Gi And Nutrition

Front 1

What are the signs and symptoms of GI pathology?

Back 1

pain
bleeding
dysphagia
nausea/vomiting
diarrhea
constipation
weight loss
jaundice

Front 2

What are the main general mechanisms of GI pathology?

Back 2

inflammation
ulceration
obstruction
dysmotility

Front 3

What are the GI functions of the mouth and oropharynx?

Back 3

taste
mechanical preparation of bolus
lubrication
transport
digestion

Front 4

What is dysguesia?

Back 4

Taste issues.
Bad taste in mouth etc.

Front 5

What is pyrosis?

Back 5

Heartburn

Front 6

What is odynophagia?

Back 6

Painful swallowing.

Front 7

What is dyspepsia?

Back 7

Discomfort in the upper abdomen.

Front 8

What is the anatomical boundary between the duodenum and jejunum?

Back 8

The ligament of Treitz.

Front 9

What are borborygmy?

Back 9

Growling noises made by the abdomen.

Front 10

What symptoms are associated with liver dysfunction?

Back 10

fatigue
anorexia
pruritus
jaundice

Diseases that are purely confined to the liver (not the biliary tree) are not typically associated with severe pain.

Front 11

What symptoms are typically associated with biliary tree problems?

Back 11

pain
jaundice
pruritus

Front 12

What symptoms are typically associated with pancreatic problems?

Back 12

pain
diarrhea
jaundice

Front 13

What is melena?

Back 13

Black, tarry, sticky stool.

Front 14

What is hematochezia?

Back 14

Fresh red blood in the stool.

Front 15

What are considered GI alarm symptoms?

Back 15

Weight loss

Blood loss:
hematemesis, coffee-grounds emesis, melena, hematochezia

Iron-deficiency anemia

Dysphagia

Nocturnal symptoms (unusual)

New-onset GI symptoms after age 45

Jaundice

Front 16

What symptoms are typically associated with esophageal problems?

Back 16

Dysphagia
Odynophagia
Heartburn (pyrosis)
Chest pain

Front 17

At what stage of embryonic development does the GI tract form?

Back 17

During fourth week of gestation.

Appears as 4 mm hollow tube.

Buccopharyngeal and cloacal membranes rupture during the third and seventh weeks respectively.

By end of 2nd trimester, organs well formed and display early function.

Front 18

What parts of the GI tract are considered foregut?

Back 18

Esophagus
Stomach
Duodenum
Liver
Gallbladder
Pancreas

Front 19

What parts of the GI tract are considered midgut?

Back 19

Jejunum
Ileum
Ascending colon
Transverse colon

Front 20

What parts of the GI tract are considered hind gut?

Back 20

Descending colon
Rectosigmoid colon

Front 21

Is there a male:female bias to esophageal atresia with or without tracheoesophageal fistula?

Back 21

No

1:3-5000 live births

~50% have other associated anomalies such as:

Polyhydraminos in 50% of mothers

Cardiovascular-PDA, VSD, ASD

Gastrointestinal-imperforate anus, duodenal atresia

Skeletal-vertebral anomalies

Genitourinary-hypospadias

Other-trisomy

Front 22

What is the most common type of tracheoesophageal fistula type malformation?

Back 22

Type C

Proximal esophageal atresia with a distal type tracheoesophageal fistula.

Accounts for ~85% of cases.

Esophageal gap 1 to 2 cm.

Distal TEF joins trachea at carina.

Diagnosis made by placing nasogastric tube.

Cough, choking, aspiration with first feed.

Front 23

What is pure esophageal atresia? (Type A)

Back 23

10% of congenital esophageal defects

Absence of gas within the GI tract

20% will have Down’s syndrome

If the gap between the esophageal pouches is > 4 cm primary anastomosis is difficult

Front 24

What is an H tracheoesophageal fistula (type E)?

Back 24

Looks like an H

3% to 5% of cases

Rarely have other anomalies

Repeated episodes of pneumonia

Esophagus and trachea otherwise normal.

Front 25

How does pyloric stenosis in newborns present?

Back 25

1:1000 live births
(more common than atresias)

Presents 1 week to 5 months

Most frequent surgical disorder of the stomach in babies.

Males to females 4-6:1

Family history in ~13%.

Non-bilious vomiting.

Hypochloremic alkalosis.

Pyloric mass on PE.

Front 26

What are some of the possible explanations of the pathogenesis of congenital pyloric stenosis?

Back 26

Pyloric muscle hypertrophy from gastric peristalsis against closed pyloric canal.

Hypergastrinemia with hyperacidity

Elevations of prostaglandins leading to smooth muscle constriction.

Front 27

How doe duodenal atresia present?

Back 27

Bilious vomiting and abdominal distension.

"Double bubble" x-ray

Thought to arise from failure of recanalization of duodenal lumina
Incidence is 1 in 10,000

50% infants premature. F to M 2:1

Down’s syndrome occurs in up to 30%

Front 28

What does a proximal jejunal atresia look like radiographically?

Back 28

Large dilated loops are seen in the upper abdomen with no distal gas.

Impossible to determine which type of atresia is involved without laparotomy.

Contrast studies are unnecessary in most cases.

Front 29

What is duplication of the GI tract?

Back 29

Typically present later than atresias and stenosis.
(mass effect from a cyst blocking the lumen does not usually happen until later)

Front 30

What is malrotation of the mid gut?

Back 30

Failure of midgut to achieve normal position.

Can live normally but predisposes to midgut volvulus.

If this happens:
Acute bowel obstruction.
Bilious vomiting.
!Surgical emergency!

Front 31

What is a Meckel's diverticulum?

Back 31

Remnant of vitelointestinal duct.

Antimesenteric border of ileum.

2-3% of population.

Painless rectal bleeding in children <2

Crampy abdominal pain.

Front 32

What is Hirschsprung's disease?

Back 32

Absence of intramural ganglion cells.

1:5000

M>F

Associated with Down's

75% Rectosigmoid colon.

Aganglionic segment permanently contracted.

Delayed passage of meconium.

Problems within the first year.

Failure to thrive, vomiting, intermittent diarrhea.

Abdominal distension.

Front 33

What tests can we use for Hirschsprung's disease?

Back 33

Unprepared barium enema

Mucosal suction biopsy

Anorectal Manometry
(internal sphincter will not relax in Hirschsprung's)

Front 34

Which substances are absorbed by active transport and which are absorbed by diffusion?

Back 34

Active transport:
amino acids
sugars
vitamins

Diffusion:
water
minerals
vitamins
lipids

Front 35

What are some examples of pathologies of motility?

Back 35

Swallowing
GERD
vomiting
gastroparesia
ileus
diarrhea
constipation

Front 36

What are some examples of pathologies of secretion?

Back 36

Ulcer disease
malabsorption
diarrhea
pernicious anemia

Front 37

What are some examples of pathologies of active transport and diffusion?

Back 37

Malabsorbtion and diarrhea can be caused by either.

Front 38

What target in the GI system is the sympathetic system able to innervate DIRECTLY?

Back 38

Blood vessels

Front 39

What are the components of the enteric nervous system (intrinsic)?

Back 39

Myenteric Plexus (Auerbach’s)
Submucosal Plexus (Meissner’s)
Deep Muscular Plexus

Front 40

What are interstitial cells of Cajal?

Back 40

Cells of mesenchymal origin most of which express a c-kit receptor which causes them to develop distinctly from smooth muscle cells.

These cells establish gap junctions with smooth muscle cells and can conduct impulses from nerves.

Some can even function as pacemakers and provide continuous depolarization.

Front 41

Where do we find the various interstitial cells of Cajal?

Back 41

Associated with the myenteric plexus the ICC-MY (Auerbach)

Associated with the submucosal plexus in the colon

Associated with the deep muscular plexus (ICC-DMP)

Found within muscle layers (ICC-IM)

Found on surface of muscle bundles (ICC-SEP)

Front 42

What neurotransmitters contract GI smooth muscle?

Back 42

AcH
Substance P

Front 43

What neurotransmitters relax GI smooth muscle?

Back 43

VIP (vasointestinal polypeptide)
Nitric oxide
ATP

Front 44

What are the four stages of response to a meal?

Back 44

Cephalic
Gastric
Intestinal
Interdigestive

Front 45

What is the cephalic phase of response to a meal?

Back 45

The sight, smell and taste of food as well as mechanical stimulation of the oral cavity participate.

Salivation is stimulated by cholinergic nerves.

Vagal reflexes inhibit contractile activity in the proximal stomach [receptive relaxation], stimulate acid secretion by parietal cells in the stomach and secretion of histamine by enterochromaffin-like (ECL) cells.

Vagal reflexes to the antrum stimulate secretion of gastrointestinal hormones and also induce a relatively small stimulation of enzyme secretion by the exocrine pancreas.

Front 46

What is the gastric phase of response to a meal?

Back 46

Distention of the stomach activates stretch receptors initiating a number of reflexes which alter gastric, intestinal, colonic and pancreatic activities.

Gastric acid secretion is stimulated by vago-vagal reflexes and reflexes mediated by the enteric nerve plexus.

If the meal contains protein, protein digestion products produced will stimulate secretion of gastrin further enhancing acid secretion.

In addition to stimulating gastric acid secretion, these reflexes stimulate gastrointestinal motility. (increase in the contractile activity of the ileum and relaxation of the ileocecal sphincter [gastroileal reflex] and mass movement in the distal colon [gastrocolic reflex].

Vagal reflexes also cause a relatively small stimulation of enzyme secretion by the exocrine pancreas.

Front 47

What is the intestinal phase of response to a meal?

Back 47

Chyme entering the small intestine initiates neural and hormonal mechanisms which alter the activities of the small intestine, pancreas, gallbladder and stomach.

As chyme empties from the stomach into the small intestine mechanical (distention) and chemical signals (osmolarity, pH, breakdown products) stimulate contractile activity and secretion.

Front 48

What is the interdigestive phase of response to a meal?

Back 48

The interdigestive phase is the period of fasting after most of the components of the previous meal have been digested and absorbed and the stomach and small intestine are relatively empty.

This phase is characterized by brief periods of intense peristaltic contractions appearing first in the stomach and then in the upper, middle and finally the distal small intestine.

These periods of intense contractile activity last for only 5-10 min and are followed by longer relatively quiescent periods. This pattern repeats at intervals of approximately 90 min and has been called the migrating motor complex (MMC).

Front 49

Where do we see tonic rather than phase contraction in the GI tract?

Back 49

Sphincters

Front 50

What pattern of electrical depolarization in the GI tract?

Back 50

There are different slow wave frequencies in every part of the GI tract.

When the waves exceed a certain potential they are coupled with contraction.

Front 51

What are the motility patterns for the various parts of the GI tract?

Back 51

Front 52

What is the normal slow wave pacemaker rate of the stomach?

Back 52

3 cycles per minute

Front 53

What causes receptive relaxation in the fundus?

Back 53

Vagal mediated relaxation.

NO and VIP are the neurotransmitters involved.

Front 54

What sort of noninvasive clinical tests look at the neuromuscular activities of the stomach?

Back 54

Scintigraphy:
isotope labelled foods

pH/motility capsule:
ingested with test foods

Electrogastrograms (EGG):
myoelectrical activity of the stomach.

Front 55

What do the patterns for liquid and solid phase gastric emptying look like?

Back 55

Liquid phase has a faster decline because of more rapid emptying.

Front 56

Which stomach neuromuscular dysfunctions are associated with which postprandial symptoms?

Back 56

Early satiety:
Poor or excessive accommodation

Nausea:
Tachygastria or bradygastria

Prolonged postprandial fullness:
Hypomotility (gastroparesis)

RUQ pain:
Pylorospasms

Nausea, pain, bloating:
Hypersensitive stomach

Front 57

What is the differential diagnosis for gastroparesis?

Back 57

Obstuctive gastropareis

Ischemic gastroparesis

Diabetic gastroparesis
(type 1 and 2)

Postsurgical gastroparesis (antrectomy, vagotomy, fundectomy, fundoplication)

Miscellaneous Causes
(CVD, amyloid, MD)

Idiopathic gastroparesis
(postviral, drug-induced, degenerative or inflammatory processes-smooth muscle, enteric n., interstitial cells of Cajal, ANS)

Front 58

What diet do we recommend for gastroparesis patients?

Back 58

Front 59

What is a neurocrine or paracrine hormone?

Back 59

One which affects neighboring cells.

Termed neurocrine if the secreting cell is a neuron.

Autocrine hormones affect the secreting cell itself.

Front 60

What is included in the gastrin family of hormones?

Back 60

Cholecystokinin
Gastrin

Cholecystokinin without a sulfate group will behave just like gastrin.

Front 61

What are the receptors that are acted upon by the gastrin family?

Back 61

CCK1 is receptor for gastrin.

CCK2 is receptor for cholecystokinin.

Binding is highly concentration dependent.

Under physiological concentrations cholecystokinin has no effect on the gastrin receptor.

Because gastrin is far more abundant in the circulation, the gastrin effect is predominant.

Front 62

How is gastrin made?

Back 62

Preprogastrin is made into progastrin which is a three domain (A,B,C) polypeptide seperated by two diarginyl cleavage sites.

Cleavage of A and C by a signal peptidase leaves progastrin which is then conveted by a prohormone convertase into one of the two active forms of gastrin.

These are:
Glycine extended gastrin 17+CTFP
and
Gastrin 17 amide.
(glysine extended form or amidated form)

Each of these forms acts on different receptors.

Front 63

What stimulates and suppresses gastrin secretion?

Back 63

Stimulation:
Presence of protein digestion products.
Gastric distention.
(various local and central reflexes)

Inhibition:
Acid
(H+ stimulates D-cells to make somatostatin which inhibits gastrin production)

Front 64

What is the main function of gastrin?

Back 64

To stimulate production of gastric acid.

Front 65

Apart from producing gastrin which directly stimulates parietal cells to make acid, what do gastrin producing cell (G-cells) do when they are activated?

Back 65

They activate ECL cells (enterochromatin light cells) which produce histamine.
Histamine binds to type 2 histamine receptors in the parietal cells and further stimulates acid production.

Gastrin made by the G-cells also activates D-cells which make somatostatin and this constitutes the negative feedback because somatostatin inhibits parietal cells, G-cells and ECL cells.

Front 66

Which of the two forms of gastrin is the one responsible for stimulating acid production?

Back 66

The amidated form

The glysine extended form is mostly important for cell proliferation.

Front 67

What are the effects of cholecystokinin?

Back 67

Stimulates bile secretion by promoting the contraction of the gallbladder and the relaxation of the sphincter of odi.

Stimulates the secretion of pancreatic enzymes.

Inhibits gastric emptying.

Increases the proliferation of pancreatic glandular cells.

Synergizes with secretin which promotes pancreatic bicarbonate formation so the presence of both hormones causes a large rise in pancreatic fluid secretion.

Front 68

What are the effects of secretin?

Back 68

Stimulates pancreatic fluid bicarbonate secretion.

Stimulates bicarbonate secretion by the liver.

Inhibits gastric acid secretion.

Promotes pancreatic cell proliferation.

Front 69

What regulates secretin release?

Back 69

Duodenal pH

Front 70

What are incretin hormones?

Back 70

Incretin hormones are those that can explain the incretin effect or the difference in insulin response to oral and IV glucose.

In normal subjects the oral response augmentation is three to four fold the IV response.

GIP:
Gastric Inhibitory Peptide aka
Glucose-dependent Insulinotropic Peptide

GLP-1:
Glucacon Like Peptide 1
Produced in the intestine in response to food ingestion.
Broken down by DPP-4
Both GLP-1 and DPP-4 are used in diabetes management.

GIP and GLP-1 also inhibit glucagon secretion and decrease gastric emptying.

GIP seems to be more important regarding insulin secretion.

GLP-1 is a more potent agonist, thus a better candidate as a potential drug.

Front 71

What stimulates GIP release

Back 71

Amino acids
Glucose
Fatty acids and monoglycerides

Front 72

What stimulates GIP release

Back 72

Amino acids
Glucose
Fatty acids and monoglycerides

Front 73

What is the main effect of the secretin family hormone, motilin?

Back 73

Causes rhythmic contractility during fasting.

Motilin receptors can be activated by erythromycin family antibiotics which can cause diarrhea even without damaging the native flora.

Front 74

What are the secretin family hormones that affect appetite and where are they synthesized?

Back 74

PYY:
Synthesized in L cells in colon

Ghrelin:
Synthesized in X (A-like) endocrine cells in stomach

Leptin:
Synthesized in adipocytes

Front 75

How does PYY affect appetite?

Back 75

Binds the Y2 receptor type

Induces sensation of satiety

Secretion of PYY is suppressed by fasting.

Front 76

How does Grehlin affect appetite?

Back 76

Binds the GHS-R receptor

Induces sensation of hunger

Also has effects on contractility.

Secretion stimulated sharply before a meal and suppressed by meal ingestion.

Front 77

How do various food affect GI hormone secretion?

Back 77

See table.

Front 78

What are the net effects of the various GI hormones?

Back 78

See table

Front 79

What are the GI paracrine hormones?

Back 79

Somatostatin

Histamine

Nitric Oxide

VIP

Serotonin

Gastrin Releasing Peptide
(GRP or Bombesin)

Front 80

What neurotransmitter relaxes sphincters?

Back 80

Nitric oxide

Front 81

Anatomically speaking, where is the esophagus?

Back 81

Posterior organ.

Starts at cricoid cartilage.

Perforates diaphragm at T10.

Front 82

What sort of muscles comprise the esophagus?

Back 82

Inner layer:
Circular muscle

Outer layer:
Proximal one-third is lined by striated muscle.
Smooth muscle lines the distal two-thirds.

Front 83

What is the lower esophageal sphincter constructed of?

Back 83

Inner circular muscle
Diaphragm

Upper esophageal sphincter is cricopharyngeal muscle.

Front 84

What innervates esophageal muscles?

Back 84

Primarily vagus nerve.

Upper striated portion is controlled primarily by Ach.

Lower smooth muscle is controlled by Ach and by nitric oxide.

Upper and lower portions are controlled by different parts of the brain.

Front 85

What happens during the pharyngeal phase of swallowing?

Back 85

Food reaches the pharynx
Swallowing center activated
Cranial nerves 5, 7, 9, 10, & 12
Tongue raises
Nasal airway closes
Epiglottis closes
UES relaxes
Pharyngeal muscles contract

Front 86

What happens during the 10 second or more esophageal phase of swallowing?

Back 86

Food reaches proximal esophagus

Vagal afferents are activated

Peristalsis begins by activation of the intrinsic esophageal nerves (myenteric plexus)

LES relaxes

Peristalsis proceeds from proximal to distal esophagus.

Front 87

What are symptoms we typically associate with the esophagus?

Back 87

Dysphagia
Odynophagia
Heartburn (“pyrosis”)
Regurgitation
Chest Pain (noncardiac)

Front 88

What symptoms are associated with oropharyngeal dysphagia?

Back 88

Food sticking in throat
Repetitive swallows
Nasal regurgitation
Coughing
Aspiration

Front 89

What are some possible etiologies of oropharyngeal dysphagia?

Back 89

Structural:
Zenker’s diverticulum, cricopharyngeal bar, webs, tumors

CNS:
Stroke, tumors, trauma
Other neurologic: Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis

Myopathy: Myasthenia gravis, polymyositis, mixed connective tissue disease

Picture shows Zenker's diverticulum.

Front 90

What tests are used to evaluate esophageal dysphagia?

Back 90

Barium Esophagram

Esophagoscopy (EGD)

Esophageal Manometry

Front 91

What is a Shatzki ring?

Back 91

An esophageal mucosal stricture right above the diaphragm.

Front 92

What are some cause of esophagitis?

Back 92

GERD
Eosinophilic esophagitis (EoE)
Infections

Medications:
tetracycline, KCl, quinidine, alendronate, 5-FU, daunorubicin, bleo

Radiation

Caustic ingestion

Front 93

What is eosinophilic esophagitis?

Back 93

Clinical symptoms of esophageal dysfunction – usually solid-food dysphagia and food impactions

> 15 eosinophils/ high-power field

Normal 24-hour pH monitoring

No response to high-dose PPI therapy.

Strong male bias.

mean age = 38

50-80 % are atopic – atopic dermatitis, allergic rhinitis, asthma

Most likely food allergens, possibly aeroallergens.

Can have multiple corrugated rings as pictured.

Front 94

What does eosinophillic esophagitis look like on endoscopy?

Back 94

Concentric rings

Linear furrows

White plaques
(eosinophilic microabscesses)

Food impaction

Front 95

How do we treat eosinophillic esophagitis?

Back 95

Acid suppression

Diet – elimination, elemental

Topical steroids – swallowed fluticasone or budesonide

Systemic steroids
Cromolyn, Montelukast

Biologics

Front 96

What are some causes of odynophagia or painful swallowing?

Back 96

Infectious esophagitis:
Fungal (Candida most common)
Viral – CMV, HSV
Idiopathic

Corrosive esophagitis

Pill-induced esophagitis

Front 97

What motility disorders can cause esophageal dysphagia?

Back 97

Achalasia and other spastic motor disorders

Diffuse esophageal spasm

Nutcracker esophagus

Hypertensive LES

Scleroderma

Other hypocontractile motor disorders

Front 98

What is esophageal achalasia?

Back 98

Failure of LES relaxation + loss of peristalsis in distal esophagus.

Elevated LES pressure: 50 % of cases

No sex bias.

Relatively uncommon.

Loss of NO and VIP vagal transmission causes a change in the balance of tone so that only Ach (contractile) is present.

Front 99

What is globus?

Back 99

The sensation of a lump in the throat.

Front 100

How do we treat esophageal achalasia?

Back 100

Nitrates and CCB's.

Botox the muscle.

Pneumatic dilation. (risk of perforation)

Surgical myotomy (best)

Front 101

What symptoms are associated with GERD?

Back 101

Heartburn (pyrosis) 83%
Regurgitation 70%
Dysphagia 37%
Respiratory symptoms 30%
Chest pain 10%
Abdominal pain 10%
Nausea 8%
Belching 7%

Front 102

What are the mechanisms of esophageal reflux?
(Important)

Back 102

Transient lower esophageal sphincter relaxations (TLESRs).

A hypotensive lower esophageal sphincter (LES).

Anatomic disruption of the gastroesophageal junction, usually associated with a hiatal hernia.

Front 103

Why does hiatal hernia cause GERD?

Back 103

Loss of the diaphragmatic pinch to help close the LES.

LES pressure becomes lowered.

The gastric pouch becomes an intrathoracic reservoir.

Front 104

What mechanisms help acid clearance from the esophagus?

Back 104

Swallowing
Salivation
Peristalsis
Esophageal bicarbonate secretion

Front 105

How do we diagnose GERD?

Back 105

Symptoms

Response to empirical trial of acid suppression therapy (PPI)

Endoscopy

24-hour pH monitoring

Front 106

What complications are associated with GERD?

Back 106

Ulcer
Stricture
Barrett’s esophagus
Adenocarcinoma

Front 107

What is Barrett's esophagus?

Back 107

Defined as a change in the lining of the esophageal mucosa from normal squamous epithelium to columnar with Intestinal metaplasia.

Occurs in 10-15% of patients with chronic GERD.

Pre-malignant condition which may eventually lead to dysplasia and adenocarcinoma of the esophagus.

Rate of progression of Barrett’s esophagus to cancer is estimated to be 0.5% per year.

Factors that promote progression of BE to cancer are unknown.

This is a highly aggressive tumor though with a 2-5% 5 year survival.

Therefore, all patients with Barrett’s esophagus undergo regular endoscopic surveillance.

Experimentally, obliteration of Barrett’s mucosa using PDT may restore squamous epithelium.

Front 108

The goals of GERD treatment are...

Back 108

Reduce or eliminate symptoms

Heal esophagitis

Prevent complications

Improve quality of life

Front 109

What are the treatment options for GERD?

Back 109

Lifestyle modifications
Antacids
H2-receptor antagonists
Proton pump inhibitors
Antireflux surgery
Prokinetic agents
New endoscopic therapies

Front 110

What are some therapeutic targets for acid inhibition?

Back 110

Histamine blockade
Ach Blockade (anticholinergics)
Proton pump inhibition

Front 111

H2 receptor antagonists end in the suffix...

Back 111

...tidine

Front 112

Proton pump inhibitors end in the suffix..

Back 112

...prazole

Front 113

Which is the better class of drugs in terms of healing and symptom control, H2RA's or PPI's?

Back 113

PPI's

Front 114

Picture of functional anatomy of the stomach.

Back 114

Front 115

What types of cells are found in the oxyntic glands of the gastric body?

Back 115

mucous neck cells
parietal cells
chief cells
ECL cells

Front 116

What types of cells are found in the pyloric glands of the gastric antrum?

Back 116

mucous cells
G cells

Front 117

What is the function of the hydrochloric acid made by the parietal cells of the stomach?

Back 117

Kills microorganisms

Cleaves pepsinogen to pepsin

Activates pepsin at pH < 4

Front 118

What is the function of intrinsic factor made by the parietal cells of the stomach?

Back 118

binds B12 (cobalamin) which allows absorption in the terminal ileum

Front 119

How does B12 absorption work?

Back 119

B12 is liberated from dietary proteins by pepsin/acid

B12 binds to salivary/gastric R factor

B12 is cleaved from R factor by pancreatic proteases

B12 binds to Intrinsic Factor

B12-IF complex binds to ileal receptor

Front 120

What is pernicious anemia?

Back 120

autoimmune gastritis

antibodies directed against:
parietal cells and/or intrinsic factor

mucosal damage is greatest in body and fundus

gland destruction leads to:
achlorhydria and vitamin B12 deficiency

gastritis - metaplasia - dysplasia - carcinoma

Front 121

What is the function of chief cells?

Back 121

They make pepsinogens which are cleaved by HCL to pepsin

pepsin is a proteolytic enzyme

Front 122

What is the function of ECL's or Enterochromaffin Like Cells?

Back 122

They produce Histamine which stimulates the parietal cell to secrete HCl.

stimulated by gastrin, acetylcholine (vagus)

inhibited by somatostatin

Front 123

What is the function of G-cells?

Back 123

Stimulates ECL cells to release histamine.

Stimulates oxyntic glands to secrete:
HCl
pepsinogens

Trophic effect on:
parietal cell mass
ECL cell mass

Gastrin release stimulated by:
gastric distention
amino acids

Gastrin release inhibited by:
somatostatin
gastric acid

Can be thought of as "go" cells.

Front 124

What are HCL secretion agonists and antagonists?

Back 124

Agonists:
histamine
gastrin
acetylcholine

Antagonists:
somatostatin
prostaglandins
epidermal growth factor (EGF)

Front 125

What is the function of D-cells?

Back 125

Produce somatostatin which inhibits histamine release by ECL cells, Gastrin release by G cells and HCL secretion by parietal cells.

stimulated by:
acid
CCK
gastrin

inhibited by:
acetylcholine (vagus)

Can be thought of as "downer" cells

Front 126

What is the cephalic phase of acid secretion?

Back 126

Elicited by sight, smell, and taste of food.

Entirely mediated by the vagus nerve.

Directly stimulates parietal cell

Stimulates ECL cells to release histamine.

Stimulates antral G cell to release gastrin.

Inhibits D cell release of somatostatin.

Feedback inhibition:
low gastric pH evokes
direct inhibition of parietal cells and G cells by inhibitory neural reflexes.

Front 127

What is the gastric phase of HCL secretion?

Back 127

gastric distention:
mechanoreceptors in the gastric wall initiate vagovagal reflexes.

Amino acids and peptides
stimulate antral G cells to secrete gastrin.

Front 128

What is the intestinal phase of acid secretion?

Back 128

acid in duodenum inhibits vagovagal reflex and
releases secretin which inhibits acid secretion through inhibition of g cell gastrin release.

Fat and protein in the duodenum
release CCK, which inhibits acid secretion through stimulation of D cell somatostatin release.

Front 129

What elements provide mucosal protection in the stomach?

Back 129

mucus secretion
bicarbonate secretion
epithelial barrier
mucosal blood flow

The pathogenesis of peptic ulcer disease is an ongoing battle between:
acid/pepsin
vs.
mucus/bicarbonate

Front 130

What are the causes of peptic ulcer disease?

Back 130

Helicobacter Pylori
NSAIDs
Stress
Gastrinoma

Front 131

What is helicobacter pylori?

Back 131

small gram negative rod with flagella

colonizes the mucous layer (not invasive)

Elaborates urease which produces ammonia and thereby neutralizes acid in the bacterial microenvironment.

Strains expressing cagA and vacA genes are the most ulcerogenic and carcinogenic.

Induces chronic gastritis through the elaboration of cytotoxins and bacterial lipopolysaccharide.

Inflamed gastric mucosa produces less mucus and bicarbonate, hindering mucosal protection.

Causes a 6-fold increase in the incidence of gastric cancer.

May cause up to 40% of all cases of gastric adenocarcinoma.

May cause up to 90% of all cases of MALT (mucosa-associated lymphoid tissue) lymphoma. MALT can be treated with antibiotics.

Front 132

What tests are used to diagnose H. Pylori?

Back 132

Antibody blood test stays high after cure.

serology
urea breath test
stool antigen assay
biopsy urease test (CLO)
histology
culture

Front 133

How do we treat H. Pylori?
(don't need to memorize)

Back 133

clarithromycin 500 mg PO bid
amoxacillin 1 gm PO bid
omeprazole 20 mg PO bid
or
clarithromycin 500 mg PO bid
metronidazole 500 mg PO bid
omeprazole 20 mg PO bid
or
bismuth subsalicylate 225 mg qid
metronidazole 250 mg PO qid
tetracycline 250 mg PO qid

All regimens include two antibiotics and PPI.

Front 134

What are the two forms of cycloxygenase?

Back 134

COX-1:
constitutive isoform of COX
produces PROSTACYCLIN (cytoprotective in gastric mucosa)

COX-2
inducible isoform
induced by inflammation, cytokines

Front 135

What is the effect of prostanglandins on the gastric mucosa?

Back 135

Increase mucosal blood flow

Stimulate the secretion of mucus and bicarbonate

Increase mucosal cell restitution

Inhibit acid secretion

NSAID's therefore:
decrease mucosal blood flow
decrease mucus production
decrease bicarbonate production
increase acid and pepsin secretion

Front 136

What is the advantage of selective COX-2 inhibitor NSAIDs?

Back 136

inhibition of COX-2 results in desired effects of decreased inflammation

inhibition of COX-1 results in undesired effects of gastrointestinal toxicity

therefore, a selective COX-2 inhibitor could theoretically provide all the benefit of an NSAID without the adverse effects.

Examples include the expensive colxicib (celebrex) and the cheaper diclofenac.

Front 137

How does EXTREME stress such as is seen in trauma, burns, head injuries and ventilator patients contribute to peptic ulcers?

Back 137

alpha-adrenergic mediated decrease in mucosal blood flow.

Front 138

What is Gastrinoma (Zollinger-Ellison syndrome) ?

Back 138

Endocrine tumors of the duodenum or pancreas (rarely stomach,liver, spleen)

1/3 patients have MEN-1

Dramatic gastrin production:
drives acid production by parietal cells.
increases parietal cell and ECL cell mass.

90% of patients have PUD

50% of patients have diarrhea

Diagnosis is based on serum gastrin level (must differentiate from pernicious anemia though)

Tumor localization:
endoscopic ultrasound, octreotide (radiolabelled somatostatin) scan, CT scan

Surgical resection is the only curative therapy

> 50% are locally invasive or metastatic at dx

PPI therapy provides best symptom palliation.

Front 139

What are the complications of peptic ulcer disease?

Back 139

pain
bleeding
perforation
gastric outlet obstruction

Front 140

What interventions are available to reduce acid production in PUD?

Back 140

Acetylcholine:
anticholinergics
vagatomy

Histamine:
H2 receptor antagonists

Gastrin:
antrectomy
proton pump inhibitors

Front 141

What mucosal protection interventions are available for PUD?

Back 141

Misoprostol (Cytotec) 200 mcg qid:
a synthetic prostaglandin E1 analog
which increases mucus and bicarbonate production and also inhibits acid production.

Sucralfate (Carafate) 1 gm qid:
adheres to ulcer base, forming a protective barrier.
Also inhibits pepsin activity.

Neither are very well tolerated and have largely been replaced with PPI therapy.

Front 142

What are the four main etiologies of the acute abdomen?

Back 142

Inflammation
(ie abscess, perforation)

Ischemia/ Necrosis

Obstruction / Distention

Bleeding:
Intraperitoneal
Intraluminal

Front 143

What do we mean by visceral abdominal pain?

Back 143

Deep, Dull, crampy pain

Caused by:
Stretch
Ischemia
Contraction against obstruction

Front 144

What do we mean by parietal abdominal pain?

Back 144

Sharp, focal, intense, constant pain.

Caused by:
Trauma to peritoneum
Infection / inflammation
Irritants

Front 145

What is the definition of referred abdominal pain?

Back 145

Sensation of pain in a somatic distribution (dermatome or myotome) derived from the same spinal cord segments as the inflamed peritoneum (visceral or parietal).

Example: Small bowel pain perceived as diffuse discomfort in T10-12 dermatomes of back and anterior abdominal wall.

Front 146

Where is phrenic irritation often referred to?

Back 146

The shoulder

Front 147

What is the best first course of action for acute abdominal pain?

Back 147

Fluids.
Resuscitate while you think.

Front 148

What descriptions of pain obtained from history can help focus the diagnosis of the acute abdomen?

Back 148

Episodic pain:
obstruction

Steadily progressive pain:
Ischemia, Peritoneal inflammation

Colicky, changing to steady pain:
Intestinal strangulation

Sudden relief of pain:
Relief of obstruction or perforation

Colicky pain is waxing and waning, comes in waves, sharp and severe.

Front 149

Instantaneous onset of acute abdominal pain pain makes us think about...

Back 149

Perforation of hollow viscus
or
Rupture of solid organ

Examples:
Duodenal perforation, cecal perforation; splenic or hepatic rupture

Front 150

Abdominal pain with a rapid onset but not instantaneous makes us think about...

Back 150

Hollow organ obstruction
Inflammatory process
Toxic or metabolic

Examples:
SBO, ureteral colic, sickle cell, porphyria, peritoneal blood, leaking perforation

Front 151

Gradual onset "acute" abdominal pain makes us think about...

Back 151

Chronic (non surgical) processes
or
Progressive inflammation

Examples:
Appendicitis (can be rapid onset pain too though), cholecystitis, PID

Front 152

What is the utility of auscultation in evaluating the acute abdomen?

Back 152

Chest auscultation to rule out pneumonia

Early bowel sounds variable

Perforation may lead to loss of bowel sounds (ileus)

Stethoscope to distract during palpation

Silent abdomen is a cause for concern.

Front 153

How do we palpate the acute abdomen?

Back 153

Start gently in quadrant opposite pain if localized.

Note rigidity will not relax with expiration.

Test rebound, tenderness last.

Front 154

What labs are important to obtain in evaluating the acute abdomen?

Back 154

CBC
Electrolytes, liver function
Amylase/lipase
Urinalysis (kidney)
Serum BHCG for pregnancy (not an option)

Front 155

What is the differential for acute abdominal pain?

Back 155

Most common:

Appendicitis
Small bowel obstruction
Acute cholecystitis
Acute pancreatitis
Diverticulitis
Pelvic inflammatory disease
Peptic ulcer disease

Front 156

What are some female sources of acute abdomen?

Back 156

Operative:
Ruptured ectopic pregnancy
Ruptured cysts

Non operative
PID / Salpingitis
Endometriosis
Mittelsmerz
Tubovarian abscess

Front 157

What are some non-surgical intra-abdominal causes of abdominal pain?

Back 157

Primary peritonitis
Porphyria, sickle cell crisis, polyserositis, uremia, DKA
Neutropenic colitis
Rectus hematoma
Addison’s crisis

Front 158

What are some non-surgical extra-abdominal causes of abdominal pain?

Back 158

Pneumonia, pleural inflammation
PE, MI, pericarditis, esophagitis
Toxins
Herpes zoster

Front 159

How good is our diagnostic history and physical in evaluating acute abdomens?

Back 159

47-76% accuracy

Front 160

What is the standard imaging technique for acute abdomen management?

Back 160

Abdominal CT

Front 161

What is a target sign on abdominal CT?

Back 161

Concentric rings seen in the appendix indicative of inflammation.

Front 162

What is an alvarado score?

Back 162

A score out of 10 for diagnosis of appendicitis.

Migration of pain=1
Anorexia=1
Nausea-vomiting=1
Tenderness in right iliac fossa=2
Rebound pain=1
Raised temperature (>37.3°C)=1
Leukocyte count >10´109/l =2
Neutrophils >75%=1

Front 163

What are the most common acute abdomen diagnoses in geriatric patients?

Back 163

Diverticulitis 18%
Bowel Obstruction 18%
Nephrolithiasis 10%
Gallbladder disease 10%

Front 164

What are some causes of bowel obstruction?

Back 164

Adhesions from prior surgery or peritonitis

Hernia
(more common in less developed countries)

Anatomic Colonic obstruction
Mass
Volvulus

Front 165

What are the three different types of hernias?

Back 165

Inguinal
Umbilical
Incisional

Front 166

Who has the highest rate of esophageal squamous cell cancer in the U.S?

Back 166

AA males

High rates in Asia, Africa and Iran

Front 167

What are the risk factors for squamous cell esophageal cancer?

Back 167

Alcohol and tobacco (synergistic):
Hard liquor is worse
Alcoholics- Selenium deficiency

HPV

Front 168

What are risk factors for esophageal adenocarcinoma?

Back 168

Caucasian 5X greater than African-American; (Caucasian males 8X)

Obesity

GERD (Barrett's metaplasia)
but
50% have no hx of symptomatic reflux disease.

!Unrelated to alcohol!

Front 169

What is the absolute risk of Barrett's esophagus turning into cancer?

Back 169

~0.5-0.8%

This represents a 30-60 fold increase over the general population though.

Front 170

Which of the two esophageal cancer has a higher risk of metastasis?

Back 170

Squamous cell carcinoma

Front 171

What are the two most common symptoms of esophageal cancer?

Back 171

Dysphagia (90%)
Odynophagia (50%)

SCC is aggressive. Vocal cord paralysis, hoarseness

Hematemesis from tumor ulceration.

Majority have advanced disease on presentation. (T1-T4 with T4=bad)

Can have hypercalcemia, hypoalbuminemia and anemia.

Front 172

What imaging do we use for esophageal cancer?

Back 172

Barium swallow vs EGD , EUS (ultrasound), PET

Front 173

5-yr survival rate in patients with esophageal cancer amenable to surgery is...

Back 173

only 5-20%

Front 174

Which countries have the highest rates of gastric cancers?

Back 174

Japan
Costa Rica
China

Men more than women.

Front 175

What are two of the risk factors for stomach cancer?

Back 175

Benign gastric ulcer disease (2-3x risk)

H.Pylori infection

Front 176

How do we diagnose gastric cancer?

Back 176

Biopsy endoscopy

Barium studies

Front 177

How do we treat gastric cancer?

Back 177

Surgery remains the only curative procedure for advanced cancer.

Front 178

What is gastric carcinoid?

Back 178

Account for 2% of all gastrointestinal carcinoids and 0.3% of all gastric neoplasms.

Pts usually asymptomatic

Arise from gastrointestinal neuroendocrine cells mostly ECL origin.

Syndrome does not occur unless there is hepatic involvement

Risk factors include pernicious anemia and chronic atrophic gastritis (25%).

Hypergastrinemia resulting in ECL cell hyperplasia.

No increased risk with proton pump inhibitors

Non-metastatic, 5-yr survival 95%. Metastatic 5-yr 50%

Front 179

What are gastrointestinal stromal tumors or GIST?

Back 179

mesenchymal tumors in the GI tract

Indolent, slow-growing tumors that are usually asymptomatic until very large.

GI bleeding, dyspepsia or obstructive sx’s.

Most have gain of function c-kit mutations and respond to Gleevec (imafinib) or other mesylate- tyrosine kinase inhibitors.

Called malignant if spread into regional lymph nodes, or with distant mets (liver, lung, peritoneal)

Front 180

Gastric MALT is strongly associated with...

Back 180

H. pylori

Can treat with antibiotics

Front 181

Small bowel lymphomas are associated with...

Back 181

Celiac sprue
Immunocompromised states

Most common small bowel cancers are metastatic such as melanomas, small cell lung cancer etc.

Front 182

Charcot's triad is

Back 182

Jaundice
RUQ pain
fever

Front 183

How do we define diarrhea?

Back 183

Increase in the volume & frequency of bowel movements as well as a change in the consistency of the stools.
OR
Passage of 3 or more stools per day that conform to the shape of their container.

Front 184

How are infectious diarrheas transmitted?

Back 184

Acute infectious diarrhea is a very common illness, esp. in the young.

On average, persons in developed countries will experience 1-2 episodes per yr, whereas in developing countries, the average will be 3 or more episodes per yr.

Almost all infections are acquired via a fecal-oral route, usually by ingestion of contaminated food or water.

Overcrowding, inadequate public sanitation, & poor personal hygiene are all major risk factors.

Front 185

What are the infectious agents that most commonly cause diarrhea?

Back 185

Potential microbial causes are quite varied and tend to be age & setting dependent.

In the US and other temperate developed countries, viruses (rotaviruses, noroviruses) are the predominant etiologic agents.

Enterotoxigenic E. coli (ETEC) are the most frequent bacterial cause of noninflammatory (watery) diarrhea.

Salmonella & Campylobacter are the primary bacteria causing inflammatory diarrhea.

Parasitic infections can also cause diarrhea.

Front 186

What are the two major pathophysiological mechanisms of infectious diarrhea?

Back 186

Excess excretion of fluid into intestinal lumen (noninflammatory):
Role of enterotoxins

Destruction of ileal &/or colonic mucosa (inflammatory):
cytotoxins or invasion of enterocytes

Front 187

What enteric infections are considered luminal?

Back 187

V. Cholera
E. Coli (heat labile or stable toxins)
Staph food poisioning
Rotavirus
Noroviruses
Giardia
Cryptosporidium

Front 188

What enteric infections are considered mucosal?

Back 188

Shigella
C. Jejuni
Salmonella
Invasive E.Coli
E. Hystolytica

Front 189

What enteric infections are considered systemic?

Back 189

S. Typhi
Yersinia
C. Fetus

Front 190

What is the difference between inflammatory and non-inflammatory diarrhea?

Back 190

Overall, noninflammatory (watery or secretory) diarrhea, which is most often mediated via enterotoxins, is estimated to account for ~90% of all cases of diarrhea.

That syndrome is characterized by watery stools that may be of large volume (>1L/d) without blood, fecal WBCs, severe abdominal pain, or significant fever.
Usual causative organisms would be viruses, ETEC, V. cholerae, & selected parasites.

Inflammatory diarrhea (dysentery) accounts for 5-10% of the total cases of diarrhea & is characterized by frequent, small-volume, mucoid or bloody stools with associated tenesmus, severe abd pain, fever (T>101.3), & fecal WBCs.
Salmonella, Shigella, & Campylobacter are prototypical causative organisms.

Front 191

What factors predispose to enteric infections?

Back 191

Immune “immaturity” (younger age)

Poor personal hygiene (eg. lack of handwashing)

Reduced gastric acidity (from age, surgery, or medications such as PPIs)

Altered enteric microflora
(induced by prior antibiotic therapy)

Front 192

What signs and symptoms are associated with infectious diarrhea?

Back 192

(Symptoms)
Systemic:
Malaise
Myalgias
Fever

Upper GI:
Nausea, vomiting

Lower GI:
Cramping, diarrhea, tenesmus

(Signs)
Systemic:
Fever
Signs of dehydration
Rash

Abdominal:
Hyperactive BS
Tenderness/ guarding
Distention;
NO rebound

Rectal:
Tenderness
Guaiac + stool

The presence of severe abdominal pain, tenesmus, & significant fever (T>101.3) all suggest infection due to a pathogen that causes inflammatory disease
(ie, Salmonella, Shigella, etc).

Front 193

Recent travel to underdeveloped countries makes us think of...

Back 193

Enterotoxigenic E. coli, Salmonella,
Shigella,
Campylobacter, Giardia, Entamoeba

Front 194

Recent Mountains/camping expereinces makes us think of...

Back 194

Giardia

Front 195

Recent antibiotic use makes us think of...

Back 195

Clostridium difficile

Front 196

People who engage in anal sex or anal-oral contact are susceptible to..

Back 196

With enteritis: Shigella,
Giardia, Entamoeba, Campylobacter

With proctitis: Neisseria gonorrheae,
HSV, Chlamydia, Campylobacter,
Treponema pallidum

Front 197

HIV patients GI systems are susceptible to...

Back 197

Cryptosporidia
Candida

Front 198

Children in day care centers are susceptible to...

Back 198

Giardia, Campylobacter, Shigella,
Rotavirus

Front 199

Dairy products can lead to infection with...

Back 199

Salmonella, Yersinia, Campylobacter

Front 200

Poultry is associated with...

Back 200

Campylobacter infections.

Front 201

Seafood ingestion is associated with...

Back 201

V. parahemolyticus,
noroviruses

Front 202

What are the typical incubation periods associated with various infectious gastroenterites?

Back 202

<2hrs.:
None

2-8 hours:
S. Aureus toxin
B. Cereus toxin

8-14 hours:
C. Perfringens
B. Cereus

>14 hours:
V. Cholera
E. Coli toxin
Shigella
Invasive E.Coli
V. parahemolyticus
Y. enterocolitica
Salmonella

If onset of symptoms is within 8 hrs of ingestion of the putatively tainted foodstuff, disease is almost certainly due to a preformed toxin.

Front 203

Which enteric infections have leukocytes in the stool?

Back 203

Salmonella spp.
Shigella spp.
Invasive E. coli Campylobacter
Yersinia
Non-cholera vibrios
and
Antibiotic associated infections.

Front 204

Which enteric infections do not have leukocytes in the stool?

Back 204

E. Coli
V. Cholera
"Food poisoning"
Viruses
Parasites

Front 205

Which agents are detected by routine stool culture?

Back 205

Salmonella Entamoeba
Shigella
Giardia
Campylobacter

By special request:
Vibrio parahaemolyticus
C. difficile
Rotaviruses Enterohemorrhagic E. coli
Yersinia

Only in specialty labs:
Enterotoxigenic E. coli Clostridium perfringens
Invasive E. coli Noroviruses

Front 206

Stool cultures should be reserved for patients with ....

Back 206

Inflammatory diarrhea

Increased risk for severe or complicated infections.

Illness which has public health implications.

Persistent diarrhea.

Front 207

Should we use antimotility agents in infectious diarrhea?

Back 207

We prefer not to because this increases the interaction time between the bugs and the mucosa.

Front 208

Most episodes of infectious diarrhea are caused by...

Back 208

viruses

Front 209

Summarize the management of infectious diarrhea?

Back 209

Aggressive rehydration is the critical intervention in persons with diarrhea.

Empiric antibiotic therapy should be considered only in those patients with a high probability of infection due to an enteroinvasive pathogen (ie, inflammatory diarrhea).

In patients with proven infection, therapy is clearly warranted for shigellosis, cholera, traveler’s diarrhea, amebiasis, giardiasis, & Cyclospora.

Always assess the public health implications of infection.

Front 210

How do we diagnose amebiasis?

Back 210

Intestinal:
3 stool exams (90% sensitive) for cysts or trophozoites esp. w/ RBC

Stool antigen detection (differentiates from E. dispar)
most with positive serum serologies by day 7. Titers remain positive for years, despite treatment (IHA)

Extraintestinal:
clinical picture, + serologies, “anchovy paste” aspirate
Note: aspiration of amebic cysts free of WBCs since amebae are cytolytic.

Front 211

How do we treat amebiasis?

Back 211

Invasive disease:
metronidazole (Flagyl)

Affects only trophozoites, NOT cysts

Intestinal cysts:
paromomycin, iodoquinol
Need to treat with these drugs subsequently to eliminate the cyst shedding state.

NO therapy needed for E. dispar, or other commensals (E. hartmanni, E. polecki, E. ginigivalis, etc.) only E. hystolitica

Front 212

How do we diagnose giardiasis?

Back 212

Microscopic exam of stool for cysts, trophozoites
“gold standard”

Identifies 50-70% of infections with 1 stool, 90%+ with 3 stools

Fecal suspension ELISA for antigen > 90% sensitive (applies to amebiasis too)

Microscopic exam of duodenal fluid (Entero-Test or string test), duodenal aspirate, tissue

Front 213

How do we treat giardiasis?

Back 213

Metronidazole
Divided doses x 7 days

Quinacrine

Front 214

How does cryptosporidium infection present?

Back 214

7-10 day incubation period

Diarrhea, crampy abdominal pain
Varies from intermittent, scant to continuous, watery, voluminous (up to 17L/day)

Self-limited in immunocompetent

Can be devastating in immunocompromised, particularly AIDS patients.

Dx:
Microscopic (modified Acid Fast Stain)
ELISA stool antigen detection

NO treatment.

Front 215

What are some of the less common intestinal parasites?

Back 215

Isospora belli
Cyclospora
Microsporidia

Front 216

What are the major intestinal helminths?

Back 216

Ascaris

Enterobius

Hookworm:
Necator americanus
Ancylostoma duodenale

Strongyloides

Front 217

What is the pathogenesis of ascariasis?

Back 217

Asymptomatic infection common in light infections. (vast majority)

Larval migratory phase:

host reactions
Pneumonitis: hypersensitivity reaction as parasite migrates through. Cough, wheezing, sob, fever, chills, malaise
Adult worms cause vague crampy abdominal pain.

Intestinal obstruction (1/500 infected persons/year)

Aberrant migration can occur into bile ducts, appendix

Causes fever, local pain
If in bile duct jaundice, pancreatitis, hepatitis.

Diagnosis through stool examination:
Ova or adult parasites. Easy to do because of large number of ova per adult female.

Front 218

How do we treat ascariasis?

Back 218

Mebendazole
Albendazole
Pyrantel pamoate

Front 219

How do we treat enterobius or pinworm infection?

Back 219

Mebendazole 1 dose or

Pyrantel pamoate 1 dose

Repeat dose at 2 weeks

May need to treat close contacts/family members

Front 220

What are the non-specific and barrier immune mechanisms of the GI system?

Back 220

Gastric Acid:
Increases infectious dose

Mucin :
Binds normal flora and antimicrobial compounds.
Some pathogens can bind mucin though.

Tight junctions

Paneth cell products:
Defensins, Lysozymes, Phospholipases, DNAases, Trypsin

Front 221

In neutropenic patients, treatment with Anti-gm positives/fungals causes...

Back 221

more gm (-) infection

Anti- gm negatives causes more fungal infection.

Front 222

By what mechanisms do native flora protect the gut?

Back 222

Competition
TLR conditioning

Antibiotic-depleted epithelium becomes MUCH more sensitive.

Front 223

What are M-cells and what is their function?

Back 223

Tight junctions exclude most antigens from direct access to submucosal antigen presenting cells

M cells are specialized cells that ‘sample’ the environmental antigens

Derived from the same precursor cell as epithelial cells

Concentrated over Peyer’s Patches

Front 224

What is the role of gut dendritic cells?

Back 224

Reside in the submucosa

‘Fed’ antigens by M cells

Present antigens to T cells in the Peyer’s patch region as immature DCs

Can be a mechanism of tolerance

If activated by other stimuli (eg. TLR stimulation, T cell products) DCs migrate to local lymph nodes and present antigen as matured DCs.

Front 225

In what order do B-cells class switch

Back 225

IgM
IgD
IgG
IgE
IgA (most common defective switch)

class switch requires T cell help.

Front 226

The most common cause of severe transfusion reaction after clerical error is...

Back 226

anti-IgA antibodies

Front 227

What is thought to be the mechanism of crohn's disease?

Back 227

Leaky barrier causes direct activation of T-cells without M-cell presentation and this causes production of interleukins, TNF and cytokines..

Front 228

What are some examples of systemic illness triggered by gut immunity?

Back 228

Extra-intestinal manifestations of IBD.

Post-diarrheal Guillian-Barre Syndrome (C. jejuni is predominant organism)

Yersinial arthritic syndromes

Pyoderma gangrenosum post gastric/jejunal bypass (gets better if the bypass is reversed or taken down)

Graft vs. Host Disease in BMT patients.

Front 229

What aspects of immune health do the antigens of normal intestinal flora like bacteroides fragilis influence?

Back 229

Th1/Th2/Treg/Th17 balance

Thymic health/development

Front 230

What are some G- rods that commonly cause systemic illness/diarrhea?

Back 230

Salmonella species
Shigella
E. coli (ETEC, EPEC)
Campylobacter
Yersinia

Front 231

What are some risk factors for salmonella infection?

Back 231

Achlorhydria greatly increases risk of infection

PPIs and advanced age risk factors

Most common sources in food supply:
Chicken
Eggs

Most common non-food sources:
Reptiles

Treatment:
fluoroquinolones,
cephalosporins,
others

Front 232

What are the risk factors for C. difficile colitis?

Back 232

Major risk factor is antibiotic therapy.
Leads to loss of normal flora and overgrowth of Clostridium difficile

Can be febrile with high WBC and very fulminant disease (even toxic megacolon)

Can also be clinically well with just troublesome diarrhea or even asymptomatic carrier status.

Diagnosis:
gold standard is sigmoidoscopy (pseudomembranes; toxin assay most common)

Treatment:
oral metronidazole for mild disease
oral vancomycin for more serious disease

Both po vancomycin AND IV metronidazole for life-threatening illness.

Front 233

What is celiac disease or gluten enteropathy?

Back 233

Gluten allergy which leads to local immune response in the small bowel.

T cells and IgA to tissue transglutaminase.

Produces inflammatory cytokines and metalloproteinases which lead to villus atrophy and malabsorption syndrome.

Improves with avoidance of gluten (wheat)

More common in patients with IgA deficiency, siblings (HLA DQ2 and DQ8 increase risk), other autoimmune diseases.

Front 234

Recent evidence has suggested that colon cancer may be linked to infection with...

Back 234

Enterotoxigenic Bacteroides fragilis

A substrain of fragilis that causes inflammatory diarrhea w/out much fever/systemic symptoms.
It is very toxic to colonic epithelium and disrupts tight junctions

Can chronically colonize thereafter and lead to chronic inflammation and eventually colon cancer because of the immune response of Th17 cells through the Stat3 pathway.

Front 235

What are the layers of the gut wall from the lumen outwards?

Back 235

Mucosa:
Epithelium and lamina propria
Muscularis mucosa

Submucosa

Muscularis externa:
Two or three layers of smooth muscle

Serosa/adventitita

Front 236

The inner lumen of the esophagus is lined with....

Back 236

stratified squamous epithelium

glands in submucosa for lubrication

Front 237

The outermost layer of the esophagus is made of...

Back 237

Esophagus is not free as it courses through the thoracic cavity (embedded in connective tissue); thus outer tunic is adventitia, not a serosa.

Front 238

The last representation of striated muscle we see in the GI tract is in the...

Back 238

Proximal esophagus

Front 239

How does the upper esophageal sphincter work?

Back 239

It pulls the larynx forward when we swallow.

Normally upper and lower sphincters closed except during swallowing to prevent entry of air from the oral cavity or reflux of stomach contents.

Front 240

What substances are absorbed in the stomach?

Back 240

Small amounts certain lipid-soluble compounds.
(including aspirin and other NSAIDs)

Ethanol

Front 241

What cell types are found in the stomach?

Back 241

Non-secretory:
Stem cells (throughout GI tract)
Secretory

Mucus:
Surface mucous cells
Mucous neck cells

Acid and Intrinsic Factor:
Parietal cells (oxyntic cells)

Enzymes:
Chief cells (peptic cells)

Peptides:
(endocrine/paracrine factors)
Enteroendocrine cells (found throughout GI tract)

Front 242

What is the role of the surface mucous cells in the stomach?

Back 242

Each contains mucinogen granules forming “mucous cup” apically; when released the mucinogen forms viscous coat that adheres to epithelial surface.

Provides mechanical protection and, because of high bicarbonate concentration, protects epithelium from acidic gastric juice.

Front 243

What is the role of mucous neck cells in the stomach?

Back 243

Shorter than surface cells, located among groups of parietal cells in neck region of gastric glands.

Contain less mucinogen and no prominent mucous cup.

Produce more soluble mucous, under the control of vagal stimulation.

Front 244

How does epithelial renewal occur in the stomach?

Back 244

Dividing stem cells primarily in isthmus region of gastric glands.

Most new cells become surface cells (live 3-5 days).

Other cell types have longer lifespans (up to 150-200 days for parietal cells) but all are replaced from the stem cells.

Front 245

What are stomach chief cells?

Back 245

Protein secreting cells

Abundant rER basally, so basophilic.

Eosinophilic apically due to presence of secretory (zymogen) granules containing enzyme precursors.

Secrete pepsinogen (converted to pepsin on contact with gastric juice) and a weak lipase.

Front 246

What do parietal cells in the stomach look like?

Back 246

oval shape

eosinophilic cytoplasm

“fried egg” appearance with prominent central nucleus

“secrete” HCL

Key player is H+/K+ ATPase ("proton pump“) in cannalicular membrane.

When the cells are actively secreting they form cannaliculi and surface microvilli to increase the surface area of the apical region.

Front 247

How does acid production occur in parietal cells?

Back 247

Dissociation water yields hydrogen ions

Hydroxyl ions formed and rapidly combine with carbon dioxide to form bicarbonate (catalyzed by carbonic anhydrase)

Bicarbonate transported out of the basolateral membrane in exchange for chloride

Chloride and potassium ions transported from cytoplasm into the lumen of the cannaliculi by passive conductance channels.

Hydrogen ions pumped out of the cell and into the lumen in exchange for potassium through the action of the proton pump (ATPase); potassium is thus recycled back into the cytoplasm.

Accumulation of osmotically-active hydrogen ions in the cannaliculus generates osmotic gradient across membrane; get outward diffusion H2O.

Acid production dependent on ATP; large numbers mitochondria account for eosinophilia of parietal cells.

Front 248

Where, in terms of anatomy, do the enteroendocrine cells secrete various hormones?

Back 248

Front 249

What epithelial cells comprise normal small intestine mucosa?

Back 249

Columnar epithelium.

Front 250

What cells secrete mucous in the small intestine?

Back 250

Goblet cells.

Front 251

What are IEL's?

Back 251

Intra-epithelial lymphocytes in the small intestine.

Usually below 10/100 epithelial cells.

Front 252

Brunner's glands are unique to...

Back 252

The duodenum.

Front 253

What structures are unique to the ileum?

Back 253

Peyer’s patches

Front 254

What is the normal villous-crypt ratio in the small bowel?

Back 254

3-5:1

Front 255

What is celiac disease (non-tropical sprue)?

Back 255

An immune mediated disorder in genetically susceptible hosts with damage to SI mucosa & malabsorption due to certain types of HLA expression.

Atrophy of villi with associated compensatory crypt hyperplasia produces a flattened avillous surface so that small bowel looks like large intestine. Plasma cells and numerous intraepithelial lymphocytes can also be seen.

Worldwide in distribution but occurs mostly in European whites.
Clinical onset anytime from infancy to late adulthood.

Abdominal pain, diarrhea, steatorrhea, dermatitis herpetiformis, fatigue.

2 or more genes involved: class I HLA-B8 & class II HLA-DR3 & DQW2

Exposure to gliadin results in humoral & cell mediated injury

Possible relationship to prior infection with adenovirus I2

E1B viral protein homologous with gliadin possibly resulting in cross reactivity

Serum endomysial and tissue transglutaminase autoantibodies.

Front 256

What is refractory sprue? (not on test)

Back 256

Sprue with absent or incomplete clinical response to gluten free diet.

Abnormalities in T cells in many patients with loss of CD4 & CD8 & with monoclonal rearrangements in TCR gamma gene

? Early T cell lymphoma

Some develop collagenous sprue

Front 257

Pyramidal or triangular structures which are eosinophillic (pink) attached to the luminal surface are indicative of..

Back 257

Giardiasis.

May look normal in low magnification.

Front 258

What is the epidemiology of Crohns disease?

Back 258

An idiopathic chronic inflammatory disorder involving any part of the GIT

Worldwide distribution

More common in western nations
In US, incidence is rising; 8/100,000

Genetic susceptibility

Most often presents in 2nd decade
2nd smaller peak in 8th decade.

Front 259

What is the pathology of Crohn's disease?

Back 259

Thickened wall with firm, stiff consistency due to fibrosis, muscular hypertrophy & fat wrapping

Strictures

Fistulas

In early or mild disease, mucosa has aphthous ulcers

With progression, fissures or wide based longitudinal ulcers; cobblestone mucosa

Skip areas

Front 260

In Crohn's resection section what do things we look for are?

Back 260

Transmural chronic inflammation

Fibrosis

Non-casseating granulomas

Increase in plasma cell in the lamina propria.

Front 261

The histopathology of Crohn's disease includes...

Back 261

Transmural chronic inflammation with lymphoid nodules (string of beads)

Fibrosis

Muscular & neuronal hypertrophy

Basilar plasmacytosis

PMNs in LP & epithelium (cryptitis)

Ulcers, including fissures

Pseudopyloric metaplasia

Non-necrotizing granulomas
(biopsies 30%; resections 60%)

Vasculitis

Variability in changes

Front 262

What do mean by osmolality?

Back 262

Osmoles of solute per kg of solvent (depends on the number of particles in solution)

Luminal contents of the intestine are isotonic compared with plasma
(~290 mOsmols/kg)

Front 263

What structural features of the intestine make it ideally suited for absorption?

Back 263

Small intestinal surface area
is amplified by the circular folds,
villi, & microvilli.

Absorption is also facilitated by
movement of the villi. This stirs the
chyme immediately adjacent to the
mucosa and presents new surfaces
for absorption. Movement of the villi
is regulated by local nervous
reflexes and hormonal mechanisms.

Extension of the microvilli is
regulated to facilitate absorption
by increasing surface area.

The intestinal mucosal surface area is under trophic influences linked to the presence of food in the GI tract.

Front 264

Hoe does intestinal blood flow change after a meal?

Back 264

At Rest:
~ 10-15% of Cardiac output
(75%-> mucosa,
5%->submucosa, 20%->muscularis externa)

After a Meal:
Blood flow increases 30-130% (especially to the mucosa) as a result of increased CO
and shunting of blood from other layers.

Postprandial blood flow to intestine ~ 1-2 L/min

Front 265

Cells in the vilus tip are primarily absorptive whereas cells in the crypts are primarily secretory, how do they mature and what are the differences?

Back 265

Cells migrate up the vilus and mature as they travel up.

After a certain point they express brush border hydrolases.

Cells at the tip of the vilus apoptose and slough into the lumen.

Front 266

Even though the colon is the most efficient at water absorption it only absorbs about 1.3L of the ~9L the duodenum sees. Why?

Back 266

~5.5L absorbed by the jejunum
~2L absorbed by the ileum

So only about 1.5L are available for resorption in the large bowel.
~200cc/24hours of water are excreted with the feces which leaves 1.3L..

Front 267

What is the cellular mechanism of intestinal water absorption?

Back 267

Water absorption is passive and dependent on absorption
of ions (principally Na+ & Cl-) and solutes (sugars, amino acids)

Water movement may be transcellular (through the cell) or paracellular (through the tight junctions between cells)

Water moves bidirectionally to keep the luminal contents isotonic with plasma

Passive solute permeability and water absorption decreases caudally.
(Highest permeability in duodenum/jejunum)

Front 268

How are various ions absorbed and secreted in the small and large intestine?

Back 268

Front 269

Test of choice for abdominal pain and fever is .....

Back 269

CT

Front 270

Test of choice for abdominal bleeding per rectum is...

Back 270

colonoscopy

Front 271

Where are lacteals located?

Back 271

In the center of an intestinal villus.

Front 272

How does ion absorption occur in the jejunum?

Back 272

Tight junctions are leaky

Na+ absorption is highest in
Jejunum; Most (~85%) of Na+
absorption is active

Na+ is actively absorbed by Na+ dependent nutrient transporters
(glucose, amino acids)

Na+ is also absorbed via Na+/H+ exchange (NHE3)

Na+ is moved across the basolateral membrane by the Na+/K+-ATPase

K+ moves passively (moves down its concentration gradient secondary to H2O
movement)

Cl- moves paracellularly down its electrical gradient (follows the Na+)

H+ secretion acidifies the lumen, reacts with HCO3- to release CO2 and water.
CO2 can then diffuse across the epithelial cell barrier into the blood

Intracellular HCO3- crosses basolateral surface

Result: Net NaCl, KCl, and NaHCO3 absorption.

Front 273

How does ion absorption occur in the colon?

Back 273

Tight junctions are tighter

Na+ is moved against a large electrochemical gradient because a lot of it has already been absorbed in the small intestine.

Little Na+/solute cotransport (short chain fatty acids; right colon)

Na+ is absorbed by the Na+ channels ENaC (electrogenic Na absorption)

Na+ is moved across the basolateral membrane
by the Na+/K+-ATPase

K+ is moves down its electrochemical gradient
into the lumen via channels (but can also be
absorbed by the apical H/K-ATPase)

Cl- is absorbed via Cl-/HCO3- exchange (DRA)
and exits through Cl channel protein. Cl- is also
absorbed paracellularly

HCO3- is secreted via Cl-/HCO3- exchange.

Front 274

Why are infants with prolonged diarrhea particularly susceptible to hypokalemia?

Back 274

Most K+ absorption in the small intestine is driven by water absorption, that increases the
lumenal K+ concentration.
Hence, significant K+ loss may occur in diarrhea, leading to
decreased extracellular levels and life-threatening consequences such as cardiac arrhythmias.

Front 275

What are the basic principles behind GI water absorption?

Back 275

Water movement in the intestine is passive & dependent
upon transport of electrolytes and other solutes

Water movement may be transcellular or paracellular
(through the tight junctions between cells)

Water moves bidirectionally to keep the luminal contents isotonic with plasma.

Ions (& solutes) are transported via transcellular and paracellular pathways into the lateral spaces, where a “standing osmotic gradient” is established for the
passive movement of water.

Front 276

What compounds that are released by enteric neurons stimulate net secretion of electrolytes and water?

Back 276

Acetylcholine
Nitric oxide
Serotonin
VIP
Substance P

Front 277

What compounds that are released by enteroendocrine cells in the mucosa or submucosa stimulate net secretion of electrolytes and water?

Back 277

Histamine
Calcitonin
Guanylin
Bradykinin
Platlet-activating factor
Prostaglandins
Leukotrienes
Arachidonic acid
Adenosine

Front 278

What compounds that are released by enteric neurons promote net absorption of electrolytes and water?

Back 278

Norepinephrine
Neuropeptide Y
Opioids

Front 279

What compounds that are released by enteric neurons stimulate net secretion of electrolytes and water?

Back 279

Somatostatin

Front 280

What hormones stimulate net secretion of electrolytes and water?

Back 280

Prostaglandins
Atrial natriuretic peptide
Gastrin
Motilin
Bombesin
GIP

Front 281

What lumenal factors stimulate net secretion of electrolytes and water?

Back 281

Bile salts
Long-chain fatty acids

Front 282

What hormones promote net absorption of electrolytes and water?

Back 282

Epinephrine
Enkephalins
Aldosterone
Glucocorticoids
Angiotensin II
Peptide YY
Prolactin
Growth hormone

Front 283

What lumenal factors promote net absorption of electrolytes and water?

Back 283

Short chain fatty acids

Front 284

Clinically we divide diarrhea into 3 main categories. What are they?

Back 284

Osmotic Diarrhea -
Poorly absorbed, low molecular weight aqueous solutes create an osmotic force that quickly pulls water (and ions) into the intestinal
lumen (in order to maintain an intra-luminal osmolality equal to that of body fluids).
Shows an abnormal Osmotic Gap (disappears with fasting)
Causes:
Lactase deficiency (lactose), foods and supplements (sorbitol,lactulose, Mg++)

Secretory Diarrhea:
Caused by overstimulation of the intestinal tract’s secretory capacity. Driving force is always either net secretion of Cl- or
HCO3-, or inhibition of net Na+ absorption. Shows a normal Osmotic Gap.
Causes:
bacterial enterotoxins, neuroendocrine tumors (overproduce pro-secretory hormones), inflammatory mediators, dihydroxy bile acids,
hydroxylated fatty acids, drugs.

Complex Diarrhea –
Most clinically significant diarrheas are complex, with multiple pathophysiologic mechanisms involving consideration of paracrine,
immune, neural, and endocrine modulators.

Front 285

What is an osmotic gap?

Back 285

We look at the pattern of stool electrolytes.

290-2x(Conc.Na+K)

(290 is the assumed osmolarity of blood plasma)

An Osmotic Gap < 50 mOsm is considered normal and can be found with secretory diarrhea.

Osmotic Gap > 50 mOsm indicates osmotic diarrhea

Front 286

What are the principal driving forces behind water absorption and secretion in the intestine?

Back 286

Na+ flux is the principle driving force for intestinal water absorption.

Cl- flux is the principle driving force for intestinal water secretion.

Net water and electrolyte transport across the intestinal mucosa represents the differences between the lumen to blood (absorption) and blood to lumen(secretion) fluxes. These flux differences normally favor water absorption.

Epithelial cells near the
villus tip are active in net
absorption

Crypt epithelium usually
functions as net secretors of
ions and water

Front 287

What is the mechanism for cholera diarrhea?

Back 287

Cholera toxin A chain
irreversibly activates adenylate
cyclase, increases cAMP, and
activates Cl- secretion via CFTR

Na+ passively follows Cl-

Water passively follows the
Cl- and Na+ flux

Cholera toxin also inhibits
non-nutrient Na+ and Cl-
absorption by villus tip cells

Cholera patients may produce
up to 20 L/day of watery stool

Front 288

How do we treat cholera diarrhea?

Back 288

Treated with oral rehydration therapy:
Administration of a solution of glucose & salt increases driving force for water absorption by increasing Na/glucose uptake.

Newer formulas are hypo-osmolar and include amylase-resistant starch (rice starch) to enhance colonic short chain fatty acid and water absorption.

Front 289

What is the mechanism of constipation in the elderly?

Back 289

Colonic CFTR expression (Cl- secretion) declines with age (major player in water secretion)

Colonic ENaC expression (Na+ absorption) is maintained with age (major player in water absorption)

This sets up a potential imbalance between intestinal water absorption and secretion where the stool becomes excessively desiccated.

Drugs that activate ClC2 chloride channels may be useful.

Front 290

What are some drugs that can be used against diarrhea?

Back 290

Opiates:
(u receptor agonists, antiperistaltic)
Diphenoxylate
Loperamide
Codeine
Morphine
Tincture of opium

Alpha adrenergic agonist:
Clonidine

Somatostatin analog:
Octreotide (carcinoid syndrome)

Bile acid biding resin:
Cholestyramine

Fiber supplements:
Psyllium
Calcium polycarbophil

Bismuth subsalicylate (Pepto-Bismol).

Front 291

What contrast materials are naturally found in the GI tract?

Back 291

GAS=Black
CALCIUM=White
FAT=Gray

Front 292

The normal bowel gas x-ray pattern in a normal patient laying supine is..

Back 292

Gas mostly in the colon.

Small bowel should look pretty empty.

Reversal of this normal gas pattern can suggest obstruction.

Front 293

Dilation of both the colon AND the small bowel on plain film can suggest...

Back 293

Adynamic ileus.
However, it can also be an obstructive neoplastic lesion in the sigmoid colon or rectum but there is no good way to tell.

Front 294

If we see the outer borders of the bowel clearly, this is an indication of...

Back 294

Pneumoperitonium.

Front 295

What plain film views are best for discerning free gas in the abdomen?

Back 295

Left lateral Decubitus or upright film

The single most sensitive test for seeing gas in the abdomen though is CT.

Front 296

When we are looking at the liver, how do we tell the difference between gas in the venous system and gas in the biliary tree?

Back 296

Go with the flow.

If the gas goes all the way out to the periphery, portal system. Usually dead bowel.

Front 297

Calcification of the border of the gallbladder sometimes called porcelain gall bladder should rouse connotations of...

Back 297

Gall bladder carcinoma.

Front 298

The reason we can see the edge of organs is....

Back 298

Fat

Front 299

Calcification in the adrenal glans can be indicative of...

Back 299

Addison's disease
or
TB

Front 300

Chilean shepherds with champagne looking abdominal films have...

Back 300

Echinococcal disease

Front 301

An extremely dilated transverse colon can be a sign of ...

Back 301

Toxic megacolon in ulcerative colitis patients.

Front 302

Winking owl sign in a vertebral body can represent...

Back 302

Metastasis

Front 303

What cavity is the pancreas in?

Back 303

It is retroperitoneal.

Front 304

What types of glands are pancreatic acini?

Back 304

Exocrine.

Front 305

What types of glands are the 1,000,000 or so islets of langerhans in the pancreas?

Back 305

Endocrine

Alpha cells make glucagon
Beta cells make insulin

Front 306

What is the significance of pancreatic stellate cells?

Back 306

As in the liver, they are responsible for fibrosis.

Front 307

What is acute pancreatitis?

Back 307

An acute inflammatory process of the pancreas which by definition has the potential to return to normal.

Front 308

What is chronic pancreatitis?

Back 308

An irreversible chronic inflammatory process characterized by fibrosis and loss of endocrine and exocrine elements of gland.

Front 309

Can a patient go straight from normal to chronic pancreatitis without recovery?

Back 309

Yes, a patient experiencing significant (>30%) pancreatic necrosis may lose sufficient pancreatic tissue to become endocrine ± exocrine insufficent, and have pancreatic scarring.

Front 310

What pH is protective for the pancreas?

Back 310

Alkaline

Front 311

How does the pancreas protect itself?

Back 311

Highly toxic enzymes (e.g. trypsin) are contained and when possible secreted in inactive (pro) forms.

Low extracellular ionized calcium.

Alpha-1antitrypsin.

Alkaline pH.

Front 312

What happens when pancreatic acinar cells experience blockage of secretion?

Back 312

Fusion of lysosome and Zymogen granules.

Inflammation

Third space losses/fluid accumulation.

Fat necrosis

Pancreatic and peripancreatic necrosis.

Front 313

What are the guidelines regarding volume replenishment in acute pancreatits?

Back 313

6-8L in the first 24 hours.

It is a common mistake to underestimate the volume of fluid replacement required by these patients.

100 cc/hr is inadequate! If the patient can tolerate a 1-2 liter fluid bolus, give it, followed by 300 or 400cc/hr

Patients with predicted severe acute pancreatitis should have their urine output carefully monitored.

Aim for at least 50cc/hr, and 100cc/hr or more is better

If you let the kidneys die, other systems quickly follow….

Front 314

What systemic complications often result from severe pancreatitis?

Back 314

Renal failure

Respiratory failure (ARDS)

Coagulopathy (DIC)

Encephalopathy

Hypocalemia (tetany)

Used to be considered a manifestation of systemic spread of pancreatic enzymes and local inflammatory factors.
Now known to result from the effects of inflammatory cytokines (Interleukins, NO, and TNF-alpha).

Front 315

For the most part, what accounts for the local effects of pancreatitis?

Back 315

largely due to pancreatic
enzymes, especially TRYPSIN

Front 316

What is the definition of SIRS?

Back 316

HR > 90/min

Body temp < 36 or > 38 deg C

RR > 20/min or PaO2 < 60

WBC < 4 or > 12,000/cc3

Front 317

How does acute pancreatitis typically present?

Back 317

Abdominal pain and tenderness.

Nausea and vomiting.

Fever.

Tachycardia.

Elevated WBC, serum amylase and serum lipase.

Front 318

What are the causes of acute pancreatitis?

Back 318

Gallstones (90%+ in US) 90%

“Alcohol” (acute-on-chronic) 10%

Drugs

Trauma

Structural (P divisum, tumors)

Autoimmune

Genetic

Front 319

Which of the two enzyme tests is more specific for pancreatitis?

Back 319

Serum lipase.

Serum amylase has a bigger differential.

Front 320

In the USA, 90-95% of acute pancreatitis attacks are related to ...

Back 320

gallstones or “sludge” (microlithiasis)

Front 321

How long does someone have to be a drinker to have episodes of acute pancreatitis?

Back 321

It takes 10-20+ years of abuse for the pancreas to respond by episodes of acute pancreatitis.

Front 322

What drugs cause acute pancreatitis?

Back 322

>300 drugs reported to cause AP

Most pancreatitis related to drugs is idiosyncratic, not dose-related

Culprits include thiazide and loop diuretics, steroids, certain antibiotics (e.g. tetracycline, sulfonamides), valproic acid, anti-metabolites, many drugs used for HIV.
(this is seldomly tested)

Front 323

What are the main metabolic causes of pancreatitis?

Back 323

Hypercalcemia:
Almost always due to hyperparathyroidism.
Increasing incidence of milk-alkali syndrome from use of Ca-containing antacids.

Hypertriglyceridemia
Usually >1,000 mg/dl with lipemic serum
Often other physical signs of hyperlipidemia (arcus, xanthelasma)

Front 324

What physical problems can cause pancreatitis?

Back 324

Congenital pancreatic divisum

Neoplasms.

Front 325

What do we know about autoimmune pancreatitis?

Back 325

Probably more common than we think.

Association with Sicca Syndrome, primary sclerosing cholangitis (PSC), autoimmune hepatitis, SLE, and maybe RA.

Bulky pancreas, irregular pancreatic duct on imaging.

1/3-1/2 have elevated IgG4.

May respond to systemic steroids.

Front 326

Can Gila monster venom cause pancreatitis?

Back 326

No, this is an urban legend.

Brown recluse and a variety of other venoms can though.

Front 327

About 80% of pancreatitis is said to be mild, this is also known as...

Back 327

Edematous or Interstitial pancreatitis

Mortality is <1%

Front 328

The 20% of pancreatitis cases that are deemed severe fall into two categories. What are they?

Back 328

Sterile Necrosis:
10% mortality

Infected Necrosis:
~25% mortality

Front 329

What do patients with pancreatitis die of?

Back 329

Early: Metabolic death

Late: Infection

Front 330

What are the three common scoring systems for pancreatitis?

Back 330

Ranson’s Score – outdated

Balthazar Score – based on CT findings of necrosis, fluid collections, etc.

APACHE-II (or III) Score

Both the current scoring systems require 24 hours to obtain data.

Front 331

What causes Chronic Pancreatitis?

Back 331

ALCOHOL! (60-70%)

GENETIC (familial, sporadic) (20%)

CHRONIC UNRELIEVED CAUSES OF ACUTE PANCREATITIS (gallstones, hyperlipidemia, hypercalcemia, maybe A1-AT deficiency, pancreas divisum, autoimmune, etc) (10-20%)

Front 332

What are the patterns of Chronic Pancreatitis?

Back 332

Asymptomatic
Recurrent acute attacks
Chronic pain alone

Front 333

What are the complications of chronic pancreatitis?

Back 333

Pain.

Recurrent attacks of pancreatitis.

Exocrine insufficiency (steatorrhea).

Endocrine insufficiency (DM)

Fluid collections secondary to pancreatic ductal disruption (e.g. pseudocysts, ascites)

Strictures of adjacent structures (e.g. duodenum, bile duct, colon)

Life-threatening bleeding from pseudoaneurysms of the splenic and related arteries in pseudocyst patients.

Front 334

What is the gender bias of IBS?

Back 334

3:1

Most common in ages 15-34.

Front 335

How does IBS affect quality of life?

Back 335

Physical functioning, bodily pain, general health, mental health, emotions, social functioning, vitality

Several studies report that IBS increases the rate of absenteeism

Front 336

What is the annual health care cost of IBS?

Back 336

>20 Billion in both direct and indirect expenditures

Front 337

What are the rome 3 diagnostic criteria for IBS?

Back 337

Abdominal pain 3 days/month in the last 12 weeks that is continuous or recurrent

Associated with >2 of the following:
Improvement with defecation, change in stool frequency, change in stool form

Onset >6 months prior to diagnosis

Supportive symptoms include:
Abnormal stool frequency (<3bm/week; > 3bm/day)‏
Abnormal stool form (lumpy, hard, loose, watery)‏
Straining with defecation
Urgency, incomplete evacuation
Bloating, passing mucous

Front 338

What is the bristol stool scale?

Back 338

Type 1 - Separate hard lumps like nuts (difficult to pass)‏

Type 2 - Sausage shaped but lumpy

Type 3 - Like a sausage but with cracks on surface

Type 4 - Like a sausage or snake, smooth and soft

Type 5 - Soft blobs with clear-cut edges (passed easily)‏

Type 6 - Fluffy pieces with ragged edges, a mushy stool

Type 7 - Watery, no solid pieces (entirely liquid)‏

Front 339

What are some possible pathophysiologic mechanisms for IBS?

Back 339

Neuromuscular dysfunction

Abnormal Brain- GI tract interactions

Immune activations

Genetic Influence

Psychological Distress

Intestinal Flora Disturbances

Front 340

What neurotransmitter is thought to play a role in the neurogenic defects of IBS?

Back 340

Serotonin (5-hydroxytryptamine, 5-HT)

Released by mucosal enterochromaffin cells with noxious stimulation.

Activates peristalsis- abnormalities cause increased/decreased transit

Activates sensory pathways that mediate pain.

Front 341

What organisms are associated with post infectious IBS?

Back 341

salmonella, shigella and Campylobacter

6-27% of pts develop PI-IBS after E. coli or C. jejuni

Front 342

What is the role of psychological distress in IBS?

Back 342

Psychological stress exacerbates gastrointestinal symptoms

Psychosocial disturbance affects illness experience and behavior (sexual and physical abuse)

IBS can lead to impaired health related quality of life.

Front 343

Is there evidence of genetic linkage in IBS?

Back 343

Yes, somewhat.

Front 344

How do we diagnose IBS in practice?

Back 344

Extensive diagnostic testing is not required unless there are red flag symptoms.
(weight loss, fevers, blood in stool, anemia, etc.)‏

Consider:
CBC, ESR, CRP, Metabolic profile, stool cx, stool O&P, WBC and c-difficile toxin

Celiac antibodies (total serum IgA and tissue transglutaminase antibodies)‏

Flexible sigmoidoscopy or colonoscopy for red flag symptoms.

Front 345

How do we treat IBS?

Back 345

Provide reassurance/education

Treat according to predominant symptom

Assess response to therapy in 4-6 weeks.

Front 346

What pharmacological agents are available for IBS?

Back 346

Bulking agents:
(psyllium)

Stimulant Laxatives:
bisacodyl, senna

Osmotic laxatives:
Magnesium Salts
Sodium phosphate
Lactulose
Sorbitol
Polyethylene Glycol

Front 347

What is lubiprostone?

Back 347

Approved for chronic functional constipation .

Increases intestinal fluid secretion by stimulating a specific intestinal chloride channel (ClC2) in apical membrane

No change in electrolyte concentrations in the serum hence safe for chronic use.

Front 348

What does Loperamide (immodium) do?

Back 348

Slows transit time through colon

Increasing resorption of intestinal water

Front 349

What does Diphenoxylate w/ atropine (Lamotil) do?

Back 349

Reduces transit time

Reduces intestinal muscle spasms

Anticholinergic activity

Front 350

How do low dose antidepressants help in IBS?

Back 350

Reduce the intensity of pain signals going from the gut to the brain.

Front 351

What medications can reduce the pain and bloating associated with IBS?

Back 351

Antispasmodics (dicyclomine, hyoscyamine) relieve abdominal pain by inhibiting smooth muscle contraction

5HT3 antagonists

5HT4 agonists

Anti-depressants: TCA and SSRI's

Antibiotics

Probiotics

Front 352

What drug that was previously approved for WOMEN with IBS was taken off the market?

Back 352

Alosetron- 5 HT3 antagonist- targets serotonin receptors in the gut. reduced visceral pain, slowed colonic transit

Side Effect: constipation; ischemic colitis

Recently reintroduced after 12 week multicenter, randomized placebo study.

Lowest dose most effective (0.5-1.0mg) with less risk of severe constipation.

Approved only for women with severe IBS-D.

Front 353

What is Tegaserod Maleate?

Back 353

5HT4 agonist

Stimulates intestinal motility via cholinergic transmission.

Augments the peristaltic reflex

Enhances intestinal secretion

Reduces visceral hypersensitivity

Removed from the U.S. market because of increased risk of serious cardiovascular adverse effects.

Front 354

Is there evidence that probiotics are effective in IBS?

Back 354

Yes.
But so far only Bifidobacterium infantis 35624

Front 355

What is ulcerative colitis?

Back 355

A recurrent acute chronic inflammatory disorder with extensive ulcers of the colon and involvement of extracolonic sites.

1:10,000

No sex bias

familial clustering

Starts in rectum and extends proximally.

Coalescing ulcers and progressive mucosal sloughing.

Pseudopolyps.

Acutely, neutrophils , cryptitis and crypt abscesses that coalesce to undermine mucosa. Marked goblet cell depletion.

Chronically, branched and irregular glands. Increased plasma cells in the lamina propria (basilar plasmocytosis) and eosinophils.

Unlike Crohn's disease, must include the colon and is mucosal based rather than transmural.

Increases risk of adenocarcinoma of the colon.

Front 356

What percentage of Crohn's has colonic involvement? (granulomatous colitis)

Back 356

~40%

Front 357

What are the main pathological differences between granulomatous colitis (Crohn's) and ulcerative colitis?

Back 357

Crohn's is segmental whereas UC is continuous.

Crohn's is predominantly right sided, UC is primarily left sided.

Crohn's has rectal sparing in about 50% of cases.UC ALWAYS involves the rectum.

Crohn's has minimal mucosal atrophy and regeneration with preserved mucin.

Crohn's has TRANSMURAL lymphoid aggregates, non-casseating granulomas, edema and fissures (ulcers).

Front 358

What are the pathological characteristics of diverticular disease?

Back 358

Hypertophy of taenia coli and circular muscle with flask shaped sacs of mucosa and submucosa protruding along the sides of the taenia.

Sigmoid involvement in 99%
(44% exclusively)

Descending colon in ~30%

Entire colon in ~16%

Complications include:
Inflammation
Pericolic abscess
Hemorrhage

Front 359

What is a hyperplastic polyp?

Back 359

Usually asymptomatic

Present in 30% of all colons

Usually multiple.

<5mm

Normal looking but elongated crypts.

Can be either penduculated (with a stalk) or sessile (no stalk).

In cross section the polyp lumen has a star fish appearance.

Front 360

What is a juvenile polyp?

Back 360

Found in children.

Completely benign.

Most common in rectum.

Pedunculated, focally ulcerated, smooth surface round polyp.

Numerous cysts.

Front 361

What are colonic adenomas?

Back 361

Most common true benign epithelial neoplasms in the colon.

Sharply circumscribed elevations of dysplastic premalignant epithelium.

Pedunculated or sessile.

Hyperchromasia.High N/C ratio.

Front 362

Why are adenomas important?

Back 362

2/3 of adenocarcinomas arise from adenomas.

Size, histology and degree of dysplasia are all predictors of how it will develop.
Over 2cm are very worrisome. Less than 1 cm= less than 1% risk.

Front 363

What is the 5 year survival of colonic carcinoma?

Back 363

~45%

Front 364

What are the two major gross appearances of colonic carcinoma?

Back 364

Polypoid mass on the right side of the colon.

Circumferential napkin ring stricture on the left side.

Front 365

What is the worst variant of colonic carcinoma?

Back 365

Mucinous aka colloid adenocarcinoma.

Worse prognosis than classic gland forming adenocarcinoma.

Front 366

What is the inheritance pattern for familial adenomatosis polyposis?

Back 366

Autosomal dominant.

Front 367

What is Lynch Syndrome (HNPCRC)

Back 367

AD inheritance of colorectal carcinoma with young age at diagnosis, right sided predominance, & multiplicity
Associated with Kidd (18q 11-12)
8 times more common than FAP
May be associated with “Flat” adenomas

Front 368

What are the two genetic pathways at play in colon cancer?

Back 368

Suppressor Pathway:
Genetic changes in APC, beta-catenin, & TCF4-80% sporadic colon cancers FAP

Mutator Pathway:
Multiple genetic changes in DNA mismatch repair gene systemResults in microsatellite instability10-20% sporadic cancers-
Many cases of CUC cancers

Front 369

What is the standard physiological response to blood loss?

Back 369

Peripheral vasoconstriction
(cold, clammy skin)

Diminished cardiac output (compensatory tachycardia and hypotension)

Oliguria

Orthostatic Hypotension
(> 25-30% blood loss)

Signs of shock
(> 50% blood loss)

Front 370

How do we describe hematemesis?

Back 370

Bright red (active hemorrhage)

Bright red with clots
(mixture of active hemorrhage and older, clotted blood)

“coffee grounds”
(older blood that has completely clotted)

Front 371

What is melena?

Back 371

Black, tarry, sticky, pungent stool.

Digested blood that has passed through the GI tract

Front 372

What is hematochezia?

Back 372

Passing of bloody stools

Usually a mixture of bright red (or maroon) blood and clots.

Usually lower GI bleed but !!upper GI bleeding can result in hematochezia!!

Front 373

What is the most common cause of upper GI bleeding?

Back 373

Ulcerative or Erosive Disease (55%)

Peptic ulcer disease
Esophagitis
Pill induced (usually esophageal)

Front 374

What is a Dieulafoy’s lesion?

Back 374

AV malformation characterized by a bleeding vessel with no surrounding ulcer.

Front 375

Gastric Antral Vascular Ectasia (GAVE) is often termed....

Back 375

“watermelon stomach”

Front 376

What are Mallory-Weiss tears?

Back 376

Tear of gastric and esophageal mucosa at the GEJ, usually after retching.

Front 377

What is the most common cause of lower GI bleeding?

Back 377

Diverticulosis (~33%)

Prevalence increases with age, 30% at age 60, 65% at age 85.
Left>>right, though right sided disease accounts for the majority of bleeding.

Front 378

What is angiodysdplasia?

Back 378

A rare cause of lower GI bleed (~8%).

Dilated tortuous submucosal vessels (usually veins) which can rupture.

More common in elderly, and those with multiple medical problems.

Front 379

When does post polypectomy bleeding usually occur?

Back 379

Can be immediate or delayed
(up to 10 days)

Front 380

What do hemotchezia and melena tell us about the location of a GI bleed?

Back 380

Hematemesis and/or melena are usually signs of an upper GI bleed.

Hematochezia is usually a sign of lower GI bleeding. However, massive upper GI bleed can also cause this.

Front 381

What does NG tube aspirate tell us about an upper GI bleed?

Back 381

Aspiration of bright red blood = active bleeding

Aspiration of clots and coffee grounds = bleeding may have stopped

Aspiration of bile = may not be an upper GI bleed

Duodenal bleeding may have a false negative NG lavage (if no blood refluxes into the stomach).

Do not check gastroccult. It will almost always be positive due to the trauma of the NG tube being placed.

Front 382

What is unique about how we manage GI bleeds with regard to transfusion?

Back 382

Transfuse blood based on hemodynamic status, not hematocrit initially.

After equilibration keep hematocrit > 30 in patients with vascular disease, >20 for others.

Correct coagulapathy (fresh frozen plasma to keep INR < 1.5)) and thrombocytopenia (platelets if needed to >50,000)

Front 383

When do we start high dose PPI's in suspected upper GI bleeding?

Back 383

As early as possible.

Decrease rebleeding rate
Decrease hospital stay
Decrease transfusion requirements


Block gastric proton pumps (H-K-ATPase) in parietal cells and quickly (in high dose IV form) increase gastric pH.

Allow more effective clotting in a more neutral pH

Improved mucosal healing in a more neutral pH

Front 384

Apart from high dose PPI's, what other medical therapies should be initiated in upper GI bleeding?

Back 384

Promotility agents (erythromycin IV) to increase gastric motility and improve visualization during upper endoscopy.

If it is a lower GI bleed, begin colon preparation with a orally administered polyethylene glycol (PEG) based saline lavage (e.g. Golytely).

Check and treat H. pylori in patients with PUD. Usually with serum IgG.

Front 385

On endoscopy, what are considered high risk upper GI bleeding lesions?

Back 385

Ulcers:
Actively bleeding
Non-bleeding visible vessels
Adherent clots
Oozing without visible vessel

Variceal hemorrhage

Front 386

On endoscopy, what are considered lower risk upper GI bleeding lesions?

Back 386

Ulcers:
Pigmented spot
Clean based

Most other etiologies of upper GI bleeding are at low risk for rebleeding, assuming they are appropriately treated
(e.g. Dieulafoy’s lesion, Mallory Weiss tears)

Front 387

What is endoscopic injection therapy?

Back 387

Usually epinephrine

Effective in immediate hemostasis, but high risk of rebleeding

Front 388

What is the danger of using endoscopic thermal contact coagulation probes?

Back 388

Can lead to perforation if used in thin walled organs (right colon).

Front 389

What is endoscopic noncontact thermal therapy?

Back 389

Argon Plasma Coagulation (APC)

Thermal energy is delivered via ionized argon gas.

Coagulation is superficial.

The probe does not touch the mucosa.

Ideal for treating angiodysplasia, especially in the colon, and GAVE .

Front 390

How do we define endoscopic failure?

Back 390

Recurrent hemorrhage after initial stabilization
(with up to two attempts at obtaining endoscopic hemostasis)

Hemodynamic instability despite vigorous resuscitation
(more than a three unit transfusion)

Shock associated with recurrent hemorrhage

Continued slow bleeding with a transfusion requirement exceeding three units per day.

Front 391

What options are there for GI bleeding intervention other than endoscopy?

Back 391

Angiography with embolization:
Particularly effective in lower GI bleeding when the source cannot be identified endoscopically.
Carries risk of infection, bleeding, damage to vessels, mucosal ischemia and necrosis (if not selective)

Surgery:
Usually reserved for endoscopic and/or angiographic failures
Can entail oversewing (ligation) of the vessel, resection, vagotomy (decrease acid secretion).

Front 392

What is occult GI bleeding?

Back 392

The initial presentation of a positive fecal occult blood test (FOBT) result and/or iron-deficiency anemia (IDA), when there is no evidence of visible blood loss to the patient or physician.

Front 393

What are the possible etiologies of occult GI bleeding?

Back 393

GI cancers (upper and lower)
Ulcers
Esophagitis
Angiodysplasia
IBD
Hemorrhoids
And all other causes of GI bleeding

Front 394

How does fecal occult blood testing work?

Back 394

Guiac (a natural compound found in certain trees) contains phenol which turns to a blue quinone mediated by a peroxidase (found in heme) in the presence of hydrogen peroxide.

Stool placed on one side of the card, the card is turned over and hydrogen peroxide is placed over the stool.

Blue = positive test
No color change = negative test

Front 395

What are the problems with fecal occult blood testing?

Back 395

High false positive rate:

Must avoid NSAIDs and other irritant drugs

Avoid red meat, turnips, and horseradish (all have peroxidase activity)

Stool obtained from digital exams can be heme positive from trauma.

Low sensitivity:
Many lesions bleed intermittently and may be missed (though the test can detect as little at 10-20 cc of blood loss/day)

Vitamin C can lead to a false negative test

Poor public acceptance rate

Front 396

What is obscure GI bleeding?

Back 396

Bleeding from the GI tract that persists or recurs without an obvious etiology after upper endoscopy, colonoscopy, and radiologic evaluation of the small bowel (such as by small bowel follow-through or enteroclysis).

2 subcategories:

Obscure-overt – clinically evident GI bleeding (e.g. hematemesis, melena, hematochezia)

Obscure-occult – clinically absent GI bleeding

Front 397

What are the etiologies of obscure GI bleeding?

Back 397

Missed lesion on EGD or colonoscopy

Angiodysplasia

Small bowel tumors

NSAID enteropathy

Meckel’s diverticulum

Cameron’s lesion

Dieulafoy lesion

GAVE

Hereditary hemorrhagic telangiectasia

Celiac Sprue

Crohn’s disease

Front 398

What areas of the world have the highest rates of colon cancer?

Back 398

Highest incidence in North America, Australia, and Western and Northern Europe.

10 times higher incidence than Africa and Asia

Thought to be due to genetics, diet, and environment.

Front 399

What are the major evidence based risks for colon cancer?

Back 399

Age
Family history (20-25%)
Inflammatory bowel disease

Front 400

What are the key genes identified as involved in the pathogenesis of colon cancer?

Back 400

K-ras:
most frequent mutation of the ras oncogene in CRC
this mutation effectively leaves the growth switch ON.

Adenomatous Polyposis Coli (APC) gene:
The most important tumor suppressor gene in CRC
mutation of this gene leaves cell growth unchecked

p53 gene:
“the guardian of the genome” produces a DNA-binding protein that activates transcription of growth inhibitory genes.
Mutation of this tumor suppressor gene can result in uncontrolled cell division.

Front 401

What is the difference in the pathogenesis of sporadic and inherited colon cancer at the level of the genome?

Back 401

Sporadic colon cancer:
Results from stepwise occurrence of multiple somatic mutations
APC – MMR – K-ras – p53

Inherited Colon Cancer Syndromes:
Result from single germline mutations.
FAP: APC gene
HNPCC: MMR gene

Front 402

How does sporadic colon cancer develop?

Back 402

APC – MMR – K-ras – p53

Front 403

What are the variant forms of Familial Adenomatous Polyposis (FAP)?

Back 403

Gardner’s Syndrome
Turcot’s Syndrome

Front 404

What are some alternative names for Hereditary Nonpolyposis Colorectal Cancer ?

Back 404

HNPCC
Lynch Syndrome

Front 405

Give an example of a familial colon cancer syndrome that is not HNPCC or FAP.

Back 405

Peutz-Jeghers Syndrome

Front 406

So what exactly is FAP?

Back 406

Autosomal dominant trait

germline mutation of the APC gene

located on chromosome 5q21-q22

1/3 of cases represent new mutations (no family history)

represents less than 1% of the total CRC risk

clinical manifestations:
more than 100 colorectal polyps
polyps begin to develop in 2nd decade
Average CRC diagnosis at age 39
compared with age 65 in the average US population.

100% will have colon cancer by age 45.

Duodenal ampullary carcinoma.

Variants of the disease include:
Gardner’s Syndrome
associated with extra-gastrointestinal tumors such as
osteomas (bone tumors, mostly of skull and mandible)
cutaneous tumors (fibromas, lipomas, epidermal cysts)
desmoid tumors (most commonly in the abdomen)

Turcot’s Syndrome:
associated with brain tumors such as medulloblastoma and glioma.

Front 407

How do we manage FAP?

Back 407

Phenotype identified endoscopically

Treatment:

Total proctocolectomy

Ileostomy

Ileal-Pouch-Anal Anastamosis (IPAA)

Timing depends on size and histology of polyps.

Many can wait until completion of high school.

Front 408

What exactly is Hereditary Nonpolypsis Colorectal Cancer orLynch Syndrome?

Back 408

Autosomal dominant germline mutations in DNA mismatch repair (MMR) genes.

more rapid adenoma-carcinoma sequence.

average age of colon cancer diagnosis is age 48

60% lifetime risk of colon cancer

predominance for the right side of the colon.

synchronous and metachronous cancers are common:
uterus (also ovary, stomach, small bowel, bile ducts, ureter)
80% overall cancer risk (colon + extra-colonic)

Strongly consider colectomy with this diagnosis. Rectum can often be preserved.

Front 409

What exactly is Peutz-Jeghers Syndrome?

Back 409

autosomal dominant

characterized by multiple pigmented spots on the lips and buccal mucosa.

Associated with hamartomas:
small bowel
colon
stomach

Typically present in third decade with:
intussusception
obstruction
bleeding

Adenomatous change occurring in hamartomas, leading to the adenoma-carcinoma sequence.

15 fold increased risk of cancer in:
colon
stomach
small intestine
pancreas
breast
ovary
lung

Front 410

What are the most common presentations of colorectal cancer?

Back 410

40% abdominal pain
40% rectal bleeding or melena
40% change in bowel habit
20% weakness
10% anemia alone
5% weight loss

Right colon lesions tend to present with blood loss.

Left colon lesions tend to present with pain, altered BM.

Patients presenting with pain have a worse prognosis.

Front 411

What are the best tests for the diagnosis of colon cancer?

Back 411

Colonoscopy -
The best test to diagnose CRC.
The best sensitivity and specificity.
Allows biopsy of any lesions found.
Detects any synchronous cancers and removal of any synchronous benign polyps.

Barium Enema:
50% sensitivity
Fallen out of favor.

CT (routine):
Poor sensitivity for intraluminal lesions.
Main utility is to detect metastases (liver, lymph nodes)

CT colonography:
Sensitivity of up to 90% for CRC
positive results require colonoscopy for biopsy.

Front 412

How do we stage colon cancer?

Back 412

Stage 0-IV are based on TNM system with IV having the worst prognosis.

Tis:
carcinoma in situ

T1:
invades submucosa

T2:
invades muscularis propria

T3:
invades through MP into subserosa

T4:
directly invades other organs, peritoneal space

N0:
no lymph node mets

N1:
mets in 1-3 regional nodes

N2:
mets in 4 or more regional nodes

M0:
no distant mets

M1:
distant mets

Front 413

How do we treat colon cancer?

Back 413

Endoscopic polypectomy:
for Tis - T1, well-differentiated cancer in pedunculated polyps

Surgical resection:
for cure-
5 cm margins and regional lymphadenectomy required for flat polyps, T2 lesions, or if poorly differentiated.
for palliation- of obstruction or bleeding.

Chemotherapy for Stage III and IV disease:
FOLFOX
(FOLinic acid, Flourouracil, OXalipitin)

Rectal Cancer:
radiation and chemotherapy (5-FU) for Stage II and III

Front 414

What is pretty unique about colon cancer from a treatment standpoint?

Back 414

Resection of mets can actually influence 5 year survival substantially.

Stage four disease with good functional status actually does better with Chemo than most other cancers.

Front 415

Average-risk screening for colon cancer begins at age 50 and can be done by...

Back 415

Fecal occult blood testing q 1 year.

Flexible Sigmoidoscopy (FS) q 5 years.

CT Colonography (CTC) q 5 years.

Colonoscopy q 10 years.

A positive test by any method gets a colonoscopy.

Front 416

What cancers are screened for in the U.S?

Back 416

Cervical cancer.

Breast cancer.

Colon cancer.

Front 417

How should a patient with a 1st degree relative with CRC age < 60 be screened?

Back 417

Start at age 40, or ten years younger than the index patient, whichever comes first.

q 5 years

Front 418

How often should a patient with a personal history of colon adenoma
be screened for CRC?

Back 418

3-5 years
Use 3 year interval if > 1 cm, more than 2 polyps, villous, or high grade dysplasia

Front 419

How often should a patient with a personal history of colon cancer be screened for CRC?

Back 419

1, 3, and 5 year interval

Then every 5 years thereafter; Looking for missed lesions and metachronous lesions.

Front 420

How often should a patient with a personal history of ulcerative colitis be screened for CRC?

Back 420

Once a year.

Start after 8-10 years of pancolitis.

Front 421

How often should a patient with a personal history of colon adenoma
be screened for CRC?

Back 421

3-5 years
Use 3 year interval if > 1 cm, more than 2 polyps, villous, or high grade dysplasia

Front 422

How often should a patient with a personal history of colon cancer be screened for CRC?

Back 422

1, 3, and 5 year interval

Then every 5 years thereafter; Looking for missed lesions and metachronous lesions.

Front 423

How often should a patient with a personal history of ulcerative colitis be screened for CRC?

Back 423

Once a year.

Start after 8-10 years of pancolitis.

Front 424

What is the differential on bloody diarrhea in a young healthy person?

Back 424

Infectious colitis

Inflammatory Bowel Disease

Unlikely: ischemic colitis or malignancy

Front 425

Fecal culture usually reports...

Back 425

salmonella,
shigella,
campylobacter,
yersinia,
E. coli 0157

Front 426

What ethnicity has the highest incidence of IBD in descending order?

Back 426

Ashkenazi jews
Non-jewish caucasians
African americans

Front 427

When is the peak age of IBD diagnosis?

Back 427

20
Second much smaller peak again at around 60.

Front 428

How can ulcerative colitis be broken down into three sub categories based on distribution?

Back 428

Ulcerative proctitis
Distal Ulcerative Colitis (left sided)
Extensive Ulcerative Colitis (pancolitis)

Front 429

Bloody diarrhea in IBD is typically indicative of...

Back 429

Colon involvement

Front 430

Perianal disease is associated with...

Back 430

Crohn's disease

Front 431

What pattern does IBD follow?

Back 431

Relapsing remitting.

Front 432

What are some of the perianal complications of Crohn's?

Back 432

Perianal fistulae and abscess.

Front 433

What are some of the extraintestinal manifestations of IBD?

Back 433

Skin disorders:
Erythema nodosum
Pyoderma gangrenosum

Joint disorders:
Peripheral arthritis
(> in large joints, no nodules and seronegative)
Sacroiliitis
Ankylosing spondylitis

Ocular disorders:
Iritis
Uveitis (treat aggressively)
Episcleritis

Hepatobiliary:
Gall stones
Sclerosing Cholangitis
Cholangiocarcinoma

Renal:
Renal stones
Amyloidosis

Other:
Apthous stomatitis

Front 434

What are some IBD therapies?

Back 434

Aminosalicylates:
5-ASA

Steroids:
Prednisone, budesonide

Immunomodulators:
Azathioprine/6-MP, methotrexate
Biologics

Anti-TNF therapy:
Infliximab, adalimumab, certolizumab

Surgery

Front 435

5-ASA drugs are approved for use in ulcerative colitis. Are they approved for Crohn's disease?

Back 435

No.
But we often try them because they are very safe.

Front 436

Why is the steroid budesonide particularly well suited to Crohn's disease?

Back 436

It is delayed release and releases in the small bowel where it is most needed.

Metabolized in the liver quickly which amounts to lower serum levels and systemic effects.

VERY expensive drug though.

Front 437

How is Azathiprine related to 6-mercaptopurine (6-MP) ?

Back 437

It is it's prodrug.

Front 438

What infection is a patient on ant TNF therapy susceptible to?

Back 438

TB

Also coccidiomycosis and histoplasmosis.

Front 439

How do we treat ulcerative colitis?

Back 439

First line therapy is 5-ASA:
Oral and or rectal

Steroids:
Short course for bad flares

Immunomodulators:
Use for steroid-dependent UC

Biologics:
Failure of standard therapy

Front 440

How do we treat mild to moderate Crohn's disease?

Back 440

Oral aminosalicylates
Budesonide

Front 441

What is the only drug that is technically FDA approved for mild to moderate Crohn's disease.

Back 441

Budesonide

Front 442

How do we treat fulminant ulcerative colitis?

Back 442

IV steroids
IV infliximab
IV cyclosporine
Surgery

Front 443

How do we treat Moderate-Severe active Crohn's disease?

Back 443

Prednisone:
short course only

Immunomodulators:
Azathioprine/6-MP
Methotrexate

Anti-TNF Therapy:
Infliximab
Certolizumab
adalimumab

Front 444

What are the indications for surgery in ulcerative colitis patients?

Back 444

Exsanguinating hemmorage
Toxicity and/or perforation
Suspected cancer
Significant dysplasia
Growth retardation
Sytemic complications
Intractibility

Front 445

What are indications for surgery in Crohn's disease?

Back 445

Failure to respond to medical therapy

Complication management:
Strictures
Fistulae
Perforations
Perianal disease
Cancer or precursors

Front 446

If we see cysts in the pancreas of someone who has never had acute or chronic pancreatitis, we assume that they have...

Back 446

Pancreatic cancer.

There is no reason they should have pseudocysts.

Front 447

What is another term for neuroendocrine lesions of the pancreas?

Back 447

Islet cell neoplasms.

Front 448

How do liver conditions affect the risk of hepatocellular carcinoma?

Back 448

Any chronic liver disease increases the risk.

HepB (biggest risk worldwide)
Hemochromatosis.
Fatty liver (NASH).
Hep C (biggest risk in U.S)
HepA is acute so it does not increase the risk.

HCC is the third leading cause of cancer death. Very common in asia and subsaharan Africa.

HCC often unresponsive to treatment (serafonib)

Front 449

How do the risk factors affect the clinical course of hepatocellular carcinoma in various geographical regions?

Back 449

Endemic regions (Asia/Africa): HBV carriers from infancy; HCC often occurs in persons ages 20-40

Western societies:
Cirrhosis precedes HCC in 80-90%; risk factors include ethanol, HCV, HBV, any chronic liver disease such as hemochromatosis.

Front 450

What are the clinical features of hepatocellular carcinoma?

Back 450

Often masked by cirrhosis; weight loss, malaise, abdominal pain/fullness, hepatomegaly

Serum alpha-fetoprotein:
elevated in 50-70% cases (also elevated in chronic hepatitis, liver necrosis, cirrhosis, gonadal germ cell tumors)

Imaging:
Ultrasound, CT, MRI, angiography if surgical resection is considered

Treatment:
Complete surgical excision (before lung and nodal metastases) is only hope of cure

5 year survival all HCC:
5% (dismal)

Front 451

What screening tests do we use for hepatocellular carcinoma?

Back 451

Imaging studies:
Ultrasound*
Computed tomography
No significant differences between spiral CT and MRI.

Blood tests:
Alpha-fetoprotein*
(not all that sensitive or specific but still used)

US screening strategy is q 6-12 months and

AFP q 6 months is the most commonly used strategy in Asia and U.S.

Rationale for 6-month screening interval:
Median doubling time = 6 mo

Front 452

What is the most common presentation of hepatobiliary malignancies?

Back 452

JAUNDICE!!!

Front 453

What are the risk factors for gallbladder cancer?

Back 453

Female sex

Age > 50 years

Gallstones > 40 years
(mostly cholesterol).

High risk populations such as Native Indians, Chile

Chronic cholecystitis

Calcified GB (porcelain GB)

Fat, Fertile, Forty, Female

Front 454

How do we treat gallbladder cancer?

Back 454

Surgery:
Only chance for cure. Prophylactic cholecystectomy for asymptomatic gallstones not recommended, even if > 40 yrs

Chemotherapy and Radiation:
Poor response

Palliation:
ERCP for jaundice / pruritus

Overall mean survival of 6 months

5%, 5-year survival

Invasion usually local (contiguous spread)

Palliative management

If detected incidentally at time of cholecystectomy, then may survive long-term.

Front 455

What are the risk factors for cholangiocarcinoma?

Back 455

Primary sclerosing cholangitis (PSC)-seen in IBD. (narrowing of the intra and extrahepatic ducts)

Basically anything that causes inflammation in the bile duct.

Front 456

What type of tumor is cholangiocarcinoma (aka klatzkin tumor if it is in the hilum)?

Back 456

Adenocarcinoma (90%),

Front 457

What is the typical presentation of cholangiocarcinoma?

Back 457

Cholestasis:
Jaundice, pruritus, weight loss
Hepatomegaly:
ascites
RUQ mass (late)

Cholangitis is rare in cholangiocarcinoma and is usually caused by stones not tumors.

Front 458

How do we diagnose cholangiocarcinoma?

Back 458

Labs:
Cholestatic obstructive LFTs
Elevated serum CA19-9
(>100 U/ml) in 55-65%

US:
Dilated intrahepatic or extrahepatic duct; no mass detected

CT:
Dilated intra or extrahepatic ducts; usually difficult to identify mass lesion

ERCP:
Detect level of stricture
Brush cytology (sensitivity 50-55%)
Stenting for palliation or bridge to surgery.

Front 459

What are the risk factors for ampullary carcinoma?

Back 459

Familial Polyposis
Ampullary adenoma

Front 460

How does ampullary carcinoma usually present?

Back 460

Cholestatic jaundice
Pruritus
Intermittent bleeding
Cholangitis
Pancreatitis
Obstructive LFTs

Front 461

How do we treat ampullary carcinoma?

Back 461

Important to distinguish from pancreatic cancer or cholangiocarcinoma

Surgical resection possible in 75%
Pancreatoduodenectomy (Whipple’s)

Front 462

When will jaundice occur with pancreatic cancer?

Back 462

Usually if the tumor is in the head of the pancreas.

Front 463

Recent onset of diabetes or anorexia gets us thinking about...

Back 463

Pancreatic cancer.

Front 464

What is Courvoisier’s sign?

Back 464

Palpable distended GB often associated with pancreatic cancer.

Front 465

What are the CT resectability criteria for pancreatic cancer?
(not crucial for step 1)

Back 465

No extrapancreatic disease.

Unobstructed SMV-PV confluence.

No tumor extension into Celiac or SMA.

Clear fat plane between around Celiac and SMA.

CT has 80% predictability using these criteria
Despite this, 5 year survival <20% and median survival 15-17 months

Front 466

What are the cystic neoplasms of the pancreas?

Back 466

Serous Cystadenoma (benign cyst):
Elderly women (>60); asymptomatic
Large lesions; multiloculated , multicystic(honeycomb)
Malignant transformation is rare.

Intraductal Papillary Mucinous Neoplasm:
Premalignant, seen in elderly men, pancreatic duct obstruction

Mucinous Cystadenoma /carcinoma:
40-60 years of age.
Unilobular or multilobular cyst containing mucin.
Should be resected.
Excellent prognosis if resected prior to carcinoma.

Front 467

What do we want to know about Pancreatic Neuroendocrine Tumors (Islet Cell neoplasms)?

Back 467

Functional vs Non-functional

All endocrine tumors appear similar histologically. Immunos/peroxidase to distinguish subtype and biochemical data.

Malignancy based on the presence of local invasion, spread to regional LN, or liver/distant mets.

Inuslinoma, VIPoma,gastrinoma, glucagonoma, somatistatinoma.

Front 468

Relative to benign salivary gland tumors, salivary gland malignancies have a tendency to...

Back 468

Grow more rapidly

To infiltrate superficial and deep tissues and thus be fixed; benign tumors are movable masses.

Invade nerves producing, pain , parasthesias and CNVIII paralysis.

Front 469

In descending order, what are the most common salivary gland tumors?

Back 469

Parotid (~80%):
Most often benign
9/2

Submandibular (~15%):
About 1/3 are malignant

Minor (~5%):
About half are malignant.

Front 470

What are the two most common types of benign salivary gland tumors?

Back 470

Pleomorphic Adenoma aka Benign mixed tumor. Well defined and encapsulated with collagen.

Warthin’s Tumor:
Almost exclusively found in the parotid gland.
Most common salivary glad tumor in elderly men.
Most common tumor that shows up with a bilateral presentation.

Front 471

On gross pathology we can differentiate Warthin's tumors from pleomorphic adenoma bcause..

Back 471

Pleomorphic adenoma has a solid glistening appearance.

Warthin's is cavitary with uneven polypoid projections.It also feels softer.

Front 472

What are the most common malignant tumors of the salivary glands?

Back 472

Mucoepidermoid CA
Adenoid Cystic CA
Polymorphous Low Grade CA
Lymphoma

Front 473

Why is there bilateral parotid enlargement (Mikulicz’s) associated with Sjogren's syndrome?

Back 473

Infiltration of lymphocytes.

Sometimes the minor salivary glands are biopsied in the lip looking for periductal lymphoid infiltrates.

Front 474

The inner mucosa of the esophagus is comprised of...

Back 474

Nonkeratinizing stratified squamous epithelium;

Glandular epithelium in distal 1-2 cm

Front 475

What is the histological change that occurs in Barrett's esophagus ?

Back 475

Epithelium goes from squamous to intestinal glandular in type.

Front 476

The vast majority of carcinoma of the esophagus is...

Back 476

Squamous cell carcinoma

Front 477

What is the pathologist's diagnostic feature of eosinophillic esophagitis?

Back 477

>20 eosinophils/HPF in mucosa

Front 478

The overall 5 year survival of esophageal cancer (SCC + AC) is...

Back 478

30%

Front 479

What puts you at greater risk for esophageal SCC?

Back 479

Food & water rich in nitrates & nitrosamines,
alcohol,
tobacco,
vitamin deficiencies,
achalasia,
Plummer-Vinson syndrome,
erosive esophagitis with strictures, HPV,
black men

Front 480

What is an increased risk for esophageal adenocarcinoma?

Back 480

Barrett's Esophagus, (especially with high grade dysplasia which has a 50-66% risk)

White men

Front 481

What are acute stress ulcers?

Back 481

Shallow ulcers.

Often multiple.

Associated with hypotension.

Front 482

What are the different types of chronic gastritis?

Back 482

Nonatrophic (H.pylori)
Multifocal atrophic
Autoimmune
Lymphocytic
Viral (systemic, CMV)
Granulomatous
Reactive

Front 483

What type of organism is H. Pylori?

Back 483

Gram negative spiral rod

Strong affinity for gastric surface epithelium

Congregates near tight junctions & in mucus

Produces urease, ammonia, acetaldehyde, phospholipases, toxins VacA & cagA, platelet activating factor

Most common in developing countries.

Occurs in children but less common in the U.S.

Front 484

What diseases are associated with H. Pylori infection?

Back 484

Nonatrophic gastritis
Multifocal atrophic gastritis
Peptic ulcers
Gastric adenocarcinoma
Gastric lymphoma

Prevalence of nonulcer dyspepsia is similar with & without infection.

Front 485

What are the pathological changes of chronic non-atrophic gastritis?

Back 485

Lymphoid follicles/nodules.

Expansion of Lamina propria by plasma cells

Neutrophils in Lamina propria & epithelium of surface & pits.

Erosions

Front 486

What is multifocal atrophic gastritis?

Back 486

Multiple areas of chronic gastritis with marked glandular atrophy & intestinal metaplasia in fundus & antrum.

H.pylori infection acquired early in life.

Front 487

What is autoimmune gastritis?

Back 487

Corpus restricted atrophic gastritis (not in the antrum) with serum anti-parietal cell & anti-IF antibodies, & IF deficiency, with or without pernicious anemia.

Iron deficiency anemia also common

Risk factor for adenomas, adenocarcinoma, endocrine tumors

Idiopathic

Front 488

Where are peptic ulcers most common?

Back 488

Duodenum (~75%)

Front 489

What are the two main types of gastric adenocarcinomas?

Back 489

Intestinal (more common):
Mean age 55
3:1 M:F ratio
H. Pylori association
Polypoid gross appearance
Gland forming histology

Diffuse (more agressive):
Mean age 45
1:1 M:F ratio
Infiltrative gross appearance
Signet ring cell histology

Front 490

What does partial gastrectomy do to gastric adenocarcinoma risk?

Back 490

Increases it.

Stump carcinomas.

Front 491

Early gastric carcinoma is defined as...

Back 491

Gastric adenocarcinoma confined to the mucosa and/or submucosa.

Prognosis is obviously better before the lymp nodes are involved.

Front 492

The most common site for extranodal non-hodgkins lymphoma is...

Back 492

The gastrointestinal tract.

Stomach is primary site in 60-65% of GI NHLs

Accounts for 5% gastric cancers

Small intestine is primary site 20-35%

Accounts for 25% of all small intestine cancers. The trend continues distally.

Predisposing factors include H. pylori infection, celiac disease, CIBD, immune deficiency states.

Front 493

What are the different types of gastric lymphomas?

Back 493

DLBC

Marginal Zone (MALToma):
Associated with H.Pylori

Burkitt's

Mantle cell

Follicular

Front 494

What are the histological features of gastric MALTomas?

Back 494

Composed of small-medium sized tumor cells with slightly irregular nuclei & clear cytoplasm

Usually confined to mucosa & submucosa as diffuse infiltrate

Lymphoepithelial lesions

Colonized benign follicles

Plasmacytoid features

Front 495

What are GI stromal tumors?

Back 495

Most patients middle aged on older

M:F 1:1

65% in stomach; 30% in SI

No known risk factors

Interstitial cells of Cajal: pacemaker cells between autonomic nerves & smooth muscle

Challenge of predicting behavior differs by location.

Gleevec (c-Kit; CKD 117)

Front 496

What are predictors of malignancy in gastric stromal tumors?

Back 496

Size >5 cm
MF count >5/50 hpf
Invasion of LP
Tumor cell necrosis
Dense cellularity

Front 497

What are the normal changes that occur in hepatocytes with age?

Back 497

Hepatocyte size varies more greatly.

Binucleation or multinucleation can occasionally be seen.

Front 498

What is chronic hepatitis?

Back 498

A syndrome of hepatocyte necrosis and inflammation with varied etiology histologic, symptomatic and lab abnormailities.

Lasts longer than 6 months.

Front 499

What are the etiologies of chronic hepatitis?

Back 499

Chronic hepatitis B
Chronic hepatitis D
Chronic hepatitis C
Autoimmune hepatitis
Drugs
Metabolic disorders

Hep B and C most common.

Front 500

What are piecemeal and bridging necrosis in chronic hepatitis?

Back 500

Piecemeal necrosis:
Periportal necrosis of hepatocytes and inflammation with disruption of the limiting plate and isolation individual cells.
(most charcteristic of autoimmune hepatitis)

Bridging necrosis:
Zones of necrosis and inflammation extending from portal tracts to connect adjacent and/or central areas.

Front 501

The extent or severity of damage in the liver is referred to as..

Back 501

Grading.

Grade 1:
Inflammation restricted to portal tracts.
No infiltration of liver parenchyma.

Grade 2:
Some infiltration of lobular parenchyma.
Piecemeal necrosis at limiting plate.

Grade 3:
More inflammation than grade 2. Somewhat subjective.

Grade 4:
Bridging necrosis. Mononuclear cells replace hepatocytes.

Front 502

What are the normal changes that occur in hepatocytes with age?

Back 502

Hepatocyte size varies more greatly.

Binucleation or multinucleation can occasionally be seen.

Front 503

What is chronic hepatitis?

Back 503

A syndrome of hepatocyte necrosis and inflammation with varied etiology histologic, symptomatic and lab abnormailities.

Lasts longer than 6 months.

Front 504

What are the etiologies of chronic hepatitis?

Back 504

Chronic hepatitis B
Chronic hepatitis D
Chronic hepatitis C
Autoimmune hepatitis
Drugs
Metabolic disorders

Hep B and C most common.

Front 505

What are piecemeal and bridging necrosis in chronic hepatitis?

Back 505

Piecemeal necrosis:
Periportal necrosis of hepatocytes and inflammation with disruption of the limiting plate and isolation individual cells.
(most charcteristic of autoimmune hepatitis)

Bridging necrosis:
Zones of necrosis and inflammation extending from portal tracts to connect adjacent and/or central areas.

Front 506

The extent or severity of damage in the liver is referred to as..

Back 506

Grading.

Grade 1:
Inflammation restricted to portal tracts.
No infiltration of liver parenchyma.

Grade 2:
Some infiltration of lobular parenchyma.
Piecemeal necrosis at limiting plate.

Grade 3:
More inflammation than grade 2. Somewhat subjective.

Grade 4:
Bridging necrosis. Mononuclear cells replace hepatocytes.

Front 507

In the context of chronic hepatitis, staging refers to....

Back 507

The amount and distribution of collagen containing connective tissue and fibrosis.
Often requires trichrome stain to evaluate.

Stage 1:
Little or no increase in fibrosis.

Stage 2:
Slight increase in connective tissue away from the portal tracts towards the central veins.

Stage 3:
Strand or bands connecting portal tracts to portal tracts or portal tracts to central veins or both.

Stage 4:
Cirrhosis. Hepatocytes form round nodules AND circumferential bands of collagen.

Front 508

A dead heaptocyte that is brilliantly eosinophillic with a very pale nucleus is reffered to as...

Back 508

Acidophil body

Front 509

The characteristic appearance of liver tissue in hepatitis C is....

Back 509

Clear little round wholes from nodular enlargement of the portal tracts.

Not diagnostic but highly characteristic.

Front 510

What are the main categories of alcoholic liver disease?

Back 510

Fatty liver
Central (perivascular) necrosis
Alcoholic hepatitis (Steatonecrosis)
Cirrhosis

Front 511

Trichrome stains are designed to highlight...

Back 511

Collagen

Front 512

Hyaline in swollen cells is highly characteristic of...

Back 512

Alcoholic hepatitis.
Not commonly seen but highly characteristic.

There is also:
hepatocyte necrosis
centrilobular ballooning
Neutrophillic infiltrates
Fatty change
Perivenular and sinusoidal fibrosis

Front 513

What exactly is cirrhosis?

Back 513

Requires two microscopic features.
Nodules,Thick cell plates
AND
Bands of fibrosis that completely encircle the regenerative nodules.

Involves the entire liver parenchyma.

Can be classified based on nodule size:
Micronodular
Macronodular
Mixed

Can also be classified by etiology.

Front 514

What are the causes of cirrhosis in descending order of incidence?

Back 514

Alcoholic liver disease (~65%)
Viral hepatitis
Biliary diseases
Hemochromatosis
Cryptogenic or idiopathic.

Front 515

What is autoimmune hepatitis?

Back 515

Chronic, genetically predisposed (HLA8,DR,DR4) liver disorder.

More comon in women (85%), with
autoantibodies & a good response to immunosupression.

Defect in suppresor T cells

Antibodies vs hepatocytic surface.

Type 1 (adults):
ANA & ASMA
(antic nuclear antibody and anti smooth muscle antibody)

Type IIa (pediatrics) :
ALKM
(anti liver kidney microsomal antibody)

Front 516

What are the pathological findings of autoimmune hepatitis?

Back 516

Gross:
normal-shriveled-cirrhotic

Chronic inflammation:
portal & periportal lymphocytes & prominent plasma cells
Piecemeal necrosis
Scattered acidophil bodies
Sinsusoidal fibrosis

Front 517

What is primary biliary cirrhosis or PBC?

Back 517

Chronic nonsuppurative duct destruction with progressive cholestasis & cirrhosis.

Attack on the bile ducts is probably autoimmune.

Antimitochondrial autoantibody is definining; directed at E2 of pyruvate dehydrogenase

90% women

Onset typically 40-60 yrs. Rare entity in children.

Gross:
slightly enlarged & bile stained to green cirrhosis

Destructive cholangitis of interlobular & septal ducts

Damage to duct BM, intraductal lymphocytes & plasma cells, epithelial cell damage & regeneration.

Florid duct lesion (rare but characteristic):
granulomatous &/or severe lymphocytic infiltrates

Lobules generally normal

Front 518

What is alpha-1-antitrypsin deficiency?

Back 518

Autosomal recessive (codominant) disorder with low serum A1AT levels

A1AT is major protease inhibitor, especially of neutrophilic enzymes, eg. elastase

~75 forms of A1AT; most are normal

PiS:
low serum levels; no disease

PiZ:
10% normal levels; most common form with disease

Emphysema

Liver effects:
Cytoplasmic inclusions in periportal hepatocytes
10-20% affected have cholestatic hepatitis of infancy with ductal and hepatocytic cholestasis & portal lymphocytic infiltrates
20% cirrhosis in mid life
2-3% Hepatocellular carcinoma

Front 519

The portal vein is derived from a confluence of the...

Back 519

splenic vein and superior mesenteric vein.

~75% of blood flow to the liver comes from the portal vein

Front 520

What tests truly measure liver function?

Back 520

Protein Synthesis:
Albumin
PT / INR
Total protein
SPEP/Globulins

T-bilirubin

Cholesterol

Front 521

What tests are indicators of hepatobiliary disease?

Back 521

Aminotransferases:
AST
ALT

Lactate dehydrogenase

Alkaline phosphatase

GGT

5’ Nucleotidase

Front 522

What are the three major functions of the liver?

Back 522

Powerplant (gluconeogenesis):
Glucose
Fatty acids
(Also produces bile to absorb fats)

Manufacturing plant:
Proteins involved in transport
Proteins involved in coagulation (vitamin K dependant factors II, VII, IX and X)

Waste management plant:
RBC breakdown.

Front 523

What are AST and ALT?

Back 523

Intracellular aminotransferring enzymes in the process of gluconeogenesis.

Aspartate Aminotransferase (AST)
(Aspartic acid ->Oxaloacetic acid)

Alanine Aminotransferase (ALT)
(Alanine->Pyruvic acid)

AST is both cytosolic and a mitochondrial isoenzyme

ALT is a cytosolic enzyme

Present in large quantities in hepatocytes.
"Leak” in serum secondary to hepatocyte injury / death.

Elevation in many forms of liver disease.
Highest in those with severe hepatocyte necrosis.

AST is NOT specific to the liver and is found in muscle too.

Front 524

What are the relative levels of AST and ALT in liver disease?

Back 524

ALT should be relatively higher.

If not, consider extrahepatic etiology.

Front 525

Does degree of AST and ALT level correlate with prognosis?

Back 525

No.
Also correlates poorly with extent of necrosis.

But serial measurements can be of value eg.
Fulminant hepatitis
Rapid AST & ALT fall with rising bilirubin and PT can mean poor prognosis.

Front 526

How does the degree of elevation of AST and ALT help in forming a differential diagnosis?

Back 526

< 500 IU can be many disorders but
>2000 IU has a relatively limited differential.

>2000IU:
Drugs or toxins, viruses or ischemia

Front 527

What are some causes of acute or toxin induced hepatitis?

Back 527

Acetaminophen
Halothane
Amanita mushrooms
CCl4

Very High Levels ( > 2000 IU/L) of aminotransferases.

Front 528

How does the time course over which aminotransferases rise to >2000IU/L help us diagnostically?

Back 528

Ischemia is the most rapid.

Viral/drug elevations can take weeks to months.

Front 529

AST/ALT ratio > 2:1 suggests...

Back 529

Alcoholic Hepatitis

>3:1 is even more specific

Mainly reflects low ALT level

Alcohol-related deficiency of pyridoxine.

CAUTION, In these patients:
AST & ALT should be < 300 IU/L
If AST > 500 IU/L we have to rule out a co-existing cause such as:
Acetaminophen toxicity
Viral hepatitis

Front 530

How do we identify alcoholic liver disease?

Back 530

The history is the key – 60 grams/day

Alcoholic cirrhosis is associated with:
Gynecomastia, parotid hypertrophy, dupuytren’s contracture of the palmar fascia.

Alcoholic hepatitis:
RUQ pain
anorexia
fever
jaundice
RUQ tender hepatomegaly Abnormal LFTs
leukocytosis

Treatment for alcoholic hepatitis:
Abstinence
Nutrition
Consider prednisolone or pentoxifylline

Front 531

LDH elevation occurs in...

Back 531

Liver, acute & chronic
Muscle injury
Skeletal
Cardiac
Hemolysis
CVA
Kidney infarction

Very non-specific and therefore rarely useful in addition to aminotransferases.

Occasionally helpful in diagnosing Ischemic hepatitis (massive elevation) or malignant infiltration (sustained elevation).

Front 532

What are alkaline phosphatases?

Back 532

Group of enzymes that function best at pH 9.

Located mostly on the cannalicular membrane in hepatocytes and on the luminar membranes of bile duct epithelium. Also seen in bone and placenta (high in pregnancy or bone disease like paget's)

Normal levels of these are age dependent.

Front 533

Transaminase means the same thing as...

Back 533

Aminotransferase

Front 534

What enzymes are found on the cannalicular membrane but NOT in bone?

Back 534

We order these with a high alk. phos.
to detemine bone or liver origin.

GGT or 5' nucleotidase.

If one of these is also high, liver problem. If it's not, bone is a more likely cause for the elevated Alk. Phos.

GGT is inducible by EtOH & drugs

Front 535

What affects albumin levels?

Back 535

Liver synthesizes 10 g/day
Liver disease=decreased synthesis
However, Serum ½ life is ~ 20 days
so no change in acute liver injury and not useful to follow progress.

Levels also influenced by:
Nutritional status
Volume status
Vascular integrity
Increased catabolism
Urinary losses

Front 536

What does prothrombin time (PT/INR) tell us about liver function?

Back 536

Coagulation factors are synthesized in the liver but not factor VIII (vascular endo / reticuloendo)

Liver disease can cause increased INR in one of two ways:

Synthetic:
Acute or chronic liver failure Cholestatic:
Biliary obstruction

The two can be distinguished with a therapeutic dose of vitamin K. If the INR corrects, the liver is fine.

Keep in mind a prolonged INR can also mean:
Vitamin K deficiency (malabsorption, malnutrition, antibiotics)
Warfarin (Coumadin)
DIC

Front 537

What are the fat soluble vitamins?

Back 537

A,D,E,K

Front 538

What are the best scoring systems for liver function?

Back 538

Chil-pugh criteria
and
MELD score for liver transplant priority.

MELD is based on bilirubin INR and creatinine.

Child-pugh also takes into account albumin, ascites and encephalopathy.

Front 539

High can billirubin result from...

Back 539

Overproduction of billrubin
(hemolysis or a big hematoma getting resorbed)

Liver dysfunction

A specific liver enzyme deficiency.

An excretion problem like a bile duct obstruction.

Front 540

Wher does UDP glucoronyl transferase conjugate biilrubin carried by ligandin after it is delivered to the liver by albumin?

Back 540

The rough ER of the hepatocyte.

Front 541

Where does conjugated billirubin exit the hepatocyte?

Back 541

Into the cannliculus

Front 542

A normal billirubin level is ~...

Back 542

1.2

Neurotoxic at about 20-25

Phototherapy for physiological jaundice of the newborn is initiated at about 12.

Front 543

What is breast milk jaundice?

Back 543

Breast milk contains an enzyme called beta glucoronidase which can deconjugate billirubin.

When this happens we stop the breastfeeding for a while until serum levels resolve.

Front 544

What is Gilbert's syndrome?

Back 544

An inherited autosomal disorder which affects up to 10% of caucasians.

Characterized by a low UDP glucoronyl transferase activity level.

Exacerbated by fasting or recurrent illness.

Front 545

Typically we start seeing jaundice with an unconjugated billirubin of about...

Back 545

3

Front 546

What do we see in the urine of a patient with Gilbert's syndrome?

Back 546

Billirubin is not seen in the urine because it is highly bound to albumin.

Front 547

What is Criggler Najjar syndrome?

Back 547

Autosomal recessive.

Another defect in UDP glucoronyl transferase.

In type II Criggler Najjar syndrome, the enzyme is inducible with phenobarbitol.

Front 548

What is Dubin Johnson syndrome?

Back 548

UDP glucoronyl transferase is fine but the transport proteins of the cannalicular membrane are dysfunctional.

Mixed hyperbillirubinemia.

Front 549

In pure billirubin metabolism disorders, AST, ALT and Alk. Phos. should be...

Back 549

Normal.

High indirect billirubin and normal to high direct billirubin. Particularly with Gilbert's.

Front 550

Hepatocellular disorders with high billirubin are characterized by very high...

Back 550

AST/ALT

Front 551

Cholestatic disorders with high billirubin are characterized by very high...

Back 551

Alk. Phos.(ALP)

Front 552

Why does transfusion cause hyperbillirubinemia?

Back 552

RBC's lyse in the bag and during the transfusion.

Front 553

Which diseases cause a predominantly hepatocellular lab picture?
(primarily AST and ALT abnormalities on a blood test)

Back 553

Viral hepatitis (A,B,C,D,E)

Alcohol

Medication-induced liver disease

Ischemic liver injury

Nonalcoholic Steatohepatitis (NASH)

Autoimmune hepatitis

Hemochromatosis

Wilson’s disease

Alpha-1 Antitrypsin Deficiency

Acute Fatty Liver of Pregnancy

Front 554

Which conditions create a cholestatic picture on labs?
(primarily Alk. Phos.)

Back 554

Extrahepatic bile duct obstruction
(Choledocholithiasis, Pancreas cancer, cholangiocarcinoma)

Primary sclerosing cholangitis

Primary biliary cirrhosis

Intrahepatic cholestasis
(Medication-induced, TPN, sepsis, post-op Intrahepatic cholestasis of pregnancy)

Infiltrative disorders
(Sarcoid, amyloid, infection, neoplasm)

Front 555

Spider angiomata (blanchable spider veins) on the skin can be an indication of...

Back 555

Cirrhosis

Front 556

Why can Cirrhosis cause splenomegaly?

Back 556

Portal hypertension.

Front 557

What is the algorithm for managing a jaundiced patient?

Back 557

Front 558

What are the three major forms of inherited liver disease?

Back 558

Hemochromatosis
Wilson's disease
Alpha 1 antitrypsin disease

Front 559

What is the leading cause of inherited Cirrhosis in children?

Back 559

Alpha 1 antitrypsin disease

Hemochromatosis is most prevalent in adults because it manifests later.

Front 560

How much iron is stored in the liver?

Back 560

Body content of iron ~ 4 g;

~ 1 g is stored in hepatocytes

Front 561

About what % of the iron we ingest do we actually absorb?

Back 561

~10%

Front 562

How is iron absorbed?

Back 562

DMT1 – Absorbs iron from gut

Iron is stored bound to ferritin

Iron is pumped into blood via Ferroportin

Ceruloplasmin converts Fe2+ ->Fe3+

In blood, iron is transported bound to transferrin

Transferrin receptor 1 (liver & other tissues) clears the iron-Transferrin complex.

Iron is stored in hepatocytes bound to ferritin.

Iron from phagocytosed red cells is stored in macrophages.

Amount of iron in circulation is controlled by the expression of Ferroportin.

Front 563

What is the acts as the iron sensor in the body?

Back 563

The hepatocyte

Sensor is made of HFE, transferrin receptor-2 and hemojuvilin.

If there is excess iron, these iron sensors increase expression of the HAMP gene and secretion of its gene product (Hepcidin).

Hepcidin bind to and inhibits Ferroportin activity and expression.

The effect is that Intestinal iron absorption is blocked; iron stays
stored bound to ferritin in macrophages and iron
homeostasis is restored.

Front 564

What is hemochromatosis?

Back 564

Autosomal dominant

Early and progressive expansion of the plasma iron storage compartment.

Progressive parenchymal iron deposition.

Nonimpaired erythropoiesis.

Responds to phlebotomy.

Defective Hepcidin synthesis or activity.

Most common defect is in hepatocyte iron sensing due to bad HFE protein.

Front 565

In hemochromatosis, where is the excess iron coming from?

Back 565

More is absorbed in the GI tract AND more is liberated from destruction of RBC's

Front 566

Where are the main parenchymal sites iron deposits in hemochromatosis causing symptoms?

Back 566

liver
heart
pancreas
endocrine glands

Front 567

What mutations in the HF gene cause hemochromatosis?

Back 567

2 major mutations:
Cysteine 282->tyrosine (C282Y)
Histidine 63->aspartic acid (H63D)

C282Y:
homozygosity produces major clinical manifestations.

Highly prevalent in individuals of Northern
European descent,
rare in Arica and Asia;
frequency of C282Y homozygotes is ~1/250 for Anglo-Celic-Nordic population.

Front 568

When do clinical manifestations of hemochromatosis usually become evident agewise?

Back 568

Typically seen in males in their 40’s-50’s and females in their 60’s
(curve is shifted in women as a result of iron loss due to menses & childbirth)

Front 569

What are some of the clinical manifestations of hemochromatosis?

Back 569

Liver:
Abnormal liver function tests
Cirrhosis
Hepatocellular carcinoma

Cardiac:
Cardiomyopathy
Arrhythmias

Joint:
Arthropathy

Endocrine:
Diabetes mellitus
Testicular atrophy
Pituitary (gonadotropin insufficiency)

Other:
Skin bronzing
Weakness or lethargy
Impotence in men

Other findings include: Hepatomegaly, splenomegaly, & other complications of chronic liver disease such as ascites, edema, and jaundice.

Serum aminotransferase elevations are usually mild.

Front 570

The what is the classic diagnostic triad of hemochromatosis and other iron overload disease?

Back 570

cirrhosis, diabetes, and skin pigmentation (“bronzed diabetes”)

rare now due to increased awareness of HH. Earlier diagnosis and treatment.

Front 571

What x-ray finding suggests hemochromatosis?

Back 571

Arthropathy
(iron accumulation in joint tissues)

Changes in the 2nd and 3rd metacarpophalangeal joints most common.

Front 572

What x-ray finding suggests hemochromatosis?

Back 572

Arthropathy
(iron accumulation in joint tissues)

Changes in the 2nd and 3rd metacarpophalangeal joints most common.

Front 573

What is increased in a hemachromatosis patient's labs?

Back 573

Fe increased
Transferrin saturation increased
Ferritin is increased

TIBC will be decreased.

Front 574

On a hemochromatosis liver biopsy with prussian blue stain, which cells do NOT contain iron?

Back 574

The resident macrophages
(kupffer cells)

Front 575

Why is liver biopsy important in hemochromatosis?

Back 575

Important to document if cirrhosis is present since this affects the prognosis.

Patients treated before development of cirrhosis have a normal life expectancy.

Front 576

How do we treat hemochromatosis?

Back 576

Perform phlebotomy of 500 mL (1 unit) of whole blood weekly
until hematocrit value drops below 37%.
( 1 unit ~ 200-250 mg iron)

The iron-chelating drug deferoxamine can be used in those patients who cannot tolerate phlebotomy.

Monitoring:

Check transferrin saturation and ferritin levels at 2- to 3-month
intervals to monitor response (optional).

Maintenance
Once iron stores are depleted (serum ferritin <50 ng/mL; transferrin saturation <50%), proceed to maintenance phlebotomy of 1 unit of whole blood every 2 to 3 months.

Aim to keep transferrin saturation <50%; if successful, ferritin should remain <50 ng/mL..

Front 577

What symptoms of hemochromatosis are reversible?

Back 577

Reversible:
Cardiac dysfunction, glucose intolerance, hepatomegaly, skin pigmentation.

Irreversible:
Cirrhosis, arthropathy, hypogonadism, risk of
hepatocellular carcinoma.

Front 578

What is Wilson's disease?

Back 578

Rare inherited metabolic, copper accumulation in liver and brain

Prevalence ~ 1:30,000 (carrier state 1: 90)

Autosomal recessive disease caused by mutation in ATP7B gene (> 300 mutations)

Defective biliary excretion of copper; copper overload affects multiple organs.

Commonly presents with liver or neurological symptoms

Variable age of onset for symptoms (usually 6 - 40 years of age)

Undiagnosed and untreated is generally fatal by age 30

Early diagnosis and treatment can yield almost complete recovery with
normal life

Treated with chelating agents or zinc (rarely with liver transplant)

Front 579

What enzymes is copper an essential cofactor for?

Back 579

Cytochrome-c oxidase,
superoxide dismutase,
Catechol oxidase,
Protein-lysine 6-oxidase, Ceruloplasmin,
Dopamine-α-monooxygenase

Front 580

What are good dietary sources of copper?

Back 580

oysters, liver, crab, shrimp, cod, yeast, olives, hazelnuts, whole wheat bread, peas

Front 581

Copper is transported in the blood primarily by...

Back 581

ceruloplasmin (>95%),
albumin (<5%)

We absorb about 50% of what copper we ingest.

Major site of storage is lever.

Excreted in the bile (major) and urine (minor).

Front 582

So the actual defects of wilson's disease are...

Back 582

Inability to mobilize copper for incorporation into ceruloplasmin.

Inability to mobilize copper to the bile cannaliculus for secretion into bile.

Deposition of copper in various tissues thus occurs.

Front 583

What are the typical initial presentations of Wilson's disease?

Back 583

40% liver disease

35% neurological

15% psychiatric

10% endocrine, renal
cardiac, hematological

Front 584

What are the manifestations of Wilson's disease?

Back 584

Liver:
Abnormal liver function tests
Acute hepatitis
Acute hepatic failure
Liver disease with hemolysis
Chronic hepatitis
Cryptogenic cirrhosis

CNS:
Parkinson-like disorders with dystonia and tremors
Psychiatric disorders

Eye:
Kayser-Fleischer rings
Sunflower cataracts

Kidney:
Fanconi syndrome with hypouricemia

Bone:
Osteopenia
Joint Arthropathy

Front 585

How do we diagnose Wilson's disease?

Back 585

Measure serum ceruloplasmin
(< 20 mg/dL)

Measure serum free copper
(> 25 mcg/dL)*

Measure 24 h urinary Copper excretion (> 40 mcg)

Slit lamp exam
(Kayser-Fleischer rings)

Liver biopsy for histology or quantitative copper measurements.

Serum free copper = total copper – [serum ceruloplasmin (in mg/dL) x 3]

Front 586

How do we treat Wilson's disease?

Back 586

Chelation (Penicillamine or trientine) plus pyridoxine
Zinc
Avoid high copper foods
Liver transplantation*
(*with acute liver failure or end-stage liver disease)

Monitoring:
Kayser-Fleischer rings
Urinary copper excretion
Serum free copper levels (non-ceruloplasmin-bound)

Results:
Prevents disease when begun early
Improves liver and CNS disease
Prolongs life

Front 587

What is alpha 1 antitrypsin deficincy?

Back 587

Common inherited metabolic disease causing lung + liver disease

Most common genetic cause of liver disease in children

Prevalence of deficiency allele combinations ~ 1:490
(North America);

Severe deficiency ~1:3500 live births
(more common in Caucasians; rarely found in African Americans or Asians)

Autosomal recessive disease

Caused by mutations in α1-antitrypsin gene (SERPINA1)

α1-AT binds and inactivates neutrophil elastase and other serine proteases;

Α1-AT is the major serine protease inhibitor in blood

α1-AT alleles are also called Protease inhibitor (Pi) alleles. Most common Pi alleles associated with disease: PiS, PiZ

Front 588

What happens when when serum α1-AT drops below ~ 11 µM?

Back 588

Risk of pulmonary emphysema rises.

Serum α1-AT levels do not strictly correlate with risk of liver disease.


Disease phenotype is defined by the serum levels and alleles

Liver disease is associated with PiZ allele
(lysine to glutamic acid at AA342)

Front 589

By what mechanisms does alpha 1 antitrypsin disease cause COPD and liver disease?

Back 589

Absence of α1-AT is the primary mechanism for premature development of pulmonary emphysema or COPD in affected patients.

Liver disease is caused by accumulation of misfolded α1-AT protein. (Z isoform)

Front 590

In (α1-AT) disease, the bad genotype to have is...

Back 590

PiZZ

Front 591

How do we treat α1-Antitrypsin (α1-AT) Disease?

Back 591

No specific therapy is currently available (avoid alcohol, smoking, weight gain and obesity)

Treatment of complications of liver and lung disease

Hepatocellular carcinoma surveillance.

Transplantation (cures the liver and lung disease)

α1-AT infusions (treats the lung disease - emphysema)

Family screening

Front 592

What is the diagnostic algorithm for alpha 1 antitrypsin disease?

Back 592

Front 593

What type of virus is hepatitis A?

Back 593

ssRNA picornavirus (hepatovirus)

Front 594

The majority of chronic viral hepatitis is caused by...

Back 594

HCV

Front 595

What explains the outbreak nature of HAV?

Back 595

It is shed in stool long before antibody titers are positive.

Young kids don't get jaundice and thus continue attending school, daycare etc.

Very Few <6 get jaundice
About half from 6-14 get jaundice
Majority >14 get jaundice.

Front 596

What are the clinical sequelae of hepatitis A?

Back 596

Acute hepatits can be come:

Cholestatic hepatitis
Relapsing hepatitis
Protracted hepatitis
Fulminant hepatitis (pt. can die)

Front 597

Is the vaccine for Hep. A effective?

Back 597

Yes

Front 598

What kind of virus is hepatitis B?

Back 598

DNA virus of the hepadnavirus family.

Multiple serotypes.

Reverse transcription in liver and other tissues.

Front 599

How long after infection with HBV do you start seeing surface antigen?

Back 599

~1 month

Increased ALT is earlier indicator.

Jaundice usually does not appear until about 8 weeks.

Front 600

How do we make a diagnosis of HBV?

Back 600

+ surface antigen
AND
+Anti core (Anti HBc)

Front 601

What do the various results on HBV serology mean?

Back 601

Acute HBV:
HBSAg + and HBcAb IgM +

Resolved HBV:
HBcAb IgG+ and HBSAb+

Chronic HBV:
HBSAg+ and HBCAb IgG+

HBV vaccinated:
HbSAb + only

Front 602

Who is at greatest risk with the carrier state of HBV?

Back 602

Neonates.
Risks diminishes with age.

Front 603

Who is at greatest risk of HBV through sexual contact?

Back 603

Heterosexuals

Front 604

How prevalent is HBV in asian populations?

Back 604

VERY.

50 % of HBV infected persons are infected from maternal perinatal transmission /early childhood family exposure.

About 1 in 4 Asians are infected

2/3 Asian men are asymptomatic and unaware they are infected.

Lifetime risk of liver cancer if infected is 1 in 4.

Screening asymptomatic Asians for HBV is essential. This is a highly cost-effective and necessary strategy

Prolonged immunotolerance phase, prolonged immune clearance phase

A Chinese study indicates that 20% of infected persons < age 25 have advanced fibrosis.

Liver cancer is listed about # 9 on priority list, but HBV is still not on the WHO list for priority concern which is almost criminal.

Front 605

How are acute and chronic HBV different in terms of transplant?

Back 605

Acute results are much better because of no immune tolerance

Front 606

The goal of HBV treatment is to...

Back 606

Prevent cirrhosis.
Prevent hepatocellular carcinoma.

Front 607

How do we treat HBV?

Back 607

Prolonged administration of nucleoside analogues is mainstay.
Currently available and approved are: lamivudine, adefovir, telbivudine, tenofovir, entecavir.

Pegylated interferon sometimes used at initiation of treatment.

Must be managed by an expert, as drug resistance is emerging threat and guidelines constantly changing.

Current guidelines available: AASLD, EASL, APASL. Generally these are updated yearly.

Front 608

How does one acquire hepatitis D infection?

Back 608

Coinfection:
Simultaneous introduction oh HBV and HDV

Superinfection:
Introduction of HDV into HBsAg + host.

Front 609

What type of virus is hepatitis C?

Back 609

ssRNA

Front 610

How do we test for HCV?

Back 610

RNA shows up much earlier (day 12) than antibodies (day70) so we usually test for that.

Only about 15 % will be symptomatic.

Viral RNA will not be present until after 10-24 days.

All will seroconvert to anti-HCV positivity, but there is a 70 day delay.

Front 611

What is the main mode of transmission of HCV?

Back 611

IV drug use.

Front 612

What is the natural history of acute HCV?

Back 612

15 % will spontaneously resolve

15% of remaining chronic HCV patients will develop Cirrhosis.

25% of those with chronic HCV will go on to HCC, transplant and or death.

Front 613

How do we treat HCV?

Back 613

Peg Interferon Alpha + Ribavirin

Front 614

What type of virus is hepatitis E?

Back 614

RNA

Front 615

How is hepatitis E transmitted?

Back 615

Fecal-oral
Water borne
Food born
Mollusk associated

Front 616

Which patients with hepatitis E are at increased risk of fulminant hepatitis and consequently death..

Back 616

Pregnant women

Front 617

How do we diagnose autoimmune hepatitis?

Back 617

Hypergammaglobulinemia (IgG)

Female gender most common

Autoantibodies:
Positive: ANA, ASMA, anti-LKMNegative: AMA, HLA DR3 or DR4
Negative for markers for viral hepatitis

Positive response to treatment

Front 618

How do we treat autoimmune hepatitis?

Back 618

Prednisone alone, prednisone & azathioprine, and azathioprine alone are effective in improving 2-year survival.

Prednisone with azathioprine preferred.

Relapse rate is 50 - 86 % if treatment is stopped. Typically, patients remain on therapy indefinitely, with prednisone taper.

Excellent prognosis.

Front 619

What is primary billiary cirrhosis?

Back 619

50-60 % asymptomatic at Dx

9:1 Female-male ratio

Peak onset 5th decade, rare < 25 years age

Organ-specific autoimmune attack

Highest incidence, Northern Europe. Range 40-400/million population

1/6 have an affected family member

Fatigue 21 %,
Pruritus 19 %,
RUQ discomfort 10 %,

Fatigue severity unrelated to severity of liver disease.

Majority of asymptomatic patients develop symptoms by 4 years; 1/3 stay asymptomatic for years.

Front 620

How do we diagnose primary billiary cirrhosis?

Back 620

Detectable AMA (antimitochondrial antibody) in serum

LFT changes, with primarily SAP elevation

All 3 above:definite Dx; 2/3 above:probable Dx

IgM elevation typical, even when AMA negative; course the same if AMA neg.

AMA positivity > chance of later PBC

Physical exam:
Normal if asymptomatic
Melanin skin pigment, excoriations, spiders.
Xanthelasma in 5-10 %; tendon xanthomas rare.
Hepatomegaly in 70 %
Splenomegaly, ascites, late

Typical liver biopsy includes granulomas.

Front 621

How do we treat primary billiary cirrhosis?

Back 621

Ursodiol at 13-15 mg/kg is mainstay of therapy

Liver transplantation for treatment failures

Front 622

What is sclerosing Cholangitis

Back 622

A chronic progressive disease, characterized by inflammation, fibrosis, and stricturing, of the medium intrahepatic and large extrahepatic bile ducts.

Etiology remains unknown, but proposed mechanisms include portal bacteremia, toxic bile acid metabolites (more lithocholic acid B/C of increased 7-alpha dehdroxylation of cheno by bacteria), toxin production by enteric bacteria, chronic viral infections, ischemic vascular damage, and altered genetic immunoregulation.

Front 623

What other disease is primary sclerosing cholangitis associated with

Back 623

Overwhelming majority of PSC patients have IBD. Ulcerative colitis > Crohn’s disease.

Estimates 75-90 %
As worldwide incidence of Crohn’s increases, PSC seen more commonly with Crohn’s

PSC may have temporal discordance with PSC (PSC can develop decades after colectomy; UC can develop after liver transplant)

Front 624

What clinical findings are typical of primary sclerosing cholangitis?

Back 624

Most are asymptomatic at Dx

Fatigue, pruritus

Fever indicates secondary bacterial cholangitis

Persistent jaundice with advanced disease

Cholestatic liver enzymes, with primarily SAP elevation

Increased gamma globulins (30%, with IgM 40-50%); + pANCA (30-80%); + DRw52A in widely varying %; AMA universally negative

70% of affected patients are men

Front 625

How do we diagnose primary sclerosing cholangitis?

Back 625

Multifocal stricturing of intrahepatic +/- extrahepatic bile ducts.

Most have extrahepatic bile ducts involved.

ERCP and MRCP are comparable.

Pancreatic duct involvement in 10%

Liver biopsy confusing and rarely diagnostic; most helpful in small duct PSC (pericholangitis)

Front 626

What is the natural history of primary sclerosing cholangitis?

Back 626

Generally a progressive disease, with median survival 10-12 years

Survival worse if symptomatic at Dx

Mortality risk increased with jaundice, advanced fibrosis on Bx, splenomegaly, age, and Mayo risk score

Transplant alters survival, obviously

Despite “general” progression, some cases spontaneously remit and are not progressive

Front 627

Summarize a good way to discern between autoimmune hepatitis, primary billiary cirrhosis and primary sclerosing cholangitis.

Back 627

Front 628

Which autoimmune liver disease carries substantial risk of cholangiocarcinoma?

Back 628

Primary sclerosing cholangitis.

Front 629

What is Non-Alcoholic Steatohepatitis (NASH)?

Back 629

Most common liver disease.

More common in women (75%)

Associated with Obesity
DM II, Hyperlipidemia (TG and/or cholesterol)

Diagnosis:
AST/ALT < 1, exclude other causes, U/S, liver bx

Treatment:
no proven therapy
treat associated conditions

Front 630

How do we define fulminant hepatic failure?

Back 630

Rapid development of hepatic dysfunction.

No prior history of liver disease.

Hepatic encephalopathy.

Front 631

How much acetominophen is toxic?

Back 631

Danger dosages (70 kg patient)

Toxicity possible > 10 gm

Severe toxicity certain > 25 gm

Lower doses potentially hepatotoxic in:
Chronic alcoholics
Malnutrition or fasting
Dilantin, Tegretol, phenobarbital, INH, rifampin
NOT in acute EtOH ingestion
NOT in non-alcoholic chronic liver disease.

Front 632

What is the pathogenesis of acetominophen toxicity?

Back 632

Day 1:
Nausea, vomiting, malaise, or asymptomatic

Day 2 – 3:
Initial symptoms resolve
AST and ALT begin to rise by 36 hours
RUQ pain, tender enlarged liver on exam

Day 4
AST and ALT peak > 3000
Liver dysfunction: INR, encephalopathy, jaundice
Acute renal failure (ATN)

Front 633

How do we treat acetominophen toxicity?

Back 633

Activated charcoal if < 4 hours from ingestion.

Administer as a single dose 1 mg/kg PO or NG

Does not adversely effect NAC efficacy

N-Acetylcysteine (NAC):

140 mg/kg loading dose PO or NG

70 mg/kg q 4 hours PO or NG X 17 doses

Continue longer until INR < 2.0 and improved

OK to DC if acetaminophen levels undetectable and normal AST at 36 hours.

Front 634

What are the etiologies of portal hypertension?

Back 634

Prehepatic:
Portal Vein Thrombosis

Intrahepatic:
Presinusoidal-schistosomiasis.
Sinusoidal-Cirrhosis and infiltrative disorders.
Postsinusoidal-Veno-Occlusive Disease

Posthepatic:
Budd-Chiari Syndrome (clots in the hepatic vein), Right Heart Failure, Constrictive Pericarditis

Front 635

What clinical clues suggest cirrhosis?

Back 635

Physical Examination:
Jaundice
Hepatomegaly
!Splenomegaly!
!Ascites!
Edema
Spider angiomata
Palmar erythema
Gynecomastia
Asterixis

Laboratory Tests:
!Thrombocytopenia!
Hypoalbuminemia
Prolonged PT
Hyperbilirubinemia

Imaging:
Nodular liver
Splenomegaly
Ascites
Large collaterals

At the end of the day, cirrhosis is a biopsy diagnosis.

Front 636

How do we measure portal hypertension?

Back 636

We don't.

There is no non-invasive way to do this.

Front 637

What are the three major complications of portal hypertension?

Back 637

GI bleeding

Ascites:
Spontaneous Bacterial Peritonitis
Hepatorenal Syndrome

Encephalopathy

Front 638

In portal hypertension, the increased pressure is not only as a result of increased resistance in the liver but also because of ....

Back 638

Increased splanchnic blood flow.

Front 639

Esophageal varices in portal hypertension are fed primarily by which vessels?

Back 639

The coronary vein coming off the portal vein on the lesser curvature of the stomach.
AND
The short gastric coming off the splenic vein on the greater curvature.

Front 640

What causes GI bleeding in the setting of portal hypertension?

Back 640

esophageal varices (most common)
gastric varices
portal hypertensive gastropathy

much less common:
rectal
stomal
anastomotic

Front 641

What is a normal portal vein pressure?

Back 641

5 – 10 mm Hg

Portal Vein Pressure Necessary
For Variceal Hemorrhage
is > 12 mm Hg

Front 642

How can we treat portal hypertension?

Back 642

Beta blockers to decrease cardiac output.

Portocaval shunt, TIPS

Medication for dealing with splanchnic vasodilation.

Esophageal variceal band ligation.

Acute therapy:
Octreotide
Endoscopic therapy
Minnesota tube
TIPS

Prevention (Primary vs. Secondary):
Beta-blocker
Endoscopic therapy
TIPS

Front 643

What are the most important primary prevention guidelines for esophageal varices hemmorage?

Back 643

Screening EGD for the diagnosis of esophageal and gastric varices is recommended when the dx of cirrhosis is made.

If varices are large, nonselective B-blockers (like propranolol and natolol) or esophagela variceal band ligation are recommended for prevention of EVH.

Front 644

What is TIPS?

Back 644

Low resistance tunnel through the liver.

Portocaval shunt done non-surgically with a stent.

Secondary prevention of esophageal variceal hemmorage.

Front 645

How do we treat an acute GI bleed in cirrhosis?

Back 645

Avoid vigorous volume resuscitation with saline.

Transfuse pRBC to maintain Hb of 8 gm/dl.

Octreotide should be given in all cases of suspected EVH and continued for 3-5 days if EVH is confirmed by EGD.

Antibiotics should be given for 7 days.(norfloxacin and ciprofloxacin)

EGD should be performed within 12 hours, and if EVH confirmed, EVL (ligation) should be performed.

TIPS is indicated when octreotide and EVL fail to control EVH.

Balloon tamponade should be used as a temporizing measure for uncontrollable bleeding until EVL or TIPS can be done.

Front 646

What is considered secondary prevention for EVH?

Back 646

Patients who survive acute variceal hemorrhage should receive therapy to prevent recurrent EVH.

Combinations of nonselective B-blockers plus EVL is the best option for secondary prophylaxis of EVH.

Front 647

In descending order, what are the causes of ascites?

Back 647

Chronic liver disease (by far)
Malignancy
Heart failure
TB
Miscellaneous

Front 648

What exactly is ascites?

Back 648

Accumulation of fluid in the peritoneal space

500 cc before clinically evident

Differential diagnosis:
Portal Hypertension
Malignant ascites, nephrotic syndrome, TB

SAAG = Serum albumin – Ascites albumin
(> 1.1 in portal hypertension)

Front 649

What portal vein pressure is required for ascites?

Back 649

> 12 mm Hg

Front 650

What are the two main mechanisms of ascites?

Back 650

Increased hydrostatic pressure from portal hypertension with decreased oncotic pressure from decreased albumin.
AND
Activation of the renin-angiotensin system for Na and water retention.

Front 651

How do we make a physical diagnosis of ascites?

Back 651

flank dullness
shifting dullness
fluid wave

These correlate best with the gold standard (ultrasound), but 1500 cc needs to be present.

Ultrasound can detect as little as 100 cc of ascites.

Ascites is unlikely in the absence of lower extremity edema.

Always remember to check neck veins in any patient with new-onset ascites.

Front 652

How do we treat ascites?

Back 652

2 gram Na diet
(most important part)

1000 cc fluid restriction only if Na<130

Avoid NSAID

Lasix 40 mg/d (160 mg/d max)

Spironolactone 100 mg/d (400 mg/d max)

Large Volume Therapeutic Paracentesis:
Consider IV albumin if removing > 5 liters to protect kidneys

TIPS

Front 653

What is spontaneous bacterial pertitonitis?

Back 653

A complication of ascites that is pretty much unique to cirrhotic ascites. Very rarely seen in malignant or cardiac ascites.

Ascitic fluid infection without an evident intraabdominal surgically treatable source.

Bacterial translocation:
Bacteria traverse colon wall and colonize lymphatics.
Small lymphatic vessels rupture into ascites.
Bacteria move from lymphatics into systemic circulation.

Diagnosis based on ascites fluid culture and ascites fluid PMN > 250 cells/mm3

Front 654

What organisms cause SBP?

Back 654

E. Coli (vast majority)
Klebsiella
S. pneumo
Alpha hemolytic strep
Group D strep
Other strep
Enterobacteriacae
Others

Front 655

How do we treat SBP?

Back 655

Patients with ascites PMN>250 should receive cefotaxime.

All patients with suspected SBP should also receive IV albumin to save kidneys.

Mortality is 20-50%.

Front 656

How do we prevent SBP?

Back 656

All cirrhotic patients with GI bleeding should be given antibiotics for 7 days.
norfloxacin or ciprofloxacin.

Patients who have survived an episode of SBP should receive long-term prophylaxis with daily norfloxacin or trimethoprim/sulfamethoxazole (bactrim).

Front 657

What is hepatorenal syndrome?

Back 657

Advanced chronic or acute liver failure with portal hypertension

Serum Cr > 1.5 or 24 hour CrCl < 40

Absence of shock, infection, massive GIB, massive renal fluid loss, nephrotoxic drugs

No sustained improvement in renal function with 1 mg/kg of IV albumin for 2 days

Less than 500 mg/dl proteinuria and no u/s evidence of obstruction or parenchymal dz

Front 658

What are the pulmonary complications of portal hypertension?

Back 658

Hepatopulmonary syndrome:
Increased A-a gradient
Liver disease
Evidence of IPVDs ; intrapulmonary vascular dilations (shunts)
Platypnea

Portopulmonary syndrome:
Pulmonary Hypertension in the setting of Portal Hypertension
Patients present with DOE, syncope, chest pain
Contraindication for liver transplant.

Hepatic Hydrothorax

Front 659

What is hepatic hydrothorax?

Back 659

Pleural effusion of >500 cc in patients with cirrhosis and no underlying cardiac or pulmonary disease.

Likely cause is passage of ascites fluid through small defects in the diaphragm.

Because of negative intrathoracic pressure, most patients have only mild ascites.

Usually unilateral right-sided effusion (85%)

Typical symptoms:
dyspnea, cough

Front 660

How doe treat hepatic hydrothorax?

Back 660

Just like ascites.

2 gram Na diet

1000 cc fluid restriction only if Na<130

Avoid NSAID

Lasix 40 mg/d
(160 mg/d max)

Spironolactone
100 mg/d (400 mg/d max)

Large Volume Therapeutic Thoracentesis
(Consider IV albumin if removing > 5 liters)

TIPS

Front 661

What is Hepatic Encephalopathy (HE)or Portosystemic Encephalopathy (PSE)?

Back 661

A syndrome of reversible brain dysfunction in the setting of significant liver disease

Pathogenesis likely multifactorial

Endogenous toxins:
ammonia
Inhibitory neurotransmitters:
GABA

Decreased hepatic clearance of ammonia due to liver dysfunction, portosystemic shunts.

Dx:
History-
sleep disturbance (insomnia/hypersomnia)
lethargy, somnolence, confusion, coma.
Exam-
asterixis (liver flap), hyperreflexia, fetor hepaticus (ammonia breath smell)
Laboratory-
BMP, drug screen, ammonia
CT head

Front 662

How do we treat hepatic encephalopathy?

Back 662

Lactulose is the treatment of choice, dosed to achieve 2-3 soft bowel movements daily. Can be used in enema form.

Antibiotics:
rifaximin, metronidazole, or neomycin

Correct precipitating factors.

Consider safety issues like driving

Front 663

What should we do for cirrhosis patients in terms of hepatocellular carcinoma?

Back 663

Patients at high risk for HCC should be entered into a surveillance program.

Ultrasound every 6-12 months.

Front 664

How much bile does the liver make a day?

Back 664

0.5L -1L

Front 665

What is the pH of bile?

Back 665

~8
Isotonic with plasma.

Front 666

What kind of control is the release of bile under?

Back 666

Chemical -
Bile salts stimulate hepatic bile flow

Neural -
Gall bladder contraction is controlled partially by nervous (vagal) stimulation.

Hormonal -
Cholecystokinin (CCK) released by the duodenal mucosa strongly induces gall bladder contraction
Fibroblast Growth Factor 19
(FGF19) stimulates gallbladder
filling.

Front 667

What sort of substances are excreted in bile?

Back 667

cholesterol, bilirubin, steroid hormone conjugates, metal cations (iron and copper), drug conjugates

Front 668

By % weight, what makes up bile?

Back 668

Water 82 %
Bile salts 12 %
Phospholipid 4 %
Cholesterol 1 %
Other 1 %

Front 669

What are the major functions of bile salts?

Back 669

Induce bile flow and biliary lipid secretion

Aid in fat solubilization and absorption
(Essential for cholesterol and fat-soluble vitamin absorption)

Major route for cholesterol elimination
(Regulation of cholesterol metabolism)

Anti-bacterial actions in the gut
(Prevention of small bowel bacterial overgrowth)

Prevent formation of Gallstones and kidney oxalate stones

Act as hormones to regulate lipid and glucose metabolism

Front 670

Bile is actually an admixture of three secretions. What are they?

Back 670

Hepatocyte Bile salt-dependent

Hepatocyte Bile salt-independent

Ductular secretion

Most bile flow is bile salt dependent though which means that bile salts are secreted as
free ions and provide the
osmotic pull for H20 and
electrolytes to move into
the canalicular space.

Front 671

Why is it important that bile salts are amphipaths?

Back 671

Above their critical micelle concentration, bile salts form micelles that “solubilize” and carry fat-soluble substances such as
cholesterol, fat-soluble vitamins (A, D, E, K), long chain fatty acids

The solubility of cholesterol in bile
is 2 million-fold greater than its
solubility in water

Front 672

What problem does bile solve in the intestine?

Back 672

Unstirred water layer (100-500 µm) acts a diffusion barrier for hydrophobic molecules.

This reduces their effective concentration at the plasma membrane.

Bile salts form mixed micelles with
cholesterol to increase its aqueous
solubility. This increases the rate of
cholesterol absorption
> 100-fold.

Front 673

How are bile salts synthesized?

Back 673

Bile salts are synthesized from
cholesterol in the liver.

Bile salts are synthesized first as
steroid acids.

The primary bile salts synthesized
by the liver are:
Cholic acid
3 OH groups
More hydrophilic
AND
Chenodeoxycholic acid
2 OH groups
More hydrophobic

~ 40% of total cholesterol removal occurs via its conversion to bile salts.

Front 674

What is the function of bile salts in antimicrobial defense?

Back 674

Proximal Intestine:
Direct bacteriostatic actions of bile salt/fatty acid mixed micelles.

Distal intestine:
Bile salts act as a hormone to induce expression of anti-microbial factors by binding to the FXR receptor.

Front 675

How do bile salts prevent enteric hyperoxaluria and formation of kidney oxalate stones?

Back 675

Oxalate in food (such as spinach, rhubarb, swiss chard, mixed nuts) usually precipitates as calcium oxalate in the intestinal lumen and is lost in the stool.

In the absence of bile salts, long chain fatty acids stay in the lumen of the intestine and compete with oxalate for the available calcium.

This blocks calcium oxalate formation and allows more dietary oxalate to be absorbed and ultimately excreted by the kidney.

This ‘enteric’ hyperoxaluria can lead to formation of calcium oxalate kidney stones.

Enteric hyperoxaluria should be considered in patients with:

any form of chronic diarrhea

inflammatory bowel disease

pancreatic insufficiency

primary biliary cirrhosis

short bowel syndrome

after bariatric surgery

Front 676

What are the concentrations of bile salts in the various compartments?

Back 676

Gallbladder 50-200 mM
Small Intestine 5 - 10 mM
Portal Blood ~0.02 mM
Peripheral Blood < 0.01 mM

Front 677

What are the general properties of bile salt circulation?

Back 677

Total bile salt pool 3 - 5 g

Cycles 2-3 times per meal 6-10X/day

Intestinal reabsorption 20-30 g/day

Bile salt loss < 400 mg/day

Intestinal (Ileal) absorption of bile salts is > 95% efficient.

Front 678

Which four categories can disorders of bile salt synthesis and cycling be divided into?

Back 678

1.
Primary Defects in Bile Salt Formation (synthesis and conjugation)

2.
Primary Defects in Membrane Transport (uptake and secretion)

3.
Disturbances involving Bacterial Transformation (deconjugation &
dehydroxylation)

4.
Disturbances in Movement Through or Between Organs (bile salt
circulation)

Front 679

How do primary Defects in Bile Salt Formation (synthesis and conjugation typically present?

Back 679

Rare congenital disorders.

Most commonly present as cholestasis or hepatitis.

3α-hydroxy-C27-steroid dehydrogenase deficiency:
Neonatal Hepatitis

Bile acid conjugation defect:
Neonatal cholestasis, fat-soluble vitamin deficiency.

Cerebrotendinous xanthomatosis (CTX) :
Progressive neurological dysfunction.

Front 680

What are some examples of Primary Defects in Membrane Transport (bile uptake and secretion)?

Back 680

Rare congenital disorders.

Progressive Familial Intrahepatic Cholestasis Types 1, 2, 3:
Caused by mutations in hepatic canalicular transporters for bile salts and phospholipids.

Primary Bile Acid Malabsorption:
Caused by mutation in the ileal bile acid transporter.

Front 681

What are Disorders of Bile Salt Synthesis and Cycling involving bacterial transformation (increased deconjugation and dehydroxylation)?

Back 681

Small Intestinal Bacterial Overgrowth

Common cause of chronic diarrhea

Increases bile salt deconjugation and dehydroxylation.

Deconjugated secondary bile salts (deoxycholic acid, lithocholic acid) are less soluble than conjugated primary bile salts. These bile acids will precipitate from solution and be excreted in the feces.

The soluble bile salt concentration needs to stay above ~ 2 millimolar in order to efficiently absorb fats and fat-soluble vitamins.

Small intestinal bacterial overgrowth -> increased bile salt loss & fat malabsorption (steatorrhea).

Front 682

Conditions associated with bacterial overgrowth include....

Back 682

Blind loop (Billroth II gastrectomy, end-to-side anastomosis)

Small intestinal diverticulosis  
Small intestinal stricture (Crohn's disease)  

Diabetes

Idiopathic intestinal pseudo-obstruction  

Scleroderma  

Acid-lowering medications

Atrophic gastritis  

Vagotomy  

Gastrocolic or enterocolic fistula

Resection of ileocecal valve  

Celiac sprue

Chronic pancreatitis  

Chronic renal failure  

Cirrhosis  

Old age  

Rheumatoid arthritis  

Radiation enteritis

Front 683

What conditions cause disturbance sin bile salt circulation?

Back 683

Biliary obstruction
(stones in biliary tract or gallbladder; biliary tract carcinoma)

Biliary Fistula (after biliary trauma) and Gallstone ileus

Cholecystectomy
(only small effect on bile salt metabolism)

Cholestasis:
Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis, drug induced cholestasis, intrahepatic cholestasis of pregnancy, biliary atresia.

Ileal Resection
(particularly > 100 cm of small bowel)

Short Bowel Syndrome

Crohn’s disease (Inflammatory Bowel Disease)

Front 684

What is cholesterol saturation index?

Back 684

Ratio of molar % of cholesterol in bile to maximum micellar solubility of cholesterol.

If CSI > 1.0 - Cholesterol precipitates out of solution and forms crystals.

Bile salts prevent gallstone formation by:
Solubilizing cholesterol in mixed micelles
Binding Ca++ to prevent formation of calcium bilirubinate, or calcium
salts of phosphate, carbonate, or palmitate (insoluble precipitates)
(calcium bile salts stay soluble)

Front 685

What three factors contribute to the formation of goal stones?

Back 685

Hypomotility
Super saturation
Nucleation

Front 686

What are the requisites of optimal nutrition?

Back 686

Access and ingestion
Digestion and absorption
Metabolic utilization

Front 687

How many amino acids are essential?

Back 687

10

Front 688

What are the essential fatty acids?

Back 688

Linoleic acid (18:2)
alpha linolenic acid (18:3)

Front 689

How much is a calorie in clinical nutrition?

Back 689

1000 "physics" calories
hence the capital C or kcal designation

Front 690

How much energy does each nutrient provide/ gram?

Back 690

CH 4
Prot 4
Fat 9
EtoH 7

Front 691

What is the average USA diet comprised of?

Back 691

Carbs 45%
Protein 20%
Fat 35%

Front 692

Glycogen is stored in ...

Back 692

Liver and muscle

Front 693

What accounts for the amount of energy we need?

Back 693

Resting energy expenditure ~60%

Thermic effect of food is ~10%

Activity energy expenditure is ~30%

Front 694

Which organs contribute substantially to resting energy expenditure?

Back 694

Liver 29%
Brain 19%
Muscle 18%
heart 10%
Kidney 7%

Front 695

Resting energy expenditure is dependent upon...

Back 695

fat free mass

Front 696

Energy balance in broad terms is....

Back 696

Intake-TEE (total energy expenditure)

TEE=
Activity Energy Expenditure (AEE)
+
Thermic Effect of Food (TEF)
+
Resting Energy Expenditure (REE)

REE=
The sum of basal metabolic energy expenditure and sedentary activities
REE is proportional to Fat Free Mass, (because fat is metabolically inert)

Front 697

Intake may be determined indirectly and directly by...

Back 697

Indirectly:
Dietary recall
Food diaries

Directly:
Prepared controlled portions
In a research ward

Front 698

How do we measure TEE (totoal energy expenditure)?

Back 698

Double labeled water
TEE calculated from isotopic clearance

Direct calorimetry.
TEE determined directly as heat production.

Indirect calorimetry.
Respiratory quotient. Most useful.

Front 699

How do we estimate total energy expenditure?

Back 699

harris benedict formulas:

(♀) = 655 + 9.5WKg + 1.9Hcm - 4.7A

(♂) = 66 + 13.8WKg + 5.0Hcm - 6.8A

Uses weight height and activity.

Doesn't work if really skinny or really fat.

Front 700

To maintain positive N balance we need...

Back 700

Adequate amino acids
AND
Ample caloric intake

Front 701

The most common primary neoplasm of the liver is...

Back 701

Hepatocellular carcinoma.

Associated with Cirrhosis

Less common in the U.S than africa and asia.

Strongest correlation with viral hepatitis and hemochromatosis.

Male predominance (~85%)

Elevated AFP in most.

Survival in U.S median 6 months.

Cells resemble hepatocytes in a sheet like pattern but with a larger nucleus an therefore increased N/C ratio. Sometimes trabeculae.

Front 702

What is the most common neoplasm of the liver?

Back 702

Most are adenocarciomas, often arising in LI, lung, breast, & pancreas;

others include other lung cancers, sarcomas, & melanomas

In a series of 8455 autopsies of cancer patients, 39% had liver metastases; of these, only 6% were solitary.

Front 703

What is the most common pancreatic cancer?

Back 703

Adenocarcinoma of the ductal system aka ductal carcinoma
~90% of all true neoplasms of the pancreas.

Risk factors:
tobacco and high fat diet

Patients usually have advanced disease at presentation.

Weight loss and abdominal pain most common presentations.

90% of patients are noresectable.
5 year survival 1%.
Median survival six months.

False positive by biopsy is very rare.

Front 704

What are the genetics of ductal carcinoma?

Back 704

!Mutations in codon 12 of K-ras oncogene in nearly 100%; occurs early!

Abnormalities in p16 in most; mutations or hypermethylation of promoter.

DPC4 (Smad4) mutations in 55%

TP53 mutations in 50%

Front 705

Ductal carcinoma is often preceded by...

Back 705

Pancreatic intraductal neoplasia.
(PanIN)

Spectrum of premalignant changes in ductal epithelium, with mucinous metaplasia the earliest & CIS the most developed.

Although most resected organs with ductal carcinoma have PanIN, natural hx is unknown

Most have genetic abnormalities of ductal CA, especially K-ras mutations.

International grading system:

1A: mucinous metaplasia
1B: tufting & nuclear stratification
2: greater proliferation & loss of polarity with mild-moderate cytologic atypia
3: greater nuclear irregularities & mitotic figures

Front 706

Abdominal pain that radiates towards the back is characterize of...

Back 706

Ductal carcinoma of the pancreas.

Front 707

What are the characteristics of islet cell tumors?

Back 707

There really are not any because manifestations are so diverse.

Sometimes secretion of hormones
Non-functional mass
Minority have multiple tumors.

!!not possible to tell benign from malignant under the microscope!!

Front 708

What are Intraductal Papillary-Mucinous Neoplasms of the pancreas?

Back 708

5% of pancreatic tumors;

80% in head

7th-8th decade;

nonspecific symptoms

Localized or multicentric

Endoscopy: mucin extrusion

Radiology: duct ectasia (dilation)

Carcinogenesis different from that of ductal CA (some overlap)

Intraductal neoplasia:
benign to malignant cytology, papillae & mucin

Assciated Invasive carcinoma in 35%;ductal or colloid types but with far better prognosis than ductal carcinoma.

Surgery; 75% 5 yr survival

Front 709

What are Intraductal Papillary-Mucinous Neoplasms of the pancreas?

Back 709

5% of pancreatic tumors;

80% in head

7th-8th decade;

nonspecific symptoms

Localized or multicentric

Endoscopy: mucin extrusion

Radiology: duct ectasia (dilation)

Carcinogenesis different from that of ductal CA (some overlap)

Intraductal neoplasia:
benign to malignant cytology, papillae & mucin

Assciated Invasive carcinoma in 35%;ductal or colloid types but with far better prognosis than ductal carcinoma.

Surgery; 75% 5 yr survival

Front 710

At what stage does the liver develop?

Back 710

Liver appears during 4th week of gestation as diverticulum arising from duodenum.

Cranial portion forms parenchymal tissue and bile ducts,

Caudal portion forms gallbladder and cystic duct.

Front 711

How do we define pathological jaundice?

Back 711

Conjugated fraction comprises more than approximately 20% of total.

Front 712

What are the extrahepatic causes of cholestasis in children?

Back 712

Biliary Atresia.

Choledochal cyst.

Spontaneous perforation of the bile duct.

Front 713

What is billiary atresia?

Back 713

Progressive disease characterized by dynamic fibroobliteration of the bile ducts. (inflammatory process)

Occurs in a range of 1 in 8000 to 25000 live births

In some cases associated malformations occur

Embryonic or fetal type:
Approximately 34% of cases. More commonly associated with other abnormalities

Perinatal type:
Approximately 66% of cases. Later onset of jaundice.

Theories:
Ductal plate abnormality
Failure of recanalization
Infantile obstructive cholangiopathy
Ischemic insults
Abnormal bile acid metabolism
Immunologic dysfunction

Jaundice often not apparent until 3 to 5 weeks of life.

Acholic (bile pigment) stools present.

Liver firm and enlarged.

Elevated alkaline phosphatase.

Front 714

What form of cholestasis in children is associated with giant cell hepatitis?

Back 714

Idiopathic

Front 715

What are choledochal cysts?

Back 715

Cystic dilation of billiary tree.

Leads to cholestasis.

Predisposes to infection.

Very rare.

1/3 diagnosed before 1 year.

More common in females.

Increased risk of carcinoma.

Front 716

How does the pancreas develop?

Back 716

Originates as dorsal bud and two ventral buds

The left ventral bud atrophies

Rotation of stomach and duodenum with elongation carries right ventral bud posteriorly

Fusion of right ventral with dorsal bud completes head and uncinate process

Front 717

What is annular pancreas?

Back 717

Hypertrophy of normal pancreatic tissue

Fusion of heterotopic pancreatic rests

Failure of left ventral bud atrophy

Failure of free rotation of right ventral bud

Front 718

How does annual pancreas present?

Back 718

Symptoms may present at any age. Approximately 50% in pediatric age

Vomiting (mostly billious)
Peptic ulceration
Abdominal pain
Jaundice
Associated with other congenital defects

Front 719

How do we diagnose annular pancreas?

Back 719

Evidence of duodenal obstruction on plain abdominal film(double bubble effect)

Sonographic evidence

Barium studies demonstrating duodenal filling defect

ERCP and laparotomy

Front 720

How do we manage annular pancreas?

Back 720

Surgical intervention mandatory in cases with obstruction.

Recommended approach is a bypass operation, preferably duodenoduodenostomy.

Front 721

What is ectopic pancreas?

Back 721

Presence of pancreatic tissue lacking anatomic and vascular continuity with the main body of pancreas.

70-90% occurs in the upper GI tract mostly in gastric antrum.

Usually incidental finding.

Front 722

What is Pancreas Divisum?

Back 722

Refers to abnormality resulting from incomplete fusion of dorsal and ventral pancreatic ductal systems.

Dorsal duct functions as main drainage system but opens into smaller accessory papilla.

Development of pancreatitis.

Front 723

What is common channel syndrome?

Back 723

Anomalous junctions of common bile duct and main pancreatic duct.

The presence of a long common channel with pancreaticobiliary junction located outside of duodenal wall associated with pancreatitis and choledochal cyst.

Reflux of pancreatic juice.

Front 724

What is the bile binding resin Colesevalam used for?

Back 724

Type 2 diabetes (insulin resistance)

Off label use:
Bile salt malabsorption-associated diarrhea
Cholestasis-associated pruritus.

Front 725

UDCA (ursadiol) is a bile salt used to treat....

Back 725

Primary billiary cirrhosis

Gall bladder stones

Front 726

CDCA (chenodiol) is a bile salt used to treat...

Back 726

Cerebrotendinous xanthomatosis

Front 727

Cholestyramine can be used to treat...

Back 727

Hypercholestrolemia

Front 728

With what bile salts do we treat inborn errors of bile synthesis?

Back 728

CDCA-CA-UDCA mixtures
Life saving and curative

Front 729

What is the difference between Cholelithiasis and Choledocholithiasis?

Back 729

Cholelithiasis=GB stones
Causes Biliary Colic and Acute !Cholecystitis!

Choledocholithiasis=CBD stones
Causes Biliary Colic and Acute !Cholangitis!

Front 730

Cholelithiasis is...

Back 730

Gallbladder stones

Front 731

Cholecystitis is...

Back 731

GB infection/inflammation

Front 732

Choledocholithiasis is...

Back 732

Common bile duct stones

Front 733

Cholangitis is..

Back 733

Common bile duct infection/inflammation

Front 734

What types of stones can cause cholelithiasis?

Back 734

Cholesterol (> 50% cholesterol) = 80%

Brown pigment:
(Calcium Bilirubinate & Palmitate)
->INFECTION secondary to biliary sepsis

Black pigment
(Calcium Carbonate & Phosphate)
->Hemolysis (Sickle Cell Disease)
cirrhosis/alcoholism

Front 735

What are risk factors for gall stones?

Back 735

Obesity (>30% over IBW)

Female gender

Ethnicity:
Native American
Hispanic

Total parenteral nutrition

Rapid weight loss

Pregnancy

Age (>40)

(fat, fertile, forty)

Front 736

What effects do stones in various parts of the gallbladder have?

Back 736

Cystic duct=cholecystitis

Infundibulum (neck)= Billiary colic

Gall bladder body =asymptomatic
(also fundus)

Front 737

How does cholelithiasis/biliary colic typically present?

Back 737

Rarely symptomatic

85% asymptomatic

Stone impacts cystic duct temporarily blocking it

Classic symptoms:
RUQ
Radiates to back or shoulder
1-2 hours post prandial
Fatty meals classic
Pain crescendos then plateaus and slowly subsides.
Can be associated with nausea and vomiting.

Front 738

What are the diagnostic options for biliary colic?

Back 738

Abdominal ultrasound
Computed Tomography
Nuclear study

Ultrasound is test of choice for suspected cholelithiasis.
Sensitivity >90%
Specificity >90%

CT:
High specificity but poor sensitivity

Front 739

What nuclear study is available for cholelithiasis?

Back 739

Hepatobiliary Scintigraphy.

Good to detect cystic duct obstruction
->Acute cholecystitis.

NOT GOOD for detecting GB stones.

Front 740

What is acute cholecystitis?

Back 740

Gallbladder wall inflammation with fever, leukocytosis, and acute RUQ pain.

Prolonged or recurrent cystic duct obstruction leading to GB wall inflammation.

Not completely understood

Minimal AST/ALT elevation,
T Bili slightly elevated.
Normal amylase/lipase

Classic Murphy’s sign
(Palpation of the RUQ upon inspiration induces pain)

Front 741

How do we diagnose acute cholecystitis?

Back 741

clinical features

Ultrasonography:
88% sensitive, 80% specific

Nuclear studies:
97% sensitive 90% specific for cystic duct obstruction

CT:
Typically required only if complicated cholecystitis is suspected.

Front 742

How do biliary colic and acute cholecystitis differ in management strategy?

Back 742

Biliary colic:
Elective surgery

Acute Cholecystitis:
Early surgery
(Dx can be made on clinical features alone and does not require imaging)

Front 743

What are the symptoms of choledocolithiasis?

Back 743

Symptoms similar to biliary colic

Typically associated with elevations of liver function tests in association with pain

Increased T.bilirubin, alkaline phosphatase, AST/ALT

Front 744

How well do Ultrasound and CT do at detecting choledocholithiasis?

Back 744

Ultrasound:
Sensitivity 20-50%
Specificity >90%

CT:
Sensitivity 30-70%
Specificity >90%

Front 745

What are the sequelae of choledocholithiasis?

Back 745

Ascending cholangitis
Obstructive jaundice
Pancreatitis

Front 746

Charcot's triad is suggestive of...

Back 746

Acute cholangitis

RUQ / epigastric pain

Jaundice (Cholestatic picture with increased AST/ALT)

Fever

EMERGENCY. Antibiotics +ERCP
(endoscopic retrograde cholangiopancreatography)

Front 747

Pancreatitis occurs when a stone becomes wedged in ...

Back 747

The distal common bile duct

Front 748

What is biliary pancreatitis?

Back 748

Features of pancreatitis clinically.

Classically pain that radiates to the back with nausea, vomiting, anorexia

May have mixed cholestatic/hepatic liver enzyme pattern.

Elevations in WBC, amylase, lipase

Endoscopic emergency if biliary obstruction is evident.

Elevated total bilirubin= ERCP

Can form pseudocysts.

Front 749

Post cholecystectomy pain, fever, WBC, elevations in AST/ALT, Bili may be...

Back 749

Bile duct injury

Front 750

Hypoechoic & Anechoic areas on ultrasound appear...

Back 750

Black

Isoechoic appears gray.

Hyperechoic appears white.

Front 751

On CT hyperdensity (bone) appears...

Back 751

White

Front 752

Hyperintensity on MRI appears...

Back 752

Bright.

Front 753

What is a hepatic abscess?

Back 753

Localized collection of pus in liver due to destruction of hepatic parenchyma.

Pathology:
Pyogenic 88%
Amebic 10%
Fungal 2%
Most commonly following diverticulitis or appendicitis

Differential diagnosis:
Metastasis

High fever and white count suggest abscess rather than mets.

Radiologic finding :
Coalescing cystic liver lesions with surrounding edema.

Front 754

What is a hepatic hemangioma?

Back 754

Benign tumor composed of multiple vascular channels.

Most common benign tumor of liver

Differential diagnosis:
Peripheral cholangiocarcinoma
Hypervascular metastasis

Focal echogenic lesion with increased through transmission on ultrasound.

!!Focal lesion with peripheral nodular enhancement on CT!!

Filling in of contrast in delayed images (follows blood flow)

Front 755

In the arterial phase of hepatocellular carcinoma, it appears on imaging as..

Back 755

Homogenously enhancing lesion

Front 756

What are the most common sources of liver metastases?

Back 756

Colon
Stomach
Pancreas
Breast and Lung

Front 757

What biliary stones can be virtually invisible on CT?

Back 757

Non-calcified stones.

Front 758

The most sensitive radiological test for stones in the bile duct is... (Choledocholithiasis)

Back 758

MRCP

Front 759

Double barrel or parallel channel sign is an indication of...

Back 759

Intrahepatic biliary ductal dilatation

Front 760

What are the complications of acute cholecystitis?

Back 760

Gangrenous or emphysematous cholecystitis

Abscess formation

Perforation

Front 761

What are the ultrasound findings of acute cholecystits?

Back 761

Diffusely thickened gallbladder wall

Impacted gall stone

Sonographic Murphy’s sign

Pericholecystic fluid

Increased doppler flow in the gallbladder wall

Front 762

What is the ultrasound finding of gallbladder carcinoma?

Back 762

Irregular mixed echogenic lesion in GB

Front 763

What would we use contrast enhanced CT for in the setting of acute pancreatitis?

Back 763

Grading

Complications:
Pseudocyst formation,
Infected necrosis
Pseduoaneurysm formation,
Venous thrombosis

Front 764

What radiologic findings do we expect in chronic pancreatitis?

Back 764

Multiple !!calcifications!! in the pancreas within an atrophic pancreas with dilated irregular pancreatic duct.

Front 765

What radiologic findings do we expect in acute pancreatitis?

Back 765

Unenhancing pancreas suggestive of pancreatic necrosis with peripancreatic inflammatory fluid tracking along the left anterior para-renal space

Front 766

What do pancreatic pseudocysts generally look like on CT?

Back 766

Unilocular cystic lesion in the tail of the pancreas.

Front 767

What does pancreatic head adenocarcinoma look like on ultrasound?

Back 767

Ill defined hypoechoic lesion in the head of pancreas with dilated intra and extrahepatic bile duct dilation

This is called double duct sign.

Front 768

When do we order ultrasound?

Back 768

Useful:
Right upper quadrant pain –Initial test

Cholelithiasis, cholecystitis

Bile duct dilatation

Assessment of vasculature:
Portal vein, TIPS (Transjugular intrahepatic portosystemic shunt)
Budd Chiari

Not very useful:
To visualize distal CBD
Pancreatitis, pancreatic neoplasm

Front 769

When do we order CT scan?

Back 769

Most useful:
Hepatic, Gall bladder and pancreatic neoplasm localizing and staging

Pancreatitis – severity index, pancreatic calcification

Cholecystitis complications
Emphysematous and gangrenous cholecystitis, perforation or abscess formation

Pre liver resection

Front 770

When do we order MRI?

Back 770

Most Useful:
Best modality for lesion characterization in liver and pancreas

MRCP
CBD stones,
Intra or extrahepatic bile duct path.
Cholangiocarcinoma

Better lesion detection compared to CT:
Before liver resection, screening for HCC in cirrhosis.

Front 771

Average thermic effect of food per meal for a 70Kg person is ~

Back 771

TEE of “average” mixed meal ~200C


Dietary Fat ->Body Fat ~ 60
Dietary Glucose-> Glycogen~ 140
Diet Protein-> Muscle Protein ~480

Front 772

What are some important caveats about nitrogen balance?

Back 772

Positive N balance:
Needs adequate caloric intake, regardless of the amount of dietary protein intake.
Cannot be “forced” by intake of large amounts of protein or amino acids alone.

Negative N balance:
In catabolic stress can be decreased (“protein sparing”) by giving enough glucose to turn off gluconeogenesis and enough amino acids to spare muscle protein.

Front 773

What is the clinical impact of protein/calorie malnutrition?

Back 773

Delayed post-surgical wound healing

Delayed recovery from severe trauma

Increased mortality in severe burns

Impaired immune response

Increased toxicity of chemotherapy

Growth failure in pediatric patients

Front 774

Where is lactase found?

Back 774

At the brush border

Front 775

What are the various sites of diestion of macromolecues?

Back 775

Some molecules like glucose do not need digestion.

Proteins are broken down intraluminally.

Lactose is broken down by lactase found in the brush border.

Some smaller peptides are digested intracellularly.

Any combination of the above.

Front 776

Where are the major enzymes made?

Back 776

Mouth & stomach:
amylase, gastric lipase (mild lipase), pepsin

Pancreatic enzymes:
lipase, proteases, DNAase

Enterocyte enzymes:
brush border & secreted

Front 777

Galactose and hence lactose is only made by...

Back 777

Mammals

Front 778

What enzymes break glycosidic bonds besides lactase and sucrase?

Back 778

Glucoamylase:
breaks starch 1:4 links

Alpha-dextrinase (isomaltase): breaks starch 1:6 links

Front 779

What are the two main monosaccharide sugar transporters?

Back 779

SGLT1:
Glucose and galactose transporter
GLUT5:
Fructose transporter

Front 780

What is lactase persistence?

Back 780

Lactase persistence is an autosomal dominant trait. LCT on chromosome 2.

Lactase is a 150,000 Kd beta-disaccharidase which appears in high levels in brush border shortly after birth.

Levels fall with weaning in all mammals and by the end of adolescence in most human populations.

In some populations there is a high frequency of persistence of high lactase levels into adulthood.

As we go from North to South and West to East the allele becomes less frequent.

Front 781

By what processes are glucose and galactose transported across each membrane?

Back 781

Luminal membrane:
Secondary active transport (Na+ related)

From cell to interstitial space:
Facilitated diffusion.

Front 782

What are the classes of amino acids?
(not on exam)

Back 782

Polar:
Gly, Ala, Ser, Thr, Asn, Asp

Aromatic:
Phe, Tyr, Trp

Charged:
Glu-, Asp-, Lys+, Arg+, His+

Branched chain:
Val, Leu, Ile

Cyclic:
Pro

Sulfur containing:
Met, Cys

Front 783

How are proteins digested and absorbed?

Back 783

Luminal Digestion - stomach
Gastric pepsin (the only acidic peptidase)

Luminal Digestion – small intestine
Pancreatic peptidases
Enterocyte peptidases

Brush Border Digestion
Aminopeptidase: di- and tri-peptides -> single AA
Amino-oligopeptidase: oligopeptides-> 2,3 AA
Dipeptidyl-aminopeptidase -> removes Ala, Pro

Transporters:
amino acid specific

Front 784

How are protease precursors activated to proteases?

Back 784

Cleavage of the "safety" fuse of trypsinogen by enterokinase.

Trypsin activates the rest.

Front 785

How does absorption efficiency vary amongst the lipids?

Back 785

Triglycerides, phospholipids: 95%
Cholesterol: 50%

Front 786

How are lipids digested and absorbed?

Back 786

Luminal Digestion - stomach:
Gastric and lingual lipases release some FA’s
Stomach mixing forms emulsion particles.

Luminal Digestion - small intestine:
Pancreatic lipase releases large amounts of fatty acids
Hydrolysis products form mixed micelles

Brush Border - passive diffusion

Intracellular Events:
Re-esterification to TG
Chylomicron assembly and secretion.

Front 787

What is the importance of gastric emulsification in lipid absorption?

Back 787

Lingual and gastric lipase hydrolyze dietary fats, liberating FA’s, mono- and di-glycerides, which serve as emulsifying agents.

This increases absorption efficiency substantially.
(from ~50% to ~95%)

Front 788

What does the lipase/co-lipase system do ?

Back 788

Breaks the fatty acyl bond from the chain and liberates monoglycerides and free fatty acids.

Lipids can then be solubilized in mixed micelles with bile that has hydroxyl groups on it.

Front 789

What happens to micelles in the lumen?

Back 789

They diffuse across the unstirred water layer and then by diffusion or transport move into the cytosol of the cell.

Front 790

What absorption processes are highly regional?

Back 790

Carbohydrates are absorbed almost entirely in the duodenum and jejunum because of the high efficiency.

Protein, fat, water and sodium are also absorbed in the duodenum but again can happen anywhere in the small bowel.

Bile salts and vitamin B12 are absorbed only in the terminal ileum. (problem in crohn's surgery)

Iron is absorbed only in the duodenum and upper jejunum.
(can be a problem in GI surgery)

Front 791

Vitamins cannot be synthesized but they are crucial for...

Back 791

DNA and protein synthesis
Enzyme and transporter function
Many other metabolic processes

Front 792

What are the water soluble vitamins?

Back 792

Thiamine (B1)
Riboflavin (B2)
Niacin (B3)
Pyridoxine (B6)
Folic Acid (B9)
Cobalamin (B12)
Ascorbate (C)
Biotin
Pantothenic Acid

Front 793

What are the fat soluble vitamins?

Back 793

Retinol (A)
Calciferol (D)*
Tocopherol (E)
Menaquinones (K)*

D and K are semi vitamins.

We can synthesize very small amounts of D (not enough though).

We can use some of the K from gut bacteria. Any condition that affects gut bacteria can thus be problematic for clotting factors.

Front 794

What molecules are considered macro minerals?

Back 794

Sodium (Na)
Potassium (K)
Calcium (Ca)
Magnesium (Mg)
Iron (Fe)
Chloride (Cl)
Phosphorus (PO4)
Sulfur (SO4)

Front 795

What molecules are considered trace minerals?

Back 795

Chromium (Cr)
Cobalt (Co)
Copper (Cu)
Iodine (I)
Manganese (Mn)
Molybdenum (Mo)
Selenium (Se)
Zinc (Zn)

Front 796

What is the importance of vitamin C?

Back 796

Cofactor for collagen biosynthesis
Facilitates iron absorption
Role in activation of folate

VERY powerful aqueous phase antioxidant. Can detoxify molecules by scavenging free electrons and ultimately becoming 2,3-diketo-1-gluconic acid.

Front 797

Scurvy or vitamin C deficiency is characterized by ...

Back 797

Severe periodontal disease
Cutaneous hemorrhage
Poor wound healing

Populations at risk include:
Cigarette smokers
Severe malnutrition, cachexia

High doses of vitamin C may cause mild diarrhea and kidney stones in susceptible patients.

Front 798

Who is at risk for folate deficiency?

Back 798

Severe Malabsorption
Drug and food antagonists
Poor diet in the elderly

Pregnant women should have HIGH levels to prevent neural tube defects.

Toxicity is not possible.

Front 799

Vitamin A,D,E and K absorption is dependent upon...

Back 799

The presence and efficient absorption of dietary fat.

They are:
Solubilized by bile in mixed micelles.

Transported into enterocytes, packaged along with fat into chylomicrons, and secreted into lymph.

Taken up by the liver in chylomicron remnants.

Re-secreted into plasma on transport proteins.

Some things to keep in mind:
Fat soluble vitamins can be stored
Fat soluble vitamins in excess can be toxic.
The body can synthesize vitamins D and K but not in sufficient amounts.

Front 800

What is the importance of folic acid?

Back 800

Cofactor in methyl transfer reactions.

Synthesis of DNA, glutathione, hormones, phospholipids, and neurotransmitters.

Front 801

Two retinol molecules bound together are a ....

Back 801

Beta carotene

Front 802

What is the importance of vitamin A?

Back 802

Visual pigment synthesis
Maintains ocular structures
Epithelial cell function
Bone growth & development
Reproduction

Vitamin A sources:
Eggs
Meat
Dairy products

Beta carotene sources:
Green leafy and intensely colored fruits and vegetables.

Front 803

What does vitamin A deficiency do to the eyes?

Back 803

Keratomalacia

Front 804

What skin lesion is associated with vitamin A deficiency?

Back 804

Hyperkeratosis

Front 805

What populations are at risk for vitamin A deficiency?

Back 805

Fat malabsorption syndromes
Poor diet in the elderly
Some 3rd world countries

Front 806

What are the pharmacologic uses for vitamin A?

Back 806

Analogs are used topically for acne and other skin disorders. Profoundly teratogenic though.

Beta-Carotene Trial:
Study was halted due to increased cancers in the treatment group.

Dietary supplements used with caution because of the potential for serious toxicity.

Toxicity:
Hypervitaminosis A syndrome
Hepatotoxicity
(polar explorers eating polar bear liver)
Teratogenic effects

Front 807

How does vitamin A deficiency present?

Back 807

Night blindness

Front 808

Apart form our skin and sunlight, where do we get vitamin D?

Back 808

Cheese
Butter
Margarine
Fortified milk
Fish
Fortified cereals

Front 809

What is the importance of vitamin D?

Back 809

It increases intestinal calcium absorption by receptor gene upregulation.

Liver or kidney disease can cause functional Vitamin D depletion even with normal absorption.

Front 810

What is vitamin D deficiency?

Back 810

Ricketts & Osteoporosis

Populations at risk include:
Fat malabsorption syndromes
The elderly and homebound
Severe kidney disease

Front 811

What is Vitamin D used for pharmacologically?

Back 811

Used to treat hypocalcemia after parathyroidectomy

Used as an adjunct in treating osteopenia and osteoporosis

Used as a dietary supplement in combination with Ca++ supplements for “bone health”.

Toxicity:
Hypercalcemia, weakness
Kidney stones

Front 812

What is the importance of vitamin E and where do we get it?

Back 812

Membrane antioxidant

Corn, nuts, olives, green leafy vegetables, vegetable oils.

Front 813

What does vitamin E deficiency do?

Back 813

Hemolytic anemia

Very rare: seen only with very severe fat malabsorption.

Populations at risk for mild deficiency:
Cystic fibrosis
Severe pancreatic insufficiency
Short bowel syndromes
Total Parenteral Nutrition
Genetic abnormalities

Front 814

What are the pharmacological uses of vitamin E?

Back 814

Prevents pulmonary oxygen toxicity in premature infants?

No activity in Parkinson’s disease, atherosclerosis, and cancer prevention studies

Widespread use as antioxidant dietary supplement.
Little evidence of efficacy
May function as a pro-oxidant?

Toxicity:
Generally safe
High doses may cause diarrhea and clotting abnormalities

Front 815

When vitamin becomes oxidized, it can regenerated by..

Back 815

Vitamin C

Front 816

Where do we get vitamin K?

Back 816

Cabbage, cauliflower, spinach and other green leafy veggies.
Cereals.

Bacteria.

Front 817

What does vitamin K deficiency do?

Back 817

Bruisability and Bleeding

Populations at risk:
Fat malabsorption syndromes
Patients on chronic antibiotics
Short bowel syndromes

Front 818

What are the pharmacological uses of vitamin K?

Back 818

Acute reversal of coumarin induced anticoagulation.

Stabilization of anticoagulation in patients taking coumarin Rx.

Toxicity:
Generally safe. Excess does NOT induce hypercoagulable state.

NOTE!!: Be very careful with giving antibiotics to patients on coumadin.

Front 819

What is the outcome of calcium deficiency?

Back 819

Osteoporosis.

Absorption aided by vitamin D.

Populations at risk:
Women, esp. post-menopause
Fat malabsorption syndromes
Short bowel syndromes
Chronic steroid use

Pharmacologic uses:
Prevention of Osteoporosis
Treatment of Osteoporosis
Antacid for Rx of GERD
Bile salt diarrhea
Oxalate kidney stones

Side effect is constipation.

Toxicity:
Safe

Front 820

How do we define malabsorption?

Back 820

Impaired absorption of individual or multiple nutrients caused by the pathologic disruption of the normal physiological processes of digestion and intestinal transport.

Front 821

What are the symptoms of malabsorption?

Back 821

General Symptoms:
Diarrhea
Steatorrhea
Weight Loss > 10%
Bloating, gassiness, flatulence

Specific Symptoms:
Peripheral edema
Pica; symptoms of anemia
Neuropathy
Night blindness
Accelerated osteoporosis

Front 822

Which symptoms are associated with which specific malabsorptions?

Back 822

Weight Loss: Total Calories

Diarrhea: CHO, Protein, Fat

Steatorrhea: Fat

Bloating, flatulence: Sugars

Edema: Protein

Pica, Sx of anemia: Iron, vitamin B12, folate

Neuropathy: Vitamin B12

Night blindness: Vitamin A

Osteoporosis: Vitamin D, Calcium

Front 823

What are the causes of malabsorption?

Back 823

Disaccharide Malabsorption:
Lactase Deficiency (common)
Fructose Intolerance (uncommon)
Sucrase Deficiency (rare)

Maldigestion (selective fat malabsorption):
Gastric resection or bypass

Bile salt deficiency - ileal resection/disease, SIBO

Pancreatic Insufficiency

Global Malabsorption (CHO, protein, fat):
Short Bowel Syndrome
Mucosal Disease - Crohn's, Celiac, Whipple's, amyloidosis, lymphoma, radiation enteritis.

Front 824

What history clues can suggest malabsorption?

Back 824

GI Surgery:
Ulcer operations (esp. vagotomy & antrectomy)
Gastric resection or bypass
Cholecystectomy
Small bowel resection (esp. terminal ileum)
Right colon resection (esp. ileo-cecal valve)

Pancreatitis or Hx of heavy EtOH abuse

Abdominal or pelvic irradiation

Collagen vascular disease

Front 825

What is lactose intolerance?

Back 825

Most common cause of chronic diarrhea in USA.

Primary:
Absent lactase persistence SNP
Highest incidence in persons of Asian, Native-American, and African-American ancestry

Secondary:
Aging
Post-infectious (enterovirus)
Chemotherapy
Celiac disease, Tropical Sprue, Giardiasis
Bacterial Overgrowth
Rapid transit syndromes

Dx:
Presumptive
Trial of a low-lactose or lactose-free diet(may give a false negative result)
!!Lactose-Hydrogen Breath Test!!

Tx:
Dietary lactose restriction
Lactase-treated milk (Lactaid®, DairyEase®)
Lactase enzyme supplements

Front 826

How does the H2 breath test work?

Back 826

Large amount of loactose is given orally.

If lactase deficient, lactose is not absorbed and metabolized by bacteria which make H2 and methane.

S pike in H2 or methane therefore suggests lactose intolerance.

Front 827

What are sucrose deficiency and dietary fructose intolerance?

Back 827

Sucrase Deficiency
Very rare autosomal recessive disorder
Sx:
diarrhea appearing in early infancy. Typically right after weaning,
Dx:
sucrose hydrogen breath test
Rx:
lifelong sucrose free diet

Dietary Fructose Intolerance:
Mild dysfunction of the GLUT 5 transporter
Sx:
diarrhea with ingestion of fruit and products containing high fructose corn syrup
Dx:
fructose hydrogen breath test
Rx:
dietary fructose restriction

Front 828

What can cause selective fat malabsorption?

Back 828

Gastric resection or dysmotility (gastroparesis)

Bile Salt Malabsorption or deficiency
(bacterial overgrowth, TI resection, cholecystectomy)

Pancreatic insufficiency:
chronic pancreatitis

Mucosal Diseases

Front 829

How do we test for steatorhoea?

Back 829

Stool Sudan Fat Stain

Can quantify with dietary fat absorption test over three days.
!!>7g/day in stool=malabsorption!!
(seldom used any more)

Front 830

Maldigestion due to bacterial overgrowth can occur because of....

Back 830

Hypomotility
(DM, scleroderma, visceral myopathy)

Achlorhydria
(gastrectomy, atrophic gastritis)

Jejunal diverticulosis

Ileo-cecal valve resection

Bile salt deconjugation->bile salt malabsorption ->decreased bile salt pool ->fat malabsorption

Chronic mucosal inflammation

Dx:
Suspicion
Jejunal aspiration for quantitative culture(gold standard, but not widely available)
14C-Glycocholate Breath Test
Glucose-Hydrogen Breath Test

Tx:
Oral systemic or non-absorbable antibiotics.
Usually requires chronic treatment
Antibiotic rotation to prevent resistance.

Front 831

What can we see on a glucose hydrogen breath test that is diagnostic of bacterial overgrowth maldigestion?

Back 831

An early intestinal peak and a late colonic peak.

Front 832

What causes maldigestion due to pancreatic insufficiency?

Back 832

Chronic pancreatitis (common)

Pancreatic cancer with duct obstruction (rare)

ZE Syndrome - lipase denaturation (rare)

Steatorrhea occurs when the secretion of pancreatic lipase falls to < 10% of normal

Disease also destroys alpha and beta cells, resulting in decreased insulin and glucagon secretion

Brittle diabetes appears in advanced disease

Front 833

What is the classic imaging picture of chronic pancreatitis?

Back 833

Duct Dilation and Calcification

Front 834

How do we diagnose maldigestion due to pancreatic insufficiency?

Back 834

Presumption

Stimulated pancreatic secretion analysis

Pancreatic imaging by CT, EUS, ERCP

Tx:
Pancreatic enzyme supplements containing at least 30,000 units of lipase at each meal.

Enteric coated tablets

PPIs, H2 blockers, or NaHCO3 keep gastric pH > 5 to prevent enzyme denaturation

Reduced fat diet

Front 835

What causes global malabsorption?

Back 835

Small Bowel Mucosal Diseases.

Celiac disease (upper small bowel)
Crohn’s disease (terminal ileum)
Whipple’s disease (duodenum, jejunum)
Intestinal lymphoma
Chronic giardiasis

Other rare disorders:
Tropical sprue
Eosinophilic gastroenteritis
Abetalipoproteinemia
Amyloidosis
Lymphangectasia

Front 836

What is the algorithm for diagnosing the cause of malabsorption?

Back 836

Front 837

What is included in a diet history?

Back 837

Review usual pattern of food intake:
24 hour diet recall
Food frequency questionnaires
Food diaries

Food intolerance or allergies

Use of supplements

Specific dietary Rx

Dining out; fast food

Front 838

What sorts of symptoms may emerge in a diet history?

Back 838

Appetite - Increased or Decreased?

Steatorrhea (malabsorption)

Rash (B vitamin or essential FA deficiency)

Night blindness (vitamin A deficiency)

Easy bruising (vitamin K deficiency)

Pica (iron deficiency)

Sore tongue (iron or B vitamin deficiency)

Edema (depleted visceral protein stores)

Front 839

What is included in a weight history?

Back 839

Current Weight and BMI

Ideal Body Weight:
Calculated
Estimated (post-adolescent weight)

% Ideal Body Weight

Recent Change in Weight
% Usual Body Weight

Rate of Weight Loss

Maximum Lifetime Weight

Desired Weight

Front 840

How do we calculate BMI?

Back 840

BMI = weight (kg) / height (m2)

1 Kg = 2.20 lbs
1 inch = 2.54 cm

Overweight=25-30

Front 841

How do we calculate ideal body weight?

Back 841

Metropolitan Life Tables
NHANES I and NHANES II Survey Data

The Hamwi method:
♀ 100 lbs for 5 ft + 5 lbs for each inch over 5 ft

♂ 106 lbs for 5 ft + 6 lbs for each inch over 5 ft

Front 842

How do we interpret % ideal body weight?

Back 842

Severe malnutrition < 70 %

100-110% appropriate

Severe obesity >200%

Front 843

How do we interpret rate of weight loss?

Back 843

One week:
1-2% significant
>2% severe

One month:
5% significant
>5% severe

6 months:
10% significant
>10% severe

Front 844

What is the best measure of body fat distribution?

Back 844

Waist/hip ratio

The higher the ratio the higher the risk of disease.

Front 845

Uveitis can be a sign of....

Back 845

Vitamin A deficiency

Front 846

What is Cheilosis?

Back 846

Cracks at the corner of the mouth.

Failure of the bodies repair system.

Front 847

What is glossitis?

Back 847

Beefy red tongue
Smooth if severe.

Front 848

What is adiposity?

Back 848

% body fat.
This can be done by:
Underwater weighing
Bioelectric impedance

Anthropometry:
Skin fold thickness measured by calipers.
Arm muscle area (determined from triceps skinfold and arm circumference)

DEXA Scan
CT and MRI scanning

Front 849

How do we interpret % body fat?

Back 849

Malnourished:
<10% women
<2% men

Obese:
>32% women
>25% men

Front 850

At what % body fat does ammenorrhea usually begin?

Back 850

10-14%

Front 851

What are good rules of thumb for energy intake in kcal/kg?

Back 851

Weight Loss 20 - 25
Weight Maintenance 25 - 30
Illness, Fever 30 - 40
Burns, Severe Trauma 40 - 50

Front 852

What are our protein requirements in g/kg/day?

Back 852

Normal 0.8 - 1.0
Moderate Stress 1.0 - 2.0
Severe Stress 2.0 - 2.5
Disease Specific 0.4 - 3.0

Front 853

How do we determine protein status?

Back 853

Visceral proteins:
Albumin - half-life = 18-21 days
Transferrin - half-life = 7-10 days
Prealbumin - half-life = 2-3 days

Nitrogen balance:
Requires 24 hr urine collection and a 24 hr dietary protein count

Lean body mass

Front 854

How do we interpret serum visceral protein levels?

Back 854

Albumin (g/dl):
5.5 – 3.5 normal
< 2.0 severe depletion

Prealbumin (g/dl):
40 – 14 normal
<5 severe depletion

Transferrin (mg/dl):
375 – 200 normal
<100 severe depletion

Front 855

Appetite stimuli can be either...

Back 855

Orexigenic:
stimuli that increase appetite

Anorexic:
stimuli that decrease appetite

Front 856

Why does too much fat interfere with reproduction?

Back 856

Fat is metabolically active.

Adipocyte interleukins and inflammatory cytokines inhibit ovulation and implantation

Front 857

How does the appetite control system in the brain work?

Back 857

Two classes of neurons in the arcuate nucleus (ARC) respond to GI hormonal signals:

NPY-AgRP neurons secrete orexigenic peptides-
Neuropeptide Y
Agouti-related peptide

POMC neurons secrete the anorexic peptide:
alpha-melanocyte stimulating hormone

These neurons project to the PVN, and from there to the NTS in the brainstem

The balance between NPY-AgRP:POMC neuron activity regulates appetite, hunger, and satiety.

Front 858

What is Grehlin?

Back 858

28 AA peptide

Strongly orexigenic

Increases gastric motility

Plasma levels oscillate and peak before meals

Secretion decreased by food

Conversely CCK is an anorexic signal.

Front 859

What is leptin?

Back 859

16 kDa protein.

Mutated in the ob/ob mouse

Plasma levels proportional to BMI and body fat mass

Long-term appetite regulator

Leptin does not directly regulate hunger and satiety

Front 860

What happens with high leptin, high insulin , low grehlin? (the well fed state)

Back 860

POMC neurons are excited
NPY/AgRP neurons are inhibited

Decreases food intake behaviours

Front 861

What happens with low leptin, low insulin , high grehlin? (the starved state)

Back 861

NPY/AgRP neurons are excited
POMC neurons are inhibited

Increases food intake behaviors.

Front 862

When we plot BMR and appetite curves, the point where they intersect is considered the...

Back 862

Setpoint of adiposity.

Shape of the curve is determined by genetics.

Front 863

What is the caloric content of fat?

Back 863

~9 kcal/gm

Front 864

In terms of % body fat, what is obesity?

Back 864

>32% for women
>25% for men

Front 865

Why do we use BMI?

Back 865

In healthy populations BMI correlates well with adiposity.

easy to compute

Shortcoming:
very muscular individuals may have a high BMI and low adiposity, but still be classified as obese

Front 866

Obesity is a strong predictor of diseases such as diabetes, hypertension, coronary artery disease, fatty liver, cancer, hyperlipidemia, osteoarthritis. How do we grade it in terms of BMI?

Back 866

Grade I: obesity 30 - 35
Grade II: severe obesity 35 - 40
Grade III: extreme obesity >40

Front 867

What is the cutoff waist/hip ratio that predisposes someone to increased risk of disease?

Back 867

> 0.95 in men
> 0.80 in women

Increases risk of:
Atherosclerosis
Cancer
Type 2 Diabetes
Infertility
Osteoarthritis
Sleep apnea

Increased ABDOMINAL fat is also associated with the Metabolic Syndrome:
Insulin resistance
Glucose intolerance
Dyslipidemia
Hypertension

Front 868

What is an example of a monogenic obesity disorder?

Back 868

Leptin deficiency

Front 869

What is an example of a population with polygenic susceptibility to obesity?

Back 869

Pima Indians

Front 870

What is the relationship between frequency of eating out at a restaurant and %body fat?

Back 870

Linear

Front 871

Alcohol has an energy content of..

Back 871

7Kcal/g

Front 872

Energy density of food is most highly correlated with...

Back 872

Water content.

Volume is the main determinant of the amount of food that is consumed at each meal.

Food fat content is a 2º correlate

Thus: Food Energy Density will determine the number of calories eaten at each meal

Front 873

The water content of adipose tissue is approximately...

Back 873

20%

Front 874

What are some easy weight loss actions?

Back 874

Don’t Drink Your Calories !
Discontinue sodas, sugared beverages, flavored lattes and coffee drinks
Reduce consumption of alcohol
Water is the best beverage

Eliminate high-fat, high-calorie snacks
Eat fresh fruits, nuts, low fat cheese sticks

Read labels at the store

Choose foods with a lower fat content, higher protein, and higher fiber content

Increase activities of daily living
Take the stairs, park in the far lot, walk!

Front 875

What is the recommended nutrient content of a Weight-Reducing Diet?

Back 875

55% or more of daily calories from carbohydrates,

15% from protein,

30% or less from fat.

In addition, specific recommendations are made regarding the composition of fat ingestion: total energy intake should be comprised of 8%-10% calories from saturated fat, 10% or less calories from polyunsaturated fats, and 15% or less calories from monounsaturated fats.

Daily cholesterol intake should not exceed 300 mg/d, and daily fiber intake should be between 20-30 g/d.

Front 876

What is orlistat?

Back 876

Orlistat is a competitive inhibitor of gastric and pancreatic lipase

Orlistat inhibits intra-luminal fat digestion and absorptionUndigested fat passes into the colon and is excreted in the stool

Combined with a moderate dietary fat reduction (<30%), Orlistat can result in modest (2-5 kg) weight loss.

Side effects:
Steatorrhea - Gas, bloating, cramping - Increased number of BMs  - Fecal incontinence - Decreased absorption of fat soluble vitamins.

Front 877

What is sibutramine?

Back 877

Sibutramine blocks neuronal monoamine (serotonin, norepinephrine, dopamine) reuptake.

Basically speed.

dry mouth, constipation, and insomnia

Front 878

What is a Roux-en-Y Gastric Bypass?

Back 878

Clinical improvement or resolution in:
60% to 100% of patients with DM
60% to 70% of patients with HBP
85% of patients with sleep apnea
60% to 100% of patients with lipids
90%+ of patients with NASH

Side Effects and Complications:
Bloating, diarrhea, nausea, vomiting
Vitamin B12 deficiency
Iron deficiency anemia
Osteoporosis
Hypoproteinemia and edema
Anastomotic stenosis; internal hernias.

Front 879

What are some specific dieatry treatments for disease?

Back 879

Phenylketonuria :
Decrease phenylalanine

Maple Syrup Urine:
Decrease branched chain AA

Glycogen storage disease: (+) nocturnal starch (uncooked)

Hereditary fructose intolerance: Decrease sucrose and fructose

Galactosemia:
(-) milk/dairy products

Sitosterolemia:
Decrease plant sterols

Adrenoleukodystrophy:
Decrease VLCT,
Increase C18:1+C22:1

Abetalipoproteinemia:
Decrease Fat,
Increase MCT,
Increase vitamins A & E

Front 880

What is abetalipoproteinemia?

Back 880

Rare autosomal recessive disorder

Neonatal diarrhea, steatorrhea

Failure to thrive & poor growth

Very low plasma TG and cholesterol

Absence of chylomicrons, VLDL, LDL, and immunologically detectable apo B

No post-prandial rise in triglycerides

Pre-chylomicrons absent in the golgi

Slice mutation in the MTP gene

Hemolytic anemia

Retinal degeneration

Progressive neurologic dysfunction because of fat soluble vitamin deficiency.

Front 881

How do we treat abetalipoproteinemia?

Back 881

Very low-fat, high carb, high protein diet.

Supplementation with MCT (medium chain triglycerides)

Pharmacologic doses of surfactant solubilized vitamin A and vitamin E.

All clinical features can be prevented.

Front 882

What sort of diet is recommended in renal failure?

Back 882

!Low protein!
Watch Sodium and potassium

Front 883

What sort of diet is recommended for constipation?

Back 883

Increased soluble fiber.

Front 884

What sort of diet is recommended post gastrectomy?

Back 884

((+) Iron, Vitamin B12)

Multiple small, frequent meals

Moderate dietary fat restriction

Oral iron supplementation
Ferrous sulfate (FeSO4) 300 mg PO qD

!Parenteral! vitamin B12
Cyanocobalamin 1 mg IM every month.

Front 885

What clinical features do we expect in post-gastrectomy patients?

Back 885

Early satiety

Dumping syndrome

Iron malabsorption:
Iron deficiency anemia

Vitamin B12 malabsorption:
Macrocytic anemia
Peripheral neuropathy

Front 886

Why does achlohydia lead to iron malabsorption?

Back 886

non-heme iron (from plants) remains in the ferric (Fe+3) form which is poorly absorbed in the duodenum.

Front 887

What is necessary for B12 absorption?

Back 887

R factor made in salivary glands.

IF made by parietal cells must be bound for recognition of the transport protein in the terminal ileum.

Front 888

What diet is recommended for seizure disorders?

Back 888

ketogenic diet

Front 889

What diet is beneficial for parkinson's?

Back 889

Time shift protein intake to help L-dopa absorption.

Protein after lunch.

Front 890

What dietary modification is useful for GERD patients?

Back 890

Decreased xanthines (Coffee, tea)

Front 891

What dietary modification is useful for Irritable bowel syndrome patients?

Back 891

Decreased stachyose (beans, onions)

Front 892

What diet is useful for patients with kidney stones?

Back 892

Decreased oxalate
Increased calcium

Front 893

What is enteric hyperoxaluria?

Back 893

Bile salt malabsorption secondary to disease or resection of the terminal ileum:
Bile salt malabsorption
Decreased Bile salt pool
Fat Malabsorption

This creates a problem with calcium absorption which leads to
increased intestinal oxalate absorption:
Increased urine oxalate concentration.
Recurrent calcium oxalate kidney stones.

Dietary calcium supplementation provides enough calcium to bind to FA’s, BA’s, !!and!! oxalate

Front 894

What is the dietary treatment for enteric hyperoxaluria?

Back 894

Supplemental Calcium
(1 gm CaCO3 qid)

High fluid intake
(>2 liters/day)

Low oxalate diet
(no root vegetables, tea, cocoa, peanuts, bran, and no rhubarb)

Moderate fat restriction

Front 895

What do we currently think helps prevent atherosclerosis?

Back 895

Increased vitamins B6, B12, C, E, folate CoQ, flavinols, isoflavones

Front 896

What do we currently think helps prevent cancer?

Back 896

Increased caroteinoids, glucosinolates, Se

Front 897

What do we think helps prevent breast cancer?

Back 897

Decreased fat
Increased isoflavones

Front 898

What do we currently think helps prevent prostate cancer?

Back 898

Increased isoflavones, lycopenes, vit E

Front 899

What do we currently think helps prevent colon cancer?

Back 899

Decreased fat
Increased calcium, Viatmin C, E and folate.

Front 900

What are three examples of functional food components?

Back 900

Phytosterols (plant sterols)
beta-sitosterol, stigmasterol, campesterol
Decrease cholesterol absorption and therefore plasma LDL

Omega-3 Fatty Acids:
ALA (18:3), EPA (20:5), DHA (22:6)
Decrease TG, anti-inflammatory, brain development

Soy Isoflavones:
genistein, diadzein, coumestrol
Prevent heart disease, osteoporosis, cancer ?

Front 901

What are some characteristics of cholesterol?

Back 901

Important component of cell membranes

Only animals make cholesterol

Cholesterol is inefficiently absorbed by the human intestine (~50% efficiency)

There is very wide person-to-person variability in absorption efficiency

Dietary cholesterol can raise LDL levels, but its impact on LDL is also variable

Front 902

What two transporters is cholesterol absorption dependent upon?

Back 902

NPC1L1:
nondiscriminatory sterol absorber that imports into the enterocyte

ABCG5/G8:
Discriminatory transporter that throws some sterols back into the intestinal lumen.
Much more efficient for plant sterols (phytosterols).

Front 903

What are phytosterols?

Back 903

Plants make Phytosterols (plant sterols):
beta-sitosterol, stigmasterol, campesterol, avenasterol, brassicasterol, and stanols

Unlike cholesterol, phytosterols are poorly absorbed by the intestine (<1% efficiency)

It has been known since the 1950’s that phytosterols inhibit cholesterol absorption

Only recently has the full mechanism of the phytosterol effect been elucidated.

Front 904

What is an example of a phytosterol functional food?

Back 904

Plant Stanol Margarines

Over 40 placebo controlled trials reported

Can achieve up to 14% lowering of plasma LDL when used alone as “monotherapy”

Could produce up to a 30 mg/dl reduction in LDL when used to replace butter in the diet

Can produce up to a 10% additional LDL lowering when taken along with a statin

Palatable, safe, no effect on fat-soluble vits.

Comes in lower calorie (“lite”) versions.

Front 905

What are omega 3 fatty acids?

Back 905

Highly unsaturated
( 3 or more double bonds)

alpha-Linolenic acid (18:3) (ALA):
Essential fatty acid – must obtain from the diet.
Precursor for longer omega 3 fatty acids
Eicosapentaenoic acid (20:5) (EPA):
Precursor for prostanoid synthesis

Docosahexaenoic acid (22:6) (DHA):
Major component of structural phospholipids in the brain (30%) and in the retina (50%)
Maternal intake during pregnancy may affect neonatal retinal and brain development.

Front 906

What are omega 6 fatty acids?

Back 906

Linoleic acid (18:2) (LA) :
Essential fatty acid - must obtain from the diet
Precursor for arachidonic acid synthesis

Gamma-Linolenic acid (18:3) (GLA):
Non-essential precursor for prostanoid synthesis

Arachidonic acid (20:4) (AA):
Substrate for the synthesis of prostaglandins, leukotrienes, and other bioactive prostanoids

Front 907

What does the omega terminology denote?

Back 907

How many carbons from the beginning of the hydrocarbon chain the first double bond appears.

Mammals cannot add double bonds further out than omega 9.

Front 908

What is the importance of EPA and DHA made from omega 3 alpha linolenic acid in contrast to the arachidonic acid made from other fatty acids?

Back 908

They alter the balance of inflammatory prostanoids so that there are less of them by inhibiting the release of arachidonic acid and it subsequent products.

They also form prostaglandins that are far less inflammatory and vasoconstricting.

Front 909

So what is the net effect of omega 3 dietary supplementation?

Back 909

CV:
Lower plasma triglycerides
Lower blood pressure
Anti-arrhythmic effect
Reduce platelet aggregation
Reduce sudden death after MI

Psychiatric:
Reduce incidence/severity of depression
May reduce aggressive behavior

Front 910

What are some newer tentative possible benefits of omega 3 fats?

Back 910

Anti-Inflammatory Activity:
Rheumatoid Arthritis
Asthma
Inflammatory bowel disease
Psoriasis

Neuro-Behavioral Disorders:
Neonatal visual/neural development
Benefit in ADHD and Autism ?
Benefit in memory disorders ?

Front 911

Where do we find omega 3 in food?

Back 911

Oily fish like salmon and anchovies.
(only fish have the longer more efficacious variety)

Flaxseed and canola oil.

Front 912

What are the shortcomings of fish as a source of omega 3?

Back 912

Wild caught fish may contain unsafe levels of methyl mercury or other toxic environmental pollutants (e.g., PCB's)

Farmed fish may have much lower levels of EPA/DHA than wild fish

Concentrated fish oil supplements can leave a fishy taste and fishy breath.

Solution:
Hens fed flax meal (a rich source of ALA) produce eggs with an 8-fold higher DHA content.

Front 913

What is the supposed benefit of eating soy?

Back 913

Soy contains estrogen-like phytochemicals with E2 receptor agonist-antagonist activity

The soy hypothesis:
Soy isoflavones, by their estrogen receptor agonist-antagonist action, protect against ASCVD and estrogen-sensitive disorders.

Addition of soy and/or soy isoflavones to the Western diet can lower the risk of ASCVD and estrogen-sensitive disorders.

Front 914

In practice, what is the benefit of soy?

Back 914

Alternative protein substitutes

Lower cost than animal source protein

Lower fat content than most meats

A "Green" Food

Consume fewer resources and less energy to produce than animal protein

Expand the vegetarian repertoire

Front 915

In summary, what do we know about current functional foods?

Back 915

Stanol fortified margarines effectively lower plasma LDL levels alone or in combination with diet and statins

Omega-3 eggs can increase the daily intake of DHA and EPA and might help modulate inflammatory diseases

Soy products may have a small effect on plasma LDL levels and hot flashes, but evidence for other actions is weak

Front 916

What are some of the currently popular fad diets?

Back 916

Atkins
South Beach
Zone
Sugar Busters
Protein Power
Blood Type
n-Day Miracle
Cabbage Soup

Front 917

What are the main types of fad diets?

Back 917

Very-low carbohydrate (<10%) (ketogenic)

Low carbohydrate, high protein (>20%)

Very-low fat (<10%), high carbohydrate

Very low calorie, rapid weight loss

Specific nutrient or category elimination

Highly regimented / prescribed foods

Front 918

What is the principle underlying the atkins diet?

Back 918

Diets containing higher amounts of protein and moderate amounts of fat may be more satiating than low fat/high carb diets.

Insulin & PG levels “normalized” by “optimum” 40/30/30 nutrient ratio.

Front 919

What is the south beach diet?

Back 919

Description:
Three-phase high protein, low glycemic index carbs, low sat. fat diet
Premise:
Insulin and glucose intolerance normalized by eliminating high GI carbs

Advantages:
Weight loss by mild caloric restriction; wide range of food choices

Disadvantages:
Weigh loss decreases in phase II

Proof:
May have initial superior weight loss efficacy, but not beyond 6 months

Front 920

The ornish and an pritikin diet's are both examples of...

Back 920

Very-Low Fat (<10%)

Front 921

What is the ornish diet?

Back 921

Description:
Ultra low fat, vege based

Premise:
Diet can reduce plasma cholesterol

Advantages:
Weight loss; exercise and stress reduction are part of the program

Disadvantages:
Requires very strong motivation; vege menus not for everyone

Proof:
Weight loss, improved lipids, and reversal of CAD shown in several studies

Front 922

What is the right for your type diet?

Back 922

Description:
Meat, grain, and/or dairy elimination based on ABO blood type

Premise:
ABO type identifies archetypical diet; eating “wrong” foods causes harm

Advantages:
Personalization of one’s diet

Disadvantages:
Book filled with pseudo-science, half-truths, and misinformation

Proof:
NY Times Best-seller

Front 923

What is nutrigenomics?

Back 923

The study of how foods interacts with our genome:

How dietary chemicals alter gene expression

How genetic differences (gene variants) affect the metabolic and physiologic response to food

How diet-regulated genes may play a role in the incidence, progression, or severity of chronic disease

How dietary interventions based on knowledge of genotype (i.e., "personalized nutrition") can be used to prevent, mitigate or cure chronic disease

Front 924

How many SNP's are in the human genome?

Back 924

>10^6

Front 925

What is an allele?

Back 925

A variant gene with a frequency of greater than 1% in a population.

Not all SNPs are alleles

Not all alleles are SNPs

Front 926

Where is the lactase persistence gene located?

Back 926

Mapped to a SNP (C/T-13910) upstream of the lactase gene on chromosome 2

Front 927

Prevalence of Lactase Persistence is highest in...

Back 927

Northwestern europe. (low sunlight)

Helps in calcium absorption in lieu of vitamin D.

Front 928

What are the genetics of taste?

Back 928

Ability to sense different tastes is mediated by five families of lingual taste receptors.

T2R is the bitter receptor.

There is a very wide individual variation in the ability to perceive bitter tastes.

Taster trait (T+) is Mendelian dominant:
Homozygous (TT) –
Supertaster (ST)

Heterozygous (Tt) –
Taster (T)

Homozygous (tt) –
Non-Taster (NT)

Trait caused by polymorphisms in theT2R family of G-protein coupled receptors

~ 35% of USA population are non-tasters

Nausea susceptibility is also highly variable:
~50% of the population has decreased susceptibility.

Non-tasters display a higher maximum nausea than Tasters or Super-tasters

Non-tasters also display a more rapid and higher magnitude rise in mean nausea scores over 16 minutes than Tasters

The traits may have therefore coevolved.

Front 929

What happens to Lipoprotein Metabolism During Lactation?

Back 929

Villus hypertrophy during the last trimester.

Prolactin shuts off peripheral lipid deposition.

If the fat goes to the liver, mom gets it. If it goes to the breast, baby gets it.

Front 930

What is the Apo A-IV-S Allele?

Back 930

S-allele frequency = 20-25% worldwide

Associated with
Increased Post-prandial chylomicron clearance

Increased BMI and increased Adiposity.

More rapid chylomicron clearance may increase the flux of dietary fat into milk.

The S-allele may have evolved to confer a neonatal nutritional advantage.

Front 931

What is the thrifty gene hypothesis?

Back 931

Proposed in 1962 by geneticist James Neel

Postulates that certain genes evolved to maximize metabolic efficiency and nutrient storage

In ancient times, thrifty genes would have conferred a selective advantage during periods of famine.

However, in abundant times, thrifty genes predispose carriers to diseases caused by dietary excess

Ethnic groups with a history of food scarcity will have undergone greater evolutionary pressure, and may harbor more thrifty genes than other populations.