Renal Regulation of Acid-Base Status - Dr. Bechtold

Hydrogen ion

a positively charged ion (H+) formed from a hydrogen atom that has lost its electron

Acid

a molecule that can release a hydrogen ion (H+)

example of acid

HCl; dissociates into H+ and Cl-, and thus is an acid

Strong acid vs weak acid

Strong-dissociates completely or more readily and releases more H+; weak partly dissociates and releases less H+

The hydrogen ion must be tightly ________. Why?

regulated; hydrogen ion concentration impacts almost all enzyme systems in the body, and even small changes in pH can disrupt cellular metabolism and protein function

Is hydrogen present in the blood in small or large quantities?

extremely small!

Base

molecule that can accept a hydrogen ion

example of a base

HCO3- is a base, as it

can combine with H+

to form H2CO3

Because normal [H+] is such a small number, it is measured with a ________ scale using ___ units

logarithm scale; pH units

pH

negative log of the hydrogen

ion concentration (log of the

inverse of the hydrogen ion concentration)

A lower pH means a _______ [H+]

A higher pH means a _______ [H+]

higher

lower

Henderson-Hasselbalch relationship

pH depends on the ratio of bicarbonate to CO2, not the absolute amounts

Henderson-Hasselbalch equation

pH = pKa + log [A-]/[HA]

pK

the value at which a buffer pair has equal amounts of weak acid and conjugate base

K

dissociation constant (the ratio of acid relative to its dissociated ions)

Buffers are most effective within +/- ___ pH unit of the pK

+/- 1 pH unit of pK

Two examples of buffers

1.) phosphate

2.) CO2

phosphate is a good _______ buffer. Why?

urinary; the pK of phosphate is the same as the typical urine pH

Two types of acids

1.) volatile acid

2.) fixed acid

volatile acid

An acid that can be eliminated by the lungs

Example of a volatile acid

CO2

CO2 is made from...

aerobic metabolism from cells

After being formed during aerobic metabolism, CO2 enters...

the blood

What happens to CO2 inside RBCs?

CO2 will combine with water to form H2CO3, which then dissociates into H+ and HCO3-

How is CO2 a volatile acid?

in the lungs, carbonic anhydrase reverses the reaction that took place in the blood, and CO2 is expired

carbonic anhydrase

enzyme that catalyzes the reaction between carbon dioxide and water to form carbonic acid, or the reverse reaction

fixed acid

acid that is excreted by the kidneys

Fixed acids are produced by the metabolism of two things:

1.) proteins

2.) phospholipids

A fixed acid formed by metabolism of proteins is...

sulfuric acid

A fixed acid formed by metabolism of phospholipids is...

phosphoric acid

Fixed acids are initially ________,

then _________ by the kidneys

buffered; excreted

Buffers

substances that help minimize changes in pH

A buffer system can either be composed of two things:

1.) weak acid + conjugate base

2.) weak base + conjugate acid

Buffer work by:

Binding ____ from strong acids

Binding ___ from strong bases

H+

OH-

Buffers work best within ___ ____ unit of their pK

1 pH

Buffers are categorized by their _______

location

Two types of buffers based on location:

1.) extracellular buffers

2.) intracellular buffers

Three examples of extracellular buffers:

1.) HCO3/CO2

2.) inorganic phosphates

3.) plasma proteins

What is the most important extracellular buffer?

bicarbonate (HCO3)

Two examples of intracellular buffers:

1.) proteins

2.) organic phosphates

Which protein is an important intracellular buffer?

hemoglobin in red blood cells

Phosphate is an important __________ and _______ buffer

intracellular; urinary

Phosphate will buffer _______ ions secreted in the urine

hydrogen

The body has three major defenses against pH disturbances:

1.) chemical buffers

2.) respiratory buffers

3.) renal buffers

chemical buffers take how long to respond?

immediately

Three examples of chemical buffers:

1.) bicarbonate

2.) protein

3.) phosphate

bicarbonate as a chemical buffer

one of the most important chemical buffers; extracellular buffer present in high quantities in the blood

protein as a chemical buffer

important intracellular buffer that contain ionizable side chains that bind hydrogen ions; example is hemoglobin in RBCs

phosphate as a chemical buffer

important buffer in both the intracellular compartment and the urine

respiratory buffers take how long to respond?

minutes

respiratory buffering involves the expiration of...

CO2

Equation for acid-base buffering system in the respiratory system

H+ + HCO3− ↔ H2CO3 ↔ H2O + CO2

If there is an increase in H+ in the respiratory system (acidosis)..

the reaction shifts to the right and produces more CO2 and H2O; the lungs respond by increasing ventilation and expiring CO2 to reduce acidity

If there is an increase in CO2 in the respiratory system (acidosis)..

this indicates ventilation is poor; the reaction shifts to the left, increasing H+ and causing respiratory acidosis

renal buffers take how long to respond?

hours to days

The kidneys are essential for _____-_____ acid-base regulation

long-term

Rather than merely buffering, the kidneys can produce...

acidic urine to excrete hydrogen ions, or can produce alkaline urine to excrete bicarbonate

The kidneys will regulate acid-base balance three main ways:

1.) reabsorbing filtered bicarbonate

2.) secreting hydrogen ions

3.) excreting acids in the urine

The kidneys respond to acidosis by...

reabsorbing bicarbonate and increasing H+ secretion

The kidneys respond to alkalosis by...

not reabsorbing all bicarbonate but allowing it to be excreted in the urine

bicarbonate is or isn't freely filtered at the glomerulus?

is freely filtered

After filtration at the glomerulus, almost all filtered bicarbonate is __________

reabsorbed

The mechanisms of bicarbonate reabsorption differs based on two locations:

1.) proximal segments

2.) distal segments

Three proximal segments of the tubules where bicarbonate reabsorption occurs:

1.) proximal tubule

2.) loop of Henle

3.) early part of distal tubule

Each bicarbonate reabsorbed requires secretion of one ________ ion to be reabsorbed

hydrogen ion

Secretion of H+ is accomplished through what mechanism?

secondary active transport with a sodium countertransport

Explain how hydrogen secretion through secondary active transport with a sodium countertransport works

1.) The Na+/K+ ATPase pump on the basolateral membrane actively pumps Na+ out of the cell, causing Na+ concentration inside the cell to decrease

2.) Since Na+ naturally wants to move into the cell from the lumen, it will enter the cell through a Na+/H+ countertransporter, where Na+ goes into the cell and H+ is secreted into the cell

Once H+ is secreted into the lumen, __________ reabsorption can begin

bicarbonate

steps of bicarbonate reabsorption in the proximal tubules

1.) in the lumen, secreted H+ combines with bicarbonate to form carbonic acid (H2CO3)

2.) carbonic acid rapidly dissociates into CO2 and H2O

3.) CO2 diffuses inside the cell and reacts with H2O to reform carbonic acid

4.) carbonic anhydrase converts carbonic acid back to H+ and bicarbonate (HCO3-)

5.) H+ is then secreted again and HCO3- enters the bloodstream (reabsorbed)

Two distal segments of the tubules where bicarbonate reabsorption occurs:

1.) late part of distal tubule

2.) collecting duct

Unlike the proximal segment, both ________ and _______ active transport are needed to secrete H+

primary; secondary

Why must primary active transport be used to secrete H+ in the distal segments?

Secondary active transport is used to help reabsorb bicarbonate, but only ATP-driven H⁺ pumps can secrete enough hydrogen ions to remove the body's metabolic acids and maintain acid-base balance

Two cells that regulate acid-base balance in the distal segment:

1.) principal cells

2.) intercalated cells

Two functions of the principal cells:

1.) reabsorb Na+

2.) secrete K+

There are two types of intercalated cells:

1.) type A intercalated cells

2.) type B intercalated cells

Two functions of type A intercalated cells:

1.) secrete H+

2). reabsorb K+

type A intercalated cells secrete H+ through...

primary active transport using H+ ATPase pump

The H+ secreted into the lumen by the H+ ATPase pump will do either two things:

1.) combines with filtered bicarbonate to aid with its reabsorption (similar to proximal segment)

2.) combines with other urine buffers

One function of type B intercalated cells:

secrete bicarbonate

Why do type B intercalated cells secrete bicarbonate?

to help during alkalosis to remove excess bicarbonate

Total mechanism of bicarbonate reabsorption in the distal segment:

1.) in the lumen, secreted H+ combines with bicarbonate to form carbonic acid (H2CO3)

2.) carbonic acid rapidly dissociates into CO2 and H2O

3.) CO2 diffuses inside the cell and reacts with H2O to reform carbonic acid

4.) carbonic anhydrase converts carbonic acid back to H+ and bicarbonate (HCO3-)

5.) H+ is actively pumped into the lumen using the H+ ATPase pump

6.) bicarbonate is reabsorbed using a Cl-/HCO3- exchanger on the basolateral membrane

*different than proximal segment

For acid-base balance, hydrogen ions are _________ into the ultrafiltrate

secreted

Where does acid in the renal tubules come from? Why must they be excreted from the kidneys?

come from protein metabolism; they cannot be excreted by the lungs, so they must be eliminated by the kidneys

Since protein metabolism generates acid, what type of diet will generate more acid?

carnivorous diet

*and herbivores are more alkali

What type of acids are excreted in the urine?

fixed acids (sulfuric acid, phosphoric acid, and organic acids)

Two stimuli for increased H+ secretion:

1.) increase in extracellular PCO2

2.) excess aldosterone production

Why will hydrogen ion secretion increase when extracellular PCO2 increases?

CO2 will enter the tubular cells, react with H2O, and through the dissociation reaction will produce more H+

Why will hydrogen ion secretion increase with excess aldosterone production?

aldosterone will stimulate intercalated Type A cells to secrete more H+

Secretion of hydrogen ions accomplishes two goals:

1.) reabsorbs filtered bicarbonate

2.) allows net acid excretion

net acid excretion

the net amount of acid the kidneys remove from the urine after accounting for any bicarbonate lost in the urine (total H+ excreted - bicarbonate secreted)

Two things must happen for there to be net acid excretion:

1.) all the filtered bicarbonate must be reabsorbed

2.) excess H+ must be secreted

The secretion of excess H+ is accomplished through two mechanisms:

1.) ammonia/ammonium

2.) titratable acidity (phosphate)

Ammonia acts as a _________ in the _______ tubule

buffer; proximal

The kidneys use the ammonia buffer system to help...

remove excess acid from the body

ammonia buffer system in the kidneys

secretes H+ in the urine while generating new bicarbonate for the blood

Ammonia vs Ammonium

Ammonia (NH3) is lipid soluble, so it can pass through cell membrane without a carrier protein

Ammonium (NH4+) is polar, so it does not easily cross membranes

Since ammonium is polar, how does it cross cell membranes?

it can bind to carrier molecules in a similar way to H+

Ammonium is formed from...

glutamine metabolism

Where does glutamine metabolism take place?

inside the proximal tubule cells

Glutamine metabolism will forms two things:

1.) 2 ammonium ions (NH4+)

2.) 2 bicarbonate ions (HCO3-)