a

Evolving Paradigm in the

Management of Malabsorption &
Maldigestion
a
Dr B Ravinder Reddy
MBBS, MS, FRCS (Edinburgh), FRCS (Glasgow)
Div. of Surgical Gastroenterology & General Surgery
Chief Division of Clinical Nutrition
Kamineni Hospitals
Hyderabad, India
a
Evolving Paradigm in the
Management of Malabsorption &
Maldigestion
I. Introduction
II. Normal Protein Absorption & Digestion
III. Protein Absorption & Digestion in Acute &
Chronic Illness
IV. Role of Peptides & Evolving Paradigm
V. Conclusions
a
Case 1
51 years old male, presented with progressive
acute abdominal pain, felt all over: 3 days. No GI
upsets
PMH: Diabetic
O/E: Rigid abdomen, tachycardia, tachypnoea,
severely acidotic, hypotensive
Emergency laparotomy
a
a
a
Case 2
52 years old male with IBD (UC) for > 15 years
Profound weakness, unable to move, restricting
his physical activity
12 to 15 loose motions per day
His disease was refractory to medical
management
Was severely malnourished
a
Preoperative nutritional optimisation
a
a
a
Case 3
42 years old male, ethanolic , transferred from
another hospital, with ANP
Was kept nil by mouth
Had MODS, needed support
a
a
a
a
a
Evolving Paradigm in the
Management of Malabsorption &
Maldigestion
I. Introduction
II. Normal Protein Absorption & Digestion
III. Protein Absorption & Digestion in Acute &
Chronic Illness
IV. Role of Peptides & Evolving Paradigm
V. Conclusions
a
Introduction
Enteral nutrition has evolved into an effective
means of providing nutritional support
Acute and chronically ill patients have an
increased need for proteins and calories, in
addition to optimal carbohydrates, & fats
Alladyce DB, et al. A comparison of nutritional gains resulting from intravenous and
enteral feeding. Surg Gynecol Obstet 1974, 139: 179-84
a
Introduction
All acute ill and most chronically ill patients
have dysfunctional gastrointestinal tract
resulting in maldigestion and malabsorption
The ability of providing adequate enteral
proteins and calories depends on the function
of gastrointestinal tract
Alladyce DB, et al. A comparison of nutritional gains resulting from intravenous and
enteral feeding. Surg Gynecol Obstet 1974, 139: 179-84
a
Introduction
Chronically ill patients also benefit from
polymeric diets when used as supplements
The standard paradigm in acutely ill is by
commencing early enteral feeds using
polymeric diets .
Alladyce DB, et al. A comparison of nutritional gains resulting from intravenous and
enteral feeding. Surg Gynecol Obstet 1974, 139: 179-84
a
Introduction
However, polymeric diets in patients with an
acute or chronic illness with an underlying
severe malnutrition may not achieve the desired
clinical outcome
Alladyce DB, et al. A comparison of nutritional gains resulting from intravenous and
enteral feeding. Surg Gynecol Obstet 1974, 139: 179-84
a
Evolving Paradigm in the
Management of Malabsorption &
Maldigestion
I. Introduction
II. Normal Protein Absorption & Digestion
III. Protein Absorption & Digestion in Acute &
Chronic Illness
IV. Role of Peptides & Evolving Paradigm
V. Conclusions
a
Normal Protein
Digestion & Absorption
Fisher RB. Protein metabolism. London: Methuen, 1954
It takes over 200 hours to completely
hydrolyze dietary proteins into
free amino acids
a
Normal Protein
Digestion & Absorption
Nolf P. Les albumoses et peptones sont-elles absorbee par lepithelium intestinal?
J Physiol Pathol Genet 1907,
Peptones which are produced by
protein digestion, rapidly disappear
from the intestinal lumen
a
Normal Protein
Digestion & Absorption
Craft IL, et al. Absorption and malabsorption of glycine peptides in man. 1968 Gut
Amino acids are more rapidly absorbed
in the form of di- or tripeptides than in
the free form, by specific carriers
a
Normal Protein
Digestion & Absorption
Fisher RB. Protein metabolism. London: Methuen, 1954
In addition, peptides also undergo
binding and mucosal hydrolysis in the
brush border membrane
a
Normal Protein
Digestion & Absorption
Fisher RB. Protein metabolism. London: Methuen, 1954
Proteins
Polypeptides
Small Peptides & Amino Acids
Pepsin
Trypsin
Chymotrypsin
a
Normal Protein
Digestion & Absorption
Fisher RB. Protein metabolism. London: Methuen, 1954
Proteins
Polypeptides
Small Peptides & Amino Acids
Luminal
Hydrolysis
a
Normal Protein
Digestion & Absorption
Fisher RB. Protein metabolism. London: Methuen, 1954
Small Peptides
Amino Acids
Absorbed directly by
Intestinal mucosa
a
Normal Protein
Digestion & Absorption
Fisher RB. Protein metabolism. London: Methuen, 1954
Small Peptides
Amino Acids
Further hydrolyzed by
aminopeptidases
present
in brush border surface
a
Normal Protein
Digestion & Absorption
Gut
lumen
phase
Brush
border
phase
(Microvilli)
Cytoplasmic
phase
(Intracellular)
HCl, Pepsin
Trypsin
Chymotrypsin
Enteropepdi-
sases
Dipeptidases
Tripeptidases
Mahan LK et al. Krauses Food, Nutrition & Diet Therapy. WB Sanders 1996
Zaloga GP. Studies comparing intact protein, peptide and amino acid formulas. In: Bounous G (ed). Elemental Diets in Clinical Situations. 1993
a
Normal Protein
Digestion & Absorption
Garner ML et al. Trans-mucosal passage of intact peptides in guinea-pig small intestine in vivo: a re-appraisal. Clinical Science. 1983
2/3rds of nitrogen from protein is absorbed as
peptides
a
Normal Protein
Digestion & Absorption
Many proteins are absorbed more efficiently in
the form of peptides than free amino acids
1. Intestinal absorption of peptides. Mathews DM. Physiological Reviews. 1975
2. Amino acid and peptide absorption from gastrointestinal tract. Webb KE. Fed Proc 1986
3. The digestion and absorption of proteins in man. The form in which proteins is absorbed. .British Journal of nutrition. 1970
33% of proteins are
absorbed as amino acids
67% of proteins are
absorbed as peptides
a
Protein Kinetics in the Body
Modified from Munro and Crim 1988
Diet
100 g / day
Fecal Loss
10 g / day
GI
Secretions
70 g/d
A Acids Reabsorbed
160 g / day
Tissue pool
Skin loss
2 g / day
Free Amino
Acid Pool
Oxidative loss
Urea/NH
3
90 g / day
a
In normal circumstances, the gut not only
digests and absorbs protein, but also
secretes about 70 grams of protein
(enzymes, shed mucosal cells)
into the lumen
Most of it is reabsorbed
Protein Kinetics in the Body
Modified from Munro and Crim 1988
a
Evolving Paradigm in the
Management of Malabsorption &
Maldigestion
I. Introduction
II. Normal Protein Absorption & Digestion
III. Protein Absorption & Digestion in Acute &
Chronic Illness
IV. Role of Peptides & Evolving Paradigm
V. Conclusions
a
Gastrointestinal Tract
GIT is the largest immune organ
60% of immune Cells
80% of
Immunoglobulins
a
Gastrointestinal Tract
Most rapid turnover of any tissue
48 to 72 hours
Enterocytes turnover is affected
by abnormalities in cell synthesis
and cell replication
a
Gastrointestinal Tract
Many factors affect cell synthesis & cell replication
1. Malnutrition
2. Chronic Maldigestion
3. Acute Malabsorption:
i. SIRS & Sepsis
syndrome
ii. Acute severe
pancreatitis
iii. Short bowel syndrome,
etc
a
Protein Digestion &
Absorption in Stress
The ability to process intact proteins may be reduced
Trauma, Sepsis & Shock
Structural
Abnormalities
Brush Border
Function
Brush Border
Atrophy
Amino acid and peptide absorption in human intestine: implications for enteral nutrition. In Blackburn GL (Ed).
Amino acids: metabolism and medical applications . Boston: John Wright. 1983
a
Protein Digestion &
Absorption in Stress
Amino acid absorption
is compromised
Peptide absorption
remains intact

Independent transporter mechanism

Peptide absorption and hydrolysis. Adibi SA. In Johnson L (ed) Physiology of the Gastrointestinal Tract. 1981
Peptide absorption. Mathew DM et al. Gastroenterology 1976
Protein uptake by intestine: evidence for absorptionj of intact macromolecules. Warshaw Al, Walker WA. Gastroenterology 1976
a
Protein Digestion &
Absorption in Stress
Appear to have an absorptive advantage when
compared with free amino acids and intact
protein based formulas
Amino acid and peptide absorption in human intestine: implications for enteral nutrition. In Blackburn GL (Ed).
Amino acids: metabolism and medical applications . Boston: John Wright. 1983
a
Stress Response
Moderate
SIRS
Moderate
CARS
Severe
SIRS
Severe
CARS
INSULT
EARLY MOF
LATE MOF
INFECTIONS
a
Stress Response
Cells of the villi receive nourishment from intestinal
contents and NOT from their blood supply
Stress & gut disuse reduce nourishment of villi
a
Stress Response
The prophylactic use of an elemental diet in experimental hemorrhagic and intestinal shock and intestinal isschemia.
Bounous G et al. Annals of Surgery. 1967
Diffuse necrosis of intestinal epithelium
Traumatic hemorrhagic Shock
Translocation Multiple Organ Failure Death
a
Stress Response
Moderate
SIRS
Moderate
CARS
Severe
SIRS
Severe
CARS
INSULT
EARLY MOF
LATE MOF
INFECTIONS
Protein synthesis
Protein absorption
HYPOALBUMINEMIA
a
Hypoalbuminemia
(< 2.6 mg%)
Gut wall edema
Ability of nutrients to pass across mucosal
membranes
Diarrhea
Nutrition support in injured patient.. Surgical Clinics of North America. 1991
a
Common Causes of
Intestinal Failure in ICU
Early Enteral Feeds Limit MOF
a
Evolving Paradigm in the
Management of Malabsorption &
Maldigestion
I. Introduction
II. Normal Protein Absorption & Digestion
III. Protein Absorption & Digestion in Acute &
Chronic Illness
IV. Role of Peptides & Evolving Paradigm
V. Conclusions
a
Role of Peptides
Peptides appear to have an absorptive
advantage when compared with free amino
acids and intact protein based formulas
Amino acid and peptide absorption in human intestine: implications for enteral nutrition. In Blackburn GL (Ed).
Amino acids: metabolism and medical applications . Boston: John Wright. 1983
a
Hypoalbuminemia
(< 2.6 mg%)
Despite gut wall edema
Proteins in peptide form are better absorbed
Studies in surgical patients showed administration of peptide-based
Formula resulted in improved prealbumin levels compared to free amino acids
Repletion of nutritional parameters in surgical patients receiving peptide versus amino acid elemental feedings
Nutrition Research 1994
a
Peptide Tolerance
In another study, postoperative and critically ill patients
on peptide based formulae showed:
1. Fewer stools
2. Less nausea & vomiting
3. Lower incidence of abdominal distention
Tolerance to enteral tube feedingdiets in hypoalbuminemic critically, geriatric patients
Borlase BD et al. Surgery, Gynaecology & Obstetrics. 1992
a
Diarrhea in Trauma Patients:
Effects of Peptide Vs. Intact Protein Diets
Peptide-Based Intact Protein
60
Patients with
Diarrhea (%)
40
20
0
44%
0%
Visceral protein levels in trauma patients are greater with peptide diet than intact protein diet
Meredith JW et al. Journal of Trauma. 1990
a
Diarrhea in Trauma Patients:
Effects of Peptide Vs. Intact Protein Diets
Peptide-Based Intact Protein
60
40
20
0
44%
0%
Visceral protein levels in trauma patients are greater with peptide diet than intact protein diet
Meredith JW et al. Journal of Trauma. 1990
Visceral
Proteins
75% had in diarrhea
when switched to
Peptide-based formula
a
Peptides & Growth
Peptide-based formula increased growth
compared to free amino acids*
Malnourished achieved higher weight gain
compared to intact proteins*
* Growth was unrelated to the total calories and proteins provided
Effects of whey protein, their oligopeptide hydrolysate and free amino acid mixtures on growth and nitrogen retention in fed and starved rats.
Poullain MG et al. Journal of Parenteral and Enteral Nutrition 1989
a
Peptides & Tissue Repair
Peptide-based formulas increased tissue
growth and tissue repair when compared to
intact proteins*
* Hypothesis: Peptide formulas may cause greater stimulation of
tissue growth factors
Effects of enteral diets on whole body and gut growth in unstressed rats
Zaloga GP. Journal of Parenteral & Enteral Nutrition. 1991
a
Peptides & Gut Integrity
There is enough clinical proof to state that
peptides maintain gut integrity in a better way
Dietary protein prevents bacterial translocation from the gut. Shou J et al. Journal of Parenteral & Enteral Nutrition. 1991
Colonic mucosal atrophy induced by a liquid elemental diet in rats. Janne P et al. Digestive Disease Science 1977
Interleukin-4 reduces chemically defined diets (CDD) induced bacterial translocation in mice. Shou J et al. JPEN 1991
a
Peptides & Gut Integrity
Peptides resulted in a higher gut mass
Peptides have an increased trophic effect
Peptides enhanced the absorption of specific
amino acids and peptides when compared to
amino acid-based or intact protein formula
A peptidebased diet with a low amount of free amino acids enhance gastrointestinal structure and function in young pigs with a
compromised GIT. Maples BA et al. Journal of Parenteral & Enteral Nutrition. 2005
a
Peptides & Gut Integrity
The prophylactic use of an elemental diet in experimental hemorrhagic and intestinal shock and intestinal isschemia. Bounous
G et al. Annals of Surgery. 1967
Diffuse necrosis of intestinal epithelium
Traumatic hemorrhagic Shock
Hydrolysed protein formula was proved to be superior
compared to intact protein formula in maintaining gut
integrity after hemorrhage
Translocation Multiple Organ Failure Death
a
Peptides & Gut Integrity
Intestinal protein loss during enteral alimentation in critically ill patients.
Anderson W et al. Journal of Parenteral and Enteral Nutrition 1990
Double-blind study of critically ill
patients with hypoalbuminemia
Peptide-Based Diet Intact Protein
Decrease in fecal
protein loss
a
Fecal Protein Loss in Critically &
Hypoalbuminic Patients
Intestinal protein loss during enteral alimentation in critically ill patients.
Anderson W et al. Journal of Parenteral and Enteral Nutrition 1990
Days
1
2
3 4
M
g

a
n
t
i
t
r
y
p
s
i
n

/

d
L
s
t
o
o
l
0
120
100
80
60
40
20
Intact Protein
Peptide-Based
a
Peptides & Wound Healing
Many studies have shown that intact proteins fail
to heal massive pressure ulcers
Critical care enteral formula improves outcomes for a patient with chronic pressure ulcer. Brasseur K et al. Nutrition in Clinical Practice. 2001
a
Peptides & Wound Healing
Preventing skin breakdown in a high risk patient. Obtaining a prealbumin and utilising a critical care tube feeding formula.
Phillips E. Presented at the 15
th
Annual Symposium on Advanced Wound Care and Medical Research Forum. 2001
In many patients, on intact protein formulas,
low prealbumin and albumin = poor healing
a
Peptides & Wound Healing
Preventing skin breakdown in a high risk patient. Obtaining a prealbumin and utilising a critical care tube feeding formula.
Phillips E. Presented at the 15
th
Annual Symposium on Advanced Wound Care and Medical Research Forum. 2001
Critical care enteral formula improves outcomes for a patient with chronic pressure ulcer. Brasseur K et al. Nutrition in Clinical Practice. 2001
Chronic massive pressure ulcers healed after commencing
peptide-based formula
Prealbumin & albumin increased due to nitrogen absorption and
retention (by peptide-based diet)
a
Peptides & Liver Function
Liver dysfunction is common in critical illness
Altered
Liver Function
Compromised
Immune Function
Removal
Endogenous Waste
Production
Vital Proteins
Improved hepatic protein responses with hydrolysed protein versus intact protein after trauma. Zaloga GP et al.
Critical Care Medicine 1992
a
Peptides & Liver Function
Peptide - based enteral formulas
Maintain
Liver Function
Albumin
Transferrin
Prealbumin
Production
Vital Proteins
Improved hepatic protein responses with hydrolysed protein versus intact protein after trauma. Zaloga GP et al.
Critical Care Medicine 1992
a
Peptides & Liver Function
Improved hepatic protein responses with hydrolysed protein versus intact protein after trauma. Zaloga GP et al.
Critical Care Medicine 1992
+ 14%
- 17%
Transferrin
20%
10%
0%
- 10%
- 20%
Peptide
Intact
Protein
a
Peptides & Liver Function
Retinol-Binding Protein
Improved hepatic protein responses with hydrolysed protein versus intact protein after trauma. Zaloga GP et al.
Critical Care Medicine 1992
- 10%
0%
- 40%
- 50%
Peptide
Intact
Protein
- 20%
- 30%
- 1%
- 28%
a
New Paradigm in
Feeding ICU Pts
The Enhanced Protein-Energy Provision via the Enteral
Route in Critically Ill Patients
The PEP uP Protocol
Daren Heyland et al. Critical Care 2010
a
New Paradigm in
Feeding ICU Pts
The Enhanced Protein-Energy Provision via the Enteral
Route in Critically Ill Patients
The PEP uP Protocol
Daren Heyland et al. Critical Care 2010
Prospective single center study
Volume-based 24-hour feeding protocol that has
shown to be safe and acceptable to critical care
nurses
Enteral formula used was a semi-elemental diet
(Peptamen 1.5

Nestle)
a
New Paradigm in
Feeding ICU Pts
I. Volume based goal
II. Trophic feeds
III. Promotility agents were commenced at the
initiation of feeds
IV. Residual volume tolerated up to 250 mls
V. Supplemental proteins (discontinued if EN
was tolerated)
Daren Heyland et al. Critical Care 2010
a
New Paradigm in
Feeding ICU Pts
Conclusion
Traditional enteral feeding practices do not
adequately provide proteins and calories to critically
ill patients
This new feeding protocol challenges the traditional
protocols and introduces an innovative method that
maximizes benefits
In this study, there was an enhanced delivery of EN
This needs a large multicenter, multinational RCT in
critically ill patients to further determine the safety
and efficacy
Daren Heyland et al. Critical Care 2010
a
Evolving Paradigm in the
Management of Malabsorption &
Maldigestion
I. Introduction
II. Normal Protein Absorption & Digestion
III. Protein Absorption & Digestion in Acute &
Chronic Illness
IV. Role of Peptides & Evolving Paradigm
V. Conclusions
a
Peptide-Based Diets
Clinical Applications
1. Patients with impaired digestion and
absorption have reduced protein
absorption
Brinson R, et al. Intestinal absorption of elemental and standard enteral formulas in hypoproteinemic rats. JPEN 1998
Bounous G, et al. Elemental diets in prophylaxis and therapy for intestinal lesions: an update. Surgery 1989
a
Peptide-Based Diets
Clinical Applications
2. Patients with hypoalbuminemia
and also associated diarrhea
e.g. Protein loosing enteropathy
Brinson R, et al. Intestinal absorption of elemental and standard enteral formulas in hypoproteinemic rats. JPEN 1998
Bounous G, et al. Elemental diets in prophylaxis and therapy for intestinal lesions: an update. Surgery 1989
a
Peptide-Based Diets
Clinical Applications
3. Patients with hypermetabolism
e.g. SIRS, sepsis, polytrauma and burns;
i.e., in whom nitrogen utilisation is very
important
Brinson R, et al. Intestinal absorption of elemental and standard enteral formulas in hypoproteinemic rats. JPEN 1998
Bounous G, et al. Elemental diets in prophylaxis and therapy for intestinal lesions: an update. Surgery 1989
a
Clinical Indications for
Peptide-Based Formulas
Nutritional
Cardiac cachexia
Short bowel syndrome
Chronic pancreatitis
Acute Kwashiorkar-like hypoalbuminemia
Cystic fibrosis
Postoperative gastrostomy / jejunostomy
Failure to thrive
Brinson BR, et al. A Reappraisal of the Peptide-Based Enteral Formulas: Clinical Applications. Nutr Clin Pract 1989, 4:211-217
a
Clinical Indications for
Peptide-Based Formulas
Protein-Losing Enteropathy
Intestinal ischemia & lymphiectasia
Inflammatory bowel disease
Radiation enteritis
Small bowel lymphoma
Infectious enteritis (AIDS)
Bacterial overgrowth
Eosinophilic gastroenteritis
Brinson BR, et al. A Reappraisal of the Peptide-Based Enteral Formulas: Clinical Applications. Nutr Clin Pract 1989, 4:211-217
a
Clinical Indications for
Peptide-Based Formulas
Hypercatabolic Syndromes
Burns
Enteric fistula
Septic shock
Transplant surgery
Trauma
Brinson BR, et al. A Reappraisal of the Peptide-Based Enteral Formulas: Clinical Applications. Nutr Clin Pract 1989, 4:211-217
a
Summary
Peptide-Based Diet
Malbsorption
Maldigestion
Malnutrition
SIRS + Sepsis Syndrome
Acute Intestinal Failure
a
Summary
Peptide-Based Diet
Improved nitrogen absorption & utilisation
Reduced diarrhea
Stimulation of gut mass
Maintenance of gut integrity
Reduction of bacterial translocation
Brinson BR, et al. A Reappraisal of the Peptide-Based Enteral Formulas: Clinical Applications. Nutr Clin Pract 1989, 4:211-217
a
Summary
Peptide-Based Diet
Enhanced immune support
Improved linear growth
Maintenance of hepatic function
Improved visceral protein synthesis
Improved wound healing
Brinson BR, et al. A Reappraisal of the Peptide-Based Enteral Formulas: Clinical Applications. Nutr Clin Pract 1989, 4:211-217
Improve Clinical Outcome
a
Cases
In all three cases, a semi-elemental, peptide-
based enteral formula was commenced with the
traditional EEN protocol and progressed to full
feeds with supplemental PN and antioxidants
Brinson BR, et al. A Reappraisal of the Peptide-Based Enteral Formulas: Clinical Applications. Nutr Clin Pract 1989, 4:211-217
a
Patients With
Maldigestion & Malabsorption
Normal
Digesti
on
Mal
Digestion
Mal
Digestion
a
Peptide-Based
Semi-elemental Diet
Normal
Digestion
Normal
Absorption
a
Thank You
a
Dr B Ravinder Reddy
drbravinderreddy@yahoo.com