Carriage Of Oxygen Flashcards
More than ____ of the oxygen normally binds to hemoglobin within the _____.
98%
Erythrocytes
True or false
The amount of O2 dissolved in blood is far too small to meet the metabolic demands of the body.
TRUE
Oxygen will move from the atmosphere to the plasma until an equilibrium is established at which time the concentration of dissolved 02 in the blood obeys _______
Henry’s law
The average 70-kg human at rest consumes oxygen at the rate of ________
~250 mL/min
Dissolved oxygen could supply the body’s metabolic demands only if cardiac output increased by a factor of _____
250/15 or nearly 17 fold
True or False: The body cannot rely on dissolved oxygen as a mechanism for O2 carriage.
True
Hemoglobin consists of _____ and ______ each of which has an iron-containing _____ and a polypeptide ______
2 alpha and 2 beta subunits
Heme
Globin
________ is a tetramer having a molecular weight of ~68 kDa each monomer consisting of a heme and globin.
Normal adult hemoglobin (Hb)
The _____ is a porphyrin compound coordinated to a single iron atom.
Heme
The _____ is a polypeptide either an alpha chain (_____) or beta chain (______)
Globin
141 amino acids
146 amino acids
The homology between the alpha and beta chains is sufficient that they have similar conformations, a series of _______.
Seven helices enveloping a single heme
The complete Hb can bind as many as ___ oxygen molecules, one for each iron atom.
4
The ______ that synthesize Hb closely coordinate the production of alpha chains, beta chains, and heme
Erythroblasts
_______ is a general term for a metal ion chelated to a porphyrin ring.
Heme
In the case of Hb, the metal is iron in the _______.
Ferrous state - Fe 2+
The porphyrin consists of _____-linked pyrrole rings that through their _______ atoms coordinate a single, centrally located Fe2+.
Four (4)
Nitrogen
Because the iron-porphyrin complex is rich in conjugated _______, it absorbs photons of relatively _______
Double bonds
Low energy
The interaction among ___,___,___, causes the complex to have a ______ when fully saturated with oxygen and a ______ when devoid of oxygen.
O2, Fe2+, Porphyrin
Red
Purple
The Fe2+ in Hb can become oxidized to _________ either spontaneously or under the influence of compoinds such as nitrites or sulfonamides.
Ferric state - Fe 3+
The resultof such an oxidation is ________ which is incapable of binding O2.
Methemoglobin (metHb)
Inside the rbc, a heme-containing enzyme _________ uses the reduced form of _________ to reduce metHb back to Hb so that only ____% of total Hb is in metHb state.
Methemoglobin reductase
Nicotinamide adenine dinucleotide (NADH)
1.5%
In the rare case in which a genetic defect results in a deficiency of this enzyme, metHb may represent _____% or more of the total Hb. Such a deficiency results in a decreased O2 carrying capacity, leading to _________.
25%
Tisse hypoxia
Even with isolated heme, oxygen _________ oxidizes Fe2+ to Fe3+.
Irreversibly
Th crucial residue is ________ that bonds to the Fe2+ and donates negative charge that stabilizes the Fe2+ - 02 complex.
Histidine
_________ is also crucial for transmitting to the rest of the Hb tetramer, the information that an oxygen molecule is or is not bound to the Fe2+.
Histidine
When all four hemes are devoid of O2, each of the four histidine pulls its Fe2+ ______ the plane of its porphyrin ring by ______ nm distorting the porphyrin ring.
Above
~0.06
The various components of the Hb tetramer are so tightly interlinked, as if by a snugly fitting system of levers and joints, that no one subunit can leave this __________ unless they all leave it together.
Tensed (T) state
Becaause the shape of the heme in the ______ sterically inhibits the approach of oxygen empty H b has a very low affinity of O2.
Tensed state
When one O2 binds to one of the Fe2+ atoms, the Fe2+ tends to move ______ into the plane of the porphyrin ring.
Down
When enough O2 molecules bind, enough energy builds up and all four subunits of the Hb simultaneously snap into ________, whether or not they are bound to O2.
Relaxed (R) state
In this R state, with its flattened heme, the Hb molecule has an O2 affinity that is ~______ fold greater that than in the T state.
150
True or False: When PO2 is zero, all Hb molecules are in the T state and have a low oxygen affinity.
True
True or False: When PO2 is very high, all Hb molecules are in R state and have a high O2 affinity.
True
At __________ values, an equilibrium exists between Hb molecules in the T and R states.
Intermediate PO2
________ is another heme-containig, O2 binding protein that is specific for muscle.
Myoglobin
True or false: The globin portion of Mb arose in a gene duplication event from a primordial globin.
True
Mb functions as a _________, homologous to either an alpha or a beta chain of Hb.
Monomer
Although capable of binding only a SINGLE O2 molecule, Mb has a much _______ O2 affinity than Hb.
Higher
True or False:
Inside the CAPILLARIES, Hb can thus hand off oxygen to an Mb inside a muscle cell; this Mb then transfers its oxygen to the NEXT Mb and so on, which speeds diffusion of O2 through the muscle cell.
True
HbA
~92%
HbA1a
0.75%
HbA1b
1.5%
HbA1c
3%-6%
HbA2
2.5%
Three genes for alpha-like chains cluster on chromosome ____
16
Five genes for beta-like chains are clustered on chromosome _____
11
Very early in life, when erythropoisesis occurs in the ________, the Hb products are the three ____________.
Yolk sac
Embryonic hemoglobins
When erythropoisesis shifts to the ______ and _______ at ~10 weeks of gestation, the hemoglobin product is ___________.
Liver and spleen
Fetal hemoglobin or HbF
True or False:
Erythrocytes containing HbF have a higher O2 affinity than those containing HbA, owing to special properties of gamma chains.
True
Even adult blood contains several normal MINOR-COMPONENT HEMOGLOBINS which account for ___ to ___% of the total blood Hb.
5 to 10%
Although the physiological significance of HbA2 is uknown, _____ chains reduce the sickling of sickle hemoglobin.
Delta
Three other minor-component hemoglobins are the result of. ________ if HbA.
Nonexnzymatic glycosylation
HbA1a, HbA1b and HbA1c form when ________________ reacts with the terminal amino groups of the beta chains of HbA.
Intracellular glucose-6-phosphate
Numerous abnormal hemoglobins exist, most of which are caused by __________ on one of the polypeptide chains. One of the most clinically important is ___________ in which a ________ replaces the glutamate normally present at position __ of the beta chain.
Single-amino-acid substitutions
HbS or sickle hemoglobin
Valine
6
As a result, in low-O2 environments, HbS can crystallize into long fibers, giving the cells a ____________.
Sickle-like appearance
The sickled erythrocytes may disrupt blood flow in small vessels, causing many of the acute symptoms of ___________ including PAIN, RENAL DYSFUNCTION, RETINAL BLEEDING and ASEPTIC NECROSIS OF BONE.
“Sickle cell crisis”
In addition, sickle cells are prone to hemolysis (mean lifetime, <20 days), which leads to ____________
Chronic hemolytic anemia
The Hb-O2 dissociation curve has a __________ because of cooperativity among the four subunits of the Hb molecule.
Sigmoidal shape
When O2 binds to the Fe2+, the heme changes from a dome-like to a planar conformation, pulling the Fe2+ _________
Downward
As the Fe2+ moves downward, it pulls the attached histidine and F helix downward as well, causing the Hb to switch from the _____ to ______ state.
T or R state
The __________ gives the O2 bound to Hb in the units (mL O2)/(dL blood)
Right-hand y axis
The left-hand y-axis gives the same data in terms of ___________
Percent O2 saturation of Hb (So2 or “Sat”)
True or False:
To compute So2, we need to know the maximal amount of O2 that can bind to Hb at extremely high PO2 values.
True
Expressed in terms of grams of Hb protein, this O2 capacity is ~ ________ mL O2/g Hb- assuming that no metHb is present.
1.39 mL O2/g Hb
In real life, the O2 capacity may be closer to _______ because oxygen cannot bind to Hb that either is in the ferric state or is bound to carbon monoxide.
1.35 mL O2/g Hb
Notice that the curve in Figure 29-3 is sigmoidal or S-shaped, owing to the ________ among the four O2 binding sites on the Hb molecule.
Cooperativity
The PO2 at which the Hb is half saturated is known at the ______.
P50
The Hb-O2 versus PO2 curve ________ at high PO2 values as the Hb saturates.
Flattens
The difference in Hb saturation at low versus high Po2 values is the basis for an important clinical tool, the ________.
Pulse oximeter
The difference in total O2 content between points a and v, _____________, is the amount of O2 that the lungs add to the blood in the pulmonary capillaries, which is the same amount that all the tissues extract from the blood in the systemic capillaries.
A-V difference
A hormone that somewhat increases the amount of Hb per erythrocyte but especially increases their number.
Erythropoietin
True or False:
A patient with peripheral cyanosis may have a perfectly normal “central” O2 saturation.
True
True or False:
It is worth noting that pulse oximetry can detect CO poisoning because the absorbance spectra of Hb-CO and Hb-O2 are similar.
False
CANNOT DETECT
___________ has also become popular as an outpatient tool for assesing the presence of hypoxemia during SLEEP and thus screening for SLEEP APNEA.
Pulse oximetry
________________ has the adverse effect of increasing blood viscosity and thus vascular resistance.
Polycythemia
Such a ventilation-perfusion mismatch leads to hypoxia and thus ________ of arterial Hb.
Desaturation
The purplish color of desaturated Hb produces the physical sign known as __________, a purplish coloration of the skin and mucous membrane.
Cyanosis
Cyanosis results not from the absence of saturated or oxygenated Hb, but from the presence of __________ Hb.
Desaturated
True or False
Decrease in temperature, CO2 and H+ all of which are characteristic of metabolically active tissues, cause Hb to dump O2.
False
INCREASE
Metabolically active tissues not only have a high demand for O2, they also are ______, produce _____________ and are ________.
Warm, large amount if CO2 and acidic
True or False:
The net effect is that metabolically active tissues can signal Hb in the systemic capillaries to release more O2 than usual, whereas less active tissues can signal Hb ro release less.
True
In the _____________, where temperature is lower than in active tissues PCO2 is relatively low and pH is high - these same properties promote O2 uptake by Hb.
Pulmonary capillaries
High temperature __________ the O2 affinity of Hb and leads to release of O2.
Decreases
The maximal temperature achieved in active muscle is _________
~40C
In 1904, Christian Bohr, a physiologist and father of atomic physicist Niels Bohr, observed that RESPIRATORY ACIDOSIS shifts the Hb-O2 dissociation curve to the _______. This decrease in O2 affinity has come to be known as the ________.
Right
Bohr effect
A _____________ occurs as physiologically as erythrocytes enter the systemic capillaries.
Mild respiratory acidosis
Both contribute to the rightward shift of the Hb-O2 dissociation curve observed by Bohr: ___________ and __________
Decrease in pH
Increase in PCO2
The effect of acidosis on the Hb-O2 dissociation curve (Fig. 29-5B)—_____________ —accounts for most of the overall Bohr effect.
pH-Bohr effect
It should not be surprising that Hb is sensitive to changes in pH because Hb is an outstanding ____________
H+ buffer
Under more physiological conditions, the binding of _________ of H+ causes Hb to release _______ of O2. This property is important in the systemic tissues, where [H+] is high.
~0.7 mol
1 mole
______________ causes a conformational change in the Hb mol-ecule, which lowers the affi nity of Hb for H+.
O2 binding
The isolated effect of hypercapnia on the Hb-O2 dissociation curve represents a small portion of the overall Bohr effect.
CO2-Bohr effect
Demonstration of such a CO2-Bohr effect requires that we study the O2 affinity of Hb at a fixed pH, increasing PCO2 and HCO3 proportionally—an example of ___________.
isohydric hypercapnia
As PCO2 increases, CO2 combines with unprotonated amino groups on Hb (Hb–NH2) to form _________________.
carbamino groups (Hb–NH–COO−)
True or False:
Although Hb has other amino groups, only the four amino termini of the globin chains are susceptible to appreciable carbamino formation, the β chains more so than the α chains.
True
The overall effect of carbamino formation is therefore a ___________ in the charge on one amino acid side chain, causing a shift in the conformation of Hb and reducing its O2 affinity.
negative shift
Thus, an increased PCO2 causes Hb to unload ________, which is important in the systemic tissues. Conversely, an increased PO2 causes Hb to unload _______, which is important in the lungs.
O2
CO2
In conclusion, the Hb-O2 dissociation curve shifts to the right under conditions prevailing in the capillaries of metabolically active systemic tissues—increased temperature, decreased pH and increased PCO2 (Fig. These right shifts are synonymous with ____________.
Decreased O2 affinity.
True or False:
Low metabolic rates promote the unloading of O2 from Hb.
False
HIGH METABOLIC RATES
Indeed, in most systemic arterioles, __________ and _________ also are powerful stimuli for VASODILATION, enhancing O2 DELIVERY to metabolically active tissues.
Local hypercapnia and acidosis
_____________________ reduces the affinity of adult, but not of fetal Hb.
2,3 - Diphosphogylcerate
The affinity of Hb for O2 is very sensitive to the presence of the glycolytic metabolite ____________________ and to a lesser extent, organic phosphates such as ______.
2,3-diphosphoglycerate (2,3-DPG)
ATP
True or False:
The concentration of 2,3-DPG is about the same as that of Hb.
True
Indeed, 2,3-DPG binds to Hb in a 1:1 stoichiometry, interacting with a central cavity formed by the __________
Two beta chains
True or False:
At physiological pH, 2,3-DPG has an average of ∼3.5 negative charges, which interact with 8 positively charged amino acid residues in this central cavity.
True
True or False:
Deoxygenated Hb has a 100-fold higher affinity for 2,3-DPG than does oxygenated Hb.
True
True or False:
Binding of 2,3-DPG to Hb destabilizes the interaction of Hb with O2 promoting the release of O2.
True
Decreasing the PO2 of RBCs stimulates _________, which leads to increased levels of 2,3-DPG.
Glycolysis
At the relatively HIGH PO2 in alveoli, where the Hb-O2 dissociation curve is fairly ________, this decrease in O2 affinity reduces O2 uptake—but only slightly.
flat
At the LOW PO2 in systemic tissues, where the Hb-O2 dissociation curve is ______, this decrease in O2 affinity markedly increaes the O2 release.
Steep
The ________ in fetal erythrocytes has a higher O2 affinity than the Hb inside adult RBCs.
Fetal hemoglobin (HbF)
The crucial difference is that the ________ chains of HbF bind 2,3-DPG less avidly than do the beta chains of HbA.
Gamma
Oxygen is not the only gas that can bind to Fe2+ of Hb; CARBON MONOXIDE, NITRIC OXIDE, H2s can also bind to Hb and snap it into ___________ state.
Relaxed (R) state
In __________, CO binds to Hb with an affinity that is ~200 fold greater than that of O2.
CO poisoning
The major reason that CO is toxic is that as it snaps Hb into the R state, CO increases the O2 affinity of Hb and shifts the Hb-O2 dissociation curve far to the ______.
Left
True or False:
When Hb reaches the systemic capillaries in CO poisoning, its tenacity for O2 is so high that the bright red blood cannot release enough O2 to the tissues.
True
