Three ‘A’s, Five ‘Y’s, Mechanisms of Abdominal Aortic Aneurysm, And Thanks Bill Cook!

As a Pathologist, “FitOldDog wonders!”

abdominal aortic aneurysm mechanism

William Alfred ‘Bill’ Cook, of Cook Medical. The man who thought and saved my life. He not only thought, he acted, to create Cook Medical.

The work of Bill Cook and colleagues led to the magic of Rupert, my Cook Zenith Stent Graft.

What are the underlying mechanisms of abdominal aortic aneurysm (AAA)?

I can’t solve this one with a coat hanger!

You’ll Need A Team To Work It Out!

The five whys. A great approach to problem solving.

Why me? Forget it Morgan, and grow up. You’re damn lucky to be alive. So stop complaining and think!

What are the underlying mechanisms of abdominal aortic aneurysm?

1: Why does AAA generally occur just proximal to the distal aortic bifurcation?

mechanisms of abdominal aortic aneurysmMay involve geometrically-dependent, local pressure wave resonance patterns? Just a thought!

“Womersley suggested that the explanation of the discrepancy between his theory of an infinitely long tube and actual systems might lie in the reflections which would occur from discontinuities such as the bifurcation of the aorta. McDonald makes the assumption that the regularly repeated heartbeat creates a steady state oscillation, i.e., that reflections from one wave are superimposed on later waves.” Barnard et al., 1966.

You underestimate the power of resonance at your peril:

There is another clue, with respect to fluid dynamics. It lies in the fact that some cases of AAA stent deployment induce hypertension. This is possibly due to geometrically-dependent, local pressure wave resonance patterns, or bounce back waves, confusing the aortic baroreceptor system. That’s my humble opinion, anyway (my BP went from 140/80 to 220/120 on receiving a Cook Zenith stent graft in 2010). I’ve found several other cases of AAA-stent-induced hypertension since my FDA adverse event report. One of these cases was quite recent. It would appear that such stent-induced hypertension is due to both the shape of the stent and it’s non-compliance properties (non-elastic), as predicted during experimental research by O’Brien et al. (2008).

Team Members #1-3: Experts in non-Newtonian fluid dynamics, cardiovascular physiology and mechanical engineering.

2: Why does the distal aortic wall expand to create an aneurysm? 

mechanism of abdominal aortic aneurysm

Image by Anton Nalivayko, and copyright for use, purchased from ShutterStock, Inc.

The aorta provides a biomechanical extension of the heart, passing the systolic pressure wave down the body towards the target capillary beds of the tissues. The wall of the aorta has multiple layers, each with specific properties. Occam’s razor would say just one of these layers is the prime problem area. Is it the outer, largely collagenous, adventitia? One of the two layers of elastic tissue? Is it the smooth muscle that weakens, or some other component of the aortic wall?

There is a potentially important clue in the form of the connective tissue diseases, such as Marfan’s syndrome. Abdominal aortic aneurysm is one feature of Marfan’s. This crippling genetic condition has been attributed to mutations in the fibrillin gene (Masien and Glanville, 1993). Fibrillin is a glycoprotein that is essential for the synthesis of elastin, a key building block of the elastic laminae of the aorta.

Presumably, defects in fibrillin, or some other vital connective tissue protein, results in weakness of the regions of the arterial wall that require such molecules as building blocks. For instance, the nutritional disease, Scurvy, is due to a deficiency of vitamin C in the diet. Vitamin C is an essential co-factor in the manufacture of the connective tissue molecule, collagen (Pullar et al., 2017). Lack of vitamin C results in breakdown of skin in cases of scurvy, which was solved for mariners years ago by the provision of an apple barrel for long voyages. Collagen is a critical component of the aortic adventitial and other layers. Maybe nutrition plays a role, especially during childhood?

Team Members #4-6: Histotechnologist, geneticist, nutritionist.

3: Why don’t we know which connective tissue molecule is deficient in AAA?

mechanisms of abdominal aortic aneurysmBecause it’s complicated, but people are working on it, thank goodness. It is nice to see some transcriptomics data again. Those were the days. You can learn so much about your tissue of interest, and your level of ignorance as to how it works, by looking at a transcriptomics data set. Sure humbled this old pathologist.

The real problem is getting transcript data from the right tissue at the right time, or you’ll be looking at sequelae rather than causes. But you have to start somewhere. Furthermore, transcriptome dynamics needs to be taken into account.

A great deal can be learned by attempting to mathematically model the underlying biology of the questions being posed. Building the model teaches you 80%, searching parameter space for values to use in the model teaches humility, and then it’s all about imagination and Occam’s razor.

But it’s not so simple!

Team Members #7-9: Molecular biologist, bioinformatician, statistician.

4: Why is AAA linked to diverticulosis, hyperlipidemia and hypertension?

mechanisms of abdominal aortic aneurysmBecause everything is linked, and they are possibly more linked!

Hey! If one person reports a problem, that’s not research, it’s an anecdote. However! If that person is you, it’s data. And yes, CT scans revealed that I not only have an AAA, but also the joys of diverticulosis, which does not appear to have advanced to diverticulitis (maybe it’s my plant-based diet, or blind luck, who knows?) That said, there is a link, which implies that weakness in my aortic wall may well be linked to weakness in my intestinal wall. That’s what Occam’s Razor suggests. This link has been reported: Mark-Christensen et al., 2017.

Such associations provide valuable avenues for further research. Finding and explaining patterns is what research is all about.

Team Members #10-12: Physiologist, internist, cardiologist.

5: Why me? Could nutrition have played a role, like skin lesions in scurvy?

mechanisms of abdominal aortic aneurysmMy Mom lived to a ripe old age. I have no knowledge of aortic aneurysms killing anyone on my mothers side of the family. Being born in 1943, I was a child of war. Apparently, my dad was a ship in the night who went off to the war in Europe, with heavy artillery, and never came back. Nutrition was poor at best in those days. Maybe that contributed to the development of that 6.9 cm. diameter aortic aneurysm that reared it’s ugly head in 2010.

If the creation of healthy collagen, fibrillin, elastin or some other connective tissue building block, plays a role in aortic aneurysms, surely diet could be critical. Maybe supplements for family members could be worth exploring?

We seem to have a growing list of suspects, but genetic connective tissue disorder is at the top of my list.

Team Members #13-15: Renaissance thinker, pharmacologist and network mathematician.

We really need a name for this condition, as aortic aneurysms are but a symptom.

How about atypical Marfan’s (like atypical pneumonia, which, btw, exhibited atypical cases, making for reported cases of atypical atypical pneumoniaforget it!).

mechanisms of abdominal aortic aneurysmIdiopathic connective tissue disorder, perhaps?

Here’s a relevant quote from an excellent book:

“An illness, at the moment of its discovery, is a fragile idea, a hothouse flower—deeply, disproportionately influenced by names and classifications. (More than a century later, in the early 1980s, another change in name—from gay related immune disease (GRID) to acquired immunodeficiency syndrome (AIDS)—would signal an epic shift in the understanding of that disease.*)” Siddhartha Mukherjee (2010).

Final food for thought:

“Plane crashes [and AAA?] are much more likely to be the result of an accumulation of minor difficulties and seemingly trivial malfunctions.” Outliers, The Story of Success, Malcolm Gladwell (p 183).

PS. If you do happen to have an aortic aneurysm, you’re in exhalted company, my friend.

mechanisms of abdominal aortic aneurysm

 

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Disclaimer: As a veterinarian, I do not provide medical advice for human animals. If you undertake or modify an exercise program, consult your medical advisors before doing so. Undertaking activities pursued by the author does not mean that he endorses your undertaking such activities, which is clearly your decision and responsibility. Be careful and sensible, please.