School’s In for Summer

Are we ever truly done with school? Personally, I think the answer is “no.” School can help young professionals enrich their careers with broader views and visions and spark their enthusiasm for topics that may not have been covered in depth during their training. My own learning inspiration comes from the integration of etiopathogenesis and the understanding of pathophysiology – a lasting fascination that motivated me to create the Dubrovnik Summer School of Pathophysiology.

The summer school was designed to present the inquiring spirits of young biomedical professionals and advanced students with cutting-edge scientific research. In 2021, many overseas students were unable to attend in person – but the class proceeded nonetheless, in a hybrid format that delivered seminars to 45 in-person students and up to 47 online attendees, who actively contributed to the sessions with questions, comments, and added case examples.

Pathophysiology’s rightful place
 

Pathophysiology can be represented in a simple Venn diagram (see Figure 1). Its laws, reactivity patterns, and homeostatic and allostatic steady states are relevant to every branch of research and clinical medicine. Rudolf Virchow, the founding father of pathophysiology, described the discipline as “the stronghold of scientific medicine.” This holds true with no exception – interconnecting elements of etiopathogenesis have much in common with even very heterogeneous diseases (see Figure 2).

Overlapping patterns of body responses are considered general pathophysiology, which is often covered as an independent subject at university. According to the International Society for Pathophysiology, at least 54 countries view general pathophysiology as a separate subject. In other regions, the same etiopathogenetic principles are studied as subdisciplines of clinical physiology, semiology, practical medicine, and general pathology.

Pathophysiology is an important part of medical education – and I intend to keep it that way. Following a century-long tradition of integral pathophysiology in Zagreb, Croatia, my group has developed a four-step method for teaching and learning. It involves the exposition of a problem (reviewing the medical history of a real case), analytical repetitions of related knowledge via multiple-choice questions, designing an etiopathogenetic algorithm from a predetermined set of disease elements, and systematizing with quantitative aspects of the same problem.

Through various activities, students are guided through pathways, regulatory interactions, connections between processes, signs, symptoms, and outcomes. They construct graphic representations of processes and defend their interpretations of relationships between elements of etiopathogenesis. This core intention triggers enthusiasm and fulfills students’ expectations – a process known as the “Lego principle of play.” Students have praised it for its ability to enable them to navigate a plethora of information, make sense of fragmentary knowledge, and feel like they are opening a treasure chest of biomedical expertise.

After hearing about the foundations and backstory of the summer school, readers may wonder – why host it in Dubrovnik? I was born and raised in the oldest continuously inhabited city (Vinkovci), so my interest in history and material artifacts of human culture naturally influences my way of thinking. Dubrovnik is a pearl of human civilization and cultural creation – it is internationally renowned, with a rich history of tradition and famous figures. Many of our summer school participants have said that they treasured the unique experiences they have had in Dubrovnik – one of my goals already achieved!

Bridging the gap
 

I view pathophysiology as a bridge between basic biomedical sciences, laboratory medicine, and clinical practice. It can be difficult to build this bridge in medicine, but I kept that concept in mind when designing the summer school curriculum. We tried to highlight the relationship via lectures, problem-oriented seminars, and practical sessions that involved clinical, laboratory, and quantitative exercises – solving algorithms and EPCs highlights the importance of recent scientific discoveries and standard clinical data and showcases the students’ ability to integrate both.

At my medical school, the pathophysiology course is taken in the third year and is interposed between preclinical and clinical disciplines – a logical position for bridging the two areas. To stay up to date with new scientific discoveries, concepts, and frameworks, we have continued with Colloquia pathophysiologica – weekly seminars held over 1,100 times in the past 25 years. In the sessions, four to five papers are presented, followed by a discussion of their interpretations within the concepts and practices of clinical medicine. In addition, we hold Seminaria pathophysiologica demonstratorum (over 150 in the past six years) for advanced students and physicians with similar goals. Each year, teachers actively participate in international experimental biology, clinical, and pathophysiology conferences to update the school’s study materials.

I follow a unique approach to solving clinical problems, which I try to apply throughout my teaching – an analytic-synthetic approach to etiopathogenetic pathways. Algorithmic elaborations have revealed an interesting regularity of the networking of etiopathogenetic pathways. There are integrative “hubs” or nodes where multiple pathways join and others are initiated. We named these hubs “etiopathogenetic clusters” (EPCs). So far, we have identified 91 EPCs that occur in various diseases – heterogenous etiological factors trigger disease pathways that have a natural tendency to form these EPCS. Simply put, human body reactivity is reduced to the networking of those 91 elements – and this simplification is useful because therapeutic intervention in some of these EPCs can lead to direct clinical improvement. For example, ventricular fibrillation conversion can save lives by preventing cardiogenic shock – one of the 91 EPCs (see Figure 2). Rapidly infusing glucose can correct the hypoglycemia EPC and prevent hypoglycemic coma and shock in diabetic patients with insulin overdose. All EPCs are elements of natural disease pathway networking and, for most of them, these improvements hold true.

This approach has received praise from educators around the world. Leonid Churilov from the University of Saint Petersburg said, “These are around 100 mosaic blocks, interplaying in all nosological forms, like elements of Mendeleyev’s table adjoined to any substance, so they give strong impetus to systemic autonomous analysis of clinical pathophysiological problems.”

The novelty of this approach lies in the independent disease processes that trigger a common part of the EPC network. Unrelated etiological factors may trigger similar reactions and thus similar EPC network events. From this concept and etiopathogenetic facts, there are clear predictions of disease cross-talks in comorbidities. In the summer school, we present reports of mutual aggravation of two comorbidities and mutual inhibition, prevention, and alleviation of other pairs of diseases.

So far, I have developed over 100 key EPCs for the course and incorporated them into Croatian medical education. Four medical schools in the country have successfully used this system for over 20 years in both teaching and examination; many other universities also use the model and, in Russia, it has been presented in a series of papers in key pathophysiology journals distributed by medical academic communities in Kaliningrad and Vladivostok. So far, 12 sets of algorithms and EPCs with solutions have been published and presented at international conferences and educational symposia (1,2,3,4).

Stay in-quiz-itive
 

It is one thing to bridge the gap between disciplines when students attend the summer school – but how do you encourage active participation? Quizzes are an attractive form of entertainment; they produce emotional, social, and intellectual dynamics, and are quickly resolved with winners and losers (just like sports). Because they’re enjoyed by modern students and older generations alike, we included a competition in our program. The quiz consisted of a written test that required thorough understanding of disease physiology, with three top teams (out of nine) selected for the oral competition. Examples of questions included:

• Name three clinical conditions with hypermetabolic state.
• Explain three direct cellular dysfunctions due to intracellular ATP shortage.

Three team members had 30 seconds to write down their answers; then, the academic judges publicly evaluated the solutions and decided on points to award. The winning team were awarded travel expenses to Kuala Lumpur to participate in the 20th Inter-Medical School Physiology Quiz, which is a large Southeast Asia competition for university quiz teams.

Proud moments
 

Since its inception, the summer school has had many significant achievements – but a few of those stand out. Despite the COVID-19 pandemic, we still managed to hold a hybrid version of the summer school, bringing together students and experts from around the world. Across three and a half days, we facilitated active discussions of human physiology via 24 lectures, two audio-visual featured topics, and a competition. Several students also presented case studies and published research throughout the program, helping to build confidence and raise awareness of the great work they’re doing. T-shirts with the school’s logo inspired team spirit in the young pathophysiology community. And, of course, both students and teachers enjoyed the beauty and beaches of Lokrum (just 10 minutes by boat from Dubrovnik), where new ideas were brought to life and a new chapter of our academic lives began.