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Pathology
Malabsorption

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‫اﻟﻠﮭم ﻻ ﺳﮭل اﻻ ﻣﺎﺟﻌﻠﺗﮫ ﺳﮭﻼ واﻧت‬

“
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‫ﺗﺟﻌل اﻟﺣزن إذا ﺷﺋت ﺳﮭﻼ‬ ★ Male’s slide

★ Female’s slide
 Objective
01 Understand the physiology of fluid in small intestine

02 Define diarrhea

03 Understand the four categories of diarrheal diseases, and list the major causes in each category.

04 List the causes of acute and chronic diarrhea

Overview
Celiac disease
Most common
Disease
Malabsorption syndrome

Lactose intolerance

Secretory diarrhea

osmotic diarrhea

Classification based on
Exudative diarrhea
pathophysiology
Most common
symptoms

motility diarrhea
Diarrhea

Acute diarrhea
Classification based on
clinical feature
Chronic diarrhea
 Normal Physiology of GI tract

❖ The main purpose of the gastrointestinal tract is to digests and absorbs

nutrients (fat, carbohydrate, and protein), micronutrients (vitamins and trace
minerals), water, minerals and electrolytes.

Malabsorption Syndrome

Definition

❖ it is the inability to absorb nutrients adequately into the bloodstream, The impairment
can be of single (for certain substances like in lactose intolerance) or multiple nutrients
(celiac disease) depending on the abnormality

mechanisms and their causes

Girls’ doctor: You don’t have to memorize them!

Inadequate Digestion: Deficient bile salt:

❖ Postgastrectomy ❖ Obstructive jaundice
❖ Deficiency of pancreatic ❖ Bacterial overgrowth
lipase ❖ Stasis in blind
❖ Chronic pancreatitis loops,diverticula
❖ Cystic fibrosis ❖ Fistulas
❖ Cystic fibrosis ❖ Hypomotility states
❖ Pancreatic resection (diabetes)
❖ Zollinger-Ellison syndrome ❖ Terminal ileal resection
❖ Crohn’s disease
❖ Precipitation of bile salts
(neomycin)
Primary mucosal Abnormalities:
❖ Celiac disease
❖ Tropical sprue inadequate small intestine:
❖ whipple’s disease ❖ intestinal resection
❖ Amyloidosis ❖ Crohn’s disease
❖ Radiation enteritis ❖ Mesenteric vascular disease
❖ Abetalipoproteinemia with infarction
❖ Giardiasis ❖ Jejunoileal bypass
 Malabsorption Syndrome
Pathophysiology
❖ Malabsorption has many mechanisms and causes, but most importantly are:
➢ Inadequate digestion
➢ small intestine abnormalities
❖ Each of these mechanisms that cause malabsorption are mainly caused by specific
affected organs.

Inadequate digestion

1 Stomach ❖ Postgastrectomy

❖ Deficiency of pancreatic lipase

❖ Chronic pancreatitis
2 Pancreas
❖ Cystic fibrosis
❖ Pancreatic resection e.g in case of pancreatic tumor

❖ Obstructive jaundice
3 Bile
❖ Terminal ileal resection, why?1

Small intestine abnormalities

❖ Celiac disease
Tropical sprue2
1 Mucosa
❖
❖ Whipple’s disease3
❖ Giardiasis

inadequate small Intestinal resection

2 ❖
intestines ❖ Crohn’s disease4 :fibrosis shortens the small intestine

❖ Intestinal lymphangiectasia5
3 Lymphatic
❖ Malignant lymphoma6
obstruction

1. Normally, to digest fat we need bile salts that play a major role in fat emulsification with the help of water to get absorbed in terminal
ileum. Thus, terminal ileal resection will prevent the bile & fat reabsorption (resulting in malabsorption ) .
2. Travellers to tropical areas get exposed to bacteria that their bodies are not used to, resulting in frequent diarrhea for about a month .
They return to normal with antibiotics but it will take a long time due to the villous atrophy that involves the entire intestine.
3. Infection by certain organisms ( mainly protozoa “amoeba”) leading to accumulation of inflammatory cells in the mucosa preventing
the absorption process.
4. IBD : chronic disease that affect part of the intestine ( mainly small intestine) leading to inflammation, fibrosis, ulceration and injury
that prevent the absorption process.
5. Dilated non communicating lymphatics
6. Obstruction of the lymphatics that are needed for the absorption process.
 Malabsorption Syndrome

Systemic Effects
❖ weight loss and anorexia ❖ Steatorrhoea, caused by malabsorption of
❖ Abdominal distension and borborygmi fat (produces pale, foul smelling stools that
(increased bowel sounds) due to increased characteristically float in water)
gas content
❖ Diarrhoea (loose, bulky stools) ❖ Muscle wasting due to malabsorption of proteins

Clinical features
❖ (Steatorrhea) : increase in fecal excretion of fat soft, yellowish, greasy
stools and the systemic effects of deficiency of fat soluble vitamins (A.
K,E & D), minerals, protein and carbohydrate
❖ Growth retardation and failure to thrive in children.
❖ weight loss despite increased oral intake of nutrient

Clinical features
depends on the type of the deficient nutrient

Deficiency of Vitamin K, Other

Deficiency of Protein
Coagulation Factors

-Swelling or edema -Bleeding tendencies

-Muscle wasting intracranial hemorrhage
and bleeding under skin

Deficiency of B12, folic Deficiency of Vitamin D,

acid and iron Calcium

-anaemias -Muscle cramp

-fatigue and -Osteomalacia
weakness -Osteoporosis

Diagnosis
There is no specific test for malabsorption ,Investigation is guided by Symptoms & Signs :
1- Stool studies : Fecal fat study/content to diagnose steatorrhoea
2- Blood tests : iron deficiency anaemia ,vitamins and albumin
3- Endoscopy (for small bowel biopsy)
 Celiac disease
-An immune reaction to gliadin fraction of the wheat protein gluten
-Usually diagnosed in childhood – mid adult.
Introduction
-Patients have raised antibodies to gluten autoantibodies
-Highly specific association with class II HLA-DQ2 or HLA-DQ8 alleles.
Gluten breakdown into fragments resulting of
gliadin which is a (33-amino acid peptide resistant
to degradation by gastric, pancreatic, and
small intestinal proteases)then it get absorbed Into
intestinal mucosa ,it will become a Deamidated gliadin
by the tissue transglutaminase (tTG).so people who
Has HLA(DQ2 or DQ8) will recognize it by(APC)
Pathophysiology antigen presenting cell and presented to the
T lymphocyte which will be activated and therefore
Activate B lymphocyte to produce Anti-gliadin,
Anti-endomysium and anti-tTG.Also activated T lymphocyte
Will produce IFNγ and mor T lymphocytes will be infiltrated
Which will increase intraepithelial lymphocyte that will
Produce factors like IL-15 and NKG2D and damage
the epithelium(loss of villi and crypt elongation)

❖ Typical presentation: GI symptoms that characteristically appear at age 9-24

months.
❖ Symptoms begin at various times after the introduction of foods
that contain gluten.
Clinical feature ❖ A relationship between the age of onset and the type of presentation;
Infants and toddlers : (GI symptoms and failure to thrive)
Childhood : (minor GI symptoms, inadequate rate of weight gain)
Young adults : (anemia is the most common form of presentation)
Loss of villi
Adults and elderly : (GI symptoms are more prevalent)

❖ Clinical documentations of malabsorption.

- Increase fat in stool (steatorrhea)
- Serology is +ve for IgA antibodies to tissue transglutaminase or IgG to
deamidated gliadin or anti-endomysial antibodies
- Small intestine biopsy demonstrate vilis atrophy

❖ Improvement of symptom and mucosal histology on gluten

Diagnosis withdrawal from diet.(wheat, barley, flour Other grains, such as
rice and corn flour, do not have such an effect)

❖ Histological appearance
-Mucosa is flattened with marked villous atrophy
-Increased intraepithelial lymphocytosis (IELs)
-Crypt elongation

-Osteopenia , osteoporosis
★ -Infertility in women due to hypoalbuminemia
Complication -Short stature, delayed puberty, anemia
-Malignancies: [intestinal T-cell lymphoma] 10 to 15% risk of developing GI lymphoma.
 Lactose intolerance

lactose intolerance low or absent activity of the enzyme lactase, which is

Definition and
needed to digest lactose to glucose and galactose.
Pathophysiology

1) Inherited lactase deficiency

-Congenital lactase deficiency : (extremely rare)
-Childhood-onset and adult-onset lactase deficiency:
(common and Genetically programmed progressive loss
of the activity of the small intestinal enzyme lactase)

Etiology 2) Acquired lactase deficiency

-Transient
-Secondary lactase deficiency due to intestinal mucosal injury by an
infectious, allergic, or inflammatory process
-Gastroenteritis: Infectious diarrhea, particularly viral gastroenteritis in
younger Acquired lactase deficiency children, may damage the intestinal
mucosa enough to reduce the quantity of the lactase enzyme injury

1 hour to a few hours after ingestion of milk products:

- Bloating
- abdominal discomfort
Clinical feature - flatulence / gases
Lactose will go from small intestine → large intestine (there will be bacteria) and
there will be fermentation with production of gases especially hydrogen gas
which will lead to ↑ motility and irritation of the bowl and then lead to the
symptoms (gases and pain).

❖ Hydrogen breath test :specific test

- An oral dose of lactose is administered
- The sole source of H 2 is bacterial fermentation;
- Unabsorbed lactose makes its way to colonic bacteria, resulting in
excess breath H2.
Diagnosis - Increased exhaled H2 after lactose ingestion suggests lactose
malabsorption.

❖ Empirical treatment : with a lactose-free diet,which results in

resolution of symptoms , 3-week trial of a diet that is free of milk and
milk products is a satisfactory trial to diagnose lactose intolerance
#438 team Summary
malabsorption

Definition ●It is inability of intestine to absorb nutrients adequate into the bloodstream.
●Highly specific association with class II HLA DQ2 (haplotypes DR-17 or DR5/7) and to a lesser
extent, DQ8 (haplotype DR-4).

causes a) Inadequate digestion:

1) Stomach: postgastrectomy
2) pancrase : Cystic fibrosis, Chronic pancreatitis
3) bile: Obstructive jaundice , Terminal ileal resection
b) Small intestine abnormalities:
1) Mucosa : Celiac disease,Giardiasis
2)Inadequate small intestine : Intestinal resection ,Crohn's disease.
3)Lymphatic obstruction: Intestinal lymphangiectasia ,Malignant Lymphoma

Diagnosis Fecal fat study to diagnose steatorrhea :

Blood tests
Stool studies
Endoscopy : Biopsy of small bowel

Celiac disease

Definition An immune reaction to gliadin fraction of the wheat protein gluten

Typical presentation GI symptoms that characteristically appear at age 9-24 months.

Histology Mucosa is flattened with marked villous atrophy.

Diagnosis Steatorrhoea Histology Improvement of symptom and histology on gluten withdrawal

from diet.

Complications 1)Osteopenia 2) Osteoporosis 3) Infertility in women Short stature 4) delayed puberty

5) anemia 6) Malignancies( intestinal T-cell lymphoma )

Lactose intolerance

Definition Low or absent activity of the enzyme lactase

causes ● Acquired lactase deficiency : Transient

● Inherited lactase deficiency:
a) Childhood-onset and adult-onset
b) Congenital lactase deficiency
=> infectious, allergic, or inflammatory process
lactase deficiency

Clinical features 1)Bloating abdominal 2) discomfort 3) flatulence After 1 hour of consuming lactose

Diagnosis 1)Hydrogen breath test

2) lactose-free diet which results in resolution of symptoms
 Pathoma
VI. LACTOSE INTOLERANCE
A. Decreased function of the lactase enzyme found in the brush border of enterocytes
1. Lactase normally breaks down lactose into glucose and galactose.
B. Presents with abdominal distension and diarrhea upon consumption of milk products;
undigested lactose is osmotically active.
C. Deficiency may be congenital (rare autosomal recessive disorder) or acquired (often
develops in late childhood); temporary deficiency is seen after small bowel infection
(lactase is highly susceptible to injury).

VII. CELIAC DISEASE :

A. Immune-mediated damage of small bowel villi due to gluten exposure; associated with
HLA-DQ2 and DQS
B. Gluten is present in wheat and grains; its most pathogenic component is gliadin.
1. Once absorbed, gliadin is deamidated by tissue transglutaminase (tTG).
2. Deamidated gliadin is presented by antigen presenting cells via MHC class II.
3. Helper T cells mediate tissue damage.

C. Clinical presentation
1. Children classically present with abdominal distension, diarrhea, and failure to thrive.
2. Adults classically present with chronic diarrhea and bloating.
3. Small, herpes-like vesicles may arise on skin (dermatitis herpetiformis). Due to IgA
deposition at the tips of dermal papillae; resolves with gluten-free diet

D. Laboratory findings
1. IgA antibodies against endomysium, tTG, or gliadin; IgG antibodies are also
present and are useful for diagnosis in individuals with IgA deficiency (increased incidence
of igA deficiency is seen in celiac disease).
2. Duodenal biopsy reveals flattening of villi, hyperplasia of crypts, and increased
intraepithelial lymphocytes (Fig. 10.18). Damage is most prominent in the duodenum;
jejunum and ileum are less involved.

E. Symptoms resolve with gluten-free diet.

1. Small bowel carcinoma and T-cell lymphoma are late complications that present as
refractory disease despite good dietary control.
 QUIZ!
MCQs
01 | which of the following is not a step of Celiac pathogenesis :

A) Gluten is digested B) it will interact with C) B-Cell activation D) all of the above are
into amino acids and HLA-DQ2/HLA-DQ8 leading to generation true
peptides including of the antigen of antibodies against
including “Gliadin” presenting cells which tTG , Gliadin and CD8
which will get will present it to CD4 will enterocytes who
deamidated by “tTG” leading to cytokines expresses surface
release MIC-A

02 | Which is not a cause for primary mucosal abnormality mechanism of malabsorption :

A) Crohn’s disease B) Radiation enteritis C) Giardiasis D) Tropical sprue

03 | Malabsorption can cause :

A) Photosensitivity B) weight loss C) depression D) calcification

04 | which disease associated with class II HLA-DQ2 or HLA-DQ8 alleles :

A) Lactose B) celiac disease C) ulcerative colitis D) colonic polyp

intolerance

05 | Which of the following complications are associated with celiac disease but not other
malabsorption diseases?

A)Osteoporosis B) Short stature C) Anemia D) Malignancies

06 | A 4-year-old girl is brought to the physician because her parents noticed that she has been
having pale, fatty, foul-smelling stools. The patient is at the 50th percentile for height and 10th
percentile for weight. Her symptoms respond dramatically to a gluten-free diet. Which of the
following is the most likely diagnosis?

A) Celiac disease B) Cystic fibrosis of the C) Ménétrier disease D) Tropical sprue

pancreas

MCQs 01 02 03 04 05 06
Answer key
D C B B D A
 “ “
‫ وانفعنا بما علمتنا وزدنا علما يارب العالمين‬، ‫اللهم علمنا ماينفعنا‬

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Hassan Mariam
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alshurafa Alruhaimi

Abdulrahman Mohammad Renad

Barashid alsayyari Alhomaidi
Mansour Mona
Faisal Alfadel
Albawardy Alabdely
Ghaida
Abdulaziz redwan Nada Bin Obied Almarshoud

Abdulelah Saad Shayma Raghad

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