1. Gas Exchange
6.4.1 – & H.6.1 – H.6.7

2. 6.4.1 Distinguish between ventilation, gas exchange and cell respiration
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)

3. IP Physiology: Anatomy of Respiration
BioFlix –
Human Respiratory System
**Transport of Respiratory Gases

4. 6.4.4  Draw an label a diagram of the ventilation system, including trachea, lungs, bronchi, bronchioles and alveoli

5. 6.4.2 Explain the need for a ventilation system
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

6. 6.4.3  Describe the features of alveoli that adapt them to gas exchange -TRIM
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 m2) 
Moist:  Some cells in the lining secrete fluid to allow gases to dissolve and to prevent alveoli from collapsing (through cohesion)

7. Cells of the Alveolus: Type I and Type II Pneumocytes
Type 1 Pneumocyte are thing alveolar cells that are adapted to carry out gas exchange.
Squamous
Type II Pneumocyte secrete a solution containing surfactant that creates a moist surface inside the alveoli to prevent the sides of the alveolus adhering to each other by reducing surface tension.
This is a section through the lung at higher magnification, showing the thin type I pneumocytes, and the type II pneumocytes. Notice how the type II pneumocytes look shorter and fatter, and have paler staining nuclei. Macrophages are also present.

8. 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).

9. Inhalation : Movement of antagonistic Muscles
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

10. Expiration 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

12. H.6.1 Define partial pressure – Daltons Law (pg 2-4)
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. O2 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
78.6% Nitrogen; 0.04% CO2; 20.9% O2 and 0.46% H2O
At Sea Level 760 mmHg
At high Altitude 440mmHg

13. H.6.2  Explain the oxygen dissociation curves of adult hemoglobin, fetal hemoglobin and myoglobin
Transport of Respiratory Gases
IP-Physiology – gas transport
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.

14. Step wise saturation of hemoglobin

15. Oxygen Dissociation Curves
Oxygen dissociation curves show the relationship between the partial pressure of oxygen and the percentage saturation of oxygen carrying molecules
At low O2 levels (i.e. hypoxic tissues) percentage saturation will be low, while at high O2 levels (e.g. in alveoli) molecules will be fully saturated
Because binding potential increases with each additional oxygen molecule, hemoglobin displays a sigmoidal (S- shaped) dissociation curve 
Notice the 3 environmental changes that can trigger
Unloading of the oxygen.

16. Adult Hemoglobin
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)

17. Fetal Hemoglobin
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

18. Myoglobin
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 O2 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

19. Myoglobin

22. Other factors that affect dissociation
Temperature:
Increase in temperature increases the unloading of oxygen at the tissues.

23. pH
DPG – 2,3-Diphosphoglycerate
created in erythrocytes during glycolysis
increase in DPG production increases the efficiency of O2 unloading

24. 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
Bohr effect vs. Haldane (Hb move CO2 @ 5 min point)
Some is bound to hemoglobin to form HbCO2
A very small fraction gets dissolved in the blood plasma (CO2 dissolves poorly in water)
The majority (~85%) diffuses into the erythrocyte and is converted into carbonic acid

25. Transport as Carbonic Acid
When CO2 enters an erythrocyte, it combines with water in a reaction catalyzed by carbonic anhydrase to form carbonic acid (H2CO3)
The carbonic acid then dissociates into hydrogen ions (H+) and bicarbonate (HCO3–)
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 (NaHCO3), 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 CO2 for expiration

27. H.6.4  Explain the role of the Bohr shift in the supply of oxygen to respiring tissues
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

28. Bohr Effect
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

30. H.6.5 Explain how and why ventilation rate varies with exercise
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 (medulla) 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, CO2 levels in the blood will drop, restoring blood pH
Long term effects of continual exercise include an improved vital capacity (max vol.)

32. H.6.6  Outline the possible causes of asthma and its effects on the gas exchange system
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

33. Asthma may be caused by a number of variable and recurring environmental triggers, including:
Allergens (e.g. pollen, molds)
Smoke and scented products (e.g. cigarettes, perfumes)
Stress and anxiety
Food preservatives and certain medications
Arthropods (e.g. dust mites)
Cold air
Exercise (increased respiratory rate)

34. H.6.7  Explain the problem of gas exchange at high altitudes and the way the body acclimatizes
At high altitudes, air pressure is lower and hence there is a lower partial pressure of oxygen (less O2 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 O2
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

35. H.6.7 Cont.,
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

36. COPD: Alveolar walls begin to break down in the reduction of surface area for gas exchange
Causes
Consequences
Mostly smoking
Long term exposure to lung irritants (coal dust, aspestoes)
Pre-term birth can lead to COPD
Genetic factors
Difficult breathing
Gradual loss of ability to exercise and eventually walking becomes difficult
Breathing oxygen through a face mask or nasal tube.

37. Emphysemas and Chronic Obstruction Pulmonary Disorder (COPD)
Healthy Long L.S.
Irritated lung tissue release immune response; WBC’s release Elastase which breaks down Elastin.

38. STOP