The document discusses biochemistry of the respiratory system and lungs. Key points:
- Lungs produce surfactant, collagen/elastin, and mucus to reduce surface tension, support structure, and protect against pathogens.
- Surfactant is composed of phospholipids like DPPC and proteins that lower surface tension at the air-liquid interface in alveoli.
- Surfactant deficiency in premature infants can cause Respiratory Distress Syndrome, as their lungs have not fully developed the ability to produce sufficient surfactant. Measurement of surfactant components in amniotic fluid is used to assess fetal lung maturity.
4. • Surface tension results in a skin at the
surface of the liquid
Balanced force
in the interior
Unbalanced forces
at the surface
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5. Surface Tension
• In the liquid state, the cohesive forces between adjacent
molecules are well developed.
▫ Molecules in the bulk of a liquid are surrounded in all
directions by other molecules for which they have an equal
attraction.
▫ Molecules at the surface (at the liquid/air interface) have
only attractive cohesive forces with other liquid molecules
which are situated below and adjacent to them.
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6. • They can develop adhesive forces of attraction with the
molecules of the other phase in the interface
• The net effect is that the molecules at the surface of the
liquid experience an inward force towards the bulk of the
liquid and pull the molecules and contract the surface with
a force F .
• Surface tension is an effect within the surface layer of a
liquid that causes that layer to behave as an elastic sheet
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7. • How do insects such as water striders, usually denser
than water, float and stride on water surface?????
• As the temperature of a liquid increases what
will be the effect on the surface tension?
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10. History of pulmonary surfactant study
• 1929 - von Neergaard
found that the pressure necessary for filling the lungs with air was
higher than whenthe lungs were filled with liquid.
he stated that the alveoli were stabilized by lowering the naturally
high surface tension ofthe air/water interface.
• 1946 - Thannhauser and co-workers
reported that lung tissue has a remarkably high content of the lipid
dipalmityl lecithin (dipalmitoylphosphatidylcholine)
• 1955 – Pattle
proposed that bubbles, made of lung fluid material, obtained their
stability through the quantity and quality of the surface-active
material
• Clements showed that it is phospholipids that play the major role
• Avery and Mead showed that the surface tension of lung extracts of
infants under 1,100– 1,200g and of those dying with hyaline
membrane disease was higher than expected
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11. • In 1967 DPPC produced during the development of the lung and
secreted into the alveolar space
• A few years later a diagnostic test, using the lecithin/sphingomyelin
ratio of amniotic fluid, was developed to determine the maturity of the
fetal lung
• 1975 - Hallman and co-workers
discovered the importance of phosphatidylglycerol (PG) in contributing to
surfactant spreading and the decreased levels of this phospholipid in children
suffering from RDS
1988
a new nomenclature for surfactant proteins was proposed
Apart from the biophysical role of surfactant, it became clear that surfactant
had also a role in lung defense
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12. Structure ofAlveolus
• Alveoli:
Thin walled, blind-end sacs
Site of gas exchange
• Epithelium composed of two cell types:
Type I: thin, responsible for gas exchange
Type II: thick, maintain fluid balance across lungs &
secrete surfactants
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13. Structure of Alveolus
• Exhalation results in a decreased surface area and a decreased surface
tension, whereas a relatively high surface tension is found when the surface
area of the lung is large (after inhalation).
• This mechanism prevents the alveoli from collapsing during expiration.
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14. Pulmonary surfactants
• PS is the layer of lipid and protein that coats the alveolar surface of the
lung.
• Helps the alveoli to remain expanded during the respiratory cycle (i.e.,
not to collapse when one exhales)
• Lowers the ST across the air-water interface of alveoli, thereby
preventing collapse of terminal respiratory chambers and conducting
airways.
Increases compliance
Decreases work of inspiration
• Helps to keep the lungs dry
• Produced by type II alveolar cells on a continuous basis
• A complex mixture of 10% proteins and 90% mixed PL
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17. Phospholipid
• There are two classes of phospholipids: those that have glycerol as a backbone and those that contain
sphingosine
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18. Protein content of surfactants
• Make up a small proportion of its total weight
• Two types of surfactant-associated proteins
(SPs):
▫ Hydrophobic
SP-B and SP-C
small peptides (35 AA), highly hydrophobic
Important in facilitating the surface activity
of the mixture
Confer surface tension-lowering properties
Important for spreading of the surfactant
▫ Hydrophilic proteins
SP-A and SP-D
Regulate surfactant secretion and
antimicrobial protection
Large glycosylated proteins ( SP-D has 355
AAs)
Members of calcium-dependent
carbohydrate-binding collectin family
• About half of the other proteins are proteins
normally found in blood plasma.
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19. Hydrophilic surfactant proteins
• SP-A and SP-D are related and belong to a subgroup of
mammalian lectins called collectins (or C-type lectins)
▫ Consist of oligomers with COOH-terminal carbohydrate
recognition domains in association with NH2-terminal
collagen- like domains.
• SP-A and SP-D may be involved in the first-line defense
system of the lung
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20. SP-A is responsible for:
• formation of tubular myelin,
• regulation of phospholipid insertion into the monolayer,
• modulation of uptake and secretion of phospholipids by type II cells,
• activation of alveolar macrophages,
• binding and clearance of bacteria and viruses,
• chemotactic stimulation of alveolar macrophages,
SP-D
• plays important role in pathogen defense
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21. Hydrophobic surfactant proteins
• SP-B and SP-C:
enhance the biophysical properties of
surfactants,
assist in rapid insertion of phospholipids into the
monolayer and molecular ordering of the
monolayer
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22. Summary _ Functions of Surfactants
• Once secreted to alveolar space, surfactant absorbs rapidly
to the air liquid interface (a newborn baby´s first breath).
• Once in the interface, surfactant films reduces surface tension
when compressed during expiration (lungs don´t collapse).
Surfactant reduces tension of the air/liquid interface to near
zero
• Surfactant proteins recognize and opsonize bacterial fungal,
viral surface oligosaccharides.
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23. Pulmonary Surface Tension
• Keep the alveoli dry
The reduction in surface tension reduces fluid accumulation in the
alveolus as the surface tension draws fluid across the alveolar wall.
• Regulate the alveolar size
The increase in surface tension (as the alveoli increase in size, the
surfactant becomes more spread out over the surface of the liquid):
Slows the rate of increase of the alveoli.
Helps all alveoli expand at the same rate (as one that increases
more quickly will experience a large rise in surface tension
slowing its rate of expansion).
Regulates the rate of shrinking( as if one reduces in size more
quickly the surface tension will reduce more so other alveoli can
contract more easily than it).
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24. Host Defense
SP-Aand D Confer innate immunity (carbohydrate recognition domains allowing
them to coat bacteria and viruses promoting phagocytosis by macrophages
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25. • Surfactant aids the oxygen to perfuse from the
atmosphere into the pulmonary capillaries
• During the breathing cycle :
o DPPC is insert into the monolayer, lowers the surface
tension of air/liquid interface
o PG is effective in spreading surfactant
o Proteins accelerate the process to lower tension
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27. Pulmonary surfactant and the developing lung
1. lecithin increases rapidly at the
start of the third trimester and
then rises rapidly to peak near
term
2. most lecithin in the mature lung
is dipalmitate, but in the
immature lung it is a less-
surface-active α-palmitate, α -
myristate species
3. phosphatidylglycerol is not
present in the lungs before the
36th week of pregnancy; and
4. before the 35th week, the
immature surfactant contains a
higher proportion of
sphingomyelin than adult
surfactant.
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28. • The fetal lung has a specialized role for glycogen stores
• Type II pulmonary cells begin to accumulate glycogen at about 26 weeks
of gestation
• Late in gestation, these cells shift their metabolism toward the synthesis
of pulmonary surfactant, with the intracellular glycogen serving as a
major substrate for the synthesis of surfactant lipids, of which
dipalmitoylphosphatidylcholine is the major component.
• The rate of de novo fatty acid synthesis is very high during
embryogenesis and in fetal lungs when there is a need for palmitic acid
to support the synthesis of dipalmitoylphosphatidylcholine-rich
pulmonary surfactant.
Pulmonary surfactant and the developing lung
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29. • Pulmonary surfactant is released into the amniotic fluid,
which can be sampled by amniocentesis to assess fetal lung
maturity.
A lecithin-to-sphingomyelin ratio above 2:1 implies that the fetus should survive
without developing respiratory distress syndrome.
• After the 35th week, the appearance of
phosphatidylglycerol in the amniotic fluid is the best
proof of the maturity of the fetal lungs
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30. Neonatal Respiratory Distress Syndrome (RDS)
• The leading cause of morbidity and mortality among
premature infants
• Its incidence varies inversely with gestational age and birth
weight
▫ More than half of newborns younger than 28 weeks’ gestational age have RDS, but
only one fifth of infants between 32 and 36 weeks do
• In addition to prematurity, other risk factors for RDS
include
1. neonatal asphyxia,
2. maternal diabetes,
3. delivery by cesarean section,
4. precipitous delivery and
5. twin pregnancy
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31. • The main cause of RDS is a shortage of surfactant, and leakage of
serum proteins to the alveolar space probably contributes to the
disease.
• Lungs of infants dying from RDS contain all normal components
except tubular myelin . As SP-A and SP-B are essential for the
formation of tubular myelin,
• this could indicate that one or both of these proteins are
nonfunctional or missing. This was confirmed by a study showing
that neonates seem to have an immature SP-A metabolism
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33. INTRODUCTION
Type II pneumocytes package surfactant into intracellular storage
granules called lamellar bodies which are excreted into the
alveolar space via exocytosis.
Once secreted, lamellar bodies become hydrated in the surface
water layer and unravel to form tubular myelin, a lattice-like
structure composed of lipids and proteins that support the
surfactant monolayer.
Fetal breathing movements in utero expel pulmonary lamellar
bodies and surfactant into the amniotic fluid.
Surfactant and lamellar bodies appear in the amniotic fluid at 28 to
32 weeks and increase exponentially as gestation continues.
Thus, measuring amniotic fluid lamellar bodies or surfactant
phospholipid components assists estimation of fetal lung
development and risk of RDS during weeks 32 to 36 of gestation.
By week 37 of gestation and beyond, the risk of RDS is so low that
laboratory assessment of fetal lung maturity (FLM) is rarely
indicated
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34. Lamellar Body Count Principles
The intact lamellar body has an average diameter of 1 to 5
microns and a volume of 1.7 to 7.3 fL, which is similar to the
size of platelets (2 to 4 microns or 5 to 7 fL).
Automated hematology analyzers accurately count platelets
in whole blood using impedance and/or light refraction to
determine particle size and distinguish them from other
cellular components.
Due to the similar size of lamellar bodies and platelets,
automated hematology analyzers can quantify amniotic fluid
lamellar bodies in the platelet channel to provide a lamellar
body count (LBC).
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35. Preanalytical Considerations
• Amniotic fluid is a heterogeneous mixture containing sloughed cells,
hair, and other fetal debris that can have varying effects on LBC
measurement.
• Blood contamination is an obvious concern since the presence of
platelets in the amniotic fluid could artificially increase the LBC.
• Addition of lysed red cells (free hemoglobin 10 g/L) lowered LBC to less
than 1,000/μL.
• However, addition of whole blood to amniotic fluid (hematocrit 1%) has
been reported to cause an immediate LBC increase of ~2,000 to
8,000/μL,11 and following incubation for 10 to 60 minutes, an absolute
decrease in LBC of 1,000 to 8,000/μL compared with baseline.
• Possible mechanisms include absorption of lamellar bodies to cellular
elements or trapping of lamellar bodies in fibrin clots.
• Meconium has been shown to lower LBC less than 5,000/μL,and mucus
in a specimen collected from a vaginal pool can artificially increase LBC.
• Therefore, specimens that are grossly contaminated with blood,
meconium, or mucus are considered unacceptable for LBC testing.
• Storage at room temperature up to 10 days and at 4ºC up to 50 days does
not affect LBC.
• Freezing amniotic fluid has been shown to decrease LBC
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36. Preanalytical Considerations…….
• To minimize sources of potential interferences, some
investigators have centrifuged amniotic fluid specimens prior
to analysis.
• Most studies show a decline in LBC following centrifugation,
with approximately a one-third decrease after centrifugation
at 500 × g for 5 minutes,and a correction factor has been
proposed to account for lamellar bodies lost during
centrifugation:
Actual LBC = Measured LBC × 1/(1–0.000129 × r × t)
• r = centrifugal rate (× g) and t = period of centrifugation (minutes).
• A fetal lung maturity LBC cutoff of 50,000/μL would be an acceptable
cutoff
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38. DPPC is synthesized in rER
Transferred to the lamellar bodies together with SP-B and
SP-C
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39. • Lamellar bodies and tubular myelin
Lamellar bodies have an acidic internal environment
and have high calcium content.
• The lamellar bodies are the storage and secreting granules
surrounded by a limiting membrane that fuses with the plasma
membrane.
• The lamellar bodies contain all lipid and protein components of
surfactant and are secreted into the fluid layer lining the alveoli.
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40. Control of Surfactant Secretion
• Several factors influence surfactant phospholipid synthesis
and secretion:
• Distortion of cells
• Hyperventilation
▫ deep breath, yawn
▫ acetylcholine (large doses)
▫ beta-agonists
▫ purinoreceptors
▫ corticoids (maturity after pre-term birth)
▫ Thyroxin
• Secretion is stimulated by mechanical stretch and various
agents, listed above, and is associated with increased
cytosolic Ca2+, cellular cAMP, and activation of protein kinases.
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41. glycerol
polar heads
fatty acids
glucose from circulation (glycogen)
choline, inositol from circulation
endogenous from lactate exogenous
Synthesis
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45. O2
e O - e 2H H O OH e H
2H O
Fe3+
MPO Px
H2O
HClO
peroxidation of lipids (phospholipids) aldehydes (malonaldehyde)
O3, NO, NOx, SiO2, smoking, infection, radiation,
hypoxia/reoxygenation, ischemia/reperfusion
.
2 2 2
e H .
.
OH
O2 + 2H2 2H2O
Cu,Zn-SOD
Cu+
Reactive Oxygen Species - ROS
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51. Collagen in the lung
• Collagen is the most abundant protein in lung, composing about
20% of the dry weight of the adult human lung.
• Collagen is an integral component of lung. It maintains alveolar
airway and vascular stability, limits lung expansion, and contributes
significantly to lung recoil at all lung volumes
• It is distributed throughout the lung, including the tracheobronchial
tree, blood vessels, and the alveolar intersitium.
• Lung collagen has been assigned a prominent role in the
differentiation, development, structure and mechanical properties
of the lung and in the pathogenesis of a wide spectrum of lung
diseases, including fibrotic lung disorders.
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52. DegradationSynthesis
Deposition
Fibrosis Emphysema
Collagen
90% I and III, type II, V, VIII
• Emphysema is a condition of the lung characterized by abnormal, permanent
enlargement of the airspaces distal to the terminal bronchiole,
accompanied by destruction of their walls and without obvious fibrosis
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54. Uptake and metabolism of vasoactive
compounds
• Lungs are able to exert a major influence on bodily
homeostasis.
• Serotonin
▫ Lungs rapidly clear serotonin (5-HT) from blood or other media
perfusing the pulmonary circulation
▫ Sodium dependent uptake of 5-HT
inhibitors of oxidative metabolism and ouabain - specific
competitive inhibitors
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55. o Uptake of serotonin by the lung is the rate limiting
step in serotonin clearance
o After uptake, serotonin is metabolized by a
monoamine oxidase (MAO) to 5-hydroxy-indoleacetic
acid.
The rate of metabolism does not significantly influence the
rate of uptake.
• The mechanism for amine transport shows specificity
histamine, another vasoactive compound, is not taken up nor
metabolized by lung to any significant extent.
norepinephrine is taken up and metabolized whereas epinephrine is
not.
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56. Converting enzymes
• Conversion of angiotensin I to angiotensin II (potent
vasoactive compound)
• Hydrolysis of peptide bonds in brandykinin (loss of
biological activity)
▫ Bradykinin is a competitive inhibitor of angiotensin
conversion
▫ The same enzyme is responsible for both reactions
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57. • Converting enzyme activity is present on the luminal
surface of the pulmonary endothelium, so that
hydrolysis occurs at the membrane surface and active
transport into the cell is not required.
• A more complex relationship with prostaglandins
the lung is an important site for uptake and
metabolism as well as synthesis, storage, and
release
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58. Xenobiotics
• The lung is exposed to a wide variety of potentially
toxic substances delivered either through inhalation
or via the circulation
• A major pathway for detoxification of foreign
components such as drugs is through hydroxylation
in the liver by cytochrome P-450-linked reactions
▫ also in lung microsomes
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59. • These organelles from lung contain, on a weight
basis, approximately 25% of the cytochrome P-450
activity
• May be important in the local detoxification of drugs
• It has also been suggested that this pathway may be
responsible for the local conversion of nontoxic
compounds into carcinogenic agents.
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60. The different physiological aspects to
the baby´s first cry
• What causes the first cry, or what motivates the baby
to breathe from the point of view of conventional
medicine?
1. The PCO2 level in the blood rises, that is, metabolic
acidosis occurs due to hypoxia during birth.
2. The baby experiences a feeling of cold caused by the great
difference in temperature between the womb and the
delivery room. (on average, the temperature drops by 15
°C.)
3. The baby undergoes a transition from a liquid
environment to a solid environment.
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62. Definitions
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According to Brönsted and Lowry:
‘An acid is defined as a substance, ion or molecule
that yields H+ ions in solution’, whereas ‘a base is an
ion, molecule or substance that can combine with H+
ions’.
The components of any solution interact with H+ and OH-
ions to either contribute or neutralize H+ ions and,
hence, are called acids or bases, respectively.
The anionic component acts as a base since it can
combine with H+ to re-form the acid. The strength of an
acid depends upon the extent of its dissociation to give
out the protons.
63. Define…..
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pH is defined as the negative logarithm of the hydrogen
ion concentration and, hence, represents the effective
concentration of hydrogen ions in any solution.
Human body produces two types of acids:
(a) Volatile acids. The volatile acids are produced within
our body as a result of sugar or fat metabolism. The
metabolic activities in the body produce CO2 and H2O.
These two can combine to give rise to carbonic acid
(H2CO3), a weak acid. Carbonic acid can dissociate into
H+ and HCO3
- ions.
(b) Non-volatile acids or fixed acids. In addition to the
volatile acids, human body also produces inorganic
acids like sulfuric acid, phosphoric acid and organic
acids such as lactic acid, pyruvic acid, citric acid and
other organic acids
64. Buffers
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Buffers, by definition, are the solutions that resist the change
in pH upon addition of acid or base.
The buffers could be formed in two ways:
(a) by mixture of a weak acid and its salt with a strong base,
and
(b) by mixture of weak alkali and its salt with a strong acid.
The pH of a buffer solution depends upon the acid to salt (or
base to salt) ratio.
Buffers work best near their pKa (pH at which the protons
dissociate from the weak acid). Around the pKa, the pH of a
solution does not change appreciably even when large
amounts of acid or base are added.
pH of a buffer solution is dependent upon the ratio of acid to
salt; if the ratio is kept constant, pH of the solution does not
change.
65. Handerson-Hasselbalch equation
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An equation that defines the relationship between pH, pKa
and the concentrations of salt and acid in a buffer solution
was given by Handerson and Hasselbalch in 1920.
The Handerson-Hasselbalch equation is applicable to most
of the acid-base issues of human system in clinical
biochemistry, as discussed below.
The imbalance in the blood (or body fluids) pH can occur
due to a change in concentration of base or acid.
Extent of the deficit or excess of salt or acid could be
calculated from the above equation by measuring any of the
two quantities, i.e., pH, [acid] or [base]; pKa being a
constant.
66. BODY BUFFER SYSTEMS
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Blood Buffers
The H+ concentration of plasma is about 4 nEq/liter and
is regulated within very narrow limits of 5-10 nEq/l. This
near constant plasma H+ concentration and, hence, the
pH is maintained with the help of blood buffers.
Although the blood contains numerous cations (e.g.,
Na+, K+, Ca2+ and Mg2+) and anions (e.g., Cl-, PO4
3-,
SO4
2- and proteins) that can, as a whole, play a role in
buffering, the primary buffers in blood are bicarbonate
ion (HCO3
-) in the plasma and hemoglobin in the red
blood cells.
Phosphate buffer (HPO4
-- H2PO4
-) might contribute
to intracellular buffering due to the higher intracellular
concentration of phosphates
67. I) Bicarbonate buffer system
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The carbonic acid-bicarbonate system is:
the major blood buffering system.
accounts for about 65% of the plasma buffering
capacity.
operates by interconversion of the two components, i.e.,
carbonic acid and bicarbonate, as shown below:
The bicarbonate buffer has another important reaction
attached to it, which makes it extremely resilient to any
changes in blood pH.
This reaction is the dissociation/association of carbonic
acid to release/bind carbon dioxide, which is exhaled
out into the atmosphere.
Integration of the bicarbonate buffer with the
68. Bicarbonate buffer….
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Carbon dioxide is produced in the body during the metabolism of
carbohydrates and lipids and gets dissolved in water to give rise to
carbonic acid.
The formation of carbonic acid essentially takes place in the red
blood cells with help of the enzyme carbonic anhydrase.
The ionization of carbonic acid to H+ and HCO3
- is spontaneous.
Carbonic acid could make the tissue/blood pH acidic, but the H+
ions given out upon its dissociation are absorbed by negatively
charged proteins (hemoglobin).
Bicarbonate diffuses out into the plasma. This facilitates the
transport of carbon dioxide as bicarbonate to the lungs where it is
exhaled out.
This effective CO2 transport process from tissues to lungs is
69. II) Hemoglobin as buffer
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The buffering action of hemoglobin in the tissues is
integrated with the unloading of oxygen and is also
known as ‘Bohr Effect’
The protons associated with the histidine of hemoglobin
are thus transported to the lungs without any effect on
the blood pH.
The reverse happens in the lungs where uptake of
oxygen, cooperatively, facilitates the conversion of ‘T’ to
‘R’ state of hemoglobin and subsequent release of the
attached protons.
70. Hemoglobin as buffer…..
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Formation of bicarbonate in the RBCs by carbonic
anhydrase creates a temporary rise in HCO3-
concentration in the cells.
This bicarbonate is released into the plasma in
exchange for chloride ions to maintain the electrical
neutrality.
Therefore, chloride ions enter the red blood cells in the
peripheral tissues and move out of the cells in lungs.
This movement of chloride ions into and out of RBCs is
known as ‘Chloride Shift’. The reciprocal relationship
between chloride and bicarbonate is also seen in
metabolic acidosis caused by the excessive loss of
bicarbonate through intestinal or renal excretion.
The loss of bicarbonate stimulates compensatory rise in
71. IMBALANCE OF ACID-BASE HOMEOSTASIS
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The physiology of human cells is designed to function at a
narrow range of pH around 7.4.
A decrease in the plasma pH is known as ‘acidemia’ and the
increase as ‘alkalemia’. The corresponding clinical disorder
associated with an accumulation of acids in the tissues (and
plasma) is known as acidosis, whereas the build-up of alkali
in the body is known as alkalosis.
The accumulation of acid or base in the body can result
either from metabolic over-production or from the failure of
the respiratory system to eliminate them. The former type is
known as metabolic, whereas the latter is known as
respiratory. Therefore, the acid-base imbalance can be
classified as follows:
Acidosis
Metabolic acidosis
Respiratory acidosis
Alkalosis
Metabolic alkalosis
Respiratory alkalosis
72. Acidosis
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Metabolic acidosis
An increase in acids in the body can take place due to any of the following
reasons:
1. Increased production of metabolic acids like keto acids (ketone bodies) or lactic
acid.
2. Loss of bicarbonate.
3. Failure of the body to excrete endogenous (fixed) acids.
All the three processes have a common denominator, i.e., all of them lead to a
decrease in the alkali reserve of the body. Increased metabolic acids would be
neutralized by the bicarbonate and, hence, plasma bicarbonate levels would fall.
The excretion of fixed acid by kidney is linked with the synthesis of bicarbonate;
therefore, in case of renal insufficiency, the failure to excrete acids by kidney is
associated with its failure to restore the alkali reserve of the body. The metabolic
acidosis is, thus, a condition characterized by ‘primary bicarbonate
deficiency’.
Causes of metabolic acidosis
Overproduction of fixed acids
Diabetic acidosis
Lactic acidosis
Salicylate poisoning
Methanol poisoning
Ethylene glycol poisoning
Loss of bicarbonate
Diarrhea
Pancreatic fistula
Ureteroenterostomy
Renal tubular
disease
Decreased renal excretion of
fixed acids
Renal failure (with uremia)
Adrenocortical insufficiency
Carbonic anhydrase
inhibitors
73. Respiratory acidosis
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Respiratory system is in close contact with the bicarbonate
buffer and plays a major regulatory role in maintaining the
bicarbonate concentration of blood.
The respiratory system, including lungs and hypothalamic
respiratory center, needs to stay in good health to provide
regular vigilance to any changes in the acid-base balance of
the body.
In case of any deficiency in the respiratory function, carbon
dioxide would not be appropriately eliminated from the body
resulting in its accumulation in blood causing acidosis.
Such an acidosis is called as respiratory acidosis.
The respiratory acidosis is seen in cases of pulmonary
disease like chronic obstructive pulmonary disease (COPD),
bronchopneumonia, status asthmaticus or in case of drug
induced (overdose of sedatives or narcotics) depression of
the respiratory center
74. Alkalosis
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Metabolic Alkalosis
Metabolic alkalosis occurs as a result of net gain of HCO3
- or
loss of nonvolatile acid (e.g., HCl loss by vomiting) from the
extracellular fluid.
Primary bicarbonate excess is the characteristic feature of
metabolic alkalosis.
Since it is unusual for alkali to be added to the body, the
disorder mostly occurs due to the loss of acid and failure of
the kidneys to excrete the excess HCO3
-.
The symptoms include mental confusion and a
predisposition to seizures, paresthesia, muscular cramping,
tetany, aggravation of arrhythmias and hypoxemia in chronic
obstructive pulmonary disease. Related electrolyte
abnormalities include hypokalemia and hypophosphatemia.
75. Respiratory alkalosis
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Alveolar hyperventilation decreases pCO2 and increases the
HCO3/pCO2 ratio, thus increasing pH.
Respiratory alkalosis, therefore, is characterized by ‘primary
carbonic acid deficit’.
Hyperventilation could be caused by hysteria, brain stem
injury and raised intracranial pressure. Respiratory alkalosis
is the first finding in Gram negative septicemia and could
also be seen in pulmonary embolism and hyperthyroidism.
Chronic respiratory alkalosis is the most common acid-base
disturbance in critically ill patients - many cardiopulmonary
disorders manifest respiratory alkalosis in their early to
intermediate stages.
Respiratory alkalosis is also prominent in liver failure, and
the severity correlates with the degree of hepatic
insufficiency. It is also seen in patients on mechanical
