Chapter 21 - Respiratory System pt. C

The Respiratory System

Overview

The respiratory system is responsible for the exchange of gases—primarily oxygen (O2) and carbon dioxide (CO2)—between the body and the environment. This process is essential for cellular respiration and maintaining homeostasis.

Oxygen Transport

Mechanisms of Oxygen Transport

Oxygen is transported in the blood in two main ways:

• Dissolved in plasma: Approximately 1.5% of molecular O2 is dissolved directly in the plasma.

• Bound to hemoglobin: About 98.5% of O2 is loosely bound to the iron (Fe) atoms in hemoglobin (Hb) within red blood cells (RBCs).

Association of Oxygen and Hemoglobin

Hemoglobin is a protein composed of four polypeptide chains, each containing an iron-rich heme group. Each hemoglobin molecule can bind up to four oxygen molecules.

• Oxyhemoglobin (HbO2): The form of hemoglobin bound to oxygen.

• Deoxyhemoglobin (HHb): Hemoglobin that has released its oxygen.

Key Reaction:

$\text{HHb} + \text{O}_2 \rightleftharpoons \text{HbO}_2 + \text{H}^+$

Hemoglobin Saturation

The loading and unloading of O2 are facilitated by conformational changes in hemoglobin:

• As O2 binds, hemoglobin's affinity for O2 increases (positive cooperativity).

• As O2 is released, affinity decreases.

• Fully saturated: All four heme groups carry O2.

• Partially saturated: Only one to three heme groups carry O2.

Factors Influencing Hemoglobin Saturation

The rate of O2 loading and unloading is regulated to ensure adequate delivery to tissues. Key factors include:

• Partial pressure of oxygen (PO2): The most significant factor.

• Temperature: Higher temperatures decrease affinity for O2.

• Blood pH: Lower pH (acidosis) decreases affinity.

• Partial pressure of carbon dioxide (PCO2): Higher PCO2 decreases affinity.

• Concentration of BPG (2,3-bisphosphoglycerate): Increased BPG decreases affinity.

Oxygen-Hemoglobin Dissociation Curve

The relationship between PO2 and hemoglobin saturation is depicted by the oxygen-hemoglobin dissociation curve, which is sigmoidal (S-shaped):

• In arterial blood (PO2 ≈ 100 mm Hg): Hemoglobin is ~98% saturated.

• In venous blood (PO2 ≈ 40 mm Hg): Hemoglobin is ~75% saturated, providing a venous reserve of oxygen.

Example: During exercise, increased temperature and CO2 production shift the curve to the right, enhancing O2 unloading to tissues.

Carbon Dioxide Transport

Mechanisms of CO2 Transport

Carbon dioxide is transported in the blood in three forms:

• Dissolved in plasma: 7–10% as PCO2.

• Bound to hemoglobin: ~20% as carbaminohemoglobin (CO2 binds to globin, not heme).

• As bicarbonate ions (HCO3-): ~70% formed via the following reaction:

$\text{CO}_2 + \text{H}_2\text{O} \xrightarrow{\text{carbonic anhydrase}} \text{H}_2\text{CO}_3 \rightarrow \text{HCO}_3^- + \text{H}^+$

In systemic capillaries, HCO3- diffuses out of RBCs, balanced by Cl- influx (chloride shift). In pulmonary capillaries, the process reverses, allowing CO2 to diffuse into alveoli.

Haldane and Bohr Effects

• Haldane effect: Lower PO2 and hemoglobin saturation allow more CO2 to be carried in blood.

• Bohr effect: Increased CO2 and H+ weaken the Hb-O2 bond, enhancing O2 unloading.

Carbonic Acid-Bicarbonate Buffer System

This system helps maintain blood pH:

• If H+ rises, excess is removed by combining with HCO3- to form H2CO3, which dissociates into CO2 and H2O.

• If H+ drops, H2CO3 dissociates, releasing H+.

Ventilation rate affects blood pH: slow, shallow breathing increases CO2 and lowers pH; rapid, deep breathing decreases CO2 and raises pH.

Hypoxia and Related Disorders

Types of Hypoxia

Hypoxia is inadequate O2 delivery to tissues, classified by cause:

• Anemic hypoxia: Too few RBCs or abnormal/insufficient hemoglobin.

• Ischemic hypoxia: Impaired or blocked blood circulation.

• Histotoxic hypoxia: Cells unable to use O2 (e.g., cyanide poisoning).

• Hypoxemic hypoxia: Abnormal ventilation or low O2 in air.

• Carbon monoxide poisoning: CO binds Hb with 200x greater affinity than O2, causing severe hypoxia.

Control of Respiration

Neural Mechanisms

Respiratory rhythms are regulated by higher brain centers, chemoreceptors, and reflexes. Key centers include:

• Ventral respiratory group (VRG): Rhythm-generating and integrative center; sets eupnea (normal rate and rhythm).

• Dorsal respiratory group (DRG): Integrates input from peripheral stretch and chemoreceptors.

• Pontine respiratory centers: Smooth transitions between inspiration and expiration; lesions cause apneustic breathing.

Breathing rhythm: Likely generated by reciprocal inhibition of pacemaker neurons in the medulla.

Factors Influencing Breathing Rate and Depth

Breathing is modified by:

• Chemical factors: Most important; include PCO2, PO2, and pH.

• Higher brain centers: Hypothalamic and cortical controls.

• Pulmonary irritant reflexes: Response to dust, mucus, fumes.

• Inflation reflex: Hering-Breuer reflex prevents over-inflation.

Chemical Regulation

• Central chemoreceptors: Located in brainstem; respond to changes in PCO2 and pH.

• Peripheral chemoreceptors: Located in aortic arch and carotid arteries; respond to PO2 and pH.

Key Points:

• Rising CO2 is the most powerful respiratory stimulant.

• Blood O2 affects breathing mainly when PO2 falls below 60 mm Hg.

• Blood pH can modify breathing even if O2 and CO2 are normal.

Exercise and Respiration

Adjustments During Exercise

Ventilation increases in response to metabolic demands (hyperpnea). Neural factors include psychological stimuli, motor activation, and proprioceptor input. Po2 and pH remain relatively constant during exercise.

High Altitude Adaptation

Acute and Chronic Responses

At high altitudes, lower atmospheric pressure and PO2 can cause acute mountain sickness. Acclimatization involves increased ventilation and erythropoietin (EPO) production, raising RBC count for long-term compensation.

Respiratory Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD)

COPD includes chronic emphysema and bronchitis, characterized by irreversible decreased ability to force air out of lungs. Most patients have a history of smoking, dyspnea, and frequent infections. Hypoventilation leads to acidosis and hypoxemia.

• Emphysema: Permanent enlargement of alveoli, destruction of walls, decreased elasticity, hyperinflation, barrel chest, and right ventricular enlargement.

• Chronic bronchitis: Excess mucus, inflamed and fibrosed mucosa, obstructed airways, frequent infections.

• "Pink puffers" vs. "Blue bloaters": Pink puffers maintain near-normal gases but expend more energy; blue bloaters have cyanosis and hypoxia.

Treatment: Bronchodilators, corticosteroids, oxygen therapy, and sometimes surgery.

Asthma

Asthma is characterized by acute episodes of airway inflammation, bronchospasm, and thickened airways due to immune responses. Symptoms include coughing, wheezing, and dyspnea.

Tuberculosis (TB)

TB is an infectious disease caused by Mycobacterium tuberculosis. Symptoms include fever, night sweats, weight loss, and coughing up blood. Treatment requires long-term antibiotics; resistant strains exist.

Lung Cancer

Lung cancer is the leading cause of cancer deaths in North America, with most cases linked to smoking. Main types:

• Adenocarcinoma: Originates in peripheral lung areas.

• Squamous cell carcinoma: Arises in bronchial epithelium.

• Small cell carcinoma: Contains lymphocyte-like cells, metastasizes rapidly.

Treatment: Early detection, surgery, radiation, chemotherapy, and emerging therapies.

Sleep Apnea

Sleep apnea is characterized by temporary cessation of breathing during sleep, leading to daytime sleepiness and increased risk of chronic diseases. Types include:

• Obstructive sleep apnea: Collapse of upper airway due to relaxed pharyngeal muscles.

• Central sleep apnea: Reduced drive from brainstem respiratory centers.

Treatment: CPAP (continuous positive airway pressure) device to keep airway open.

Summary Table: Oxygen and Carbon Dioxide Transport

Gas	Transport Form	Percentage	Key Mechanism
Oxygen (O2)	Dissolved in plasma	1.5%	Direct solubility
Oxygen (O2)	Bound to hemoglobin	98.5%	Oxyhemoglobin formation
Carbon dioxide (CO2)	Dissolved in plasma	7–10%	Direct solubility
Carbon dioxide (CO2)	Bound to hemoglobin	~20%	Carbaminohemoglobin formation
Carbon dioxide (CO2)	As bicarbonate ions	~70%	Carbonic anhydrase reaction

Additional info: The above notes expand on brief slide points to provide full academic context, definitions, and examples suitable for college-level Anatomy & Physiology students.