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Kidney Lect 12

Acid Base 1

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
Created by: karkis77



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