4. Evaluation of the GIT: Introduction
• GIT
– Composed of organs and tissues that have
diverse forms and functions
– Esophagus, stomach, small intestine, large
intestine, colon, rectum, biliary tract,
gallbladder, liver, and pancreas
• Patient history and physical examination remain
important for initial assessment, triage
• In addition diagnostic procedures are essential
in the evaluation of GI disorders
5. Symptoms of Gastrointestinal
Dysfunction
• Heartburn, dyspepsia, abdominal pain,
nausea, vomiting, diarrhea, constipation,
and gastrointestinal bleeding
• Signs and symptoms of malabsorption,
hepatitis, and GI infection
• Warning symptoms include :
– weight loss, intractable vomiting, anemia,
dysphagia, and bleeding
– All clinicians should give due attention
6. Methods commonly used to assess
pts with GI complaints
• Include:
–Careful patient's history
–Comprehensive physical examination
–Routine laboratory tests
–Diagnostic studies and procedures
7. Patient History
• Comprehensive pt history is the cornerstone
• A clear, detailed, chronologic account of the
patient's problems
• Should include:
– the onset of the problem
– the setting in which it developed
– factors that alleviate and aggravate the
problem
– its manifestations
8. Patient History…..
• Lifestyle,…..diet and alcohol intake, use of
medications, …(non-steroidal anti-inflammatory
drugs)
• Travel and potential exposure to infection is
relevant
• Pain or discomfort must be characterized and
localized, and aggravating or relieving factors
ascertained.
• Altered bowel habit, particularly of recent onset, is
significant, as is recent nausea, vomiting or
anorexia (loss of appetite).
9. Patient History…..
• Describe any vomitus and stool
– haematemesis, stool black and tarry (shows
upper GIT bleeding)…. stool fresh blood…
(lower GIT bleeding)
• Weight loss…. malabsorption, chronic
inflammation or cancer
• Liver, gallbladder, pancreas, stomach, small
intestine and colon disorders ….vague, poorly
localized symptoms.
• Family history…. inflammatory bowel disease or
colorectal cancer.
10. General Questions in a GI History
• Tell me about the problem that you are
experiencing. When did it start? What were you
doing when the symptoms began?
• Your pain location? Please point to the area where
you feel pain.
• How rapidly did the pain come on? Is your pain
constant or intermittent? What factors exacerbate
or alleviate your pain? Does the pain awaken you
at night?
• Have you had these symptoms in the past?
• What medications are you taking to help alleviate
the pain? How much do you take? Do these
medications work? ……………………….
11. Drugs that May Cause GI Injury
GI mucosal injury
• Aspirin
• Bisphosphonates
• Chemotherapeutic agents
• Corticosteroids
• Iron preparations
• NSAIDs
• Pancreatic enzymes
• Potassium chloride
• Warfarin
Jaundice
• Androgens
• Chlorpropamide
• Corticosteroids
• Erythromycin
• Estrogens
• Ethanol
• Gold salts
• Nitrofurantoin
• Phenothiazines
• Warfarin
13. Drugs that May Cause GI Injury
Pancreatitis
• Corticosteroids
• Didanosine
• Estrogens
• Ethacrynic acid
• Ethanol
Pancreatitis cont’d….
• Opiates
• Pentamidine
• Sulfonamides
• Tetracycline
• Thiazides
• Furosemide
• Metronidazole
14. Physical Examination
• A comprehensive evaluation of the patient
should be performed
General examination
• Skin turgor (dehydration)
• Skin and sclerae …pallor, jaundice and any
rash.
• Lymphadenopathy … node in the root of the
neck, may indicate gastric cancer.
15. Physical Examination
• A careful examination of the abdomen
– Includes inspection, auscultation, percussion,
and palpation in this order
• Inspection:
– may reveal scars, hernias, bulges, or
peristalsis
• Auscultation
– mainly focused on analysis of bowel sounds
and identification of bruits
– should be performed prior to percussion
and/or palpation
16. Physical Examination
• Percussion of the abdomen
– allows for detection of tympany, measurement of
visceral organ size, and detection of ascites
• Palpation
– allow the clinician to identify tenderness, rigidity,
masses, and hernias
• Digital rectal examination
– used to detect rectal masses and tenderness,
and to assess muscle tone
– Stool on the examiner's glove obtained subjected
to testing for detection of occult blood
17. Laboratory and Microbiologic Tests
• Used to
– assess organ function
– screen for certain GI disorders
– evaluate the effectiveness of therapy
• Should be viewed largely as supportive to an
accurate history and physical examination
– e.g. CBC, A serum chemistry panel
• More specific lab blood tests can be done
• Microbiologic and related studies are useful
in evaluating patients
– Stool examination
18. Laboratory and Microbiologic Tests
Stool examination
• Volume, consistency, colour and the
presence of fat …..indicating malabsorption
• Microscope ….parasites, ova or cysts and
leucocytes or pus cells, which occur in
dysentery or intestinal inflammation
19. Laboratory and Microbiologic Tests
Blood Examination
• Blood count: RBC, platelet and white cell count and
red cell indices, levels of iron, ferritin, vitamin B12
and folic acid…..may be abnormal in malabsorption,
inflammatory bowel disease, liver disease, PUD,
intestinal cancer
• Clotting tests: prolonged PT may indicate synthetic
liver failure or vitamin K deficiency
20. Laboratory and Microbiologic Tests
Liver chemistry:
• Increased Alanine and aspartate transaminase
level …liver cell damage and ….increased alkaline
phosphatase (ALP) and ɣ-glutamyl transferase
(ɣ GT) ….biliary tract disease
• Inflammatory markers: Increased levels of C-
reactive protein (CRP) and a raised erythrocyte
sedimentation rate (ESR) may indicate
inflammatory bowel disease (IBD), acute
pancreatitis or infection.
• Amylase and lipase levels: Acute pancreatitis
causes massively raised amylase or lipase levels
21. Diagnostic studies and procedures
• Radiology
– Radiologic procedures rely on differential
absorption of radiation of adjacent tissues to
highlight anatomy and pathology
• Two divisions
– Non-computer assisted radiologic
procedures
– Computer assisted radiologic procedures
22. Non-computer assisted radiologic procedures
Upper GI Series Radiography
– Refers to the radiographic visualization of the
esophagus, stomach, and small intestine
– Instruct pts to refrain from eating or drinking 8 to
12 hours prior to testing, which allows the upper
GI tract to empty
– contrast agent(Barium sulfate and/or gastrograffin)
is administered to the patient at the beginning of
the study
– commonly uncovers gastric cancer, peptic ulcer
disease, esophagitis, gastric outlet obstruction,
and can be suggestive of Crohn's disease
23. Non-computer assisted radiologic procedures
Lower GI Series Radiography
– used to examine the colon and rectum and is particularly
useful if a colonic obstruction is suspected
– Pts complaining of lower abdominal pain, constipation, or
diarrhea are often referred for a lower GI series, also
called a barium enema
– Patient preparation
• Instruct pts to refrain from eating or drinking 8 to 12 hours prior
to testing
• administering bowel-cleansing agents such as bisacodyl,
magnesium citrate, magnesium hydroxide, or polyethylene
glycol electrolyte (PEG) solution.
– detect and evaluate enterocolitis, obstructions,
volvulus, and mucosal and structural lesions
24. Computer assisted radiologic procedures
• Imaging Studies
– Frequently used imaging procedures for evaluating
digestive disorders
• Transabdominal ultrasonography
• Computed tomography
• Radionuclide scanning
• Magnetic resonance imaging
• GI tract endoscopy
– used to examine the interior of a hollow viscus or
canal
26. Case Studies
• A 53-year-old man, who is otherwise healthy and
has a 20-year history of occasional heartburn,
reports having had worsening heartburn for the
past 12 months, with daily symptoms that disturb
his sleep
• He reports having had no dysphagia, GI bleeding,
or weight loss and in fact has recently gained 20
lb (9 kg)
• What would you advise regarding his evaluation
and treatment?
27. GERD: Introduction
• Definition of GERD:
– A condition that occurs when the refluxed
stomach contents lead to troublesome
symptoms and/or complications
– Esophageal Vs Extraesophageal
28. GERD: Introduction
• Esophageal GERD syndromes classified as
– symptom-based or tissue injury based
• Extraesophageal reflux syndromes
– GERD symptoms associated with disease processes
in organs other than the esophagus
– Patients with extraesophageal reflux syndromes may
present with reflux chest pain syndrome, laryngitis, or
asthma(Atypical symptoms)
29. Epidemiology
• GERD occurs in people of all ages
– Most common in those older than age 40 years
• No major difference b/n men and women
except during pregnancy
• Prevalence depends on geographic region
• Important risk factors and co morbid conditions
– Family history, obesity, smoking, alcohol
consumption, certain medications and foods,
respiratory diseases
30. Pathophysiology
• Key factor in the development of GERD is
– abnormal reflux of gastric contents from the stomach
into the esophagus
• Gastroesophageal reflux is associated with
– defective lower esophageal sphincter (LES) pressure
or function
• Aggressive factors that damage esophagus
up on reflux:
– gastric acid, pepsin, bile acids, and pancreatic
enzymes
31.
32.
33. Complications
• Esophagitis
• Esophageal strictures
• Barrett esophagus
• Esophageal adenocarcinoma
• Esophageal bleeding
– Use of NSAIDs drugs or Aspirin is an additional risk
factor worsening of GERD complications
34. Clinical Presentation
• Symptom-based esophageal GERD syndromes
(with or without esophageal tissue injury)
– Typical symptoms
• Heartburn
• Water brash (hypersalivation)
• Belching
• Regurgitation
– Alarm symptoms (may be indicative of complications)
– Dysphagia , Odynophagia
35. Clinical Presentation
• Tissue injury–based esophageal GERD
syndromes (with or without esophageal
symptoms)
– Symptoms (May present with alarm symptoms such
as dysphagia, odynophagia or unexplained weight
loss.)
• Esophagitis
• Strictures
• Barrett esophagus
• Esophageal adenocarcinoma
36. Clinical Presentation
• Extraesophageal GERD syndromes
– Symptoms (These symptoms have an association
with GERD, but causality should only be considered if
a concomitant esophageal GERD syndrome is also
present.)
• Chronic cough
• Laryngitis
• Asthma
• Dental enamel erosion
37. Diagnostic tests for GERD
• Clinical history
• Barium radiography
• Endoscopy
• Ambulatory pH monitoring
– Identifies patients with excessive esophageal acid
exposure and helps determine if symptoms are acid
related.
• Empiric trial of a proton pump inhibitor as a
diagnostic test for GERD
38. Treatment
• Desired Outcomes
– alleviate or eliminate the patient's symptoms
– decrease the frequency or recurrence and
duration of gastroesophageal reflux
– promote healing of the injured mucosa, and
– prevent the development of complications
• Therapy is directed at :
– augmenting defense mechanisms that prevent
reflux and/or
– decrease the aggressive factors that worsen
reflux or mucosal damage
39. Therapeutic interventions in the mgt of
GERD disease
Pharmacologic interventions are
targeted at improving defense
mechanisms or decreasing aggressive
factors (LES, lower esophageal
sphincter).
40. Two approach: Pharmacotherapy
• Step up approach:
– Starting with noninvasive lifestyle modifications and
patient-directed therapy and progressing to
pharmacologic management or anti-reflux surgery
• Step-down approach,
– starting with a proton pump inhibitor given once or
twice daily instead of an H2-receptor antagonist
– and then stepping down to the lowest dose of acid
suppression (either an H2-receptor antagonist or
proton pump inhibitor) needed to control symptoms
• Neither step up or down approach is superior
41. Evidence-Based Treatment
Recommendations for GERD
• Lifestyle modifications
• Patient-directed therapy
– Nonprescription antacids, H2-receptor antagonists, and PPIs (2
weeks limit if no response) for mild, infrequent heartburn/regur
• Acid-suppression therapy
– The preferred treatment for GERD
– PPIs provide more rapid relief of symptoms and are more
effective at healing the esophageal mucosa compared to H2RAs
in patients with moderate to severe GERD
• Promotility therapy (not as monotherapy)
• Maintenance therapy
– Most need continuous therapy to control sx and complications
• Antireflux surgery
42. Fig: Algorithm for Management of gastroesophageal reflux disease.
H2RA, H2-receptor antagonist; PPI, proton pump inhibitor.
43. Therapeutic Approach to GERD in Adults
• Intermittent, mild heartburn
– Lifestyle modifications plus
– patient-directed therapy
• Antacids: Maalox 30 mL as needed or after meals
and at bedtime and/or
• Nonprescription H2-receptor antagonists (taken up
to twice daily): Cimetidine 200 mg or
• Nonprescription proton pump inhibitor (taken once
daily): Omeprazole 20 mg
• If symptoms are unrelieved with lifestyle
modifications and nonprescription medications after
2 weeks, patient should seek medical attention.
44. Therapeutic Approach to GERD in Adults
• Symptomatic relief of GERD
– Lifestyle modifications plus
– Prescription-strength acid-suppression therapy
• H2RA (for 6–12 weeks): Cimetidine 400 mg twice daily
or
• PPI(for 4–8 weeks): Omeprazole 20 mg once daily
• Treat with maintenance dose if sx recurs, std dose of
PPI or H2RA
• Mild GERD can usually be treated effectively with
H2RA
• Patients with moderate to severe symptoms should
receive a PPI as initial therapy
45. Therapeutic Approach to GERD in Adults
• Healing of erosive esophagitis or treatment of
patients presenting with moderate to severe
symptoms or complications
– Lifestyle modifications Plus
– PPIs for 4–16 weeks (up to twice daily) Omeprazole 20 mg
daily or
– High-dose H2RA(for 8–12 weeks): Cimetidine 400 mg four
times daily or 800 mg twice daily
– For atypical or alarm symptoms, obtain endoscopy
– Give a trial of a PPI. If symptoms are relieved, consider
MT(maintenace therapy)
– PPIs are the most effective MT for patients with atypical
symptoms, complications, and erosive disease
46. Therapeutic Approach to GERD in Adults
• Interventional therapies
– Antireflux surgery
• a viable maintenance alternative for select patients with well-
documented GERD.
– Endoscopic therapies
• Patients not responding to pharmacologic
therapy, including those with persistent atypical
symptoms, should be evaluated to confirm the
diagnosis of GERD
48. Learning Objectives
Recognize differences between ulcers induced by
Helicobacter pylori, nonsteroidal anti-inflammatory drugs
(NSAIDs), and stress-related mucosal damage (SRMD) in
terms of risk factors, pathogenesis, signs and symptoms,
clinical course, and prognosis.
Identify desired therapeutic outcomes for patients with H.
pylori–associated ulcers and NSAIDinduced ulcers.
Identify factors that guide selection of an H. pylori eradication
regimen and improve adherence with these regimens.
Determine the appropriate management for a patient taking a
nonselective NSAID who is at high risk for ulcer-related GI
complications (e.g., GI bleed) or who develops an ulcer.
Devise an algorithm for the evaluation and treatment of a
patient with signs and symptoms suggestive of an H. pylori–
associated or NSAID-induced ulcer.
48 2/8/2023
49. Case Study
A 29 year old man presents with intermittent
epigastric discomfort, without weight loss or
evidence of GI-bleeding. He reports no use of
aspirin or NSAIDs. Abdominal examination
reveals epigastric tenderness. A serologic test for
Helicobacter pylori is positive, and he receives a
10-day course of triple therapy (omeprazole,
amoxicillin, and clarithromycin. Six weeks later, he
returns with the same symptoms.
How should his case be further evaluated and
managed?
49 2/8/2023
50. Peptic Ulcer Diseases
PUD refers to a defect in the gastric or
duodenal mucosal wall that extends through
the muscularis mucosa into the deeper layers
of the submucosa.
Duodenal Ulcer(DU):
Most common form of peptic ulcer
Located in the proximal duodenum
Incidence, death rates, need for surgery, and
physician visits have decreased by 50% over the
past 30 years.
Due to Eradication of H. pylori
Unlike to GU Malignant DUs are extremely rare
50 2/8/2023
51. Peptic Ulcer Diseases…..
Gastric Ulcer(GU)
Less common than DU in absence of NSAIDs
Found distal to the junction b/n the antrum
and the acid secretory mucosa
Occur later in life (peak incidence 6th decade)
Silent ……… presenting only after a
complication
More than half occur in males
PUD can also occur in the
Esophagus, secondery to GERD
Small bowel adjacent to gastroenteric anastomoses
51 2/8/2023
53. Epidemiology
In the USA, PUD affects approximately 4.5
million people annually with lifetime prevalence
estimated to be 11% to 14% in men and 8% to
11% in women.
53 2/8/2023
59. Etiology: Others
Stress-Related Mucosal Damage
Physiologically stressful situations that lead to SRMD
include sepsis, organ failure, prolonged
mechanicalventilation, thermal injury, trauma, and
surgery
Zollinger–Ellison Syndrome
A gastrin-secreting tumor or gastrinoma (Zollinger-
Ellison syndrome) accounts for <1% of all PUs from
uncontrolled acid production
Cigarette smoking is associated with a higher
prevalence of ulcers in patients infected with H.
pylori; however, it does not seem to increase the
risk of recurrence once H. pylori has been
eradicated
59 2/8/2023
60. Etiology: Others
Dietary factors such as coffee, tea, cola,
alcohol, and a spicy diet may cause dyspepsia
but have not been shown independently to increase
PUD risk.
Medications: Corticosteroids, bisphosphonates,
KCl, chemotherapeutic agents, etc
60 2/8/2023
61. Comparison of Common Forms of
PUD
2/8/2023
61
Characteristi
c
H. pylori
Induced
NSAID Induced SRMD
Condition Chronic Chronic Acute
Site of
damage
Duodenum >
stomach
Stomach >
duodenum
Stomach >
duodenum
Intragastric
pH
More dependent Less dependent Less dependent
Symptoms Usually epigastric
pain
Often asymptomatic Asymptomatic
Ulcer depth Superficial Deep Most superficial
GI bleeding Less severe,
single vessel
More severe, single
vessel
More severe,
superficial
mucosal
capillaries
62. PUD: Pathophysiology
PU develop as a result of imbalance between:
Aggressive/Injurious factors e.g., gastric
acid, pepsin, bile salts, pancreatic enzymes
and
Defensive factors maintaining mucosal
integrity e.g., mucus, bicarbonate, blood flow,
prostaglandins, growth factors, cell turnover
62 2/8/2023
63. Figure 2. Balance between injurious and protective factors in peptic ulceration. Injurious
factors (on left-hand side) guide investigations; protective factors (on lower right-hand
side) indicate possible treatment
63 2/8/2023
66. Diagnosis of PUD
Diagnosis of ulcer
either by upper GI radiography or upper endoscopy
Diagnosis of H. Pylori
Non-invasive
C13 or C14 Urea Breath Test- best test for detection of
active infection
Stool antigen test, H. pylori IgG titer (serology)
Invasive
Biopsy and Rapid Urease test
It should be ensured that patients undergoing a breath test, stool
antigen test, or endoscopy are free from medication with PPIs or
H2RAs for a minimum of 2 weeks and antibiotics for 4 weeks prior to
testing
66 2/8/2023
67. Testing to Document H. Pylori Eradication
Should be confirmed after end of therapy;
noninvasive testing with UBT is preferred, 4-8
weeks after completion of therapy
If ulcer recurs after eradication therapy, a more
careful search for reinfection or eradication
failure should be carried out by testing for
presence of active infection (e.g. by histologic
examination & culture, together with antibiotic-
sensitivity test)
67 2/8/2023
68. PUD Treatment: Goal
Rapid relief of symptoms
Healing of ulcer
Preventing ulcer recurrences
Reducing ulcer-related complications
Reduce the morbidity and mortality
68 2/8/2023
69. PUD Treatment: General Strategy
Treat complications aggressively if present
Determine the etiology of ulcer
Discontinue NSAID use if possible
Eradicate H. pylori infection if present or
strongly suspected, even if other risk factors
(e.g., NSAID use) are also present;
Use antisecretory therapy to heal the ulcer if H.
pylori infection is not present
Approach to the patient presenting with ulcer-
like symptoms. Next slide
69 2/8/2023
71. PUD Treatment: General Measures
Lifestyle advice (e.g. diet, smoking, drinking)
Alcohol, strong coffee or tea taken with
moderation
Late snacks are best avoided, b/c stimulate
nocturnal gastric secretion.
Inform Pts to avoid foods that provoke or
aggravate Sxs
Strongly discourage smoking and alcohol
Warn pts against taking any medication : aspirin
& NSAIDs
Anxiety and stress should be reduced if possible
71 2/8/2023
72. PUD Treatment: Pharmacotherapy
H2-Receptors antagonists
Proton pump inhibitors
Cyto-protective agents
Prostaglandin agonists
Antacids
Antimicrobials for H. pylori eradication
Such as clarithromycin, metronidazole, amoxicillin
72 2/8/2023
73. Therapy of H. pylori Eradication
Recommended for HP-infected patients with GU, DU,
ulcer-related complications
First-line eradication therapy
a) PPI–based, three-drug regimen containing two
antibiotics
Usually clarithromycin and amoxicillin
Reserving metronidazole for back-up therapy (e.g.,
clarithromycin–metronidazole in penicillin-allergic
patients)
PPI should be taken 30 to 60 minutes before a meal along
with the two antibiotics.
Although treatment is minimally effective if used for 7 days,
10–14 days of treatment is recommended
Antisecretory drug may be continued beyond antimicrobial treatment
in patients with a history of complicated ulcer (e.g., bleeding or in
73 2/8/2023
74. Therapy of H. pylori Eradication
b) Quadruple therapy using a PPI (with bismuth,
metronidazole, and tetracycline)
achieves similar eradication rates as PPI based
triple therapy and permits a shorter treatment
duration (7 days)
However, this regimen is often recommended as
second-line treatment when a clarithromycin–
amoxicillin regimen is used initially.
All medications except the PPI should be taken with
meals and at bedtime.
74 2/8/2023
75. If the initial treatment fails to eradicate HP, second-
line empiric treatment should:
use antibiotics that were not included in the initial
regimen
include antibiotics that do not have resistance
problems
use a drug that has a topical effect (e.g., bismuth)
be extended to 14 days
Thus, if a PPI–amoxicillin–clarithromycin regimen fails, therapy
should be instituted with a PPI, bismuth subsalicylate,
metronidazole, and TTC for 14 days
Maintenance therapy with a PPI or H2RA is
recommended for high-risk pts with
ulcer complications, pts who fail HP eradication, and
75 2/8/2023
Therapy of H. pylori Eradication
78. Treatment of NSAID-induced ulcers
Nonselective NSAIDs should be discontinued
(when possible) if an active ulcer is confirmed
Most uncomplicated NSAID-induced ulcers heal
with standard regimens of an H2RA, PPI, or
sucralfate if the NSAID is discontinued
If the NSAID must be continued, consideration
should be given to reducing the NSAID dose or
switching to acetaminophen, or a selective COX-
2 inhibitor
PPIs are the drugs of choice when NSAIDs must
be continued because potent acid suppression is
required to accelerate ulcer healing.
78 2/8/2023
79. Treatment of NSAID-induced ulcers
If HP is present, treatment should be initiated with an
eradication regimen that contains a PPI.
Patients at risk of developing serious ulcer-related
complications while on NSAIDs should receive
prophylactic cotherapy with misoprostol or a PPI.
Patients with ulcers refractory to treatment should
undergo upper endoscopy to confirm a nonhealing ulcer,
exclude malignancy, and assess HP status
HP-positive patients should receive eradication therapy.
In HP negative pts, higher PPI doses (e.g., omeprazole
40 mg/day) heal the majority of ulcers.
Continuous PPI treatment is often necessary to maintain
healing.
79 2/8/2023
81. Prevention of Stress-Related Mucosal
Damage
Prevention of stress ulcers involves maintaining
hemodynamic stability to maximize mesenteric
perfusion and pharmacologic suppression of
gastric acid production.
SUP is only indicated in intensive care unit (ICU)
patients with certain risk factors
Indications for stress ulcer prophylaxis include
Major trauma, major surgery, severe head trauma,
multiple organ failure, burns covering more than
25% to 30% of body, severe sepsis, shock,
mechanical ventilation, coagulopathy, and high-
dose steroid use
81 2/8/2023
83. Long-Term Maintenance of Ulcer Healing
Low-dose maintenance therapy with a PPI or
H2RA is only indicated in
patients with severe complications secondary to
PUD such as gastric outlet obstruction or
patients who need to be on long-term NSAIDs or
high-dose corticosteroids and are at high risk for
bleeding.
83 2/8/2023
84. Treatment of GI Bleeding
The immediate priorities in treating patients with a
bleeding peptic ulcer are to achieve IV access,
correct fluid losses, and restore hemodynamic
stability.
Patients should be started on IV PPI therapy
because optimal platelet aggregation, partially
inhibited fibrinolysis, and better clot stabilization on
the ulcer are achieved when the gastric pH is
greater than 6.
IV PPI therapy should be continued for 72 hours
because most rebleeding occurs during this time
followed by oral PPI.
Three-day PPI infusion therapy has been shown to
84 2/8/2023
85. Treatment of Refractory Ulcers
Refractory ulcers are defined as ulcers that fail to
heal despite 8 to 12 weeks of acid suppressive
therapy
The presence of refractory ulcers requires a
thorough assessment, including
evaluation of medication adherence,
extensive counseling and questioning regarding recent
over-thecounter and prescription medication use, and
testing for H. pylori using a different method than
previously done if testing was negative.
85 2/8/2023
86. Treatment of Refractory Ulcers
Treatment strategies
Changing from H2RA therapy to a PPI should be
considered
esophagogastroduodenoscopy (EGD) with biopsy of the
ulcer to exclude malignancy
H. pylori testing (if not done initially)
serum gastrin measurement to exclude ZES, and gastric
acid studies
Increasing the starting dose of PPI therapy may heal up
to 90% of refractory ulcers after 8 weeks of therapy
86 2/8/2023
87. Evaluation of Therapeutic Outcomes
Monitor pts for efficacy and safety of therapy
Ulcer pain typically resolves in a few days when NSAIDs
are discontinued and within 7 days upon initiation of
antiulcer therapy.
The persistence or recurrence of symptoms within 14 days
after the end of treatment suggests failure of ulcer healing
or HP eradication, or an alternative Dx such as GERD.
High-risk pts on NSAIDs should be closely monitored for
signs and symptoms of bleeding, obstruction, penetration,
and perforation
Follow-up endoscopy in pts with
frequent symptomatic recurrence, refractory disease,
complications, or suspected hypersecretory states
87 2/8/2023
89. Patient case
89
C.R., a 28-year-old man, presents to the ED with
jaundice, complaints of fatigue, and vague
intermittent abdominal pain for the past month. C.R.
was diagnosed with hepatitis B 2 years before
admission. His social history includes IV drug abuse
and alcohol abuse (none for 2 years). Several weeks
ago, C.R. noted darkening of his urine and yellowing
of his eyes.
90. Patient case…
90
Physical examination reveals a thin man in no
apparent distress. He is afebrile, and his BP, HR,
and RR are within normal limits. Moderate scleral
icterus is noted. The abdomen is soft and non-
distended. The liver is enlarged, and smooth with
an edge palpable 5 cm below the costal margin
The spleen is palpable. The cardiac, pulmonary,
neurologic, and extremity examinations all are
within normal limits.
91. Patient case…
91
Lab test
PT, 15.4 sec , INR, 1.8; AST, 326 U/L ; ALT, 382 U/L ;
alkaline phosphatase, 142 U/mL ; total bilirubin, 4.2
mg/dL ; and albumin, 2.8 g/dL .
Hepatitis serologic tests are positive for HBsAg,
HBeAg, and anti-HBc and negative for IgM, anti-HBc,
IgM anti-HAV, and anti-HCV.
1. What clinical findings does C.R. have that support
the diagnosis of chronic hepatitis B infection?
2. Does C.R. require treatment for chronic hepatitis
secondary to hepatitis B?
92. Cause of Hepatitis
92
Hepatitis: inflammation of liver; presence of
inflammatory cells in organ tissue
Different causes
infectious (i.e, viral, bacterial, fungal, and parasitic
organisms)
noninfectious (e.g, alcohol, drugs, autoimmune diseases)
A viral hepatitis is a inflammation of the liver due
to viral infection called hepatitis virus
There are five main types of viral hepatitis: A, B, C, D, E
93. Acute and Chronic Hepatitis
93
Viral hepatitis can present as either an acute or
chronic illness.
Acute hepatitis is an illness with a discrete date
of onset with jaundice or increased serum
aminotransferase concentrations >2.5 times the
upper limit of normal.
Acute viral hepatitis infection is a systemic
process and lasts as long as, but not exceeding,
6 months.
Chronic hepatitis is an inflammatory condition of
the liver that involves ongoing hepatocellular
necrosis for 6 months or more
94. Hepatitis virus transmission
94
Hepatitis A and E are typically caused by
ingestion of contaminated food or water (feco-
oral)…. shows acute hepatitis
Hepatitis B, C and D are typically caused by
contact with contaminated blood or body
fluids…..chronic hepatitis (cirrhosis and hepatic
cancer)
Viral hepatitis types B and C together, are the
most common cause of liver cirrhosis and
cancer
95. Epidemiology
95
An estimated 57% of liver cirrhosis and 78% of liver
cancer are due to hepatitis B virus (HBV and HCV
infection
About 150 million people are chronically infected
with HCV
Only 1 in 5 persons exposed to the hepatitis B and
C virus develops acute symptoms, but chronic
infection is common
96. Pathogenesis
96
Both direct and indirect, immune mediated
responses instigated by the virus.
Direct cellular injury …..caused by the accumulation
of intact virus or viral proteins.
Host cellular and humoral immune responses are
linked to T lymphocytes, which enhance viral
clearance from hepatocytes and cause liver injury
host immune responses are more important than
virologic factors in the pathogenesis of liver
injury.
97. Diagnosis of hepatitis virus
97
Physical Exam
Low-grade fever
Significant vomiting and anorexia tachycardia, dry
mucous membranes, loss of skin turgor
Icteric phase: icterus of the sclerae or mucous
membranes
The skin may be jaundiced and may reveal urticarial
rashes.
Liver may be tender and diffusely enlarged with a
firm, sharp, smooth edge.
98. Diagnosis…
98
Lab test
Elevation of serum transaminases not diagnostic,
but useful
ALT elevated more than AST
Acute Hepatitis: ALT > 1000
Chronic HCV: ALT is generally lower than 1000
Serum bilirubin: elevated…Bilirubin levels higher
than 30 mg/dL indicate more severe disease.
99. Serologic evaluation
99
Because the clinical manifestations and
incubation periods are similar among patients
with hepatitis, serologies are useful in
diagnosing the type of viral infection
Detecting specific;
antibodies against hepatitis A virus (anti-HAV),
hepatitis B surface antigen (HBsAg)
hepatitis C antibody (anti-HCV)
hepatitis B envelope antigen (HBeAg)
HBV-DNA
hepatitis D antibody (anti-HDV)
100. Hepatitis A
100
Mild self-limited disease and confers lifelong
immunity to hepatitis A virus. Resolves with in 6
months
Transmission occurs primarily through the fecal–
oral route.
Highest attack rates in 5-14 year olds….children
serve as reservoir of infection
Symptoms and severity of HAV vary according to
age. Children younger than 6 years of age typically
are asymptomatic
102. Clinical manifestation
102
The host is usually asymptomatic during this stage of
the infection
Older children and adults have symptomatic disease
with jaundice occurring in >70% of cases.
Fatigue, weakness, anorexia, nausea, and vomiting.
Abdominal pain and hepatomegaly are common.
Less common symptoms include fever, headache,
arthralgias, myalgias, and diarrhea.
Within 1 to 2 wks patients may enter an icteric phase
with symptoms, including clay-colored stools, dark urine,
scleral icterus, and jaundice.
103. Diagnosis: HAV
103
AST & ALT levels usually return to reference ranges
over 5-20 weeks.
Serum Serology: presence of serum antigens and
immunoglobins
Anti-HAV IgM : positive at the time of onset of
symptoms; results remain positive for 3-6 months
after the primary infection
Anti-HAV IgG appears soon after IgM and generally
persists for many years….. indicative of previous
exposure and immunity to HAV
104. Treatment and Prevention
104
Usually a self-limited disease that does not require
a specific therapy.
Patients should abstain from alcohol during the
acute phase of the disease
Potentially hepatotoxic medications should be
avoided during the acute phase of the illness
Prophylaxis can be administered before (pre-
exposure prophylaxis) or after exposure (post-
exposure prophylaxis
105. Treatment and Prevention…
105
Immunoglobulin…passive immunization
• Pre-exposure(travelers to intermediate and high
HAV-endemic regions)….dose of 0.02 mL/kg of
immunoglobulin administered intramuscularly confers
protection for <3 months, and an IM dose of 0.06 mL/kg
confers protection for 5 months.
• Could be used for post-exposure prophylaxis but not later
than 2 wks…. 0.02 mL/kg IM dose as soon as possible.
Vaccine
Formulations of inactivated hepatitis A vaccine
available (Havrix and Vaqta)
Programs have targeted children as the most
effective means to control HAV.
106. Hepatitis B
106
Approximately 5% of the world’s population is
infected with HBV.
It can occur in the form of chronic persistent hepatitis
asymptomatic or chronic active hepatitis –
symptomatic exacerbations of hepatitis
Causes Cirrhosis of Liver and Hepatocellular
Carcinoma
108. High Moderate
Low/Not
Detectable
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
Concentration of Hepatitis B Virus in
Various Body Fluids
108
109. Sexual: Sex workers and homosexuals are
particular at risk.
Parenteral: IVDA, health workers are at increased
risk.
Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring than
those who are not.
Hepatitis B Virus : Modes of
Transmission
109
110. Clinical Manifestations
110
The clinical features of acute HBV infection are
similar to those described for HAV
infection….nausea, vomiting, anorexia, scleral
icterus, and jaundice.
Extrahepatic manifestations, such as arthralgias,
rash, edema
Complication
most significant complication of acute HBV infection is
acute liver failure (onset of hepatic encephalopathy within
8 wks of the onset of symptoms)
111. 111
Serology evaluation of HBV
I) HBsAg-- anti-HBs system
coating HBV
found in patients with acute or chronic HBV
infection and chronic carriers.
Detectable 1 to 2 weeks after infection….
Persist for 1 to 6 wks in acute hepatitis
HBsAg can be found in : salive, urine, semina,
tears, sweat and breast milk
HBsAb - used to document recovery and/or
immunity to HBV infection.
112. Serology evaluation of HBV…
112
II) HBeAg
Appears shortly after HBsAg
Secreted product of the nucleocapsid core of HBV
Indicates viral replication and infectivity
Anti-HBe is a marker of reduced infectivity
113. Serology evaluation of HBV…
113
III) HBcAg—anti-HBc system
HBcAg can be found in the nuclei of liver cells, no
free HBcAg in serum
HBcAg is the marker of replication of HBV
Anti-HBc IgM is a marker of acute infection and
acute attack of chronic infection of HBV.
Anti-HBc IgG is the marker of past infection
114. Progression
114
Acute HBV Infection: 90% resolve by themselves;
less than 1% develop fulminant hepatic failure
Chronic HBV Infection: 2-10% progress to chronic
state
90% in children under five progress to chronic state
5% to 10% of people progress to HCC
115. Treatment
115
Progression of chronic hepatitis to cirrhosis is
thought to be related to continued replication of
the hepatitis B virus.
Seroconversion from HBeAg-positive to HBeAg-
negative (with appearance of antiHBe),
reductions in serum aminotransferase activity,
elimination of circulating HBV DNA
The most effective agents for treating chronic
hepatitis B have been interferons
116. Treatment ….
116
Interferon
Method of action is the inhibition of viral replication of
cells thus assisting the immune system
Interferon alpha: SQ 5,000,000 U QD or 10,
000,000 U 3x weekly for 1 to 12 months.
Peg interferon available…180 mcg
weekly SQ
117. Treatment ….
117
Adverse effects associated with standard and
PegIFN-a therapy are similar and quite common
Early side effects appear hours after
administration and resemble an influenza-like
syndrome with fever, chills, anorexia, nausea,
myalgias, fatigue, and headache.
Resolve after repeated exposure
Late side effects that may necessitate dose
reduction or discontinuation of therapy altogether.
118. Treatment ….
118
In addition to IFN-a several antiviral agents for
treatment of chronic hepatitis B infection
(lamivudine, adefovir, entecavir, and telbivudine)
• Lamivudine –100 mg PO daily (anti HIV drug)
a nucleoside analogue reverse transcriptase
inhibitor.
Well tolerated, most patients will respond
favorably.
However, tendency to relapse on cessation of
treatment, rapid emergence of drug
resistance.
119. Prevention…per-exposure
119
Vaccination
The preferred vaccination schedule uses a
three-dose regimen. The first dose is
followed 1 month later by a second dose, and
the third dose is administered 6 months after
the initial dose.
Recipients of blood products, household
and sexual contacts of HBV carriers,
travelers to HBV-endemic areas, injecting
drug users, all infants
Side effect is pain at the injection, Transient
febrile, nausea, rash, headache,myalgias, and
120. Prevention…Post-exposure
120
Following exposure to HBV, prophylactic
treatment with hepatitis vaccination and passive
immunization with hepatitis B immunoglobulin
(HBIG)
Percutaneous exposure: single dose of HBIG
0.06 mL/kg (3.4 mL) as an IM
Sexual contact: 0.06 mL/kg of HBIG as a single
IM dose within 14days of the last exposure
Infants born to mothers who are HBsAg
positive IM hepatitis B vaccine and HBIG (0.5
mL) within 12 hours of birth.
121. Hepatitis C
121
HCV causes both acute and chronic infection. Acute
HCV infection is usually asymptomatic, and is only very
rarely associated with life-threatening disease.
About 15–45% of infected persons spontaneously
clear the virus within 6 months of infection without
any treatment.
The remaining 55–85% of persons will develop chronic
HCV infection…..Of those with chronic HCV infection,
the risk of cirrhosis of the liver is between 15–30%
within 20 years
122. 122
Highest incidence is among persons aged 20 to
39 years with a male predominance
HBV and HCV coinfection is common, results in
more severe liver disease than infection with
either virus alone, including increased risk of
liver cancer
123. Transmission
123
Percutaneous Transmission
Blood transfusion (5-10%)
Injection drug users (48-90%)
Non-percutaneous transmission …transmission
between sexual partners and from mother to
child….. Less contagious
124. Clinical Manifestations
124
Most patients with acute HCV infection are
asymptomatic.
Patients with chronic HCV infection generally
complain of fatigue.
Nonspecific symptoms are similar to those seen
with HBV infection, including nausea, anorexia,
abdominal discomfort, and depression.
125. Diagnosis: HCV
125
Serum detection of Anti-HCV; cannot distinguish
acute from chronic infection
Antibodies against core protein and nonstructural
proteins; may appear 3 – 5 months after infection
Confirmed by qualitative HCV RNA (PCR) assay with
a lower limit of detection of 50 IU/mL
126. Treatment
126
Acute infection: if early identification is possible,
interferon therapy is rational.
Chronic active hepatitis.. Combination Peg
interferon and oral daily dose of ribavirin.
Peginterferon alfa-2a.. 180 mcg SQ per week.
Ribavirin is given in divided daily doses (twice per
day): the Ribavirin dose is 1000 mg for patients
who weigh ≤75 kg or 1200 mg for those who weigh
>75 kg.
Treatment with peginterferon plus ribavirin should
be administered for 24 weeks in patients
127. Prevention
127
Pre-exposure Prophylaxis
No vaccines are effective against HCV
Post-exposure Prophylaxis
Immunoglobulin is no longer recommended for post-
exposure prophylaxis of hepatitis C infection because it
is not effective
Others; Screening of blood, organ, tissue donors, High-
risk behavior modification
128. Hepatitis D
128
Only as co-infection with acute HBV or with
superinfection in chronic HBV carrier
Requires outer envelope of HBsAg for replication and
transmission
Can progress to chronic disease
Incubation Period 30 to 150 days
Serology
Hepatitis D antibody (Anti-HDV)
Ab not always present in acute infection---requires
repeating the testing
Risk Factors - Same high risk groups as those for HBV
TX: IFN-alpha
129. Hepatitis E
129
Enterically transmitted infection; fecal-oral route,
typically self-limited
Most outbreaks occur in developing countries.
Symptoms of acute hepatitis
Incubation period of hepatitis E virus is 2-9 weeks
Case fatality rate is 4%
130. Hepatitis E: diagnosis
130
Serum, liver, and stool samples can be tested for
HEV RNA
Anti-HEV antibodies: IgM (acute) and IgG (chronic)
AST & ALT are elevated several days before the
onset of symptoms; return to normal within 1-2
months after the peak severity of disease.
Treatment: supportive
132. Portal Hypertension and Cirrhosis:
Introduction
Definition : Cirrhosis, or end-stage liver disease,
defined as
a diffuse process characterized by fibrosis and a
conversion of the normal hepatic architecture into
structurally abnormal nodules
Results increased resistance to blood flow in
portal hypertension and the development of
varices and ascites
Hepatocyte loss and intrahepatic shunting of
blood results in diminished metabolic and
synthetic function, which leads to hepatic
encephalopathy (HE) and coagulopathy 132
133. Portal Hypertension and Cirrhosis:
Introduction
Clinical consequences of cirrhosis include
impaired hepatocyte function, increased
intrahepatic resistance of portal hypertension, and
hepatocellular carcinoma
Circulatory irregularities such as splanchnic
vasodilation, vasoconstriction and hypoperfusion of
the kidneys, water and salt retention, and
increased cardiac output
133
134.
135. Pathophysiology and Etiology
Cirrhosis results in
Elevation of portal
blood pressure
because of fibrotic
changes within the
hepatic sinusoids
Changes in the levels
of vasodilatory and
Vasoconstrictor
mediators, and
An increase in blood
flow to the splanchnic
vasculature
136. Cont’d… patho
Fatty liver or steatosis from ethanol:
the first stage of liver injury - is characterized by
lipid deposition in the hepatocytes
Steatosis is followed by liver inflammation
(steatohepatitis), hepatocyte death, and collagen
deposition leading to fibrosis
The specific mechanisms: not clear but
suggestions
ethanol-induced oxidative stress on the liver
137. Consequences:
Cirrhosis and the pathophysiologic
abnormalities that cause it result in
Ascites
Portal Hypertension
Esophageal varices
Hepatic encephalopathy, and
Coagulation disorders
138.
139. Clinical Presentation: Sn and
Sx
Anorexia, nausea, abdominal discomfort, weight
loss, and malaise
Ascites, peripheral edema, jaundice, palmar
erythema
Gynecomastia, testicle atrophy, amenorrhea,
pubical hair lost
Hepatomegaly, spleenomegaly, encephalopathy,
and bleeding
140. Laboratory Findings
Initially elevated ALT and AST level but at the end
stage they can be normal or below normal
Elevated bilrubin most of the time
Low albumin level
Prolong prothrombin time (PT) and APTT
Elevated serum creatinine and blood urea nitrogen
(BUN)
An elevation of prothrombin time was the single
most reliable manifestation of cirrhosis.
The combination of thrombocytopenia,
encephalopathy, and ascites had the highest
predictive value.
141. Goal of therapy
The major goals of treating patients with
cirrhosis include:
Slowing or reversing the progression of liver
disease
Preventing superimposed insults to the liver
Preventing and treating the complications
Determining the appropriateness and optimal
timing for liver transplantation
142. Portal Hypertension
Portal pressure is a function of flow and resistance
to that flow across the hepatic vasculature
Normal portal pressure is below 6mmHg, and in
cirrhotic patients may increase to 7 to 9mmHg
Portal hypertension:
results from both an increase in resistance to
portal flow
increased intrahepatic resistance due on
intrahepatic vasoconstriction, sinusoidal
compression, and fibrosis
and also an increase in portal venous inflow
Caused by splanchnic vasodilation
143. Portal Hypertension and Varices
Portal pressure increases to 5 mmHg more than
the pressure in the inferior vena cava
Development of varices and alternative routes of
blood flow
Risk of varices when portal pressure exceed the
vena cava pressure by > 12 mmHg
Hemorrhage from varices occurs in 25-40% of
cirrhotic patients
Each episode of bleeding carries a 30% risk of
death
144. How Varices form
Portal hypertension causes
blood flow to be forced
backward, causing veins to
enlarge and varices to develop
across the esophagus and
stomach from the pressure in
the portal vein
The backup of pressure also
causes the spleen to become
enlarged
145. Management of varices
Involves three strategies:
Primary prophylaxis (prevention of the first
bleeding episode);
Treatment of acute variceal hemorrhage; and
Secondary prophylaxis (prevention of
rebleeding in patients who have previously
bled)
146. Primary Prophylaxis
Nonselective Beta -Adrenergic
Blockade(Propranolol or nadolol)
The mainstay of primary prophylaxis
reduce portal pressure by reducing portal
venous inflow via two mechanisms:
a decrease in cardiac output through beta1-
adrenergic blockade and a decrease in
splanchnic blood flow through beta2-
adrenergic blockade.
HR not less than 55 beats/min & SBP not less
than 90 mm Hg
Adverse effects in 27% of patients
should be continued for life unless it is not
147. BB in Varices…cont’d
Only nonselective β-blockers :
have an adrenergic dilatory effect in mesenteric
arterioles ---- decrease in portal blood circulation and
pressure
Propanolol & Nadolol :
start: Propranolol 20 mg BID or 10 mg three times a day
or nadolol 20 mg once daily
dose titration to a reduction in resting heart rate of 20%
to 25%, an absolute heart rate of 55 to 60 beats/min, or
the development of adverse effects.
Selective β-blockers (e.g., atenolol and metoprolol)
have little effect on mesenteric arterioles
have not been shown to be effective in primary prophylaxis
Isosorbide-5-mononitrate: mentioned; alone vs with
148. Cont’d primary Px
Treatment Recommendations: Variceal Bleeding—
Primary Prophylaxis
Prophylaxis therapy with a nonselective beta -
adrenergic blocker
pts with small varices (< 5 mm) who have not bled
& have no criteria for increased risk of bleeding
……controversy, most agree
Pts with small varices plus risk factors
medium to large varices (varices > 5 mm} & have
not bled plus high risk factor
endoscopic variceal ligation can be used
instead of BB
149. Acute Variceal Hemorrhage
An emergency and feared cxn of cirrhosis
Treatment goals include:
Volume resuscitation, acute treatment of bleeding, and
prevention of recurrence of variceal bleeding
Replenishment of blood volume and correction of
coagulopathy must be done with packed erythrocytes (to
increase Hb concentration to 10 g/dL) and fresh frozen
plasma and platelets
Protection of airway from aspiration of blood
Antibiotics to prevent SBP and G-ve systemic infection
Control of bleeding
Prevention of rebleeding, and preservation of liver
function
150. Drug therapy: Acute variceal Bleeding
Drug Therapy
Drugs employed to manage acute variceal bleeding
include:
The somatostatin analogue octreotide or vapreotide and
Vasopressin, terlipressin,
Work as splanchnic vasoconstrictors, thus
decreasing portal blood flow and pressure
Endoscopic Therapy may be indicated
Endoscopic variceal band ligation (EVL)
151. Drug therapy: Acute variceal Bleeding [2]
Infection Prophylaxis—Short-Term Antibiotics
Norfloxacin 400 mg BID for 7 days Vs no
treatment controls: Norfloxacin group
had a significantly lower incidence of SBP
No significant difference was seen in mortality
Guidelines recommend: 7 days of antibiotic
prophylaxis for prevention of SBP in patients with
variceal hemorrhage with oral norfloxacin (400 mg
BID) or ciprofloxacin IV (400 mg BID) if P.O. no
possible
Ceftriaxone IV (1 g/day) for 7 days : FQ
resistance high
152. Secondary
Prophylaxis/Prevention of
Rebleeding
Secondary Prophylaxis: Prevention of
Rebleeding
Prevent a recurrence of bleeding if survived first
episode of bleeding
Combination therapy with beta-adrenergic
blockers and chronic EVL : best option
Combo : BB + ISDN : unable to undergo EVL
initiation of β-blockers be delayed until after
recovery of the initial variceal hemorrhage
Block the patient’s acute tachycardia if pt
hypotension
Initiate: pt has had no bleeding for at least 24
153. Ascites and Spontaneous Bacterial
Peritonitis
Ascites is the accumulation of
fluid within the peritoneal cavity
Most common complication of
cirrhosis
Spontaneous bacterial
peritonitis (SBP)
is an infection of preexisting
ascitic fluid without evidence
for an intra-abdominal
secondary source such as a
perforated viscus
SBP is almost always seen in
154. Ascites mgt
Goals of therapy
To mobilize ascitic fluid
To diminish abdominal discomfort, back pain,
and difficulty in ambulation
To prevent major complications
Non pharmacological management
Na+ and water restriction, therapuetic
paracentesis
Pharmacological management
Diuretics
Combination of spironolactone and
furosemide
156. Diuretics Therapy: Ascites
Diuretics Therapy: Choice of agent
High level of circulating aldosterone
Decrease execration and increase production
Activation of RAS
hepatic impairment prolongs the half life of aldosterone
Low concentration of albumin
Spironolactone is rational choice
Dose 100 mg to 200 mg up to 400 mg
Combination with other diuretics, Furosemide
Spironolactone to furosemide ratio (100 : 40 mg)
Can be increased every 3 to 5 days simultaneously
keeping ratio
157. Ascite Rx cont’d…
Monitoring: diuretic therapy
Triamterene and amiloride : alternative to spironolactone
if intolerable side effects
goal is a weight loss of 0.5 to 1 kg/day
net fluid volume loss of about 0.5 to 1 L/day
If presented with both edema and ascites : initial fluid
loss of up to 1 L/day would be reasonable
Diuresis > 0.5 to 1 kg/day (0.5–1 L) : associated with
volume depletion, hypotension, and compromised renal
function
Monitoring fluid intake and urine output
urine output should exceed fluid intake by about 300 to
1,000 mL/day
158. Diuretic Complications and
Management
Initiate: with single morning doses of spironolactone
100 mg and furosemide 40 mg administered orally
Titrate diuretic therapy every 3 to 5 days using the
100 mg:40 mg ratio to attain adequate natriuresis
and weight loss
reasonable daily weight loss goal is 0.5 kg
Maximum daily doses are 400 mg spironolactone
and 160 mg furosemide….. maintains
normokalemia
D/C diuretic: experience uncontrolled or recurrent
encephalopathy, severe hyponatremia, renal
insufficiency
159. Cxn…cont’d..
Electrolyte And Acid-base Disturbances
Hyponatremia, hyperkalemia, metabolic alkalosis
Hyponatremia : temporary withdrawal of
diuretics and free water restriction
Hyperkalemia [in refractory ascites and
impaired renal function requiring high doses of
spironolactone]
Decreasing or holding spironolactone
depending on renal function and serum
potassium
Metabolic alkalosis [hypokalemia] : Furosemide
can be temporarily withheld
160. Drug therapy: SBP
SBP
>92% of all cases of SBP are monomicrobial, with
Escheria coli (the most common isolate),Klebsiella
species, Other G-ve bacteria
G+ve organisms, Streptococcal (25%)
Anaerobic infection (rare <5%)
Consider antibiotic coverage for these condition
Third-generation cephalosporin : DOC for SBP
Prophylaxis against SBP
Short-term antibiotic prophylaxis should be used for 7
days to prevent SBP in cirrhosis patients with
gastrointestinal hemorrhage
Patients who survive an episode of SBP should receive
long-term prophylaxis with either daily norfloxacin or
162. Hepatic Encephalopathy (HE)
Hepatic encephalopathy is a neuropsychiatry syndrome
caused by liver disease
The principles of mgt are
To treat or remove precipitating causes
To reduce or eliminate protein intake and
To suppress production of neurotoxins by bacteria in
the bowel
The mainstay of therapy of HE involves measures to
lower blood ammonia concentrations and includes diet
therapy, lactulose, and antibiotics alone or in combination
with lactulose
Lactulose (15-30 ml 8-hourly) administration lowers
ammonia levels in the blood in several ways
163. HE… cont’d…
Lactulose lowers ammonia levels in the blood
creation of a laxative effect
reduces the time period available for ammonia
absorption
leaching of ammonia from the circulation into the
colon
increasing bacterial uptake of ammonia by
colonic bacteria
reducing ammonia production by the small
intestine
By interfering directly with the uptake of
glutamine by the intestinal wall and its
164. HE… Rx…cont’d…
Metronidazole or Neomycin : inhibiting the activity of
urease-producing bacteria
decrease production of ammonia
Metronidazole initiated at 250 mg twice daily but
titrated up to four times daily
should not be considered first-line therapy
Indicated: who have not responded to diet and
lactulose therapy & if deemed necessary for
improved outcome
Rifaximin 400 mg three times daily provides similar
effectiveness with less risk
Zinc replacement: decreasing ammonia levels and
improving symptoms of HE
165. Evaluation of Therapeutic Outcomes
Monitoring Parameter
Ascites
Daily assessment of weight
Spontaneous bacterial peritonitis
Evidence of clinical deterioration (e.g., abdominal pain, fever,
anorexia, malaise, fatigue)
Variceal bleeding
Child-Pugh score, endoscopy, CBC, evidence of overt bleeding
Hepatic encephalopathy
Grade of encephalopathy, EEG, psychological testing, mental
status changes, concurrent drug therapy
168. Patient case #1
168
A 49-year-old man was admitted with a nine-month
history of intermittent attacks of epigastric pain,
jaundice and fever. These attacks usually last up to
several days associated with nausea and vomiting.
He was well in between attacks and had no loss of
weight
What is likely diagnosis for this patients?
169. s
169
Function of the pancreas is to release digestive enzymes
and insulin and glucagon .
Ampull
a of
Vater
171. Definition
171
Pancreatitis is an inflammation of the pancreas
Two forms:
Acute pancreatitis
Sudden…...mild to sever
often non-reoccurring …..90% self-limiting and
resolves in a wk
Do not progress to chronic form
Chronic Pancreatitis
ongoing occurrence of inflammation
marked by ON and OFF abdominal pain
172. Epidemiology
172
300,000 case annually in US
10-20% are severe
Biliary and alcoholic cases account 90% ….biliary
pancreatitis being the most prevalent type.
Incidence among AIDS patients 4-22%
Incidence ……..increase w/ age.
Onset in the first decade suggests ….a hereditary
cause, infection (e.g., mumps), or trauma.
173. Etiology - I GET SMASHED…
173
I -idiopathic………no etiology is identified
G -gallstone…..Gallstones may get stuck in
the Ampulla of Vater causing to backflow then into
pancrease
E -ethanol (alcohol)….60-90% of patients have a
history of alcohol abuse…. Second next to gall stone
for acute case
T -trauma
S -steroids
M -mumps and other viruses (Epstein-Barrvirus,
Cytomegalovirus)
175. Etiology - I GET SMASHED…
175
A -autoimmune disease (Systemic lupus
erythematosus)
S -scorpion sting (e.g. Tityus trinitatis), and
also snake bites
H-hypercalcemia, hyperlipidemia and hypotermia
E - Endoscopic Retrograde Cholangio-
Pancreatography………a procedure that
combines endoscopy and fluoroscopy
D -Drugs………….four categories
176. Etiology - I GET SMASHED…
176
Four Categories……………..drugs account for 2%
incidence
Drugs that exacerbate high triglycerides
Estrogens, steroids, isotretinoin, hydrochlorothiazide,
furosemide, and protease inhibitors
Drugs that cause hypersensitivity
Aminosalicylates, tetracycline, azathioprine, TMP/SMX, or
ACEI
Drugs that have a toxic effect
Valproic acid, statins, sulindac, metformin, and didanosine
Drugs that cause pancreatic spasm.
Opiates and octreotide are thought to cause spasms of
the sphincter of Oddi
177. Pathophysiology
177
• The events that initiate an inflammatory process
are still NOT well understood
• Trypsinogen- (a proteolytic enzyme)is normally
released into the small intestine, where it is
activated to trypsin
• Acute pancreatitis involves premature activation
of trypsinogen in to trypsin with in the
pancreas, leading to activation of other digestive
enzymes and autodigestion of the gland
178. Clinical manifestation#1
178
Abdominal pain:
may be continuous, intermittent or absent
Pattern is often atypical
RUQ or LUQ of the back
Diffuse throughout upper abdomen
Typical form:
Persistent , deep-seated,
Unresponsive to antacids
Worsened by alcohol intake or a heavy meal
(especially fatty foods)
Often need narcotics
Acute pancreatitis related to alcohol occur …..one to
three days after cessation of drinking.
179. Clinical manifestation#2
179
Nausea and vomiting
Incidence………90 percent of patients
Duration……….may persists for many hours
Associated symptoms………. Restlessness,
agitation, and relief on bending forward
Patients with fulminant attacks may …… present in
shock or coma.
Painless disease….in only………….5 to 10%
Most the pain is severe……….Emergency
department visit and hospital admission is required
180. Clinical manifestation #3
180
Pancreatic insufficiency
Weight loss
Fat malabsorption:
Steatorrhea: 15% of patients present with
steatorrhea and no pain… occur in chronic
pancreatitis(>90% of pancreas is lost)
Pancreatic diabetes:
Like DM1 needs insulin
181. Complications
181
Necrotizing pancreatitis…….when pancreatic cell die
Leads to cyst or pocket like space
May lead into leakage of fluid containing toxins and
enzymes leaks from the pancreas through the abdomen.
This can damage blood vessels and lead to internal bleed
Respiratory Complications – due to irritation of
diaphragm
shallow breathing
inflammatory exudates, and dyspnea
182. Complications
182
Ecchymotic discoloration of the flanks …….
the escape of blood into the tissues from ruptured blood
vessels
Grey-Turner's sign .
Bruise like …….b/n ribs and hip bones
The periumbilical region (Cullen's sign) ….
Retroperitoneal bleeding in patients with pancreatic
necrosis.
Incidence: 1%......They reflect intra-abdominal
hemorrhage - a poor prognosis.
185. Chronic pancreatitis
185
Chronic pancreatitis results from long standing
inflammation leading to irreversible
parenchymal destruction leading to pancreatic
dysfunction
Chronic alcohol consumption , especially heavy
drinking remain leading cause
Leads to………Persistent, recurrent episodes of
severe pain
Symptoms;
Anorexia, nausea
Constipation, flatulence
Steatorrhea
Diabetes
186. Prognosis
186
The overall mortality rate……..10-15%
May be as high as…………..30%
Patients with biliary pancreatitis tend to………
have a higher mortality rate than patients with alcoholic
pancreatitis.
In the first week of illness……………….most deaths
result from multi-organ system failure.
In subsequent weeks………………….infection
plays a more significant role
187. Diagnosis#1
187
Physical exam
Palpable epigastric mass - pseudocyst
Less common features:
subcutaneous nodular fat necrosis (panniculitis),
thrombophlebitis in the legs, and polyarthritis.
Fat necrosis lesions……0.5 to 2 cm
tender red nodules, located over the distal extremities but
may occur elsewhere.
188. 188
Laboratory Evaluation/ Pancreatic enzymes
Early in the course of acute pancreatitis……..
there is a breakdown in the synthesis-secretion coupling of
pancreatic digestive enzymes
i.e synthesis continues while there is a blockade of
secretion.
As a result………….
digestive enzymes leak out of acinar cells through the
basolateral membrane to the interstitial space and….then
the systemic circulation.
Diagnosis #2
189. Diagnosis#3
189
Amylase…Nonspecific !!!
Amylase levels > 3x normal very suggestive of
acute pancreatitis
May be Normal in chronic pancreatitis!!!
Enzyme level severity
False (-)……..EtOH…………..or …………….Hyper-
TG
False (+) …….renal failure, other abdominal or
salivary gland process, acidemia
190. Diagnosis#4
190
Serum amylase (70-200 u/mL)
Is the most frequently ordered test to diagnose
acute pancreatitis.
Rises within …6 to 12 hours of onset
Cleared fairly rapidly from the blood
half-life 10 hours
In uncomplicated attacks………..
serum amylase is usually elevated for three to
five days.
191. Diagnosis#5
191
Serum Lipase (0 – 160 U/mL)
Less frequently ordered than amylase b/s…...Difficult
to perform and lacked precision
Inclusion of co-lipase in the assay of commercially
available kits has improved… diagnostic accuracy.
Sensitivity…………85 to 100 percent
However………..nonspecific elevations of lipase have
been reported in almost as many diseases as
amylase.
192. Diagnosis#6
192
Other inflammatory markers will be elevated
ALT > 3x normal gallstone pancreatitis
96% specific but …………only 48% sensitive
Depending on severity may see:
Ca WBC
Hct BUN
glucose
Bilirubin…..25% pancreatic edema leads to compression of
the bile duct
193. Diagnosis#7
193
Radiographic Evaluation
US or CT
show enlarged pancreas with stranding, abscess,
fluid collections, hemorrhage, necrosis or
pseudocyst
MRI…………..the newest
Better visualization of fluid collections
Endoscopic/Ultrasonography …………
even newer but used less
Useful in obese patients
194. Management
194
Supportive care is very important part of the
management
Control of Pain……..Narcotic analgesics
Maintain Fluid/electrolyte balance
Correction of malabsorption with
………….adequate enzyme replacement and
nutrition
Remove offending agent ………..if possible
195. Non-pharmacological#1
195
No oral food ………….until pain free…..pancreatic
rest
Avoid fatty food to decrease pancreatic stimulation
Nasojejunal suction for patients with emesis
TPN may be needed
Aggressive volume repletion with IVF
Keep an eye on fluid balance/sequestration and electrolyte
disturbances
Avoidance of alcohol/other offending agents
Prevention of Shock – hemodynamic stability
* Administer Blood, Plasma expanders,
Albumin
196. Non-pharmacological #2
196
Treatment Endoscopic therapy
controls pain in some patients who have a prominent
stricture in the proximal pancreatic duct.
dilation is followed by ……………stent placement across
the stricture.
Pain improves in ………….55 to 100% of selected patients
with an isolated proximal stricture during 2 to 69 months of
follow-up.
Surgery…………….
If all measures fail to relieve pain, which is superior to
endoscopic drainage
197. Pharmacological#1
197
Treatment- Pain control
Cause …………Pancreatic ductal hypertension
secondary to pancreatic outflow obstruction
Medications:
Acetaminophen or NSAIDs
Opiate analgesics
Meperidine 50-100 mg Q3to 4 hrs IV… max
dose 600mg/day
Hydrocodone, 10 mg every 6 hours as needed
198. Pharmacological#2
198
Meperidine ……….. Pethidine
Favored over morphine
Human studies showed that morphine caused …….an
increase in sphincter of Oddi pressure.
Despite these data there is no ………..clinical evidence to
suggest that morphine can aggravate or cause pancreatitis
or cholecystitis.
Problem with Meperidine
normeperidine accumulation after repeated doses of
meperidine……………. in renal failure
seizures - neuromuscular irritation
199. Pharmacological#3
199
Pain Control - Fentanyl IV
An alternative agent ………..if large doses of
meperidine needed
ADR…………..Respiratory function depression
Drug Interaction………..
Concurrent use of a calcium channel blocker and
a beta-adrenergic blocker with fentanyl has
resulted in severe hypotension.
200. Pharmacological#4
200
Treatment Hyperlipidemia
high TG >500 mg/dl should be treated……………..
Fibric acid derivatives, ……Gemfibrozil,
fenofibrate
Niacin, and omega-3 fatty acids.
High doses of a strong statin ……………
simvastatin, atorvastatin, rosuvastatin
also…….lower triglycerides, by as much as
approximately 50%.
e.g., atorvastatin starting at 10 to 20 mg/day
201. Pharmacological#5
201
The somatostatin analogue …octreotide
Mechansim………….
inhibits pancreatic secretion and has visceral
analgesic effects.
Octreotide may also ………..
have a role in the management of refractory
pancreatic fistulas or pseudocysts.
202. Pharmacological#6
202
Oral pancreatic enzymes
Pancreatic steatorrhea …….stool becomes smelly
A reduction in dietary fat
Pancreatic Enzyme
25,000 to 30,000 units of lipase per meal
H2-receptor antagonists or proton pump inhibitors
Increase effectiveness of enzyme therapy for
malabsorption and steatorrhea
Also for stress ulcer
204. Pharmacological#7
204
Treatment autoimmune chronic pancreatitis
Steroids……dramatic response within 4 weeks.
Prednisolone is initiated at …………
30 to 40 mg/day for 1 to 2 months and
tapered by 5 mg every 2 to 4 weeks.
Maintenance dose…………..
5-10 mg/day of prednisolone needed to prevent relapse.
205. Complication: Infection
205
Acute necrotizing pancreatitis…….
leading cause of morbidity and mortality
Incidence……… 30%
Patients who develop infection tend to have
more extensive necrosis compared to those in
whom the necrotic tissue remains sterile.
Occurs late……..
in the course of necrotizing pancreatitis
206. Complications: Infection
206
Many areas for concern…………..
abscess, pancreatic necrosis, infected
pseudocyst, cholangitis,
SEPSIS may occur
Use of broad-spectrum antimicrobials
Multiple organisms…..bowel flora
Prophylactic antibiotics………is NOT
recommended
Necrotizing pancreatitis
Significantly increases morbidity & mortality
Usually found on CT with IV contrast
207. Pancreatitis: Infection
207
Organisms…………..gut-derived
Escherichia coli, Pseudomonas, Klebsiella, and
Enterococcus spp.
Initiate with in 48 hrs and continue for 2 to 3
wks.. Imipenim –cilastatin 500mg TID
FQ + metronidazole … 2nd line
Fungal infection /Gram positive……. Uncommon
prophylactic antibiotic use for more than 10 to 14
days…….Is not recommended.
208. Complications: Pseudocysts
208
Defined as accumulation of pancreatic fluid in a
cavity like structure
Incidence……….25%
More common with alcoholic pancreatitis
Resolves spontaneously in most cases
Persistent pain or continued high amylase levels
may be present for 4-6 wks afterward
Cyst may become …….
infected, rupture, hemorrhage or obstruct adjacent
structures
Asymptomatic, non-enlarging pseudocysts can be……
watched and followed with imaging
Symptomatic, rapidly enlarging or complicated
pseudocysts… need to be decompressed
