- polyarteritis nodosa. this is a medium vessel vasculitis that affects many arteries. and so, if we break it down,we can see poly means many, arter refers to the arteries,and itis is inflammation, just like any vasculitisyou see some inflammation, and nodosa means nodular. so, when you break thisname down, we see that many arteries haveinflammation and are nodular.
so, why is it nodular? well, to understand that,let's draw out a blood vessel. remember that bloodvessels are like pipes. they carry blood and distributenutrients throughout the body. and so, here i'm shading inthe wall of the blood vessel, and in the back, i'm kind of drawing this little circular appearance. i'm trying to show you it'sa little bit of a 3d drawing. so, imagine you take a cross section
through the blood vessel,right down the middle. so, you can see that blood and nutrients would travel down this blood vessel. so, remember with vasculitis the body is mistaking the blood vessels to be a foreign proteinor something foreign, and so antibodies,little y-shaped proteins that are released by the immune system, are targeting the blood vessel wall,
because they think it's foreign. remember, antibodies actas markers to draw in white blood cells to causesome damage to the area, because these white bloodcells release molecules that are very destructive. the intent is to kill pathogens, but here you're accidentallykilling the blood vessels. and so, one theory asto why the antibodies are accidentally targeting blood vessels
is the theory of molecularmimicry, molecular mimicry. what is molecular mimicry? well, it's the theorythat foreign proteins, such as bacteria, viruses,or really anything bad, any pathogen that gets in your body, are recognized by the immune system. the immune system, of course,creates these antibodies to target these bad foreign proteins. and so, this is good.
this is what antibodies are used for. they're supposed totarget foreign proteins, to mark them for destructionfor white blood cells, but in the process of recognizingthese foreign proteins, many antibodies are created. so now the immune system is ramping up to find and seek outthese foreign proteins if they ever appear again. now the idea of molecular mimicry
is that there are self proteins, such as maybe proteins fromthe blood vessel walls, that look identical to foreign proteins. now, i know i've drawn themas little circles here, but let's say that they're identical, and these antibodies that were created in response to these foreign proteins now also are recognizing self proteins, because the self looks very similar
to these foreign proteins. this is the core of molecular mimicry. in polyarteritis nodosa, hepatitis b is actually found in about20 to 30% of patients, so it's believed that maybe hepatitis b, the proteins that are in this virus, can cause a molecular mimicry and look very identical to self, and so these foreign hepatitis b molecules
look like self and induce this entire autoimmune destruction of blood vessels. and so, that's why i make thispoint of molecular mimicry. now, in polyarteritis nodosa,again white blood cells release all these immune peptides and cause destruction ofthe blood vessel wall. damage to the wall causes molecules like collagen and tissue factor, which are normally not exposed to blood,
to be released, and when they're released, they interact with clottingfactors in the blood, such as fibrin. fibrin reacts with the stuff inthe wall of the blood vessels and creates a net-like mesh. this net-like mesh is a clot. so, fibrin is integral in clot formation. another word you might hearfor clot is thrombosis. thrombosis is the formation of clots.
and so, along with this acute inflammation and clot formation, you can also have oldwounds in blood vessels, where the fibrin has alreadytried to patch up the wall. now, this wall right here is very weak, and so the vessels go through this damage over and over again, and the blood vesselwall continues to weaken. now blood vessels, obviously,are just like pipes,
and they're used tocarry blood downstream. if red blood cells, or any other contents, hit the wall of the blood vessel, they're supposed to bounce off and just continue on their merry way. but the problem here is witha weakened blood vessel, when red blood cells push against this, the wall is so weak that it bulges out. this bulging of the blood vesselwall is called an aneurysm.
it's a weakened part ofthe wall that bulges out from the pressure on theinside of the blood vessel. and lastly, if the bloodvessel wall weakens so much and receives way too much pressure, it can rupture, and thisallows blood to spill out of the blood vessel. in medium size blood vessels, rupture of this cancause a lot of bleeding, and so rupture is a feared complication
of polyarteritis nodosa. now, if you were to take aslice of this blood vessel wall and take a look at it under a microscope, you'd be taking a biopsy. that's what a biopsy is, a slice of tissue that you take a lookat under a microscope. and so, in polyarteritis nodosa, we see this fibrinoid necrosis. there are fibrin clots inthe wall of blood vessels
and a lot of debris in theretoo and cells that are dead. and so, you go through fibrinoid necrosis, and the blood vessels alsogo through some scarring, so it's an attempt to try to heal. once the scar is finished, once the blood vessel has been patched up, this is the process of healing, and so you continue togo through this cycle over and over and over again,
and this continuous processwill cause weakening of the blood vessel walls, and i make this pointbecause the weakening can get very severe, and theblood vessels will bulge out, just like i was showing above. these aneurysms appear allthroughout the blood vessel and give its classic appearance. so, this blood vessel wall bulge, blood vessel wall bulge,blood vessel wall bulge
is noted to look likea string full of beads, and this is actually a classic appearance of polyarteritis nodosa, thisbeads on a string pattern. this pattern can beseen under a microscope, and it can also be seen when you take a look at an arteriogram. this picture right here isan arteriogram of the kidney. here's the kidney right here. kidneys kind of look likea kidney bean, right?
and so, here's blood vesselsthat are going through, passing into the kidney,and if you look closely at the blood vessels,you can see some of these little dots that are in the blood vessels. these are the nodes. this is the nodularity. there's some here. there's one right there. there's one over here.
and this isn't very prominent. this arteriogram righthere, which allows you to visualize the insideof the blood vessels, can actually show very severe aneurysms, very severe bulging ofthe blood vessel walls. and so, i'm exaggerating and showing these little black circles, and just like our beadson a string drawing above, you might see nodularity ofthe blood vessels like that,
looking like a bead on a string pattern. and so, polyarteritis nodosais infamous for causing a lot of damage to manydifferent medium blood vessels all over the place, bloodvessels in your intestines, blood vessels in the spleen,blood vessels in the kidneys, blood vessels of theskin, and it can actually commonly be in the legs as well, even blood vessels serving the nerves or the genitals or the heart.
as you can guess, this causesa wide variety of symptoms. not only will you getyour generalized symptoms, such as fever, chills, and night sweats, just like any other vasculitis, but also you're gettinglocal damage of organs. so, damage in the intestinesmay lead to bloody diarrhea. damage to blood vesselssupplying the skin may give you a sort of rash appearanceand other skin lesions. these ulcers are formed because blood
isn't supplying the skin as it should. blood not supplying the heartcan lead to heart attacks. the heart muscle won't contract anymore. if nerves don't get blood, you may see something called neuropathy. neuropathy means neuralpain or neural issues, and so you might not be ableto move the foot as well, if the nerves supplyingyour foot is damaged, or you may feel a tingling sensation
or decreased sensations in the foot. lastly, i wanted to touch on the kidneys. when the kidneys receivevery low blood volume, because remember, thesearteries are being damaged and maybe on the inside it's very narrow, and so blood can't bedelivered to the kidney tissue, when the kidney sensesdecreased blood volume, it thinks, oh, i needto increase pressure, and so, its sensation oflow blood volume makes it
go through therenin-aldosterone-angiotensin system. this system is the kidneys wayto hold onto water and fluid, and so you get an increasein blood pressure. this increase in bloodpressure, of course, is also known as hypertension. now, how do you remember all of this? there's so many differentvessels that are damaged. among all the arteries that are damaged, pulmonary arteries, bloodvessels supplying the lungs,
are not damaged. we actually don't knowwhy this is the case, but this ends up being agreat mnemonic for you, to help you remember this. polyarteritis nodosa, pulmonaryarteries are not damaged. and treatment is done withtwo different medications. steroids. steroids inhibit the abilityfor white blood cells to communicate withother white blood cells.
so, for example, here's apart of the blood vessel wall, and let's say this white blood cell wants to cause damage to this wall. it'll also recruit its buddies by sending these molecules to communicate and say, hey, come on over here. however, steroids shut down the communication creationof these immune molecules. these are called cytokines, by the way.
it's a way for cells to communicate, and so, shutting this down prevents more white blood cellsfrom being recruited to the blood vessel wall, which decreases thedamage of this disease. and cyclophosphamideis the other medication that's used to treat this disease. cyclophosphamide actsto cause damage to dna. that seems very disastrous.
the point of this medication is to target cells that rapidly divide. immune cells actually go throughrapid growth and division. you have new creation ofimmune cells every single day. so, by killing off some ofthese rapidly dividing cells, it slows down the immune system. so, by preventing thecells from causing damage, we slow down inflammation to arteries.