Term
| What is the Isohydric principle and how does it relate to pH buffering? |
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Definition
Isohydric principle states that
1) The ratio between undissociated and dissociated forms of any buffer pair is dependent only on the pH and pKa of the pair
2) All body buffers are in equilibrium
3) Any change in the ratio of any one buffer pair will be reflected in all body buffer pairs. |
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Term
How does the bicarbonic-carbonic acid buffer pair prevent precipitous changes in body pH?
How does it explain resistance to changing pH when a strong acid is added to the blood? |
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Definition
Regulated by PCo2 (lungs) and HCO3- (kidneys)
H2CO3 ----H+ & HCO3- pKA is 6.1
H2CO3----CO2 & H20 (in presence of carbonic anhydrase)
1) If strong acid is added, H2CO3 will increase and HCO3- will decrease.
2) H2CO3 will become CO2 and H2O, and CO2 will be vented out of the lungs to prevent changes in pH
They breathe hard and get it out! |
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Term
| How is acid produced normally in the body and how does it relate to normal Acid-Base homeostasis? |
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Definition
Cellular metabolism makes both Acid and Base, but feces only gets rid of Base.
1) Volative acid produced from oxidative metabolism of caloric intake (carbonic acid), and then excreted through the lungs as CO2
2) Fixed acids are excreted by the kidney with HCO3- to maintaing body H+ balance. |
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Term
| How is Base produced normally in the body and how does it relate to normal Acid-Base homeostasis? |
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Definition
1) Bicarbonate
- Metabolism of Aspartate and Glutamate
- Metabolism of some organic anions (citrate) |
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Term
| How does carbon dioxide production regulate respiratory rate? |
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Definition
High CO2 levels produced because of metabolic acidosis leads to increased RR
Low CO2 leads to decreased RR |
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Term
| How is respiratory acid-base homeostasis achieved? |
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Definition
1) CO2 produced by metabolism enters RBCs and becomes Carbonic acid (CA mediated)
** Extra H+ ion binds Hb in case of low PO2 to buffer**
2) In pulmonary capillaries CO2 is released and excreted by lungs. |
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Term
| How does the kidney regulate acid-based homeostasis? |
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Definition
Remember, it deals with non-volatile fixed-acid
1) Reclaims filtered bicarbonate
- 90% is PT (high capacity, low gradient) and 10% in distal nephron to prevent metabolic acidosis
2) Excretes metabolically generated fixed acid
- Each H+ ion is buffered by HCO3- and excreted.(distal tubule acid secretion and ammonium generation)
- Kidney then regenerates lost HCO3- |
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Term
| How is fixed-acid excreted achieved in the proximal tubule of the kidney? |
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Definition
For each H+ secreted into tubular lumen, HCO3- is generated and secreted across basolateral membrane.
If Threshold is exceeded, additional HCO3- is excreted
1) In Proximal tubule, HCO3- is reabsorbed
- H+/Na+ antiport exchange (Na+ enters cell, driven by passive gradient)
2) Secreted H+ combines with filtered HCO3- and becomes carbonic acid, which becomes CO2 and H2O (CA-mediated)
3) Water and CO2 re-enter cell and become Carbonic acid again (CA-mediated), which then becomes HCO3- and H+ again
4) Electrogenic Na+/3HCO3- cotrapsort (driven by Na/K+ ATPase) |
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Term
| How does alkalinization of the blood influence carbon dioxide release in the lungs? |
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Definition
More base means that less HCO3- will form H2CO2, so the PCO2 will be lower (since CO2 is a voltaile acid) and less will be vented out of the lungs.
The buffer system is trying to maintain the number of H+ ions so as to keep pH normal. |
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Term
How is renal fixed-acid excretion via the PT regulated by each of the following?
1) Intravascular volume
2) Chloride Depletion
3) Acid-Base Status
4) Serum Potassium
5) PCO2 |
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Definition
Remember, when Proximal tubule HCO3- reabsorption exceeds the threshold, acid will be secreted.
1) Low IV volume will increase sodium reabsorption (RAAS) and also increase H+ secretion, which will ultimately increase HCO3- reabsorption.
2) If Cl- cannot be reabsorbed with Na+, there is an INCREASE in Na+/HCO3- coupled transport
3) Intracellular Acidemia increases H+ secretion and therefore increases HCO3- reabsorption
**Alkilemia will leads to less H+ secretion and less HCO3- reabsorption**
4) Hypokalemia- loss of intracellular K+ and gain in intracellular H+, which will increase H+ secretion and HCO3- reabsorption.
**Opposite is true in hyperkalemia**
5) Hypercapnia increases intracellular PCO2, increasing carbonic acid and decreasing pH. Resulting secretion of H+ leads to HCO3- reabsorption. |
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Term
| How is H+ secreted in the distal tubule of the nephron? |
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Definition
1) H+ for secretion is generated from intracellular CO2 and H2O (CA mediated) (HCO3- is also generated)
2) H+ secreted from intercalated cells of collecting duct via ATP-driven pumps (H+ ATPase and H,K ATPase)
**buffering in urine enables acid load secretion in normal pH range**
3) HCO3- generated is secreted across teh basolateral membrane via Cl-, HCO3- exchanger |
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Term
| How does H+ secretion differ in the proximal tubule and distal nephron? |
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Definition
1) In the proximal tubule, H+ generated from CO2 and H20 (intracellular CA-mediated) is exchanged PASSIVELY for Na+ across the apical plasma membrane
- Generated intracellular HCO3- is secreted into the blood via electrogenic Na+/3HCO3- co-transporters in the basolateral membrane
2) In the intercalated cells of the collecting duct, generated H+ is ACTIVELY transported across the apical membrane via H-ATPase and H,K ATPase.
- Generated HCO3- is secreted into the blood via HCO3, Cl exchangers in the basolateral membrane |
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Term
| What urinary buffers allow excretion of a significant acid load without drastic changes to pH? |
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Definition
1) Titratable acids (HPO4-, sulfates and organic acids)
2) Ammonium
3) Bicarbonate (slow because no extracellular CA)
- Diffusion barrier across urinary bladder creates blood:urine PCO2 gradient |
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Term
How is renal fixed-acid excretion via the distal neprhon regulated by each of the following?
1) Distal tubular sodium delivery and reabsorption
2) Urinary buffer deficiency
3) Mineralcorticoids
4) K+ |
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Definition
1) Increased Na+ reabsorption via ENaC in DT increases tubular electronegatively (Na+ is not exchanged for H+ cation as in the proximal tubule) and increases H+ secretion.
**remember, major determinant is apical membrane pump in intercalated cells**
2) Titrate secreted H+. When they are low gradient is increased and LESS is secreted.
3) Aldosterone directly stimulated H+ secretion and indirectly increases it by increased Na+ reabsorption.
4) Hypokalemia potentiates mineralcorticoid effects to increase H+ secretion, perhaps via increased activity of the H+/K+ ATPase in the apical membrane of intercalated cells (more K+ will be reabsorbed). |
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Term
| What are the 3 major steps of renal ammonium handling to buffer urinary acid? |
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Definition
Urinary ammonia increases during acidosis!
1) Proximal tubular ammoniagenesis
- 2 NH4+ molecules are generated from glutamine and transported into the proximal tubule via the apical membrane
- 2 HCO3- ions are also generated and reabsorbed across the basolateral membrane
**metabolic acidemia and hypokalemia decrease intracellular pH and stimulate ammonia production**
2) Medullary shunting
- NH4+ secreted in PT is reabsorbed in medullary interstium via Na,K,2Cl- in TAL
- Collecting duct is impermeable to NH4+, but permeable to NH3, so NH4+ dissociates and re-enters the collecting duct as NH3 and H+.
3) Collecting duct trapping
- NH3 and H+ are "trapped" as NH4+
- As urine pH decreases, NH4+ gradient between CD and IT increases, and more NH4+ is excreted. |
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Term
How does metabolic acidosis influence ammoniagenesis in the Proximal tube epithelia?
What about Hypokalemia? |
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Definition
Both decrease intracellular pH and STIMULATE ammonium production.
Remember, NH4+ is secreted into the PT is reabsorbed in the medullary interstitium of the TAL via the Na,K,2Cl- transporter, and then secreted into the collecting duct a NH3 and H+, where it is trapped as NH4+. |
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Term
| How does urine pH influence urinary ammonium levels? |
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Definition
Acid urine has high NH4+
Lower urine pH increases the NH4+ gradient between collecting duct and medullary interstitium, and increases the amount found in urine. |
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Term
True or False:
Any bicarbonate lost in the urine represents a net gain of H+ ion to the body. |
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Definition
True!
Since a bicarbonate ion is returned to the body for EVERY H+ ion (in the PT or DT) or NH4+ molecule lost in the urine, the opposite is also true.
So in metabolic alkalemia, H+ is conserved and HCO3- is lost in the urine. |
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Term
| How is Net Acid Secretion expressed mathematically? |
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Definition
(Urinary titratabile acid concentration)(V) + (Urinary NH4+)(V) - (Urinary HCO3-)(V)
In normal state, NAS= body's acid production
**amount of new HCO3- generated by kidney and returned to blood should equal the quantity of bicarbonate consumed in buffering fixed-acid production by metabolism** |
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Term
| What are the pH determinants of Acidemia vs. Alkalemia? |
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Definition
Acidemia= pH <7.36
Alkalemia= pH > 7.44
Different from Acidosis and Aklylosis |
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Term
What do each of the following terms refer to in terms of acidosis/alkylosis?
1) Metabolic disturbance
2) Respiratory disturbance
3) Compensation
4) Simple disturbance
5) Mixed disturbance |
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Definition
1) Primary change to HCO3-
2) Change to PO2
3) Physiological metabolic (renal) and respiratory changes to return pH to normal (NOT COMPLETE)
- Buffering (minutes to 6h)
- Respiratory (minutes to 12 hours)
- Metabolic (24-72 hours)
4) Single acid-base process and compensation
5) 2 or more disturbances |
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Term
What type of compensation occurs for each of the following
1) Metabolic acidosis
2) Metabolic alkylosis
3) Respiratory acidosis
4) Respiratory alkylosis |
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Definition
1) Decrease in [HCO3-] leads to decreased PCO2 compensation
2) Opposite
3) Increased PCO2 leads to Increased [HCO3-]
4) Opposite |
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Term
| What is the difference between hypercholoremic metabolic acidosis and anion-gap metabolic acidosis? |
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Definition
Both involve depletion of body bicarbonate buffers, with anion replacement
AG= Serum Na - Cl - HCO3
1) Hypercholoremic
- Chloride replaces HCO3-, so no net increase in AG
2) AG
- Decrease in HCO3- is due to addition of strong organic acid (e.g. lactic acid) and AG increases |
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Term
What is the pathophysiological basis of Diabetic ketoacidosis?
What about Alcoholic ketolactic acidosis? |
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Definition
Both are high AG metabolic acidoses with decreased HCO3-
1) Insulin deficiency results in abnormal production of ketoacids
2) Alcoholic ketolactic acidosis occurs from fasting after binge drinking with decreased glucose, insulin and ketosis.
**Hypoperfusion also causes hepatic production of lactic acid** |
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Term
| What are the 3 plausable mechanisms producing Hypercholorermic metabolic acidosis? |
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Definition
Remember, this is a neutral AG metabolic acidosis.
1) Impaired renal acid excretion
- Renal failure
- Distal renal tubular acidosis (Type I-hypokalemic or IV-hyperkalemic)
2) Renal HCO3- losses
- Proximal renal tubular acidosis (type II)
- CA inhibitors
- Therapy of diabetic ketoacidosis (urinary excretion of organic acids depletes store to regenerate HCO3-)
3) Acid gain (H+)
- Hyperalimentation solutions
- Ammonium chloride ingestion |
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Term
| What is proximal tubular acidosis (Type II) and how can it contribute to hypercholoremic metabolic acidosis? |
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Definition
Contributes to Renal HCO3- loss because
1) Impaired H+ ion secretion in proximal nephron (increased in distal nephron)
2) Lowered threshold for HCO3- reclamation
- Start excreting it too soon
3) Hypokalemia develops from
- increased distal K+ secretion (caused by hyperaldosteronism from mld chronic volume depletion via RAAS)
- Increased distal delivery of HCO3- |
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Term
| What is the difference between Type 1 and Type IV renal tubular acidosis and how do they contribute hypercholoremic metabolic acidosis. |
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Definition
Impaired renal acid secretion
1) Type 1 (classic)
- Intercalated cell defect in
a) distal proton pumps
b) back-leak of secreted H+ ion
c) CA defect
d) Defective HCO3-/Cl- exchanger
**Can be secondary to hypercalciuria and nephrocalcinosis**
2) Type IV Hyperkalemic
- Aldosterone deficiency/resistance prevents proximal tubular ammoniagenesis and produces acidosis
**Urinary acidification is in tact**
OR
- Voltage-dependent defect in H+ ion secretion because of defect in proximal sodium reabsorption (decreases gradient for H+ excretion)
**Urinary acidification is not intact** |
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Term
| How can Kidney disease produce a metabolic acidosis? |
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Definition
In early stages of CKD, patients develop hypercholoremic metabolic acidosis because of REDUCED urinary buffers
**Later can become high AG because of phosphate, sulfate and organic ion retention** |
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Term
| How can the urinary anion gap be used to assess hypercholoremic metabolic acidosis? |
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Definition
The UAG is NOT the same of the AG that is always normal in hypercholeoremic metabolic acidosis.
UAG= Urinary cations - Urinary anions.
1) If it is due to non-renal causes, Ammonium release will be high and UAG will be negative
2) If it due to renal causes, Ammonium production will be impaired and UAG will be zero or positive. |
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Term
| What is the use of Winter's Formula in analyzing metabolic acidosis? |
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Definition
It is a way to calculate PCo2 to look at respiratory compensation for metabolic acidosis (e.g. to determine if the compensation is normal, or if there is respiratory alkylosis or acidosis).
PCO2= 1.5 X [HCO3-] +8 +/- 2 |
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Term
| How can you treat acute and chronic metabolic acidosis? |
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Definition
Remove underlying cause, or try Alkali replacement
1) Acute
- if pH< 7.1 (maximum respiratory compensation), give Alkali Replacement since there is significant risk of myocardial depression
HCO3- dose= (0.5)(BW) X (HCO3 desired - HCO3 actual)
*DON'T fully correct, just get to a safe level**
2) Chronic
- Prevent long-term sequele by normalizing serum bicarbonate concentration over time (probably not replacement) |
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Term
| What factors can generate metabolic alkylosis? |
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Definition
Maintained because of an issue with renal bicarbonate excretion
1) Increased bicarbonate
- HCO3 administration
- Milk-alkali syndrome
- Organic acid infusion
- Rapid correction of hypercapnia
2) Loss of acid from body
- Renal
- GI |
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Term
| What 3 factors contribute the maintenance of metabolic alkylosis? |
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Definition
Renal bicarbonate excretion issue
1) Decreased GFR
- low EABV
- renal insufficiency
2) Increased proximal tubular bicarbonate reclamation
- decreased EABV
- chloride depletion
3) Increased H+ ion excretion.
- Mineralcorticoid excess
- Hypokalemia |
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Term
| How can you determine the precise etiology of a metabolic alkalosis? |
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Definition
1) Urinary chloride concentration
- <20 means volume depletion
- >20 means mineralocorticoid effect or Bartter's
** Not reliable if taking diuretic**
2) Urinary sodium less helpful |
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Term
| How can you treat metabolic alkaloses? |
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Definition
Depends on maintainence mechanism
1) Volume contraction
- Give saline to decrease proximal tubular bicarbonate reabsorption
2) Mineralcorticoid excess
- Spironolactone/Eplenerone or surgical ablation of adrenal glands
3) Hypokalemia
- leads to enhanced H+ ion excretion, increased ammoniagenesis and chloride wasting.
- K+ repletion and perhaps K+ sparing diuretics |
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Term
A patient presents with headache, asterixis, confusion, lethargy and obtundation.
Lab work comes back you discover very high PCO2.
What is physiological compensation for this condition and how do you treat? |
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Definition
Respiratory acidosis (symptoms of Hypercapnia) due to abnormality in respiratory function
1) Renal increase in HCO3- (takes 48h, so only really helps in chronic state)
2) Underlying problem correction and perhaps mechanical ventilation (Hypoxemia becomes major stimulus for ventilation, since PCO2 is so high, so use OXYGEN WITH CARE) |
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Term
A patient presents with lightheadedness, parasthesias, cramps and seizures.
You discover low PCO2 and the patient is breathing rapidly.
What is the compensation for this situation and how do you treat? |
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Definition
Respiratory Alkylosis with Hypocapnea from excess hyperventilation.
- caused by Hypoxemia, intrapulmonary disease, mechoventilation or medullary respiratory center stimulation
1) Renal compensation is to decrease serum HCO3-, so as to preserve H+ in the form of acid (SLOW)
2) Rebreathing into a paper bag may slow down breathing, but treat underlying cause. |
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Term
| What is a good systematic strategy for diagnosing acid-base disorders? |
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Definition
1) H/X looking for
- Diuretics and vomiting (metabolic alkalosis)
- Diarrhea, Alcoholsim or DM (metabolic acidosis)
- Chronic lung disease, CHF or pneumonia (respiratory acidosis/alkylosis
2) PE clues
- Liver disease (Respiratory alkalosis)
- Volume contraction (Metabolic alkalosis)
- CHF (respiratory alkalosis)
- Fruity odor of breath (ketotic metabolic acidosis)
3) Electrolytes
- Total CO2 (approximates HCO3-)
- Low in metabolci acidosis or compensation for respiratory alkylosis
- High in metabolic alkylosis or compensation for respiratory acidosis
4) Lab data (creatinine and glycemic index for metabolic)
5) Arterial blood gas |
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Term
What are the changes to pH, pCO2 and HCO3 seen in each of the following.
1) Metabolic acidemia
2) Metabolic alkalemia
3) Respiratory acidemia
4) Respiratory alkalemia |
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Definition
1) low pH, low pCO2 (compensate), low HCO3
2) high pH, high pCO2 (compensate), high HCO3
3) low pH, high pCO2, high HCO3 (compensate)
4) high pH, low pCO2, low HCO3 (compensate) |
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Term
| What are the major causes of metabolic acidosis? |
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Definition
MUDPALES
1) Methanol
2) Uremia
3) Diabetic ketoacidosis
4) Paraldehyde/Propolyne glycol
5) Alcoholic ketoacidosis
6) Lactic acidosis
7) Ethylene glycol
8) Salicylates |
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Term
What are the NORMAL ranges for each of the following?
1) pH
2) pCO2
3) Na
4) HCO3-
5) K
6) Cl |
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Definition
1) 7.4-7.44
2) 40-44 mmHg
3) 140-144
4) 24-28
5) 3.8-4.4
6) 99-104 |
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Term
| How can you calculate the anion gap? What does it tell you? |
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Definition
AG= [Na]- (HCO3 + Cl)
If >20, indicates metabolic acidosis
For every 1 g/dl albumin less than 4, add 2.5 to anion gap |
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