Resp 5 Flashcards
mechanisms to transport oxygen in blood
Two mechanisms:
* Dissolved in plasma
* Bound to hemoglobin (Hb) in erythrocytes
-O2 is poorly soluble in water & plasma
-Even after pulmonary capillary blood has equilibrated with alveolar O2
tension (about 100 mm Hg), it is only carrying about 3 μL of dissolved
oxygen per mL of blood – just 2% of the oxygen normally carried by arterial blood
hemoglobin in blood
-Hemoglobin transports 98% of the O2 in blood
-Oxygen is not sufficiently soluble in aqueous fluid to provide adequate delivery to tissues at physiologic cardiac outputs and normal environmental conditions
hemoglobin
- Composed of four subunits, each consisting of one protein (α or β globin) and one heme group
- Each heme group contains one iron that can bind reversibly with one O2
molecule, so each hemoglobin molecule can carry up to four O2 molecules - Globin prevents O2 from covalently binding the iron atom, allowing the
uptake and release of O2 in response to local oxygen tension (PO 2)
porphryin and porphyria
- A heme group consists of an iron ion (Fe2+) bonded to a porphyrin
molecule - Eight enzymes are involved in the synthesis of heme from iron and
porphyrins - A mutation in any of these genes may lead to a buildup of porphyrins
in the body: Porphyria
heme-heme interactions
-Up to 4 O2 molecules bind to a single hemoglobin molecule.
-Saturation of a single hemoglobin molecule is a 4-step process
Heme-heme interactions:
-Binding of first O2 -> conformational change -> more rapid binding of next O2
- This means that as heme enters lung and begins to pick up O2, its affinity for O2 increases à saturates more and more rapidly
- As heme enters tissues it tends not to release O2 unless gradient is high
(i.e. tissues are deoxygenated); as it begins to lose O2, oxygen affinity drops -> O2 release becomes more rapid in these deoxygenated tissues
oxyhemoglobin dissociation curve
-Reflects the changing affinity of hemoglobin for O2 (non-linear) with different oxygen concentrations (tensions).
-Note: hemoglobin is almost fully saturated at ~70-80 mm Hg oxygen tension
-When PaO 2 = 40mm Hg (i.e. blood
in peripheral tissues), affinity of
Hb for O2 is lower; Hb saturation is
about 70-80% (depending on the
species)
-When PaO 2 = 100 mm Hg (i.e. blood leaving lungs), Hb saturation is almost 100%
-Because hemoglobin is almost fully saturated at ~70-80 mm Hg oxygen tension, if you can get PaO2 up to near 100 mm Hg, you can deliver oxygen effectively to tissues, but if not, you will severely compromise O2 delivery.
-If O2 saturation is already near 100%, extra O2 won’t markedly change oxygen delivery to tissues.
-O2 is provided to patients in an attempt to increase hemoglobin saturation to 100%
factors that affect oxygen transportation by hemoglobin
- PO 2: Hb affinity for O2 varies directly with the oxygen tension of its environment.
- Temperature: Increased metabolism increases O2 consumption, which elevates tissue temperature. As temperature rises, Hb’s affinity for O2 falls -> more
O2 is released in warm tissues where O2 consumption is highest - PCO 2 & pH: CO 2 is in equilibrium with carbonic acid in the bloodstream (CO2 + H2O ↔ H2CO3), so where CO2 levels are highest, pH is lowest.
-Tissues with high CO2 tensions are
therefore more acidic than those with lower CO2 tensions. Hb affinity for O2 is directly related to pH, so affinity for O2 is lowest at low pH where CO 2 levels are highest.
-Another way to say this is that the drop in pH arising from CO2 accumulation shifts the oxyhemoglobin dissociation curve to the right (known as the Bohr Shift or Bohr Effect; yellow arrow), so more O2 is released (white arrow) - Organic phosphates: 2,3- diphosphoglycerate (DPG) is present in RBCs at the same concentration as Hb. DPG inhibits the binding of O2 to Hb.
-When oxygen levels are low (e.g. with anemia or at high altitude), DPG
levels rise and the oxyhemoglobin
dissociation curve is shifted to the
right -> oxygen release from Hb is
facilitated. Note that this comes at
the cost of saturation – PO2 has to
be higher to achieve the same Hb
saturation level
blood colour changes with Hb saturation
-As Hb is depleted of oxygen, its colour changes from bright red to
reddish-blue. This colour change is known as cyanosis (this is why mucous membranes of hypoxic animals appear bluish red).
-Cyanosis can be caused by reduced O2 uptake via the lungs or by reduced blood flow to a tissue.
-The colour difference between oxyhemoglobin and deoxyhemoglobin is the basis for pulse oximetry
pulse oximetry
- A device containing two light-emitting diodes is placed on the earlobe, tongue, paw, or other thin appendage
- Two wavelengths of light, red & infra-red, are passed through the tissue to a detector
- Oxy-Hb absorbs more infrared light, deoxy-Hb absorbs more red light; the oximeter uses the relative absorption to calculate the percentage of Hb that is oxygenated
- Main use is for monitoring during anesthesia (should always be >95% saturation)
O2 and CO2 parameters routinely measured in blood
- Blood gas analysis directly measures pH, Pa O 2 & Pa CO 2 and
calculates the O2 saturation of hemoglobin using those values - Pulse oximetry measures the absorbance of light by Hb and
calculates Hb saturation
release of O2 in the issues
- Active tissues produce CO2 carbonic and lactic acid, which lowers pH, which in turn facilitates the release of oxygen from Hb via the “Bohr effect”
- This is one adaptation for coping with sudden increases in O2 consumption by tissues – leads to greater delivery at sites of low pH
tissue oxygen demand is highly variable; increased through what
-Oxygen demand varies with metabolism and exercise
-Demand can increase to >30 times resting levels during exercise. In response, O2 delivery is increased through:
1) A 5-fold increase in cardiac output
* This is accompanied by a redistribution of blood to the
skeletal muscles during exercise à overall 20-fold increase in blood flow to muscles.
2) A 50% increase in Hb in bloodstream via contraction of spleen, causing release of ~50% more RBCs into circulation.
3) A marked increase in O2 gradient between capillaries and muscle tissue: Tissue PO2 drops markedly
carbon monoxide poisoning
-CO binds to the same site on hemoglobin as O2, but with much
greater affinity, displacing O2
-Affinity of Hb for CO is about 240 x greater than its affinity for O2, so breathing even 1% CO in air for some time can be fatal
-CO poisoning can produce a cherry red colour in mucous membranes and skin – HbCO complex is bright red in colour
the haldane effect
- Deoxygenated the blood has
increased ability to carry CO2. This
property is called the Haldane Effect - Removal of oxygen from hemoglobin increases hemoglobin’s affinity for carbon dioxide
- This allows carbon dioxide to “ride” on the empty hemoglobin molecule.
- Conversely, oxygenated blood
(hemoglobin) has a reduced capacity for carbon dioxide
CO2 carried in blood in different ways
- CO2 is produced in the tissue, so tissue PCO 2 is greater than P CO 2 of the blood
- CO2 diffuses down its tension gradient from the tissues into the blood
Remember: In blood, CO 2 is carried in three different ways:
1) 65% is converted to bicarbonate ions (HCO 3- ) by the enzyme carbonic anhydrase, by the reaction:
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3−
(Most of this bicarbonate is produced inside RBCs and then diffuses out into the plasma)
2) 27% is bound to hemoglobin as carbamino compounds (bound to the globin rather than to heme)
3) 8% of the CO2 remains dissolved intact in the plasma
