> point mutation with G to A transitions resulting in an arginine (R) to histidine (H) substitution ( called R122H)
> affects a site on the cationic trypsinogen molecule essential for the cleavage (inactivation) of trypsin by trypsin itself resistant inactivation abnormally active trypsin activates other digestive proenzymes pancreatitis
Earlier changes are represented by acinar cell homogenization, ductal dilatation with epithelial degeneration, diffuse interstitial edema, leukocytic infiltration, and fibroblastic reaction extensive necrosis and hemorrhage of pancreatic tissue
Anatomic changes strongly suggest autodigestion of the pancreatic substance by inappropriately activated pancreatic enzymes
Activation of trypsin is an important triggering event in acute pancreatitis
Trypsin Trypsinogen Activate other proenzymes Phospholipase Proelastase Disintegration of fat cells Damage elastic fibers of b.v. Acute Pancreatitis Prekallikrein Kallikrein Kinin system Hageman factor Clotting system Complement system Inflammation Small vessel thromboses
Pain is constant and intense and is often referred to the upper back
Full-blown acute pancreatitis is a medical emergency of the first magnitude
Symptoms are due to release of toxic enzymes, cytokines, and other mediators with explosive activation of the systemic inflammatory response leukocytosis, hemolysis, DIC, fluid sequestration, ARDS, and diffuse fat necrosis
Peripheral vascular collapse and shock with acute renal tubular necrosis may occur
Acute pancreatitis perilobular fibrosis, duct distortion, and altered pancreatic secretions over time and with multiple episodes loss of pancreatic parenchyma and fibrosis
*** Chemokines have been identified in chronic pancreatitis (IL-8, MCP-1) plus TGF- β , PDGF induce the activation and proliferation of periacinar myofibroblasts (pancreatic stellate cells) deposition of collagen fibrosis
Location : head of the pancreas (60%), body (15%) or tail (5%)
Multiple tumors are found in 20% of cases
Majority are ductal adenocarcinomas
Poorly delineated and firm, with a yellow cut-surface
May undergo massive cystic degeneration
Duodenal wall is invaded by direct extension in tumors involving the head of the pancreas causing obstruction of the distal CBD
Involved pancreatic ducts are dilated and plugged with necrotic tumor
A cross-section through the head of the pancreas and adjacent CBD showing both an ill-defined mass in the pancreatic substance and the green discoloration of the duct resulting from total obstruction to bile flow.
Graded as well-differentiated, moderately differentiated, and poorly differentiated
LPO = glands are well formed, have a large lumen, and are lined by one or few layers of cylindrical or cuboidal epithelium
Their overall LPO appearanace may be be particularly suggestive of carcinoma except for the irregularities in the shape and distribution of the glands and the peculiar concentric desmoplastic stroma that surrounds them
Tends to metastasize to multiple LN located around the organ
Most commonly involved the LN around the common hepatic artery, hepatoduodenal ligament, posterior pancreaticoduodenal, around the superior mesenteric artery, para-aortic, and anterior pancreatico-duodenal
Microscopic metastasis were found in T1 and T2 lesions
TGF-B1 expression – associated with well-differentiated tumor
American Joint Committee for Cancer Staging for Carcinoma of the Pancreas TNM classification criteria T1 No direct extension of the primary beyond the pancreas T2 Limited direct extension to the duodenum, bile duct, or stomach T3 Advanced direct extension incompatible with surgical resection TX Direct extension not assessed N0 Regional nodes not involved N1 Regional nodes involved NX Regional LN not assessed
American Joint Committee for Cancer Staging for Carcinoma of the Pancreas TNM classification criteria M0 No distant metastasis M1 Distant metastasis present MX Distant metastasis not assessed TNM Stages Stage I T1-2, N0, M0 Stage II T3, N0, M0 Stage III T1-T3, N1, M0 Stage IV Any T or N, M1
Carbohydrates broken down by salivary, gastric & intestinal (pancreatic) enzymes into simple sugars
absorbed by the intestines ( α -glucosidase) into the bloodstream
G G G G G
What is glucose? Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. MAN needs glucose to work CAR needs fuel to move FUEL
Blood Glycogenolysis (-) GLUCAGON (+) INSULIN Fed State Pyruvate/Lactate Amino acids Glycerol / FFA Glycogenesis X X *All cells
Blood Glycogenolysis (+) GLUCAGON (-) INSULIN Postabsorptive / Fasting State Pyruvate/Lactate Amino acids Glycerol / FFA Glycogenesis *6-8hrs after a meal First 24-48hrs Preferentially used by brain, & other non-insulin dependent tissues X
Blood Glycogenolysis (+) GLUCAGON EPINEPHRINE CORTISOL GROWTH HORMONE (-) INSULIN Postabsorptive / Fasting State Glycogenesis After 48hrs of fast Lipolysis Proteolysis Ketogenesis Ketones for brain Pyruvate/Lactate Amino acids Glycerol / FFA
Cell = Powerplant Keyhole = Insulin Receptor G G G G G G G Key = Insulin Glucose
Keyhole = Insulin Receptor G G G G G Key = Insulin CELL = POWERPLANT
G G G G G CELL = POWERPLANT Energy G G G G G G
DIABETES Greek MELLITUS Latin Sweet as honey To pass water like a siphon
G G G G G Type 1 DM insulin (key) absent G G G G G Type 2 DM defective insulin receptor (keyhole) with insufficient insulin Insufficient production of insulin or the inability of cells to use insulin (insulin resistance). What causes it?
“ Sweet Urine” Diabetes Mellitus group of metabolic disorders characterized by high blood sugar levels Hyperglycemia can lead to spillage of glucose into the urine (> 180 renal threshold)
Visceral Obesity common (contributes to insulin resistance)
Three Pathophysiologic Mechanisms of Type 2 Diabetes Glucose (G) Insulin (I) I I I I I I I G G G G G G G G I G G G I G Fasting hyperglycemia Postprandial hyperglycemia Carbohydrate Impaired insulin secretion Excessive fatty acid release Reduced peripheral glucose Uptake and usage Excess liver glucose output (gluconeogenesis) Resistance to the action of insulin
Natural history of type 2 diabetes: a progressive disease Post-prandial glucose Abnormal glucose tolerance Insulin resistance Increased insulin resistance Fasting glucose Hyperglycemia Insulin secretion Hyperinsulinemia, then -cell failure Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota. Normal IGT Type 2 diabetes
Checking your blood sugar with a meter helps see how food, physical activity and medicines affect blood sugar level.
The readings can help you manage diabetes day by day.
Keep a record of the test results to review with your doctor.
What is a good self-testing blood glucose goal? Your doctor will set the appropriate goal for you. The self-testing blood glucose goals for most people with diabetes are as follows: Premeals 80-120mg/dL At bedtime 100-140mg/dL
Caring for Your TEETH A film of bacteria, saliva and food particles (dental plaque) constantly forms on the teeth. Bacteria feed on sugars and starches in foods and produce acids that damage teeth enamel.
Caring for Your TEETH High blood sugar gives bacteria more food supply producing more acid, damaging the enamel leading to tooth decay.
Caring for Your TEETH If plaques are not removed with brushing and flossing, it hardens under the gumline into “tartar”. Tartar irritates the gums causing gum inflammation (gingivitis).
Brush your teeth at least twice a day especially after each meal and snack. Use soft-bristled brush. Floss daily . Caring for Your TEETH
See your dentist at least 2x a year. Consult your diabetes doctor prior to any dental extraction. Caring for Your TEETH
LIVING WITH DIABETES EDUCATION DIET EXERCISE MEDICINES
B LOOD G L U C O S E mg/dL Hypoglycemia: Symptoms & Signs LETHARGY COMA CONVULSIONS Sweating Tremor Palpitations Irritablity PERMANENT DAMAGE DEATH HEADACHE 90 - 80 - 70 - 60 - 50 - 40 - 30 - 20 - 10 -