Test 5 Lecture 1 Flashcards
What does the acid-base balance help to maintain in the body?
Normal hydrogen ion concentration in the body fluids
How is the balance of hydrogen ions achieved?
- utilization of buffers in extracellular fluid and intracellular fluid (mins to hours)
- Respiratory mechanisms that excrete CO2 (mins to hours)
- Renal mechanisms that reabsorb bicarbonate and secrete hydrogen ions (hours to days)
What type of relationship exists between H+ concentration and pH?
logarithmic, equal changes in pH do not reflect equal changes in H concentration
What is the normal range of arterial pH?
7.37 - 7.42
What is considered acidemia? Alkalemia?
Acidema = < 7.37 Alkalemia = > 7.42
Is the hydrogen concentration relatively high or low?
Low, 6 times lower than the sodium concentration
As H concentration increase, pH _______.
Decreases
Arterial pH is slightly _____ despite production of large amounts of acid on a daily basis.
alkaline (7.4)
What are the 2 forms of acid production?
Volatile acid (CO2) Nonvolatile/fixed acid
What acid can CO2 be converted into? What does it need to react with?
H2CO3
Reacts with H20
What enzyme catalyzes the reaction between H20 and CO2? Is it a reversible reaction?
Carbonic anhydrase
Yes
How much fixed acid is produced per day?
50 mmol/day
What produces fixed acid?
Catabolism of proteins and phospholipids
What type of acid is formed from proteins containing amino acids?
Sulfuric
What type of acid is formed from phospholipids?
Phosphoric acid
What do fixed acids need to do in order to be removed from the body?
First must be buffered in body fluids until can be excreted by the kidneys
When are beta hydroxybutyric acid and acetoacetic acid formed?
Ketoacids formed in untreated diabetes mellitus
When is lactic acid formed?
During strenuous exercise or when tissues are hypoxic
What are some examples of ingested fixed acids?
Salicylic acid (aspirin overdose) Formic acid (methanol) Glycolic and oxalic (ethylene glycol)
What occurs with an overproduction or ingestion of fixed acids?
metabolic acidosis
What is a buffer?
Weak acid + conjugate base
Weak base + conjugate acid
Weak Acid
Acid = HA, H+ donor Base = A-, H+ acceptor
Weak Base
Base = BH, H+ donor Acid = B, H+ acceptor
What occurs when H+ is added or removed from a buffered solution?
minimal change in pH
Do weak acids have high or low pKs?
High, less dissociated and have lower equilibrium constants
What shape is the titration curve?
sigmoid
Where is the linear portion of the titration curve?
1 pH unit above and below the pK, most effective buffering occurs here (only small changes in pH occur when H is added or removed)
What are the major buffers of the ECF?
bicarbonate and phosphate
What are the A and HA forms of bicarbonate?
A = HCO3 HA = CO2
What are the A and HA forms of phosphate?
A = HPO4 HA = H2PO4
Which buffer is most important in the ECF?
HCO3/CO2 buffer, utilized as the first line of defense when H is gained or lost from the body
What characteristics of HCO3/CO2 cause it to be so important?
1) concentration of A form is high (24 mEq/L)
2) pK is 6.1, fairly close to pH of ECF
3) CO2 is volatile and can be expired by the lungs
Explain the HCO3/CO2 buffer’s role when HCl is added to the body
H combines HCO3 to form H2CO3 (strong acid converted to weak) further dissociates into CO2 and H2O (expired by lungs)
What is the pH for the 2 ECF buffers?
HCO3/CO2 = 6.1 (5.1-7.1) HPO42/H2PO4 = 6.8
Why isn’t PPO42/H2PO4 as effective as a buffer?
1) low concentration (1-2 mmol/L vs 24 mmol/L0
2) Is nonvolatile
What are 2 main types of ICF buffers?
Organic phosphates and proteins
What are 3 mechanisms that H must use to cross the cell membrane?
1) CO2 can cross membranes
2) with an organic anion (ex, lactate)
3) H exchanges with K
H and Ca2 can bind to…
negatively charged groups on plasma proteins
What changes in Ca2 free concentration occur with acidemia? Alkalemia?
Acidemia = more free, H is bound to plasma proteins Alkalemia = less free Ca, hypocalcemia
What are the symptoms of hypocalcemia?
Occurs in respiratory alkalosis, includes tingling, numbness, tetany
What are the organic phosphates in the ICF?
ATP, ADP, AMP, gluocse-1-phosphate, and 2,3_DPG
What is the pK values for the organic phosphates?
6 to 7.5
Why do intracellular proteins serve as buffers?
they contain a large number of acidic or basic groups
Which dissociable groups on proteins have a pK within the physiologic range?
Imidazole group of histadine (6.4-7)
Alpha amino groups (7.4-7.9)
What ist the most significant intracellular buffer?
hemoglobin, has 36 histidine residues
Which form of hemoglobin is the most effective buffer?
Deoxyhemoglobin (pK 7.9)
Oxyhemoglobin has a lower pK (6.7) not as effective
What are the major roles of the kidneys in maintaining the normal acid-base balance?
1) reabsorption of HCO3
2) excretion of H (produced from protein and phospholipid catabolism)
What are the 2 mechanisms for excreting H?
1) as a titratable acid buffered by urinary phosphate
2) as NH4
**both mechanisms are accompanied by synthesis and reabsorption of new HCO3
How much of HCO3 is reabsorbed?
99.9%
Where does most reabsorption of HCO3 occur?
proximal tubule
What are the steps for reabsorption of HCO3?
1) conversion of HCO3 to CO2 in the lumen
2) diffusion of CO2 into the cell
3) conversion back to HCO3 in the cell
4) reabsorption of HCO3 into the blood
What type of transport mechanism is the NaH exchanger?
Na dependent secondary active transport
What occurs with the NaH exchanger?
Na moves from lumen down its gradient, H moves into lumen against its gradient
What occurs when H is secreted into lumen?
combines with HCO3 to form H2CO3, decomposes into CO2 and H20, crosses back into the cell
What enzyme catalyzes H2CO3 into CO2 and H2O?
brush border carbonic anhydrase
What happens when CO2 and H2O enter the cell?
recombine into H2CO3, converted back into H and HCO3, H is secreted by NaH exchanger, HCO3 transported into the blood
What enzyme catalyzes CO2 and H2O into H2CO3?
intracellular carbonic anhydrase
What 2 mechanisms allow HCO3 to enter the blood?
1) NaHCO3 contransport
2) ClHCO3 exchange
What are the special features of the mechanism for reabsorption of HCO3?
- results in net reabsorption of Na and HCO3 (portion is directly linked)
- no net secretion of H
- produces little change in tubular fluid pH
When HCO3 concentration is greater than _____ some must be excreted.
40 mEq/L
What effects does ECF volume expansion have on HCO3 reabsorption? ECF volume contraction?
Expansion = inhibits isosmotic reabsorption in proximal tubule, inhibits HCO3 reabsorption Contraction = stimulates it
What effects does Angiotensin II have on HCO3 reabsorption?
stimulates NaH exchange in proximal tubule, thus stimulating HCO3 reabsorption and blood HCO3 concentration
What is contraction alkalosis?
Metabolic alkalosis that occurs secondary to ECF volume contraction
When does contraction alkalosis occur?
Loop or thiazide diuretics, caused by vomiting. Treated by infusing isotonic NaCl
What effects do an increase in PCO2 have on HCO3 reabsorption?
increase it
What occurs, in terms of PCO2, in respiratory acidosis?
PCO2 increases, more is available to renal cells to generate H for secretion, more HCO3 can be reabsorbed (increases pH as compensation)
What is the amount of H produced and excreted by a normal person eating a relatively high protein diet?
Produced = 50 (100%) excreted
Excreted as titratable acid = 20 (40%)
Excreted as NH4 = 30 (60%)
What is the amount of H produced and excreted by a person with diabetic ketoacidosis?
Produced = 500 (10 fold that of normal value)
Titratable acid = 100
NH4 = 400
What is the amount of H produced and excreted by a person with chronic renal failure?
Produced = 50
Titratable acid = 10
NH4 = 5
What 2 reasons cause the renal mechanisms for excreting acid to become impaired in chronic renal failure?
1) Titratable acid excretion is reduced because GFR is reduced, which reduces filtered load of phosphate, thus amount of phosphate that serve as a buffer
2) NH4 is reduced because synthesis of NH3 is impaired in diseased nephrons
What causes metabolic acidosis?
decrease in HCO3 concentration, leads to decrease in pH
What causes respiratory acidosis?
hypoventilation, CO2 retention, increased PCO2, decreased pH
What are the defense mechanisms to keep the pH in the normal range?
1) ECF and ICF buffering
2) Respiratory and Renal compensation
What are the 2 rules of thumb for respiratory and renal compensation?
1) If acid-base disturbance is metabolic, compensatory response is respiratory
2) In metabolic acidosis, disturbance decreases HCO3, respiratory compensation also decreases PCO2 (same direction)
What are cations and anions that are usually measured in the anion gap?
Cation = Na Anions = HCO3 and Cl
What does plasma use to fill the gap?
Unmeasured anions including proteins, phosphate, citrate and sulfate
What is the equation for the plasma anion gap?
Na - (HCO3 + Cl)
What is the normal range for the gap?
8 to 16 mEq/L
What is the anion gap useful for?
Differential diagnosis of metabolic acidosis
When might there be an increase in the anion gap during metabolic acidosis?
Diabetic ketoacidosis, lactic acidosis, salicylate poisoning, methanol poisoing, ethylene glycol poisoning, chronic renal failure
What occurs additionally with methanol and ethylene poisoning?
Osmolar gap, gap between measured and estimated plasma osmolarity
When does the anion gap remain normal during metabolic acidosis?
diarrhea, renal tubular acidosis
How does the body offset for the decrease in HCO3 if the anion gap doesn’t increase?
Increase Cl concentration, called hypercholermic metabolic acidosis with a normal anion gap
What is the arterial blood profile during metabolic acidosis?
decrease pH
decrease HCO3
decrease PCO2
What does the body do in order to correct excessive production/ingestion of H?
increase anion gap (also increase osmolar gap with ethylene and methanol poisoning)
What does the body do in order to correct for a loss of HCO3 from diarrhea and Type 2 RTA?
normal anion gap, hypercholeremia
What does the body do when it is unable to excrete H due to renal failure and Type 1,4 RTA?
CRF = increase anion gap
Type 1 = normal gap
Type 4 = normal gap
What are the steps involved in metabolic acidosis?
1) Gain H in body through some sort of mechanism
2) Excess H is buffered, produces decrease HCO3 concentration, hyperkalemia occurs
3) Hyperventilation, decreased PCO2
4) Days later, renal correction, H excreted
What is the arterial blood profile for metabolic alkalosis?
increased pH
increased HCO3
increased PCO2
What does the body do to compensate for a loss of H due to vomiting or hyperaldosternism?
vomit = volume contraction
hypokalemia
What does the body due to compensate for a gain of HCO3 from NaHCO3 ingestion?
renal failure
