Week 4 Flashcards
How does the nephrotic syndrome cause oedema?
Disorder in glomerular filtration results in protein (mainly albumin) appearing in urine, causing proteinuria
Loss of protein = decreased oncotic pressure = increased formation of interstitial fluid which causes oedema
Increased fluid in the interstitium also = less blood volume and cardiac output = activation of RAAS = retention of Na+ and H2O = oedema
How does congestive heart failure cause oedema?
Reduced cardiac output = renal hypoperfusion = activation of RAAS
RAAS activation results in expansion of blood volume = increased pressure in vessels, plus reduced osmotic pressure = pulmonary and peripheral oedema
How does hepatic cirrhosis with ascites cause oedema?
Increased pressure in the hepatic portal vein + decreased production of albumin = loss of fluid into peritoneal cavity and ascites
RAAS activated in response to decreased circulating volume
What is secreted and reabsorped at the proximal convoluted tubule?
How permeable is this segment of the nephron to water?
Secreted
- glucose
- ions
- H2O
- amino acids
Reabsorbed
- urea
Highly permeable to water
What is secreted at the descending limb of the Loop of Henle?
How does this affect osmolarity inside the nephron?
How permeable is this segment of the nephron to water?
Water is secreted but NaCl is retained
This causes the osmolarity inside the tubule to rise
This segment is highly permeable to water
What is secreted at the ascending limb of the Loop of Henle?
How does this affect the osmolarity within the tubule?
How permeable is this segment of the nephron to water?
NaCl is secreted, but water is retained
This causes the osmolarity within the tubule to fall
This segment is completely impermeable to water
What is reabsorbed at the distal convoluted tubule?
How permeable is this segment of the nephron to water?
H2O
Ca2+
Na+
Cl-
This segment is variably permeable to water
What is secreted at the collecting duct?
How permeable is this segment of the nephron to water?
H2O
Ca2+
Na+
Cl-
This segment is variably permeable to water
What diuretics target the proximal convoluted tubule?
What specifically do they target here?
Carbonic anhydrase inhibitors e.g. acetazolamide
Target the Na+/H+ exchanger
What diuretics target the Loop of Henle?
What specifically do they target here?
Loop diuretics e.g. furosemide and bumetanide
Target the Na+/K+/Cl- triple co-transporter
What diuretics target the distal convoluted tubule?
What specifically do they target here?
Carbonic anhydrase inhibitors e.g. acetazolamide
Also Thiazide diuretics e.g. chlorothiazide, indapamide
Carbonic anhydrase inhibitors target Na+/H+ exchange
Thiazides target the Na+/Cl- co-transporter
What diuretics target the collecting tubule?
What specifically do they target here?
What is the benefit of this particular group of diuretics?
Potassium-sparing diuretics target the collecting tubule e.g. spironolactone, eplerenone, amiloride and triamterene
Potassium-sparing diuretics target Na+/K+ exchange. By blocking Na+ reabsorption here, these drugs inadvertantly block K+ secretion, thus avoiding hypokalaemia
Why does even a small inhibition of reuptake of NaCl in the kidneys have a significant increase in Na+ excretion?
Because the vast majority of NaCl and H2O that passes into the filtrate via the glomerulus is reabsorbed
The site of action of many diuretic drugs is the apical/basolateral membrane of the tubule
Apical membrane
What transport system is used in to move acidic drugs into the renal tubule?
Give some examples of diuretics that operate via this system
Organic Anion Transporters (OATS)
Diuretics using these tranporters include thiazides and loop diuretics
What transport system is used in to move basic drugs into the renal tubule?
Give some examples of diuretics that operate via this system
Organic Cation Transporters (OCTs)
Diuretics using these tranporters include triamterene and amiloride (both potassium-sparing diuretics)
Name some Loop Diuretics
What do they target?
This type of diuretic acts rapidly/slowly
Furosemide, Bumetanide
Target the Na+/K+/Cl- triple co-transporter by binding to the Cl- site
Rapid onset following IV administration
What other benefit do loop diuretics confer when used to treat pulmonary oedema caused by heart failure?
Have an additional indirect venodilator action
What are some of the clinical indications for using loop diuretics?
To reduce salt and water overload in…
- Acute pulmonary oedema
- CKD
- Hepatic cirrhosis with ascites
- Chronic heart failure
- Nephrotic syndrome
To increase urine volume in acute kidney failure
To treat hypertension
To treat acute hypercalcaemia
What are some of the potential side effects of loop diuretics?
Hypokalaemia
Metabolic acidosis
Hypovolaemia and hypertension (especially in the elderly)
Depletion of Ca2+ and Mg2+
Hyperuricaemia = gout
What do thiazide diuretics target?
Give some examples of this class of drug
They target the Na+/Cl- co-transporter on the apical membrane in the distal convoluted tubule
Bendroflumethiazide
Indapamide
What is the main adverse effect associated with thiazide diuretics?
Hypokalaemia
They do this by inhibiting the Na+/Cl- carrier via binding to the Cl- site, which results in an increased Na+ load being delivered to the distal tubule, and which in turn causes a loss of K+
What addititonal effect do thiazide diuretics have, and how does this affect their use?
As well as a moderate diuretic effect, thiazides also have an indirect vasodilator action
This is what makes them useful in the treatment of hypertension, and why they are used in combination with other antihypertensive agents to manage blood pressure
Where do thiazide diuretics enter the nephron?
They enter in the proximal convoluted tubule because they are protein-bound and cannot pass through at the glomerulus
This also means that their absorption into the tubule is dependent upon the GFR - if GFR is low, less of the drug will be taken up into the tubule
What are some of the adverse effects of thiazide diuretics?
Hypokalaemia
Metabolic alkalosis
Hyperuricaemia - may predispose to development of gout
Male sexual dysfunction
Impaired glucose tolerance
How do thiazides relate to stone formation?
They can be used in the treatment of renal stone disease as they reduce urinary excretion of Ca2+
This does however make patients more susceptible to developing gout