chapter 31 renal lecture 4 acid base Flashcards
what are the 3 systems that regulate the acid concentration in body fluids to prevent acidosis/alkalosis
1) 1st line of defense-chemical acid base buffer systems of body fluids-combine with acid or base to prevent excessive changes in H concentration
2) 2nd line of defense-respiratory center regulates the removal of CO2 and H2CO3 from ECF
3) the kidneys, which can exert either acid or alkaline urine which adjusts ECF H concentration during acidosis or alkalosis
Do Buffer systems eliminate or create acid in body?
no, just minimize changes by combining with acid/base until balance is reestablished
although slow to respond to acid/base changes, this system is the most powerful acid base regulation system
kidneys-eliminate excess base or acid from body
what is a buffer, describe right and left shifts in H buffer reactions
substance that can reversibly bind to H
when H concentration increases, reaction goes to right and more H binds to buffer
when H concentration decreases, reaction goes to left and H is released from buffer
where is carbonic anhydrase present
walls of lung alveoli where CO2 released, epithelial cells of the renal tubules where CO2 reacts with H2O to form H2CO3
speeds up reversible reaction of H2O+CO2 forming carbonic acid H2CO3
what part of the body regulates HCO3
kidneys-decreased HCO3=metabolic acidosis, increased HCO3=metabolic alkalosis
what part of the body regulates CO2
lungs, rate of respiration. Increased RR=more CO2 elimination=respiratory alkalosis. decreased RR=CO2 buildup=respiratory acidosis
what is the most important extracellular buffer? why?
the HCO3 buffer system, with its two components CO2 regulation via lungs and HCO3 regulation via kidneys, precisely control pH of ECF by rate of removal of CO2 via lungs, and rate of removal/addition of HCO3 by kidneys
what buffer system buffers renal tubular fluid and intracellular fluids
phosphate buffer system-low PH in renal tubules and ICF +high concentration of PO4 makes for a favorable system in these areas
why is phosphate buffer system important
1) phosphate is concentrated in renal tubules, increasing the buffer capacity of renal system
2) tubular fluid has a low pH than ECF, and buffer system has pKa of 6.8
what are the most plentiful buffers in the body
proteins, high concentration
How does the pH of cells (negative pH) adapt to changes in the ECF environment?
-hydrogen and bicarbonate diffuse out of cell but take several hours to come into equilibrium with ECF environment
-CO2 diffuses rapidly
the diffusion of the elements of the HCO3 system cause the pH in the ICF to change when there are changes in ECF
what percentage of total chemical buffering results from intracellular proteins?
what contributes to their buffering power?
- 60-70%-occurs inside of the cells
- high concentration of intracellular proteins, relatively close pK and intracellular pH
describe the isohydric principle
all buffering systems work synergistically because they all share the common element, hydrogen, so when there is a change in the H concentration of the ECF, the balance of all buffer systems shifts simultaneously, so any condition that changes the balance of one of the buffer systems also changes the balance of all the others because the buffer systems buffer each other out by shifting H back and forth between them
increases and decreases in ventilation effect the ECF how
- increased ECF concentration of CO2=increased acid concentration
- decreased ECF concentration of CO2, and thereby reduction in acid concentration
describe CO2 formation and elimination
CO2 formed continuously by cells (ICF) and CO2 diffuses as waste product to ECF, which is transferred to blood, to alveoli, and eliminated via respiration, with about 1.2mol/L=pCO2 of 40
How is ECF PCO2 changed 2 things
changes in rate of formation by tissues
changes in rate of elimination by pulmonary ventilation
When CO2 increases, what other two elements are formed to lower ECF pH
H2CO3 (carbonic acid) and H (hydrogen ion) concentration increased, which lower pH
which is more effective, respiratory compensation for an increased or decreased pH
decreased pH, because with elevated H concentration the alveolar ventilation rate decreases as a result of an increase in pH the amount of O2 added to the blood decreases and the partial pressure or O2 in the blood decreases, which stimulates the ventilation rate
whenever H concentration increases, the respiratory system is ______ and alveolar ventilation ______
stimulation, increases
this reduces the PCO2 in the ECF and reduces H concentration
if H concentration decreases, the respiratory system is ______, and alveolar ventilation _____
depressed, decreases
this causes H concentration to rise and come back to normal
describe how the buffering system is hindered in someone with emphysema
patients have damaged alveoli, which results in accumulation of CO2 (acid) and these individuals cannot adequately respond with elimination of CO2 via normal ventilatory mechanisms=respiratory acidosis. Patients compensatory mechanisms to metabolic acidosis are blunted, so kidneys are sole physiologic mechanisms for returning pH back to normal after initial chemical buffering in ECF has occurred
how do kidneys control acid base balance
in times of acidosis, kidneys excrete acidic urine, and in times of alkalosis, kidneys excrete basic urine
How much non volatile acid is made by body, what is primary mechanism of creating non-volatile acid
80mEq, via metabolism of proteins
not carbonic acid, so cannot be excreted by lungs
what is more important to kidneys prevention of loss of HCO3 in the urine, or excretion of non volatile acids?
prevention of loss of HCO3, most HCO3 is reabsorbed from tubules which conserves primary buffer system of ECF
secretion of acid from tubules into urine is accomplished by what
reabsorption of HCO3 and excretion of H.
H must react with HCO3 to form H2CO3 before HCO3 can be reabsorbed back into blood stream
4320 of H must be secreted for reabsorption of previously filtered HCO3, and 80mEq of H must be secreted to rid body of non volatile acids=4400mEq of H secreted each day into urine
describe kidney in alkalosis
decreased H in ECF, kidneys secrete less H and fails to reabsorb HCO3, so HCO3 is lost in urine, which raises ECF H concentration back to normal
describe kidneys in acidosis
kidneys secrete more H and do not excrete HCO3 into the urine but reabsorb all HCO3 and produce new HCO3 which is added back to ECF, which reduces H concentration in ECF
name 3 processes that the kidneys regulate ECF H concentration
1) secretion of H
2) reabsorption of filtered HCO3
3) production of new HCO3
what parts of the renal tubule can H ion secretion and HCO3 reabsorption not occur
descending and ascending THIN limbs of the LOH
where does the largest percentage of H ion secretion and HCO3 reabsorption occur
in PCT 80-90%, only a small portion of HCO3 flows in DCT and collecting ducts because most of remaining HCO3 is reabsorbed in THICK ascending LOH
which process and where in the renal tubules is H secreted?
secondary active transport via NA H counter transport-H out, Na in via NA H exchanger protein, with energy from NA gradient driving H out into urine against its concentration gradient, via NA/K/ATPase at basolateral cell membrane
in the PCT, thick ascending LOH, and early distal tubule H is secreted, but urine does not become very acidic until it reaches the collecting tubules and ducts
95% HCO3 reabsorbed, 4000mEQ H secreted
How does H secretion into urine cause HCO3 reabsorption
1) CO2 diffuses into tubular cells or is formed in tubular cells
2) CO2 with carbonic anhydrase combines with water to form carbonic acid which dissociates into bicarb and hydrogen ion
3) H secreted from cell into tubular lumen (urine) by NA/K counter transport, with Na entering cell down its concentration gradient via NA/K/ATPase in basolateral membrane, and provides energy for H to go into urine
3) HCO3 generated into cell goes through basolateral membrane to peritubular capillaries, where it is reabsorbed into body
* for every H secreted, a HCO3 is reabsorbed
can HCO3 filtered by glomerulus be directly reabsorbed?
no, it must combine with H to form carbonic acid, and eventually become H2O and CO2. CO2 moves easily across membrane, and reforms carbonic acid on tubular (urine side) and dissociates into bicarb and hydrogen ion, with HCO3 reabsorbed into basolateral membrane and peritubular capillaries
what two mechanisms facilitate the transport of HCO3 across basolateral membrane
1) NA HCO3 cotransport in PCT
2) CL HCO3 exchange in late PCT, thick LOH, and collecting tubules and ducts
each time an H is formed in tubular epithelial cells, what happens
a bicarb is also formed and released back to blood which drives reabsorption of HCO3
per day what is normal rate of tubular H secretion and HCO3 formation
H secretion=4400mEQ
HCO3 formation=4320 mEQ
how doe HCO3 and H titrate each other
quantities of these two elements entering the tubules are almost equal, combine to form CO2 and H2O so they titrate each other in the tubules, the excess 80mEQ H normally produced combines with other elements (ammonia and phosphate) and is excreted
what is the basic mechanism for kidneys to correct metabolic acidosis or alkalosis
incomplete titration of H against HCO3 leaving one or the other to pass into the urine and be removed from ECF
describe 2 primary active secretion of H in intercalated cells of late DCT and CD
at luminal membrane of tubular cell, H is 1)transported via hydrogen ATPase and a 2)hydrogen K ATPase
where does primary active secretion of H occur
in the late distal tubule and collecting tubules, by type A intercalated cells
1)dissolved CO2 in their cell combines with H2O to form carbonic acid
2)the carbonic acid dissociates into bicarb which is reabsorbed into blood plus H which is secreted into urine uses active H ATP pump*
important for forming maximally acidic urine, about %5 of
where can H secretion be increased the most, the PCT or the collecting tubules
although the secretion of H in the DCT and CD is only 5% of total H secreted, this mechanism is important in forming maximally acidic urine. In the PCT, H concentration can be increased only 3 fold with tubular pH only made about 6.7 but in the collecting tubules H concentration can be increased 900 fold to pH of 4.5
for every L of urine formed, how much free H ion
0.03mEQ/L, most acid secretion occurs with H ion combining with phosphate and ammonia buffers
How does phosphate buffer system carry excess H into urine and make new HCO3
1) phosphate is abundant in tubular fluid
2) pK of this system is near pH of tubular fluid at 6.8
3) excess H combines with PO4 system and is excreted as a salt in urine, carrying away excess H
whenever H combines with a buffer other than bicarb in tubular fluid (urine) what does this mean for HCO3
HCO3 is added to the blood because H combines with something else and is excreted
what is the precursor for ammonia
glutathione
describe excretion of excess H and generation of new HCO3 by the NH3 buffer system
AA metabolism by liver results in glutathione which is delivered to kidneys. glutathione is transferred to the PCT, thick ascending limb of LOH, and distal tubules. Once inside the cell, glutathione is metabolized to ammonium ion and bicarbonate. NH3 is secreted in tubular fluid in exchange for NA, HCO3 is reabsorbed across basolateral membrane, taken up by peritubular capillaries.
for each molecule of glutathione, how much HCO3 is reabsorbed
two NH4s are made and excreted, two HCO3s are reabsorbed in the PCT, and in collecting ducts for each molecule of NH4 made and excreted a new HCO3 is made and reabsorbed
with chronic acidosis what is most important mechanism for creating new bicarb by kidneys
liver breaks down more protein for glutathione, more acid excreted in urine, more HCO3 retained to buffer pH
How is bicarbonate excretion calculated, what does bicarbonate excretion fix?
urine flow rate multiplied by urinary HCO3 concentration, indicates how rapidly the kidneys are removing HCO3 from the blood, loss of HCO3 via urine fixes alkalosis in the plasma
how is HCO3 added to blood calculated
equal to the amount of H secreted that ends up in the tubular lumen with non-bicarbonate urinary buffers (NH4 and phosphate buffers) so we measure NH4 secretion levels, and multiply urine flow rate x NH4 secretion in urine
titratable acid
NAOH is used to titrate urine ph to 7.4 and amount of miliequivalents used to buffer urine to this pH is equivalent to the amount of H added to urine
Net acid secretion
=NH4 excretion+urinary titratable acid-HCO3 excretion
net acid excretion is equal to what?
non volatile acid production in the body
and the rate of net HCO3 addition to the blood
what happens to net acid excretion in acidosis and in alkalosis
acidosis-there is a net addition of HCO3 back to blood as more NH4 and urinary titratable acid are secreted.
alkalosis-there is a negative net acid secretion so there is a net loss of bicarb from the blood, and no new HCO3 is added back to body
describe retaining of HCO3 and excretion of non volatile acids under normal conditions
there must be enough H in kidneys to reabsorb HCO3, and there must be enough left over H to make NH4 or other titratable acids to rid body of non volatile acids (produced by metabolism)
what happens to titratable acids during alkalosis? acidosis?
alkalosis-tubular secretion of H is reduced so that HCO3 is not reabsorbed, and is urinated out, so titratable acids and NH4 are kept in body and not excreted
acidosis-tubular secretion of H is increased to reabsorb all the filtered HCO3 with enough H left over to excrete NH4 and titratable acids, which makes lots of new HCO3 for ECF
what are the 2 most important stimuli for increasing H secretion by the tubules in acidosis
1) increase in PCO2 of ECF in respiratory acidosis
2) an increase in H concentration of the ECF (decreased pH) respiratory or metabolic acidosis
what does excessive aldosterone do
increase secretion of H ions by intercalated cells of collecting ducts
in instances of decreased ECF volume, increased Angio II causes acidosis or alkalosis?
=alkalosis because NA is reabsorbed, H is secreted into urine in PCT and Thick ascending LOH, resulting in increased HCO3 reabsorption as well
how does hypokalemia and hyperkalemia effect H secretion
hypokalemia stimulates H secretion=alkalosis
hyperkalemia stimulates H reabsorption in the PCT=acidosis
6 factors that increase H secretion and HCO3 reabsorption
increased PCO2 increased H, decreased HCO3 decreased ECF volume increased angio II increased aldosterone (Conn's) hypokalemia
6 factors that cause decreased H secretion and HCO3 reabsorption
decreased PCO2 decreased H concentration, increased HCO3 increased ECF volume decreased angio II decreased aldosterone hyperkalemia
what does acidosis do to the HCO3/H ratio in the renal tubular fluid
respiratory and metabolic acidosis cause a DECREASE in ratio of HCO3 to H concentration in the renal tubular fluid
metabolic acidosis-decreased filtration of HCO3
respiratory acidosis-excess H in tubular fluid due to rise in ECF PCO2 which stimulates H secretion
describe findings in respiratory acidosis in terms of PH, H conc, PCO2, and HCO3. what is compensatory mechanism?
reduced pH increase in ECF H concentration, increase in PCO2, compensation involves increase in plasma HCO3
describe metabolic acidosis and compensation
decrease in pH rise in H concentration but a huge decrease in HCO3. compensation involves increased ventilation which reduces PCO2 and renal compensation which adds HCO3 to ECF
what happens in respiratory alkalosis
decrease in ECF H concentration and an increase in pH, caused by hypoventilation, causing decreased H secretion, which results in no net creation of HCO3 in kidneys because of an acid shortage, but accumulation of HCO3 in plasma will correct the alkalosis with reduction in plasma pH back to normal
what happens in metabolic acidosis
decreased plasma H concentration and increased pH due to rise in ECF HOC3 concentration, so compensatory mechanisms are decrease in respiratory rate which increases pCO2 and helps return ECF pH to normal and increased HCO3 filtration causes excess HCO3 secretion in urine
decreased ventilation causes
respiratory acidosis, increased CO2, increased carbonic acid and H concentration
can be caused by damage to respiratory center in brain, obstruction to airway, pneumonia, etc.
increased ventilation, high altitude
respiratory alkalosis, breathing off excess CO2 or low O2 content of the air stimulating excess respiration
metabolic acidosis
failure of kidneys to excrete metabolic acids
formation of excess quantities of metabolic acids
addition of metabolic acids from ingestion or infusion of acids
loss of base from body fluids
renal tubular acidosis=RF, insufficient aldosterone secretion (addison) fanconi syndrome, diarrhea, vomiting of intentional contents, DM
metabolic alkalosis
excess retention of HCO3 or loss of H from the body
diuretics(except carbonic acid anhydrase inhibitors)
aldosterone excess
vomiting of gastric contents, ingestion of alkaline drugs
treatment of excess acid
HCO3, sodium gluconate, sodium lactate
treatment of alkalosis
ammonium chloride
steps to analyzing acid base disorder
1)look at pH 2) look at pCO2 and HCO3
