Mammalian Transport System

Part II

Venous return flow

• Unidirectional flow• How achieved??• Muscular Pump• activity of skeletal muscle that

surrounds veins. The contraction and relaxation of muscles surrounding deep veins helps to push blood upwards. Valves (semilunar) prevent the return of blood in the other direction, keep blood going flow towards the heart.

Return flow problems

• People who stand still for a long time faint because of venous return to the heart.

• People who stand for a long time swelled legs and ankles because blood is collecting and there is no skeletal muscle activity leads to varicose veins.

Breathing (Respiratory Pump)

• As thoracic volume increases, pressure inside the thorax decreases. This decreases the pressure in the blood vessels of the thorax. The effect is very small in the arteries but more significant in the veins.

P

P

Breathing (Respiratory Pump)

• The relatively low pressure of the blood in the veins in the thorax, compared with the pressure in veins elsewhere in the body, produces a pressure difference causing blood movement towards the thorax.

• When we exhale blood will not go back away from the heart because of the semilunar valves.

P

P

Cardiac Suction

• When the ventricle contract they move down and blood is pushed out.

• Because the great vessels hold the heart in place This draws blood into the atria, stretching its walls and decreasing the atrial pressure.

Blood pressures throughout the system

• Arteries – 90-120• Arterioles – 70-90• Capillaries – 30-10• Veins- 5• Pulmonary arteries – 20-25• Pulmonary veins – 5

Blood plasma and tissue fluid

• Blood plasma – mostly water, pale yellow liquid, dissolved materials; nutrients (glucose), waste products (urea), and plasma proteins

• Tissue fluid – 1/6 of your body consists of spaces between cells, this space is filled with plasma that leaks between cells of the capillary cell wall.

Tissue Fluid

• - similar in composition to plasma, fewer protein molecules (too large to seep through the spaces in the endothelium), no RBCs (also too large), some WBCs can squeeze through

blood pressure vs osmotic pressure

• blood pressure – on the arterial end of the capillary bed, blood pressure is enough to push fluid out into the tissue.

blood pressure vs osmotic pressure

• Osmotic pressure – tissue fluids lack the high concentration of proteins (solutes), there is an imbalance in osmotic pressure and water tends to move back into the capillaries.

• Competing processes – overall net result – tissue fluid flows out at the arterial end of the capillary bed and into the capillaries at the venous end of the bed, no net loss

Homeostasis

• maintenance of a constant internal environment, including regulation of glucose concentrations, water, pH, metabolic wastes, and temperature.

Lymph

• 90 % of the fluid that leaks from capillaries eventually seeps back into them

• 10% is collected and returned to the blood system by a series of tubes known as lymph vessels or lymphatics

• lymph vessels or lymphatics – found in almost all tissues, tissue fluid can flow into the vessels through tiny valves but not out

Lymph

• valves are large enough for large proteins to enter the lymph system, unable to enter capillaries

• if lymphatics were unable to remove protein in tissue fluid, you could die within 24 hrs.

Lymph• oedema – imbalance in the protein concentration

and rate of loss from plasma compared to the concentration and rate of loss from tissue fluid.

• Lymph – fluid inside lymphatics, virtually identical to tissue fluids but has a different name because of its origin

• Lymph in different organs; tissue fluid and lymph in the liver have high concentrations of protein, tissue fluid and lymph in the walls of the small intestine have high concentrations of lipids, found in each villi as they absorb lipids after a meal

Kwashiorkor• Kwashiorkor is a condition

resulting from inadequate protein intake.

• Early symptoms include fatigue, irritability, and lethargy.

• As protein deprivation continues, one sees growth failure, loss of muscle mass, generalized swelling (edema), and decreased immunity.

• A large, protuberant belly is common.

• The incidence of kwashiorkor in children in the U.S. is extremely small and it is typically found in countries where there is drought and famine.

Lymphatics

• Lymphatics join together to form lymph vessels which transport the lymph back to the veins which run just beneath the collar bone, the subclavian veins.

• Movement of the fluid in lymphatics is largely caused by muscle contraction and valves keep it going in the right direction

• Lymph vessels have smooth muscle which can contract to push lymph along

Lymph flow

• Lymph flow through the largest vessel, the thoracic duct is very slow, about 100 cm3 per hour compared to the rate of blood flow, about 80 cm3 per second.

• Lymph nodes – involved in the protection against disease, bacteria and other unwanted particles are removed from lymph by some types of WBCs as the lymph passes through a node, while other WBCs secrete antibodies.

Blood

• 5 dm3 in the body• Weighing 5 kg• 2.5 x 1013 RBCs

(25,000,000,000,000)• 5 x 1011 WBCs (500,000,000,000)• 6 x 1012 platelets (6,000,000,000,000)

Red Blood Cells (RBCs)

• erythrocytes – red in color because of the globular protein pigment hemoglobin

• hemoglobin functions in oxygen transport• first RBCs form in the fetal liver but by

birth, the RBCs are formed in bone marrow, first in the long bones, humerus and femur, then in the skull, ribs, pelvis, and vertebrae

Red Blood Cells

• RBCs do not live long, membranes become more and more fragile, eventually rupture within some “right spot”, often the spleen

• RBCs are very small – 7 um• Average liver cell 40 um• Smallness ensures that hemoglobin is

close to the cell membrane and gas exchange can occur quickly

RBCs

• Capillaries can be as small as 7 um and still allow RBCs to squeeze through

• RBCs are shaped like a biconcave disc – dent increases the amount of surface area to volume ratio again accounting for rapid oxygen diffusion

• RBCs have no nucleus, no mitochondria, and no endoplasmic reticulum, maximizing the room for hemoglobin and its oxygen carrying potential

White Blood Cells (WBCs)

• Leucocytes – are made in the bone marrow

• Have a nucleus, most are larger then RBCs (lymphocytes may be smaller)

• Spherical or irregularly shaped

White Blood Cells (WBCs)

• Many different types and functions:• phagocytes – destroy invading

microorganisms, identifiable by lobed nucleus and granular cytoplasm

• lymphocytes – also destroy microorganisms but not by phagocytosis, they secrete antibodies which attach to and destroy the invading cells, large round nucleus with only a small amount of cytoplasm, different types of lymphocytes

Hemoglobin

Hemoglobin

• Hb + 4 O2 -> Hb O8

• 1 dm3 of blood carries about 150 g of hemoglobin (1 dm3 = 1000 cm3)

• 1 g of hemoglobin can combine with 1.3 cm3 of oxygen at normal body temperature of 37oC

Hemoglobin SAQs

• SAQ 8.12 a - if 1 dm3 of blood carries about 150 g of hemoglobin, then it would be 150 x 1.3 cm3 = 195 cm3

• SAQ 8.12 b – if 1 cm3 of water carries 0.025 cm3 of oxygen, and blood plasma is mostly water, then 1 dm3 (1000 cm3) of blood without hemoglobin could carry 1000 x 0.025 cm3 = 25 cm3

Hemoglobin dissociation curve

• in a muscle, the partial pressure is low and the hemoglobin will be about 20-25% saturated

• as hemoglobin reaches a muscle it releases about 75% of its oxygen that diffuses out of the RBC into the muscle where it is used for respiration

Hemoglobin dissociation curve

• saturated hemoglobin – has combined with the maximum amount of oxygen

• partial pressure of oxygen – at high partial pressures of oxygen, the percentage saturation of hemoglobin is very high, at low partial pressures the percentage saturation is very low

• at the capillary in the lungs the partial pressure is high and the hemoglobin is 95-97% saturated with oxygen

Hemoglobin dissociation curve

problems• SAQ 8.13 a (i) - partial pressure of

oxygen in the alveoli is about 12 kPa, this reflects about 96.5% saturation

• SAQ 8.13 a (ii) - if 1 g fully saturated hemoglobin can combine with 1.3 cm3 of oxygen, then in the capillaries of the lung where the partial pressure is 12 kPa representing 96.5% saturation, 96.5% of 1.3 cm3 is 1.25 cm3

Hemoglobin dissociation curve

problems• SAQ 8.13 b (i) – muscle partial pressure

is about 2 kPa which represents about 24% saturation

• SAQ 8.13 b (ii) - if 1 g fully saturated hemoglobin can combine with 1.3 cm3 of oxygen, then in the capillaries of the muscle where the partial pressure is 2 kPa representing 24% saturation, 24% of 1.3 cm3 is 0.31 cm3

The S-shaped Curve

• when one oxygen molecule combines with one haem group, the hemoglobin molecule is distorted

• this distortion makes it easier for a second oxygen to combine with the second haem group,

• then easier for the third and easier for the fourth

• the shape of the hemoglobin dissociation curve explains this behavior

The S-shaped Curve

• up to a partial pressure of 2 kPa, on average only one oxygen molecule is combine with each hemoglobin

• once this molecule is combined it becomes successively easier for the second , then the third, etc. molecules to combine

• thus the curve rises very steeply, a small change in partial pressure can cause a large change in the amount of oxygen carried

The Bohr Shift

• carbon dioxide continually produced by respiring cells, diffuses from the cells, into the blood plasma, and some into the cytoplasm of the RBCs

• carbonic anhydrase – an enzyme in the cytoplasm of RBCs catalyzes the reaction of carbon dioxide and water forming carbon acid

The Bohr Shift

• CO2 + H2O -> H2CO3

• (catalyzed by carbonic anhydrase)• The carbonic acid quickly dissociated

forming hydrogen and hydrogencarbonate ions

• H2CO3 <-> H+ + HCO3-

• Hemoglobin readily combines with these hydrogen ions forming hemoglobinic acid, HHb, in doing so it releases the oxygen which it was carrying

Bohr Shift Net Results

• hemoglobin removes the hydrogen ions formed when carbon dioxide dissolves and dissociates

• high concentration of hydrogen ions means a low pH which would make the blood acidic, removing them helps maintain the pH of the blood close to neutral, it acts as a buffer

Bohr Shift Net Results

• high partial pressure of carbon dioxide (caused by respiring cells) causes the hemoglobin to release oxygen which is exactly what the respiring cells need – i.e. the Bohr effect

• the dissociation curve for hemoglobin would shift to the right if high partial pressure of carbon dioxide because the hemoglobin would release oxygen instead of carrying more

Carbon dioxide transport

• The hydrogencarbonate ions, HCO3-,

formed in the RBCs where the enzyme carbonic anhydrase is found, diffuse out of the RBCs into the blood plasma where it is carried in solution, 85% of carbon dioxide is transported by the blood in this manner

Carbon dioxide transport

• Some carbon dioxide does not dissociate but remains carbon dioxide, about 5%

• About 10% of the carbon dioxide diffuses into the RBCs but combine directly with the terminal amine group (-NH2) of some of the hemoglobin molecules forming a compound carbamino-hemoglobin

Carbon dioxide transport• When the blood reaches the lungs the

reactions go in reverse, since the carbon dioxide levels in the lung alveoli are low, the carbon dioxide diffuses from the blood into the air in the alveoli, stimulating the carbon dioxide of the carbamino-hemoglobin to leave the RBC

• the hydrogencarbonate and hydrogen ions recombine to form carbon dioxide,

• this leaves the hemoglobin molecules free to combine with oxygen again

Fetal hemoglobin

• the developing fetus obtains its oxygen from its mother’s blood

• in the placenta, the mother’s blood is brought very close to that of the fetus allowing diffusion of various substances from mother to fetus and vice versa

Fetal hemoglobin

• the partial pressure of oxygen in the blood vessels in the placenta is relatively low, the partial pressure of oxygen in the fetus’s blood is only a little lower than that in its mother’s blood

Fetal hemoglobin

• the fetal hemoglobin is different from its mother’s hemoglobin and has a greater affinity and will pick the oxygen the mother’s hemoglobin dropped

• the dissociation curve for fetal hemoglobin shows it is slightly more saturated than adult hemoglobin

Fetal hemoglobin

• This greater affinity for oxygen is explained by fetal hemoglobin's interaction with 2,3-bisphosphoglycerate (2,3-BPG or 2,3-DPG). In adult red blood cells, this substance decreases the affinity of hemoglobin for oxygen.

• It is also present in fetal red blood cells, but does not interact with fetal hemoglobin, leaving its affinity for oxygen unchanged.

• Adult hemoglobin alone actually has a higher affinity for oxygen than its fetal equivalent, but the levels of 2,3-BPG reduce it.

Myoglobin

• a red pigment which combines reversibly with oxygen

• not found in blood• found inside cells in some tissues of the

body, i.e muscle• each myoglobin is made of only one

polypeptide, one heme group which can combine with one oxygen molecule

Myoglobin

• very stable, and will not release its oxygen unless the partial pressure around it is very low

• acts as an oxygen store

Myoglobin

• myoglobin will not release its oxygen unless the oxygen concentration in the muscle drops very low, i.e. the muscle is using up oxygen at a faster rate than the hemoglobin in the blood can supply it

Problems with oxygen transport

Carbon monoxide

• hemoglobin combines readily and almost irreversibly with CO

• CO readily diffuses across the walls of the alveoli, into the blood, into the RBCs

• enters the RBCs and forms carboxyhemoglobin

• CO combines with hemoglobin 250 times more readily than it does with oxygen

Carbon monoxide

• Carboxyhemoglobin is very stable and remains combined with hemoglobin for a long time

• Co asphyxiation can occur in CO concentrations of as low as 0.1% of the air

• CO asphyxiation, the body appears blue to gray from lack of oxygen binding

Carbon monoxide

• Treatment – a mixture of pure oxygen and carbon dioxide

• - oxygen to bind with the hemoglobin• - carbon dioxide to stimulate breathing• Cigarette smoke can contain up to 5% CO• 5% of hemoglobin in a regular smoker is

permanently combined with CO, this reduces the ability to carry oxygen

High altitude

• Partial pressure of oxygen at sea level is about 20 kPa

• in alveoli of lungs, 13 kPa (97% saturation)

• at 6500m (21,000 ft), 10 kPa in the air, and only 5.3kPa in the lungs resulting in only 70% saturation)

High altitude

• carrying less oxygen the person feels breathless and ill – altitude sickness

• altitude sickness symptoms –increase in heart rate, increase in depth of breathing, feeling of dizziness, and weakness

• arterioles in the brain dilate, increasing the amount of blood flowing into the capillaries

High altitude

• carrying less oxygen the person feels breathless and ill – altitude sickness

• altitude sickness symptoms – – increase in heart rate, increase in depth of

breathing, feeling of dizziness, and weakness

– arterioles in the brain dilate, increasing the amount of blood flowing into the capillaries

High altitude sickness

• fluid leaks into the surrounding brain tissue

• can cause disorientation

• fluid can leak into the lung tissue preventing proper function

• acute altitude sickness can be fatal

High altitude acclimatization

• acclimatizing (adjustments) for people at high altitude

• - increase in the number of red blood cells from 40-50% of he blood to 50-70% (would require 2-3 weeks at high altitude)

High altitude acclimatization

• People that live permanently at high altitude have adaptations for the low oxygen environment

• - large broad chests• - large lung capacity• - larger heart, especially the right side that

pumps to the lungs• - more hemoglobin in the blood, that

increases the efficiency of oxygen transport