unit4 IBD PPT BKG.pptx Pathophysiology B.pharma 2nd sem

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1. PATHOPHYSIOLOGY b.Pharma 2 nd semester unit-IV TH Mr. Bulet Kumar Gupta Assistant Professor Sai College of Pharmacy, Mau

2. INFLAMMATORY BOWEL DISEASE (IBD) IBD is comprised of two major disorders: Ulcerative colitis (UC) and Crohn’s disease(CD) also include Microscopic Colitis & Indeterminate (Undetermined) Colitis When it’s difficult to distinguish between Crohn’s Disease & Ulcerative Colitis. IBD is the common name used to describe two chronic diseases of the intestinal tract ―  Crohn’s disease  and  ulcerative colitis ― that cause inflammation in the intestines. EPIDEMIOLOGY ● More common in the west, but the incidence is increasing in the developing countries including Saudi Arabia. IBD can present at any age:- ● The peak: 15-30 years ● A second peak is 50 years old

3. Crohn’s disease- It can affect any part of the gastrointestinal tract from the mouth to the anus. It is immune related disorders triggered by Pathogens. Such as- Mycobacterium, Pseudomonas & Listeria. Ulcerative colitis- It can affect any part of the large intestine. It is Autoimmune disease triggered by itself. A third category indeterminate colitis inflammatory bowel disease, refers to IBD that has features of both Crohn’s disease and ulcerative colitis.  ETIOLOGY OF IBD Defective Mucosal integrity *Dysregulated immune response Diet (Frozen) *Environmental factors(Smoking) Persistent infection Dysbiosis ( Change in microbiota of the gut: ↓protective bacteria ↑aggressive commensals)

4. Pathophysiology of IBD Bacterial antigens are taken up by specialized M cells, pass between leaky epithelial cells or enter the lamina propria through ulcerated mucosa. After processing, they are presented to type 1 T-helper cells by antigen- presenting cells (APCs) in the lamina propria. T-cell activation and differentiation results in a Th1 T cell-mediated cytokine response. with secretion of cytokines, including interferon gamma (IFN-γ). Further amplification of T cells perpetuates the inflammatory process with activation of non-immune cells and release of other important cytokines, including interleukin 12 (IL-12), IL-23, IL-1, IL-6 and tumour necrosis factor alpha (TNF-α). These pathways occur in all normal individuals exposed to an inflammatory insult and this is self-limiting in healthy subjects. In genetically predisposed persons, dysregulation of innate immunity may trigger inflammatory bowel disease.

5. Common IBD symptoms include: Diagnosis- Abdominal pain (pain in the stomach area) Thorough health and family history and physical exam Diarrhea, sometimes with blood Colonoscopy with Biopsy Rectal bleeding Upper endoscopy with biopsy Weight loss Stool sample analysis Fever Imaging (X-ray, CT scan, MRI) Anemia IBD Medications Malnutrition and delayed growth in people Immunosuppressant who develop IBD as children. Topical anti-inflammatory inflammation Anxiety and depression. Pain Killer Antibiotics Steroids.

6. Irritable bowel syndrome (IBS) Irritable bowel syndrome (IBS) is  a common disorder that affects the stomach and intestines, also called the gastrointestinal tract . Symptoms include cramping, abdominal pain, bloating, gas, and diarrhea or constipation, or both.

7. Jaundice Jaundice is a serious medical condition that makes your skin and the whites of your eyes look yellowish. This happens when too much bilirubin builds up in your blood. Bilirubin is a yellowish pigment created as hemoglobin — a component of red blood cells — is broken down. Normally, bilirubin is delivered from the bloodstream into your liver. Then, it passes through tubes called bile ducts. These ducts carry a substance called bile into your small intestine. Eventually, bilirubin is passed out of your body through urine or stool. There are mainly 3 types of Jaundice-- 1) Pre- Hepatic Jaundice 2) Hepatic Jaundice 3 ) Post- Hepatic Jaundice

8. Pre-hepatic jaundice:  Health conditions that affect the blood’s rate of breaking down blood cells cause bilirubin to overflow into bodily tissues. It occurs before the blood reaches the liver. Hepatic jaundice:  Hepatic jaundice happens when your liver tissue becomes less effective at filtering out bilirubin from your blood. Post-hepatic jaundice:  This type of jaundice happens when bilirubin filtered from the blood can’t drain properly into the bile ducts or digestive tract to be passed out of the body. It occurs after bilirubin is filtered out in the liver and occurs because of a blockage. Causes of pre-hepatic jaundice Symptoms of jaundice Malaria Fever, chills, cold sweats. Sickle cell anemia Abdominal pain. Thalassemia Dark urine & Pale yellow Stool. Abnormal weight loss.

9. PATHOGENESIS OF JAUNDICE

10. Diagnosis of jaundice HIDA Scan ( hepatobiliary iminodiacetic acid is an imaging procedure used to diagnose problems of the liver, gallbladder and bile ducts. ) Urine Analysis Blood test Imagine test Treatment for jaundice Anti-malarial drug Blood infusion Folic acid supplements Low protein diet. Anti-viral medication.

11. HEPATITIS

12. Virus enter into the body Specific T-Cell receptor activated Helper T-cell activated Cytotoxic T-cell activated B-cell activated Produce Antibodies Recognize HCV infected cells Lysis of infected cells Liver cell damage PATHOGENESIS OF HEPATITIS-D

13. Virus enter into the body Multiplies for 35 Days(Incubation period) Virions & Antigen can be detected in the Faeces & Lever Show symptoms of Cholestasis Elevated Bilirubin & Alkaline Phosphatase PATHOGENESIS OF HEPATITIS-E

14. Sign & Symptoms Hepatitis-A Hepatitis-C Hepatitis-E Dark Urine Jaundice, Fever Nausea & Vomiting Severe Itching Dark urine Reduce Appetite Fatigue Nausea & Vomiting Yellow colour Skin Mild Fever Diarrhoea Raise Body temperature Hepatitis-B Hepatitis-D Severe Weakness Fever, Jaundice Jaundice Treatment Nausea & Vomiting Cirrhosis Anti-viral medication Joint Pain Increase Bilirubin in blood Interferon injection Headache, Weakness Fever Liver Transplant Loss of Appetite Physical weakness

15. ALCOHOLIC LIVER DISEASE Introduction Alcohol-related liver disease (ARLD) is caused by damage to the liver from years of excessive drinking. Years of alcohol abuse can cause the liver to become inflamed and swollen. This damage can also cause scarring known as cirrhosis. Cirrhosis is the final stage of liver disease. Causes Main Causative factor is heavy alcohol consumption: ✓ Men:> 40 g/day ✓ Women: 20 g/day Risk factors for the development of alcoholic liver disease include: ✓ Women with increased susceptibility & Hepatitis-C virus. ✓ High-fat diet Smoking & Diabetes.

16. Pathogenesis of Alcoholic Liver Disease Ethanol Metabolism There are multiple pathways, but the major one is the acetaldehyde pathway: Acetaldehyde and reduced nicotinamide adenine dinucleotide (NAD+) are generated. Acetaldehyde is metabolized to acetate by acetaldehyde dehydrogenase. Acetaldehyde dehydrogenase has multiple isoforms with different levels of activity. Accumulation of acetaldehyde is one factor responsible for liver injury.

17. Signs and symptoms Complication Abdominal discomfort Portal Hypertension Low-grade fever Splenomegaly Loss of appetite Jaundice Nausea Hepatorenal syndrome Jaundice Hepatocellular Carcinoma Hepatomegaly Lethargy Alopecia Confusion Fatigue

18. Rheumatoid arthritis(RA) Rheumatoid arthritis is a chronic inflammatory disorder that can affect more than just your joints. In some people, the condition can damage a wide variety of body systems, including the skin, eyes, lungs, heart and blood vessels. An autoimmune disorder, rheumatoid arthritis occurs when your immune system mistakenly attacks your own body's tissues. The inflammation associated with rheumatoid arthritis is what can damage other parts of the body as well. While new types of medications have improved treatment options dramatically, severe rheumatoid arthritis can still cause physical disabilities.

19. Unknown trigger promote inflammation in synovial membrane attracting Leukocytes into the tissue PATHOGENESIS OF RHEUMATOID ARTHRITIS Autoreactive CD4 T Cells activate macrophage resulting in pro-inflammatory cytokines Production Cytokines induce MMP & RANK ligand production by Fibroblast RANK ligand activate osteoclast & MMP destroy tissue, resulting in joint destruction.

20. Causes Rheumatoid arthritis is an autoimmune disease. Normally, your immune system helps protect your body from infection and disease. In rheumatoid arthritis, your immune system attacks healthy tissue in your joints. It can also cause medical problems with your heart, lungs, nerves, eyes and skin. E nvironmental factors — such as infection with certain viruses and bacteria — that may trigger the disease. Symptoms Signs and symptoms of rheumatoid arthritis may include: W arm, swollen joints Joint stiffness that is usually worse in the mornings and after inactivity Fatigue, fever and loss of appetite

21. Risk factors Age (Mostly begins in middle age) Sex (In women more than men) Family History Smoking Excess weight Complication Osteoporosis Carpal tunnel syndrome Dry eye & Mouth Heart problems Infection Lungs disease A bnormal body composition Lymphoma

22. OSTEOPOROSIS Introduction- Osteoporosis bone "Osteoporosis (OP) is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture risk. Osteoporosis causes bones to become weak and brittle so brittle that a fall or even mild stresses such as bending over or coughing can cause a fracture. Osteoporosis-related fractures most commonly occur in the hip, wrist or spine. CAUSES Menopausal in female Heavy Alcohol consumption Genetic factor Inactive lifestyle Deficiency of Calcium Use of certain medication (Anti-convulsion) Low amount of calcium in diet

23. PATHOGENESIS OF OSTEOPOROSIS

24. Sign & Symptoms Complication B ack Pain Disabling & limiting your physical activity Loss of height Weight gain Stiffness Increase stress Depression Heart disease & Diabetes Swelling Pneumonia Intense pain Blood clots Distorted body image

25. GOUT Introduction- Gout is a metabolic disorder of purine metabolism, characterized by intermittent attacks of acute pain, swelling and inflammation. It always preceded by hyperuricemia (6.0mg/dl) Hyperuricemia due to excessive amount of uric acid production or decreased excretion. Hyperuricemia - primary or secondary. Primary hyperuricemia classified as "Overproducers" or "under execrator” Causes Uric acid under secretion(80%-90%) Urate overproduction HGPRT Deficiency Developed during other disease(Chemotherapy)

26. PATHOGENESIS OF GOUT

27. Sign & Symptoms Complication Sudden Redness, Swelling, Heat & Pain Swelling in joint regularly Acute pain during night Kidney stone Affect Peripheral joints like- Kidney Failure Elbow Joint Urate crystal may collect in Urinary tract Thumb joint Knee Joint Fingers Joint Ankles Joints

28. Cancer Cancer is a serious disease in which the cells start dividing abnormally in an uncontrolled manner.  Most cancer cells are found in the shape of tumors, with a few notable exceptions such as leukemia. All tumours are not cancerous. Some tumors, such as moles, stop growing and are not malignant. 

29. Classification The following types of cancer are classified according to their tissues: Carcinoma It is the most common form of cancer that affects the epithelial cells which form the lining of internal organs or the skin. Lung cancer B) Skin cancer C) Pancreatic cancer  D) Ovarian cancer . 2) Sarcoma These cancer cells develop in the bones and soft tissues such as fat tissues, cartilages, blood vessels, lymph and other supporting tissues of  tendons and ligaments . 3) Leukaemia Commonly known as blood cancer,   leukaemia affects the tissues of the bone marrow which is responsible for blood production. It is one of the fatal forms of cancer.

30. 4) Lymphoma- Lymphoma is a form of cancer that affects the lymphocytes in the lymph nodes, which are a part of the immune system. There are two kinds of lymphoma: Hodgkin lymphoma  –  originates in the B cells Non-Hodgkin lymphoma ,  – originates in B or T cells. 5) Melanoma It is a form of skin cancer that targets melanin – the pigment responsible for skin colour . In this form of cancer, the melanocytes are affected resulting in the abnormal formation of melanin. It may also affect other tissues that are pigmented, such as the eyes. 6) Myeloma Myeloma targets another part of the immune system- the plasma cells. The affected plasma cells, called myeloma cells divide in the bone marrow causing multiple tumours in the bones (Multiple Myeloma also called Kahler disease).

31. PATHOGENESIS OF CANCER

32. Symptoms of Cancer Cancer can be identified by a variety of symptoms. In some cases, symptoms could vary or may not show any signs and symptoms. There are a few general symptoms: Irregular loss of weight Recurrent fever & Fatigue Continuous pain in a certain area Irregular changes in the skin Causes of Cancer Genetics, Alcohol, Diet and lifestyle , Infections Tobacco and other related narcotics & Unhealthy environment Exposure to unnatural radiation (such as UV rays) for an extended period of time Exposure to certain chemicals for a long time

33. DIAGNOSIS METHOD FOR CANCER