Most Things Biology

20.5 Acid–Base Balance & the Bicarbonate Buffer System

Case home  ·  Start at the beginning  ·  The Reveal

Time To Read

24–36 minutes

Date Last Modified

Fluids, Electrolytes & Acid–Base Balance · Chapter 5 of 7

You make acid all day — from protein, exercise, fat and every breath’s carbon dioxide — and never the matching base; blood pH is held between 7.35 and 7.45 anyway, by three tiers at three speeds. This chapter builds the hydrogen ion and the pH scale, the three buffers, the bicarbonate sponge with its two ends, and the kidney’s two tricks on a slide — and reads her bicarbonate of 20 as a sentence about which end is failing.

The question you will answer

The bicarbonate reaction runs both ways, the lungs on one end and the kidneys on the other. If one organ fails, whose job cannot be covered — and how would the numbers say so?

Opener · It’s All About the H⁺ · about 1¾ minutes

The opener is the same narrated animation you will watch in Scene 1.

Watch it in Scene 1 ↓

Watch the opener first. It sets the question; the chapter answers it.

1

Read the chart

Patient chart · Stina

2025 · age 50 · venous panel; ABG the next visit

Venous
Bicarbonate 20 mEq/L (22–26); chloride 108; anion gap 10 (normal); potassium 4.9.

Arterial (next visit)
pH 7.33 (7.35–7.45); PCO₂ 33 mmHg (35–45); HCO₃⁻ 19; PO₂ 94.

Exam
Respiratory rate 18, breaths a little deeper than she notices. No nausea. Urine pH 5.0.

For contrast
Mr. Wu (the site’s case): pH 7.28, PCO₂ 28, HCO₃⁻ 14, 22 breaths/min — renal acidosis.

Told
“Slightly low bicarb — we’ll recheck.”

Chart clues this module: 1 · The ankles · 2 · Compartments · 3 · The pull · 4 · The calcium · 5 · this chapter

Before you go on · your prediction

Bicarbonate 20, pH 7.33, PCO₂ 33, a normal anion gap. The disturbance is…

Open the one you lean toward. Nothing is recorded and nothing is revealed — you come back to it at the end.

Respiratory — her lungs are the organ breathing off CO₂, and her CO₂ is low

Ask what the pH does when CO₂ is the cause of a disturbance versus when CO₂ is the answer to one. Watch which direction pH and CO₂ move relative to each other.

Metabolic — bicarbonate is the number that moved first, and the low CO₂ is the lungs covering for a kidney

Ask what makes bicarbonate fall (lost from the gut, consumed by acid, not reclaimed or made by the kidney) and which of those her chart supports. Then ask what a normal anion gap adds.

Nothing — a bicarbonate of 20 is a rounding error and the pH is nearly normal

Ask what “nearly” means for a number held within a tenth of a unit by three organ systems, and what the lungs are doing to keep it there.

From Stina’s diary

2024 · age 49 · “A little protein”

2

The story

Three short movements: the case, the anatomy and physiology, then the tie back to Stina. Each links to the scene where you’ll see it move.

I · A number that drifts

The venous panel that flagged her calcium also carried a bicarbonate of 20, two points below the range, and a chloride at the top of its range. Nobody chased it. At the next visit someone drew an arterial sample: pH 7.33, carbon dioxide 33, bicarbonate 19. She was breathing eighteen times a minute, a little deeper than she knew. The site’s own case patient, Mr. Wu, had the same shape in a worse key — pH 7.28, bicarbonate 14, twenty-two breaths a minute, lungs working hard for failed kidneys. Hers is early. It is also the one flag on her page that is not downstream of albumin, and it points at the same organ by a different road.

See it move: Scene 1 · It’s All About the H⁺ · Scene 5 · Two Organs, Two Ends

II · The acid you make, and the three tiers that answer it

The pH lecture begins with a confession: water is not just H₂O; it exists as H⁺ and OH⁻ — Mickey Mouse with an ear chopped off, the proton leaving without its electron. pH measures the ratio of the two on a logarithmic scale from 0 to 14: 7 neutral, blood 7.35–7.45 — arterial 7.4, venous and interstitial 7.35 because of the CO₂, inside a cell about 7.0. You make hydrogen ions all day and never the matching hydroxide: from phosphorus-containing proteins and nucleic acids (phosphoric acid), anaerobic respiration (lactic), fat metabolism (ketones), and the carbon dioxide that becomes carbonic acid in every red cell. Life is a battle not to be acidic. Three tiers fight it, ranked by speed. Chemical buffers act in seconds: an acid is a proton donor (hydrochloric strong, carbonic weak), a base a proton acceptor (sodium hydroxide strong, sodium bicarbonate weak), and a buffer binds hydrogen ions when pH falls and releases them when it rises — bicarbonate in the ECF; phosphate in urine and inside cells; protein, two-thirds of the blood’s buffering, hemoglobin above all, which loads a proton every time it drops an oxygen. The respiratory centres act in minutes: carbon dioxide is an acid, so breathe faster and pH rises — doubling the rate for a minute raises it by about 0.2. The kidney acts in hours to days, and reluctantly: if the kidney is managing your pH, you are on thin ice.

See it move: Scene 1 · It’s All About the H⁺ · Scene 2 · Three Tiers, Three Speeds · Scene 5 · Two Organs, Two Ends

III · The sponge with two ends

The bicarbonate buffer is one reversible reaction: carbon dioxide plus water, through carbonic anhydrase in the red cell, gives carbonic acid, which splits into bicarbonate and a hydrogen ion — and it runs both ways, all the time. When acid rises, bicarbonate soaks it up and the reaction runs toward CO₂, which the lungs exhale; when acid falls, it runs the other way. Blood keeps an alkaline reserve of free bicarbonate, twenty parts to one of carbonic acid at a pH of 7.4, and an almost limitless supply of carbonic acid from the CO₂ every cell makes. Two organs command the two ends. The lungs work the CO₂ end: a panicked person who overbreathes blows it off and goes alkaline; a child with a toy stuck in the airway holds it and goes acidic. The kidney works the bicarbonate end with two tricks the Urinary slides show: the proximal tubule secretes hydrogen ions to reclaim every filtered bicarbonate; the collecting duct’s intercalated cells secrete hydrogen under aldosterone, and when the blood is acidic the tubule cells strip the amine from glutamine to make two ammonia molecules and two new bicarbonates — ammonia into the urine to trap hydrogen as ammonium, phosphate buffering the rest, down to a urine pH of 4.5. Only the kidney can remove the fixed acids — ketones, lactate, urate, phosphate, sulfate. A disturbance is named for the end that moved first: respiratory if CO₂ is the cause, metabolic if bicarbonate or fixed acid is. Her bicarbonate fell first; her CO₂ fell afterward, because her lungs are answering. That is a metabolic acidosis, and the organ that owns the bicarbonate end is the one with amyloid in it.

See it move: Scene 3 · The Bicarbonate Sponge · Scene 4 · The Kidney’s End, on a Slide · Scene 5 · Two Organs, Two Ends

3

Watch · explore · think · check

5 scenes. Each one has a short animation or a slide, something to explore, a true/false spot-check of your thinking, and a quick check. Every scene gives you an evidence card for your board.

How to read the scenes

  • Animation (dark teal) — a short animated explainer, one idea each
  • Slide (dark teal) — a still to study: a micrograph, a diagram or a map
  • Explore (purple) — something to push on while you watch
  • Game (purple) — a quick challenge
  • Think (gold) — reason it out, then spot-check yourself with a few true/false questions; not graded
  • Check (gold) — a quick H5P that scores itself

Scene 1 of 5

It’s All About the H⁺

Mickey Mouse loses an ear; the body makes acid all day.

Animation · in production · 1 min 50 s

It’s All About the H⁺

Water as H⁺ and OH⁻; the proton leaves without its electron. pH as the ratio, logarithmic, 0–14; 7 neutral; blood 7.35–7.45 (arterial 7.4, venous/IF 7.35, ICF 7.0); orange juice, coffee, stomach acid near battery acid; Tums, egg whites, bleach on the other side; and the student who asked whether 0 is the floor (it is not). The four sources of H⁺: protein/nucleic-acid breakdown (phosphoric acid), anaerobic respiration (lactic), fat metabolism (ketones), CO₂ transport (carbonic). The body’s default drift is acid; three tiers push back.

Prefer the full lecture? pH and Buffers (original video on the site)

Explore

Count the protons

Proton count

Open four acid taps on a beaker of blood and predict how far the pH moves. Then find each tap’s drain, look for a bottle of OH⁻, and count the protons at 7.33.

Text description of this explore

A beaker of blood drawn as a swarm of dots, one dot for each nanomole of free H⁺ per litre: 40 dots at pH 7.40. The beaker has blood’s buffers but no lungs or kidney attached. A legend shows filled dots for the starting H⁺ and open rings for H⁺ added since 7.40. Step 1: choose one of four taps (a day of protein breakdown, a hard sprint, a day of fasting, or every breath’s CO₂ held in for a minute), predict whether the pH barely moves, falls a little, falls hard or rises, then run it; the swarm gains dots and a readout lists the acid poured, bicarbonate, PCO₂, the bicarbonate to carbonic acid ratio, free H⁺ and pH. Step 2: for each tap, choose the drain that clears it (the lungs, the kidney, or the liver and muscle) and the acid it pours. Step 3: after the sprint (79 dots, pH 7.10), a bottle labelled OH⁻ stands beside the beaker; decide where the body gets OH⁻. Step 4: set the pH with a slider from 7.00 to 7.50 (it starts at 7.33), predict how much more free H⁺ there is than at 7.40, then run it; the readout gives free H⁺, the percentage change and the bicarbonate to carbonic acid ratio. Step 5: name what has happened to that ratio at 7.33.

Think · not graded

pH is a ratio, not a count, and the scale is logarithmic. A pH of 7.33 instead of 7.40 sounds trivial. Work out how much the hydrogen-ion concentration has actually changed, and say why three organ systems are built to prevent exactly that.

Spot-check your thinking: true or false?

Check · Single Choice

Why does the body’s default pH drift toward acid?

Evidence card 1

Add it to your evidence board

She makes acid like everyone; the question is which tier stopped answering.

Scene 2 of 5

Three Tiers, Three Speeds

Seconds, minutes, days — buffers, lungs, kidney.

Slide · a still to study

How the Body Manages H⁺

Three tiers, three speeds

  • Chemical buffers, in seconds: bicarbonate in the ECF, phosphate inside cells and in urine, and proteins, including hemoglobin, which hold most of the body’s buffering power.
  • Lungs, in minutes: CO₂ is an acid. Faster breathing blows it off and raises the pH; chemoreceptors in the carotid bodies, aorta and medulla set the rate.
  • Kidneys, in hours to days: reclaim bicarbonate, make new bicarbonate and excrete fixed acid.

Two definitions

  • A buffer is a weak acid and its base, which soak up or release H⁺.
  • A strong acid, like hydrochloric acid, gives up all its H⁺; a weak acid, like carbonic acid, gives up some.

When the kidney is the tier that is failing, nothing else can finish the job.

Fast and shallow, then slow and deep: the tier that fixes it for good is the one with amyloid in it.

Prefer the full lecture? pH and Buffers (original video on the site)

Game

Three stopwatches

Three stopwatches

Drop an acid load into a body with three stopwatches. Predict which tier answers when, take one tier away at a time, then put five buffers where they work.

Text description of this game

Three stopwatches labelled buffers, lungs and kidney sit above a pH trace that runs from an acid load through 1 minute, 1 hour and 1 day, with a shaded normal band from 7.35 to 7.45. Step 1: for each tier, choose when it acts (seconds, minutes, or hours to days) and what it does with the H⁺ (holds it, covers for it, or removes it); after you commit, the stopwatches show their times and the healthy trace draws: 7.29 at a minute, 7.36 at an hour, 7.39 at a day. Step 2: remove one tier (none, hemoglobin buffering, breathing, or the kidney) and choose a time point, predict whether the pH is near normal, a little low, low or very low, then run it; the trace draws to that point and a readout lists the tiers working, bicarbonate, PCO₂ and pH. Step 3: Stina’s kidney is the failing tier; decide where her trace parts company with a healthy one. Step 4: put five buffers (bicarbonate, phosphate, hemoglobin, albumin and other plasma proteins, ammonia) where they work.

Think · not graded

Buffers buy seconds, lungs buy minutes, the kidney buys the day. Her kidney is the tier that is failing. Predict what her pH trace looks like after an ordinary acid load — a run, a fever — compared with a healthy person’s, at one minute, one hour and one day.

Spot-check your thinking: true or false?

Check · Drag the Words

Order the three tiers of pH defense by speed.

Evidence card 2

Add it to your evidence board

Three tiers; the slowest is the only one that fixes a fixed acid, and it is hers.

Scene 3 of 5

The Bicarbonate Sponge

One reversible reaction, twenty to one, and the lungs’ end.

Animation · in production · 1 min 50 s

The Bicarbonate Sponge

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻, with carbonic anhydrase in the red cell; both directions, all the time. Add acid: bicarbonate soaks it, the reaction runs to CO₂, the lungs exhale it. The alkaline reserve; 20 : 1 at pH 7.4; a limitless carbonic-acid supply from the CO₂ cells make. The lungs’ end: overbreathing (CO₂ off, alkaline), a toy stuck in the airway (CO₂ held, acidic), breathing into a bag; the dorsal and ventral respiratory groups. Flood the body with acid and the reserve runs out — then the other organs must act.

Prefer the full lecture? Bicarbonate Buffer System (original video on the site)

Explore

Push the reaction

Seesaw

Push the bicarbonate reaction from either end. Predict which way the seesaw tips, read the pH from the ratio, then drain the reserve and choose the body’s first move.

Text description of this explore

The bicarbonate reaction, CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻, drawn as a seesaw: CO₂ in a pan on the left (the lungs’ end) and bicarbonate in a pan on the right (the kidney’s end), with the pH written above. The beam tips down on the CO₂ side when the blood turns acid and on the bicarbonate side when it turns alkaline. Step 1: choose an event (add a drop of acid, hold the breath, or hyperventilate), predict which way the reaction runs and whether the pH falls or rises, then run it; a readout lists PCO₂, bicarbonate, the ratio, the pH and what the lungs do. Step 2: set the ratio of bicarbonate to carbonic acid (40, 20, 15, 10 or 5 to 1), predict the pH, then run it; the readout works through pH = 6.1 + log(ratio). Step 3: the bicarbonate reserve is drained to 19 with CO₂ still 40 (pH 7.30); choose which dial the body turns first, and the seesaw redraws with faster breathing (PCO₂ 35, pH 7.36). Step 4: sort five jobs by whether the lungs, the kidney or both can do them.

Think · not graded

The reaction runs both ways, so the lungs can lower acid by blowing off CO₂ — but the bicarbonate they used to soak the acid is gone with it. What can the lungs never do about a bicarbonate of 19, and which organ can?

Spot-check your thinking: true or false?

Check · Drag the Words

Order the CO₂ / carbonic acid / bicarbonate / H⁺ reaction.

Evidence card 3

Add it to your evidence board

The sponge works; the lungs can wring it; only the kidney can replace it.

Scene 4 of 5

The Kidney’s End, on a Slide

Proximal tubule, intercalated cell, glutamine — two tricks and a new bicarbonate.

Slide · a still to study

Renal Control of Acid–Base

Slide 210, PAS stain: renal medulla with tubules labeled, their basement membranes outlined in purple.
Slide 210, PAS: the tubules that do the acid work.
Slide 210, renal medulla: collecting ducts labeled, round lumens lined by pale cuboidal cells with crisp borders.
Slide 210: collecting ducts, home of the intercalated cells.

The kidney’s three jobs

  1. Reclaim: the proximal tubule secretes H⁺ to recover the filtered bicarbonate.
  2. Excrete: intercalated cells of the late distal tubule and collecting duct secrete H⁺; phosphate and ammonia carry it out, so urine pH can fall to about 4.5.
  3. Make new: when blood is acidic, tubule cells break down glutamine, excreting ammonium and returning new bicarbonate to the blood.

Only the kidney excretes fixed acids such as sulfuric and phosphoric acid. When blood is too alkaline, it secretes bicarbonate instead.

On the PAS slide the brush border is the pink fringe; the cells behind it do the reclaiming.

Prefer the full lecture? pH and Buffers (original video on the site) · histology page: Renal Tubule

Game

Reclaim, make, excrete

Three stations

Run a filtrate stream past three stations of the nephron. Predict what each sends out and brings back, load the blood with acid, then add amyloid.

Text description of this game

A nephron drawn as three stations stacked between a column of blood on the left and the filtrate stream on the right: a PCT cell with its brush border, the glutamine machine in the PCT cells, and an intercalated cell in the collecting duct. The stream carries bicarbonate, H⁺, phosphate (HPO₄²⁻) and ammonia down toward the urine. Step 1: for each station, choose what it sends into the filtrate (H⁺, ammonium or bicarbonate) and what comes back to the blood (a reclaimed bicarbonate, a brand-new bicarbonate, or nothing). Step 2: choose one station, predict what it does to the urine pH (barely changes it, lowers it a little, lowers it a lot toward 4.5, or raises it), then run the stream; arrows show what goes out and what comes back, and a readout lists the acid that leaves and the urine pH. Step 3: set the blood pH to 7.40, 7.33 or 7.20, predict which station works hardest and how much new bicarbonate the kidney makes a day, then run it; the readout lists ammonium, acid on phosphate, new bicarbonate and urine pH. Step 4: amyloid in Stina’s glomeruli leaves fewer working nephrons (eGFR 48); with her urine pH 5.0, low urine ammonium and bicarbonate 19, choose for each station the lab line that would move if it failed (bicarbonate, glucose and phosphate spilling into the urine; urine pH stuck above 5.5; low urine ammonium with a falling bicarbonate and a normal anion gap; or a climbing anion gap), then decide whether it is failing or still working in her.

Think · not graded

Her urine pH is 5.0, so her tubules can still acidify. Her bicarbonate is 19 anyway. Which of the kidney’s three jobs — reclaim, make new, excrete fixed acid — can be failing while the urine stays acidic, and what does that say about where in the kidney her disease sits?

Spot-check your thinking: true or false?

Check · Multiple Choice

Which organ controls the bicarbonate end of the buffer?

Evidence card 4

Add it to your evidence board

Reclaim, make, excrete: the kidney’s three jobs on the bicarbonate end — the end with amyloid in it.

Scene 5 of 5

Two Organs, Two Ends

Lungs on CO₂, kidneys on bicarbonate — and naming her disturbance.

Animation · in production · 1 min 50 s

Two Organs, Two Ends

The reaction with a lung on the left end and a kidney on the right. A disturbance is named for the end that moved first: respiratory if CO₂, metabolic if bicarbonate or fixed acid. Four shapes drawn as the reaction tipping. Then her numbers: bicarbonate 20 → 19 fell first; pH 7.33; PCO₂ 33 — low because the lungs are answering, not causing. Metabolic acidosis, respiratory compensation under way. Mr. Wu beside her: the same shape, further along, 22 breaths a minute.

Prefer the full lecture? Bicarbonate Buffer System (original video on the site)

Explore

Which end moved first?

Three dials

Read three dials for each patient. Decide which end of the reaction moved first and which is answering, name the disturbance, then place Mr. Wu.

Text description of this explore

The reaction CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ is drawn with the lungs under the CO₂ end and the kidney under the bicarbonate end. Step 1: four patient cards, each with three dials (pH, PCO₂ and bicarbonate) showing a green normal band: a child who inhaled a toy minutes ago (pH 7.24, PCO₂ 60, bicarbonate 25); a panicked hyperventilator (pH 7.52, PCO₂ 28, bicarbonate 22); a patient vomiting for two days (pH 7.49, PCO₂ 46, bicarbonate 34); and Stina in 2025, breathing 18 times a minute (pH 7.33, PCO₂ 33, bicarbonate 19). For each, choose which end moved first and whether the other is answering, and name the disturbance (respiratory or metabolic, acidosis or alkalosis); after you commit, the dials are marked “moved first” and “answering”. Step 2: Mr. Wu has the same shape as Stina, further along; choose his gas from four. Step 3: write the one line that names her disturbance and the organ that owns it, then compare with a model answer.

Think · not graded

Her CO₂ is low. In a respiratory alkalosis a low CO₂ is the cause; in her it is the answer. What single relationship between pH and CO₂ tells you which — and why does it matter for what you do next?

Spot-check your thinking: true or false?

Check · Drag the Words

Sort the four disturbances by their primary change.

Evidence card 5

Add it to your evidence board

Bicarbonate moved first, CO₂ is answering: metabolic acidosis — the kidney’s end.

4

Your evidence board

Every scene gave you an evidence card, and the chart adds more. Sort each card into the column it supports: Metabolic — the kidney’s end moved first, Neither on its own, or Respiratory — the lungs’ end moved first. Some cards can honestly go in more than one place — that’s allowed, and the feedback tells you which cards decide the case.

5

Your verdict

Time to decide. Look back at your bet, then build your verdict from statements that hold up — no writing needed.

Look back at your prediction

Bicarbonate 20, pH 7.33, PCO₂ 33, normal anion gap — the disturbance is…

Find the one you chose at the top. Does the evidence support it, refute it, or revise it?

  • Respiratory — her lungs are the organ breathing off CO₂, and her CO₂ is low
  • Metabolic — bicarbonate is the number that moved first, and the low CO₂ is the lungs covering for a kidney
  • Nothing — a bicarbonate of 20 is a rounding error and the pH is nearly normal

Build your verdict · no writing

Choose the statement that holds in each set. The ones you keep become your argument.

6

The finding

Finding · a low-bicarbonate drift = metabolic acidosis

The End With Amyloid in It

Bicarbonate 20 then 19; pH 7.33; PCO₂ 33 — low because her lungs are answering, not causing; respirations 18 and a little deep; a normal anion gap with a high-normal chloride; a urine pH of 5.0 that says the tubules can still acidify. Chart entry: an early metabolic acidosis — a bicarbonate problem, not a CO₂ problem — owned by the organ that reclaims and manufactures bicarbonate and excretes the day’s fixed acid: the kidney with amyloid in it. “We’ll recheck” named nothing. The next chapter reads the full gas, names the compensation and asks what only a healthy kidney can do.

Next · Chapter 6

Metabolic Acidosis from a Failing Kidney

A buffer buys time; it does not fix the source. The real correction comes from two organs working together — and in her, one of them is the organ that is failing. Three questions read any blood gas.

Continue to Chapter 6 →

Reliable information on rare diseases

NORD · NIH GARD · Orphanet · MedlinePlus Genetics: FMF · FMF & AID Global Association · Autoinflammatory Alliance · Global Genes · Amyloidosis Foundation

Stina has one rare disease. In the United States, about 1 in 10 people live with one of the more than 7,000 known rare diseases. These organizations are where patients, families and clinicians go for trustworthy information.

Hop to:

← Familial Mediterranean Fever — case home

All pages for Module 20 — Fluids, Electrolytes & Acid–Base Balance

20.0 Module Overview
20.1 The Swollen Ankles That Point Back to the Kidney
20.2 The Body’s Fluid Compartments & Water Movement
20.3 Hydrostatic vs Oncotic Pressure
20.4 The Major Electrolytes & the Albumin-Corrected Calcium
20.5 Acid-Base Balance & the Bicarbonate Buffer System
20.6 Metabolic Acidosis from a Failing Kidney
20.7 One Filter, Not Three Problems
20.8 Conclusion and Assessment
20.9 Evidence Behind the Case

All Modules
  1. Anatomical Language, Membranes & Homeostasis
  2. Just Enough Chemistry
  3. The Cell & Its Transport
  4. Making Cells & Proteins
  5. The Integumentary System
  6. The Skeletal System
  7. The Muscular System
  8. Nervous Tissue & the Senses
  9. The Spinal Cord
  10. The Brain & the Blood–Brain Barrier
  11. The Autonomic Nervous System
  12. Special Senses (in development)
  13. The Endocrine System
  14. Blood
  15. The Heart
  16. Blood Vessels
  17. The Digestive System
  18. The Respiratory System
  19. The Urinary System
  20. Fluids, Electrolytes & Acid–Base Balance
  21. The Reproductive System
  22. The Immune System

List of terms