ACID-PEPTIC DISORDERS

Sylvester Chuks Nwokediuko

Professor of Medicine, University of Nigeria Ituku/Ozalla Campus,
Consultant Physisian & Gastroenterologist, University of Nigeria
Teaching Hospital Ituku/Ozalla
Outline
• Definition
• Types
GERD
▪ Etiopathogenesis
▪ DIAGNOSIS
▪ Treatment
PUD
❖Etiopathogenesis
❖Problem of Helicobacter pylori eradication
Conclusion
Introduction/Definitions
• Acid-peptic disorders include a Other Acid-peptic
number of conditions whose disorders
pathophysiology is believed to
be the result of damage from • Gastritis
acid and pepsin activity in the
gastric secretion. • Zollinger-Ellison
• The 2 most common and well- syndrome
defined entities are: • Meckel’s diverticular
1) Gastroesophageal reflux ulcer
disease (GERD)
2) Peptic ulcer disease (PUD) • Functional dyspepsia
Gastroesophageal reflux disease (GERD)
Definition of GERD Heartburn and
A condition which develops Regurgitation have
when the reflux of stomach
contents causes modest sensitivity
troublesome symptoms and specificity for the
and/or complications. diagnosis of GERD
Montreal Consensus Definition 2006
Dent et al. Gut 2010; 59:714-721
Vakil et al Am J Gastroenterol 2006; 101: 1900-
1920
 Montreal definition contd.
Esophageal Symptoms
Extraesophageal Symptoms

Symptomatic Syndrome with

syndrome Esophageal Injury
Established Proposed
Associations Association
1. Typical reflux 1. Reflux Esophagitis
syndrome 2. Reflux Stricture
2. Reflux chest pain 3. Barret’s esophagus
syndrome 4. Esophageal
AdenoCA

1. Reflux cough 1. Pharyngitis

syndrome 2. Sinusitis
2. Reflux laryngitis 3. Idiopathic
syndrome pulmonary fibrosis
3. Reflux dental erosion 4.Recurrent otitis media
syndrome
Montreal
Strengths
• Symptom-based, patient
centered
• Obviates need for elaborate
investigation
• Early deployment of acid
suppressants
• Recognized the role of non-
acid reflux albeit undetailed.
Flip side
• Functional disorders (RH, FH)
lumped together with other
GERD phenotypes
• Typical symptoms lack sensitivity
and specificity; PPI use neither
sensitive nor specific
• Different meanings of heartburn
to clinicians/pts
• Varying role of acid in generation
of different symptoms
Determinants of GERD symptoms
• the number of reflux episodes,
• the proximal extent to which the refluxate
migrates,
• the acidity of the refluxate,
• oesophageal hypersensitivity and
• cognitive hypervigilance.
GERD phenotypes
Esophageal hypersensivity-mechanisms
Esophageal hypersensitivity is defined as the perception of non-painful esophageal stimuli as being
painful and the perception of painful esophageal stimuli as being more painful
• Peripheral sensitization
• Central sensitization
• Altered central processing of esophageal stimuli,
• Hypervigilance,
• Altered autonomic activity,
• Psychological co-morbidity

1. Hershcovici T, Fass R. Nonerosive reflux disease (NERD) - an update. J Neurogastroenterol Motil. 2010;16:8–21
2. Miwa H, Kondo T, Oshima T, Fukui H, Tomita T, Watari J. Esophageal sensation and esophageal hypersensitivity -
overview from bench to bedside. J Neurogastroenterol Motil. 2010;16:353–362
3. Dickman R, Maradey-Romero C, Fass R. The role of pain modulators in esophageal disorders - no pain no
gain. Neurogastroenterol Motil. 2014;26:603–610
Heartburn not synonymous with GERD but a
presentation of GERD
Other causes of heartburn
•Reflux hypersensitivity**
•Functional heartburn**
**(now classified as esophageal disorders in
the Rome IV FGIDs)
Symptoms and response to acid suppressants
Hugin et al. Am J Gastroenterol 2019; 114: 414-421
The Lyon Consensus evaluated GERD diagnostic tests from the standpoint of the
heterogeneity of the condition, and test results were categorised as being adequate
to establish or refute a GERD diagnosis or inconclusive in the absence of additional
supportive evidence. Gyawali et al. Gut 2018; 67: 1351-1362
Physiology of major GERD syndromes
Katzka et al. Clin Gastroenterol Hepatol 2020;18:767-776
Montreal, Rome, and Lyon
• It is increasingly clear that many presentations of GERD represent distinct
phenotypes with unique predisposing cofactors and pathophysiology
• Three major consensus initiatives have grappled with this dilemma (the
Montreal Consensus, The Rome Foundation, and the Lyon Consensus),
each from a different perspective.
• Montreal struggled to define the disease,
• Rome sought to characterize its functional attributes,
• while Lyon examined its physiological attributes.
• Available evidence supports the view that GERD is actually a family of
syndromes with a complex matrix of contributing pathophysiology.
Global prevalence of GERD, Gut 2005;54:710–7 Worldwide prevalence of GERD symptoms, El-Serag et al 2014
Eusebi et al. Global prevalence of, Global prevalence: Ashworth et al Lancet gastroenterol
and risk factors for, gastro-oesophageal Hepatol 2020; 5; 561-81
reflux symptoms: a meta-analysis.
Gut. 2018 Mar;67(3):430-440.
Prevalence
• Global prevalence of 2.5%-51.2% (different definitions)
• Pooled prevalence of 13.3%(using weekly frequency of heartburn or
regurgitation)
Eusebi et al. Gut 2018; 67: 430-440
• In 2015, the total direct economic impact of GERD and its
complications was estimated to be over $18 billion, with use of
proton pump inhibitors (PPIs) accounting for $12.4 billion, while the
indirect costs driven by decreased work productivity were as much as
$75 billion.
Peery et al. Gastroenterology 2019; 156: 254-272
Prevalence of GERD in Nigeria = 7.6%
Nwokediuko et al. BMC Gastroenterology 2020; 20: 107-114

Risk factors
• Use of NSAIDs
•Use of Herbs
BMI: no effect
Risk Factors
• Age • Connective tissue disease
• Race/Gene/Geography (Scleroderma)
• Sex • IBS
• BMI (Obesity) • COAD
• Hiatus Hernia • Helicobacter pylori eradication
• Smoking, Alcohol, Coffee, • Drugs
Chocolate
Medications that can cause GERD or esophagitis
Decrease LES Pressure Cause Direct Mucosal Injury

Alendronate
b-Adrenergic agonists, including inhalers
Aspirin

a-Adrenergic antagonists Iron salts

Anticholinergics Nonsteroidal anti-inflammatory drugs

Calcium channel blockers Potassium chloride tablets

Diazepam Quinidine
Estrogens Tetracycline
Narcotics
Progesterone
Theophylline
Tricyclic antidepressants
Pathophysiology:
The Lower
Esophageal
Sphincter is
The primary
focus relating
to GERD.

Image with permission from Dr. Scott Tenner

Pathophysiology
• The antireflux mechanism • Pump (Motility, Saliva,
consists of a valvular cardia,
the propulsive pump action of
Gravity, Anatomy)
the esophagus and a • Valve (Pressure,
reservoir function of the Length, Position)
stomach. Failure of any of
these components may lead • Reservoir (Pressure,
to abnormal esophageal Dilatation, Impaired
exposure to gastric juice.
emptying, Secretion)
Savarino et al. Nat Rev Gastroenterol Hepatol 2017; 14: 665-676
Acid pocket
Diagnosis:
• Symptom/Questionnaire
• PPI trial
• Endoscopy and Biopsy (Histology)
• Ambulatory reflux monitoring
• Impedance reflux monitoring
• High resolution manometry
It is interesting that the place of manometry in the management of GERD has
expanded from being merely an adjunctive investigation for a subset of patients
requiring fundoplication, to being a significant diagnostic tool.
Gyawali C.P., Roman S., Bredenoord A.J., et al. Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions
from an international consensus group. Neurogastroenterol Motil. 2017;29.
Novel metrics:
• Post reflux swallow induced peristaltic wave (PSPW),
• Mean nocturnal baseline impedance (MNBI)
• Baseline impedance at endoscopy,
• EGJ barrier function (HRM)
• Esophageal peristaltic function. Distal contractile integral (DCI on HRM
• Provocative tests like multiple rapid swallows (MRS) and rapid drink challenge
(RDC)
• Functional lumen imaging probe (FLIP). This can evaluate esophageal
distensibility and contractility and diagnose obstructive motility disorders
masquerading as GERD during the same index endoscopy).
Management
If classic symptoms of
heartburn and
regurgitation exist in
the absence of “alarm
symptoms” the
diagnosis of GERD can
be made clinically and
treatment can be
initiated
Alarms
Alarm Signs/Symptoms
• Dysphagia
• Early satiety
• GI bleeding
• Odynophagia
• Vomiting
• Weight loss
• Iron deficiency anemia
Other indications for gastroscopy

• Persistent symptoms despite an adequate trial of proton pump

inhibitor therapy
• Treatment of complications such as dilatation of oesophageal
strictures
• Evaluation of patients before and after anti-reflux surgical procedures
• Screening for Barrett’s oesophagus in high-risk patients (may be
considered, e.g. in overweight men over 50 years, however evidence
that screening improves outcomes is lacking
Table 1
Currently Available Therapeutic Modalities for Gastroesophageal Reflux Disease

Type of therapy Subtype

Lifestyle modifications Raising head end of the bed
Avoiding meals within 3 hours of bedtime
Weight loss
Medical Antacids
Gaviscon
Proton pump inhibitors
H2 receptor antagonists
Prokinetics
Baclofen
Carafate
Surgical Fundoplication
Linx™ magnetic ring
Endoluminal therapies Transoral incisionless fundoplication
Stretta
Drugs
• Antacids PPI is first line treatment for GERD
• Alginates • PPIs have demonstrated clear
• Mucosal protectants eg Sucralfate superiority to H2RAs and as such
are recommended as first line
• H2 receptor antagonists agents for GERD patients
• PPIs Maintenance treatment with PPI
• Prokinetics • Recurrence of symptoms following
• tLESR inhibitors (Baclofen) discontinuation of PPI
• Antidepressants • Erosive reflux disease
• Barret’s esophagus
Reflux hypersensitivity and functional heartburn are
commonly managed with neuro-modulators which
include:
• Tricyclic antidepressants,
• Selective serotonin reuptake inhibitors,
• Serotonin-norepinephrine reuptake inhibitors and
• Trazodone.
Barrett’s mucosa
• Barrett’s Esophagus
• Acid damages lining of
esophagus and causes chronic
esophagitis
• Damaged area heals in a
metaplastic process and
abnormal columnar cells
replace squamous cells
• This specialized intestinal
metaplasia can progress to
dysplasia and adenocarcinoma
Complex relationship
between H pylori and the
common cancers of the
esophagus and stomach.
Data are shown as odds
ratios for the
development of cancer in
H pylori–infected vs
uninfected persons.
Safety of long term PPI
• Nutritional deficiencies (magnesium, vitamin B12),
• Increased risk of gastroenteritis, travelers’ diarrhea,
• Clostridium difficile colitis,
• Osteoporosis and bone fracture,
• Microscopic colitis,
• Community-acquired pneumonia may be more common during short term use.
• Ischemic heart disease,
• Chronic kidney injury and
• Dementia.
• Most recently, HCC
Overall, the risk of any of the aforementioned side effects due to long-term treatment
with a PPI is relatively modest, studies mainly population-based and retrospective.
GERD in pregnancy
❖GERD may affect 30-50% of pregnant women
❖Weight gain in pregnancy and increased maternal age are risk factors
❖Data on safety of PPI in pregnancy still conflicting.
❖Lifestyle modification and antacids may be adequate for most
patients
❖Need for acid suppression to be determined on case-by-case basis.
 Surgery
• A long-term option
• Outcome similar to medical treatment
for a selected group of patients
• Gold standard procedure is
laparoscopic fundoplication
• May be an option for those who wish
to discontinue PPI or failure to
respond to PPI
• Bariatric surgery an option for the
morbidly obese
: Candidates for surgery
• Side effects from medical therapy
• Poor compliance with medical therapy
• Concern about or wish to discontinue
chronic medical therapy
• Symptomatic with a large hiatal hernia
• Regurgitation
• Not interested in medical therapy
• Abnormal pH test on maximum PPI
dose
• Symptoms correlate with nonacid
reflux while on maximum PPI dose
The LINX Device
• designed to augment the lower
esophageal sphincter.
• The system is a small flexible band
that is placed laparoscopically
around the esophagus just above
the stomach to create a natural
barrier to reflux.
• The band consists of interlinked
titanium beads with magnetic
cores. The act of swallowing
temporarily breaks the magnetic
bond, allowing food and liquid to
pass normally.
Endoscopic therapies for GERD

• EsophyX –Endoluminal fundoplication technique: also

known as transoral incisionless fundoplication (TIF), is
used to restore the angle of His by creating a valve at the
esophagogastric junction (EGJ). This is achieved by
wrapping the stomach’s fundus around the distal
esophagus and securing it with poly-propylene fasteners.
• Stretta- a balloon-tipped four-needle catheter that delivers
radiofrequency energy into the smooth muscle of the EGJ.
PEPTIC ULCER DISEASE
• Definition: Defects in the
mucosa of stomach,
pylorus or duodenum
that penetrate the
muscularis mucosa
• Exceptions: Zollinger –
Ellison syndrome,
meckel’s diverticulum
• Basic Physiology
• Parietal cells secrete HCl
• Chief Cells secrete
pepsinogen
• G cells secrete gastrin
• D cells secrete somatostatin
• Ach from vagal efferent
neurones
• Histamine from mast cells
• H+ K+ ATpase
Aetiopathogenesis
• No acid, no ulcer
• Balance between protective and
aggressive factors
• Current understanding
1. Helicobacter pylori
2. NSAIDs
3. Hypersecretory state
Other factors
• Accelerated gastric emptying for
liquids (DU)
• Delayed gastric emptying for solids
(GU)
• Duodenogastric reflux
• Genetic – Blood group O and DU
• Smoking
• Psychological stress
• No definite role for diet
Helicobacter pylori
• Discovered by Marshall and Warren in 1982, for
which they worn the Nobel prize in
Medicine/Physiology in 2005
• A spiral-shaped flagellated microaerophilic Gram
negative bacterium
• Grows in the mucus layer of the gastric mucosa
• Secretes an enzyme, Urease, which enables it
survive the harsh acidic environment in the
stomach.
• As in many chronic infections, most infected
individuals remain asymptomatic.
• Has been implicated in the causation of chronic
gastritis, duodenal ulcer, gastric ulcer, gastric
adenocarcinoma and mucosa-associated lymphoid
tissue lymphoma (MALToma) + some extra-
gastrointestinal diseases.
• Was declared a class 1 (definite)
human carcinogen in 1994 by the
International Agency for research on
cancer (an organ of the WHO)
• Thought to spread through
contaminated food and water and
through direct mouth-to-mouth
contamination.
• Infections tend to occur in childhood
and is facilitated by poverty,
overcrowding and poor sanitation.
• Over 50% of global population
infected.
 Vacuolating Cytotoxin (VacA)
• Forms vacuoles in eukaryotic cells.
• It is also responsible for membrane channel formation,
cytochrome c release from mitochondria leading to
apoptosis, and binding to cell- membrane receptors for the
initiation of proinflammatory response.
• VacA can specifically inhibit T-cell activation and proliferation
by manipulating the T-cell receptor pathway and the cell
cycle.
Cytotoxin-associated gene A (CagA) & type IV secretion system
(T4SS)
• CagA is a bacterium derived oncoprotein which is injected
into host cells via a pilus structure called type IV secretion
system (T4SS).
• After being injected into host cells, CagA alters intracellular
signal transduction pathways that facilitate the malignant
transformation of gastric epithelial cells.
• CagA and T4SS also increase gastric inflammation (via NFκB
signaling pathway) and increase IL-8 secretion which
predisposes to genetic instability and carcinogenesis.
Correa Cascade and the role of H.pylori
The African Enigma

Incongruence
between the
infection prevalence
and gastric cancer
incidence.
African enigma contd.
• The role of bacterial strains with less oncogenic potential
• Modulation of the immune response towards a Th2 cytokine profile
induced by helminthic co-infections in Africans
• Effect of antioxidant-rich diet
• Genetic susceptibility
• Topography of geographical areas
Need to sustain the enigma using the instrumentality of the
modifiable factors (Healthy stomach initiative)
54
Lee et al. Ann Transl Med. 2015;3(1):10
NSAIDS
• NSAIDs are the most common
cause of peptic ulcer disease in
patients without H. pylori infection.
• By inhibiting cyclooxygenase,
NSAIDs inhibit the formation of
prostaglandins and their protective
cyclooxygenase-2–mediated
effects:
Enhancing gastric mucosal
protection by stimulating mucus
and bicarbonate secretion and
epithelial cell proliferation and
increasing mucosal blood flow.
Pathology
DU – 95% in D1 Clinical presentation
• < 1cm in diameter
• Giant ulcers (3-6cm) A major cause of
• Rarely malignant organic dyspepsia
GU
• Benign forms rare in the fundus (epigastric pain,
• Distal to the junction between epigastric burning,
the antrum and body
• NSAIDS cause chemical
gastropathy
postprandial fullness
and easy satiety)
Abdominal Pain Approach to management
• Epigastric Alarm Symptoms (Indications for Early
Endoscopy)
• Burning or gnawing • Anorexia
• 90 mins to 3 hours after • Dysphagia
food • GIT bleeding
• Awakened about 3.00 am • New onset symptoms in persons
(DU) > 45 years of age
• Worsened by food (GU) • Presence of a mass
• Silent, present with • Presence of anaemia
complications • Significant weight loss
• Weight change ?? • Vomiting
When there are no alarm features:
• Patients with recent onset dyspepsia who are over 45
years of age should have early endoscopy.
• In communities with high prevalence of Helicobacter
pylori, such as Nigeria, all dyspepsia patients below 45
years should be tested and treated if positive (non-
invasive testing).
The age threshold depends on the local prevalence of gastric
malignancies
Goals of treatment Challenges of Helicobacter pylori
• Symptom relief eradication
• Promote healing
• Prevent recurrence • Drug combination employed (PPI
• Prevent complications
plus antimicrobials)
Drugs • Many regimes currently
• Antacids ineffective because of increasing
• H2 – receptor antagonists
antibiotic resistance
• PPI Salvado et al. Prevalence of antibiotic resistance in Helicobacter pylori: a
systematic review and meta-analysis in WHO regions. Gastroenterology
• Cytoprotective agents (Sucralfate, bismuth) 2018; 155(5):1372-1382 e17.

• Prostaglandin analogues
Challenges of Helicobacter pylori management
in Africa
• Prevalence not known with exactitude
• Lack of current data to reflect the changes in the epidemiology of the
diseases associated with H. pylori
• Studies focused mainly on patients with symptoms, lack of
population-based studies: Dynamics in Africa different fom what
obtains in the Western world.
• Lack of guidelines in Africa
• Available guidelines promote the test and treat approach, a strategy
that might have contributed to antibiotic resistance. Sensitivity
testing on gastric biopsies not routinely done.
Challenges contd.
• Endoscopy required to obtain material for testing
The culture of gastric biopsy specimens has a specificity of
100% and allows for antimicrobial resistance testing.
However, H. pylori culture requires
• stringent transport conditions,
• takes several days, and can be difficult to perform even in
experienced hands.
• Its success is further complicated by the recent use of PPIs
or antibiotics
Challenges contd.
• Although treatment guidelines strongly recommend using local
susceptibility and resistance patterns for selecting H. pylori
therapy, such data are lacking in Africa and indeed many parts of
the world.
• Lack of molecular methods to identify genetic mutations
responsible for antibiotic resistance.
• Pre-treatment stool-based molecular testing, which obviates the
need for endoscopy, should allow for a more universal transition
from empiric to resistance-guided therapy but requires further
development.
Newer drugs/Strategies
• High dose dual therapy (PPI + Amoxicillin). Fewer side effects
• Rifabutin-based therapy (eg PPI, Rifabutin and Amoxicillin). Rifabutin
may be myelotoxic in high doses.
• Acid suppression with potassium –competitive blockers (p-CAB)-
typical example is Vonoprazan.
• Probiotics
• Helicobacter pylori vaccine.
Complications of PUD
• Bleeding
• Perforation
• Penetration
• Gastric outlet obstruction
• ?Malignant transformation
Conclusion
• Acid-peptic disorders are common disordersinI which gastric acid and
pepsin play significant etiopathogenic roles
• GERD and PUD are the major diseases in this group
• There have been tremendous improvements in the understanding of
the aetiopathogenesis of these conditions.
• GERD is now viewed as a heterogeneous disease with varied
mechanisms of symptom generation and overlap with esophageal
FGIDs.
• Eradication of Helicobacter pylori remains a big challenge because of
antibiotic resistance
Thank you .