Transcription
Hey guys, Medicos was perfection Alice, where medicine makes perfect sense. Another day, another video about hematology. Today, we'll talk about acquired angioedema. In the previous video, we talked about hereditary angioedema. Today, it's acquired angioedema. The patient is older now. Let's get started. [Music]
Quick review of the previous videos: We start with high-molecular-weight kininogen converting into bradykinin. High-molecular-weight kininogen activates kallikrein. Kallikrein only activates factor XII. People think: when kallikrein's gonna make factor XII, when factor XII is gonna make kallikrein? It's a feedback loop. Kallikrein activates factor XII into activated factor XII, which activates prekallikrein to kallikrein, which activates factor XII again and again and again. High-molecular-weight kininogen, by kallikrein and bradykinin. Bradykinin does all of the stuff, as you know. If you are in the plasma, you have high-molecular-weight kininogen, plasma kallikrein, and bradykinin. If you are in the tissue, you have low-molecular-weight kininogen, tissue kallikrein, kallikrein, and stimulates this step. This step is going to inhibit this step. Not only this, it's going to degrade bradykinin into inactive metabolites. That's why we call it a tiny nays. Side effects of ACE inhibitors: As you know, ACE inhibitors inhibit ACE, which means lots of bradykinin because it's uninhibited. Dry cough and angioedema, hypotension, renal impairment, metabolic acidosis, and hyperkalemia. Angiotensin receptor blockers, on the other hand, they rarely have cough or angioedema.
There are different types of angioedema, believe it or not. We are talking here about the complement-related kinin-mediated angioedema. We've talked about hereditary angioedema in the previous video. Today is time for acquired angioedema. Quick review of hereditary angioedema: Normally, we have C1 esterase inhibitor inhibiting kallikrein, leading to no secretion of bradykinin. However, in hereditary angioedema, there is no C1 esterase inhibitor. Kallikrein is left uninhibited, converting high-molecular-weight kininogen into lots of bradykinin, causing symptoms. It's an autosomal dominant disorder. No C1 esterase inhibitor, lots of kallikrein, and lots of bradykinin, causing symptoms. The three types of hereditary angioedema—I had a mnemonic about them in the previous video. You are missing a lot if you are not getting my 50 hematology cases by going to patreon.com/medicosis. Come on, guys, they are awesome.
What are the functions of C1 esterase inhibitor? It inactivates kallikrein, inactivates C1 esterase in the classical complement pathway, inactivates factor XII in the intrinsic coagulation pathway. Why do we call it complement? Because it complements the body's action. We have three pathways: classical, alternative, and lectin. The only difference is who will pull the trigger, who will start the cascade. In the classical pathway, it's the antigen-antibody complex. So here's the classical pathway: antigen-antibody complex, C1 into C1 active by the C1 esterase, C4 and C2 into C4b2a and C4a, C3 convertase, C5 convertase, the MAC, which will attack. In hereditary angioedema, you don't have the C1 esterase inhibitor. C1 esterase is left uninhibited to go crazy, activating the complement. The clinical picture of hereditary angioedema is the same clinical picture as acquired angioedema, so pay attention. Two birds by one stone. So we have lots of bradykinin, increased vascular permeability, recurrent attacks of angioedema, face, neck, extremities, eyelids, and genitalia. Context of abdominal pain that can mimic pancreatitis and colitis. The patient may have a history of unnecessary surgeries because many surgeons are idiots. Then the recurrent episodes they last one to three days, and the resolution in one to two days. The patient is probably an adolescent. This is different in hereditary; the patient is young, and in acquired angioedema, the patient is older because it's acquired; it's not a genetic problem; it's not a hereditary problem. So you may think that the patient is older, and you will be correct. No urticaria, no kidding, no itching, which distinguishes the hereditary angioedema from the allergic angioedema.
The lab results in hereditary angioedema and acquired angioedema are a little different. So here is hereditary angioedema: C1 normal, C1 INH or C1 inhibitor decreased, decreased bradykinin, high prekallikrein, low kininogen, low C4, as it's not an allergy. Treatment of hereditary angioedema is the exact same treatment as acquired angioedema, so pay attention again. Don't get the stuff because it's not an allergy; it's not histamine; it's bradykinin, baby. ACE inhibitors are contraindicated in acute attacks. C1 inhibitor by infusion, Icatibant, which is a receptor blocker, Ecallantide, which is a kallikrein inhibitor. If you don't have all of these, use racemic epinephrine to help the airways. If you don't have these, fresh frozen plasma. Keep it for the prevention, prophylaxis. It's not recommended during the acute attacks, and of course, if you don't have all of these, intubate, baby, and in some cases, even tracheostomy. Prevention of future attacks, prophylaxis, then is all C1 inhibitor protein infusion and the fresh frozen plasma. Why? Because the fresh frozen plasma contains the missing C1 inhibitor.
Now welcome to today's topic: acquired angioedema. So let's nip it in the bud and kick it in the butt. Acquired angioedema: It's acquired, so it's not a genetic problem. They are owed to antibodies against C1 esterase inhibitor. Remember hereditary angioedema? We had a genetic deficiency of C1 esterase inhibitor. In acquired angioedema, on the other hand, we have autoantibodies. Got you next. No family history because it's not hereditary; it's acquired. Less common than hereditary. Okay. Manifests later in life because it's acquired; it's not hereditary. It affects patients with monoclonal gammopathy. Remember the myeloproliferative neoplasms, also an S-pair protein amyloidosis, as well as malignancies, especially lymphoma. Diagnosis: C1 here is low. If you remember hereditary angioedema, C1 was normal, but here C1 function and C1 level are decreased. C2 and C4 are decreased because they are overconsumed by the activated classical complement pathway. How to treat them? They are exactly the same, the same as hereditary angioedema.
In the next video, we'll compare between hereditary and acquired angioedema. In the meantime, please subscribe to my channel. Follow me on Patreon. You can support this channel there. You can get all of my notes and my 50 hematology cases. Thank you for watching. Until next time, be safe, stay happy, and study hard. This is Medicos was perfection Alice.