Malabsorption Aseel - PowerPoint Presentation

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Malabsorption

Aseel

Jamil

Al-twaije

r

lina

abdullah

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References

WALKER’S PEDIATRIC GASTROINTESTINAL DISEASE PATHOPHYSIOLOGY • DIAGNOSIS •

MANAGEMENT

SIXTH EDITION

Nelson:s

textbook 20

th

edition

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For Normal Digestion & Absorption; the followings are needed:1-Intact Mucosa 2-Normal Motility [coordinated

peristalisis

]

3- Intact secretions 4- Pancreatic secretionsIf any Defect it will lead to

Malabsorption

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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

.

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Lipid DigestionThe 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

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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

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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)

"

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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.

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Does an Acute Gastrointestinal Infection Lead to Malabsorption?

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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.

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Disorders of Carbohydrate absorption

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Carbohydrate intolerance of all forms is characterized by diarrhea thatsubsides 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.

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Glucose–galactose

malabsorption

(GGM) is a rare autosomal recessiveDisorder 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

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Lactase deficiency

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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

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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

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DISORDERS OF AMINO ACID AND PEPTIDEASSIMILATION

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

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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

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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

.

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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.

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Clinical ManifestationsThe 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.

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Serum samples should be analyzed for evidence of β-lipoprotein (VLDL

and chylomicron) deficiencies.

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Cystic fibrosisCystic fibrosis results in impairment of pancreatic

exocrine function and generalized

malabsorptive

symptoms, as pancreaticenzymes 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.

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DISORDERS OF MINERAL AND ELECTROLYTE ABSORPTION AND SECRETIONCongenital 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

.

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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.

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