Malabsorption syndrome · 2020. 10. 4. · 3- Gastrointestinal manifestations of malabsorption...

Malabsorption syndrome By : Yara Saleh

Tasneem Anagreh

Definition

- Diminished intestinal absorption of one or more dietary nutrients due to either defective nutrient digestion or mucosal absorption .

Normal physiology

For Normal Digestion & Absorption; the followings are needed:

1-Intact Mucosa

2-Normal Motility [coordinated peristalisis]

3- Intact secretions

4- Pancreatic secretions

If any DefectMalabsorption

Phases of digestion & absorption process : The digestive and absorptive process usually is categorized into : • Luminal phase : dietary fats, proteins, and carbohydrates are

hydrolyzed and solubilized depending largely on pancreatic and biliary secretions.

• Mucosal phase :final hydrolysis and uptake of saccharides and peptides takes place from lumen into cells and

lipids taken up by epithelial cells are processed and packaged tor cellular export. • Post-absor ptive phase :transported via lymphatics and portal circulation from epithelial cels to other parts of the body. • Thus defect in any of these phases leads to malabsorption.

Carbohydrate digestion

Some enzymatic digestion of starch occurs in the mouth, due to the action of the

enzyme salivary amylase

. This enzyme starts to break the long glucose chains of starch into shorter chains,

some as small as maltose.

The low pH in the stomach inactivates salivary amylase, so it no longer works once it

arrives at the stomach. Although there's more mechanical digestion in the stomach,

there's little chemical digestion of carbohydrates here.

Most carbohydrate digestion occurs in

the small intestine, thanks to a suite of

enzymes. Pancreatic amylase is

secreted from the pancreas into the

small intestine, and like salivary amylase,

it breaks starch down to small oligosaccharides

(containing 3 to 10 glucose molecules)

and maltose.

Cont,,

The rest of the work of carbohydrate digestion is done by enzymes produced by the enterocytes, the cells lining the small intestine. •Maltose is digested by maltase, forming 2 glucose molecules •Lactose is digested by lactase, forming glucose and galactose •Sucrose is digested by sucrase, forming glucose and fructose

By the end of this process of enzymatic digestion, we're left with three monosaccharides: glucose, fructose, and galactose. These can now be absorbed across the enterocytes of the small intestine and into the bloodstream to be transported to the liver.

Lipids and proteins digestion

Lipids 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

Proteins digestion

• 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.

Etiology

1- Impaired digestion Hepatic: - Biliary atresia (bile salt insufficiency) - Chronic hepatitis Pancreatic: - Prolonged protein calorie malnutrition - Cystic fibrosis - Chronic pancreatitis - Shwachman-Diamond syndrome

Cont,,

2- Intestinal stasis

- Protein caloric malnutrition (acini atrophy).

- Stagnant loop syndrome.

- Inflammatory bowel diseases:- Crohns’ disease

-Ulcerative colitis

Cont,,

3- Impaired absorption a. Generalized malabsorption: -Chronic infections: e.g. giardia lamblia, tuberculous enteritis

,bilharziasis -Congenital: chloride diarrhea, sodium diarrhea -Defective enterocyte differentiation: microvillous inclusion

disease, congenital tufting enteropathy -Short bowel syndrome -Celiac disease -Auto immune entropathy -Allergy: Multiple food protein hypersensitivity -Intestinal tumors

Cont,,

Clinical picture

1- Features suggesting a cause e.g. - Hepatomegaly & jaundice in chronic liver disease. - Relation to certain food in celiac disease.

2- General ill health with pallor, weakness & failure to thrive 3- Gastrointestinal manifestations of malabsorption -Mouth ulcers & glossitis -Abdominal distension & flatulence -Steatorrhea : pale, bulky, greasy, offensive stool -Chronic diarrhea

Manifestations of Malabsorption syndromes ARE HIGHLY DEPENDANT on the affected Site

Cont,,

4- Nutritional deficiency manifestations

-Fat : Loss of subcutaneous fat

-Proteins: Nutritional edema , muscle wasting & loss of weight

-Carbohydrates : Hypoglycemia

-Minerals and vitamin deficiency :

Vit.D = Rickets

Vit.K = Bleeding

Vit.A = scleritis – night blindness – Xerophthalmia – corneal ulcers

Vit.E = manifestations similar to that of Vit.b12 defiency; Decrease Reflexes-Impaired sensation-Ataxia

Disorders of Carbohydrate absorption

1- Lactose intolerance • also called lactase deficiency or hypolactasia, is the inability to digest

and metabolize lactose, a sugar found in milk. • Lactose intolerance is not an allergy because it is not an immune

response but caused by lactase deficiency. • Lactose intolerance can occur in any age group or population.

Symptoms

• Abdominal bloating and cramps

• Flatulence

• Diarrhoea

• Nausea

• Vomiting (particularly in adolescents).

• Allergic rash

Types

• Congenital lactase deficiency

-very rare

-autosomal recessive

-prevents lactase expression from the first feed.

-serious disorder in which the infants may fail to thrive unless given lactose free formula feed.

Cont,,

• Primary lactase deficiency -Develops over time -Body begins to produce less lactase. -Inheritable • Secondary lactase deficiency -results from injury to the small intestine Severe diarrheal ilIness Celiac disease Crohn's disease Chemotherapy.

Diagnosis

-Genetic testing

-lactose breath test with a rise in breath hydrogen content due to fermentation of undigested lactose by normal colonic flora

-lactose load test in which blood glucose fails to rise more than 10 mg/ dL after ingestion of 1 g/kg of lactose.

Management

• Avoiding lactose-containing products

• Alternative products such as Plant- based milks and derivatives are inherently lactose free: soy milk, rice milk, almond milk, hazelnut milk, oat milk, peanut milk.

2-fructose intolerance / fructose malabsorption

-Fructose is a simple ketonic monosaccharide found in many foods such as fresh fruits and honey.

-After ingestion, fructose is converted into fructose-1-phosphate in the liver by fructokinase.

-Fructose-1-phosphate is metabolized by aldolase B into dihydroxyacetone phosphate and glyceraldehyde.

Fructose malabsorption, formerly called dietary fructose intolerance

• Some people cannot completely absorb fructose in their small intestine.

• The undigested fructose is then carried to colon where our normal bacteria rapidly devour it.

• In this process, the bacteria produces gases which cause the intestine to swell. This is experience by the person as bloating, cramping, gas and distention and diarrhea may also occur due to the undigested particles of fructose.

Fructose intolerance is also known as hereditary fructose intolerance

• It is an inbron error of fructose metabloism caused by a deficiency of the enzyme aldolase B

• Individual affected with HFI are asymptomatic until they ingest fructose, sucrose, or sorbitol.

• If the fructose is ingested, the enzymatic block at aldolase B cause an accumulation of fructose-1- phosphate which, overtime result in the death of liver cells ·

Symptoms

• Abdominal cramps

• Diarrhea

• Increased intestinal sounds

• Gas production

• Nausea or vomiting

• Poor feeding

Diagnosis

• The only definitive way to ascertain if one is suffering from HFI is to have one of two test.

• An enzymatic assay to determine aldolase activity. The aldolase is obtained from patient liver tissue by liver biopsy.

• A fructose tolerance test, fructose is injected introvenously under controlled condition where acute glucose, fructose & phosphate levels are monitered.

• And hydrogen breathe test it is a method currently used to diagnosis following ingestion of fructose, the hydrogen concentration of the patients breathe is measured at various time intervals.

Treatment

• avoiding fructose, sucrose or sorbitol from diet to avoid foods like honey, palm or coconut sugar etc.

• Treatment with dietary supplements of xylose isomerase may reduce the sympotoms of FI

• Xylose isomerase acts to convert fructose sugar to glucose.

3-Glucose-Galactose Malabsorption

• It is a rare disorder in which the sodium-glucose transport protein is defective.

• Transport of glucose in the intestinal epithelium and renal tubule is impaired.

• Diarrhea begins with the first feedings, accompanied by reducing sugar in the stool and acidosis

• Diarrhea subsides promptly on withdrawal of glucose and galactose from the diet.

• The acquired, transient form of glucose-galactose malabsorption occurs mainly in infants younger than 6 months, usually following acute viral or bacterial enteritis.

• In the congenital disease, exclusion of glucose and galactose from the diet is mandatory. A carbohydrate-free base formula is used with added fructose.

• The prognosis is good if diagnosed early. • Tolerance for glucose and galactose improves with

age. • In the secondary (acquired) form, prolonged PN may

be required until healing.

DISORDERS OF AMINO ACID AND PEPTIDE ASSIMILATION :

Disease: Hartnup’s • is an autosomal recessive metabolic disorder affecting the absorption of

nonpolar amino acids ; particularly tryptophan.

• The causative gene, SLC6A19, is located on ch5.

• a person with Hartnup disease cannot absorb amino acids properly from the intestine and cannot reabsorb them properly from tubules in the kidneys. Excessive amounts of amino acids, such as tryptophan, are excreted in the urine.

• Signs and symptoms:

• may begin in infancy or early childhood, but sometimes they begin as late as early adulthood .

• Triggers : sunlight, fever, drugs, or emotional or physical stress. A period of poor nutrition.

• Infancyfailure to thrive, photosensitivity, intermittent ataxia, nystagmus, and tremor.

• Rash , Mental retardation, short stature, headaches, unsteady gait, fainting , Psychiatric problems.

• Diagnosis : • urine chromatography, increased levels of neutral amino acids and indican

are found in the urine.

• Treatment : • High-protein diet . • Sun avoidance • Supplements(vitamin B complex or niacin supplements, such as nicatonic

acid).

• ----------------------------------------------------------- • DDX: • Pellagra . • Fanconi syndrome.

(PLE)enteropathylosing -Protein

• The exact mechanisms for PLE are not known , but it generally occurs because of excessive weeping of serum protein into the bowel beyond what subsequently can be digested and reabsorbed downstream in the gut.

• Numerous causes PLE generally are attributable to:

1- intestinal damage

2- impediment of mesenteric lymphatic flow

3- impediment of mesenteric venous flow.

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• Clinical presentation :

diarrhea, fever, and general abdominal discomfort . Swelling of the legs due to peripheral edema , however, if the PLE is related to a systemic disease then the symptoms could be of the primary disease development.

• Diagnosis : 1)fecal alpha- 1-antitrypsin excretion test (FA1AT) ,

2-Other tests:

• Measurement of fat-soluble vitamin levels

• Vitamins: A, E, and 25-OH D,

PT-prothrombin time.

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Tretment : depends upon the underlying condition .

Management :

• Mild dietary adjustment , slowly inc food and water intake , supplements , diarrhea medications .

• Severe TPN , SB transplant .

DISORDERS OF FAT ASSIMILATION

Abetalipoproteinemia : Abetalipoproteinemia (ABL) is the classic and most well characterized 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,. ------------------------------------------------------------------------- Serum samples should be analyzed for evidence of β-lipoprotein (VLDL and chylomicron) deficiencies.

Cystic Fibrosis

Overveiw :

The reported incidence of CF in Caucasians in the United States ranges from 1 in 2,000 to 4,000 live births. Approximately 1 in 25 Caucasians carries at least one CF DNA mutation; these individuals are asymptomatic.

(note :CF is rare but does occur in non-caucasians.)

CF is caused by mutations in the CFTR gene, which is located on chromosome 7 at position 7q31. The most common mutation is Delta F508.

PATHOPHYSIOLOGY:

The primary pathophysiologic abnormality in CF is defective chloride channel function that results in generalized dysregulation of salt and water flux across epithelial glandular cells.

• There is multiorgan involvement, with characteristic disease of lung and pancreas and variable disease in the gastrointestinal tract, hepatobiliary system, and the reproductive tract.

• Disease results from inspissated plugging by proteinaceous secretions in affected organs.

Clinical Manifestations :

the diease will differ in different Ages accordingly:

1- Infants:

• The most common presentation of CF is an infant are Respiratory symptoms: of persistent cough, congestion, and also symptoms of failure to thrive.

• The stools are bulky or sometimes loose.

• Generalized edema, hypo Na

• Some affected neonates have cholestasis or meconium ileus.

• 2- Childhood:

children who have CF could present initially with:

• Recurrent lung infections

• FTT, steatorrhea

• Acute pancreatitis.

• Rectal prolapse.

DIAGNOSIS:

• CF usually is diagnosed by performing a sweat chloride test.

CF DNA mutation tests can be obtained, but, this testing may miss some cases.

Other presumptive diagnostic tests include: • assessing for the presence of inspissated proteinaceous

material in tissue biopsies, transnasal conductance measurements, and tests for pancreatic insufficiency.

• The test performed most easily for pancreatic insufficiency in a young infant is the semiquantitative test for trypsin in the stool; This test is not useful for older children and adults.

• Pancreatic enzyme levels also can be measured by direct endoscopic sampling of ductal secretions from the ampulla of Vater.

MANAGEMENT:

• • High calorie , high fat diet

• • Fat soluble vitamin supplement

• • Pancreatic enzyme replacement

• • Management of liver disease

• • Management of lung disease

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.

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.

• 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.

Diagnosis :

A diagnosis of CCD is suggested if fecal chloride concentration is high (>90 mmol/L) and exceeds the concentration of cations (Na+ and K+)

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Management :

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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