Renal System and Diuretics Flashcards
What is the functional unit of the kidney?
Nephron
What does the Glomerulus do?
Filters the blood that enters via the afferent arteriole
What is the structure of the glomerulus?
1) Endothelia - Filters cells
2) Basement membrane - Has negative charge so repels proteins
3) Epithelial cells (podocytes) - Filters remaining proteins
What drives filtration at the glomerulus?
Hydrostatic pressure
What transporters are located in the proximal convoluted tubule?
Na+/H+ secondary transporter
Na+/K+ ATPase
How does the Na+/H+ transporter gets its H+ ions?
Via the breakdown of carbonic acid by carbonic anhydrase
What are the membranes that the transporters are located on?
Apical membrane - separates lumen and space
Basolateral membrane - separates space and peritubular capillaries
What is the advantage of the Na+/K+ ATPase transporter?
Maintains concentration gradients
What are the transporters present in the loop of henle?
Ascending loop of henle - NKCC2 transporter
How does the NKCC2 transporter work?
1) Na+ down concentration gradient
2) Allows 2Cl- to go up its gradient - secondary couples transporter
3) K+ flows in and out to maintain membrane potential
What transporters are located in the distal convoluted tubule?
NCC couples transporter on apical membrane - Na+/2Cl-
Where does aldosterone and ADH act on?
Collecting duct
What does aldosterone do?
Increases opening of Na+ channels
Increased Na+ being reabsorbed
what does ADH do?
Increase permeability of distal tubule and collecting ducts to increase reabsorption,
Increases aquaporins
What diuretics target the Proximal convoluted tubule?
Carbonic anhydrase inhibitors - Aromatic Sulphonamides
What type of enzyme is carbonic anhydrase?
Metalloprotease - Zn2+
What type of inhibitor is a sulphonamide?
COMPETITIVE - Competes with water against nitrogen on sulphonamide functional group.
What part do thiazide diuretics target?
NCC transporters in distal convoluted tubule
Summarise the key groups that a thiazide needs to be active
1) 2 sulphanilamide’s
What factors enhance the activity of a thiazide med chem?
1) Electron withdrawing group next to sulphonamide group
2) Lipophilic group next to dihydropyridine group
3) Alkylation substitution of amine
4) Double bond saturation
What amino acids bind with Zn2+ in carbonic anhydrase enzyme
3 Histidine
Summarise the effect of diuretics and the role in hypertension
Decrease Na+ reabsorption by targeting transporters
Decreased water reabsorption
Decreased blood volume
Decreased peripheral resistance
Decreased blood pressure
What stage of the NICE guidelines are thiazides introduced?
Stage 3
Who should not be given thiazides and why?
People with Gout - blocks secretion of uric acid
Pregnant women
Renal and liver impairment
Summarise the development of carbonic anhydrase inhibitors to thiazides
Sulphonamide derivative
Acylation = closed product ring = increased activity
