This slides gives you the Facts & Salient features of Liver Cysts / Interesting Case Reports covering Main Departments of Clinical side with Recent Advances made in the treatment of Liver cyst & Key points.
Adhesions may be acquired or congenital; however, most are acquired as a result of peritoneal injury, the most common cause of which is abdomino-pelvic surgery. 4. Less commonly, adhesions may form as the result of inflammatory conditions, intraperitoneal infection or abdominal trauma.
This is a powerpoint slideshow discussing some of the commonest disorders of colon; namely Hirschsprung's disease, Diverticular diseases of colon, ulcerative colitis, pseudomembranous colitis and ischemic colitis.
Gastroparesis is a syndrome of objectively delayed gastric emptying in the absence of a mechanical obstruction and cardinal symptoms of nausea, vomiting, early satiety, bloating, and/or upper abdominal pain
This slides gives you the Facts & Salient features of Liver Cysts / Interesting Case Reports covering Main Departments of Clinical side with Recent Advances made in the treatment of Liver cyst & Key points.
Adhesions may be acquired or congenital; however, most are acquired as a result of peritoneal injury, the most common cause of which is abdomino-pelvic surgery. 4. Less commonly, adhesions may form as the result of inflammatory conditions, intraperitoneal infection or abdominal trauma.
This is a powerpoint slideshow discussing some of the commonest disorders of colon; namely Hirschsprung's disease, Diverticular diseases of colon, ulcerative colitis, pseudomembranous colitis and ischemic colitis.
Gastroparesis is a syndrome of objectively delayed gastric emptying in the absence of a mechanical obstruction and cardinal symptoms of nausea, vomiting, early satiety, bloating, and/or upper abdominal pain
Evaluation and management of patients with Dyspepsia.pptxgarvitnanecha
Evaluation and management of patients with Dyspepsia.
Dyspeptic symptoms.
Causes of dyspepsia
Approach to adult with Dyspepsia.
Newer advancement about diagnosing dyspepsia causes.
GERD and peptic ulcer and many more organic diseases.
Functional Dyspepsia and organic dyspepsia
Nursing assessment and Management clients with Pancreatic disordersANILKUMAR BR
The pancreas, located in the upper abdomen, has endocrine as well as exocrine functions .
The secretion of pancreatic enzymes into the gastrointestinal tract through the pancreatic duct represents its exocrine function.
The secretion of insulin, glucagon, and somatostatin directly into the bloodstream represents its endocrine function.
Pancreatitis (inflammation of the pancreas) is a serious disorder. The most basic classification system used to describe or categorize the various stages and forms of pancreatitis divides the disorder into acute or chronic forms.
Acute pancreatitis can be a medical emergency associated with a high risk for life-threatening complications and mortality, whereas chronic pancreatitis often goes undetected until 80% to 90% of the exocrine and endocrine tissue is destroyed.
Acute pancreatitis does not usually lead to chronic pancreatitis unless complications develop.
An inflammatory condition of the pancreas
Acute pancreatitis is a reversible process,
whereas Chronic pancreatitis (CP) is irreversible
Acinar Cell Injury
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. Definition: Chronic pancreatitis is a disease process characterised by irreversible
damage to pancreas. and condition is defined by presence of histological abnormalities,
including chronic inflammation, fibrosis and progressive destruction of both exocrine
and eventually endocrine pancreatic tissue(atrophy)
-Harrisons 20th Ed.
Acute pancreatitis and chronic pancreatitis are assumed to be
different disease processes, and most cases of acute
pancreatitis do not result in chronic disease.
PREVALANCE:
10-15/1,00,000 in western countries (alcohol misuse).
114-200/1,00,000 in southern India (severe chronic calcific pancreatitis in
non-alcoholics, possibly due to malnutrition, deficient trace elements and
nutrients and cassava consumption). Other causes are listed in next slide.
Typical age 35-55
3. Etiologic factors associated With CP (mnemonic-TIGAR-O)
Developed by Midwest multicenter pancreatic study group
-Harrisons 20th
Toxic –metabolic
Alcohol, Hyperlipidemia,
Tobacco smoking Chronic Renal Failure
Hypercalcemia Medications/ toxins (Organotin compound)
Idiopathic
Tropical Early onset/ Late onset
Genetic
Cataionic trypsinogen (PRSS 1), Pancreatic secretory trypsin inhibitor gene(SPINK1)
Cystic Fibrosis transamembrane conductance regulator
gene (CFTR)
Calcium-sensing receptor(CASR),
Chymotrypsin C gene(CTRC),
Autoimmune
Type-1/Type-2 IgG4 systemic
Recurrent and severe acute pancreatitis
Recurrent acute pancreatitis Post-necrotic
Obstructive
Pancreas divisum Duct obstruction(tumor),
Preampulary ductal wall cyst Post traumatic pancreatic ductal scar
*Gall stones do not cause CP but may be observed as an incidental finding
5. Sentinel acute pancreatitis event
hypothesis
• According to this theory, First episode of acute pancreatitis is as a
result of unregulated trypsin activation leads to massive
inflammatory response divided into early and late phases.
• Early phase response due to –inflammatory cells and
cytokines(TGF-BETA1, IL-1, IL-6) –fibrosis and activation of
pancreatic stellate cells. If no further exposure to noxious stimulus
pancreas should heal and recover. If noxious stimulus persists then
activated PSC will directly stimulate cytokines leading to fibrosis
and CP. PSC pathway somehow unifies other theories and describes
common pathway.
• Recent studies also noted that PSC are also activated by its own
intrinsic activation through macrophages this may be a reason for
continuous process of inflammation and fibrosis of pancreas even
after removal of noxious stimulus after diagnosis of CP.
6. • Chronic pancreatitis is a relapsing condition.
• Predominant symptoms 1. Abdominal pain or maladigestion and weight loss.
• Hall mark of CP is Abdominal pain, occurring in 95% of cases. Pain may be quit variable in
location, severity and frequency and can be episodic, lasting hours to days, or it can persist
for months or even years.
• The pain is characteristically steady in the epigastrium also some patients describes it as
stabbing pain, and it frequently radiates to the back. Importantly Eating may exacerbate
pain , leading to fear of eating with consequent weight loss.
• Chronic Diarrhea, Steatorrhea, fatigue.
• Creatrorrhea in late stage of disease.
• Patients with CP have significant morbidity.
• Despite steatorrhea, clinically apparent deficiency of fat soluble vitamins are
uncommon.
Clinical features
7. Pathogenesis of pain
• 1. Compartmental syndrome pain due to large and small duct obstruction.
• 2. Neurogenic pain due to stretching of nerves.
• 3. Pain due to ongoing inflammation due to release of local mediators like bradykinine,
serotonin, tachykinine etc.
• 4. Neuronal damage due to peripheral sensitization and resultant central sensitization
fundamental to development of persistent and refractory pain in CP.
• 5. Trypsin also having effect on sensory neurons.
• 6. ‘Salutogenic response’ –
Involvement of immune system-modulation of immune response by centres in brain.
Abnormal immune response linked to brain mediated mechanisms, sustained the visceral
inflammation and prolonged duration of pain-mal adaptive brain response.
Which is treated by ‘Transcranial magnetic stimuli’.-IN TRIAL
8. Investigations
Investigations
To establish diagnosis
1. Ultra sound abdomen
2. CT- may show atrophy, ductal dilatation or calcification
3. Abdominal X-Ray-may show calcification
4. MRCP
5. Endoscopic USG
Test to define pancreatic function
1. Collect of pure pancreatic juice after secretin injection(invasive test seldom used)
2. Faecal pancreatic elastase
Test to demonstrate anatomy prior to surgery
MRCP
12. Step wise approach to diagnose CP -Harrisons 20th Ed
Initial
imaging
modality
• Clinical signs and symptoms suggestive of CP disease: Abdominal pain, weight loss, steatorrhea, malabsorption, history of
alcohol abuse, recurrent pancreatitis, fatty-food intolerance
• History, physical examination, review of laboratory reports and consider local elastase measurement
STEP-1
•CT Scan- CP Diagnostic criteria: calcification in combination with atrophy and/or dilated duct
•Diagnostic criteria-No further imaging needed
•Inconclusive/ no diagnostic results-continue step-2
STEP-2
•MRI/MRCP with secretin enhancement(s MRCP)- CP Diagnostic criteria: Cambridge class III, dilated duct, atrophy of gland, filling
defect in duct s/o stones
•Diagnostic criteria-No further imaging needed
•Inconclusive/ no diagnostic results-continue step-3
STEP-3
• Endoscopic ultra sound(EUS) with quantification of parenchymal and ductal criteria- Diagnostic criteria: 5 or >5 EUS
criteria
• Diagnostic criteria-No further imaging needed
• Inconclusive/ no diagnostic results-continue step-4
STEP-4
• Pancreas function test(with secretin)-gastroduodinal or endoscopic collection method- CP diagnostic criteria: <80
mmol/L
• Diagnostic criteria-No further imaging needed
• Inconclusive/ no diagnostic results-continue step-5
STEP-
5
•ERCP- Diagnostic criteria: Cambridge class III, dilated main pancreatic duct, and greater than 3 dilated side branch
•Diagnostic criteria-No further imaging needed
•Inconclusive/ no diagnostic results require monitoring of signs and symptoms and repeat testing in 6 months- 1year
13. Initial imaging modalities
1. X-ray Plain film of the abdomen.
2. Measurement of fecal pancreatic enzyme elastase
Decreased Elastase 1 activity (FE-1) in stools is found in CP and Cystic
Fibrosis
FE-1 LEVEL >200 microg/g is normal <100microgm/gm considered as
Pancreatic Exocrine Insufficiency.
3. Serum pancreatic enzymes-amylase, lipase
14. Tests for exocrine pancreatic
function
1. Direct stimulation of pancreas by I/V infusion of
secretin followed by measurement of duodinal
contents (principle –the pancreatic secretory response
is directly related to the functional mass of pancreas)
*Bicarbonate concentration <80 mmol/L is considered
abnormal secretory function and s/o CP.
2. Measurement of fecal pancreatic enzyme elastase
*Decreased Elastase 1 activity (FE-1) in stools is found in
CP and Cystic FibrosisFE-1 LEVEL >200 microg/g is
normal <100microg/g considered as PEI.
15. Treatment
• Aim – Lifestyle modifications, pain management, PERT and management of complications
• 1. Lifestyle modifications:
• Complete cessation of alcohol/tobacco smocking
• Low fat meals
• Regular exercises and nutrient rich food
• 2. Pain management
• Anti-pain medications– narcotics tramadol, codeine(addiction), pregalin
• Surgical pain control :
• Endoscopic treatment: Sphinctoretomy, dilatation of strictures, caliculi removal, duct
stenting and drainage of pseudocyst.
• Partial/total pacreatectomy
• 3. Pancreatic enzyme replacement treatment (CREON, ULTRESA). Because of
gastroparesis PERT fails to reduce pain therefore prokinetic drugs along with PPI are
beneficial.
• 4. Complications– acute pancreatitis, abscess, ductal damage
16. Complications of chronic pancreatitis
include:
Pancreatic Pseudocyst DM
Obstructive jaundice Pancreatic cancer
Pancreatic main duct stricture
Duodenal stricture
17. Summary
• CP and the pain associated with it, is a complex clinical syndrome that has
devastating effect on those who are suffering from it.
• It can also be described as a group of disorder with diverse etiologies and
multiple pathological processes, leading to the physiological destruction of
pancreas.
• Management needs multidisciplinary approach includes-Primary care
physician, Gastro-enterologist, Endocrinologist, Psychiatrists, Pancreatic
surgeon, Anaesthetics.
• Pathophysiology of CP disease is yet to be learned deeply IN PERTICULAR THE
PATHOGENESIS OF PAIN.
• CNS-HAS A ROLE IN GENERATING MODULATING AND MAGNIFYING THE
PAIN OF CP.
My topic of presentation is Chronic pancreatitis in which I will highlights it’s definition, prevalence, Pathophysiology & etiology, Clinical features, Treatment part and related complications of the disease.
The reason why I selected this topic is 1. Presently we have two case of CP and 2. Severe morbidity especially due to continuous abdominal pain (which is very difficult to treat), which propelled them into frequent hospital admission. Patient’s general health, near cacchexic depriving them from leading normal life.
Here in these cases I have also noticed their dependence on TAB. TRAMADOL for their pain - though results of this medicine are questionable.
So Pancreas is a mixed type of gland and situated retro- peritoneal and in horizontal position at the level of L1. Its main function is to secrete digestive enzymes and aid in digestion of food in gut and regulation of metabolism by its endocrine hormone secretions.
One of it’s disease is ‘Chronic pancreatitis’
It is a disease process characterized by irreversible damage to pancreas which is evident by histological abnormalities including chronic inflammation, fibrosis and progressive destruction of both exocrine and eventually endocrine pancreatic tissue.
Please note, Acute and chronic pancreatitis are assumed to be different disease process and most cases of acute pancreatitis does not result in chronic pancreatitis.
The depic-ed picture shows excised pancreas which is shrunk in size (i.e atrophied) with dilated pancreatic duct and also shows calcifications in pancreatic duct
Now coming to its prevalence,
in western countries it is 10-15/100000 population about 10 % of which is related to alcohol misuse.
In southern India it is 114-200/100000 population and it is characterized by chronic calcific pancreatitis in non-alcoholics, possibly due to malnutrition, deficient trace elements & nutrients and cassava consumption. Other etiological factors are listed in next slide.
C P usually occurs in the age group is 35-55 years and male are more affected than females (1:
Alcohol is the most common cause in clinically apparent CP and Cystic fibrosis in children. About 25 % adults with CP is alcohol related. Recent study shows out of this 25 % about 15 % are of due to genetic defects.
Smoking is an independent dose dependent risk factor for CP and recurrent acute pancreatitis.
Genetic defects that affects the gene encoding for trypsinogen. The defect in gene prevents destruction of prematurely activated trypsin and allows it to be resistant to intracellular protective effect of trypsin inhibitor. This repeated and continuous activation of digestive enzyme within the gland leads to acute injury and finally chronic pancreatitis.
There is documented mutation of CFTR gene. This gene functions as a cyclic AMP-REGULATED CHLORIDE channel, which leads to high concentration of macromolecules which can block the pancreatic duct.
Combination of N34S SPINK1 pancreatic secretary trypsin inhibitor gene mutation along with CFTR mutation increase risk by 900 folds.
Basically the gene defects which lead to failure of protective mechanism of pancreas from auto digestion will lead to chronic pancreatitis.
Auto immune pancreatitis (AIP) is an uncommon disorder of presumed autoimmune causation with characteristic histopathological, laboratory and morphological findings.
Two type AIP AND Idiopathic duct centric pancreatitis (IDCP).
In AIP pancreas is involved as part bof IgG4 systemic disease- histological findings include lymphoplasmocytic infiltrate, storiform fibrosis and abundant IgG4 cells. In IDCP- granulocytic infiltrate of duct wall with out IgG4 positve cells and systemic invovement.
The Myo clinic HISTORt criteria indicates that AIP can be diagnosed by the presence of one or more of the following
Histology 2. imaging, 3. eleveted IgG4, 4. other organ involvement and 5. response to Glucocorticoid therapy.
Alcohol and other risk factors may trigger chronic pancreatitis through multiple mechanisms.
The first sentinel episode of acute pancreatitis initiates an inflammatory response involving T-helper cell (Th). Then ongoing exposure to alcohol or other risk stimuli drives further inflammation but this is modified by regulatory T-cells(Treg).
Toxic metabolic risk – Direct toxic injury to ductal and acinar cells of pancreas and oxidative damage due to ethyl ester a by product of alcohol in acinar cell, predisposes acinal cells to destroy trypsinogen which leads to auto digestion of acinar cell.
Also directly stimulate CholeCystoKinin(CCK) production (duodenal I cells) – activation of pro-inflammatory transcription factor.
Genetic defects that affects the gene encoding for trypsinogen. The defect in gene prevents destruction of prematurely activated trypsin and allows it to be resistant to intracellular protective effect of trypsin inhibitor. This repeated and continuous activation of digestive enzyme within the gland leads to acute injury and finally chronic pancreatitis.
Combination of N34S SPINK1 pancreatic secretary trypsin inhibitor gene mutation along with CFTR mutation increase risk by 900 folds.
CFTR –cystic fibrosis trans-membrane conductance regulator -- associated with abnormalities of HCO3 secretion, ductal dilatation, ppt formation, pancreatic atrophy.
PRSS1 –cationic trypsinogen gene -- Once trypsinogen is activated to trypsin, becomes resistant to inactivation and activate other proenzymes leading to episodes of acute pancreatitis.
SPINK1 –serine protease inhibitor Kazal type -- Seen in pediatric Idiopathic CP, hereditary Pancreatitis, Tropical Pancreatitis, but not in chronic alcoholic pancreatitis
Necrosis fibrosis hypothesis -- Repeated episodes of acute pancreatitis with cellular necrosis or apoptosis, healing replaces necrotic tissue with fibrosis.
Ductal obstruction hypothesis –
Toxic stimuli- Protein rich pancreatic juice low in volume and HCO3 - Formation of protein presipitates ppt -plug - Calcification of ppt-duct stone formation- Ductul obstruction- Parenchymal damage
According to this theory, First episode of acute pancreatitis is as a result of unregulated trypsin activation leads to massive inflammatory response divided into early and late phases.
Early phase response due to –inflammatory cells and cytokines(TGF-BETA1, IL-1, IL-6) –fibrosis and activation of pancreatic stellate cells. If no further exposure to noxious stimulus pancreas should heal and recover. If noxious stimulus persists then activated PSC will directly stimulate cytokines leading to fibrosis and CP. PSC pathway somehow unifies other theories and describes common pathway. Recent studies also noted that PSC are also activated by its own intrinsic activation through macrophages this may be a reason for continuous process of inflammation and fibrosis of pancreas even after removal of noxious stimulus after diagnosis of CP.
Patients with CP seek medical attention predominantly because of two symptoms 1. abdominal pain or maldigestion and weight loss.
Abdominal pain may be quit variable in location, severity and frequency. The pain can be constant or intermittent with frequent pain free intervals.
Eating may exacerbate the pain, leading to a fear of eating with consequent weight loss. The spectrum of pain ranges for mild to quite severe, with narcotic dependence as frequent consequence. Pain may be releived by leaning forward or by drinking alcohol.
Maldigestion is manifested as chronic diarrhea, steatorrhea, weight loss and fatigue. Steatorrhea occurs when more than 90 % of pancreas tissue has been destroyed.. Protein malabsorption develops only in the most advance case (creatorrhea) About 20 % patients will present with symptoms of maldigestion without h/o abdominal pain..
Despite steatorrhea apparent deficiency of fat soluble vitamins is surprisingly uncommon.
Physical sign usually unimpressive, so there is disparity between the severity of abdominal pain and physical sign that usually consists of some mild tenderness.
Physical examination reveals thin, malnourished patient with epigastric tenderness.
There is no biomarker test for the disease. Incontrast to acute pancreatitis serum amylase and lipase levels are not strikingly elevated. Many patients may have IFG.The fecal elastase levels will be abnormal and small bowel biopsy will be normal in this patients. Fecal elastase level <100micro grmasgm of stools suggest severe pancreatic exocrine insufficiency.
Compartmental syndrome pain due to large and small duct obstruction
2. Neurogenic pain due to strtching of nerves
3. Pain due to ongoing inflammation due to release of local mediators likebradykinine, serotonin, tachykinine etc.
4. Neuronal damage due to peripheral sensitization and resultant central sensitization fundamental to development of persistant and refractory pain in CP.
5. Trypsin also having efect on sensory neurons
6. ‘Salutogenic response’ –
Invovement of immune system-modulation of immune response by centres in brain. Abnormal immune response linked to brain mediated mechanisms, sustained the visceral inflammation and prolonged duration of pain-mal adaptive brain response.
Which is treated by ‘Transcranial magnetic stimuli’.-IN TRIAL
Diagnosis of CP requires permanent histological irregularity with persistent pain, with clinical and functional impairment of pancreatic function.
Patients disease history i.e. h/o abdominal pain or malabsorption, steatorrhea, weight loss and DM in late stages, shall give rise to suspicion of the underlining disease. These patient shall undergo initial imaging modalities to r/o CP. Investigations can be divided in to three parts i.e. to establish diagnosis 2. To define pancreatic function and 3. To demonstrate anatomy before surgery
Patients history, clinical signs and symptoms (abdominal pain, weight loss steatorrhea, malabsorption, h/o alcohol abuse, recurrent pancreatitis, fatty food intolerance- s/o CP
Initial imagining shall be done with review of laboratory reports and faecal elastase measurement shall be considered.
STEP-01-CT Scan-which may shows pancreatic calcification with atrophy of pancreas tissue and dilated pancreatic duct. Inconclusive go for
STEP-02 -MRI/sMRCP: Cambridge class III, dilated duct atrophy of gland and filling defects in duct. Inconclusive go for
STEP-03- Endoscopic ultrasound (EUS) 5 or >5 EUS criteria, Inconclusive go for
STEP -04 - Pancreas function test(with secretin)-gastroduodinal or endoscopic collection method- CP diagnostic criteria: <80 mmol/L. Inconclusive go for
STEP-05 -ERCP- Diagnostic criteria: Cambridge class III, dilated main pancreatic duct, and greater than 3 dilated side branch
This I have already mentioned shall be done when suspicion arises
Already mentioned
Currently available diagnostic and treatment options for chronic pancreas are unsatisfactory in terms of early detection and prevention of it’s progression.
As CP is a slowly progressing and uncurable disease that continues to afflict patients life, treatments are relatively limited.4Oncetha patent is diagnosed we should actively support lifestyle modifications (mainly cessation of alcohol consumption and smoking). Pain control should be managed carefully to prevent drug addiction. Exocrine insufficiency shall be treated with pancreatic enzymes replacement (i.e.PERT) and strict control of DM to prevent secondary complications