Unit VI- Intestines I Flashcards
1
Q
Small intestine
A
- begins distal to the pyloric sphincter of the stomach and extends some 21 feet to the cecum
- three parts: duodenum: 1 foot long
- jejenum: promiximal 2/5, 8 feet long
- ileum: distal 3/5, 12 feet long
2
Q
Absorptive Surface Area per cm of Gut
A
- surface area of simple cylinder- jejunum (10); ileum (10)
- mucosal folds of Kerkring- jejunum (75); ileum (24)
- villi- jejunum (750); ileum (240)
- microvilli- jejunum (15000); ileum (4800)
- jejunum has 3x more surface area than ileum, consistent with greater absorption occuring in jejunum as compared with ileum
- in cardiovascular and pulmonary systems, increases surface area is achieved by successive bifurcations leading to 10 billion capillaries and 300 million alveoli
- in GI system, increased surface area is achieved by successive foldings of the the surface
3
Q
Comparison of the anatomy of the small and large intestines
A
- the surface of the sm intestine: macroscopic folds of Kerckring, microscopic villi and crypts of Lieberkuhn and submicroscopic microvilli
- the surface of colon- macroscopic semilunar folds, crypts but not villi, and microvilli
4
Q
Total Intestinal Absorptive Area
A
- average length of sm intestine: 700 cm= 21 feet
- total absorptive surface area: 700 sq meters about about 26-27 meters square, or about 1/3 size of a football field (same size as total capillary surface area)
- above half absorptive surface area is required for absorption; about half can be surgically removed without compromising absorptive function
5
Q
Celiac Disease
A
- malabsorptive syndrome/ non-tropical sprue or Sprue
- gluten is the insoluble protein of wheat and other grains in bread
- gluten by some means destroys absorptive cells and decreases the number of functional villi
- since food that is digested cannot be absorbed, diarrhea and malnutrition result. Dehydration can be fatal
- requires restricted diet- avoid wheat grains
- tropical sprue- an infectious disease present in certain areas of tropical countries associated with diarrhea, malabsorption and nutritional defiencies
6
Q
Renewel of intestinal cells
A
- cells are being constantly generated at the base of the villi and migrate toward the tip
- extruded 3-8 days later
- 250 grams of cells are shed daily
- 5 days for a cell to mature and reach the tip of villus
- every week you get a new intestinal epithelium
- digested in gut and useful contents recycled
- cell renewal is reduces as a result of radiation malnutrition or sprue
7
Q
Cells in villi
A
- comprised of absorptive cells called enterocytes- columnar epithelial cells in a single layer
- goblet cells- secrete mucus in response to ACh from parasympathetic cholinergic nerve fibers- protective barrier and peristalsis
- undiff cells of crypt secrete NaCl from the blood into the lumen and water follows osmotically
- the crypt cells stop secreting as they migrate up the villus and take on an absorptive function (NaHCO3 or NaCL)
8
Q
Radiation Sickness
A
- goblet cells and enterocytes have a common stem cell at the base of the crypts
- because of high turnover of intestinal mucosa there is a great sensitivity to radiation damage
- radiation victums experience intestinal bleeding, diarrhea, and slow death from malabsorption and dehydration
- side effects of certain types of radiation cancer therapy are similar
- Hiroshima and Chernobyl
9
Q
Enterocyte- intestinal absorptive cell
A
- intestinal absorptive cell
- transfer materials via two parallel pathways
- transcellular pathway- across brush border and then through cytoplasm and finally across basolateral membrane
- shunt pathway (paracellular pathway) through tight junction and extracellular space (low resistance, high conductance, pathway)
10
Q
Enterocyte- brush border
A
- or apical membrane
- has a glycoprotein matrix and is the major membrane for absorption of nutrients
- has ectoenzymes (enterokinase, disaccharidases and peptidases) that complete the digestive process
- the basement membrane, or lamina propria, contains capillaries and lacteals
11
Q
Junctional Permeability
A
- tight junction wraps around cell like a collar
- paracellular pathway also called pericellular pathway or shunt pathway
- shunt is permeable to H2O and cations but has low permeability to anions
- jejunum>ileum> colon : from leaky to tight
12
Q
Intestinal Fluid and Electrolyte Balance
A
- Input: diet (2.5L), saliva (1L), gastric juices (2 L), Bile (1 L), Pancreatic juice (2L), succus entericus (1L) = 9.5L
- Output: jejunal absorption (5L), ileal absorption (2.5L), colonic absorption (1.8L), feces (0.2L) = 9.5L
13
Q
Sites of Intestinal Absorption of Solutes and Nutrients
A
- water and most nutrient substances are absorbed from duodenum and upper jejunum, and completely absorved by the end of jejunum
- exception: B12- requires combination with intrinsic factor and ionized bile salts which undergo enterohepatic circulation. Both of these substances are absorbed in the distal ileum
- ileum absorbs some fluid and electrolytes an B12 and ionized bile salts by sodium dependent co transport, if jejunum is removed the ileum takes over function, if ileum taken out there is also adaptation
14
Q
Vitamin B12
A
- deficiency causes pernicious anemia, a type of macrocytic anemia characterized by unusually large red blood cells;
- intrinsic factor is a mucoprotein secreted by gastric parietal cells, it combines Vit B12 in the stomach forming a complex that is absorbed in the distal ileum
15
Q
Jejunal absorptive cell
A
- jejunal enterocyte absorbs Na+ and HCO3- along with glucose and amino acids
- pancreas secretes NaHCO3 which serves to neutralize acid from the stomach
- the jejunal absorptive cell shown above avidly absorbs NaHCO3 to maintain fluid balance and thereby prevents diarrhea
16
Q
Na+ entry in absorptive
A
- by Na+/glucose and by Na+/amino acid cotransport, an important mechanism for absorption of Na+, glucose and amino acids in the jejunum
- by Na+/H+ antiport, a mechanism that serves to keep the internal pH of the enterocyte near neutral, and away from electrochemical equilibrium
- Na+ entry is balanced by active efflux of Na+ across the basolateral membrane mediated by the Na+/K+ pump
- membrane potential is +5mV at rest on the serosal side and rises to about +15 mV during absorption after a meal due to the electrogenicity of the Na+/K+ pump
17
Q
Modes of Na+ absorption in intestine
A
- nutrient coupled Na absorption: in villous cells of the jejunum and ileum and is the primary mechanism for postprandial Na+ absorption
- electroneutral Na-H exchange at the apical membrane in the absence of Cl-HCO3 exchange, is stimulated by the high pH of the -rich luminal contents
- Na-H and Cl-HCO3 exchange is coupled by a change in intracellular pH that results in electroneutral NaCl absorption which is the primary mechanisms for interdigestive Na+ absorption
- In electrogenic Na+ absorption, the apical step of Na+ movement occurs through the ENaC
18
Q
NaCl Absorption by Ileal Absorptive Cell
A
- a lot of Na and Cl is secreted by the liver and the pancreas and then reabsorbed by the ileal absorptive cell (and also in the colon)
- Na and CL enter the ileal absorptive cell via Na+/H+ antiport in parallel with Cl-/HCO3- exchange
- H+ and HCO3- that are extruded into the lumen are recycled back into the ileal cell after forming carbonic acid which equilibriates with CO2 and H2O
- a Cl- channel in the basolateral membrane allows Cl- to pass down its electrical gradient into the serosal fluid and into the blood
- cyclic AMP inhibits NaCl absorption by the ileum
- ACh stimulates cAMP production, thereby decreasing NaCl absorption
19
Q
VIP
A
-vasointestinal peptide, a neurotransmitter in the gut that increases pancreatic secretion)
normally the minor importance in stimulating cAMP production in the ileum but in vipoma tumors, the amount of VIP is greatly increases resulting in greatly decreased NaCl absorption, leading to increased osmolarity in the lumen, and osmotic diarrhea
-E coli and Vibriocholera toxins also stimulate production of cAMP, causing diarrhea which is massive in the case of cholera infection
20
Q
NaCl secretion by crypt cells
A
- function to secrete NaCl into the lumen
- apical membrane contains a CFTR Cl- channel permitting movement of Cl- from the crypt cell to the lumen across the apical membrane
- Na+, K+, Cl- enter the crypt via Na+/K+/2Cl- cotransporter in the basolateral membrane
- this transporter in ascending limp of loop of Henley is lost during maturation of crypt cells into absorptive cells and is sensitive to furosemide, bumetanide, and other loop diuretics
- increased cAMP increases CFTR conductance to Cl-, Cl driven out of the cell by negative internal electrical potential
- cholera toxin and VIP increase cAMP greatly increase secretion of NaCl leading to diarrhea, dehydration, and possible death
- ACh increases intracellular Ca via ITP causing increased conductance to K+ the resultant hyperpolarization of the membrane potential drives Cl- out of the cell, thereby increasing secretion of NaCl
21
Q
Cholera
A
- vibriocholera toxin increases cAMP
- inhibits absorption of NaCL in the ileum
- increases secretion of NaCl by jejunal crypt cekks
- Vipoma tumors increase VIP and increase cAMP, producing even more diarrhea than cholera
- cholera toxin activates adenylyl cyclase, increasing cyclic adneosine monophosphate (cAMP) production and opening Cl- channels in the apical membrane
22
Q
Oral rehydration solution
A
- 1971 Bangladesh
- orally a mixture of saline and glucose to rehydrate individuals suffering from dehydration with cholera because no IV
- one of the most important life saving medical treatments of the twentieth century
- sodium glocuse co transporter
23
Q
Endogenous Secretory Stimuli
A
- ACh (from parasympathetic cholinergic neurons, increases Ca_
- Histamine (also stimulates gastric secretion, increases Ca)
- Cholecystokinin (also stimulates pancreatic enzyme secretion and gallbladder contraction)
- Secretin (also stimulate gastric secretion of pepsinogin and pancreatic secretion of bicarbonate, increases cAMP)
- Gastrin (hormone that also stimulates gastric secretion of HCl)
- Gastric inhibitory polypeptide (GIP, decreases gastric secretion)
- Motilin (hormone that initiates migrating motor complex, MMC)
- Vasoactive intestinal (VIP, a neurotransmitter, increases cAMP)
24
Q
Exogenous Secretory Stimuli
A
- Vibrio choleae (increases cAMP)
- E. coli (increases cAMP)
- Salmonella (increases cAMP)
- other microbial enterotoxins
- bile salts and fatty acids
- laxatives
25
Absorptive Stimuli
Endogenous
- alpha-adrenergic agonists (epi, norepi)
- dopamine
- enkephalins (endogenous opoids such as endorphins which were discovered in the intestine and later found to occur in the brain; responsible for runn'ers high and other opoids (morphine)
- somatostatin (also inhibits gastric secretions)
- mineralocorticoids (aldosterone in the colon)
Exogenous
-nurients (glucose, amino acids, peptides)
- substances that promote secretion tend to inhibit absorption
- substances that promote absorption tend to inhibit secretion
26
Body Iron Balance
- 1 mg Fe++ absorbed daily as needed; otherwise stored bound to ferritin
- 20 mg Fe++ (2+ ferrous) ingested daily, but most is Fe+++ (3+ ferric) which cannot be absorbed, only 5% of ingested iron is absorbed
- most ferritin bound Fe++ is lost when cell exfoliates; a small amount as needed is released to transferrin (TF) and absorbed
- if body Fe++ is low, number of brush border transporters increases
- if body Fe++ is high, number of brush border transporters decreases while amount of ferritin increases
27
Absorption of Iron
- need 1 mg of Fe everyday but ingest 20 mg Fe/day
- most Fe ingested is Fe3+ which cannot be absorbed, but Fe2+ may be transported across the basolateral membrane or be stored in the absorptive enterocyte as ferritin, DCTI is a divalent cation transporter
- Heme iron- more efficient pathway is iron absorbed as heme, iron is freed within the cell by heme oxygenase and bound to intracellular mobilferrin
- non-heme iron- Fe 2+ forms insoluble complexes with food but more soluble at acid pH, so Fe is released by gastric acid
- ascorbate and citrate in the stomach help reduce Fe+++ to Fe++
- some heme bound to ferritin and stored within the cell
- transferrins are iron-binding proteins with a stoichiometry of 2 Fe+++/TF
- Dcytb reduces non-heme Fe3+ to Fe2+
- DCT1 cotransports Fe2+ with H+
- heme iron enters by unknown mechanisms
- heme oxygenase release Fe3+
- Fe2+ transfers to mobilferrin
- Fe2+ leaves the cell via IREG1 and after oxidation to Fe3+ binds to transferrin in plasma
28
Features of Iron Absorption
- Heme iron in red meat of major dietary source of Fe++
- non-heme Fe++ is absorbed via cotransport with a proton
- inorganic Fe++ is absorbed in preference to Fe+++
- ascorbic and citric acids in stomach can reduce Fe+++ to Fe++
- Fe++ is more soluble at acid pH and isreleased from food by gastric acid. Fe ++ forms insoluble complexes with food
- Px deficient in gastric acid secretion absorb less iron leading to iron deficiency anemia
29
Duodenal absorption of calcium
- concentration of calcium in the blood is around 2 mM with about 1/2 of that bound to albumin
- overal transport if calcium is against its electrochemical gradient
- Ca-ATPase activated by calmodulin actively transports Ca++ from the cell into the serosal solution
- 1,25(OH)2D3 stimulates the synthesis of calbindin a Ca binding protein which is supposedly the membrane carrier for Ca++ across the brush border membrane
- soluble intracellular calbinden binds and buffers Ca++ within the cell
- intracellular calcium cannot rise too much without initiating a variety of toxic reactions involving Ca-activated proteases (breaks down protein), phospholipases (hydrolyzes phospholipids) and transglutaminases (crosslinks the cytoskelton)
30
Active Ca2+ uptake in the duodenum
- the small intestine absorbs Ca2+ by two mechanisms
- the passive, paracellular absorption of Ca2+ occurs throughout the small intestine
- predominates but is not under control of Vitamin D
- the second mechanism- the active, transcellular absorption of Ca2+ occurs only in the duodenum
- Ca2+ enters the cell across the apical membrane through a channel
- inside the cell, the Ca2+ is buffered by binding proteins, such as calbindin, and is also taken up into intracellular organelles, such as the endoplasmic reticulum
- the enterocyte then extrudes Ca2+ across the basolateral membrane through a Ca2+ pump and an Na-Ca exchanger
- the net effect is Ca2+ absorption
- active form of Vitamin D stimulates all three steps of transcellular Ca 2+ absorption
31
Vitamin D
- 7- Dehydrocholesterol in skin forms Vitamen D3 (cholecalciferol) under the influence of the UV component of sunlight
- in the liver Vitamin D3 is hydroxylated to 25(OH)D3
- and then hydroxylated again in the kidney to form the active form 1,25-Dihydroxycholecaliferol or 1,25 (OH)2D3, a reaction stimulated by parathyroid hormone (PTH)
32
Regulation of Body Calcium Balance
-increased absorption of Ca++ increases the plasma concentration of Ca++ which in turn decreases the secretion of parathyroid hormone which inhibits formation of 1,25(OH)2D3 which decreases the synthesis of calbindin which decreases absorption of Ca2+
