GI 9, (13-15) , (49-54) Flashcards
1
Q
Meconium voiding
A
Initial physiological weight loss on the 3rd-4th day after birth due to meconium voiding, hunger, dehydration
max 10% of birth weight, regained after 10th day
150-250g/week increase
2
Q
meconium ileus what is it
A
Failure to pass the first stool in neonates (usually passes within the first 24-48h after birth)
3
Q
meconium ileus etiology
A
Etiology: 90% caused by cystic fibrosis
can also be Hirschprungs disease
4
Q
Clinical presentation of meconium ileus
A
signs of a distal small bowel obstruction (thick meconium plugs the distal ileum)
Bilious vomiting
Abdominal distention
No passing of meconium or stool
5
Q
diagnostics in meconium ileus
specific signs seen??
A
X-ray abdomen (with contrast agent)
* Dilated small bowel loops
* Microcolon: narrow caliber of the colon, as it is still unused (meconium has not been passed through yet)
* Neuhauser sign (soap bubble appearance): bubble-like appearance in the distal ileum and/or cecum as a result of meconium mixing with swallowed air
* Air-fluid levels are uncommon because of the viscous consistency of meconium. (missing air fluid level)
6
Q
Treatment of meconium ileus
A
- Enema with contrast agent, irrigoscopy (colon x-ray with contrast)
- Surgery is required in complicated cases (eg perforation, volvulus)
7
Q
Intestinal atresia - what is it
A
Congenital defect that can occur at any point along the GI tract leading to complete (atresia) or incomplete (stenosis) occlusion of the affected lumen
often associated with chromosomal anomalies (eg. Down syndrome)
8
Q
Clinical presentation- Intestinal atresia
A
- Intrauterine: Polyhydramios (excess of amniotic fluid during gestation)
- Postpartum: signs of intestinal obstuction
*abdominal distension
*Bilious vomiting
*Failed or delayed meconium passage
9
Q
Epidemiology Intestinal atresia
A
approx. 7:10,000 live births
10
Q
Intestinal atresia etiology
A
Often associated with chromosomal anomalies eg. Down syndrome
11
Q
Common types of intestinal atresia
A
- dudenal atresia
- jejuno-ileal atresia
12
Q
Diagnosis of intestinal atresia
A
◦ Prenatal Ultrasound
◦ Abdominal X-ray: Double-bubble sign (stomach and duodenum contains air in duodenal atresia), dilated bowel loops
◦ Evaluation for associated anomalies
* echocardiogram,
* US of brain/abdomen/spine
13
Q
Treatment of intestinal atresia
A
- Preoperative:
*placement of gastric tube for suction,
*parenteral nutrition
*fluid replacement - Surgery: bypass of the atresia or stenosis, possible to start with stoma to let dilated
14
Q
Pyloric stenosis - pathogenesis
A
Hypertrophy and hyperplasia of the pyloric sphincter in the first months of life
*Most common cause of gastric outlet obstruction in infants
15
Q
Pyloric stenosis- epidemiology
A
0,5-5:1000 live births, boys > girls
16
Q
Pyloric stenosis etiology
A
- Environmental factors:
*exposure to nicotine during pregnancy
*bottle feeding (drink more milk in less time —> pylorus muscle hypertrophy through overstimulation) - Genetic factors: increased risk with affected relatives
- Macrolide antibiotics is associated with higher risk
17
Q
Pyloric stenosis - clinical presentation develop at what age
A
Develop usually btw 2nd-7th week of age
18
Q
Pyloric stenosis - clinical presentation
A
- Frequent regurgitation progressing to projectile, nonbilious vomiting after feeding
- Enlarged, thickened, olive-shaped, no tender pylorus should be palpable in the epigastrium
- “Hungry vomiter”: demands re-feeding after vomiting
- If left untreated —> dehydration, weight loss, failure to thrive
19
Q
Pyloric stenosis diagnosis
A
- Abdominal US: elongated and thickened pylorus
- Barium studies: narrow pyloric orifice, Beak sign (dilation of stomach + narrowing at pylorus)
- Endoscopy
20
Q
Pyloric stenosis treatment
A
- Conservative therapy before surgery:
*correct electrolyte imbalance,
*IV resuscitation,
*frequent administration of small meals, *elevate head - Surgery: Ramstedt pyloromyotomy (longitudinal muscle-splitting incision of the hypertrophic sphincter)
21
Q
Diaphragmatic hernia- pathogenesis
A
Protrusion of intra-abdominal contents into thorax through an abnormal opening in the diaphragm
- Congenital (developmental defect, infants)
*Congenital diaphragmatic hernias (CDH) are common developmental defects from incomplete fusion of embryonic components of the diaphragm
or - acquired (from trauma/injury, adults)
22
Q
Types of diaphragmatic hernia
A
- Left-sided postero-lateral diaphragmatic defects: Bochdalek hernias (most common)
- Anterior defects: Morgagni hernias
23
Q
50% of infants have additional conformational malformations in which congenital anomaly
A
diaphragmatic hernia
24
Q
diaphragmatic hernia clinical presentation
A
- Postnatal presentation of respiratory distress + absent breath sounds —> due to
*severe pulmonary hypoplasia,
*persistent pulmonary hypertension of the newborn (PPHN),
*poor surfactant production - Respiratory distress is the cause of high mortality, NOT the hernia itself
- Auscultation of bowel sounds in the chest
25
Diagnosis of Diaphragmatic hernia
* Antenatal US:
*fluid-filled stomach/bowel seen in thorax, *peristalsis in chest (fetal endoscopy)
* Chest x-ray:
*abdominal contents
*+ air/fluid-filled bowel
*+ poorly aerated lung in thorax
26
Treatment of Diaphragmatic hernia
* Prenatal therapy:
*antenatal glucocorticoids,
*in utero surgery in selected cases
* Postnatal therapy:
*correction of hypoxia,
*surfactant administration,
*gastric suction,
*surgery when stable
Gentle ventilation in newborn! (Prevent bronchopulmonary dysplasia)
27
Intussusception
When a proximal part of the bowel invaginates into distal part of *
bowel —> mechanical obstruction + ischemia
28
what age group intussusception is common
Infants aged 3–24 months are most commonly affected, usually with no identifiable underlying cause.
more common in males
29
most common causes of bowel obstruction in children
Intussusception,
incarcerated hernia,
30
Intussusception etiology
* Mostly idiopathic 75% ( common in 3m-5yr old)
* Pathological lead points:
*intraperitoneal anomalies or abnormalities that obstruct or tether the bowel and act as lead points in the process of intussusception
31
intraperitoneal anomalies or abnormalities that obstruct or tether the bowel and act as lead points in the process of intussusception examples
* **Meckel diverticulum **(most common in children)
* Intestinal polyps or other benign tumors (most common in adults and 2nd most common in general)
* Enlarged Peyer patches: individuals with a history of a recent viral infection or immunization (e.g., rotavirus or adenovirus)
*** Bowel wall thickening in IgA vasculitis
* Cystic fibrosis**
* Hematoma, hemangioma
* Enlarged lymph nodes, lymphomas
* Adhesions
32
pathophysiology of intussusception
Imbalance in the bowel wall (idiopathic or via a pathological lead point) → invagination or “telescoping” of a portion of intestinal bowel (intussusceptum) into the distal adjacent bowel loop (intussuscipiens)
→ impaired lymphatic drainage and increasing pressure in intussusceptum bowel wall
→ venous impairment
→ mesenteric vessels congestion
→ ischemia of intussusceptum bowel wall
→ sloughing of bowel mucosa (most sensitive to bowel ischemia since it is the furthest from the arterial supply)
→ transmural necrosis and perforation with prolonged ischemia
dysfunctional passage leads to mechanical bowel obstruction → vomiting
33
most common site for intussusception
**Ileocecal invagination** (most common; accounts for 85–90% of cases)
Ileoileal invagination
Ileocolic invagination
Colosigmoidal invagination
Appendicocecal invagination (very rare)
34
symptoms of intussusception
* Periodic colicky cramping **abdominal pain** ◦
* “**Currant jelly” bloody stool** (mixture of blood and mucus)
* **Sausage-shaped mass in the RUQ**, retraction in RLQ
* High pitched bowel sounds on auscultation
* Lethargy , pallor, and other symptoms of shock or altered mental status may be present.
* Vomiting (initially nonbilious)
35
diagnosis of intussusception
- specific signs seen on US
If clinical suspicion is high —> perform an enema ◦
If diagnosis is unclear —> perform an US or abdominal X-ray
* Abdominal US: ‣
*Target sign: invaginated portion of bowel appears as rings on a target in transverse view)
*Pseudokidney sign: lead point of invagination resembles a kidney
* Contrast or air enema:
*Interruption of contrast or air at site of invagination *
* Abdominal x-ray: ‣
*Inhomogenous distribution of gas with absence of air at the site of invagination
36
intussusception treatment
* Initial step: nasogastric decompression and fluid resuscitation
* Nonsurgical management: performed under continuous US or fluoroscopy guidance ◦
*Air enema, hydrostatic reduction ‣
* Surgical reduction: when pathological lead point is suspected, failed conservative treatment, ◦
suspected gangrenous or perforated bowel, critically ill patient
*Hutchinson maneuver (manual proximal bowel compression and reduction),
resection + end- to-end anastomoses (for necrotic segments)
37
Volvulus
Twisting of a loop of bowel on its mesentery *
One of the most common causes of intestinal obstruction *
Almost always present as a midgut volvulus secondary to intestinal malrotation
Intestinal malrotation: arrest in normal rotation of the gut in utero, resulting in abnormal orientation
of the bowel and mesentery within the abdominal cavity
38
Intestinal malrotation:
arrest in normal rotation of the gut in utero, resulting in abnormal orientation
of the bowel and mesentery within the abdominal cavity
39
volvulus typical age group and location
Effects neonates and infants (sigmoid volvulus usually affects adults)
40
symptoms of volvulus
* Bilious vomiting with abdominal distension in a neonate/infant
* Abdominal pain, inability to pass nasogastric tube
* Signs of bowel ischemia: hematochezia, hematemesis, hypotension, tachycardia
41
Diagnosis of volvulus
* Barium swallow test: duodenal obstruction, corkscrew duodenum ◦
* Barium enema: bird’s beak sign ◦
* Abdominal US: whirlpool sign (color doppler) ◦
* Abdominal x-ray: often normal, but can demonstrate bowel perforation —> air above diaphragm ◦
Lab:
* Metabolic alkalosis + hypokalemia (from vomiting)
* Neutrophilic leukocytosis + metabolic acidosis + elevated serum lactate (from bowel ischemia/
necrosis)
42
treatment of volvulus
* Initial resuscitation: NPO, nasogastric tube insertion, IV fluids, electrolytes, broad-spectrum IV AB
* Emergency surgery! Urgent operation is necessary
Short bowel syndrome from surgery —> parenteral feed, but die at early age
43
Incarcerated hernia
Type of hernia in which the contents of the hernial sac cannot return back through the abdominal wall *
defect into the peritoneal cavity with the application of gentle external pressure
Increased risk of strangulation and bowel obstruction
44
Appendicitis
Inflammation of the appendix, typically due to an obstruction of the appendiceal lumen
45
Etiology of appendicitis
Caused by obstruction of the appendiceal lumen due to:
1. Lymphoid tissue hyperplasia (60% of cases): most common cause in children and young adults
2. Appendiceal fecalith and fecal stasis (35% of cases): most common cause in adults
3. Neoplasm (uncommon): more likely in patients > 50 years of age [4]
4. Parasitic infestation (uncommon): e.g., Enterobius vermicularis, Ascaris lumbricoides, and species of the Taenia and Schistosoma gener
46
peak incidence of appendicitis
10-19 years of age
Lifetime risk= 8%
more common in males
47
symptoms of appendicitis
* Reliability of signs and symptoms in children is lower
* Most reliable: emesis, duration of pain, abdominal tenderness, pain with walking/jumping/coughing, ◦
fever, RLQ pain
48
diagnosis of appendicitis
* Lab: CRP ≥ 10 mg/mL, WBC count > 16,000/mL
* Pediatric appendicitis score: estimates likelihood of appendicitis in patients 3-18 years of age
* Ultrasound
49
treatment of appendicitis
* Supportive care: NPO (bowel rest), IV fluids, electrolyte imbalance resuscitation, antiemetics, ◦
antipyretics
* Empiric antibiotic therapy in all patients with acute appendicitis ◦
* Surgery: appendectomy
50
what disease does appendectomy protect from?
Ulcerative colitis ( also smoking protects from it too )
51
Obstipation
complete inability to pass stool or gas)
Caused by some type of bowel obstruction
52
types of bowel obstruction
* Congenital intestinal atresia (eg duodenal atresia, jejunal atresia)
* Intussusception (eg secondary to Meckel diverticulum)
* Congenital strictures and bands (eg Ladd bands (abnormal fibrous tissue attaching cecum to
peritoneum and liver) in intestinal malrotation)
* Hirschsprung disease
* Meconium ileus
* Rectal atresia
53
Associated symptoms of obstipation
abdominal pain,
vomiting,
abdominal distension,
decreased bowel sounds
54
Hirschsprung disease (congenital aganglionic megacolon)
Inherited disorder primarily affecting newborns
1 in 5000 live births
55
associated diseases with hirschprung disease
Down syndrome,
multiple endocrine neoplasia type 2 (MEN2), Waardenburg syndrome,
neuroblastoma
56
Pathophysiology of Hirschsprung
disease
Hirschsprung disease is caused by defective caudal migration of parasympathetic neuroblasts (precursors of ganglion cells) from the neural crest to the distal colon.
This process takes place between the 4th and 7th week of development.
Affected segments are histologically characterized by the absence of the Meissner plexus and Auerbach plexus (submucosal and myenteric plexus ganglion) beginning at the anorectal line, leading to:
* Inability of the myenteric plexus to control the intestinal wall muscles → uncoordinated peristalsis and slowed motility
* Spastic contraction of intestinal muscles → stenosis and functional obstruction
* Expansion of the colon segment proximal to the aganglionic section (possible megacolon)
57
Extent of the disease Hirschsprung disease
* Ultra-short segment: limited to the distal rectum below the pelvic floor and the anus
* Short-segment: limited to the rectosigmoid region (approx. 80% of cases)
* Long-segment: involvement of the distal colon up to the splenic flexure (approx. 10% of cases)
* Total colonic: entire colon (3–8% of cases)
58
early clinical presentation of hirschsprung disease
Early presentation:
delayed passage of meconium (>48h),
abdominal distension,
bilious vomiting,
tight anal sphincter, empty rectum, squirt sign (explosive release of stool and air upon removal of the finger),
palpation of feces via the abdominal wall
59
Late presentation of hirschprungs disease
chronic constipation,
inability to pass gas,
failure to thrive/poor feeding
60
Hirschsprung disease (congenital aganglionic megacolon) diagnosis
* Abdominal x-ray: decreased or absent air in rectum, dilated colon segment, distal intestinal
obstruction
* Barium enema: change in caliber in affected intestinal segment, retention of barium for 24-48h
* Anorectal manometry: absent relaxation reflex of internal sphincter after stretching of rectum
Measures the relaxation pressure of the internal anal sphincter after distension with a balloon ‣
(difficult to perform in newborns)
* Rectal biopsy: absence of ganglion cells, elevated ACh activity, hyperplasia of parasymp fibers ◦
Confirmatory test
61
Hirschsprung disease (congenital aganglionic megacolon) treatment
* Surgical treatment ◦
*Definitive treatment to remove the affected segment of the colon and bring the normal ‣
ganglionic intestinal ends together
* Pharmacological treatment
Fluid resuscitation, nasogastric decompression, antibiotics if indicated, colonic irrigation
62
malabsorption classification
* impaired intraluminal digestion
* Intestinal malabsorption
* Malabsorption due to fermentation (maldigestion of carbohydrates)
In many cases more factors elicit the malabsorption (eg bacterial overgrowth
63
Impaired intraluminal digestion *
Etiology
* cystic fibrosis,
* Schwachman syndrome,
* isolated lipase or co-lipase deficiency,
* impaired bile acid synthesis,
* bile duct atresia (commonly in neonatal period),
* interrupted enterohepatic circulation (ileal resection,
* Crohn’s disease = malabsorption + maldigestion,
* congenital malabsorption of bile acids),
* congenital trypsinogen or enterokinase deficiency
64
Intestinal malabsorption *
Etiology:
* celiac disease,
* sensitization to food proteins (cow’s milk, soy, rice, wheat),
* Giardia infection,
* postenteritis syndrome,
* immunodeficiency syndromes,
* acrodermatitis enteropathica,
* bacterial overgrowth,
* Crohn’s disease,
* short bowel syndrome,
* intestinal lymphangiectasia,
* autoimmune enteropathy,
* congenital microvillus atrophy,
* selective transport defects
65
Malabsorption due to fermentation
Disaccharide deficiencies
* Lactose (congenital, secondary, adult)
* Sucrose (congenital, secondary)
* Isomaltoze (congenital, secondary)'
Monosaccharidde malabsorptions ◦
* Glucose/galactose
* Fructose (toddler’s diarrhea —> usually grow out of it)
66
Malabsorption due to fermentation primary forms vs secondary
In primary forms the small intestines has normal structure (due to an enzyme deficiency),
in secondary form the small intestines are damaged
67
Celiac disease
Immune mediated systemic disorder elicited by
gluten in genetically susceptible individuals
* Characterized by the presence of
*variable combination of gluten-dependent clinical manifestations,
*CD specific antibodies,
*HLA-DQ2 and HLA-DQ8 haplotype, and *enteropathy
68
patients at increased risk of celiac disease
* T1DM,
* Down sy,
* Turner sy,
* Williams sy,
* autoimmune thyroid disease,
* selective IgA deficiency,
* autoimmune liver disease,
* first relatives with CD
69
Symptoms of celiac disease
* Chronic abdominal pain, distension
* Chronic fatigue
* Failure to thrive, weight loss, stunted growth
* Iron-deficiency anemia
* Dermatitis herpetiformis rash (Duhring disease)
* Diarrhea, obstipation
* Delayed puberty, amenorrhea
* Nausea, vomiting
* Recurrent aphthosus stomatitis
* Abnormal live biochemistry
* Osteoporosis, osteopenia
70
diagnosis of celiac disease steps
1. Clinical suspicion of CD or risk group for CD? yes
2. Measure transglutaminase antibodies (TGA-IgA) & total IgA, positive
*If negative —> esophagogastroduodenoscopy for biopsies from distal duodenum
3. Test for endomysial antibodies (EMA-IgA), positive
*If negative —> esophagogastroduodenoscopy for biopsies from distal duodenum .
4. CONFIRMED CD
*Biopsy is not done unless necessary in children
Taken from distal duodenum (min 4x) and duodenal bulb (min 1x) ‣
71
histology of celiac disease
Histology:
* villous atrophy,
* elongated crypts,
* increased intraepithelial lining density,
* increased intraepithelial lining mitotic index,
* infiltration of plasma cells + lymphocytes + mast cells into lamina propria
*
Diagnosis without biopsy if anti-TAG titer >10x upper limit + symptoms + EMA positivity
72
diagnosis without a biopsy in celiac disease if
Diagnosis without biopsy if
anti-TAG titer >10x upper limit
+ symptoms
+ + EMA positivity
73
treatment of celiac disease
GLUTEN-FREE DIET
74
NOT allowed food in celiac disease
Not allowed:
* wheat,
* barley,
* bulgur,
* cuscus,
* malt,
* normal beer,
* cans,
* instant coffee
75
long term complication of celiac disease
* Lymphoma,
* esophageal carcinoma,
* ulcerative jejunitis,
* other autoimmune diseases,
* cardiomyopathy,
* infertility
76
Cholestatic liver disease
Impaired bile flow —> accumulation in liver and serum of substances that normally are secreted in the bile:
* bilirubin,
* bile acids,
* cholesterol
77
Cholestatic liver disease most recognizable laboratory manifestation
**Hyperbilirubinemia** is the most recognizable laboratory manifestation of cholestasis
◦Direct/conjugated bilirubin > 40 micromol/l and/or > 15-20% of total bilirubin
78
bilirubin level in cholestasis
is it conjugated or unconjugated?
◦Direct/conjugated bilirubin > 40 micromol/l
and/or > 15-20% of total bilirubin
79
Cholestasis etiology
intrahepatic vs extrahepatic
* Biliary atresia
* Alagille syndrome
* Alpha-1 antitrypsin deficiency
80
Biliary atresia is it common in infants?
Uncommon disease in infants
81
Biliary atresia
what is it
Closed/discontinuous biliary tracts
* Destructive, obliterative cholangiopathy that affects both intra- and extrahepatic bile ducts
82
biliary atresia complications
if left untreated —> early liver cirrhosis (at approx. 9 weeks of age),
may die within first 2 years of life
83
Forms of biliary atresia:
* Congenital/syndromic/fetal/embryonic type (10%)
* Postnatal/non-syndromic/perinatal type (90%)
84
Congenital/syndromic/fetal/embryonic type of biliary atresia
10% of biliary atresia
* Associated with anatomical anomalies in 10-20%
* Part of biliary atresia splenic malformation (BASM) syndrome:
*asplenia/polysplenia
*abnormal abdominal situs,
*intestinal malrotation,
*abdominal vascular anomalies,
*congenital heart disease,
*pancreatic malformations
Bad prognosis
85
Congenital/syndromic/fetal/embryonic type of biliary atresia
Bad prognosis
86
biliary atresia splenic malformation (BASM) syndrome
Congenital/syndromic/fetal/embryonic type of biliary atresia is part of it
* asplenia/polysplenia
* abnormal abdominal situs
* intestinal malrotation
* abdominal vascular anomalies
* congenital heart disease
* pancreatic malformations
87
Postnatal/non-syndromic/perinatal type of biliary atresia
90% of biliary atresias
Not associated with anatomical
malformations
88
biliary atresia clinical presentation
* Prolonged icterus/jaundice
* Acholic stool (clay-colored, lacking bile pigment)
* dark urine
* Hepatomegaly
* Bleeding (from disturbed coagulatory protein production)
* Portal hypertension
* Cirrhosis
89
biliary atresia diagnosis laboratory
Direct serum bilirubin↑
transaminase↑
ALP↑
GGT ↑
Synthetic dysfunction —> coagulopathy, hypoalbuminemia
90
imaging in biliary atresia
* US: small and absent gallbladder, no bile duct dilation, malformations
Done after 4-6h of fasting
* Liver biopsy: active inflammation with bile duct degeneration and fibrosis, bile duct
proliferation, portal stromal edema
* Hepatobiliary scintiscanning (HBSS) (scintigraphy): failed excretion of the tracer into the bowel
* Intraoperative cholangiography: confirms diagnosis
91
what confirms diagnosis of biliary atresia
Intraoperative cholangiography:
92
biliary atresia treatment
* Kasai procedure (hepatoportoenterostomy): connection is created between the liver and the small intestines to allow for bile drainage
* Liver transplantation: in case of liver cirrhosis
93
Alagille syndrome
* Uncommon genetic condition characterized by intrahepatic biliary duct aplasia or hypoplasia
* Autosomal dominant inheritance of mutation in the JAG1 gene
94
Alagille syndrome clinical presentation
* Hepatic manifestations: cholestasis, jaundice, pruritus, cirrhosis
* Facial dysmorphism: triangular face,
deep set eyes, broad nasal bridge
Congenital heart defects (eg peripheral pulmonary stenosis)
* Butterfly vertebrae
* Posterior embryotoxon (thickening of
Schwalbe’s ring in cornea)
* Renal dysplasia
95
Alagille syndrome diagnosis - major criteria
5 major criteria: 3 is needed (interlobular bile duct atresia + 2)
* Interlobular bile duct absence/cholestasis
* Cardiac malformation/insufficiency
* Spine deformity
* Characteristic face
* Ocular abnormality
Confirmation via genetic testing (JAG1 gene mutation
96
Confirmation of alagille syndrome
via genetic testing (JAG1 gene mutation
97
Alagille syndrome treatment
* Depends on affected organ
* Conservative treatment of cholestasis and pruritus (eg ursodeoxycholic acid, cholestyramine )
98
Alpha-1 antitrypsin deficiency
Genetic disorder characterized by the accumulation of defective alpha-1 antitrypsin enzyme
99
mutation in alpha 1 antitrypsin deficiency
severity of disease depends on ?
Caused by mutation in the SERPINA1 gene,
the severity of the disease depends on the specific genotyping expression
which correlates with the amount of alpha1-antitrypsin synthesis
100
Alpha-1 antitrypsin deficiency pathophysiology
* Alpha-1 antitrypsin is a protease inhibitor that is synthesized in the liver and protects cells from breakdown by neutrophil elastase (protease)
* Gene mutation induces a conformational change in the structure of AAT —dysfunctional (or absent) AAT
* Effect on liver: accumulation of faulty AAT in hepatocellular endoplasmic reticulum —>
hepatocyte destruction —> hepatitis and liver cirrhosis
Effect on lungs: deficient AAT —> uninhibited protease activity —> destruction of pulmonary parenchyma —> panacinar emphysema (differ from centrilobular emphysema from smoking)
101
Alpha-1 antitrypsin deficiency clinical presentation
* Pulmonary manifestations: cough, wheezing, dyspnea, diminished breath sounds, barrel chest
* Hepatic manifestations: prolonged neonatal jaundice, hepatitis, cirrhosis, increased risk of
HCC
102
Alpha-1 antitrypsin deficiency diagnosis
* Serum: decreased AAT
* Electrophoresis: decreased alpha 1 peak
* Chest x-ray: low + flat diaphragm, widened intercostal spaces, hyperinflation and increased basilar radiolucency on both lungs
* Chest CT: paracinar emphysema, bronchiectasis, bullae
* Liver biopsy: PAS-positive, spherical inclusion bodies (accumulated proteins) in periportal
hepatocytes, signs of cirrhosis
103
Alpha-1 antitrypsin deficiency treatment
* General measures: ‣Avoid active and passive smoking, preventative vaccination (eg influenza)
* Symptomatic treatment: ‣Bronchodilators, pulmonary rehabilitation, nutritional support
* Antitrypsin replacement: ‣In patients with severe AAT deficiency
* Liver transplantation: ‣Considered for end-stage liver disease
104
51. Hepatitis in childhood
* Viral hepatitis
* Non-alcoholic fatty liver disease (NAFLD)
* Autoimmune hepatitis (AIH)
105
Viral hepatitis pathogens
Hepatitis A —> fecal-oral transmission
Hepatitis B —> blood/sexual transmission
Hepatitis C —> blood/sexual transmission
106
symptoms of viral hepatitis
* Fever,
* fatigue,
* malaise,
* anorexia,
* nausea,
* arthralgia,
* RUQ pain, jaundice +/- hepatomegaly
* splenomegaly
* adenoma they
* urticaria
107
diagnosis of viral hepatitis
* Increased liver enzymes: ◦ ↑ALT, ↑AST, ↑GGT, ↑ALP
* Viral serology (IgM antibodies), viral PCR, blood culture
108
treatment of viral hepatitis
usually self-limiting *
Unless immunocompromised —> no antivirals ◦If fulminant hepatitis —> ICU transfer, liver transplantation
109
what to do in case of fulminant hepatitis
—> ICU transfer, liver transplantation
110
what is fulminant hepatitis
clinical syndrome of severe liver function impairment, which causes
hepatic coma and
the decrease in synthesizing capacity of liver, and
develops within eight weeks of the onset of hepatitis.
111
complications of viral hepatitis
Chronic hepatitis (especially HCV), hepatocellular carcinoma,
cirrhosis
112
preventive measure against viral hepatitis
Hepatitis A + B vaccination
113
Recommendations for hepatitis B immunization what ages
Active immunization is recommended for all infants in three doses:
At birth
At 1–2 months
At 6–18 months
Infants weighing < 2,000 g: Administer the first dose at 1 month of age or at hospital discharge (whichever is earlier).
114
Non-alcoholic fatty liver disease (NAFLD)
what is it
epidemiology
More than 5% fatty transformation of hepatocytes in liver biopsy (macrovesicular)
Epidemiology:
7,6% in general population,
34% in obese children
One of the most common causes of chronic liver disease in young people in the developed world
115
One of the most common causes of chronic liver disease in young people in the developed world
NAFLD
116
NAFLD Pathogenesis
increased insulin resistance —> *
↑Hepatic uptake of fatty acids ◦
↑Triglyceride synthesis ◦
↑Peripheral lipolysis
117
clinical presentation of NAFLD
Non-alcoholic steatohepatitis (NASH)
Fibrosis, cirrhosis
Hepatocellular carcinoma
Obesity
118
DIAGNOSIS of NAFLD
* Ultrasound: low sensitivity
* MRI
* Fibroscan: transient elastography
* Biopsy: to exclude other treatable diseases before starting drug or surgical treatment, last step in diagnosis
119
What do we have to exclude when diagnosing NAFLD
Need to exclude:
* excessive alcohol consumption,
* viral infections,
* autoimmune liver injury,
* drug induced liver injury (DILI)
* malabsorption,
* metabolic diseases (eg Wilson disease, fructosemia)
120
Treatment of NAFLD
few efficient ones in pediatrics
* Vitamin E (conflicting results)
* Docosahexaenoic acid (DHA) (encouraging results)
* Probiotics (potential effect)
Insulin sensitisers (not recommended)
Statins (only in adults)
121
Autoimmune hepatitis (AIH)
Rare form of chronic hepatitis that predominantly affects girls
122
Autoimmune hepatitis is associated with
Commonly associated with
other autoimmune disorders (eg type 1 DM, celiac disease
123
Types of autoimmune hepatitis
* Autoimmune hepatitis type 1 *(80%): characteristic ANAs, ASMAs, anti-soluble liver antigen Abs
* **Autoimmune hepatitis type 2**: characteristic anti-liver-kidney microsomal Abs, anti-liver cytosol Abs **
* Seronegative autoimmune hepatitis/ hepatitis associated aplastic anemia (HAA) **
* Giant cell hepatitis with autoimmune hemolytic anemia **
* **De novo -alloimmune- hepatitis post liver transplantation**
124
autoimmune hepatitis type 1
(80%):
characteristic
ANAs,
ASMAs,
anti-soluble liver antigen Abs
125
Autoimmune hepatitis type 2
characteristic
anti-liver-kidney microsomal Abs,
anti-liver cytosol Abs
126
symptoms of autoimmune hepatitis
* Non-specific symptoms:
*fatigue,
*upper abdominal pain,
*weight loss
* Signs of acute liver failure:
*jaundice,
*RUQ pain,
*fever,
*hepatomegaly,
*splenomegaly,
*ascites
127
diagnosis
lab values of autoimmune hepatitis
◦Lab
* ↑↑ALT, ↑AST, ↑GGT, ↑ALP
* Serum antibodies
* Serum protein electrophoresis: hypergammaglobulinemia (↑IgG)
* Normochromic anemia,
* thrombocytopenia,
* mild leukoplakia,
* ↑ESR
128
diagnosis of autoimmune hepatitis -other than labs
Liver biopsy
* Biopsy should be performed following the detection of AIH antibodies to confirm the diagnosis
—> findings:
**lymphoplasmacytic interface hepatitis** (ongoing inflammatory process with
*lymphocytic infiltration,
*necrosis,
*fibrotic changes,
*bile duct changes)
129
treatment of autoimmune hepatitis
* Immunosuppressive medications ◦
***Induction therapy** ‣
1st line: prednisone with or without azathioprine *
2nd line: mycophenolate, cyclosporine, tacrolimus *
***Maintenance therapy**: low doses of azathioprine or prednisone ‣
* Liver cirrhosis treatment > Liver transplantation
130
autoimmune hepatitis induction therapy
1st line:
*prednisone with or without azathioprine
2nd line:
*mycophenolate,
*cyclosporine,
*tacrolimus
131
autoimmune hepatitis maintenance therapy
low doses of azathioprine or prednisone
132
treatment of liver cirrhosis
Liver transplantation
133
Most common infectious enteritises
Infectious gastroenteritis
* Viral gastroenteritis
* bacterial enteritis
134
Most common diarrheal disorder
Infectious gastroenteritis-
Viral gastroenteritis
Can occur throughout the year, but peak during fall-winter period
135
what time of year does viral gastroenteritis peaks
Can occur throughout the year, but peak during fall-winter period
136
transmission of viral gastroenteritis
* oral-fecal contamination,
* possible airborne transmission of Rotavirus + Norovirus
* contaminated food and water
137
viral gastroenteritis common symptoms
* non-bloody diarrhea,
* vomiting, fever,
* abdominal pain,
* anorexia,
* headache,
* myalgia
138
uncommon symptoms of infectious viral gastroenteritis
gross blood or mucus in the stool —> consider bacterial etiology
139
diagnosis of viral gastroenteritis
* Diagnosis: clinically, stool testing is typically not necessary in viral infections
* Precise etiology is only required in *outbreaks,
*patient isolation,
*immunocompromised patients
diarrhea lasting >7 days
uncertain diagnosis —> done with PCR, ELISA, latex agglutination
140
precise etiology of viral gastroenteritis is required only in ?
* Precise etiology is only required in *outbreaks,
*patient isolation,
*immunocompromised patients
diarrhea lasting >7 days
141
uncertain diagnosis of viral gastroenteritis is done by
—> done with
PCR,
ELISA,
latex agglutination
142
pathogenesis of viral gastroenteritis
intestinal infection —> destruction of enterocytes —> transudation of fluid into
intestinal lumen —> diarrhea —>
net loss of fluid and salt + decreased ability to digest food and absorb its components
143
common pathogens in infectious gastroenteritis depending on time of year
* Fall-winter:
*Rotavirus (6 months-2 years)
*Astrovirus (<4 years)
* All around the year:
*Norovirus (all ages, highly contagious, can cause outbreaks)
*Sapovirus (infants/toddlers, milder than Rotavirus enteritis)
144
which is milder viral enteritis
Sapovirus (infants/toddlers, milder than Rotavirus enteritis)
145
what virus can cause outbreaks of viral gastroenteritis
norovirus
highly contagious
146
complications of viral gastroenteritis
* hypovolemia/dehydration
* electrolyte imbalance
* carbohydrate intolerance
* irritant diaper dermatitis
* CNS symptoms (seizures)
147
treatment of viral gastroenteritis
fluid resuscitation
148
preventitive measures against viral gastroenteritis
* contact precaution,
* hand hygiene,
* environmental cleaning
149
Bacterial enteritis is typical in what age
Typically in patients > 2 years
150
transmission of bacterial enteritis
* oral-fecal contamination
* exposure to poultry/farm animals/contaminated meat
151
symptoms of bacterial enteritis
high fever,
tenesmus (s a frequent urge to go to the bathroom without being able to go. )
severe abdominal pain,
gross blood or mucus in the stool
152
diagnosis of bacterial enteritis
* stool culture
* PCR for some bacteria (Campylobacter, Shigella)
153
what bacteria do we use PCR for in bacterial enteritis
Campylobacter, Shigella
154
common pathogens in bacterial enteritis
* Shiga-toxin producing E. Coli (STEC),
* Salmonella
* Shigella
* Clostridium difficile
* Campylobacter Jejuni
* Yersinia enterocolitica
155
complications of bacterial enteritis
* sepsis
* peritonitis
* rash
* arthritis
* Guilaine-Barré syndrome (Campylobacter)
* CNS symptoms (seizures, encephalopathy)
* hemolytic uremic syndrome (Shigella, STEC)
156
treatment of bacterial enteritis
fluid resuscitation,
antibiotics (in case of severe illness, young patients)
157
antibiotic of choice in salmonella gastroenteritis
Salmonella gastroenteritis —>
* Fluoroquinolones
* TMP-SMX
* Azithromycin
* 2nd/3rd gen cephalosporins
AB does not shorten duration of carriage (approx. 5 weeks)
158
antibiotic of choice in camplybacter jejuni bacterial enteritis
Campylobacter jejuni —>
* Azithromycin,
* Fluoroquinolones
159
antibiotic of choice in shigella bacterial enteritis
Ceftriaxone,
Ciprofloxacin,
Azithromycin
160
therapy of choice in shiga toxin producing e.coli (STEC) bacterial enteritis
antibiotics are NOT recommended, only give fluids
161
Oral rehydration therapy (ORT) in bacterial enteritis
Less glucose + Na —> lower osmolar activity —> reduced stool volume and shorter
duration of diarrhea
1) rehydration phase: frequent small boluses
2) maintenance phase: after each diarrhea
(10ml/kg) + vomit (2ml/kg)
Switch to IV fluids if: severe dehydration, altered mental status, risk of aspiration, limited *
intestinal capacity, excessive stool output and no improvement with ORT, persistent vomiting resulting in inadequate intake of ORT
162
when to switch to IV fluids instead of ORT in bacterial enteritis
Switch to IV fluids if:
* severe dehydration,
* altered mental status
* risk of aspiration,
* limited intestinal capacity
* excessive stool output
* and no improvement with ORT
* persistent vomiting resulting in inadequate intake of ORT
163
inflammatory bowel diseases
Ulcerative colitis (UC) or Crohn’s disease
164
Incidence of IBD in childhood
in childhood is 7,5/100.000
165
which is more common UC or CD
Crohn’s disease is 2x more common
166
IBD risk factors for infants
* Antibiotic administration
* smoking
* lack of breastfeeding
* familial IBD (2-8x higher risk if parent has IBD)
* Breast milk reduces incidence of CD by
33% and UC by 23%
167
crohns disease wall involvement
transmural, with knife-like fissures
168
location of crohns disease
anywhere from mouth —> anus with skip lesions, terminal ileum is the most common
169
symptoms of crohns disease
* right lower quadrant pain (ileum)
* with non-bloody diarrhea,
* weight loss, appetite loss
170
histology of crohns
lymphoid aggregates with granulomas
171
gross appearance of crohns disease
* cobblestone mucosa (from healing process)
* creeping fat (fat pulled up by myofibroblast contractions of granulation tissue)
* strictures (extreme narrowing of bowel lumen) —> “string” sign
172
complication of crohns disease
* malabsorption with nutritional deficiency
* calcium oxalate nephrolithiasis
* fistula formation
* carcinoma
173
Ulcerative colitis (UC) wall involvement
mucosal + submucosal
174
UC localization
ONLY colon, begins in rectum —> spreads proximal up to cecum (continuous/segmental)
1st: proctitis —>
2nd: proctosigmoiditis (“left-side colitis”) —> 3rd: extensive colitis —>
4th: ‣pancolitis
175
UC symptoms
* left lower quadrant pain (rectum)
* bloody diarrhea
* increased number of stool
* mucus in stool
* urgency
* fecal incontinence
* 25% experience obstipation
* tenesmus (feeling of fecal residue)
176
UC histo
crypt abscesses with neutrophils
177
Gross appearance of UC
* psedupolyps (two necrotic areas of close proximity form “polyp” btw)
* loss of haustra due to extensive inflammation —> “lead-pipe” sign
178
complications of UC
toxic megacolon (massive dilation with rupture risk)
carcinoma
179
what protects against UC
smoking
appendectomy
180
Extraintestinal manifestations: of IBD
and are they common?
more common in childhood (30% experience them
* Eye symptoms: uveitis, episcleritis, keratopathy
* Skin symptoms: erythema nodosum, pyoderma gangrenosum, metastatic Crohn’s disease (skin lesions in areas not connected to GI tract)
* Joint symptoms: arthritis, sacroileitis
* Other: fever, growth retardation, delayed puberty, hepatitis, pancreatitis
181
diagnosis of CD
* Stool culture :
*Yersinia
*TBC
* Laboratory
*albumin
*ASCA (auto-antibodies)
*CRP, PLT, Iron
* Imaging
*Abdominal US: intestinal wall thickening
*MR enterography: determine which bowel ‣segment is involved
* Endoscopy CD: granuloma
182
what imaging method used to determine segment involvement in IBD
MR enterography: determine which bowel ‣
segment is involved
183
diagnosis of UC
* Stool culture UC:
*Shigella
*salmonella
*campylobacter
*EHEC (enterohemorrhagic E. coli )
*Clostridium
* laboratory :
*ANCA (auto-antibodies)
*Both: CRP, platelets, iron
* Imaging
*Abdominal US: intestinal wall thickening ‣
*MR enterography: determine which bowel ‣
segment is involved
* Endoscopy UC: cryptabscesses
184
induction therapy of CD
Induction therapy CD:
* exclusive enteral nutrition (EEN):
*nasogastric tube insertion and
*strict formula-based (no-solid-food) diet for 6-8 weeks
More efficient than steroids, and no side effects
Same efficacy as biological therapy
185
maintenance therapy in CD
CD:
* partial enteral nutrition (PEN),
* immunomodulators (AZT/MTX)
186
relapse therapy in CD
CD:
EEN exclusive enteral nutrition
187
induction therapy in UC
* anti-inflammatory (5-ASA: aminosalicylate)
* steroids
188
maintenance therapy UC
anti-inflammatory (5-ASA), immunomodulators
189
relapse therapy UC
steroids
190
Rescue therapy in IBD
Both:
biological treatment,
surgery:
CD: only for a small section if possible —> ileocecal resection w/ diversion stoma
UC: colon removal is definite —> total colectomy w/ pouch preparation
191
biological theraoy in IBD
as rescue therapy
Biologicals are extracted from or produced by a biological source
Types‣ :
* TNFalpha inhibitors:
*Infliximab
*Adalimumab
* Integrin inibitor: Vedolizumab
* Anti-IL12/23 antibody: Ustekinumab
* JAK inhibitors: Tofacitinib
192
Alarming signs of acute abdominal diseases & differential diagnosis
* Ileus:
*constipation,
*vomiting
*delayed passing of meconium
* Appendicitis:
*strong pain in McBurney point/periumbilical, *Cullen sign
*Grey-Turner sign
*defense
*vomiting
*fever
* Pancreatitis: belt-like pain radiating to back, rebound tenderness
* Perforated bowels: free abdominal air = decreased dullness over liver
* NEC [preterm infants]:
*feeding intolerance
*bloody stool
*distended abdomen
*vomiting, diarrhea
*sepsis-like symptoms
* Trauma
* Ectopic pregnancy
* Ovarian torsion:
*sudden-onset unilateral abdominal/pelvic pain,
*nausea/vomiting
*adnexal mass may be palpable
* Internal bleeding: *hematemesis/hematochesia/melena, *hypovolemia, shock, anemia
* Pyloric stenosis [2-7 weeks, usually boys]: *vomiting after feeding
*palpable olive-shaped mass in epigastrium, *“hungry vomiter”
*dehydration,
*weight loss, failure to thrive
* Cholecystitis: Murphy sign
* Intussusception [usually <5 years]:
*currant jelly bloody stool
*pain is coming and going (periodic), *retraction in RLQ
*high-pitched bowel sounds on auscultation
* Volvulus: bilious vomiting, abdominal distension, abdominal pain, inability to pass NG tube *
* Bowel ischemia:
*hematochesia, hematemesis
*hypotension, tachycardia, shock
193
Neonatal jaundice bilirubin level
* One of the most common conditions occurring in newborns and infants
* Characterized by elevated levels of bilirubin in the blood
Total serum bilirubin concentration > 5 mg/dL (normal: 0,1-1,2 mg/dL)
194
Classification of neonatal jaundice
physiological or pathological
195
Physiological neonatal jaundice
- type of hyperalbuminemia
- onset
- peak total serum bilirubin
- daily rise in bilirubin
- type of hyperalbuminemia: always conjugated
- onset > 24 hours after birth
- peak total serum bilirubin: <15mg/dl (if full term, breast fed)
- daily rise in bilirubin <5mg/dl/day
196
pathological neonatal jaundice
- type of hyperalbuminemia
- onset
- peak total serum bilirubin
- daily rise in bilirubin
- type of hyperalbuminemia: conjugated or Unconjugated
- onset: can be present <24hrs after birth
- peak total serum bilirubin > 15 mg/dl
- daily rise in bilirubin < 5mg/dl
197
etiology of physiological jaundice
hemolysis of fetal hemoglobin and an immature hepatic metabolism of bilirubin
198
etiology of pathological unconjugated jaundice
* Hemolytic: increased production of bilirubin
* Non-hemolytic: *
*Decreased conjugation of bilirubin
Gilbert syndrome,
Crigler-Najjar syndrome,
Hypothyroidism
*Decreased stool passage —> increased enterohepatic circulation of bilirubin ◦
GI obstruction,
Hirschsprung disease,
cystic fibrosis,
breastfeeding jaundice
199
pathological unconjugated hyperbilirubinemia-
Hemolytic causes
*ABO or Rh incompatibility
*erythrocyte enzyme defect (G6PD deficiency),
*hemoglobinopathies (sickle cell anemia), *hematomas (vacuum-assisted delivery), *infection/sepsis,
*polycythemia
200
non hemolytic causes of pathological unconjugated hyperbilirubinemia
Non-hemolytic: *
* Decreased conjugation of bilirubin ◦
*Gilbert syndrome,
*Crigler-Najjar syndrome,
*Hypothyroidism ‣
* Decreased stool passage —> increased enterohepatic circulation of bilirubin ◦
*GI obstruction,
*Hirschsprung disease,
*cystic fibrosis,
*breastfeeding jaundice
201
Pathological conjugated hyperbilirubinemia classification
* intra hepatic
*decreased hepatic uptake of bilirubin
decreased excretion of bilirubin
* extra hepatic
202
Pathological conjugated hyperbilirubinemia ‣
Intrahepatic
* Decreased hepatic uptake of bilirubin
*Rotor syndrome
* Decreased excretion of bilirubin ◦
*Alagille syndrome,
*TORCH infections,
*Dubin-Johnson syndrome,
*sepsis (MOF
203
Pathological conjugated hyperbilirubinemia
extrahepatic causes
Extrahepatic *
* Decreased excretion of bilirubin ◦
*Biliary atresia
*biliary/choledochal cyst,
*tumors/strictures
204
Mixed hyperbilirubinemia ‣
Hepatitis, cirrhosis
205
diagnosis of neonatal jaundice
* Physical finding of icterus/jaundice
* Bilirubin tests:
*total serum bilirubin
*differentiation of direct (conjugated) and indirect (unconjugated) bilirubin
* Other lab tests:
*CBC (including reticulocyte count),
*blood group,
*direct + indirect Coombs test (for ◦
Rh incompatibility),
*inflammatory markers,
*liver enzymes,
*total serum protein and albumin,
*TSH,
*G6PD activity
206
treatment of neonatal jaundice
* Phototherapy: primary treatment in neonates with unconjugated hyperbilirubinemia
* Exchange transfusion: most rapid method for lowering bilirubin concentrations
*Use ABO-matched and Rh-negative erythrocyte concentrate and exchange blood via ‣umbilical venous catheter
* IV immunoglobulins: in cases with immunologically mediated conditions or in presence of Rh,
*ABO or other blood group incompatibilities that cause jaundice
207
phototherapy in neonatal jaundice
Exposure to blue light —> photoisomerization (major mechanism) and photooxidation (minor mechanism) of unconjugated (hydrophobic) bilirubin in skin to water-soluble form that can be excreted through urine and/or bile
Adequate fluid supplementation to prevent dehydration + eye protection to prevent damage
208
contraindication of phototherapy in neonatal jaundice
congenital erythropoietin porphyria (severe photosensitivity)
209
side effects of phototherapy
Side effects:
* diarrhea,
* dehydration,
* changes in skin hue (bronzing),
* separation of neonate from mother,
* increased risk of AML
210
indications of Exchange transfusion
* inadequate response to phototherapy or rapid rise in bilirubin level,
* acute bilirubin encephalopathy,
* hemolytic disease,
* severe anemia
211
exchange tranfusion side effect
higher mortality and morbidity from infections,
acidosis,
thrombosis,
hypotension,
electrolyte imbalance
212
IV immunoglobulin is given in what
in cases with
* immunologically mediated conditions
* or in presence of Rh,
* ABO or other blood group incompatibilities that cause jaundice
213
prevention of neonatal jaundice
adequate enteral nutrition —> frequent feeds with breast milk or other protein-rich nutritions
