Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

GI Final > Genetics of GI Disorders > Flashcards

Genetics of GI Disorders Flashcards

1
Q

What initiates heme metabolism?

A

macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the steps to heme metabolism?

A

RBC –> macrophage –> heme dissociates from globin –> iron dissociates from heme –> porphyrin ring –> porphyrin ring opens to become bilirubin (yellow and toxic) –> bilirubin + albumin to liver — UDP glucoronyl transferase —> conjugated bilirubin –> stercobilinogen in intestines — oxidation —> stercobilin (brown)

stercobilinogen –> urobilinogen –> urobilin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Is unconjugated bilirubin water soluble?

A

NO

must attach to albumin when traveling in the blood to the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Is conjugated bilirubin water soluble?

A

YES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where does the bilirubin and albumin dissociate in the liver?

A

space of Disse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are conjugated bilirubin?

A

soluble bilirubin that UDP glucuronyl tranferase has added glucuronic acid (1= mono, 2= di)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What transports conjugated bilirubin to the canuliculi?

A

MRP2 multidrug resistance associated protein 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Crigler Najjar syndrome?

A

autosomal recessive
major deficiency in UDP glucuronyl transferase
build up of unconjugated bilirubin in blood
brain damage in infants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Gilbert’s syndrome?

A

autosomal dominant or autosomal recessive
deficiency of UDP glucuronyl transferase from a defect in the gene promotor of UGT1A1
usually asymptomatic
during periods of increased hemolysis mild jaundice can occur
5-10% of population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Dubin Johnson syndrome?

A

autosomal recessive
mutation in MRP2 protein
conjugated bilirubin is not excreted into bile in gut
build up of conjugated bilirubin
asymptomatic besides jaundice
grossly black liver due to impaired excretion of epi metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Rotor’s syndrome?

A

autosomal recessive
similar to Dubin Johnson
causes increase in conjugated bilirubin in blood
Mutation in OATP1B1 and OATP1B3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What type of genetic condition is Gilbert’s syndrome?

A

autosomal recessive or autosomal dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is a common cause of mild isolated hyperbilirubinemia with all other LFTs normal?

A

Gilbert’s syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What can exacerbate periods of jaundice in Gilbert’s syndrome?
What can improve the periods of jaundice?

A
  • fasting
  • alcohol
  • acute illness
  • estrogen
  • Nicotinic acid from IV

improved by low dose barbituates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the treatment for Gilbert’s syndrome?

A

none
avoid certain meds (irinotecan)
if severe jaundice, phenobarbitone can decrease the concentration of unconjugated bilirubin in serum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Wilson’s disease?

A

genetic disorder
excess copper kept in tissues
can form hydroxyl radical when exposed to hydrogen peroxide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What does ATP7B do?

A
  1. binds copper to apoceruloplasmin

2. package into vesicles for exocytosis to bile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the genetic defect in Wilson’s disease?

A

autosomal recessive defect in ATP7B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Wilson’s disease

-neural effects

A
  • basal ganglia = movement disorder
  • cerebral cortex = dementia
  • deterioration in school performance
  • behavioral changes
  • inco-ordination (handwriting deteriorates)
  • dystonia
  • dysarthria
  • excessive salvation
  • mask-like facies
  • dysphagia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is a symptom of Wilson’s disease that is useful for diagnosis?

A

Kayser-Fleischer ring

copper deposit in Descemet’s membrane of the cornea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the first symptoms of Wilson’s disease?

When do they appear?

A

acute hepatitis –> cirrhosis

late childhood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is significant about the blood and urine in Wilson’s disease?

A

blood

  1. decrease ceruloplasmin
  2. increased free copper

urine
1. increased free copper

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are complications of Wilson’s disease?

A
  • hepatosplenomegaly
  • renal disease
  • hemolytic anemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the genetic defect in classic galactosemia?

A
  • autosomal recessive disorder with the abscence of -galactose 1 phosphate uridyltransferase
  • normally catalyzes reaction galactose 1 phosphate to glucose 1 phosphate
  • causes accumulation of galactose 1 phosphate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What are the symptoms of classic galactosemia?
infantile cataracts, failure to thrive, hepatomegaly, and jaundice brain damage --> mental retardation
26
What is the treatment of classic galactosemia?
complete removal of lactose and galactose from the diet
27
What are symptoms of Crigler Najjar syndrome type I?
severe jaundice and kernicterus
28
What is more severe Crigler Najjar type I or II
type I
29
When does Crigler najjar present?
early in life
30
What is the gene for Crigler Najjar? - type I vs type II - also metabolizes
UGT1A1 type I - totally absent or not expressed type II - (Arias syndrome) - defective, less active than normal -also metabolizes anti-cancer drugs and other molecules
31
What are symptoms and PE findings for Crigler Najjar?
- neonatal jaundice - sepsis - hypotonia - kernicterus: deafness, poor mental progression/development caused by bilirubin deposition in brain PE findings - jaundice - oculomotor palsy
32
What is the treatment for Crigler Najjar?
- plasmapheresis - phototherapy - phenobarbital - UGT1A1 inducer for type II - liver transplant??
33
What are the tests for Gilbert's syndrome?
- unconjugated hyperbilirubinemia without evidence of hepatitis or hemolysis - genetic testing - fasting test: unconjugated bilirubin will rise after a day of fasting with low lipid 400 kcal diet - rifampin test: unconjugated bilirubin rises after a dose of Rifampin (less specific b/c can also rise with chronic liver disease)
34
More than ___ of the serum bilirubin is conjugated in Rotor's syndrome
50%
35
What is a black liver indicative of?
Dubin-Johnson syndrome
36
What is found in the urine in Rotor's syndrome?
bilirubinuria
37
When may someone with Rotor's syndrome become jaundice or icteric?
during fatigue, pregnancy, or with oral contraceptives
38
What are lab findings for Dubin-Johnson?
- direct hyperbilirubinemia and resulting increased in total bilirubin - coproporphyrin III:corproporphyrin I ratio 1:3-4 opposite of normal - total urine corproporphyrin levels normal
39
What are the lab findings for Rotor's syndrome?
- coproporphyrin III:corproporphyrin I ratio 1:3-4 opposite of normal - total urine corproporphyrin levels elevated
40
What tissues does copper accumulate in with Wilson's disease?
- liver - brain - cornea - joints
41
What is the other name for Wilson's disease? | What is the gene mutation?
hepatolenticular degeneration | ATP7B
42
What is wrong in Wilson's disease?
- inadequate copper excretion by liver into bile | - failure of copper to enter circulation bound to ceruloplasmin
43
What is ceruloplasmin?
transport protein for copper | -usually represents the largest fraction of copper in the body
44
What does free copper generate?
free radicals that damage tissue
45
What is the inheritance pattern for Wilson's disease?
autosomal recessive
46
What are symptoms of Wilson's disease?
- parkinson-like symptoms secondary to copper deposits in putamen - hemiballismus- flailing, ballistic, undesired movements of the limbs secondary to copper deposits in subthalamic nucleus - dementia secondary to copper deposits in cerebral cortex
47
What are PE findings for Wilson's disease?
- cirrhosis - corneal deposits on slip lamp examination - Kayser-Fleischer rings RARELY seen in other conditions that may result in increased copper such as primary biliary cirrhosis.
48
What are lab results for Wilson's disease?
- low total serum copper (due to decreased ceruloplasmin) - elevated serum non-ceruloplasmin bound copper - elevated urine/serum free copper - heemolytic anemia
49
What will a liver biopsy show for Wilson's Disease?
increased hepatic copper
50
What are the treatment options for Wilson's Disease?
Medical -ammonium tetrathiomolybdate --> facilitates urinary excretion of copper -penicillamine --> copper chelating agent -trientine --> copper chelating agent -zinc --> competes with copper for absorption in the gut via the same transporter (ATPB7) Surgical -consider liver transplantation as clinical condition deteriorates
51
What is Wilson's disease a risk factor for?
- hepatitis - cirrhosis - hepatocellular carcinoma - Fanconi's disease of the proximal tubules
52
A 10 week old boy was presented to the metabolic unit of a pediatric hospital for irregularities in brain development. He was born by vaginal delivery after 38 week gestation with a birth weight of 2.7 kg (5.95 lb) to a 33 yo woman of hispanic descent. From week 10 of gestation ultrasonography had shown progressive enlargement of ventricles, absence of corpora collosa, and hypoplasia of the brainstem and cerebellum. After birth he had been in respiratory distress, showed hypotonia, was feeding poorly, and had frequent seizures. Labs: blood pH 7.2, serum pyruvate, lactate, and Alanine elevated, citrate reduced. Imaging: H-MRI at 1.5 T cconfirmed the US findings, 2D chemical shift at 2.37 ppm-attributed to lactate and pyruvate respectively - in the cerebrospinal fluid. What should the pt be treated with? A. low galactose diet B. coenzyme Q and carnitine C. uncooked corn starch meals in the evening D. allopurinol E. dichloroacetate, thiamine, and citrate
E. dichloroacetate, thiamine, and citrate
53
What is classic galactosemia? | -symptoms
- galactose in the blood - occurs when the conversion of galactose to glucose 1 phosphate is prevented due to galactose 1-P uridyltransferase deficiency Symptoms in neonates - failure to thrive - liver failure, jaundice - sepsis - bleeding - hepatomegaly Treatment: restrict galactose intake
54
What is Duarte varient of galactosemia?
milder form -5-25% residual GALT activity in erythrocytes Treatment: restrict galactose intake
55
What is nonclassic galactosemia?
- conversion of galactose to galactose 1 phosphate is prevented due to a defect in galactokinase - galactose and galactitol accumulate in the blood and urine (galactosuria) - galactitol deposition in the eye leads to cataracts in early infancy Treatment: restrict galactose intake
56
What is essential fructosuria?
- fructosuria = presence of high concentrations of fructose in the urine - caused by genetic mutations that cause deficiencies in enzymes involved in fructose metabolism - autosomal recessive disorder marked by hepatic deficiency in fructokinase (phosphorylates fructose to fructose 1 phosphate - asymptomatic
57
What is hereditary fructose intolerance?
- autosomal recessive disorder caused by a deficiency in hepatic aldolase B, an enzyme that cleaves fructose 1 phosphate into glyceraldehyde and dihydroxyacetone phosphate (DHAP) - fructose and fructose 1 phosphate accumulate - fructose 1 phosphate sequesters cellular phosphorus (needed for generation of ATP) - damages liver and leads to kidney disease/failure - low blood levels of phosphorus (hypophosphatemia) - hypoglycemia - low tolerance for foods high in fructose and sucrose
58
What is fasting?
voluntary not eating for various lengths of time - body adapts to this by depleting energy stores - days 1-2: glycogen stores in liver - followed by lipolysis
59
What is starvation?
- body energy stores are depleted and the body resorts to using essential tissues for energy - result is reduction in organ volume with gradual loss of function, loss of muscle mass, weakness, anemia, diarrhea, reduction in mental capacity, immune deficiency, and death
60
What is Von Gierke disease?
type Ia glycogen storage disease - autosomal recessive disorder - 1/100,000 live births - deficiency in glucose 6 phosphatase activity (mutation in catalytic unit) (releases free glucose into blood by liver) --> no glycogenoloysis and gluconeogenesis Symptoms - marked fasting hypoglycemia - lactic acidosis - hepatomegaly - hyperlipidemia and lactic acidemia in patients with retarded growth
61
What is glycogen storage disease Ib (GSD Ib)?
-caused by defect of transport protein that moves glucose-6-phosphate from the cytosol into the lumen of the ER of hepatocytes (GLUT7) Treatment: liver transplant, surgical transposition of teh portal vein (redirects nutrient-rich blood from the intestine to the peripheral circulation, improves tissue supply with glucose, reduces glucose uptake in the liver) -uncooked cornstarch before bedtime to keep blood glucose up during the night
62
What is PEPCK deficiency?
rare autosomal recessive disorder of carbohydrate metabolism - normally catalyzes the conversion of oxaloacetate into phosphoenolpyruvate - increased acid in the blood (acidemia) - hypoglycemia - loss of muscle tone - liver enlargement and impairment of function - failure to thrive
63
How is PEP produced in mitochondria?
- mitochondrial PEP carboxykinase converts OAA to PEP in the mitochondria - PEP is transported into cytosol where it is converted to glucose via gluconeogenesis when lactate levels are elevated - conversion of lactate to pyruvate by lactate dehydrogenase generates NADH, which does not favor coversion of malate to OAA in cytosol, so OAA is directly converted to PAP by mitochondrial PEP carboxykinase

GI Final (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions