Cellular Mechanisms of Resorption Flashcards
What are the zones of the nephron?
-Renal corpuscle =glomerulus the knot of capillaries surrounded by Bowman's capsule -Proximal tubule -Henle's loop -Distal tubule
What is the difference between a proximal and distal tubule under a microscope?
Proximal tubules have microvilli at apical side of cell, whereas distal tubules do not
Describe the epithelial structure
- Apical side= lumen (microvilli)
- Basal side= in contact with basal membrane
- Simple epithelium= one layer of cells, polarised so nucleus towards the base
- Tight (stops flow of fluid) and adherent junctions (stick cells to each other) (proximal tubule= leaky tight junctions)
What molecules do nephron epithelia have to recover?
-Ions =Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, PO4(2-), H2O -Amino acids -Glucose -Proteins
How does nephron epithelia recover these molecules?
-Primary Active Transporters (Na+/K+ ATPase and H+ ATPase are the only common ones in the plasma membrane)
-Solute Carrier Family (SLC) proteins
=About 300, many are co-transporters/antiporters powered by established concentration gradients (sodium), secondary active transporters
-Aquaporins (water channels)
-Ion channels
-Protein endocytosis receptors
Why do we need ATP to selectively recover small molecules?
Primary filtrate from Bowman’s capsule and plasma in equilibrium
Examples of co-transport that occurs in the tubules
- Hydrolysis of ATP to import 2 K+ and export 3 Na+
- Na+ imported and H+ exported
- Na+ and Cl- imported
- Renal Outer Medullary K channel= regulated leakage of K+
- Neutral amino acid + 2Cl- and Na+
- Glucose with Na+
How are organic molecules recovered?
- Organic anion transporters (OATs)
- Organic cation transporters (OCTs)
- Organic Cation/ Carnitine transporters (OCNTs)
- transports drugs and metabolites of drugs
Describe OCTs
-Allow passive movement in either direction
-Proton in for organic cation out (actively kick out), passively in, apical side of cell
-Carries:
=tetraethylammonium (TEA)
● 1-methyl-4-phenylpyridinium
(MPP)
● endogenous amines, such as dopamine
●
therapeutic drugs, such as
cimetidine and morphine
● cationic xenobiotics, such as antihistamines
Describe OATs
-Anions= push in, drift out
-Basal side, a-ketoglutarate in with sodium
-A-ketoglutarate out in exchange for anion (OAT antiporter)
-Dangerous cells- drift out passively, so toxic anions can build up in cell
=Methotrexate
=Furosemide
=Penicillin
What is an inhibitor of OAT (1,2,3)?
Probenecid
- Inhibits penicillin
- Stops penicillin being expelled, stays active for longer
Describe phosphate recovery
- In through apical side with sodium
- Actively exported from cell at basal side
Describe bicarbonate recovery
- Proton exporter, sodium in and proton out
- Proton with bicarbonate= carbonic acid
- Carbonic anhydrase converts/hydrolyses into CO2 and water
- CO2 passively into cell
- In cell, carbonic anhydrase back into carbonic acid- naturally dissociates into proton and bicarbonate
- Co-transporter back into body (SLC)
- no effect on pH as regenerate H+/ no net loss of bicarbonate and H+
What happens in acidosis?
- Net secretion of H+
- HPO4(2-) combines with H+ to make H2PO4- which leaves body in urine to correct acidosis
- NH3 combines with H+ to make NH4+ to expel H+
Where does the ammonia come from?
-Catabolism of amino acids
=Glutamine= bicarbonate, proton and ammonia (crosses into urine passively)
-Proton kicked into urine space via channel and combine with ammonia
-Brings bicarbonate in in basal side
