Renal6 - Renal physiology Lecture 6 Hydrogen ion...

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Unformatted text preview: Renal physiology Lecture 6 Hydrogen ion regulation-2 Diuretics and kidney disease Addition of new HCO3- to the plasma is achieved 1. by H+ secretion and excretion on nonbicarbonate buffers (such as phosphate). 2. by glutamine metabolism with NH4+ excretion. Both processes could be viewed as H+ excretion by the kidney. The kidneys normally contribute enough new HCO3- to the plasma to compensate for the hydrogen ions from nonvolatile acids generated in the body (40-80 mmol/day). Addition of new HCO3- to the plasma-1 can also be viewed as the elimination of H+ This happens only after all the HCO3has been reabsorbed and is no longer available in the lumen. - takes place in the later part of the tubule like the CCD Addition of new HCO3- to the plasma-2 Mainly in proximal tubule This process is also called “H+ excretion bound to NH3” ammonium is secreted in exchange for Na+ reabsorption Classification of acidosis and alkalosis Low H+ concentration (high pH): alkalosis Respiratory alkalosis (results from altered respiration) Metabolic alkalosis (results from other causes) all other causes other than respiratory problems problem in the elimination of carbon dioxide High H+ concentration (low pH): acidosis Respiratory acidosis (results from altered respiration) Metabolic acidosis (results from other causes) Renal responses to acidosis and alkalosis Responses to acidosis (high H+ concentration) - respond by changing (increase) bicarbonate concentrations in the plasma and therefore decrease proton concentrations 1. Sufficient H+ are secreted to reabsorb all the filtered HCO3-. 2. Still more H+ are secreted and this contributes new HCO3- to the plasma as these H+ are excreted bound to non-HCO3- buffer such as HPO42-. 3. Tubular glutamine metabolism and ammonium excretion are enhanced, which also contributes new HCO3- to the plasma. Net result: More new HCO3- than usual are added to the plasma, thereby compensating for the acidosis. The urine is highly acidic (lowest attainable pH = 4.4). more acid is excreted in urine in the form of protons Renal responses to acidosis and alkalosis Responses to alkalosis (low H+ concentration) - respond by eliminating bicarbonate from the plasma therefore increasing proton concentrations 1. Rate of H+ secretion is inadequate to reabsorb all the filtered HCO3-, so the significant amounts of HCO3- are excreted in the urine. normally bicarbonate is almost all reabsorbed in the tubule 2. There is little or no H+ secretion on non-HCO3- urinary buffers. 3. Tubular glutamine metabolism and ammonium excretion are decreased, so that little or no new HCO3- is contributed to the plasma from this source. Net result: Plasma HCO3- will decrease, thereby compensating for the alkalosis. The urine is highly alkaline (pH > 7.4). Classification of acidosis and alkalosis 1) by definition, acidosis means high concentration of hydrogen ions and alkalosis means low concentration of hydrogen ions 4) for metabolic acidosis, you must fill the bicarbonate cell first - the primary change in a decrease in bicarbonate - in response, the body will compensate by lowering carbon dioxide concentrations Classification of acidosis and alkalosis H+ HCO3PCO2 2) think what concentrations of carbon dioxide will cause high or low concentrations of hydrogen ions - high concentrations of carbon dioxide will cause increased levels of protons Resp acidosis Resp alkalosis Met acidosis Met alkalosis CO2 + H2O pH = 6.1 + log10 - once you determine the primary change in carbon dioxide, the compensation in bicarbonate concentration will always be in the same direction H2CO3 [HCO3-] [CO2] 3) determine bicarbonate disturbance - must determine if the bicarbonate disturbance is primary (met acidosis/alkalosis --> det. bicarbonate first) or secondary (resp acidosis/ alkalosis --> det. carbon dioxide first) - in acidosis, hydrogen levels are increased, and to minimize this change the body will increase bicarbonate levels to compensate for the increased carbon dioxide concentrations HCO3- + H+ Clinical examples Respiratory acidosis: respiratory failure with CO2 retention Respiratory alkalosis: hyperventilation (e.g. high altitude) Metabolic acidosis: diarrhea (loss of HCO3- in diarrhea), renal failure (accumulation of inorganic acids) leading to low bicarbonate concentrations Metabolic alkalosis: vomiting (loss of H+ in vomits), hyperaldosteronism (increased H+ secretion in DCT and along with water and sodium reabsorption and potassium secretion, increased fluid volume, high blood pressure CCD) Diuretics Drugs used clinically to increase the volume of urine excreted are known as diuretics. Diuretics act on the tubules to inhibit the reabsorption of sodium, along with chloride and/or bicarbonate, resulting in increased excretion of these ions. Water excretion - water reabsorption increases, too. happens together is decreased as well, as sodium and water regulation always - because sodium is a cation, its excretion is usually accompanied by an anion too Vander’s 10th : Chapter 14, section E (p569) Loop diuretics • Acts on the thick ascending limb of the loop of Henle. • Inhibits cotransport of sodium, chloride and potassium (Na+-K+-2Cl- cotransporter). on the lumenal side • One of the commonly used diuretics. • e.g. furosemide / Lasix Na reabsorption Loop diuretics (e.g. furosemide) - blocks the reabsorption of Na in the thick ascending limb - very potent and dramatic effect - 25% is a large contribution to sodium reabsorption Potassium-sparing diuretics - furosemide like diuretics will usually cause a decrease in potassium concentrations and will have to take supplements • Inhibit sodium reabsorption in the CCD, and also inhibits potassium secretion there. Thus, unlike the other diuretics, plasma concentration of potassium does not decrease. • Either block the action of aldosterone or block the (aldosterone-regulated) epithelial sodium channel in the CCD. • e.g. amiloride, spironolactone Potassium-sparing diuretics - blocks the process of Na reabsorption and K secretion on the lumenal side (amiloride) - spironolactone blocks the aldosterone receptor which when stimulated actively promotes K secretion Aldosterone Upregulate expression Clinical use of diuretics • Renal retention of salt and water: abnormal expansion of the extracellular fluid (edema) Example 1: congestive heart failure (cardiac failure by an attempt to leading to lower cardiac output) fluid is retainedas athe body in concentrations increase CO result, salt retained are also increased Example 2: hypertension. In some patients with hypertension, renal retention of salt and water of and water can contribute to high blood pressure. rehandlinghighsodiumpressure --> be a cause for blood decrease dietary intake of salt Kidney disease/Kidney (renal) failure Common features of kidney disease/kidney failure the normal glomerular filtration barrier Proteinuria (protein in the urine) shoulda not be permeable to protein often sign of kidney disease Accumulation of waste products in the blood volatile acids (urea, creatinine, phosphate, sulfate) High potassium concentration in the blood potassium secretion is impaired accumulation of non-volatile acids eat up Metabolic acidosis bicarbonate concentrations Anemia (decreased secretion of erythropoietin) Decreased secretion of 1,25-(OH)2vitamin D decreased reabsorption (leading to hypocalcemia) from the intestines of calcium Treatment of kidney (renal) failure When more than 90 % of nephrons stop working, one can not sustain life. In order to continue living, one has to have renal replacement therapy. necessary when kidney function is 10% or less Renal replacement therapy: 1. Hemodialysis 2. Peritoneal dialysis 3. Kidney transplantation the best treatment by far, but availability is limited Hemodialysis Blood pump Anticoagulant - blood cleaning treatment - blood is taken from a vein of the patient and pumped (at 200-300mL/min) and sent through dialysis tubing in a dialyzer (artificial kidney) “Arterial” blood from patient - in the dialyzer, clean dialysis fluid is running from bottom to top - waste products and removed from the blood and necessary ions are added to the blood Dialysis fluid and ultrafiltrate of plasma output Strands of dialysis tubing Dialyzer Removes waste products from blood Dialysis fluid drain “Venous” blood returned to patient Air trap and air detector Dialysis fluid input Dialysis fluid pump Fresh dialysis fluid (concentrate and purified water) - exchange of waste products takes place at the peritoneal membrane of the patient's own body - done four times a day - there is a machine that can do the exchange automatically when the patient is sleeping Peritoneal dialysis - treatment can be done at home as opposed to hemodialysis treatment The lining of the patient’s own abdominal cavity (peritoneum) is used as a dialysis membrane. Fluid is injected into the cavity via a tube inserted through the abdominal wall. Solutes diffuse into the fluid from the person’s blood. Fluid is exchanged several time per day. - also replaces the hormonal function of the kidney in addition to waste product removal and ion replacement Kidney transplantation Either from recently deceased persons (cadaveric transplant) or from a living related/unrelated donor. Anti-rejection treatments have improved dramatically in recent years. Organ shortage is a problem. Donors can function quite normally with one kidney. ...
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This note was uploaded on 04/26/2011 for the course PHGY 210 taught by Professor Trippenbach during the Winter '08 term at McGill.

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