How to study Physiology, Biochemistry and Histology

In the basic cycle, the most common feeling is one of endless volume: each class brings a new pathway, a new hormone, a new tissue, and the list seems to grow faster than memory. The way out is not to memorize faster. It is to change what you try to keep: instead of lists, mechanisms; instead of repeated reading, questions; instead of slides seen once, many slides compared.

NEXO is a daily medical diagnosis game: one clinical case a day, six progressive clues, and ICD-10 proximity feedback across five levels.

This text shows how to study Physiology, Biochemistry and Histology with that focus, on five fronts: understand the mechanism, apply questions to the three subjects, draw the pathway, train the eye in Histology and bring the content to the clinical case. General memory techniques, such as active recall and the testing effect, are in the text about how to fit games into the study routine; here they appear only applied to the three subjects.

Main points

• In the view of Physiology professors, the subject is difficult because it demands causal reasoning and integration, and many students treat learning as a synonym for memorizing.
• Organizing study around a few central principles, such as homeostasis and flow down gradients, helps fit each new content into place.
• Asking "why?" and explaining the mechanism to yourself or to a colleague yields more understanding than rereading.
• Drawing the pathway helps, especially when the drawing is done from memory and checked afterwards.
• In Histology, the eye is trained with many slides, compared with each other and linked to function.
• Bringing the basics to the clinical case gives meaning to the content and helps you remember it later.

Summary

• Why the basics seem endless
• Mechanism, not list
• Questions and active recall in the three subjects
• Drawing the pathway
• Histology by image
• Bringing it to the case
• A possible week in the basic cycle
• Frequently asked questions
• Checklist for studying the basic cycle

Why the basics seem endless

Physiology, Biochemistry and Histology arrive at the beginning of the course, when there is still no patient to give meaning to the content. The result is a pile of loose information that seems useful only for the exam. Understanding why this happens helps you choose how to study.

What professors point out

In a survey with 63 Physiology professors, the characteristics of the subject and of the students weighed more than the way of teaching to explain why Physiology is difficult (Michael, 2007). On the subject side, the professors cited causal reasoning, the use of graphs and mathematics and the highly integrative nature; on the student side, the belief that learning and memorizing are the same thing and the tendency to separate content into compartments (Michael, 2007).

It is the professors' view, not an experiment. Even so, it points to a practical path: if the difficulty lies in linking causes and effects, studying lists does not solve it.

How much of the basics stays

A review on retention of basic science knowledge estimated that about two thirds to three quarters of the content is retained after one year, dropping to just below half in the following year (Custers, 2010). In a cross-sectional study with students and physicians in the Netherlands, performance on a basic science test fell from about 40% correct among students to 25% to 30% among physicians with many years of practice (Custers and ten Cate, 2011).

The same study found little loss in the first one and a half to two years after the last use of the content (Custers and ten Cate, 2011). The authors conclude that the idea that almost everything from the basics is lost soon after graduation is not supported by the data (Custers and ten Cate, 2011). That is: part of forgetting is inevitable, and the way you study defines what stays and what can be reconstructed later.

Mechanism, not list

The mechanism is the answer to "why does this happen?". A list says what happens; the mechanism says why, and that is what allows you to reconstruct the list when memory fails.

A few central principles

Physiology professors from various institutions, consulted in two rounds of research, described 15 central principles of the subject (Michael and McFarland, 2011). The five considered most important were cell membrane, homeostasis, communication between cells, interdependence and flow down gradients (Michael and McFarland, 2011).

In practice, this becomes a fixed question in front of every new piece of content: which principle is at stake here? Filtration in the kidney, gas exchange in the alveolus and the action potential are all cases of flow along gradients. Studying each one as an example of the same principle reduces the apparent volume and increases the connection between the topics.

Misconceptions are common

In a survey with undergraduate students from 12 courses at 8 institutions, the frequency of 13 misconceptions about cardiovascular function ranged from 20% to 81% (Michael et al., 2002). The authors suggest that part of these errors comes from the difficulty of applying simple general models to specific cardiovascular phenomena (Michael et al., 2002). Knowing the right answer to a question does not guarantee that the model behind it is right; explaining why is the test.

Asking "why?" and explaining to yourself

Two techniques work directly on the mechanism: elaborative interrogation, which is asking why a fact is true, and self-explanation, which is explaining to yourself how new information connects to what you already know. In a large review of study techniques, both received moderate utility, with the caveat that they have still been little evaluated in real educational settings (Dunlosky et al., 2013).

Explaining to a colleague

In a randomized trial with 317 first-year medical students, discussing Physiology concepts with colleagues improved understanding more than self-explanation: a gain of 35% versus 23% (Versteeg et al., 2019). Both methods performed better than the control on transfer questions, which ask you to apply the concept in a new situation (Versteeg et al., 2019). Many students who started with the wrong answer improved even after discussing with a colleague who had also gotten it wrong (Versteeg et al., 2019).

An example in Physiology

Cardiac output is the amount of blood pumped by the heart per minute, and the body adjusts it by modulating heart rate and stroke volume (StatPearls, Physiology, Cardiac Output). Regulation involves the autonomic nervous system and endocrine and paracrine signals (StatPearls, Physiology, Cardiac Output). Instead of memorizing each factor that changes cardiac output, ask through which of the two paths it acts, heart rate or stroke volume, and why.

An example in Biochemistry

Thiamine, or vitamin B1, in the form of thiamine pyrophosphate, is a coenzyme of alpha-keto acid decarboxylation reactions and of transketolase, central to energy generation (StatPearls, Vitamin B1 Deficiency). Deficiency affects the cardiovascular, nervous and immune systems and appears as wet beriberi, dry beriberi or Wernicke-Korsakoff syndrome (StatPearls, Vitamin B1 Deficiency). Linking the coenzyme to the pathway, and the pathway to the affected organs, replaces the name of a vitamin with reasoning you can redo.

Physiology and Biochemistry together

The two disciplines are usually taught in separate blocks, but they describe the same organism. Fasting and feeding are a good exercise: on one side, the hormones and the response of the organs; on the other, the pathways that are turned on and off in each state. Studying both sides in the same session counters the tendency to separate content into compartments, which Physiology professors pointed out as one of the causes of the difficulty (Michael, 2007). Editorial guidance.

Graphs without fear

Graphs and math are among the difficulties of Physiology cited by professors (Michael, 2007). A simple path is to read each graph in three steps: what is on each axis, what happens when a variable rises and which mechanism explains the shape of the curve. Then close the book and draw the graph again, marking what changes in an altered situation. Editorial guidance.

Questions and active recall in the three disciplines

The general principles of testing memory are in the text about how to fit games into your study routine. Here one specific point is worth making: the type of question. Tests that require effortful recall, such as short-answer ones, promote more retention than recognition ones, such as multiple-choice (Larsen et al., 2008).

In Physiology

Replace "what is the normal value of..." with cause and effect questions: if resistance increases, what happens to flow? If stroke volume falls, how does the body try to maintain output? Questions like these test the model, not just the fact. Graphs, which teachers point to as a source of difficulty (Michael, 2007), also become a question: draw the memory curve and explain what each axis shows.

In Biochemistry

The most useful questions are about regulation and consequence: which enzyme limits the speed of the pathway, which hormone turns it on or off, what accumulates when it is missing. Answering without looking and only then checking the book is what separates studying the pathway from recognizing it. The question "what accumulates?" is the natural bridge to the clinical case.

In Histology

In Histology, the question is visual: what is this structure, how do I know, and which function explains this shape? Cover the slide's caption, say the name and the criteria you used, and only then check. The criterion matters more than the name, because it is what you will use on a new slide.

Drawing the pathway

Drawing a metabolic pathway, a hormonal regulation circuit or a feedback loop is a way to organize the content. A review of 35 studies on concept maps in medical education described four main functions: promoting meaningful learning, serving as an additional resource, allowing the teacher to give feedback and assessing learning (Daley and Torre, 2010). The review describes uses, but does not estimate the size of the effect.

Drawing from memory

In an experiment with science texts, retrieval practice yielded more learning than studying by building concept maps, including on inference questions and even when the final test asked for a concept map (Karpicke and Blunt, 2011). The natural combination, therefore, is to draw the pathway from memory, without looking, and only then compare it with the book. The drawing becomes a test, and the gaps show what to study.

What to put in the drawing

A simple script, as editorial guidance:

1. Input and output: where the substrate comes from and where the product goes.
2. Steps that spend or generate energy: ATP, NADH, FADH2.
3. Regulating enzyme: the point at which the pathway is turned on or off.
4. Commanding signal: hormone or state of the body, such as fasting or feeding.
5. Link with other pathways: what leaves here to feed another.
6. Consequence of failure: what accumulates or is missing when a step stops.

Editorial guidance; the details of each pathway must be checked in the textbook.

Do not try to memorize every step

Not every intermediate deserves the same effort. The points of regulation, of energy use and of connection with other pathways are usually the ones that explain diseases and drug effects. If you can rebuild the logic of the pathway, the names of the intermediates become easier to retrieve when they are needed.

Histology through images

Histology is, above all, a training of the eye. The comparison between virtual and optical microscopy is in the text about games for medical students; here the focus is how to study slides, whatever the format.

Many slides, not one

Recognizing a tissue is learning a category from examples, and categories are learned better with varied examples. That is why it is worth seeing the same tissue in different cuts, magnifications and stains. Mixing slides of similar tissues, instead of studying one block at a time, follows the same logic of interleaving described in the text about study routine.

Describe before naming

A slide reading script, as editorial guidance:

1. Lower magnification first: what is the general organization, are there layers, is there a lumen?
2. Type of cell and nucleus: shape, position, amount of cytoplasm.
3. Matrix and fibers: what fills the space between the cells.
4. Decisive criterion: the finding that separates this tissue from the most similar one.
5. Function: why this shape serves this job.

Editorial guidance.

Drawing the slide

Drawing what you see under the microscope, even in a simple way, forces you to look carefully at the arrangement of the cells and at the details that separate one tissue from another. The same rule as for the pathways applies: draw first from memory and only then compare with the slide or the atlas, noting what was missing. Editorial guidance.

Form and function

The question "why this shape?" links Histology to Physiology. In the renal corpuscle in the image above, the PAS stain highlights the basement membranes (Ed Uthman, file description on Wikimedia Commons), which are part of the filtration barrier. Studying the slide and filtration together makes each one explain the other.

From normal to altered

Normal Histology is the ruler for Pathology. Hepatic steatosis, for example, is defined by the accumulation of fat in the liver, visible on imaging or in histology (StatPearls, MASLD). The current name, metabolic dysfunction-associated steatotic liver disease, links the slide directly to the Biochemistry of metabolism (StatPearls, MASLD). Seeing the normal liver beforehand makes the altered one evident.

Bringing it to the case

The basics gain meaning when they explain a patient. Studies on this are few and small, but they point in the same direction.

The mechanism helps you remember

In a small, short-term study, 36 students learned four neuromuscular diseases through basic science explanations or through probabilities between symptoms and diseases (Woods et al., 2005). On the immediate test there was no difference; one week later, the accuracy of the mechanism group was 0.52, and that of the probabilities group fell to 0.43 (Woods et al., 2005). The authors suggest that basic knowledge helps you remember or reconstruct the relationship between findings and diagnoses (Woods et al., 2005).

Explaining the pathophysiology of the case

In an experiment with 39 fourth-year students, explaining to yourself the pathophysiology of the findings during practice with cases did not improve diagnostic performance overall (Peixoto et al., 2017). There was improvement in the jaundice cases, but not in the chest pain cases, and the authors suggest that the benefit depends on the diseases studied sharing similar pathophysiological mechanisms (Peixoto et al., 2017). The lesson for studying: the mechanism pays off more when it helps separate diseases that look alike on the outside.

Cases within Biochemistry

In a trial with 100 first-year students, exposure to clinical cases integrated into Biochemistry teaching led to higher post-test scores than the traditional lecture, both on multiple-choice questions (9.34 versus 7.24) and on problems (6.89 versus 5.72) (Bj et al., 2025). Between 94% and 98% of students agreed that the cases helped link Biochemistry concepts to clinical practice (Bj et al., 2025). It is a single-institution study with short follow-up. Medical education researchers who want to study the link between the basics and the clinical case can learn about NEXO Researcher.

Using it keeps the knowledge

In the study with Dutch physicians, when the authors controlled for use of the content in the interval, unused knowledge followed a forgetting curve, reaching 15% to 20% correct after 25 years or more (Custers and ten Cate, 2011). The practical conclusion, as an editorial reading, is that the basics that come back often in cases tend to be what stays. Every time a mechanism explains a patient, it is used again.

How to make the link

When you finish a basic topic, ask: in which patient does this appear? What sign or test would show the failure of this mechanism? Which slide would be altered? A short answer is enough. The text on clinical reasoning shows how this link later becomes the basis of illness scripts.

One case per topic

A possible routine, as editorial guidance: when you finish each major topic, choose a clinical picture that depends on it and write, in a few lines, the complete chain. For example, from the defect in the pathway to the accumulation of a substance, from the accumulation to the altered tissue, and from the tissue to the sign that appears on the exam. If the chain gets stuck at some point, that is where the study gap is. Over time, these chains become a notebook of bridges between the basics and clinical practice, also useful for exam review.

Bring it to the case in NEXO

Short clinical cases are a good place for that bridge, even in the basic cycle. In NEXO, each case arrives in up to six clues, and you formulate hypotheses from the findings, which is the moment to ask which mechanism explains each one. Each guess shows the proximity in ICD-10 at five levels; on the third clue the area of the case appears and, on the fifth, the ICD range.

Multimedia brings cases with images, audio and other exams, among them histopathology and blood smear, which brings the Histology you studied into a case. The Daily brings one case per day, the same for everyone, good for discussing with the class the mechanism behind each clue, and the Archive gathers previous cases. The Anki button creates the card directly from NEXO and opens it in the Anki app, searches for the cards you already have and, when the case has an image, brings the image to the card. To understand the limits of each mode, see the NEXO economy page. If you coordinate a medical school or league and want to use cases like this in the basic cycle, check out NEXO Closer; doctors who want to review cases can check out NEXO Curator, and those who produce medical content, NEXO Creators.

Common mistakes in the basic cycle

Some habits are frequent and easy to correct. The items below are editorial guidance, with the source indicated when there is one.

• Rereading as the main study method: rereading and highlighting are among the low-utility techniques in the review of study techniques (Dunlosky et al., 2013); the text on study routine explains why.
• Memorizing the pathway step by step: without the logic of input, output and regulation, the names disappear soon after the exam.
• Studying each subject in isolation: compartmentalization is one of the difficulties pointed out by teachers (Michael, 2007).
• Seeing each slide only once: one image per tissue is not enough to recognize the same tissue in a different section.
• Confusing getting it right with understanding: wrong conceptions about cardiovascular function were common even among students who answered questions (Michael et al., 2002).
• Leaving the clinical case for later: the connection with the patient helps you remember and gives a reason to study the mechanism.

A possible week in the basic cycle

An example, as editorial guidance, for those who have the three subjects in the same semester:

Day	Physiology	Biochemistry	Histology
Monday	Class and summary of the central principle	New pathway drawn from memory	Slides of the topic, with the caption covered
Tuesday	Cause and effect questions	Regulation questions	Slides of similar tissues mixed together
Wednesday	Explain a mechanism to a colleague	Check the drawing of the pathway	Form and function of each slide
Thursday	Graphs drawn from memory	What accumulates when the pathway fails	Normal versus altered
Friday	Clinical case linked to the topic	Clinical case linked to the pathway	Case with image
Weekend	Mixed questions from the three subjects	Review of mistakes	Review of the wrong slides

Editorial guidance; adjust to your school's calendar.

How to adjust

If a subject has an exam coming up, increase its weight without zeroing the others. If time is short, keep the minimum of each front: one mechanism question, one pathway from memory and a few slides per day. The point is not to complete the table, it is not to let studying become only reading.

Frequently asked questions

How to study Physiology?

Organize the content around a few central principles, such as homeostasis and flow down gradients (Michael and McFarland, 2011). Replace rereading with cause and effect questions, draw graphs from memory and explain the mechanisms to a colleague, which improved understanding in a trial with medical students (Versteeg et al., 2019).

How to study Biochemistry without memorizing everything?

Focus on the logic of the pathway: input, output, regulation, energy expenditure and what happens when it fails. Draw from memory and check afterwards, since practicing retrieval yielded more than just building concept maps (Karpicke and Blunt, 2011).

How to study Histology?

Look at many slides of the same tissue, in different sections and stains, mix similar tissues and describe before naming. Link each form to its function. The comparison between virtual and optical microscopy is in the text about games for medical students.

Will I forget everything from the basic cycle?

Part of it is lost, but less than people usually say: the review on the topic estimated retention of two thirds to three quarters after one year (Custers, 2010). Studying the mechanism helps reconstruct what is forgotten.

Does a mind map or concept map work?

It helps organize, but it pays off more when done from memory and checked afterward. In an experiment, retrieval practice outperformed studying with concept maps (Karpicke and Blunt, 2011).

How much time per day should I dedicate to each subject?

The number varies from person to person. What matters most is spreading study across the week, instead of concentrating everything before the exam: distributed practice is one of the two highly useful techniques in the review of study techniques (Dunlosky et al., 2013). A little of each subject, almost every day, usually pays off more than long and rare blocks.

Book, summary or recorded lecture?

The format matters less than what you do with it. Any material serves as a base, as long as reading is followed by questions, drawing from memory and checking. The risk of a ready-made summary is that it turns into rereading, which has low utility in the review of study techniques (Dunlosky et al., 2013).

Does studying in a group work for the basic cycle?

It works well for mechanisms. In a trial with first-year students, discussing Physiology concepts with peers improved understanding more than explaining only to oneself (Versteeg et al., 2019). Agree on the topic beforehand and bring cause-and-effect questions.

Is it worth studying clinical cases already in the basic cycle?

It is, in small doses. Studies suggest that the mechanism helps remember the relationship between findings and diagnoses (Woods et al., 2005) and that cases integrated into Biochemistry teaching improved grades in a trial (Bj et al., 2025).

How does NEXO help in the basic cycle?

NEXO helps bring the basics to the case: each case arrives in up to six clues, and Multimedia brings cases with histopathology and blood smear. It is the moment to ask which mechanism explains each clue and which slide would be altered.

Checklist for studying the basic cycle

1. Identify the central principle of each new content.
2. Ask "why?" in the face of each fact.
3. Explain the mechanism out loud or to a colleague.
4. Ask short-answer questions, not only multiple choice.
5. Draw the memory pathway and check afterward.
6. Mark the regulation and what accumulates when the pathway fails.
7. Look at many slides and mix similar tissues.
8. Describe before naming and link form and function.
9. Take each topic to a short clinical case.
10. Review the mistakes at the end of the week.

Want to practice today? Play the case of the day on NEXO.

References

1. Michael J. What makes physiology hard for students to learn? Results of a faculty survey. Adv Physiol Educ. 2007. https://pubmed.ncbi.nlm.nih.gov/17327580/
2. Custers EJFM. Long-term retention of basic science knowledge: a review study. Adv Health Sci Educ Theory Pract. 2010. https://pubmed.ncbi.nlm.nih.gov/18274876/
3. Custers EJ, Ten Cate OT. Very long-term retention of basic science knowledge in doctors after graduation. Med Educ. 2011. https://pubmed.ncbi.nlm.nih.gov/21401691/
4. Michael J, McFarland J. The core principles ("big ideas") of physiology: results of faculty surveys. Adv Physiol Educ. 2011. https://pubmed.ncbi.nlm.nih.gov/22139767/
5. Michael JA, Wenderoth MP, Modell HI, et al. Undergraduates' understanding of cardiovascular phenomena. Adv Physiol Educ. 2002. https://pubmed.ncbi.nlm.nih.gov/12031940/
6. Dunlosky J, Rawson KA, Marsh EJ, et al. Improving Students' Learning With Effective Learning Techniques: Promising Directions From Cognitive and Educational Psychology. Psychol Sci Public Interest. 2013. https://pubmed.ncbi.nlm.nih.gov/26173288/
7. Versteeg M, van Blankenstein FM, Putter H, et al. Peer instruction improves comprehension and transfer of physiological concepts: a randomized comparison with self-explanation. Adv Health Sci Educ Theory Pract. 2019. https://pubmed.ncbi.nlm.nih.gov/30343408/
8. StatPearls. Physiology, Cardiac Output. StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/29262215/
9. StatPearls. Vitamin B1 (Thiamine) Deficiency. StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/30725889/
10. Larsen DP, Butler AC, Roediger HL. Test-enhanced learning in medical education. Med Educ. 2008. https://pubmed.ncbi.nlm.nih.gov/18823514/
11. Daley BJ, Torre DM. Concept maps in medical education: an analytical literature review. Med Educ. 2010. https://pubmed.ncbi.nlm.nih.gov/20374475/
12. Karpicke JD, Blunt JR. Retrieval practice produces more learning than elaborative studying with concept mapping. Science. 2011. https://pubmed.ncbi.nlm.nih.gov/21252317/
13. StatPearls. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/31082077/
14. Woods NN, Brooks LR, Norman GR. The value of basic science in clinical diagnosis: creating coherence among signs and symptoms. Med Educ. 2005. https://pubmed.ncbi.nlm.nih.gov/15612907/
15. Peixoto JM, Mamede S, de Faria RMD, et al. The effect of self-explanation of pathophysiological mechanisms of diseases on medical students' diagnostic performance. Adv Health Sci Educ Theory Pract. 2017. https://pubmed.ncbi.nlm.nih.gov/28144797/
16. Bj S, Mishra G, Sukul RR, et al. Impact of integrated clinical case exposure on phase I MBBS students in their learning process in biochemistry. BMC Med Educ. 2025. https://pubmed.ncbi.nlm.nih.gov/41199200/