Pancreas Path Flashcards
Exocrine Pancreas
Acute Pancreatitis
Chronic pancreatitis
Pancreatic tumors
Acute pancreatitis
Acute onset of abdominal pain resulting from enzymatic necrosis and inflammation of the pancreas
An acute inflammatory process that spreads to other areas (retroperitoneal)
-E.g., spleen, duodenum, distal portion of CBD, lesser omental sac, pararenal spaces, and diaphragm
Occurs as a spectrum in both duration and severity
Acute pancreatitis etiology
Most cases due to:
Gallstones (biliary tract disease) at end of CBD
As a complication of alcoholism
-These two causes constitute 80% of cases
The remaining cases are evenly divided between idiopathic and miscellaneous:
-Drugs, metabolic causes, infectious agents (common viruses, mycobacteria)
-Trauma is leading cause in kids
Recurrence high if inciting agent not removed
Acute pancreatitis path
Involves activation of zymogens and increased duct permeability
Three proposed pathways
-Pancreatic duct obstruction
-Primary acinar injury
-Defective intracellular transport of proenzymes in acinar cells
Occurs by intra-acinar activation of trypsin from trypsinogen — THE KEY INITIATING EVENT
Trypsin, in turn activates:
-Prothrombin (potential for DIC)
-Complement (anaphylaxins)
-Phospholipases (potential for ARDS)
-Elastases (destroys vesselshemorrhage)
-Kinin system (shock)
-Lipases (fat necrosis)
Necrotic pancreatic tissue becomes infected 40-60% of time
Increased ductal permeability gland fibrosis and atrophy
Acute pancreatitis clinical features
fever A steady, burning, midepigastric pain -Penetrates straight through to the back -Radiates to the periumbilical area -Pain is relieved by bending forward -Pain worsens when patient is supine -Bowel sounds (localized ileus) *Produces cutoff sign on X-ray Patient may be in shock Complications in ~25% of cases -Most occur in 2nd and 3rd weeks -Pancreatic necrosis (80%) -Pseudocyst formation *Lacks a true cystic lining *Fluid accumulates in a walled-off area *Often Dx by persistent amylase > 1 week
Acute Pancreatitis x-ray
normal or localized ileus (“sentinel loop”) or “colon cut-off sign” due to spasm of descending colon from inflammation
Acute Pancreatitis complications
Most multifunction complications occur in 1st week
Mortality rate
-As high as 20-25% in kids
-10% in adults ( usually secondary to pancreatic infection and ARDS)
Acute pancreatitis lab
ELEVATION OF SERUM AMYLASE and SERUM LIPASE beginning in 2-12 hours and remaining for 3-5 days
Absolute neutrophilic leukocytosis (L shift)
Hypocalcemia
Elevated transaminases and cholestasis enzymes
CT scan imaging method of choice for Dx
Chronic pancreatitis
It’s a continuing inflammatory disease
It’s irreversible, painful and causes permanent functional loss
-Need to ascertain status of pancreas prior to any episode of panceatitis
70-80% of cases due to alcoholism
-Oxidative stress related
-40-50% of these cases also have alcoholic liver disease
Cystic fibrosis most common cause in kids
Pseudocysts more common than in acute
Chronic pancreatitis 2 types
Chronic calcifying pancreatitis
Chronic obstructive pancreatitis
Chronic calcifying pancreatitis
More common and alcohol associated
Pathogenesis relates to:
-Deposition of fibrillar protein in ducts
-Subsequent
Chronic obstructive pancreatitis
Involves obstruction of major ducts and absence of calcification
Tumor and duct stricture most common associations
Chronic Pancreatitis clinical features
Present with intermittent attacks Persistent mid-epigastric pain and radiation to back Weight loss secondary to malabsorption Diabetes mellitus is a late complication (70%) Predisposes to pancreatic carcinoma Diagnosis related to triad of: -Pancreatic calcification -Steatorrhea -Diabetes mellitus 50% of patients are dead in 5-12 years
Chronic pancreatitis lab
More likely encountered with functional tests of pancreas
Enzymes usually not elevated unless acute exacerbation
Dystrophic calcification in ULQ on imaging
ERCP (endoscopic retrograde cholangiopancreatography) for use in equivocal diagnoses
Pancreatic tumors
~ 90% involve the pancreatic duct
-Pancreatic adenocarcinoma (see below)
Remaining 10% affect the islet cells
Most common benign tumors are serous and mucinous cystadenomas
Pancreatic adenocarcinoma
The most common exocrine cancer
More common in men
Generally occurs in the 60-80 year olds
Risk factors: age>60, male sex, tobacco use, chronic pancreatitis (9-fold risk), family history of nonpolyposis cancer syndrome
Involve mutations in TP53 suppressor gene of chromosome 17 and the ras oncogene (75%)
Most carcinomas are located in the HEAD of the pancreas (70%) followed by the body and tail
Pancreatic adenocarcinoma lab
inc CA19-9 and CEA may be elevated
-No single marker specific
Minimal elevation of serum amylase and lipase
Pancreatic adenocarcinoma clinical features
Pain in midepigastrum worsens when supine Weight loss Jaundice and clay–colored stools Hepatomegaly Glucose intolerance Palpable gallbladder Surgery only cure (Whipple’s procedure)
Diabetes
29 million people (10% of the population) have diabetes
21 million diagnosed
8 million undiagnosed
2 million new cases / year
7th leading cause of death
-70,000 death certificates listing it as the underlying cause of death
-230,000 death certificates listing diabetes as an underlying or contributing cause of death
DM is not a single disease entity
It is a group of metabolic disorders sharing the common underlying feature of hyperglycemia
Hyperglycemia results from defects in insulin secretion, insulin action, or (usually), both
The chronic hyperglycemia and attendant metabolic dysregulation may be associated with secondary damage to organs, especially, the kidneys, eyes, nerves and blood vessels
Metabolic syndrome
The term metabolic syndrome (previously called “syndrome X”) has been applied to an increasingly common condition wherein abdominal obesity and insulin resistance are accompanied by a constellation of risk factors for cardiovascular disease like abnormal lipid profiles
Persons with metabolic syndrome benefit greatly from changes in their life style, including dietary modification and weight reduction;
a similar benefit is observed in individuals with frank type 2 diabetes
DM classification
Most common and important forms arise from primary disorders in the islet cell insulin signaling system
May be a result of:
1. An absolute deficiency of insulin (Type 1)
2. Inadequate insulin secretion coupled with insulin resistance in the peripheral tissue (Type 2)
Defective or deficient insulin secretory response
-Impaired CHO (glucose ) use
-Hyperglycemia
Less common type (MODY) differs in specific genetic defects of -cell function
Primary DM
subclassified into type 1 insulin dependent DM (formerly, IDDM) and type 2 non-insulin dependent DM (formerly, NIDDM)
- Type 1 (previously called juvenile type DM) accounts for ~10% of cases of primary DM
- Type 2 (previously called adult-onset type DM) accounts for most of the remaining cases
- Maturity onset diabetes of the young (MODY)
MODY
An AD inherited DM exhibiting defects in insulin secretion due to genetic defects in B-cell function that result in mild hyperglycemia
while the major types of DM have DIFFERENT pathogenic mechanisms, the long term complications are the SAME and are the major causes of morbidity and mortality
Gestational DM
Glucose tolerance that 1st develops in pregnancy
-inc placental size and anti-insulin effect of human placental lactogen have been implicated
-At 24-28 weeks gestation, pregnant women are screened with a 50g 1-hour glucose challenge test
increased morbidity and mortality of the newborn
-Results in macrosomia, respiratory distress syndrome, open neural tube defects, and transposition of the great vessels
35% of these women will develop overt DM in 5-10 years
DM incidence
~108 (1.3X106 in U.S.) have DM 7th leading cause of death in U.S. Prevalence with age -55% of patients are > 50 yo Lifetime risk is 5-7% for Type 2 and 0.5% for Type 1
Type I path
Severe absolute lack of insulin caused by -cell mass
Patients absolutely dependent on exogenous insulin
Three interlocking mechanisms for islet cell destruction:
1. Genetic susceptibility
2. Autoimmunity
3. Environmental insult
Type I path 2
Genetic susceptibility linked to specific alleles of Class II MHC
Autoimmunity develops spontaneously or is triggered by an environmental event such as a viral infection
DM appears when sufficient -cells have been destroyed
Occurs most often in people of Northern European ethnicity
Can aggregate in families
Autoimmunity
-Clinical disease appears abruptly but only after chronic attack of -cells and subsequent loss
