tbl 4 physiology: colon Flashcards

1
Q

The colon is also called the large intestine. It is wider in diameter than the small intestine, but shorter. The ileum empties into the _____. The __________ lies at the junction of the ileum and colon and keeps bacteria rich colonic material from refluxing into the small intestine. The remainder of the colon consists of the ascending, transverse, descending and sigmoid colon, rectum and anal canal. The anal canal is situated between the rectum and anus below the pelvic diaphragm. In the anal canal, above the dentate line (a.k.a. ________), the mucosa is __________ epithelium. Below the dentate line, the mucosa is ___________ epithelium.

A

caecum; Ileocolic sphincter; pectinate line

simple columnar; squamous

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2
Q

The surface area of the colon is amplified at 4 levels: 1) Haustra, 2) Macroscopic semilunar folds (correspond to _____________ in the SI), 3) crypts but no villi, 4) microvilli.

  1. Taenia coli and haustra increase surface area: The external muscle layer of the colon is organized into three longitudinal bands of smooth muscle called taenia coli. They are found on the outside of the ascending, transverse, descending and sigmoid colons. They are visible and can be seen just below the serosa. The taenia coli contract lengthwise to produce bulges (haustra) between the gaps in the taenia coli.
  2. Colonic crypts:
    • Progenitor cells at the base of the crypt migrate along the crypt axis and eventually differentiate into the _________ after undergoing substantial changes in its morphology and function. They then slough off into the intestinal lumen. The overall period from the initiation of cell proliferation to sloughing is approximately 48- 96 hours.
    • Goblet cells in the colonic crypt secrete mucus.
    • Enteroendrocrine cells in the colon secrete __________________, while nerve fibers secrete _________________.
A

circular folds of Kerckring;

enterocyte absorptive cell;

peptide YY (PYY) and neurotensin;

cholecystokinin, VIP, Substance P

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3
Q

[Innervation of colon]

Parasympathetic nerves: Pre-ganglionic parasympathetic fibers from the spinal cord form synapses with the enteric nervous system in the GI tract. The _________ is supplied by the Vagus nerve (cranial nerve X), while the _________________ is supplied by the Pelvic nerve.

Sympathetic nerves: Pre-ganglionic fibers from the spinal cord synapse with neurons in sympathetic ganglia. Post-ganglionic fibers from the ganglia synapse with the enteric nervous system. Post-ganglionic fibers from the celiac ganglion supply the _______________. Post-ganglionic fibers from the superior mesenteric ganglion supply the ______________ . Post-ganglionic fibers from the inferior mesenteric ganglion supply the majority of the descending colon, sigmoid colon, rectum and anal canal down to the __________.

Somatic nerves: In the anal canal, below the dentate line, the nerve supply is somatic, receiving its supply from the ____________, which are branches of the pudendal nerve. As it is somatically innervated, it is sensitive to pain, temperature, and touch. The pudendal nerve innervates the external anal sphincter.

Internal anal sphincter: Parasympathetic fibers are inhibitory to the internal anal sphincter (relaxation), while sympathetic fibers are excitatory.

A

ascending colon; remainder of the colon down to the dentate line;

ascending and transverse colon; proximal descending colon; dentate line

inferior rectal nerves

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4
Q

Hirschsprung’s disease: Patients have massively _______ colon and rectum because ganglion cells are absent in plexi (Congenital aganglionosis), most commonly in a short segment of the rectum and/or sigmoid colon. The distention may be local or diffuse. The _________ fails to relax. In some hereditary cases, mutations in the ____________________ results in the failure of migration of neuroblasts into the gut wall during embryogenesis.

A

distended; internal anal sphincter; RET tyrosine kinase signaling system

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5
Q

[Blood supply to the colon]
- The large intestine is supplied by the superior mesenteric artery (with the middle colic artery being a branch) and inferior mesenteric artery
o Superior mesenteric artery supplies till the _______________
o Extensive anastomoses are present between the blood supply of the large intestine

  • Cancer between the cecum and ascending colon
    requires a right colectomy (i.e. segment supplied
    by superior mesenteric artery) – after removing the
    tumour, the superior mesenteric artery needs to be
    ligated
  • Tumours in the transverse colon require a transverse colectomy
    o The __________ is ligated, and the ascending and descending colon are anastomosed
A

proximal 2/3 of the transverse colon;

middle colic artery

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6
Q

[Colonic Motility]

  1. Receptive relaxation: Each time a peristaltic wave reaches the ileocecal valve, the ____________ opens briefly and the cecum and the ascending colon relax i.e undergo receptive relaxation. This permits ileal chyme to be squirted into the cecum and ascending colon. This process is similar to receptive relaxation of the orad region of the stomach. Receptive relaxation does not occur in the transverse colon, descending colon, sigmoid colon and rectum.
  2. ___________ (segmental contractions): This is the most common form of colonic motility. Haustral shuttling does not propel the food forward but rather the fecal mass is slowly knead (mixed), facilitating water absorption. Such contractions in the _______ are responsible for the cylindrical shape of well-formed feces.
  3. Peristaltic contractions: The contents of one haustra and expelled into the next haustrum. The movement may be away from the mouth (aboral, propulsion) or towards the mouth (adOral; retropulsion). Propulsion predominates over retropulsion. Peristaltic movements are propagated over short distances.
  4. Mass contractions: This type of motility begins in the _______ with several adjacent sections contracting simultaneously and transporting the bowel contents as far as the rectum. They last 18-20 seconds and span several cycles of the electrical waves. Mass movements occur about 1 to 3 times per day. The mass movement propels the fecal contents into the rectum, where it is stored until defecation occurs. They are propagated over ____________, whereas peristaltic contractions move contents of one haustra to the next. Noxious stimuli trigger mass movements: Castor oil, vinegar on the mucosa, parasites, ________ and ionizing radiation all trigger mass contraction. Mass contraction can be produced reflexly by the ___________
A

ileocecal sphincter;

Haustral shuttling; sigmoid colon;

transverse colon;

long distance; enterotoxins; gastro-colic reflex.

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7
Q

[Colonic Transit]

Ileocecal valve: The portion of the ileum containing the ileocecal valve projects slightly into the cecum, so that a rise in ___________ squeezes it shut, whereas a rise in ___________ pushes it open. It is normally closed and prevents reflux of colonic contents (especially bacteria) into the small intestine.

Colon: An ingested meal reaches the

  • Cecum in ~4 hour
  • Hepatic flexure (junction of ascending and transverse colon) in ~6 hours
  • Splenic flexure (junction of transverse and descending colon) in ~9 hours
  • Sigmoid colon in ~12 hours
  • Rectum within a day. Feces can be stored for up to 3 days, complete expulsion may take ~ 1 week. ____________ pass more rapidly through the GI tract.
A

colonic pressure, ileal pressure;

High-fiber diets

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8
Q

[Colonic reflexes]

  • Intestine-intestinal reflex: refers to a _________ of intestinal motility that may be caused by large distention of the intestine, injury to the intestinal wall, or various intestinal bacterial infections.
  • Peristaltic rushes: very intense peristaltic waves that may occur in _____________-.
  • Paralytic ileus: Paralytic ileus is the occurrence of intestinal blockage in the absence of an actual physical obstruction. Causes of ileus include __________ (post-surgical ileus), electrolyte imbalances, __________ (inflammation or infection of the stomach or intestines), appendicitis, acute pancreatitis, and obstruction of the ____________, which supplies blood to the abdomen. Certain drugs and medications, such as opioids and sedatives, can cause ileus by slowing peristalsis. Paralytic ileus can cause a distended abdomen, fullness, excessive gas, abdominal spasms, constipation, diarrhea, nausea, vomiting, and foul-smelling breath.
A

complete cessation;

intestinal obstruction;

abdominal surgery; gastroenteritis; mesenteric artery

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9
Q

[Defecation reflex]
The anal canal is situated between the rectum and anus below the pelvic diaphragm. In humans it is approximately 2.5 to 4 cm long. It is surrounded by the internal anal sphincter (smooth muscle) which is under involuntary control, and the external anal sphincter (striated muscle), which is under voluntary control.

Parasympathetic fibers are inhibitory to the internal anal sphincter (relaxation), while sympathetic fibers are excitatory.

Rectal pressures: Distention is sensed by mechanoreceptors located in the wall of the anal canal. The urge to defecate is first felt when rectal pressure increases to ~_______. When rectal pressure reaches _______, the internal anal sphincter relaxes reflexly, which is called the rectoanal inhibitory reflex.

The external anal sphincter is under voluntary control. It can be voluntarily relaxed by signals coming from the brain to the external anal sphincter via the pudendal nerve. Defecation can be voluntarily inhibited by keeping the external anal sphincter contracted. Defecation can be voluntarily initiated at any time when the rectal pressure is between 18-55 mm Hg, by voluntarily relaxing the external anal sphincter, and
straining, that is, by performing the ______________ (expiring against a closed glottis) to increase the intra-abdominal pressure. Voluntary defecation is not possible at rectal pressures below 18 mm Hg.

A

18 mm Hg; 55 mm Hg;

Valsalva maneuver

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10
Q

[Defecation reflex]
Spinal reflex is initiated by the distention of the rectum with feces.
• Afferent nerve: Fibers from the rectum reach the spinal cord through the _____________.
• Efferent nerve: _________ parasympathetic fibers from the S2 (sacral) segment of the spinal cord reach the rectum through the pelvic splanchnic nerve. Patients with spinal cord injuries involving the sacral spinal cord do not have the defecation reflex.
• External anal sphincter is under voluntary control and innervated by the pudendal nerve (somatic nerve). Patients with spinal cord injuries above ____________, which would disrupt the CNS signals sent through the pudendal nerve, have no voluntary control of defecation.

A

pelvic splanchnic nerve;

Cholinergic;

sacral segments

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11
Q

[Gastrocolic reflex]
Gastrocolic reflex is a __________ of the colon brought about by the distention of the stomach. Because of this reflex, infants and young children defecate almost routinely after meals. In adults, bowel training suppresses this reflex. The reflex consists of an early neural phase (within 10 min), which is abolished by ___________, and a late hormonal phase, which coincides with the peak blood level of ______.

A

mass contraction; anti-cholinergic agents; gastrin

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12
Q

[Balance of secretions and absorption]
• There is net reabsorption of water and _____.
• Most of the water must be absorbed in the ___________, otherwise the colon becomes overwhelmed.
• In the colon, most of the water and electrolytes are absorbed in the ____________________.
• The colon is a target for aldosterone, a hormone from the adrenal gland that increases Na+ and water reabsorption and K+ secretion.
• Because there is a net secretion of HCO3- and K+, diarrhea usually leads to a loss of bicarbonate and potassium, which results in _____________.

  • 2 liters of fluid presented to the colon daily.
  • 1.9 liters fluid (Na+, Cl-, H2O) reabsorbed.
  • 0.1 L in feces.
  • Bicarbonate and potassium are secreted in the distal colon.
A

NaCl, small intestine, ascending and transverse colon,

metabolic acidosis and hypokalemia

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13
Q

[Proximal colon: Na+ and Cl- absorption, HCO3- secretion]

Steps in Na+ and Cl- reabsorption and HCO3- secretion in the proximal colon

  1. H+ and HCO3- are generated from carbonic acid (H2CO3).
  2. H+ is extruded into the intestinal lumen in exchange for Na+ uptake via the Na-H exchanger. HCO3- is extruded into the lumen in exchange for absorption of Cl- via the Cl- - HCO3- exchanger (anion exchanger). Chloride also flows through _____________ (not shown) from the lumen to the blood to balance the absorption of Na+.
  3. Na+ enters enterocytes via the Na+/H+ exchanger as it does in the entire small intestine. This protein is encoded by the ___________. Mutations or deletions causes intractable congenital sodium diarrhea of intrauterine onset with fecal sodium loss. Some of these patients develop ___________ later in life.
  4. Na+ that enters the enterocyte is pumped across the basolateral membrane by Na-K ATPase. K+ that enters the cell via the pump is extruded through a K+ channel in the basolateral membrane. Cl- that enters the cell is extruded through a Cl channel in the basolateral membrane.
  5. Na+ absorption is electroneutral because it is balanced by counter-transport of ions with the same charge (K+ and H+).
  6. H2O is absorbed _____________________ (between cells) to balance the absorption of ions. About 1.9 L of fluid is absorbed in the colon.
A

paracellular pathways;

SLC9A3 gene; inflammatory bowel disease;

passively paracellularly

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14
Q

Steps in Na+ absorption in the distal colon

  1. In the distal colon, Na+ enters the enterocyte via _____________ channels. This channel is blocked by micromolar concentrations of the diurectic drug ___________ and is therefore also called an amiloride-sensitive channel.
  2. The hormone aldosterone secreted by the adrenal gland increases Na+ uptake in the distal colon by:
    a) Within seconds opening the ENaC channel;
    b) Within minutes increasing the insertion of preformed ENaC (internally stored) channels into the apical membrane;
    c) Within hours increasing the synthesis of both ENaC channels and ___________.
  3. Na+ absorption in the distal colon is __________ because movement of Na+ contributes to the establishment of the transmembrane potential.
  4. _____________ are absorbed passively paracellularly (between cells).
A

Epithelial Sodium Channel (ENaC); amiloride

Na-KATPase;

electrogenic ; H2O and Cl-

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15
Q

[Feces]
Solids: About 25% of fecal weight is from solids.
Constituents of fecal solids:
1. Bacteria: The bulk of the fecal solids are dead bacteria. The jejunum contains few if any bacteria, the ileum contains more microorganisms, and the colon contains large numbers of bacteria. Bacteria in the intestine are of three types: _______ (help the human), __________ (no particular effect), pathogenic. In immunosuppressed individuals, pathogenic colonic bacteria can enter the blood stream and cause fatal
septicemia. Even in normal individuals, the spread of colonic bacteria to the urinary tract can cause severe infections.

  1. Fats and Proteins in feces are NOT of dietary origin: The fat and proteins in feces are not from dietary origin, but come from _____________ . Hence, fecal composition is relatively unaffected by variations in diet because a large part of fecal material is NON-DIETARY. This is why appreciable amounts of feces continue to be passed during prolonged starvation.
  2. Undigested roughage etc: About 30% of the fecal solids are undigested roughage, undigested plant fibers (cellulose), sloughed epithelial cells, bile pigments (stercobilin).
  3. Inorganic material: Accounts for 10-20 % of fecal solids.
  4. pH of feces: slightly acidic due to the organic acids formed from unabsorbed carbohydrates by intestinal bacteria.
  5. Color: brown color is due to ___________, a product of bilirubin. Feces will be pale and clay colored if less stercobilin/urobilin is present in feces.
A

Symbionts; commensals;

dead bacteria and cellular debris;

urobilin/stercobilin

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16
Q

Intestinal microbiome: The human body contains 100 trillion human cells and carries 10 times that number of bacteria in the intestines. About 500 different species of bacteria live in the intestine.
Benefits of intestinal bacteria
• Vitamin synthesis: Symbiotic colonic bacteria synthesize a water-soluble vitamin K (_______), vitamin B and _________. These are absorbed in significant amounts and supplement dietary intake.
• Short-chain fatty acids: _______________ is converted to short-chain fatty acids by colonic bacteria. These fatty acids enhance colonic absorption of Na+ and water, and also have a trophic effect on the colonic mucosa.
• Alter immune reactions.
• Alter metabolism.
• Microbiome metabolites influence CNS, respiratory tract etc.

A

menaquinone; folic acid;

Undigested lactose and undigested fiber

17
Q

Detrimental bacterial reactions:
• Consumption of Vitamin C, __________ and ___________ can contribute to deficiency.
• Production of ammonia: Colonic bacteria generate ammonia from fecal urea, which is quickly absorbed into the portal circulation, taken to the liver, where it is detoxified. In patients with liver dysfunction (e.g. alcoholic cirrhosis), the ammonia cannot be detoxified in the liver and instead enters the systemic circulation to cause _____________. This causes a neurological syndrome called hepatic encephalopathy. The laxative, ___________, is used to treat hepatic encephalopathy.
• Higher LDL and higher cholesterol: Colonic bacterial activity is associated with higher LDL and cholesterol. Antibiotics such as _______ are poorly absorbed and therefore modify the colonic bacterial flora, and this is associated with a lowering of LDL and cholesterol.
• Intestinal microbial strains have been associated with depression, cancer, lung diseases, obesity, metabolic diseases, cancer.

A

Vitamin B12; Choline

hyperammonemia; lactulose

neomycin;

18
Q

Indifferent bacterial reactions:
• Synthesize smelly compounds: Colonic bacteria synthesize ______________, indole, skatole, mercaptans, and even methane, which contribute to fecal odor.
• Formation of hydrogen: Commensal bacteria form hydrogen from unabsorbed carbohydrates; the hydrogen is absorbed and expired in breath. In lactose
intolerance, breath hydrogen increases following a dietary load of lactose, and this is used as a diagnostic test called the hydrogen breath test.
• Flatulence: Gas within the colon is derived primarily from fermentation of undigested material by intestinal bacteria to produce _______________. The digestive tract normally contains about 150 to 200 mL of gas, most of which is in the colon (100 to 150 mL). Diffusion of gas from the blood to the intestinal lumen is responsible for the N2 present in intestinal gas and is influenced by the atmospheric pressure.

A

hydrogen sulfide;

CO2, H2, and methane;

19
Q

[Drugs for IBD ]

5-ASAs

  • Pro-drugs (sulfasalazine, olsalazine and balsalazide) – cleaved in the intestine by resident bacteria to release active 5-ASA
  • Mechanism – modulate _____________
  • Mesalamine formulations deliver 5-ASAs to different segments of the small or large intestine – ________ (small intestine), _______ (distal ileum, proximal colon), ________ (sigmoid colon), ________ (rectum)

Glucocorticoids

  • Drugs – hydrocortisone enemas, budesonide, prednisone, prednisolone, IV steroids
  • Mechanism – inhibit inflammatory mediators, reduce inflammatory cell adhesion molecules
A

cytokine release

pentesa; asacol; rowasa; canasa

20
Q

[Drugs for IBD ]

Thiopurines (6-metacaptopurine)

  • ________ is a pro-drug which is converted into 6-mercaptopurine in the liver
  • 6-mercaptopurine is metabolized to ____________ which inhibits purine synthesis
  • Mechanism – inhibition of purine synthesis leads to leading to reduced DNA and RNA synthesis especially in immune cells, resulting in immunosuppression

Anti-tnf antibodies

  • Drugs – infliximab (chimeric anti-TNF monoclonal antibody),________ (totally humanized recombinant monoclonal anti-TNF antibody)
  • Mechanism – Binds soluble ___________ and prevents the cytokine from binding to its receptor; Binds to membrane-bound TNF-α and neutralizes it activity.
A

Azathioprine; 6-thioguanine nucleotides;

adalimumab;

TNF-α trimers

21
Q

Laxatives for constipation
1. Dietary fiber (e.g. __________) is fermented by colonic bacteria to short-chain fatty acids that are trophic to the colonic epithelium and they increase the mass of stool.

  1. Bulk-Forming laxatives (e.g. Psyllium husk [fybogel], __________, calcium polycarbophil) attract water and increase the mass of stool.
  2. Stool softening compounds:
    a) ___________, lower surface tension of stool and allow water and lipids to penetrate the stool to hydrate and soften faecal.
    b) _________ penetrates the stool and softens it, lubricates stool and gut lining to facilitate defecation. May result in malabsorption of fat-soluble vitamins.
  3. Osmotic agents: extracts fluid into the intestinal lumen by osmosis, causing diarrhoea

a) Saline laxatives: e.g. Mg citrate, MgSO4, milk of magnesia, Na-Phosphate) osmotically-mediate water retention; produce inflammatory mediators, and may stimulate the release of _________, which leads to intraluminal fluid and electrolyte accumulation and increased intestinal motility.
• Oral Na-phosphate has been associated with ______________ and acute phosphate nephropathy
• Mg-based cathartics has been associated with hyperMg in renal impaired patients

b ) Non-digestible and non-absorbed sugars (e.g. lactulose, sorbitol,) are hydrolyzed in the intestine to organic acids, which acidify the luminal contents and osmotically draw water into the lumen, stimulating colonic motility.

c) ___________-: non-absorbable, not metabolized by colonic bacteria, binds to water and keeps water retention inside the lumen and osmotically increases intraluminal fluid

A

wheat bran;

Methylcellulose;

Docusate sodium; Mineral oil

cholecystokinin;

hyperPO4, hypoCa, hypoK,

Polyethylene glycol (PEG);

22
Q

Laxatives for constipation

  1. Stimulant laxatives (e.g. senna, __________, Na picosulfate) induce/increase intestinal motility via alteration of electrolyte transport by intestinal mucosa. They also increases intestinal secretions (prevents absorption and stimulate secretion of Na and H20 into colonic lumen)
  2. Serotinin 5-HT4 receptor agonist:
    • ___________, a selective high-affinity 5HT4 receptor agonist, and accelerates gastric, small bowel and colonic transit.
  3. Secretagogues:
    • _________ activates chloride channels (ClC-2) on intestinal epithelial cells, causing the secretion of chloride and water into the gut lumen, resulting in accelerated small bowel and colonic transit.
  4. Peripherally acting μ-opioid receptor antagonist (POMAR) (Eg ________, naloxegol, naldemedine) blocks the u-opioid receptors, thereby restoring the function of the enteric nervous system and is used for opioid-induced constipation.
A

bisacodyl;

Prucalopride;

Lubiprostone;

Methylnatrexone;