Miscellaneous Liver And Gastrointestinal Diseases Part 2

Front 1

Inborn Errors of Metabolism:

Commonly involve the metabolic factory,
detoxification center and Fedex hub of
the body (the _____)
Most clinically important inborn errors of
metabolism present in _____
(or can be diagnosed in infancy)
Neonatal presentations: often at _____ hrs:
poor feeding, lethargy, vomiting, seizures,
shock (CAN MIMIC _____)
Later presentations: often >__ days:
failure to thrive, _____,
vomiting, respiratory or pyschomotor stuff

Back 1

Commonly involve the metabolic factory,
detoxification center and Fedex hub of
the body (the liver)
Most clinically important inborn errors of
metabolism present in babies
(or can be diagnosed in infancy)
Neonatal presentations: often at 24-72 hrs:
poor feeding, lethargy, vomiting, seizures,
shock (CAN MIMIC SEPSIS)
Later presentations: often >28 days:
failure to thrive, developmental delay,
vomiting, respiratory or pyschomotor stuff

Front 2

What is the urine smell of each?

Tyrosinemia

Phenylketonuria

Trimethylaminuria

Isovalaric acidemia

Maple syrup urine disease

Smell:

Mousy or musty

Maple syrup

Sweaty feet

Boiled cabbage

Rotting fish

Back 2

Front 3

How do you diagnose tyrosinemia?

Back 3

Front 4

Back 4

Front 5

“Inborn errors of metabolism of a given pedigree
run true to type.”

Family history is important, esp. _____,
because many are autosomal recessive.

_____ history is important because specific
components (sugars, proteins, etc.) can cause
the manifestations of disease.

Poor feeding + lethargy + seizures suggests
_____ or _____

Older children may present with _____
acute manifestations of disease.

Back 5

“Inborn errors of metabolism of a given pedigree
run true to type.”

Family history is important, esp. consanguinity,
because many are autosomal recessive.

Dietary history is important because specific
components (sugars, proteins, etc.) can cause
the manifestations of disease.

Poor feeding + lethargy + seizures suggests
hypoglycemia or hypocalcemia

Older children may present with EPISODIC
acute manifestations of disease.

Front 6

INBORN ERRORS OF METABOLISM

Helpful tests: ammonia, _____, pH, glucose,
electrolytes, bilirubin (total and direct), _____,
complete blood count, urine dipstick, urine
“Clinitest” for reducing substances

If ammonia, bicarbonate and pH all _____,
it could be an _____.

In episodic disease, lab tests can normalize
between episodes.

If diagnosis unclear and liver biopsy done,
_____ a piece STAT for possible enzyme assays.

Back 6

INBORN ERRORS OF METABOLISM

Helpful tests: ammonia, bicarbonate, pH, glucose,
electrolytes, bilirubin (total and direct), lactate,
complete blood count, urine dipstick, urine
“Clinitest” for reducing substances

If ammonia, bicarbonate and pH all normal,
it could be an aminoacidopathy.

In episodic disease, lab tests can normalize
between episodes.

If diagnosis unclear and liver biopsy done,
freeze a piece STAT for possible enzyme assays.

Front 7

Tyrosinemia type I

Aminoacidopathy due to
_____ deficiency
Prevalent in _____
Autosomal _____

Backup of metabolism of _____ leads to
buildup of metabolites that are toxic to liver
and kidney, and mutagenic in liver

Liver toxicity manifested by _____,
_____, nodular regeneration with
cholangiolar proliferation, cirrhosis,
dysplasia and (in up to 37%) hepatocellular
_____

Back 7

Tyrosinemia type I

Aminoacidopathy due to
fumaryl-aceto-acetase deficiency
Prevalent in French Canadians
Autosomal recessive

Backup of metabolism of tyrosine leads to
buildup of metabolites that are toxic to liver
and kidney, and mutagenic in liver

Liver toxicity manifested by steatosis,
cholestasis, nodular regeneration with
cholangiolar proliferation, cirrhosis,
dysplasia and (in up to 37%) hepatocellular
carcinoma

Front 8

What is the gross pathology for tyrosinemia type I?

Back 8

Front 9

Steatosis, cholestatis (dark bile plugs, almost black). Diagnosis?

Back 9

Front 10

Tyrosinemia type I:

Classic presentation: in first few months of life:
failure to thrive, then vomiting, _____ (gets
bloody), _____, lethargy, coma, death
[fulminant hepatic failure]
Diagnosis: high urine _____,
DNA test for specific mutation (in 100% of
French Canadians, 28% worldwide)
Treatment: low-tyrosine diet, herbicide called
_____ (inhibits upstream enzyme that causes
tyrosinemia type II [converts type I to type II
{but that is a much milder disease}]), liver
_____
Prognosis: much better if treated early

Back 10

Tyrosinemia type I

Classic presentation: in first few months of life:
failure to thrive, then vomiting, diarrhea (gets
bloody), jaundice, lethargy, coma, death
[fulminant hepatic failure]
Diagnosis: high urine succinylacetone,
DNA test for specific mutation (in 100% of
French Canadians, 28% worldwide)
Treatment: low-tyrosine diet, herbicide called
NTBC (inhibits upstream enzyme that causes
tyrosinemia type II [converts type I to type II
{but that is a much milder disease}]), liver
transplantation
Prognosis: much better if treated early

Front 11

Ornithine Transcarbamylase (OTC) Deficiency

The most common _____ cycle disorder
___-linked
Patients normal at birth until fed protein,
then develop irritability, _____,
vomiting, lethargy, respiratory distress,
_____, seizures, coma and
respiratory arrest due to hyperammonemia
(clinical picture mimicking sepsis)
Diagnosis: blood and urine _____ acid levels,
liver enzyme assay or _____ test
Treatment: emergency: IV benzoate,
_____ and _____
long-term: protein restriction, liver transplant

Back 11

Ornithine Transcarbamylase (OTC) Deficiency

The most common urea cycle disorder
X-linked
Patients normal at birth until fed protein,
then develop irritability, poor feeding,
vomiting, lethargy, respiratory distress,
hypotonia, seizures, coma and
respiratory arrest due to hyperammonemia
(clinical picture mimicking sepsis)
Diagnosis: blood and urine amino acid levels,
liver enzyme assay or DNA test
Treatment: emergency: IV benzoate,
phenylacetate and citrulline
long-term: protein restriction, liver transplant

Front 12

Back 12

Front 13

GAUCHER’S DISEASE

___________
deficiency

adult form = the most common
__________ disease

autosomal __________,
common in Jews

Back 13

GAUCHER’S DISEASE

beta-glucocerebrosidase
deficiency

adult form = the most common
lysosomal storage disease

autosomal recessive,
common in Jews

Front 14

Kupffer cells and macrophages with expanded crinkled cytoplasm. Diagnosis?

Back 14

Gaucher's disease

Front 15

GAUCHER’S DISEASE

________= most common initial sign, Other manifestations: pancytopenia, bone pain

Diagnosis by assay of __________e in white blood cells

Treatment: enzyme replacement
therapy available ($$$)

Back 15

GAUCHER’S DISEASE

Splenomegaly = most common initial sign, Other manifestations: pancytopenia, bone pain

Diagnosis by assay of beta-
glucosidase in white blood cells

Treatment: enzyme replacement
therapy available ($$$)

Front 16

Glycogen Storage Disease type I (Von Gierke)

Deficiency of ________,
the enzyme catalyzing the conversion of
glucose-6-phosphate to glucose, resulting in
decreased hepatic _____ production and
accumulation of _____ in liver, kidney
and intestine
Classic presentation: in the first year of life:
marked _____ and _____
Other metabolic manifestations: lactic
acidosis, hyperlipidemia, hyperuricemia
Diagnosis: DNA test

Back 16

Glycogen Storage Disease type I (Von Gierke)

Deficiency of glucose-6-phosphatase,
the enzyme catalyzing the conversion of
glucose-6-phosphate to glucose, resulting in
decreased hepatic glucose production and
accumulation of glycogen in liver, kidney
and intestine
Classic presentation: in the first year of life:
marked hepatomegaly and hypoglycemia
Other metabolic manifestations: lactic
acidosis, hyperlipidemia, hyperuricemia
Diagnosis: DNA test

Front 17

Cytoplasmic glycogen accumulation. Diagnosis?

Back 17

Front 18

Back 18

Front 19

What is a diverse group of inverse errors of metabolism involving enzymes in heme synthesis (not all in bone marrow, 20% in liver)?

What are the two subgroups?

Back 19

Porphyrias

Acute and subcutaneous

Front 20

What is the most common porphyria?

When does it present? Common presentation (skin and mechanism that follows)?

Back 20

Front 21

What is shown here?

How do these lesions heal?

Back 21

Front 22

What is the acute intermittent porphyria mechanism?

Back 22

Front 23

Acute intermittent porphyria:

Most common in which sex? Symptoms precipitated by which five things?

Back 23

Front 24

How do you diagnose acute intermittent porphyria?

What is the treatment?

How do you prevent?

Back 24

Front 25

Epidemiology: Common, most common in adolescents and young adults,
males affected slightly more often than females, lifetime risk of 7%.

Epidemiology of what disease?

Back 25

Acute appendicitis

Front 26

Draw the pathway of acute appendicitis pathogenesis:

Back 26

Pathogenesis: thought to be initiated by progressive increases in intraluminal
pressure that compromise venous outflow. In 50% to 80% of cases, acute
appendicitis is associated with overt luminal obstruction, usually caused by a
small stone-like mass of stool, or fecalith, or, less commonly, a gallstone,
tumor, or mass of worms (oxyuriasis vermicularis). Stasis of luminal contents,
which favors bacterial proliferation, triggers ischemia and inflammatory
responses, resulting in tissue edema and neutrophilic infiltration of the lumen,
muscular wall, and periappendiceal soft tissues.

Front 27

Pathology of appendicitis: In early acute appendicitis _____ vessels are congested and
there is a modest perivascular _____ infiltrate within all layers of the
wall. The inflammatory reaction transforms the normal glistening serosa into
a dull, granular, ______ surface. Although mucosal _____ and
focal superficial ulceration are often present, these are not specific markers
of acute appendicitis. Diagnosis of acute _____ requires neutrophilic
infiltration of the ______. In more severe cases a prominent
neutrophilic exudate generates a serosal _____ reaction. As the
process continues, focal abscesses may form within the wall (acute
______ appendicitis). Further compromise of appendiceal vessels leads
to large areas of hemorrhagic _____ and gangrenous necrosis that
extends to the serosa creating acute ______ appendicitis, which can be
followed by rupture and suppurative peritonitis.

Back 27

Pathology: In early acute appendicitis subserosal vessels are congested and
there is a modest perivascular neutrophilic infiltrate within all layers of the
wall. The inflammatory reaction transforms the normal glistening serosa into
a dull, granular, erythematous surface. Although mucosal neutrophils and
focal superficial ulceration are often present, these are not specific markers
of acute appendicitis. Diagnosis of acute appendicitis requires neutrophilic
infiltration of the muscularis propria. In more severe cases a prominent
neutrophilic exudate generates a serosal fibrinopurulent reaction. As the
process continues, focal abscesses may form within the wall (acute
suppurative appendicitis). Further compromise of appendiceal vessels leads
to large areas of hemorrhagic ulceration and gangrenous necrosis that
extends to the serosa creating acute gangrenous appendicitis, which can be
followed by rupture and suppurative peritonitis.

Front 28

What is shown here?

Back 28

Acute appendicitis

Front 29

Classic presentation: periumbilical pain that gradually localizes
to the right lower quadrant, followed by nausea +/- vomiting
(once or twice), low-grade fever and mildly elevated WBC count.

A classic physical finding is the McBurney sign,
deep tenderness located two thirds of the distance from
the umbilicus to the right anterior superior iliac spine
(McBurney point).

CLASSIC PRESENTATIONS AND FINDINGS FOR WHAT?

Back 29

Acute appendicitis

Front 30

Classic signs and symptoms of acute appendicitis are often absent:

In some cases, a ______ appendix may generate right flank or pelvic pain,
while a _____ colon may give rise to appendicitis in the left upper quadrant.

As with other causes of acute inflammation there is ______ leukocytosis,
but the leukocytosis may be minimal or so great that other causes are considered.

The diagnosis of acute appendicitis in young children and the very old is
particularly problematic, since other causes of abdominal emergencies are
prevalent in these populations, and the very young and old are also more likely
to have _______ clinical presentations.

Back 30

Classic signs and symptoms of acute appendicitis are often absent.

In some cases, a retrocecal appendix may generate right flank or pelvic pain,
while a malrotated colon may give rise to appendicitis in the left upper quadrant.

As with other causes of acute inflammation there is neutrophilic leukocytosis,
but the leukocytosis may be minimal or so great that other causes are considered.

The diagnosis of acute appendicitis in young children and the very old is
particularly problematic, since other causes of abdominal emergencies are
prevalent in these populations, and the very young and old are also more likely
to have atypical clinical presentations.

Front 31

Back 31

Front 32

What are five things that a diagnosis of acute appendicitis be confused with?

Back 32

1. Mesenteric lymphadenitis (secondardy to unrecognized Yersinia infection or viral enterocolitis)

2. Ectopic pregnancy

3. Acute salpingitis

4. Mittelschmerz (pain cause by minor bleeding at time of ovulation)

5. Meckel diverticulitis

Front 33

What are the five complications of acute appendicitis?

Back 33

Complications of appendicitis include (1) perforation*, (2) peritonitis,
(3) pyelophle­bitis, (4) portal venous thrombosis, (5) bacteremia
and (5) liver abscess.

Front 34

If you can only remember one differential diagnosis and one complication from acute appendicitis, what should you remember?

Back 34

Mesenteric lymphadenitis (children)

Ectopic pregnancy (adults)

Perforation

Front 35

What is shown here?

Common/uncommon?

What tumor type?

Benign/malignant?

What part of appendix?

Back 35

Front 36

Tumors of the Appendix:

Conventional adenomas or _____ producing
adenocarcinomas also occur in the appendix and may cause
obstruction and enlargement that mimics acute ______.

Mucocele, a dilated appendix filled with _____, may simply
represent an obstructed appendix containing inspissated
mucin or be a consequence of mucinous _____ or
mucinous ________.
Mucinous adenocarcinoma invading through the appendiceal
wall can lead to intraperitoneal ______ and spread.
In women the resulting peritoneal implants may be mistaken
for mucinous ______ tumors.
In the most advanced cases the abdomen fills with
tenacious, semisolid _____, a condition called
pseudomyxoma peritonei. This disseminated
intraperitoneal disease may be held in check for years by
repeated debulking but, in most instances, follows an
inexorably fatal course.

Back 36

Tumors of the Appendix

Conventional adenomas or non–mucin-producing
adenocarcinomas also occur in the appendix and may cause
obstruction and enlargement that mimics acute appendicitis.

Mucocele, a dilated appendix filled with mucin, may simply
represent an obstructed appendix containing inspissated
mucin or be a consequence of mucinous cystadenoma or
mucinous cystadenocarcinoma.
Mucinous adenocarcinoma invading through the appendiceal
wall can lead to intraperitoneal seeding and spread.
In women the resulting peritoneal implants may be mistaken
for mucinous ovarian tumors.
In the most advanced cases the abdomen fills with
tenacious, semisolid mucin, a condition called
pseudomyxoma peritonei. This disseminated
intraperitoneal disease may be held in check for years by
repeated debulking but, in most instances, follows an
inexorably fatal course.

Front 37

Pyloric Stenosis

Uncommon, but up to 0.35% of live births
5X more common in _____
Pathogenesis: genetic predisposition and
environmental triggers: 200X more likely if
_____ twin had it, 4.62X more likely
with _____-feeding, erythromycin associated
Pathology: hypertrophy of _____ muscle

Classic presentation __- to __-week-old baby
who develops immediate postprandial,
non-bilious, often projectile vomiting and
demands to be re-fed soon afterwards
(a "hungry vomiter").

Back 37

Pyloric Stenosis

Uncommon, but up to 0.35% of live births
5X more common in males
Pathogenesis: genetic predisposition and
environmental triggers: 200X more likely if
monozygotic twin had it, 4.62X more likely
with bottle-feeding, erythromycin associated
Pathology: hypertrophy of pyloric muscle

Classic presentation 3- to 6-week-old baby
who develops immediate postprandial,
non-bilious, often projectile vomiting and
demands to be re-fed soon afterwards
(a "hungry vomiter").

Front 38

What is the classic presentation of pyloric stenosis?

What is the size of the palpable nodule?

What can you see progressing across the child's upper abdomen from left to right just before emesis?

What is the treatment?

Back 38

Front 39

Differential for vomiting in an infant?

Back 39