General GI Flashcards
Acid ingestions versus basic cause what type of necrosis?
Acid: coagulation necrosis
Basic: liquefaction necrosis –> 1000 fold lifetime risk for developing esophageal CA
Meds that affect tacrolimus level
Increase level: Azole antifungals, calcium channel blockers, and macrolides inhibit the P450 system
Decrease level: Antiseizure agents (such as dilantin) and anti-TB agents can induce the P450 system
Metoclopramide MOA
Inhibition of D2 and 5-HT3-> anti-emetic effcts
Stimulation of 5-HT4 with release of Ach->prokinetic effects
Reye’s Syndrome
Reye’s syndrome involves mitochondrial defects in fatty acid oxidation, caused by a double insult of viral infection (flu, gastroenteritis) and mitochondrial toxins (i.e. salicylates). It is best characterized as an event occurring after aspirin is given for a viral illness, and presents as vomiting/lethargy followed by encephalopathy and hepatocyte damage (ALT and AST 3X > normal). Liver biopsies show microvesicular steatosis without necrosis, and electron microscopy shows mitochondrial changes. Bilirubin levels are usually normal or only slightly increased, and if cholestasis is present other diagnoses should also be considered.
What is the most sensitive indicator for renal cyclosporine toxicity? A. cyclosporine level B. blood pressure C. GFR calculated using creatinine D. Creatinine E. GFR based on inulin
E
Cyclosporine binds with cyclophilin, which in turn inhibits calcineurin. Active calcineurin normally dephosphorylates nuclear factor of activated T cells (NFAT-1), allowing it to enter the nucleus and promote transcription of IL-2 and other pro-T and B cell cytokines. Hence, cyclosporine is known as a calcineurin inhibitor (Tacrolimus works in a similar way, binding to its partner FK-506 binding protein to inhibit calcineurin).
Cyclosporine causes two forms of renal toxicity: acute and chronic. Acute toxicity is characterized by afferent and efferent arteriole vasoconstriction, secondary to endothelial cell dysfunction. This results in a drop in GFR and acute renal failure. Chronic toxicity occurs from vasoconstriction leading to ischemia and structural changes in the kidneys. Acute toxicity is reversible by withdrawing the medication, whereas chronic toxicity is thought to be permanent.
Clinically, patients with cyclosporine toxicity present with decreased GFR. They have hypertension secondary to sodium/volume retention, as the kidneys try to preserve perfusion in the setting of arteriole constriction. The lowered GFR also leads to an increase in BUN and creatinine. Hence, the most sensitive test to determine toxicity would be one that identifies an impaired GFR. Inulin, an inert substance that is freely filtered through the glomerulus and not reabsorbed, is used to accurately determine GFR.
A 7 month old infant is brought to you for evaluation because of recurrent vomiting and lethargy for 3 months. Dietary history reveals that she was exclusively breastfed until 5 months and her diet now consists of cereal, fruits, fruit juice, and vegetables. What enzyme deficiency is likely? A. fructose-6-phosphate B. triokinase C. aldolase B D. lactase E. sucrase isomaltase
c Aldolase B
This patient tolerates lactose from breast milk but does not tolerate foods with sucrose/fructose (lactose is a disaccharide made from glucose and galactose, whereas sucrose is a disaccharide made from glucose and fructose). Sucrose is digested by the brush border enzyme complex sucrose isomaltase, which has both sucrase and alpha1,6 dextrin hydrolyzing activity. Deficiencies in this enzyme result in sugar malabsorption and diarrhea.
Fructose, once transported into the enterocytes by facilitate diffusion, becomes phosphorylated to fructose-1-phosphate by fructokinase. Aldolase B then controls the fate of the molecule, cleaving it into products that enter the glycolytic, gluconeogenic, or glycogen synthesis pathways. Without this enzyme, fructose-1-phosphate accumulates. Such patients with hereditary fructose intolerance develop poor feeding, vomiting, lethargy, hypoglycemia, failure
Cobalamin (Vitamin B12) absorption may be impaired in each of the following conditions EXCEPT: A. pernicious anemia B. cholestatic jaundice C. Crohn’s ileitis D. Zollinger-Ellison syndrome E. Small bowel bacterial overgrowth F. Pancreatic insufficiency
B. Vitamin B12 (cobalamin) comes mainly from the cobalamin-containing meats, but gut bacteria produce small amounts that are absorbed. The absorption of B12 from foodstuffs is a well-characterized process. First, cobalamin must make it through the acidic stomach, by binding to haptocorrin (R binder) at low pH. Most of the gastric haptocorrin originates from saliva. In the duodenum, pancreatic proteases activate in the presence of bicarbonate, hydrolyze haptocorrin, and liberate cobalamin. The cobalamin in turn binds to intrinsic factor (made by gastric parietal cells) and becomes resistant to pancreatic proteases. The cobalamin/intrinsic factor complex binds to an ileal brush border receptor and enters enterocytes. Given this sequence, B12 absorption can be impaired at multiple steps. Pernicious anemia leads to low intrinsic factor, due to autoimmune attack on parietal cells. Zollinger-Ellison syndrome causes the duodenum to be too acidic, preventing protease activation and degradation of the haptocorrin/cobalamin complex. In the same way, pancreatic insufficiency prevents degradation of haptocorrin/cobalamin. Bacterial overgrowth in the small intestine disrupts the cobalamin/intrinsic factor interaction, and ileal disease affects cobalamin/intrinsic factor binding at the ileal brush border. Cholestasis does not alter B12 absorption. Bile does contain haptocorrin, but salivary haptocorrin is clinically the most important.
Which of the following is not a recognized disease association of hepatitis C viral infection?
A. Cryoglobulinemia
B. Porphyria cutanea tarda
C. Membranoproliferative glomerulonephritis
D. Diabetes mellitus
E. Increased risk of myocardial infarction
E.
There are many extrahepatic manifestations of Hepatitis C. Cryoglobulinemia occurs when Hepatitis C-antibody complexes form in the blood. “Mixed” cryoglobulinemia refers to complexes with IgG against the Hepatitis C antigen and IgM against the IgG. To diagnose cryoglobulinemia, blood samples must be kept warm because the complexes precipitate when cooled.
Porphyria cutanea tarda is a common skin manifestation of Hepatitis C. As a result of liver dysfunction, the UROD gene (uroporphyrinogen decarboxylase) is impaired, heme synthesis is halted, and porphyrins build up. The porphyrins collect in the skin absorb visible violet light, producing free radicals that damage nearby tissue. In the skin, the most common findings are erosions, blisters, and scarring.
Membranoproliferative glomerulonephritis is also seen with Heptitis C, perhaps from a vasculitis produced by the antibody-antigen complexes. Diabetes mellitus (adult-onset, insulin resistant) is 4X more likely in Hepatitis C patients for unknown reasons. Some have speculated that the antibody response induced by Hepatitis C results in an autoimmune attack of the pancreas. No association between Hepatitis C and myocardial infarction has been demonstrated.
Sorbitol ingestion
Soft drinks and sugar free gum
Can cause persistent, osmotic diarrhea. Abdominal pain and bloating
DNA hepatitis virus
HBV
Hepatitis virus-RNA and without envelope
HEV and HAV
HEV transmission
When is it most dangerous?
spread through contaminated water. Most dangerous during pregnancy
Pancreatitis genes
CFTR, PRSS1, CTC1, SPINK 1
sTIMULANTS OF ACID
Gastrin, Histamine, Ach
Hirschprungs Disease stain
AchE
HD gene and its association
Ret gene
Ret also assc with MEN2B
Delayed Gastric emptying
> 90% at 1 hr
60% at 3 hrs
10% at 4 hrs
Rapid gastric emptying
retained meal <30% at 1 hr
Alagille
ductopenia (<8 ducts per portal tract) paucity of interlobular bile ducts cholestasis 2/2impaired micelle formation JAG1/NOTCH 2 pulmonic stenosis
Lactose breath test indicative of lactose malabsorption
increase in H by 20 ppm in >3 hrs is positive or failure of blood sugar to rise to 20 by 30 min after ingestion
breath test for SIBO
Rise for than 20 in <90 min
toxic megacolon
transverse colon > 56 mm
Normal sensation for ARM
30-40 mL
Normal Urge for ARM
90-110 mL
MMC where in stomach
Fundus
Resting tone of LES
~20 mmHg
Microvillus inclusion Ds mutation
MYO5B
Tufting enteropathy mutation
SPRINT2
IBD pANCA
UC
IBD ASCA
CD
Vedolizumab
Entyvio
IgG monoclonal Ab against B7 intern
Tofacitinib
Xeljanz
Selective JAK1 and JAK3 inhibitor
What is assc with strictures and perfs in CD
Anti-12 and OmpC
What mutation causes severe colitis in young patients
IL-10
Where is protein stuck in A1AT Deficiency
ER (PAS +)
Hepatoblastoma associations
Beckwidth Weidemann FAP Trisomy 18 GSD Type 1 Li-Fraumen Syn
HCC Associations
PFIC
BA
A1AT
Tyrosinemia
Fibrolamellar CA
variant of HCC
Normal AFP
homogenous lesion with central scar
poor prognosis
Infantile Hemangioma association
Hemihypertrophy
Beckwidth-Weidemann
Focal Nodular Hyperplasia
Central vascular stellate scar (compare to Fibrolamellar CA)
On CT, hypoattenuates early and enhances on DELAYED images UNLIKE fibrolamellar CA
Drug likely to affect VIt D
Phenytoin
Vit E deficiency
loss of position sense
Selenium deficiency
decrease glutathione peroxidase (muscle weakness)
cardiac fibrosis
hypopigmentation
Essential FA deficiency
Omega 6 Scaly rash, Thrombocytopenia, FTT Linoleic Acid deficiency increases production of Mead Acid via Omega 9 pathway •Triene:Tetraene ratio < 0.05 Normal
Copper deficiency
neutropenia
anemia
bone abnormalities
Zinc deficiency
acrodermatitis enteropathica
FTT
diarrhea
muscle weakness
Manganese toxicity
-basal ganglia deposition
Copper toxiticity
Hepatotoxicity
Aluminum toxicity
bone deposition
Is fat, protein or starch most likely to be poorly digested in a 4 month old
Starch
Protein is best
Human milk has higher or lower quantity of protein than formula
lower
Galactokinase deficiency
cataracts
GSD Type 2
Pompe’s = cardiomegaly
GSD Type I
Von Gierke disease. It is caused by a deficiency is glucose-6-phosphatase, the last step in glycogenolysis (and the final step in gluconeogenesis). Patients have doll-like facies and hepatomegaly, and laboratory results are significant for marked hypoglycemia and lactic acidosis. Patients usually present when they begin to sleep through the night and have longer periods without feeds. Treatment includes frequent glucose feeds during the day and continuous feeds at night, usually with uncooked starch that releases glucose slowly.
Hep A outbreak in daycare with kids that do not wear diapers. Admin Immunoglobulin?
Admin to kids only
Y/N
Prophylactic chole in DM
Y
Only DNA hepatitis virus
HBV
PFIC 1 gene
ATPB8
PFIC2 gene
ABC11
PFIC 3 gene
ABCB4
portal tract fibrosis (not seen with PFIC 1/2)
elevated GGT
LAL-D aka Wolman Ds
hepatocellalar micro vesicular steatosis with foamy/enlarged Kupffer cells
Unable to break down fats and cholesterol in cells, so increase cholesterol
Punctate adrenal calcifications, HSM, abdominal distention, FTT, steatorrhea
bethanachol MOA
cholinergic agonist
Olgilve Syndrome
What is it and what is treatment
Acute colonic psuedoobstruction syndrome
Tx with Neostigmine= acetylcholinesterase inhibitor
Lactose breath test would not be accurate with what Abx and in what conditions
TMP-SMX
Diabetic gastroparesis
Systemic Sclerosis
SBS
What is the most important factor that promotes IgA class switching
TGF B
Stool osmotic gap
290-2(Na + K)
>100= osmotic
<50=secretory
Non celiac sensitivity to wheat is due to ___
Fructan, most commonly inulin
Virulence factor produced by H pylori
Cag A–> more likely to get MALToma
H pylori also has Vac A which blocks proliferation of T cells (less likely to get MALToma)
Urease–>protects from gastric acid
Johanson Blizzard Syndrome
AR UBR1 mutation EPI small beaked nose (aplasia of alae ansi) Normal LFTs FTT Short stature Hypothyroidism FTT Sparse dry BLONDE hair Micropenis and microdontia, hearing loss, DD, imperforate anus, VSD
Dubin Johnson
MRP2 gene, ABCC2
Black liver with conj hyperbili
normal LFTs
urine coproporphyrin compromises 80%
Rotor Syndrome
SLC01B1/SLC01B3
Conj hyperbili
total urine coproprophyrins are elevated 2 to 5 fold with 2/3 being coproporphyrins 1
Normal liver histology
UGTA1
Unconj hyperbili
Gilbert and Crigler Najjer
Celiac screening in kids < 2 yoa
Deamindated Gliadin peptide IgG
With what bug do you see demarcated cystic liver lesions with internal septations
Echinococcus granulosa
Alport Syndrome
Deafness
X linked dominant
Microscopic hematuria
Esophageal leiomatosis- no LES relaxation, high pressure with no propagating waves
Drugs with SE of pancreatitis
PEG asparaginase, 6MP and Mesalamine
Menetier
Assc with CMV
Can see PLE, periorbital edema, ascites and pericardial effusion
Hormones that stimulate appetite
Gherlin and Neuropeptide Y
Hormones that suppress appetite
Leptin, Peptide YY, GLP 1
Allgrove Syndrome
Triple A
Achalasia, Alacrima abd Adrenal insuff
AR
Aladdin gene
Syndromes with increased risk of achalasia
Downs Rosycki (deafness, vitiligo, muscle wasting, short stature)
Factors in ALF
DECREASED 5,7,9 (made in hepatocyte)
NORMAL or high 8 (shortest half life) (made in endothelial cells)
In DIC, all are low
Toxin in amanitin-containing mushrooms inhibits
RNA synthesis
Tylenol OD
NAPQI which depletes glutathione, affects zone 3
NAC provides cysteine which increases glutathione
Diverticular ds in kids should make you think of what syndrome
Marfan
Fibrillin 1 gene
GALD
Presents in infancy
Hypoglycemia, hypoalbuminemia, coagulopathy, normal LFTs and elevated ferritin
Marsh Criteria
1: increased lymphocytes
2: crypt hyperplasia
3a: partial villous atrophy
3b: subtotal
3c: total
Juvenile polyposis gene
SMAD4 (more CA risk) and BMPR1A
reflux associated with
chronic otitis media
IBS associated with
previous salmonella infx
Thickened gastric folds
PGE
Menetiers
When do you see elevated BUN/Cr ratio? UGI or LGI bleed
UGI as urea is produced by blood (greater tan 30)
Octreatide
decreases gastrin synthesis
decreases gastric acid output and motility
decreases sphlanic flow
Can PPI increase tacro concentration
Yes, also increased MTX level
dUBIN joHNSON
MRP2 or ABCC22
Ascites
The concentration of albumin in serum minus the concentration of albumin in ascitic fluid, called the serum ascites albumin gradient, can reliably separate ascites into 2 categories: high gradient (≥1.1 g/dL) and low gradient (<1.1 g/dL). High-gradient ascites is present when there is portal hypertension, in conditions such as cirrhosis, fulminant hepatic failure, Budd-Chiari syndrome, and portal vein thrombosis. Low-gradient ascites occurs in the absence of portal hypertension in conditions such as peritoneal carcinomatosis, tuberculous peritonitis, pancreatic ascites, biliary leak ascites, nephrotic syndrome, and serositis.
Immunostaining for Tufting enteropathy vs microvillus inclusion
TE: MOC31
MVI:CD10
Ab for PSC
AMA
Ab with worst prognosis in AIH
SLA
diet for PLE
HIGH PROTEIN and LOW FAT
MEN 1
3 P’S
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumor`
MEN 2A
Parathyroid hyperplasia, Medullary thyroid CA, Pheochromocytoma
MEN 2B
Mucosal neuromas, Marfanoid, MTC, Pheo
higher bioavailable ZINC Formula vs BM
BM
A1AT accumulates where
ER
What immunoglobulin is low in Type 2 AIH
IgA
Urine ketones negative with kid who had abnormal electrolytes Dx
MCAD
Ketogenic diet – what is most common GI complaint
Diarrhea and abdominal pain
Kidney stone
MC IBD med to give pancreatitis?
AZA
What cells produce antibodies in your gut mucosa?
M cells
Apomorphine where does it act?
Chemoreceptor
Patient with refeeding, edema and cardiac failure. They are deficient in what Vitamin?
Thiamine
Short stature with ok weight that will have hyperconvex nails and cubitus valgus. Diagnosis?
Turner syndrome
What peptides increase intragastric pressure?
Motilin, cck, somastatin
Patient with increase liver enzymes, coagulation, increase INR, hemolytic anemia. Diagnosis
Wilson’s disease
How to test for Trysinonemia
urine succinylacetone
What type of kidney stones do you get in IBD
Oxalate
TEF associated with…
VACTERL
Most common reason for stenosis in distal esophagus
Tracheobronchial rest
What do you see with Cricopharyngeal achalasia
Chiari malformation
Chief cells what do they do?
protein metabolism because they secrete pepsinogen
Celiac ds, should avoid what
Gluten, Barley and Rye
What causes pancreatic enzyme secretion
CCK
Congenital Cl diarrhea, do you see acidosis or alkalosis
metabolic alkalosis
What Vitamin do you supplement in abetalipoproteinemia?
Vitamin E
What is the active metabolite for 6-MP
6-TG
Egg diarrhea caused by
Salmonella
What do you see on biopsy in Hirschprung’s disease?
Calretinin stain
What is the side effect of Ceftriaxone?
Biliary sludge
Ascites with a SAAG of <0.8 what do they have?
Malignancy
- Wilson disease what is the defect?
Copper P-type
Tacrolimus toxicity
Hyperglycemia
PRSS1 inheritance
AD
Nutrition in CKD
Decreased protein and low phos
Toxicity of what would cause HA and tremors in pt on TPN
manganese
What do you see in breastmilk microbiome?
Bifidobacteria
MOA of hyocyamine?
Anticholinergic
What does a Case Control study look at?
Odds ratio
What is the most common cause for a distal esophagus stenosis?
Tracheobronchial remnant/rest
Associated with APC gene
Gardner and Turcot
SMAD4 association
Juvenile polyposis syndrome
Hereditary hemorrhagic telangiectasia
NOD2 in CD predisposes you to what phenotype?
Stricturing
What risk factors are good for UC
Smoking and appendectomy
What medicine can you give for radiation colitis?
Mesalamine
Why do short gut patients with connect colon salvage more energy than those with ileostomies?
SCFA
A liver transplant patient is taking tacrolimus as his immunosuppressant. He develops gastroparesis. He is started on erythromycin and shortly thereafter he begins to get a headache, what is the likely reason?
Taco toxicity
Patient with CGD has a liver abscess. What is the most likely organism?
Staph
A patient is found to have elevated urine succinylacetone. What is the treatment?
NTBC (Nitisone)
Has tyrosinemia
Little boy has high ammonia and elevated bicarbonate levels. What is the etiology?
OTC deficiency
Organomegaly + adrenal calcifications
Wolman Syndrome
Pregnant mom develops HELLP syndrome annd fatty liver. What do you think of?
LCHAD deficiency
Mechanism of PRSS1
Increased Trypsin
AD
develop adenocarcinoma
Mechanism of SPINK1?
Uninhibited activation of trypsin
Patient has FTT, steatorrhea, mild anemia, low platelets, low neutrophils. What is diagnosis?
Shwachman Diamond
What meds induce phase 3 MMC
Erythromycin
Octreotide
Stool pH in carb malabsorption
ph<6 and significant perianal excoriation
Patients with X-linked hyper-IgM syndrome are at high risk for what infection? Treatment?
Cryptosporidium infection of the biliary tract
Nitazoxanide
Vit A toxicity
dry skin, headaches, hepatomegaly, and increased CSF pressures (pseudotumor cerebri)
Vit A stoarge and defiency
Ito cells (liver) xerophthalmia (abnormal keratinization of conjunctiva secondary to poor lacrimal gland secretion), poor bone growth, non-specific skin problems, and decreased humoral and cell mediated immune function. Vitamin A deficiency can also lead to anemia, presumably by inhibiting the normal metabolism of iron. Supplementation can reverse many of these problems; however, advanced corneal scarring may be irreversible.
kwashiorkor vs marasmus.
Kwashiorkor is characterized by muscle atrophy and increased body fat, secondary to poor protein intake in the setting of adequate energy intake. Marasums, on the other hand, is characterized by muscle wasting and depleted fat stores, secondary to inadequate intake of all nutrients.
Severe PEM of both types produces a number of signs and symptoms: irritability, decreased serum lipoproteins, increased infection risk, and anemia. However, kwashiorkor classically presents with severely low serum albumin concomitant with edema. Marasmus presents with low-normal serum albumin with wasting but no edema.
kwashiorkor vs marasmus.
Kwashiorkor is characterized by muscle atrophy and increased body fat, secondary to poor protein intake in the setting of adequate energy intake. Marasums, on the other hand, is characterized by muscle wasting and depleted fat stores, secondary to inadequate intake of all nutrients.
Severe PEM of both types produces a number of signs and symptoms: irritability, decreased serum lipoproteins, increased infection risk, and anemia. However, kwashiorkor classically presents with severely low serum albumin concomitant with edema. Marasmus presents with low-normal serum albumin with wasting but no edema.
Which of the following is NOT found in Wolman’s disease (cholesterol ester storage disease)
A. Orange coloured liver
B. Lipid laden macrophages in the portal triad
C. Blueish hue to some hepatocytes
D. Diffuse steatosis
E. Inflammation
C. Blueish hue to some hepatocytes
Wolman disease is caused by a defect in lysosomal acid lipase (LAL). As a result, lysozymes receive endocytosed lipoproteins properly, but they cannot hydrolyze the triglycerides and cholesterol esters. The triglycerides and cholesterol esters accumulate inside cells, leading to bowel wall thickening (accumulation in enterocytes and macrophages) and severe life-threatening diarrhea and malnutrition. In Wolman disease, the adrenal glands are also calcified.
The liver in Wolman disease is enlarged and appears yellow/orange and greasy in appearance (the orange comes more from the cholesterol esters than the triglycerides). There is extensive fibrosis, associated with lymphoid infiltration and accumulation of triglycerides/cholesterol esters in hepatocytes, Kupffer’s cells, and portal area macrophages. In iron storage disorders, rather than Wolman disease, hepatocytes stained for iron may have bluish-hue reflecting excess ferritin in the cytoplasm.
A 6-year-old boy just arriving from Eastern Europe has had malodorous diarrhea since early infancy, even though he was breast-fed. He is small, has some bruises from bumping into furniture going to the bathroom at night, and has recently developed some difficulty walking. Physical examination shows that he is small and undernourished, with depleted subcutaneous fat. He has a protuberant abdomen and 1+ edema in his lower extremities. He has no deep tendon reflexes in his lower extremities. Which one of the following explains the finding on the small intestinal biopsy from this patient?
A. gluten enteropathy
B. congenital lactase deficiency
C. abetalipoproteinemia
D. glucose-galactose transport defect
E. chronic nonspecific diarrhea of childhood
C
This patient has evidence of fat malabsorption (wasting), including Vitamin K (bruising), Vitamin E (decreased deep tendon reflexes), and perhaps even Vitamin A (night blindness or retinitis pigmentosa). Abetalipoproteinemia (ABL) can cause such symptoms.
Vitamins and minerals are incorporated into infant formulas in the United States to provide an essentially complete diet.
Which of the following minerals or trace minerals must be SUPPLEMENTED in ready-to-feed infant formulas to meet the recommended daily allowances?
A. Calcium
B. Fluoride
C. Iron
D. Magnesium
E. Selenium
Fluoride
A 5-month-old boy with frequent vomiting is switched from human milk to formula. His symptoms immediately worsen, and he becomes highly irritable. Shortly afterward, he becomes comatose. Physical examination reveals a small, hypotonic child responsive only to pain. Laboratory studies reveal: increased anion gap; metabolic acidosis; serum ammonia concentration, 150 mg/dL; and serum glucose level, 85 mg/dL.
Which of the following classes of inborn errors of metabolism is MOST likely in this patient?
A. Disorder of fatty acid oxidation
B. Glycogen storage disease
C. Lysosomal disease
D. Organic acidemia
E. Urea cycle defect
Urea cycle defects should be considered in patients with an anion gap, high ammonia, and normal glucose. Urea cycle defects lead to high ammonia, because there is a defect in converting ammonia to the secreted product urea. High ammonia causes neurological deficits through mechanisms incompletely understood. High ammonia also causes an anion gap, possibly by impairing brain mitochondria, forcing anaerobic metabolism of sugar, and producing lactic acid as a by-product. This patient showed mild symptoms with human milk (i.e. frequent vomiting), because human milk has low protein levels (2.3 g/dL protein at birth and decreasing to 1.5-1.8 g/dL after 2-4 weeks). The symptoms increased with formula, because formula has more protein (approximately 2.1-2.2 g/dL) which led to an increased accumulation of ammonia.
For patients with hypoglycemia and no ketones what disorder do you think of
, a disorder in fatty acid metabolism should be suspected. MCAD
Which of the following is not part of the Currarino triad characterizing caudal regression syndrome which can present as infantile constipation?
a. dysplasic sacrum b. anal abnormalities c. tethered cord
d. pre-sacral mass
C
A 6-week-old infant born at term has a hemoglobin level of 11 gm/dL and is diagnosed with physiologic anemia of the newborn. The MOST likely cause is:
A. inadequate iron stores in the bone marrow B. inadequate serum levels of vitamin E
C. increased excretion of iron in the stool
D. low levels of serum erythropoietin
E. persistent fetal hemoglobin
D. Physiologic anemia of the newborn occurs when fetal hemoglobin normally declines at 6 to 8 weeks. Because fetal hemoglobin has a higher affinity for oxygen, serum erythropoietin levels are initially low. Erythropoietin levels eventually rise again with time, correcting the anemia. Some have investigated whether Vitamin E mitigate the normal hemoglobin nadir, with equivocal results.
A 3-year-old boy underwent a hepatoportoenterostomy (Kasai procedure) for extrahepatic biliary atresia at 6 weeks of age. He has been receiving cholestyramine to treat severe pruritus for the past 2 months. Of the following, the nutrient MOST likely to be malabsorbed because of this patients underlying liver disease and its treatment is: A. carbohydrate B. fat C. protein D. trace elements E. water-soluble vitamins
B. This patient will have low luminal bile acids for two reasons: 1) poor bile acid secretion into the gut, secondary to biliary atresia; and 2) poor bile acid activity in the gut, secondary to binding with cholestyramine. Bile acids, pancreatic lipase, and pancreatic colipase work together to digest fats efficiently. Without bile acids, fat malabsorption will occur. Neither BA nor cholestyramine impairs duodenal or pancreatic function, so protein and carbohydrate absorption should be intact.
Oral ulcers, genital ulcers, uveitis, aceiform facial rash
Behcet
HLA B51
Linaclotide
Linzess
Guanylate cyclase agonist
Low fecal fat (pH<6) should make you think of what diagnosis
Carb malabsorption
Reducing substance should make you think of what diagnosis
Sugar malabsorption
GIST (originate from, express what in adults vs kids, increased incidence of what)
interstitial cells of canal
-KIT in adults
-12% in kids succinate dehydrogenase (SDH) enzyme mutation
- increased incidence of NF1
Carney Strata’s syndrome
GIST and paragangliomas in kids with SDH mutation in absence of KIT or PDGFRA mutations
Carney triad
GIST, paraganglioma, and pulmonary chondroma
Lipomas most commonly found where in the GI tract
Ileum and Duodenum
-Arise from submucosal or serial adipose tissue
Carcinoid tumors most commonly found where in the GI tract
Appendix
-Then stomach, SI, rectum
Carcinoid crisis
Secretion of serotonin, histamine, and catecholamines
-Flushing diarrhea and pain, tachycardia, BP variation, and heart failure
- Often in foregut tumors or if large
-Dx: 5-hydroxyindoleacetic acid
-tx: resect
Tx of acromegaly with octreotide can predispose to what?
gallstone formation (due to suppression of CCK release and GB emptying)
Hyperparathyroidism can present as what GI disorder
-Gastroparesis bc increase Ca leads to reduction of NM excitability
-Peptic acid ds bc of gastric acid hyper secretion
-Constipation
-Acute pancreatitis
AI hepatitis type I
Ana +/- SMA
OLDER kids
Typically present with cirrhosis
Can wean meds
AI hepatitis type 2
LKM/LC1
Young kids
Acute presentation
Lifelong suppression
Syndrome assoc with AIH
AI polyendocrinopathy candiasis ectodermal dystrophy syndrome (APCED)
Immunodysregulation, poly endocrinopathy enteropathy X-linked syndrome (IPEX)
CVID
hyper IgM syndrome
What antibodies, signifies worse, autoimmune hepatitis disease
Soluble liver, antigen (SLA)
A1AT deficiency path
PAS positive diastase resistant globules in peripheral region
Globules have clear halo surrounding zone 1
PFIC 1 gene
Atp8B1 FIC1
PFIC 1 location
Apical membranes of hepatocyte, colon, intestine, pancreas
PFIC 1 histology
Bland cholestasis with course granular canalicular bile on electron microscopy
Labs PFIC 1
Normal or low GGT, increase serum bile acid, decrease biliary bile acid
Labs PFIC 2
Normal or low GGT, increase serum bile acid, decrease biliary bile acid
Characteristics PFIC 1
Progressive cholestasis, severe pruritis , diarrhea, pancreatic involvement, growth, failure, hearing loss
PFIC 2 gene
ABCB1/ BSEP
PFIC 2 gene location
Cannalicular membranes of hepatocytes
PFIC 2 histology
Neonatal giant cell hepatitis and amorphous canalicular bile on EM
PFIC 2 characteristics
Growth failure, pruritus, severe fat soluble deficiency, rapidly progressing, cholestatic giant cell hepatitis
Risk of portal hypertension in PFIC
2>1
Risk of hepatocellular, carcinoma, or cholangiocarcinoma in PFIC
PFIC 2
PFIC 3 gene
ANCB4/MDR3
PFIC 3 location
Canalicular membrane of hepatocyte
PFIC 3 histology
Bile duct proliferation and periportal bile on EM
PFIC 3 labs
Increase GGT, normal bile acid concentration
PFIC 3 characteristics
Later onset of cholestasis, minimal itching, portal HTN, gallstones
PFIC 3 tx
Urso and liver transplant
PFIC 1 & 2 tx
Supportive, antipruritic, biliary diversion, liver transplant
New PFIC GENE
TJP2
New PFIC Histology
Tight junctions between hepatocytes and biliary, canaliculi, elongated and liking densest part of Zona occludens
Findings in all PFIC
Absence of Xanthomas
Near normal serum cholesterol
Severe fat soluble vitamin deficiency growth failure
Progression to cirrhosis
Benign recurrent, intrahepatic, cholestasis gene
AR
ATP8B1
ABCB1/BSEP
Benign recurrent, intrahepatic, cholestasis histology
Centrilobular cholestasis and canalicular cholestasis
Benign recurrent, intrahepatic, cholestasis labs
Increased GGT and serum bile acid
Johansson Blizzard triad
EPI
Absence of permanent teeth,
Nasal wing aplasia or hypoplasia
AR
Johansson Blizzard assoc with what other manifestations
Congenital deafness
Scalp defects
Cognitive impairment
Short stature
Hypothyroidism
Microcephalic
iUGr
Imperforate anus
Congenital heart defects
Genital malformations
Renal abnormalities
Diabetes
gH deficiency
Scwachman-Diamond syndrome triad
EPI
Bone marrow dysfunction
Skeletal abnormalities
AR
Johansson blizzard pathogenesis
Chromosome 15q
UBR1 mutation
Shwachman diamond pathogenesis
Chromosome 7
SBDS gene
Pearson marrow pancreas syndrome
Rare mito disorder
EPI
Bone marrow vacuolization of cells
Siderblastic anemia
Lactic acidosis
Early death
Jeune syndrome
Rare AR disorder
EPI
Respiratory difficulties and asphyxiating thoracic dystrophy
Comparing CF to SDS sweat Cl
Sds: normal
Cf: high
Comparing CF to SDS trypsinogen
Sds: low in infants; normal over 3 yoa
Cf: High in newborns, low after 1 yoa
Comparing CF to SDS histology
Sds: normal ductwork elements. Fatty replacement of acunar tissue
Cf: duct obstruction and fibrosis
Comparing CF to SDS pancreatic enzyme output
Sds: increase output over time with normal fat absorption in 50% by 4 yoa. Output is not dependent on genotype
Cf: output dependent on genotype
Primary stimulant of GI motility
Ach
Primary inhibitor of GI motility
Norepi
Allgrove syndrome
Triple A
Achalasia, Addison, alacrima
Delayed gastric emptying definition
> 60% remaining at 2 hours or >10% at 4 hours
Type 1 achalasia
Minimal pressurization
100% failed peristalsis
Type 2 achalasia
Failed peristalsis with panesophageal pressurization with >20% of swallows
Type 3 achalasia
Failed peristalsis
Preserved fragments of nonpropagating distal peristalsis or spastic contractions
Cm unlikely to pass pylorus
2.5 cm
Cm unlikely to pass duodenal sweep
6 cm
If no progression of object is —days recommend removal
3 days
Remove object if still retained in —weeks
2-4 weeks
Hepatitis in adolescent females, indolent finding of cirrhosis
AI hepatitis type 1
Smooth muscle Ab
Hepatitis in young kids with liver failure
Liver kidney microsomal
AIH type 2
Anti mitochondrial antibody
Primary biliary cirrhosis
Ana positive
AIH 1
Can also see SMA positive
IGG can be elevated in AIH? T/F
True
What Abx can unmask AIH type 1
Minocycline
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome is associated with what othe r AI disease?
AIH type 2
T/F therapy is typically lifelong in AIH type 2
True
Methotrexate SE
Hepatotoxicity
Nausea and vomiting (all reduced with folate)
Defect seen in infants of young mothers, nicotine, cocaine and aspirin/ibuprofen exposure
Gastroschisis (right of umbilicus)
Not associated with syndromes
Associated with malrotation
Defect seen in advanced maternal age and twin births
Omphalecele (midline defect)
Associated with syndrome (beckwicth weideman, CHARGE, and pentalogy of Cantrell) and malrotation
If IGA deficiency, how to screen for celiac disease
Deamidated gliadin peptide IgG
Diarrhea that leads to alkalosis
Congenital chloride diarrhea
SLC26A3
Rx of congenital chloride diarrhea
Enteral Kcl NaCl supplement, PPI, chilestyramine
Lymphocytic colitis assoc with
Celiac disease and PPI
Apostolic cells hallmark in
Acute GVHD
21-100 days after BMT
Zollinger Ellison syndrome
Men 1
Elevated gastrin
Positive secretin test
Low gastric pH
Multiple ulcers on egd
Alkali ingestion
Liquefactive necrosis
Transmural
Esophageal>gastric
ACidic ingestion
Coagulative necrosis
More gastric injury
True sucking occurs at how many weeks
18-24
At how many weeks can you sustain nutrition orally
34-37 weeks
Triple A
Allgrove
Alacrima
Achalasia
ACTH insensitivity
Gene 12q13
Hypoglycemia within 5 years of life
Rozycki syndrome
Achalasia
AR deafness
Short stature
Vitiligo
Muscle wasting
Assc with chagas, downs, sarcoidosis, HD, pyloric stenosis, paraneoplastic syndrome, Hodgkins
Foregut duplications associations
Lung sequestration
Vertebral anomalies
Intra abdominal intestinal cysts
TEF gene with tracheoesophageal ridge
Sonic hedgehog
EA and TEF associations
VACTERL
CHARGE
SCHISIS syndrome
Pyloric stenosis
Hirschprungs disease assc with
RET, EDNRB,SOX gene
Downs, wandeeburg, ACTG2, MEN2B, MEN2A
Type I AIH
Anti smooth Ab
Type 2 AIH
Anti liver kidney
Type I AIH
SMA ANA
HLA DR3/4
Older onset
Acute hepatitis, cirrhosis
Type 2 AIH
LKM, LC1 (liver cytosol)
HLA DR7/3
Younger onset
Acute hepatitis, liver failure
Type 1 AIH assc
UC
PSC
ITP
AIH histology
Interface hepatitis
Lymphoasmacytic infiltrate
Rosetting of HC
Periportal necrosis
ANCA in AIH
Poor prognosis
Picornavirus
Hep a
Virus secreted in bile, transmitted to stool
Extra intestinal features of Hep B
Membranous GN
Serum sickness(skin rash, polyarteritis)
Cryoglobinemia
Aplastic anemia
Zone 3
Drug metabolism
Ketogenesis
Bile acid synthesis
Glycolysis
PKU phenylketonuria
Error in phenylalanine hydroxylase
Death, MR and growth failure
Maple syrup urine
Error in ketoacid dehydrogenase
Hypoglycemia, death, MR, and increased urinary and plasma leucine
Phenylalanine deficiency
In infants being treated for pku
FTT, neurological signs and eczema
Isoleucine deficiency
Infants receiving branch chain AA free formula for MSUD
FTT and acrodermatitis Enteropathica
What anticonvulsants will increase GGT
Phenobarbital and phenytoin
Teglutide side effect
GLP 2
Bowel obstruction, colonic polyps and fluid overload
SMAD4 Assc with what 2 conditions
JPS and hereditary hemorrhagic telangiectasia
