Pancreas Patho B 2

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  • The consequences of insulin resistance at the tissue level include reduced insulin-dependent glucose uptake into liver, adipose tissue and muscle. Combined with excessive glucose production by the liver, this leads to hyperglycemia, which in turn causes a compensatory increase in insulin secretion. The  -cells of the pancreas are unable to sustain this increase in insulin secretion, thus the  -cells fail, and insulin secretion becomes defective (  -cell dysfunction). In addition, excessive breakdown of triglycerides in the adipose tissue leads to increased circulating free fatty acids. This is particularly important since, not only do free fatty acids compete for glucose during metabolism, but there is also increasing evidence that elevated free fatty acids are toxic to the pancreas, in addition to promoting further hepatic glucose output. DeFronzo RA, et al . Diabetes Care 1992; 15: 318–354.
  • Insulin resistance is a reduced biological response to circulating insulin in target tissues 1 Insulin resistance causes an increase in the level of endogenous insulin required to achieve glycemic control, forcing the pancreas to release more insulin 2 When the  -cells are unable to produce sufficient insulin to compensate for insulin resistance, fasting plasma glucose rises, leading to the onset of type 2 diabetes 2 1. Groop LC. Etiology of non-insulin-dependent diabetes mellitus. In Molecular Pathogenesis of Diabetes Mellitus , vol. 22, 1997; pp. 131–156. Edited by RDG Leslie. Basel: Karger. 2. Edelman SV. Type II diabetes mellitus. Adv Intern Med 1998; 43: 449–500.
  • Circulating serum glucose binds irreversibly to the N-terminal valine within the beta chain of the haemoglobin (Hb) molecule, creating A1C 1 It is currently accepted that A1C yields the best overall measurement of blood glucose control 2 A1C levels provide an objective index of glycaemic control for the past 2 to 3 months, based on the turnover of Hb in red blood cells 3 Importantly, increases in A1C levels reflect both the rise in fasting/preprandial blood glucose levels and postprandial glucose levels; thus, normalisation of A1C levels may require control of both pre- and postprandial glucose levels 3 1. Pickup JC. Diabetic control and its measurement. In: Pickup JC, Williams G, eds. Textbook of Diabetes . 3rd ed. Boston, Mass: Blackwell Science; 2003. 2. Clark N. Goals of treatment. In: Leahy JL, Cefalu WT, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002:13-20. 3. Cefalu WT. Rationale for and strategies to achieve glycemic control. In: Leahy JL, Cefalu WT, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002:1-11.

Transcript

  • 1. PATHOLOGY 2B PANCREAS ROBERTO D. PADUA JR.,MD,DPSP DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE
  • 2. Organ Considerations
        • Greek pankreas means “all flesh”
        • Endocrine and exocrine functions
        • Retroperitoneal location
        • 20 cm in length
        • 90 grams in men; 85 grams in women
        • Has 3 parts = head, body, and tail
        • Pancreatic duct system:
          • Duct of Wirsung = main pancreatic duct that drains into the duodenum at the papilla of Vater
          • Duct of Santorini = accessory pancreatic duct that drains into the duodenum through a separate minor papilla
  • 3. Organ Considerations
        • Embryologically arises from the fusion of dorsal and ventral outpouchings of the foregut
        • Exocrine pancreas
            • Constitutes 80-85% of the pancreas
            • Composed of acinar cells
            • Produce digestive enzymes
        • Endocrine pancreas
            • Composed of islets of Langerhans that constitutes only 1-2% of the pancreas
            • Secretes insulin, glucagon, and somatostatin
  • 4.  
  • 5. Normal pancreatic anatomy
  • 6.  
  • 7. Congenital Anomalies
    • Agenesis
        • Total absence of the pancreas
        • Rare; associated with widespread severe malformation
        • incompatible with life
        • Homozygous mutations in the IPF1 gene on chromosome 13q12.1
  • 8. Congenital Anomalies
    • Pancreas Divisum
        • Most common congenital anomaly
        • Incidence : 3-10%
        • Failure of the fetal duct systems of the dorsal and ventral pancreatic primordia to fuse
        • Predisposes to development of chronic pancreatitis
  • 9.  
  • 10. Congenital Anomalies
    • Annular Pancreas
        • Ventral primordium of the pancreas fails to rotate properly
        • Congenital abnormalities of the GIT can be seen
        • Down syndrome is a predisposing condition
        • Encirclement of the duodenum by pancreatic parenchyma  constriction of the duodenal lumen
        • Contains large number of PP cells in its many irregularly shaped islets
        • Presents with duodenal obstruction
  • 11. Congenital Anomalies
    • Heterotopic Pancreas
        • Most common in the duodenum (2 nd portion)
        • Seen in the stomach, jejunum, ileum, Meckel’s diverticulum, gastric and intestinal diverticula, GB and bile ducts, large bowel, spleen, omentum, abdominal wall
        • Grossly, resembles normal pancreas  firm, yellow, lobulated nodules measuring up to 4 cm, sharply circumscribed from the surrounding tissues
        • Central umbilication is present corresponding to the central duct that opens into the lumen (important diagnostic sign)
        • Microscopically, acinar and ductal tissues are always present; islet tissue is found only in 1/3 of cases
  • 12.  
  • 13. Acute Pancreatitis
        • Group of reversible lesions characterized by inflammation of the pancreas ranging in severity from edema and fat necrosis to parenchymal necrosis with severe hemorrhage
        • Incidence rate : 10-20 cases/100,000 (Western)
        • Approximately 80% of cases = biliary tract disease or alcoholism
            • Gallstones present in 35-60% of cases of acute pancreatits
            • Severe alcoholoc intake = 65% in the US
        • Idiopathic = 10-20% of cases
  • 14.  
  • 15. Acute Pancreatitis
    • Genetic alterations
      • Cationic Trypsinogen (PRSS1)
      • > 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
  • 16. Acute Pancreatitis
    • Genetic alterations
      • Cationic Trypsinogen (PRSS1)
      • > hereditary pancreatitis
      • > autosomal dominant disease with
      • 80% penetrance
      • > recurrent attacks of severe
      • pancreatitis usually beginning in
      • childhood
  • 17. Acute Pancreatitis
    • Genetic alterations
      • 2. Serine Protease Inhibitor, Kazal Type 1 (SPINK1)
      • > the gene codes for a pancreatic trypsin inhibitor
      • > mutations in the SPINK1 gene  pancreatitis
  • 18. Acute Pancreatitis
    • Morphology – Gross
        • Gross changes vary from a swollen and edematous well-preserved organ to a hemorrhagic and necrotic mass of tissue
        • Pancreatic substance exhibits areas of red-black hemorrhage interspersed with foci of yellow-white, chalky fat necrosis
        • Foci of fat necrosis may also be found in the extrapancreatic fat depots, (omentum, mesentery, subcutis)
  • 19. Acute Pancreatitis
    • Morphology - Gross
        • Peritoneal cavity contains serous, slightly turbid, brown-tinged fluid in which globules of fat can be identified
        • Hemorrhagic pancreatitis
            • Most severe form
            • Extensive parenchymal necrosis accompanied by diffuse hemorrhage within the substance of the gland
  • 20.  
  • 21.  
  • 22.  
  • 23. Acute Pancreatitis
    • Morphology - Microscopic
        • Ranges from trivial inflammation and edema to severe extensive necrosis and hemorrhage
        • Morphologic changes
            • Microvascular leakage causing edema
            • Necrosis of fat by lipolytic enzymes
            • An acute inflammatory reaction
            • Proteolytic destruction of pancreatic parenchyma
            • Destruction of blood vessels with subsequent interstitial hemorrhage
  • 24. Acute Pancreatitis
    • Morphology - Microscopic
        • Acute interstitial pancreatitis
            • Milder form
            • Morphologic changes limited to interstitial edema and focal areas of fat necrosis in the pancreatic substance and peripancreatic fat
        • Acute necrotizing pancreatitis
            • Severe form
            • Pancreatic tissue necrosis affects acinar and ductal tissues as well as the islets of Langerhans
            • Hemorrhage results from damage to the vasculature
  • 25. Acute Pancreatitis
    • Morphology – Microscopic
        • 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
  • 26.  
  • 27. Acute Pancreatitis
    • Pathogenesis
        • Remains controversial
        • 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
  • 28. 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
  • 29. Acute Pancreatitis
    • Pathogenesis
        • The manner by which alcohol causes pancreatitis is unknown
            • Transient increases in pancreatic exocrine secretion
            • Contraction of the Sphincter of Oddi
            • Direct toxic effects on acinar cells
        • Many authorities think that most cases of alcoholic pancreatitis are sudden exacerbations of chronic pancreatitis, presenting as apparent de novo acute pancreatitis
            • Chronic alcohol ingestion causes secretion of protein-rich pancreatic fluid  deposition of inspissated protein plugs and obstruction of small pancreatic ducts
  • 30.  
  • 31. Acute Pancreatitis
    • Clinical Features
        • Cardinal manifestation = abdominal pain
            • 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
  • 32. Acute Pancreatitis
    • Clinical Features
        • Pancreatic necrotic foci can undergo secondary infection  infected pancreatic necrosis
          • Currently regarded as the most common, most severe, and most lethal of the infectious complications
          • Occurs in 40-60% of patients with acute necrotizing pancreatitis
          • Usually involves Gram-negative organisms from the alimentary tract
        • can evolve into a chronic form
  • 33. Acute Pancreatitis
    • Clinical Features
        • Laboratory findings
            • Serum amylase level elevation in the first 24 hours
            • Elevation of serum lipase within 72 to 96 hours
            • Glycosuria occurs in 10% of cases
            • Elevated serum C-reactive protein is a reliable marker for the presence of pancreatic necrosis
            • Hypocalcemia – a poor prognostic sign
            •  results from precipitation of calcium soaps in the fat necrosis
  • 34. Acute Pancreatitis
    • Clinical Features
        • Management
            • “ Resting” the pancreas by total restriction of food and fluids and by supportive therapy
            • Medical (4-6 hrs)  deteriorate  emergency laparotomy
            • Others : emergency endoscopic retrograde cholangiopancreatography with or w/o endoscopic papillotomy
            • Presence of an upper abdominal mass suspected of being pseudocyst and persistent rising jaundice are indications for surgical intervention
  • 35. SEQUELAE OF ACUTE PANCREATITIS
  • 36. Chronic Pancreatitis
        • Characterized by inflammation of the pancreas with destruction of exocrine parenchyma, fibrosis, and, in the late stages, the destruction of endocrine parenchyma
        • Irreversible impairment of pancreatic function
        • Prevalence : 0.04-5%
  • 37. Chronic Pancreatitis
    • Etiologic factors
        • Long-term alcohol abuse
        • Long-standing obstruction of the pancreatic duct
        • Tropical pancreatitis
            • Attributed to malnutrition
            • Seen in Africa and Asia
        • Hereditary pancreatitis
            • Mutations in the PRSS1 and SPINK1 genes
        • Idiopathic chronic pancreatitis
            • Mutations in cystic fibrosis transmembrane conductance regulator ( CFTR ) gene
  • 38. Chronic Pancreatitis
        • Etiologic factors (Rosai and Ackerman, 9 th ed)
          • Obstruction of the ductal system by carcinoma or stones
          • Chronic alcoholism  most common
          • Hyperparathyroidism
          • Genetic factors
          • Polyarteritis nodosa
          • Mumps
          • A “tropical” form
          • TB
          • Sarcoidosis
          • Malakoplakia
          • Secondary extension of sclerosing cholangitis
          • HIV
  • 39. Chronic Pancreatitis
    • Pathogenesis – Hypotheses
        • Ductal obstruction by concretions
            • Alcohol  increase protein concentrations in the pancreatic juice  ductal plugs  obstruct the pancreatic ducts
        • Toxic-metabolic
            • Toxins including alcohol and its metabolites can exert toxic effect on acinar cells  accumulation of lipids in acinar cells  acinar cell loss  parenchymal fibrosis
  • 40. Chronic Pancreatitis
    • Pathogenesis – Hypotheses
        • Oxidative stress
            • Alcohol-induced oxidative stress  generate free radicals in acinar cells  membrane lipid oxidation and activation of transcription factors (AP1 and NF κβ )  expression of chemokines  attracts mononuclear cells
            • Promotes fusion of lysosomes and zymogen granules, acinar cell necrosis, inflammation, and fibrosis
  • 41. Chronic Pancreatitis
    • Pathogenesis – Hypotheses
        • Necrosis-fibrosis
            • 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
  • 42. Chronic Pancreatitis
    • Morphology – Gross
        • Gland is hard
        • Extremely dilated ducts
        • Visible calcified concretions
  • 43.  
  • 44. Chronic Pancreatitis
    • Morphology – Microscopic
        • Parenchymal fibrosis
        • Reduced number and size of acini with relative sparing of the islets of Langerhans
        • Variable dilation of the pancreatic ducts
        • Chronic inflammatory infiltrate around lobules and ducts
        • Interlobular and intralobar ducts are dilated with protein plugs in their lumens
        • Ductal epithelium is atrophied or hyperplastic or may show squamous metaplasia
        • Ductal concretions may be evident
  • 45.  
  • 46.  
  • 47. Chronic Pancreatitis
    • Clinical Features
        • S/Sx varies = recurrent attacks of abdominal pain/back pain
        • May be entirely silent until pancreatic insufficiency or DM develops
        • Attacks are precipitated by alcohol abuse, overeating, or the use of opiates and other drugs that increase the tone of the sphincter of Oddi
        • Diagnosis requires a high degree of suspicion
  • 48. Chronic Pancreatitis
    • Clinical Features
        • Attack of abdominal pain  mild fever and mild to moderate elevation of serum amylase (absent with destruction of acinar cells)
        • Gallstone-induced obstruction
            • Jaundice
            • Elevation of alkaline phosphatase
            • CT and UTS – visualize calcification
        • Weight loss and hypoalbuminemic edema from malabsorption caused by exocrine pancreatic insufficiency
  • 49. Chronic Pancreatitis
        • Acinar necrosis and acute inflammation are seen more often in patients with persistent pain than in those who are free of pain
        • Treatment
          • Pancreatic duct drainage (through pancreacojejunostomy or endoscopic removal of ductal stones)
          • Partial pancreatic resection
          • Near-total pancreatectomy with or without islet autotransplantation
  • 50. Chronic Pancreatitis
    • Prognosis
        • Not an immediately life-threatening condition, long term outlook is poor
        • 20-25 year mortality rate of 50%
        • Hereditary pancreatitis – 40% lifetime risk of developing pancreatic cancer; unclear for other forms
  • 51. SEQUELAE OF CHRONIC PANCREATITIS
  • 52. Pancreatic Transplantation
        • Two main indications
            • Chronic pancreatitis
            • Insulin-resistant diabetes mellitus
        • At present, pancreatic graft survival rates approach 90% at 1 year
        • Two complications
            • “ graft pancreatitis”
            • Pancreatic thrombosis
  • 53. Abscess
        • Most often seen as complications of acute pancreatitis
        • Characterized by the presence of pus and the microbiologic identification of bacteria in over 90% of cases
  • 54. Non-Neoplastic Cysts
    • Congenital Cysts
        • Result from anomalous development of the pancreatic ducts
        • May be associated with polycystic disease and von Hippel-Lindau disease
        • Range from microscopic lesions to 3-5 cm in diameter
        • Lined by a glistening duct type cuboidal epithelium or by a completely attenuated cell layer
        • enclosed in a thin fibrous capsule filled with clear to turbid mucoid or serous fluid
  • 55. Non-Neoplastic Cysts
    • Pseudocysts
        • Related to pancreatitis, trauma, and rarely, to neoplastic obstruction of large ducts
        • They can become very large, and spread beyond the substance of the pancreas
        • Microscopic
          • Lack of epithelial lining
        • Gross
          • Wall is thick and irregular
          • Inner surface is ragged
          • Intraluminal content is cloudy or bloody
  • 56. Non-Neoplastic Cysts
    • Pseudocysts
        • Complications = perforation and hemorrhage (splenic artery)
        • Treatment
          • Small pseudocysts located in the body or tail of the pancreas = excision
          • External drainage (preferred for the infected cysts)
            • Contraindicated if the cysts connect with the ductal system
          • Internal drainage
            • Transgastric cystgastrostomy
            • Cystojenunostomy to a Roux-en-Y loop of jejunum
  • 57.  
  • 58. Cystic Neoplasms
        • Only 5-15% of pancreatic cysts are neoplastic
        • 5% of all pancreatic neoplasms
        • Can be benign, borderline malignant, or malignant
  • 59. Cystic Neoplasms
    • Serous cystadenomas
        • Benign cystic neoplasms consists of glycogen-rich low-cuboidal cells surrounding small cysts
        • Contains clear, thin, straw-colored fluid
        • Account for about 25% of all cystic neoplasms of the pancreas
        • Occurs twice in women than in men; 7 th decade of life
        • Non-specific S/Sx like abdominal pain or palpable abdominal mass
        • Treatment : surgical resection
  • 60.  
  • 61. Cystic Neoplasms
    • Mucinous cystic neoplasms
        • Almost always arise in women
        • Can be benign, borderline malignant, or malignant
        • Arises in the body or tail
        • Present as painless, slow-growing masses
        • Cysts are lined by columnar mucinous epithelium containing thick, tenacious mucin
        • Diagnosis is only done after removal
        • Treatment is distal pancreatectomy
  • 62.  
  • 63. Cystic Neoplasms
    • Intraductal papillary mucinous neoplasms ( IPMNs )
        • Produce cysts containing mucin
        • Can be benign, borderline malignant, or malignant
        • Occurs more frequently in men
        • Involve the head of the pancreas more often than the tail
        • Characteristic Features
            • Lack the dense “ovarian” stroma
            • Arise in the main pancreatic ducts
  • 64.  
  • 65. Cystic Neoplasms
    • Solid-pseudopapillary tumor
        • Seen mainly in adolescent girls and young women
        • Large, well-circumscribed masses with solid and cystic areas
        • Cystic areas are filled with hemorrhagic debris and neoplastic cells grow in solid sheets or as papillary projections
        • Can present with abdominal discomfort because of their large size
        • Alteration of the β -catenin/adenomatous polyposis coli genetic pathway
        • Locally aggressive
        • Treatment : surgical resection
  • 66. Pancreatic Carcinoma
        • 85% of all cases of pancreatic malignancy
        • 4 th most common cause of death from cancer (US)
        • Incidence is increasing, particularly in women
        • Risk factors : B-naphthylamine or benzidine exposure, cigarette smoking, diet rich in fats, chronic pancreatitis, and DM
        • 10% show familial aggregation consistent with genetic susceptibility
        • Most patients are elderly (60-80 y/o), with slight male preponderance (1.6:1 ratio)
  • 67. Pancreatic Carcinoma
        • Diagnosis is made when tumor becomes relatively large (about 5 cm) and has extended beyond the pancreas (85% of cases)
        • Carcinomas of the body and tail grow insidiously and often have already metastasized at the time of diagnosis
            • Associated with peripheral venous thrombi in 25% of patients
        • Diagnosis : CT-scan, MRI, celiac angiography, UTZ, ERCP, seleno-methionine scan, duodenal aspirate, serum test
        • Tumor markers : SPan1 and CA19-9 antigen
  • 68. Pancreatic Carcinoma
    • Precursors to Pancreatic Cancer
        • Lesions are called “pancreatic intraepithelial neoplasias” (PaINs)
        • Supported by the following observations
            • The distribution parallels that of invasive cancer
            • Often found in pancreatic parenchyma adjacent to infiltrating carcinomas
            • Patients with PaINs later developed an invasive pancreatic cancer
            • The genetic alterations identified in PaINs are similar to those present in invasive cancers
            • The epithelial cells in PaINs show dramatic telomere shortening  predispose these lesions to accumulate progressive chromosomal abnormalities and to develop invasive carcinoma
  • 69.  
  • 70.  
  • 71. Pancreatic Carcinoma
    • Molecular Carcinogenesis
      • K-RAS
        • K-RAS gene is the most commonly altered oncogene
        • Activated by point mutation  impair GTPase activity of K-ras gene  active protein  Ras activates several intracellular transduction pathways  activation of transcription factors fos and jun
  • 72. Pancreatic Carcinoma
    • Molecular Carcinogenesis
      • p16
        • p16 gene (chromosome 9p) is the most frequently inactivated tumor suppressor gene in pancreatic cancer
        • Inactivated in 95% of cases
        • p16 plays a critical role in the control of the cell cycle
      • p53
        • Inactivation of the p53 tumor suppressor gene (chromosome 17p) seen in 50-70% of pancreatic Ca
        • Gene product is nuclear DNA-binding protein that acts both as a cell cycle checkpoint and as inducer of cell death (apoptosis)
  • 73. Pancreatic Carcinoma
    • Molecular Carcinogenesis
      • SMAD4
        • Tumor suppressor gene (chromosome 18q) is inactivated in 55% of pancreatic cancers
        • Also known as DPC4 , codes for protein that plays an important role in signal transduction from the TGF- β family of cell surface receptors
        • Normal function of this gene is to suppress growth and promote apoptosis
  • 74. Pancreatic Carcinoma
    • Molecular Carcinogenesis
      • Genes amplified
        • AKT2 gene
        • MYB gene
      • Inactivated tumor suppressor genes
        • AIB1 gene
        • BRCA2 gene
        • LKB1/STK11 genes
        • MKK4 gene
        • TGF β -R1 and R2 genes
        • RB1 gene
  • 75. Pancreatic Carcinoma
    • Molecular Carcinogenesis
      • Methylation abnormalities
        • Hypermethylation of the promoter of a number of suppressor genes is associated with transcriptional silencing of the genes
      • Gene expression
        • Identified a number of genes that are highly overexpressed in pancreatic cancers
        • Potential targets for therapeutics and may form the basis for future screening tests
  • 76.  
  • 77. Pancreatic Carcinoma
        • 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
  • 78. 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.
  • 79.  
  • 80. Pancreatic Carcinoma
        • Microscopic features
            • 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
            • Perineural invasion – 90% of cases
  • 81.  
  • 82. Poorly formed glands are present in densely fibrotic stroma within the pancreatic substance with presence of some inflammatory cells.
  • 83. Pancreatic Carcinoma
    • Histochemical and Immunohistochemical features
        • Positive for mucin stains
        • Consistent reactivity for keratins and EMA
        • Glycoprotein MUC1 is expressed in over 60% of conventional invasive ductal carcinoma
        • Others : CEA, CA19-9, B72.3, DUPAN-2, YPan-1, SPan-1, Tn and sialosyl-Tn antigens, DF3
  • 84. Pancreatic Carcinoma
    • Spread and metastasis
        • 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
  • 85. Pancreatic Carcinoma
    • Spread and metastasis
        • Most common sites of distant metastasis are liver, peritoneum, lung, adrenal, bone, distant LN groups, skin, and CNS
        • Supraclavicular LN metastasis is sometimes the first manifestation of pancreatic carcinoma
  • 86. Pancreatic Carcinoma
    • Diagnosis
        • Cytology
            • Duodenal secretion
            • Pancreatic juice
            • FNAB
            • percutaneous
            • intraoperative
        • Frozen section
  • 87. Pancreatic Carcinoma
    • Treatment
        • Surgical
    • Prognosis
        • Overall 5-year survival rate = 4% or less with over 90% of patients dying within 1 year of diagnosis
        • Mean survival of 3 months for untreated patients
        • Even if the tumor is confined at the pancreas at the time of diagnosis, the 5-year survival rate does not exceed 15%
  • 88. Pancreatic Carcinoma
    • Prognostic Factors
        • Tumor stage – most important prognostic indicator
        • Microscopic grade – well-differentiated tumor have longer survival rate
        • Tumor size - <4.5 cm have better chance of curative operation
        • Blood vessel invasion and retroperitoneal margin of resection – decreased survival
        • LN metastasis
  • 89. Pancreatic Carcinoma
    • Prognostic Factors
        • DNA ploidy
        • TGF-B1 expression – associated with well-differentiated tumor
  • 90. 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
  • 91. 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
  • 92. Pancreatoblastoma
        • Most common form of pancreatic neoplasia in childhood, but can also occur in adults
        • Reported in patients with Beckwith-Wiedemann syndrome and familial adenomatous polyposis of the colon
        • Bimodal age distribution = mean of 2.4 and 33 years
        • No sex predilection
        • Mean tumor size is 10 cm and partial encapsulation is the rule
  • 93. Pancreatoblastoma
        • Microscopic
            • Very cellular tumors, made up of uniform epithelial cells arranged in solid sheets and nests, admixed with well-formed acinar structures and occasional ductular formations
            • “ Squamoid corpuscles” are a constant and characteristic finding
        • Immunochemistry
            • Positivity for pancreatic enzymes, endocrine markers, and CEA
            • Alpha-fetoprotein may be produced by the tumor
  • 94.  
  • 95.  
  • 96. Pancreatoblastoma
        • Treatment : Surgical resection
  • 97. ENDOCRINE PANCREAS ROBERTO D. PADUA JR.,MD,DPSP DEPARTMENT OF PATHOLOGY FATIMA COLLEGE OF MEDICINE
  • 98. Endocrine Pancreas
        • Consists of about 1 million microscopic clusters of cells, the islets of Langerhans
        • Aggregate weight of 1-1.5 grams
        • Four major cell types
            • Β eta cells – 68%; insulin
            • Alpha cells – 20%; glucagon
            • Delta cells – 10%; somatostatin
            • PP cells – 2%; pancreatic polypeptide that exerts its effect on the GIT  stimulation of secretion of gastric and intestinal enzymes and inhibition of intestinal motility
  • 99. Endocrine Pancreas
        • Two minor cell types
            • D1 cells – elaborates VIP, a hormone that induces glycogenolysis and hyperglycemia; stimulates gastrointestinal fluid secretion and causes secretory diarrhea
            • Enterochromaffin cells – synthesize serotonin and are sources of pancreatic tumors that cause the carcinoid syndrome
  • 100.  
  • 101. Diabetes Mellitus
        • A group of metabolic disorder sharing the common underlying feature of hyperglycemia
        • Hyperglycemia results from defects in insulin secretion, insulin action, or both
        • Causes multi-organ damage affecting the kidneys, eyes, nerves, and blood vesels
  • 102. Carbohydrate Metabolism
    • 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
  • 103. 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
  • 104. Blood Glycogenolysis (-) GLUCAGON (+) INSULIN Fed State Pyruvate/Lactate Amino acids Glycerol / FFA Glycogenesis X X *All cells
  • 105. 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
  • 106. 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
  • 107. Insulin
    • 4 major cell types in the islets of
    • Langerhans:
      •  cell glucagon
      •  cell insulin
      •  cell somatostatin
      • F (or PP) cell pancreatic polypeptide.
    Islets of Langerhans
  • 108. INSULIN BIOSYNTHESIS
    • Initially synthesized as preproinsulin
    • Signal peptide (blue)
    • Proinsulin
  • 109. INSULIN BIOSYNTHESIS
    • Proinsulin
    • Enzymatic cleavage produces
    • equimolar amounts of :
      • C-peptide and
      • active molecule insulin
      • “ secreted in equal amounts”
  • 110. INSULIN BIOSYNTHESIS
    • C-peptide
    • Less susceptible to hepatic degradation
    • marker of insulin secretion
  • 111. INSULIN BIOSYNTHESIS
    • Insulin
    • MW 6000
    • 2 polypeptide chains
    • A chain of 21 amino acids
    • B chain of 30 amino acids
    • chains held together by two disulfide
    • bonds
  • 112. Classification of Glucose Transport According to Their Tissue Distribution and Functional Regulation Glucose Organ Transporter HK Coupler Classification Brain GLUT 1 HK-I Insulin independent Erythrocyte GLUT 1 HK-I Insulin independent Adipocyte GLUT 4 HK-II Insulin dependent Muscle GLUT 4 HK-II Insulin dependent Liver GLUT 2 HK-IVL Glucose sensor GK  -cell GLUT 2 HK-IVB Glucose sensor (Glucokinase) Gut GLUT 3-symporter - Sodium dependent Kidney GLUT 3-symporter - Sodium dependent    
  • 113. INSULIN SECRETION by beta cells GLUT-2 Voltage-gated Ca ++ channel K + ATP Ca ++
    • III. Increased ATP closes K-channels resulting in membrane depolarization
    • I. blood glucose high, taken up by B cells via GLUT2
    • II. Metabolism of glucose generates ATP
    • V. Rise in calcium promotes margination, fusion with membrane, and release of insulin & c-peptide
    • IV. Membrane depolarization opens Ca-channel with influx of calcium
     cell (-) SUR G Glucose-6-P Kreb’s cycle (glycolysis) ATP production
  • 114. PHYSIOLOGIC INSULIN SECRETION 7:00am 7:00pm noon midnight 7:00am
      • prandial insulin secretion, (spikes in response to food)
      • Continuous basal insulin secretion (unstimulated) 50%
    Polonsky. N Engl J Med. 1996;334:777-783 Pancreas secretes approximately 40-50 units of insulin per day Breakfast Lunch Breakfast
  • 115. Meal-stimulated Biphasic Insulin Secretion
    • Initial Phase:
    • rapid burst
    • first few minutes
    • releases preformed insulin
    • Second Phase:
    • - occurs after 10 minutes
    • - continues as long as an hour
    • release of preformed insulin, newly synthesized insulin
  • 116. Early Insulin Secretion Helps Control Post-meal Glucose Levels & DM
  • 117. Immediate Tissue Membrane transport of glucose Muscle, adipose, liver Intermediate Carbohydrate metabolism  Glycogen synthesis Muscle, liver  Glycogenolysis Muscle, Liver  Gluconeogenesis Liver Lipid metabolism  Lipogenesis Liver, adipose  Lipolysis Adipose  Cholesterol synthesis Liver  Ketogenesis Liver Protein metabolism  Protein synthesis Liver, muscle, adipose INSULIN ACTION
  • 118.  
  • 119.  
  • 120.
    • catabolized primarily in the liver and kidney
    • insulin-specific protease (insulinase)
    INSULIN CATABOLISM
  • 121. Cell = Powerplant Keyhole = Insulin Receptor G G G G G G G Key = Insulin Glucose
  • 122. Keyhole = Insulin Receptor G G G G G Key = Insulin CELL = POWERPLANT
  • 123. G G G G G CELL = POWERPLANT Energy G G G G G G
  • 124. DIABETES Greek MELLITUS Latin Sweet as honey To pass water like a siphon
  • 125. 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?
  • 126. “ 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)
  • 127. Diabetes Mellitus
    • Chronic disease
    • Metabolic abnormality involving protein, fat and carbohydrate processing
    • Leading to multi-organs complications
  • 128. SYMPTOMS OF DIABETES Polyuria Polydipsia Polyphagia
  • 129. SYMPTOMS OF DIABETES Poor Wound Healing Weight Loss Weakness and Fatigue Blurring of Vision
  • 130. SYMPTOMS OF DIABETES Many have no symptoms. They are noted to have high blood sugar on testing.
  • 131. RISK FACTORS FOR DIABETES Heredity Old Age Obesity Mothers of large babies
  • 132. Criteria for diagnosis of DM ADA 2004 Note: criteria should be confirmed by repeat testing on a different day.
  • 133. CRITERIA FOR DIAGNOSIS OF DIABETES MELLITUS “ prediabetics” – risk for developing type 2 DM (40% risk over 5yrs) & CV disease Level of glycemia at which diabetic chronic complications occur American Diabetes Association 8 hr Fasting Blood Sugar 2 hours after 75g glucose (OGTT) NORMAL < 100 mg/dL < 140 mg/dL IMPAIRED FASTING GLYCEMIA (IFG)  100 and < 126 mg/dL --- IMPAIRED GLUCOSE TOLERANCE (IGT) ---  140 and < 200 mg/dL DIABETES MELLITUS  126 mg/dL  200 mg/dL Symptoms of diabetes and Random Blood Sugar of  200 mg/dL
  • 134. Etiology of DM
    • Insulin:
      • Insulin secretion defect
      • Insulin action defect (insulin resistance/ receptor defect)
    • Excess counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone)
  • 135. Etiologic Classification of DM exocrine I. II. III. IV. Based on pathologic process that leads to hyperglycemia
  • 136. Etiologic Classification of DM
    • Previous terms: juvenile-onset DM, IDDM
    • absolute insulin deficiency due to autoimmune beta cell destruction
    • Triggered by infectious or environmental stimulus
    • Pathology: “insulitis” pancreas infiltrated by lymphocytes
    • Major susceptibility gene: HLA on chrom6
      • TYPE IA : presence of immunologic markers (islet cell autoAbs, anti-GAD, anti-insulin abs)
      • TYPE IB : idiopathic, immunologic markers absent
    • Ketosis prone
    • Needs insulin therapy
    I. II. III. IV.
  • 137. Diabetes Mellitus Type 1
    • Mechanisms of B-cell dysfunction
        • T lymphocytes react against B-cell antigens and cause cell damage
        • Locally produced cytokines damage β cells
            • IFN- γ , TNF, IL-1
        • Autoantibodies against islet cells and insulin are also detected in the blood of 70-80% of patients
  • 138. Etiologic Classification of DM I. II. III. IV. Genetic predisposition Immunologic trigger No DM with DM Beta cell mass (%) 100 50 20 0 Time (years) Overt DM
  • 139.  
  • 140.  
  • 141. Etiologic Classification of DM
    • 90% of cases
    • Previous names: NIDDM, adult-onset DM
    • polygenic
    • Strong genetic component
    I. II. III. IV.
    • Visceral Obesity common (contributes to insulin resistance)
  • 142. 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
  • 143.  
  • 144. 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
  • 145. Diabetes Mellitus Type 2
    • β -cell dysfunction
        • Inability to adapt to the long-term demands of peripheral insulin resistance and increased insulin secretion
        • Loss of normal pulsatile, oscillating pattern of insulin secretion and attenuation of the first phase of insulin secretion triggered by elevation in plasma glucose
        • Reflected by a decrease in β -cell mass, islet degeneration, and deposition of islet amyloid (amylin)
  • 146.  
  • 147. Etiologic Classification of DM
    • MODY (Maturity-onset diabetes of the young)
    • 2-5% incidence
    • primary defect in β -cell function that occurs without β -cell loss, affecting either β -cell mass and/or insulin production
    • single gene mutation (monogenic)
      • glucokinase
      • islet cell transcription factor (HNF)
    • AD inheritance
    • early-onset, < 25 y/o
    • Absence of obesity
    • Lack of islet cell autoantibodies and insulin resistance syndrome
  • 148. Etiologic Classification of DM
    • Mutation in insulin receptor leading to severe insulin resistance
    • Type A insulin resistance
    • Leprechaunism
    • Rabson-Mendenhall syndrome
    • Lipodystrophy syndromes
    • Defects in proinsulin conversion
    • Insulin gene mutations
  • 149. Etiologic Classification of DM exocrine
    • >80% of pancreas destroyed
    • Chronic Pancreatitis
    • Pancreatectomy
    • Neoplasm
    • Cystic fibrosis
    • Hemochromatosis
    • Fibrocalculous pancreatopathy
  • 150. Etiologic Classification of DM
    • Acromegaly (growth hormone)
    • Cushing’s syndrome (cortisol)
    • Glucagonoma
    • Pheochromocytoma (catecholamines)
    • Hyperthyroidism
  • 151. Etiologic Classification of DM
    • Vacor
    • Pentamidine
    • Nicotinic Acid
    • Glucocorticoids
    • Thyroid hormones
    • Diazoxide
    • Beta-adrenergic agonists
    • Thiazides
    • Phenytoin
    • alpha interferon
    • protease inhibitors
    • clozapine
    • B-blockers
  • 152. Etiologic Classification of DM
    • Viral infections
    • Autoimmune beta cell destruction
    • congenital rubella
    • coxsackie virus
    • cytomegalovirus
  • 153. Etiologic Classification of DM
    • Down syndrome
    • Klinefelter syndrome
    • Turner syndrome
    Genetic syndromes associated with diabetes
  • 154. Etiologic Classification of DM
    • onset or
    • 1st recognition during
    • pregnancy
    • usually reverts to normal
    • postpartum
    • associated with
    • macrosomic babies
    • 30-60% risk of developing
    • DM later in life
    • Screening at 24-28 weeks
    • 50g OGCT (glucose challenge test)
      • - Initial screening
      • - measure plasma glucose 1hr after
      • 50g oral glucose load
      • Threshold: ≥ 130-140mg/dL
    • 100g OGTT
      • Dx criteria: ≥95mg/dl fasting
          • ≥ 180mg/dl at 1h
          • ≥ 155mg/dl at 2h
          • ≥ 140mg/dl at 3h
    IV.
  • 155.
    • 1 . > 45 yrs, if normal, repeat at 3-year intervals
    • 2. Check at a younger age:
    • - have a first-degree relative with diabetes
    • - high-risk ethnic population (e.g., African- American, Hispanic American, Native American, Asian-American, Pacific Islander)
    • - are obese
    • - have delivered a baby > 9 lb
    • - have been diagnosed with GDM
    • - IGT or IFG
    • - hypertensive ( > 140/90)
    • - have HDL < 35 mg/dl and/or triglyceride > 150 mg/dl
    • - cardiovascular, cerebrovascular diseases
    Recommendations for DM Testing (ADA 2004)
  • 156. Glycemic goals 1 American Diabetes Association. Diabetes Care 2004; 27:S15–S35. 2 American Diabetes Association. Diabetes Care 2002; 25:S35–S49. 3 American Association of Clinical Endocrinologists. Endocrine Pract 2002; 8 (Suppl. 1):40–82. 4 European Diabetes Policy Group. Diabet Med 1999; 16:716–730. Fasting/pre-prandial plasma glucose < 140 < 180 Postprandial plasma glucose < 110 90–130 Biochemical index AACE 3 ADA 1,2 mg/dl mmol/l mg/dl mmol/l 5.0–7.2 < 10.0 < 6.5 < 7 HbA 1c (%) < 6.0 < 7.8
  • 157. HBA1c
    • Excess blood sugar non-enzymatically binds to portion of Hgb (irreversible)
    • A1C levels provide a 2- to 3-month index of glycemic control
    • Assess overall blood glucose control
    • Albumin  Fructosamine (1-2 weeks)
    1. Pickup JC. In: Pickup JC, Williams G, eds. Textbook of Diabetes . 3rd ed. Boston, Mass: Blackwell Science; 2003. 2. Clark N. In: Leahy JL, Cefalu WT, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002. 3. Cefalu WT. In: Leahy JL, Cefalu WT, eds. Insulin Therapy . New York, NY: Marcel Dekker, Inc.; 2002.
  • 158.  
  • 159. It cannot be cured. But it can be controlled by keeping blood sugar level within normal range. Diabetes Mellitus
  • 160. Why do I need to control Diabetes?
  • 161.  
  • 162. COMPLICATIONS OF UNCONTROLLED DIABETES
  • 163. Morphology of Diabetes
    • Pancreas
        • Reduction in the number and size of islets
        • Leukocytic infiltration of the islets (insulitis)
        • β -cell degranulation by EM
        • Subtle reduction in islet cell mass – DM 2
        • Amyloid replacement of islets – DM 2
        • Islet cell hyperplasia in newborns of diabetic mothers
  • 164.  
  • 165. MACROVASCULAR COMPLICATIONS
    • Diabetics are prone to have high bad cholesterol.
    • When cholesterol is too high, the walls of large blood vessels become narrowed, even clogged.
    • This problem is called accelerated atherosclerosis.
        • Hallmark of diabetic macrovascular disease
  • 166.
    • Narrowed and clogged blood vessels decrease blood flow to all parts of your body especially the heart and brain.
    • This can lead to heart attack and stroke.
        • MI is the most common cause of death in diabetics
    MACROVASCULAR COMPLICATIONS
  • 167.
    • Gangrene of the lower extremities
        • result of advanced vascular disease
        • 100X more common in diabetics
    • Hyaline arteriosclerosis
        • vascular lesion associated with hypertension
    MACROVASCULAR COMPLICATIONS
  • 168.  
  • 169.
    • Longstanding high blood sugar also damages the small blood vessels supplying the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy)
    • Erectile difficulty and impotence may happen due to damage to nerves going to the sexual organ.
    MICROVASCULAR COMPLICATIONS
  • 170. Normal retina Diabetic retinopathy Preproliferative Proliferative Vitreous Hemorrhage BLINDNESS
  • 171. Diabetic Neuropathy Peripheral Neuropathy Autonomic Neuropathy Erectile difficulty Constipation
  • 172. Diabetic Nephropathy
        • Renal failure is 2 nd only to MI as a cause of death
        • Three lesions encountered
            • glomerular lesions
            • renal vascular lesions – arteriosclerosis
            • pyelonephritis and necrotizing papillitis
  • 173. Diabetic Nephropathy
    • Glomerular lesions
        • Capillary basement membrane thickening
            • Occur throughout their entire length
            • Detected by EM within a few years of onset
        • Diffuse mesangial sclerosis
            • Diffuse increase in mesangial matrix and is always associated with basement membrane thickening
            • Seen in most patients with disease of >10years
            • Manifest with nephrotic syndrome  proteinuria, hypoalbuminemia, edema
        • Nodular glomerulosclerosis
  • 174. Diabetic Nephropathy
    • Glomerular lesions
        • Nodular glomerulosclerosis
            • Kimmeltiel-Wilson lesion -- ball-like deposits of a laminated matrix situated in the periphery of the glomerulus
            • PAS positive containing trapped mesangial cells
            • Seen in 15-30% of long-term diabetics
            • Major cause of morbidity and mortality
  • 175.  
  • 176.  
  • 177. Diabetic Nephropathy
    • Renal vascular lesions
        • Renal atherosclerosis and arteriosclerosis
        • Hyaline arteriosclerosis affects both the afferent and efferent arterioles
  • 178.  
  • 179. POORLY-CONTROLLED DIABETICS are …
    • 2-4 times more prone to HEART DISEASE
    • 25 times more prone to BLINDNESS
    • 90 times more prone to NEUROPATHY
    • 5 times more prone to GANGRENE
    • 17 times more prone to KIDNEY DISEASE
  • 180. HOW DO I PREVENT COMPLICATIONS?
  • 181. Checking Your Blood Sugar
  • 182. Why do I need to check my blood sugar?
    • 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.
  • 183. 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
  • 184. Guarding Your Heart
  • 185. Guarding the Heart
    • Keep blood pressure under 130 / 80
    • Keep blood sugar controlled
    • Keep cholesterol controlled
      • LDL (bad cholesterol) < 100mg/dL
      • HDL (good cholesterol) > 40 (men) > 50 (women)
      • Triglyceride < 150mg/dL
    • Exercise. Lose weight if needed.
    • Quit smoking
    • Take an aspirin once a day.
  • 186. Guarding Your Kidneys
  • 187. Guarding the Kidneys
      • Keep blood pressure under 130 / 80
      • Keep blood sugar well-controlled
      • Avoid dehydration. If there's vomiting
      • or diarrhea, consult your doctor.
      • Do not self-medicate especially with
      • painkillers.
      • If you have proteinuria, see a dietitian
      • for individualized meal planning.
  • 188. Guarding the Kidneys
      • See a doctor for bladder or kidney infections.
      • You may have an infection if you have:
      • pain or burning when you urinate
      • frequent urge to go to the bathroom
      • urine looks cloudy or reddish
      • fever or chilliness
      • back pain or on the side below the ribs
  • 189. Caring for Your Eyes
  • 190. PROPER EYE CARE
    • Good blood sugar control.
    • Visit your eye doctor at least once a year.
  • 191. Caring for Your SKIN
  • 192. Skin care
    • Keep skin clean and dry.
    • Use talcum powder in areas where skin touches skin, such as armpits and groin.
  • 193. Skin care
    • Use an oil-in-water skin cream or lotion.
    • Moisturizing soaps may help.
    • Don't take bubble baths if your skin is dry.
  • 194. Skin care
    • Moisturize your skin to prevent chapping, especially in cold or windy weather.
    • See a dermatologist about skin problems you are not able to solve yourself.
    • Do not scratch dry or itchy skin.
  • 195. Skin care
    • Treat cuts right away.
    • Wash minor cuts with soap and water.
    • Use an antibiotic cream or ointment if your doctor says it's okay.
    • Cover minor cuts with sterile gauze.
    • See a doctor right away if you get a major cut, burn, or infection.
    • Do not use Mercurochrome antiseptic, alcohol, or iodine to clean skin because they are too harsh .
  • 196. Caring for Your FEET
  • 197. Footcare
    • Wash your feet in lukewarm, NOT HOT ,
    • water and mild soap.
    • Dry your feet well especially between the toes.
    • Talcum powder may be used in between the toes.
    Wash your feet everyday
  • 198. Check your feet everyday
    • Check for cuts, sores, red spots, swelling, and
    • infected toenails.
    • If you have trouble bending over, a mirror
    • may be used or ask a family member to
    • help you.
    Footcare
  • 199. Keep your skin soft and smooth
    • Rub a thin coat of lotion or cream over the top and bottom of your feet.
    Footcare
    • Do not put lotion between your toes.
  • 200. Trim toenails each weekend and when needed
    • Trim the toenails straight across and smooth them with an emery board or nail file.
    Footcare
    • Do not cut into the corners or rip off hangnails.
    • Do not scrape calluses with blades.
  • 201. Wear shoes and socks at all times
    • Wear shoes that fit well and protect your feet.
    • Always wear socks.
    • Check the insides of the shoes before putting them on.
    Footcare
    • Do not wear tight socks, rubber bands, or garters around your legs.
    • Do not wear restrictive or ill-fitting shoes.
  • 202. Protect your feet from hot and cold
    • Wear shoes at the beach or on hot pavement.
    • If your feet are cold, wear seamless socks at night.
    Footcare
    • Never walk barefooted.
    • Do not put hot water bottle or heating pad on your feet.
  • 203. Do not wade in floodwaters without boots Footcare
  • 204.
    • Put feet up when you are sitting.
    • Wiggle toes for 5 min, 2-3 x a day.
    • Move ankles up, down and sideways to improve blood flow.
    Footcare Keep blood flowing to your feet
    • DO NOT cross your legs for long periods of time.
    • DO NOT smoke. Smoking reduces blood flow to your feet.
    • 
  • 205. Caring for Your TEETH
  • 206. 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.
  • 207. Caring for Your TEETH High blood sugar gives bacteria more food supply producing more acid, damaging the enamel leading to tooth decay.
  • 208. 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).
  • 209. Brush your teeth at least twice a day especially after each meal and snack. Use soft-bristled brush. Floss daily . Caring for Your TEETH
  • 210. See your dentist at least 2x a year. Consult your diabetes doctor prior to any dental extraction. Caring for Your TEETH
  • 211. LIVING WITH DIABETES EDUCATION DIET EXERCISE MEDICINES
  • 212. EDUCATION
  • 213. BALANCED DIET Benefits
    • Control weight
    • Lower blood sugar level
    • Reduce fat in the body
  • 214. BALANCED DIET wellnessbread.com Eat more of the foods at the bottom. Eat less of the foods at the top.
  • 215. BALANCED DIET
      • Eat your meals and snacks at about the same times each day.
      • Do not skip meals or snacks.
      • Take your medicines at about the same times each day.
      • Exercise at about the same times each day.
    How can I keep my blood glucose at a healthy level? National Diabetes Information Clearinghouse (NIDDK, NIH)
  • 216.
    • Eat more of whole grain breads
    • and cereals, vegetables and fruits.
            • Use table salt and sugar in moderation.
            • Eat fewer fried and high-fat foods such as potato chips, french fries or biscuits.
    • Trim off extra fat from pork and beef. Eat chicken without the skin.
    • Limit alcoholic drinks to one or two a day.
    • Avoid sweet drinks.
    Healthy Eating National Diabetes Information Clearinghouse (NIDDK, NIH)
  • 217. EXERCISE
    • Lowers blood glucose levels
    • Helps weight loss
    • Relieves stress
    • Strengthens muscles
    • Promotes healthier heart & circulation
    Benefits
  • 218. AEROBIC EXERCISES
    • exercise the cardiovascular system
    • (heart, lungs, circulation)
    • Brisk Walking
    • or Jogging
    • Swimming
    • Bicycling
    • Aerobics
  • 219. EXERCISE
    • 20 to 30 minutes workout 4 to 5 times a week
    • Start slowly and increase gradually
    • Warm up and cool down for at least 5 to 10 minutes before and after workout.
    • Include stretching exercises.
    How Often?
  • 220.
    • Talk with your doctor about exercise especially if you have eye, nerve, or vascular complications. Some exercises may not be appropriate for you.
    • Exercise every day at about the same time.
    • Exercise soon after eating, when blood glucose levels are highest.
    • Carry simple sugars with you.
    • Wear well-fitting shoes and socks.
    • Exercise with a friend if possible.
    Exercise Dos
  • 221. Diabetes Pills Insulin Medicines
  • 222. DIABETES PILLS
    • Diabetes pills are not insulin.
    • Instead, they help lower blood sugar in other ways.
  • 223. DIABETES PILLS
    • Diabetes pills work in one of three ways:
    • stimulate the pancreas to release more insulin
    • sulfonylureas meglitinides
    • increase the body's sensitivity to insulin
    • metformin thiazolidinediones
    • slow breakdown of starches into glucose
    • alpha-glucosidase inhibitors
  • 224. DIABETES PILLS
    • Sulfonylureas
    • - stimulate the pancreas to release more insulin
    • - generally taken one to two times daily before meals
    • Glibenclamide / Glyburide (Euglucon, Glynorm)
    • Gliclazide (Diamicron, Glubitor)
    • Glipizide (Minidiab)
    • Glimepiride (Solosa)
  • 225. DIABETES PILLS
    • Sulfonylureas
    • possible side effects:
    • hypoglycemia
    • an upset stomach
    • a skin rash or itching
    • weight gain
  • 226. DIABETES PILLS
    • Meglitinides
    • - stimulate the pancreas to release more insulin
    • - taken before each of three meals
    • Nateglinide (Novonorm)
    • Repaglinide (Starlix)
  • 227. DIABETES PILLS
    • Meglitinides
    • possible side effects:
    • hypoglycemia
    • an upset stomach
    • a skin rash or itching
    • weight gain
  • 228. DIABETES PILLS
    • Biguanides
    • - increase the body's sensitivity to insulin
    • decrease glucose made by the liver
    • - best taken with food
    • Metformin (Glumet, I-max, Humamet)
  • 229. DIABETES PILLS
    • Biguanides
    • possible side effects:
    • It can make you sick if you drink more than about 2 to 4 alcoholic drinks a week.
    • nausea, diarrhea, and other stomach symptoms. These usually go away.
    • metallic taste in the mouth
  • 230. DIABETES PILLS
    • Thiazolidinediones
    • - increase the body's sensitivity to insulin
    • - taken once or twice daily with food
    • Pioglitazone (Actos)
    • Rosiglitazone (Avandia)
  • 231. DIABETES PILLS
    • Thiazolidinediones
    • possible side effects:
    • Liver problems
    • Nausea, vomiting and other stomach symptoms.
    • Swelling of the legs
    • Anemia
  • 232. DIABETES PILLS
    • Alpha-glucosidase inhibitors
    • - slow breakdown of starches into glucose
    • - should be taken with first bite of each meal
    • Acarbose (Glucobay, Gluconase)
    • Voglibose (Basen)
  • 233. DIABETES PILLS
    • Alpha-glucosidase Inhibitors
    • possible side effects:
    • stomach problems (gas, bloating, and diarrhea) that most often go away after taking the medicine for awhile
  • 234. INSULIN If your pancreas no longer makes enough insulin, you need to take insulin. You inject the insulin just under the skin with a small, short needle.
  • 235. TYPES OF INSULIN
  • 236. Hyperglycemia and Hypoglycemia “ When controlling diabetes, blood sugar may become too high or too low. This should be taken seriously.”
  • 237. Hyperglycemia Guide
  • 238. Hyperglycemia Hyper (Latin) – more Glycemia (Latin) – sugar in blood +
  • 239. Hyperglycemia: Causes
    • Eating too much sweets
    • Not taking medications
    • Infection or stress
    If not treated, can lead to Coma & Death.
  • 240. Hyperglycemia: Signs and Symptoms
    • Dry mouth
    • Thirst
    • Frequent urination
    • Fatigue
    • drowsiness
  • 241. Hyperglycemia: What to do?
    • Drink lots of water
    • Stick to diet plan
    • Check blood sugar
    • Consult doctor
  • 242. Hypoglycemia Guide
  • 243. Hypoglycemia Hypo (Latin) – low Glycemia (Latin) – sugar in blood +
  • 244. Hypoglycemia: Causes
    • delaying or skipping a meal
    • eating too little food at a meal
    • getting more exercise than usual
    • taking too much diabetes medicine
    • Drinking excessive amount of alcohol
  • 245. 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 -
  • 246. Hypoglycemia: What to do?
    • Have one of these quick-acting sugars:
    • 1 cup (8 oz.) of milk
    • 1 or 2 teaspoons of sugar or honey
    • 1/2 cup (4 oz.) of any fruit juice
    • 1/2 cup (4 oz.) of regular soda
    • 5 or 6 pieces of hard candy
    • glucose gel or tablets
  • 247. Hypoglycemia: What to do?
    • Take the right amount of medicine at the right time.
    • Try to keep a regular meal schedule.
    • Carry an ID card with your name and emergency response
    • number always.
    • Carry fast-acting sugar at all times.
    • Do not drive or operate equipment if
    • you feel your blood sugar is low.
    • Make sure family and friends know
    • how to treat low blood sugar.
    • If they find you not making sense
    • or unconscious, they should take
    • you to the nearest hospital immediately.
  • 248. Sick-Day Guide
  • 249. Sick-day Guide
    • Tell your doctor that you are sick.
    • If you have a glucose meter, test your blood sugar every 4 hours. Write down the results of the test.
    • Drink plenty of fluids if your blood sugar is too high.
    • Try eating crackers or soup if you can't eat your usual food.
    • Drink clear liquids if you can't eat at all. You can eat or drink something with sugar in it if you have trouble keeping food down.
  • 250. Sick-day Guide
    • Call your doctor RIGHT AWAY if:
    • your blood sugar is over 300 for two tests in a row
    • you can't keep fluid down
    • you feel more sleepy than usual
    • you have trouble breathing
    • you can't think clearly
    • you throw up
    • you have diarrhea
    • you have an infection
  • 251. Patient education is the key to success in diabetes management
  • 252.  
  • 253.  
  • 254. Pancreatic Endocrine Neoplasms
        • Islet cell tumors
        • Account for 2% of all pancreatic neoplasms
        • Most common in adults
        • Occur anywhere along the length of the pancreas
        • Propensity to elaborate pancreatic hormones
        • 3 most distinctive clinical syndrome
            • Hyperinsulinism
            • Hypergasrinemia
            • MEN syndromes
  • 255. Hyperinsulinism (Insulinoma)
        • Most common of the pancreatic endocrine neoplasms
        • Clinical triad
            • Attacks of hypoglycemia occur with blood glucose levels below 50mg/dl
            • The attacks consist principally of such CNS manifestations of confusion, stupor, and loss of consciousness
            • The attacks are precipitated by fasting or exercise and are promptly relieved by feeding or parenteral administration of glucose
  • 256. Hyperinsulinism (Insulinoma)
        • Morphology
            • Generally benign (90%), solitary, arises within the pancreas
            • Small (<2cm), encapsulated, pale to red-brown nodules
            • Microscopically, giant islets with preservation of the regular cords of monotonous cells and their orientation to the vasculature
            • Immunohistochemistry, insulin positive tumor cells
  • 257.  
  • 258. Zollinger-Ellison Syndrome (Gastrinomas)
        • Marked hypersecretion of gastrin by a gastrin-producing tumor
        • Association of pancreatic islet cell lesion with hypersecretion of gastric acid and severe peptic ulceration (90-95% of patients)
        • May arise in the pancreas, peripancreatic region, or the wall of the duodenum
        • More than half are locally invasive or have already metastasized at the time of diagnosis
        • May be associated with MEN syndrome
  • 259. Other Pancreatic Endocrine Neoplasm
    • Alpha-cell tumors (Glucagonoma)
        • Associated with increased serum levels of glucagon
        • Presents with mild DM, characteristic skin rash (necrolytic migratory erythema), and anemia
        • Occur most frequently in pre- and postmenopausal women
  • 260. Other Pancreatic Endocrine Neoplasm
    • Delta-cells tumors (Somatostatinomas)
        • Associated with DM, cholelithiasis, steatorrhea, and hypochlorydria
        • Difficult to localized pre-operatively
        • Requires high plasma level of somatostatin for diagnosis
  • 261. Other Pancreatic Endocrine Neoplasm
    • VIPoma
        • Watery diarrhea, hypokalemia, achlorydria, or WDHA syndrome
        • Associated with increased release of vasoactive intestinal polypeptide (VIP) from a tumor
  • 262. Other Pancreatic Endocrine Neoplasm
    • Pancreatic carcinoid tumors
        • Produces serotonin
        • Rare
        • Endocrinologically asymptomatic despite the presence of high levels in plasma
  • 263. THANK YOU!