Oropharyngeal Dysfunction

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Oropharyngeal Dysfunction

• SYMPTOMS OF OROPHARYNGEAL DYSFUNCTION
• (Oropharyngeal Dysphagia)
• Weakness of the lips and tongue can cause
  drooling and inability to propel the food back
  into the pharynx with ineffective voluntary
  initiation of the swallow.
• Failure of elevation of the soft palate against
  the posterior pharyngeal wall causes nasal
  regurgitation
• Failure of closure of the laryngeal vestibule, of
  elevation of the glottis out of the food pathway,
  and failure of the epiglottic deflection causes
  food penetration into the glottis and aspiration
  into the trachea of swallowed material with
  resulting choking, coughing, and contamination of
  the tracheobronchial tree. This can lead to
  recurrent tracheobronchial and pulmonary
  infections.
• Weakness of the pharyngeal constrictors or the
  tongue results in poor propulsion of the bolus
  through the relaxed upper sphincter into the
  esophagus with incomplete emptying of the pharynx
  and potential for aspiration of retained material
  between swallows when the trachea is not
  protected.

• Diseases That Cause Oropharyngeal Dysphagia
• Neurologic disorders of cranial nerves IX, X, and
  XII, and of their motor nuclei and swallowing
  center damage. This can be caused by CVAs in the
  vertebrobasilar artery and posterior, inferior,
  cerebellar artery distribution
• Bilateral cerebrovascular disease with bilateral
  cortical injury can lead to decreased cortical
  input (pseudobulbar palsy) with oropharyngeal
  dysphagia.
• Parkinsons Disease can affect both the oral and
  pharyngeal phases of swallowing with upper
  sphincter dysfunction and pharyngeal stasis.
• Other neurologic disorders (bulbar polio,
  amyotrophic lateral sclerosis, multiple
  sclerosis, and Huntingtons Disease.)
• Striated muscle diseases such as the inflammatory
  myopathies and inclusion body myostitis.
• Muscular Dystrophies (occulopharyngeal dystrophy,
  and myotonia dystrophica).
• Motor end plate disorder (myasthenia gravis).
• Hyperthyroidism and hypothyroidism.

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Esophageal disorders
Note pregnancy (progesterone lowers LES pressure)
Dysphagia, where foods and liquids thru mouth.
Solids Mechanical Obstruction
Solids Liquids Neuromuscular Obst.
Normal Barium Swallow
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Physiology and Pathophysiology of Esophagus
Nervous System Sensory CN V, VII, IX, X gt
solitary tract nucleus via vagus n. Motor
Excitatory and Inhibitory both via vagus n. from
dorsal motor nucleus gt ganglion in myenteric
(Auerbach) plexus gt postganglionics (excitatory
Ach, inhibitory NO/VIP) Peristalsis is
initiated by vagal firing in the upper esophagus,
but then smooth muscle in the rest of esophagus
has local enteric nervous system
coordination Deglutitive inhibition With rapid
swallowing, peristalsis stops and the esophagus
is tonically inhibited. The more distal segments
have longer inhibition periods, so when
excitation reemerges after this inhibition, there
is peristaltic coordination to it. LES has tonic
MYOGENIC tone mediated by calcium. Hence calcium
channel blockers help lower LES pressure. There
is are also vagal excitatory and inhibitory
neursons (Ach, and NO/VIP)
Waterbrash This is the filling of the mouth with
a liquid which is probably saliva, and is
precipitated by gastroesophageal reflux. This
reflux stimulates swallowing of bicarbonate rich
saliva, and is protective against acid reflux
injury. Odynophagia (Pain with
Swallowing) Esophageal pain is most often caused
by inflammatory processes involving the mucosa or
deeper tissue, such as infectious esophagitis,
pill-induced esophagitis or esophageal cancer.
Spastic motility disorders can also cause
esophageal pain. Globus This is a sensation of a
lump or tightness in the throat. The sensation is
not associated with swallowing. The mechanism of
the sensation is not known, but it is generally
associated with intense emotions such as anxiety
and depression, and it may be confused with
dysphagia.
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Achalasia
Birds beak xray
LES Pressure UP!
Peak onset in the third to fourth decade of life.
A disorder of esophageal motility characterized
by the absence of peristalsis, elevated pressure
of the lower esophageal sphincter, and the
failure of the lower sphincter to relax during
swallowing. Achalasias cause is unknown, though
Chagass disease mimics it. Chagass Disease is
caused by a Trypanosoma cruzi prevalent in South
Americ (Brazil). Decreased number of myenteric
plexus (Auerbachs) neurons as well as
degenerative changes in the vagal nerves. The
cause of the degenerative changes is
unknown. Selective loss of VIP/NO inhibitory
post-ganglionic neurons. Anti-mACH AGONIST
antibody turns on contraction. (Botox therapy)
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Scleroderma
Dilation and stricture
LES Pressure UP!
The esophageal lesion in scleroderma is a patchy
smooth muscle atrophy with fibrosis which leads
to decreased esophageal contractility and a low
or absent resting LES pressure. Leads to free
reflux. Pathophysiology of Heartburn -
Contributing Factors A. Weak basal LES B.
Inadequate LES response to increased abdominal
pressure, as with coughing, straining C.
Transient relaxation of LES D. Hiatal hernia
(association exists between severe reflux
esophagitis and large hiatal hernias) E. High
gastric volume due to delayed gastric emptying F.
Diminished esophageal clearance G. Reduction in
salivation H. Inadequate mucosal resistance
Nighttime coughing is due to spill-over of
gastric contents into her lungs, resulting- in
not only coughing and wheezing but aspiration
pneumonia as she lies down.
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GERD
Defensive factors include the gastroesophageal
junction as discussed, salivation and swallowing
and secondary peristaltic contractions stimulated
by reflux, esophageal mucosal bicarbonate
secretion and gravity.
Aggressive factors include increased intra
abdominal pressure, gastric acid and pepsin bile
salts and pancreatic enzymes, slow gastric
emptying and drugs and hormones that cause LES
relaxation. Inappropriate LES relaxation is a
major aggressive factor.
gt
Esophagitis ? Barretts Epithelium ?
Adenocarcinoma

• Pathophysiology of Reflux Disease
• LES 2 sphincters intrinsic and diaphragm crural
• The crura of the diaphragm seem to have maximum
  affect during increases in intra-abdominal
  pressure, such as with inspiration, coughing, or
  straining.
• There are two major mechanisms by which reflux
  occurs
• Transient LES relaxations. Mild reflux disease.
  When the LES relaxes independent of belching and
  swallows
• Intrinsic weakness of the LES. With a sliding
  hiatus hernia, the LES is totally in an
  intrathoracic location such that the bolstering
  effect of the crura is not available and the LES
  is exposed to negative intrathoracic pressure.
• Many foods cause LES relaxation, specially fried
  foods and other fatty foods, chocolate, coffee,
  and tomato sauce. Fatty foods also slow gastric
  emptying after meals and prolong the period of
  reflux.

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Stomach Stuff
A vagotomy (where the vagus nerve is sectioned)
always leads to a delay of gastric emptying of
solids. A vagotomy is generally combined with a
pyloroplasty, a surgical procedure that widens
the pylorus to more readily allow food to pass
through and usually results in rapid emptying of
liquids but solids may still be slowed. This
leads to the dumping syndrome. Rapid emptying of
gastric contents into the small intestine can
cause a dumping syndrome characterized by
nausea, pallor, or sweating within minutes after
eating a meal, especially if it contains a
hyperosmotic drink. This is usually
post-gastrectomy (surgery for peptic ulcer). The
most frequent conditions associated with
mechanical gastric outlet obstruction are peptic
ulcer, tumor, or bezoar. Delayed gastric
emptying in the absence of mechanical obstruction
is known as gastroparesis (as in diabetes).
Patients with gastroparesis may be asymptomatic
or have a range of GI symptoms including
persistent belching, bloating, abdominal pain,
anorexia, early satiety, nausea with or without
vomiting and weight loss.

• Proximal Stomach
• Proximal stomach receives and stores foodstuffs
  and acts, therefore, as a reservoir.
• Receptive relaxation, the ability to relax in
  anticipation of swallowed foodstuffs.
• Accommodation, the capacity to distend without
  increasing intragastric pressure.
• Vagally mediated and due likely to release of
  nitric oxide (NO).
• Distal Stomach
• The principal functions are
• Retain and grind foodstuffs lt 1mm.
• Peristaltic waves pacemaker located in the
• longitudinal muscle of the greater curvature
• Retropulsion occurs when the pylorus is partially
  closed during antral systole and the antral
  contents are thrown backwards for further
  grinding.

Normal Upper GI
Delayed Gastric Emptying
Normal ab xray
Giant stomach
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Peptic Ulcer, H pylori, and NSAIDS

• Stomach Defense Mechanisms
• Mucous barrier, unstirred water layer
• Bicarb pH gradient
• Tight junctions
• Regeneration
• Blood Flow washes out acid that crossed mucosa
• PGs gt do everything
• Duodenum secretes bicarb.

H pylori Colonization factors adhesins, spiral
shape, microaerophilic, flagella, urease (cleaves
urea gt NH3 CO2, the NH3 neutralizes the HCl),
acid inhibitory protein, heat shock proteins,
Immune avoidance catalase, superoxide
dismutase Host Damage ammonia hydroxide (cleaved
from urea) is toxic, lipase, protease, CagA
(inserted into host cell, where it stimulates
cytokine production recruiting PMNs that cause
epithelial damage), VacA (targets the
mitochondria, releasing cyt C gt apoptosis),
growth inhibitory factors prevent
reepithelialization, stimulates a Th1 response
instead of Th2 (more inflammatory) Altered Acid
Secretion in Host increased gastrin due to
ammonia increasing pH which stimulates G cells
(also inflammatory mediators stim G cells),
increased acid output per gastrin (incr parietal
cell mass), inhibition of D cells, less duodenal
bicarb Dx Ingest 13C-urea, exhale 13CO2 (broken
down by urease in stomach gt blood gt
exhaled) Duodenal Ulcer H pylori attaches to
areas of gastric metaplasia in the duodenum gt
duodenitis gt further acid damage gt
ulcer Stomach gastritis, metaplasia,
intestinal/diffuse carcinoma, MALT Tx Proton
pump inhibitor/Clarithro/Amoxi or
Pepto/Tetracycline/Flagyl

• NSAIDS
• Toxic effect (ASA weak acid gt protonated, move
  into mucosa, unprotonate causing damage)
• COX block PGs (COX 1 is constitutively expressed
  in all cells, COX 2 produced in response to
  inflammatory stimuli in macrophages)
• iincrease endothelial adhesion molecules,
  promoting leukocyte adherence, formation of white
  thrombi, causing stasis and local mucosal necrosis

Hypergastrinemias Zollinger Ellison Pancreatic
non-beta islet cell tumorgt gastrin, positive
secretin test, IV secretin causes an increase,
not decrease in gastrin! Atrophic
gastritis/Pernicious anemia ?
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Menetriers Disease
Ménétrier's Disease Ménétrier's disease is a rare
entity characterized by large, tortuous gastric
mucosal folds. The differential diagnosis of
large gastric folds includes ZES, malignancy,
infectious etiologies (CMV, histoplasmosis,
syphilis), and infiltrative disorders such as
sarcoidosis. The mucosal folds in Ménétrier's
disease are often most prominent in the body and
fundus. Histologically, massive foveolar
hyperplasia (hyperplasia of surface and glandular
mucous cells) is noted, which replaces most of
the chief and parietal cells. This hyperplasia
produces the prominent folds observed. The pits
of the gastric glands elongate and may become
extremely tortuous. Although the lamina propria
may contain a mild chronic inflammatory
infiltrate, Ménétrier's disease is not
considered a form of gastritis. The etiology of
this unusual clinical picture is unknown.
Overexpression of growth factors such as TGF-
may be involved in the process. Epigastric pain
at times accompanied by nausea, vomiting,
anorexia, and weight loss are signs and symptoms
in patients with Ménétrier's disease. Occult
gastrointestinal bleeding may occur, but overt
bleeding is unusual and, when present, is due to
superficial mucosal erosions. Between 20 and 100
of patients (depending on time of presentation)
develop a protein-losing gastropathy accompanied
by hypoalbuminemia and edema. Gastric acid
secretion is usually reduced or absent because of
the replacement of parietal cells. Large gastric
folds are readily detectable by either
radiographic (barium meal) or endoscopic methods.
Endoscopy with deep mucosal biopsy (and cytology)
is required to establish the diagnosis and
exclude the other entities that may present in a
similar manner. A nondiagnostic biopsy may lead
to a surgically obtained full-thickness biopsy to
exclude malignancy.
gastrectomy is the only definitive treatment for
this ménétrier's disease gastrectomy eliminates
the protein losing gastropathy, blood loss due to
erosions, symptoms such as intractable nausea
and/or vomiting, and associated risk of gastric
malignancy
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Ulcerative Colitis
GROSS Diffuse confluent erythema, coarse
granularity ('cobblestone' appearance) and
mucosal ulcerations extending from anorectal
junction proximally with a sharp line of
demarcation between the involved and uninvolved
colon MICRO Diffuse shallow mucosal ulcerations
and pseudopolyps active inflammation of mucosa
with cryptitis and crypt abscesses no
granulomas no transmural inflammation.
Crypt abscess
extra colonic complications of ulcerative
colitis skin lesions (pyoderma
gangrenosum/erythema nodosum) , primary
sclerosing cholangitis , arthritis ,amyloidosis
,ankylosing spondylitis ,uveitis
MUCOSAL DAMAGE only
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Crohns Disease
GROSS THICKENED BOWEL WALL WITH LUMINAL
NARROWING AND LONGITUDINAL (SERPIGINOUS) MUCOSAL
ULCERATION. MICRO TRANSMURAL FISSURING
ULCERATION, FOCAL COLITIS WITH NORMAL "SKIP"
AREAS, granulomas THE MASS IS AN INFLAMMATORY
PROCESS (PHLEGMON) not shown

• Clinical Course
• CHRONIC EXACERBATIONS AND REMISSIONS WITH
  POSSIBLE ADDITIONAL COMPLICATIONS RELATED TO
  TRANSMURAL INFLAMMATION (FISTULAE ADHESIONS WITH
  OBSTRUCTION, ETC.)
• MALABSORPTIVE COMPLICATIONS OF ILEAL DISEASE OR
  RESECTION (ESPECIALLY OF VITAMIN B12)
• INCREASED RISK OF SMALL AND LARGE BOWEL
  MALIGNANCY
• EXTRA-GI TRACT COMPLICATIONS
• a. POLYARTERITIS
• b. UVEITIS
• c. ANKYLOSING SPONDYLITIS
• d. ERYTHEMA NODOSUM
• e. AMYLOIDOSIS

Mechanisms of Diarrhea terminal ileal disease
(bile salt diarrhea), loss of absorptive area,
stricture gt bacterial overgrowth, intestinal
resections
Crypt abscesses
Transmural fissure
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Familial Polyposis Coli
GROSS MUCOSA DIFFUSELY STUDDED BY HUNDREDS OF
SMALL POLYPS MICRO POLYPS ARE TUBULAR
ADENOMAS, SOME STALKED, SOME STILL MINUTE AND
STALKLESS
Illustrates the adenoma to carcinoma sequence
Randomly FAP cancers express COX2
Mad adenomas (aka polyp), stalked or sessile
(bump)
Adenomatous epithelial changes elongated,
hyperchromatic nuclei, loss of mucin and
increased mitotic activity compared to normal
colonic glandular epithelium with small
basally-located nuclei, numerous goblet cells and
no mitotic figures
HNPCC is mediated by a different mechanism,
microsatellite instability, in which mismatch
repair gene mutations dont fix microsatellite
mismatches in genes, they dont express COX-2, it
is resistant to anti-DNA agents, and 5FU
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Ischemic Bowel

• Mesenteric ischemia is caused by an interruption
  in blood flow to all or part of the small
  intestine or the right colon.
• SMA occlusion or not full occlusion
• IMA occlusion, venous thrombosis, arteritis
• Pain may be acute (embolism) or chronic (usually
  the case)
• Older patients with CHF, hypovolemia, CAD, CHF,
  digoxin, hypercoagulable states are at risk
• The classic triad of superior mesenteric artery
  (SMA) embolism includes GI emptying, abdominal
  pain, and underlying cardiac disease.
• The sine qua non of mesenteric ischemia is a
  relatively normal abdominal examination in the
  face of severe abdominal pain.

• Watershed areas Splenic flexure (M colic SMA
  and L colic IMA), R colon (decreased arcade
  supply), Sigmoid Colon (L colic and superior
  rectal watershed).
• As the intestinal epithelium dies, it can no
  longer prevent the intestinal contents from
  entering the dying circulation. Consequently,
  noxious materials are absorbed., including
  bacterial enterotoxins, lysosomal hydrolases, and
  cathepsins. The release of these toxins into the
  blood stream in addition to the severe intestinal
  ischemia leads to shock and death unless
  diagnosis and treatment are instituted promptly.

O2 gradient
More O2 diffusion across to vein, leading to
necrosis at tip
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Maldigestion and Malabsorption

• Maldigestion
• Pancreatic Insufficiency
• Zollinger Ellison
• (dec pH gt inactivate pancreatic enzymes)
• 3. Cholestasis/Bile Salt deficiency
• 4. Lack brush border enzymes
• 5. Nutrient digestion by bacterial overgrowth

• Malabsorption
• 3 causes Lumenal Digestion, Terminal Digestion
  (brush border), Transepithelial Transport
• Celiac sprue
• Gastroenteritis (Whipple, Giardiasis)
• Crohns affecting the small bowel ileal
  resection (B12 and bile salts)
• Lymph obstruction

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Diarrhea and Malabsorption

• Diarrhea
• Small bowel disease more watery than colonic b/c
  more water absorbed there
• Stool osmotic gap 290 2(Na K)
• Osmotic Loss of brush border lactase (H2 breath
  test), Bacterial fermentation of carbohydrates
  yield short chain fatty acids (osmoles/secretagogu
  es), which also lower the pH of the stool,
  increased stool osmotic gap, low sodium in stool
• Secretory Turns on crypt secretion of Cl and
  H20, stool anion gap is normal, high stool sodium
• Exudative injury and inflammation caused by
  infection, ischemia, radiation, medication, PGs
  as secretagogues, also loss of absorptive surface
  area gt osmotic diarrhea,
• Motility Decreased motility gt bacterial
  overgrowth gt bile salt deconjugated, reabsorbed,
  leads to fat malabsorption, loss of B12, also
  bacterial fermentation of carbohydrates.

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Intestinal Infections
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Liver Function Tests
Liver Enzymes How does the location of liver
enzymes (specifically AST, ALT, alkaline
phosphatase) affect their blood levels in certain
diseases? The locations of these enzymes are
related to their functions. AST (the enzyme
formerly known as SGOT) and ALT (the enzyme
formerly known as SGPT) allow the liver to
utilize amino acids for energy by transferring an
amino group from the amino acid to
alpha-ketoglutarate to form glutamate. AST and
ALT are integral enzymes of the hepatocyte, are
located in the cytosol (although some AST is
found in mitochondria), and spill into blood when
there is damage to hepatocytes. While ALT is
highly specific to the liver, remember that AST
is found in other tissues including brain,
kidney, heart, muscle, pancreas, and red blood
cells and will therefore be found in blood when
there is damage to these tissues. Alkaline
phosphatase, gamma-glutamyl transpeptidase (GGT),
and 5'-nucleotidase are membrane proteins located
along the canalicular surface of the hepatocyte.
In the liver, alkaline phosphatase is also
synthesized by bile duct epithelial lining cells.
Alkaline phosphatase actually refers to a family
of enzymes that catalyze hydrolysis of phosphate
esters at alkaline pH. Like AST, alkaline
phosphatase is nonspecific to liver, being also
located in bone, placenta, kidney, and
intestine.When there is blockage of bile flow,
the response of the epithelial lining cells is to
increase synthesis and release of alkaline
phosphatase, leading to increased levels in the
serum. These enzymes are released into blood when
bile flow is blocked and there is bile backing up
into the liver and causing cell membrane damage.
Therefore, elevation of these enzymes in blood is
suggestive of cholestasis. It is sometimes
helpful to think of liver function tests in terms
of pairs of enzymes, with one member of the pair
(e.g. AST) being sensitive but not specific for
liver processes, and the other member of the pair
(e.g. ALT) usually being specific and confirming
that the dysfunction is related to the liver.
Alkaline phosphatase can be thought of as paired
with GGT or 5'-nucleotidase in this way (although
neither of these latter two enzymes are specific
to liver, they are sometimes used as confirmatory
tests for hepatobiliary origin of alkaline
phosphatase).
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Alcoholic Liver Disease

• Labs ASTALT gt 2 , both elevated, but always lt
  500 iu/L, macrocytosis
• EtOH metabolism EtOH ADHgt acetaldehyde
  ALDHgt acetate, Disulfiram works by blocking
  ALDH
• Histopathology Alcoholic Fatty Liver (aka
  steatosis) gt Alcoholic Hepatis gt Cirrhosis
• Mechanisms of Damage centrilobular (ischemia due
  to EtOH metabolism consuming O2), PMNs (unique in
  hepatities), acetaldehyde radicals adduct to
  proteins leading to dysfxn and provoking immune
  response as neoantigens, possible LPS gt
  inflammation
• Risk factors Amt of EtOH, Hep B/C (EtOH may
  allow Hep C to replicate more effectively) ,
  obesity, toxic stuff, iron overload, poor
  nutrition
• The stellate cell (Ito cell) is the principal
  source of fibrosis in cirrhosis. In normal liver,
  stellate cells are perisinusoidal cells
  distributed throughout the liver which are
  important for storing the bulk of hepatic vitamin
  A. With liver injury, these cells undergo a
  characteristic "activation" (by neighboring cell
  paracrine cytokines and lipid aldehydes) in which
  they lose vitamin A, proliferate, and become
  fibrogenic.

Pathogenesis of Ascites Portal Hypertension ?
Splanchnic Vasodilation (possibly due to
endotoxinemia (due to shunting of blood past the
Kupfer cells, increased bacterial overgrowth,
increased intestinal permeability) gt
upregulation of NO-synthase) ? Pooling of blood
in splanchnic circulation ? Decreased renal
perfusion, decreased SVR, decreased MAP, ? RAA,
Sympathetic Nervous constriction, ADH secretion ?
Water retention, Na retention, increased plasma
volume

• Liver cell necrosis
• Mallory bodies
• Infiltration by neutrophils
• Perivenular distribution of inflammation

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Pancreatitis
Her calcium is quite low. (The serum albumin is
not given but was 4.1 mg). Lipase released from
the pancreas can cleave fatty acids from
triglyceride which then can combine with calcium
to form fatty acid soaps, in the peritoneal
cavity. Patients with pancreatitis due to
alcoholism often have low serum magnesium which
decreases parathyroid release of PTH which can
also contribute to low serum calcium.
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Gallstones

• Black pigment stones
• Calcium bilirubinate
• Conjugated bilirubin is secreted into gallbladder
• It can be deconjugated by B glucoronidase on the
  biliary epithelium or by bacteria
• Unconjugated bilirubin precipitates with calcium,
  polymerizes as a black polymer
• Risk factors chronic hemolysis, chronic liver
  disease (increase the amt of unconjugated
  bilirubin), age, Crohns disease (increased
  resorption of of unconjugated bilirubin)

• Cholesterol Stones
• Cholesterol is turned into bile salts via 7
  alpha hydroxylase (this enzyme decreases in old
  people)
• Cholesterol supersaturated bile gt gallbladder
  hypomotility increased gallbladder mucin
  secretion
• Gallbladder ceases to function as a reservoir for
  bile, instead it is a locus for crystallization
• Newly synthesized bile is secreted into intestine
  instead of gall bladder. Spending more time in
  the intestine, it is turned into the strong
  detergent deoxycholate by bacteria. Once
  reabsorbed, this strong detergent clings onto
  even more cholesterol, seeding more stones!
• Risk factors age, ethnicity, female, pregnancy,
  obesity (incr. HMG coA, adoption of low fat diet
  decreasing CCK decreasing gall bladder motility),
  hypercholesterolemic agents (fibrates, niacins
  increase amt of cholesterol secreted into bile),
  hypertriglyceridemia, gallbladder stasis

• Brown Pigment Stones
• Lipids degraded by bacterial phospholipase A2
  form calcium salts
• Deconjugation of bilirubin by B glucoronidase
• Typically found in infection of bile ducts
  post-obstruction
• Bacteria also deconjugate free bile acids gt less
  cholesterol solubility