You know, on the endothelial cells, what are these?
Endothelial cells of pulmonary capillary beds.
On the endothelial cells there is a unique enzyme expressed.
This enzyme is expressed on the surface of endothelial cells.
That is why this enzyme is called "Ectoenzyme".
Because this is not intracellular enzyme, this enzyme is expressed on the surface of
endothelial cells.
Right?
Not released into blood.
But now they believe that not only pulmonary capillaries have capacity to convert angiotensin
I into angiotensin II, even some other capillary beds can also do this function, but for your
level you just remember that in pulmonary capillary endothelial lining, they are expressing
enzyme called.
What is the name of these enzymes?
You know they are very angry because you don't remember where they are.
Look at their expression!
Right?
These are which enzymes?
Angiotensin converting enzyme!
What they are doing?
Actually, they are responsible to convert angiotensin I into angiotensin II.
This is the function of these enzymes.
This is the function of these enzymes which are called "angiotensin converting enzymes".
That they convert angiotensin I into angiotensin II.
When we talk about the drugs like captopril, enalapril, lisinopril or other angiotensin
converting enzyme inhibitors, those drugs basically bind with these proteins and block
their function.
When we say there are whole group of drugs called "angiotensin converting enzyme inhibitors".
What is the function of those drugs?
These drugs basically bind with these enzymes and blocking their action.
Every doctor knows that these enzymes are converting angiotensin I into angiotensin
II but some good doctors know they also do one more function.
What is the second function of these enzymes?
There is another product in the blood which is called "Bradykinen".There is another product
in the blood which is called Bradykinen.
Bradykinen is broken down by these enzymes, Bradykinen you know look at it, because it
is "inactivated".
Bradykinen inactivation.
Inactivation.
Bradykinen is vasodilator and angiotensin II is vasoconstrictor.
So what is the function of this enzyme?
These enzymes break down the vasodilators and produce vasoconstrictors.
Of course when blood vessels will constrict, blood pressure will go up.
Am i clear?
Now!
So, again lets recap up to this.
Patient was actively bleeding.
Right?
It will take some time, Renal perfusion is reduced.
Then angio.... your what is this?
Blood pressure sensitive cells release renin + Macula Densa senses low sodium coming here,
a sign of low GFR that also forces these cells to release renin.
Moreover falling blood pressure activates the sympathetic outflow and sympathetic fibers
coming to the juxtaglomerular apparatus results in further release of renin.
This renin is an enzyme which comes into general circulation and break down the angiotensinogin
into angiotensin I and when angiotensin I is passing through the, mainly, when it is
passing through the pulmonary circulation then angiotensin converting enzymes which
are normally expressed on the endothelial cells of the pulmonary circulation, they convert
angiotensin I into angiotensin II.
So they produce very powerful vasoconstrictors and of course these enzymes are very active
very intelligent, while they are producing vasoconstrictors they don't forget to inactivate
the vasodilators like Bradykinen.
Now we have the angiotensin II in our circulation.
Now we have to see what angiotensin II will do in the body.
What it should do?
It should bring the blood pressure up and the blood volume up.
That was the problem right?
So now we see how angiotensin II is going to achieve its function.
Lets come to the actions of angiotensin II.
First we will talk about the classical action.
No 1: Angiotensin II, Ok, I will draw here circulatory system in a little detail, the
left heart and these are the arterioles.
From the aorta, these are the arterioles, and here is your right heart, this is the
venous system, and of course in between these arterio venous system there are, what are
these?
Capillary beds!
I hope you remember.
Blood comes from arterial side, passes through the capillary beds and than it is drained
to the venous side.
Right?
This is right heart and that is left heart and of course you will not forget to draw
that there must be lung over there, that this is your pulmonary circulation, and blood gets
oxygenated over there and then it comes to the left atrium and of course here is your,
what is this?
Air spaces.
Clear?
Now we will see first of all what is the action of angiotensin II on this system?
Because pressure and volume is falling into this system.
First of all, angiotensin II has receptors on the arteriolar smooth muscle, what are
these?
Arteriolar smooth muscle.
Angiotensin II receptors are present on arteriolar smooth muscle + angiotensin II receptors are
also present on the veinular smooth muscle, so they are also present over here.
Right?
Now what really happens?
No 1: Angiotensin II will work on, what is this?
Venous smooth muscle.
When angiotensin II acts on the angiotensin II receptors on venous smooth muscles, veins
constrict.
When veins will constrict can blood remain pooled into veins?
No.
Most of our blood is, normally present in the veins, veins contain about 70% of the
total blood volume, that is why we call them the vascular component with highest capacity
or simply veins are called "capacitance vessels".
So angiotensin II will constrict the veins, when veins are squeezing, pressure in veins
will go up and blood will rush towards, where?
where the blood is going?
To the heart and then to the eventually left heart.
So under venoconstriction blood going to the left heart is less or more?
When you squeeze the veins venous return to the heart is increased.
Now listen, when blood flow increases to the left heart, it means cardiac filling is more.
So venous return is...venoconstriction lead to increased venous return, that lead to increased
cardiac filling.
Increased cardiac filling leads to increased end diastolic volume and increased end diastolic
pressure.
At the end of the diastole volume and pressure is more in the ventricle.
So ventricle is stretched, and according to frank starling law, the more you stretch the
ventricle the more it contracts.
Frank starling law states that within physiological limits more you stretch the myocardial cells
more they contract.
Of course within physiological limits.
Don't rupture them.
Right?
Now.
So, whenever venous return is more, end diastolic volume is more, we say that preload on the
heart is more and whenever preload on the heart is more, preload is the amount of blood
in the ventricle on which it has to produce contraction.
Is that right?
So, whenever there is more blood accumulated here, more it is stretched, more it contracts,
so stroke volume will become more.
So that will lead to increased stroke volume.
That will lead to increased stroke volume and of course when stroke volume is more than
what is there increased cardiac output.
When there is increased cardiac output that will lead to increase in systolic blood pressure.
That is the point we wanted to reach!
You know our systolic blood pressure was falling, as well as diastolic blood pressure was falling.
When your bleeding was going on, for example bleeding was from here so blood pressure was
falling.
So by venoconstriction and increasing the venous return to the heart and increasing
the end diastolic volume and of course increasing the contractility and increasing the stroke
volume resulting into increased cardiac output eventually increases systolic blood pressure
because systolic blood pressure mainly depends on cardiac output.
Am I clear?
During the systole blood pressure will go up.
Meanwhile angiotensin II will also work on, what is this?
Arterial smooth muscle and arterioles will constrict.