Skip to content

CONGENITAL DISORDERS OF PANCREAS

Pancreas Development

  • The ventral duct is an off-shoot of the bile duct and maintains this bile duct connection throughout.
  • The dorsal anlage will give rise to the head, body, and tail of the pancreas
  • the ventral bud will form the inferior pancreatic head and the uncinate process.
  • fifth week of gestation, the ventral bud rotates clockwise with the developing duodenum to fuse with the dorsal pancreatic bud.
  • PP cells localize to the area derived from the ventral anlage, while the dorsal pancreas has larger lobules with PP-poor islets

Ans B The first endocrine cells to form are the insulin-producing b-cells

Ans D Nkx2.2 expression eventually becomes restricted to NeuroG3-positive cells, persisting in all endocrine lineages except for d-cells

Ans B

  • The pancreas of a healthy adult has approximately one million islets
  • Islets are evenly distributed throughout the pancreatic gland
  • account for 1% to 2% of the organ's mass
  • Each islet ranges in size from 50 to 300 mcm in diameter

Ans B

  • pancreatic a-cells, which principally secrete glucagon, represent approximately 35% of all islet cells
  • Pancreatic b-cells, which are responsible for the production and secretion of insulin and amylin, represent approximately 55% of islet cells
  • Pancreatic d-cells, which principally secrete somatostatin, represent less than 10% of the islet cells
  • pancreatic F cells, which secrete pancreatic polypeptide (PP), account for less than 5%
  • epsilon cells, which secrete ghrelin, account for less than 1% of human islet cells

Ans D

  • Islets located in the body and tail of the pancreas have a higher proportion of alfa cells and a lower proportion of F cells
  • islets located in the uncinate process have a higher proportion of F cells and a lower proportion of alfa-cells
  • b-cells and d-cells are present in nearly equal proportions throughout the pancreas

Explanation

Insulin Gene Location

  • The gene responsible for encoding insulin is located on the short arm of chromosome 11, not the long arm.

Preproinsulin Structure and Cleavage

  • Preproinsulin consists of a leading sequence of 24 amino acids followed by three domains named "B," "C," and "A."
  • The first cleavage of the leading sequence occurs in the endoplasmic reticulum, forming proinsulin.

Proinsulin to Insulin Conversion

  • In the trans-Golgi, proinsulin is packaged into secretory granules.
  • Additional proteases cleave the central 31 amino acid C-peptide, resulting in mature insulin.

Mature Insulin

  • Mature insulin peptide consists of an A-chain and B-chain held together by two disulfide bonds.
  • It has a plasma half-life of 4 minutes and is degraded by the kidneys and liver.

C-peptide Characteristics

  • C-peptide has a plasma half-life of 30 minutes and is excreted unchanged by the kidneys.

Explanation

Pancreas Location

  • The neck of the pancreas lies over the vertebra bodies L1 and L2, not T12 and L1.

Endocrine Pancreas

  • The endocrine pancreas comprises only 2% of the adult pancreatic mass.

Pancreatic Head Position

  • The pancreatic head lies in front of the inferior vena cava and the right renal artery.

Pancreas Length

  • The length of the pancreas is usually around 12 to 15 cm.

Multiple Choice Question: Incretin Hormones

Explanation:

  • Glucose-dependent insulinotropic peptide (GIP) and gastric inhibitory peptide are names for the same hormone.
  • Glucagon-like peptide 1 (GLP-1) is also an incretin hormone.
  • Thus, all the options listed are incretin hormones.

Multiple Choice Question: Inhibitors of Insulin Release

Explanation:

  • Humoral inhibitors for insulin release include somatostatin, amylin, leptin, pancreastatin, substance P, vasoactive intestinal peptide, and neurotensin.
  • Glutamate stimulates insulin secretion.

Multiple Choice Question: Glucose Sensor Enzyme in Beta Cells

Explanation:

  • Glucokinase acts as the glucose sensor in pancreatic beta cells, playing a critical role in glucose metabolism and insulin release.

Multiple Choice Question: Feedback Inhibition of Pancreatic Exocrine Secretion

Explanation:

  • Monitor peptide, luminal CCK releasing factor (LCRF), secretin-releasing factors (e.g., phospholipase A2), and peptide tyrosine tyrosine (PYY) are all involved in feedback inhibition of pancreatic exocrine secretion.
  • Trypsin inactivates monitor peptide and LCRF, thereby preventing augmentation of CCK release from the I cell.
  • PYY is released by neuroendocrine L cells in the ileum and colon, stimulated by intraluminal oleic acid.

Additional Notes:

  • Insulin Secretion Stimulation:
    • Glucose
    • Amino acids (e.g., arginine)
    • Acetylcholine (ACh)
    • Glutamate
    • Incretins such as gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1)
  • Neuroendocrine L cells in the ileum and colon are stimulated by intraluminal oleic acid to release PYY, which acts on the area postrema of the brain, decreasing vagal cholinergic mediation of CCK-stimulated pancreatic secretion.

Multiple Choice Question: Indirect Tests for Pancreatic Exocrine Function Assessment

Explanation:

  • The Lundh test is a direct test for pancreatic exocrine function.

  • 13C-Mixed triglyceride breath test and 72-hour stool fat estimation test are indirect tests.

    Untitled

Multiple Choice Question: Pancreatic Function Assessment

Explanation:

  • More than 90% of pancreatic parenchyma must be lost before overt steatorrhea becomes evident.
  • Serum trypsinogen is considered a sensitive and specific test for advanced pancreatic insufficiency but is less accurate for earlier stages.
  • Elastase-1 is not influenced by exogenous pancreatic enzyme administration and is more stable during intestinal transit.
  • Chymotrypsin is less stable during intestinal transit and is influenced by exogenous pancreatic enzyme administration.

Additional Notes:

  • Fecal Fat Estimation Test:
    • Patients are required to follow a diet of 100 g/day fat for 5 days.
    • Collect the complete volume of feces for 3 days, starting on day 3.
    • Fecal fat content greater than 7 g/day is considered abnormal and diagnostic for steatorrhea.
  • Serum Trypsinogen:
    • A sensitive and specific test for advanced pancreatic insufficiency.
    • A serum trypsinogen concentration of less than 20 ng/mL is a reasonable cutoff for diagnosing pancreatic insufficiency.
  • Chymotrypsin:
    • Synthesized and secreted by the acinar cells of the pancreas.
    • The test is influenced by exogenous pancreatic enzyme administration and requires suspension of enzyme administration for at least 2 days before the test.
  • Fecal Elastase-1:
    • Not influenced by exogenous pancreatic enzyme administration.
    • More stable than chymotrypsin during intestinal transit.
    • Levels of fecal elastase-1 less than or equal to 15 mg/g of stool are diagnostic for pancreatic insufficiencies in patients with chronic pancreatitis (CP).
    • Tests are often unreliable after pancreatic resection and cannot be used to evaluate the response to pancreatic enzyme replacement therapy.
  • Secretin Test:
    • Exocrine insufficiency is evident when bicarbonate concentrations are less than 80 mEq/L.
    • Severe exocrine insufficiency is diagnosed when bicarbonate concentration is less than 50 mEq/L.
  • CCK Test:
    • Measures lipase concentration from duodenal fluid collected over an 80-minute period.
    • Uses a cutoff lipase value of 780 IU/L.

Multiple Choice Question: Exocrine Function of the Pancreas

Explanation:

  • The exocrine function is traditionally divided into three phases:
    • Cephalic phase: 10% to 20%
    • Gastric phase: 15% to 20%
    • Intestinal phase: 60% to 70% of meal-stimulated pancreatic excretion
  • Bicarbonate-rich fluid release from ductal cells is facilitated by:
    • Acidification
    • Entry of fatty acids along with bile salts into the duodenum
    • Stimulation of secretin and VIP
  • Digestive enzyme-rich fluid secretion from acinar cells is facilitated by:
    • Vagal stimulation
    • Entry of peptides or fatty acids into the duodenum
    • Release of CCK and acetylcholine

Multiple Choice Question: Pancreatic Enzymes

Explanation:

  • Pancreatic enzymes synthesized in active form include:
    • Amylase
    • Lipase
    • RNase
    • DNase
  • The intestinal brush border enzyme, enteropeptidase, cleaves trypsinogen to its active form, trypsin.

Multiple Choice Question: Serum Amylase Levels

Explanation:

  • Serum amylase levels usually rise 2.5 times normal within 6 hours after the onset of an acute episode.
  • Serum amylase levels return to normal within 3 to 7 days.
  • The major limitation of serum amylase measurement to diagnose pancreatitis is the lack of specificity.
  • A normal serum amylase certainly does not exclude pancreatitis.

Multiple Choice Question: Amylase to Creatinine Ratio (ACR)

Explanation:

  • ACR more than 5% suggests acute pancreatitis.
  • ACR less than 1% suggests macroamylasemia.

MCQ - Pancreatitis Markers

Explanation:

  • Serum lipase levels are more specific in diagnosing acute pancreatitis.
  • Lipase is only produced in the pancreas and tends to be higher in alcoholic pancreatitis.
  • The amylase level is higher in gallstone pancreatitis.
  • Amylase is produced by both the pancreas and other tissues such as salivary glands, thus it is not more sensitive compared to lipase for diagnosing acute pancreatitis.

MCQ - Pancreas Development

Explanation:

  • Cardiac mesoderm promotes liver formation but inhibits pancreas development.
  • High beta catenin levels in the posterior endoderm promote intestinal development, not pancreas development.
  • Neurogenin 3 is a prerequisite for pancreatic endocrine lineage development.

Pancreas Development Factors

Factors Influencing Pancreas and Liver Development:

  • Cardiac mesoderm:
    • Promotes: Liver formation
    • Inhibits: Pancreas development
  • FGF4:
    • Promotes: Intestinal endoderm development
    • Inhibits: Foregut development into liver and pancreas
  • Beta catenin:
    • Repression in anterior endoderm:
      • Promotes: Liver and pancreas development
    • High levels in posterior endoderm:
      • Promotes: Intestinal development
      • Inhibits: Foregut development into liver and pancreas
    • Repression in posterior endoderm:
      • Promotes: Ectopic liver bud initiation and pancreas development
  • Neurogenin 3:
    • Promotes: Pancreatic endocrine lineage development

Untitled

MCQ - Pancreatic Gene Expression and Function

Explanation:

  • The neural cell adhesion molecule (NCAM) is expressed in mature alpha and PP cells and is necessary for the aggregation of endocrine cells within the islet.
  • Pdx1 is one of the earliest markers of pancreatic progenitors and is later expressed only in beta cells.
  • PTF1a nonfunctioning mutation results in humans being born without a pancreas.
  • Nkx2.2 normally induces insulin-positive differentiation and represses alpha-cell formation.

MCQ - Neonatal Diabetes with Bowel Atresia

Explanation:

  • A human syndrome of neonatal diabetes (patients lack pancreatic endocrine cells) with bowel atresia has been shown to have mutations in the Rfx6 gene.

MCQ - Congenital Variants of Pancreatic Ductal Anatomy

Explanation:

  • Pancreas divisum (PD) is the most common congenital variation of pancreatic ductal anatomy.

MCQ - Annular Pancreas

Explanation:

  • Annular pancreas generally presents in the newborn period, with 75% of cases presenting in the first week of life.
  • Radiographs showing the "double bubble" sign, classically attributed to duodenal atresia, may be seen in more than 88% of patients.
  • Emesis may be bilious (up to 50%) or more commonly nonbilious (>90%).
  • Duodenoduodenostomy is the treatment of choice for annular pancreas due to the lower incidence of obstruction and blind-loop syndromes.
  • The most common congenital abnormality associated with annular pancreas is Down syndrome.

Theories in Annular Pancreas:

  • Lecco Theory: Adherence of the right ventral pancreatic bud to the duodenum before gut rotation results in a partial or complete ring of pancreatic tissue around the duodenum.
  • Baldwin Theory: The left ventral bud persists to form the annular pancreas.
  • Kamisawa Theory: The tip of the left ventral bud adheres to the duodenum and stretches to form a ring. The exact location of this attachment in relation to the bile duct determines the final arrangement of the annular duct.
  • Preampullary obstruction resulting in nonbilious vomiting has been reported to be more common in annular pancreas than in other causes of duodenal obstruction (94% vs. 10%).

GI Abnormalities Associated with Annular Pancreas:

  • Intestinal malrotation
  • Tracheoesophageal fistula
  • Mobile right colon
  • Omphalocele
  • Nonrotation
  • Duodenal atresia
  • Situs inversus
  • Cardiac anomalies
  • Genitourinary abnormalities

MCQ - Anomalous Pancreaticobiliary Ductal Junction

Explanation:

  • In anomalous pancreaticobiliary ductal junction, the main pancreatic and common bile ducts join to form a common channel (usually measuring more than 15 mm) proximal to the sphincter of Oddi.

MCQ - Heterotopic Pancreatic Tissue

Explanation:

  • Heterotopic pancreatic tissue is found in:
    • Stomach (24%)
    • Duodenum (32%) ? ? ?
    • Jejunum (29%)
    • Meckel diverticulum (15%)
    • Gallbladder (3%)
  • Heinrich histological classification of heterotopic pancreas:
    • Type 1: Normal pancreatic tissue components present, including ducts, acini, and islets.
    • Type 2: Few acini and multiple ducts, absence of endocrine elements.
    • Type 3: Presence of ducts. Acini and islet cells are absent.

MCQ - Congenital Hyperinsulinemia

Explanation:

  • Congenital hyperinsulinemia involves an inactivating mutation in the subunit of the ATP-dependent potassium channel.
  • It is the malfunction, not the proliferation, of beta cells that is responsible for the condition of hyperinsulinemia.
  • The preferred terminology now is idiopathic hyperinsulinism of infant or adult.
  • The term nesidioblastosis is not recommended for hyperinsulinism or islet aggregates in an atrophic pancreas.

MCQ - Congenital Hyperinsulinism Severity and Treatment

Explanation:

  • Inactivating mutations in the KATP channel are the most common and severe form of congenital hyperinsulinism (CHI).
  • GDH CHI (glutamate dehydrogenase CHI) is the second most common form and is known as hyperinsulinism and hyperammonemia (HI/HA) syndrome. It presents with recurrent episodes of hypoglycemia that are less severe than in KATP-CHI.
  • First-line medical therapy for infants with CHI is diazoxide, a KATP channel agonist. Patients with GDH-CHI, SCHAD-CHI, and perinatal stress-induced hyperinsulinism typically respond well to diazoxide.
  • Octreotide is used as a second-line medical therapy for infants unresponsive to diazoxide.

Additional Information:

  • CONGENITAL HYPERINSULINISM (CHI):
    • Dysregulated insulin secretion resulting in persistent mild to severe hypoglycemia.
    • Occurs at a frequency of 1 in 30,000 to 50,000 live births.
    • Mutations in six genes are associated with CHI:
      • Sulfonylurea receptor 1 (SUR-1; encoded by ABCC8)
      • Potassium inward rectifying channel (Kir6.2; encoded by KCNJ11)
      • Glucokinase (GK; encoded by GCK)
      • Glutamate dehydrogenase (GDH; encoded by GLUD1)
      • Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD; encoded by HADH)
      • Ectopic expression on beta-cell plasma membrane of SLC16A1 (encodes monocarboxylate transporter 1 [MCT1])
  • Inactivating mutations in the KATP channel: Most common and severe form of CHI.
  • GDH CHI: Second most common form, also known as hyperinsulinism and hyperammonemia (HI/HA) syndrome.
  • First-line pharmacologic therapy: Diazoxide.
  • Second-line medical therapy: Octreotide for infants unresponsive to diazoxide.
  • Diffuse form of CHI: Diffuse hyperfunction of pancreatic beta cells with enlarged nuclei, without increased beta-cell proliferation rate or mass.

MCQ - Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS)

Explanation:

  • Insulinoma is indeed the most common cause of hyperinsulinemic hypoglycemia.
  • NIPHS (Noninsulinoma Pancreatogenous Hypoglycemia Syndrome) is characterized by excessive pancreatic beta cell function, with pathologic changes including pancreatic islet hyperplasia and dysplasia, and beta cells budding from and in apposition to pancreatic ductal structures.
  • NIPHS is typically a disease of infancy but can occur in adults, where it can be challenging to differentiate from insulinoma. Postprandial hypoglycemia within 4 hours of a meal is the hallmark of NIPHS, helping to differentiate it from insulinoma.
  • Like insulinoma, patients with NIPHS may have a positive 72-hour fast, with episodes of hypoglycemia associated with inappropriate elevation of insulin, C-peptide, and proinsulin levels.
  • Nesidioblastosis is a clinical diagnosis of exclusion, confirmed on pathologic examination of the pancreas and clinical response to treatment.
  • Treatment for NIPHS includes 95% distal pancreatectomy, dietary control, and medical therapy with diazoxide and somatostatin analogues.

Additional Information:

NIPHS vs. Insulinoma:

  • NIPHS:
    • Postprandial hypoglycemia within 4 hours of a meal.
    • Pathologic changes in the pancreas including islet hyperplasia and dysplasia.
    • Diagnosis confirmed through exclusion of insulinoma and pathologic examination.
    • Treatment involves pancreatectomy, dietary control, and medical therapy.
  • Insulinoma:
    • Typically presents with fasting hypoglycemia.
    • Diagnosis confirmed through imaging studies and biochemical tests.
    • Treatment usually involves surgical removal of the tumor.