Renal System and Diuretics Flashcards

1
Q

What is the functional unit of the kidney?

A

Nephron

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2
Q

What does the Glomerulus do?

A

Filters the blood that enters via the afferent arteriole

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3
Q

What is the structure of the glomerulus?

A

1) Endothelia - Filters cells
2) Basement membrane - Has negative charge so repels proteins
3) Epithelial cells (podocytes) - Filters remaining proteins

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4
Q

What drives filtration at the glomerulus?

A

Hydrostatic pressure

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5
Q

What transporters are located in the proximal convoluted tubule?

A

Na+/H+ secondary transporter
Na+/K+ ATPase

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6
Q

How does the Na+/H+ transporter gets its H+ ions?

A

Via the breakdown of carbonic acid by carbonic anhydrase

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7
Q

What are the membranes that the transporters are located on?

A

Apical membrane - separates lumen and space
Basolateral membrane - separates space and peritubular capillaries

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8
Q

What is the advantage of the Na+/K+ ATPase transporter?

A

Maintains concentration gradients

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9
Q

What are the transporters present in the loop of henle?

A

Ascending loop of henle - NKCC2 transporter

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10
Q

How does the NKCC2 transporter work?

A

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

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11
Q

What transporters are located in the distal convoluted tubule?

A

NCC couples transporter on apical membrane - Na+/2Cl-

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12
Q

Where does aldosterone and ADH act on?

A

Collecting duct

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13
Q

What does aldosterone do?

A

Increases opening of Na+ channels
Increased Na+ being reabsorbed

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14
Q

what does ADH do?

A

Increase permeability of distal tubule and collecting ducts to increase reabsorption,
Increases aquaporins

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15
Q

What diuretics target the Proximal convoluted tubule?

A

Carbonic anhydrase inhibitors - Aromatic Sulphonamides

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16
Q

What type of enzyme is carbonic anhydrase?

A

Metalloprotease - Zn2+

17
Q

What type of inhibitor is a sulphonamide?

A

COMPETITIVE - Competes with water against nitrogen on sulphonamide functional group.

18
Q

What part do thiazide diuretics target?

A

NCC transporters in distal convoluted tubule

19
Q

Summarise the key groups that a thiazide needs to be active

A

1) 2 sulphanilamide’s

20
Q

What factors enhance the activity of a thiazide med chem?

A

1) Electron withdrawing group next to sulphonamide group
2) Lipophilic group next to dihydropyridine group
3) Alkylation substitution of amine
4) Double bond saturation

21
Q

What amino acids bind with Zn2+ in carbonic anhydrase enzyme

A

3 Histidine

22
Q

Summarise the effect of diuretics and the role in hypertension

A

Decrease Na+ reabsorption by targeting transporters
Decreased water reabsorption
Decreased blood volume
Decreased peripheral resistance
Decreased blood pressure

23
Q

What stage of the NICE guidelines are thiazides introduced?

A

Stage 3

24
Q

Who should not be given thiazides and why?

A

People with Gout - blocks secretion of uric acid
Pregnant women
Renal and liver impairment

25
Q

Summarise the development of carbonic anhydrase inhibitors to thiazides

A

Sulphonamide derivative
Acylation = closed product ring = increased activity