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Optimizing the
Intestinal Health Of Baby Calves
Rob Costello, Dairy Technical Specialist
Introduction
Structure Of the Intestinal Mucosa
Water Movement In the Small Intestine
Innate Defenses of the Intestinal Mucosa
Water Secretion
Mucus Secretion
Antimicrobial Peptides
Water Loss (Diarrhea)
Dehydration
Efficacy Of Treatment
Milk/Milk Replacer Feeding
Management Factors Affecting Intestinal Health
Ingredients/Supplements
References and Reviews
Introduction
The intestinal mucosa is a single cell layer that separates the intestinal
contents from the biological compartments of the animal. This expansive surface
facilitates nutrient absorption while protecting the body from both the normal
beneficial flora resident within the intestinal lumen as well as unwelcome
pathogens. The intestinal mucosa provides a physical barrier to intrusion, and
is also armed with more active methods of keeping intestinal microflora in
check.
The first 3-4 weeks after birth may well be the most challenging period of the
calf's life. It is certainly a period of great change. The calf is born with a
sterile digestive tract that rapidly becomes populated with organisms. The calf
is also dependant on appropriate management and administration of colostrum for
passive transfer of immunity, while at the same time beginning a transition
process from monogastric to ruminant digestion. A sizable list of challenges
can readily be assembled.
The more we learn and understand about the function and environment of the
small intestine, the more effective our efforts to manage the calf and it's
environment for optimum growth and performance. This review provides a brief
discussion of the structure and function of the small intestine, an overview of
innate intestinal defense mechanisms, the effects of scours on intestinal
health and a summary of management practices, feed additives and supplements
that benefit intestinal health.
Structure Of the Intestinal Mucosa
The mucosa, or lining of the small intestine is made up of villi and
crypts. Figure 1. Villi project into the open space, or lumen, of
the small intestine and are mainly involved in nutrient absorption. Each villus
is well supplied with blood and lymph vessels that rapidly move absorbed
nutrients away from the digestive tract and into the body. Crypt cells, on the
other hand, are primarily concerned with secretion of substances, including
water, into the intestinal lumen.
Figure 1.
Enterocytes are the absorptive cells of the villi. Goblet cells produce mucin
that primarily serves a protective function. Although not shown in Figure 1,
another type of cell found on the villi is the enteroendocrine cell. These
cells are part of the endocrine system and continuously test and evaluate the
intestinal contents. When stimulated, they secrete hormones into the
bloodstream that communicate messages to other structures and organs to modify
their activity in response to conditions within the intestine.
The fourth type of mucosa cell is located in the crypt. They are called Paneth
cells, and produce antimicrobial substances. The cells that make up the
intestinal mucosa are short lived. The life span of villus cells is 4-6 days
while Paneth cells are active for about 14 days. Stem cells located near the
base of the crypt are the source of enterocytes, goblet cells, enteroendocrine
and Paneth cells. Stem cells develop and differentiate as they migrate from the
crypt up to the villus.
Water Movement In the Small Intestine
In healthy animals, large amounts of water are regularly secreted into the
small intestine to help digest and absorb nutrients. Most of this water is
recovered as the nutrients are digested and absorbed. As food enters the small
intestine, water readily “leaks” between the mucosa cells of the upper small
intestine into the lumen. During digestion large food particles are broken down
to small absorbable nutrients, increasing the concentration of particles inside
the intestine. This concentration, referred to as osmotic pressure, is much
greater inside the intestine than it is in the cells and fluids of the body
surrounding the digestive tract. Since water flows toward areas of high osmotic
pressure, water moves from the body into the intestinal lumen. Figure 2.
Figure 2. Water Movement Into the Small Intestine
Water is resorbed from the digestive tract as a result of nutrient absorption,
with sodium playing an important role in this process. As a rule: water follows
sodium. Sodium is free to move across mucosa cell membranes in
response to osmotic differences, moving from areas of high to areas of lower
osmotic pressure. Figure 3.
Figure 3. Sodium Movement
Although this passive diffusion of Na+ results in water movement out
of the digestive tract, it is insufficient for adequate water resorption.
Sodium is also actively moved across the mucosa cell membrane along with other
nutrients. For example, amino acids and carbohydrates are co-transported with
Na+out of the lumen and into the mucosa cells of the small
intestine. Once inside the cell, Na+ is rapidly pumped into the
extracellular fluid surrounding the cell, away from the intestinal lumen. As a
result of these nutrient movements, a series of osmotic gradients are created
which move water from the lumen into the cell, and then from the cell into the
extracellular fluid. Figure 4. The Na+ and water then
diffuse into the blood stream.
Figure 4.
This ability to concentrate Na+ in the extracellular fluid surrounding mucosa
cells, drawing water from the digestive tract, increases as food particles move
through the small intestine. By the time food reaches the large intestine,
about 80% of the water has been resorbed.
Innate Defenses of the Intestinal Mucosa
Within the digestive tract, examples of innate defenses include physical
processes such as peristaltic movements of the intestine, shedding of
epithelial cells, chemical barriers such as gastric acidity, bile acids,
antimicrobial peptides and mucus as well as water secretion. The last three -
water, mucus and peptide secretion -- will be reviewed in this text.
Water Secretion. A simple method of responding to the
presence of intestinal pathogens is water secretion. The idea is that rapid and
increased flow of fluid across the intestinal epithelium flushes organisms from
the intestinal lumen preventing attachment and maybe dislodging some that are
already adhered. The presence of bacterial factors, such as cholera and E. coli
toxins initiates intestinal secretion of electrolytes and water. This process
involves moving water into the intestine through specific action of crypt
cells. By pumping chloride ions (Cl-) into the crypt space of the
lumen, crypt cells actively draw water into the intestine. These (Cl-)ions
attract sodium ions Na+ into the crypt space, increasing the local osmotic
pressure. Figure 5A. As the osmotic pressure increases, water is pulled into
the intestine. Figure 5B. Some bacteria, such as cholera, cause this pump
system to lock in the “ON” position. In addition, invasive organisms such as Salmonella
typhimurium and certain strains of E. coli infect the epithelial
cells causing the host to initiate this form of secretory diarrhea.
Figure 5. Water Secretion Into the Intestinal Crypt Space
Mucus secretion. Goblet cells located on the surface
of the intestinal villi produce highly complex mucus glycoproteins, or mucin,
which coats the upper surfaces of the villi. This gel-like layer provides a
front line defense against pathogens. The carbohydrates in the mucus layer are
quite diverse and provide numerous binding sites for both commensal and
pathogenic organisms. In this way, the mucus layer serves as a platform for
microbial colonization. This process may slow microbial interaction with
epithelial cells of the villi and help prevent injury. In addition, the mucus
layer may also enhance removal of microorganisms through peristaltic movements.
Mucus volume and composition, intestinal motility and fluid flow rate influence
whether a harmful or beneficial effect occurs as an outcome of microbial
attachment. Probiotic organisms such as lactic acid bacteria have been shown to
stimulate mucus production in the small intestine (4), enhancing the beneficial
effect of the mucus layer.
Antimicrobial peptides. Stem cells located near the
base of the intestinal crypts continuously produce cells that differentiate and
repopulate the intestinal mucosa. The turnover rate of the intestinal mucosa is
rapid with total repopulation occurring every four to six days. Closely
associated with stem cells are the Paneth cells, (Figure 6), which are
strategically located at the very base of the crypts. Paneth cells help protect
the cell renewal process from bacterial infestation by providing a chemical
barrier of immunity.
Figure 6.
Paneth cells actively sense bacteria and release antimicrobial peptides, called
defensins. Defensin production is an innate immune response that kills bacteria
immediately on contact without having to produce specific antibodies. These
defensins interact with the bacteria, causing pores to form in the bacterial
membrane that lead to cell death. By inhibiting bacterial colonization of the
crypt, Paneth cells protect stem cells and allow their replication to proceed
continuously to maintain mucosal integrity.
Defensins appear to be an important aspect of immunity even in very young
calves. One day old calves were dosed with a non-fatal dose of Cryptosporidium
parvum which typically causes diarrhea for 5-10 days (10). This
organism invades the intestinal epithelium causing blunting of the villi,
tissue inflammation and increased crypt cell growth. Calves were euthanized at
5 days of age when the first signs of scours appeared. The intestinal tissues
of the calves showed up to a 10-fold increase in defensin mRNA, indicating
increased defensin production in response to cryptosporidium infection.
Paneth cells also appear to communicate with the body. For example, Paneth
cells have been shown to respond to the presence of bacteria by promoting
development of blood vessels in the intestinal lining (7), and certain
defensins have been shown to enhance systemic IgG (6).
Water Loss (Diarrhea)
Scours is the most prevalent disease of pre-weaned calves in the U.S.,
accounting for 62% of pre-weaned heifer calf deaths on dairy farms. Conditions
that cause water loss can have a significant impact on intestinal health. The
converse is also true. Pathogens, feed characteristics and management influence
digestive function and can result in water loss through the digestive tract.
There are four types of digestive water loss. A diarrheic animal may actually
suffer from more than one type of water loss at the same time.
Increased
Permeability. Microbes cause inflammation and damage to the intestinal
mucosa resulting in increased water movement into the intestine. This type of
water loss is commonly caused by viruses (rotavirus, coronavirus) and protozoa
(coccidia, cryptosporidia). Inflammation may also lead to host-generated
hypersecretion.
Hypersecretion This type of water loss is similar to
increased permeability in that large amounts of water move into the intestine,
but there is no tissue damage. Bacterial enterotoxins stimulate cellular pumps
in the crypt cells of the intestinal mucosa to secrete large amounts of ions
into the intestinal lumen. These ions draw water into the small intestine.
Hypersecretion in calves is commonly caused by E. coli.
Malabsorption.
Epithelial damage of the small intestine reduces nutrient
absorption. Viruses and protozoa damage the villi in the small intestine
leading to villous atrophy, and can damage mucosa of the large intestine as
well. Normal amounts of water may be secreted into the digestive tract, but
tissue damage results in poor nutrient and water absorption. Malabsorption
results in increased nutrients reaching the large intestine. These additional
nutrients can cause bacterial overgrowth and excessive production of volatile
fatty acids (VFAs). As a result, osmotic changes can occur that increase fluid
loss.
Maldigestion. Changes in feed management may lead to
maldigestion. A sudden change in feed, use of poor quality ingredients, the
presence of feed allergens or other detrimental factors and digestive disorders
can lead to maldigestion. Maldigestion usually results in malabsorption.
Dehydration. A calf can lose as much as 6% of its body
weight before showing visible signs of dehydration. Giving fluids too little,
too late allows progressive fluid loss. As a result, the calf's condition
continues to deteriorate. Most calves that die of scours usually die from loss
of water and electrolytes rather than any direct action of pathogenic
organisms. During dehydration water moves from the extracellular fluid into the
digestive tract. Water moves from the blood and the space between cells (the
interstitial space) into the intestinal lumen. Figure 7A. As more water moves
into the intestine, the concentration of substances in the extracellular fluid
rises, Figure 7B, increasing its osmotic pressure.
Figure 7. Process of Dehydration Due to Scours
Since water moves toward areas of higher osmotic pressure, water leaves the
cells and moves into the extracellular fluid. Figure 7C. This process of
cellular dehydration helps maintain the plasma fluid volume. (A more detailed
description of dehydration can be found by following this link to Electrolyte And Water Balance In Calves
Efficacy of Treatment. The amount and timing of electrolyte
replacement therapy is critical for rapid recovery from dehydration and to
minimize the impact on the intestinal mucosa. The focus of any treatment plan
should be on replacing lost fluids and restoring acid base balance.
Enterotoxigenic E. coli causes a hypersecretion type of water loss. In
this situation, only about 60% of the electrolyte solution is absorbed (12), so
the frequency of administration needs to be increased. In this case, 40% of the
electrolyte solution will pass through the calf's digestive tract, adding to
the calf's fecal water loss. This makes the diarrhea appear to be worsening
with electrolyte therapy even though the treatment is effective.
Rotavirus, coronavirus and cryptosporidia invade and damage the intestinal
villi causing an increased permeability type of water loss. These organisms
tend to affect calves over a week old causing a somewhat slower rate of water
loss and a more prolonged infection than with Enterotoxigenic E. coli.
Electrolyte therapy reduces the metabolic acidosis associated with these
infections. As a result, the suckling reflex increases, helping the animal to
recover without other treatments.
Milk/Milk Replacer Feeding. Substituting an
electrolyte solution for milk replacer does nothing to correct fluid loss. When
normal digestive and absorptive functions of the intestine are impaired, calves
cannot absorb adequate nutrients from the diet. Since young calves have
precious little in the form of stored nutrients to sustain them, digestive and
absorptive problems can progressively lead to rapid weight loss, weakness and
death. This situation is made worse when milk replacer is withheld during the
treatment process.
Figure 8.
Withholding milk replacer does reduce nutrients available for gut pathogens,
but also reduces nutrients for the calf. This reduction in nutrients not only
compromises the normal gut flora, it also reduces nutrients available for
immune function and contributes to intestinal villi atrophy. The villi on the
left of Figure 8 are healthy intestinal villi of a pig at weaning. The picture
on the right shows villi two days later before the pig has adjusted to the new
diet, and clearly shows the effects on the intestinal mucosa of withholding
nutrients.
The digestive tract requires more energy to keep it going than any other organ
in the body. If the inflow of nutrients is greatly reduced, the digestive tract
begins to shut down, conserving energy by reducing functions. Villus atrophy
reduces nutrient absorption and compromises the protective barrier function
they provide against pathogens. There is strong evidence that withholding
nutrients also prolongs the duration of diarrhea and slows recovery.
Management Factors Affecting Intestinal Health
Whether intentionally or accidentally, a host of management factors are brought
to bear on the intestinal health of baby calves. We can reach all the way back
to the last trimester of the dam for factors that affect the calf's
susceptibility to disease and other stressors. Calving facilities,
vaccinations, feeding protocol and sanitation procedures all deserve
exploration, but are beyond the scope of this review. There are, however, three
areas of calf management that have a direct and significant effect on the
intestinal integrity of young calves and deserve some discussion.
Colostrum. Much has been written about the critical
importance of the quality, quantity and timing of feeding colostrum. Colostrum
management is arguably the single most important calf management factor that
sets the tone for what will follow in the calf's life.
Colostrum is a critical source of immunoglobulins (Ig) or antibodies for the
calf's immune system. IgA makes up 10-15% of the immunoglobulins in colostrum
and protects mucus membranes such as those around the eyes, nasal passages and
the intestines. Another 10-15% of colostral immunoglobulins are IgM. This large
antibody circulates in the bloodstream, protecting the calf from septicemia. If
the integrity of the intestinal mucosa were compromised to the extent that
bacterial pathogens entered the calf's bloodstream, IgM would be a major line
of defense. IgG comprises between 70-80% of immunoglobulins in colostrum. IgG
is also the most plentiful immunoglobulin in the bloodstream. Its small size
allows it to move out of the blood into other areas of the body, including the
digestive tract. The amount of IgG secreted back into the small intestine over
time is related to the amount circulating in the blood. The higher the IgG
absorbed from colostrum, the higher the level in calf's bloodstream. The higher
the IgG in the blood, the higher the percentage secreted into the small
intestine. In the digestive tract, IgG can have a direct effect on pathogens
and may also have a direct beneficial effect on the intestinal mucosa.
Nutrition. Calf nutrition is a broad subject area
with many consequences on intestinal health. The calf's overall plane of
nutrition is a broad category that has significant effects on its ability to
maintain intestinal integrity. Stress conditions, at the most basic
physiological level, decrease blood flow to the intestines, compromising the
integrity of the mucosal barrier.
Milk replacer. Economic considerations and the
desire to convert calves to ruminants as soon as possible after birth are major
motivators behind the traditional approach of feeding a 20% protein, 20% fat
milk replacer at a rate of one pound of powder per day. This formula and
feeding rate provides enough protein and energy to support a calf up to about
115 lb. Any additional growth will come from the intake of starter feed. This
situation can put a tremendous amount of stress on the calf, especially if
there are any pathogen, weather or other stress factors that can quickly
compromise intestinal health. Increasing nutrient intake through a higher
feeding rate of milk replacer will go a long way toward providing the calf a
better nutritional foundation. In this situation, the milk replacer formula
should be appropriate for the feeding level for best growth and performance
results. A variety of formula and feeding rate combinations are available.
There are sizable differences in the economics of different programs. Spending
some time evaluating options can be well worth the effort.
Waste milk. One of the major advantages of milk replacer
over waste milk is that it is a commodity with a known nutrient profile that
can easily be adjusted to achieve specific results. Waste milk, on the other
hand, can be quite variable over time, even from day to day. Although a gallon
of waste milk will typically provide more nutrients than a gallon of a 20/20
milk replacer reconstituted to label specifications, the nutrient variability
can cause digestive challenges and upsets. If waste milk variability is an
issue, adjusting the solids content to a specific level by using appropriate
amounts of a milk replacer, fortifier or extender can reduce nutrient
fluctuations. Waste milk is also a potential source of bacteria and pathogens
that can have a deleterious effect on intestinal health. Although
pasteurization does not eliminate all bacteria from waste milk, it is an
important safeguard with major impact on calf health. Scours.
Although the subject of calf scours was previously reviewed,
management philosophies and approaches to scour treatments are quite variable
and deserve an additional mention. While scours volume and consistency are
important measures, they should not be the focus of attention. As previously
mentioned, effective rehydration therapy often increases the amount of water
passing through the calf. Basically, it is just simple mathematics. Water loss
and intestinal damage due to the pathogen plus decreased ability to fully
absorb the electrolyte solution equals increased water loss. This result runs
counter to the desire to reduce output and solidify manure, and may lead to a
reluctance to implement effective rehydration practices. Something is obviously
out of perspective when 1 in 10 pre-weaned dairy heifers in the U. S. dies,
most likely from scours. Implementing an effective rehydration program can
certainly be a step toward reducing calf mortality.
From a practical standpoint, calf attitude will likely be a more realistic
early measure of treatment progress. As rehydration is achieved and healing
progresses, improvements in output volume and consistency will follow. Creating
an environment for healing should be the focus of a rehydration/scours
treatment program.
Electrolyte solutions should be formulated to maximize water absorption and
facilitate gut repair. A proper balance of sodium, glucose and amino acid(s)
facilitate water absorption. Adequate levels of chloride and potassium help
replenish the major electrolytes involved in water balance within the body. A
brief review of several ingredients/supplements that facilitate gut repair and
a return to normal function is provided in the next section. Several of these
supplements can be incorporated into electrolyte products.
Ingredients/Supplements
Many ingredients and products are now available that demonstrate beneficial
effects in the calf's digestive tract. The following list provides a brief
description of several of the more common ingredients or supplements fed to
calves to enhance or complement digestive and absorptive functions.
Direct-Fed Microbials (DFMs). DFMs are beneficial organisms
that colonize in the digestive tract, produce organic acids and other
beneficial compounds and compete against pathogens. A wide variety of organisms
are used as DFMs. The primary DFMs used to colonize the small intestine are
lactic acid bacteria (LAB). They are very rapid colonizers in the small
intestine and compete very effectively against pathogens such as E coli.
LAB have also been shown to enhance the production of protective mucin in the
small intestine.
Fructooligosaccharides (FOS). FOS are naturally occurring
plant sugars that provide a source of nutrients for beneficial bacteria in the
large intestine such as Bifidobacteria. FOS have been shown to increase
volatile fatty acid (VFA) production in the large intestine and improve calcium
and magnesium absorption. FOS cannot be digested by the animal or by pathogenic
bacteria.
Mannan oligosaccharides (MOS). Mannan oligosaccharides
contain yeast cell wall fragments. These fragments contain mannans which
competitively bind gram negative bacteria, preventing their attachment to the
intestinal mucosa. Since mannans are not digestible in the intestine, the bound
pathogen likely passes through the digestive tract. MOS may also stimulate
antibody production and enhance intestinal structure and function.
Plant extracts/spices. This group of feed ingredients
includes allicin (garlic extract) and a variety of spices. These ingredients
vary in their modes of action but proposed activities include stimulation of
digestive enzymes, antimicrobial activity, immune stimulation, improved VFA
production and feed intake enhancement.
Animal Plasma. Animal plasma is obtained by centrifuging
whole blood into its major components, plasma and blood cells. The two main
types of animal plasma are bovine (ruminant) and porcine (swine). These
products provide a source of both protein and immunoglobulins, primarily IgG
and are usually added to milk or milk replacer. In the digestive tract, IgG has
a direct affect on pathogens and may also have a direct effect on the
intestinal mucosa.
Glutamine/Glutamate are amino acids that have been shown to
improve villi height and overall intestinal morphology during periods of stress
and following injury. Both glutamine and glutamate provide a local fuel source
for enterocytes, the absorptive cells of intestinal villi.
References and Reviews
1. Austgen, L; Bowen, R.A; Rouge, M. Pathophysiology of the digestive system.
Colorado State University. 2001. http:/arbl.cvmbs.colostate.edu/hbooks.
2. Ayabe, T., D.P. Satchell, C.L.Wilson, etc. Secretion of microbicidal
alpha-defensins by intestinal Paneth cells in response to bacteria. Nature
Immunol 1: 113-118, 2000.
3. Fisher, E.W.; McEwan, A.D. Death in neonatal calf diarrhoea. Pt. II: The
role of oxygen and potassium. Br. Vet. J. 123:4-7, 1967.
4. Hecht, G. Innate mechanisms of epithelial host defense: spotlight on
intestine. Am J Physiol Cell Physiol 227:C351-C358, 1999
5. Heinrichs, A.J., C.M. Jones, B.S. Heinrichs: Effects of mannan
ologosaccharides or antibiotics in neonatal diets on health and growth of dairy
calves. J Dairy Sci 86:4064-4069, 2003
6. Karam, S. Lineage commitment and maturation of epithelial cells in the gut.
Frontiers in Bioscience 4:d286-298, 1999.
7. Lillard, J.R., P.N. Boyaka, O. Chertov, etc. Mechanisms for induction of
acquired host immunity by neutrophil peptide defensins. Proc Natl Acad Sci
96:651-656,1999.
8. Stappenbeck, T.S., L.V. Hooper, J.I. Gordon: Developmental regulation of
intestinal angiogenesis by indigenous microbes via paneth cells. Proc Natl Acad
Sci Nov. 2002
9. Naylor, J.M: A retrospective study of the relationship between clinical
signs and severity of acidosis in diarrheic calves. Can. Vet. J., 1989;
30:577-580.
10. Naylor, J.M: Severity and nature of acidosis in diarrheic calves over and
under one week of age. Can. Vet. J., 1987; 28:168-173.
11. Tarver, A.P., D.P. Clark, G. Diamond, etc: Enteric beta-defensin: molecular
cloning and characterization of a gene with inducible intestinal epithelial
cell expression associated with cryptosporidium parvum infection.
Infection and Immunity 66:1045-1056, 1998.
12. Tyler, Howard: Personal communication. Iowa State University, Ames Iowa.
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