The Urinary System

Acid-Base Homeostasis
Lecture 4

Jennifer Carbrey Ph.D.

Department of Cell Biology
j.carbrey@cellbio.duke.edu

The Urinary System

Lecture 1
Fluid and Electrolyte Homeostasis
Lecture 2
Transport Properties of Nephron
Segments
Lecture 3
Regulation of Extracellular Fluid Volume
Lecture 4
Acid-Base Homeostasis

Learning Objectives
Describe how the body buffers free H+ that either
enter from the diet or are generated by metabolism
each day.
Explain the role of the lungs and of HCO3-/CO2 buffer
pair in maintaining the stability of the pH in the
body.
Explain the role of the kidney in eliminating filtered
H+ and HCO3- to maintain plasma pH.
Explain how new bicarbonate is generated when
fixed acids and ammonia are eliminated by the
body.

Acids and Bases

ACIDS - substances that donate protons (H +).
BASES substances that accept protons (H+).
pH of a solution is a measure of its free H+ concentration.
Every one pH unit = 10 fold change in H+ concentration.
For example, at pH 7.0 the H+ concentration is 10 -7 M.

*** Bodys pH is usually pH 7.35 - 7.45

pH Homeostasis
Fatty acids
Amino acids

H+ INPUT
70 mEq/dy*

CO2 + H2O
Lactic acid
Ketoacids
metabolism

diet

Buffers: Intracellular proteins, Hb

Extracellular fluid HCO3-

CO2 + H2O

(exhale)

Urine excretion
plasma [H+]
40 nEq/L = pH 7.4
(fixed acids &
ammonium ion)

(* 1 mEq/kg body weight/dy)

Important Terms
Acidemia
- state in which arterial blood pH < 7.35
Alkalemia
- state in which arterial blood pH > 7.45
Acidosis
- disorder that lowers arterial blood pH to < 7.35
Alkalosis
- disorder that raises arterial blood pH to > 7.45

Lung Versus Kidney

CO2 + H2O = H2CO3 = H+ + HCO3Ratio of HCO3- to CO2
determines pH!
As PaCO2 increases, more acidic
As PaCO2 decreases, more basic
As HCO3- decreases, more acidic
As HCO3- increases, more basic
If the lungs are not functioning properly, then changes in PaCO 2
If the kidneys are not functioning properly, then changes in HCO 3-

Reabsorption of
Filtered HCO3- in PCT
lumen

PCT cell

blood

Na+
H

ATP

H+

ClHCO3-

Requires carbonic
anhydrase activity

HCO3- +
H+
H20 + CO2
H2CO3

PCT reabsorbs
70-80% HCO3-

H+ secreted into lumen by

co-transporter with Na+
& by H+ATPase

Reabsorption of Filtered
HCO3- in DCT & CD
lumen

Type A cell

blood

Na+
H+

HCO3 + H
-

H2CO3

ATP

H+

ClHCO3-

H2O + CO2

Intercalated cells of DCT

and CD.
Type A secrete H+,
reabsorb HCO3(Acidic urine)
Type B secrete HCO3-,
reabsorb H+
(Basic urine)

Kidney Makes NH4+

and NEW Bicarbonate
lumen

blood

glutamine

glutamine

Na

NH4+
Na+

Cl
HCO3-

PCT cell

Glutamine is
catabolized to
NH4+ and HCO3PCT cells
generate HCO3and secrete
NH4+

DCT & CD Excrete

Fixed Acids and NEW HCO3lumen

blood

Na+
H+

HPO4- + H+

ATP

H+

ClHCO3c.a.

H2PO4

H2O + CO2
CO2

Fixed acids include

sulfuric,
hydrochloric, and
phosphoric acid
from protein
metabolism
CD principal cells
trap H+ as fixed
acids & generate
new HCO3- to
increase blood pH

Mass Balance
[Net Acid Excretion (NAE)]
Acid Input = ~70 mEq/dy
Acid Output = ~ 40nEq/dy = pH
7.4 urine
Specific daily total acid secretion by the kidney includes:
Fixed acids produced
34 mEq
NH4+ produced
35 mEq
Acidic urine pH (free H+)
negligible
NAE = (UNH4 x V) + (UFA x V) (UHCO3- x V)

Renal Responses to Acid-Base

Disturbances

Acid-Base
Disturbances
CO2 + H2O = H2CO3 = H+ + HCO3Primary
Disorder

Blood pH PaCO2

Causes of PaCO2
Change

Respirat
ory
acidosis

decrease *
increase

decreased
ventilation

Respirat
ory
alkalosis

increase

Metaboli
c
acidosis

decrease **
decreased
decrease bicarbonate

*
increased
decrease ventilation

* = initiating
cause;
** = compensation
by lung
Metaboli
increase
**increas increased
c
e
bicarbonate

Analysis of Acid-Base
Disorders
What is pH of arterial blood?
This determines state: normal, acidemia, or alkalemia.
Is it metabolic or respiratory disorder and is the
process acidosis or alkalosis or mixed?
Examine the [HCO3-] (normal 24 mEq/L) and PaCO2
(normal 40 mm Hg). Compensation is never complete so
change in pH reflects
disorder.
What is the compensatory mechanism?
Metabolic disorders result in compensatory changes in
PaCO2.
Respiratory disorders result in compensatory changes in
[HCO3-].

Key Concepts
1. Daily diet and metabolism generates a net increase in
acids.
2. The kidneys with the lungs maintain the bodys pH by
regulating the HCO3-/CO2 buffer pair. The lungs exert an
immediate effect by controlling PCO2; the kidneys exert a
slower effect by controlling HCO3- and H+ concentration.
3. The kidneys maintain acid-base homeostasis by
reabsorbing filtered
bicarbonate, forming titratable
(fixed) acids and excreting ammonium (NH4).
4. There are four types of acid-base disturbances. They are
classified as to the direction of change in pH (acidosis or
alkalosis) and by the underlying problem (ventilation or
metabolism).

Questions
1. Predict the effect that 2 days of vomiting would have on
the pH of the blood (increase, decrease, unchanged). Will
this affect minute ventilation? If so, how? Predict the
response of the kidney to this condition.
2. A 50 year old male is dehydrated from 2 days of severe
diarrhea. His electrolyte results are: Na+ 134, Cl- 108, HCO316, pH 7.31, PaCO2 33 mm Hg.
What is his acid-base status? (normal, alkalemia, acidemia)
Which of the following processes is underlying this state?
A. metabolic acidosis
B. metabolic alkalosis
C. respiratory acidosis
D. respiratory alkalosis