So this is the same cross-section diagram of the three layers of the blood vessel wall. Here you can see this is intima. Intima is made up of endothelial cells and just below the intima, just below the endothelial cells, there is subendothelium tissue which is having connective tissue. So endothelium and sub-endothelium together constitute intima.

In the media, there are smooth muscle cells. All these cells are smooth muscle cells, and in the externa or adventitia, there is connective tissue. This is the structure of the wall of a blood vessel. Before understanding the inflammation in the wall of the blood vessel, you must understand what is the structure of the wall of the blood vessel.

Classification of Vasculitis

Now, coming to the classification of vasculitis, we can classify vasculitis in two ways: what are the two ways? First, based on the size of the blood vessel which is involved, whether it is large, medium, or small, and second, based on the type of inflammation. So based on the size of the blood vessel and based on the type of inflammation, we will be classifying vasculitis in two ways.

Classification Based on Vessel Size

So let me teach you the first type of classification, that is based on the size of the blood vessel wall. So there are three sizes of the blood vessel: large, medium, and small, based on which we can classify entire vasculitis. So in a large vessel, basically the aorta or its arteries, the large arteries are involved.

In large vessel vasculitis, there are only two large vessel vasculitides, that is temporal arteritis and Takayasu arteritis. You can learn them like TT, the mnemonic T and T: temporal also known as giant cell arteritis and Takayasu arteritis. So these two arteritis, either the aorta or the branches of the aorta, that is large arteries, are involved, that’s why they are known as large vessel arteritis.

Medium and Small Vessel Vasculitis

So coming on the medium vessel, we have only two, that is polyarteritis nodosa known as PAN and Kawasaki disease. So P and K, that is the mnemonic. So TT, that is temporal arteritis, are involved, and here in small vessel arteritis, the small vessels, we can divide them whether they are ANCA positive or ANCA negative.

What are ANCAs?

So I will be explaining to you. There are two types of ANCAs, so whether these antibodies are positive, these are immune-associated or non-immune, non-ANCA associated. If they are associated again, ANCAs of two types, PR3-ANCA and MPO-ANCA, in the next diagram I will be showing you.

So here Wegener’s granulomatosis, microscopic polyangiitis, these are ANCA positive in which the PR3 is c-ANCA positive, MPO is p-ANCA positive, and remaining two, that is Churg-Strauss and microscopic PAN, are p-ANCA positive, and in non-ANCA associated there are many others. The most important is Behçet’s. So these are the important types of vasculitis you must study.

Explanation of ANCA Types

So what is ANCA?. A and C, ANCA. So basically these are the antibodies against the neutrophils, the granules present in the cytoplasm of the neutrophils. So you can see the two types of the ANCA I will be showing you in this diagram.

So you can see this is a neutrophil, this is the nucleus of the neutrophil, in the cytoplasm granules are present and these antibodies, please appreciate, these antibodies, these are against the granules in the cytoplasm of the neutrophils. Now what is PR3-ANCA and MPO-ANCA?

Location of ANCA Antibodies

So MPO-ANCA C stands for cytoplasmic; these are present in the cytoplasm randomly anywhere in the cytoplasm, and what is P for PR3-ANCA? Here P stands for perinuclear; they are also present in cytoplasm but not randomly, they are present around the nucleus.

Let me show you PR3-ANCA and MPO-ANCA. Can you see the green color is the antibody? So this is c-ANCA, so I appreciate green color everywhere on the side, randomly present everywhere in the cytoplasm, not only around the nucleus — that is c-ANCA.

And as for this, appreciate PR3-ANCA. So PR3-ANCA is present only around the nucleus, not everywhere around the cytoplasm. It is present only around the nucleus, that is perinuclear. So this one is cytoplasmic anti-neutrophilic cytoplasmic antibody and this one is perinuclear antibody, so c-ANCA and p-ANCA appreciate the two types in the diagram, appreciate these.

Recap of Vasculitis Classification

Coming on the classification again, so we have studied the classification dividing based on the size of the blood vessel. We can divide the vasculitis into three types: the large vessel, medium vessel, small vessel. In large vessels, the two types are in front of you, temporal and Takayasu. In a medium vessel, the two types are in front of you, PAN and Kawasaki, and in small vessels, we divide based on ANCA positive or ANCA negative. If again positive, whether it is only Wegener and PR3-ANCA or Churg-Strauss and microscopic PAN. So this is the simplified way of classifying them, divide them into three parts: large, medium, and small. So in the large, we have only two: temporal and Takayasu, that’s it. In the medium again, we have only two: PAN and Kawasaki, that’s it.

So large is done, medium is done — large vessel arteritis, medium vessel vasculitis or arteritis. Coming on small vessels, small vessels are a little bit complicated but not much one. So you can see we can classify them based on whether they are positive, then we divide them whether they are PR3-ANCA positive or whether they are MPO-ANCA positive. Like this, we can divide them.

So let me tell you the names inside each of them: only one Wegener, PR3-ANCA positive; Churg-Strauss and microscopic PAN, microscopic polyarteritis nodosa — so these are the PR3-ANCA positive. The important one is HSP disease. These are the important ones.

Vessel Sizes and Types Involved

So you can see the important type of vasculitis classifying vasculitis based on the size of the blood vessel. Coming to the second type of classification, okay, yeah, you can see these are the large vessels, in which either aorta or the large arteries are involved, that is giant cell arteritis and Takayasu. These are the medium ones. You can see in the medium one the arterioles are involved, small arteries and arterioles are small vessels, and in the small one, you can see basically capillaries are involved. In the small one, arterioles and capillaries are involved. Now whether they are negative, not associated with ANCA or ANCA positive, so we can divide them like this.

Types of Inflammation in Vasculitis

So coming on the second type of classification, that is type of inflammation. There are two types of inflammation. So we will see in the wall of the blood vessel what is inflammation, which type of inflammation — whether it is granulomatous or necrotizing. So the two types of inflammation are in front of you: granulomatous and necrotizing. You can appreciate it. So some of them show — you can see, first see the diagram. Can you see the wall of the blood vessel in these two diagrams? Please appreciate the granulomas here. Can you appreciate a granuloma here, a granuloma here, a granuloma here? Appreciate the giant cells inside the granuloma. So this is the media, you can see this is the lumen, this is the lumen of the blood vessel, this is intima, this is an entire media. In the media, you can appreciate the multiple granulomas on this diagram having giant cells. So this type of arteritis or vasculitis is granulomatous vasculitis.

Here you can see in the media there is necrotizing, there is necrosis, there is fibrinoid necrosis in the media. You can appreciate the new one — it is normal, you can appreciate in the media a pink color structureless acellular material is there; that material is the necrosis. Here it is fibrinoid necrosis, so it is necrotizing inflammation. So based whether it is granuloma in the wall or whether it is necrotizing inflammation in the wall, the inflammation is of two types: granulomatous and necrotizing, based on what is there in the wall: granuloma or fibrinoid necrosis. So basically in the morphology, the pathologists have to see whether in the wall granuloma is present or whether in the wall fibrinoid necrosis is present. So based on that, we will decide the type of the inflammation.

Vasculitis Types Based on Inflammation

So we divide the vasculitis based on them. Some of them, that is PAN, Churg-Strauss, Wegener, and microscopic PAN, have necrotizing inflammation. You can appreciate two things: Wegener is on both sides, and Churg-Strauss is on both sides. So Wegener and Churg-Strauss have both types of inflammation in the wall. You can see the Wegener and Churg-Strauss have granulomatous inflammation as well as necrotizing inflammation. Very, very important MCQ repeated many times in the previous year’s question papers. You can see in the previous year exam papers this question is repeated. Now I always ask students to make a comparative table between the various types of vasculitis so that you will have better retention to compare them.

Large Vessel Vasculitis: Temporal Arteritis

Coming on the first type, that is large vessel vasculitis. In the large vessel vasculitis, I will be teaching you two. So starting with the first one, that is temporal. You can see I am starting with the temporal arteritis, large vessel arteritis. I am starting with temporal. The other name of the temporal is giant cell arteritis. It is the most common arteritis among all here. Large arteries are involved. So name the large arteries which are involved in the temporal arteritis. So as the name indicates, temporal, temporal arteritis, so temporal arteries on board. So basically the branches, the extracranial branches of the carotid arteries are involved. So most commonly it is temporal, but sometimes it can be 40% of the hemolytic, so most commonly it is temporal but sometimes it is vertebral and ophthalmic also. So you can see this is the temporal artery, so basically middle-aged females are involved and ESR will be raised.

Symptoms and Morphology of Temporal Arteritis

So appreciate, this is the temporal artery which is involved here, and patients have typical pain in the temporal area and there is a hardening of the artery, the temporal artery you can appreciate here, here. You can appreciate the temporal artery. So this is a live diagram of a patient. Please appreciate the hardness here, please appreciate the thickness of the artery. So this is the temporal artery. The wall of the temporal artery becomes thickened and patients have temporal headaches. This is a typical symptom or complaint of the patient. You can appreciate here morphologically if we take the biopsy from here and see the biopsy, we will find the segmental involvement. What do you mean by segmental? So it is not the country. So this area is involved having random inflammation, this is normal again this area is involved, then normal, then involved. So this is known as segmental involvement with skip areas; that is there in temporal arteritis.

You can see, and because of the inflammation of the wall of the temporal artery, the temporal artery develops nodular thickness. So if you palpate the temporal artery of the patient, you can feel it like a thick rod. So there is thickness, there is thickness, and in the morphology, you can see the temporal arteritis of giant cell arteritis in which granulomatous inflammation is noticed. So on taking a biopsy, this is the biopsy image. In the biopsy image you can appreciate the granulomas here. I appreciate this one, appreciate this one and this one. See the arrows inside the granulomas, try to appreciate the giant cells. This is the giant cell, this is the giant cell.

See the type of giant cells: Langerhans giant cell and foreign body giant cells, both giant cells are seen here. You can see here, just a second, you can see here also I appreciate the giant cell here. So it is a Langerhans giant cell. It is a granuloma, you can appreciate this one as a granuloma. So first thing is the granulomatous inflammation, the granulomas are there. In the granulomas the giant cells are there. The giant cells are foreign body giant cells or Langerhans giant cells, both types are seen in the granulomas. The second thing, there is fragmentation of the intima. You can appreciate very well in this diagram, you can appreciate this intima here. It is continuous, continuous, continuous, but here it is fragmented. Appreciate the fragmentation here. So fragmentation of intima is also a morphological feature. Here, so let me show you the morphological features here. So only two morphological features: granulomas in the wall and fragmentation of the intima. These are the morphological features which we appreciate on biopsy.

Diagnosis and Treatment of Temporal Arteritis

Now, if a middle-aged female has raised ESR with all these symptoms, so your suspicion, the doctor’s suspicion should be temporal arteritis and the doctor should take the biopsy to confirm. What is the treatment? The treatment is to immediately start the steroid. Why? If the patient is coming only with temporal headache, not blindness, so to prevent the blindness, if you don’t give the steroid, the inflammation will progress, progress, and ultimately it will involve the ophthalmic artery and patient can come to you with directly blindness and it will be irreversible. Once blindness, of course, it will be irreversible. So give steroids to avoid such complications. So steroids are the treatment. So we are done with temporal arteritis, all important points on which MCQs can be framed.

Takayasu Arteritis Overview

Coming on the second, that is Takayasu arteritis, another large vessel arteritis. It usually occurs in adolescent girls and young women. So you can see it is also known as pulseless disease. Why is it known as pulseless disease? Because here basically the brachiocephalic, the branches of the aortic arch are involved.. So patients have involvement of the upper limb arteries. So because of the thickening of the arteries, the pulse cannot be palpated, that’s why it is known as pulseless disease. So pulseless disease, it is known as which arteries are involved?

The most commonly subclavian arteries are involved. Apart from it, other branches of the arch of aorta, brachiocephalic and carotid, are also involved. You can appreciate the narrowing here, you can appreciate the narrowing here. So you can appreciate this is the arch of aorta; these are the branches of the arch of aorta. So you can appreciate the narrowing here. So I appreciate the narrowing of the brachiocephalic, carotid, and subclavian artery in this diagram. These are the two carotid arteries of a cadaver, or on postmortem you can see, on autopsy these are the sections of the carotid artery. Appreciate the luminal narrowing here. I appreciate the thickness of the wall and the luminal narrowing in the bilateral carotid artery of a toxic specimen. In the morphology, it is the same, exactly the same as that of temporal arteritis. We will find granulomatous inflammation. So giant cell arteritis like we are finding here, granulomatous inflammation, that’s it. So giant cell arteritis as well, arteritis, both of them having granulomatous inflammation.

Symptoms and Treatment of Takayasu Arteritis

Symptoms: the patient has no palpation of the pulse, no pulse will be absent in the upper limb, not in lower limb. So the pulse will be absent in the upper limbs but not in the lower limb. It can be felt in the lower limb. The BP in the blood pressure in the upper limb is lower as compared to lower limb. The reason is the same, because the branches of the aortic arch, that is brachiocephalic and subclavian artery, supply the upper limb but not the lower limb. So the pulse and blood pressure of the upper limb will be lower as compared to pulse and blood pressure of the lower limb. So there is a discrepancy in the blood pressure of the upper limb and lower limb. This is the biggest clue given in the questions for identifying this Takayasu disease; that is the thing. So lower BP and weak pulse in the upper limb as compared to lower limb. Apart from it, ocular claudication can happen. You can see you cannot palpate the pulse here of the patient in the wrist. The radial artery cannot be palpated, it cannot be felt. The pulse cannot be felt. So these are the terms. Treatment is the same, steroids.

Summary of Large Vessel Vasculitis

So in this session, we have studied the two types of large vessel vasculitis. Still, we have to continue. So in this table, we have continued; we have completed two, giant cells and the Takayasu. Still, we have to continue with the medium vessel and small vessel arteritis.