Digestion And Absorption

Front 1

Which Carbohydrates can be absorbed in the gut?

Back 1

only monosacc.
- the rest can be absorbed by colonic bacteria

Front 2

Amylase

Back 2

Amylase is an enzyme that catalyses the breakdown of starch into sugars.
- found in saliva and pancreas

Front 3

Amylase only targets which bonds?

Back 3

All amylases are glycoside hydrolases and act on α-1,4-glycosidic bonds.

Targets alpha 1,4 glucosidic bonds except when they are terminal or adjacent to an alpha 1,6 glucosidic bond.

Front 4

Main function of salivary amylase

Back 4

Salivary amylase functions as a protection mechanism for teeth by breaking down sugars thereby reducing their availablility for bacterial use.

Front 5

Brush border membrane enzymes

Back 5

produced by the villi cells and attach to the apical membrane on the luminal surface. They are important in the digestion of di/trisaccharides and peptides

Front 6

Brush Border Carbohydrate enzymes

Back 6


Sucrase -Isomaltase (breaks down alpha 1,6 bonds of alpha limit dextrins)

Lactase (targets lactose); lactase is at the very tip of the villi thus the first to go and last to recover in a GIT illness

Glucoamylase

Front 7

Monosaccharide absorption mainly

Back 7

bulk occurs in the top 3rd of jejunum and duodenum

Front 8

3 key transporters of Monosacc

Back 8

1. Na+/Glucose cotransporter (SGLT1). ACTIVE
□It will also transport galactose and mannose.
□Blocked by phlorizin.

PASSIVE:
2. GLUT5 will transport fructose and glucose.
3. GLUT2 lies on the interstitial side of the membrane which then transports glucose/fructose to the interstitium.

Front 9

Pepsin produced by

Back 9

gastric chief cells (as zymogen pepsinogen activated by low pH).

Front 10

Zymogen

Back 10

A zymogen (or proenzyme) is an inactive enzyme precursor.

Front 11

Pepsin Action

Back 11

Pepsin breaks down protein into AA that act to signal various digestive mechanisms.

Front 12

Pancreatic Proteases

Back 12

Pancreatic proteases (all produced as inactive zymogens).
1. Trypsinogen -[enteropeptidase]-> Trypsin
2. Chymotrypsinogen -[trypsin]-> Chymotrypsin
3. Proelastase -[trypsin]-> Elastase

Front 13

Endoproteases

Back 13

Endoproteases cleave various peptide bonds within a polypeptide: Trypsin, chymotrypsin, elastase, kallikrein


Front 14

Exoproteases

Back 14

Exoproteases start at the end of the polypeptide: carboxypeptidase A and B

Front 15

Main difference between the abs of CHO and CHN is...

Back 15

that CHN can be absorbed to a certain extent as peptides as well as amino acids

Front 16

Brush Border Protein Enzymes

Back 16

also found in the cytossol side of the lumen to digest the peptide more

Peptidases
Aminopeptidases

Front 17

Absorption of Protein via

Back 17

1. PEPT1; H+/protein which is then broken down into a.a through peptidase in the cell
2. System B is a Na+/AA cotransporter that absorbs neutral amino acids into the cell.
3. b0+ -> rBAT/b0+AT (chaperone)/transporter)
This transporter is mutated in Hartnup's disease -> An autosomal-recessive disorder characterized by defective neutral amino acid transporter on renal and intestinal epithelial cells. Causes tryptophan excretion in urine and decreased absorption from the gut. Leads to pellagra like dermatoses.

Front 18

Lipases Found in..

Back 18

Saliva
Pharynx
Gastric mucosa
Pancreas

Front 19

Pancreatic Lipase

Back 19

- TGs broken down by oancreatic lipase to 2 FA + 2-monoacylglycerol

Pancreatic lipase is extremely pH sensitive. It will not function below pH 6.

It also needs colipase which is also secreted by the pancreas as procolipase. It facilitates the binding of pancreatic lipase to the lipid globules.

Front 20

Bile Salts

Back 20

○Bile Salts: detergents that increase the surface area for lipases to attach.

- forming micelles

Front 21

Absorption process of Lipids

Back 21

1. CD36 receptor
2. FA + 2 monoacylglycerol -[intestinal cell]-> Triglycerol
3. Phospholipase A2: release fatty acids from the second carbon group of glycerol.
4. Cholesterol esterase
5. Intestinal cells then package as a chylomicron which is secreted into the interstitium to be absorbed by lymphatics.

Front 22

Macronutrients in the diet

Back 22

Protein 20%
Fat 40%
CHO 40%

Front 23

Inhested Fats

Back 23

• Triglyceride
• Phospholipids
• Cholesterol
>95% of ingested fat is triglyceride:
cooking oils, margarine, butter, lard,
animal fats

Front 24

Triglycerides

Back 24

• Long chain ≥ C14
• Medium chain > C6-C12
• Short chain >C4-C6

Front 25

Colipase

Back 25

lipase is repeled by bile acids forming around the TGs thus colipase interdigitas b/w them allowing attraction

Front 26

Mixed Micelle

Back 26

inhibits both colipase and lipase so need to get rid of the phospholipids first

- PLA2 removes the phospholipids, hydrolysed to lysoPC

Front 27

Fats metabolism + absorption

Back 27

Front 28

Definition of Fat Malabsorption

Back 28

In a 3 to 5 day fat balance study,
measured faecal fat is >7% of fat
ingested

Front 29

Mechanisms of Fat Malabsorption

Back 29

• Maldigestion of ingested fat:
• pancreatic insufficiency
• Inadequate micellar solubilisation of
digested fat:
• bile acid deficiency, as in cholestatic
liver disease
• Impaired mucosal absorption of fat:
• mucosal disease, eg coeliac disease
- impaired fat transfer from enterocytes to lymphatics
; lymphatic disease; lymphoma, lympangiectasia

- inherited disease; abetalipoproteinaemia

Front 30

Maldigestion of Fat
Pancreatic disease with
Pancreatic Insufficiency (PI)

Back 30

• PI occurs when >98% of exocrine
pancreas is destroyed or removed
• In this circumstance, fat appears in stool
as undigested triglyceride, ie oil
• In the childhood disorder Cystic
Fibrosis, 85% of patients have PI
• Approximately 66% of the patients will
demonstrate faecal fats between 30 to
50% of fat intake

Front 31

Back 31

Fat droplets in stool
- PI until proven otherwise

Front 32

Back 32

marked faecal fat (stool from a baby with biliary atresis; a completely blocked bile duct)

Front 33

Impaired Micelle Formation

Back 33

Usually seen in cholestatic liver disease,
eg bile duct obstruction
Cause: Impaired bile acid output
into the duodenum
• Subsequent low concentration of bile
acids below the CMC (critical micellar
concentration), approximately 3 mmol/L
• Low bile acid concentration
• Impaired micelle formation and poor
solubilisation of fatty acids and
monoglyceride → fat malabsorption
– faecal fat 30 to 40% of fat intake

Front 34

Impaired Mucosal Absorption

Back 34

eg Coeliac disease
• Fat malabsorption is quite variable,
from 10% to 40% of fat intake
• Microscopically, fatty acid crystals (NOT FAT DROPLETS) are
found in the stool:
Digestion is normal, but discased
small intestine fails to absorb fatty
acids and monoglycerides

Front 35

Lymphangiectasia

Back 35

Lymphangiectasia

Front 36

Abetalipoproteinaemia

Back 36

cant get out because of Apopprotein B isnt around

Front 37

Major Consequences of
Fat Malabsorption

Back 37

1. Intestinal
2. Systemic
3. Nutritional

Front 38

1. Intestinal Consequences of fat malabsorption

Back 38

• Diarrhoea
– fatty acids causing fluid secretion
– bile acids causing fluid secretion
• Bulky, malodorous stools
– colonic dilatation
• Colonic fermentation
– flatulence, gaseous distension of colon

Front 39

Systemic Consequences of fat malabsorption

Back 39

• Bile acid malabsorption
• Interruption of bile acid reabsorption at
terminal ileum
• Interruption of enterohepatic circulation
• Decreased bile acid pool size
• Decreased secretion of bile acid
formation of lithogenic bile & gallstones

Front 40

Nutritional Consequences of fat malabsorption

Back 40

• Fat malabsorption
– Energy loss, wasting, stunting (long-term)
• Fat soluble vitamin malabsorption
– Vitamin A
D
E
K deficiencies

Front 41

Vitamin A deficiency

Back 41

• Ocular:
– Impaired dark adaptation (night blindness)
– Xerophthalmia (conjunctival dryness)
*Bitots spots (small triangular patches in
sclera lateral to cornea)
– Corneal dryness
• Dermatological: - Follicular hyperkeratosis
• Neuro: - Benign intracranial hypertension
(bulging fontanelle in infancy)

Front 42

Vitamin E deficiency

Back 42

• Premature Infants:
– haemolytic anaemia
• Older Children:
– progressive neurologic syndrome
– areflexia
– ataxia
– paresis of gaze
– spinocerebellar degeneration

Front 43

Vitamin D deficiency

Back 43

Children: Rickets
Adults: Osteomalacia

Front 44

Vit K Def.

Back 44

Coagulopathy

Front 45

Causes of Protein Maldigestion
/Malabsorption

Back 45

• Maldigestion
• Malabsorption
• Pancreatic insufficiency
– Cystic fibrosis
– Chronic pancreatitis
– Tumours
– Resection
• Mucosal disease
– Coeliac disease
– Short gut syndrome
• Protein losing enteropathies
• Primary (gut related):
– Hypertrophic gastritis (Menetriére’s disease)
– H.Pylori gastritis
– Inherited lymphangiectasia
– Coeliac disease
– Inflammatory bowel disease, including eosinophilic
gastroenteritis
• Secondary:
– Cardiac (Constrictive pericarditis, TB, autoimmune)
– Liver diseases
– Lymphatic obstruction, lymphoma

Front 46

Consequences of Gut Protein Loss
ACUTE

Back 46

• Acute
Hypoproteinaemia – loss of oncotic
pressure, subsequent loss of fluid to
extracellular fluid space with
occurrence of oedema, ascites and
pleural effusions

Front 47

Consequences of Gut Protein Loss
• Chronic

Back 47

– Adults – decrease of lean body mass with
occurrence of muscle wasting (shoulder,
girdle and buttock wasting) and (if total
body protein drops below 60% of normal)
cardiac muscle wasting and cardiac
failure
– Children – Impaired protein deposition
and linear growth failure, noting the most
common cause of linear growth failure
worldwide is chronic undernutrition /
starvation

Front 48

Disaccharide Digestion

Back 48

Front 49

Consequences of Carbohydrate
Malabsorption

Back 49

• Failure to digest and/or absorb simple
carbohydrates → osmotic diarrhoea
• Colonic fermentation of unabsorbed
carbohydrate, production of H2, CH4,
gaseous distension and flatulence
• Colonic production of short chain fatty
acids and colonic secretion of fluid

Front 50

Osmotic Diarrhoea vs Secretory Diarrhoea

Back 50

Front 51

Carbohydrate Malabsorption Inherited

Back 51

• glucose-galactose malabsorption
• lactase deficiency
• sucrase-isomaltase deficiency

Front 52

Carbohydrate Malabsorption Acquired

Back 52

• glucose-galactose malabsorption
• disaccharidase deficiencies
(severe enteropathies)
• excessive intake of fructose and
alcoholic sugars (sorbitol & mannitol)

Front 53

Marasmus

Back 53

•Protein, energy, vitamin, mineral deficiency
•infancy (weaning or decreased breast milk)
•severe weight loss (<60% wt for age)
•stunting of linear growth
•muscle wasting (when food(energy) intake is insufficient, somatic(muscle) protein is used for gluconeogenesis)
•wasting of fat, subcutaneous tissue
•oedema not characteristic
•Irritable, hyper-alert, ravenous, aged appearance

Front 54

Kwashiorkor

Back 54

•Pure protein deficiency: inadequate intake &/or increased susceptibility to infection
•older infants and young children
•Oedema (decreased serum albumen: decreased protein intake/production (fatty liver)
•protein depletion in viscera (liver, gut)
•skin (pigmentation, scaling, peeling)
•hair (thin, dull, sparse, unnaturally blond)
•apathetic, anorexia

Front 55

Kwashiorkor vs Marasmus

Back 55

1. Marasmus patients suffer from a peeling and alternately pigmented skin. Kwashiorkor patients are characterized by a distended stomach, burns on the skin and diarrhea.
2. Marasmus affects kids because of a lack of nutritional elements in the diet. Kwashiorkor affects kids who do not receive enough protein in the diet.
3. Marasmus affects infants and very young kids. Kwashiorkor affects kids who are a bit older.
4. Marasmus patients need to be treated with additional doses of vitamin B and a nutritious diet. Kwashiorkor patients are treated by adding more protein in their diet

Front 56

What is malnutrition?

Back 56

Insufficient absorption of nutrients essential for growth and development
•inadequate amount or poor quality food
•abnormal absorption of nutrients
•increased losses from gut (diarrhoea)
•increased energy utilisation eg chronic disease
•chronic or recurrent infection eg AIDS
Young children more vulnerable
•increased growth rate, higher caloric requirements

Front 57

Burden of malnutrition?

Back 57

PEM affects 1 in 4 children worldwide
•27% (150 million) children underweight
•33% (182 million) children stunted
•70% live in Asia, 26% Africa, 4% Latin America
•a spectrum including deficits of protein, energy, vitamins and minerals

Front 58

Stunted

Back 58

•Stunted: Stunted growth refers to low height-for-age, when a child is short for his/her age but not necessarily thin.
•Also known as chronic malnutrition, this carries long-term developmental risks.

Front 59

Under-weight

Back 59

•Under-weight: Under-weight refers to low weight-for-age, when a child can be either thin or short for his/her age.
•This reflects a combination of chronic and acute malnutrition.
•Stunted and Under-weight children are most likely to suffer from impaired development and are more vulnerable to disease and illness.

Front 60

Wasted

Back 60

• Wasted: Wasted refers to low weight-for-height where a child is thin for his/her height but not necessarily short. Also known as acute malnutrition, this carries an immediate increased risk of morbidity and mortality. Wasted children have a 5-20 times higher risk of dying from common diseases like diarrhoea or pneumonia than normally nourished children.

Front 61

Re-feeding Syndrome

Back 61

Any individual who has had negligible nutrient intake for more than 5 consecutive days is at risk of refeeding syndrome. Refeeding syndrome usually occurs within four days of starting to feed. Patients can develop fluid and electrolyte disorders, especially hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications.

Front 62

Burden of diarrhoeal disease

Back 62

•Diarrhoeal disease is the second leading cause of death in children under five years old. It is both preventable and treatable.
•Diarrhoeal disease kills 1.5 million children every year.
•Globally, there are about two billion cases of diarrhoeal disease every year.
•Diarrhoeal disease mainly affects children under two years old.
•Diarrhoea is a leading cause of malnutrition in children under five years old.

Front 63

How are diarrhoea and malabsorption interrelated?

Back 63

•
Decreased food intake
anorexia,
pain,
therapy
•
Decreased absorption
mucosal damage, motility,
osmotic
disaccharidases abnormality
•
Increased energy utilisation (infection)
•
Recurrent episodes: failure of catch-up
•
Vulnerability to other
infections eg measles
•Chronic diarrhoea: >14 days:
•reinfection,
• ongoing losses:
• lactose glucose intolerance,
•antigen entry: food intolerance

Front 64

Breaking the cycle
- measures to prevent diarrhoea

Back 64

•
Key measures to prevent diarrhoea include:
•
access to safe drinking-water
•
improved sanitation
•
exclusive breastfeeding for the first six months of life
•
good personal and food hygiene
•
health education about how infections spread
•
rotavirus vaccination.

Front 65

Breaking the cycle
- appropriate Tx

Back 65

Appropriate treatment
•
glucose-electrolyte solution (oral, nasogastric)
•
Zinc and vitamin A supplementation in the malnourished child
•
food-based OES
•
early re-introduction of normal diet
•
minimise drugs
•
antibiotics, antiemetics, anti-diarrheals
•
Management of complications
•
lactose intolerance
•
CMPI
•
recognition re-infection

Front 66

Breaking the cycle: Malnutrition and chronic diarrhoea
6 Rs

Back 66

•
Recognise
•
Resuscitate
•
Re-feed:
•
nutrient rich food, breast feeding during an episode
•
Exclusive breast feeding for first 6 months of life
•
Replace specific vitamin and mineral deficiencies
•
Rehabilitate
•
Rx intercurrent infection

Front 67

Fat Digestion

Back 67

•
Hydolysis by gastric acid
•
Bile salts solubilise the fat
•
Pancreatic enzymes such as lipase and colipase digest the fat
•
Intact intestinal mucosa is required for absorption
•
Diffusion across enterocyte apical membrane
•
Reconstitution into chylomicrons with carrier proteins such as apolipoproteinB
•
Transport via the lymphatic system into the systemic circulation
•
Small chain triglycerides can bypass this system and enter the portal venous system directly

Front 68

Steatorrhoea (fatty stools)
- aetiology

Back 68

•
Conditions that cause steatorrhoea can also be associated with protein maldigestion and/or malabsorption
•
symptoms most commonly relate to the malabsorption of fat.
•
The presence of fat in the stool is also more readily observed than protein.
•
Diseases of the pancreas and small intestine are the usual causes of steatorrhoea in childhood

Front 69

Assessment of fatty stools

Back 69

- crystals means brokendown but not absorbed
- and globules = not digested

Front 70

Pancreatic Disease: Cystic Fibrosis

Back 70

•
1:2,500 Caucasians
•
Chromosome 7, ΔF508 mutation
•
Meconium ileus
•
Bilious vomiting newborn
•
Chronic diarrhoea
•
pancreatic insufficient
•
Failure to thirive
•
Fat soluble vitamin deficiencies (A,D,E,K)
•
Respiratory illness

Front 71

Back 71

This child presented with bile stained vomiting due to meconium ileus (secondary to cystic fibrosis) has a temporary ileostomy. She has abdominal distension, a transverse scar and increased skin folds in the inner thigh suggesting poor nutrition.

Front 72

Back 72

Clubbing is characteristic of cystic fibrosis but is also seen in a number of other gastro-intestinal disorders including chronic inflammatory bowel disease (particularly Crohn’s disease), coeliac disease and biliary cirrhosis.

Front 73

Steatorrhoea in chronic liver disease

Back 73

•
Extrahepatic biliary atresia
(other causes neonatal obstructive jaundice)
•
Cirrhosis
Decreased intraluminal bile salts - impaired fat digestion.

Front 74

Back 74

This jaundiced child aged 4 months, has marked hepatosplenomegaly, umbilical herniation and abdominal distension.
The width of the liver and spleen from the lower costal margin at the mid-clavicular point should be documented.
The liver span can be determined by percussion of the upper border. Liver span varies with age and tables giving normal values are available. Consistency of enlarged organs should also be noted.
In this case, the child has extra-hepatic biliary atresia with biliary cirrhosis and secondary portal hypertension and the liver was firm.
In children, temporary enlargement of the liver and spleen with viral infections is not uncommon.

Front 75

Coeliac disease
Who should be tested?

Back 75

•
Persistent diarrhoea
•
Failure to thrive
•
Consider screening in persistent
•
Abdominal pain
•
Vomiting
•
Constipation
•
Abdominal distension
•
Irritability
* Exclude infection e.g. giardiasis

Front 76

Coeliac disease
From 3 years, even if asymptomatic,

Back 76

•Delayed puberty
•Dermatitis herpetiformis
•Enamel defects permanent teeth
•Osteoporosis
•Type 1 diabetes
•Short stature

Front 77

Coeliac disease
Regular Screening for

Back 77

•Iron deficiency anaemia (Fe resistant or unexplained)
•IgA deficiency, (screening test may be difficult to interpret)
•Down syndrome
•Turner syndrome
•Williams syndrome
•1o relatives with CD

Front 78

Coeliac disease: treatment
Gluten free diet for life

Back 78

•
Reverses GI symptoms
•
Maximises growth
•
Improve bone mineralization
•
Behaviour change
Adults
•
Decreased intestinal cancers
•
Decreases spontaneous abortions, LBW infants
•
Lowers mortality to general population rate
? Gluten dose threshold for harm

Front 79

Carbohydrate Digestion

Back 79

•
Dietary carbohydrates are primarily starch
•
Starch is comprised of long chains of glucose
•
Acted on by salivary and pancreatic amylase to trisaccharides, disaccharides, and oligosaccharides
•
Brush border enzymes disaccaridases break these down to monosaccharides
•
Sucrase breaks sucrose down to glucose and fructose
•
Lactase breaks down lactose into glucose and galactose
•
Glucose and galactose are absorbed by the enterocyte sodium–glucose cotransporter (SGLT), which absorbs the monosaccharides in an energy dependent fashion
•
Fructose is absorbed by facilitated diffusion (non-energy-dependent) by the transporter termed GLUT-5.

Front 80

Disaccharide Malabsorption

Back 80

•
Causes of disaccharidase deficiencies include:
•
viral gastroenteritis
•
coeliac disease
•
chronic giardiasis
•
milk protein enteropathy
•
small bowel bacterial overgrowth syndrome
•
immunodeficiency disorders
•
autoimmune enteropathy.

Front 81

Monosaccharide malabsorption

Back 81

•
Monosaccharide transporters are less susceptible to injury because, they are deeply embedded in the brush border membrane
•
Severe enteropathies can occasionally result in monosaccharide malabsorption. Examples include:
•
congential villous atrophy (which presents in newborns)
•
severe postinfectious enteritis
•
milk protein intolerance
•
autoimmune enteropathy.
•
Monosaccharide malabsorption is life-threatening
•
requires tertiary paediatric level care
•
treatment is to remove the offending carbohydrate from the diet
•
substitute an alternative.
•
In acquired disorders, treatment is required for the primary mucosal disease.

Front 82

Congenital monosaccharide malabsorption

Back 82

•
Congenital monosaccharide malabsorption refers to defective glucose/galactose malabsorption. Features are:
•
mutations in SGLT1
•
recessively inherited
•
present in the neonatal period.
•
Treatment is substitution to fructose for glucose–galactose

Front 83

glucose/galactose malabsorption

Back 83

Glucose-galactose malabsorption is a condition in which the cells lining the intestine cannot take in the sugars glucose and galactose, which prevents proper digestion of these molecules and larger molecules made from them.
Glucose and galactose are called simple sugars, or monosaccharides. Sucrose and lactose are called disaccharides because they are made from two simple sugars, and are broken down into these simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and lactose is broken down into glucose and galactose. As a result, lactose, sucrose and other compounds made from carbohydrates cannot be digested by individuals with glucose-galactose malabsorption.