An 85-year-old female with LOC, haematemesis & blood in stool
An 85-year-old female with a past medical history of hypertension was admitted to A&E after experiencing a sudden episode of loss of consciousness (LOC), haematemesis and melaena. On arrival, she displayed symptoms of shock including profuse sweating and hypotension (BP 57/42 mmHg), and required 2L of oxygen to adequately maintain her target oxygen saturation. Her heart rate is 83bpm. She had no history of abdominal surgery, gallstones or allergies, however, additional information on her medical history was challenging to obtain due to acute confusion. She did report experiencing epigastric pain over the past week and mentioned regular use of non-steroidal anti-inflammatory drugs (NSAIDs) for her back pain.
Physical examination revealed generalised abdominal tenderness. Blood tests showed she had metabolic acidosis (pH 7.27) and anaemia (Hb of 77 g/L). After transfusing the patient with 2 units of red blood cells, 1L of crystalloid solution, and the initiation of noradrenaline support (administered at a rate of 4.8 ml/hr), her condition stabilised. A CT scan of the abdomen was performed, revealing a choledocho-duodenal fistula (CDF) with concomitant cholangitis as well as proximal duodenitis and evidence of blood in the stomach. Notably, no gallstones were detected on CT.
A nasogastric (NG) tube was placed to remove the blood in her stomach after which an oesophagogastroduodenoscopy (OGD) was then performed, which detected an actively bleeding Forrest 1A posterior duodenal ulcer. The gastro-duodenal artery was found to be the source of the bleed and this was managed endoscopically using clipping.
Following the procedure, the patient was transferred to the ICU where her condition remained stable. Gradual withdrawal of the noradrenaline support was initiated, and no further blood transfusions were necessary. The patient underwent further testing and was found to have a gastric infection, for which she was treated with antibiotics. After a stay of 9 days in the hospital, the patient was discharged and had no further issues on follow-up.
From left to right:
1) CT abdomen showing (A) the presence of blood in the stomach, aerobilia (yellow arrow) and (B) inflammation of the first part of duodenum (red arrow)
2) Endoscopic picture showing the 1A Forrest duodenal ulcer with the presence of a choledocho-duodenal fistula (CDF) and an active bleeding of the gastro-duodenal artery around the fistula (B).
3) Endoscopic picture showing the 1A forrest duodenal ulcer treated with an over the scope clip.
4) Picture adapted from the article of Ikeda et al., illustrating the two types of CDF according to the location of the fistula
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This patient was admitted with symptomatic anaemia resulting from an upper GI bleed caused by a perforated posterior duodenal ulcer. The cause of the patient’s ulcer will likely have been the H.pylori infection that the case summary alludes to, however, the patient’s regular use of NSAID medication to control their back pain will have been a likely contributive factor.
Peptic Ulcer Disease (PUD) is characterised by the presence of a solitary mucosal ulcer in either the proximal duodenum (more common) or the distal stomach (less common). PUD is a global problem with a lifetime risk of development ranging from 5% to 10%. Overall, there is a decrease in the incidence of PUD worldwide due to both improved treatment and sanitation methods. Duodenal ulcers are four times more common than gastric ulcers, and the condition occurs more frequently in males than females.
References:
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Peptic ulcer disease (PUD) results from an imbalance between the protective and destructive factors of the gastric mucosa.
Gastric protective factors:
Mucin layer produced by foveolar cells (protective barrier)
Bicarbonate secretion by surface epithelium (neutralises stomach acid)
Adequate blood supply (provides nutrients and picks up leaked acid)
Foveolar cells contain the enzyme cyclooxygenase (COX) and are able to produce various prostaglandins, including prostaglandin E2 (PGE2) which is the main factor that stimulates the defences listed above. In addition, PGE2 is able to inhibit both HCl & pepsinogen secretion, thereby reducing the likelihood of acidic damage to the gastric epithelium.
Risk factors that promote inflammation (gastritis):
Severe burns (Curling ulcer):
These patients lose fluid through dehydration and become hypovolaemic
Hypovolaemia leads to decreased local blood supply
NSAIDs (e.g. ibuprofen):
These medications block COX and therefore decrease local levels of PGE2 in the stomach
Heavy alcohol consumption:
Alcohol is toxic to the gastric mucosa and causes direct damage
Chemotherapy:
Destroys intestinal stem cells
Most commonly results in dose-related gastritis/enteritis, however, ulcer formation is a rare but possible consequence of treatment
Increased intracranial pressure (ICP):
AKA Cushing Ulcer
Increased ICP —> increased stimulation of vagus nerve —> increased stimulation of gastric parietal cells —> increased HCl production —> greater likelihood of acidic damage to gastric mucosa
Shock:
Hypovolaemia leads to decreased local blood supply
Damage to the gastric mucosa occurs in stages according to the extent of injury to the local area:
Superficial inflammation (inflammation of epithelium)
Erosion (loss of superficial epithelium)
Ulcer (loss of mucosal layer)
Ongoing inflammation of the gastric mucosa can eventually result in ulcer formation. Whilst the previously listed risk factors can certainly contribute towards the development of PUD, most cases of PUD are in fact caused by an H.pylori infection.
H. pylorus is a gram-negative bacillus that is found within the gastric epithelial cells. This bacterium is responsible for ~90% of duodenal ulcers and ~70-90% of gastric ulcers. H. pylori infection is more prevalent among those with lower socioeconomic status and is commonly acquired during childhood. The organism has a wide spectrum of virulence factors allowing it to adhere to and inflame the gastric mucosa. This results in hypochlorhydria/achlorhydria, leading to gastric ulceration.
Virulence Factors of Helicobacter Pylori
Urease: The secretion of urease breaks down urea into ammonia and protects the organism by neutralizing the acidic gastric environment.
Toxins: CagA/VacA is associated with stomach mucosal inflammation and host tissue damage.
Flagella: Provides motility and allows movement toward the gastric epithelium.
References:
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Symptoms and complications of PUD will vary according to the location of the ulcer:
Gastric ulcer:
Epigastric pain that worsens with meals (due to increased acid production)
Ulcer usually located on the lesser curvature of the antrum (rupture carries risk of bleeding from the left gastric artery)
Duodenal ulcer:
Epigastric pain that improves with meals (but then usually recurs 2-3hrs after)
Diagnostic endoscopic biopsy will show ulcer with hypertrophy of Brunner glands (function of Brunner glands is to secrete an alkaline fluid containing mucin, which protects the mucosa from the acidic stomach contents entering the duodenum)
Ulcer usually arises in the anterior duodenum - when present in the posterior duodenum, rupture can lead to bleeding from the gastroduodenal artery or acute pancreatitis.
Epigastric pain is the most common symptom of both gastric and duodenal ulcers. Food or antacids relieve the pain of duodenal ulcers but provide minimal relief of gastric ulcer pain.
Duodenal ulcer pain often awakens the patient at night. About 50-80% of patients with duodenal ulcers experience nightly pain, as opposed to only 30-40% of patients with gastric ulcers and 20-40% of patients with non-ulcer dyspepsia (NUD). Pain typically follows a daily pattern specific to the patient. Pain with radiation to the back is suggestive of a posterior penetrating gastric ulcer complicated by pancreatitis.
Other possible manifestations include the following:
Dyspepsia:
Belching, bloating, distention, and fatty food intolerance
Always ask about ALARM symptoms when evaluating patients >55yrs with dyspepsia - these patients warrant urgent referral for endoscopy under the 2WW rule:
Anaemia
Loss of weight
Anorexia
Recent onset of progressive symptoms (<3 months)
Melaena or haematemesis
Heartburn/ chest discomfort
Signs up upper GI bleed (UGIB):
Haematemesis
Melaena:
May be intermittent over several days or multiple episodes in a single day
Symptomatic anaemia (e.g. fatigue, pallor, dyspnoea etc.)
NSAID-induced gastritis or ulcers may be silent, especially in elderly patients:
Only 20-25% of patients with symptoms suggestive of PUD are found to have an ulcer
Diarrhoea:
Signs of dyspepsia & diarrhoea may indicate Zollinger-Ellison syndrome
References:
1) https://www.ncbi.nlm.nih.gov/books/NBK534792/
2) https://emedicine.medscape.com/article/181753-overview#a3
3) https://cks.nice.org.uk/topics/dyspepsia-unidentified-cause/
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Gastritis - an inflammatory process of the gastric mucosa from immune-mediated or infectious aetiology presenting with upper abdominal pain and nausea
Gastroesophageal reflux disease (GORD) - patients usually describe a burning retrosternal chest pain, excessive salivation and intermittent regurgitation of food material
Gastric cancer - think ALARM symptoms:
Gastric ulcers are much more likely to be malignant compared to duodenal ulcers (duodenal carcinoma is extremely rare)
Gastric ulcers can be caused by gastric carcinoma (intestinal type):
Benign peptic ulcers are usually small (<3cm), sharply demarcated (“punched-out”) and surrounded by radiating folds of mucosa
Malignant ulcers are large (>3cm), irregular in shape and with heaped up margins
Biopsy is required for definitive diagnosis
Pancreatitis - epigastric/RUQ pain that is more persistent and severe when lying flat. Patients usually have a history of alcoholism or gallstones. Consider this differential if the patient has a raised serum amylase or lipase
Biliary colic - “colicky” (i.e. intermittent and severe) deep pain in the RUQ or epigastrium precipitated by fatty meals.
Cholecystitis - RUQ or epigastric pain that usually lasts for hours, is exacerbated by fatty meals and is associated with nausea and vomiting. Fever, tachycardia, positive Murphy sign, leukocytosis, and abnormal liver functions help further distinguish this from biliary colic
Non-ulcer dyspepsia (NUD) or functional dyspepsia - this is a diagnosis of exclusion made in patients with chronic persistent epigastric pain where no evidence of disease is found (after thorough investigation).
Crohn’s disease - ulceration can involve any part of the gastrointestinal tract from the buccal mucosa to the rectum. Isolated Crohn ulceration of the stomach is rare, although it may cause duodenal or ileal ulcerations.
Zollinger-Ellison syndrome (ZES) is a rare disorder that can cause gastric or duodenal ulcers (usually multiple) from excessive acid secretion. Consider ZES if a patient has severe peptic ulceration, kidney stones, watery diarrhea, or malabsorption. ZES can also be associated with multiple endocrine neoplasia type I (MENI), which occurs earlier than isolated ZES.
References:
1) https://www.ncbi.nlm.nih.gov/books/NBK534792/
2) https://cks.nice.org.uk/topics/dyspepsia-unidentified-cause/
3) https://emedicine.medscape.com/article/181753-differential
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Patients with PUD will initially present with symptoms of dyspepsia and will normally present to their GP first.
Provided there are no ALARM symptoms present, it is appropriate to initially offer advice on diet and lifestyles modification such as:
Healthy eating, weight reduction and smoking cessation:
Factors which are known to provoke symptoms of dyspepsia include smoking, alcohol, coffee, chocolate, fatty foods and being overweight and so these factors should be addressed first
Psychological therapies, such as cognitive behavioural therapy and psychotherapy may also play a role in relieving symptoms of dyspepsia in certain patient groups
NICE guidelines recommend a 4-week trial of a PPI to help with symptom control whilst also implementing lifestyles changes and to re-review the patient at 4 weeks.
If the patient’s symptoms are still uncontrolled after a 4 week trial of a PPI and implementation of lifestyle changes, testing for H.pylori should be performed. NICE advise to leave a 2‑week washout period after PPI use before testing for H.pylori with a breath test or a stool antigen test.
If the patient is H.pylori positive then they should undergo H.pylori eradication therapy for 7 days:
First-line therapy:
PPI:
e.g. Omeprazole 20mg od, Lansoprazole 30mg od etc.
Amoxicillin:
500-1000mg po tds
Second Antibiotic (either clarithromycin, metronidazole or doxycycline):
If the patient has had recent clarithromycin exposure, then metronidazole is recommended
If the patient has tried both clarithromycin and metronidazole, then doxycycline should be used here instead (further guidance regarding specific antibiotic therapy can be found on the NICE website)
If penicillin allergic:
PPI:
e.g. Omeprazole 20mg od, Lansoprazole 30mg od etc.
Metronidazole 400mg po bd
Levofloxacin/Doxycycline:
Levofloxacin 250mg po bd
Doxycyline 200mg on first day, followed by 100mg od for 6 days (7 day course total)
If the patient has no response to H.pylori eradication therapy, then they should be trialled on regular, low-dose PPIs (e.g. Omeprazole 10mg od) +/- H2 receptor antagonist (e.g. Famotidine 20-40mg po od for 4-8 weeks).
If the patient fails to respond to all of the above then specialist referral should be performed for further management (+/- consideration for endoscopy).
If at any point during this period the patient develops ALARM symptoms which would be suggestive of underlying GI malignancy, they should be referred for a urgent upper GI endoscopy under the 2WW rule.
ALARM symptoms include:
Anaemia
Loss of weight
Anorexia
Recent onset of progressive symptoms (<3 months)
Melaena or haematemesis
Endoscopy is the gold-standard for diagnosis of PUD.
For patients with a confirmed ulcer on endoscopy NICE advise the following:
Offer H.pylori eradication therapy to people who have tested positive for H pylori and who have peptic ulcer disease. (even if already completed one course of antibiotics previously, e.g. with GP)
For people using NSAIDs with diagnosed peptic ulcer, stop the use of NSAIDs (where possible) & offer full-dose PPI or H2RA therapy for 8 weeks and, if H pylori is present, subsequently offer eradication therapy.
Offer people with gastric ulcer and H. pylori repeat endoscopy 6 to 8 weeks after beginning treatment, depending on the size of the lesion.
Offer people with peptic ulcer (gastric or duodenal) and H. pylori retesting for H. pylori 6 to 8 weeks after beginning treatment, depending on the size of the lesion.
Offer full-dose PPI or H2RA therapy for 4 to 8 weeks to people who have tested negative for H pylori who are not taking NSAIDs.
For people continuing to take NSAIDs after a peptic ulcer has healed, discuss the potential harm from NSAID treatment. Review the need for NSAID use regularly (at least every 6 months) and offer a trial of use on a limited, 'as-needed' basis.
Also consider reducing the dose, substituting an NSAID with paracetamol, or using an alternative analgesic or low-dose ibuprofen (1.2 g daily).
In people at high risk (previous ulceration) and for whom NSAID continuation is necessary, consider a COX-2 selective NSAID instead of a standard NSAID. In either case, prescribe with a PPI for gastroprotection.
In people with an unhealed ulcer, exclude non-adherence, malignancy, failure to detect H pylori, inadvertent NSAID use, other ulcer‑inducing medication and rare causes such as Zollinger–Ellison syndrome or Crohn's disease.
If symptoms recur after initial treatment, offer a PPI to be taken at the lowest dose possible to control symptoms. Discuss using the treatment on an 'as-needed' basis with people to manage their own symptoms.
Offer H2RA therapy if there is an inadequate response to a PPI.
References:
1) https://www.nice.org.uk/guidance/cg184/chapter/1-Recommendations#referral-guidance-for-endoscopy-2
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An upper gastrointestinal bleed (UGIB) is a serious condition defined as bleeding that originates in the oesophagus, stomach, or duodenum. Eighty percent of patients with UGIB seen in A&E require admission to the hospital. Gastroduodenal ulcers are one possible cause of UGIB and these patients can experience symptomatic anaemia secondary to ongoing blood loss from an actively bleeding ulcer.
Symptoms of anaemia can include:
Shortness of breath
Pallor
Fatigue
Dizziness etc.
In addition, these patients can also show signs of an upper GI bleed including:
haematemesis
melaena
abdominal pain (usually epigastric)
NICE recommendations are listed below on assessment and management of a patient with suspected acute UGIB:
Risk assess the patients using the following scores:
Glasgow-Blatchford Score:
Use at first assessment
GBS helps identify which patients with UGIB may be safely discharged from A&E
Scores range from 0-23 —> the higher the score, the greater the likelihood of the patient needing to be admitted (higher scores directly proportional to mortality)
A score of 0 suggests low risk of complications (0.5%) and these patients may likely not need to be admitted for workup.
Scores >0 do not imply that the patient must be admitted —> always use clinical judgment!
the full Rockall score after endoscopy.
s
1.1.2Consider early discharge for patients with a pre-endoscopy Blatchford score of 0.
References:
1) https://www.nice.org.uk/guidance/cg141/chapter/Recommendations
2) https://www.medscape.com/s/viewarticle/975422
3) https://www.mdcalc.com/calc/518/glasgow-blatchford-bleeding-score-gbs
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PUD has an excellent prognosis provided the underlying cause is addressed. Most patients are treated successfully with H.pylori eradication therapy, NSAID avoidance and the appropriate use of anti-secretory therapy. Eradication of H pylori infection changes the natural history of the disease, with a decrease in the ulcer recurrence rate from 60-90% to approximately 10-20%. However, this is recurrence rate is still a little high by historical standards suggesting that there is an increased number of ulcers not caused by H.pylori.
For NSAID-associated ulcers, the incidence of perforation is ~0.3% per patient year, and the incidence of obstruction is ~0.1% per patient year. Combining both duodenal ulcers and gastric ulcers, the rate of any complication in all age groups combined is approximately 1-2% per ulcer per year.
The mortality rate for PUD (which has decreased in the last few decades) is ~1 death per 100,000 cases. If one considers all patients with duodenal ulcers, the mortality rate due to ulcer haemorrhage is approximately 5% (and it has been so for the last 20 years). However, evidence from meta-analyses and other studies has shown a decreased mortality rate from bleeding peptic ulcers when intravenous PPIs are used after successful endoscopic therapy.
Emergency operations for peptic ulcer perforation carry a mortality risk of anywhere between 6-30%.
Factors associated with higher mortality in this setting include the following:
Shock
Kidney disease
Delay in surgery >12hrs after presentation
Presence of co-morbidities - e.g. cardiovascular disease, diabetes mellitus
Age >70yrs
Cirrhosis
Immunocompromised state
Location of ulcer (mortality associated with perforated gastric ulcer is twice that associated with perforated duodenal ulcer)
References:
1) https://emedicine.medscape.com/article/181753-overview#a8
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This particular article discusses the case of an 85-year-old female admitted to A&E in haemorrhagic shock due to an acute upper gastro-intestinal bleed. In addition to the actively bleeding Forrest 1A ulcer that was found on endoscopy, this patient was also found to have a choledocho-duodenal fistula (CDF) as well as a H.pylori infection for which she was treated with eradication therapy.
PUD is responsible for most upper GI bleeds (30%–60% of cases). Oesophagogastroduodenoscopy (OGD) is an effective first line procedure, which allows one to simultaneously identify the source of haemorrhage and treat it. When performed early (i.e. ≤24 h of admission), it significantly improves patient outcomes (e.g. fewer bloods tranfusions required, reduced hospital stay, decreased mortality etc.).
An entero-biliary fistula is an abnormal communication between the biliary and GI tract and, in ~90% of cases, is due to gallstones. It is a rare condition which can also result from PUD, tumours or Crohn disease (when inflammation involves the duodenum). Different types of fistulas exist, however, the most common is CDF (68%–90% of all entero-biliary fistula cases). The diagnosis of entero-biliary fistula is challenging and is often made incidentally during endoscopy or radiological imaging, especially because patients usually remain asymptomatic or report non-specific symptoms such as abdominal pain, nausea, fever, bowel obstruction or jaundice.
The “Forrest classification,” created by Dr John A.H. Forrest in 1974, includes 3 stages:
Stage 1 - active bleed present:
1a spurting bleed
1b oozing bleed
Stage 2 - recent bleed:
2a visible non-bleeding vessel
2b adherent clot
2c haematin covered ulcer
Stage 3 - presence of lesion but no signs of haemorrhage
Stages 1a —> 2a require an endoscopic haemostasis, which can be achieved by several modalities such as epinephrine injection, haemospray or Over The Scope Clip
Several therapies have been proposed to treat entero-biliary fistula but no guidelines have been established yet. Whilst there are no set guidelines to treat entero-biliary fistula, it is recommended to treat cholecysto-duodenal fistula surgically with cholecystectomy and closure of the fistula tract. CDF that is incidentally diagnosed and caused by PUD could be managed conservatively, with PPIs.
References:
2) https://www.mdcalc.com/calc/3923/forrest-classification-upper-gi-bleeding
Source: https://doi.org/10.3389/fsurg.2023.1206828
Case Summary & Questions written by Dr Ahmed Kazie
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