Transport in mammals

1. Transport in mammals

2. Different types of circulatory system Closed circulatory systemVertebrates, and a few invertebrates, have a closed circulatory system. Closed circulatory systems have the blood closed at all times within vessels of different size and wall thickness. In this type of system, blood is pumped by a heart through vessels, and does not normally fill body cavities.                        Open circulatory systemThe open circulatory system is common to molluscs and arthropods. Open circulatory systems (evolved in crustaceans, insects, molluscs and other invertebrates) pump blood into a hemocoel with the blood diffusing back to the circulatory system between cells. Blood is pumped by a heart into the body cavities, where tissues are surrounded by the blood.

3. The Structure of the Heart http://uk.youtube.com/watch?v=D3ZDJgFDdk0 http://www.sumanasinc.com/webcontent/animations/content/human_heart.html

4. The Cardiac Cycle Your heart beats around 70 times a minute. The cardiac cycle is the sequence of events which makes up one heart beat. The cycle is made up of 3 main stages: • Heart relaxes • Chambers fill with blood • Ventricles contract • Blood forced into arteries • Atria start to re-fill • Atria contract • Blood forced into ventricles

5. Pressure Changes during the Cardiac Cycle • Questions • What is the longest stage in the cardiac cycle? • Why do you think this is? • How long does it last? • Why do you think Ventricular systole lasts longer than Atrial systole? • When is the pressure in the Aorta at its highest?

6. Blood Vessels Blood is pumped by the heart into thick-walled vessels called ARTERIES, these split up into smaller vessels called ARTERIOLES, from which the blood passes into the CAPILLARIES. The capillaries form a networks which penetrate all the tissue and organs of the body. Blood from the capillaries collects into VENULES, which in turn empty blood into VEINS, which return it to the heart. Arteries and Veins have the same basic three layers but their proportions vary: • The innermost layer (ENDOTHELIUM or TUNICA INTIMA) is one cell thick and provides a smooth lining with minimum resistance to blood flow • The middle layer (TUNICA MEDIA) is made of elastic fibres and smooth muscle. It is thicker in arteries than in veins. • The outer layer (TUNICA EXTERNA) is made of collagen fibres and is resistant to over stretching.

7. Images:

8. Micrographs:

9. The Blood Blood is a tissue made up of cells in a fluid plasma. It is composed of the following: • 55% plasma: mostly water, carries CO2, glucose, urea, amino-acids, hormones, heat and cells! • 45% cells: all made in bone marrow; short life; destroyed in liver; only WBC’s have nucleus, reproduce • RBCs (Erythrocytes) carry O2; no nucleus; biconcave (↑ SA); contain haemoglobin; small (8μm so ↑mobility) • WBCs (Luecocytes): fight disease; have nucleus, larger than RBCs; 2 main groups: Lymphocytes (secrete antibodies); Phagocytes (‘eat’ bacteria); • Platelets (Thrombocytes): fragments of cells vital for blood clotting (and tissue repair)

10. Photomicrographs of blood cells:

11. The Lymphatic System When blood reaches the arteriole end of a capillary it is under pressure due to the pumping action of the heart. The hydrostatic pressure forces the fluid part of the blood through the capillary walls into the spaces between the cells. This tissue fluid at the venous end picks up CO2 and other excretory products. Blood pressure, diffusion and osmosis are the forces involved in the movement of water and solutes IN and OUT of capillaries. Most fluid passes back into the capillaries but some drains into the lymphatic system and is returned to the blood later.

12. Lymph Lymph is the tissue fluid that drains into blind-ending lymphatic capillaries among the tissues that join up to form larger vessels. It is moved by contractions of muscles through which the vessels pass. Tissue fluid flows into them through tiny valves (which allow it to flow IN but not out). There are lymph glands and nodes associated with lymph vessels which play an important role in the making of lymphocytes. Lymph vessels transport the lymph back to the large veins which run just beneath the collarbone (subclavian veins).

13. The Role of Haemoglobin Oxygen Carriage Respiratory pigment such as haemoglobin have a high affinity for O2 when the concentration is high, but a low affinity when the concentration is low. When exposed to a gradual increase in oxygen partial pressure (oxygen tension) haemoglobin absorbs O2 rapidly at first but more slowly as the partial pressure increases further, [see Fig. 3, p.129 in text & graph on handout]. The release (offloading) of O2 is facilitated by the presence of CO2 – this called the Bohr Effect. • When the partial pressure of O2 is high (i.e. in lungs), it joins with haemoglobin to form oxyhaemoglobin • When the partial pressure of oxygen is low (i.e. in muscles), the O2 dissociates from the haemoglobin • When the partial pressure of CO2 is high, haemoglobin is less efficient at taking up (uploading) O2 and more efficient at releasing (offloading) it.

14. Partial Pressure (Oxygen Tension) • Partial Pressure is the pressure exerted by one gas in a mixture of gases. • Atmospheric pressure (at sea level) is about 100 kPa. • One fifth of the air is oxygen. So one fifth of atmospheric pressure is due to oxygen. • Therefore the PARTIAL PRESSURE OF OXYGEN is about 20 kPa. • (Partial pressure of oxygen can be written as ppO2) Some key values for ppO2 are: Atmospheric 20 kPa Alveolar 13 kPa And a typical value for blood flowing through tissues of the body: 5kPa

15. Review of Haemoglobin Structure • So to function efficiently, haemoglobin must attract oxygen under certain conditions, but lose it under other conditions. • Uploading/offloading is a reversible reaction, in which one haemoglobin (Hb) can attract up to 4 oxygen molecules: Hb + 4O2 HbO8 • Haemoglobin is a conjugated quaternary protein comprising: • two alpha-globulins • two beta-globulins • four haem groups, each with an iron atom at its core • It is the iron atoms which bind oxygen.

16. 100 100 In the upper part of the graph Hb is loaded with oxygen. 80 80 lungs 60 60 Saturation of blood with O2 (%) Saturation of blood with O2 (%) 40 40 In the lower part Hb is unloading its oxygen. 20 20 tissues 0 0 2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16 partial pressure of oxygen (kPa) partial pressure of oxygen (kPa) Oxygen dissociation curve OXYGEN DISSOCIATION CURVES are graphs which show the relationship between the ppO2 and the degree of haemoglobin saturation. What happens in the lungs and in the tissues?

17. 100 What happens to %saturation when there is a small change in ppO2 a) in the lungs? b) in the tissues? See how actively respiring tissues promote more O2 unloading. 80 60 Saturation of blood with O2 (%) 40 20 tissues lungs 0 2 4 6 8 10 12 14 16 partial pressure of oxygen (kPa) Effects of changes in ppO2

18. Carbon Dioxide Carriage The amount of oxygen haemoglobin carries is affected not only by the partial pressure of oxygen (ppO2) but also by the partial pressure of carbon dioxide (ppCO2). CO2 is transported in blood cells and plasma in 3 ways: 85% as hydrogencarbonate, 5% in solution in plasma and 10% in RBCs combined to haemoglobin as carbaminohaemoglobin. • CO2 diffuses into red cells where it becomes carbonic acid (H2CO3) – catalysed by carbonic anhydrase • This acid dissociates into protons (H+) and hydrogencarbonate ions (HCO3-) • HCO3- ions diffuse out of the cell & are transported in the plasma • Chloride ions (Cl-) diffuse inwards from plasma to maintain pH – the chloride shift • Protons left inside cell are mopped up by haemoglobin forming haemoglobinic acid (HHb). This forces the haemoglobin to release its O2 – hence the Bohr Shift. See Fig. 5, p.129 in text

19. CO2 reacting with water inside cells: carbonic anhydrase + H2O H2CO3 CO2 CO2 CO2 from respiring tissues enters the red blood cell and combines with water, forming carbonic acid. The reaction is accelerated by CARBONIC ANHYDRASE.

20. Dissociation of Carbonic acid: carbonic anhydrase CO2 CO2 + H2O H2CO3 HCO3- H+ Cl- Carbonic acid dissociates and HCO3- is transported out of the RBC, in exchange for Cl-. (This is the CHLORIDE SHIFT)

21. Offloading of O2 carbonic anhydrase CO2 CO2 + H2O H2CO3 HCO3- H+ Cl- HHb HbO2 O2 H+ displaces O2 from haemoglobin, forming HHb - reduced haemoglobin. The O2 is liberated to the tissues.

22. Explanation of Bohr Shift: carbonic anhydrase CO2 CO2 + H2O H2CO3 HCO3- H+ Cl- HHb HbO2 O2 The more CO2 , the greater the displacement of O2 from Hb. CO2 reduces the affinity of Hb for O2 . This explains the Bohr effect.

23. The release of CO2: it’s reversible! carbonic anhydrase H2CO3 CO2 CO2 + H2O HCO3- H+ Cl- HHb HbO2 O2 In the lung capillaries ppO2 is higher and ppCO2 is lower, so now O2 binds to Hb and this results in the release of CO2 Don’t worry - you don’t have to learn these reactions!

24. 100 80 If the black curve is ‘normal’, which curve represents the effect of elevated levels of carbon dioxide? 60 Saturation of blood with O2 (%) 40 20 0 2 4 6 8 10 12 14 16 partial pressure of oxygen (kPa) Questions If the black curve is human maternal haemoglobin, which curve represents foetal Hb?

25. 100 What happens to %saturation when there is a small change in ppO2 a) in the lungs? b) in the tissues? See how actively respiring tissues promote more O2 unloading. 80 60 Saturation of blood with O2 (%) 40 20 tissues lungs 0 2 4 6 8 10 12 14 16 partial pressure of oxygen (kPa) Shift to the right - the Bohr effect of higher ppCO2

26. Most oxygen is transported bound to haemoglobin, as oxyhaemoglobin • The oxygen saturation of haemoglobin is affected by: • ppO2 • ppCO2 • pH • temperature • CO2 is transported in three ways: • dissolved in plasma • bound to haemoglobin as carbamino-haemoglobin • converted to hydrogencarbonate ions in the red cells • High levels of CO2 facilitate O2 offloading from haemoglobin through the formation of hydrogen ions. The effect of increased CO2 / decreased pH on O2 offloading is called the Bohr effect. • High levels of O2 facilitate CO2 offloading from the blood. Summary

27. Problems with Oxygen Transport The efficient transport of oxygen around the body can be impaired by many different factors. We will focus on one particular problem, this is surviving athigh altitude. At sea level, the partial pressure of oxygen in the atmosphere is just over 20kPa, and the partial pressure of oxygen in the alveoli is around 13kPa. At altitudes of 6500 metres or above, the air pressure is much less, and the ppO2 is about 10kPa, dropping to 5.3kPa in the lungs. This results in haemoglobin becoming only about 75% saturated in the lungs – resulting in less oxygen being carried around the body. This can cause altitude sickness – where the sufferer begins to feel ill, dizzy, weak and short of breath. It can even be fatal! Luckily the body can adapt to gradual changes in altitude by producing more red blood cells and haemoglobin, (increasing from 40% or 50% up to 70%). However, this can take several weeks.

28. Questions: • Explain how an increase in the number of red blood cells can help to compensate for the lack of oxygen in the air at high altitudes • Athletes often prepare themselves for important competitions by spending several months training at high altitude. Explain how this could improve their performance Answers: • More RBCs = more haemoglobin greater oxygen carriage. Compensates for the lower saturation on haemoglobin in each cell. • Over the months their blood will produce more RBCs and haemoglobin, which will increase the amount of oxygen they can carry in their blood to their respiring muscle cells whilst exercising