Acid/Base Physiology

The concentration of hydrogen ions (H+) in a solution

What does pH indicate?

They are inversely related—high H+ means low pH (acidic); low H+ means high pH (basic)

What is the relationship between H+ concentration and pH?

7.35–7.45

What is the normal pH range of extracellular fluid (blood)?

Acidemia

Blood pH below 7.35 is called what?

Alkalemia

Blood pH above 7.45 is called what?

< 6.8 or > 8.0

What blood pH values are incompatible with life?

~7.2

What is the normal intracellular pH?

Its hydrogen ion concentration (more H+ = acidic; fewer H+ = basic)

What determines if something is acidic or basic?

Slightly alkaline at ~7.4.

Despite producing large amounts of acid daily, what is arterial pH?

Volatile acid and nonvolatile (fixed) acid

What are the two forms of acid produced in the body?

CO₂ (which becomes carbonic acid when combined with water)

What is the main volatile acid in the body?

Through the lungs (exhalation of CO₂)

How is volatile acid eliminated?

Sulfuric acid and phosphoric acid

What are examples of nonvolatile (fixed) acids?

By the kidneys (filtered and excreted)

How are nonvolatile acids eliminated?

CO₂

What is the end product of aerobic metabolism?

No, but when combined with water it forms carbonic acid (H₂CO₃).

Is CO₂ itself an acid?

Carbonic anhydrase

What enzyme catalyzes CO₂ + H₂O → H₂CO₃?

About 50 mmol/day.

How much fixed acid is produced daily from normal metabolism?

Proteins with sulfur-containing amino acids.

What produces sulfuric acid?

Phospholipids

What produces phosphoric acid?

They must be buffered in body fluids.

How are fixed acids handled before elimination?

The kidneys

What organ primarily manages fixed acid elimination

Ketoacids: B-hydroxybutyric acid and acetoacetic acid.

What fixed acids are increased in untreated diabetes mellitus?

Lactic acid

What fixed acid is produced during strenuous exercise or tissue hypoxia

Salicylic acid, formic acid, glycolic acid, and oxalic acid.

What toxic ingestions can increase fixed acids?

A normal hydrogen ion (H*) concentration in body fluids.

What is acid-base balance concerned with maintaining?

ECF and ICF

CO2

bicarbonate; H+

three major mechanisms that maintain acid-base balance

1. Buffer systems in the ___ and ___

2. Respiratory excretion of ___

3. Renal reabsorption of ____ and secretion of ___

buffer

A mixture of a weak acid and its conjugate base, or a weak base and its conjugate acid

They resist changes in pH by neutralizing added acids or bases.

What is the role of buffers in acid-base balance? (what do they resist)

The bicarbonate (HCOs) buffer system.

What is the most important extracellular buffer?

Organic phosphates and proteins (including deoxyhemoglobin).

What are the main ICF buffers?

It rapidly regulates pH when CO2 or bicarbonate levels change.

Why is the bicarbonate/CO2 buffer system considered the first line of defense?

Bicarbonate (HCO3 ) and phosphate (HPO.).

What are the main ECF buffers

HCO₃

H₂CO₃

CO₂ + H₂O

lungs

When hydrochloric acid (HCl) enters the bloodstream
___⁻ buffers the excess H⁺, forming ___, which breaks down into ____ and is exhaled by the ____.

HCl is converted into H₂CO₃

What strong acid is converted into a weak acid when buffered by bicarbonate?

Deoxyhemoglobin

What is the main protein buffer in the ICF?

H⁺ must cross the cell membrane

Before ICF buffers can neutralize H⁺, what must happen?

1. CO₂

2. H⁺

3. H⁺; K+ 

three mechanisms by which H⁺ can enter cells for ICF buffering

1. ____ diffuses into the cell (primary mechanism)

2. ___ enters/leaves with an organic anion (e.g., lactate)

3. ___ exchanges with __ via H⁺/K⁺ ATPase

CO₂ entering cells via simple diffusion

Which diffusion process is the primary way ICF buffers become involved in acid-base disturbances?

Because the weak acid/base pair can neutralize added H⁺ or OH⁻, minimizing pH shifts.

Why can a buffered solution resist changes in pH?

Hemoglobin (Hgb), particularly in its deoxyhemoglobin form.

What is the most significant intracellular buffer?

In the systemic capillaries, as 02 leaves blood for tissues.

Where does conversion of oxyhemoglobin to deoxyhemoglobin occur?

CO2 diffuses from tissues to the RBCs, and combines with H20 to form H2CO3.

What happens to CO2 as blood flows through systemic capillaries?

H+ and HCO3- (bicarbonate).

What are the products of carbonic acid (H2CO3) dissociation?

Deoxyhemoglobin, which binds H+

What buffers the H+ produced from H2CO3 dissociation inside RBCs?

It is transported out of the RBC to help buffer the ECF.

What happens to the bicarbonate (HCO3) produced in RBCs?

It readily accepts H+ after releasing O2

Why is deoxyhemoglobin an effective buffer?

Metabolic acidosis and metabolic alkalosis.

Respiratory compensation occurs for which acid-base disorders?

By increasing or decreasing exhalation of COz, a component of carbonic acid.

How do the lungs help regulate acid levels?

Acidemia (low pH) stimulates chemoreceptors in carotid bodies, increasing ventilation

What triggers hyperventilation in metabolic acidosis?

CO2

carbonic acid

pH

Hyperventilation help correct metabolic acidosis

Exhaling more ___ → reduces ___ - raises __ back toward normal.

immediate: respiratory system

Long-term: kidneys

What is the immediate vs. long-term regulator of acid-base balance?

Too much CO2 → low pH (acidemia)

In acidosis, what is the relationship between CO2 and pH?

1. Reabsorption of bicarbonate

2. Excretion of fixed acid

what are the two major roles of the kidneys in acid base balance?

To ensure this important EC extracellular buffer is not lost in the urine

Why must the kidneys reabsorb bicarbonate?

As titratable acid (buffered by urinary phosphate) and as ammonium ion (NH₄⁺)

What are the two ways the kidneys excrete fixed acid (H⁺)?

Synthesis and reabsorption of new HCO₃⁻

What accompanies the excretion of H⁺ in the kidneys?

Because fixed acids cannot be exhaled, so the kidneys must remove them to maintain acid-base balance.

Why must the kidneys excrete fixed acid?

99.9%

What percentage of filtered HCO₃⁻ is reabsorbed by the kidneys?

extracellular buffer

reabsorption of HCO₃⁻ is important because it conserves a major ____, helping maintain acid–base balance.

proximal tubule

Where does the majority of HCO₃⁻ reabsorption occur?

isosmotic

Reabsorption in the proximal tubule is described as ________.

• Loop of Henle

• Distal tubule

• Collecting duct

Besides the proximal tubule, where else is small amounts of HCO₃⁻ reabsorbed?

No

Is H⁺ significantly secreted into the tubular fluid during HCO₃⁻ reabsorption?

Because secreted H⁺ is buffered and returned to the cell via the bicarbonate buffering process.

Why does tubular fluid pH change minimally during HCO₃⁻ reabsorption?

Na+ moving into the cell down its electrochemical gradient, which powers H⁺ movement into the lumen

What drives the secondary active countertransport of H⁺ into the tubular lumen?

They form H₂CO₃ → CO₂ + H₂O.

What happens when H⁺ secreted into the lumen meets filtered HCO₃⁻?

• CO₂ is a gas and diffuses easily

• The proximal tubule is highly permeable to water

Why can CO₂ and H₂O easily enter proximal tubule cells?

They undergo reverse reactions to reform H⁺ and HCO₃⁻.

Inside the proximal tubule cell, what happens to CO₂ and H₂O?

1. With Na+ (co-transport)

2. In exchange for Cl−

How is HCO₃⁻ reabsorbed across the basolateral membrane?

Excess HCO₃⁻ is excreted in the urine.

What happens when filtered HCO₃⁻ exceeds the kidney’s reabsorption capacity?

metabolic alkalosis

In what clinical condition does filtered HCO₃⁻ exceed reabsorptive capacity, causing excretion?

> 40 mEq/L.

At what blood HCO₃⁻ concentration does filtered load exceed reabsorption capacity?

To restore normal acid–base balance by removing excess bicarbonate.

What is the purpose of excreting HCO₃⁻ in metabolic alkalosis?

In the proximal tubule as part of isosmotic reabsorption.

Where is most filtered HCO₃⁻ reabsorbed?

Na⁺, K⁺, HCO₃⁻, and water

What solutes are reabsorbed isosmotically in the proximal tubule?

isosmotic reabsorption

Na⁺, K⁺, water, and HCO₃⁻ reabsorption

ECF volume expansion affects HCO₃⁻ reabsorption by inhibiting _____ in the proximal tubule…this then decreases _______.

It stimulates isosmotic reabsorption → increases reabsorption of Na⁺, K⁺, water, and HCO₃⁻

How does ECF volume contraction affect HCO₃⁻ reabsorption?

Low ECF → low BP → activates the renin–angiotensin II–aldosterone system

What happens to RAAS with low ECF volume?

The Na⁺–H⁺ exchanger (NHE3)

Which transporter does angiotensin II stimulate in the proximal tubule?

Increased reabsorption of Na⁺, water, and HCO₃⁻ → raises blood HCO₃⁻ concentration

What does stimulation of the Na⁺–H⁺ exchanger cause?

They alter HCO₃⁻ reabsorption and provide renal compensation for chronic respiratory acid–base disorders.

How do chronic changes in PCO₂ affect HCO₃⁻ reabsorption?

HCO₃⁻ reabsorption increases (because more CO₂ → more H⁺ → body retains more base)

What happens to HCO₃⁻ reabsorption when PCO₂ is elevated?

HCO₃⁻ reabsorption decreases.

What happens to HCO₃⁻ reabsorption when PCO₂ is decreased?

Approximately 50 mEq/day

How much fixed H⁺ is produced per day from metabolism?

20mEq/day

How much fixed H⁺ is excreted as titratable acid?

Inorganic phosphate

What is the most important urinary buffer for titratable H⁺ excretion?

15%

What percentage of filtered phosphate is not reabsorbed and available to buffer H⁺?

30 mEq/day

How much fixed H⁺ is excreted as NH₄⁺?

Proximal tubule, thick ascending limb of the Loop of Henle, and collecting ducts

Where is NH₄⁺ (ammonia) produced and secreted in the nephron?

acidemia

defined as increased H⁺ concentration in the blood, causing a decrease in pH

alkalemia

defined as decreased H⁺ concentration in the blood, causing an increase in pH

1. Primary disturbance of bicarbonate (HCO₃⁻) concentration.

2. Primary disturbance of carbon dioxide (PaCO₂).

What are the two primary causes of changes in blood pH?

CO₂ (volatile acid), caused by disorders of respiration

Respiratory acid–base disorders involve abnormalities in what?

Hypoventilation → increased CO₂ retention

What causes respiratory acidosis?

Hyperventilation → decreased CO₂ levels

What causes respiratory alkalosis?

bicarbonate

Metabolic acid–base disorders involve primary disturbances in what?

metabolic acidosis

acid/base disorder where there is a renal decrease in HCO₃⁻ concentration leading to decreased pH

metabolic alkalosis 

acid/base disorder where there is a renal iincrease in HCO₃⁻ concentration leading to increased pH.

7.35-7.45

Normal arterial pH range?