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Kidney Lect 12
Acid Base 1
Question | Answer |
---|---|
What is the normal blood pH? What is the range for a normal pH? | ~7.40; 6.8 to 7.8 |
Buffer | solutes that, in an aqueous solution, are able to take-up or release H + such that changes in pH are minimized |
isohydric principle | The ratio between the undissociated and dissociated forms of any buffer pair depends only on pH and pK for the buffer pair; All body buffers are in equilibrium; change in the ratio of any one buffer pair-->all body buffer pairs change. |
What is the most important body buffer system? | The bicarbonate-carbonic acid buffer pair: CO2 + H2O <-> H2CO3 <-> H+ + HCO3- |
What catalyzes the conversion of CO2 and H2O into bicarbonate? Where is it found? | Carbonic anhydrase; found in RBCs |
What feature of the circulatory system allows the HCO3-/H2CO3 system to be a better buffer than the Henderson Hasselbach equation implies? | It is an OPEN system, meaning that any excess CO2 in the serum will be "blown" off; thus, the effective "capacity" of HCO3- to buffer spikes in pH is much greater than in a closed system. |
Volatile acid | Carbon dioxide (carbonic acid) produced by the oxidative metabolism of carbohydrates, proteins and fats; volatile acid production depends on caloric utilization and substrate mix. On average, 15,000 – 20,000 mmol of carbon dioxide are generated dail |
How is volatile acid excreted? | Through the lungs |
Fixed Acid (non-volatile acid) | Hydrogen ions created through metabolic processes (H2SO4, H3PO4, beta-hydroxybuteric acid, lactic acid, and HCl); production ~1 mmol/kg/day |
How are fixed acids excreted? | Through the kidney |
How does the body produce bases? | Bicarbonate (HCO3-) produced through metabolism of aspartate, glutamate, and some organic anions (e.g. citrate) |
Changes in carbon dioxide production are rapidly matched by corresponding changes in excretion through stimulation or inhibition of ___. This response is mediated by the ___ in the brain stem | ventilation; ventilatory center |
Afferent stimuli on the ventilatory center in the brain stem | 1) direct responses to a change in pH or pCO2 2) afferent neural stimuli from chemoreceptors in the aortic arch and carotid bodies |
Efferent stimuli of the ventilatory center in the brain stem | modulating the respiratory rate and tidal volume, thereby altering minute ventilation |
Respiratory compesantion | primary change in respiratory rate due to pH changes in the serum; acid increases, alkali decreases; seeks to return [HCO3]:PCO2 ratio back towards normal ratio of 0.6 |
What are the two major functions in the maintenance of acid-base balance? | 1. Reclamation of filtered bicarbonate 2. Excretion of metabolically generated fixed-acid (non-volatile acid) |
Renal handling of bicarbonate | Freely filtered at glomerulus; completely reabsorbed to prevent acidosis; 90% reabsorbed in proximal tubule, rest in distal nephron; high capacity, low gradient system |
What are the two major processes involved in renal excretion of fixed acid? | 1) Distal tubular acid secretion and 2) ammonium generation and subsequent excretion |
How does the proximal tubule handle HCO3-? | NOT directly reabsorbed; reclaimed by converting it to H2CO3 (by acidifying the lumen via the Na+H+ antiporter) and then absorbing passively; inside cell, converted via CA back to H2CO3-->convert to HCO3- -->secreted into blood via Na+,3HCO3- cotransport |
What drives the Na+H+antiporter? | Exchanger works passively, driven by Na+ gradient |
What is the capacity of the nephron to reabsorb filtered bicarbonate? | Reabsorption matches filtered load ~100%; at levels > ~26-28 mmol/L, bicarbonate starts being excreted |
How does intravascular volume alter bicarbonate handling in the kidney? | link of H+ and Na+: volume depletion->stimulate H+ secretion-->bicarbonate reabsorption; volume expansion inhibits proximal tubular sodium reasorption-->inhibits bicarbonate reabsorption |
How does chloride depletion alter bicarbonate handling in the kidney? | Usually accompanied by volume depletion; No chloride-->unavailable for Na+ cotransport-->increase in Na+/HCO3 coupled transport |
How does pH affect bicarbonate handling in kidney? | drop in intracellular pH-->more H+ filtered-->enhances hydrogen ion secretion-->more bicarbonate reabsoprtion |
How does serum potassium affect bicarbonate handling? | Hypokalemia-->drop in intracellular K+-->some K replaced by H+-->intracell pH drops-->increased bicarbonate reabsorption; hyperkalemia results in opposite effect |
How doe pCO2 affect bicarbonate handling? | Hypercapnia-->increased intracell PCO2->increase intracell carbonic acid-->pH intracell drop-->increased Na+H+ exchanger activity-->more bicarbonate reabsorption |
In the distal tubule, what cell is responsible for HCO3- reabsorption? | intercalated cell (principal cell sets up gradient driving reabsorption, though) |
What establishes the hydrogen ion secretion in the distal nephron? | Occurs via ATP driven hydrogen pumps (H+ATPase and H+K+ATPase |
What cell (and what cell surface protein) is responsible for movement of HCO3 from the distal nephron to the serum? | HCO3-/Cl- exchanger on the intercalated cell; moves coverted HCO3- from the intercell environment through the basolateral memebrane |
The ability to excrete an acid load is therefore dependent upon the presence of ____ | urinary buffers |
Titratable acids in the distal nephron | non-amonia buffers in the urine; principal titratable acid is filtered HPO4- which is titrated to H2PO4- and excreed in the urine (others are sulfates and organic acids) |
Ammonium in the distal nephron | A major form of buffered hydrogen ion; oversimplification to say that NH4+ formed by combining NH3 and H+ and trapped in the lumen |
Bicarbonate as a urinary buffer in the distal nephron | secreted H+ combines with remaining bicarb that is not reclaimed in proximal tubule-->H2CO3-->decomposed slowly to CO2 since NO CA in luminal membrane of distal nephron; CO2 reabsorbed in bladder |
Although the apical membrane proton pump is the primary determinant of H + secretion, in the cortical collecting duct, H + secretion is also ___ dependent | voltage |
How does distal tubular sodium delivery and reabsorption alter bicarb handling in the kidney? | Increased sodium load in tubule-->increased Na+ transport through ENaC-->drives voltage of lumen down (more negative)-->increased H+ secretion-->more bicarb absorption |
any process that increases collecting duct sodium transport will increase tubular electronegativity and augment hydrogen ion secretion: | -increased distal tubular sodium delivery -increased sodium reabsorption through ENaC -increased delivery of a poorly reabsorbed (non Cl - ) anion -mineralocorticoid (aldosterone) excess |
Conversely, any factor that decreases tubular lumen electronegativity will decrease hydrogen ion secretion | -decreased distal tubular sodium delivery -inhibition of sodium reabsorption through ENaC -mineralocorticoid deficiency |
What effect will urinary buffer deficiency have on H+ secretion? | Deficiency-->drop in pH more agumented by small changes in [H]-->H+ secretion inhibited |
How do mineralcorticoid affect H+ secretion in the distal tubule? | Aldosterone stimulates distal tubular acidification both through the effect on sodium reabsorption and through direct stimulation of H + secretion. Mineralocorticoid deficiency is associated with decreased distal H + secretion. |
How are K+ and H+ related in the distal kidney | Usually hypokalemia --->metabolic alkalosis + impaired urinary acidifcation; direct effects of K on H complicated by aldosterone secretion |
____ represents a major urinary buffer and is responsible for 1/2 to 2/3 of net hydrogen ion secretion | Ammonium |
Renal ammonium handling can be viewed as consisting of three steps: | Proximal tubular ammoniagenesis, Medullary shunting, Collecting Duct trapping |
How is ammonia generated in the proximal tubule? | Glutamine daminated-->2NH4+ and alpha-ketoglutarate; NH4+ transported out of apical side. alphaKG metabolized (either into glucose or CO2 + H2O), consuming 2 H+ (this produces 2HCO3-, which is secreted through basolateral side |
The deamination of glutamine is ___. It is stimulated by... | pH sensitive; acidemia and hypokalemia, both of which cause a fall in intracellular pH, and is inhibited by alkalemia and hyperkalemia, which cause an increase in intracellular pH. |
the majority of ammonium secreted into the proximal tubule is transported to the collecting duct through a ___ | medullary “shunt” |
How is NH4+ transported from the ascending limb of the loop of Henle into the collecting duct? | NH4+ transported from the thick ascending limb of Henle into the medullary interstitium in place of K+ on the Na + ,K + ,2Cl - -transporter-->turns to NH3-->permeates across collecting duct membrane-->trapped in urine as NH4+ |
For each hydrogen ion secreted (either in the proximal or distal tubule) or ammonium ion excreted in the urine, a ___ ion is returned to the blood. Any __ lost in the urine represents a net gain of hydrogen ion to the body. | bicarbonate; bicarbonate |