[Acid-Base Balance] [Dr. Bashir Khasawneh] [5 th February 2012] Acid-Base Basic Concepts: The relationship between H+,PaCO₂ and HCO₃ are expressed in the equation of: Which is modified from Henderson-Hasselbach equation: PaCO 2 and HCO 3 - are two titers that responsible to keep H+ in the system under control. H+ are referring to the intracellular hydrogen ions that leak a little bit to the blood. That is why people with crash injury will get acidosis as the hydrogen ions get out from intracellular, just like potassium. But they present in a small amount in the blood to keep an appropriate acidity. So from the equation, you can see that when PaCO₂ increase, HCO 3 - will increase too. Same thing happen if HCO 3 - decrease, PaCO₂ will have to decrease with it to keep the H+ in balance. Regarding [H+], the problem is that it presents in the body in a very minute amount (by neq or nmol/l), this problem has been overcome by using the concept of ph. So instead of saying: "the normal [H+] in blood is 40nEq", we can say: "the normal physiological blood ph is 7.40" Since ph is a logarithm, the relation will be in an opposite way. If H+ concentration is high, ph will drop and vice versa and they are not proportional.
Take a look at this table (slide 3) If we increase H+ from 40nEq (normal) 62nEq; the ph will decrease by 0.15. while if we decrease H+ by same amount from 40nEq 18nEq, the ph will increase by 0.35. And you can see that the ph is more sensitive towards the alkalosis side(high ph); small change of H+ concentration will cause a greater shift of the ph because alkalosis is more dangerous than acidosis. Normal values So here are few numbers that you have to remember: [H+] = 40 neq/l ph = 7.40 (7.35-7.45) PaCO 2 = 40 mm Hg (35-45) HCO 3 = 24 meq/l (22-26) You have to know that the normal value of ph is 7.40 while 7.35-7.45 are the acceptable physiological range which means any ph within this range is acceptable, but it is not normal. Some people say 7.42 is normal, it is not, it is acceptable. The normal one is 7.40. Same thing for the PaCO 2, HCO 3, H+, you have the normal and acceptable physiological range. Now, simply: PaCO 2 = Acid PaCO 2 = ph (Acidemia) PaCO 2 = ph (Alkalemia) HCO 3 = Base HCO 3 = ph (Alkalemia) HCO 3 = ph (Acidemia)
While in numbers, if PaCO₂ is more than 40mmHg, it is acidosis and if it is less than that, it is alkalosis. And the opposite way to HCO 3, if it is more than 24mEq/L, it is alkalosis while less than that value will be acidosis. And for ph, just think the same. As simple as that Acid-Base Analysis Now, how do we do the acid-base analysis? It is by: 1. Arterial Blood Gases(ABG). We draw out a unit of arterial blood and from there we can get ph and PaCO₂. While for HCO₃, we calculate it using the Henderson-Hasselbach equation. Or, you can get it from 2. Serum chemistry where you can measure HCO 3 with Na, K, Cl. This way actually increases the costs while the value actually doesn t differ that much from the calculated one. So now, we usually depend on the calculated HCO from ABG. Since PaCO₂ is regulated by respiration, abnormalities that primarily alter the PaCO₂ are referred to as respiratory acidosis (high PaCO₂) and respiratory alkalosis (low PaCO₂). In contrast, [HCO3-] is regulated primarily by renal processes. Abnormalities that primarily alter the [HCO3-] are referred to as metabolic acidosis (low [HCO3-]) and metabolic alkalosis (high [HCO3-]). Simple acid base disorders -Disorders that is either metabolic or respiratory. Type of Disorder ph PaCO 2 [HCO 3 ] Metabolic Acidosis Metabolic Alkalosis Acute Respiratory Acidosis Chronic Respiratory Acidosis Acute Respiratory Alkalosis Chronic Respiratory Alkalosis Mixed acid base disorders -More than one acid base disturbance present. ph may be normal or abnormal. Let me give you an example of mixed acid base disorder.
A patient has COPD from a long time ago. Because of this, he always has high PaCO₂. So this is what we call chronic respiratory acidosis. And suddenly he has septic shock which caused him to have metabolic acidosis.*causes of disorders will be explained later* Now he has both respiratory and metabolic acidosis. So when he is admitted to the hospital, he is treated with steroids and diuretics which cause him to have metabolic alkalosis. So now, he has both respiratory acidosis and metabolic alkalosis. So the imbalances do exist in such order. Now, to solve this case, first we have to look for the primary disorder. The primary disorder for this patient is chronic respiratory acidosis (PaCO₂ high). What happen next is compensatory mechanism. We have two types of compensation. 1. Respiratory compensation which will compensate for metabolic disorder. 2. Metabolic compensation which will compensate for respiratory disorder. Compensation 1.RESPIRATORY COMPENSATION It is a prompt response towards metabolic acidosis or alkalosis. In case of metabolic acidosis, hyperventilation will occur in order to get rid of CO₂, compensating for the decreased HCO 3. While in metabolic alkalosis, the opposite happens. Metabolic acidosis Hyperventilation - PaCO 2 Metabolic alkalosis Hypoventilation - PaCO 2 For example in a DKA patient who develop sudden acidosis. The HCO 3 in this patient is decreased. So what is going to happen? The respiratory system will compensate this by having hyperventilation. But now, how do we know that this response is an appropriate one or not?by using these formulae: Metabolic Acidosis PaCO₂ = [1.5 x HCO 3 + 8] 2 Metabolic Alkalosis PaCO₂ = 0.9 HCO 3 For example in a patient with metabolic acidosis which means primarily his HCO 3 is low. So, after compensation, the expected PaCO₂ should be calculated using this formula. If his HCO 3 is for example 10, you are expecting his compensated PaCO₂ to be around 23 (21-25). If his PaCO₂ is below this range, we will say that this patient
is having another disorder which is respiratory acidosis. So now he has both metabolic and respiratory acidosis In metabolic alkalosis, similar concept is applied. For every HCO 3 increases, the PaCO₂ will increase. For example if the HCO 3 is increase to 30 (normal is 24), the HCO 3 is 6}. How much will the PaCO 2 increase? PaCO₂ = 5.4}, normal PaCO₂ is 40, so you will expect the PaCO₂ to be compensated to 45.4. 44-46 is still acceptable, but what happen if the value is 25? It means this patient has both metabolic alkalosis and respiratory alkalosis. So these are what we call the rule of compensation. 2.METABOLIC COMPENSATION The kidney will work on the HCO 3 to compensate for chronic respiratory disorder. That s why those with COPD, they have chronic CO₂ retention, and therefore they will have high HCO 3. Pregnant woman, liver cirrhosis patient who have chronic hyperventilation, their HCO 3 will chronically decreased. However, this compensation by the kidney is not prompt or immediate. So in a patient with acute respiratory acidosis like one given 10mg morphine because of certain procedure, don t expect the HCO 3 to follow straight away. But once they increase after a few days, they are very appropriate because kidney doesn t get tired as much as lung. From slide 13 Slow response -Starts in 6-12 hours -Steady state in few days Respiratory acidosis -Stimulates HCO 3 reabsorption - HCO 3 Respiratory alkalosis -Inhibits HCO 3 reabsorption - HCO 3 Metabolic Compensation (continuation): Now the compensation rules for that Chronic Respiratory Acidosis HCO 3 = 0.35 PaCO 2 So approximately HCO 3 changes by one third (1/3) of what PaCO 2 changes
Chronic Respiratory Alkalosis HCO 3 = 0.5 PaCO 2 Let s give you an example: A patient with COPD presented with PaCO 2 = 80 meq/l increased by 40 According to the equation the expected change in HCO 3 will be: HCO 3 = 0.35 x 40 = 14 meq/l so we expect from the kidney to retain HCO 3 and HCO 3 will elevate to be = 14 + 24 = 38 (doctor said 40) So he came to the ER with PaCO 2 = 80 and HCO 3 = 40 it s a compensated respiratory acidosis The importance of this is that I know there is no acute problem. When I see such readings it means that the patients is having chronic compensated respiratory acidosis, it s true that the patient is chronically ill but at least he is stable, he doesn t need immediate intervention On the other hand if a patient came with PaCO 2 = 65 meq/l and HCO 3 =26 meq/l PaCO 2 = 25 HCO3= 0.35 x 25 8 expected HCO3 = 8 + 24 = 32 meq/l In this case there is an acute problem and the patient needs more attention. The two serious problems in acid base imbalance are Metabolic acidosis and Respiratory acidosis Metabolic Acidosis: Metabolic acidosis is grouped according to the anion gap (AG). What is anion gap? It is the difference between the sum of the measured cations and measured anions in the plasma or serum calculated as follows: {[Na +] ([Cl-] + [HCO3-])}. The word 'gap' is misleading, because in our body anions must equal cations otherwise the body won't be neutral! So why is there a 'gap'? There are hidden anions like the negatively charged plasma proteins that are unmeasured; this anion gap estimates the unmeasured anions.
Normal AG= (9-12 meq/l), if AG is > 20, we call it wide AG Usually the normal value is around 10, any number above 15 or 20 means we have a fixed acid in the serum Wide Anion Gap Metabolic Acidosis: (Usually caused by serious problems). -Causes of wide anion gap metabolic acidosis are best remembered by the popular mnemonic MUDPILES or KULT: M = Methanol U = Uremia (renal failure). D = DKA and ketoacidosis P = Paraldehyde I = Iron & Isoniazid INH L = Lactic acidosis (usually due to sepsis). E = Ethanol and Ethylene Glycol S = Salycilate K = Ketoacidosis (DKA, alcoholic ketoacidosis, starvation) U = Uremia (Renal Failure) L =Lactic acidosis T = Toxins (Ethylene glycol, methanol, paraldehyde, salicylate) If you look at them they are all serious, but in our country you may see DKA, lactic acidosis, and Uremia (renal failure). The common cause of lactic acidosis is shock. Methanol is serious, it affects the eyes and cause blindness. Ethylene glycol causes renal failure, its crystals deposit in the glomeruli. Salicylate can be fatal also If I get a patient with HCO 3 =12 and low PaCO 2, this looks like a pure metabolic acidosis, it is important for this patient to be investigated further: lactic acid level, blood sugar, salicylate overdose, ethanol level, KFT This is different from normal anion gap, which is a more benign condition Non (normal) Anion Gap Metabolic Acidosis Hyperalimentation (over IV feeding). Acetazolamide (drug we use it to induce metabolic acidosis), amphotericin B (patients who have immunosuppression take it for fungal infections) RTA Renal Tubular Acidosis. Ureteral Diversions. Diarrhea- obvious cause, the patient loses HCO 3 with diarrhea Pancreatic fistula. Saline resuscitation.
So the causes of Normal anion gap metabolic acidosis are not serious and more easily managed Metabolic Alkalosis : Characterized by : - Primary in HCO 3 concentration - Compensatory in PaCO 2 Classified according to urinary chloride - Chloride responsive: when Cl is high in urine. Usually, the cause is vomiting in this group. - Chloride resistant. Metabolic Alkalosis -Chloride Responsive: Urine Cl - > 20 meq/l. Caused by: Volume Contraction: - Nasogastric suctioning - Vomiting - Diuretics Post Hypercapnia, when PaCO 2 is high HCO 3 increases to compensate, suddenly the hypercapnia is relieved by hyperventilation or HCO 3. What will remain? HCO 3 alone! Because it takes time to go back to normal. Hypokalemia. Hypomagnesemia. - these 2 disorders are missed in medicine. Penicillin. Diuresis.
Metabolic Alkalosis - Chloride Unresponsive: Urine Cl - < 20 meq/l. Caused by: Mineralcorticoid excess Exogenous steroids (most common cause) Alkali Ingestion Licorice Too much wine Tobacco chewers Bartter s Syndrome (they like to put questions about it in the exam) Cl - responsive if you give them normal saline infusion they will get benefit, whereas Cl - unresponsive they won't. Solving Acid Base Disorders :
This is a way to validate blood gases to know if its value is correct or not [H + ] = 24 PaCO 2 / [HCO 3 - ] For example the normal [H + ] = 24 40/ 24 = 40 80 40 = 40 ph = 7.40 So if you looked at the blood gases and it says the ph= 7.57 this means the values are wrong because if the PaCO 2 is 40 and the HCO 3 is 24 then we expect the ph to be normal or around that like 7.39 or 7.38 but if it is 7.57 then I don t rely on this reading there must be something wrong with it. We look at the blood gases if the ph < 7.40 this means that the primary concern is Acidosis if the ph > 7.40 then the primary concern is Alkalosis Now if the primary concern is on the acidosis site and the PaCO 2 explains it (meaning it s high), then this is respiratory acidosis while if the HCO 3 is very low and explains it then it s metabolic acidosis, in this simple way. So if the ph= 7.30 and the HCO 3 = 15 metabolic Acidosis if the ph= 7.50 and the PaCO 2 = 20 respiratory alkalosis This is how you do it in a simple manner. Here we calculate the compensation rules that we talked about if it is outside the range then it s a mixed disorder, and there are some examples later on. If the patient s PaCO 2 = 80 then the HCO 3 should be 40, if the HCO 3 = 20 then this indicates Mixed metabolic acidosis, while if the HCO 3 = 50 then mixed metabolic alkalosis. Let s give you some case studies : Case Study - 1: A 39 year old woman was admitted with a history of generalized weakness, dyspnea, continuous nausea and diarrhea. Bowel motions were frequent and watery. ABG: ph 7.29, PaCO2 25.6, PaO2 98 Na+=125, K+=2.8, Cl-=101, HCO3=14
I know that diarrhea causes non anion gap metabolic acidosis Let s look at the ABG: the ph 7.29 acidosis, what explains it from these readings? the low HCO 3 this is metabolic acidosis Calculate the anion gap [Na +] ([Cl-] + [HCO3-]) 125 (101 + 14) = 12 So this is a normal anion gap metabolic acidosis most likely caused by the diarrhea Case Study - 2: A 78 year old lady presented with at a 1 week history of abdominal pain and vomiting. ABG: ph 7.49, PaCO2 52, PaO2 78 Na 137, K 2.2, CL 91, HCO3 38 Urine CI 43 meq/l. Vomiting causes metabolic alkalosis because you lose H + in the vomitus ph = 7.49 explained by HCO 3 = 38 metabolic alkalosis We said in metabolic alkalosis for every HCO 3 by 1 then the PaCO 2 by 1 (give or take, it s not a strict rule) HCO 3 is increased by 14 and the PaCO 2 is increased by 12 it s compensated So this is a simple metabolic alkalosis secondary to vomiting Whatever the acid base disorder, if there is a wide anion gap this indicates presence of metabolic acidosis.
Case Study - 3: A 21 year old MS is brought to the ER at ~3 am, stuporous and tachypneic. History is remarkable for failing the respiratory module in 2nd year. An ABG and electrolytes have been drawn by the ER nurse. ABG: ph=7.43, PaCO2=18 Na + =143, K + =3.8, Cl - =106, HCO3=12 ph =7.43 slightly on the alkalosis side PaCO 2 = 18! Very low respiratory alkalosis. HCO 3 = 12. low; Compensatory? Mixed? compensation HCO3 = (0.5) PaCO 2 HCO3 = 11 so we expect the HCO 3 to decrease by 11 24-11 = 13 Then this is a chronic respiratory alkalosis We have to calculate the anion gap. AG = 143 (106+12) = 25 wide AG metabolic acidosis; that s why the ph is like this What can cause such a condition? It s toxicity the ethanol and methanol depress the respiratory center, whereas aspirin stimulates the respiratory center so this is a classic aspirin overdose Primary Respiratory Disorders- Acute vs. Chronic: ACUTE PaCO2 = 10 ph=0.08 (~0.1) CHRONIC PaCO2 = 10 ph=0.03 In acute respiratory acidosis, ph = 0.008 Δ PaCO2 In chronic respiratory acidosis, ph = 0.003 Δ PaCO2. Acute usually is serious and needs intervention like bipap machine or whatever mechanical ventilation while Chronic needs only outpatient care
Another example PaCO 2 = 40 if it is acute ph = 0.008 40 0.4 the ph expected to be 7.00 If it is chronic ph = 0.003 40 = 0.12 the ph will be 7.28 if it is chronic The ph =7.33 because he has a chronic metabolic alkalosis, these patients are usually on steroids and diuretics Case Study - 4: A 55 year old woman presented to the ER with dyspnea and wheezes. She is heavy smoker. An ABG and electrolytes have been drawn by the ER nurse. ABG: ph=7.33, PaCO 2 =65 Na + =144, K + =4.2, Cl - =104, HCO 3 = 32 ph =7.33 acidosis. PaCO2 = 65! Respiratory acidosis. HCO3 high (compensatory). Compensation : Δ HCO3= 1/3 Δ PaCO2 Δ PaCO2 = 65 40 = 25 Δ HCO3= 1/3 25 =~ 8 8 + 24 = 32 AG = 144 (104+32) = 8 normal. Chronic compensated respiratory acidosis. What is the significance of knowing whether the case is acute or chronic? When a patient comes to the ER with respiratory acidosis we have to assess his case if it is acute or chronic, because if I know that his case is chronic I will be sure that nothing new has happened to him, I can give him nebulizers and steroids then send him home..the END. Done by, Siti Zulaikha Hairuddin (B1) Big thanks to those who help me for this lecture. May Allah bless you in everything you do enshallah