Disorders Of Malabsorption Flashcards
Celiac disease specific antibodies include:
Triggered by dietary:
Associated with human leukocyte antigen:
Autoantibodies against TG2, including endomysial antibodies, and antibodies against deamidated forms of gliadin peptides.
Wheat gluten, and related prolamines from barley, rye
HLA-DQ2.5 (90% celiacs)
HLA-DQ2.2 confers lesser risk
All celiacs negative for HLA-DQ2 are positive for HLA-DQ8
Celiac disease
Innate immunity involvement:
Role of TG2:
Some gliadin peptides are able to activate innate immunity by inducing IL-15
IL-15 is implicated in the expression of natural killer receptors CD94 and NKG2D, as well as epithelial expression of stress molecules which enhance cytotoxicity, cell apoptosis, and villous atrophy
TG2 converts glutamine residues to glutamic acid, which results in higher affinity of these Gliadin peptides for HLA-DQ2 or DQ8.
Clinical presentation celiac disease
<2y
Less common sx <2y
Extraintestinal manifestations become more common in later childhood. Most common of which is :
And others include:
<2 yr intestinal symptoms are common:FTT, chronic diarrhoea, vomiting, abdominal distension, muscle wasting, anorexia, irritability are present in most cases
-Constipation, rectal prolapse, intususseption
Iron deficiency anaemia unresponsive to oral iron. Short stature, arthritis & arthralgia, peripheral neuropathy, cardiomyopathy, epilepsy with bil occipital calcification, isolated hypertransaminases, apthous ulcers, alopecia
At risk groups
Celiac associated disorders
First degree relatives Down’s syndrome Turners syndrome Williams syndrome Unexplained infertility Recurrent miscarriages Epilepsy with bilateral occipital calcification Osteoporosis Autoimmune endocrinopathies - T1DM, Alopecia, Ataxia, Apthous ulcers Addisons, Sjogrens, IBD, autoimmune liver disease Short stature, delayed puberty Dental enamel hypoplasia Polyneuropathy Selective IgA deficiency
Diagnosis of celiac disease
- symptomatic
- a symptomatic
- test anti-TG2 IgA antibodies and total IgA in serum to exclude IgA deficiency.
- IgG anti-deaminated forms of gliadin peptide antibodies is an alternative
- if anti-TG2 is <10x ULN, need duodenal biopsies
- if anti-TG2 >10x ULN, test HLA & EMA. If both positive do not need biopsy
- asymptommatic all need biopsy
Microvillous inclusion disease
- onset
- symptoms
- gene associated
- features on light microscopy
- prognosis
- onset at birth
- profuse watery secretory diarrhoea 200-330mL/kg/d: dehydrated & FTT
- MYO5B; AR
- thinning of mucosa, hypoplastic villous atrophy, no inflammatory infiltrate
- fatal without longterm TPN, intestinal transplant
Tufting enteropathy
- onset
- features on biopsy
- gene associated
- associated anomalies in the syndromic form
First few weeks of life with persistent watery diarrhoea
Focal epithelial tufts involving 80-90% of epithelial surface
EPCAM gene, encodes epithelial cell adhesion molecule
Superficial punctate keratitis, oesophageal choanal or intestinal atresia, imperforate anus, hair dysplasia, facial anomalies, bone abnormalities
Autoimmune enteropathy
- onset
- Sx
- small bowel histology
- difference in histo compared to celiac
- associated antibodies
- associated syndrome
- treatment
Onset > 6 mo
Chronic diarrhoea, PLE, FTT, malabsorption
Inflammation of SB & Colon
Villous atrophy, crypt hyperplasia, increased inflammation in lamina propria
Celiac enteropathy shows increase intraepithelial lymphocytes
Anti-enterocyte abs, anti-autoimmune enteropathy 75kDa, anti globletcell abs
IPEX syndrome (x linked)
T Cell suppression immunosuppressant
Bile acid malabsorption
Mutation to what gene
Sx
SLC10A2
Congenital diarrhoea, steatorrhoea, low cholesterol, fat vitamin deficiency
Unabsorbed bile acids stimulate chloride secretion/ resulting in diarrhoea
Responds to cholestyramine, an anion binding resin
Intestinal lymphangectasia Congenital form associated with: Secondary causes: What happens Manifestations Diagnosis Management
Turners, noonans, klippel-trenaunay-weber
Constrictive pericarditis, CHF, retro peritoneal fibrosis, TB, retroperitoneal malignancy
Lymph rich in protein, lipid, lymphocytes leak into bowel lumen
Causes PLE, steatorrhoea, lypmhopenia, hypoalbuminemia, hypogammaglobulinemia
Alpha1antitrypsin
Reduce intake LCFA, MCFA formula
Congenital chloride diarrhoea
Gene Gene encodes for Presentation Lab tests show Treatment Complications
SLC26A3 gene Sodium independent Cl- / HCO3- exchanger Severe diarrhoea onset in 1st wk life Metabolic alkalosis, hypokalaemia, hypochloraemia, hyponatraemia, high plasma renin-aldosterone activity, faecal chloride >90mmol/L Treatment: enteral substitution chloride Proton pump inhibitors Cholestyramine Butyrate
Menkes kinky hair disease
Name of protein Action Cells affected: high levels / low levels Clinical features Prognosis Treatment trial with:
MNK
Copper transporting ATPase
Cu transfer to enzymes in secretory pathway and to endosomes to allow Cu efflux
Progressive cerebral degeneration Seizures FTT, feeding issues, hypothermia, apnoea, UTI, facies, kinky hair Usually die by age 3 Trial copper-histinidase prior to 6w
Eosinophilic gastroenteritis Sx Ddx Histo Tx
Abdo pain (90%) Vomiting (60%), nausea, distension Parasitic or allergic disease Likely caused by hypersensitivity to food Eosinophilic infiltrates Mucosal erythema, villous atrophy Elemental diet, corticosteroids
Campylobacter Incubation Signs/sx Duration illness Assoc food Tx
2-5 d incubation
Fever, bloody diarrhoea
2-10 days duration
Assoc raw & undercooked poultry, unpasteurised milk, contaminated water
Supportive
If severe: azithromycin or quinolone early in illness
GBS can be a complication
Clostridium botulinum
Children & adults
Incubation Sx/signs Duration illness Associated food Testing Treatment
12-72h
GI, diplopia, descending muscular weakness, dysphagia
Days to months duration
Home or improperly canned, herb infused oils, potatoes in foil, food kept warm for long period s, cheese sauce, bottled garlic
Supportive care, can cause respiratory failure & death
Botulism antitoxin needs to be given early
Pernicious anaemia
Inheritance
Deficiency (2)
Presentations (2)
AR
Inability to secrete intrinsic factor
Structurally abnormal intrinsic factor
Macrocytic anaemia 9 months to 11 years
Subacute degeneration of spinal cord, presentating as gross motor delay
Ataxia, paraesthesia, hyporeflexia, clonus, coma
Pernicious anaemia
Labs
Schilling test
Macrocytic anaemia Elevated retics, LDH, bili Low B12, normal folate High methylmalonic acid & homocysteine Antibodies rare
Give IM B12, urine collect
Urinary excretion <2%: B12 malabsorption
Give IF- if normalises; IF def
If not- Treatment w antibiotics: ? Bacterial overgrowth
Otherwise think IF-receptor deficiency
Celiac
Foods to avoid
Monozygotic twin concordance
Risk if 1st degree relative affected
Risk if HLA identical sibling
Skin disorder associated
BROW
Barley, rye, oats, wheat
10% occult coeliac disease
2-5% overt disease
30-40% if HLA identical sibling
Dermatitis herpetiformis
Intensely pruritic vesicular rash
Improves slowly w diet and dapsone
Frequency of IDDM in coeliac
Selective IgA
Downs
Turners
Autoimmune thyroid disease
JIA
4%
2%
5-10%
3%
2-5%
Coeliac disease
Changes to bowel
Proximal SB
Spreads distally as disease progresses
Continuous, not patchy, only SB biopsies required (3rd part duodenum)
Recovery occurs distal to proximal
Sens/spec
IgG Gliadib
IgA gliadin
Antiendomysial (IgA)
Tissue transglutaminase (IgA)
100% ; 86% specific- seen in cows milk enteropathy, Crohn disease, tropical sprue
89%; 95.5%
100%; 98%
95; 95-98%
Anti TTG false positives
T1DM, liver disease, arthritis, heart failure
Disappear with treatment
Titre correlates with degree of mucosal damage
Celiac
Features on biopsy
Mononuclear infiltrate in lamina propria
Deepening & hyperplasia of crypts
T cell infiltrate of epithelium
Changes to surface enterocytes
- loss of brushborder enzymes
- columnar epithelium becomes cuboid or flat
- basophilic cytoplasm
Differential diagnosis of villous atrophy
Acute enteritis
Bacterial, viral, radiation, protozoal
Chronic enteritis
Tropical sprue, Whipples disease
Intractable enterocolitis
Lymphoma
Allergic
Milk-soy protein allergy
Coeliac
Eosinophilic ge
Immune
Immunodeficiency
Graft vs Host
Malnutrition
Iron/folate; protein/calorie
Congenital
Congenital villous atrophy
Coeliac
Follow up
What antibody
Long term complications
Screen siblings how frequently
Antiendomysial: falls if compliant
Nutritional deficiency
SB lymphoma
Oesophageal carcinoma
SB adenocarcinoma
Tissue transglutaminase alternate years
Congenital gastric outlet obstruction
3 causes
Investigations
Pyloric atresia
Antral webs
Gastric duplications
Metabolic alkalosis
Dilated stomach on AXR
Barium meal
Endoscopy ( best for webs )
Giardia Lamblia
Organism type
Live where in body
Attach to
Histology
Cysts can live how long in water
Protozoa
Duodenum & jejunum
Attached to brush border
Partial villous atrophy
3 months
Giardiasis
Sx
Dx
Watery stools that become greasy & foul smelling
Pain, bloat, anorexia, FTT
Intermittent diarrhoea & constipation
Cysts or trophozoites in stool
3 stool specs: increases rate of dx to 80%
Teduglutide
What
Effects (3)
GLP-2 analogue
trophic hormone secreted by enteroendocrine L cells
Increased villous height
Increased citrulline
Reduces PN requirement
