Respiratory: CO2 Transport, CO, and Cyanide

Dissolved CO2 =

PaCO2 x solubility * Only. about 5% is dissolved in the plasma.

Why is there a high Cl- content in venous blood?

Carbon dioxide can passively diffuse into red cells, and red cells contain carbonic anhydrase that can convert CO2 into bicarbonate. The bicarbonate leaves the red cells for the plasma, and H+ remains in red cells. However, since bicarbonate has a negative charge when it leaves the cell, a negative charge must replace the negative charge. So, Cl- enters red cells in exchange for bicarbonate to maintain electroneutrality. This is known as the chloride shift. This is why, in the venous blood, there is a high Cl- content.

Why is more dissolved CO2 present in the blood than dissolved O2?

CO2 is more soluble than O2, so more CO2 is carried in the blood dissolved than O2.

What are carbamino-compounds?

Carbamino-compounds are compounds produced when CO2 combines with the terminal amine groups of Hb and other proteins in the blood. The formation of these compounds do not require an enzyme.

What is carbaminohemoglobin?

Carbaminohemoglobin is a compound that is formed when hemoglobin is bound to CO2. Deoxyhemoglobin binds more CO2 than oxyhemoglobin. This occurs because hemoglobin binds CO2 in a different site from O2. Once CO2 binds, it alters the binding affinity for oxygen. So, when more CO2 is bound to hemoglobin, hemoglobin releases more oxygen. As a result, Co2 decreases hemoglobin's affinity for oxygen.

What is the effect of cyanide on the oxygen-hemoglobin dissociation curve?

Cyanide does not affect the oxygen-hemoglobin dissociation curve.

The amount of dissolved CO2 is determined by ________.

Henry's law

Location: Tissues pO2: pCO2: H+: pH: Oxygen Loading or Unloading: CO2 Loading or Unloading:

Location: Tissues pO2: low (consumption) pCO2: high (metabolism) H+: high pH: low Oxygen Loading or Unloading: O2 unloading via the Bohr effect CO2 Loading or Unloading: CO2 loading via the Haldane effect

Location: Tissues/Veins pO2: pCO2: HCO3-: pH: Deoxyhemoglobin: Red Cell Cl-: Dissolved CO2: Carbaminohemoglobin:

Location: Tissues/Veins pO2: ↓ pCO2: ↑ HCO3-: ↑ pH: ↓ Deoxyhemoglobin: ↑ Red Cell Cl-: ↑ Dissolved CO2: ↑ Carbaminohemoglobin: ↑

Symptom of Cyanide Poisoning (6)

1. Bitter Almond-Smelling Breath 2. Cardiovascular Collapse 3. Pink or Cherry Skin 4. Seizures 5. Coma 6. The O2 saturation initially appears normal.

Symptoms of Methemoglobinemia (5)

1. Cyanosis: If methemoglobin > 15%, the cyanosis occurs. 2. Fatigue 3. Headache 4. Tachycardia 5. Dizziness * Symptoms usually do not present until methemoglobin 20-30%.

Carbon dioxide is transported to the lungs via three mechanisms:

1. dissolved (5%). Dissolved CO2 is determined by Henry's law. 2. bound to hemoglobin (3%). 3. bicarbonate (90%). Any time that CO2 is in the presence of water, it can react to form carbonic acid, which can dissociate tinto HCO3- and H+.

What is the effect of carbon monoxide on metabolism?

Carbon monoxide inhibits complex IV of the electron transport chain, thereby inhibiting aerobic metabolism.

True or False: Cyanide poisoning can be treated with hyperbaric oxygen.

False

Carbon dioxide is produced by ______.

cellular metabolism

Carbon monoxide shifts the oxygen-hemoglobin dissociation curve to the ______.

left

How is cyanide poisoning treated?

1. Cyanide poisoning is treated with hydroxocobalamin, which forms cyanocobalamin. 2. Cyanide poisoning can be treated by inducing the formation of methemoglobin with nitrites and sodium thiosulfate. Methemoglobin has a high affinity for CN. Then, methylene blue can be used to treat the methemoglobin. * Both are renally excreted.

What is the Bohr effect?

Anytime CO2 is produced through metabolism, H+ is generated in red blood cells. This means that an increase in H+ and a decrease in pH are indicators of metabolism. Therefore, H+ and a low pH triggers the release of O2 by hemoglobin. This phenomenon is known as the Bohr effect. The way that the Bohr effect works is that deoxyhemoglobin has a high affinity for H+. This is what buffers the pH inside of red cells. When H+ bind to hemoglobin, then the red cell is in an area with low O2 and high CO2. Therefore, the binding of hemoglobin to a H+ converts hemoglobin to the taut form, which releases O2 and shifts the O2 curve to the right. The net result, because of the Bohr effect, hemoglobin releases more oxygen, which is useful for metabolism.

What is the effect of high altitude on pO2, pCO2, and pH?

At higher altitudes, there is a lower atmospheric pressure, which leads to a lower pO2. This leads to hypoxia, which causes compensatory hyperventilation. When patients hyperventilate, this increases pO2, and decreases pCO2. This leads to a respiratory alkalosis, where pH rises. After about 24 to 48 hours, the kidneys will excrete HCO3-, and the pH will fall back to normal.

What is the effect of exercise on pO2, pCO2, pH, and oxygen consumption?

Because more carbon dioxide is produced by the muscles during exercise, the carbon dioxide level in the venous blood rises. In addition, because more oxygen is being consumed by muscles, the oxygen levels in the venous blood falls. However, the arterial pO2 and pCO2 remain normal despite metabolic changes since the lungs should be functionally normal, and ventilation rate increases.

How do red blood cells transport bicarbonate?

Carbon dioxide can passively diffuse into red cells, and red cells contain carbonic anhydrase, which increases the rate of H2CO3 production by 13000x, that can convert CO2 into bicarbonate. The bicarbonate leaves the red cells for the plasma, and H+ remains in red cells. However, since bicarbonate has a negative charge when it leaves the cell, a negative charge must replace the negative charge. So, Cl- enters red cells in exchange for bicarbonate to maintain electroneutrality. This is known as the chloride shift. This is why, in the venous blood, there is a high Cl- content.

What is the effect of cyanide on metabolism?

Cyanide can be released from burning common synthetic products, such as rubber, silk, and plastic. CN inhibits the electron transport chain complex IV, thereby inhibiting aerobic metabolism.

How do red blood cells buffer H+ from bicarbonate production?

H+ produced when bicarbonate is generated could cause a dangerous fall in pH, which can be deadly to the red cell. However, this does not occur because deoxyhemoglobin buffers H+ in red cells, preventing the pH from becoming low. When high metabolism occurs, both H+ is produced as well as deoxyhemoglobin. So, oxygen is pulled from the heme moieties in hemoglobin. As oxygen is pulled, it forms deoxyhemoglobin, which can then bind H+ and prevent the red cell pH from becoming low.

What is the response to long-term hypoxia?

In response to long-term hypoxia, the production of HIF-1α is generated. HIF-1α is produced constitutively; however, it is degraded by the proteasome following hydroxylation. When there is a lack of oxygen, then hydroxylation of HIF-1α is prevented, and HIF-1α will bind to HIF-1β and form the transcription factor, HIF-1. HIF-1 will bind to a variety of genes to enhance glucose utilization and help the cells survive under low oxygen conditions. HIF-1 increases EPO mRNA and EPO production, leading to increased production of red blood cells.

How does the body use bicarbonate to transfer carbon dioxide?

In the tissues, oxygen is consumed for metabolism, and carbon dioxide is produced. This carbon dioxide passively diffuses into red cells. Once in red cells, red cells convert it into bicarbonate, which is transported in the venous blood. The bicarbonate moves through the venous system to the lungs, where it is converted back into CO2, where it is exhaled.

Location: Lungs pO2: pCO2: H+: pH: Oxygen Loading or Unloading: CO2 Loading or Unloading:

Location: Lungs pO2: high (air) pCO2: low (exhalation) H+: low pH: high Oxygen Loading or Unloading: O2 loading via the Bohr effect CO2 Loading or Unloading: CO2 unloading via the Haldane effect

Location: Lungs/Arteries pO2: pCO2: HCO3-: pH: Deoxyhemoglobin: Red Cell Cl-: Dissolved CO2: Carbaminohemoglobin:

Location: Lungs/Arteries pO2: 100 mmHg pCO2: 40 mmHg HCO3-: 24 mmHg pH: 7.4 Deoxyhemoglobin: ↓ Red Cell Cl-: ↓ Dissolved CO2: ↓ Carbaminohemoglobin: ↓

In what form is most CO2 transported?

Most CO2 is transported as bicarbonate. It is a carrier form of CO2. In order to synthesize HCO3-, red blood cells contain carbonic anhydrase to convert CO2 to bicarbonate.

Does anemia alter the shape of the oxygen-hemoglobin dissociation curve? Explain.

No, anemia does not alter the shape of the oxygen-hemoglobin dissociation curve. The S-shaped curve is still present. However, anemia does alter the oxygen carrying capacity of the blood. This is because there is lower oxygen being carried in the blood due to a lower concentration of hemoglobin. Dissolved pO2 does not change either.

What is the CO2 dissociation curve? Explain.

The CO2 dissociation curve depicts whole blood CO2 content vs. pCO2. The dissociation curve differs when the blood contains less deoxyhemoglobin than more oxyhemoglobin. In the arterial blood, the CO2 dissociation curve is the lower curve. Around 40 mmHg, then there are 48 mL CO2/100 mL of blood. However, in the venous blood, this curve shifts to the left. This is because there is less oxyhemoglobin. Around 40 mmHg, then there are 52.5 mL CO2/100 mL of blood. This shift in the curve is called the Haldane effect, or the isohydric shift. This is the shift of the CO2 dissociation curve to the left in the presence of deoxyHb and the right when HbO2 present.

What is the Haldane effect?

The Haldane effect is essentially the opposite of the Bohr effect. The Haldane effect describes how oxygen binding alters the affinity of hemoglobin for CO2. In the Haldane effect, with a low O2 environment, hemoglobin binds more CO2. This is good because, in our tissues, there is high CO2, and it needs to be bound and transported to the lungs. On the other hand, when there is abundant oxygen around in the lungs, hemoglobin binds less CO2. This is good because it causes hemoglobin to release more CO2 in the lungs so that it can be excreted from the body. So essentially, the Haldane effect basically states that deoxyhemoglobin binds more CO2 than oxyhemoglobin since deoxyhemoglobin is a weaker acid than oxyhemoglobin, which allows more CO2 load in areas of high oxygen consumption and allows more CO2 unloading with high O2.

Hypoxia

a decrease in O2 delivery to the tissues

Hypoxemia

a decrease in arterial O2

Oxygen delivery is altered by _______.

the amount of hemoglobin in the blood