3-17 Large Intestine & Liver Flashcards
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A: Large Intestine is made of the Cecum–>Colon (ascending vs. transverse vs. descending)—>Sigmoid Colon —> Rectum —> Anus. Large Intestine contains [commensal bacteria] tht destroy other bacteria and work on EXOgenous & endogenous substrates. Can be Disrupted by Broad-spectrum Abx.
B: Large Intestine MAIN goal is to
- ReAbsorb Water & Reabsorb/Secrete Electrolytes
-Store Waste from a meal
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C: EMPTYING OF THE [small intestinal iLEUM]
*[iLeocecal sphincter] is normally closed but short range peristalsis opens it and allows chyme to squirt into the Cecum. SMALL INTESTINE ELECTRICAL ACTIVITY DOES NOT PROPAGATE THRU THE iLEOCECAL VALVE
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D: Colonic Function is regulated neurally!
1) Local Reflexes= activated by mvmnt of fecal material
–>stimulates short burst of (Cl) and fluid secretion “lubes it up” so that it can help chyme propel forward. This process involves 5HT and ACh
vs.
2) LONG REFLEX ARCS
ºGastrocolic Reflex= Stomach Distension INC colonic motility and mass mvmnt of fecal material. This ALSO involves 5HT and ACh
º Orthocolic Reflex= standing up promotes morning urge to defecate in some people
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iLEAL BRAKE! “puts a BRAKE on intestinal motility mvmnt”
A: [EnteroEndocrine cells] in the [terminal iLeum] and Colon secrete [Peptide YY] for an iLEAL BRAKE! This process DEC [Cl and Fluid secretion] and [overall intestinal motility mvmnt] when there is STILL Lipids in the colon lumen. —->allows more time to digest and Absorb in small intestine
B: Haustrations are segments created by [short 8 second contractions] of circular muscles in the colon. These segmental contractions mix & circulate stuff to optimize absorption of residual water & salts.
B2: Haustrations in 1st half of colon are controlled by [Vagus intramural plexus] but controlled by [Pelvic n. sacral spine] in 2nd half.
C: [Taeniae Coli] ACTUALLY PRODUCE contractions but produces [LONG 20-60 SECOND CONTRACTIONS]. They are NON-overlapping bands
D: Bolus propulsion is Less vigorous in Large Intestine and is moved back and forth between Haustra to maximize contact with epithelium
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A: Colon is cleared Out by [High-Amplitude propagating Contractions] which occurs 10x/day.
B: Sympathetic Innervation DEC motility
-SUP Mesenteric Plexus=intramural plexi in Cecum/Ascending & Transverse Colons
- [Inferior mesenteric Plexus & SUP hypOgastric Plexus]= intramural plexi of descending & sigmoid colons
- [Inferior hypOgastric Plexus]= intramural plexi of descending & sigmoid colons
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A: The Colon is histologically similar to [small intestine] except there are…
- No Paneth Cells
- No CONTINUOUS longitudinal muscle
- Absorb mostly [short-chain fatty acids] from colonic bacteria who symbiotically break it down for our use as colonic energy
B: [short chain fatty acids] like BUTYRATE are produced from non-abosrbed Carbs BY colonic bacteria. [SCFA] are Symported into our blood with Na+ using a [SMCT1 Symporter].
B2: Na+ is only able to diffuse down its gradient into cell because [basolateral Na/K ATPase] pumps it OUT of cell into blood
C: Na+ in colon is ALSO ReAbsorbed in Distal Colon with an [ENaC Na+ channel] . [ENaC] is opened by NTS or hormones. It creates gradient for Water and Cl- ions to ReAbsorb PASSIVELY thru tight junctions in attempt to maintain electrical neutrality–>Prevents excess water Loss in Stool
D: DEC [ENaC Na+ channel] Expression–>Bowel inflammation—>Diarrheal sx
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A: Fecal Transplant= Transplanting feces from healthy person to the gut of a sick person with a dangerous bacterial infection resistant to abx (i.e. (C.Diff)). ALSO used for infants with [kwashiorkor].
B: The infection occurs in the first place due to broad spectrum abx that destroy [flora commensal bacteria] –>predisposes people to C.Diff.
D1: Defecation involve [High amplitude propagating contractions] that produce mass mvmnt of feces and fills Rectum with it. Filling of the Rectum causes release of (VIP and NO) which relaxes [Internal Anal Sphincter]
D2: Although [Internal Anal Sphincter] is relaxed Defecation will NOT occur until the [tonically contracted EXTERNAL Anal Sphincter] is voluntarily relaxed & rectal contractions move Feces out
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A: The Rectum does NOT have a circular muscle= only used for waste storage. It joins to the Anal Canal which DOES have both smooth & skeletal Muscles.
B: [Internal Anal Sphincter]= THICK CIRCULAR SMOOTH M.
Colon Cancer:
*Because of rapid turnover of the colonic epithelium and constant exposure to bacteria and toxins–>vulnerability to Colon Cancer. = initially starts as polyps –>can become invasive & metastatic.
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Hirschsprung’s Dz:
Condition where a part of the colon is PERMANENTLY CONTRACTED!–>OBSTRUCTION. Usually occurs in infants.
It is caused by failure of the [Enteric nervous system] to develop. This occurs with mutations to glial-derived neutrophic factor / endothelin III and their receptors
Tx= Surgical Excision of segment
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A: Liver is a large multi-lobed organ that receives Portal blood from ALL GI organs. Most of Liver’s blood supply is venous from Portal Vein. Main Functions:
- Metabolism
- DeToxification
- Excretion
B: Hepatic Triad = [Hepatic Artery] / [Portal Vein] / [Bile Duct]. The Triad defines the lobules into zones:
-Zone 1= PeriPortal cells= CLOSEST TO TRIAD and therefore MOST SENSITIVE to Oxidative injury and MOST ACTIVE in DeToxification
- Zone 2 = intermediate cells
- Zone 3= pericentral cells= closest to [Central Vein] and most sensitive to ischemia and most active in bile synthesis
C: Hepatocytes are arranged in anastomosing cords which form plates. These plates are supplied by [low-resistance Sinusoid cavities] which themselves are supplied by [Hepatic Artery] and [Portal Vein].
C2: Hepatic artery brings in high amounts of O2 & nutrients. Blood Drains FROM Liver–>[Central Vein]—>[SubLobular Vein] —> Hepatic Vein—> VENA CAVA
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A: [Bile canaliculi] are found in between hepatocytes on their apical side to drain them of their Bile and then transport that Bile to [Hering’s Canal]–> [Bile Duct]—> [Common Hepatic Duct].
The [BILE Duct] is lined with [cholangiocyte columnar epithelium] which modify bile
A2: Once Bile has left the [Common Hepatic Duct] it is either
1) Sent to Gallbladder via [cystic duct] for storage
B: Hepatocytes are the origination point of [Biliary system]. There are Stellate Cells between the Sinusoid and hepatocyte that if pathogenically activated produce collagen = fibrosis and destruction to Hepatocytes!
C: [Kupffer macrophages] are Macrophages that wrap around Hepatocytes as immune support
D: HIGH levels of ALT or AST = hepatocyte damage
and
HIGH levels of [Alkaline phosphatase] (which is made by Bile canaliculi) = BILE BLOCKAGE
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A: Hepatocytes DO help metabolize major nutrients like carbs/lipids/proteins. Liver has IMPORTANT ROLE in
SUGAR
1. Gluconeogenesis (converting other sugars–>glucose)
- Glucose Buffering= liver stores excess glucose as glycogen and releases it when needed. So in Liver damage=–> Hyperglycemia during/after meals and hypOglycemia between meals
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A: Hepatocytes DO help metabolize major nutrients like carbs/lipids/proteins. Liver has IMPORTANT ROLE in
LIPIDS
1. Hepatocytes have enzymes for [fatty acid oxidation] and can ALSO convert Carbs into Lipids–> lipoproteins / cholesterol and phospholipids
- Hepatocytes uses Cholesterol to make [Bile Acids]
Cholesterol and [Bilirubin bile pigments] can form Gallstones if too concentrated
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A: Hepatocytes DO help metabolize major nutrients like carbs/lipids/proteins. Liver has IMPORTANT ROLE in
PROTEIN
- Liver makes ALL of the [NON-ESSENTIAL AMINO ACIDS] and can modify AA so they enter pathways for making Carbs
- Liver makes MOST of the Plasma Proteins including albumin and clotting factors. So in Liver damage—> hypOalbuminemia –>peripheral edema & clotting disorders
- Converts Ammonia —> Urea which is excreted in urine
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A: During DeToxification the Liver protects the body from ENdogenous AND EXOgenous substances by modifying them in [1ST PASS METABOLISM] so that little-to-none can enter systemic circulation. [1ST PASS METABOLISM] is done in 2 parts:
Phase 1: [cytochrome P450 enzymes] catalyze oxidation and hydroxylation of substances
Phase 2: Conjugate the substances with Glucuronide/Sulfate/AA or Glutathione
B: Products of [1ST PASS METABOLISM] are then excreted in [feces via Bile] or [Urine via kidneys]
C: Although Kidneys are IMPORTANT in excreting small water-soluble catabolites, LARGE WATER-SOLUBLE CATABOLITES and molecules bound to plasma proteins or steroid hormones–>Excreted by Liver using [feces via Bile]
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BILE ACID SYNTHESIS:
A: Hepatocytes synthesizes 2 PRIMARY BILE ACIDS
º Cholic Bile Acid
º Chenodeoxycholic Bile Acid
B: These PRIMARY BILE ACIDS are then converted into [SECONDARY BILE ACIDS] by Colonic Bacterial Enzymes
º[Ursodeoxycholic 2º Bile Acid]
º[Deoxycholic 2º Bile Acid]
º[Lithocholic 2º Bile Acid]
C: ALL of these Bile Acids are [Conjugated Charged] with glycine or taurine in Liver by Hepatocytes—>allows them to be water soluble.
[Conjugated Charged] Bile Acids are fully ionized in intestinal lumen–>Actively ReAbsorbed in [terminal iLeum]–>some escapes to colon where it is DEConjugated by bacterial enzymes in order passively ReAbsorb into portal vein
D: iLeal Resection–> DEC Bile Acid in Blood—>which will INC Bile Acid Synthesis.
vs.
[Bile Acids FEEDING]—>INC Bile Acid in Blood—>will DEC bile Acid Synthesis
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A: [Bile Acid] is modified by [cholangiocyte columnar epithelium] in the Bile Duct. Modification includes
1.Glucose & AA ReABsorbed by specific transporters
- [Cl/HCO3 exchanger] that ReAbsorbs Cl! = Alkaline Bile. (Cl) is initially secreted INTO bile via CFTR and then is ReAbsorbed with the [Cl/HCO3 exchanger].
- Glutathione is broken down into AA by [glutamyl transpeptidase]
- Bile is ALSO diluted here because Secretin stimulates aquaporin water channels and allows water in
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A: The Gallbladder STORES BILE and in between meals outflow of bile from Gallbladder is BLOCKED by constriction of [sphincter of Oddi]. Bile becomes concentrated here.
B: Both [Vagal Efferent ACh] and [CCK] stimulate Gallbladder contraction.
C: In the [DORSAL VAGAL COMPLEX]
1. Nutrients in Duodenum stimulate CCK release
- CCK stimulates Vagal AFFerents and activate [DORSAL VAGAL COMPLEX]
- CCK also DIRECTLY stimulate Gallbladder contraction
- ## Vagal Efferents then release ACh to stimulate Gallbladder contraction and DVC releases NO & VIP to relax [Sphincter of Oddi]B: Bile Ejection from Gallbladder begins within 30 min of meal ingestion. The Major stimulus for this is CCK. Other internal neural reflexes & vagal pathways are also involved
