Tijmen Lourens Summary Medical Physiology
Lecture 5:
There are 3 functions of the blood:
- Transport
- Coagulation
- Immune defence
o Important for the blood that it reaches all the tissues
In leukemia there is a much bigger buffy coat and less erythrocytes. It is harder to produce
erythrocytes.
Globulins are for the immune system, fibrogen is for coagulation. Serum has no fibrogen.
Cells in the blood are called corpuscular elements. They miss namely some components that
a ‘cell’ has. The elements do not last long (maybe months). Therefore you need to make a lot
more of these cells.
Production and degradation of the blood:
- All blood cells originate from the same stem cells!
- Differentiation in red bone marrow dependent on colony stimulating factors (CSFs)
o EPO (erythropoietin) is responsible for stimulating production of
erythrocytes.
▪ Is a drug that can improve performance, but too much results in slimy
blood because of the increased amount of red blood cells. The heart
has to pump harder to circulate this slimy blood.
Production of erythrocytes:
1) Stimulus: hypoxia (inadequate O2 delivery) due to:
a. Decreased RBC count
b. Decreased amount of hemoglobin
c. Decreased availability of O2
2) Kidney (and little bit liver) releases EPO
3) Erythropoietin
4) ???
From stem cell to erythrocyte:
- After EPO is released, the stem cell is transforming into an erythrocyte.
- One of the earliest phases: production of Hemoglobin starts → therefore you need
Fe2+ (iron). After a time the nucleus will be shedded.
- Vitamin B12, intrinsic factor and folic acid are required for RBC maturation! If you
miss those components in your diet you can feel tired.
,Tijmen Lourens Summary Medical Physiology
A red blood cell has no nucleus / mitochondria / ER / Golgi system. Its lifespan is around 120
days. Because of its flat biconcave shape, it is very good in squeezing itself through narrow
capillaries. Another function of this shape: it makes it very easy to transport gas which is the
main function of an erythrocyte! If the cell gets destructed, it is mostly due to membrane
rupture (haemolysis).
Hemoglobin:
- 4 globins with a hemegroup (tetramer of 4 proteins)
- Hemegroup is responsible for the colour of blood: bright-red (oxygenated) blue-red
(deoxygenated).
- Every heme group can bind to one molecule of oxygen!
CO intoxication results in a ‘cherry-red skin’. CO has high affinity for Hb (hemoglobin) and
prevents O2 binding as well as unloading.
- IF CO binds to only 2 hemoglobin molecules it already blocks 2 places, but it makes it
also more different for oxygen to bind to the other 2 hemoglobins proteins.
After a while (around 120 days) the membrane of erythrocytes becomes very fragile and will
tear apart. But what will happen to the hemoglobin?
- The 4 globin proteins will become amino acids.
- From the heme group: first the iron will be removed and transported in the blood
- The rest of the heme group will become bilirubin, which is picked up by the liver
o Bilirubin is then one time secreted into intestine in bile where it is
metabolized to stercobilin by bacteria
o This stercobilin is secreted in feces and responsible for the brown colour of
your feces.
▪ No stercobilin = white feces.
o Stercobilin is also taken up from the digestive tract and taken up in the blood
and excreted by kidney → makes the yellow colour of your urine.
Gas transport: take up O2 where abundant (lungs) and release where required (tissues).
- Almost all oxygen is bound to hemoglobin, but also there is O2 dissolved in blood.
There are two factors important to see how much oxygen is going from the air being
dissolved in the blood. Pressure of the oxygen molecules is here very important. Low
pressure → lot of oxygen still in the air. High pressure → much more dissolved in the blood.
The partial pressure of oxygen is important here. Solubility constant for oxygen is 0.03
while the constant for CO2 is 0.7. So CO2 much is better dissolved in the blood.
This means that in 100 ml blood there is 3 ml oxygen dissolved. But how much O2 is bound
to hemoglobin:
- HbO2 = Hb binding capacity x [Hb] x saturation Hb
,Tijmen Lourens Summary Medical Physiology
The higher the pO2, the higher the Hb is going to be. The curve Is not linear, in the beginning
the steepness is very low and after a while very steep, at the end low again (S-shaped line).
This is because of Hb’s properties (O2 binding strength changes with saturation.
When oxygen binds, the Hb molecule changes conformation → after this the Hb becomes
more accessible for even more oxygen. After a while all pockets are filled so it makes it more
difficult to bind any more oxygen. This S-shaped curve is biological great because a drop in
PO2 (from 100% to 80% for example) does not greatly reduce Hb affinity to O2. In this drop
in pressure the saturation of oxygen to hemoglobin only drops 2% or so.
But if the pressure is low already, in rest for example, there is a huge difference:
- In resting tissues, at a pO2 of 40 mmHg, HB is 75% saturation. So only 25%
- In metabolically active tissues, at a pO2 of 20 mmHG. the Hb is only 40% saturated –
an additional …
High PO2 (in alveoli): a drop in PO2 does not greatly reduce affinity to O2.
- Change in PO2 at sea level or in mountains does not have a great effect on saturation
while the pressure drops 20 (from 100 to 80).
Low PO2 (tissues): a drop in PO2 greatly reduces Hb affinity to O2.
- A change in resting state to exercise state does affect the saturation of Hb greatly in
tissues.
Bohr effect: less O2 bound to Hb when Temperature is increased, [CO2] increased, pH drops
and 2,3-BPG increased.
- Dissociation curve shifts to the right. (slide 27, 28)
Pressure over the lung wall = the pressure inside the lungs (alveoli) minus the pressure in
the pleural space. If we are not breathing, the pressure in the alveoli was zero and the
pressure in the pleural space was negative. This results in a positive pressure over the wall
which results in that the alveoli are pushed open. Transmural pressures are always
calculated by the pressure inside minus the pressure outside.
Anemia: decreased hemoglobin concentration in the blood: multiple causes:
- Blood loss (acute / chronic)
- Problems with synthesis
o Lack of certain compounds
▪ Iron
▪ Vitamin B12
▪ Folic acid
▪ EPO
- Disease
o Leukemia
- Increased degradation (hemolysis)
- Inherited
o Sickle cell anemia
, Tijmen Lourens Summary Medical Physiology
o Thalassemia
- Acquired
o Infections
o Mechanical destruction
o Chemical destruction
Sickle cell anemia and thalassemia:
- Are regional to certain parts of the world, sickle cell is advantageous
- Doctors can determine if somebody has anemia by volumes of RBC divided by the
amount of RBC. This determines how big the RBC are and how much they weight.
o If you have a problem in the differentiation process from stem cell to
erythrocyte you will have bigger RBC’s. This is because in the differentiation
process the cell only becomes smaller.
Smaller (microcytic) MCV < 80 → due to iron deficiency
Bigger (macrocytic) MCV > 100 → vitamin B12 and / or folic acid deficiency
Anemia does not (only hardly) affect saturation curve. But it does greatly affect HbO2. The
concentration Hb is affected!
Coagulation: wound healing / forming blood cloths
1) Vasoconstriction (less blood going to the wound / you lose less blood
2) Platelet plug formation
3) Fibrin formation (coagulation)
a. Fibrin forms a mesh that traps red blood cells and platelets, forming the clot
4) Fibrinolysis: clot degradation after healing of the wound
Glycoproteins on platelets repulses adherence to normal endothelium, yet induces
adherence to injured areas. You only want clot forming when there is a wound, otherwise
you have thrombosis. Blood clots also form when blood flows slowly → more likely for
platelets to stick together and form a clot. This prevents clot forming normally, but because
patients in hospital only lay in their bed the blood is flowing slower → huge risk for
thrombosis.
- Activated platelets enlarge and bind other platelets → which is positive feedback!
- Too much coagulation and/or too few fibrinolysis: thrombosis
- Too little coagulation and/or too much fibrinolysis: uncontrolled bleeding
- Blood thinners like heparin and warfarin can be given to prevent thrombosis in
patients.
Lecture 5:
There are 3 functions of the blood:
- Transport
- Coagulation
- Immune defence
o Important for the blood that it reaches all the tissues
In leukemia there is a much bigger buffy coat and less erythrocytes. It is harder to produce
erythrocytes.
Globulins are for the immune system, fibrogen is for coagulation. Serum has no fibrogen.
Cells in the blood are called corpuscular elements. They miss namely some components that
a ‘cell’ has. The elements do not last long (maybe months). Therefore you need to make a lot
more of these cells.
Production and degradation of the blood:
- All blood cells originate from the same stem cells!
- Differentiation in red bone marrow dependent on colony stimulating factors (CSFs)
o EPO (erythropoietin) is responsible for stimulating production of
erythrocytes.
▪ Is a drug that can improve performance, but too much results in slimy
blood because of the increased amount of red blood cells. The heart
has to pump harder to circulate this slimy blood.
Production of erythrocytes:
1) Stimulus: hypoxia (inadequate O2 delivery) due to:
a. Decreased RBC count
b. Decreased amount of hemoglobin
c. Decreased availability of O2
2) Kidney (and little bit liver) releases EPO
3) Erythropoietin
4) ???
From stem cell to erythrocyte:
- After EPO is released, the stem cell is transforming into an erythrocyte.
- One of the earliest phases: production of Hemoglobin starts → therefore you need
Fe2+ (iron). After a time the nucleus will be shedded.
- Vitamin B12, intrinsic factor and folic acid are required for RBC maturation! If you
miss those components in your diet you can feel tired.
,Tijmen Lourens Summary Medical Physiology
A red blood cell has no nucleus / mitochondria / ER / Golgi system. Its lifespan is around 120
days. Because of its flat biconcave shape, it is very good in squeezing itself through narrow
capillaries. Another function of this shape: it makes it very easy to transport gas which is the
main function of an erythrocyte! If the cell gets destructed, it is mostly due to membrane
rupture (haemolysis).
Hemoglobin:
- 4 globins with a hemegroup (tetramer of 4 proteins)
- Hemegroup is responsible for the colour of blood: bright-red (oxygenated) blue-red
(deoxygenated).
- Every heme group can bind to one molecule of oxygen!
CO intoxication results in a ‘cherry-red skin’. CO has high affinity for Hb (hemoglobin) and
prevents O2 binding as well as unloading.
- IF CO binds to only 2 hemoglobin molecules it already blocks 2 places, but it makes it
also more different for oxygen to bind to the other 2 hemoglobins proteins.
After a while (around 120 days) the membrane of erythrocytes becomes very fragile and will
tear apart. But what will happen to the hemoglobin?
- The 4 globin proteins will become amino acids.
- From the heme group: first the iron will be removed and transported in the blood
- The rest of the heme group will become bilirubin, which is picked up by the liver
o Bilirubin is then one time secreted into intestine in bile where it is
metabolized to stercobilin by bacteria
o This stercobilin is secreted in feces and responsible for the brown colour of
your feces.
▪ No stercobilin = white feces.
o Stercobilin is also taken up from the digestive tract and taken up in the blood
and excreted by kidney → makes the yellow colour of your urine.
Gas transport: take up O2 where abundant (lungs) and release where required (tissues).
- Almost all oxygen is bound to hemoglobin, but also there is O2 dissolved in blood.
There are two factors important to see how much oxygen is going from the air being
dissolved in the blood. Pressure of the oxygen molecules is here very important. Low
pressure → lot of oxygen still in the air. High pressure → much more dissolved in the blood.
The partial pressure of oxygen is important here. Solubility constant for oxygen is 0.03
while the constant for CO2 is 0.7. So CO2 much is better dissolved in the blood.
This means that in 100 ml blood there is 3 ml oxygen dissolved. But how much O2 is bound
to hemoglobin:
- HbO2 = Hb binding capacity x [Hb] x saturation Hb
,Tijmen Lourens Summary Medical Physiology
The higher the pO2, the higher the Hb is going to be. The curve Is not linear, in the beginning
the steepness is very low and after a while very steep, at the end low again (S-shaped line).
This is because of Hb’s properties (O2 binding strength changes with saturation.
When oxygen binds, the Hb molecule changes conformation → after this the Hb becomes
more accessible for even more oxygen. After a while all pockets are filled so it makes it more
difficult to bind any more oxygen. This S-shaped curve is biological great because a drop in
PO2 (from 100% to 80% for example) does not greatly reduce Hb affinity to O2. In this drop
in pressure the saturation of oxygen to hemoglobin only drops 2% or so.
But if the pressure is low already, in rest for example, there is a huge difference:
- In resting tissues, at a pO2 of 40 mmHg, HB is 75% saturation. So only 25%
- In metabolically active tissues, at a pO2 of 20 mmHG. the Hb is only 40% saturated –
an additional …
High PO2 (in alveoli): a drop in PO2 does not greatly reduce affinity to O2.
- Change in PO2 at sea level or in mountains does not have a great effect on saturation
while the pressure drops 20 (from 100 to 80).
Low PO2 (tissues): a drop in PO2 greatly reduces Hb affinity to O2.
- A change in resting state to exercise state does affect the saturation of Hb greatly in
tissues.
Bohr effect: less O2 bound to Hb when Temperature is increased, [CO2] increased, pH drops
and 2,3-BPG increased.
- Dissociation curve shifts to the right. (slide 27, 28)
Pressure over the lung wall = the pressure inside the lungs (alveoli) minus the pressure in
the pleural space. If we are not breathing, the pressure in the alveoli was zero and the
pressure in the pleural space was negative. This results in a positive pressure over the wall
which results in that the alveoli are pushed open. Transmural pressures are always
calculated by the pressure inside minus the pressure outside.
Anemia: decreased hemoglobin concentration in the blood: multiple causes:
- Blood loss (acute / chronic)
- Problems with synthesis
o Lack of certain compounds
▪ Iron
▪ Vitamin B12
▪ Folic acid
▪ EPO
- Disease
o Leukemia
- Increased degradation (hemolysis)
- Inherited
o Sickle cell anemia
, Tijmen Lourens Summary Medical Physiology
o Thalassemia
- Acquired
o Infections
o Mechanical destruction
o Chemical destruction
Sickle cell anemia and thalassemia:
- Are regional to certain parts of the world, sickle cell is advantageous
- Doctors can determine if somebody has anemia by volumes of RBC divided by the
amount of RBC. This determines how big the RBC are and how much they weight.
o If you have a problem in the differentiation process from stem cell to
erythrocyte you will have bigger RBC’s. This is because in the differentiation
process the cell only becomes smaller.
Smaller (microcytic) MCV < 80 → due to iron deficiency
Bigger (macrocytic) MCV > 100 → vitamin B12 and / or folic acid deficiency
Anemia does not (only hardly) affect saturation curve. But it does greatly affect HbO2. The
concentration Hb is affected!
Coagulation: wound healing / forming blood cloths
1) Vasoconstriction (less blood going to the wound / you lose less blood
2) Platelet plug formation
3) Fibrin formation (coagulation)
a. Fibrin forms a mesh that traps red blood cells and platelets, forming the clot
4) Fibrinolysis: clot degradation after healing of the wound
Glycoproteins on platelets repulses adherence to normal endothelium, yet induces
adherence to injured areas. You only want clot forming when there is a wound, otherwise
you have thrombosis. Blood clots also form when blood flows slowly → more likely for
platelets to stick together and form a clot. This prevents clot forming normally, but because
patients in hospital only lay in their bed the blood is flowing slower → huge risk for
thrombosis.
- Activated platelets enlarge and bind other platelets → which is positive feedback!
- Too much coagulation and/or too few fibrinolysis: thrombosis
- Too little coagulation and/or too much fibrinolysis: uncontrolled bleeding
- Blood thinners like heparin and warfarin can be given to prevent thrombosis in
patients.
