Digestion and absorption of the Gastrointestinal Tract Flashcards
Characteristics of Lactose intolerance
Failure in ability to digest dairy carbohydrates
Brush border lactase enzyme activity is deficient or absent resulting in undigested and unabsorbed lactose
Low lactase activity: 75 percent oflactose can pass unabsorbed through the small intestine
Lactose converted to SCFAs and hydrogen gas thus producing acetate, butarate, and propionate
- remains in lumen, holds H20 in lumen leading to osmottic diarrhea
- Ferments into methane and H+ gas
What are the major sugars in human diet?
Primary: Sucrose, lactose, starch
Secondary: amylose, glycogen, EtOH/alcohol, lactic acid, pyruvic acid, pectins, destrins
Cellulose: no digestive enzymes
where does carbohydrate digestion occur? what enzymes are important in each location?
Mouth:
- begins breaking down some starch
- Salivary amylase (enzyme)
- starch into maltose and 3-9 polymers of glucose
Small intestine:
- most starch is broken down here
- Pancreatic amylase
- starch into maltose and 3-9 polymers of glucose
- many disaccharides reach small intestine tract
what does each compound break down into and what enzyme does it: maltose trehalose lactose sucrose maltotriose a-dextrins
Maltose: maltase
-glucose + glucose
Trehalose: trehalase
-glucose + glucose
Lactose: lactase
-glucose + galactose
Sucrose: sucrase
-glucose+ fructose
Maltotriose: sucrase
-glucose
a-dextrins: a-dextrinase
-glucose
what are the three transpors imporatant in absorption from the lumen of carbohydrates, and how does it leave the epithelial cell and enter the blood?
Na+/K+ ATPase creates concentration gradient to help facilitate diffusion
Secondary active transport for glucose and galactose (SG:T1)
-transports glucose and galactose from the lumen
Facilitated diffusion for fructose is GLUT5
all sugars to get into the blood is via GLUT2
How to test for Carbohydrate assimilation problems?
Following a fast give 25g of D-xylose and collect urine for next 5 hours
- D-xylose can be absorbed but not utilized
- if absorption is abnormal if less than 4g excreted in urine
other breath tests:
- methane
- isotopically labelled CO2 from different sugars
- sucrose breath test
what are 5 different protein assimilation disorders?
- chronic pancreatitis
- Congenital trypsin absence
- cystinuria
- hartnup disease
- cystic fibrosis
what is deficient in chronic pancreatitis?
deficiency in pancreatic enzymes: lack of proteases especially trypsinogen
-important for protein absorption
what is deficient in congenital trypsin absence?
absence of trypsin, all pancreatic enzymes are gone
what is deficient in cystinuria?
defect in the transporter (S:C3A1) or absence of di-basic AA transporter (SLC7A9)
-cysteine, lysine, arginine, ornithine are not reabsorbed at the proximal tubule
what is deficient in hartnups disease
Cannot absorb neutral AA
-autosomal recessive genetic disorder (SLC6A19) gene or a sodium dependent neutral amino acid transporter B(0)AT1)
symptoms:
- diarrhea
- mood changes and neurological problens
- red, scaly skin
- photosensitivity
- high excretion of neutral amino acids (tryptopan)
what is deficient in cystic fibrosis?
CFTR gene that is a regulated Cl- channel on apical membrane of duct cells
- pancreas problems persist
- loss of HCO3- secretion
what enzymes are found at the stomach that break down protein?
Pepsin is secreted as pepsinogen, activated at ow pH
- responsible for 10-20% of protein breakdown
- not essential for protein digestion
what enzymes are found at the pancreas that break down protein? how are they released and how are they activated
Pancreatic enzymes are secreted as zymogens that are activated by either enterokinase (trypsinogen) or trypsin its self
Mostly breaks proteins down into di- and tripeptides, some amino acids
Enzymes: trypsin, chymotrypsin, carboxypeptidase, elastase
Trypsin and chymotrypsin break down small peptides
Carboxypeptidase cleaves AA into carboxyl ends
what enzymes are found at the small intestine that break down protein?
Enzymes: aminopokypeptidase, dipeptidases
amino acids, di and tri peptides are absorbed into enterocytes
How are proteins absorbed into the epithelial cell of the small intestine? how are peptides absorbed?
Seperated Na+ co-transporters for each amino acid type:
- Neutral
- acidic
- basic
- Imino
they are facilitated through diffusion based on the Na+/K+ ATPase estab;ishing a Na gradient
also the di- and tri-peptides are abosrbed via H+ cotranporters
-peptidase inside the cell will cleave to amino acids
How are proteins and peptides tranported from the epithelial cell into the blood?
Seperate facilitated diffusion mechanisms for each amino acid type:
- neutral
- acidic
- basic
- imino
same with dipeptides and tripeptides
Problems with Fat digestion and absorption: Celica Sprue characteristics?
Autoimmune disorder with hereditary component
-antibodies develop against a glutent component gliadin leading to destruction of small intestine villi and hyperplasia of the intestinal crypts
Malabsorption related to deficiencies in folate, iron, calcium, vitamins A, B12, and D
prevalence: most common in caucasions and persons of european ancestary, and women
GI symptoms: abdomina; pain, constipation, diarrhea, unexplained weith loss, vomiting, nausea, steatorrhea
other symptoms: tingling of extremities, rash, fatigue, seizures, bruising, bone fractures
Management: gluten free diet
what is the significance of the structure of the intestinal mucosa for its function?
Lumen surface of small intestine arranged in longitudinal folds of kerckring as well as villi and microvilli all contribute to increased surface area for absorption
-villi longest in duodenum
the Microvillar surface or brush border is site of activity of number of digestive enzymes
-barrie that must be transversed by nutrients, water and electrolytes
what are three cell types of intestinal epithelium?
Enterocytes: epitehlial cells
- digestion,absorption,secretion
- turnover rate 3-6 days
- susceptible to irradiation and chemotherapy
Goblet cells: mucus secreting cells
-mucus provides physical,chemical and immunological protection
Paneth cells: part of mucosal defenses against infection
-secret agents that destroy bacteria or produce inflammatory responses
what are routes of passage into the enterocytes?
Pinocytosis: base of microvilli, major mechanism for uptake of protein
Passive diffusion: through pores in cell membrane, between cells
Membrane transporters:
- facillitated diffusion
- active transport
what are the barriers that solutes moving across enterocyes from the lumen to the blood have to cross?
- Unstirred layer of fluid
- Glycocalyx
- apical membrane
- cytoplasm of cell
- basolateral membrane
- basement membrane
- wall of blood capillary/wall of lymphatic vessel
why must fats be emulsified inorder to be digested and what does that?
Since fats are insoluble
-TAGS, diglycerides,monoglycerides,fatty acids,cholesterol esters, phospholipids
they must become emulsified inorder to become partially soluble
this is done by bile salts and lectithin
Fat digestion and enzymes in the stomach?
- lingual and gastric lipase act on TAGs
- Dietary proteins perform emulsification here
- 10% of TAG digestion
- CCK: time is required, so CCK inhibits gastric emptying for more mixing along with activating gallbladder emptying
Fat digestion and enzymes in the small intestine
Most digestion of lipids occurs in the small intestine
Bile salts emulsify the lipids
Pancreatic enzymes secreted into small intestine
Pancreatic lipase: secreted as active enzyme
- inactivated by bile salts without colipase
- colipase activated by trypsin, once activated displaces bile salts by binding to pancreatic lipase
Cholesterol ester hydrolase (secreted as active enzyme)
- catalyzes production of free cholesterol
- hydrolyzes triglycerides to glycerol
Phospholipase A2 (secreted as proenzyme activated by trypsin)
5 steps in Fat absorption?
1) solubilization by micelles
2) diffusion of micellar content across apical membrane into the epithelial cell
3) Re-esterification
4) chylomicron formation
5) exocytosis of chylomicrons into lymphatics
what happens if their is a lack of ApoB?
lack of ApoB leads to abetalipoproteinemia meaining there is no lipid absorption
Problems with fat digestion and absorption: Pancreatic insufficiency?
failure to secrete proper amounts of pancreatic enzymes
Problems with fat digestion and absorption: Zollinger-ellison syndrom
- Gastrin secreting tumor of pancreas
- increased H+ secretion by gastric parietal cells
- overload of acid into duodenum
Problems with fat digestion and absorption: Pancreatitis
Pancreatic enzymes (Trypsin) become activated and self-digest the pancrease -impaired HCO3 and enzyme secretions
what are factors that can cause defects in bile salts?
ileal resection: total bile salt pool is reduced
-loss of enterohepatic recirculation of bile salts
small intestinal bacterial overgrowth (SIBO)
- bacteria deconjugate bile salts, impairing micelle formation
- severe bacterial overgrowth damages the intestinal mucosa
- two main causes: too little gastric secretion and small intestine motility
what does Small intestine bacterial overgrowth lead too? and how to detect
inappropriate growth of bacteria in small intestine, causes pain, bloating, gas, and diarrhea/constipation
can result in malabsorption issues, steatorrhea, vitamin/mineral deficiency
changes in pH result in improper activity of lipase enzymes in small intestine
Breath test: detect methane and hydrogen
what vitamins are fat soluble and what are water soluble?
Fat soluble vitamins: A, D, E, K
-same absorption mechanisms as lipids
Water-soluble vitamins (B and C)
-most are absorbed via Na+ dependent cotransport, except Vitamin B12 forms complexes with other proteins to be absorbed: need R proteins and intrinsic factor and transcobalamin II
what happens in a Vitamin B12 deficiency? what are some common causes of Vitamin B12 deficiency?
Pernicious anemia is caused by failure of red blood cell maturation when vitamin B12 is deficient
-important in DNA synthesis in red blood cells
Common causes is that the stomach does not produce enough IF:
- Atropic gastritis: chronic inflammation of the stomach mucosa that leads to loss of parietal cells
- Autoimmune metaplastic atrophic gastritis: immune system attacks IF protein or gastric parietal cells
what are two surgical implications that lead to Vitamin B12 malabsorption?
Gastrectomy: loss of parietal cells which is a source of IF
Gastric Bypass: Exclusion of the stomach, duodenum and proximal jejunum alters absorption of vitamin B12
How is calcium absorbed?
Calcium absorption depends on the presence of vitamin D (1,25-dihydroxycholecalciferol)
- absorbed across enterocytes, but also reabsorbed in kidney
- in small intestine, vitamin D-dependent Ca+ binding protein
- Calcitrol and PTH govern
what disease presents with Vitamin D deficiency?
- Rickets (children)
- Osteomalacia (adults)
How is iron absorbed?
Liver secrets apotransferrin into bile, enters duodenum
apotransferrin binds with free iron and with hemoglobin forming transferrin
Transferrin binds to receptors on membranes of intestinal epithelial cells, absorbed into cells via pinocytosis and later released
Characteristics of electrolyte absorption?
The first step in this process is the absorption of solute, followed by the absorption of water
Absorbate is always isomotic, meaning that solute and water absorption occur in proportion to each other
Electrolyte Absorption: small intestine
Jejunum: lots of sodium
Ileum: sodium absorbed, HCO3 secreted
Electrolyte absorption Colon
Colon: Na absorption and K secretion
-aldosterone modulates
how does chlorea affect the electrolyte absorption of the colon?
Chlorea increases cAMP resulting in increased Cl secretion
The resulting Cl- secretion is accompanied by secretion of Na+ and H20
Volume of fluid secreted into the intestinal lumen overwhelms the absorptive mechanisms of the small intestine and colon leading to massive secretory diarrhea
Total absorption of the Proximal small intestine?
- Fat
- Sugars
- Peptides and amino acids
- iron
- folate
- calcium
- water
- electrolytes
Total absorption of the middle small intestine
- Sugars
- peptides and amino acids
- calcium
- water
- electrolytes especially sodium
Total absorption of the distal small intestine
- bile acids
- Vitamin B12
- water
- electrolytes
Total absorption of the colon
- water
- electrolytes
- MCTs
- calcium
- amino acids
Products of digestion, site of absorption, mechanism: Carbohydrate
Products of digestion: glucose, galactose, fructose
site of absorption: small intestine
Mechanism:
- Na+ glucose transport,
- Na+ galactose transport
- Facillitated diffusion
Products of digestion, site of absorption, mechanism: proteins
Products of digestion: Amino acids, dipeptides, tripeptides
site of absorption: small intestine
Mechanism:
- Na+ amino acid transporter
- H+ dipeptide and H+ tripeptide co transporter
Products of digestion, site of absorption, mechanism: lipids
Products of digestion: fatty acids, monoglycerides, cholesterol
site of absorption: small intestine
Mechanism:
- bile salts from micelles
- diffusion of FA, MAG, and cholesterol
- Reesterification in cell to TG and PLs, chylomicrons form and cell and transferred to lymph
Products of digestion, site of absorption, mechanism: Water soluble vitamins and Vitamin B12
Products of digestion:
Small intestine
ileum
Mechanism:
- Na+ dependent cotransporter
- intrinsic factor
Products of digestion, site of absorption, mechanism: Bile salts
site of absorption: ileum
mechanism:
- Na+ bile salt co transporter
Products of digestion, site of absorption, mechanism: Ca+
site of absorption: small intestine
Mechanism:
-vitamin D dependent Ca+ binding protein
Products of digestion, site of absorption, mechanism: Fe+
Products of digestion: Fe3+ reduced to Fe2+
Site of absorption: small intestine
Mechanism: Binds to apoferrintin in intestinal cells; binds to transferrin in blood
