The Balance of Acid and Base — Two Hands on a Seesaw, the Quick Lungs and the Slow Kidneys

"The Blood Has Tipped Toward the Acid Side"

During visiting hours in the intensive care unit, the attending physician looks at the results of blood drawn from an artery and says, "The blood has tipped toward the acid side." The family nods, but they do not really know what it means for blood to tip toward the acid side, or why it is a cause for worry.

Similar words are exchanged in the emergency room. A person who has had diarrhea for days due to gastroenteritis and another who has vomited repeatedly take blood tests side by side. Both have upset stomachs, yet they are told that one has tipped toward the acid side, and the other toward the opposite side.

This primer follows only as far as needed to understand those words. The acid and base of the blood balance like a seesaw placed in the middle, and two hands hold the two ends of that seesaw. One hand is the fast-moving lungs, and the other is the slow-moving kidneys.

The lungs are organs located one on each side inside the chest, exchanging oxygen and carbon dioxide between the inhaled air and the blood. The kidneys are bean-shaped organs, one on the left and one on the right in the upper back, that filter the blood to send waste products and excess water out in the urine. In Sino-Korean vocabulary, they are called sinjang.

We will look in turn at which end of the seesaw moved first and which way the seesaw tipped, going as far as how the three boxes on the test report record it. Reading the report and sorting out the cause is the doctor's job, so this article does not teach you how to make that diagnosis.

A Mountain Made Every Day, a Narrow Range of pH

The human body makes acid every single day without fail. It is acid made while burning the protein in food and while cells do their work, and this acid must be sent out or neutralized by the kidneys and lungs every day (PMID 3931455).

How much acid is present is shown by a single scale. pH is a scale showing whether something dissolved in water leans toward acid or base, with smaller numbers being more acidic and larger numbers being more basic. 7 is right in the middle. Lemon juice sits on the acidic side, and soapy water sits on the basic side.

The blood of a healthy person moves within a very narrow band between pH 7.35 and 7.45 (PMID 30066586). It is ever so slightly on the basic side of the middle. Even when what you eat, how you move, and the height of where you live change, this band must always be kept (PMID 30066586). Moving even a little outside this band brings large consequences for the body (PMID 38536494).

There are two directions to states that shake this scale. Acidosis is a state where acid builds up or base is lost in the body, making the blood lean toward the acidic side. Alkalosis is a state where base builds up or acid is lost, making the blood lean toward the basic side.

When it tilts, the body finds it hard to hold on. If acid builds up suddenly and the blood tilts toward the acidic side, the blood pumped out by the heart decreases, blood vessels widen so blood pressure drops, and the heart's rhythm easily becomes disordered (PMID 20308999). If acidosis continues for a long time, muscles break down more and bone metabolism gets thrown off (PMID 20308999). Even if base builds up and it tilts toward the basic side, the brain, heart muscle, body muscles, and liver are affected (PMID 16736446).

That is why the body holds onto this scale with multiple devices. They are chemical absorption devices inside the blood, the kidneys sending out acid, and the lungs changing the depth and speed of breathing (PMID 3931455). The pH of blood must stay within a very narrow span, and the body uses both the lungs and the kidneys together to protect that span.

Catching It First — Buffering and Bicarbonate

When acid enters the blood, before the lungs or kidneys move, the blood catches it right inside. Buffering is when acid or base enters the blood and is caught by being held onto, so the pH does not swing wildly.

The leading substance in charge of that job is bicarbonate. Bicarbonate is the primary substance in the blood that catches acid, and it stands on the side of bases. On a test result, it is written as HCO3.

The acid caught by bicarbonate becomes carbon dioxide and leaves through the breath (PMID 37341662). In exchange, that much bicarbonate is reduced (PMID 17936961). Refilling that reduced bicarbonate is the job of the kidneys (PMID 40175031).

Carbon dioxide is also an acid. Among the acids the body makes every day, the much larger share by amount is the carbon dioxide produced when burning fats and carbohydrates, which we then breathe out (PMID 37341662). Therefore, blood acid and base have two main characters. Carbon dioxide stands on the acid side, and bicarbonate stands on the base side. Blood pH is determined by the ratio of these two amounts (PMID 2648667).

Here, picture a seesaw. Carbon dioxide sits on the left end, bicarbonate sits on the right end, and when the seesaw is flat, the pH is within the normal range. If the carbon dioxide end gets heavier, the seesaw tilts toward the acid side; if the bicarbonate end gets heavier, it tilts toward the base side. The lungs hold the carbon dioxide end, and the kidneys hold the bicarbonate end.

Blood pH is determined by the ratio of carbon dioxide and bicarbonate, with the lungs holding the carbon dioxide end and the kidneys holding the bicarbonate end.

A Fast Hand, the Lungs

Every time we breathe out, we get rid of carbon dioxide. How hard this hand is working is measured by the carbon dioxide left in the blood. Partial pressure of carbon dioxide is the amount of carbon dioxide dissolved in arterial blood expressed as a pressure unit, and it is written on the report as PaCO2.

If you breathe rapidly and deeply, this value goes down; if you breathe slowly and shallowly, it goes up (PMID 30725604). Just by changing the depth and speed of your breath, you can move one end of the seesaw in a short time, which makes the lungs a fast hand. We will look once more later at cases where this speed actually causes problems.

The lungs are a fast hand that sends out carbon dioxide with breath, and the PaCO2 on the report shows the tip of that hand.

Slow Hands, the Kidneys

The kidneys maintain the balance between acid and base by excreting acid into the urine, reclaiming filtered bicarbonate, and generating new bicarbonate (PMID 40175031). The mechanism by which bicarbonate is filtered and reclaimed was already traced in "How Do the Kidneys Filter Blood? — A Sieve That Takes Almost Everything Back". This article simply inherits the fact that this work is the hand holding down the bicarbonate end of the seesaw.

This hand is slow. In people whose carbon dioxide has remained high for a long time due to breathing problems, the kidneys retain bicarbonate, causing bicarbonate to rise much higher than it would during a sudden spike (PMID 11262556). It is about filling the bicarbonate end to match the heavier carbon dioxide end. The kidneys do this work slowly in tune with prolonged changes, and this picture of one hand making up for the other will be revisited later.

The hand itself can also break. Chronic kidney disease is a state where the kidneys are damaged or kidney function is impaired for three months or longer. In chronic kidney disease, the blood tilting toward the acid side is a common complication (PMID 38791238). Rarely, only the tiny tubes inside the kidneys that excrete acid or reclaim bicarbonate break, resulting in a disease where the kidneys fail to maintain the balance between acid and base (PMID 33367987).

Although the seesaw has only two hands, the liver is known along with the kidneys and lungs as an important organ in the body that lends a hand to the balance between acid and base (PMID 28684104). That third hand is left outside the picture in this article.

The kidneys are slow hands that discard acid and reclaim bicarbonate, moving slowly in tune with prolonged changes.

The Four Branches — Which End, and in Which Direction

Now we divide the tipping of the seesaw into two pairs. First is which end moved first, and second is which direction it tipped. Acid-base imbalances are divided into those that begin with a change in carbon dioxide and those that begin with a change in bicarbonate (PMID 3931455). If it starts at the carbon dioxide end, we call it respiratory; if it starts at the bicarbonate end, we call it metabolic.

The name metabolic means that the bicarbonate end moved first, not that the kidneys are broken. It is also metabolic when too much acid is made inside the body or when bicarbonate is lost through the intestines, and many causes lie outside the kidneys (PMID 40175031, PMID 17936961). Respiratory also means that the carbon dioxide end moved first, not always that the lungs are broken.

Respiratory acidosis is a state where the lungs fail to exhale all the carbon dioxide, leading to a buildup of carbon dioxide and a tilt of the blood toward the acid side. Examples include when breathing is suppressed by taking too many pills, or when a disease that narrows the airways like asthma suddenly worsens (PMID 11262556). Broadly, it is divided into diseases of the lungs, diseases of the chest wall and breathing muscles, and cases where the brain that regulates breathing is suppressed (PMID 37341662).

Respiratory alkalosis is a state where a person breathes more than necessary, causing carbon dioxide to be lost excessively and tilting the blood toward the base side. Diseases that increase breathing are usually the cause (PMID 37341662). This is the most common acid-base imbalance in chronic liver disease (PMID 28684104).

Metabolic acidosis is a state where acid builds up or bicarbonate is lost, tilting the blood toward the acid side. There are three paths. They are when acid is made rapidly and in large amounts, when a lot of bicarbonate is lost, and when the kidneys fail to excrete acid (PMID 40175031). The representative cause for losing bicarbonate is diarrhea, and it can also be lost through the kidneys (PMID 17936961).

The representative causes for making a lot of acid are twofold. One is ketoacidosis arising from diabetes. Diabetic ketoacidosis is an emergency state in which a lack of insulin lets acidic substances called ketones build up in the blood, tilting the blood toward acidity.

The other is when lactic acid increases. Lactic acidosis is a state where lactic acid in the blood is elevated while the blood tilts toward the acid side (PMID 26378980).

A common setting for lactic acidosis is severe infection. Sepsis is a state where the body's response to infection backfires and harms the body, preventing organs from doing their jobs. Lactic acidosis is common when sepsis is severe, and it goes hand in hand with a poor course (PMID 26378980).

Metabolic alkalosis is a state where bicarbonate builds up or acid is lost, tilting the blood toward the base side. Whether acid is lost or bicarbonate builds up, on the seesaw it is the side where the bicarbonate end becomes heavier (PMID 35525634). Acid can be lost through the gastrointestinal tract or the kidneys, and vomiting and certain diuretics are commonly cited together as causes (PMID 35525634).

Which end moved first separates respiratory from metabolic, and which direction it tipped separates acidosis from alkalosis.

Another Hand Steps In — Compensation

When one end of a seesaw dips, the other hand does not stay still. Compensation is the response where, when one side of acid and base shifts, the other organ changes how much it handles to pull the pH back toward normal.

In metabolic acidosis, the lungs breathe more to lower carbon dioxide (PMID 3931455, PMID 20308999). As much as the bicarbonate end has grown light, the lung's hand lifts the carbon dioxide end as well, pulling the seesaw back toward flat. In metabolic alkalosis, the opposite happens: breathing less lets carbon dioxide rise (PMID 35525634). If respiratory acidosis lasts a long time, the kidneys hold onto more bicarbonate (PMID 11262556).

That is why, when compensation happens, other boxes on the report move too. One end is the side that first shifted, and the other end is the side that moved to fill the gap. One of the things a doctor looks for on a report is whether this filling movement matches what is expected (PMID 40728495).

The difference in speed between the two hands shows up in compensation too. Someone whose carbon dioxide end has been heavy for a long time—like a person with lung disease whose airways stay narrowed—has had their kidneys fill the bicarbonate end to match, keeping the seesaw balanced. If a machine is then used to quickly increase breathing and suddenly lighten only the carbon dioxide end, the heavily filled bicarbonate end stays behind because the kidneys cannot clear it away just as fast. As a result, the seesaw can tip severely over to the alkaline side (PMID 37434801). It is a picture where the fast hand has gone back to its place, but the slow hand has not caught up yet.

You can see how long the slow hand takes by looking at high places. When someone suddenly goes to a high altitude, respiratory alkalosis occurs—meaning the carbon dioxide end becomes too light—and kidney compensation partly corrects it (PMID 16544968). The kidneys send more bicarbonate out in the urine, which is a move that lightens the bicarbonate end as well, reducing the tilt toward the alkaline side.

There is an experiment where 48 healthy adults spent a day each in a room with lowered air pressure, like being on a mountain (a hypobaric chamber), and their urine was measured. After six hours, the kidneys at all altitudes were noticeably sending out more bicarbonate in the urine. At the three lower of the four altitudes tested, this response settled down within a day, but at the highest condition, it continued even after a day had passed (PMID 16544968). This means the slow hand moves over the course of several hours to a day, and at the highest places, a day was not enough. This experiment is a single chamber study that measured only urine, and did not measure people who climbed an actual mountain.

There are also cases that are easy to confuse with compensation. If two or more abnormalities overlap in one person, pushing against each other can bring the pH close to normal, and pushing in the same direction can tilt it much further (PMID 40728495). Even when the pH is close to normal, acid and base abnormalities may be hiding underneath.

The Same Enteritis, Opposite Directions

We return to the two people in the emergency room we saw at the start. Both have enteritis, but what they have lost is different.

A person who has had diarrhea for days loses bicarbonate through the intestines (PMID 17936961, PMID 25405229). Because the bicarbonate end of the seesaw grows lighter, the blood tilts toward the acidic side, resulting in metabolic acidosis. In metabolic acidosis, a compensation follows where the lungs breathe more to lower carbon dioxide (PMID 3931455).

A person who has repeatedly vomited loses acid while vomiting. When acid is lost, an equivalent amount of bicarbonate remains, making the bicarbonate end of the seesaw heavier. Therefore, the blood tilts toward the basic side, resulting in metabolic alkalosis (PMID 35525634). At this time, a compensation follows where breathing slows down so that carbon dioxide rises (PMID 35525634). When body water decreases or potassium is lacking, the kidneys are hindered in excreting the excess bicarbonate, making alkalosis develop or preventing it from resolving easily (PMID 35525634).

The test results of the two people point in opposite directions. Even with the same upset stomach, what was lost determines which side the seesaw tilts toward.

When diarrhea and vomiting occur together in one person, changes from both directions overlap. When abnormalities in opposite directions overlap, the test results vary depending on which one is greater, and the pH may even appear close to normal (PMID 40728495). You cannot tell whether someone is well from that single pH value alone. How much of each direction has overlapped is sorted out by the doctor, who looks at other boxes on the report sheet and the medical history together.

Even the same enteritis tilts the seesaw toward the acid side if bicarbonate is lost, and toward the base side if acid is lost.

The Three Boxes on the Report

The results heard by a guardian in the intensive care unit usually come from a blood gas test. A blood gas test is a single blood draw that looks at pH, the amounts of oxygen and carbon dioxide, and bicarbonate all at once (PMID 41473681).

When looking at acid and base, the report has three boxes you check first. pH shows which way the seesaw is tipping, PaCO2 shows the carbon dioxide end, and HCO3 shows the bicarbonate end. PaCO2 tells us how well breath is moving in and out, while the oxygen box on the same report tells us how much oxygen the blood has received (PMID 30725604).

The three boxes do not all come about in the same way. A blood gas machine usually measures pH and PaCO2 directly, and calculates bicarbonate from the two (PMID 30725604). A box labeled "CO2" or "total carbon dioxide" on a routine blood test report is a directly measured value, which is a box read alongside the bicarbonate calculated from the blood gas. Because one value is calculated and the other is measured, the two values usually come out a little different, and in intensive care patients they can differ by more (PMID 30725604).

Drawing blood from an artery hurts and can bring complications, so measurements are sometimes taken from venous blood instead. The pH of venous blood matches arterial blood well, and bicarbonate usually matches well too, but how well carbon dioxide matches is debated, and oxygen differs greatly (PMID 40870384).

Reading the report involves a method of interpretation that follows a set order. You check in turn which of the three boxes moved first, and whether the movement of the other boxes can be explained as compensation (PMID 37125739). That order incorporates medical history, physical examination, and other tests together.

When metabolic acidosis appears, there is one more value calculated. The anion gap is a value calculated from the electrolyte numbers on a routine blood test, and is used to divide metabolic acidosis into two groups depending on the cause (PMID 34400023). This calculated value grows larger in ketoacidosis and lactic acidosis, and does not grow larger when bicarbonate is lost through diarrhea (PMID 17936961). The range of normal values varies widely depending on the measurement method and the person (PMID 17699401).

The three boxes on the report show the tip of the seesaw and its two ends, and reading them in order is the doctor's task.

Reading the Four Kinds on a Report — With Arrows

Put the three boxes on the report against the seesaw, and the four kinds can be read by whether each box went up or down. First look at pH to see which way the seesaw tipped; then see which of PaCO2 and HCO3 produced that tip, and whether the other box moved to make up for it (PMID 37125739).

Metabolic acidosis is low pH and low HCO3, with PaCO2 falling as breathing increases to make up (PMID 3931455, PMID 20308999). In metabolic alkalosis, HCO3 and pH rise first, and PaCO2 follows upward as breathing slows (PMID 35525634). Respiratory acidosis is PaCO2 rising first, and when it lasts, the kidneys adapt and HCO3 rises further (PMID 11262556). Respiratory alkalosis is PaCO2 falling first from breathing too much (PMID 37341662), and, as in the decompression-chamber experiment above, the kidneys follow by letting more bicarbonate out in the urine (PMID 16544968).

Read the table down its columns and one thing stands out. In all four kinds, PaCO2 and HCO3 move in the same direction. When one end gets lighter, the other hand lightens its end too; when one end gets heavier, the other hand adds to its end. And pH tips the way the box that moved first points.

For someone brought in with ketoacidosis, a report with pH down, HCO3 down, and PaCO2 also down from deep, fast breathing is the picture of metabolic acidosis (PMID 3931455, PMID 32409703). Whether the making-up box moved by the right amount, though, has to be judged separately. If that movement does not fit, two or more disturbances may be overlapping, and sorting this out is the job of a doctor looking at the history, the examination and other tests together (PMID 40728495).

In all four kinds PaCO2 and HCO3 move in the same direction, and pH tips toward the box that moved first — which box moved first decides the kind.

Causes Over Numbers

When you receive a lab report that leans toward the acidic side, treatment generally looks to the cause rather than the number. Acid-base imbalances are mostly treated by addressing the underlying disease that caused the imbalance, rather than trying to fix the acid and base directly (PMID 37758428).

There is also treatment that directly supplies bicarbonate. In sudden metabolic acidosis, administering bicarbonate has no evidence of reducing mortality. However, in high-risk patients complicated by moderate or severe acute kidney injury—where the kidneys suddenly do less work over the course of a few days—it reduced the instances where treatments like dialysis became necessary (PMID 41328521). That review concludes that the risks and benefits must be weighed for each individual patient, and that more randomized trials are needed (PMID 41328521). This treatment also comes with side effects, such as the inside of cells actually leaning toward the acidic side, and drops in potassium and calcium (PMID 27876158).

Chronic kidney disease is slightly different. A 2017 review advised caution or against using bicarbonate in most cases of metabolic acidosis, yet singled out kidney disease as an exception where bicarbonate might be useful (PMID 27876158). A 2024 review summarizes that the results of clinical trials attempting to protect kidney function have been mixed, and that large trials to sort out efficacy and safety are needed (PMID 38791238).

Acid-base imbalances are mostly treated by addressing the cause, and the evidence for treatments that add bicarbonate varies depending on the situation.

What the Test Report Cannot Tell You

The report shows which way the seesaw has tipped, but it does not write down why it tipped. The cause is usually revealed by the medical history and physical examination. This is why, if a person with diabetes has very high blood sugar, doctors think of ketoacidosis first, or if someone has sepsis and low blood pressure, they think of lactic acidosis first (PMID 36175073). However, there is also ketoacidosis without very high blood sugar (below). When the cause is not clear, doctors narrow down the range using values like the anion gap to choose further tests (PMID 36175073).

What each number on the report means for that specific person is decided by the doctor who knows the patient's illness. Even if the pH is near normal, multiple abnormalities can overlap (PMID 40728495), and even if the numbers are skewed, their meaning must be determined by reading them alongside the person's illness.

There are also cases where time changes the outcome. Diabetic ketoacidosis is a life-threatening complication, and it can be the way the disease first appears in someone who did not know they had diabetes (PMID 39556629). The most common symptoms are increased urination and severe thirst, followed commonly by nausea and vomiting, abdominal pain, weight loss, severe fatigue, and shortness of breath. There are also cases where the person had a fever-causing illness beforehand (PMID 39556629). Because ketoacidosis without very high blood sugar has increased, recent guidelines have lowered the weight given to blood sugar in diagnosis (PMID 39556629).

Treatments include intravenous fluids, insulin, electrolyte replacement, and treating the underlying trigger. Catching it early and treating it early is most important for improving outcomes (PMID 32409703). If not treated properly the harm is great, but that harm can mostly be prevented (PMID 32409703).

The acid-base report shows which way the seesaw has tipped and which hand is compensating, but a doctor reads why it tipped together with the medical history, physical examination, and other tests.

Where to Look Next

The principle by which the kidneys filter and reclaim bicarbonate is covered in "How Do the Kidneys Filter Blood? — A Sieve That Takes Almost Everything Back", while creatinine and eGFR on a test report are covered in "Reading Your Kidney Test Results — A Sieve You Cannot See, What Stays Behind and What Leaks Through". The disease where kidney function weakens over a long period is followed in "What Is Chronic Kidney Disease? — Lamps Going Out One by One, and the Load on Those Still Lit", cases where it stops suddenly in "What Is Acute Kidney Injury? — A Tap That Suddenly Runs Dry, and Three Places to Look", and treatments that filter the blood in place of the kidneys in "Dialysis and Kidney Transplantation — Three Sieves That Stand In, and the Path That Uses None".

On the lung side, "How Do We Breathe? — An Upside-Down Tree, and the Leaves Where Air Meets Blood" looks at the place where air and blood meet, and "What Is COPD? — A Balloon That Won't Empty, and the Breath That Leaves in the First Second" and "Reading A Spirometry Report — One Point Among Your Peers, Two Graphs Drawn by a Breath" look at the disease where airways narrow for a long time and that test. The issue of airways closing during sleep is handled by "Insomnia and Sleep Apnea — The Alarm That Won't Switch Off, the Airway That Closes".

The disease that leads to ketoacidosis is covered in "What Is Diabetes? — The Letter That Never Comes, the Letter That Isn't Read", and the general principles for drawing the line for test numbers in "What a Test Actually Tells You — An Introduction to Sensitivity, Specificity, and Pretest Probability".

Whether using bicarbonate for the acidosis of chronic kidney disease protects the kidneys and the body is still a question trials are gathering answers for.

Source Papers

• "Simple acid-base disorders." (1985) — PMID 3931455 — Acids generated from protein oxidation and tissue metabolism are daily sent out or neutralized by the kidneys and lungs; acid-base homeostasis is maintained by chemical buffering, renal hydrogen ion excretion, and alveolar ventilation; metabolic involves primary changes in bicarbonate, respiratory in Pco2; metabolic acidosis shows a compensatory drop in Pco2 through hyperventilation.
• "Lactic Acidosis in Sepsis: It's Not All Anaerobic: Implications for Diagnosis and Management." (2016) — PMID 26378980 — Lactic acidosis (hyperlactatemia + pH below 7.35) is common in severe sepsis and septic shock and linked to morbidity and mortality; not all lactate production is due to tissue hypoxia.
• "Metabolic acidosis: pathophysiology, diagnosis and management." (2010) — PMID 20308999 — Metabolic acidosis features a primary decrease in bicarbonate, secondary decrease in PaCO2, and drop in pH; acute forms predispose to decreased cardiac output, hypotension, and arrhythmias; chronic forms increase muscle breakdown and bone metabolism abnormalities; acute base treatment remains controversial.
• "Metabolic alkalosis." (2006) — PMID 16736446 — Metabolic alkalosis is caused by an increase in bicarbonate or loss of non-volatile acid, affecting the central nervous system, myocardium, skeletal muscle, and liver.
• "Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023." (2023) — PMID 37341662 — Normal ventilation is an open buffering system that clears CO2 produced by the reaction of non-volatile acids and bicarbonate; quantitatively, CO2 elimination from the complete oxidation of fats and carbohydrates is much greater; three causes of respiratory acidosis (gas exchange, chest wall and respiratory muscles, medullary respiratory center depression); respiratory alkalosis is a condition of increased alveolar ventilation; both can cause life-threatening complications.
• "Metabolic acidosis." (2007) — PMID 17936961 — Metabolic acidosis results from endogenous acid accumulation that consumes bicarbonate (increased anion gap: lactic acid, ketoacids, etc.) or gastrointestinal and renal bicarbonate loss (normal anion gap: gastrointestinal loss, etc.); administering bicarbonate in acute organic acidosis improves markers but does not reduce morbidity or mortality.
• "Simple acid-base disorders." (1989) — PMID 2648667 — Blood pH is a function of the ratio between bicarbonate concentration and PCO2; there are four simple acid-base disorders; treatment focuses on diagnosis and correction of the underlying disease.
• "Post-Hypercapnic Alkalosis: A Brief Review." (2023) — PMID 37434801 — Rapidly correcting hyperventilation in chronic hypercapnia patients normalizes pCO2 quickly, but renal compensation lags behind, leaving high bicarbonate and resulting in severe metabolic alkalosis, which is linked to increased ICU stay and mortality.
• "Respiratory acidosis." (2001) — PMID 11262556 — Respiratory acidosis is a primary rise in arterial carbon dioxide partial pressure; acute events involve the pulmonary parenchyma, airways (COPD, asthma), chest wall, neuromuscular system, or central nervous system (drug overdose); chronic forms show a greater rise in bicarbonate due to renal adaptation; primary impacts are on the central nervous system and cardiovascular system.
• "Metabolic Acidosis." (2025) — PMID 40175031 — The kidneys maintain acid-base homeostasis through proton excretion and bicarbonate reabsorption/generation; metabolic acidosis occurs from rapid non-volatile acid production, excessive bicarbonate loss, or impaired renal acid excretion; checking the anion gap is the first step in identifying the cause.
• "Metabolic Acidosis in CKD: Pathogenesis, Adverse Effects, and Treatment Effects." (2024) — PMID 38791238 — Metabolic acidosis is a common complication of chronic kidney disease and linked to adverse outcomes; clinical trial results on preserving renal function with bicarbonate are mixed, and trials of sufficient scale to determine efficacy and safety are needed.
• "Renal Tubular Acidosis and Management Strategies: A Narrative Review." (2021) — PMID 33367987 — Renal tubular acidosis occurs when the kidneys fail to maintain acid-base homeostasis due to defects in tubular acid excretion or bicarbonate reabsorption; types include distal, proximal, and hyperkalemic.
• "Acid-base disorders in liver disease." (2017) — PMID 28684104 — Along with the kidneys and lungs, the liver is an important regulator of acid-base homeostasis; the most common acid-base disorder in chronic liver disease is respiratory alkalosis; multiple metabolic abnormalities may offset one another.
• "Diabetic ketoacidosis." (2020) — PMID 32409703 — DKA diagnosis relies on three criteria: elevated blood glucose or a family history of diabetes, ketonemia, and metabolic acidosis with an increased anion gap; treatment centers on restoring circulating blood volume, insulin, electrolyte replacement, and treating the trigger; without optimal treatment, morbidity and mortality are substantial but mostly preventable.
• "Metabolic Alkalosis Pathogenesis, Diagnosis, and Treatment: Core Curriculum 2022." (2022) — PMID 35525634 — Metabolic alkalosis is characterized by a primary rise in bicarbonate and pH, with a compensatory rise in Pco2 driven by adaptive hypoventilation; acid loss occurs via the gastrointestinal tract or kidneys; volume depletion or potassium deficiency impairs renal bicarbonate excretion; it is associated with vomiting, diuretics, and other factors.
• "Mixed Acid-Base Disturbances: Core Curriculum 2025." (2025) — PMID 40728495 — Opposing effects of multiple disorders can yield a near-normal pH, while matching directions cause larger shifts; diagnosis relies on systematic evaluation, including assessing the appropriateness of compensatory mechanisms.
• "Sodium bicarbonate therapy in patients with metabolic acidosis." (2014) — PMID 25405229 — Supplementation is useful for patients who have lost bicarbonate due to diarrhea or proximal renal tubular acidosis; there is no definitive evidence that administering bicarbonate in acute metabolic acidosis benefits outcomes or mortality.
• "Blood gas analysis: Clinical applications, interpretation and future directions (Review)." (2026) — PMID 41473681 — Blood gas analysis rapidly evaluates respiratory and metabolic status using pH, oxygen partial pressure, carbon dioxide partial pressure, and bicarbonate.
• "The Role of Venous Blood Gas Analysis in Critical Care: A Narrative Review." (2025) — PMID 40870384 — Arterial blood gas is the standard but is invasive, uncomfortable, and carries complications; venous blood gas shows a strong correlation for pH and a good correlation as a bicarbonate substitute; pCO2 results are controversial; pO2 differs significantly.
• "A Systematic Approach to Understanding Acid-Base Disorders in the Critically Ill." (2024) — PMID 37125739 — Essential steps in arterial blood gas interpretation and a systematic approach to evaluating the four types of acid-base disorders.
• "Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021." (2021) — PMID 34400023 — The anion gap is a calculated value comparing sodium against chloride and bicarbonate, dividing metabolic acidosis into two categories to narrow down the range of causes.
• "Serum anion gap: its uses and limitations in clinical medicine." (2007) — PMID 17699401 — The anion gap is calculated from laboratory electrolytes; normal values vary widely due to differences in testing methods and inter-individual variation, yet it remains a cheap and useful tool.
• "Metabolic Acid-Base Disorders." (2023) — PMID 37758428 — Acid-base disorders in the emergency department are usually diagnosed through history and physical examination, and most require treating the underlying disease rather than the acid-base disturbance itself.
• "Treatment of acute metabolic acidosis." (2026) — PMID 41328521 — Sodium bicarbonate correction was not associated with reduced mortality, but it reduced the need for renal replacement therapy in high-risk patients with moderate-to-severe acute kidney injury; risks and benefits must be weighed, and further randomized trials are needed.
• "Is Bicarbonate Therapy Useful?" (2017) — PMID 27876158 — Evidence supporting the efficacy of bicarbonate administration is sparse, and it carries side effects such as intracellular paradoxical acidosis, hypokalemia, and hypocalcemia; focus should be on resolving the root cause, using it cautiously or avoiding it entirely, with kidney disease being a potential exception where bicarbonate may be useful.
• "Review of Clinical Disorders Causing Metabolic Acidosis." (2022) — PMID 36175073 — The causes of metabolic acidosis are usually revealed by history and physical exam (ketoacidosis if diabetic hyperglycemia is present, lactic acidosis if sepsis or hypotension); if unclear, cases are classified by anion gap type and investigated step-by-step.
• "Diabetic Ketoacidosis: Evaluation and Treatment." (2024) — PMID 39556629 — DKA is a life-threatening complication and may be the initial presentation of diabetes; polyuria and polydipsia are most common, alongside nausea, vomiting, abdominal pain, weight loss, severe fatigue, dyspnea, and preceding febrile illness; with rising rates of euglycemic DKA, recent guidelines place less weight on hyperglycemia.
• "Acid-base regulation in the renal proximal tubules: using novel pH sensors to maintain homeostasis." (2018) — PMID 30066586 — Plasma pH in healthy individuals is maintained within a very narrow range of 7.35 to 7.45 and must be constantly protected against meals, activity, and altitude changes; the proximal tubule is crucial for renal pH homeostasis.
• "The role of Na+-coupled bicarbonate transporters (NCBT) in health and disease." (2024) — PMID 38536494 — Even slight deviations of blood pH outside the normal range (7.35 to 7.45) have major consequences; sodium-coupled bicarbonate transporters protect intracellular pH in nearly all cells.
• "Urine acid-base compensation at simulated moderate altitude." (2006) — PMID 16544968 — 48 healthy men and women exposed to 4 stages of simulated altitude in a decompression chamber for 24 hours each: respiratory alkalosis from acute high-altitude exposure is partially corrected by renal compensation, with increased urinary bicarbonate at 6 hours; compensation is completed within 24 hours at low-to-moderate altitudes, but remains incomplete at the highest altitude.
• "Arterial Blood Gas Analysis: Fundamentals, Interpretation, and Clinical Utility." (2026) — PMID 30725604 — PaO2 in arterial blood gas provides information on oxygenation, PaCO2 on ventilation status; most machines measure pH and PaCO2 directly and calculate bicarbonate, whereas routine blood tests measure total CO2 directly, so minor differences between the two values are expected and can be larger in critically ill patients.