Acid base imbalances Flashcards
Henderson Hasselbach Equation
pH = pK + log [HCO3]/alpha*pCO2
What dose H+ secretion result in? in terms of HCO3
HCO3 reabsorption
Generation of new HCO3. only after after all filtered HCO3 has been reabsorbed
Where does HCO3 reabsorption and H+ secretion occur?
In the proximal tubule and collecting duct
How does H+ secretion in the proximal tubule occur?
In the cell: CO2+H2O –> HCO3- + H+
Na/H exchanger absorbs Na, pushes out H+ into the urine
H+ + HCO3 (freely filtered from glomerulus) –> H2O + CO2
The CO2 can diffuse back into the cell! This is the CO2 that we use in the first equation
Then that HCO3 from the first equation can go into the blood with the Na/HCO3 cotransporter
Net = Na reabsorbed, H+ excreted, bicarb reabsorbed into blood
How does H+ secreiton occur in the collecting duct?
H2O + CO2 –> H+ + HCO3-
The H+ is pumped into the lumen with H+ ATPase
In the lumen, NH3 combines with the H+ to form NH4+, which stayis in the urine
The HCO3 from the first equation goes into the blood with a Cl:HCO3 exchanger
Net: reabsorb one HCO3, excrete one H+
Metabolic acidosis: pH, primary, and compensation
pH<7.4
Primary: low HCO3
Compensation: low pCO2
Respiratory acidosis: pH, primary, and compensation
pH < 7.4
Primary: high pCO2
Compensation: high HCO3
Metabolic alkalosis: pH, primary, and compensation
pH >7.40
Primary: high HCO3
Compensation: high pCO2
Respiratory alkalosis: pH, primary, and compensation
pH >7.40
Primary: low pCO2
Compensation: low HCO3
What can cause metabolic acidosis?
Increased metabolic acid production: lactic or ketoacids
HCO3 losses: renal, non-renal (GI)
Renal failure
Acid ingestion
Formula for net acid excretion
NH4 + Titratable acid - HCO3
How does acid ingestion increase ammonia synthesis and excretion?
As you ingest more acid, your body makes and excretes more NH3
Up to a point!! It’s saturable
Which type of renal disease decrease NH3 production?
In tubulo-interstitial diseases, where you have atrophic tubules; when you get <20% normal nephrons, the daily NH3 production is too low so they present as acidotic!
Not in glomerular diseases, where they have normal tubules
What is the anion gap?
Na - (Cl+HCO3)
What does a high anion gap mean?
That metabolic acidosis is due to the presence of some unmeasured anion
What can cause high anion gap metabolic acidosis?
Lactic acidosis (lactate)
Diabetic ketoacidosis (beta-OH butyrate)
Renal failure
Toxins: salicylate (lactate, salicylate), ethanol (formate), ethylene glycol (oxalate)
What can cause lactic acidosis?
Ischemia/hypoxia: ischemia, hypoxia due to pulm dz, severe anemia
With normal pO2: can be: severe exercise, malignancies, thiamine deficiency, severe liver dz
Drugs: metformin
D-lactic acidosis
What causes diabetic ketoacidosis?
Insulin leads to increased glucose uptake into muscle but also increases lipogenesis
Low insuiln –> increased free fatty acid levels from lipolysis
What are the 3 components of diabetic ketoacidosis?
Hyperglycemia (osmotic diuresis, volume depletion)
Metabolic acidosis
High anion gap (beta-OH butyrate, acetoacetate, somewhat elevated lactate levels)
What can cause normal anion gap metabolic acidosis?
It’s going to be hypercholoremic
Can be due to non-renal HCO3 loss: diarrhea (bc increased Cl delivery to colon –> HCO3 secretion via Cl: HCO3 exchanger), uretero-sigmoidostomy
Renal HCO3 wasting
What can cause proximal renal tubular acidosis?
Hereditary: cystinosis, hereditary fructose intolerance, CLC5 mutations, Lowe’s syndrome, Wilson’s dz, phosphorylase kinase deficiency, pyruvate carboxylase deficiency, CAII
Toxins: lead, mercury, cadmium, outdated tetracycline
Multiple myeloma
Renal transplant rejection
Hyperparathyroidism
Auto-immune dz: sjogren’s syndrome
What can cause distal renal tubular acidosis
Mutations in: AE1, H+ ATPase, CAII, Mineralocerticoid receptor, epithelial Na channel
Toxins: amphotericin B, Li, toluene
Nephrocalcinosis
Sickle cell dz
Urinary obstruction
Autoimmune dz: sjogren’s syndrome
What can cause type IV renal tubular acidosis?
Interstitial renal dz
Hyperkalemia
Hypo-reninemic hypoaldosteronism
How can you get metabolic alkalosis?
Generation of excess HCO3: acid loss (vomiting, upper GI suction), HCO3 generation from metabolizable anions e.g. lactate, citrate, or beta-OH butyrate, HCO3 ingestion
Maintenance of excess HCO3: increased renal H+ secretion due to:
- decreased filtration rate
- volume depletion encourages proximal HCO3 reabsorption by high filtration fraction and AII stimulates Na/H exchanger
- high aldosterone increases collecting duct H+ secretion and HCO3 generation
How can you get high aldosterone levels that can contribute to the alkalosis?
- primary hyperaldosteronism
- secondary hyperaldosteronism: high renin, high ang II
- volume depletion
- diuretics
- CHF
- cirrhosis of the liver
How do respiratory acid/base abnormalities cause changes in pH?
Primary event is change in rate of ventilation leading to a change in blood pCO2
CO2 diffuses into the cell changing the cell pH, which in turn changes the cell calcium
Increased Calcium causes exocytosis of H+ ATPase containing vesicles
Decreased calcium causes their endocytosis
What can cause respiratory alkalosis?
Hyperventilation due to:
Hypoxia
Lung dz - pneumonia
Heard dz - pulm edema
Liver dz
Cerebral dz- encephalitis, meningitis
Drugs- aspirin
Hormones- progesterone
What is the most common acid-base disorder?
Respiratory alkalosis
What can cause respiratory acidosis?
Hypoventilation
Lung disease: emphysema, chronic bronchitis, asthma
Tracheal obstruction
CNS: coma, stroke, central hypoventilation with obesity
Generalized muscle weakness: ALS, myasthenia gravis
Drugs: morphine and opiates in general
What is the effect of metabolic acidosis in renal failure?
Increases the progression of renal failure
Unknown mechanism
Correcting the acidosis reduces the rate of progression