Renal Module III Flashcards
What does pH represent?
Concentration of plasma H+
Normal plasma pH?
7.4 (7.35-7.45)
Plasma pH in acidosis?
< 7.35
Plasma pH of alkalosis?
> 7.45
How much H+ is in the blood compared to other plasma ions (Na+, HCO3-, K+, etc.) in a healthy individual?
Small amount when compared to other ions (but critical to maintain plasma pH w/ narrow optimal range):
H+= 0.00004 mEq/L
Na+= 140 mEq/L
HCO3-= 24 mEq/L (22-26 mEq/L)
K+= 3.5-5 mEq/L
What happens to oxygen transport and delivery if plasma pH is not maintained within optimal range?
Impairment of O2 transport/delivery:
-Acidosis: R shift in oxyhemoglobin
-Alkalosis: L shift in oxyhemoglobin
What happens to cell function if plasma pH is not maintained within optimal range?
Disrupted cell function:
-acidosis/alkalosis disrupts structure of cell membrane proteins (ion channels, receptors, etc.) –> impairs cellular & enzyme function in all cells of the body
Death may occur within hours if pH reaches what levels?
Below 6.8 or above 8.0
*loss of cell function/O2 transport leads to system failure (cardio, CNS, pulmonary, renal, liver, etc.) and ultimately death
How is H+ produced from metabolism of proteins (amino acids)?
Body is constantly breaking down cellular/dietary proteins/amino acids to smaller byproducts
*catabolic rxns constantly producing H+ ions
What are protein/amino acid byproducts used for?
Biosynthesis of new proteins/amino acids needed for cell growth/fxn, NTs, NO, etc.
*these rxns recycle a majority of H+ ions preventing/buffers plasma from drastic decrease in pH
How are the remaining protein/amino acid byproducts excreted?
Through the ammonia/urea cycle that influences plasma/urine pH equilibrium
How is glutamine (protein/amino acid) broken down for H+ production?
Broken down into H+ and glutamate (an excitatory NT that plays a central role in regulation of amino acid pH buffering in liver/kidneys)
What happens in the liver during alkalosis?
Converts ammonia to urea which consumes bicarb and produces H+
What happens in the liver during acidosis?
Converts ammonia to glutamine which consumes H+ and produces bicarb
Where does converted glutamine circulate/travel?
Circulates to PCT pof kidney to feed ammoniagenesis-converts glutamine to ammontia and H+ that is secreted into urine
What happens during glycolysis/glucose metabolism?
if O2 not available, glucose is broken down into lactic acid to make ATP –> lactic acid dissociates into lactate and H+ & enter plasma –> lactate & H+ ions circulate to liver where they are recycled back into glucose (Cori cycle)
Does lactic acid contribute to plasma H+ accumulation?
No, except during pathology or extreme exertion
What happens during fat metabolism/ketogenesis?
Fatty acids broken down by liver to acetoacetate which dissociates into B-hydroxybutyrate and H+ / enters the plasma
Where do B-hydroxybutate and H+ circulate to? What happens to them?
Circulate to cells of the body where they will be oxidized/converted back to acetyl CoA & used for energy
Does ketogenesis occur continuously in a healthy individuals?
Yes
Dopes ketogenesis contribute to plasma H+?
No, except when excessive ketogenesis occurs (like in DKA)
How does aerobic metabolism of glucose and fats take place?
if O2 present, glucose and fats (FFA) are broken down/feed TCA/ETC to produce ATP and CO2
*CO2 diffuses into bloodstream, ATP used as energy
Is CO2 in the plasma hydrated?
Yes
What does hydrated CO2 in the plasma form?
Carbonic acid - can dissociate into H+ and bicarb
CO2’s ability to form H+ and HCO3- influences what?
Plasma pH equilibrium
Does aerobic metabolism continuously produce CO2 for dissociation into H+ and CO3-?
Yes
CO2 concentration influences what?
How easily carbonic acid dissociates into H+ and HCO3-
Increased CO2 will increase what?
H+ and HCO3- concentration
Decreased CO2 will decrease what?
H+ and HCO3- concentration
What organ system is responsible for regulating CO2 concentration?
The lungs
Hypoventilation will have what effect on CO2 concentration?
Increases
Hyperventilation will have what effect on CO2 concentration?
Decreases
What are the three mechanisms which regulate plasma pH?
Renal compensation, Respiratory compensation, Carbonic acid bicarbonate buffer system
How does renal compensation regulate plasma pH?
Kidneys regulate rate of H+ excretion and HCO3- reabsorption
Does renal compensation have a slow or fast response time?
Slow- kidneys take 1-2 hrs to start and take up to 24-72 hrs to to reach max effect
How does respiratory compensation regulate plasma pH?
Lungs regulate rate of CO2 excretion (CO@ conc. regulates how easily carbonic acid dissociates into H+ and HCO3-)
Does respiratory compensation have a fast or slow response time?
Fast- lungs take 1-2 min to start and take up to 12-24 hours to reach max effect
Does the carbonic acid bicarbonate buffer system have a fast or slow response time?
FAST, IMMEDIATE RESPONSE TIME
How does the carbonic acid bicarbonate buffer system regulate plasma pH?
H+, HCO3-, or CO2 cncentrations instantly regulate preference of carbonic acid to either form:
CO2 & H2O
or
H+ & HCO3-
How does the carbonic acid bicarbonate buffer system react to a left shift?
Carbonic acid is favored to form CO2 and H2O to buffer the excess H+
How does the carbonic acid bicarbonate buffer system react to a right shift?
Carbonic acid is favored to form H+ and HCO3- to buffer too little H+
The carbonic acid bicarbonate equation will maintain optimal H+ concentration if what remains at a constant ratio?
Ratio of HCO3- and CO2
Stable pH maintained at 7.35-7.45 if:
-normal CO2 and HCO3- values
-equally raised CO2 and HCO3- values
-equally lowered CO2 and HCO3- values
What is respiratory acidosis?
Too much CO2
What is respiratory alkalosis?
Too little CO2
What is high anion gap metabolic acidosis caused by?
Conditions that create too much H+
What is normal anion gap metabolic acidosis caused by?
Conditions that create too little HCO3-
What is metabolic alkalosis?
Too little H+ or too much HCO3-
What is mixed acid-base disorder?
Patient has two or more acid-base disorders
What kind of conditions cause too much CO2/respiratory acidosis?
Conditions that cause hypoventilation
Which medications depress the CNS or respiratory tract (increase CO2)?
Opioids, sedatives, tranquilizers, anticholinesterases, anesthetics
Which neuromuscular diseases/conditions depress the respiratory muscles (increase CO2)?
Stroke, spinal cord injury, ALS, GBS, myasthenia gravis, botulism, tetanus, muscular dystrophy, etc.
What conditions can cause airway obstruction (increase CO2)?
Obstructive sleep apnea (OSA)
What conditions can cause respiratory failure (increase CO2)?
Cardiac arrest, pneumonia, pulmonary edema, ARDS, restrictive lung disease, PE, pneumothorax, chest trauma, smoke inhalation
What other conditions can cause an increase in CO2 from hypoventilation?
COPD, extreme obesity
Hypoventilation increases CO2 and changes which ratio making the equation out of balance?
HCO3-/CO2 ratio
What is the carbonic acid bicarbonate (immediate) response to excess CO2?
Makes carbonic acid favor to form H+ and HCO3- (increases H+ concentration, creates an acidosis)
What is the renal compensation (slow, 1-2 hour to start) response to excess CO2?
Increase H+ excretion and increasing HCO3- reabsorption
After 24-72 hours, what is the result of renal compensation to excess CO2?
-Plasma H+ decreases (pH increases almost back to normal)
-Plasma HCO3- increases to match the high plasma CO2 (balances the equation to maintain the new pH)
Does compensation return pH completely back to normal?
Rarely
What is the expected renal compensation for acute respiratory acidosis?
HCO3- should increase by 1 for every 10 mmHg increase in pCO2
What is the expected renal compensation for chronic respiratory acidosis?
HCO3- should increase by 4 for every 10 mmHg increase in pCO2
If HCO3- does not equal the expected value, what does is suggest?
Second acid-base disorder is present
Normal values for pCO2 and HCO3-?
HCO3- = 24 mEq/L (22-26)
pCO2 = 40 mmHg
Which conditions cause hyperventilation and too little CO2/respiratory alkalosis?
Fear/anxiety
Early shock
Pregnancy
Salicylate toxicity
Altitude and anemia
Pulmonary disease
Sepsis
Hyperthyroidism
Stroke/TBI
What is the earliest acid-base disorder of hypovolemic shock (early shock)?
Respiratory alkalosis
How does pregnancy cause hyperventilation (too little CO2)?
Progesterone stimulation of brainstem respiratory centers causes hyperventilation
What does salicylate toxicity stimulate to cause hyperventilation?
Brainstem respiratory centers
How do altitude and anemia cause hyperventilation (too little CO2)
Hypoxia/Hypoxemia stimulate hyperventilation
Which pulmonary diseases can cause hyperventilation?
CHF, asthma, pneumonia, PE
Carbonic acid bicarbonate (immediate) response to too little CO2?
Carbonic acid favors turning into CO2 and H2O (decreases H+ concentration, creates an alkalosis)
Renal compensation (slow 1-2 hr start) response to too little CO2?
Decrease H+ excretion and increase HCO3- reabsporption
After 24-72 hours, what is the result of renal compensation to too little CO2?
-Plasma H+ increases, pH decreases almost back to normal
-Plasma HCO3- decreases to match the low plasma CO2/balance the equation & maintain new pH
Expected renal compensation in acute respiratory alkalosis?
HCO3- should decrease by 2 for every 10 mmHg decrease in pCO2
Expected renal compensation in chronic respiratory distress?
HCO3- should decrease by 5 for every 10 mmHg decrease in pCO2
Metabolic acidosis can be caused by what two mechanisms?
too much H+ & too little HCO3-
If metabolic acidosis is caused by conditions that cause too much H+, what is this known as?
High anion gap metabolic acidosis (HAGMA)
If metabolic acidosis is caused by conditions that cause too little HCO3-, what is this known as?
Normal anion gap metabolic acidosis (NAGMA)
What happens in excess in HAGMA?
Lactic acid synthesis, ketogenesis, acid metabolites/inability to excrete acid
Conditions that cause H+ accumulation (HAGMA)?
“GOLDMARK”
Glycols
Oxoproline
L-Lactate
D-Lactate
Methanol
Aspirin (salicylic acid)
Renal failure (uremic acidosis)
Ketogenesis
How do glycols cause H+ accumulation (HAGMA)?
Ethylene glycol & propylene glycol produce acids when metabolized in the liver
How does oxoproline cause H+ accumulation (HAGMA)?
Pyroglutamic acid: acid metabolite of excessive acetaminophen or paracetamol
How does L-Lactate cause H+ accumulation (HAGMA)?
Lactic acid is produced in anaerobic metabolism caused by hypoxia (shock, CHF, anemia, CO, poisoning) or from drug metabolism (cyanide, ibuprofen, INH, iron)
How does D-Lactate cause H+ accumulation (HAGMA)?
Lactic acid produced by gut bacteria
How does Aspirin cause H+ accumulation (HAGMA)?
Produce acidic metabolites in liver
How does renal failure cause H+ accumulation (HAGMA)?
unable to excrete H+ (uremic acidosis)
What kinds of ketogenesis cause H+ accumulation (HAGMA)?
Diabetic, alcoholic, starvation ketosis
Carbonic acid bicarbonate (immediate) response to too much H+?
Carbonic acid favors turning into CO2 and H2O, increases CO2 and decreases HCO3- concentration and equation is now out of balance
What is the respiratory compensation (fast, 1-2 minute to start) response to excess H+?
Lungs hyperventilate to solve pH problem, increase CO2 excretion to balance equation
After 12-24 hours, what will the result of respiratory compensation to excess H+ be?
-Plasma H+ decreases, pH increases almost back to normal
-Plasma CO2 decreases to match the low plasma HCO3-, balances equation to maintain new pH
Expected respiratory compensation for metabolic acidosis?
PaCO2 = [1.5 x (serum HCO3-)] + 8 (+/- 2)
If pCO2 does not equal the expected value, what is suggested?
Second acid-base disorder
If patients pCO2 is higher than expected, what secondary acid-base disorder is present?
Respiratory acidosis
If patients pCO2 is lower than expected, what secondary acid-base disorder is present?
Respiratory alkalosis
Patients can’t typically hyperventilate beyond a pCO2 of what value in response to metabolic acidosis?
12-14 mmHg
Metabolic alkalosis can be caused by what two mechanisms?
too little H+ & too much HCO3-
Are there high or normal anion gaps for metabolic alkalosis?
No
What conditions cause too little H+ (metabolic alkalosis)?
GI loss of H+
Renal loss of H+
Hypokalemia
How does the GI tract lose excess acid?
vomiting, NG suctioning
How do the kidneys lose excess H+?
-Thiazide diuretics (inhibit NaCl in early DCT but promote K+ excretion (hypokalemia) and H+ excretion downstream in DCT/CD
-Hyperaldosteronism (Conn’s syndrome-adrenal tumor) promotes K+ and H+ excretion in DCT/CD
How does Hypokalemia cause excess loss of H+?
Shifts K+ out of cells and H+ into cells (moves H+ from blood)
Carbonic acid bicarbonate (immediate) response to too little H+?
Carbonic acid favors turning into H+ and HCO3-, decreasing CO2 and increasing HCO3- making equation out of balance
Respiratory comensation (fast, 1-2 minute start) response to too little H+?
Lungs hypoventilate to solve pH problem by decreasing CO2 excretion
Expected result of respiratory compensation to decreased H+ after 12-24 hours?
-Plasma H+ increases, pH decreases almost back to normal
-Plasma CO2 increases to match increased plasma HCO3- to maintain new pH
Conditions that cause excess HCO3- accumulation (metabolic alkalosis)?
GI ingestion of bicarb (sodium bicarb, sodium citrate, antacids) & Cystic fibrosis (alters chloride/bicarb balance)
Carbonic acid bicarbonate (immediate) response to excess HCO3-?
Instantly buffers with H+ and creates alkalosis, equation is out of balance
Carbonic acid now favors turning into H+ and HCO3-, decreasing CO2
Respiratory comensation (fast, 1-2 min start) response to excess HCO3-?
Lungs hypoventilate to solve pH problem by decreasing CO2 excretion
Expected result of respiratory compensation in response to excess HCO3-?
-Plasma H+ increases, pH decreases almost back to normal
-Plasma CO2 increases to match high plasma HCO3- to maintain new pH
Expected respiratory compensation for metabolic alkalosis?
The increase of PaCO2 should = (0.6 x increase of HCO3-) (+/- 2)
A patient with metabolic alkalosis typically can’t hypoventilate past what pCO2 value without potential respiratory arrest?
pCO2 value of 55-60 mmHg
What does the anion gap compare?
Cations and anions, electroneutrality of the plasma
Anion gap (AG) measurement only includes what three major electrolytes?
Na+, HCO3-, Cl-
Values reported in labs (BMP, chem7, chem panel, etc.)
Equation to assess anion gap?
Anion gap = Na+ - (HCO3- + Cl-)
Normal anion gap value?
8-12
What is the clinical goal of measuring the anion gap?
Determine if AG gap is normal or high (NAGMA or HAGMA)
Normal values for sodium ions?
140 mEq/L
Normal value for chloride ions?
104 mEq/L
Normal value for HCO3- ions?
24 mEq/L (“CO2”)
The higher the anion gap, the more likely the patient has what?
High anion gap metabolic acidosis
Anion gap is used to determine what?
Cause of metabolic acidosis
High AG: conditions that create too much H+
Normal AG: conditions that create too little HCO3-
Anion gap can also detect if what condition is also present in patients that have another type of acid-base disorder?
HAGMA
Ex. if patient has respiratory alkalosis and a high AG, also have a high anion gap metabolic acidosis
Important to always check what value regardless of acid-base disorder?
AG
The loss of HCO3- in NAGMA will be replaced with what anion to maintain the “normal” gap of 8-10?
Cl-
What is NAGMA sometimes referred to as?
Hyperchloremic metabolic acidosis
HAGMA anion gap value?
AG >12
What is the lost HCO3- in HAGMA replaced with to cause the gap to increase >12?
lactates, B-hydroxybutyrate, etc.
Ex. lactic acid dissociates into H+ and lactate C3H5O3-, lactate replaces decreased plasma HCO3- to maintain electroneutrality
Short-cut approaches (like acid-base tic tac toe) to assess acid-base diosorders are often limited to which disorders?
More complex acid-base disorders
HCO3- is sometimes referred to CO2 in some lab panels, what is this NOT the same as?
NOT the same as PaCO2 measures in ABG
*It measures plasma HCO3- and is used as an estimate of plasma CO2
Normal arterial blood gas (ABG) values?
pH= 7.4
PaCO2= 40 mmHg
PaO2= 100 mmHg
HCO3- = 24 mEq/L
Acid-base is estimated (calculated) in the BG report based on PaCO2 and PaO2
*can be used if needed, but better to use chem screen
What is an important tip for acid-base assessment?
Try to recognize patterns, de-emphasize memorization of equations and tables
Step 1 of acid-base assessment?
Determine pH status (acidemia or alkalemia)
Step 2 of acid-base assessment?
Determine the primary disturbance (respiratory acidosis/alkalosis or metabolic acidosis/alkalosis?)
How:
-Figure out if HCO3- or CO2 is consistent with the pH
Low CO2 or high HCO3- are consistent with what?
alkalosis
High CO2 or low HCO3- are consistent with what?
acidosis
Low PCO2 (<40 mmHg) and high pH (>7.4) is consistent with what?
Respiratory alkalosis
High PCO2 (>40 mmHg) and low pH (<7.4) is consistent with what?
Respiratory alkalosis
Low HCO3- (<24 nm) and low pH (<7.4) is consistent with what?
Metabolic acidosis
High HCO3- (>24 nm) and high pH (>7.4) is consistent with what?
Metabolic alkalosis
Step 3 of acid-base assessment?
Determine type of compensation
If respiratory = renal compensation
If metabolic = respiratory compensation
AND
If expected compensation has occurred (use equations) to determine if single or mixed acid-base disorder
What is the Step 3 acid-base clinical short cut “1,2,3,4,5” rule for assessing renal compensation in patients with respiratory acidosis and alkalosis?
Simple table to calculate metabolic compensation:
-Resp. acidosis: increased PaCO2, for every 10mmHg rise should have INCREASE in HCO3- by 1 (acute) or 4 (chronic) for compensation
-Resp. alkalosis: decreased PaCO2, for every 10mmHg rise should have DECREASE in HCO3- by 2 (acute) or 5 (chronic) for compensation
What is “Winter’s formula” for assessing respiratory compensation in patients with metabolic acidosis?
PaCO2= [1.5 x (serum HCO3-)] + 8 (+/- 2)
If the patients PaCO2 is lower than expected PaCO2, the patient also has what disorder?
Respiratory alkalosis
Clinical shortcut to bypass Winter’s formula?
The expected PaCO2 is approximately equal to the last two digits of the pH -/+ 2
Step 4 of acid-base assessment?
Determine if the anion gap is normal or high
High AG: pathology that produces excess acid or ingests acid
Low AG: Pathology that causes loss of HCO3-
Determine with AG= Na+ - (Cl- + HCO3-)
Step 5 of acid-base assessment?
Calculate the “delta-delta”
helps detect previously undetected metabolic disorder not discovered on previous 4 steps
Delta ratio = change in anion gap (AG-12) / change in HCO3- (24-HCO3-)
