Title: Pancreas.Objectives: to1. Describe shortly the anatomy , histology, andembryology of pancreas.2. Explain congenital anomalies of pancreas.3. Study both acute and chronic pancreatitis.
Anatomy: From Greek word (pankreas) , meaning "all flesh“. Retroperitoneal organ extending from "C" loop ofduodenum to hilum of spleen . Divided into three parts: head, body, and tail. Main pancreatic duct (duct of Wirsung) drainsinto duodenum at major papilla of Vater.
Accessory pancreatic duct (duct of Santorini)drains into duodenum through a separate minor papilla. In many adults, main pancreatic duct merges withcommon bile duct thus creating ampulla of Vater.
Histology: Complex lobulated organ with distinct exocrineand endocrine components. The exocrine portion: composed of acini(produce enzymes needed for digestion), ductulesand ducts. it constitutes 80% to 85% of pancreas. The endocrine portion: composed of about 1 millionclusters of cells( islets of Langerhans); secrete insulin,glucagon, and somatostatin. it constitute 1% to 2%of pancreas.
Embryology: pancreas arises from fusion of dorsaland ventral outpouchings of foregut.o The majority of gland ( body, tail, superior/anterioraspect of head, and accessory duct of Santorini )is derived from dorsal primordium .o Ventral primordium gives rise to posterior/inferiorpart of head and duct of Wirsung .
Congenital Anomalies:1. AGENESIS : Very rare, pancreas is totally absent (agenesis),incompatible with life. The transcription factor IPF1 (PDX1) is criticalfor development of pancreas. Germ line homozygous mutation in IPF1 gene onchromosome 13 reported in these patient.
2. PANCREAS DIVISUM: Clinically significant. Caused by failure of duct systems of dorsal andventral primordia to fuse. So bulk of pancreas (formed by dorsal primordium)drains through duct of Santorini. Duct of Wirsung is very short and drains only smallportion of head of pancreas.
Accumulated pancreatic secretionspredispose patients to chronic pancreatitis.
3. ANNULAR PANCREAS: develops when one portion of ventral pancreaticprimordium becomes fixed, while other portionis drawn around duodenum. When this portion fuses with head of pancreas,it forms bandlike ring that completely encirclessecond portion of duodenum . present with signs and symptoms of duodenal obstructionsuch as gastric distention and vomiting.
4. ECTOPIC PANCREAS : Found in 2% of routine postmortem examination. Favored sites are stomach and duodenum,followed by jejunum, and ileum. Usually located in submucosa. Histologically: pancreatic acini , occasionally with isletsof Langerhans. May be visualized as a sessile mass. May cause pain from localized inflammation, or rarelymay cause mucosal bleeding. 2% of islet cell tumors arise in ectopic pancreatic tissue.
Pancreatitis:Acute pancreatitis: Reversible lesion. Ranging in severity from edema and fat necrosis ; toparenchymal necrosis with severe hemorrhage.Etiologic Factors :Metabolic: Alcoholism, Hyperlipoproteinemia , andHypercalcemia.Drugs: thiazide diuretics.Genetic : mutation in genes encoding pancreatic enzymesand their inhibitors [ trypsinogen (PRSS1) andtrypsin inhibitor (SPINK1) genes ].
Morphology:Gross: areas of red-black hemorrhage, withfoci of yellow-white chalky fat necrosis .Microscope:(1) microvascular leakage causing edema.(2) fat necrosis by lipolytic enzymes.(3) acute inflammatory reaction.(4) proteolytic destruction of pancreatic parenchyma.(5) destruction of blood vessels with subsequentinterstitial hemorrhage.
Acute pancreatitis: low power shows : hemorrhage, paranchymalnecrosis, fat necrosis , and acute inflammatory cells .
Pathogenesis: pancreatic enzymes present in acinar cellsin proenzyme form and have to be activated. Lysosomal hydrolases permitting proenzyme activation,and local release of activated enzymes. Mechanisms of activation:1. pancreatic duct obstruction.2. primary acinar cell injury.3. defective intracellular transport of proenzymeswithin acinar cells.
Clinical Features and Diagnosis : Pain is constant and intense , often radiated to upper back. Systemic features due to release of toxic enzymes andcytokines into circulation resulting in : leukocytosis,hemolysis, DIC , ARDS, and diffuse fat necrosis. Peripheral vascular collapse and shock withacute renal tubular necrosis due to profound fluid loss.
Lab. findings: Marked elevation of serum amylase levels duringfirst 24 hours, followed within 72 to 96 hours byrising serum lipase level. Glycosuria: in 10% of cases. Hypocalcemia: result from precipitation of calcium soapsin fat necrosis, if persistent it is poor prognostic sign. Direct visualization of enlarged inflamed pancreasby radiographic means.
Treatment: Resting the pancreas by total restriction oforal food and fluids intake. Supportive therapy.Prognosis: Most patients recover fully. 5% die from shock during first week of illness. ARDS and ARF are ominous complications. In surviving patients sequel include: sterile pancreaticabscess and pancreatic pseudo cyst .
CHRONIC PANCREATITIS: Inflammation of pancreas with destruction ofexocrine parenchyma, and fibrosis. In late stages: destruction of endocrine parenchyma. Irreversible impairment in pancreatic function.Etiology:1. Most common cause is Long-term alcohol abuse.
2. Less common causes include:o Long-standing obstruction of pancreatic duct by:calculi, trauma, neoplasms, or pancreas divisum.o Tropical pancreatitis: in Africa and Asia, attributedto malnutrition.o Hereditary pancreatitis: germ line mutations in PRSS1 orSPINK1 genes.o Idiopathic: as in cystic fibrosis.
Pathogenesis: Four hypotheses:1. Ductal obstruction by concretions:accumulation of pancreatic enzymes.2. Toxic-metabolic:toxins including alcohol and its metabolites,can exert direct toxic effect on acinar cells.3. Oxidative stress:Alcohol-induced oxidative stress may generatefree radicals in acinar cells.4. Necrosis-fibrosis:in hereditary pancreatitis autolysis-resistant trypsinmolecule causes acute pancreatitis, repeated episodesof acute pancreatitis almost later develop chronicpancreatitis.
Morphology:Gross: pancreas is hard, sometimes with extremelydilated ducts and visible calcified concretions.Microscope: Parenchymal fibrosis. Reduced number and size of acini with sparing ofislets of Langerhans. Dilation of pancreatic ducts. Chronic inflammatory infiltrate around lobules and ducts. Ductal epithelium may be atrophied or hyperplasticor may show squamous metaplasia. Islets of Langerhans become embedded insclerotic tissue, eventually they may too disappear.
Chronic pancreatitis : Markedly-diminished pancreatic parenchyma with relativelyincrease in fattty tissue. The interstitimum: increases in fibrous component alongwith chronic inflammatory cells.
Clinical Features and Diagnosis : Repeated attacks of mild or moderate abdominal pain,or persistent abdominal and back pain. The disease may be entirely silent until pancreaticinsufficiency and diabetes mellitus develop. In others, recurrent attacks of jaundice or indigestion. Attacks may be precipitated by alcohol abuse, orover eating .
Lab. Findings: Mild-to-moderate elevations of serum amylase. Elevation in serum levels of alkaline phosphatase. Visualization of calcifications within pancreas byCT scan and US. Hypoalbuminemia and hypoalbuminemic edema frommalabsorption caused by pancreatic exocrine insufficiency .
Prognosis: Long -term outlook is poor, with mortality rateover 20 to 25 years is 50%. Severe pancreatic exocrine insufficiency and chronicmalabsorption may develop, as can diabetes mellitus. Pancreatic pseudocysts develop in 10% of patients. Hereditary pancreatitis have 40% risk of developingpancreatic cancer ; other forms predisposition is unclear.
Summary :1. Pancreas is retroperitoneal organ dividedinto three parts: head, body, and tail.2. It has distinct exocrine and endocrine components.3. Congenital anomalies include : Agenesis , divisum ,annular , and ectopic pancreas.4. Pancreatitis can be acute reversible, or chronicirreversible lesion.
Questions:1. Enumerate congenital anomalies of pancreas, andwrite short notes on one of them?2. Write short assay on pathogenesis of chronicpancreatitis?THANK YOU