Pancreas

Question 1

Etiological Factors for Pancreatitis

Answer 1

• Metabolic:
• _^Alcohol
• _{^{Hypercalcemia}}
• _{^{Drugs <u><em>(Thiazide Diuretics)</em></u>}}
• Mechanical:
• _{^{Gall stone}}
• _{^{Traumatic injury}}
• Vascular:
• _{^{<strong>Shock & acute ischemia</strong>}}
• _{^{<strong>Athero-embolism</strong>}}
• Infection:
• _^Mumps
• _{^{Mycoplasma pneumonia}}
• _{^{Cosackievirus}}

Question 2

Acute pancreatitis

Answer 2

• Initial presentation HYPERcalcemia
• Alcoholics=_{^{Contraction of sphincter of Oddi leads to decrease in drainage from pancreas}}
• Gallstones=_{^{Obstruct drainage from pancreas @ common bile duct <strong>(jaundice)</strong>}}
• Drugs-_{^{sulfonamides, diuretics, Immunosupressive}}
• Autodigestion of Pancreas:
• _{^{Neutrophils + Necrosis + <strong>Hemorr</strong> <u>(Elastase marker)</u>}}
• _{^{Premature activation of Trypsinogen>Trypsin><u>Activation of clots</u>}}
• _{^{Chalky white=Foci of fat necrosis}}
• Presentation:
• _{^{Pain radiates to back <strong>(retroperitoneal)</strong>}}
• _{^{Shock=Release of <em><u>bradykinine</u></em>}}
• _{^{Hyperglycemia <strong>(damage to islets)</strong>}}
• _{^{Hypocalcemia=Poor prognosis due to <u><em>saponification</em></u>}}
• _{^{<u><em>DIC </em></u>due enzyme leakage}}
• Serum markers:
• _{^{<strong><u><em>Increase </em></u></strong>of <em><strong>serum amylase</strong></em> w/in <em><strong>24 hrs </strong></em>w/increase <em><strong>72-96 hrs </strong></em>in <em><strong>lipase</strong></em>}}

Question 3

Chronic Pancreatitis

Answer 3

• Most common in Alcoholics _^(adults)
• Mutation in CFTR gene-Cystic fibrosis w/o common etiologies _^(children)
  
  • _{^{Possible obstruction due to <u><strong>thick secretions</strong></u>}}
  • ^{_{Sweat chloride lvls NORMAL}}
• Progressive fibrosis of paranchyema
• Atrophy of acinar cells
• Cyst formation (pseudocyst)
• Calcification
• Presents:
• _{^{Duct obstruction <u>(gall stones)</u>}}
• _{^{Jaundice, Malabsorption<u><em>=Steatorrhea</em></u>}}
  
  • _{^{Vit A, D, E, K def}}
• _{^{<strong>Damage to islets=<em><u>Diabetes Mellitus</u></em></strong>}}
• Pseudocyst-Walled off by fibrous tissue
  
  • _{^{Necrotic liquefied tissue}}
  • _{^{Presents in both} <u>acute/chronic</u>}

Question 4

Tumors of Pancreas

Answer 4

• Pt 60-80 yrs of age _{<strong>^{(Thin w/Type 2 diabetes)}</strong>}
• High risk: Smoking, chronic pancreatitis, Diabetes mellitus
• Pathogenesis (arise from the ducts):
• Mutation of:
  
  • _^K-Ras
  • _^CDKN2A
  • _^TP53
• Loss of DPC4=SMAD 4
• ID w/mutation of _BOTH _{^{K-RAS & CDKN2A}}_
• Demoplastic response=Malignant infiltration w/fibrosis
• Presentation:
• _{^{Epigastric pain w/weight loss}}
• _{^{Necrolytic migratory erythema <u>(Glucagonoma)</u>}}
• High lvls of conj. bilirubin _{^{(Head of pancreas)}}
  
  • _{^{<strong>Jaundice</strong>}}
  • _{^{<strong>Pale stool</strong>}}
  • _{^{Palpable gallbladder=Obstruction}}

Question 5

Endocrine Pancreas

Answer 5

• Islet of langerhans surrounded by Acinar tissue
• Alpha=Glucagon
• Beta _{^{(Tail periphery)}}=Insulin
• Delta_{^(everywhere)}=Somatostatin _{^{(down regs both)}}
• elevated lvls=Fatty stool, dry mouth, increase in urine w/mild diabetes
• Insulin:
• Glucose uptake (Glut-4) Adipose, Skeletal
  
  • _{^{Liver (Glut-2)}}
• Lipogenesis _^(adipose)
• Protein synthesis _{^{(Skeletal Muscle)}}
• Glycogen & Lipogenesis _^(Liver)

Question 6

MODY

Answer 6

• Monogenic DM
• Primary defect in Beta cell function occurs W/O beta cell loss
• Mutation of hepatocyte nuclear factors
• Autosomal dominant
• **EARLY onset **
• Absence of obesity
• LACK of islet cell auto-Ab & Insulin resistance syndrome
• Responds well to:
• oral hypoglycemics
• Isulin therapy

Question 7

Type 1

Answer 7

• Viral infection trigger it by mol. mimicry:
• Coxsackie _{^{(group B)}}
• Mumps
• Infectious mono ^{_{(High IgM in serum)}}
• Genetic predeposition: HLA DR3/4
• AutoAb against beta cells
  
  • _{^{<em><strong>Insulitis <u>(infiltration of lymph)</u></strong></em>}}
  • _{^{Beta cell depletion}}
  • _{^{Hyperglycemia}}
• Beta cells depleted due to CD8+ & IFN-Y
  
  • _{^{IFN-Y needed in formation of<u><em> epi granuloma</em></u>}}
• Type 4 HS rxn=T cell destruction
• Requires Insulin for survival
• Present in childhood:
• _{^{<em><u>Loss of muscle mass w/Fat</u></em> due to unopposed glucagon}}
• _{^{Bouts of stress>ncrease in Epi>Increase in glucagon>FA breakdown <em><u>(Ketoacidosis)</u></em>}}
• _{^{<em><strong>Ketone bodies=</strong></em>Acetoacetate&B-hydroxybutyrate <u>(metab acidosis) </u><strong>W/Kussmaul breathing=Resp alkalosis</strong>}}

Question 8

Type 2

Answer 8

• Pt presents in early 30’s _{^{(hispanic, Native American)}}
• Risk factors:
• Obesity=High insulin demand w/increasing peripheral resistance _{^{(Accelerates hyperplasia)}}
• Genetics __{^{(FH of DM2 or Obesity)}}_
  
  • _{^{Higher incidence in twins}}
• Causes: peripheral resistance to insulin
• Unused insulin accumulates
• Blood sugar increase (Hyper)
• Stimulates B-Cell Hyperplasia
  
  • _{^{Insulin production down w/Presistent hyperglycemia}}
  • _{^{Pink hyalinization due to <strong><u><em>amyloid deposition</em></u></strong>}}
• Nonketotic Hyperosmolar coma-Due to HYPERglycemia leading to dehydration
• Serum glucose over 200

Question 9

Gestational Diabetes

Answer 9

• Present in DM2 mothers
• Present @ 2nd trimester commonly resolves after delivery
• Newborn presents:
• Beta cell hyperplasia
• Hypoglycemia right after birth _{^{<strong>(seizure)</strong>}}
• LARGE newborns
• Complications:
• NRDS _{^{(Resp distress syndrome)}}
  
  • _{^{Uncomplete maturation of surfactant}}
• Hypoglycemia-Seizures life threatening

Question 10

Complications W/DM-Non enzymatic glycosylation

Answer 10

• Non-enzymatic glycosylation
• _{^{Excess Glucose binds to Tissue}}
• _{^{Complex w/Glucose=Advanced glycosylation end product (AGE)}}
• _{^{Tissue injury=Irreversible}}
• Extracellular-
• _{^{BV binds to Type 4 collagen=<em><strong>Macroangiopathy</strong></em>}}
• _{^{<em><strong>Microangiopathy</strong></em>=Neuropathy/Retinopathy}}
• _{^{Benign HT}}
• Intracellular-
• _{^{HbA1c = good indicator for management of diabetes}}

Question 11

Complications w/DM-Intracellular Hyperglycemia

Answer 11

• Accumulating sorbitol (glucose)=Osmotic lysis
• Injury to nerves, lens, pericytes/BV
• Neuropathy _{^{(schawnn injury)}}
• ^{_{<strong>Stain w/Hematoxylin & Eosin</strong>}}
• ^{_{<strong>Loss of sensation</strong>}}
• ^{_{<strong>Muscle weakness<u> (hand/foot drop &amp; ED)</u></strong>}}
• ^{_{<strong>Autonomic neuropathy (GI, Cardio, UT)-<u>(Early satiety/Lack of bladder control)</u></strong>}}
• Cataract
• _{^{Swelling of cornea (common in type 1) “Accumulation of water crystals”}}
• _{^{<em><strong>Macular edema</strong></em>=Non-prolif Blurry vision <u>(infarct or aneurysm)</u>“cotton wool spots”}}
• _{^{Fibrosis/Neovasc of disc=<u>Prolif Blindness</u>}}
• Microangiopathy
• _{^{Plaque narrows artery “<u>Claudication"</u>}}
• _{^{Reccurent infection & delayed wound healing > <u>Gangrene</u>}}
• _{^{Firbosis of small vessels=Hyaline (<u>secondary hypertension)</u>}}

Question 12

Complications w/DM-Diabetic Nephropathy

Answer 12

• Leading cause of kidney failure (10-20 yrs)
• Microalbuminuria _{^{(less 30 mg a day=NORM)}} Greater than 300 in early stage
• Nephrotic syndrome (late stage)
• Glomerular lesions
• _{^{Capillary basement membrane thickening (AGE)=Sclerosis>compression}}
• _{^{Nodular glomerulosclerosis<u><strong> (Kimmelstiel-Wilson)</strong></u>=Ball deposits of laminated matrix}}
• Renal vascular lesions
• _{^{Acute pyelonephritis w/Pap necrosis}}
• _{^{Abscesses in cortex}}
• _{^{Hemorrhagic infacrts in Pap region}}