MINISTRY OF PUBLIC HEALTH OF UKRAINE
BUKOVINIAN STATE MEDICAL UNIVERSITY
Approval on methodological meeting
of the department of pathophisiology
Protocol №
Chief of department of the pathophysiology,
professor
Yu.Ye.Rohovyy
“___” ___________ 2008 year.
Methodological Instruction
to Practical Lesson
Мodule 1 : GENERAL PATHOLOGY.
Contenting module 3. Typical disorders of metabolism.
Theme20: Acid-base imbalance.
Chernivtsi – 2008
1.Actuality of the theme. The normal functioning of an organism is
possible only under condition of biochemical stability of its liquids, which is
named homeostasis. The acid-base balance, maintenance of concentration of
hydrogen ions (рН) in blood, lymph, tissues, spinal cord and other liquids in a
rather narrow range (for blood 7,35-7,45) concerns to major elements of the
homeostasis. This persistance of рН is necessary, the first of all, for maintenance
of enzyme activity. It is provided with buffer systems of blood (bicarbonate,
phosphate, protein, hemoglobin buffers) and some organs (lungs, kidneys,
stomach, intestine). The disorder of acid-base balance can be considered as the
original form of pathology metabolism. Its essence is in increase of the contents
of liquids of an organism of substances of acid or alkaline character. The state, for
which the acid compound prevail is named acidosis, the opposite one is alkalosis.
The disorders of acid-base balance arise very frequently. For example, acidosis
is accompanied by such diseases and pathological states as diabetes mellitus,
starvation, deep hypoxia, shock, collaps, damage of liver and kidneys, oppression
of respiratory centre by drugs, lungs edema, pneumonia. Аlkalosis arise after
introduction of big quantities of sodium bicarbonate, as a result of significant loss
of gastric juice (pylorostenosis, cancer, unrestrained vomiting of pregnant
women), in hyperthermia, encephalitis, attacks of epylepsia and hysteria, breathing
by rare air, excessive artificial ventilation of the lungs. The significant fluctuations
of blood рН leads to irreversible changes of the vital organs and death of an
organism. Shifts of рН become dangerous to life, if the mechanisms of regulation
of acid-base balance are not capable to compensate influence of acid or basic
substances. In these cases the correction of acid-base balance becomes extremely
necessary. It is realized after preliminary definition of indexes, which characterize
state of acid-base balance of the patient.
2.Length of the employment – 2 hours.
3.Aim:
To khow: Acid-base metabolism is characterised by function such organs as
respiratory system, blood, renal system. Maintaining acid-base homeostasis depend
on 4 buffer’s system: 1. Hydrocarbonate buffer system H 2CO3 / NaHCO3 = 1 / 20
maintains constantly pH in plasma of blood and interstitial fluid 2. Phosphate
buffer system NaH2PO4 / Na2HPO4 = 1 / 4. Participate in regulation acid-base
condition in kidneys. 3. Hemoglobin buffer acts in erythrocytes. 4. Protein buffer
regulates intracytes pH.
To be able: to analyse of the pathogenesis of the respiratory acidosis,
metabolic acidosis, respiratory alkalosis, metabolic alkalosis.
To perform practical work: Characteristic of acid-base condition.
Disorders of acidbalance
Etiological factors
homeostasis
Acute respiratory Acute respiratory insufficiency,
acidosis
cardiacpulmonary insufficiency,
trauma of brestbone, asphyxia,
trauma/tumor CNS, damage of
the respiratiry muscles.
Clinical
manifestation
Tachycardia,
tachypnoe, sweating,
headache, letargy
coma, cyanosis,
arrhythmias,
hypotension.
Dyspnea or
tachypnea, confused,
coma
pH
CO2
HCO3-
↓
decr.
↑
incr.
Don’t
change
↓
↑
↑
↓
↓
↓
Chronic
respiratory
acidosis
(compensatory
form)
Acute metabolic
acidosis
Chronic obstructive diseases of
lungs, obesity (Pickwick’s
syndrome)
Chronic
metabolic
acidosis
Chronic kidneys’ insufficiency
Acute respiratiry
alcalosis
Hyperventilation, hypoxia as
result pneumonia, lung edema,
damage of the CNS
Hepar insufficiency, damage of
the CNS, pregnancy.
Dizziness,
paresthesias
especially in fingers.
Asymptomatic
↑
↓ less
than
under
acute
form
↓
↑
↓
↓
Wasting HCl under vomiting,
hyperadrenocorticism
(Cushing’s syndrome),
aldosteronism.
Prolonged vomiting
Muscle weakness,
arrhythmias, apathy,
confused, stuporos.
↑
↑
↑
Don’t clinical
manifestation
↑
↑
↑
Chronic
respiratory
alcalosis
Acute metabolic
alcalosis
Chronic
metabolic
alkalosis
Diabetus mellitus, starvation
(complete), shock, heart
blockade, breathe colapse.
Kussmaul respiration
(hyperpnea),
hypotension,
sweating cold skin,
coma, arrhythmias.
Weakness
↓
↓
Don’t
change
4. Basic level.
The name of the previous disciplines
The receiving of the skills
1.
2.
3.
Buffer systems of the organism
Mechanisms of regulation of acid-base
balance
histology
biochemistry
physiology
5. The advices for students.
1. The buffer systems of organism include:
1. Bicarbonate buffer. It consists of carbonic acid (acid buffer components)
and anion of carbonic acid (alkaline buffer component). Alkaline component is in
20 times stronger, than acid one. Bicarbonate buffer can be represented by
following image: H2CO3/HCO3– = 1/20.
2. Phosphate buffer. It consist of once-replaced salt of phosphoric acid (acid
component) and twice-replaced salt of phosphoric acid (alkaline component).
Alkaline component is in 4 times stronger, than acid one. Phosphate buffer can be
represented thus: NaH2PO4/ Na2HPO4 = 1/4.
3. Protein buffer. Proteins are ampholites. They react in both ways: as acid,
and as alkali.
4. Hemoglobin buffer. Oxidized hemoglobin (desoxyhemoglobin) has alkali
properties. Oxyhemoglobin is in 70 times stronger as acid, than
desoxyhemoglobin. Hemoglobin buffer can be presented this way: HbO 2 (acid)/
Hb (basis) = 70/1.
Besides buffer systems, some organs play an important role in regulation of
acid-base balance :
1. Lungs – eliminate carbonic acid (850 g in day).
2. Stomach – in stomach cavity hydrochloryc acid is secreted.
3. Bowels – in bowels cavity bicarbonates are secreted.
4. Kidney participation in regulation of acid-base balance veries. Firstly –
kidney support bicarbonates level in blood by augmentation dint of diminution of
their reabsorbtion in canaliculi. Secondly - the kidney secrete the various acid nonvolatile substances, which are hydrogen ions.
The hydrogen ions excretion is performed in three ways:
2. Acidogenesis – free organic acids excretion. Organic acids anions in form
of sodium salts get filtered in glomeruli and arrive into the primary urine. Besides
in space of canaliculi hydrogen ions are secreted. So, in space of canaliculi pure
organic acids derivate to go into secondary urine: NaAn + Н+ → Na+ + НАn.
Sodium return into blood.
3. Ammoniogenesis – inorganic acids excretion in form of ammonium salts.
Ammoniogenesis takes place in distal canaliculi and in collective tubules.
Inorganic acids are more stronger, than organic. Therefore it is impossible to
excrete them in free form. In effect of urine (рН beneath 4,5) canaliculious
epithelium can be destroyed. There is also other mechanism of inorganic acids
excretion. It consists of following. Sodium salts of inorganic acids get filtered in
glomeruli into primary urine. In cells of distal canaliculi and in collective tubules
ammonia (NН3+) is synthesized from glutamine acid. In space of canaliculi
ammonia salts of inorganic acids are derivated. They go to secondary urine, and
sodium returns into blood. We will show this mechanism on example of sulfuric
acid: NaHSO4 + NH3+ → (NH4)2SO4 + Na+.
4. Transformation of alkaline phosphates into acid: Na2HPO4 + H+ →
NaH2PO4 + Na+. Last are excreted from organism. The sodium ions return into
blood.
Except рН, there are other indexes, which describe acid-base balance. Main of
them are following: а) pСО2 – pressure of carbonic acid in blood (physiological
range – 34-45 mm Hg average norm – 40 mm Hg); b) SB – standard blood
bicarbonate (norm – 21-25 mmol/l); c) BB – sum of buffer blood bases (norm –
45-52 mmol/l);
d) BЕ – surplus or deficit of buffer bases (norm is (-2,3)(+2,3) (mmol/l).
5. Types of acid-base balance disorder
Acid-base balance can displace in both in acid, and alkaline side. Hereupon
arise states, which are called acidosis and alkalosis. Acidosis is such an acid-base
disorder, which arises when a surplus amount of acids in organism accumulates
and concentration of hydrogen ions increases. Alkalosis appears, when amount of
bases in organism increases and concentration of hydrogen ions decreases.
Accoding to рН changes acidoses and alkaloses are divided into groups:
а) сompensated – if рН holds in range of physiological norm (7,34-7,45);
b) decompensated – if рН is out of norm range.
Life is possible in case of the extreme values of рН, egual to 6,8-7,8.
According to origin acidoses and alkaloses are also divided into groups –
metabolic and gas.
6. Metabolic acidosis
This is very freguent and very serious form of acid-base balance disorder.
There are two types of metabolic acidosis: а) metabolic acidosis with raised anion
difference (delta-acidosis); b) metabolic acidosis with normal anion difference
(nondelta-acidosis).
Anion difference, or anion interval is the difference between of sodium and
potassium (Na+, K+) ions concentrations the sum in blood plasma, due to chlorine
and bicarbonate (Clˉ, НСОˉ3) ions concentrations sum. A difference between
kations and anions is designated by letter and is named simply “delta”. However,
there is a little quantity of potassium ions in plasma, their concentration is changes
unsignificantly. Therefore potassium ions can be neglected. Then value “delta” can
be represented in equalization appearance: ∆ = (Na+) - ([Clˉ] + [HCOˉ3]). In norm
the average anion difference is 12±4 mmol/l. It is conditioned by the presence of
many negatively charged anions in plasma – sulipoproteinshates, phosphates,
anions of organic acids, negatively charged proteins. In usual practice the
mentioned anions are determined. The determination of their summary amount
(anion difference) has a diagnostic importance.
Metabolic acidosis with raised anion difference (delta-acidosis). Such
acidosis arises when, strong organic acids act up on organism. Classic example of
delta-acidosis is diabetic ketoacidosis. It is typical for insulin-dependent diabetes
mellitus. Attached to diabetes ketones react with bicarbonates (NaНСО3) and
carbonic acid is derivated (Н2СО3). It disintegrates to carbonic gas (СО2) and
water (Н2О). Carbonic gas is excreted by lungs. As a result, bicarbonate
concentration diminishes, while sodium and chlorine ions concentration does not
change. Therefore the anion difference increases.
Delta-acidosis also includes lactic-acidosis. It is conditioned by accumulation
of acid. More freguent lactic-acidosis is observed attached to shock, collapse, heart
stop, large vessels compression.
Acidosis with high anion difference arises to much hereditary metabolic
disturbances in children, for example attached to glycogenesis of type І (Girke’s
disease), glutaraciduria, unsufficiency of piruvate-dehydrogenase, etc. All of these
metabolic disorders are attended with strong organic acids derivation and
accumulation in organism.
Another typical example of delta-acidosis is diarrhea in infants. Pathogenicity
of this acidosis is complicated. Firstly, children with metabolic disorders badly
consume food. They are frequently in state of starvation. Consequently, ketone
bodies are derivated. Secondly, undigested food stays too long in digestive tract of
such children. Under the oral bacterium influence, digestive tract strong acids are
derivated. They are absorbed to blood. Thirdly, these children have frequently got
a dehydratation development, therefore glomerular filtration diminishes in kidneys.
Accordingly to that acids excretion diminishes.
Delta-acidosis development is also attached to nephritic insufficiency (uremic
acidosis). This acidosis is conditioned mainly by diminution of ammonium ions
excretion. Inorganic acids (sulfuric, phosphoric) are excreted with urine nominally
as ammonium salts. Attached to nephritic unsufficiency they accumulate in blood
and titer bicarbonate. Its amount gets diminished. The hydrogen ions run from
blood into cells, mainly into osseous tissue. Calcium salts leave bones for blood in
exchange on hydrogen ions. Bones lose mineral components. The osteodistrophy
develops.
Some poisons can also cause acidosis with high anion difference. Ethyl
alcohol changes an intermediate metabolism and cause final derivation of lactic
acid and ketones amount. Poisoning by methyl alcohol leads to acidosis, because
methanole turns into methyle acid. Attached to poisoning by ethylenglycole, oxalic
and glyoxalic acids are derivated. Thus, all of enumerated poisons cause derivation
of organic acids. These acids titer bicarbonate and multiply anion difference.
Metabolic acidosis with normal anion difference (non-delta-acidosis). This
kind of metabolic acidosis is characterised by: а) diminution of bicarbonate
concentration in blood; b) augmentation of chlorine ions concentration in blood,
which is hyperchorinemia; c) contrary bicarbonate and chlorine mutually
equilibrate, therefore anion difference does not change.
Prime example is acidosis due to bicarbonate loss over bowels (diarrea in
adult, fistula of pancreas). Attached to these states there is loss of liquid. Volume
of circulatory blood diminishes. Synthesis of aldosterone in adrenal cortex
increases. It reinforces sodium chloride reabsorbtion in kidney. Hyperchlorinemia
occurs. Thus, bicarbonate loss over bowels is compensated by chlorine delay in
kidney. Anion difference does not change.
Non-delta-acidosis occur also in infants with hereditary metabolic
disturbances. Such children are treated by artificial mixtures, which contain
synthetic amino acids. Attached to their katabolism big amount of hydrogen ions is
derivated. This leads to acidosis.
Another type of hyperchlorinemic metabolic acidosis is nephritic canalicular
acidosis. There are two type of such nephritic canalicular acidosis and proximal
nephritic canalicular acidosis.
A cause of distal acidosis arises in fact, that distal department of nephrone can
not secrete sufficient amount of hydrogen ionin space of canaliculus. Urine pН is
not lower than 6,0. Alkaline urine substances do not titer. Endogenic acids stay too
long in organism. There are hereditary and acquired distal canalicular acidoses. It
is observed attached to such illness: kidney kystosis, chronic pyelonephritis,
systematic rheumatic disease, sickle-cell anemia, hyperparathyreosis, fructosuria.
Proximal canalicular acidosis is related to disorder of bicarbonate
reabsorption in proximal canaliculi. Because of this many bicarbonates are getting
lost with urine. Bicarbonate concentration in blood lowers. Simultaneously volume
of extracellular liquid diminishes. There are many causes of proximal acidosis.
Usually, this is hereditary or acquired disorders of metabolism. Proximal acidosis
can be caused by medicines, for example sulfanilamides. They oppress
carboanhydrase of canalicular epithelium, and this enzyme is necessary for
reabsorbtion of bicarbonates. Proximal canalicular acidosis is frequently combined
with Fankoni’s syndrome. Attached to this disease reabsorption of many
substances – amino acids, glucose, including bicarbonate, is violated.
Other causes of proximal canalicular acidosis are galactosemia, some types of
glycogenoses, Wilson’s disease, poisoning by salts of heavy metals.
Compensatory mechanisms of metabolic acidosis are:
1. Bicarbonate buffer. Attached to augmentation of acids in blood,
bicarbonate neutralizes them. Neutralization mechanism is following. Alkaline
anion НСОˉ3 (mainly sodium salt) bind hydrogen ion. Carbonic acid is formed. It
rapidly dissociates to Н2О and СО2. During acids neutralization amount of
bicarbonate diminishes. Diminution of bicarbonate is very typical index of
metabolic acidosis.
2. Reinforcement of pulmonary ventilation. Accumulation of carbonic acid
stimulates respiratory centre. Breathing becomes deep and frequent. СО2 is the
strongest physiological stimulator of respiratory centre. Heightening of carbonic
acid (рСО2) pressure in blood up to 10 mm Hg multiplies pulmonary ventilation in
4 times. Hyperventilation of lungs is the major compensatory mechanism of
metabolic acidosis. It reaches maximum already in a few hours from acidosis
beginning.
3. Nephritic mechanisms – heightening of acidosis and ammoniagenesis,
heightened excretion of acid phosphates.
4. Interchange of ions between blood and cells also has some compensatory
importance. The hydrogen ions come into erythrocytes, osteocytes. Alkaline metals
– potassium calcium ions exit from cells in blood. Thus, there is another typical
sign of metabolic acidosis – hyperpotassemia.
Negative consequences of metabolic acidosis include:
1. Secondary hypocapnia. Because of continuous hyperventilation of lungs,
pressure of СО2 in blood and other liquids decreases. Accordingly to this decreases
excitability of respiratory centre. A breathing pauses – coma treads.
2. Hypotonia – weakening of smooth muscles. Collapse treads after
diminution of cardiac volume. Blood pressure decreases. Nephritic filtration
diminishes. Anuria treads.
3. Electrolytes loss in cells. Erythrocytes, osteocytes and other cells lose the
potassium and calcium ions. Amount of them in cells diminishes, but in
extracellular liquid – increases. Osmotic pressure of extracellular liquid increases.
Water delays in tissues oedema develops. Simultaneously liquid leaves cells.
Intracellular dehydratation develops.
Main pathogenic medical arrangement, which is attached to metabolic
acidosis of any origin, is intravenous infusion of bicarbonate solution.
7. Gas acidosis
This form of acidosis occurs seldom and it’s cours is less serious. Acidosis is
caused by carbonic acid delaing in organism. СО2 pressure increases in blood.
Reason of gas acidosis are: respiratory system diseases and disorder of gases
interchange between blood and air – lung oedema pneumonia, atelectasis,
emphysema, asphyxia, pneumothorax; oppression of respiratory centre by
botulotoxine, morphia, barbiturates; artificial respiration by aerial mixture with
high content of CO2; damage of diaphragmal nerves and intercostal muscles.
Hemoglobin buffer is the main compensatory mechanism of gas acidosis.
This is intracellular, erythrocyte buffer. It includes 75 % of all blood buffer
capacities.
During the blood flowing over tissue capillaries it receives from cells some
number of acid products. They are the intermediate and final products of
metabolism, which produce hydrogen ions in plasma and attampt to рН decrease.
This displacement is prevented by hemoglobin. In capillaries oxygemoglobin gives
up oxygen and turns into reduced form. Herewith it loses its acid properties.
Desoxyhemoglobin behaves a like weak base. It binds up hydrogen ions and gives
up the free potassium ions, which bind whis erythrocytes.
Attached to gas acidosis organism is literally saturated by carbonic gas. СО2
also arrives into erythrocytes, carbonic acid is derivated there. Then acid binds up
potassium ions and turns into bicarbonate (КНСО3). By such method pH holds out
within the norm range for a long time.
In lungs hemoglobin buffer acts other gates. A venous blood contacts with
alveolar air in pulmonary capillaries. Oxygen goes into blood, while carbonic acid
goes from blood into alveolar air. First of all the carbon gas pressure lowers in
plasma, and in erythrocytes later. Рh begins to increase. However in-parallel
hemoglobin with oxygen reduces. Acid oxyhemoglobin is formed up (to 98 %). It
prevents рН increasing.
Kidneys are very important in gas acidosis compensation. There is straight
dependence between carbonic acid pressure in blood and bicarbonate reabsorbtion
speed. Tension СО2 rises – bicarbonate gets reabsorped faster, СО2 pressure
desrease – reabsorption of bicarbonate slows down. Maximum effect of nephritic
gas acidosis compensation treads over a few days from the beginning of acidosis.
The main consequence of gas acidosis is hypercapnia. It causes smooth
muscles of vessels spasm. Arterial hypertension treads. Heart work becames
difficult.
Medical arrangements: а) cause of CO2 delay removal in organism;
b) introduction of antispasmic medicines; c) artificial respiration by air with high
oxygen contents.
8. Metabolic alkalosis
Metabolic alkalosis is a result of bases accumulation in organism or nonvolatile acids losses. Herewith a bicarbonate concentration in blood rises, рН
iscreases. Causes: 1. Consuming of big amount of alkali. Usually, this happens to
patients with ulcerous stomach disease. Sometimes they consume a lot of soda. 2.
Cure of acidemia. For example, cure of ketoacidic coma in patients with diabetus
mellitus sometimes leads to alkalosis. 3. Loss of big amount of gastric
hydrochloric acid in pregnant with indomitable vomiting, pylorostenosis, pyloric
cancer. In all of cases hydrochloric acid is lost and a strong base НСО3‾ remains.
Thus, this is hydrochloremic alkalosis. 4. Hyperproduction of mineralocorticoids
(primary aldosteronism). Mechanism of alkalosis is following. Attached to
aldosteronism potassium reabsorption in kidney decreases, it is lost with urine.
Potassium leave cells for blood as compensation. In exchange on potassium cells
enter hydrogen ions. Hypopotassemia alkalosis occurs.
Major compensation mechanisms of metabolic alkalosis – lung
hypoventilation, nephritic mechanisms.
Serious consequences of metabolic acidosis are increasing of nervouslymuscular excitability (tetany). Plural muscles contractions, cramps occur. Tetany is
caused by diminution of ionized calcium in blood.
9. Gas alkalosis
This is very rare and very light form of acid-base balance disorder. Primary
mechanism is lowering of carbonic acid pressure in blood because of lung
hyperventilation. Carbonic acid and hydrogen ions concentration decreases in
blood. Causes: breathing by rarefied air on height, lack of breath attached to
organic defeat of cerebrum (encephalitis, hypothalamus tumor, bleeding),
functional central nervous system changes (epilepsy, hysteria), lack of breath
attached to hyperthermia, strong weeping in children, very intensive artificial
breathing.
Nephritic mechanisms stand in first place among compensation mechanisms.
Some role plays protein buffer.
5.1. Content of the theme. The buffer systems of organism.
Acidogenesis. Ammoniogenesis.Transformation of alkaline phosphates into acid.
Types of acid-base balance disorder. Metabolic acidosis. Gas acidosis. Metabolic
alkalosis. Gas alkalosis.
5.2. Control questions of the theme:
1.The buffer systems of organism.
2.Acidogenesis.
3.Ammoniogenesis.
4.Transformation of alkaline phosphates into acid.
5.Types of acid-base balance disorder.
6. Metabolic acidosis.
7.Gas acidosis.
8.Metabolic alkalosis.
9.Gas alkalosis.
5.3. Practice Examination.
Task 1. During the heavy form of diabetes mellitus acidosis develops. The
components of what buffer system are changed the first of all?
А. Bicarbonate В. Phosphate С. Hemoglobin D. Oxyhemoglobin
Е. Protein
Task 2. It is known, that free Н +-ions play defining role in creation of actual
reaction of blood. Which organ regulating the acid-base balance, has the
most important meaning in elimination of Н+?
А. Skin В. Lungs С. Liver D. Stomach Е. Kidney
Task 3. It is known that in regulaiton of acid-base balance the large role belongs to
external breathing. The change of content of which substance provides
maintenance of normal рН of the lungs?
А. Methemoglobin В. Carbonic gas С. Urea D. Ammonium chloride
Е. Carbonic acid
Task 4. In the patient in time of the operation the following parameters of acidbase balance are determined: рН of blood - 7,3, pСО2 - 70 mm Hg.
Frequency of heart contractions - 108/min., pulse is arythmical, arterial
pressure - 145/94 mm Hg. For what kind of disorder of acid-base balance
these changes are most typical?
А. Gas аcidosis В. Gas alkalosis С. Metaboilc acidosis
D. Metabolic alkalosis Е. Mixed forms
Task 5. In the patient in time of the operation the following was found: рН of
blood - 7,5, pСО2 - 20 mm Hg, arterial pressure - 95/70 mm Hg. These
disorders of acid-base balance are characterized for
А. Gas acidosis В. Gas alkalosis С. Metabolic acidosis
D. Metabolic alkalosis Е. Mixed forms
N2
A-?
B-?
C- ?
Value of pH
Acidosis
7,35-7,40
7,34-7,20
7,19-6,80
N3
A-?
B- ?
C- ?
Value of pH
Alkalosis
7,40-7,45
7,46-7,55
7,56-7,80
Literature:
1. Gozhenko A.I., Makulkin R.F., Gurcalova I.P. at al. General and clinical
pathophysiology/ Workbook for medical students and practitioners.-Odessa, 2001.
2. Gozhenko A.I., Gurcalova I.P. General and clinical pathophysiology/ Study
guide for medical students and practitioners.-Odessa, 2003.
3. Robbins Pathologic basis of disease.-6th ed./Ramzi S.Cotnar, Vinay Kumar,
Tucker Collins.-Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.-1999.