Explain the pathogenesis with common clinical presentation of celiac disease Analyze the pathophysiology of Cohan€™s disease and relate genetic issues Differentiate between the five main infectious forms of hepatitis (A, B, C, D, E) from the two main non-infectious types of hepatitis (toxic and autoimmune) Elaborate on the pathogenesis and pathophysiology of pancreatic cancer

Explain the pathogenesis with common clinical presentation of celiac disease Analyze the pathophysiology of Cohan€™s disease and relate genetic issues Differentiate between the five main infectious forms of hepatitis (A, B, C, D, E) from the two main non-infectious types of hepatitis (toxic and autoimmune) Elaborate on the pathogenesis and pathophysiology of pancreatic cancer

Explain the pathogenesis with common clinical presentation of celiac disease Analyze the pathophysiology of Cohan€™s disease and relate genetic issues Differentiate between the five main infectious forms of hepatitis (A, B, C, D, E) from the two main non-infectious types of hepatitis (toxic and autoimmune) Elaborate on the pathogenesis and pathophysiology of pancreatic cancer

Alterations in the Digestive System

The digestive system is affected by a wide range of diseases spanning from infectious, and autoimmune, to non-infectious genetic mutations. The most common repercussion of malabsorption is fondly characterized by weight loss, diarrhea, and anemia. The purpose of this paper is fourfold; to explain the pathogenesis and clinical presentation of celiac disease, to analyze the pathophysiology and genetic issues in Crohn’s disease, to differentiate between infectious and non-infectious hepatitis, and to elucidate the pathogenesis and pathophysiology of pancreatic cancer.

ORDER A PLAGIARISM-FREE PAPER HERE ON;Explain the pathogenesis with common clinical presentation of celiac disease Analyze the pathophysiology of Cohan€™s disease and relate genetic issues Differentiate between the five main infectious forms of hepatitis (A, B, C, D, E) from the two main non-infectious types of hepatitis (toxic and autoimmune) Elaborate on the pathogenesis and pathophysiology of pancreatic cancer

Explain the Pathogenesis and Common Clinical Presentations on Celiac Disease

Celiac disease is a systemic and immune-mediated gluten-sensitive enteropathy. It results from the interaction of genetic and environmental factors. The genetic factors that play a role in Celiac disease pathophysiology include HLA-DQ2 and HLA-DQ8. The genetic and environmental factors have a complex interplay in the development of Celiac disease. Gluten is a protein mainly found in wheat products, barley, and rye. When the antigen is presented to the CD4+ cells, they are activated to produce pro-inflammatory cytokines such as IL-2, IL-4, IL-6, and the IFN-gamma.  There is a resultant clonal proliferation and maturation of B lymphocytes to form plasma cells and antibodies which mediate intestinal epithelial damage (Kumar et al., 2018). These antibodies are the antibodies against IgA. They include anti-endomysial and antigliadin antibodies. Damage to the epithelial cells induces the production of IL-15 which leads to a resultant increase and activation of the CD8+ T-helper cells. This is the sure feature of the disease.

Celiac disease presents as a malabsorptive disease. The clinical presentation of Celiac disease is different in children and adults. In adults, it commonly presents as protracted diarrhea, bloating, easy fatiguability, and anemia due to inadequate absorption of nutrients such as iron and vitamin B12. In children, the symptoms include diarrhea, wasting and weight loss, irritability, abdominal distension, failure to thrive, pain in the abdomen, vomiting, and a characteristic vesicular and pruritic dermatological rash referred to as dermatitis herpetiformis.

Analyze the Pathophysiology Of Crohn’s Disease and Relate Genetic Issues

Diverse factors play a role in the development of Crohn’s disease. These factors include genetics, deranged individual mucosal immune responses, microbiota, and epithelial defects. All these factors form a complex reciprocity interplay in the etiopathogenesis of Crohn’s disease. Susceptibility to Crohn’s disease has been studied in several genes such as Nuclear Oligomerization Binding Domain 2 (NOD2), Autophagy Related 16-like-1 (ATG16L1), and Immunity Related GTPase M (IRGM). NOD2 is postulated to be involved in the modulation of immune responses by control of the action of the intraluminal microbiota and also by encoding proteins that activate the NF-kβ (Szymanski & Ombrello, 2018). ATG16L1 and IRGM are both involved in the phagocytosis and lysis of luminal bacteria. A defect in all these genes is an important factor in celiac disease development. Crohn’s disease has a higher concordance rate in monozygotic twins. This feature stresses the implication of genetics in the pathogenesis of this disease. The divarication of the TH17 cells of IL-23 and TNF-β which are proinflammatory cytokines further disturb the immune system regulatory mechanisms. IL-10 and TGF-β are inhibitory cytokines produced by the CD4+ T helper cells. These cytokines inhibit inflammation of the intestinal epithelium. A defect in the production of these cytokines interferes with this inhibitory mechanism hence there is unchecked inflammation of the gut wall that spreads transmurally. The epithelium plays a significant role in the release of antimicrobial peptides. A derangement in the epithelial function prompts a buildup of pathogenic microbiota to extremely high levels that may not be averted by the normal body responses to microbes. Salmonella, Shigella, mycobacterium paratuberculosis, Escherichia, and other microbes have been implicated (Harsh Mohan & Damjanov, 2019). Smoking, oral contraceptives, and adverse life conditions like constant family conflicts are associated with the development of Crohn’s disease. Crohn’s disease is characterized by a transmural granulomatous inflammation, with skip lesions commonly involving the terminal small intestines, and fibrosis is a common complication. The development of lymphoma from Crohn’s disease is a common complication.

Differentiate between the 5 main Infectious forms of Hepatitis (A, B, C, D, and E) from the two Main Non-Infectious Types of Hepatitis (Toxic and Autoimmune)

Hepatitis is an inflammatory disease of the liver parenchyma. Viral hepatitis A and E are transmitted through the fecal-oral route by ingestion of contaminated food or water. Hepatitis B, C, and E are transmitted through exposure to infected body fluids such as blood, and semen (sexual transmission), among others. The diagnosis of viral hepatitis is through the detection of antibodies in serum against the specific viruses. Hepatitis B and C commonly lead to chronic disease and Hepatocellular carcinoma. Hepatitis A and E are usually self-limiting. Hepatitis D commonly occurs as a superinfection with Hepatitis B. Prevention of hepatitis A, B, C, and D can be accomplished by the use of vaccines. Treatment of viral hepatitis employs the use of antiretrovirals, especially in chronic hepatitis that meets the treatment criteria. Viral hepatitis can be spread from one person to another. Toxic hepatitis is due to poisons, alcohol, herbs, chemicals like carbon tetrachloride, or toxic drugs and their metabolites as in the case of paracetamol. The pathogenesis of toxic hepatitis is heralded by the liver cells suffering oxidative stress from mitochondrial damage by the toxins which culminates into necrosis of the cells. Different toxins have diverse patterns of necrosis. These patterns include centrilobular and peri lobular. Toxic hepatitis is managed by withdrawal or stoppage of toxic agents such as alcohol. These toxins rarely induce genetic changes. Toxic and autoimmune hepatitis are not transmissible from one person to the other. Autoimmune hepatitis is mediated by the presence of auto-antibodies against the hepatocytes. This can be an isolated disease of the liver or a consequence of a systemic autoimmune disorder. Anti-smooth muscle autoantibodies and antimitochondrial antibodies are commonly implicated. Autoimmune hepatitis is usually negative for serologic markers present in viral hepatitis. Autoimmunity results from an interplay between the environmental and genetic factors which occur over time. Just like other autoimmune disorders, it is more prevalent among the female population. There is a genetic inclination in the development of autoimmune hepatitis. Immune modulating agents are the main course of therapy in autoimmune hepatitis. Prednisolone and azathioprine are commonly used among other immunomodulators. Treatment is only indicated in the presence of severely deranged liver function tests (AST and ALT 5 times the upper limit), presence of bridging necrosis affirmed by a liver biopsy, and severely elevated gamma globulin in serum (Linzay et al., 2021). Autoimmune hepatitis diagnosis still faces a challenge as there are no biomarkers that have a high sensitivity and specificity.

Elaborate on the Pathogenesis and Pathophysiology of Pancreatic Cancer

Pancreatic cancer is a lethal malignancy with a very low survival rate. Pancreatic cancer is influenced by inherited mutations, acquired mutations, and environmental factors. The risk factors include smoking, advanced age, diabetes, chronic pancreatitis, family history, obesity, alcohol abuse, male gender, and ethnicity; it is more common in blacks and Ashkenazi Jews. The progression to pancreatic cancer is a multistage process that involves advancement from a non-cancerous lesion, precancerous lesion (Pancreatic Intraepithelial neoplasia), and finally to invasive cancer. This happens as a consequence of the accumulation of genetic mutations. Somatic mutations involving KRAS, p16, SMAD4, and TP53 genes. Point mutations in the KRAS gene are the commonest implicated genetic mutations. This mutation interferes with the cell signaling pathway resulting in uninhibited cell growth which is a pillar in carcinogenesis. The Tumor Suppressor Gene p16 functions to regulate a checkpoint in the cell cycle at G1 to S phase (Iwatate et al., 2020). It accomplishes this by inhibiting cyclin-dependent kinase. Mutations in the p16 culminate into a defective apoptotic pathway where cells do not die. Tp53 acts to induce programmed cell death. The mutation involving deletion of the SMAD4 gene promotes cancer progression and spread to other structures. KRAS and SMAD4 mutations are associated with poor prognosis. All these mutations interfere with either apoptosis or cell division resulting in prolonged cell life. Pancreatic cancer also commonly occurs in the Lynch syndrome, Hereditary Non-Polyposis Colorectal Cancer, and Familial Pancreatic Cancer Syndromes The clinical manifestations of pancreatic cancer include unintended weight loss, jaundice, pale stools, cola-colored urine, loss of appetite, abdominal pain, pain on the back, diarrhea due to malabsorption, and uncontrollable blood sugars. Most diagnoses of pancreatic malignancies are done at an advanced stage when the tumor is nonresectable.

References

Harsh Mohan, & Damjanov, I. (2019). Textbook of pathology. Jaypee Brothers Medical Publishers.

Iwatate, Y., Hoshino, I., Ishige, F., Itami, M., Chiba, S., Arimitsu, H., Yanagibashi, H., Nagase, H., Yokota, H., & Takayama, W. (2020). Prognostic significance of p16 protein in pancreatic ductal adenocarcinoma. Molecular and Clinical Oncology, 13(1), 83–91. https://doi.org/10.3892/mco.2020.2047

Kumar, V., Abbas, A. K., Aster, J. C., & Perkins, J. A. (2018). Robbins Basic Pathology (9th ed.). Philadelphia, Pennsylvania Elsevier.

Linzay, C. D., Sharma, B., & Pandit, S. (2021). Autoimmune Hepatitis. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK459186/

Szymanski, A. M., & Ombrello, M. J. (2018). Using genes to triangulate the pathophysiology of granulomatous autoinflammatory disease: NOD2, PLCG2, and LACC1. International Immunology, 30(5), 205–213. https://doi.org/10.1093/intimm/dxy021

BUY A CUSTOM- PAPER HERE ON;Explain the pathogenesis with common clinical presentation of celiac disease Analyze the pathophysiology of Cohan€™s disease and relate genetic issues Differentiate between the five main infectious forms of hepatitis (A, B, C, D, E) from the two main non-infectious types of hepatitis (toxic and autoimmune) Elaborate on the pathogenesis and pathophysiology of pancreatic cancer

Explain the pathogenesis with common clinical presentation of celiac disease
Analyze the pathophysiology Cohan€™s disease and relate genetic issues
Differentiate between the five main infectious forms of hepatitis (A, B, C, D, E) from the two main non-infectious types of hepatitis (toxic and autoimmune) Elaborate on the pathogenesis and pathophysiology of pancreatic cancer