Session 1 - Intro, absorption and secretion Flashcards
What are the key structures of the urinary system?
Kidneys
Ureters
Bladder
Describe the location of the kidneys.
Retroperitoneal organs
At the level T11/12
What is the main function of the kidneys?
Maintain a stable internal environment. (Urinary)
Regulation: key substances/ extracellular fluid
Excretion: Excretes waste product
Endocrine: Synthesis of renin, erythropoietin, prostaglandins
Metabolism: Active form of vitamin D, catabolism of insulin, PTH, calcitonin.
What are the volumes of fluid in the extracellular compartments?
70kg person
42 L water (60%)
Intracellular: 28L
Extracellular (14L):
- Interstitial 11L
- Intravascular 3L
- Lymph
What would the osmolar value be of 1 mole of NaCl in 1L of solution?
2 Osmolar solution
What is the normal osmolality of blood plasma?
280-310 mOsm/kg
Which ions mainly determine the osmolality in extracellular fluid?
Na+ and Cl-
Which ions mainly determine the osmolality of intracellular fluid?
K+
How do the kidneys play a part in maintaining extracellular pH?
Kidneys control bicarbonate concentration.
How much urine is produced per day?
Around 1.5 L
What is a nephron?
A functional unit of the kidney.
A kidney can contain around 1 million of these!
How much of the food we eat goes to keep the kidneys functioning?
Almost 1/4!
Kidneys use 22% of the cardiac output at rest.
How is blood filtered at the kidney?
At the glomerulus.
Highly specialised filter.
Water, electrolytes and small molecules forced out. (By constant filtration pressure in capillaries)
Which hormonal system controls sodium reabsorption?
Renin-angiotensin system
Which hormone system controls water recovery? How?
Anti-diuretic hormone.
Controls permeability of DCT and collecting duct to water.
Name the main PRIMARY active transporters in the nephrons.
Na/K ATPase (3Na in, 2K out)
Plasma membrane calcium ATPase (Ca2+ out)
Proton ATPase (Pump H+ out into lumen)
Which important channels aid sodium uptake in the Thick ascending limb?
Na/K ATPase creates a gradient.
NKCC2 - sodium, potassium, 2 chloride co-transporter moves sodium in also.
ROMK - renal outer medullary K channel, move potassium back into lumen.
Potassium chloride co-transporter moves 1K+ and 1Cl- into capillary.
Chloride channels also allow Cl- into capillary.
Where do loop diuretics act in the kidneys?
At the thick ascending limb, loop diuretics block sodium, potassium, 2 chloride co-transporter, reducing Na uptake, and reduce water uptake.
This will increase urinary volume.
Which membrane channels and transporters allow sodium re-uptake in the distal convoluted tubule?
Na/K ATPase gradient established.
- NCCT Sodium chloride co-transporter, brings Na and Cl in.
- ENaC - epithelial sodium channel. If open, sodium moves into cell from lumen, down electrochemical gradient.
(-ve gradient in cell) - Chloride channels - allow Cl that was brought in, to leave in capillary.
- Possible that some chloride leaves via potassium chloride co-transporter (KClCT)
How does the drug thiazide act on the kidney?
Block the sodium chloride co-transporter in the distal convoluted tubule.
How does the drug Amiloride act on the nephron?
1) Amiloride blocks ENaC channels in the cortical collecting duct.
Urine.
2) It also blocks the sodium proton exchanger in the proximal tubules, reducing Na re-absorption.
How does anti-diuretic hormone affect the cortical collecting duct?
Increases water uptake by aquaporin water channel from lumen to cell.
How does aldosterone increase sodium reuptake in the cortical collecting duct of the nephron?
Aldosterone - steroid hormone acting on nuclear receptors.
Increases the expression of transporters in the cells which are responsible for Na re-uptake.
How does spironolactone work?
Is an ANTAGONIST of the aldosterone receptor, which prevents the action of aldosterone, and reduces the amount of Na re-uptake (less expression of transporters/channels)
How is bicarbonate reabsorbed in the early proximal tubule?
As before, Na/K ATPase causes sodium gradient.
NHE- sodium hydrogen exchanger.
Sodium moves into cell, and hydrogen ions leave into lumen.
In lumen, H+ joins bicarbonate, to form carbonic acid.
Carbonic anhydrase metabolises this to water and CO2, which diffuse back into the cell.
In the cell, the same enzyme reverses the reaction, allowing H+ to be reused.
The bicarbonate is transported into the capillary by the Anion Exchanger (and Cl brought in).
How is chloride re-absorbed in the proximal tubule?
Similar to how bicarbonate is re-absorbed using H+ ions.
NHE- H+ moved into lumen.
Formate HCOO- bonds with H+ to make Formic acid.
This diffuses back into the cell (small uncharged molecule)
It dissociates into formate ions again.
At the anion exchanger, Cl- moves in, where formate moves into the lumen, allowing Cl to be re-absorbed.
In the LATE proximal tubule, how do sodium and chloride ions pass paracellularly into the capillary?
As bicarbonate is reabsorbed earlier on, Cl- becomes the major concentrated anion, so diffuses through tight junctions into the cell, along with sodium.
How is phosphate reabsorbed into the tubular cells of the nephron?
Through a Sodium-phosphate co-transporter (2Na+ and one Pi in).
Once in the cell, phosphate conc. increases.
Diffuses by passive phosphate transporters into the capillary.
How is glucose reabsorbed into the blood in the nephrons?
In proximal tubules.
SGLT2 - 3Na, 1 glucose
Into cell.
> Concentration in cell.
Diffuses via GLUT2 - passive transporter, into capillary.
How does amino acid re-uptake occur, and where?
Proximal Tubules
Sodium-dependent amino acid transporters.
Passive diffusion into the capillary.
How does urea get absorbed back into the blood from the lumen?
Sodium-dependent urea transporter.
Passive diffusion back into the blood.
(Na/K ATPase driven)
How much urea that enters the lumen is reabsorbed?
Around 50% of urea is reabsorbed, and 50% lost as waste.
What is receptor-mediated endocytosis?
Substance binds to receptor on cell surface.
(In a coated pit)
Coated pit moves into cell, becoming coated vesicle.
Coated Vesicle become uncoated.
Moves to Endosome, where lower pH causes product to dissociate from the receptor.
Endosome fuses with lysosome.
Receptor recycled.
A small amount of albumin leaks into the lumen in the kidneys. How is this reabsorbed?
Receptor mediated process into lysosomes.
Lysosome cleaves albumin into amino acids.
Amino acids re-enter the circulation by passive transport.
How is vitamin B12 reabsorbed in the proximal tubule of the nephron.
Binds to a protein called Transcobalamin
Transcobalamin binds to the Megalin receptor.
Then absorbed by receptor mediated endocytosis.
Which proteins are involved in reabsorbing vitamin D3 from the lumen?
Vitamin D- binding protein.
Binds to Vitamin D3.
This then binds to Megalin Receptor for receptor mediated endocytosis.
What happens to the vitamin D3 when it enters the tubule cells?
Enters as 25-(OH) Vitamin D3.
Is ACTIVATED, to 1,25-(OH) Vitamin D3.
How are calcium ions reabsorbed in the proximal kidney tubules?
TRPV6 channel (Ca and Mg enter into cell.
From cell, travels vie NCX (3Na in, 1Ca out) into blood.
How is calcium reabsorption in the kidneys controlled?
Activated Vitamin D3 binds to Vitamin D receptor.
This receptor stimulates increased expression of the TRPV6 Calcium channels on the apical membrane of the tubule, increasing reabsorption.
Augments expression of calcium transporters.
What occurs in a high calcium diet at the kidneys?
Calcium ions can enter paracellularly.
