Therapeutics Exam 3 (Acid/Base) Flashcards
What is a normal physiological pH?
7.35-7.45
Acid-Base disorders fall into what 2 categories?
Metabolic
Respiratory
Kidney/Metabolic acid-base disorders refer to which 2 ions?
H+ and HCO3-
Lungs/Respiratory acid-base disorders refer to which 2 ions?
CO2 and H2O
Which type of acid-base disorder is easier to overcome? Metabolic or Respiratory?
Metabolic
-the lungs compensate much faster than the kidneys
-compensation for a disorder comes from the OPPOSITE SIDE
What is a normal PaCO2 value?
35-45 mmHg (40)
What is a normal HCO3 value?
22-26 meq/L (24)
What is a normal PaO2 value?
95-100 mm Hg
What is a normal SaO2 value?
> or = 95%
What are the consequences of acidemia?
Cardiac: Decreased output, Impaired contractility, Increased pulmonary vascular resistance
Metabolic: Insulin resistance, Inhibition of anaerobic glycolysis, *Hyperkalemia
CNS: Coma, Altered mental status
Other: Decreased respiratory muscle strength, hyperventilation, dyspnea
What are the consequences of alkalemia?
Cardiac: Decreased coronary blood flow, Arteriolar constriction, Anginal threshold, Arrhythmias
Metabolic: *Hypokalemia, Low Ca, Low Mg, Stimulation of anerobic glycolysis
CNS: Decreased cerebral blood flow, Seizures
Other: Decreased respirations
Where does acid come from?
Diet (1 mEq/day consumed)
Aerobic metabolism of glucose
Nonvolatile acid formation
-Anaerobic metabolism, Triglyceride oxidation, Metabolism of sulfur-containing amino acids and phospholipids
What are the 3 mechanisms of acid regulation?
Buffering
Renal regulation
Ventilatory regulation
What is the body’s first line of defense for acid regulation?
Extracellular/Intracellular buffering systems
What are the 3 main buffers in the body?
Bicarb/Carbonic Acid
Phosphate
Proteins
What is the principle buffer in the body?
Bicarbonate
*present in the largest concentration extracellularly over any of the other buffers
What happens when acid is added to your system?
HCO3- picks up H+ and becomes H2CO3 (carbonic acid)
H2CO3 dissociates to CO2 and H2O
How much new bicarb needs to be ingested by the body each day?
The body needs new bicarb added to the system in an amount that is equivalent to the H+ load ingested every day
What properties do phosphates have as a buffer?
Intermediate onset and capacity
-Slower
-Not as many available compared to bicarb
What properties do proteins have as buffers?
Rapid onset
Limited capacity
*very quick but limited
–more effective intracellularly than extracellularly
What are the 2 main purposes of the kidneys?
- Reabsorb filtered bicarb
- Excrete H+ ions released from nonvolatile acids (help regenerate new bicarb through hydrogen excretion)
How much bicarb gets reabsorbed by the body?
*Body is supposed to reabsorb all bicarb daily
-should have virtually none present in the urine
*Bicarb is also reabsorbed with no net loss of H+
Where does bicarb reabsorption take place?
85-90% is reabsorbed in the proximal tubule
10-15% is reabsorbed via distal tubule or collecting duct
Which enzyme is responsible for the dissociation of carbonic acid to for H2O + CO2?
Carbonic anhydrase
H+ Is excreted into the urine/tubular lumen in exchange for what?
Na+
How do bicarbonate losses in the urine occur?
When anything limits H+ secretion into the proximal tubule lumen and bicarb is not able to convert to carbonic acid, then to H2O + CO2 and get reabsorbed
-ex: carbonic anhydrase inhibitors
How do carbonic anhydrase inhibitors work?
-Inhibit activity of carbonic anhydrase
-Carbonic acid is not able to change to H2O + CO2 and cross into the proximal tubule
Note that metabolic acidosis occurs with increased bicarb excretion
*this is a way to correct alkylosis
Why must bicarbonate be generated?
Reclamation of all filtered bicarb is not sufficient to maintain normal blood pH
**Where does H+ excretion primarily take place?
Distal tubule
*this is a different area than where reabsorption is occurring
What are the 2 ways H+ excreted?
Ammonium Excretion
Secreted H+ ions combine with ammonia (NH3) in the distal tubule to make ammonium (NH4+) which cannot cross membranes
-this is excreted
Titratable Activity
Phosphoric acid (HPO4^2-) combines with secreted H+ in the distal tubule to become dihydrogen phosphate (H2PO4-)
It is too big to cross the membrane and gets excreted
Ammonium excretion is able to produce how much bicarb?
New HCO3- (40 mEq/day) can be increased to 300 mEq/day
Titratable activity (phosphate H+ excretion) is able to account for how much bicarb?
30 mEq/day of new bicarb
*capacity is smaller than ammonium excretion
*cannot be increased because it is limited by the buffer
Hydrogen ion secretion in the distal tubule comprises what % of net acid excretion?
50%
How does ventilatory regulation of acid occur?
-Rapid onset and large capacity
-Chemoreceptors detect increased PaCO2 and increase the rate and depth of ventilation
-More CO2 is expelled through ventilation
What is the primary change in metabolic acidosis?
Decreased HCO3-
Compensation: Decreased PaCO2 (lowers this to blow acid off)
What is the primary change in metabolic alkalosis?
Increased HCO3-
Compensation: Increased PaCO2 (retains CO2 and breathing slows down)
What is the primary change in respiratory acidosis?
Increased PaCO2
Compensation: Increased HCO3 (kidneys increase bicarb synthesis)
What is the primary change in respiratory alkalosis?
Decreased PaCO2
Compensation: Decreased HCO3- (kidneys stop bicarb synthesis)
When may a mixed disorder be indicated?
If the primary change and compensation arrows do not go in the same direction for a disorder or if values fall out of specified ranges
What are the characteristics of metabolic acidosis?
Low pH (<7.35)
Low serum HCO3- (<24 mEq/L)
Compensatory decrease in PaCO2
What are the 2 types of metabolic acidosis?
Anion Gap (when anion gap is high)
Non-Anion gap (when anion gap is normal or low)
How do we calculate anion gap?
Anion Gap= Na - (Cl + HCO3)
What is a normal anion gap?
3-11 mEq/L
What happens in non-anion gap acidosis?
Loss of plasma HCO3- that is replaced by Cl-
What are the 3 causes of non-anion gap acidosis?
GI bicarb losses
Renal bicarb losses
Reduced renal H excretion
What are common causes of GI bicarb loss?
Diarrhea *very common
-not enough time to reabsorb bicarb
Pancreatic fistulas/Biliary drainage
-these fluids are rich in bicarb
What causes renal bicarb loss?
Type II renal tubular acidosis (proximal)
-patients cannot reabsorb bicarb in the proximal tubule due to something happening there (disease or drug)
When there is more bicarb loss, what else happens?
Increased Na+ and fluid loss
-activates the renin-angiotensin system which leads to hyperaldosteronism
- Aldosterone tries to compensate and K gets excreted, leading to hypokalemia
What are the 3 types of Reduced renal H+ excretion that can lead to non-anion gap acidosis?
Type 1 RTA
Type IV RTA
Chronic renal failure
What are the causes of Type 1 Renal Tubule Acidosis (RTA) [Hypokalemia RTA]?
-Damage in the distal tubule, patient cannot regenerate bicarb
-H+ cannot be pumped into the tubule lumen by cells of the collecting duct
-Urine cannot be maximally acidified
-Increased K+ excretion to try and replace H+
What are the causes of Type 2 Renal Tubule Acidosis (RTA) [Hypoaldosteronism/ Hyperkalemia RTA]?
-Body has low aldosterone/is resistant to it
-Aldosterone stimulates H+ excretion
-Less aldosterone = H+ retention (acidosis)
-Hyperkalemia also leads to H+ retention (acidosis)
How does chronic renal failure lead to acidosis?
Decreased H+ secretion
Less ammonia production (decreases ability to make bicarb)
What things are able to lead to anion gap acidosis?
MUDPILES
M: Methanol intoxication
U: Uremia
D: Diabetic ketoacidosis
P: poisoning/Propylene glycol ingestion
I: Intoxication/infection
L: Lactic acidosis
E: Ethylene glycol
S: Salicylate/sepsis
What is the cause of anion gap acidosis?
HCO3- losses are replaced with another anion besides Cl-
After determining anion gap, if a patient has anion gap acidosis what is the next step?
Calculate delta gap
How do we calculate delta gap?
Delta Gap= Patient’s Anion Gap - Normal Anion Gap
What does the anion gap tell us?
Whether a mixed disorder is present
*When the delta gap is added to a patient’s measured bicarb, the result should be in the normal bicarb range
-If these are added and the result is an elevated HCO3-. it tells you there is metabolic alkalosis with the acidosis
What is the most common cause of Anion Gap metabolic acidosis?
Lactic acidosis
What is lactic acidosis?
Lactate is a normal part of anaerobic metabolism
-Essential for tissues needing NAD+ to generate energy
Increased lactic acid levels almost aways result from what?
Decreased clearance
(not overproduction)
What is the normal level of lactic acid?
1 mEq/L
What is considered a high lactic acid level?
> 5 mEq/L
What is the main way that lactic acid is eliminated?
Gets reconverted to pyruvate (NAD+ to NADH)
Disposed by liver, kidney, and muscle
What are the causes of lactic acidosis?
Shock
Drugs:
-Ethanol
-Metformin
-NRTIs
-Linezolid, Isoniazid, Propofol, Topiramate, Viekera
-Propylene Glycol
-Seizures
-Leukemia
-Hepatic/Renal Failure
-Diabetes
-Others: Malnutrition, Rhabdomyolysis
If a patient has a salicylate toxicity, what can happen?
-Respiratory alkalosis (stimulated respiratory drive)
-Metabolic acidosis (accumulation of organic acids)
*pH looks normal
What is the treatment for lactic acidosis?
Acute bicarbonate therapy
What are the indications for giving a patient bicarb?
-Hyperkalemia
***pH <7.1 with cardiac arrest after defibrillation, ventilation, and medications have been used
-Overdoses
How do we dose bicarb?
Dose (mEq) = [0.5 x IBW] x [12 - Actual HCO3]
*note that 12= desired bicarb
Once we calculate the bicarb dose, how much is actually administered to the patient?
Give 1/3 to 1/2 the calculated dose
**want to be super conservative
During cardiac arrest, how much bicarb may be given?
1 mEq/kg
What is the average dose of bicarb for chronic metabolic acidosis therapy?
1-3 mEq/kg/day
What are the characteristics of metabolic alkalosis?
Increased pH (>7.45)
Increased bicarb (>30 mEq/L)
Compensatory hypoventilation resulting in increased CO2
What are the 3 main ways plasma bicarb levels can rise?
Loss of acid from GI tract or urine
Administration of bicarb or precursor
Contraction alkalosis (Loss of Cl rich fluid and bicarb poor fluid)
What else can contribute to metabolic alkalosis?
Volume and Chloride depletion
-decreased blood volume
-decreased ability for kidney to excrete bicarb
-increased ability to reabsorb bicarb in the proximal tubule
What are the 2 types of alkalosis?
Saline responsive
Saline resistant
What urinary chloride indicates saline responsive alkalosis?
<10-20 mEq/L
What are the 3 causes of saline responsive alkalosis?
Diuretic therapy
Vomiting and ng suction
Exogenous bicarb administration or blood transfusion
What is the main cause of saline responsive alkalosis?
Diuretic therapy
-excretion of NaCl and water is increased
-Extracellular volume contraction results
-This stimulates aldosterone release
-Increases Na reabsorption and H+ and K+ secretion
-H+ secretion leads to bicarb reabsorption
-Hypokalemia stimulates hydrogen ion movement intracellularly while K moves out
-Na+ exchanges with K and gets reabsorbed with bicarb
How is alkalosis maintained?
Na reabsorption increases which leads to H+ secretion and bicarb reabsorption
Less K+ leads to more H+ secretion and Na+ reabsorption
What urinary chloride level indicated saline resistant alkalosis?
> 20 mEq/L
How is saline resistant alkalosis different from saline responsive?
Enhanced renal H+ excretion and bicarb reabsorption
-Difference: No chloride depletion, Cl is normal
What are the causes of saline resistant alkalosis?
Increased mineralcorticoid activity (Na and K exchange is increased, H+ secretion increases, bicarb is absorbed)
Hypokalemia
Renal tubular chloride wasting
How do we treat saline responsive alkylosis?
Fluid/electrolyte replacement with NaCl or KCl
In patients who cannot tolerate excess fluid or sodium, what can we use for alkylosis?
Carbonic anhydrate inhibitors (Acetohexamide)
*note that this can make hypokalemia worse
What is an alternative last-line therapy for alkalosis?
HCl acid
Ammonium chloride
Arginine monochloride
How do we treat saline resistant alkalosis?
-Correct hypokalemia
-Decrease dose of mineralcorticoid (hydrocortisone)
-Administer spironolactone
-Correct hyperaldosteronism
