acid base balance Flashcards
Normal pH range and the range of pH that can be tolerated
normal: 7.35-7.45. Tolerated: 7.0-7.7
1.state the production rate of metabolic, nonvolatile acid in a healthy, average-sized individual.
Typically a 70kg person will produce 60 meq/day of nonvolatile acid, i.e. every day 60 mmol of H+ are added to the ECF.
Common types of nonvolatile acids
H2SO4 and H3PO4 are produced from catabolism of proteins and nucleic acids
2.state the major acid buffering mechanisms in the ECF.
Carboxylates, amines, and the histidine side group are all capable of binding hydrogen ions, thus are a large buffer component of the ECF, but can only buffer to a pH of ~5. Bicarbonate anion (HCO3-) is capable of buffering to physiological pH
3.describe the chemical reaction scheme and role of bicarbonate in the buffering of nonvolatile acid.
H+ + HCO3- > H2CO3 > CO2 + H2O This mechanism allows for nonvolatile acids to be converted to a gaseous volatile form that can be eliminated
How does the body get rid of acid anions (ie. HSO4- and H2PO4-)
They are small and can be filtered at glomerulus and excreted in urine
Total amount of bicarbin ECF and how long this supply will last to eliminate nonvolatile acid
300mmol total bicarb in ECF will last 5 days. There is a need for replenishment of bicarb
Generally, how do the kidneys regulate bicarb levels
The kidneys synthesize bicarbonate to replace exactly what is lost in the acid elimination process and reabsorbs bicarb filtered at glomerulus
5.describe the cellular mechanisms, tubular localization, and daily magnitude of bicarbonate reabsorption.
85% of filtered bicarb is reabsorbed at proximal tubules (obligatory). Here, the sodium hydrogen exchanger secretes an H ion from the cell into the lumen. H in lumen combines with bicarb forming carbonic acid (H2CO3), which breaks down into CO2 and water. The apical membrane is highly permeable to CO2, so CO2 diffuses into the cell. Inside the cell, CO2 recombines with a water molecule to reform carbonic acid, which then dissociates into H + HCO3. The bicarb is then transported across basolateral membrane by a sodium-bicarb co-transporter
How does bicarb reabsorption affect ECF acid/base balance
It does not change anything. The H that is secreted into the lumen recycles with each bicarb transported into the cell
How is electrical neutrality maintained with bicarb reabsorption
The sodium hydrogen exchanger on the apical side and the sodium bicarb cotransporter on the basolateral side move Na from lumen into the ECF with bicarb movement to maintain neutrality
What enzyme speeds up the breakdown of H2CO3 into water and CO2
carbonic anhydrase localized in the apical membrane surface and within the cell
6.describe the cellular mechanisms, tubular localization, and daily magnitude of bicarbonate synthesis.
In epithelial intercalated cells of the distal segments, CO2 is brought into the cell from ECF, then it combines with water to form H2CO3 (helped by carbonic anhydrase), then that is converted into bicarb and H+. The H ion is excreted into the tubule lumen while the bicarb is transported from the cell into the serosal ECF by the bicarb chloride exchanger.
Problem with H secretion from bicarb synthesis? Solution?
High amounts of H ions secreted into urine could damage cells of urinary tract and it would be energetically expensive to secrete H ions from cell into lumen if the concentration gradient were so high. The solution is that the secreted acid is buffered with urinary buffers
Types of urinary buffers
Titrable acid: acid refers to the complexing of hydrogen ion to a filtered acid anion, such as HPO42-, creatinine and urate. Ammonia trapping: tubular cells break down glutamine to free ammonia (NH3). Since this substance is readily soluble and neutral, it diffuses through the apical membranes of the epithelium into the tubule. Once in the tubule, it has a very high affinity for H+, buffering it to form ammonium ion which is impermeable to apical membrane, so the ammonia and H are excreted in urine
Main similarities and differences btw bicarb reabsorption and synthesis
Uses same transporters and enzymes. Synthesis starts with CO2 entry from the serosa, whereas with reabsorption the CO2 comes from tubule lumen. Bicarb reabsorption is neutral, whereas synthesis results in elimination of acid in the urine
How much bicarb must a person make in a day and how much must be reabsorbed
60mmol is synthesized and 3800mmol is reabsorbed
Is bicarb reabsorption or secretion predominant
Reabsorption -no synthesis can occur until bicarb reabsorption is complete and as long as there is bicarb in the tubular fluid, only reabsorption will occur
How is bicarb regulated during acidosis or alkalossi
In metabolic acidosis, nonvolatile acid can be eliminated by bicarb system, requiring excess bicarb synthesis. In metabolic alkalosis, the kidneys can excrete extra bicarb in urine while retaining H ions
Rate limiting factors for bicarb homeostasis
apical secretion of H and basolateral extrusion of bicarb are rate limiting. ECF pH and CO2 levels determine the rates of these processes by increasing (during acidosis) or decreasing (during alkalossi) the number of transporters
Renal response to metabolic acidosis
increased H > increased buffering with bicarb > decreased bicarb concentration > decreased filtered load of bicarb > decreased H secretion required for bicarb reabsorption > increased H secretion available for bicarb synthesis > increased bicarb synthesis to replenish lost bicarb. Also increased H increases number of apical H pumps for synthesis. Also, increased bicarb buffering leads to increased CO2 production which is eliminated by lungs
renal response to respiratory acidosis
decreased ventilation > increased CO2 (leads to increased bicarb by mass action which actually causes more acidification due to production of H)> increased H in ECF > increased number apical H pumps (slowly over days) > increased H secretion allows for bicarb synthesis > increased bicarb in plasma establishes a new steady state > increased filtered load of bicarb > increased H secretion for bicarb reabsorption but decreased H secretion for synthesis > maintain constant elevated bicarb.
Effect of K on acid/base status
Alkalosis leads to increased K secretion and hypokalemia AND primary hypokalemia can cause alkalosis. hypokalemia-induced shift of H+ into tubular cells results in inappropriately increased H+ secretion and urinary excretion, inducing the alkalosis. The opposite is true for hyperkalemia and acidosis
