Disease, pathophysiology, symptoms/clinical presentation, diagnosis, treatment

1. Akash Mahadev Iyer
S2 M.Sc Biochemistry
University of Kerala
Karyavattom Campus

2. MALABSORPTION SYNDROME
Group of disorders (celiac disease, cystic fibrosis, Crohn's disease,
chronic pancreatitis, Tropical sprue) characterized by reduced
intestinal absorption of dietary components and excessive loss of
nutrients in the stool.

3. Sprue
Tropical
Non-Tropical
(Celiac disease)
Tropical sprue-an acquired disorder (an enteropathic condition) that presents
with chronic diarrhea, weight loss etc..
Etiology-often bacterial, viral , or parasitic infection or toxins in spoiled food
Most common causes- intestinal infection with small intestinal protozoa including
Giardia intestinalis, Cryptosporidium parvum, Isospora
belli, Cyclospora cayetenensis and the microsporidia
Epidemiology: Tropical sprue may occur after travelling to tropical areas
such as the Caribbean, Southern India, Southeast Asia.

4. SYMPTOMS- Clinical features
 Villi of the small intestinal mucosa become blunted or obliterated.
 Diarrhea, steatorrhea, abdominal pain, weight loss, fatigue, Megaloblastic
anemia (Malabsorption of folate and vitamin B12 deficiency), light colored
stools, pallor.
 Sore tongue (Vit B12 deficiency) ,Easy bruising (Vit K deficiency)
 Multiple nutritional deficiencies and anorexia
Diagnosis
Endoscopy
Low levels of vitamins, hypoalbuminemia, prolonged PT
Low levels of β-carotene
Excess fat in feces
The D xylose test & folic acid levels are abnormally low
Macrocytic anemia
Indirect pancreatic test (e.g., Pancreolauryl test -abnormal in as many as 64%
cases due to reversible exocrine pancreatic insufficiency related to low pancreatic
hormonal stimulation caused by the loss of enterocyte)

5. Treatment
 Broad spectrum antibiotics such as tetracycline and folic acid are the
treatment of choice
 Rapid clinical response
 Recurrence is uncommon, especially if the patient is not a resident of or a
frequent traveler to tropical areas
 Other antibiotics such as sulfonamides , Rifamixin is also used
Diet for adults suffering from tropical sprue
 Cereals and cereal products
 Half fat milk, eggs, cheese fleshy fruits( Banana, papaya, mango, apple ,
Cane sugar
 Multivitamin tablets, curd, cooked rice
 Probiotic such as yoghurt with active cultures of Lactobacillus acidophilus,
lactinex, bacid, to help re-colonize normal intestinal flora in people with
antibiotic therapy
 Basic sanitation

7. Celiac disease
 Also known as celiac sprue, non tropical sprue, or gluten- sensitive enteropathy.
 Celiac disease can be defined as pathological intolerance of the intestinal mucosa
to prolamines, which are storage proteins in cereal grains, that occurs in
genetically predisposed individuals of all ages
 The disease is caused by a reaction to a protein (gluten) found in grain (wheat,
barely, oats, and rye).
 Upon exposure to gluten, the immune system cross reacts, causing chronic
inflammation and primary lesions of the intestinal mucosa.
 This disorder can result in the malabsorption of all nutrients as a result of the
shortening or total loss of intestinal villi, which reduces the mucosal enzymes for
nutrient digestion and the mucosal surface for absorption.
 Gluten comprises two different protein types, gliadins and glutelins
 Epidemiology Celiac sprue occurs in about 1 to 6 of 10,000 people in the Western world. The
highest incidence is in western Ireland, where the prevalence is as high as 3 of 1,000 people
 Most prevalent chronic disease across Europe.
 More frequent in females (by about 2:1) than in males

9. • Prolamins are a group of plant storage
proteins having a high proline content and found on
plant materials mainly like in the seeds of cereal
grains: wheat (gliadin), barley (hordein), rye (secalin)
, corn (zein), sorghum (kafirin) and as a minor
protein, avenin in oats. They are characterised by a
high glutamine and proline content and are
generally soluble only in strong alcohol[70-80%]
solutions,light acids,alkaline solution

10. Pathogenesis
 Celiac disease is polygenic and multifactorial, (it requires triggering by the
environment in the form of gluten, HL antigens, DQ2 and DQ8 risk factors).
 These genes are expressed on the surface of B cells, T cells, and macrophages
where they code for class ll MHC that has the function of presenting short peptide
antigens to receptors on CD4+ (helper)T cells
 The histological damage -mediated by up-regulation of zonulin, a protein responsible
for altering gut permeability.
 Tight junctions of intestine regulate passage of molecules of varying sizes
 In celiac disease , disruption of this controlled transit of larger
molecules may allow antigenic peptide component of gluten to pass
into the lamina propria,- where they are recognized by inflammatory
cells, containing DQ 2 or DQ8 genes- setting up an autoimmune
reaction and resulting immune mediated damage.

13. Clinical presentation
 Profuse secretion of mucus interferes -absorption of nutrients and especially fat
 Diarrhea, Steatorrhea which occurs in about 50% of the patients, weight loss, growth
failure
 Histology shows villous atrophy and crypt hyperplasia.
Other symptoms
 Bloating, Gas, Indigestion, constipation
 Stools that float are foul smelling bloody or fatty
Non intestinal symptoms
 Anemia
 Abnormal liver tests
 Osteoporosis, depression, fatigue, joint pain, mouth ulcers, unexplained weight loss,
under nutrition
 Muscle weakness
 Epilepsy ,migraine
 A set of associated conditions with the celiac disease .
 The term associated condition refers to states that are found more frequently in
patients affected by celiac disease. These conditions include genetic disorders such
as Down syndrome, Turner syndrome and auto immune or neurological disorder

15. Diagnosis
• Small bowel biopsies-gold standard
Serological test
 Celiac disease is characterized by the development of antibodies directed
against the components of gliadin
 It is important that the patient not reduce or exclude gluten in diet before
testing,as all tests may become negative
 Detection of IgA anti tissue glutaminase antibodies tTGA by ELISA - highly
sensitive
 Anti gliadin - low sensitivity
Treatment
 Gluten free diet- Clinical improvement- Mucosal damage recovery
 Multivitamins
 Gluten degrading enzymes enzyme supplement therapy
 Bacterial prolyl endopeptidases

18. Steatorrhoea
 Fatty diarrhoea resulting from malabsorption of dietary fat.
 Diarrhoea is characterized by pale, bulky, greasy foul-smelling stools that float
(because of increased air content and are difficult to flush away.
 Passage of stools that contain fat (>17 mmol or 6 g per day) and indicates fat
malabsorption as a result of small bowel, pancreatic disease (pancreatic
insufficiency resulting in lipase deficiency), or cholestatic liver/biliary disease
(resulting in intestinal bile salt deficiency)., celiac disease, bacterial overgrowth,
CD, parasitic disease and Whipple disease.
 (25%) Weight loss medications such as orlistat and fat substitutes such as olestra
can also be a causative.

19.  Common symptoms include anorexia, bloating, flatulence.
 Fat malabsorption results in secondary nutrient deficiencies and
systemic disease such as anemia, hypoalbuminemia, osteoporosis ,
cramps and paraesthesias.
 Occurs only after fat-containing meals and therefore not a daily
symptom. As steatorrhea occurs after meals, it typically happens 2
to 3 times a day in individuals with a normal lipid-content diet.
Weight loss and anorexia may also develop over time due to
malnutrition.
 2-6 g of ingested fat -normally excreted each day , -60 g may be lost
in steatorrhea.
 Weight loss requires an increased energy intake
 High dietary protein and carbohydrates
 Fat soluble vitamins and minerals such as Ca Zn, Mg, and Fe
should be supplemented
 Detection by Sudan staining

20.  The following features should be inquired about in a patient's medical
history.
 Prior surgical resection of the stomach, pancreas (e.g., Whipple operation,
pancreatectomy), gastrectomy).
 Recurrent episodes of acute pancreatitis
 History of malabsorptive conditions (e.g., celiac disease,
giardiasis, Whipple disease, HIV/AIDS, lymphoma, gastrointestinal
amyloidosis).
 Use of tetrahydrolipstatin (orlistat), meclofenamate sodium, or olestra (fat
substitute used in cooking).
 Alcohol dependence (as it is a risk factor for cirrhosis and chronic
pancreatitis).
 Diabetes, which can occur in chronic pancreatitis.
 Recurrent pulmonary/upper respiratory tract infections suggestive of cystic
fibrosis gene mutations

21. Diagnosis
• Sudan stain of a random sample of homogenized stool
• Steatocrit is quantitative measure of fat as a proportion of a whole
centrifuged homogenized stool sample. [
• 72-hour fat chemical analysis (van de Kamer method) is considered the most
accurate test for fecal fat quantification, although a 24-hour sample is more
commonly obtained. (time-consuming and infrequently performed properly
by physicians).
• The following investigations can help determine whether it is
only fat that is being malabsorbed, or other nutrients also.

22. Laboratory
 Fecal pancreatic elastase-1 -investigating pancreatic exocrine insufficiency -chronic
pancreatitis
 Stool microscopy and culture for ova, cysts, and parasites when investigating possible
infection with Cryptosporidium, Giardia, microsporidia, Cyclosporidium, or Clostridium
difficile.
 Direct serum bilirubin, ALP, GGT tests
 IgA tissue transglutaminase titer, serum IgA level, and duodenal biopsy in a patient with
suspected celiac disease (e.g., anemia, chronic diarrhea, distended abdomen, young age).
 Genetic mutation analysis, when considering inherited diseases of the pancreas, such as
cystic fibrosis.
 Thyroid evaluation with TSH, free thyroid hormones, and thyroid radioiodine uptake scan
(scintigraphy) to assess for hyperthyroidism.
Imaging
 Abdominal CT scan with oral and IV contrast
 Ultrasound of the pancreas
 Magnetic resonance cholangiopancreatography (MRCP)
 Esophagogastroduodenoscopy (EGD) and small-bowel biopsy
 Colonoscopy

23. Chyluria
 Chyluria -fistulous communication between urinary and lymphatics.
 Chyluria, which is passage of chyle in urine that gives its milky appearance,
 Causes, -parasitic and nonparasitic.
 The lymph laden with fat -absorbed from intestine is responsible for the milky
appearance. Large amount of chyle in urine can be easily identified on naked eye
examination.
 Commonly encountered in the tropics and subtropics (filarial belt) ;uncommon in
the western world.
 Though classified in to parasitic / non-parasitic causes the former predominate
mainly due to filariasis

26. Clinical features
• Often asymptomatic (monosymptomatic)
• May be also polysymptomatic at times -existence of associated
conditions such as dysuria, hematuria,, backache, UTI, edema,
hydroceles, hypoproteinemia,, weight loss and malnutrition.
• Urological manifestation of lymphatic system disease which when
prolonged may lead to nutritional deficiency, UTI, hematuria
(hematochyluria) and a state of compensated immunosuppression.
• Prolonged massive chyluria -serious immunological and homeostasis
deficits due to increasing IgG, and particularly IgA deficiency- -
• State of depressed immunity (lymphocytopenia) with
• Opportunistic fungal infections and
• Promotion of malignant tumors (due to suppression of cellular
immunity).

27. Diagnosis
• Confirmed by evaluating a sample of a postprandial urine
for chylomicrons and triglycerides.
• Milky cloudy urine should be differentiated from
phosphaturia (clears on adding 10% acetic acid),
• All patients should also be screened for filariasis with: Hb,
TC and DC (eosinophilia), serum proteins, blood urea and
serum creatinine, urine for acid-fast bacilli and UTI.
• Intravenous urography, retrograde pyelography and
lymphangiography have been traditionally used to
demonstrate abnormal lymphaticourinary fistulas

28. Cholelithiasis
 Gallstones are hardened
deposits of the digestive
fluid bile, that can form
within the gallbladder.
 Vary in size and shape
from as small as a grain of
sand to as large as a golf
ball.
 Gallstones occur when
there is an imbalance in
the chemical constituents
of bile that result in
precipitation of one or
more of the components.

29. Composition of Gall stones
 Gallstones -composed mainly of cholesterol, bilirubin, and calcium salts, with
smaller amounts of protein and other materials
 Three types of gallstones
 (i) Pure cholesterol stones-contain at least 90% cholesterol,
 (ii) pigment stones (brown or black)-contain at least 90% bilirubin
 Brown pigment stones are mainly composed of calcium bilirubinate and Black
pigment stones contain bilirubin, calcium and/or tribasic phosphate
 Brown pigment stones are soft and greasy, consisting of bilirubinate and fatty
acids (Ca palmitate or stearate). They form during infection, inflammation, and
parasitic infestation
 (iii) mixed composition stones, which contain varying proportions of
cholesterol, bilirubin and other substances such as CaCO₃, Ca₃(PO₄)₂ and
calcium palmitate

32. • Cholesterol gallstone formation begins with the secretion of bile
supersaturated with cholesterol from the liver. Initiated by nucleating
factors such as mucin, microscopic crystals then precipitate in the
gallbladder
• Excessive cholesterol biosynthesis, -main lithogenic mechanism in obese
persons.
• In the non-obese, defective conversion of cholesterol to bile acids, due to
a relatively low activity of cholesterol 7α hydroxylase, the rate limiting
enzyme for bile acid biosynthesis and cholesterol elimination could result
in excessive cholesterol secretion.
• Interruption of the enterohepatic circulation of bile acids could increase
bile saturation.
• Pigment stones occur when RBCs are destroyed, leading to excessive
bilirubin in the bile.
• Gallbladder sludge, i.e., Thickened gallbladder mucoprotein with tiny
entrapped cholesterol crystals is thought to be the usual precursor of
gallstones

33. Common symptoms of cholelithiasis
 Abdominal pain (typically localized to the right upper quadrant of the abdomen)
 Abdominal swelling, distension or bloating
 Abdominal tenderness
 Clay-colored stools
 Fever and chills
 Loss of appetite
 Nausea with or without vomiting
 Pain that radiates from the abdomen to the right shoulder or back
 Sweating
 Yellowing of the skin and whites of the eyes (jaundice).
Prevalent in developed nations, but it is less prevalent in the developing populations that
still consume traditional diets
Its prevalence is especially high in the Scandinavian countries and Chile and among Native
Americans. Gallstones are more common in North America, Europe, and Australia, and are
less prevalent in Africa, India, China, Japan, Kashmir, and Egypt.[

38. Factors influencing gallstone disease
Age, Gender, parity, and oral contraceptives
Genetics
Obesity and body fat distribution
Rapid weight loss
Diet
Physical activity
Drugs
Diabetes

39. Diagnosis of Gallstone Disease
 Diagnosed by history of recurrent episodes of right-upper-quadrant or epigastric pain,
 The three primary methods used to diagnose gallbladder disease are
 Ultrasonography,
 Nuclear scanning (cholescintigraphy), and
 Oral cholecystography.
 Treatment
 Open cholecystectomy was formerly the gold standard of treatment for gallstones, until the
advent of laparoscopic cholecystectomy
 Chenodeoxycholic acid (chenodiol) and ursodeoxycholic acid (ursodiol) -dissolve gallstones,
but chenodiol causes diarrhoea and abnormal aminotransferase levels, while ursodiol does
not.
 Contact dissolution therapy of cholesterol gallstones -instilling solvents like the organic
solvent methyl tert-butyl ether into the gallbladder through a percutaneous catheter
placed through the liver. (technically difficult and hazardous procedure),
 Mixture of plant terpenes may also be useful for dissolving gallstones, when used in
combination with a bile acid.

41. Pancreatitis
 Inflammation of the pancreas.
 Range in severity from-relatively mild, self limiting disorder to a rapidly fatal
disease that does not respond to any treatment.
Acute pancreatitis is commonly described as an autodigestion of the
pancreas by the exocrine enzymes It produces, principally trypsin.
 80% of patients with acute pancreatitis have biliary tract disease or a history of
long-term alcohol abuse.
 Other less common causes of pancreatitis include bacterial or viral infection,
with pancreatitis occasionally developing as a complication of mumps virus.
 Mortality is high because of shock, anoxia, hypotension, or fluid and
electrolyte imbalances.
 Attacks of acute pancreatitis may result in complete recovery, may recur
without permanent damage, or may progress to chronic pancreatitis.

47. Clinical Manifestations
 Severe abdominal pain is the major symptom.
 Pain in the mid epigastrium.
 Decreased peristalsis; and vomiting that fails to relieve the pain or nausea.
 Pain is frequently acute in onset (24 to 48 hours after a heavy meal or alcohol
ingestion); may be more severe after meals and unrelieved by antacids.
 Ecchymosis around the umbilicus, which may indicate severe hemorrhagic
pancreatitis.
 Nausea and vomiting, fever, jaundice, mental confusion, agitation.
 Hypotension related to hypovolemia and shock.
 May develop tachycardia, cyanosis, cold, clammy skin.
 Respiratory distress and hypoxia.
 Myocardial depression, hypocalcemia, hyperglycemia, and disseminated
intravascular coagulation (DIC).

49. Assessment and Diagnostic Findings
 Diagnosis- based on history of abdominal pain, the presence of known risk factors, physical
examination findings, and diagnostic findings (increased urine amylase level WBC count;
 Hypocalcemia; glucosuria and increased serum bilirubin levels in some patients.
 X-rays of abdomen and chest, ultrasound, and contrast-enhanced computed tomography
(CT) scan.
 Hematocrit and hemoglobin levels are used to monitor the patient for bleeding.
 Serum amylase and lipase levels are most indicative (elevated within 24 hours; amylase
returns to normal within 48 to 72 hours; lipase remains elevated for longer period).
Gerontologic Considerations
 The mortality from acute pancreatitis increases with advancing age.
 Patterns of complications change with age (eg, the incidence of multiple organ failure
increases with age).
 Close monitoring of major organ function (lungs and kidneys) is essential, and aggressive
treatment is necessary to reduce mortality in the elderly.

50.  Care includes witholding food (NPO-nil per os) and drink and
administering IV fluids ( IV dextrose 5% in water (D5W) )and
parenteral analgesia
 Bowel rest reduces pain
 Impaired microcirculation- major cause for pancreatic
necrosis
 80% of patients with acute pancreatitis, who are admitted to
a hospital recover with a few days of IV fluids and bowel rest

51. Chronic pancreatitis
 Inflammatory disorder -progressive fibrosis leading to anatomic and functional
destruction of the pancreas.
 Cells -replaced by fibrous tissue. The end result is obstruction of the pancreatic
and common bile ducts and duodenum.
 Atrophy of the epithelium of the ducts, inflammation, and destruction of the
secreting cells of the pancreas.
 Alcohol consumption in Western societies and malnutrition
worldwide are the major causes.
 FREQUENCY OF INCIDENCE: among alcoholics is 50 times the rate in the
 Non drinking population.

53. Pathophysiology
 Long-term alcohol consumption causes hypersecretion of protein in pancreatic secretions, -protein
plugs and calculi within the pancreatic ducts.
 Alcohol -toxic effect on the cells of the pancreas.
 Damage more severe in patients with diets low in protein and very high or very low in fat.
 Smoking heavy drinkers usually smoke.
 Fibrosis -common pathological characteristic feature -major risk factor for pancreatic cancer
 The major clinical characteristics of pancreatitis are abdominal pain localized to the upper-to-middle
Abdomen,
 Abdominal distension,
 Nausea,
 Fever,
 Vomiting,
 Back pain,
 Jaundice,
 Hematemesis,
 Melena
 Diarrhea with foul-smelling, oily bowel movements and weight loss.
 Abdominal pain is the most common symptom found in 50% to 80% of cases, and it is the major
cause for hospitalizations of patients related to pancreatitis.

55. Clinical Manifestations
 • Recurring attacks of severe upper abdominal and back pain, accompanied by vomiting;
opioids may not provide relief.
 Weight loss is a major problem.
 Altered digestion (malabsorption) of foods (proteins and fats) results in frequent,
frothy, and foul- smelling stools with a high fat content (steatorrhea).
 •As disease progresses, calcification of the gland may occur and calcium stones may
form within the ducts.
 Assessment and Diagnostic Methods
 Endoscopic retrograde cholangiopancreatography (ERCP) is the most useful study.
 Various imaging procedures, including magnetic resonance imaging (MRI), CT scans, and
U ltrasound.
 A glucose tolerance test evaluates pancreatic islet cell function.
 Steatorrhea is best confirmed by laboratory analysis of fecal fat content.

57. Medical Management
 Preventing and managing acute attacks, relieving pain and discomfort, and
managing exocrine and endocrine insufficiency of pancreatitis.
 Endoscopy -remove pancreatic duct stones, -manage pain and relieve
obstruction.
 Pain and discomfort-analgesics; yoga -effective non pharmacologic method for
pain reduction and for relief of other coexisting symptoms.
 Alcohol and foods that produce abdominal pain and discomfort. no other
treatment will relieve pain if patient continues to consume alcohol.
 Diabetes mellitus resulting from dysfunction of pancreatic islet cells is treated
with diet, insulin/ oral hypoglycemic agents.
 Pancreatic enzyme replacement therapy -for malabsorption and steatorrhea.
 Surgery to relieve abdominal pain and discomfort, restore drainage of
pancreatic secretions,

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