GI,Hepatobiliary,Pancreas Flashcards
-GI -Hepatobiliary -Pancreas
Hirschsprung disease structural chromosomal abnormality.
Trisomy 21 (10% of cases)
Syndromes ass. w/ Hirschsprung.
- NF1
- MEN2A
- Waardenburg syndrome
- Congenital Central Hypoventilation (Haddad)
- Familial Dysautonomia (Riley-Day)
- Smith-Lemli-Opitz syndrome
Osler-Weber-Rendu syndrome inheritance/mutation.
- Autosomal Dominant
- ENG gene or ACVRL1 gene
Osler-Weber-Rendu syndrome features.
- Epistaxis (Children)
- Skin lesions (Adolescence)
- GI bleeding (Adults)
MCC of malabsorption in neonatal period.
Microvillus Inclusion Disease (MDD)
Microvillus Inclusion Disease (MDD) features.
- Autosomal Recessive
- Wall of sm. bowel is “paper thin” with villous blunting
- Intracellular inclusions (PAS, CEA, CD10 Positive)
MC location of Intestinal Atresia.
Ileum
Intestinal Atresia inheritance.
- 30% ass. w/ Down Syndrome.
- Most are isolated defects.
Gastroschisis is strongly associated with what?
DECREASED maternal age
Gastroschisis has very high levels of what?
Maternal Serum AFP
Gastroschisis vs. Omphalocele:
-Located midline, essentially within the umbilicus
Omphalocele
Gastroschisis is to the Right of the umbilicus
Gastroschisis vs. Omphalocele:
-Typically an Isolated Defect
Gastroschisis
(Omphalocele is associated with major cardiac defects, chromosomal abnormalities (trisomies 21, 18, 13), or Beckwith-Wiedman syndrome
Which HLA allele is associated with Celiac Sprue?
-HLA-DQ2 (~95%) (30% of general population)
Caroli disease mutation.
PKHD1 gene on chr6p (same as ARPKD)
Caroli disease features.
- Segmental dilation of the intrahepatic bile ducts
- Recurrent stone formation
- Bacterial cholangitis
Alagille syndrome inheritance/mutation.
- Autosomal Dominant
- JAG1 gene
Alagille syndrome features.
- Dysmorphic features
- Noninflammatory LOSS of interlobular BILE DUCTS
- Cholestasis (neonatal period)
Hereditary Hemochromatosis (HH) inheritance/ mutation.
- Autosomal Recessive
- HFE gene located within the MHC region on chr6p
MC clinically significant mutation in HH.
-C282Y
2nd MC is H63D; found in 25% of whites
T/F: Men are 2X more likely to develop complications of HH.
True
-Example of Autosomal Recessive condition with variable penetrance
Pathophysiology of Hereditary Hemochromatosis.
- Enhanced Intestinal Iron Absorption
- Low HEPCIDIN levels
- Iron deposition within hepatocytes, pancreas, pituitary, etc.
- Cirrhosis
- Pancreatic Fibrosis (DM)
- Hypogonadotrophic Hypogonadism
- Infertility
- Osteoarthritis
- Cardiomyopathy
- BRONZE SKIN
Wilson Disease (Hepatolenticular Degeneration) inheritance/mutation.
- Autosomal Recessive
- ATP7B gene (encodes an ATPase utilized in copper binding to ceruloplasmin)
Wilson disease presentation.
- Liver disease
- Neuropsychiatric (Kayser-Fleischer rings)
- Hemolysis
Wilson disease Liver Biopsy findings:
- Glycogenated nuclei
- Steatosis
- Inflammation (similar to chronic viral hepatitis)
- Ultimately Cirrhosis
Wilson disease Lab findings.
-LOW Ceruloplasmin
- HIGH urinary Copper excretion
- Serum Copper is UNRELIABLE
Alpha1-Antitrypsin (AAT) deficiency inheritance/gene/chr.
- Autosomal Recessive
- SERPINA1 (P1) gene on chr14
(Polymorphic)
Most healthy adults are homozygous for which SERPINA1 gene allele?
M allele (Pi-MM)
AAT deficiency is usually caused by what SERPINA1 genotype?
-Z allele (Pi-ZZ)
or Pi-ZS
Bilirubin Excretion disorder subclasses.
- Conjugation disorders
- Secretion disorders
What are the two Bilirubin Conjugation disorders?
- Gilbert syndrome
- Crigler-Najjar syndrome
What are the two Bilirubin Secretion disorders?
- Dubin-Johnson syndrome
- Rotar syndrome
Gene involved in Bilirubin Conjugation disorders?
-UGT1A1 gene
What enzyme is deficient in the Bilirubin Conjugation disorders (Gilbert and Crigler-Najjar)? What does this lead to?
- Bilirubin Glucoronosyltransferase
- Increased Unconjugated bilirubin
Gilbert syndrome mutation.
5’ TATA box in UGT1A1 promoter (5% of pop.)
Mildly deficient bilirubin conjugation
Type I Vs. Type II Crigler-Najjar:
-NO glucoronosyltransferase activity.
Type I
Type II has <10% of normal
Pathophysiology of Dubin-Johnson and Rotor syndromes.
- Defective secretion of conjugated bilirubin into the canaliculus.
- Mild Conjugated hyperbilirubinemia
Dubin-Johnson mutation.
MRP2 (multidrug resistance protein 2) gene
Main difference between Dubin-Johnson and Rotar syndrome.
Rotar syndrome does NOT have Pigmentated Hepatic Parenchyma
Cystic Fibrosis gene/mutation.
-CFTR gene on chr7
chloride channel expressed in respiratory, GI, Skin, Hepatobiliary, Pancreas, Vas Deferens
T/F: CF is the most common Autosomal Recessive condition in Whites.
True
-carrier frequency is 1 in 25 (affects 1 in 2,000 births)
What syndrome is ass. w/ Autosomal Dominant Pancreatitis and Bone Marrow failure.
Pearson syndrome
Pearson syndrome genetics.
Chromosomal breakage syndrome affecting the Mitochondrial DNA
(microdeletion within the mtDNA)
Syndrome characterized by marrow failure and pancreatic insufficiency. The pancreas shows fatty metamorphosis with preservation of pancreatic islets.
Shwachman-Diamond Syndrome
SBDS gene
Syndrome characterized by hypoplasia of the nasal alae, pancreatic exocrine insufficiency with pancreatic lipomatosis, hypothyroidism, and deafness.
Johnason-Blizzard syndrome
