6.4.1 – 6.4.5 & H.6.1 – H.6.7

• Quiz
• Lecture:
• 6.4.1 – 6.4.5
• HW
•
TEST Moved to Tuesday, February 10 th [Transportation and Gas Exchange
– 100 pts.]
•
BioFlix: Part I and II
• IP Physiology: Respiration
• Anatomy Review: Respiratory Structure
• Questions: 1-3; 9-12; 15-21; 28,30 & 32 [17 questions total]
• For some of the questions you will need to print the images and label accordingly. Print all material first, then begin watching and answering the questions as you go along.
• This is for a grade!!!

• Respiration is the transport of oxygen to cells where energy production takes place, and involves three key processes:
• Ventilation: The exchange of air between the lungs and the atmosphere; it is achieved by the physical act of breathing
• Gas exchange: The exchange of oxygen and carbon dioxide in the alveoli and the bloodstream; it occurs passively via diffusion
• Cell Respiration: The release of ATP from organic molecules; it is greatly enhanced by the presence of oxygen (aerobic respiration)

• BioFlix –
• Human Respiratory System
•
Transport of Respiratory Gases

•
Because gas exchange is a passive process, a ventilation system is needed to maintain a concentration gradient within the alveoli
• Oxygen is needed by cells to make ATP via aerobic respiration, while carbon dioxide is a waste product of this process and must be removed
•
Therefore, oxygen must diffuse from the lungs into the blood, while carbon dioxide must diffuse from the blood into the lungs
• This requires a high concentration of oxygen - and a low concentration of carbon dioxide - in the lungs
•
A ventilation system maintains this concentration gradient by continually cycling the air in the lungs with the atmosphere

• Thin wall: Made of a single layer of flattened cells so that diffusion distance is small
• Rich capillary network: Alveoli are covered by a dense network of capillaries that help to maintain a concentration gradient
• Increased SA:Vol ratio: High numbers of spherically-shaped alveoli optimize surface area for gas exchange (600 million alveoli =
80 m 2 )
• Moist: Some cells in the lining secrete fluid to allow gases to dissolve and to prevent alveoli from collapsing (through cohesion)

6.4.5 Explain the mechanism of ventilation of the lungs in terms of volume and pressure changes caused by the internal and external intercostal muscles, the diaphragm and abdominal muscles
• Breathing is the active movement of respiratory muscles that enable the passage of air to and from the lung
• The mechanism of breathing is described as negative pressure breathing as it is driven by the creation of a negative pressure vacuum within the lungs, according to Boyle's Law
(pressure is inversely proportional to volume).

• Diaphragm muscles contract and flatten downwards
• External intercostal muscles contract, pulling ribs upwards and outwards
• This increases the volume of the thoracic cavity (and therefore lung volume)
• The pressure of air in the lungs is decreased below atmospheric pressure
• Air flows into the lungs to equalize the pressure

• Diaphragm muscles relax and diaphragm curves upwards
• Abdominal muscles contract, pushing diaphragm upwards
• External intercostal muscles relax, allowing the ribs to fall
• Internal intercostal muscles contract, pulling ribs downwards
• This decreases the volume of the thoracic cavity
(and therefore lung volume)
• The pressure of air in the lungs is increased above atmospheric pressure
• Air flows out of the lungs to equalize the pressure

• Partial pressure is the pressure exerted by a single type of gas when it is found within a mixture of gases
• The partial pressure of a given gas will depend on:
• The concentration of the gas in the mixture (e.g. O
2 levels may differ in certain environments)
• The total pressure of the mixture (air pressure decreases at higher altitudes)
*the partial pressures of the gases within the alveoli are not the same as their atmospheric partial pressures

• Transport of Respiratory Gases
• Hemoglobin is composed of four polypeptide chains, each with an iron-containing heme group capable of reversibly binding oxygen
• As each oxygen molecule binds, it alters the conformation of hemoglobin, making it easier for others to be loaded ( cooperative binding )
• Conversely, as each oxygen molecule is released, the change in hemoglobin makes it easier for other molecules to be unloaded.

• Oxygen dissociation curves show the relationship between the partial pressure of oxygen and the percentage saturation of oxygen carrying molecules
• At low O
2 levels (i.e. hypoxic tissues) percentage saturation will be low, while at high O
2 levels (e.g. in alveoli) molecules will be fully saturated
• Because binding potential increases with each additional oxygen molecule, hemoglobin displays a sigmoidal (Sshaped) dissociation curve

• Dissociation curves displays a typical sigmoidal shape (due to cooperative binding)
• There is low saturation of oxygen when partial pressure is low (corresponds to environment of the tissue, when oxygen is released)
• There is high saturation of oxygen when partial pressure is high (corresponds to environment of the alveoli, when oxygen is taken up)

• The hemoglobin of the fetus has a slightly different molecular composition to adult hemoglobin
• Dissociation curve is to the left of the adult hemoglobin curve (indicating a higher affinity for oxygen)
• This is important as it means that oxygen will move from adult hemoglobin to fetal hemoglobin in the capillaries of the uterus

• Myoglobin is an oxygen-binding molecule found in muscles that is made of a single polypeptide with only one heme group
• Dissociation curve is to the left of the hemoglobin curve and does not display a sigmoidal shape
(myoglobin cannot undergo cooperative binding)
• Myoglobin's affinity for oxygen is greater than hemoglobin and becomes saturated at low oxygen concentrations.
• Under normal conditions (at rest) myoglobin is saturated with oxygen and will store it until O
2 levels in the body drop with intense exercise
• This allows it to provide oxygen when levels are very low (e.g. in a respiring muscle) and so delays anaerobic respiration and lactic acid formation

• Temperature:
• Increase in temperature increases the unloading of oxygen at the tissues.

• pH • DPG – 2,3-Diphosphoglycerate
• created in erythrocytes during glycolysis
• increase in DPG production increases the efficiency of O
2 unloading

H.6.3 Describe how carbon dioxide is carried by the blood, including the action of carbonic anhydrase, the chloride shift and buffering by plasma proteins
• Carbon dioxide is transported from the tissues to the lungs in one of three ways:
• IP Physiology: pg 16 - 19
• Bohr effect vs. Haldane
• Some is bound to hemoglobin to form HbCO
2
• A very small fraction gets dissolved in the blood plasma (CO
2 water) dissolves poorly in
• The majority (~85%) diffuses into the erythrocyte and is converted into carbonic acid

• When CO
2 enters an erythrocyte, it combines with water in a reaction catalyzed by carbonic anhydrase to form carbonic acid (H
2
CO
3
)
• The carbonic acid then dissociates into hydrogen ions (H + ) and bicarbonate (HCO
3
–
)
• Bicarbonate is pumped out of the cell and exchanged with chloride ions to ensure the erythrocyte remains uncharged – this is called the chloride shift
• The bicarbonate combines with sodium ions in the blood plasma to form sodium bicarbonate
(NaHCO
3
), which travels to the lungs
• The hydrogen ions in the erythrocyte make the environment less alkaline, causing the hemoglobin to release its oxygen to be used by cells
• The hemoglobin absorbs the H + ions and acts as a buffer to restore pH, the H + ions will be released in the lungs to reform CO
2 for expiration

• The oxyhemoglobin dissociation curve describes the saturation of hemoglobin by oxygen in cells under normal metabolism
• Cells with increased metabolism (e.g. hypoxic tissue) release greater amounts of carbon dioxide into the blood
• Carbon dioxide lowers the pH of the blood (via its conversion into carbonic acid) which causes hemoglobin to release its oxygen
• This is known as the Bohr effect – a decrease in pH shifts the oxygen dissociation curve to the right in tissues
• Hence more oxygen is released at the same partial pressure of oxygen, ensuring respiring tissues have enough oxygen when their need is greatest

• Cells with increased metabolism (e.g. hypoxic tissue) release greater amounts of carbon dioxide into the blood
• Carbon dioxide lowers the pH of the blood (via its conversion into carbonic acid) which causes hemoglobin to release its oxygen
• This is known as the Bohr effect – a decrease in pH shifts the oxygen dissociation curve to the right in tissues
• Hence more oxygen is released at the same partial pressure of oxygen, ensuring respiring tissues have enough oxygen when their need is greatest

• During exercise metabolism is increased, oxygen is becoming limited and there is a build up of both carbon dioxide and lactic acid in the blood
• This lowers the blood pH, which is detected by chemoreceptors in the carotid artery and the aorta
• These chemoreceptors send impulses to the breathing center in the brain stem to increase the rate of respiration
• Impulses are sent to the diaphragm and intercostal muscles to change the rate of muscular contraction, hence changing the rate of breathing
• This process is under involuntary control (reflex response) – as breathing rate increases, CO
2 levels in the blood will drop, restoring blood pH
• Long term effects of continual exercise include an improved vital capacity

• Asthma is a common, chronic inflammation of the airways to the lungs (i.e. bronchi / bronchioles)
• Inflammation leads to swelling and mucus production, resulting in reduced airflow and bronchospasms
• During an acute asthma attack, constriction of the bronchi smooth muscle may cause significant airflow obstruction, which may be life threatening
• Common asthma symptoms include shortness of breath, chest tightness, wheezing and coughing

• A llergens (e.g. pollen, molds)
• S moke and scented products (e.g. cigarettes, perfumes)
•
F ood preservatives and certain medications
• A rthropods (e.g. dust mites)
• C old air
• E xercise (increased respiratory rate)
• S tress and anxiety

• At high altitudes, air pressure is lower and hence there is a lower partial pressure of oxygen (less O
2 in the air)
• This makes it more difficult for hemoglobin to take up and transport oxygen from the alveoli (lower Hb % saturation), meaning tissues receive less O
2
• A person unaccustomed to these conditions will display symptoms of low oxygen intake – fatigue, breathlessness, rapid pulse, nausea and headaches
• Over time, the body will begin to acclimatize to the lower oxygen levels at high altitudes:
• Red blood cell production increases to increase oxygen transport

• Red blood cells will have a higher hemoglobin content with an increased affinity for oxygen
• Ventilation rate increases to increase gas exchange (including a larger vital capacity)
• Muscles produce more myoglobin and have increased vascularization (denser capillary networks) to encourage oxygen to diffuse into muscles
• Kidneys will begin to secrete alkaline urine (improved buffering of blood pH) and there is increased lactate clearance within the body
• People living permanently at high altitudes will have a greater lung surface area and larger chest sizes