Lecture 6: Acid/Base Flashcards
pH =
pH = log[H+] -1
What is a basic pH? Lethal? What happens at this pH?
pH > 7.6 considered basic (low H+). Over 8 is lethal.
over excitability of peripheral then central nervous systems
muscle twitching / spasms (respiratory impairment)
CNS actions - convulsions
What is acidic pH? What happens at this pH? lethal?
pH < 7.2 considered acidic (high H+). Lower than 6.8 is lethal
depression of CNS
disorientation
coma
What is normal blood pH?
7.4 (slightly basic)
What is the major source of volatile acids?
oxidative metabolism of carbohydrates and triglycerides
Metabolism produces CO2, which is converted to carbonic acid (H2CO3) and back to CO2 for excretion by the lungs.
CO2 + H2O H2CO3 H+ + HCO3-
What catalyzes the CO2 + H2O H2CO3 H+ + HCO3- reaction?
carbonic anhydrase (CA)
Reversible
What types of oxidative metabolism do not produce carbon dioxide?
hypoxia (lactic acid) oxidation
fat oxidation in diabetes mellitus (ketoacids)
What are non-volatile acids?
Acids produced in the body from sources other than CO2
For example, with diets high in protein, there is a net production of acids
Where are non-volatile acids excreted?
Not broken down to CO2
Not excreted by the lungs
Excreted by the kidneys
What are other means of losing acids and bases?
Vomit - H+ loss
diarrhea - HCO3- loss
urine - HCO3- loss
What is the relationship between pH, CO2 and HCO3- ?
Henderson Hasselbalch Equation
pH α concentration of HCO3-/dissolved CO2
What do buffers in the blood and tissue do?
Acutely prevent large shifts in pH
What are the buffers in the blood?
- Plasma - bicarbonate buffers (account for 75% of plasma buffering), plasma proteins, phosphate buffers
- Erythrocytes - bicarbonate buffers, hemoglobin
What are the buffers in the tissue?
- Skeletal muscle - contains large % of total body HCO3-
- Bone - large store of calcium carbonate, main source for neutralizing non-carbonic acid, chronic metabolic acidosis (e.g. lactic acidosis, ketoacidosis)
is associated with bone deterioration
Respiration in A/B balance
eliminates CO2 from the blood and shifts the equilibrium away from H2CO3 (and vice versa).
incr RR -> dear CO2 -> incr pH
decr RR -> incr CO2 -> dear pH
What happens during hyperventilation?
we lose CO2 and plasma CO2 goes down
The equation is driven to the left and plasma H+ decreases
What happens during hypoventilation?
we retain CO2 and plasma CO2 goes up
The equation is driven to the right and plasma H+ increases
What does long term pH control require?
long-term pH control requires the kidney
What are the three renal mechanisms for responding to pH changes?
- bicarbonate reabsorption (in the proximal tubule)
- formation of new bicarbonate and ammonium (from glutamate) - ammonium (NH4) stored as ammonia (NH3) in the medullary
interstitum - active secretion of hydrogen ions, titratable acids (ammonia/phosphate) and aldosterone production
Where does bicarbonate reabsorption occur primarily?
Proximal tubule (85%)
Some reabsorption in collecting ducts (15%)
How is bicarbonate reabsorption accomplished?
bicarbonate in the filtrate is broken down and reformed
in the cell for reabsorption
See figure
What would happen to bicarbonate excretion and plasma pH if carbonic anhydrase was not working (blocked?)
loss of HCO3 in the urine
consequently, plasma pH would decrease
What would happen to bicarbonate excretion and plasma pH if the Na:H exchange was not working
loss of HCO3 in the urine
consequently, plasma pH would decrease
What is glutamine converted to during acidemia? Where?
NH4+ and HCO3- (formation of new bicarbonate)
in proximal tubule
What happens to NH4+ and HCO3- that are produced during acidemia?
the bicarbonate is reabsorbed (not excreted)
the NH4+ is secreted into the tubule lumen (but not excreted) -
reabsorbed in loop of Henle (uses Na:Cl:K transporter) into the medullary intersitium
converted to NH3 (ammonia) + H
NH3 stored for when kidney needs to excrete large amounts of H (but note - H not excreted either)
this process is “neutral” - HCO3- + H are added to the body
See figure
What system is important for storing NH3 in medullary interstitium?
Formation of new bicarbonate
What is the major method for neutralizing acid in urine?
NH3 produced during formation of new bicarbonate
Thereby increasing H secretion
What limits H+ secretion into the lumen of the CT by the ATPases? What fixes this?
H+ gradient between the plasma and the tubule lumen
Titratable buffers (phosphate and ammonia) allow more hydrogen ions to be excreted
See figure
What is the major titratable acid ?
NH3 produced in glutamine metabolism in proximal tubule
Allows renal excretion of an increased acid load
What hormone stimulates H secretion?
Aldosterone
See figure
Net Acid Excretion (NAE) =
NAE = (UNH4V + UTAV) – UHCO3V
U = urine V = urine volume per unit of time
UNH4V
urine ammonium excretion
most important, ammonia to ammonium allows excretion of large amounts
UNTAV
titratable acid excretion - eg phosphate
useful but limited
UHCO3V
bicarbonate excretion
important in recycling bicarbonate
Types of renal tubular acidosis
Inappropriate response by kidney
Type 1 - distal nephron
Type 2 - proximal type
Type 4 - hypoaltosteronism
Type 1 RTA
distal nephron (late nephron segments)
unable to excrete acid load
due to failure to secrete H into lumen
Type 2 RTA
proximal type
reduced ability to reabsorb bicarbonate
Type 4 RTA
hypoaldosteronism
aldosterone deficiency or action
adrenal gland fails to secrete aldosterone (most often cause)
decreased ability to secrete H (so titratable acids can’t work)
How the kidney regulate acid/base in long term?
Proximal tubule
Collecting tubules
Proximal tubule regulation of acid/base in long term?
increase or decrease in bicarbonate reabsorption
increase or decrease in glutamine conversion to HCO3 + NH4 - HCO3 reabsorbed, NH4 converted to NH3 and stored in medullary interstitium next
to collecting tubules(H not excreted)
Collecting tubules regulation of acid/base in long term?
increase or decrease active H secretion (into tubule lumen)
increase or decrease active H secretion due to aldosterone
increase or decrease in titratable acids
NH3 diffusion from medullary interstitum to tubule lumen - binds free H
Expected compensatory responses during acidosis and alkalosis
See figure
Anion gap caculation
Na+ – (HCO3- + Cl-)
What is the normal anion gap in a healthy person?
11 mEq/L
What does an increased anion gap indicate about metabolic acidosis?
Increased acid production (lactic acidosis, ketoacidosis - diabetes, starvation, alcohol related)
Increased acid ingestion (methanol, ethylene glycol, aspirin, propylene glycol)
What does no change in anion gap indicate about metabolic acidosis?
loss of bicarbonate (diarrhea-intestinal loss, type 2 RTA-proximal tubule)
Decreased renal acid secretion (type 1 RT - distal, type 4 RTA -hypoaldosteronism)
What happens when there is metabolic acidosis due to gain of acid
Na : HCO3
Na:Cl
Na : ??? - represents normal 11 mEg/L of an unmeasured anion
Na : ???? - ???? represents unmeasured acid (ingested or produced)
the added acid associated with sodium - increases gap
Why doesn’t the anion gap change when there is metabolic acidosis due to loss of HCO3-?
hyperchloremic metabolic acidosis
lost HCO3- replaced by Cl-
Na+ – (HCO3- + Cl-) remains unchanged
