Wall: Acid-Base Flashcards
1
Q
What are the two categories of acids?
A
-
Carbonic: volatile, can be converted to CO2 (about 15,000 mmol/d) -> eliminated by the lungs
1. CO2 is an acid b/c we are 60% water
2. Carb + fat metabolism = CO2 -
Non-carbonic: non-volatile acids, like phosphoric H3PO4 and sulfuric, H2SO4 (50-100 mEq/d) -> combine with buffers, then excreted by the kidney
1. Fixed acids that can’t be converted to carbonic acid (protein + phospholipid metabolism)
2. Job of the kidney to regenerate the bicarbonate used up in buffering these
2
Q
What is an acid? Base?
A
- Acid: can donate H+
- Base: can accept H+
3
Q
What is the clinical pH range?
A
- 6.80-7.80 (H+ conc. b/t 16-160 nEq/L
- Arterial blood gas machine measures CO2, pH, and O2 in arterial samples
- Bicarbonate can be calculated via Henderson equation
- Highly regulated in body b/c virtually all enzymes, proteins have pH-dependent functions
4
Q
How do we calculate the plasma bicarbonate concentration? What is normal?
A
- Labs measure total CO2 concentration -> dissolved carbon dioxide plus bicarbonate concentration; ~25-26 meq/l in venous samples
- Due to this technique, total CO2 conc. exceeds plasma bicarbonate concentration by 1.0 to 1.5 mEq/L
- Normal plasma bicarbonate concentration is approximately 24 mEq/L
5
Q
What are acidemia and alkalemia?
A
-
Acidemia: reduced pH, or elevated H+ concentration
1. Acidosis: process that lowers pH -
Alkalemia: increased pH, or reduced H+ conc.
1. Alkalosis: process that elevates pH - NORMAL HUMAN pH = 7.4
6
Q
What is the bicarbonate buffer system formula?
IMPORTANT!!!
A
CO2 + H2O = H2CO3 = H+ + HCO3-
- If closed sytem, pKa = 6.1 (weak acid); normal pH = 7.4
- We are an open system via the lungs excreting CO2, making this system a highly efficient buffer
- Bicarbonate is the major EC buffer
7
Q
What is the only way to change the pH in the body?
A
- By changing:
1. PaCO2 (dissolved = CO2 + H2O) or
2. HCO3-
8
Q
How do we calculate H+? From pH?
A
- H+ = 24 (CO2/HCO3-)
- pH must be converted to H+ (nEq/L)
1. pH = 7.4 = 40 nEq/L - 7.40 = 40 = 24 (40/24)
1. Overall, H+ = 80 - decimal digits of pH (more or less)
9
Q
What are the normal pH, pCO2, and HCO3- values?
A
- pH = 7.35 - 7.45 (7.40) = -log(H+)
1. [H+] = 24 x pCO2/HCO3- - pCO2 = 36-44 mmHg (40 mmHg)
- HCO3- = 22-26 mEq/L = 24 mEq/L
10
Q
What are metabolic disorders?
A
- Processes that directly alter bicarbonate concentration
1. Metabolic acidosis: decreased bicarbonate (increased H+)
2. Metabolic alkalosis: increased bicarbonate
11
Q
What are respiratory disorders? What is the buffer effect?
A
- Processes that directly alter CO2
1. Respiratory acidosis: increased CO2
2. Respiratory alkalosis: decreased CO2 - Buffer effect: slightly increased HCO3- with respiratory acidosis -> slightly decreased HCO3- with respiratory alkalosis
12
Q
What is buffering?
A
- Prevents wide changes in pH in response to the addition of acid or base
- Bicarbonate: major EC buffer (can be easily measured); there are also IC buffers
- Buffers attenuate changes in pH in response to acid-base disorders -> immediate onset
- Isohydric principle: all buffers change in the same direction
13
Q
What is the purpose of the acid-base system? What are the 4 key buffer pairs?
A
- To maintain normal pH via buffer systems: H+ donor and acceptor
- Bicarbonate (ECFV): HCO3-, H2CO3
- Phosphate (urine): H2PO42-, H2PO4
- Ammonia (urine): NH3, NH4+ (can be metabolically regulated by the kidney)
- Protein: protein, protein (IC buffer)
- NOTE: we need something more than buffers b/c we want a whole body response (secondary mechanisms)
14
Q
What are secondary (compensatory) mechanisms?
A
- Additional physiologic responses that occur in response to changes in pH -> move back toward normal, but never completely correct
- INVARIABLY PRESENT in simple acid-base disorders (if not present, it is a mixed disorder)
15
Q
What are the compensatory mechanisms for metabolic and respiratory disorders?
A
-
Metabolic disorders: respiratory system compensates by altering CO2 -> via lungs
1. Hyperventilation
2. Rapid onset: minutes -
Respiratory disorders: compensation via alterations in bicarbonate concentration -> via kidney
1. Slower onset: 1-2 days (there will be difference b/t acute and chronic disorders b/c this response takes longer)
16
Q
What are 4 important mechanisms that buffer an acid load?
A
- Buffer systems (primarily bicarbonate) -> EC fluid -> immediate (H+ + HCO3- = H2CO3 = H2O + CO2)
- Increased rate and depth of breathing to decrease CO2 -> via lungs -> minutes to hours
- Buffer systems (bicarbonate, phosphate, protein) -> IC fluid -> 2-4 hours
- H+ excretion, H2CO3- reabsorption, bicarb generation -> kidneys -> hours to days
17
Q
Summarize how the 4 disorders affect pH, HCO3-, and pCO2.
A
- Metabolic acidosis: DEC, DEC, DEC (compensatory)
- Metabolic alkalosis: INC, INC, INC (compensatory)
- Resp. acidosis: DEC, INC (compensatory), INC
- Resp. alkalosis: INC, DEC (compensatory), DEC
- NOTE: it is far more difficult to stop breathing than to increase it, so lung response to metabolic acidosis much more precise than that to metabolic alkalosis
1. Notice trends above to aid in memorization
18
Q
What are the golden rules for simple acid-base disorders?
A
- PCO2 and HCO3 always change in the same direction
- Secondary physiologic compensatory mechanisms must be present (if not present, it’s a mixed disorder)
- Compensatory mechanisms never fully correct pH (bring it back to normal, but never fully correct or overshoot)
- NOTE: if any of these rules are violated, you know it is mixed, and there is more than one disorder going on simultaneously
19
Q
What is metabolic acidosis? Etiology?
A
- Process that reduces plasma bicarbonate conc.
- Etiology:
1. Decreased renal acid excretion (renal tubular acidification defect)
2. Direct bicarbonate losses (GI tract, urine): prox tubule problem (where most H2CO3 reabsorbed) or gastric secretion
a. Drugs that inhibit carbonic anhydrase in renal tubule (acetazolamide: glaucoma tx)
3. INC acid generation (exogenous or endogenous) -> only 2 clinically common endogenous acids are:
a. Lactic acidosis (shock, oxygen debt)
b. Ketoacidosis (starvation, type 1 diabetic)
20
Q
What are the 3 causes of metabolic acidosis?
A
- INC acid generation: lactic acidosis, ketoacidosis, ingestion of acids (ASA, ethylene glycol - suicide attempts, methanol w/alcohol), dietary protein intake (animal source)
- Loss of bicarbonate: GI (diarrhea, intestinal fistulas), renal (type 2 prox renal tubular acidosis)
-
Decreased acid excretion (impaired ammonium excretion): renal failure (DEC GFR), type 1 distal renal tubular acidosis, type 4 renal tubular acidosis (hypoaldosteronism -> not pumping enough H+ ion into urine in exchange for K+, so also hyperkalemia)
1. Defect in H+ pumps could be congenital
2. Chronic kidney disease: less nephrons working
21
Q
What is respiratory acidosis?
A
- Induced by hypercapnia (decreased alveolar ventilation): CO2 retention
- Buffering mechanisms raise plasma bicarbonate concentration (rapid, but limited response: 1-2 mEq/L)
- Kidney minimizes change in EC pH by increasing acid excretion (NH4+), generating new bicarbonate ions (delayed response: 2-3 days)
22
Q
What are some of the causes of respiratory acidosis?
A
- Acute: something that creates hypoxemia or blocks your airway
- Chronic: COPD
23
Q
What is respiratory alkalosis?
A
- Reduced CO2 due to increased alveolar ventilation: blown off too much CO2
- Buffering processes lower plasma bicarbonate conc (rapid, but limited response: 1-2 mEq/L)
- Kidney response is to reduce net acid excretion: elim bicarbonate into the urine, or decrease ammonium secretion -> delayed response: 1-2 days
24
Q
What are some of the causes of respiratory alkalosis?
A
- Anything that injures the brain, or causes you to be hypoxic, provoking hyperventilation
25
Q
Describe some of the key features of acid-base respiratory disorders.
A
- Acute respiratory acid base disorders always have a greater change in pH than chronic disorders (b/c kidney compensation is slow-acting)
- Plasma Cl changes equally and inversely with plasma HCO3 (to maintain electroneutrality)
- Plasma anion gap does NOT change with respiratory disorders
- Plasma sodium is NOT directly altered by acid base disorders
26
Q
A
- Acute respiratory alkalosis
- CO2 below normal, so probably respiratory
- Small change in bicarbonate, so this would fit better with acute
27
Q
What is metabolic alkalosis? Etiology?
A
- Processes that raise plasma bicarbonate concentration
- Etiology: loss of H+ from GI tract (vomiting) or into the urine (diuretic therapy) -> i.e., excessive urinary net acid excretion (primary hyperaldosteronism: high aldosterone stimulates acid excretion by intercalated cells in collecting duct)
28
Q
What are the major causes of metabolic alkalosis?
A
- Red cells packed in citrate, which gets converted to bicarbonate (blood transfusion)
- Loop diuretics or thiazides cause you to lose more chloride than sodium, so some negative charge has to compensate (bicarbonate)
29
Q
How does metabolic alkalosis affect urine chloride concentration?
A
-
Cl responsive: urine Cl <20 mEq/L (usually <10 mEq/L)
1. In causes of metabolic alkalosis assoc w/DEC ECV, stimulus for Na and Cl reabsorption to replenish ECV. In these settings, urinary Cl should be expected to be very low
2. If urinary Cl low, admin of NaCl and water to replenish ECV should stop aldosterone release and lead to excretion of excess HCO3- and improvement of hypokalemia, leading to correction of the metabolic alkalosis - Cl resistant: urine Cl >20 mEq/L (usually >50 mEq/L)
30
Q
What are the expected pH changes for respiratory disorders?
A
- Acute Respiratory Acidosis: HCO3- increases 1 mEq for each 10 mm increase in PCO2
- Chronic Respiratory Acidosis: HCO3- increases 4 mEq for each 10 mm increase in PCO2
- Acute Respiratory Alkalosis: HCO3- decreases 2 mEq for each 10 mm decrease in PCO2
- Chronic Respiratory Alkalosis: HCO3- decreases 5 mEq for each 10 mm decrease in PCO2
31
Q
How is the proximal tubule involved in NaHCO3- reabsorption?
A
- Toward the later parts of the proximal tubule, the chloride concentration is now quite high -> big driver for paracellular transport through claudin proteins to get chloride reabsorbed (generating a lumen + charge; nice electrochemical gradient for sodium entry)
- Sodium-bicarbonate generation exchange contributes to salt reabsorption
32
Q
How are the alpha-intercalated cells in the collecting duct involved in acid-base balance?
A
- Other major acid-base cell (other than proximal tubule cells) in collecting duct: alpha-intercalated cells
- H+ ATPase or H+/K ATPase
- Bicarbonate leaves cell via Cl/bicarbonate exchanged
- In acidosis, need to INC acid excretion -> happens here: CO2 goes up, carbonic anhydrase, H exits as ammonium, so acid leaves the body, and bicarbonate goes to the blood (for each H+, you get a bicarbonate)
- Acid-base homeostasis
33
Q
How are beta-intercalated cells involved in acid-base homeostasis?
A
- Vegetarians: eating alkali every day
- Metabolic alkalosis prevention: Chlorine/bicarbonate exchanger in the beta-intercalated cells -> built for bicarbonate excretion to maintain homeostasis
34
Q
What goes on in the principal cell in the collecting duct?
A
- Job is mainly sodium
- Renin/aldosterone influenced thing
- Also responsible for K secretion -> always going to come back to what’s happening at the cortical collecting duct in the principal cell
35
Q
What is the plasma anion gap?
A
- Na - (Cl + HCO3-) = usually about 10-12 (bulk from albumin b/c major protein and multiple (-) charges)
- Strong acids (HA) fully dissociate at physiologic pH (7.40) into H+ and A-
1. H+ is buffered by HC03-
2. A- is either excreted into the urine, i.e., phosphate or sulfate (normal plasma anion gap, INC plasma Cl concentration)
3. Or, A- reabsorbed by the kidney and retained in plasma, as an unmeasured anion (INC plasma anion gap, minimal change in plasma Cl conc) - Sodium NEVER changed by acid-base disorder. If you retain the organic anion, you’re neutral, but if you’ve excreted that acid anion, bicarbonate fell, and the only other anion you can really alter is chloride
- Anion gap helps us figure out our differential dx of metabolic acidosis
36
Q
What are the normal concentrations of unmeasured cations and anions?
A
- K usually not included
- Bulk usually from albumin because major protein, and multiple (-) charges
37
Q
How does metabolic acidosis affect the chloride concentration and anion gap?
A
- Every time you get a normal gap acidosis, you will have hyperchloremia (you cannot violate this)
38
Q
What are the major causes of acidosis according to anion gap?
A
39
Q
Describe how you get to this answer.
A
- Metabolic acidosis with increased plasma anion gap
- Look at pH first -> acidosis
- Look at CO2 -> down, and acidotic, so must be a metabolic acidosis
- Is backup system working? Yes, because lungs are hyperventilating (last 2 digits of pH tend to be about what the CO2 should be)
- Very low bicarbonate: 2 processes can do this -> resp alkalosis, metabolic acidosis (if below 16 or so, must be metabolic b/c respiratory can’t get it that low)
- AG: 140 – 114 = 26 -> extremely high (only forms of metabolic acidosis give plasma anion gaps this high)
- Most of the time clinically, don’t order arterial blood gas on every patient
40
Q
What is the law of electroneutrality?
A
- The total number of positive charges in a solution always equals the total number of negative charges
- This law can not be violated
41
Q
What are the major causes of metabolic acidosis?
A
42
Q
How do you assess low serum HCO3- concentration?
A
- Normal gap: kidney or non-kidney problem
- Common sense says measure urinary ammonium, but labs don’t do that, so you have to do urine anion gap (sodium + potassium – chloride; tends to be about +10 - +20, but if making a lot of ammonium, chloride has to accompany that, and the difference will be a lower number, approaching zero, or even be negative)
- Normal gap metabolic acidosis with +20 urine anion gap, then kidney is the problem; it’s not making ammonium. Indirect way of looking at acid excretion by the kidney
43
Q
In brief, what must happen in renal acid excretion?
A
- All of the filter of bicarbonate must be reabsorbed (primarily in the proximal tubule and loop of Henle)
- Final excretion of the daily acid load occurs primarily in the collecting duct (approximately 50-100 mEq/d)
44
Q
How does the kidney maintain phosphate homeostasis?
A
- Phosphate (H3PO4) homeostasis maintained by urinary excretion of dietary phosphate
- Monobasic phosphate is an effective urinary buffer, esp. at lower urinary pH
- Accounts for excretion of 10 to 40 mEq of hydrogen ion daily
- Cannot be increased beyond this due to the fixed amount of phosphate in urine
45
Q
How is ammonium excretion involved in acid-base homeostasis?
A
- Contributes the major adaptive response to an acid load
- Can be increased in response to physiologic needs
- Normally 30-40 mEq/d and maximal excretion is approximately 300 mEq/d
- NH4+ is lipid insoluble and, therefore, trapped in the urinary lumen
46
Q
What is the urine anion gap?
A
- An indirect estimate of urinary NH4+ excretion
- Urine Na + K minus urine Cl
- Normally positive: ~10 meq/l
- Becomes less positive and may even become neg with incr urinary NH4+ excretion (Cl- must accompany NH4+)
47
Q
What does this graph show?
A
- Normal person can augment ammonium excretion to compensate for acidosis, unlike person with chronic kidney disease
48
Q
What is the sodium-chloride relationship?
A
- Law of electroneutrality:
1. Na concentration not directly altered by acid base disorders
2. Plasma Cl altered in all acid base disorders (except INC plasma anion gap metaboic acidosis) - Conclusion: if Na concetration stays constant, but Cl conc changes, an acid base disorder is present
49
Q
What are mixed acid-base disorders?
A
- The presence of more than one simple acid-base disorder simultaneously:
1. Respiratory acidosis and metabolic acidosis (profound acidemia)
2. Respiratory alkalosis and metabolic alkalosis (profound alkalemia)
3. Metabolic alkalosis and respiratory acidosis
4. Metabolic acidosis and respiratory alkalosis
