REB 21. Renal Tubule Function and Physiology Flashcards by Jennita Ariaratnam

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

electrolytes
glucose
proteins
amino acids
urea

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Solute absorption occurs through 2 processes which are:

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

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

K+
H+
NH4+
Creatinine
Urea
Some Hormones
Some Drugs

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Why is secretion of urea into the tubular fluid important?

important in FORMATION OF URINE

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

important for MAINTAINING BLOOD pH

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

[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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What type of cells make up the proximal convoluted tubules?

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

squamous cells

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

cuboidal cells

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

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

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

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

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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What are the 3 main types of epithelial transport protein?

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

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

[1] Co-Transporters
- symporters

[2] Exchangers
- antiporters

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What is the main mechanism that drives transepithelial solute transport?

Na+/K+ ATPase pump

- it creates the electrochemical gradient

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

3 Na+ out of cell

- 2 K+ into the cell

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Explain the structure of ion channels.

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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Water crosses the cell membranes by 2 routes which are:

[1] through Tight Junctions and Paracellular Space

[2] Aquaporins - water channels

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

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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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?

Aquaporin 1

- mediates constitutive H2O resorption

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?

Aquaporins 2, 3 and 4

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

What solutes are reabsorbed in the early proximal convoluted tubules?

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

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

Na+/Nutrient Cotransporters:

Na+/Glucose CT
Na+/Pi CT
Na+/Amino Acid CT
Na+/Lactate CT

How is water reabsorbed in the proximal convoluted tubule?

reasborbed passively by osmosis

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

Na+ enteres via: [1] apical Na+/solute co-transporters [2] Na+/H+ exchangers (NHE's) - HCO3- gets reabsorbed with the Cl-

What is the PCT impermeable to for reabsorption?

Cl- cannot be reabsorbed by the proximal convoluted tubule - late PCT is permeable to Cl- and Cl- is reabsorbed passively through the paracellular pathway

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

Tmg = 2 mmol/min

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

- 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)

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

[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

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

it is a target for Gliglozins (e.g. dapagliflozin) | - it helps lower blood glucose in diabetes

In glycosuria, what is the Tmg values?

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

What are the causes of glycosuria?

[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

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

plasma glucose > 11 mmol/L

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

plasma glucose < 7.8 mmol/L

What does the glomerular filtration of protein dependent on?

[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!!

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

[1] Filtered Load - glomerular permeability, plasma concentration.. - how much is filtered and reabsorbed [2] Efficiency of Proximal Tubular Reabsorption Process

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

[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

What is foamy urine an indicator of?

- proteinuria (increased amounts of protein in the urine)

What are the 3 main causes of proteinuria?

[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

Why does Glomerular Proteinuria occur?

- due to damage of glomerulus | - more protein is filtered

Why does Tubular Proteinuria occur?

- due to alterations in tubular reabsorption | - e.g. Fanconi Syndrome

Why does Overload Proteinuria occur?

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

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

in the first 1/3 of the PCT | - when filtered levels are elevated, the rest of the proximal tubule becomes involved

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

[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...)

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

[1] Thin Descending Limb [2] Thin Ascending Limb [3] Thick Ascending Limb

What is the function of the Loop of Henle?

- the maintenance of a highly concentrated medullary interstitium - it drives water reabsorption from the tubules

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

[1] Entering LoH - 300 mOsm/L [2] Medulla - 1200 mOsm/L - water leaves at this point (water reabsorbed) [3] Leaving LoH - 100 mOsm/L

What is the thin descending limb impermeable and permeable to?

PERMEABLE: - highly permeable to water IMPERMEABLE: - ions - solutes

What is the thin ascending limb impermeable and permeable to?

PERMEABLE: - ions (e.g. NaCl) IMPERMEABLE: - water

The thick ascending limb reabsorbs ---- through which transporter?

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