1.

Describe a globin chain as to: its helices and the relation of the
helices to the heme plane
HEMOGLOBIN
.

A.Structure4 subunits:o 2 alpha chains o 2 beta chains o Bound mainly by

non covalent forces Normal adult hemoglobin content: o Variants:HgbA
(22) 95%HgbA2 (22) 4% (minimal)HgbF (22) 1% (very
minimal)
Heme Plane:
o Most closely associated with helix F
o Iron at the center with 6 coordination points: 4 occupied by Pyrrole
th

nitrogen5 bound to proximal histidine or the F8; has direct contact with
th
heme.6 occupied by oxygen (oxyhemoglobin); ifempty (deoxyhemoglobin).
th
Has direct contact with E7 (7 amino acid on helix E) or distal histidine.

2. Compare and contrast: proximal and distal histidine as to its relation to the heme plane.
Proximal Histidine
F8 or 8th amino acid residue in helix F
In direct contact with iron of the heme plane
Most closely associated with heme plane (hence the term proximal reference point is heme)
Distal Histidine
E7 or 7th amino acid residue in helix E
In direct contact with oxygen which is bound to heme plane (not in contact with iron/heme;
hence, the term distal)
3. Describe a globin chain as to its: helices and the relation of the helices to the heme plane.
Hemoglobin: 4 polypeptide chains; 4 globin chains of hemoglobin contain 1 heme per globin
chain = Hgb contains 4 heme planes per hemoglobin molecule
Myoglobin: consists of eight alpha helical segments which are linked to one another by turns to
form a globular structure
Myoglobin can bind only one molecule of oxygen, because it contains only one heme group. In
contrast, hemoglobin can bind four oxygen molecules one at each of its four heme groups.
BINDING SITES ON THE HEMOGLOBIN MOLECULE
Carboxy terminus: formation of salt bridges
Amino terminus: H proton binding and CO2 binding
Heme Plane exclusive for Oxygen
4. Define: oxygen saturation curve, partial pressure of oxygen, fraction of inspired oxygen, oxygen
affinity.
a. How is oxygen affinity measured?
Y
axis: Hgb saturation or O2 sat; expressed in %
X axis: partial pressure of O2 levels (pO2)
The oxygen dissociation curve for hemo globin is sigmoidal in shape (in contrast to that of
myoglobin, which is hyperbolic), indicating that the subunits cooperate in binding oxygen.

Oxygen binding curve plot of fractional saturation (Y axis) versus concentration of oxygen (X
axis)
o The value of Y range from 0 (all sites empty) to 1 (all sites filled).
Partial Pressure of Oxygen:
Diffusion of gases is from areas of high pressure to areas of low pressure
Process: Arterialization of venous/deoxygenated blood:
CO2 that is rich in venous blood from tissues contact with alveoli diffuse CO2
into alveoli then out to atmosphere
CO2 partial pressure barely changed (45 to 40 mmHg) so it becomes a reference
value. (This is the reason why CO2 is the true measure of alveolar ventilation and not
oxygen.)
Measuring oxygen affinity:
The states can readily depict the oxygen affinity of hemoglobin.
o T (tensed) state:
Associated with deoxyhemoglobin
Shift to the right: low affinity to O2
More stable
o R (relaxed state):
Associated with oxyhemoglobin
Shift to the left: high affinity to O2 (exposes more oxygen binding sites)

5.1 Compare and contrast myoglobin (Mb) and Hemoglobin (Hgb) as to:
A. Structure protein structure, helices, and heme plane
B. Function

Myoglobin
Structure:
One globin chain and one heme plane (O2
binding site), consists of eight alpha helical
segments which are linked to one another by
turns to form a globular structure.
A protein in tertiary structure, single
polypeptide chain with domains divided into
helices
Function:
O2 storage (in times of increased demand)
Transports O2, CO2 and H+ = isohydric
mechanism

Hemoglobin
Structure:
4
subunits:
o 2 alpha chains
o 2 beta chains
o Bound mainly by non covalent forces
Heme Plane:
o Most closely associated with helix F
o Iron at the center with 6 coordination points:
4 occupied by Pyrrole nitrogen
5th bound to proximal histidine or the F8;
has
direct contact with heme.
6th occupied by oxygen (oxyhemoglobin); if
empty (deoxyhemoglobin). Has direct
contact with E7 (7th amino acid on helix E)
or distal histidine.
Function:
-transport O2 and CO2

5.2 Compare and contrast the oxygen saturation curve of Mb, Hbf, and Hba, in the peripheral
tissue and lungs

Oxygen saturation curves for myoglobin and hemoglobin.

The saturation curve for myoglobin shows the typical rapid oxygen concentration-dependent
saturation of this monomeric oxygen-binding protein.
The other two curves show the typical sigmoidal saturation curves for cooperative oxygen binding
exhibited by fetal hemoglobin (HbF) and adult hemoglobin (HbA).
Also indicated in the diagram are the typical oxygen concentrations in peripheral tissues and the
lungs.
Note that whereas, myoglobin can be fully oxygen saturated in the tissues, hemoglobin requires
much higher oxygen tension to become fully saturated which only occurs in the lungs.
The position of HbF saturation to the left of HbA (i.e. at lower oxygen tension) reflects the fact that
fetal hemoglobin binds oxygen with higher affinity than adult hemoglobin and this is so that the
fetus can acquire oxygen from the maternal circulation.
(from themedicalbiochemistrypage.com)
Lungs:
o 96% sat: pO2: 80-100 (normal) located in Plateau
o Hemoglobin takes oxygen maximally
Lungs to Tissues: Descent of the curve/Steep Curve going Down
o Rapid release of oxygen into the tissues/cells/extrapulmonary cells
o Rapid effective delivery of O2 into the tissues after its rapid decline in % saturation or
arterial O2 tension (from old trans)

 Tissues to Lungs: Rapid rise of the curve/ Steep Curve going Up

o From systemic venous blood (40mmHg), there is a rapid uptake or increase in %
saturation and arterial O2 tension
6. Compare and contrast the oxygen saturation curve of Hbf and HbA in the fetal venous blood,
fetal arterial blood, and adult venous blood.

(Refer to graph in #5)

Typically, fetal arterial oxygen pressures (for HbF) are lower than adult arterial oxygen pressures
(HbA). Hence higher affinity to bind oxygen is required at lower levels of partial pressure in the
fetus to allow diffusion of oxygen across the placenta.
Not super sure here, pero ito na closest I could find for #6 :( Wala sa transes.
7. Define cooperativity in oxygen binding of globin proteins.
Cooperativity - activity at one functional site affects the activity at others. As a consequence, a
slight change in substrate concentration can produce substantial changes in activity.
Significance of cooperative binding:
Oxygen must be transported in the blood from the lungs to the tissues.
If there is no cooperativity, only 67% (max.) is saturated with O2, which is not enough to
support our metabolic processes (example is in the lungs)
For the cells in the tissues, with PO2 at 20 torr level, only 38% is delivered
Since the 4 globin chains in Hgb exhibits cooperativity, Hgb becomes nearly saturated with
oxygen such that 96% oxygen saturation with PO2 level at 100 torr. When hemoglobin moves to
the tissues, the saturation level drops to 32% therefore there is release of oxygen content by
around 66%.
Since Mgb has only 1 heme plane, can only contribute around 7% delivery to tissues.
Binding would require more cooperativity. Because of interface interaction of four globin
chains, they are able to maximize uptake of oxygen. But if each globin chain acts separately then
there would be no significant conformational changes thus there would be significantly less
uptake of oxygen by hemoglobin.

8. Compare and contrast cooperativity in Hb and Mb.

Cooperativity - activity at one functional site affects the activity at

others. As a consequence, a slight change in substrate concentration
can produce substantial changes in activity.
Significance of cooperative binding:
Oxygen must be transported in the blood from the lungs to the
tissues.
If there is no cooperativity, only 67% (max.) is saturated with O2,
which is not enough to support our metabolic processes (example is in
the lungs)
For the cells in the tissues, with PO2 at 20 torr level, only 38% is
delivered
Since the 4 globin chains in Hgb exhibits cooperativity, Hgb
becomes nearly saturated with oxygen such that 96% oxygen
saturation with PO2 level at 100 torr. When hemoglobin moves to the
tissues, the saturation level drops to 32% therefore there is release of
oxygen content by around 66%.
Since Mgb has only 1 heme plane, can only contribute around 7%
delivery to tissues.
Binding would require more cooperativity. Because of interface
interaction of four globin chains, they are able to maximize uptake of
oxygen. But if each globin chain acts separately then there would be
no significant conformational changes thus there would be significantly
less uptake of oxygen by hemoglobin.
9.) Compare and contrast T and R state of Hb as to:

Relation of Fe to the heme plane

Presence of salt bridges
Heme pockets

T (tensed) state:
Associated with deoxyhemoglobin
Shift to the right: low affinity to O2
More stable

isulat haha

Dinagdag ko lang to kahit wag na

R (relaxed state):
Associated with oxyhemoglobin
Shift to the left: high affinity to O2 (exposes
more oxygen binding sites)

10.) Compare and contrast the affinity of Hb and Mb to carbon

monoxide
CO has higher affinity to Hgb compared to O2.
CO prefers to bind to the heme plane of hemoglobin in a
perpendicular manner.
Myoglobin, having only a single binding site at heme plane,
insists that oxygen should bind at a slightly oblique angle. This is
due to the effect of distal histidine. Myoglobin is more protective
of its heme plane, hence, it has slight resistance to the harmful
effects of CO.
12.) Describe the biochemical basis of Bohr effect.

11. Enumerate the allosteric effectors of Hb and their relevance on oxygen delivery to tissues.
1. The Bohr Effect
The binding of protons by Hgb which lowers its affinity for oxygen
High hydrogen concentration, w/c is measured by low pH, would favor a more
extensive combination, more salt bridges of the T state, hence it would favor oxygen
release.
The more tense Hgb is, the higher the tendency for O2 release
Acidity enhances the release of oxygen. Advantageous because O2 cannot stay
bound to Hgb. It must be released to the tissues.
T state is more stable
Lungs
Actively metabolizing tissues
pH
pH due to H+ secretion
Hgb binds O2
Hgb releases O2
Hgb releases H+
Hgb binds H+
2. pH
Low pH: positive allosteric effector
High pH: negative allosteric effector
Shifted to the right
Shifted to the left

Slightly low pH
Less affinity of O2 to Hgb more
release of O2
High pH
More affinity of O2 to Hgb less O2
release into tissues

3. Temperature
Increased Temperature
Positive allosteric effector
Advantages:
a) Support Oxygen demand in fever
b) Support Oxygen demand in exercise
Increase in core body temperature will require more oxygen
Hypothermia
Compensatory Mechanisms

 a) O2 utilization
b) O2 solubility in plasma (from 2.3 to 4 or 5 mL O2/L)
c) CO2 solubility
Because of the effect of temperature, there is an added 21% higher release of O2 into the
tissues Positive allosteric effect
4. Effect of BPG (Bisphosphoglycerate)
BPG: mild tissue hypoxia
a) Mild Anemia (Hgb , 12g/dL)
b) Mild CP (cardiopulmonary) insufficiency (e.g. smoking)
c) altitude
If there is no BPG on RBCs:
o Sigmoidal dissociation curve becomes more hyperbolic
o This means there is a significant 8% of O2 which will not be released into the tissues
readily.
5. CO2
Most of the CO2 produced in metabolism is
hydrated and transported as bicarbonate ion. However,
some CO2 is carried as carbamate bound to the N-terminal amino
groups of hemoglobin (forming carbaminohemoglobin), which can be represented
schematically as follows:
Hb NH2 + CO2 Hb NH COO + H+
The binding of CO2 stabilizes the T (taut) or deoxy form of
hemoglobin, resulting in a decrease in its affinity for oxygen and a right shift in the oxygen
dissociation. In the lungs, CO2 dissociates from the hemoglobin, and is released in the
breath.

14. Review the formation of BPG in the cell

SOURCE: MARKS MEDICAL BIOCHEMISTRY

2,3Bisphosphoglycerate(2,3BPG)isformedinredbloodcellsfromthe
glycolyticintermediate1,3bisphosphoglycerate,asindicatedinFigure.2,3BPG
bindstohemoglobininthecentralcavityformedbythefoursubunits,increasing
theenergyrequiredfortheconformationalchangesthatfacilitatethebindingof
oxygen.Thus,2,3BPGlowerstheaffinityofhemoglobinforoxygen.Therefore,
oxygenislessreadilybound(i.e.,morereadilyreleasedintissues)when
hemoglobincontains2,3BPG.

15.
and
a.
BPG to HBa and HBf

Compare
contrast:
Binding of

Hgb dissociation curve: HgbF vs HgbAo His143 is replaced by

serine (uncharged) 2 less (+)charged siteso Resistant to BPG
because of absence of His143o Hyperbolic curve: O2 is extracted from
maternal bloodto fetal RBC

HgbF binds to BPG less than HgbA because of serine residue in

HgbF; this optimizes the transfer of O2 from maternal to fetal
circulation The fetal red blood cells have a higher oxygen affinity than
maternal red blood cells because fetal hgb does not bind 2,3-BPG,
theres a substitution of a serine residue of His 143 in the chain, part
of 2,3-BPG binding site. (Stryer)
NOTE: At 3 months old, infant will have HgbA

b. the effect on oxygen affinity and its delivery to tissues

Figure 10. BPG/2,3-DPG competitively binds with O2; Hgb becomes T

state

2,3BPGlowerstheaffinityofhemoglobinforoxygen.Therefore,oxygenisless
readilybound(i.e.,morereadilyreleasedintissues)whenhemoglobincontains
2,3BPG.

(+) allosteric effector

BPG can occur in cases of mild tissue hypoxia(i.e. mild anemia, mild
cardiopulmonary insufficiency, high altitude)

Relatively high BPG concentrations in RBC (Lehninger)

BPG greatly reduces the affinity of hemoglobin for oxygen (inverse

relationship between binding of O2 and binding of BPG). (Lehninger)

Compensatory mechanism = BPG (which will lead to O2 release)

High O2 affinity = better CO2 unloading

Increases cooperativity

Favors T state o -chains of Hgb form cavity for BPG- generated from
alignment of multiple (+) charges o With no BPG, hemoglobin is easily
converted to the R state (Lehninger)
16.) Describe the role of the lungs and the kidneys and RBC in
the excretion of CO2 from the body.
RBC and lungs

Kidneys
CO2 levels in the blood are affected by kidney and lung function. The
kidneys help maintain the normal bicarbonate levels
17.) Enumerate the forms by which CO2 exists in the body and
describe how each contribute to the excretion of CO2

Describe Haldane effect; Chlorate shift; isohydride mechanism

Describe the mechanism of action of carbonic anhydrase.

Haldane Effect
Increase in the concentration of carbon dioxide will displace oxygen from hemoglobin
and binding of Oxygen with Hemoglobin in turn will displace Carbon dioxide from
blood.

Isohydride mechanism and Chlorate shift

MOA of Carbonic anhydrase

His will catalyze the release of one hydrogen, so there will be
available binding site for its substrate (CO2).
In the process, CO2 is converted to bicarbonate and is released.
To regenerate the binding site, it has to bind to another molecule
of water.

18. Describe the role of the lungs in the maintenance of acid-base balance in the body:
The respiratory system has an important role in the maintenance of acid base balance this is
through the regulation of carbon dioxide and it is important because the major blood buffer is the
carbon dioxide - bicarbonate buffer system and it has an important role in the maintenance of
normal body pH and acid-base balance and then the body, in normal condition would always
maintain normal oxygenation status to ensure adequate oxygen to supply our metabolic
processes. (Magat, 2013)

a. Enumerate and define the body buffer system

A buffer is a solution that resists change in pH following the addition of an acid or base.
Body Buffer System:
B
uffers in blood maintain the pH at about 7.40.
Cellular production of acids leads to an acidification of blood where the H+ is buffered by
several different bases including HCO3, hemoglobin, and HPO4 (Devlin, 7th ed.)
Mainly by formation of carbaminohemoglobin
HEMOGLOBIN (50%)
Acts as a buffer of blood pH by binding the hydrogen ions produced by the metabolizing cells
and preventing the blood pH from becoming too acidic. (Devlin, 7th ed.)
Transports about 40% of the total H+ and 15 20% of the CO2 formed in the tissues in the
tissues to the lungs and kidneys.
The remainder of the H+ is absorbed by the plasmas HCO3 buffer; remainder of CO2 is
transported as dissolved HCO3 and CO2.
OTHER BUFFERS (10%)
Organic phosphate (RBC)
o Mainly intracellular
o Concentration of phosphate is low in the extracellular fluid but the phosphate buffer
system is an important urinary buffer
Plasma proteins
o Absolute amount is small compared to intracellular protein
ISOHYDRIC MECHANISM (40%)
Transport of CO2 from tissues to lung in plasma as HCO3
Bicarbonate (HCO3)
Maintain a relatively constant plasma pH
b. Review Henderson-Hasselback reaction
The quantitative relationship between the pH of the solution and concentration of a weak acid
(HA) and its conjugate base (A) is described by the Henderson-Hasselbach equation.
(Lippincott)
The relationship between the pH of a solution, the Ka of an acid, and the extent of its dissociation
are given by the Henderson-Hasselbalch equation. (Marks)
In the Henderson-Hasselbalch equation, the formula for the dissociation constant
of a weak acid is converted to a convenient logarithmic equation (Equation 4.5).
The term pKa represents the negative log of Ka. If the pKa for a weak acid is known,
this equation can be used to calculate the ratio of the unprotonated to the protonated
form at any pH. From this equation, you can see that a weak acid is 50% dissociated
at a pH equal to its pKa.
Equation 4.5. The Henderson-Hasselbalch equation.
For the weak acid HA,

ph= pK a +log

c. Know the formula of the HCO3 buffer system, review how the body handles CO2
CO2 Excretion:
In
periphery:
o Passive diffusion of CO2 into the RBC
o Catalytic effect of carbonic anhydrase (enzymatic action)
o Facilitated diffusion of bicarbonate from the RBC into the plasma (includes Chloride
shift)
In lungs:
o Facilitated diffusion of bicarbonate from the plasma into the RBC
o Catalytic effect of carbonic anhydrase forming CO2 and H2O
o Excretion of CO2 into the atmosphere
In this system, carbon dioxide (CO2) combines with water (H2O) to form carbonic acid (H2CO3),
which in turn rapidly dissociates to form hydrogen ions (H+) and bicarbonate (HCO3- ) as shown in
the reactions below:

19.)

What are arterial blood gases?

What is measured by ABGs?
How are the concentration of gases expressed?
What is the clinical relevance of ABG?

An arterial blood gas (ABG) test measures the acidity (pH) and the
levels of oxygen and carbon dioxide in the blood from an artery. This
test is used to check how well your lungs are able to move oxygen into
the blood and remove carbon dioxide from the blood.
What is measured by ABGs and How are the concentration of gases
expressed?
Partial pressure of oxygen (PaO2). This measures the pressure of
oxygen dissolved in the blood and how well oxygen is able to move
from the airspace of the lungs into the blood.
Partial pressure of carbon dioxide (PaCO2). This measures the pressure
of carbon dioxide dissolved in the blood and how well carbon dioxide is
able to move out of the body.
pH. The pH measures hydrogen ions (H+) in blood. The pH of blood is
usually between 7.35 and 7.45. A pH of less than 7.0 is called acid and
a pH greater than 7.0 is called basic (alkaline). So blood is slightly
basic.
Bicarbonate (HCO3). Bicarbonate is a chemical (buffer) that keeps the
pH of blood from becoming too acidic or too basic.
Oxygen content (O2CT) and oxygen saturation (O2Sat) values. O2
content measures the amount of oxygen in the blood. Oxygen
saturation measures how much of the hemoglobin in the red blood
cells is carrying oxygen (O2).

Clinical relevance
An arterial blood gas (ABG) test is done to:
Check for severe breathing problems and lung diseases, such as
asthma, cystic fibrosis, or chronic obstructive pulmonary disease
(COPD).
See how well treatment for lung diseases is working.
Find out if you need extra oxygen or help with breathing
(mechanical ventilation).
Find out if you are receiving the right amount of oxygen when
you are using oxygen in the hospital.
Measure the acid-base level in the blood of people who have
heart failure, kidney failure, uncontrolled diabetes, sleep
disorders, severe infections, or after a drug overdose.

20. Compare/Contrast partial pressures of CO2, & O2 in the

atmospheric air, alveoli and blood

Fig1.ComparisonbetweenpartialpressureofO2andCO2

Diffusion of gases is from areas of high pressure to areas of low pressure

Process: Arterialization of venous/deoxygenated blood:

From atmosphere (150mmHg), alveolar O2 isobtained and no CO2

From the atmosphere, pAO2 = 150 mmHg and pCO2 = 0 are taken
up by alveoli (pCO2 = 0 since we are not supposed to inhale carbon
dioxide)

Because of gas exchange, venous blood (40mmHg) will become

arterialized/oxygenated (100mmHg)
O2 from high pressure alveoli (150 mmHg from the atmosphere)
venous blood arterial

CO2 that is rich in venous blood from tissues contact with alveoli diffuse
CO2 into alveoli then out to atmosphere
CO2 partial pressure barely changed (45 to 40 mmHg) so it becomes a
reference value. (ThisisthereasonwhyCO2isthetruemeasureofalveolarventilation
andnotoxygen.)
L
7 21.) Compare the role of the lungs, kidney and RBC in the
maintenance of acid-base balance in the body.
L
L Pulmonary regulation: CO2 concentration is finely regulated by
changes in tidal volume and respiratory rate (minute ventilation).
A decrease in pH is sensed by arterial chemoreceptors and leads
to increases in tidal volume or respiratory rate; CO2 is exhaled
and blood pH increases. In contrast to chemical buffering, which
is immediate, pulmonary regulation occurs over minutes to
hours. It is about 50 to 75% effective and does not completely
normalize pH.
L
L Renal regulation: The kidneys control pH by adjusting the amount
of HCO3 that is excreted or reabsorbed. Reabsorption of
HCO3 is equivalent to removing free H+. Changes in renal acidbase handling occur hours to days after changes in acid-base
status.
L
L RBC: Red blood cell contains hemoglobin which acts as an
important buffer.

22. Compare/Contrast how the RBC handles carbon dioxide in the

tissue and in the lungs

(ENOUGH NA ACTUALLY YUNG DIAGRAM ITSELF PERO HERES OTHER

INFO NA LANG)

Buffers in blood maintain the pH at about 7.40.

Cellular production of acids leads to an acidification of blood where the H+ is
buffered by several different bases including HCO3,hemoglobin, and HPO4
(Devlin, 7th ed.)
Mainly by formation of carbaminohemoglobin
4 amino terminal groups the binding sites of hydrogen protons
In less frequency, hydrogen can also bind to histidine residues. In each globin,
chain there are 30. HEMOGLOBIN(50%)
Acts as a buffer of blood pH by binding the hydrogen ions produced by the
metabolizing cells and preventing the blood pH from becoming too acidic.
(Devlin, 7th ed.)
Transports about 40% of the total H+ and 15 20% of the CO2 formed in the
tissues in the tissues to the lungs and kidneys.
The remainder of the H+ is absorbed by the plasmas HCO3 buffer; remainder of
CO2 is transported as dissolved HCO3 and CO2.
Ionizable groups with pK values close to RBC pH
Contains 4 N terminal groups and imidazole side chains of histidine residues
(#38) OTHERBUFFERS(10%)Organic phosphate (RBC)o Mainly intracellularo
Concentration of phosphate is low in the extracellular fluid but the phosphate
buffer system is an important urinary buffer Plasmaproteins o Absolute amount
is small compared to intracellular protein ISOHYDRICMECHANISM(40%)
Transport of CO2 from tissues to lung in plasma as HCO3
Bicarbonate(HCO3) Maintain a relatively constant plasma pH
.

B.CarbonDioxideExcretion

Inperiphery:

o Passive diffusion of CO2 into the RBC

o Catalytic effect of carbonic anhydrase (enzymatic action)

o Facilitated diffusion of bicarbonate from the RBC into the plasma (includes
Chloride shift) Inlungs:

o Facilitated diffusion of bicarbonate from the plasma into the RBC

.
.

o Catalytic effect of carbonic anhydrase forming CO2 and H2O

o Excretion of CO2 into the atmosphere

23. Describe intracellular buffering in acidosis

Respiratory Compensation
In metabolic acidosis:
The rate and depth of breathing are elevated
Blood pH is below 7.35 and bicarbonate level is low
As carbon dioxide is eliminated by the respiratory system, P CO2 falls below normal
Renal Compensation
Acidosis has high PCO2 and high bicarbonate levels
The high PCO2 s the cause of acidosis
The high bicarbonate levels indicate the kidneys are retaining bicarbonate to offset the
acidosis
A. Describe the role of proteins and phospholipids
Phosphate Buffer System

Nearly identical to the bicarbonate system

Its components are:

Sodium salts of dihydrogen phosphate (H2PO4), a weak acid

Monohydrogen phosphate (HPO42), a weak base

This system is an effective buffer in urine and intracellular fluid

Protein Buffer System

Plasma and intracellular proteins are the body's most plentiful and powerful buffers

Some amino acids of proteins have:

Free organic acid groups (weak acids)

Groups that act as weak bases (e.g., amino groups)

Amphoteric molecules are protein molecules that can function as both a weak acid and a
weak base

24.) Describe the role of the kidney in acid-base balance.

Renal system
1. Reabsorption of bicarbonate
Carbonic acid formed in the RBC moves to the glomerulus, the
tubular cell and tubular lumen. Carbonic acid will get into the tubular
cell where it will dissociate into acid and bicarbonate. Bicarbonate will
be reabsorbed. Acid is excreted through the buffer system. The proton
excreted to the lumen will be exchanged for another cation, Na+.
This process is limited by the fact that it requires exchanging with a
cation, Na+. The amount of Na+ in the body is limited. This process is
also limited by the dissociation constant of the blood buffer system.
2. Excretion of titrable acidity
During illness, the dissociation constant of the blood buffer
system is exceeded. As a result, another process is needed for
excretion of acids. This is achieved through the phosphate buffer
system, excretion of titrable acidity. The excretion starts through the
CO2-HCO3- buffer system, then once its dissociation constant has been
exceeded, acid will then be excreted through the phosphate buffer
system. The amount of H+ in the urine can be measure by determining
the amount of alkali required to neutralize the urine. This is called
titrable acidity. It is called titrable acidity, since the condition in the
tubular cell would be maintained within normal by the same buffer
system. The amount of acid excreted requires that the same amount of
acid would be replaced within the system to minimize pH change.
3. Excretion as ammonia
Sometimes, during severe illness, even the phosphate buffer
systems dissociation constant is exceeded. Therefore, excretion of
acid by ammonia then is needed. Ammonium is produced through the
degradation of amino acids. During illness, a lot of cells are destroyed.
This results to the degradation of more amino acids, producing a lot of
ammonia. Acid can now be excreted as ammonia. This explains how
the kidneys compensate for acidosis completely, but this requires time
since it has to wait for amino acids to be degraded. The kidneys can
respond in three (3) days, but the compensation is complete. Within
minutes to six (6) hours, the lungs can respond more quickly, although
the response is incomplete. In the liver, ammonia is converted to urea
and is eliminated from the body through the urine. The remaining
ammonia combines with H+ to form the ammonium ion (NH4+) in the
renal tubules. NH4+ also displaces Na+ and is eliminated in the urine.

25. Name, describe and compare the different acid-base disorders

Acidosis
O Respiratory - alveolar hypoventilation (ex. Heavily sedated, heavily
intoxicated, with head injury)
+

O Metabolic H overproduction (ex. Severe dehydration, renal

problems, diabetic ketoacidosis, lactic acidosis)
- HCO3 over excretion (in cases of renal tubular acidosis give patient
bicarbonate tablets as replacement)
Alkalosis
O Respiratory Alveolar hyperventilation (ex. Hysteria)
O Metabolic Alkali ingestion (iatrogenic, doctor-induced)

26. Describe how compensatory mechanisms take place in cases of

acid-base disorders.

DISORDER
Metabolic Acidosis
Metabolic Alkalosis
Respiratory
Acidosis
Respiratory
Alkalosis

Compensatory
Mechanisms
DECREASE pCO2
INCREASE pCO2
INCREASE Renal HCO3,
re absorption & plasma
HCO2- concentration
DECREASE Renal HCO3
reabsorption & plasma
HCO3 concentration

Onset of
Compensation
Minutes/Hours
Minutes/Hours
Days
Days