WEEK 1: Malabsorption and Malnutrition

Question 1

DIGESTION: PREREQUISITE FOR ABSORPTION.

State the 3 main factors involved in successful absorption of food.

Answer 1

*Intact GIT motility (nerves, muscle )
*Intact enzyme secretion
*Intact mucosal integrity

Question 2

Outline the LAYERS OF THE GIT.

Answer 2

Mucosa
Submucosa
Muscularis
Serosa

Question 3

Describe the following layers of the GIT.

Mucosa
Submucosa
Muscularis
Serosa

Answer 3

1. Mucosa: villus projections
2. Submucosa
   Meissner plexus for GIT secretion & local blood flow
3. Muscularis
   -Inner & thicker circular layer

-Outer longitudinal layer

-Myenteric /Auerbach plexus btwn the two muscle layers for GIT motion

4. Serosa / adventitia containing mesentery

Question 4

What is the Enteric nervous system?

How is it different from other divisions of the ANS?

Answer 4

The enteric nervous system (ENS) is a division of the autonomic nervous system (ANS) that is responsible for controlling the function of the gastrointestinal (GI) tract.

It is often referred to as the “second brain” due to its ability to operate independently of the central nervous system (CNS) and regulate GI functions.

Unlike other divisions of the ANS, the ENS can function autonomously, meaning it can control GI functions without input from the CNS. However, it does communicate with the CNS through the parasympathetic and sympathetic nervous systems.

The parasympathetic system, primarily through the vagus nerve, enhances GI functions, while the sympathetic system inhibits them.

Question 5

Outline the 3 phases of digestion

Answer 5

Intraluminal
Mucosal
transport into the circulation

Question 6

Outline the substances absorbed at the following sites.
1. Duodenum and proximal jejunum :
2. Distal / terminal ileum
3. Colon

Answer 6

1. Duodenum and proximal jejunum:
   Iron
   Carbohydrates, protein, and fat
   Electrolytes
2. Distal / terminal ileum
   Bile salts
   vitamin B12 (intrinsic factor)
3. Colon: water

Question 7

Discuss the process of fat digestion.

Answer 7

Action of lipases (acid / gastric & pancreatic)

1. Bile salts → micelles (emulsions) for better action of pancreatic enzymes
2. Intraluminal fat digestion
   Fatty acids:

*Long chain FAs → epithelial cell chylomicrons → lymphatics → venous circulation → liver for metabolism & repackaging

*Short & medium chain FA → transported directly to liver via mesenteric venous blood flow.

-Phospholipase A2 , cholesterol esterase

Question 8

Discuss gastric and pancreatic lipase role in the digestion of fats.

Answer 8

Gastric Lipase:
*Gastric lipase is primarily secreted by the chief cells in the stomach.
*Its main function is to initiate the digestion of dietary fats in the stomach.
*Gastric lipase acts on triglycerides, breaking them down into diglycerides and free fatty acids.
*The activity of gastric lipase is optimal in the acidic environment of the stomach.

Pancreatic Lipase:
*Pancreatic lipase is secreted by the pancreas into the small intestine.
*It is the primary enzyme responsible for the digestion of dietary fats in the small intestine.
*Pancreatic lipase acts on triglycerides, breaking them down into monoglycerides and free fatty acids.

Question 9

Discuss the Etiology of fat malabsorption.

Answer 9

*Pancreatic insufficiency (low lipases ) eg cystic fibrosis , chronic pancreatitis

*Enteropathies (reduced absorptive surface area) eg coeliac disease, AIDS enteropathy

*Abnormal bile acid metabolism e.g., cholestatic liver disease (biliary atresia etc. )

*Lymphatic flow abnormalities e.g., lymphangiectasias

Question 10

Outline the fat-soluble vitamins.

State their functions.

Answer 10

ADEK refers to a combination of fat-soluble vitamins, including vitamin A, vitamin D, vitamin E, and vitamin K.

1. Vitamin A:
   *Vitamin A is important for vision, immune function, and cell growth and differentiation.
   *It is found in animal sources as retinol and in plant sources as beta-carotene, which the body can convert into vitamin A.
   *Vitamin A deficiency can lead to night blindness, impaired immune function, and skin problems.
2. Vitamin D:
   *Vitamin D plays a crucial role in calcium and phosphorus metabolism, bone health, and immune function.
   *The body can produce vitamin D when the skin is exposed to sunlight, and it is also found in certain foods.
   *Vitamin D deficiency can lead to weakened bones, increased risk of fractures, and impaired immune function.
3. Vitamin E:
   *Vitamin E is an antioxidant that helps protect cells from damage caused by free radicals.
   *It is found in various foods, such as nuts, seeds, and vegetable oils.
   *Vitamin E deficiency is rare but can lead to neurological problems and muscle weakness.
4. Vitamin K:
   *Vitamin K is essential for blood clotting and bone health.
   *It is found in leafy green vegetables, vegetable oils, and some animal products.
   *Vitamin K deficiency can lead to bleeding disorders and impaired bone health.

Question 11

Carbohydrates absorption.

State the following compositions of carbohydrates.
1. Monosaccharides
2. Disaccharides:
3. Polysaccharides:

Answer 11

Different compositions :
1. Monosaccharides (hexoses) : glucose /galactose / fructose /sorbitol

2. Disaccharides:
   lactose (glucose + galactose)
   sucrose (fructose + glucose)
   maltose (2x glucose)
3. Polysaccharides: starch , dextrins & glycogen

Question 12

What are the Final products of carbohydrate metabolism called?

Answer 12

Final products of carbohydrate metabolism are all monosaccharides.

Question 13

Outline enzymes involves in carbohydrates digestion.

Answer 13

Enzymes:
*Salivary amylase
*Pancreatic amylase

Membrane (brush border) disaccharidases / hydrolases
Are primarily located in the duodenum and jejunum of the small intestine.
*Lactase
*Sucrase
*Maltase
*α- dextrinase

Question 14

Discuss the Etiology of carbohydrate malabsorption.

Answer 14

CHO malabsorption may be due to :
*Excessive intake
*Pancreatic insufficiency
*Any cause of mucosal damage e.g., acute post-infectious *Diarrhoea
*Short bowel syndrome
*Congenital brush border transport / enzyme deficiency
Bacterial overgrowth syndrome

NOTE: Short bowel syndrome (SBS) is a condition in which a significant portion of the small intestine is missing or has been surgically removed, leading to malabsorption and nutritional deficiencies.

Question 15

Discuss the hydrogen Breath test for malabsorption.

Describe its basis.

Answer 15

The mucosal phase of digestion typically is defective in cases of CHO metabolism:

1. Osmotic properties of malabsorbed CHO → excessive accumulation of intraluminal fluid & diarrhea
2. Ileocolic bacteria ferment malabsorbed dietary sugars & CHO in distal ileum & colon into simple sugars, organic acids (e.g., short chain FAs) & gases (methane, carbon dioxide , hydrogen) which can be used to detect CHO metabolism

Hydrogen Breath Test → non- invasive test that quantifies amount of hydrogen produced by gut fermentation in exhaled air

Question 16

Discuss protein digestion.

Answer 16

All enzymes released as proenzymes

Stomach:
1. Pepsinogen to pepsin → conversion of protein to polypeptides → stimulation of cholecystokinin release from enterocytes

Small intestine:
CCK stimulates release of pancreatic juice

*Trypsinogen → trypsin through enterocyte enterokinase (enteropeptidase )
*Trypsin → generalized proenzyme activation (e.g., chymotrypsin / elastase)

2. POLYPEPTIDES» POLYPEPTIDES AND AMINO ACIDS (TRYPSIN, CHYMOTRYPSIN, CARBOXYLPEPTIDASE, PROESTALASE)»> Amino acids (peptides)

Final products of protein digestion : amino acids , dipeptides & tripeptides

Question 17

State the pro-enzymes of protein digestion released from the pancreas and discuss how each of them is activated.

Answer 17

1. Trypsinogen:
   *Trypsinogen is the inactive form of the enzyme trypsin.

*Trypsinogen is activated by the enzyme enterokinase, which is embedded in the intestinal mucosa.

Once activated, trypsin can further activate additional molecules of trypsinogen, resulting in a cascade of trypsin activation.

The activation of trypsinogen to trypsin is a crucial step in protein digestion, as trypsin is responsible for the activation of other pancreatic enzymes and the breakdown of proteins into peptides.

2. Chymotrypsinogen:
   *Chymotrypsinogen is the inactive form of the enzyme chymotrypsin.

*Trypsin, once activated, can cleave chymotrypsinogen to its active form, chymotrypsin.

*Chymotrypsin is involved in the breakdown of proteins into peptides.

3. Procarboxypeptidase:
   *Procarboxypeptidase is the inactive form of the enzyme carboxypeptidase.

*Trypsin, once activated, can cleave Pro-carboxypeptidase to its active form, carboxypeptidase.

*Carboxypeptidase is responsible for the breakdown of peptides into individual amino acids.

4. Proelastase:
   *Proelastase is the inactive form of the enzyme elastase.

*Trypsin, once activated, can cleave Pro elastase to its active form, elastase.

*Elastase is involved in the breakdown of elastin, a protein found in connective tissues.

Question 18

Define azotorrhea.

Answer 18

Azotorrhoea = protein malabsorption

Rare in generalized malabsorption defects (often combination of reduced intake & enteropathy)

Question 19

Children who have intraluminal malabsorptive defects (e.g., cystic fibrosis) don’t have PLE. Why?

Answer 19

Children who have intraluminal malabsorptive defects (e.g., cystic fibrosis) don’t have PLE coz their digestive defect doesn’t involve mucosal damage.

Children who have intraluminal malabsorptive defects, such as cystic fibrosis, typically do not have protein-losing enteropathy (PLE). This is because the primary mechanism of protein loss in PLE is through leakage into the intestine, which is not a characteristic feature of cystic fibrosis.

Cystic fibrosis is an inherited condition that affects various organs, including the lungs and digestive system.

In cystic fibrosis, the production of thick and sticky mucus can lead to lung infections and problems with digesting food. Most people with cystic fibrosis have difficulty absorbing nutrients from food properly, which can result in malnutrition.

However, the mechanism of malabsorption in cystic fibrosis is primarily related to the impaired function of the pancreas and the production of digestive enzymes, rather than protein leakage into the intestine.
.
In cystic fibrosis, the defective CFTR (cystic fibrosis transmembrane conductance regulator) gene causes changes in the body’s electrolyte transport system, leading to problems with the glands that produce sweat and mucus.

The thickened mucus can affect the function of the pancreas, leading to poor digestion and malabsorption of nutrients.

Question 20

What is Protein-losing enteropathies?

Answer 20

Protein-losing enteropathy (PLE) is a condition characterized by the loss of proteins from the body due to leakage into the intestine.

PLE is typically caused by underlying gastrointestinal (GI) conditions that trigger inflammation in the bowels.

This inflammation can interfere with the normal digestion and absorption of proteins, leading to their loss in the intestine.

PLE is considered a syndrome rather than a specific disease, as it is associated with various long-term conditions such as Crohn’s disease.

Question 21

Describe the screening test for protein-losing enteropathy (PLE) and interpret the results.

Answer 21

Screening test for PLE : fecal alpha- 1 antitrypsin (FA1AT)

Distinguishes intraluminal from mucosal maladies.

If raised suggests a disorder such as inflammatory bowel disease or celiac disease rather than cystic fibrosis or liver disease

Question 22

Discuss alpha 1 antitrypsin and its function.

Answer 22

Alpha-1 antitrypsin (AAT) is a protein produced by the liver and is an acute-phase reactant.

Its primary function is to protect the lungs from protease-mediated tissue destruction.

AAT acts as a neutrophil elastase inhibitor, controlling the activity of neutrophil elastase, an enzyme that can break down elastin and cause damage to lung tissue.

By inhibiting neutrophil elastase, AAT helps maintain the elasticity and integrity of the lungs.

AAT deficiency is a genetic disorder where the body’s production of AAT is impaired. This deficiency can lead to a higher risk of lung diseases such as chronic obstructive pulmonary disease (COPD) and emphysema.

Without enough functional AAT, the uncontrolled activity of neutrophil elastase can result in the destruction of lung tissue and respiratory complications.

In addition to its role in lung protection, AAT has been found to have other functions. It is an acute-phase reactant, meaning its production increases in response to inflammation.

AAT has been implicated in modulating immune responses, regulating inflammation, and influencing various cellular processes.

Ongoing research is exploring the potential therapeutic applications of AAT in conditions beyond AAT deficiency, such as sepsis and inflammatory diseases.

Question 23

When to suspect malabsorption disorder?

Answer 23

*FTT / subnormal growth (short stature , stunting )
*malodorous , voluminous watery stools
*chronic diarrhoea
*Weight loss
*Macrocytic anaemia (B12 deficiency )

Other signs of severe malnutrition
*Oedema
*Rickets (vit D)
*Excessive bleeding / bruising (vit K)
*Reduced muscle mass
*“pot belly ”

Vit E deficiency
-Ataxia
-Reduced / absent DTRs
-Ocular palsy
-Haemolytic anaemia

Question 24

What can Weight for age diagnose or mean?

Describe weight for age according to Z scores.

Answer 24

Underweight for either acute or chronic malnutrition.

Btwn 0 & -1 Z scores= not underweight.
Btwn -1 & -2 Z scores = mild underweight
Btwn -2 & -3 Z scores = moderate underweight
Below -3 Z scores = severe underweight

Question 25

What can Weight for Height diagnose or mean?

Describe weight for height according to Z scores.

Answer 25

Weight for height
Wasting for acute malnutrition
Btwn 0 & -1 Z scores = no wasting
Btwn -1 & -2 Z scores = mild wasting
Btwn -2 & -3 Z scores = moderate wasting
Below -3 Z scores = severe wasting

Question 26

What can height for age diagnose or mean?

Describe height for age according to Z scores.

Answer 26

Height for age
Stunting for chronic malnutrition
Btwn 0 & -1 Z scores = no stunting
Btwn -1 & -2 Z scores = mild stunting
Btwn -2 & -3 Z scores = moderate stunting
Below -3 Z scores = severe stunting

Question 27

Discuss Approach to malabsorption & malnutrition.

Answer 27

1. Take thorough history eg
   *Family /genetic history : HIV status /allergy/milk intolerance
   *Duration of symptoms (acute / chronic )
   *Dietary history
   *Stool : watery / pale / foul-smelling/ blood & mucus
   *Social neglect (? Inorganic aetiology)
2. Do a thorough physical examination including
   *accurate plotting on appropriate growth charts
   *Stigmata of chronic liver disease
   *Clinical signs of malnutrition
3. Stool
   *MC&S
   *Reducing substances
   *Faecal osmolar gap
   *Faecal α-1-antitrypsin
   *Urine MC&S

FBC
Biochemistry

4. Others
   -Immunological evaluation
   -Stool steatocrit /elastase/72hr fat determination
   -Breath hydrogen test
   -Sweat test
   -coeliac antibody serology
5. Radiologic assessment
   -Abdo USS ? TB lymph nodes
   -Contrast imaging ? anatomical abnormalities
   -Endoscopy with intestinal biopsy
   -CT abdomen

Question 28

Discuss the treatment of malabsorption and malnutrition.

Answer 28

Treatment
-Provide nutritional support
-Supplement fat-soluble vitamins
-Correct dehydration & electrolytes
-Treat infection
-Prevent & treat complications