Celiac Disease and CF Flashcards
Protein and carbohydrate assimilation may also be adversely impacted by disease states that reduce the absorptive surface area of the
Small intestine
This usually occurs via a selective loss of mature
Villus enterocytes
Perhaps the most common disorder in which such a change occurs is
Celiac disease
Results in an inappropriate immune response to a dietary constituent known as α-gliadin
Celiac disease
A constituent of gluten that is a key structural component of wheat and some other grains
α-gliadin
The most severe form of celiacs disease shows what type of mucosa in the small intestine?
Flat mucosa
This results in the total loss of intestinal
Villi
The site to which both brush border hydrolases and nutrient transporters are localized
Small intestine Villi
Patients with celiac’s disease may present with symptoms of impaired
Nutrient uptake
Celiac patients also hve undigested/absorbed nutrients remaining in the lumen that are then acted on by bacteria. This results in the symptoms of
-similar to lactose intolerance
Bloating and abdominal cramps
The treatment for patients with celiac disease is strict avoidance of foods containing
α-gliadin
Within a short time, exclusion of these substances from the diet results not only in the resolution of symptoms, but also restoration of the
Intestinal mucosa
What is the classic presentation of Celiac disease?
Chronic diarrhea, steatorrhea, and weight loss
-also iron and vitamin deficiencies
Affects women 1.5 times more than men
Celiacs disease
Celiac disease develops only in people that habe the
HLA-DQ2 or HLA-DQ8 Haplotype
These haplotypes expressed on antigen presenting cell surfaces can bind the deaminated gluten peptide found in
Wheat, Rye, and Barley
This triggers the abnormal
Immune response
The result is then the development of antibodies against
Gliadin, transglutaminase, and endomysin
Seen in 27-50% of patients
Diarrhea
May develop due to vitamin D deficiency and secondary hyperparathyroidism that can accompany Celiac disease
Osteopenia and osteoporosis
Celiac disease is strongly associated with
-develops secondary to antibodies against epidermal transglutaminase
Dermatitis herpetiformis
Celiac disease is far more common in patients with
Down Syndrome
Celiac disease increases the risk of other autoimmune disorders including
Thyroiditis and type 1 DM
The gold standard for diagnosing Celiac disease is
Duodenal biopsy
Highly accurate to diagnose celiacs but not perfect
Serological testing
The initial serologic test for celiacs is to test
Tissue glutaminase antibody (IgA tGT)
What is the sensitivity and specificity of the Tissue glutaminase antibody (IgA tGT)
87% sensitive and 97% specific
Another very accurate test which is 87% sensitive and 99% specific
Endomysial antibody (IgA EMA)
Virtually all patients with celiac disease express
HLA-DQ2 or HLA-DQ8 heterodimers
Is 100% sensitive, but only 57-75% specific
HLA typing
Celiac disease can be virtually ruled out in patients who are negative for
HLA-DQ2 or HLA-DQ8
May be useful in patients who instituted a gluten-free diet before evaluation in whom IgA-tGT and IgA EMA antibody levels may be low due to decreased disease activity
HLA typing
The most widespread autosomal recessive disorder among the caucasian population
Cystic Fibrosis
A life-limiting disease which involves multisystem dysfunction mainly in the respiratory tract, gastrointestinal system, pancreas, and reproductive organs
Cystic Fibrosis (CF)
CF involves a mutation in
CFTR
Mediates Cl- secretion and it is expressed on the apical surface of all exocrine epithelia that includes lung airways, pancreas, intestine, testis
CFTR
Shown to regulate the secretion of bicarbonate, glutathione and a variety of other transport proteins and cellular processes
CFTR
CFTR belong to which family of transporters?
ATP-Binding Cassette (ABC)
CFTR is primarily regulated by cAMP signaling and
Protein phosphorylation
Loss of function of CFTR affects all exocrine epithelia due to a failure to
Hydrate Macromolecules
In the lung, CF results in
-causes chronic infection and inflammation of the local airways
Mucus retention
In the pancreas, CF leads to decreased secretion and more acidic fluid causing precipitation of
Zymogens
Falls into six groups according to their mechanism by which they affect the synthesis, traffic and function of CFTR
CFTR Mutations
The most severe among the groups and results in no protein production
Class I
Include the synthesis of a misfolded improperly leading to its degradation by the ubiquitin-proteasome pathway
Class II Mutations
The most common mutation in CF is falls into class II and it is due to the deletion of
Phenylalanine at position 508
Cause defects in the Cl− channel regulation
-One of the mutations is G551D.
Class III
Acts as a potentiator by increasing the flow of Cl- ions through the activated CFTR
-Can be used to treat Class III
Ivacaftor
Mostly due to missense mutations leading to correctly trafficked protein, but with low Cl- flow
Class IV mutations
Results in reduced levels of, but otherwise normal CFTR
Class V Mutations
Cause reduced stability of CFTR
Class VI
The first four classes of CFTR mutations which are more severe than the last two classes lead to
Panreatic Insufficiency
Pancreatic sufficient mutations
Classes V and VI
Secrete digestive enzymes including zymogens into the acinar lumen
Pancreatic Acinar Cells
This is accompanied with the secretion of Cl- and HCO3-
into the ductal lumen which move fluid with them to neutralize the acidic chyme emptied from the stomach into the duodenum and also increase the activity and solubility of these
Digestive Enzymes
In CF, absence of bicarbonate secretion, hyperacidity, not only leads to the precipitation of the digestive enzymes, but also precipitation of
Bile Acids
This precipitation of Bile Acids leads to the development of
Meconium Ileus
Also associated with increased trypsinogen autoactivation into trypsin leading to activation of the activation of zymogens damaging the endocrine functions of the pancreas
Hyperacidity in CF
Obstruction of ducts starts in utero and continues after birth releasing pancreatic proteins into the circulation, hence the immunoreactive trypsinogen (IRT) for newborn screening of
CF
