REB 21. Renal Tubule Function and Physiology Flashcards
What are some of the substances that are reabsorbed from the tubules?
- electrolytes
- glucose
- proteins
- amino acids
- urea
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
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
What are some of the substances that are secreted into the tubules?
- K+
- H+
- NH4+
- Creatinine
- Urea
- Some Hormones
- Some Drugs
Why is secretion of urea into the tubular fluid important?
important in FORMATION OF URINE
Why is secretion of H+ and NH4 into the tubular fluid important?
important for MAINTAINING BLOOD pH
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
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
What type of cell makes up the thin limb of the Loop of Henle? (thin ascending and thin descending)
squamous cells
What type of cell makes up the thick limb of the Loop of Henle?
cuboidal cells
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)
What are the 3 main proteins that make up the tight junctions?
[1] Occludins
[2] Claudins
[3] Junctional Adhesion Molecule (JAM)
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
What are the 3 main types of epithelial transport protein?
[1] ATPase Pumps [2] Channels [3] Carriers (a) Co-Transporters (b) Exchangers
What are the 2 sub-types of the Carrier type of epithelial transport proteins?
[1] Co-Transporters
- symporters
[2] Exchangers
- antiporters
What is the main mechanism that drives transepithelial solute transport?
Na+/K+ ATPase pump
- it creates the electrochemical gradient
How does the Na+/K+ ATPase pump work?
- 3 Na+ out of cell
- 2 K+ into the cell
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
Water crosses the cell membranes by 2 routes which are:
[1] through Tight Junctions and Paracellular Space
[2] Aquaporins - water channels
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
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
