Digestion and Absorption Processes in the Gastrointestinal Tract Lecture (TEST 2) Flashcards
Digestion and Absorption are the ultimate function of the GI
1) DIGESTION begins in the Stomach and is COMPLETED in the Small Intestine
2) ABSORPTION takes place Primarily in the Small Intestine
- Movement of Nutrients, H2O, and Electrolytes from the Lumen of the Intestine into the Blood
Two Main paths of Absorption:
1) CELLULAR:
- Lumen —> Apical Membranes —> Intestinal Epithelial Cell —> Basolateral Membrane —> Blood
- TRANSPORTERS in Membranes
2) PARACELLULAR (Across an Epithelium)
- Intestinal Epithelial Cell —> Lateral Intercellular Space —> Intestinal Epithelial Cell
- TIGHT JUNCTIONS!!!!
Enzymes Secreted along the GI Tract are key for the Digestion of Nutrients
- Amylase
- Pepsin
- Gastric Lipase
- Trypsin
- Chymotrypsin
- Carboxypeptidase
- Elastase
- Enterokinase (ENTEROPEPTIDASE)
- Maltase
- Sucrase
- Aminooligopeptidase
There is two types of Digestive Activity
1) CAVITAL (Luminal) Digestion:
- Refers to Digestion resulting from the action of Enzymes Secreted by the Salivary Glands, Stomach, and Pancreas
2) MEMBRANE (Contact) Digestion
- Refers to Hydrolysis by Enzymes synthesized by Epithelial Cells
Structure of the Intestinal Mucosa is ideal for Absorption of Large amount of Nutrients
- The surface of the Small Intestine is arranged in LONGITUDINAL FOLDS- Folds of KERCKRING!!!!!!!!!!
- Willi and Microvilli INCREASE Surface Area of the Small Intestine
- Villi are Longest in the DUODENUM and Shorter in the Terminal ILEUM!
Villi and Microvilli INCREASE the Intestine Total Surface Area by 600 fold!!!!!!!!!!!!!!**
The Microvillar Surface
- Is the site of activity for a number of DIGESTIVE ENZYMES
- Is also the Barrier that must be TRAVERSE by Nutrients, Water, and Electrolytes on the way to the Blood or Lymph
Several Cell Types compose the Intestinal Epithelium
1) ENTEROCYTES: Epithelial Cells
- Function in Digestion, Absorption, and Secretion
- Turnover Rate; Cells are replaced 3 to 6 days!!!!!!
- Susceptible to Irradiation and Chemotherapy
2) GOBLET CELLS: Mucus secreting Cells
- Physical, Chemical, and Immunologic Protection
3) PANETH CELLS
- Part of the Mucosal Defenses against Infection
- Secrete agents that DESTRUCT BACTERIA or produce Inflammatory responses
The Enterocyte Membrane Control the Flux of Solutes and Fluid between the Lumen and Blood
How the Enterocyte Membrane does it?
1) PINOCYTOSIS
- At the Base of the MICROVILLI
- Major Mechanism in the UPTAKE of Protein
2) PASSIVE DIFFUSION
- Particles move through pores in the Cell Membrane or through Intercellular Spaces
3) FACILITATED DIFFUSION
4) ACTIVE TRANSPORT
Transmural Movement takes place during Absorption
Solute moving across the Enterocyte, from the Lumen to the Blood, must cross SEVERAL BARRIERS:
- Unstirred layer to Fluid
- Glycocalyx
- Apical Membrane
- Cytoplasm of the Cell
- Basolateral Membrane
- Basement Membrane
- Wall of Blood Capillary or Lymphatic Vessel
Digestion and Absorption processes Exhibit Adaptions
- Adaptions are alterations in Function to MAINTAIN HOMEOSTASIS
- The Capacity of the Intestine to adapt is KEY in Several Clinical Scenarios
a) Small Bowel Resection
b) Bypass - Adaptation is limited in Some Instances
a) If Terminal Ileum is resected, Absorption of Vitamin B12 and Bile Salts to abolished - Certain Genetic Abnormalities lead to a LOST ADAPTATION
a) Ex: Lactase Deficiency
Only Monosaccharides are Absorbed by the Enterocytes
- All ingested Carbohydrates must be Digested to MONOSACCHARIDES
- Three ends products of Carbohydrate Digestion:
1) Glucose
2) Galactose
3) Fructose
Co-transport and Facilitated Diffusion are Key Transport Mechanisms in the Absorption of Carbohydrates
APICAL SURFACE:
1) Glucose and Galactose use a SGLT1 Transporter (Secondary Active Transport) to get into the Cell
* Carbohydrate goes against gradient while Na+ goes with Gradient***
2) Fructose uses GLUT 5 (Facilitated Diffusion) to get into the cell
BASOLATERAL SURFACE:
1) Glucose, Galactose, and Fructose all use the GLUT 2 transporter to get into the blood
Lactose Intolerance is a Common Example of Failure to Digest Carbohydrates
- Brush Border LACTASE is Deficient or Lacking
- Undigested Lactose remains in the Lumen and holds H2O, and causes OSMOTIC DIARRHEA!!!!!!!
- Undigested and Unabsorbed LACTOSE is fermented into Methane and Hydrogen Gas, causing EXCESS GAS!!!
Ingested Proteins are digested to Absorbable forms by Proteases in the Stomach and Small Intestine
STOMACH:
1) Pepsinogen –(low pH)–> Pepsin
SMALL INTESTINE
1) Trypsinogen — (ENTEROPEPTIDASE in Brush Border)—–> TRYPSIN
2) Trypsin creates:
a) Trypsin (again)
b) Chymotrypsin
c) Elastase
d) Carboxypeptidase A
e) Carboxypeptidase B
ENDOPEPTIDASES:
- Pepsin
- Trypsin
- Chymotrypsin
- Elastase
EXOPEPTIDASES:
- Carboxypeptidase A
- Carboxypeptidase B
Ingested Proteins are digested to Absorbable forms by Proteases in the Stomach and Small Intestine
1) Protein —-> Amino Acids/ Oligopeptides
- Facilitated by PEPSIN!!!!!!
2a) Protein —-> AA, Dipeptide, Tripeptide
- Facilitated by Trypsin, Chymotrypsin, Elastase, Carboxypeptidaase A, Carboxypeptidase B (Lumen)
2b) Protein —->Oligopeptides
- Facilitated by Trypsin, Chymotrypsin, Elastase, Carboxypeptidaase A, Carboxypeptidase B (Lumen)
3b) Oligopeptides —> AA, Dipeptide, Tripeptide
- Facilitated by PEPTIDASE (Brush Border)
***Trypsin catalyzes the HYDROLYSIS of Trypsinogen (Autocatalysis)
*****The Pancreatic Proteases digest themselves and Each other
Co-transport and Facilitated Diffusion are Key transport Mechanisms in the Absorption of Proteins
***There are 4 separate COTRANSPORTERS: one for each NEUTRAL, ACIDIC, BASIC, and IMINO Amino Acid!!!!!!!!!
***There are 4 separate FACILITATED DIFFUSION Mechanisms: One for each NEUTRAL, ACIDIC, BASIC, and IMINO Amino Acid!!!!!
Disorders or Protein Assimilation
- Occurs when terse is a Deficiency of PANCREATIC ENZYMES or a Defect in Transporters of the Intestinal Epithelial Cells
1) CHRONIC PANCREATITIS and CYSTIC FIBROSIS: - Deficiency pf Pancreatic Enzymes
2) CONGENITAL TRYPSIN ABSENCE
- In the Absence of Trypsin it seems like all the Pancreatic Enzymes are gone, Why? Because Trypsin cleaves all of the Pancreatic Enzymes into their active forms
3) CYSTINURIA:
- Defect in or Absence of Na+ Amino Acid Cotransporters
- Transporter for DI-BASIC Amino Acids (Cystine, Lysine, Arginine, Ornithine) is ABSENT form the Small Intestine and Kidney
- GENETIC DISORDER
- As a Result of the Intestinal Deficiency, Amino Acids are SECRETED IN FECES
Hartnup Disease
- Cannot ABSORB NEUTRAL AMINO ACIDS (Ex Tryptophan)
- RECESSIVE Genetic Disorder (SLC6A19 Gene)
- Symptoms resemble those caused by PELLAGRA (Deficiency of NIACIN)
- Urine Sample from Hartnup Disease patient reveal an ABNORMALLY HIGH EXCRETION of NEUTRAL AMINO ACIDS (Tryptophan) and their Byproducts (Serotonin)
Symptoms may include:
- Diarrhea
- Mood Changes
- Neurologic Problems, such as Abnormal Muscle Tone
- Red, Scaly Skin Rash, Usually when skin is Exposed to Sunlight
- Photosensitivity
- Short Stature
- uncoordinated Movements
Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator is associated with Deficiency of Pancreatic Enzymes
- *****CYSTIC FIBROSIS Transmembrane Conductance Regulator (CFTR):
- Regulated ANION Channel that is located at the Apical Surface of the Duct Cell. CHLORIDE ION CHANNEL!!!!!!!
- The Pancreas is one of the First Organs to FAIL in CYSTIC FIBROSIS
- Some CFTR Mutations seem to be associated with a LOSS of Bicarbonate Secretion
- Ability to FLUSH Active Enzymes out of the Duct MAY BE LOST!!!
- May lead to RECURRENT ACUTE and CHRONIC PANCREATITIS
Ingested Lipids are Digested to Absorbable forms by Lipases in the Stomach and Small Intestine
Insolubility of Lipids Complicates their Assimilation:
- Lipids NEED TO BE SOLUBILIZED in MICELLES and transported to the Apical membrane of Intestinal Epithelial Cells for ABSORPTION
Products of Lipid Digestion are Solubilized in MIXED MICELLES*
Stomach and Lipid Digestion
- Lingual and Gastric Lipases INITIATE Lipid Digestion in the Stomach
a) 10% of Ingestin Triglycerides are HYDROLYZED to Glycerol and Fatty Acids
b) Lipids are broken down into SMALL DROPLETS
c) Lipid Droplets are EMULSIFIED in the Stomach
d) No Bile acids in the Stomach, so DIETARY PROTEINS Perform the EMULSIFYING Action
- In order to allow Sufficient time for Lipids to get digested properly, CCK is released, slowing the rate of Gastric Emptying
- CCK is SECRETED when Dietary Lipids first appear in the Small Intestine
Small Intestine and lipids Digestion
- Most lipid Digestion OCCURS IN THE SMALL INTESTINE
- Bile Salts EMULSIFY LIPIDS
- Pancreatic Enzymes are Secreted into the Small Intestine to COMPLETE THE DIGESTIVE WORK
1) PANCREATIC LIPASE (Secreted as ACTIVE Enzyme):
- Inactivated by BILE SALTS but COLIPASE solves this problem
* The Optimum pH for Pancreatic Lipase is 6!!!!!!!!!*******
2) COLIPASE:
- Secreted in PANCREATIC JUICE in an INACTIVE FORM (Procolipase)
- Secreted as Inactive Form, it is activated by TRYPSIN
- Once activated, it binds to PANCREATIC LIPASE Displacing Bile Salts
3) CHOLESTEROL ESTER HYDROLASE:
- In addition to Catalyze the production of Cholesterol, it also HYDROLYZES TRIGLYCERIDES to PRODUCE GLYCEROL
4) PHOSPHOLIPASE A2
- Its PROENZYME is activated by TRYPSIN!!!!!
Mechanisms of processing Lipids are more complex than those for Carbohydrates and Proteins
1) Solubilization by MICELLES
2) Diffusion of Micellar Content across
3) Reesterification
4) Chylomicron Formation
* No ApoB leads to ABETALIPOPROTEINEMIA, which means there is no ABSORPTION of Dietary lipids!!!!!!**
5) Exocytosis of Chylomicron
Disorder of Lipid Assimilation
Abnormalities can occur in any of the Key Steps in lipid Formation:
- Pancreatic Enzyme Secretion
- Bile Acid Secretion
- Emulsification
- Micelle formation
- Diffusion of Lipids into Intestinal Epithelial Cells
- Chylomicron formation
- Transfer of Chylomicrons into Lymph
An ABRNOMALITY in any of these steps results in STEATORRHEA!!!!!!!!*****
Abnormalities in Pancreatic Enzyme Secretion
1) PANCREATIC INSUFFICIENCY: Failure to secrete adequate amounts of Pancreatic Enzymes
2) Regulation of the acidity of DUODENAL Content is CRITICAL for the Integrity of Pancreatic Enzyme Function
a) Duodenum needs to be adequately NEUTRALIZED by HCO3-, containing Pancreatic Secretions
3) ZOLLINGER-ELLISON SYNDROME:
- GASTRIN Secreting Tumor of the Pancreas
- INCREASE H+ Secretin by Gastric Parietal Cells
- Overload of Acid in the Duodenum
4) PANCREATITIS:
- Impaired HCO3- Secretion
- Impaired Enzyme Secretion
Deficiency of Bile Salts
- Interferes with the formation of MICELLES
Examples of Factors that cause Deficits in Bile Salts:
1) ILEAL RESECTION interrupt the ENTEROHEPATIC CIRCULATION of BILE SALTS
- Total Bile Salt pool is REDUCED!!!!
2) SMALL INTESTINAL BACTERIAL OVERGROWTH
- The Bacteria DECONJUGATE Bile Salts, causing Failure of Micelle formation and subsequent Fat Malabsorption
- Severe Bacterial Overgrowth also damages the Intestinal Mucosa
- To main causes are: DECREASED Gastric Secretion and Small Intestine Dysmotility
- Clinical presentation varies, from patient being only MILDLY Symptomatic to Suffering from CHRONIC DIARRHEA, Weight Loss, and Malabsorption
Decreased Intestinal Epithelial Cells affects Lipid Absoprtion
1) TROPICAL SPRUE:
- Reduction in the number of Intestinal Epithelial Cells which in turn REDUCES the MICROVILLAR SURFACE AREA
- The Cause of TROPIC SPRUE has NOT BEEN IDENTIFIED, but many experts suspect that an Intestinal Infection is to Blame
- LIPID ABSOPRTION is IMPAIRED because the SURFACE AREA for ABSORPTION is DECREASED!!!!!!!
(STEATORRHEA) - Nutritional Deficiencies, ESPECIALLY of FOLATE and VITAMIN B12
- Diarrhea is the Main Symptom
- Other Symptoms include Cramps, Nausea, Weight Loss, Gas, and Indigestion
- Treatment is with TETRACYCLINE and FOLATE FOR 6 MONTHS!!!!!!!!!
Deficits in Digestion and Aborption cause Malabsorption
Stomach:
- Decreased Churning
- Decreased Acid Secretion
Duodenum:
- Decreased Enzyme Secretin (Primary Duodenal, Pancreatic, or Biliary Disease)
Jejunum:
- Decreased Surface Area
- Decreased Transport Lymphatic Obstruction
Vitamins must be acquired from the Diet and absorbed by the GI Tract
FAT SOLUBLE VITAMINS:
- A, D, E, and K
- Same mechanism of Absorption as Lipids
WATER SOLUBLE VITAMINS:
- B1, B2, B3, B12, C, Biotin, Folic Acid, Nicotinic Acid, and Patothenic Acid
- Most of them are Absorbed via a Na+ Dependent COTRANSPORT Mechanism in the Small Bowel
- VITAMIN B12 (COBALAMIN) form complexes with other proteins in order to be Absorbed:
a) R PROTEINS (Secreted in Salivary Juices)
b) INTRINSIC FACTOR, IF (Secreted by Gastric Parietal Cells)
c) TRANSBCOBALAMIN II
Disruption in the Absorption of Vitamin B12
- GASTRECTOMY: Loss of Pareital Cells, he source of IF
- GASTRIC BYPASS: Exclusion of the Stomach, Duodenum, and Proximal Jejunum alters Absorption of Vitamin B12!!!!!
Pernicious Anemis is a type of Vitamin B12 Anemia
- Stomach DOES NOT Produce enough IF, therefore there is a DECREASE in Vitamin B12
Common Causes of Pernicious Anemia:
1) ATROPHIC GASTRITIC in which there is Chronic Inflammation of the Stomach Mucosa, leading to LOSS of PARIETAL CELLS
2) An AUTOIMMUNE CONDITION in which the Immune System attacks IF Protein of Gastric Parietal Cells (Autoimmune Metaplastic Atrophic Gastritis)
Mechanisms and Abnormalities in the Absorption of Vitamin D
Mechanisms:
- Needs active Vitamin D (1,25 Dihydroxy Cholecalciferol) to absorb Calcium!!!
Vitamin D is activated by 1 alpha Hydroxylase!!!!!!**
Abnormalities:
- Inadequate Ca2+ Absorption:
1) Rickets (Children)
2) Osteomalacia (Adults)
Stomach and Lipid Digestion
1) Lingual and Gastric LIPASES INITIATE Lipid Digestion in the Stomach
- 10% of Ingested Triglycerides are HYDROLYZED to GLYCEROL and FATTY ACIDS
- Lipids are Broken Down into SMALL DROPLETS
- Lipid Droplets are EMULSIFIED IN THE STOMACH
- ** NO BILE ACIDS in the Stomach, Dietary Proteins PERFORM the EMULSIFYING ACTION
2) In order to allow Sufficient time for Lipids to get DIGESTED PROPERLY, CCK is Released, SLOWING THE RATE of Gastric Emptying
- CCK is Secreted when Dietary lipids first appear in the Small Intestine
Small Intestine and Lipid Digestion
- MOST LIPID DIGESTION Occurs in the SMALL INTESTINE
- Bile Salts EMULSIFY LIPIDS
- PANCREATIC Enzymes are SECRETED into the Small Intestine to COMPLETE the Digestive Work
1) PANCREATIC LIPASE (Secreted as the ACTIVE ENZYME)
- INACTIVATED by Bile Salts; COLIPASE solves this Problem
2) COLIPASE:
- Secreted in PANCREATIC JUICE in an INACTIVE form (Procolipase)
- Secreted as Inactive form, and is ACTIVATED by TRYPSIN
- Once activated, it binds to PANCREATIC LIPASE displacing BILE SALTS
3) CHOLESTEROL ESTER HYDROLASE
- In addition to CATALYZING the Production of Cholesterol, it also HYDROLYZES TRIGLYCERIDES to PRODUCE GLYCEROL
4) PHOSPHOLIPASE A2
- Its PROENZYME is ACTIVATED by TRYPSIN!!!!!
**The OPTIMUM pH for PANCREATIC LIPASE is 6!!!!!!!!!!***
Non- Tropical Spure (CELIAC DISEASE)
- AUTOIMMUNE DISORDER
- It is thought to BEGIN in CHILDHOOD with the Introduction of WHEAT GLUTEN
- Antibodies develop against a component of Gluten - GLIADIN - that leads to Destruction of the Villi in the Small Intestine (ATROPHY) as well as HYPERPLASIA of the INTESTINAL CRYPTS
- MALABSORPTION related to Deficiencies in VITAMIN B12, FOLATE, IRON, CALCIUM, VITAMIN D, and VITAMIN A
Prevalence:
A) Most Common in CAUCASIANS and person of EUROPEAN ANCESTRY
B) WOMEN are AFFECTED MORE OFTEN than Men
- There is a HEREDITARY COMPONENT
Some GI Symptoms:
- Abdominal Pain
- Constipation
- Diarrhea
- Unexplained Wight Loss
- Vomiting and Nausea
- Steatorrhea
Other Symptoms related to Malabsorption of Nutrients:
- Tingling or Numbness in the Hands or Feet
- Itchy Skin with a Rash
- Fatigue
- Seizures
- Easy Bruising
- Bone Fractures
Major Cancers associated with ZONULIN (Pre-HP2)
- Brain Cancers (Gliomas)
- Breast Cancers
- Lung Adenocarcinoma
- Ovarian Cancer
- Pancreatic Cancer
Zonulin: is a protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract
Major Cancers associated with Chromosome 16
- Acute Nonymphocytic Leukemia
- Breast Cancer
- Fanconi’s Anemia
- Lymphoma, Diffuse Large B Cell
- Myeloid Leukemia, Acute
- Prostate Cancers
Travel of B12
1) MOUTH
- Unbound B12 may be ABSORBED UNDER the TONGUE
2) STOMACH
- Enzymes and Acid cause PROTEIN-BOUND B12 to DETACH from Protein
- R PROTEIN PICKS UP B12
- IF SECRETED
3) UPPER SMALL INTESTINE
- R PROTEIN Releases B12
- IF PICKS UP B12
4) LOWER SMALL INTESTINE
- IF-B12 attaches to IF-B12-RECEPTOR on Intestinal Cell
- Some UNBOUND B12 ABSORBED into Intestinal Cell through Passive Diffusion
5) INTESTINAL CELL
- B12 attaches to TRANSCOBALAMIN II
6) BLOOD
- TRANSCOBALAMIN II carriers B12 to the Body’s Cells where it is used, and to the Liver where it is Stored on TRANSCOBALAMIN II
- TRANSCOBALAMIN III also Circulated in the Blood
7) LIVER
- B12 is STORED and RELEASED into the Small Intestine via the BILE
