malabsorption · 2020. 9. 18. · glucose–galactose malabsorption (ggm) is a rare autosomal...
TRANSCRIPT
MALABSORPTION
Aseel Jamil Al-twaijer lina abdullah
References
WALKER’S PEDIATRIC GASTROINTESTINAL DISEASE PATHOPHYSIOLOGY • DIAGNOSIS •
MANAGEMENT
SIXTH EDITION
Nelson:s textbook 20th edition
For Normal Digestion & Absorption; the followings are needed:
1-Intact Mucosa 2-Normal Motility [coordinated peristalisis]
3- Intact secretions 4- Pancreatic secretions
If any Defect it will lead to Malabsorption
What steps are involved in digestion and absorption?
Three phases are involved:
Luminal phase - Dietary fats, proteins and carbohydrates are hydrolyzed and solubilized,
largely by pancreatic and biliary secretions.
Mucosal phase - Terminal hydrolysis of carbohydrate and peptides occurs and fats are
processed and ;then packaged for cellular export.
Removal phase - Absorbed nutrients enter the vascular or lymphatic circulation.
Thus defect in any of these phases leads to malabsorption.
Lipid Digestion
The most common dietary lipids are triglycerides, which are made up of a glycerol
molecule bound to three fatty acid chains. Small amounts of dietary cholesterol and
phospholipids are also consumed.
The three lipases responsible for lipid digestion are lingual lipase, gastric lipase,
and pancreatic lipase. However, because the pancreas is the only consequential source
of lipase, virtually all lipid digestion occurs in the small intestine. Pancreatic lipase
breaks down each triglyceride into two free fatty acids and a monoglyceride. The fatty
acids include both short-chain (less than 10 to 12 carbons) and long-chain fatty acids
The digestion of protein starts in the stomach, where HCl and pepsin
break proteins into smaller polypeptides, which then travel to the
small intestine. Chemical digestion in the small intestine is continued
by pancreatic enzymes, including chymotrypsin and trypsin, each of
which act on specific bonds in amino acid sequences. At the same
time, the cells of the brush border secrete enzymes such
as aminopeptidase and dipeptidase, which further break down
peptide chains. This results in molecules small enough to enter the
bloodstream
Chronic Diarrhea
Persistent or chronic diarrhea refers to a pattern of loose stools (with orwithout an increase in stool
frequency) that lasts for at least two weeks.
This definition, supported by the World Health Organization (WHO)"
APPROACH TO THE CHILD WITH PERSISTENT
DIARRHEA
The starting point in the approach to the child with persistent diarrhea is
the evaluation of weight curve, age at onset, pattern of stools and
association with other signs or symptoms.69
A careful history and physical examination are needed for optimal
diagnostic approach.
A family history of atopic or autoimmune diseases points toward
allergy or autoimmunity. The same is often true for children with cystic
fibrosis or IBD. However, CDDs are very frequently inherited as
autosomic recessive manner and some specific diseases are more frequent
in ethnic groups where consanguineous marriages are common, or in some
geographic areas due to founder effects.62,68 A familiar history of early
onset chronic diarrhea, polyhydramnios, and/or dilated bowel loops at
ultrasound examination during pregnancy is highly suggestive of CDDs
and diarrhea often dates to early neonatal period.
Does an Acute Gastrointestinal Infection
Lead to Malabsorption?
Classifying the type of diarrhea may be done with either a trial of fasting or by analysis
of stool electrolytes while on a complete diet.
In fact, the majority of patients with
abnormal intestinal histology have a mixed form of diarrhea that has both
osmotic and secretory components.
Disorders of Carbohydrate absorption
Carbohydrate intolerance of all forms is characterized by diarrhea that
subsides shortly after carbohydrates are reduced or eliminated from the
diet. Therefore, abnormal carbohydrate assimilation results in the presence
of major osmotic forces in colonic luminal fluid derived from oligosaccharides, lactose, sucrose
or glucose.
Unabsorbed carbohydrates are fermented by the resident colonic microflora to gas (hydrogen,
methane, and carbon dioxide) and volatile short-chain fatty acids such as acetate, butyrate, and
propionate. A proportion of these SCFAs are absorbed across the colonic epithelium by poorly defined
diffusion and transporter-mediated mechanisms.
Glucose–galactose malabsorption (GGM) is a rare autosomal recessive
Disorder that causes severe life- threatening diarrhea and dehydration during the neonatal period
Diarrhea is most frequently detected during the first several weeks of life in breastfed
or bottle-fed children, and will result in severe metabolic acidosis and
hyperosmolar dehydration. Diarrhea ceases at bowel rest and resumes
when the child receives the same feeding again, protein hydrolysate or
elemental diet (amino acid–based formula). If not properly diagnosed in a
timely manner and if dietary management is not implemented, GGM is frequently fatal.
several formulas are available for managing GGM patients
during early infancy, including Ross Carbohydrate Free Formula
Lactase deficiency
Fructose malabsorption
Fructose is the primary monosaccharide found in fruits and fruit juices.
Fruit juices that contain a high proportion of fructose to glucose or an
excessive amount of the nonabsorbable carbohydrate sorbitol have been
associated with infant diarrhea and abdominal pain
Fructose malabsorption can be assessed by either placing the patient on a
fructose elimination diet or performing a fructose breath hydrogen test.
Fructose given at 1 g/kg body weight or a maximum of 25 g can be used to
perform these studies1
Patients experiencing significant fructose-induced diarrhea should either
reduce or eliminate their dietary fructose load to resolve symptoms.
Because fructose malabsorption is generally limited to early infancy, attempts to
reintroduce fructose should be considered as patients enter into the school-aged years
DISORDERS OF AMINO ACID AND PEPTIDE ASSIMILATION
Hartnup’s Disease
Hartnup’s disease and iminoglycinuria)
are two other autosomal recessive disorders that have been well
characterized clinically. Hartnup’s disease is characterized by a
malabsorption and renal excretion of neutral amino acids (neutral
aminoaciduria) and a heterogeneous set of symptoms ranging from a
pellagra-like rash to neurologic disorders
DISORDERS OF FAT ASSIMILATION
The clinical consequences of disorders of fat assimilation include
failure to thrive, steatorrhea, and neurologic deficits that result from the
malabsorption of fat-soluble vitamins
Because pancreatic exocrine function in particular is not fully formed during early infancy, fat
absorption in this age group primarily depends on the action of gastric lipase.
A congenital deficiency of pancreatic lipase is an exceedingly rare autosomal recessive disorder
that leads to fat malabsorption
Fatty acid and diglyceride are the products of triglyceride hydrolysis,
and their solubilization to the aqueous phase of luminal content requires
adequate levels of conjugated bile salts, and therefore various disorders of
intrahepatic and extrahepatic cholestasis will impede the delivery of
luminal bile salts and result in fat malabsorption.
Abetalipoproteinemia
Abetalipoproteinemia (ABL) (MIM #200100) is the classic and most wellcharacterized
disorder of fat absorption and results from failure to
reassemble dietary fat in the form of β-lipoproteins.
Patients generally present shortly after birth with failure to thrive and steatorrhea and if untreated
will develop irreversible neurologic problems in late infancy.
Clinical Manifestations
The typical clinical presentation is often failure to thrive, emesis, and low volume
diarrhea. Poor growth despite adequate caloric intake is an early
clinical characteristic that should hasten the assessment of a possible
defect of fat malabsorption. In the long term, patients may develop an
aversion to fatty meals as a way to diminish their diarrheal symptoms. The
first evidence of neuromuscular abnormalities is frequently the loss of
deep tendon reflexes, which results from prolonged vitamin E deficiency;
additional neuromuscular manifestations, including retinitis pigmentosa,
ataxia, and spinocerebellar degeneration, may be mistaken for various
forms of Friedreich ataxia.
Serum samples should be analyzed for evidence of β-lipoprotein (VLDL
and chylomicron) deficiencies.
Cystic fibrosis
Cystic fibrosis results in impairment of pancreatic
exocrine function and generalized malabsorptive symptoms, as pancreatic
enzymes hydrolyze dietary fats and complex carbohydrates.119 However,
disorders of pancreatic insufficiency are not associated with malabsorption
of either monosaccharides (glucose, galactose, or fructose) or amino acids.
DISORDERS OF MINERAL AND ELECTROLYTE ABSORPTION AND SECRETION
Congenital Chloride Diarrhea
The most common cause of severe congenital secretory diarrhea in the
presence of normal intestinal mucosa is the autosomal recessive disorder
congenital chloride diarrhea
Clinical Manifestations
The earliest clinical symptoms may occur in utero with severe polyhydramnios and dilated loops of small
bowel detectible by ultrasonography that may resemble a distal intestinal obstruction.150 The
severity of the polyhydramnios frequently leads to preterm labor or planned premature delivery by
cesarean section. Patients with CCD generally present during the first weeks of life with severe life-
threatening secretory diarrhea. The serum electrolytes prior to treatment are unique
among the various congenital diarrheal disorders and include metabolic alkalosis, hypochloremia,
hypokalemia, and hyponatremia.
A diagnosis of CCD is suggested if fecal chloride concentration is high
(>90 mmol/L) and exceeds the concentration of cations (Na+ and K+)
The mainstay of therapy is life-long enteral administration of KCl and NaCl supplements, in the
range of 2.8 mmol/kg/d for infants, However, occasional assessment of serum and
urine electrolyte and pH balance is recommended to optimize the Cl– replacement doses.