Natriuretic Peptides and Blood Pressure Homeostasis: Implications for MANP, a Novel Guanylyl Cyclase a Receptor Activator for Hypertension
Crohn's Disease: What It Is, Why It Happens, And How It Affects You
Crohn's disease, also known as Crohn's disease, is a type of chronic inflammatory bowel disease (IBD) that causes irritation and swelling in the digestive tract. Regional enteritis is another term often used to describe Crohn's disease. Unlike some other bowel disorders, Crohn's doesn't just affect one area—it can show up anywhere from the mouth to the anus. But most commonly, it tends to strike the tail end of the small intestine (the terminal ileum) and the start of the colon [6], [7]. One of the unique features of Crohn's is that it doesn't spread evenly. Instead, it creates "skip lesions," or patches of inflammation with healthy tissue in between. The chronic inflammation also goes deep into the wall of the intestine, which can lead to more severe complications over time.
Table of Contents
Key Characteristics of Crohn's DiseaseCrohn's stands out because of its wide-reaching and unpredictable nature. In many cases, people experience inflammation that's deep and widespread, leading to significant symptoms like severe diarrhea. This is called transmural involvement, and it means the entire thickness of the intestinal wall is affected—not just the surface. That's part of what makes Crohn's more complex and often more aggressive than similar conditions affecting the gastrointestinal tract.
Areas of InvolvementCrohn's disease is known for targeting:
This ability to "jump around" and affect different sections is one of the key traits that helps doctors tell Crohn's apart from ulcerative colitis, a closely related form of IBD.
Common Symptoms: Abdominal PainSymptoms can vary quite a bit depending on where the inflammation occurs, but the most common ones include:
In severe cases, symptoms may be more intense and require aggressive treatment, including surgical intervention.
These symptoms might come and go, with periods of relative calm followed by sudden flare-ups. The unpredictability is part of what makes daily life with Crohn's difficult for many people.
Complications Beyond the GutCrohn's isn't just a digestive problem—it can also have extraintestinal manifestations, meaning issues that pop up in other parts of the body. Some people experience:
Internally, long-term inflammation can lead to serious problems like strictures (narrowing of the intestines), fistulas (abnormal connections between organs), and abscesses (infected pockets).
What Causes Crohn's Disease?There's no single cause, but researchers believe the exact cause of Crohn's is triggered by a mix of genetic, environmental, and immune system factors. Understanding who may develop Crohn's disease is crucial, as genetic predisposition, environmental influences, and lifestyle choices such as smoking play significant roles.
Contributing Factors: Immune SystemTwo major risk factors stand out:
Crohn's is on the rise around the world, affecting more people with Crohn's disease in both high-income and low-income countries than ever before. This increase in cases is leading to more severe disease, making it a growing global health concern [3], [4]. Cases are being diagnosed in both adults and children, which means more focus is being put on early detection and better management strategies.
How Is It Diagnosed?Because symptoms can overlap with other digestive disorders, getting Crohn's disease diagnosed involves piecing together a full picture. A blood test is often part of the diagnostic process, checking for anemia and signs of infection to help confirm the condition alongside other tests and procedures:
Doctors may use:
There's also growing interest in biomarkers, which are substances in the blood or stool that can help diagnose or track the disease [7], [8].
Living with Crohn's: Quality of Life MattersLiving with Crohn's means managing not just physical symptoms but also emotional and psychological challenges. The disease often affects:
Because of its chronic nature, long-term support and a good healthcare team can make a huge difference in maintaining a fulfilling and more normal life. Effective treatment options can help decrease inflammation and relieve symptoms, making it easier to manage the condition.
Final ThoughtsCrohn's disease is more than just an upset stomach—it's a lifelong inflammatory condition that can impact every part of a person's life. There is no known cure for Crohn's disease, but ongoing research and treatment options aim to manage symptoms and promote long-term remission. With its patchy inflammation, deep tissue damage, and wide-ranging symptoms, it requires a thoughtful, multi-pronged approach to care. Scientists are still unraveling its mysteries, especially when it comes to triggers and biomarkers, but progress is happening. Early diagnosis, personalized treatment, and ongoing support are all key to helping people live well with Crohn's disease.
References[1] Roda, G., Chien Ng, S., Kotze, P. G., Argollo, M., Panaccione, R., Spinelli, A., Kaser, A., Peyrin-Biroulet, L., & Danese, S. (2020). Crohn's disease. Nature reviews. Disease primers, 6(1), 22. Https://doi.Org/10.1038/s41572-020-0156-2
[2] Feuerstein, J. D., & Cheifetz, A. S. (2017). Crohn Disease: Epidemiology, Diagnosis, and Management. Mayo Clinic proceedings, 92(7), 1088–1103. Https://doi.Org/10.1016/j.Mayocp.2017.04.010
[3] Torres, J., Mehandru, S., Colombel, J. F., & Peyrin-Biroulet, L. (2017). Crohn's disease. Lancet (London, England), 389(10080), 1741–1755. Https://doi.Org/10.1016/S0140-6736(16)31711-1
[4] Veauthier, B., & Hornecker, J. R. (2018). Crohn's Disease: Diagnosis and Management. American family physician, 98(11), 661–669. Https://pubmed.Ncbi.Nlm.Nih.Gov/30485038/
[5] Gajendran, M., Loganathan, P., Catinella, A. P., & Hashash, J. G. (2018). A comprehensive review and update on Crohn's disease. Disease-a-month : DM, 64(2), 20–57. Https://doi.Org/10.1016/j.Disamonth.2017.07.001
[6] Dolinger, M., Torres, J., & Vermeire, S. (2024). Crohn's disease. Lancet (London, England), 403(10432), 1177–1191. Https://doi.Org/10.1016/S0140-6736(23)02586-2
[7] Laass, M. W., Roggenbuck, D., & Conrad, K. (2014). Diagnosis and classification of Crohn's disease. Autoimmunity reviews, 13(4-5), 467–471. Https://doi.Org/10.1016/j.Autrev.2014.01.029
[8] Pasternak, G., Chrzanowski, G., Aebisher, D., Myśliwiec, A., Dynarowicz, K., Bartusik-Aebisher, D., Sosna, B., Cieślar, G., Kawczyk-Krupka, A., & Filip, R. (2023). Crohn's Disease: Basic Characteristics of the Disease, Diagnostic Methods, the Role of Biomarkers, and Analysis of Metalloproteinases: A Review. Life (Basel, Switzerland), 13(10), 2062. Https://doi.Org/10.3390/life13102062
[9] Ballester Ferré, M. P., Boscá-Watts, M. M., & Mínguez Pérez, M. (2018). Crohn's disease. Enfermedad de Crohn. Medicina clinica, 151(1), 26–33. Https://doi.Org/10.1016/j.Medcli.2017.10.036
[10] Wilkins, T., Jarvis, K., & Patel, J. (2011). Diagnosis and management of Crohn's disease. American family physician, 84(12), 1365–1375. Https://pubmed.Ncbi.Nlm.Nih.Gov/22230271/
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Cholera: Why Is A Preventable Disease Still Taking Lives?
Chifuniro bathing her son. Malawi, 2023
WaterAid
The global toll of a preventable diseaseCholera is a deadly diarrhoeal disease spread through ingesting contaminated food and water. Entirely preventable, it can kill within hours if a severe case is left untreated.
The World Health Organization estimates that each year, cholera affects up to 4 million people globally and causes as many as 143,000 deaths. But these figures fall far short of the true toll. Stigma, concerns over trade and tourism and weak surveillance systems mean many cases go unreported, leaving the full scale of the crisis hidden from view.
Sange's experience: the devastating impact of choleraSange Mbilishi is a nurse and midwife at a hospital in Lusaka, Zambia. She recalls what it was like to treat patients during Zambia's worst cholera epidemic last year.
"We had no option but to source nurses from other wards. Even midwives ended up being recruited into cholera medical tents to help. It was emotional because cholera is preventable and yet, we see a huge number of people dying. You become attached to these patients. You see somebody walking in and before you know it, they are gone."
Cholera: a disease of vulnerability"We were never told exactly what caused the cholera that took my grandmother, but I think it was from run-off water." – Chifuniro, a young mother from Namizimbe in Malawi.
"Every death from cholera is a failure in providing basic water, sanitation and hygiene services," says Irene Owusu-Poku, Health Policy Analyst at WaterAid. "It is a disease of vulnerability – thriving in places where people lack or have limited access to clean water and sanitation, where health systems are fragile and where shocks like drought and flooding displace entire communities."
And yet, 411 million people in the world – 1 in 20 – have no choice but to drink dirty water.
Repeated cholera outbreaks signal a chronic lack of investment in water, sanitation and hygiene, a failure to tackle the root cause of the disease and to meet the needs of people most affected by it. The burden falls disproportionately on communities in regions such as Africa, the Eastern Mediterranean and South-East Asia, where access to these basic services remains limited.
Women and girls are often at a greater risk of contracting the disease due to their roles as primary caregivers, cooks and water collectors.
Increasing water scarcity is making access to clean water harder for many communities. Extreme floods and prolonged droughts are damaging fragile water and sanitation systems, increasing the risk of outbreaks.
"Unless governments act now to improve water-sanitation and hygiene services, cholera will continue to threaten lives, particularly in the world's most vulnerable places," says Owusu-Poku. "Tackling this crisis requires not only infrastructure and investment, but also a commitment to addressing the needs of vulnerable populations."
WaterAid's global analysis: how to fast-track cholera preventionAccording to WaterAid's recent global political economy analysis, cholera is regularly given lower priority over other economic issues. Water, sanitation and hygiene services are treated as a secondary concern and cholera prevention remains reactive rather than strategic.
"And now reductions in assistance from numerous governments are worsening the cholera crisis, as it struggles for political attention and resources – much like many other pressing challenges."
"Improving access to clean water in high-risk regions could halve cholera and other diarrhoeal disease cases and deaths—and save over a billion dollars," says Owusu-Poku, citing findings from Southern Africa, including Malawi and Zambia.
This research underscores clear opportunities for action. "Nobody should lose their lives or loved ones to a disease that's been eliminated in many parts of the world."
A simple solutionThe suffering caused by cholera is needless. The disease can be stopped in its tracks – and sustainably prevented – through adequate investment in clean water, sanitation and hygiene services.
Focused investment in these essentials in cholera-affected areas is the best long-term way to stop the disease. It tackles the root causes of outbreaks and brings wider health and economic benefits – with each dollar spent generating an estimated tenfold benefit.
Estevão Manuel David, a general practitioner and the Director of the Etatara Health Unit in Mozambique shares his experience after running water was installed in his health unit for the first time. "During a cholera outbreak, access to water made a huge difference. Patients could wash their hands when they arrived, helping stop the disease from spreading. They didn't take cholera back home with them. It really helped to break the cycle of transmission," he said.
Making cholera a disease of the pastWhen cholera surges anywhere, it threatens to spread farther with no respect for national borders. World leaders have the power to eliminate the disease by prioritising the provision of clean water, decent toilets, and good hygiene services for all.
"WaterAid will continue to work with people, supporting communities to build and maintain water, sanitation and hygiene infrastructure. But governments must step up," says Owusu-Poku. "Ending cholera means working together – across health, water and humanitarian sectors – with a coordinated, long-term plan and strong partnerships at every level. No one should die from a preventable disease."
With universal access to clean water, sanitation, and hygiene, cholera can become a disease of the past – for everyone, everywhere.
Read the full report here.
Why Treating Your Diarrhea Could Make Things Worse
This contradictory condition affects thousands, yet many suffer in silence due to misdiagnosis and embarrassment
For those experiencing paradoxical diarrhea, the body sends confusing signals that can leave both patients and healthcare providers perplexed. This unusual digestive condition creates a seemingly impossible situation: constipation and diarrhea occurring simultaneously. The medical reality behind this contradiction reveals important insights about digestive health that too many people overlook.
Also known as overflow diarrhea, this condition develops when watery stool leaks around a hardened mass of stool that has become lodged in the colon. Far from being rare, paradoxical diarrhea affects thousands of Americans each year, though precise statistics remain elusive due to underreporting and misdiagnosis. Understanding this condition can help those suffering recognize the signs and seek appropriate treatment rather than addressing only the most obvious symptoms.
The mechanical mystery behind the conditionParadoxical diarrhea develops through a specific sequence of events within the digestive tract. When constipation persists for an extended period, stool remains in the colon longer than normal, allowing excessive water absorption. This creates hardened stool that can form a blockage, known medically as fecal impaction.
As this impaction grows, it can partially or completely obstruct the intestinal passage. New digestive material continuing to enter the system has nowhere to go, building up behind the blockage. The body, sensing this accumulation, increases intestinal secretions to try dislodging the obstruction.
These excess secretions, combined with newly formed stool, create liquid waste that literally flows around the hardened mass. This watery stool then leaks past the impaction and exits the body, presenting as diarrhea despite the underlying constipation remaining unresolved.
The mechanics explain why treating only the diarrhea symptoms can actually worsen the condition. Anti-diarrheal medications reduce intestinal motility and fluid secretion, potentially making the impaction more severe while doing nothing to address the root cause.
Who faces the highest riskCertain populations face elevated risk for developing paradoxical diarrhea. Older adults represent the largest affected group, with studies showing that up to 50% of nursing home residents experience fecal impaction at some point, often leading to overflow diarrhea.
This heightened risk stems from multiple factors common in older populations: decreased physical activity, weakened abdominal muscles, medications with constipating side effects, and reduced sensation of the need to defecate. The body's natural warning systems that signal bowel movements become less effective with age, allowing constipation to develop unnoticed.
Children can also develop paradoxical diarrhea, particularly those with chronic constipation issues or those who habitually withhold bowel movements. In pediatric cases, psychological factors often play a role, with some children avoiding bowel movements due to previous painful experiences or inconvenient timing.
Individuals with neuromuscular conditions face particular vulnerability to this condition. Diseases like multiple sclerosis, Parkinson's disease, and spinal cord injuries can disrupt the normal nerve signals that control bowel function, leading to severe constipation and subsequent overflow.
Patients with Irritable Bowel Syndrome with Mixed Bowel Habits (IBS-M) represent another high-risk group. This gastrointestinal disorder creates alternating patterns of constipation and diarrhea, which can mask or exacerbate paradoxical diarrhea episodes.
Recognizing the contradictory symptomsThe confusing nature of paradoxical diarrhea stems from its contradictory symptoms. Most patients initially notice frequent episodes of loose, watery stool that suggest typical diarrhea. However, closer examination reveals these symptoms coincide with constipation markers:
Abdominal distension and bloating remain persistent despite diarrhea episodes, indicating stool retention. Many patients report feeling that their bowels never completely empty, even after multiple diarrhea episodes. Digital rectal examinations typically reveal hard stool present in the rectum despite recent watery bowel movements.
The pattern of bowel movements also provides important clues. Paradoxical diarrhea often follows a pattern where small amounts of liquid stool pass multiple times throughout the day, rather than the larger volume typical of infectious or inflammatory diarrhea.
Pain patterns differ from ordinary diarrhea as well. While typical diarrhea usually involves cramping that resolves after bowel movements, paradoxical diarrhea patients often experience constant discomfort or pain in the lower abdomen that diarrhea episodes fail to relieve.
Perhaps most distinctively, patients with this condition may notice streaks of liquid stool on the outside of formed, hard stool when they do pass solid waste. This visual evidence directly demonstrates the overflow mechanism occurring within the intestines.
Medical detection methodsHealthcare providers employ several approaches to confirm suspected cases of paradoxical diarrhea. The diagnostic process typically begins with a comprehensive medical history focused on bowel habits, medication use, diet, and activity levels. The timing, frequency, and characteristics of bowel movements provide crucial context.
Physical examination focuses on abdominal assessment, checking for distension, tenderness, and palpable masses that might indicate impacted stool. The digital rectal examination represents a particularly important diagnostic tool, allowing direct detection of impacted stool in the rectum.
When physical findings prove inconclusive, imaging studies become necessary. Plain abdominal X-rays can reveal significant stool accumulation throughout the colon, while contrast studies like barium enemas provide more detailed visualization of potential obstructions.
In cases where the cause remains unclear, colonoscopy may be recommended to rule out structural abnormalities or inflammatory conditions that might contribute to the symptoms. This procedure allows direct visualization of the colon's interior and collection of tissue samples if needed.
Laboratory tests generally play a supporting role in diagnosis, primarily helping exclude other causes of diarrhea such as infections or inflammatory bowel disease. Stool samples may be analyzed for pathogens, blood, inflammatory markers, or fat content to rule out alternative diagnoses.
Effective treatment approachesSuccessfully treating paradoxical diarrhea requires addressing the underlying impaction rather than merely controlling diarrhea symptoms. The treatment approach depends on the severity of the impaction and the patient's overall health status.
For mild cases, oral hydration combined with osmotic laxatives often proves sufficient. Polyethylene glycol solutions draw water into the intestines, softening impacted stool and facilitating passage. These treatments typically work over 1-3 days to gradually resolve the impaction.
Moderate impactions may require more aggressive interventions like suppositories or enemas. These treatments deliver softening agents directly to the site of the impaction, helping break down the hardened stool mass. Mineral oil enemas prove particularly effective as they both soften stool and lubricate the intestinal passage.
Severe impactions necessitate manual disimpaction, a procedure performed by healthcare providers where the hardened stool is physically broken up and removed. This procedure typically requires sedation or analgesia to minimize discomfort and may be followed by enemas to clear remaining material.
For recurring cases, maintenance therapy becomes essential after resolving the acute impaction. This typically involves scheduled laxative regimens, dietary modifications, and sometimes prokinetic medications that enhance intestinal motility to prevent future impactions.
Prevention strategies and lifestyle modificationsPreventing recurrence requires addressing the factors that led to the initial constipation. Dietary modifications play a central role, with increased fiber intake being particularly beneficial. Soluble fiber from sources like oats, beans, and psyllium helps form soft, bulky stools that move more easily through the intestines.
Adequate hydration supports proper stool consistency, with medical guidelines recommending 2-3 liters of fluid daily for most adults. This ensures sufficient water remains in the intestinal contents to prevent excessive hardening of stool.
Regular physical activity stimulates intestinal motility through multiple mechanisms. Exercise increases blood flow to digestive organs, stimulates movement of intestinal muscles, and promotes regular passage of stool through the colon. Even moderate activity like walking for 30 minutes daily can significantly reduce constipation risk.
Toilet habits also influence constipation risk. Establishing a regular bowel routine, ideally after breakfast when the gastrocolic reflex is strongest, helps train the body to move stool consistently. Responding promptly to the urge to defecate prevents stool from becoming harder through prolonged water absorption.
For high-risk individuals, particularly older adults and those with mobility limitations, preventive laxative regimens may be recommended. These scheduled mild laxatives prevent constipation from developing rather than treating it after it occurs.
When to seek immediate medical attentionWhile paradoxical diarrhea often resolves with appropriate treatment, certain warning signs indicate the need for urgent medical evaluation. Severe abdominal pain, especially if constant or worsening, may signal complications like bowel perforation or obstruction that require emergency intervention.
Bloody diarrhea with substantial volume rather than minor streaking suggests inflammation or tissue damage beyond simple impaction. This may indicate inflammatory bowel disease, infection, or ischemia that requires prompt diagnosis and treatment.
Fever occurring alongside paradoxical diarrhea symptoms raises concern for infection, particularly if the impacted stool has damaged the intestinal lining, allowing bacteria to enter the bloodstream. This potential sepsis risk necessitates immediate medical care.
Signs of dehydration, including decreased urination, dry mouth, extreme thirst, or dizziness, require prompt attention. The combination of fluid loss through diarrhea and reduced oral intake due to discomfort can rapidly lead to dangerous dehydration, particularly in older adults and young children.
Vomiting that accompanies paradoxical diarrhea symptoms may indicate complete bowel obstruction, a medical emergency requiring immediate evaluation and possibly surgical intervention.
Long-term complications and managementWhen paradoxical diarrhea recurs or persists, several potential complications may develop. Chronic overflow can weaken the anal sphincters through repeated stretching, potentially leading to fecal incontinence that persists even after resolving the impaction.
Recurrent impactions may stretch the colon over time, potentially leading to megacolon where portions of the intestine become permanently dilated. This condition further compromises normal bowel function and increases the risk of serious complications including toxic megacolon.
The cycle of constipation and overflow can disrupt the gut microbiome, altering the balance of beneficial bacteria in the intestines. This dysbiosis may contribute to prolonged digestive symptoms and increased vulnerability to intestinal infections.
Long-term management focuses on preventing these complications through regular follow-up with healthcare providers, maintenance treatment plans, and lifestyle modifications. For some patients, particularly those with neurological conditions affecting bowel function, bowel management programs may be necessary, involving scheduled toileting, regular use of suppositories, and sometimes manual evacuation techniques.
Breaking the silence around paradoxical diarrheaPerhaps the greatest challenge in addressing paradoxical diarrhea is overcoming the stigma that prevents many sufferers from seeking help. Bowel symptoms rank among the most embarrassing health topics for many people, leading to delayed diagnosis and unnecessary suffering.
Healthcare providers can help by normalizing discussions about bowel habits during routine examinations and creating opportunities for patients to raise concerns in a comfortable environment. Patient education materials that clearly explain the mechanical nature of the condition can help remove shame by emphasizing that paradoxical diarrhea represents a physical process rather than a personal failing.
Support groups, whether in-person or online, provide valuable spaces for sharing experiences and coping strategies. For many patients, simply knowing they aren't alone in experiencing this contradictory condition provides significant psychological relief.
Understanding paradoxical diarrhea requires recognizing the complex interplay between anatomical structures, physiological processes, and lifestyle factors that influence bowel function. By addressing this condition comprehensively rather than treating only the most obvious symptoms, healthcare providers can help patients resolve both the embarrassing overflow and the underlying constipation that causes it.
For anyone experiencing the confusing combination of constipation and diarrhea, the most important step is seeking proper medical evaluation. With appropriate diagnosis and treatment, this puzzling condition can be effectively resolved, restoring comfortable and predictable bowel function.
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