Material de estudio Trabajo Practico Regulacin de la glicemia

BIO135c

Why Understanding Carbohydrate Digestion, Absorption and

Metabolism is Important in Nursing
Malnutrition is a common problem that is encountered frequently, both among
patients and also friends. Whereas once malnutrition and starvation were
associated in our minds, increasingly we think of obesity and diabetes in
association with malnutrition. To understand these problems and their
management, it is essential to understand the fundamental physiology of
digestion, absorption and metabolism of carbohydrates and how this is
controlled.

A little history
Banting and Best are usually given the credit for the discovery of insulin. What
they in fact discovered was a way to extract insulin from pancreatic islet cells
without the pancreatic enzymes breaking it down. In 1922, they injected insulin
extracted from ox pancreas into a patient, resulting in complete reversal of the
symptoms and restoration of normal blood glucose levels.
It is difficult for us now to appreciate the impact of this discovery. Overnight, an
inevitably fatal disease affecting children was curable. From this time until the
1980s, pork and beef insulin was used to keep patients healthy. Then,
recombinant insulin and long-acting insulin were prepared, making glucose
control easier. Nurses are increasingly playing a central role in talking to
patients and educating them about taking control of their glucose.
A fascinating archive documenting the discovery and early development of
insulin, complete with photos and details of some of the experiences of early
patients, is found at http://link.library.utoronto.ca/insulin/

Claude Bernard (18131878), a preeminent French physiologist, discovered the role of the liver in storing and
synthesizing glucose in 18489.

Digestion
Ingested nutrients, ions and water are absorbed from the gastrointestinal (GI) tract. Complex carbohydrates,
proteins and fats must be digested into substances which can be absorbed and assimilated by the body. The
digestive process begins in the mouth where nutrients are mixed with saliva, which contains the enzyme
amylase, and carbohydrate digestion begins. The stomach secretes hydrochloric acid (HCl) that denatures
protein and is bactericidal, protecting the intestine from any potentially infectious agents. The stomach also
secretes pepsin, which initiates protein digestion.
The bulk of digestion occurs in the small intestine, which is divided into three areas: the duodenum, jejunum
and ileum. The enzymes amylase and lipase are secreted from the pancreas into the duodenum, and bile is
released from the gall bladder, which assists in lipid digestion. The final stages of digestion occur at the
intestinal epithelial cell surface where enzymes on the microvilli complete the digestion of carbohydrates and
proteins. The jejunum is the major site of absorption of digested nutrients, ions and water.

Figure 1. The major divisions of the gastrointestinal tract.

What Determines the Rate of Absorption of Nutrients?

The rate of nutrient absorption is limited by the rate at which the ingested food is delivered to the duodenum
from the stomach, and the rate at which it is absorbed in the jejunum. The rate of gastric emptying is
determined by the consistency and the nature of the ingested food. As the stomach fills with food and drink,
distension of its walls, together with a variety of nervous and hormonal inputs, results in increased gastric
motility. Liquid leaves the stomach much faster than solid material does. The presence of fat in a meal delays
gastric emptying

Figure 2. Effects of fat on the rate of gastric emptying

Figure 3. Rate of gastric emptying after a typical meal.

Between contractions, the pyloric sphincter is relaxed. As a peristaltic wave spreads over the surface of the
stomach, the stomach contents (chyme) are propelled towards the pyloric sphincter. However, the sphincter
contracts before the bulk of this chyme can pass through it. Thus, with each contraction, only a very small
percentage of the total gastric contents pass into the duodenum. The rest, hitting a closed sphincter, is
propelled back into the body of the stomach (a process referred to as retropulsion), causing mixing and
breakdown of the material. The more liquid the stomach contents are, the greater the amount that can pass
into the duodenum with each contraction.

As chyme enters the duodenum, its volume and composition, including acidity, are monitored.

Enteric nervous reflexes are initiated these reflexes may be either intrinsic or extrinsic. Intrinsic

reflexes have a direct effect on the gut, while extrinsic reflexes require mediation by the central nervous system
for an effect on the gut.
Hormones (cholecystokinin and secretin) are released; these adjust the rate of gastric emptying to
match the duodenums ability to handle the load being delivered to it.
The rate of digestion is determined by the amount of enzymes secreted by the pancreas and the nature of the
material to be digested. For example, complex carbohydrates such as starch will take longer to digest than
disaccharides. Monosaccharides like glucose require no digestion and start to be absorbed immediately.

Figure 4. Chemical structure of glucose, C6H12O6.

Figure 5. Schematic showing the branched structure of polysaccharides, starch and glycogen

Effects of Glucose in the Intestinal Lumen

The presence of glucose in the lumen stimulates the release of the incretins, which are GI hormones that
stimulate insulin release from pancreatic -cells. Two established incretins are glucose-dependent
insulinotropic peptide (also known as gastric inhibitory peptide) and glucagon-like peptide-1 (GLP-1). Thus,
before glucose is absorbed to any extent, circulating insulin levels are elevated. The enteric nervous system
(the gut part of the autonomic nervous system) also plays a role in regulating the release of hormones from the

pancreas after a meal. In addition, the parasympathetic system stimulates insulin release whereas the
sympathetic system stimulates glucagon release and inhibits insulin release.

Figure 6. Schematic of histology of the small intestine.

Carbohydrate Absorption
The wall of the small intestine is made up of finger like projections called villi that increase the small intestinal
surface area. These villi are covered with epithelial cells. The luminal membrane of each epithelial cell is
covered with microvilli. These are responsible for the brush border appearance of the luminal surface of the
small intestine. The microvilli contain disaccharidases that convert disaccharides to monosaccharides for
absorption. Starch digestion generates maltose which is cleaved by a maltase, producing two molecules of
glucose.
Glucose is absorbed from the intestine together with sodium. This is why rehydration fluids for the treatment of
diarrhea contain sodium as well as glucose.

The fate of the absorbed glucose

Normally, glucose is not metabolized to any extent by the intestinal cells themselves. Instead it is transferred to
the interstitial fluid surrounding the intestinal epithelial cells. From there it diffuses into portal vein capillaries to
be taken first to the liver before entering the systemic circulation. Of the glucose load absorbed, about one
third is taken up by the liver, one third is taken up into skeletal muscle and fat cells by GLUT 4, which is
an insulin-dependent glucose transporter, and one third enters tissues such as the brain which do not
require insulin for glucose uptake (Figure 7).

Figure 7. Distribution of an oral glucose load over a 4 hour period.

Regulation of Carbohydrate Metabolism

1.

2.

Two hormones that are released from the Islets of Langerhans in the pancreas are involved in the reciprocal
regulation of carbohydrate metabolism:
Insulin can be regarded as the hormone of plenty it is secreted when there are nutrients that need
to be stored away. It is released from the pancreatic -cells into the blood stream. It causes uptake of glucose,
amino acids and lipids into cells, and promotes the conversion of these building blocks into larger molecules
for storage (glycogen, proteins and fats). See Figure 8 below.
Glucagon can be regarded as the hormone of starvation. It is released from pancreatic -cells
and promotes release into the blood stream of glucose, amino acids and lipids, and the breakdown of stored
carbohydrates, protein and fats.

Figure 8. Graph showing the relationship between blood glucose and insulin following normal, high starch
meals. Note that the dotted lines show the more rapid rise in glucose and insulin levels in response to sugary
foods

Figure 9. Histological section of a pancreas showing an Islet of Langerhans (1) and exocrine acinar cells (2)

Hormonal Control of Blood Glucose Levels

After a meal, the rise in blood glucose further stimulates pancreatic insulin release, while the release of
hormones that tend to elevate blood glucose levels (including glucagon, epinephrine, growth hormone and
cortisol) is inhibited. The uptake of glucose by the liver in the presence of insulin results in inhibition
of glycogenolysis and gluconeogenesis, and the stimulation of glycogen synthesis. Thus a large fraction of the
dietary intake of glucose is stored for subsequent use when the blood glucose level falls again.

Renal Handling of Glucose

Normally, all glucose filtered at the glomerulus is reabsorbed by the end of the proximal tubule. The filtered
glucose can only be reabsorbed at a set rate by the cells of the renal tubule. When glucose levels go above
around 11 mmol per liter (such levels are often seen in type 1 diabetics and can also occur in type 2 diabetics),
the cells of the kidney reach what is known as their transport maximum, and cannot reabsorb the
glucose. The remaining glucose then appears in the urine (glycosuria). The osmotic effect of all of this extra
glucose holding onto water also explains why diabetics can have polyuria (large amounts of urine) and become
so dehydrated that their lives are endangered.
Note that the blood glucose concentration has to virtually double from the normal range of 5-6 mmol/L before
any glucose starts to appear in the urine. Because, in a healthy person, insulin is released following a meal,
the absorbed glucose is rapidly taken up by cells, blood glucose does not rise that much and the kidneys
transport capacity for glucose is not exceeded. Thus we retain all the glucose that we absorb from the food we
eat.

Disorders of Glucose Metabolism

Diabetes Mellitus
In Type 1 diabetes mellitus, there is a decrease in insulin production by the pancreatic islet cells as a result of
an autoimmune response that destroys the cells. In Type 2 diabetes, there is a decrease in the effectiveness of

insulin receptors in tissues that may eventually be associated with decreased insulin production. In both forms
of diabetes, cells are bathed in extracellular fluid with excessive levels of glucose but the reduced entry of
glucose into cells leads to very low glucose levels inside cells, which disrupts normal cellular metabolism.
Diabetes can be described as "a state of starvation in a sea of plenty".
Type 1 diabetes can develop very rapidly and often begins in childhood. As insulin levels fall,
liver gluconeogenesis predominates, and blood sugar rises. Symptoms include polyuria (from glucose in the
urine, excreted with water), dehydration and weight loss (from loss of water and disturbed metabolism), hunger
and tiredness. If the diabetes is left untreated, the compensatory increase in fatty acid metabolism that occurs
when cell glucose is low, leads to ketoacidosis, coma and death.
Type 2 diabetes usually develops more slowly and is often diagnosed from blood glucose elevation in a routine
medical checkup. Ketoacidosis is rare.

Diagnosis
The diagnosis of diabetes is made from blood glucose levels. A fasting level above 7 mmol/L (126 mg/dL) is
indicative of the disease. It can be confirmed by a glucose tolerance test where a standard oral dose of 75 g
glucose is given and blood levels followed over the next two to three hours. Commonly samples are now taken
just before the dose and two hours after it. A blood glucose 11.1 mmol/L (200 mg/dL) or higher confirms the
diagnosis.
Measurements of glycosylated (glycated) hemoglobin (HbA1c) are used to follow how well blood sugar is
controlled in diabetics. Normal human red blood cells have a life span of 120 days. During this time, some
hemoglobin molecules react non-reversibly with glucose forming glycated hemoglobin. The higher the glucose
concentration, the higher the levels of HbA1c formed during the life of the cell. HbA1c was expressed as
a percentage but it is now recommended that it be expressed as mmol/mol of Hb. Normal values range
between 4.06.0 % or 2042 mmol/mol.

Complications of Diabetes
Both Type 1 and Type 2 diabetes are chronic diseases that can result in a variety of serious complications.

Acute complications
These include hypoglycemia and hyperglycemia, as well as ketoacidosis (Type 1) and non-ketotic
hyperosmolar coma (most often seen in Type 2).
Acute hypoglycemia arises when too much insulin is taken. Symptoms result from increased secretion of
hormones that can raise blood glucose (epinephrine, glucagon) e.g. anxiety, tachycardia, sweating, pallor
and from the decreased energy available in the brain e.g. confusion, personality changes, slurred speech,
loss of coordination. If untreated, coma and death can follow.
Acute hyperglycemia occurs when there is insufficient insulin for normal glucose uptake by cells. Symptoms
include polydipsia (excessive thirst) and polyuria (excessive urination). Vision may blur because raised glucose
concentration in the aqueous humor results in changes in lens volume.

Chronic complications
In both Type 1 and Type 2 diabetes, complications include cardiovascular disease, renal failure, eye damage
(cataracts, retinopathy) and neuropathy. Peripheral neuropathy can include disturbances of autonomic function
as well as sensory and motor effects. Damage to tissues and organs is thought to reflect injury to small blood
vessels with capillary basement membrane thickening and endothelial hyperplasia (increased production of
normal cells).

What you will do in the class

During the class you will study the rate of glucose absorption by making serial measurements of blood glucose
levels using a glucose meter (glucometer). This is a device that reads the glucose concentration in a drop of
blood, which is obtained by a finger prick and then placed on a chemically-coated test strip. The test strip is
placed in a glucometer which reads the sample and digitally displays the blood glucose concentration in
mmol/L or mg/dL (US).
For these exercises, it is important not to limit the rate at which the ingested fluid and food reaches the
intestine. To avoid delays in gastric emptying it is essential that all volunteers should have refrained from eating
and drinking for at least two hoursprior to the in-class session!