  • indicative of reduced tubular reabsorptive capacity
  • in pregnancy, increased renal blood flow results in increased glucose being filtered
  • Fanconi Syndrome: dysfunction of the PCT (genetic basis)
  • PROBLEMS IN KIDNEYS
34
Q

What is the plasma glucose level in hyperglycaemia that leads to glycosuria?

A

plasma glucose > 11 mmol/L

35
Q

What is the plasma glucose level in normoglycaemia that leads to glycosuria?

A

plasma glucose < 7.8 mmol/L

36
Q

What does the glomerular filtration of protein dependent on?

A

[1] Molecular Size
- low MW proteins are readily filtered

[2] Ionic Charge

  • extracellular matrix within the basement membrane of filtration barrier contains negatively charged proteins
  • the negatively charged proteins repels the negatively charged proteins in the plasma

[3] Molecular Shape
- deformable molecules can pass through more readily rigid ones

[4] Plasma Concentrations
- elevated plasma levels of a protein lead to increased filtration

[5] normally, small peptide hormones + albumin are filtered!!

37
Q

The amount of urinary protein depends on 2 factors which are:

A

[1] Filtered Load

  • glomerular permeability, plasma concentration..
  • how much is filtered and reabsorbed

[2] Efficiency of Proximal Tubular Reabsorption Process

38
Q

What is the mechanism/steps that protein resorption from the PCT occurs through?

A

[1] occurs by receptor-mediated endocytosis
- endosomes formed to enter the cell

[2] proteins are degraded in the intracellular lysosomes
- degrade them into amino acids

[3] resulting amino acids exit via the basolateral transporters
- amino acids back into the blood

39
Q

What is foamy urine an indicator of?

A
  • proteinuria (increased amounts of protein in the urine)
40
Q

What are the 3 main causes of proteinuria?

A

[1] Glomerular Proteinuria

  • due to damage of glomerulus
  • more protein is filtered

[2] Tubular Proteinuria

  • due to alterations in tubular reabsorption
  • e.g. Fanconi Syndrome

[3] Overload Proteinuria

  • increased plasma concentration of low MW proteins
  • e.g. immune response going on
  • — many exceed PCT to be reabsorbed
41
Q

Why does Glomerular Proteinuria occur?

A
  • due to damage of glomerulus

- more protein is filtered

42
Q

Why does Tubular Proteinuria occur?

A
  • due to alterations in tubular reabsorption

- e.g. Fanconi Syndrome

43
Q

Why does Overload Proteinuria occur?

A
  • increased plasma concentration of low MW proteins
  • e.g. immune response going on
  • — many exceed PCT to be reabsorbed
44
Q

Where is most of the amino acids reabsorbed in the tubules?

A

in the first 1/3 of the PCT

- when filtered levels are elevated, the rest of the proximal tubule becomes involved

45
Q

What is the process/steps involved in amino acid reabsorption in the proximal tubule?

A

[1] Amino acids enter cell from Na/AA secondary active transport (from gradient created by Na/K ATPase)

[2] there are separate carriers that exist on the apical and basolateral membranes for different types of AAs (acidic, neutral, basic…)

46
Q

What are the 3 functional divisions of the Loop of Henle?

A

[1] Thin Descending Limb

[2] Thin Ascending Limb

[3] Thick Ascending Limb

47
Q

What is the function of the Loop of Henle?

A
  • the maintenance of a highly concentrated medullary interstitium
  • it drives water reabsorption from the tubules
48
Q

Explain the 3 main changes of the osmolarity in the Loop of Henle.

A

[1] Entering LoH
- 300 mOsm/L

[2] Medulla

  • 1200 mOsm/L
  • water leaves at this point (water reabsorbed)

[3] Leaving LoH
- 100 mOsm/L

49
Q

What is the thin descending limb impermeable and permeable to?

A

PERMEABLE:
- highly permeable to water

IMPERMEABLE:

  • ions
  • solutes
50
Q

What is the thin ascending limb impermeable and permeable to?

A

PERMEABLE:
- ions (e.g. NaCl)

IMPERMEABLE:
- water

51
Q

The thick ascending limb reabsorbs —- through which transporter?

A
  • it reabsorbs Na+, K+ and Cl-
  • it gets filtered through the Na/K/Cl cotransporter - NKCC2
  • it concentrates the medullary interstitium

Renal and Endocrine Biology (25 decks)

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