Intestinal Transport I Flashcards
1
Q
small intestine
A
- begins just distal to the pyloric sphincter of stomach and extends 21 feet to cecum
- duodenum-1 foot long
- jejunum- proximal 2/5, 8 feet
- ileum- distal 3/5, 12 feet
2
Q
absorptive surface area per cm of gut
A
- jejunum has 3x more SA than ileum, greater absorption occurring in jejunum
- SA increased by foldings
- mucosal folds- 75 vs 24
- villi- 750 vs 240
- microvilli 15000 vs 4800
3
Q
small vs large intestine
A
- SI amplified at three levels: macroscopic folds, microscopic villi and crypts of liberkuhn, and submicroscopic villi
- colon has folds, crypts but not villi, and micro villi
4
Q
total intestinal absorptive area
A
- average length- 21 feet, 700 cm
- area of simple cylinder=7,000 cm2
- increase due to mucosal folds- 35,000 cm (5x)
- due to villi- 350,000cm2 (10x)
- microvilli- 7 million, 20x
- absorptive SA is 700 sq meters- 1000x- 1/3 of a football field
- half of it required, half can be surgically removed
5
Q
celiac disease
A
- gluten is insoluble protein of wheat and other grains
- destroys absorptive cells and decreases number of functional villi
- food can’t be absorbed, diarrhea and malnutrition
- dehydration can be fatal
- restricted diet
- tropical sprune is and infectious disease present in certain areas of tropical countries associated with diarrhea, malabsorption, and nutritional deficiencies
6
Q
two villi and a crypt
A
- villi composed of layer of absorptive enterocytes
- goblet cells stimulated by Ach from PNS fibers to secrete protective mucous
- crypt cells migrate towards top of villi and are extruded 3-8 days later
- quick turnover
- 250g shed each day
- replaced after 1 week
- 5 days to mature and reach tip
- extruded cells digested in the gut
- crypt cells secrete Nacl from the blood to the lumen and water follows
- they stop as they migrate up villus and take on absorptive function
7
Q
radiation sickness
A
- goblet cells and enterocytes have a common stem cell base of the crypts
- high turnover leads to sensitivity to radiation damage
- radiation victims experience intestinal bleeding, diarrhea, and slow death from malabsorption and dehydration
- side effects of certain types of radiation cancer therapy are similar
8
Q
enterocyte
A
- microvilli on brush border
- tight junctions, intercellular spaces, basolateral membrane, basement membrane
- transcellular and paracellular pathway
- trancellular across brush border then through cyto then basolateral
- paracellular is shunt, through tight junction and extracellular space
- low perm to anions
9
Q
brush border
A
- glycoprotein matrix and major membrane for absorption
- contains ectoenzymes that complete digestive process
10
Q
basement membrane
A
- lamina propria
- contains capillaries and lacteals
11
Q
junctional permeability
A
- tight junction wraps around like a collar
- shunt is permeable to water and cations, not to anions
- intestine gets tighter as you go down
- liquid rapidly absorbed in jejunum
12
Q
intestinal fluid and electrolyte balance
A
- input equals output- 9.5L
- 2.5 input from diet, 1 from saliva, 2 from gastric juices, 1 from bile, 2 from pancreatic juice, 1 from intestinal secretions
- output-5 from jejunal absorption, 2.5 from ileal, 1.8 from colonic, 0.2 in feces
- difference between dietary intake and fecal output equals loss through kidney, lungs, and sweat to maintain body fluid in steady state
13
Q
site of intestinal absorption of solutes and nutrients
A
- water and most nutrients to duodenum and upper jejunum
- completely absorbed by end of jejunum
- except B12, need intrinsic factor;and ionized bile salts which undergo enteroheptatic circulation
- ileum absorbs some fluid and electrolytes, along with B12 and takes up ionized bile salts
- if jejunum is removed, ileum will take over
- if distal ileum removed, other parts can’t adapt
- B12 gone-pernicious anemia-macrocytic anemia with large RBCs
- intrinsic factor is secreted by parietal cells, complex is absorbed in distal ileum
14
Q
NaHCO3 Absorption by jejunal absorptive cell
A
- jejunal enterocyte absorbs Na and HCO3, glucose and aa
- panreas secretes NaHCO3 which serves to neutralize acid from the stomach
- the jejunal cell absorbs it to maintain fluid balance
- Na enters by Na/glu and Na/aa cotransport Na/H antiport
- antiport serves to keep internal pH of the enterocyte near neutral and away from electrochemical eq
- Na influx balanced by active efflux across basolateral membrane with Na/K pump
- 1 Na and HCO3 from lumen goes to the blood
- membrane potential 5mV on serosal side and 15mV during absorption after a meal
- HCO3 dissociates, crosses, and re-associates`
15
Q
modes of active Na absorption by intestine
A
- nutrient coupled in villous cells of jejunum and ileum, primary mechanism
- Na/H exchanger-jejunum and duodenum
- parallel Na-H and Cl-HCO3 exchangers in ileium and proximal colon
- epithelial Na channel in distal colon
16
Q
NaCl absorption by ileal absorptive cell
A
- parallel Na-H and Cl-HCO3 exchangers
- secreted by liver and pancreas and absorbed by ileum
- H and HCO3 that are extruded into the lumen are recycled back into the ileal cell after forming carbonic acid, equilibrates with CO2 and water
- a cl channel in the basolateral membrane allows cl to pass down its electical gradient into the serosal fluid and into the blood
- cAMP inhibits NaCl absorption
- Ach stimulates cAMP production
- VIP only important in vipoma tumors, decreased NACl absorption, increased osmolarity and diarrhea
- E coli and cholera stimulate cAMP
17
Q
NaCl secretion by crypt cell
A
- secret NaCl into lumen
- apical membrane contains a CFTR Cl channel for Cl from crypt cell to the lumen
- Na/K/Cl enter crypt via Na/K/2Cl cotransporter in the basolateral membrane
- lost during move from crypt to absorptive cells
- K lost through K channel
- Na and K move down electrochemical gradients via electrodiffusion from the serosal to mucosal solution
- in crypt cell, increased cAMP increases conductance of CFTR
- cl driven out of cell by negative internal electrical potential
- cholera and VIP increase cAMP and increase secretion of NaCl
- Ach increases Ca via, ITP, causing increased conductance of K- which hyperpolarizes the potential, drives Cl out, and increases secretion of NaCl
18
Q
cholera
A
-increases cAMP by activating adenylate cyclase, opens Cl channels
-inhibits absorption of NaCl in ileum
-increases secretion of NaCl be jejunal crypt cells
-vipoma tumors increase VIP and increase cAMP, producing more diarrhea
-
19
Q
oral rehydration solution
A
- 1971 in a refugee camp
- intestinal sodium/glucose co-transporter discovered
- administered oral saline and glucose
- didn’t have sterile IV solutions
- one of the most important life saving therapies in 21st century
20
Q
secretory stimuli
A
endogenous:
- Ach-inc Ca
- Histamine- inc Ca
- CCK- stimulates pancreatic enzyme secretion and gallbladder contraction
- secretin- increases cAMP
- gastrin, gastric secretion of HCl
- gastric inhibitory polypeptide, decreases gastric secretion
- motilin, initiates migrating motor complex
- VIP
exogenous:
- cholera increases cAMP
- e coli
- salmonella
- other enterotoxins
- bile salts and fatty acids
- laxatives
21
Q
absorptive stimuli
A
endogenous:
- alpha adrenergic agonists
- dopa
- enkephalins
- somatostatin
- mineralocorticoids
exogenous
-nutrients
-substances that promote secretion tend to inhibit absorption
22
Q
body iron balance
A
- 1 mg Fe2+ absorbed daily as needed, otherwise stored bound to ferritin
- 20mg Fe2+ ingested daily, but most is Fe3+ which cannot be absorbed, only 5% of ingested iron is absorbed
- most ferritin bound Fe2+ is lost cell exfoliates, a small amount as needed is released to transferrin and absorbed
- if body iron is low, number of brush border transporters increases
- if body iron is high, number of brush border transporters decreases and amt of ferritin increases (storage)
23
Q
absorption of iron
A
- heme iron- absorbed as heme, then freed within the cell by heme oxygenase and bound to intracellular mobilferrin
- non heme iron- Fe2+ forms insoluble complexes within food, more soluble at acid pH
- released from food by gastric acid
- patients with less gastric acid can’t absorb as much
- Fe2+ spontaneously to Fe3+- ascorbate and citrate take it back
- some bound to ferritin and stored-lost when cell exfoliates, some transported across serosal membrane and binds to plasma transferrin, carries it to bone marrow/liver
- transferrins bind to Fe3+
24
Q
features of iron absorption
A
- heme iron in red meat is a major dietary source of Fe2+ and is the form most easily absorbed
- non-heme Fe2+ is absorbed via co-transport with a proton
- inorganic Fe2+ absorbed in preference to Fe3+
- ascorbic acid and citric acid in stomach can reduce
- Fe2+ is more soluble at acid pH and is released from food by gastric acid
25
calcium absorption
- against electrochemical gradient
- concentration is 2mM, 1/2 bound to albumin
- Ca-ATPase activated by calmodulin, actively transports Ca from cell into serosal solution
- 1,25 (OH)2D3 stimulates synthesis of calbindin, supposedly the membrane carrier for Ca across brush border
- soluble intracellular calbinden binds and buffers Ca within the cell
- intracellular Ca buffered by mitochondrial stores
- intracellular Ca can't rise too much-toxicity-proteases and phospholipases and transglutaminases
26
jejunal calcium absorption
-passive:
-paracellular in SI, not under control of vitamin D
active:
-transcellular, only in duodenum
-enters at apical membrane, buffered, taken up, extrudes across basolateral membrane through pump and Na/Ca exchanger
-net effect is absorption
-active form of Vitamin D stimulates all three steps of transcellular Ca2+ absorption
27
vitamin D
-7-Dehydrocholesterol in UV and skin-->
-Vitamin D3 (cholecalciferol)--> liver makes
-25-OH Vitamin D3 --> PTH and Kidney makes
1,25 (OH)2-Vitamin D
-stimulates synthesis of calcium binding protein in the intestine
28
regulation of body calcium balance
- increase Ca in plasma
- decreased secretion of PTH
- decreased formation of 1,25 (OH)2 Vitamin D3
- decrease synthesis of calcium binding proteins (CaBP)
- decreased Ca absorption
