Respiratory System: gas transport, use of oxygen, cell respiration, disorders (lecture 16)

Gas Exchange

• Gas exchange involves the movement of gases from the alveoli to systemic tissues, and back to the alveoli.
• The primary focus during gas exchange is on oxygen (O₂) and carbon dioxide (CO₂).

Oxygen in Blood

• About 98.5% of oxygen is bound to hemoglobin in red blood cells (RBCs).
• Only 1.5% of oxygen is dissolved in blood.
• Hemoglobin is specialized for oxygen transport.
• It consists of 4 globin chains, each with one heme group
• Each heme group binds one O₂ molecule to an iron atom.
• 100% saturation of hemoglobin means that all 4 O₂ binding sites are occupied.
• 25% saturation of hemoglobin means that 1 O₂ binding site is occupied.
• Hemoglobin changes shape when binding O₂ to enhance binding affinity (ability to bind) for O₂.
• Carbon monoxide is a toxic gas because it competes with oxygen for the binding sites on hemoglobin.

Carbon Dioxide in Blood

• Carbon dioxide is transported into the blood in three main forms: carbonic acid (90%), carbamino compounds (5%), and as a dissolved gas (5%).
• Carbonic acid forms when CO₂ reacts with water (H₂O), eventually dissociating into hydrogen ions (H+) and bicarbonate ions (HCO3-).
• Carbamino compounds, like carboaminohemoglobin, forms when CO₂ binds to plasma proteins and hemoglobin (HbCO₂), binding to polypeptide chains rather than the heme.
• CO₂ can bind along with O₂, but each gas inhibits the transport of the other.
• Blood gives up dissolved CO₂ and HbCO₂ easier.
• Only 70% of exchanged CO₂ comes from H₂CO₃.

Systemic Circulation

• Systemic gas exchange involves the unloading of O₂ and loading of CO₂ in systemic capillaries.
• Oxygen is unloaded, and CO₂ enters the blood.
• Carbon dioxide reacts with water to form carbonic acid, which then dissociates into bicarbonate and hydrogen ions (H+).
• Some H+ can bind to hemoglobin inside RBCs to lower its affinity for O₂, promoting O₂ release.
• Oxygen consumption by respiring tissues keeps the partial pressure of oxygen (PO₂) in tissue fluid relatively low (around 40 mm Hg).
• The blood arriving at systemic capillaries is about 97% saturated and leaves at 75% saturation, giving up around 22% of its oxygen load.
• The remaining oxygen provides a venous reserve, which can sustain life for about 4 to 5 minutes even in the event of respiratory distress.

Differential Oxygen Delivery

• Four factors that can adjust the rate of oxygen unloading depending on different tissue's metabolic rates and oxygen needs.
• These factors include partial pressure of oxygen (PO₂), temperature, pH, and bisphosphoglycerate (BPG).
• Cells using more O₂ maintain a steeper pressure gradient, leading to more unloading.
  • Metabolizing/active tissues are warmed than less active ones and thus extract more oxygen from the blood passing through them
• Higher temperatures promote O₂ unloading.
• More CO₂ results in more H+, weakening the O₂-hemoglobin bond, and promotes oxygen unloading.
• Red blood cells use anaerobic fermentation to produce BPG, which binds to hemoglobin and promotes O₂ unloading. RBCs use anaerobic fermentation to meet needs because they don't have a mitochondria.
• An elevated body temperature (as in fever) stimulates BPG synthesis, as do thyroxine, growth hormone, testosterone, and epinephrine. All these hormones promote oxygen unloading to the tissues.

Respiratory Rhythm

• The rate and depth of breathing are adjusted to maintain pH, PCO₂, and PO₂.
• These values are: pH (7.35-7.45), PCO₂ (40 mm Hg), and PO₂ (95 mm Hg).
• Chemoreceptors detect changes in pH, carbon and oxygen and trigger responses to regulate breathing.
• 75% of the receptors are central receptors, and 25% are peripheral.
• Central receptors in the medulla oblongata mediate changes in respiration.
• CO₂ reacts with water in the CSF to produce carbonic acid in, little buffers are present which makes the fluid more sensitive to pH changes.

Respiratory Rhythm (Acidosis/Alkalosis)

• Acidosis occurs when the pH drops below 7.35, often due to hypoventilation or breath-holding.
• Compensating for acidosis involves hyperventilating to remove excess CO₂.
  • As CO₂ is eliminated from the body, the carbonic acid reaction shifts to the left. Thus, the H+ on the right is consumed. As the H+ concentration declines, the pH rises to normal.
• Alkalosis occurs when the pH rises above 7.45, often due to hyperventilation, for example, during a panic attack.
• Compensating for alkalosis involve hypoventilating, or breathing from a bag
  • Hypoventilation shifts the reaction to the right, raising the H+ concentration and lowering the pH to normal.

Exercise

• Heavy breathing during exercise is not due to increased CO₂ levels or decreased pH, but rather is driven by other factors.
• The anticipatory effect is when the brain ends motor commands to the muscles and to the respiratory centers. Anticipating physical activity is what increases respiration.
• Exercise stimulates proprioceptors (muscles & joints) to send info to the respiratory centers, which increases breathing. This increase in breathing is because the respiratory centers are informed that the muscles have been told to move or are actually moving.

Oxygen Imbalances

• Hypoxia is defined as oxygen deficiency in tissue or the inability to use oxygen
• Hypoxemic hypoxia occurs due to inadequate oxygen uptake in the lungs, leading to low arterial oxygen levels (PO2)
  • Causes include: high elevation, impaired ventilation (as in drowning or aspiration of foreign matter), lung disease, or carbon monoxide poisoning
• Anemic hypoxia is a result of low RBC count resulting in the inability of the blood to carry adequate oxygen.
  • Anemia is a condition where you lack enough healthy RBCs to carry adequate oxygen to your body's tissues
• Ischemic hypoxia caused by poor blood circulation preventing oxygen delivery to tissues. A cause could be heart failure which reduces the hearts ability to pump blood efficiently.
• Histotoxic hypoxia is causes by metabolic poison (like cyanide) that prevents tissues from using oxygen
• Hypoxia is often marked by cyanosis (blueness of the skin). Its primary danger is necrosis of oxygen starved tissues. This is critical in organs with high metabolic demands, such as the brain, heart, and kidneys.

Pulmonary Hypertension (PH)

• Pulmonary hypertension is high blood pressure in pulmonary vessels
• Pulmonary vessels are the blood vessels that carry blood from the heart to the lungs.
• Caused by blood vessels narrowed or destroyed, blood clots, tumors, genetics, COPD, or sometimes the cause is unknown.
• COPD (chronic obstructive pulmonary diseases) is defined as long term obstrcution of airflow and substantial reduction of pulmonary ventilation. There are two main COPDs: chronic bronchitis and emphysema.
  • Chronic bronchitis is severe, persistent inflammation of the lower respiratory tract.
  • Emphysema is when alveolar walls break down and alveoli converge into fewer and larger spaces. This causes less respiratory membrane to be available for gas exchange.
• There is a disproportionate effect on the right side of the heart because more force is needed to deliver blood to the lungs. It affects the right side of the heart because the right ventricle is what is responsible for pumping blood into pulmonary arteries. Increased workload can cause heart failure.

Pneumothorax - Spontaneous

• Air in the pleural cavity
• Occurs when the visceral pleura is punctured
• Blebs occur
• Spontaneous pneumothorax is the sudden onset of a collapsed lung without apparent cause, such as a traumatic injury to the chest or a known lung disease
• In most cases, a bleb ruptures and air leaks into the space around the lung, causing pressure on the lung. This makes the lung not be able to expand as much as it normally does and leads to a collapsed lung.
  • A bleb is a small collection of air between the lung and the visceral pleura
• Physicians use a chest tube to create negative pressure in the chest cavity and allow re-expansion of the lung. It helps remove air (pneumothorax), blood (hemothorax), fluid (pleural effusion or hydrothorax), chyle (chylothorax), or purulence (emphyema) from the intrathoracic space.
  • Chylothorax: accumulation of lymphatic fluid in the pleural cavity
  • Emphyema: collection of pus in the pleural cavity due to infection
• This tube remains in the chest until all or most of the air or fluid has drained out, usually within a few days.