Lets take the Nephron apart and look at some of the components...
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Proximal Convoluted Tubule
• Approximately 2/3 of the filtered water and Na are reabsorbed into the blood in the PCT
• All Glucose (up to 300 level in blood) is reabsorbed in the PCT, as are some BUN, Phos, Mg, Ca, etc.
• PCT plays an important role in pH balance of both blood and urine
• PCT damage is a common cause of Acute Renal Failure (ATN-discussed later)
Key to Image:
1.Because protein is concentrated in blood of efferent arteries, osmotic pressure in arteries is high and water follows
2.Na flows out of filtrate into cell, down gradient, with water following. This flow generates power that opens channels to allow other solutes to follow. An Na-K pump at the cell/artery boundary keeps intracellular Na low maintaining gradient.
3.If blood is acidic, H acumulates intracellularly and exchanges for additional Na, thereby lowering the body pH and acidifying the urine. H can also be pumped out of cell where it combines with filtered HCO3, forming H2CO3, which is excreted. One other method of lowering acid levels is to pump out NH3 from cell in addition to H, which when combined, forms NH4 and is excreted.
• Approximately 2/3 of the filtered water and Na are reabsorbed into the blood in the PCT
• All Glucose (up to 300 level in blood) is reabsorbed in the PCT, as are some BUN, Phos, Mg, Ca, etc.
• PCT plays an important role in pH balance of both blood and urine
• PCT damage is a common cause of Acute Renal Failure (ATN-discussed later)
Key to Image:
1.Because protein is concentrated in blood of efferent arteries, osmotic pressure in arteries is high and water follows
2.Na flows out of filtrate into cell, down gradient, with water following. This flow generates power that opens channels to allow other solutes to follow. An Na-K pump at the cell/artery boundary keeps intracellular Na low maintaining gradient.
3.If blood is acidic, H acumulates intracellularly and exchanges for additional Na, thereby lowering the body pH and acidifying the urine. H can also be pumped out of cell where it combines with filtered HCO3, forming H2CO3, which is excreted. One other method of lowering acid levels is to pump out NH3 from cell in addition to H, which when combined, forms NH4 and is excreted.
Loop of Henle• Approximately 20% of filtered water and Na are reabsorbed in the Loop
• Water is absorbed in the D-loop, while Na is absorbed in the A-loop
• Reabsorbed Na plays a major role in creating a gradient for descending water to leave the filtrate: the more Na reabsorbed, the more water is reabsorbed
• Reabsorbed Na also powers the reabsorption of other electrolytes by opening channels specific to their transport
Pharm Tip: Loop Diuretics (Lasix, Bumex, Ethacrinic acid) block Na reabsorption here which leads to no absorption of water or other electrolytes, and moderate diuresis. The diuresis is a bit too much for daily treatment of HT, but plays a role in the acute excretion of fluids in cases of volume overload like Congestive Heart Failure and Pulmonary edema. Since other electrolytes are excreted you must be cautious for electrolyte abnormalities such as hypokalemia and hypocalcemia.
• Water is absorbed in the D-loop, while Na is absorbed in the A-loop
• Reabsorbed Na plays a major role in creating a gradient for descending water to leave the filtrate: the more Na reabsorbed, the more water is reabsorbed
• Reabsorbed Na also powers the reabsorption of other electrolytes by opening channels specific to their transport
Pharm Tip: Loop Diuretics (Lasix, Bumex, Ethacrinic acid) block Na reabsorption here which leads to no absorption of water or other electrolytes, and moderate diuresis. The diuresis is a bit too much for daily treatment of HT, but plays a role in the acute excretion of fluids in cases of volume overload like Congestive Heart Failure and Pulmonary edema. Since other electrolytes are excreted you must be cautious for electrolyte abnormalities such as hypokalemia and hypocalcemia.
Distal Convoluted Tubule
• Approximately 7% of Water and Na reabsorption occur in the DCT
• Na once again powers the reabsorption of Cl
• Ca excretion occurs here (in exchange for Na) under the control of Parathyroid hormone (PTH)
Pharm Tip: Thiazide diuretics (Hydrochlorothiazide: HCTZ) blocks Na reabsorption here which subsequently leads to mild diuresis. Because of reduced amount of water reabsorbed here, loss of this water through the use of thiazides carries less risk of dehydration and hypokalemia, while effectively reducing fluids enough to have decent effects on BP. For this reason, HCTZ is often the first line medication in the treatment of Hypertension.
But Thiazides, while blocking the Na channel from reabsorbing urine Na also block the excretion of Ca through that channel, which while useful in someone with Ca stones or Osteoporosis, is dangerous in someone with already high levels of Ca.
This blockage of Ca channels also means vascular smooth muscle can not contract as well leading to slight vasodilation, further enhancing their anti-hypertensive effect.
Collecting Duct•Only 5% of Na and Water reabsorption occurs here so only minor diuresis occurs with drugs that target the CD
•Important for more than just diuresis…
1.Aldosterone, released by the adrenal glands, opens Na channels which leads to some increase in water reabsorption and increased blood volume. A Na-K pump keeps intracellular Na low to maintain the gradient, as well as K high for exchange with filtrate Na.
2.When the blood is acidic, H enters cell in place of K. The blood becomes hyperkalemic, and Na now exchanges for H, which is excreted in the urine.
3.ADH, released by the pituitary, opens aquaporins in the CD, which allows reentry of free water. Alcohol stops this hormone from working.
Pharm Tip: Spironalctone and Amiloride block Na reabsorption and subsequent K excretion, which is why they are K-sparing diuretics that can lead to hyperkalemia. They are often used in combo with K-wasting diuretics to offset the K loss. Ace Inhibitors also have an effect by blocking release of Aldosterone.
• Approximately 7% of Water and Na reabsorption occur in the DCT
• Na once again powers the reabsorption of Cl
• Ca excretion occurs here (in exchange for Na) under the control of Parathyroid hormone (PTH)
Pharm Tip: Thiazide diuretics (Hydrochlorothiazide: HCTZ) blocks Na reabsorption here which subsequently leads to mild diuresis. Because of reduced amount of water reabsorbed here, loss of this water through the use of thiazides carries less risk of dehydration and hypokalemia, while effectively reducing fluids enough to have decent effects on BP. For this reason, HCTZ is often the first line medication in the treatment of Hypertension.
But Thiazides, while blocking the Na channel from reabsorbing urine Na also block the excretion of Ca through that channel, which while useful in someone with Ca stones or Osteoporosis, is dangerous in someone with already high levels of Ca.
This blockage of Ca channels also means vascular smooth muscle can not contract as well leading to slight vasodilation, further enhancing their anti-hypertensive effect.
Collecting Duct•Only 5% of Na and Water reabsorption occurs here so only minor diuresis occurs with drugs that target the CD
•Important for more than just diuresis…
1.Aldosterone, released by the adrenal glands, opens Na channels which leads to some increase in water reabsorption and increased blood volume. A Na-K pump keeps intracellular Na low to maintain the gradient, as well as K high for exchange with filtrate Na.
2.When the blood is acidic, H enters cell in place of K. The blood becomes hyperkalemic, and Na now exchanges for H, which is excreted in the urine.
3.ADH, released by the pituitary, opens aquaporins in the CD, which allows reentry of free water. Alcohol stops this hormone from working.
Pharm Tip: Spironalctone and Amiloride block Na reabsorption and subsequent K excretion, which is why they are K-sparing diuretics that can lead to hyperkalemia. They are often used in combo with K-wasting diuretics to offset the K loss. Ace Inhibitors also have an effect by blocking release of Aldosterone.
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