Role of Kidneys in Acid/Base Balance

Describe the chemical reaction scheme and role of bicarbonate in the buffering of nonvolatile acid.

MAJOR: BICARB BUFFERING SYSTEM H+ + HCO3- → H2CO3 → CO2 + H2O (removed by lungs via expiration) -buffers H+ and eliminates it from the body -low PCO2 is required for optimal function of BBS -->Drives equation to the right --> acidemia stimulates ventilation, drives to right EFFECT OF PCO2 ON BBS: -At tissue: O2 consumption --> addition of CO2 to capillaries -Two conditions result in accumulation of CO2 at tissue level 1) Rise in metabolic rate w/o proportional increase in BF 2) Decrease in BF w/o a change/decrease in metabolic rate -Either scenario impairs function of BBS -Less H+ is removed/eliminated by the BBS -Excess H+ bind to proteins and disrupt function

State the major acid buffering mechanisms in the ECF.

MAJOR: BICARB BUFFERING SYSTEM H+ + HCO3- → H2CO3 → CO2 + H2O (removed by lungs via expiration) -buffers H+ and eliminates it from the body -low PCO2 is required for optimal function of BBS -->Drives equation to the right --> acidemia stimulates ventilation, drives to right EFFECT OF PCO2 ON BBS: -At tissue: O2 consumption --> addition of CO2 to capillaries -Two conditions result in accumulation of CO2 at tissue level 1) Rise in metabolic rate w/o proportional increase in BF 2) Decrease in BF w/o a change/decrease in metabolic rate -Either scenario impairs function of BBS -Less H+ is removed/eliminated by the BBS -Excess H+ bind to proteins and disrupt function ECF PROTEINS **Bind H+ but the H+ is not eliminated -albumin -immunoglobulins OTHER BUFFERS -amines -carboxylates -histidines -bone: acidosis suppresses osteoblasts and stimulates osteoclasts; Releases Na, K, CO32-, and HPO3- from bone

State the role of the kidney in the maintenance of bicarbonate levels.

ROLE OF KIDNEY TO MAINTAIN ACID BALANCE 1) ELIMINATE ACID ANIONS -HSO4- and H2PO4- -Filtered by glomerulus and excreted 2) REABSORB ALL OF FILTERED BICARB [proximal tubule; neutral process] -Freely filtered by the glomerulus -Avidly reabsorbed: majority in prox tubule (85-90%) 3) SYNTHESIZE/GENERATE NEW BICARB [distal tubule; net acid excretion] -HCO3- is continuously consumed via H+ buffering (60-70mmol/day) -ECF contains only 360 mmol of total HCO3- 24mmol/L x 15 L = 360 mmol 5-6 day supply of HCO3- in ECF -Must synthesize/generate 60-70mmol of HCO3- daily to maintain HCO3- balance -Occurs primarily in distal tubule -Intercalated cells in the collecting duct **Bicarb reabsorption (4000) >> bicarb synthesis (60)

Describe the renal responses to respiratory acidosis

with primary respiratory acidosis--> bicarb will increase and then hit a steady state

Describe the cellular mechanisms, tubular localization, and daily magnitude of bicarbonate synthesis.

**all occurs in the collecting duct via the intercalated cells -Nonvolatile acids are main source of H+ that kidneys must excrete -Come from protein/nucleic acids in diet -Each H+ consumes a HCO3- Kidneys must: -Eliminate excess H+ -Eliminate the acid anions from which H+ came H2SO4 --> H+ + HSO4- H3PO4 --> H+ + H2PO4- -Regenerate new HCO3- to replace consumed HCO3- **For every H+ that is secreted/excreted, a new HCO3- is generated/reabsorbed Kidneys generate/synthesize mmol of bicarb: 60-70 mmol/day

Describe the cellular mechanisms, tubular localization, and daily magnitude of bicarbonate reabsorption.

**no net acid secretion in the proximal tubule -if had issues with proton, CA, or transporters, would not be able to reabsorb bicarb --> acidosis (Renal tubule acidosis) Normal Kidneys reabsorb/day serum bicarb x GFR where 180 = GFR 24mmol/L * 180 L = 4000 mmol *compared to synthesis, reabsorrption requires 60x the capacity of NHEs, NBCs, H pumps -As long as HCO3- is in tubular lumen, HCO3- will be reabsorbed, but not synthesized

State the production rate of metabolic, nonvolatile acid in a healthy, average-sized individual.

-person will produce 1 mmol/kg/day of nonvolatile acid **for a 60 kg person, every day 60mEq of H+ are added to the ECF -Most of acid generated is eliminated as volatile acid (CO2) via lungs -Under normal/basal conditions, acid generated = acid eliminated -Bicarbonate buffering system

Ammonia Trapping

Alpha intercalated cell

Net acid excretion

CHROINIC METABOLIC ACIDOSIS -NH4+ excretion↑'s -Titratable acid excretion unchanged -Bicarb excretion remains zero CHRONIC METABOLIC ALKALOSIS -Bicarb excretion ↑'s -Up to 80mmol/day -Decreased reabsorption -NH4+ and titratable acid excretion ↓'s **H+ secretion and HCO3- reabsorption are the rate limiting steps -Dependent on ECF pH and CO2 levels -Upregulate/downregulate # of apical + basolateral transporters

Renal response to hypokalemia (acid base balance)

HYPOKALEMIA = decreased ECF [k] -K+ will shift out of cells into the ECF Exchanges for H+: shifts into cells -More intracellular H+ available in renal tubules for secretion (mass effect) -Increased ammoniagenesis --> more H+ trapping and excretion Intercalated cells will preferentially reabsorb K+ and secrete H+ -Via H+/K+ -ATPase on apical membrane More H+ secretion/excretion = More HCO3- synthesis ([HCO3-]serum) **So, hypokalemia predisposes to metabolic alkalosis

Describe the long term effects of primary changes in ECF potassium levels on plasma pH.

URINARY ACID BUFFERING -Consider that ~60mmol of H+ are secreted in ~1.5L of urine daily; What would be the urine pH? log (60mmol/1500ml) = 1.4 !! -Toxic to epithelial cells lining urinary tract -Secretion of H+ would be energetically expensive/impossible -Lowest urine pH is ~4.5 Two main urinary buffering systems 1) Titratable acid 2) Ammonia trapping **Acid-Base balance is affected by potassium balance and vice versa -Hypokalemia --> metabolic alkalosis -Hyperkalemia --> metabolic acidosis

Describe the renal responses to metabolic acidoses.

increase in protons --> drives equation to the right H+ + HCO3- --> H2CO3 --> CO2 + H2O