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Page 1: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Gastrointestinal Physiology IIThe Microbiome, The Liver and The Pancreas

Nancy Long Sieber, PhDDecember 8, 2014

Page 2: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

http://sportsci.org/news/history/beaumont/Wbeaumont.jpg

Dr. William Beaumont with Alexis St. Martin

Brief Historical Interlude…

Page 3: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

St. Martin’s wound

Page 4: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

The Development of the Gut Microbiome

• Colonization of the gut begins with the passage through the birth canal. Maybe even in utero.

• Breastfeeding also supports development of healthy biome.

• Mature biome established by age 2-3, with more diverse diet.

Page 5: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Development of the Gut Microbiome

From: “Diet and the development of the human intestinal microbiome” by Noah Voreades, Anne Kozil, abd Tiffany L. Weir.  Front. Microbiol., 22 September 2014

Page 7: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Prebiotic Foods Contain substances that feed your gut bacteria - specifically insoluble fiber from plants.

In addition:Breast milk also contains prebioticsThat support the baby’s microbiome.

Page 8: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

What kinds of physiological responses and diseases are linked to an unhealthy microbiome?

Diarrhea

Obesity and metabolic syndrome

Other inflammatory conditions, especially autoimmune diseases, may also be exacerbated by pro-inflammatory gut bacteria.

Page 9: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Fecal Transplantation

•Used to treat persistent C. difficile infection.

•90% effective

•Other uses?

Page 10: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Important GI Organs:

The Pancreas and the Liver

And, of course,

What can go wrong with them?

Page 11: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

The pancreas releases the major digestive enzymes, which are needed to break down starch, proteins and fats.

Page 12: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Pancreatic enzymes are usually released in an inactive form.

Page 13: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Cystic Fibrosis (CF) and the pancreas•Pancreatic enzyme secretion uses the same CFTR

chloride channel we heard about with cholera

•This channel is defective in people with CF, and causes them to have problems with the digestion of food and absorption of nutrients.

•They need supplemental enzymes

Page 14: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Acute Pancreatitis

• Results from acute inflammation and autodigestion of pancreas• Causes

• Alcohol abuse – activates trypsin intracellularly, also can cause inflammation of the sphincter of Oddi & reduce its tone• Gallstones – can be impacted in the pancreatic duct.

Page 15: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Manifestations of acute pancreatitis:

• Pain• Nausea & vomiting• Fever• Shock• Amylase and lipase in blood• Jaundice• Acidosis• Hyperkalemia

Page 16: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Chronic Pancreatitis

• Characterized by fibrosis and calcification

• Loss of exocrine function

• Usually caused by alcoholism

Page 17: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Pancreatic Insufficiency

•Usually caused by chronic pancreatitis• Leads to :•Malabsorption• Fat in stool (fat not absorbed)• Diarrhea (but not as bad as from intestinal

malabsorption, such as celiac disease)•Can give replacement enzymes

Page 18: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Pancreatic Cancer

•High mortality rate (95%)

•Symptoms usually do not develop until disease has spread.

Page 19: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

The Liver

Page 20: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

The liver does many things:

• Fat digestion – via production of bile• Nutrient storage, synthesis, and mobilization

• Storage of carbohydrates as glycogen and gluconeogenesis• Fat metabolism and cholesterol synthesis• Vitamin and trace mineral storage

• Biotransformation of drugs and toxins• Metabolism of hormones• Production of plasma proteins• Immune surveillance

Page 21: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

http://www.niaaa.nih.gov/Resources/GraphicsGallery/Liver/214c.htm

Page 22: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Kupffer cells stained with vital stain (blue)

Page 23: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.
Page 24: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

http://www.siumed.edu/~dking2/erg/liver.htm

The openings (fenestrations) in the capillaries mean that the hepatocytes are essentially in direct contact with the blood.

Page 25: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Bile duct and sphincter of Oddi

Page 26: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.
Page 27: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.
Page 28: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.
Page 29: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Bile Pigments

• Bile pigments are breakdown products of hemoglobin. Most important is bilirubin.

• The pigments are carried to the liver, where they are combined with bile, and are converted into a form that the body can excrete.

• When this process fails, and bilirubin accumulates in the tissues, it causes the skin and eyes to become yellowish.

Page 30: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Bile Pigments

http://www.mfi.ku.dk/ppaulev/chapter23/images/23-1.jpg

When bilirubin metabolism is insufficient, then bile pigments accumulate in the tissues, giving the skin and eyes a jaundiced (yellowish) appearance.

Page 31: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Cirrhosis of the Liver

Page 32: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Cirrhosis occurs when scarring and fibrosis lead to the death of hepatocytes.

Page 33: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Portal hypertension can cause bleeding into the GI tract, as well as congestion of blood in the spleen, leading to destruction of platelets

http://www.clevelandclinic.org/health/health-info/pictures/tipspre.gif

Page 34: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

The yellow coloring of the eye in a patient with jaundice reflects the accumulation of bile pigments in the connective tissues. Skin also becomes yellowish.

Page 35: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Consequences of Liver Failure•Portal Hypertension – blood backs up into the GI tract•Blood does not pass through liver, so nutrients are

not absorbed, also loss of immune surveillance•Varices•Promotes development of ascites•Congestion of blood in spleen, leads to RBC

destruction

Page 36: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Consequences of Liver Failure, (cont.)

•Ascites formation – watery fluid in the abdominal cavity•Infection•Generalized edema•Neurologic disorders (from accumulation of ammonia and other toxins)

Page 37: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Consequences of Liver Failure, (cont.)•Increased bleeding from • lack of liver-produced clotting factors, • lack of absorption of vitamin K, •hyperactivity of the spleen

•Endocrine disorders•Lack of liver-produced hormone carriers•Inability to degrade estrogen

Page 38: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Consequences of Liver Failure, (cont.)•Manifestations of decreased bile production• Jaundice (build-up of bile pigments leading to

yellowish color of eyes and skin)•Decreased fat absorption (diarrhea, steatorrhea,

deficiencies of fat-soluble vitamins)

Page 39: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Consequences of Liver Failure, (cont.)•Problems with glucose metabolism – sometimes

hypoglycemia (since liver is site of gluconeogenesis, sometimes hyperglycemia (since blood bypasses liver, glucose is not absorbed from it).

•Problems with lipid metabolism – liver is the only place where fatty acid can be converted to ketones, which provide energy during fasting.

Page 40: Gastrointestinal Physiology II The Microbiome, The Liver and The Pancreas Nancy Long Sieber, PhD December 8, 2014.

Consequences of Liver Failure, (cont.)• Increased plasma levels of liver enzymes

(aminotransferase and alkaline phosphatase) are indicators of liver damage

•Problems with salt and water balance – due to lack of albumin and angiotensinogen.


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