Renal lecture 4
Kidney & acid-base balance
Acid-Base Balance
• Refers to precise regulation of free H+ concentration in
body fluids
• Acids
– Group of H+ containing substances that dissociate in solution to
release free H+ and anions
• Bases
– Substance that can combine with free H+ and remove it from
solution
• pH
–
–
–
–
Designation used to express the concentration of H+
pH 7 – neutral
pH less than 7 → acidic
pH greater than 7 → basic
1
Comparison of pH Values of
Common Substances
Acid-Base Balance
• Arterial pH less than 6.8 or greater than
8.0 is not compatible with life
• Acidosis
– Exists when blood pH falls below 7.35
• Alkalosis
– Occurs when blood pH is above 7.45
2
pH
Acid-Base Balance
• Consequences of fluctuations in pH
– Changes in excitability of nerve and muscle
cells
– Marked influence on enzyme activity
– Changes influence K+ levels in body
3
•Sources of H+ in the body
–Carbonic acid formation
–Inorganic nutrients produced during breakdown of nutrients
–Organic acids resulting from intermediary metabolism
4
Sources of H+ gain and loss
• H+ Gain
–
–
–
–
CO2 in blood (combine with H2O via carbonic anhydrase)
Nonvolatile acids from metabolism (e.g. lactic)
Loss of HCO3- in diarrhoea or non-gastric GI fluids
Loss of HCO3- in urine
• H+ Loss
–
–
–
–
Use of H+ in metabolism of organic anions
Loss of H+ in vomit
Loss of H+ in urine
Hyperventilation (blow off CO2)
• Loss of H+ like gaining HCO3• Loss of HCO3- like gaining H+
Lines of Defense Against pH Changes
• Chemical buffer systems
• Respiratory system
• Kidneys
5
The Carbonic-Acid-Bicarbonate Buffer in the Blood
Most important buffer for maintaining acid-base balance in the blood.
The simultaneous equilibrium reactions of interest are:
• The kidneys help remove excess chemicals from the blood.
It is the kidneys that ultimately remove (from the body) H+ ions and other
components of the pH buffers that build up in excess. Acidosis that results from
failure of the kidneys to perform this excretory function is known as metabolic
acidosis. However, excretion by the kidneys is a relatively slow process, and
may take too long to prevent acute acidosis resulting from a sudden decrease in
pH (e.g., during exercise).
• The lungs provide a faster way to help control the pH of the blood.
The increased-breathing response to exercise helps to counteract the pHlowering effects of exercise by removing CO2, a component of the principal pH
buffer in the blood. Acidosis that results from failure of the lungs to eliminate CO2
as fast as it is produced is known as respiratory acidosis.
6
Chemical Buffer Systems
• Minimize changes in pH by binding with or
yielding free H+
• First line of defense
• Body has four buffer systems
– H2CO3-, HCO3- buffer system
• Primary ECF buffer for noncarbonic acids
– Protein buffer system
• Primary ICF buffer; also buffers ECF
– Hemoglobin buffer system
• Primary buffer against carbonic acid changes
– Phosphate buffer system
• Important urinary buffer; also buffers ICF
Carbonic Acid – Bicarbonate Buffer System
Respiratory component
Renal component
Carbonic anhydrase
CO2
+
H 2O
H2CO3
Carbonic acid
H+
+ HCO3 –
bicarbonate
(H2CO3 is a ‘volatile’ acid as → CO2 exhaled )
7
Respiratory System
• Second line of defense again changes in
pH
• Acts at a moderate speed
• Regulates pH by controlling rate of CO2
removal
8
• Carbon dioxide in the blood is converted to
bicarbonate ion and transported in the
plasma
• Increases in hydrogen ion concentration
produces more carbonic acid
• Excess hydrogen ion can be blown off with
the release of carbon dioxide from the lungs
• Respiratory rate can rise and fall depending
on changing blood pH
Kidneys
• Third line of defense against change in
hydrogen ion concentration
• Kidneys require hours to days to
compensate for changes in body-fluid pH
• Control pH of body fluids by adjusting
– H+ excretion
– HCO3- excretion
– Ammonia secretion
9
CO2
HCO3- + H+
HCO3-
H+ : Phosphoric
acid, NH4+
HCO3- reabsorption and H+ secretion
10
HCO3- Reabsorption
(main physiological buffer)
• Kidneys alter/replenish H+ by altering plasma [HCO3-].
• HCO3- filtered then practically all reabsorbed under normal conditions.
• Prevents you gradually becoming acidotic because of metabolism.
Gains = Losses, means maintain HOMEOSTASIS.
• The secreted H+ combines with filtered HCO3- in tubule to form CO2 and
H2O.
11
Addition of new HCO3- to plasma by
secretion of H+
• When you use up filtered HCO3- in tubule and still have excess H+
(acidosis), then you must combine H+ with another buffer e.g.
HPO42-.
• Unusual since lots of HCO3- in tubular fluid!
• Gives net gain of HCO3- to plasma.
Addition of new HCO3- to plasma by
excretion of ammonium (NH4+)
• Another way of
adding HCO3- to
plasma by
metabolising
glutamine.
• Takes long time,
usually only occurs
in chronic acidosis
e.g. diabetes.
glutamine
12
Acid-Base Imbalances
• Can arise from either respiratory
dysfunction or metabolic disturbances
• Deviations divided into four general
categories
– Respiratory acidosis
– Respiratory alkalosis
– Metabolic acidosis
– Metabolic alkalosis
Respiratory Acidosis
• Result of abnormal CO2 retention arising from
hypoventilation
• Possible causes
–
–
–
–
Lung disease
Depression of respiratory center by drugs or disease
Nerve or muscle disorders that reduce respiratory muscle activity
Holding breath
• Compensations
– Chemical buffers immediately take up additional H+
– Kidneys are most important in compensating for respiratory
acidosis
13
Respiratory Alkalosis
• Primarily due to excessive loss of CO2 from body as
result of hyperventilation
• Possible causes
–
–
–
–
Fever
Anxiety
Aspirin poisoning
Physiologic mechanisms at high altitude
• Compensations
– Chemical buffer systems liberate H+
– If situation continues a few days, kidneys compensate by
conserving H+ and excreting more HCO3-
Metabolic Acidosis
• Includes all types of acidosis other than those caused by
excess CO2 in body fluids
• Causes
–
–
–
–
Severe diarrhea
Diabetes mellitus
Strenuous exercise
Uremic acidosis
• Compensations
– Buffers take up extra H+
– Lungs blow off additional H+ generating CO2
– Kidneys excrete more H+ and conserve more HCO3-
14
Metabolic Alkalosis
• Reduction in plasma pH caused by relative deficiency of
noncarbonic acids
• Causes
– Vomiting
– Ingestion of alkaline drugs
• Compensations
– Chemical buffer systems immediately liberate H+
– Ventilation is reduced
– If condition persists for several days, kidneys
conserve H+ and excrete excess HCO3- in the urine
Patient evaluation The presence of an acid-base disturbance may be
suspected on the basis of clinical presentation or by results of laboratory data
(eg, a low HCO3-). Evaluation of any acid-base disorder can then be
approached in a stepwise manner
ACID-BASE Parameters
15
Vit D and the kidney
-conversion of Vit D to calcitriol
-Enhances Ca2+ absorption
-Increases Ca2+ in plasma
Kidney, bone and calcium balance
99% of Ca2+ in bone
PTH - parathyroid hormone
Calcitonin - thyroid gland
16