Seminar 8 - Alcohol and Upper GI Bleeds Flashcards
List risk factors for oesophageal variceal bleeding
Raised portal pressure
Variceal size - larger size = higher risk of rupture
Endoscopic features of the variceal wall - red colour signs
Bacterial infection
Active alcohol intake - if alcohol-related disease
Advanced liver disease
Local changes in distal oesophagus e.g., GORD
Which cells in the pancreas secrete digestive enzymes
Acinar cells
Describe survival rates from oesophageal cancer
Lymph node and solid organ metastasis will significantly reduce survival
Without mets 5yr survival is roughly 75-80%
With mets, which is common at adenocarcinoma presentation, 5yr survival roughly 20%
Which lymph nodes to oesophageal cancers metastasize to
Depends on where the cancer is in the oesophagus
Tumour in the upper 3rd (SCC) go to cervical nodes
Tumour in the middle 3rd (SCC) go to mediastinal, paratracheal and tracheobronchial nodes
Tumour in the bottom 3rd (SCC and adenocarcinoma) go to gastric and celiac nodes
List the microscopic features of a Mallory-Weiss tear
Lesions are non-transmural, with only the mucosa and potentially the submucosa affected
Describe the microscopic features of a well differentiated gastric adenocarcinoma
Tumor arises from mucosa, infiltrates submucosa then muscularis externa then serosa
What is the underlying pathophysiology of portal hypertension
Increased resistance to portal blood flow
and/or
Increase in portal venous in flow
H pylori is associated with which gastric pathologies
Chronic gastritis
Peptic ulcers
Gastric cancer
Describe the microscopic features of oesophageal SCC
These tumours tend to be moderately to well differentiated
Describe the structure of the muscularis externa in the stomach
Inner oblique, middle circular, outer longitudinal muscle layers (3 layers)
Myenteric plexus between circular and longitudinal muscles – coordinate peristaltic waves
Describe the normal composition of ascites fluid
Fluid is generally serous with <3g/dL of protein (largely albumin), and a serum-to-ascites albumin gradient of ⩾1.1g/dL.
The fluid may also contain some mesothelial cells & mononuclear leukocytes.
How are symptomatic subdural haemorrhages managed
They must be surgically evacuated usually via craniotomy or a burr hole washout.
Surgery is usually immediate - within 4 hours
If there are clotting abnormalities these should be reversed immediately.
Should also address the initial cause of the trauma if possible (e.g. assess fall risk or treat alcoholism.)
List causes of peptic ulcer disease
H. pylori infection
NSAID use
Lifestyle factors - smoking, potentially caffeine
Severe physiologic stress - systemic illness, stress
Hypersecretory states (uncommon) e.g. cystic fibrosis, hyperparathyroidism, gastrinoma
Zollinger-Ellison syndrome - acid hypersecretion caused by gastrin secreting neuro-endocrine tumour
Genetic factors
Crohn’s
Other infections
Other drugs - bisphosphonates, KCl`
What determines the absorption rate of alcohol
It is dependent on rate of gastric emptying (affected by food etc.) and type of drink
Describe the zones in the liver
Functionally, the liver can be divided into three zones, based upon oxygen supply
Zone 1 encircles the portal tracts where the oxygenated blood from hepatic arteries enters (more O2)
Zone 3 is located around central veins, where oxygenation is poor.
Zone 2 is located in between
How does alcohol cause gastritis
Alcohol causes direct cellular damage to gastric mucosa.
Which mutations can contribute to gastric cancer
Germline loss-of-function mutations in tumour suppressor gene CDH1 (encodes cell adhesion protein E-cadherin)
Seen in 50% sporadic diffuse gastric tumors
Intestinal-type gastric cancers are strongly associated with mutations that result in increased signaling via the Wnt pathway
Loss-of-function mutations in the adenomatous polyposis coli (APC) tumor suppressor gene - leads to FAP
Gain-of-function mutations in the gene encoding b-catenin
Other genes commonly affected by loss-of-function mutations or silencing
The rate of alcohol metabolism is the same for everyone - true or false
False
There is individual variation in metabolism rate.
Rate is much higher in chronic alcoholics as they build tolerance - means they need to consume more alcohol to reach the same blood level
Gastric cancer is more common in individuals with which gastric/intestinal conditions
multifocal mucosal atrophy and intestinal metaplasia
What are the most common causes of pancreatitis
Gallstones - gallstonepassage/impaction is most common
Idiopathic - evidence suggests that most cases are associated with congenital duct abnormalities
Ethanol (alcohol) - most common cause of chronic
Trauma
List the macroscopic features of chronic pancreatitis
The gland is hard
Sometimes with visibly dilated ducts containing calcified concretions
List the clinical features of chronic pancreatitis
May follow multiple bouts of acute pancreatitis
Attacks precipitated by alcohol, overeating, opiates (other drugs which increase sphincter tone)
Attack may feature a mild fever + elevated serum amylase
Gallstone induced may be present w jaundice
Weight loss may also be present
Chronic pain is also a problem,
List the main sites of portosystemic shunt formation
Gastro-oesophageal junction (varices*)
Paraumbilical + abdominal wall collaterals
The retroperitoneum
Rectal/anal canal veins (PC: haemorrhoids)
Which microscopic features are seen in autoimmune type 1 chronic pancreatitis
swirling / storiform fibrosis, phlebitis
Which microscopic features are seen in autoimmune type 2 chronic pancreatitis
neutrophilic infiltrates within epithelium and lumen of medium sized pancreatic ducts
What is the mean age of presentation for gastric cancer
55
How does alcohol affect the pancreas
Can cause both acute and chronic pancreatitis
How does alcohol cause pancreatitis
Alcohol damages the acinar cells of the pancreas through oxidative stress which causes inappropriate release of enzymes that damage the pancreas itself.
Also increases contraction of the sphincter of Odi and secretion of protein rich fluid that is likely to cause plugs. Both processes cause blockage of the ducts.
How does H pylori cause an ulcer
H. pylori bacteria weakens the protective mucous coating of the stomach and duodenum
Acid gets through to the sensitive lining beneath
Acid + bacteria cause irritation to the lining which causes the ulcer
Also causes impaired secretion of somatostatin and gastrin which leads to acid hypersecretion
Rebleeding can occur in cases of subdural haematoma - true or false
True
Multiple episodes of rebleeding can occur from damaged vessels
This is most common soon after the initial haemorrhage and occurs in 10-30% of cases.
Which surgical treatments are available for a bleeding peptic ulcer
Surgical hemostasis / angiographic embolization after failure of repeated endoscopy
Refractory bleeding peptic ulcer: surgical intervention with open surgery
Intraoperative endoscopy
How may the spleen appear in those with portal hypertension
Enlarged - splenomegaly
Degree of enlargement varies widely – weight can reach as much as 1000g (5-6x its normal)
Irregular pale-tan plaques of collagen over the purple capsule (aka. “sugar icing” or “hyaline peri-splenitis”).
Stomach perforations can have hat effect on other organs
May cause penetration of other organs, such as the pancreas, without spreading into the peritoneum
A BAC of over 300mg/100ml is likely to have what effect
Results in stupor.
Anything over this puts the individual at risk of brainstem depression and therefore respiratory depression.
What are the Kupffer cells
The resident macrophages of hepatic sinusoids
They are attached to the luminal surface of endothelial cells
Which type of alcohol is found in drinks
Ethanol
Where does the oesophagus run
cricoid cartilage to gastroesophageal junction
How do lower GI bleeds present
Haematochezia - fresh blood in stool, either mixed in or present on wiping
What is the most common type of oesophageal cancer
SCC is the most common worldwide but adenocarcinoma is becoming increasingly common in the US and western world
Subdural haematomas can occur bilaterally - true or false
True
Only in 10% of cases though and more common in infants
Describe the epidemiology of adenocarcinoma of the oesophagus
7X more common in men and most common in Caucasians
Highest rates in US, UK, Canada, Australia, Netherlands and brazil
Lowest rates in Korea, Thailand, Japan and Ecuador
>1/2 of all oesophageal cancers in the US
What makes up a portal triad
Bile duct
Portal vein
Hepatic artery
A yellow liver suggests what
Fatty change
Can be caused by alcoholism
What is Sinusoidal capillarisation
Loss of sinusoidal endothelial cells fenestration
what is the principle treatment for gastric cancer
Surgical resection
Can do a total, subtotal, or distal gastrectomy
Attempt to maintain a 5-cm surgical margin proximally and distally to primary lesion
Esophagogastrectomy for tumors of cardia & gastroesophageal junction
Subtotal gastrectomy for tumors of distal stomach
Describe the structure of the centroacinar cells
They are spindle-shapedcellsin the exocrine pancreas
Their nuclei and cytoplasm do not stain as intensely as the secretory cells
List the causes of GORD
Incompetence of LOS - hiatus hernias, pregnancy, Transient oesophageal sphincter relaxation
Raised intra-abdominal pressure - obesity, pregnancy, asthma, increased gastric volume, coughing, straining and bending down
Slow transit of food -diabetes, peptic ulcer disease, CTDs
Alcohol and tobacco use
CNS depression
What is the main cause of the acute effects of alcohol
Many of the effects are due to the toxic nature of acetaldehyde
List the clinical features of peptic ulcer disease
Epigastric burning / Aching pain - occurs 1-3 hours after meals, worse at night (11-2), relieved by alkali or food
Present with iron deficiency anemia, hemorrhage, or perforation
Nausea, vomiting, bloating, belching, significant weight loss
What is secreted in the cardia of the stomach and what are their functions
Lots of mucus and lysozymes - protection
HCl secreted from parietal cells -
Chronic h pylori infections are most commonly seen in which part of the stomach
The pyloric antrum
Ascites suggests a poor prognosis in pancreatic cancer patients - true or false
True
How can the by-products of alcohol metabolism damage the liver
Metabolism cause release of ROS which causes lipid peroxidation of liver cells and provokes endotoxin release by GI flora which causes further liver damage
Where are the p-450 enzymes found
In the smooth endoplasmic reticulum of hepatocytes
Which gastric cancers receive neo-adjuvant chemo
Operable gastric cancers beyond T1N0
What is the cause of hereditary pancreatitis
SPINK1gene mutation
Autosomal dominant
The portal vein is formed by which other vessels coming together
Splenic and superior mesenteric veins
This occurs behind the neck of the pancreas
Management plan for a subdural haematoma is dependent on what
The size and location of the haematoma
List some of the stigmata of cirrhosis
Spider naevi Palmar erythema Clubbing Gynaecomastia - impaired oestrogen metabolism Splenomegaly Hepatomegaly None!!
You should start empirical antibiotics before H-pylori confirmed - true or false
False
Not recommended
List the microscopic features of chronic pancreatitis
Evident chronic inflammatory infiltrate that surround slobules and ducts
Acinar loss is a constant feature w sparing of Islets of Langerhans (become embedded in sclerotic tissue)
Ductal epithelium = atrophic or hyperplastic or metaplastic
List causes of rectal and anal bleeds
Haemorrhoids
Anal Fissures
Describe the process of scar formation and regression in cirrhosis
Hepatic stellate cells differentiate into highly myofibroblasts in response to injury.
Release cytokines, growth factors, chemotactic Kupffer cells or recruited macrophages & lymphocytes.
ECM deposition + scar formation often in space of Disse.
Loss of sinusoidal endothelial cells fenestration (sinusoidal capillarisation).
What is the MELD Score
Model for End-Stage Liver Disease
Created to predict survival of patients undergoing Transjugular intrahepatic portosystemic shunts (TIPS) procedure
Used to predict 3-month mortality in cirrhosis and aid liver transplant allocation (US).
List intra-hepatic causes of portal hypertension
Primary biliary cholangitis (even in absence of cirrhosis)
Infiltrative malignancy, primary or metastatic
Pre-sinusoidal:
Schistosomiasis
Diffuse, fibrosing granulomatous disease e.g., sarcoid
Sinusoidal:
Cirrhosis (any cause; accounts for most cases of portal HTN).
Nodular regenerative hyperplasia (effects portal microcirculation).
Massive fatty change (steatohepatitis)
Amyloidosis
Post-sinusoidal:
Focal malignancy w/ invasion into hepatic vein (esp. hepatocellular carcinoma)
Budd-Chiari syndrome
Describe the ceiling effect when using the Child-Pugh Score
Unable to differentiate disease severity in the top subgroup of cirrhotic patients.
E.g., those with serum bilirubin >3mg/dL had the same CTP score as those with levels 20+mg/dL
What is the most common cause of acute pancreatitis in children
Trauma
How do you treat acute pancreatitis
Treatment centers on resting the inflamed pancreas by total elimination of oral intake and supportive therapy via analgesia and IV fluids
Prognosis of a subdural haematoma is dependent on what
The extent of associated brain damage
Are antifungals used as standard therapy in perforated peptic ulcers
No
May however be appropriate in high risk patients
The presence of neutrophils in ascites fluid suggests what
Infection
What does the UKMELD score include
Comprises serum bilirubin, INR, creatinine, and sodium
What is the normal pressure of the portal vein
Normal portal blood flow: 1000-1500ml/min.
Normal portal vein pressure: 5-10mmHg
List the major complication of portal hypertension
Hepatic encephalopathy
Ascites
Portosystemic venous shunts
Congestive splenomegaly
Describe micronodular cirrhosis
Has consistently sized nodules on liver
Diameter <3mm
Rare in portal area.
List the parts of the stomach
Cardia
Fundus
Body
Pylorus - has antrum, canal and sphincter
What characterises acute pancreatitis
Reversible pancreatic parenchymal injury
How may advanced pancreatic cancer present
Paraumbilical subcutaneous metastases (or Sister Mary Joseph nodule or nodules)
Describe the epidemiology of Barretts oesophagus
Incidence is rising rapidly
10% of symptomatic GORD patients and 2% of the general population will be affected
More common in Caucasians, 3X as common in men and increases in incidence with age ( usually being seen between 40-60yrs)
List cardiovascular conditions that can be caused alcohol
Dilated, congestive cardiomyopathy - caused by injury to the myocardium
Hypertension
Coronary Heart Disease
Describe the structure of the liver sinusoids
They are found between plates of hepatocytes
Lined with fenestrated endothelium making sinusoids very leaky - allows for easy movement of large proteins backwards and forwards
Space of Disse lies beneath these endothelial cells and the hepatocytes
As well as jaundice, encephalopathy and coagulopathy, what are some other significant features of chronic liver failure?
Hyper-oestrogenaemia form impaired oestrogen metabolism, pruritus, and hypogonadism in females
Describe the structure of the submucosae of the oesophagus
Loose connective tissue
Contains; vessels, lymphatics, miessners plexus and nerves, occasional white cells, lymphoid follicles and submucosal glands *
Glands lined by mucinous cells producing acid mucin that drains through ducts lined by cuboidal or squamous cells
The islets of Langerhans make up a large part of the pancreas - true or false
Flase
They are scattered and so only occupy a small volume.
Which virulence factors are present in h pylori
Flagella – allow bacteria to be motile in viscous mucus
Urease – generate ammonia -> elevate gastric pH -> enhance survival
Adhesins – enhance bacterial adherence
Toxins – e.g. cytotoxin-associated gene A
Where is alcohol absorbed
20% in stomach and 80% in small intestine
Not altered at this stage
The source of GI bleeding is always identified on colonoscopy’s - true or false
False
In approx. 25% of cases, the source of bleeding cannot be definitively identified
What causes hepatic encephalopathy
Elevated ammonia levels - cause impaired neuronal function and cerebral oedema
Principle source is the GIT (produced by microorganisms and enterocytes during glutamine metabolism)
Ammonia is normally transported in the portal vein to the liver (for urea cycle).
In severe liver disease, BBB and astrocytes clear it (glutamate -> glutamine); excess glutamine -> osmotic imbalance and a shift of fluid into these cells -> cerebral oedema
Eradication of HP can cause long term remission of peptic ulcer - true or false
True
List the 3 meningeal layers
dura mater, arachnoid mater and pia mater.
Describe the blood flow and pressure in the hepatic artery and vein
Hepatic artery has highest pressure (100mg/Hg) but carries least amount of blood (ml)/min and the hepatic vein has the lowest pressure (4mmHg) but transports the most blood(ml)/min
How is hepatic encephalopathy graded
I: Altered mood/behaviour; sleep disturbance (e.g., reversed sleep pattern); dyspraxia; poor arithmetic. No liver flap.
II: increasing drowsiness, confusion, slurred speech ± liver flap, inappropriate behaviour/personality change.
III: incoherent; liver flap; stupor.
IV: coma
Short segments of Barrett’s have a lower risk of dysplasia - true or false
True
Lower risk of dysplasia and therefore adenocarcinoma too
Usually asymptomatic of GORD
List some of the signs and symptoms of liver failure
Jaundice Ascites Encephalopathy Anorexia, weight loss Bruising
Describe the natural history of subdural haematoma
After the vessels are torn, blood will accumulate in the subdural space .
As blood accumulates it puts more pressure on the brain, causing injury and gradually raising ICP.
If untreated this can cause shifting of the brain and eventual herniation
This can be fatal
List the sections of the duodenum
Superior
Descending
Horizontal
Ascending
Which groups are at an increased risk of subdural haematoma and why
Infants and children – veins are still relatively thin-walled
The elderly – higher fall risk and veins more fragile due to stretching from brain atrophy
Alcoholics are also at an increased risk due to their propensity for falls and head trauma alongside the disordered bleeding associated with alcoholism (thrombocytopenia, prolonged bleeding times)
Describe the macroscopic features of gastric cancer
Most early gastric cancers are small, measuring 2 to 5 cm in size
Often located at lesser curvature around angularis
Can be multifocal (indicative of a worse prognosis)
Features classified by Borrman classification - other card
Describe how the liver is remodeled in cirrhosis
Undergoes diffuse remodelling into parenchymal nodules (often regenerative) surrounded by fibrous bands & variable degrees of vascular shunting (circulation is rebuilt)
The whole liver can become deformed and hardened
Describe the pathogenesis of a subdural haematoma
Trauma/impact to the head causes the bridging veins to tear and venous blood escapes into the subdural space
They are vulnerable to tearing as they are fixed relative to the dura – on impact the brain suddenly moves and pulls on the fixed structure (shearing force)
Which nonoperative & endoscopic strategies are used for bleeding peptic ulcer
Administration of pre-endoscopy erythromycin
Endoscopic treatment: achieve hemostasis + prevent rebleeding
Nonoperative management: 1st –line management after endoscopy
Initiation of PPI therapy asap (high-dose PPI as a continuous infusion for the first 72 hours) + PPI for 6-8 weeks after endoscopic treatment
Which protective mechanisms exist to prevent the pancreas autodigestion
Digestive enzymes are synthesized as inactive proenzymes and packed into secretory granules
They are activated by trypsin which itself is activated by an enzyme from the small bowel (intrapancreatic activation is minimal)
Acinar and ductal cells also secrete tryptin inhibitors – all of these minimize the activation of digestive enzymes
Pancreatitis occurs when these protective mechanisms are disrupted
What type of epithelium lines the oesophagus
Non keratinised stratified squamous epithelium
How do subdural haematomas present on CT
Classic crescent moon appearance
Describe the structure of the cells within the pancreatic acinus
The basal part of the cells are typically basophilic due to extensive RER, while the apical part is very eosinophilic due to the presence of zymogen (pre-enzyme) granules
What causes palmar erythema in cirrhosis
Impaired oestrogen metabolism
It reflects local vasodilation
What is the main cause of increased portal venous flow
Primarily due to arterial vasodilatation in the splanchnic circulation. Increased arteriolar blood flow -> increased venous efflux into portal venous system. Nitric oxide (NO) is the most significant mediator in splanchnic arterial vasodilatation (others: prostacyclin, TNF).
How is the transplant benefit score calculated
By measuring the difference between the area under the waiting list survival curve and the area under the post-transplant survival cure over a 5-year interval
Difference between the expected survival with the transplant and the expected survival on the waiting list
Utility – Need = Transplant benefit
Utility – liver offered to patient with shortest predicted survival time without liver transplant.
Need – liver offered to longest predicted survival time with a liver transplant
List the potential complications of endoscopic mucosal resection
bleeding, perforation, stricture formation, narrowed oesophagus = dysphagia
List causes of subdural haematomas
Head trauma is the leading cause of subdural haemorrhage.
However, in vulnerable groups such as the elderly this trauma can seem minor
Other rarer causes include coagulation disorders, vascular malformations and glutaric aciduria type 1.
List the clinical features of Barrett’s
Symptoms of chronic GORD
Rarely can be completely asymptomatic
May have globus sensation as well as dysphagia
Describe the epidemiology of squamous cell carcinoma of the oesophagus
4X as common in males and usually >45yrs
Most common in Europe and Asia
In Us much more common in African Americans than Caucasians due to alcohol and tobacco use as well as other unidentified factors
How do you treat peptic ulcers
All ulcers seen on endoscopy should be biopsied to assess for malignancy
Patients may require stabilisation and resuscitation
Most haemorrhage can be treated endoscopically via a mechanical method such as clips, coagulation, or fibrin +/- adrenaline
The use of PPIs should be considered, especially as prophylaxis where NSAID use cannot be stopped
Describe the structure of the pancreas capsule
The pancreas has a thin connective tissue capsule that is continuous with connective tissue septa that divide the gland into lobules.
What is peptic ulcer disease
Chronic mucosal ulceration affecting the duodenum or stomach
List the macroscopic features of cirrhosis
Bumpy surface nodules Hardened liver Thickened capsule Depressed areas of fibrosis. Yellow hue: fatty change
Where does the portal vein drain blood from
Drains blood from the small + large intestines, stomach, spleen, pancreas and gallbladder
What is the prominent pathological feature in most cirrhotic livers
Regenerative nodules
They are formed from the surviving hepatocytes in CLD replicating in an attempt to restore the parenchyma
If a patients with PUD is on NSAIDs what should you do
Withdraw the drug
Same goes for any other offending agents that may interfere with mucosal healing
How do you manage pancreatic cancer
Surgery
Chemotherapy
Neoadjuvant therapy
Behaviour caused by drunkeness comes with significant risk - true or false
True
50% of alcohol related deaths caused by DUI, homicide and suicide
When is ascites clinically detectable?
Usually clinically detectable when at least 500ml has accumulated
What is the gold standard treatment for GORD
PPI
Which part of the stomach holds broken-down food until it is ready to be released
the pyloric antrum
Is endoscopy required for the diagnosis of GORD
NO
unless refractory after PPI
List causes of altered consciousness in cirrhosis patients
Hepatic encephalopathy Hypoglycaemia Sepsis Head trauma Post-ictal Wernicke’s encephalopathy Hyponatraemia Withdrawal syndromes
List the structures found in the mucosa and submucosa of the small intestine
Plicae circulares - folded from mucosa & submucosa
Intestinal villi (mucosal outgrowths) - for absorption
Intestinal crypts
Submucosa of duodenum has Brunner’s glands - branched tubular mucous glands
Lamina propria & submucosa in ileum - Peyer’s patches (a component of GALT)
Hypogonadism in females with cirrhosis is caused by what
Nutritional deficiencies associated with chronic liver failure or a primary hormonal alteration which disrupts the HPA
Those with ADH disorders at higher risk of oesophageal cancer - true or false
True
List the macroscopic features of a peptic ulcer
Solitary in more than 80% of patients
Most common in duodenum
Form a round to oval, sharply punched-out defect - clear margin
Mucosal margin is usually level with surrounding mucosa
May overhang the base (particularly on proximal side)
Depth of ulcer correlated with diameter
Base of peptic ulcers is smooth and clean as a result of peptic digestion of exudate
may be evidence of infiltrated vessels and evidence of thrombosis
Is surveillance required after ablation in BO
Yes
Surveillance is still required as several treatments may be needed to eliminate the lesion
Describe the process of fatty hepatocyte degeneration
You get lipid accumulation, and fat vacuoles formed within cytoplasm of the liver cell
List the types of hepatocyte degeneration seen in cirrhosis
Ballooning degeneration
Fatty degeneration
Describe the natural progression of cirrhosis
Starts with the causal disease
This causes recurrent inflammation and fibrosis
This will lead to compensated cirrhosis
Then decompensated - causing acute-on-chronic liver failure
Eventually death
Which zone of the liver is most affected by iron overload
Zone 1
Due to higher exposure level and more oxygen present
Which proportion of duodenal and gastric ulcers are H.pylori positive
Over 60%
Excluding patients who use NSAIDs
How does alcohol cause acute pancreatitis
Via duct obstruction, acinar cell damage
How do you treat alcohol withdrawal
Treated with chlordiazepoxide and may need thiamine replacement
What is the prognosis of acute pancreatitis
Most recover but about 5% with severe cases die in first week
The pancreas is a retroperitoneal organ - true or false
True
List potential causes of death in cirrhosis
Hepatic Encephalopathy
Ruptured oesophageal varices
Bacterial infection
Hepatocellular carcinoma
Impaired oestrogen metabolism in cirrhosis can have what effects
Leads to hyper-oestrogenaemia
Palmar erythema + spider angioma
Males: hypogonadism + gynaecomastia
Describe the pathogenesis of Mallory-Weiss tears
Thought to be due to a failure to relax the gastroesophageal musculature during prolonged vomiting
During prolonged vomiting or intense coughing fits, there is a sudden rise in abdominal pressure
The gastroesophageal mucosa tears as it is unable to fully distend
How can you identify the extent of fibrosis in cirrhosis cases
Stain for collagen fibres (e.g., Masson’s trichome)
Type 1 collagen & nerve fibres blue; cytoplasm/muscle red; nucleus black/blue
How do you treat BO with confirmed low grade dysplasia
endoscopic ablative therapy or 6-12 month surveillance plan
If oesophageal adenocarcinoma is symptomatic what has likely already happened
likely already have haematogenous and lymphatic spread
Gastric cancer is more common in lower socioeconomic groups - true or false
True
What is contributing to a increase in gastric cancer cases
Barrett’s esophagus
Increasing incidence of chronic GERD
Obesity
What makes the acinar glands in the pancreas different to all others
Unlike in other acinar glands, such as the parotid, the smallest ducts in the pancreas (the intercalated ducts) do not start where the acinus ends, but rather extend into the acinus
They represent an extension of the intercalated duct into each pancreatic acinus.
At which vertebral level is the gastroesophageal junction found
T11
What causes oesophageal varices
Portal hypertension
Usually as a result of liver disease - cirrhosis
What are the main complications of GORD
The main one is that if left untreated it can progress onto Barrett’s oesophagus
It also has the potential to cause ulceration and strictures due to chronic inflammation
List neurological conditions that can be caused by alcohol
Peripheral neuropathies
Wernicke-Korsakoff Syndrome
(later cerebral atrophy, cerebellar degeneration and optic neuropathy can occur)
What can cause an obstruction in a GI bleed
Can occur as lesions or ulcers heal as scarring leads to stenosis, particularly at the gastric outlet
What is secreted by the centroacinar cells
aqueous bicarbonate solution
This occurs under stimulation by the hormone secretin
Deterioration is fast in subdural haemorrhage – true or false
False
It can be if there is herniation etc. but typically it is slow and progressive
Describe the prevalence and mortality of oesophageal varices in cirrhotic patients
Appear in ~40% of individuals with advanced liver cirrhosis
Cause massive haematemesis and death in about 50% of those affected.
Each episode of bleeding is assoc. with ~30% mortality
List the macroscopic features of oesophageal varices
Varices protruding into oesophageal lumen
May be inflammation or ulceration present along with evidence of past episodes of bleeding
Describe the structure of the falciform ligament
It divides liver into the larger right and smaller left lobes.
It has 2 layers of peritoneum and attaches the antero-superior surface of the liver to the anterior abdominal wall and diaphragm.
The free edge of this ligament contains the ligamentum teres hepatis
Describe the effects of moderate alcohol consumption
In general, this doesnt lead to long term harms (if you follow safe drinking guidelines)
Studies have shown that moderate consumption of around 20 to 30g of alcohol per day actually appears to protect against coronary heart disease.
May be due to increasing HDL levels, inhibition of platelet aggregation and lower fibrinogen levels
How does h pylori cause gastritis
Interaction of H. pylori with surface mucosa -causes the release of IL-8
This leads to recruitment of PMNs which begin inflammatory process
This is enhanced by Class II molecules expressed by gastric epithelial cells as they cause activation of transcription factors
This leads to further cytokine release and more inflammation
Describe how acinar cell injury can cause acute pancreatitis
Acinar cells can be damaged by a variety of endogenous, exogenous and iatrogenic insults – oxidative stress, generation of free radicals, membrane lipid oxidation, transcription factor activation and various other molecular pathologies
This damage causes the release of intracellular enzymes
What is chronic pancreatitis
It is prolonged inflammation of the pancreas associated with irreversible destruction of exocrine parenchyma, fibrosis, and in the later stages endocrine parenchyma
Describe the neoadjuvant therapy used in oesophageal cancer
Neoadjuvant therapy can be given in the form of chemo +/_ radiotherapy
What is the most characteristic sign of cancer of head of the pancreas
Painless obstructive jaundice
What are some of the complications of H2 antagonist treatment
ED, depression, gynaecomastia, hallucination, liver dysfunction, leukopenia, agranulocytosis, AV block, pancytopenia, thrombocytopenia and vasculitis
Which microscopic features are seen in chronic pancreatitis caused by alcohol
ductal dilation + protein plugs and calcifications
What pressure is required for oesophageal varices to form
Varices form when pressure in collaterals is >10mmHg
Bleeding will occur if pressure >12mmHg
Which types of chemo are used in the treatment of gastric cancer
Platinum-based combination chemotherapy
Trastuzumab + cisplatin + capecitabine/5-FU
Ramucirumab following a fluoropyrimidine- or platinum-containing regimen
Pembrolizumab
How is the liver divided histologically
Divided into 1-2mm hexagonal lobules oriented around the terminal tributaries of the hepatic vein (central veins).
So the central vein is in the centre of the lobule
At the periphery of the lobule are portal triads
List some of the potential complications of a GI bleed
Hypovolaemic Shock -common
Obstruction
Perforation - rare but serious
How do you treat inoperable or metastatic gastric cancer
Palliative chemotherapy / Supportive care
Is gastric cancer more common in men or women
Men
M:F ratio: 2:1
List the classical clinical features of acute pancreatitis
Acute onset of severe central epigastric pain (over 30-60 min)
Poorly localised tenderness and pain
exacerbated by supine positioning
Radiates through to the back in 50% of patients
What are some of the complications of endoscopy
infection, bleeding, perforation, sedation caused hypotension, breathing difficulties or reaction
Describe the structure of the ligamentum teres hepatis
Attached to inferior surface of liver between segment IV on right and III on left
What is the Child-Pugh classification used for
It was introduced as a prognostic tool for operative mortality assoc. with portocaval shunt surgery for variceal bleeding
Current use is to predict life expectancy in patients with advanced cirrhosis
e.g. a CTP score 10 or above is assoc. with 50% chance of death within 1 year.
List the pros of the Child-Pugh score
Variables for ascites and hepatic encephalopathy (HE) are included in the score
Which cell types are found in the fundus and body of the stomach and what are their functions
Mucous neck cells - secrete mucus at neck region
Parietal cells - secrete HCl, gastric intrinsic factor and mucous coating at neck region
Chief cells - synthesize & release zymogens (including pepsinogen and precursors of rennin & lipase) at base region
Enteroendocrine cells - secrete various peptide hormones and act as neurotransmitters
Undifferentiated cells - they have high mitosis rates and give rise to the above cell types
What types of cancer make up the majority of oesophageal cancer cases
adenocarcinoma or squamous cell carcinoma
What structures are you looking for at the porta hepatis (liver hilum)?
Portal vein, hepatic artery proper, common bile duct.
How does alcohol cause gastric ulcers
Ulcers generally occur on a background of chronic gastritis which is also caused by alcohol
Which cells in the pancreas secrete insulin and glucagon
Islets of Langerhans
How do you treat a Mallory-Weiss tear
80-90% of cases are self-limiting
Else, treatment with clips or ligation are performed endoscopically, often in conjunction with adrenaline administration
Describe the caudate lobe of the liver
It is actually segment 1 and not a lobe
It lies in the lesser sac between the IVC on the right, the ligamentum venosum on the left and porta hepatis in front
The caudate process attaches the caudate lobe to the right lobe.
What is the characteristic feature of pancreatic cancer
Significant wait loss
What is the purpose of intrinsic factor
Allows for Vitamin B12 absorption in the small intestine
List the pathological features of mild GORD
Grossly – redness of the oesophagus representing hyperaemia
Microscopically – histology is often unremarkable
Where do scars typically form in cirrhosis
Often in the space of DIsse
List the macroscopic features of diverticulitis
Visible outpouchings of colonic mucosa - may contain impacted stool
In the case of infection or inflammation, this may be seen as hyperaemia, ulceration or rupture
List the component parts of the pancreas
The head - relatively short at only 1-2cm and lies over the superior mesenteric vessels.
The uncinate process - small projection from the inferior part of the head of the pancreas and lies posterior to the superior mesenteric artery.
The body - continues from the neck, lies over the aorta and L2 vertebra.
The tail - lies anterior to the left kidney
Management of subdural haematoma comes with what risks
Any form of brain surgery comes with many risks – brain damage, infection etc.
Risk of recurrence.
Oesophageal cancers can spread down into the cardia of the stomach - true or false
True
Cirrhosis can be asymptomatic until late stage disease - true or false
True
~40% are asymptomatic until most advanced stages of disease.
Where is the majority of alcohol metabolised
In the liver
What is the difference between diverticulitis and diverticulosis
Diverticulosis – formation of diverticular
Diverticulitis – inflammation of diverticular
List the cell types found in the intestinal crypts of the small intestine
Goblet Cells
Paneth cells - secretion of antibacterial, defensins, lysozyme
Columnar epithelial cells - – for absorption (brush border enzymes)
Enteroendocrine cells – secrete Gi hormones
Undifferentiated cells
Describe the macroscopic features of oesophageal adenocarcinoma
Usually occurs in distal 3rd of oesophagus and may involve the gastric cardia
Initially comprised of patches that are raised or flat within an intact mucosae
Eventually it will become a large mass 5cm or more in diameter
Alternatively the tumours can ulcerate and invade deeply or can infiltrate diffusely
Where does blood enter the liver
Both supplies enter on inferior aspect of liver at hilum (aka. porta hepatis).
List GI disease that can be caused alcohol
Gastritis
Gastric Ulcers
Oesophageal Varices
What is the main cause of Barrett’s oesophagus
GORD
Which structures are included in the upper GI tract
Runs from the oral cavity up to and including the duodenum
Oral cavity
Pharynx - nasopharynx, oropharynx and larnygopharynx
Oesophagus
Stomach
Duodenum
Which 3 enzymes are responsible for alcohol metabolism
ADH is the main enzyme and is found in the cytosol of hepatocytes.
The p-450 enzymes become more important at high alcohol levels - part of the microsomal ethanol-oxidising system
Catalase has minor effect - only deals with around 5% of the alcohol
How does the pain present in a penetrating peptic ulcer
Pain is occasionally referred to the back , left upper quadrant, or chest
May be misinterpreted as cardiac in origin
List post-sinusoidal causes of increased resistance in the portal vein
Central vein lesions caused by perivenous fibrosis etc.
Veno-occlusive changes
What is the most common mechanism of death in GI bleeds
Hypovolaemic Shock
How are people selected for liver transplant in the UK
UKMELD used in conjunction with the Transplant Benefit Score (TBS)
UKELD must be calculated monthly to update patient illness severity.
Which body systems are most affected by alcohol (acutely)
Mainly affects the CNS but can also impact the GI system and the liver acutely
Chronic pancreatitis is common in alcoholics - true or false
True
Persistent or repeated episodes of acute pancreatitis will lead onto chronic pancreatitis
Alcoholics are at a risk of repeated pancreatitis
What is the definition of portal hypertension
Hepatic venous pressure gradient (HVPG): Gradient between portal vein and IVC >10mmHg
How can a hepatic hydrothorax form in cirrhotic patients
With long-standing ascites, seepage of peritoneal fluid through trans-diaphragmatic lymphatics may lead to the hydrothorax
How is alcohol distributed around the body
Around 10% is excreted unchanged via the urine, sweat and breath.
The rest is distributed around the body via the bloodstream.
This distribution is dependent on blood level and water content of tissues
Smoking alongside alcohol consumption increases your cancer risk - true or false
True
It has a synergistic effect
What is pancreatitis
Pancreatitis is initiated by an injury that leads to auto-digestion of the pancreas by its own pancreatic enzymes
Normally regulation would stop this so it occurs when the protective mechanisms are disrupted
Describe the natural history of Barrett’s
First will have chronic GORD before progressing to BO
There is a risk if left untreated that it will progress, although slowly, to adenocarcinoma
What is significant about the parietal cells in the pylorus
Fewer cells present
Secrete less HCl than other regions
H. pylori can grow here
List the morphological classification of cirrhosis
Micronodular
Macronodular
Mixed
What is the most common malignancy of the stomach
Adenocarcinoma
Accounts for more than 90% of all gastric cancers
List post-hepatic causes of portal hypertension
Severe right-sided heart failure
Congestive pericarditis
Hepatic vein outflow obstruction
List the ligaments of the liver
Falciform ligament
Ligamentum teres hepatis
Ligamentum venosum
Left and right triangular ligaments – branches of the coronary ligament
Describe the pathogenesis of diverticulitis
Exact mechanism unknown
Infections may develop in diverticular as a result of food particles or faecal matter
This leads to inflammation, ischaemia, necrosis, ulceration
Describe the structure of the muscularis propria of the oesophagus
Has inner and outer longitudinal layers
Skeletal muscle at top and smooth muscle distally
Has myenteric plexus
How does NSAID use cause peptic ulcer disease
NSAIDs disrupt the permeability barrier
30% of adults taking NSAIDs have GI adverse effects
What blood results would suggest acute pancreatitis
Elevation of serumamylase and lipaseare 90-95% specific for the diagnosis
Can be normal though - especially on an background of chronic
Describe the palliative care options in oesophageal cancer
Involves both chemo and radiotherapy in order to control disease and its symptoms
List the parts of the stomach
Comprised of a cardia, fundus, body/corpus and pyloric antrum
Describe the structure of gastric glands
Found in the fundus and body
Straight, branched at base
Have an isthmus, Neck, Base
Secretion regulated by vagus nerve & hormones
How are subdural haematomas classed
If less than 72 hours old they are classed as acute, subacute from days 3-21 and chronic from 3 weeks onwards
How do you manage early stage oesophageal cancer
Endoscopic mucosal resection if small and confined to inner lining of oesophagus
If it has spread out with the inner lining then oesopahgectomy is done
Chemoradiation may be done if cant have/doesn’t want surgery or neoadjuvantly
List intra-sinusoidal causes of increased resistance in the portal vein
Contraction of vascular smooth muscle cells + myofibroblasts - increases portal flow.
Hepatocyte degeneration and remodelling can reduce sinusoid calibre
Collagen deposition in space of Disse alters the elastic properties of the sinusoidal wall
Periportal inflammation, fibrosis and/or necrosis can block sinusoids
Decreased NO production, increased endothelin-1 + angiotensinogen release -> intra-hepatic vasoconstriction
Intrahepatic shunts interfere with the metabolic exchange between sinusoidal blood & hepatocyte
Which is more common, upper or lower GI bleeding
Upper GI
Lower is approx 20% as common as upper GI bleeding
List aggressive factors which contribute to peptic ulcer disease
NSAIDs H. pylori infection Alcohol Bile salts Acid Pepsin
List causes of stomach bleeds
Peptic Ulcer Disease
Gastritis
Gastric Cancer
What is the most common cause of acute pancreatitis in pregnancy
Hypercalcaemia
What is the connection between the portal and systemic systems in the oesophagus that allows shunts
Superior part of oesophagus drains to azygous vein
Inferior part drains to hepatic portal vein
Describe the structure of the mucosa in the stomach
Has several sublayers
Epithelium - changes from stratified squamous in esophagus to simple columnar (for absorption)
Lamina propria - loose connective tissues, lymphatics, fenestrated blood vessels, mucosal gland, unencapsulated lymphoid nodules and plasma cells
Muscularis mucosae (controlled by Meissner’s plexus) Raises into folds – rugae
Gastric pits: tiny epithelial recess where glands open into
Mucous lining to protect against acidity
H pylori can be picked up by which stains
Strongly urease positive
Silver stain: Warthin-Starry stain
What determines the extent of the morphological signs of pancreatitis
The duration and severity of the pancreatitis
e.g. acute interstitial pancreatitis vs acute necrotizing and haemorrhagic pancreatitis
How do you manage advanced stage oesophageal cancer
Managed with chemo +/- radiotherapy
Potentially herceptin or immunological therapy depending on cancer type
Where does the portal vein enter the liver
Portal vein enters at hilum
It then splits into the right and left portal vein
Right supplies segments 5-8 and left supplies segments 1-4
How common are subdural haemorrhages
They occur in around 15% of head trauma cases and up to 30% of fatal trauma cases.
More common in men than women (3:1 ratio) and highest incidence in the 50s-70s
Describe the epidemiology of GORD
Most common cause of oesophagitis
Prevalence of 10-20% in the west but only 5% in Asia
Most common in individuals >40yrs
Describe macronodular cirrhosis
Has differing size of nodules
Diameter >3mm (can be >1cm+)
May contain >1 portal vein + central vein
How are the causes of portal HTN divided
Into pre, intra- and post-hepatic causes
Pre-hepatic – alterations to portal venous system (tributaries: splenic and SM veins).
Intra-hepatic – disease which affects the liver architecture or microcirculation.
Post-hepatic – aka. Supra-hepatic disease, from the IVC and beyond
How are GI bleeds classified
typically classified by their location in relation to the ligament of Treitz (suspensory muscles of the duodenum)
UGI = Oesophagus, stomach and duodenum LGI = Jejunum, ileum, colon, rectum and anus
H pylori is positive in which proportion of ulcers
~95% of duodenal ulcer and~75% of gastric ulcer patients
List the microscopic features of a subdural haematoma
Signs of clot lysis after 1 week.
After around 2 weeks, fibroblasts will be seen in the haematoma.
Hyalinised connective tissue can form after 1-3 months.
What is the preferred diagnostic test for peptic ulcer disease
Upper GI endoscopy
List the clinical features of oesophageal cancer
dysphagia/odynophagia - usually starts with solids and progresses Weight loss Anaemia and heamatemesis Epigastric or retrosternal pain Pain over bony structures of neck Hoarseness Persistent cough Recurrent pneumonia
How do you treat Barrett’s (in general)
Once diagnosed are put onto optimum dose PPI therapy and given periodic endoscopy and biopsy to monitor for disease progression
A BAC of between 200-300 mg/100ml is likely to have what effect
Get depression of the limbic system and cerebellum.
Leads to confusion, loss of memory/orientation and problems with movement and speech.
What is the prevalence of peptic ulcer disease
Prevalence increases with age
Affecting approx. 4.6 million in the US
Non-variceal causes have mortality of 8-14%
How can alcohol affect an unborn baby
It can cause Foetal Alcohol Syndrome
Caused by ethanol intake during pregnancy - particularly during the first trimester
How does E-cadherin dysfunction lead to gastric cancer
Caused by mutations in the CDH1 gene
Causes dysfunction of gastric epithelial cells
This causes a failure to maintain cell polarity and differentiation
Leads to tumour invasion & progression
Splenomegaly in portal HTN can induce which secondary effects
May secondarily induce haematologic abnormalities attributable to “hypersplenism” – esp. thrombocytopenia or even pancytopenia
Largely due to sequestration of blood elements in the expanded splenic red pulp.
List the cons of the Child-Pugh score
Ascites and HE are subjective and the use of diuretics and lactulose (treatment) can vary.
INR reflects hepatic synthetic function but not naturally occurring anticoagulants like protein C and S.
Inter-laboratory variation in INR calculation.
What is the typical incidence of peptic ulcer disease
approximately 1 case per 100 person per year
Damage to the bile ducts in cirrhosis has what effects
It leads to cholestasis in the small bile ducts - pruritus
Can lead to new ducts forming in fibrous tissue.
Where is Virchows node
behind the medial end of the left clavicle
What is the mortality from subdural haematoma
Mortality in symptomatic cases is very high – 50-90%.
Describe the pathogenesis of oesophageal adenocarcinoma
Progression of the BO to the adenocarcinoma over an extended period of time due to step wise acquisition of genetic and epigenetic changes
Specific changes not well understood but thought to be due to mutations within tp53 and CDKN2A as well as amplification of EGFR, ERBB2, MET, cyclin D and cyclin E oncogenes
Obesity also plays a role additional to causing GORD as the hypertrophied adipocytes and inflammatory cells within fat deposits create an environment of low grade inflammation and promote tumour development by releasing adipokines and cytokines
Also supply energy and support tumour growth
Which specialised cell type will you find in the space of Disse?
Hepatic stellate cells
List the microscopic features of oesophageal varices
Dilated vessels sitting within the mucosa and submucosa
May be associated with inflammation +/- tissue necrosis
Is h pylori a carcinogen
Yes
Class 1 carcinogen (WHO)
Describe the pathogenesis of oesophageal varices
Increase in vascular resistance in portal system leads to development of collateral vessels to allow some shunting of blood around the liver
This causes congestion and dilation of venous plexuses within the oesophagus and stomach
List factors associated with an increased risk of duodenal ulcers in the setting of NSAID use
Hx of previous peptic ulcer disease Older age Female sex High doses or combinations of NSAIDs Long-term NSAID use Concomitant use of anticoagulants Severe comorbid illnesses
What is the connection between the portal and systemic systems in the rectum/anus that allows shunts
Rectum and superior anal canal drain to IMV; inferior part of GI tract drains to internal iliac veins.
How are small subdural haematomas managed
May be managed conservatively with serial head CTs.
This is because venous bleeding usually self-limiting and the haematoma may resorb
If there are clotting abnormalities these should be reversed immediately.
Should also address the initial cause of the trauma if possible (e.g. assess fall risk or treat alcoholism.)
How do you confirm dysplasia in BO
Biopsy
If biopsy shows dysplasia this must be confirmed by a second pathologist experienced with BO neoplasia
List the 5 characteristic morphological signs of acute pancreatitis
Microvascular leak and oedema Fat necrosis Acute inflammation Damage Blood vessel destruction with interstitial haemorrhage
Describe the structure of the muscularis externa of the small intestine
inner circular, outer longitudinal smooth muscles
Which score is used MELD or Child-Pugh
More research needs to be done to define which score should be used and when
Each is better in different sitautions
Cirrhosis can cause impaired oestrogen metabolism - true or false
True
Describe the structure of the lamina propria of the oesophagus
Made of fibrovascular connective tissue
Has scattered inflammatory cells and mucus glands lined with foveolar like cells releasing neutral mucin
Will fold into papillae that protrude into epithelium
What is the recommended antimicrobial regimen for a perforated peptic ulcer
Administration of broad-spectrum antibiotics
Microbiological sample collection for analysis of pathogen
Initiation of empiric broad-spectrum antibiotics asap
Targeting gram-negative, gram-positive and anaerobic bacteria
Short course of 3-5 days or until inflammatory markers normalize
List the clinical features of gastric cancer
A palpable enlarges stomach with succussion splash
Hepatomegaly
Periumbilical metastasis (Sister Mary Joseph nodule)
Enlarged lymph nodes e.g. Left supraclavicular node & anterior axillary node
Blumer shelf - tumour in pouch of Douglas
Weight loss
Melena
Pallor from anemia
What are the 3 main processes behind acute pancreatitis
Duct obstruction
Acinar cell injury
Defective intracellular transport
Describe the microscopic features of a poorly differentiated gastric adenocarcinoma
Glands are not visible
Rows of infiltrating neoplastic cells with marked pleomorphism
Neoplastic cells have clear vacuoles of mucin pushing cell nucleus to one side -> signet ring
What does the MELD score include
Measures total bilirubin, creatinine, INR and serum sodium levels
What is the purpose of the pyloric sphincter
Acts as a valve and prevents backflow of contents to stomach
What is a subdural haematoma
It is bleeding between the dura and arachnoid layers - in the subdural space
List the 4 layers of the stomach
Mucosa - composed of epithelium, lamina propria, muscularis mucosa
Submucosa
Muscularis externa
Serosa
Describe the prevalence of diverticular disease
Prevalence increases with age with approximately 50% of over 50s having some degree of disease.
Thought to account for 15-40% of LGI bleeds
Describe the microscopic features of gastric cancer
Hyperchromatic (big N/C ratio)
Increased mitosis
Describe how pancreatic enzymes are activated
The enzymes are produced as inactive proenzymes.
Once the pancreatic secretion arrives in the duodenum an enteropeptidase converts the inactive proteolytic enzyme trypsinogen into the active form, trypsin.
This begins a cascade that results in the activation of the other enzymes.
How might compensated cirrhosis present
Stigmata of cirrhosis
May be an incidental finding
May have portal HTN
Symptoms of cause - may have been present earlier
What is the outlook for chronic pancreatitis
Outlook is poor: 25 year mortality rate of 50%
How may advanced pancreatic cancer present if there is intra-abdominal disease
Presence of ascites, a palpable abdominal mass, hepatomegaly from liver metastases, or splenomegaly from portal vein obstruction
List symptoms of pancreatic cancer
Significant weight loss
Mid-epigastric pain - sometimes with radiation of the pain to the midback or lower-back region
Often, unrelenting pain: Night-time pain often a predominant complaint
Onset of diabetes mellitus within the previous year
Painless obstructive jaundice
Pruritus: Often the patient’s most distressing symptom
Depression
Migratory thrombophlebitis (ie, Trousseau sign) and venous thrombosis: May be the first presentation
Palpable gallbladder (ie, Courvoisier sign)
Describe the pathogenesis of ascites
It is a complex process involving sinusoidal hypertension, hypoalbuminemia, increased hepatic lymph flow, and splanchnic vasodilatation and hyperdynamic circulation
How do genetics contribute to peptic ulcer disease
More than 20% of patients have a family history of duodenal ulcers, compared with only 5-10% in the control groups
If features of upper GI bleeding are present, there is no way the source is lower - true or false
Though there are certain features that are more characteristic of one source of bleeding or the other, these are not always the case
In 15% of patients who present with LGI bleeding, the source is actually an UGI bleed
UGI bleeds may present as frank blood in stool if severe enough
List the microscopic features of peptic ulcers
There will be loss of the normal histological structure of the gut wall
Active ulcers may be lined by a thin layer of fibrinoid debris with a predominantly neutrophilic inflammatory infiltrate
Granulation tissue with immature vessels, mononuclear leukocytes, a fibrous/collagenous scar forms ulcer base
Scarring usually at base but may involve the entire thickness of the wall - this can draw surrounding mucosa into folds that radiate outward
There may also be some metaplastic changes present
What is the mechanism of death in GORD
GORD can lead to Barretts Oesophagus and then Adenocarcinoma which can be fatal
Ulceration has the potential to cause an upper GI bleed
How is non dysplastic BO treated
PPI irrespective of symptoms and surveyed every 3-5yrs
List features of alcohol withdrawal
tremor, nausea & vomiting, malaise, headache, insomnia, weakness, sweating, tachycardia, hypertension, anxiety, depression, irritability
Hallucinations - particualrly visual or tactile - insect crawling is a common one
In severe cases patients can have withdrawal fits or develop delirium tremens (DTs) which involves sudden onset of confusion and hallucinations alongside the other symptoms.
When does Barrett’s oesophagus become intramucosal carcinoma
Once the epithelial cells invade the lamina propria - defining feature
Where is alcohol excreted unchanged (i.e. before metabolism)
The urine, sweat and breath
Excretion via breath is the reason why you can do breath tests
Does h pylori reduce the risk of any types of cancer
YES
Reduced risk of gastric cardia cancer
Thought to be related to decline in stomach acidity which is often seen after decades of H. pylori colonization
How do you treat oesophageal varices
Stabilisation and resuscitation if needed
Endoscopy within 12 hrs – if haemorrhage found, then Endoscopic Variceal Ligation (EVL) performed
TIPS – Trans-jugular Intrahepatic Porto-systemic Shunt
What is happening to the incidence of peptic ulcer disease
Falling due to the reduced prevalence of H. pylori infection
BUT
Increasing in patients older than 60 years due to growing NSAIDs use - these cases can be amplified by H.pylori
List the pathological features of significant GORD
Grossly – there may be erosions on top of the hyperaemia (redness)
Microscopically – eosinophils within the squamous mucosae, elongation of the papillae of the lamina propria and basal zone hyperplasia are all often seen
List the macroscopic features of a subdural haematoma
Appears as a collection of freshly clotted blood on the brain surface.
It is not limited by the skull sutures but instead by the dural reflections.
The clot does not extend into the sulci of the brain and the arachnoid space is usually clear.
The underlying brain can be flattened by the pressure and after a long period the area can become atrophied.
Once organisation has occurred the haematoma can become firmly attached to the dura but free from the arachnoid.
May retract until it is only a thin layer of connective tissue or repeated bleeding can form a chronic haematoma.
Describe the pathophysiology of chronic pancreatitis
Chronic pancreatitis often follows repeated episodes of acute pancreatitis
It has been proposed that the acute episodes initiate a sequence of perilobular fibrosis, duct distortion and altered secretions lead to loss of exocrine parenchyma and fibrosis
What are some of the complications of the Nissen Fundoplication used in GORD
bleed at surgical site, peritonism, dysphagia, perforation/tear of oesophageal lining, slippage of the wrapped stomach
What is the function of the pancreas
It is an accessory digestive organ
Has exocrine and endocrine functions
Exocrine - releases pancreatic digestive enzymes (produces 1L of juice per day)
Endocrine - releases insulin and glucagon
Long-standing portal HTN may cause massive splenomegaly - true or false
True
What is alcohol
The alcohols are a group of chemical compounds containing a hydroxyl group and a varying number of carbons
Produced via the fermentation of various products such as grains, fruit and vegetables
What causes the formation of portosystemic shunts
Chronic portal hypertensions leads to vascular dilation + remodelling
Creates thin-walled collateral venous circulation (shunts) between portal & systemic circulations (bypass the liver)
Shunts can form anywhere the systemic & portal circulations share pre-existing vascular beds
A BAC of under 100mg/100ml is likely to have what effect
Depression of higher cortical function.
Leads to excitement, loss of self consciousness, typical drunk/tipsy behaviour
Where are most ulcers found in PUD
Most frequently found in proximal duodenum within a few cm of pyloric valve
List the defense mechanisms of the stomach and small intestine
Tight intercellular junctions Mucus Bicarbonate Mucosal blood flow Cellular restitution Epithelial renewal
All help prevent ulceration normally
Why must cirrhosis patients have a predicted mortality worse than 9% to be considered for a liver transplant
1-year post-liver transplant mortality (UK) is ~9%.
So they must have a worse mortality than that for the transplant to give them a survival benefit
What are the characteristic features of chronic pancreatitis
parenchymal fibrosis, acinar atrophy and dropout, and variable ductal dilation
Which structures run on the surface of the oesophagus
RLN runs on its surface with thoracic duct to left and carotid sheath down the side
What is the main complication of Barrett’s
Can develop into adenocarcinoma
Most cases will NOT
List the main causes of acute pancreatitis
Idiopathic Gallstones (rare : genetic e.g. CF) Ethanol (alcohol) Trauma - BF, surgery etc. Steroids Mumps(and other infections)/malignancy Autoimmune - SLE etc Scorpion stings/spider bites Hyperlipidaemia/hypercalcaemia/hyperparathyroidism (aka the metabolic disorders) ERCP Drugs (tetracyclines, furosemide, azathioprine, thiazides and many others)
The islets cells stain less intensely than the cells of the exocrine pancreas - true or false
True
What are the indications for surgery in a perforated peptic ulcer
significant pneumoperitoneum, extraluminal contrast extravasation, or signs of peritonitis
Performing surgery asap (particularly in patients w/ delayed presentation or those >70 yo)
What is the most common cause of oesophagitis
GORD
List potential causes of cirrhosis
Viral hepatitis (B/C/D) Alcoholism NAFLD Metabolic disease Cholestasis Hepatic venous outflow obstruction Toxins & some drug-induced (MTX) hepatitis Intestinal bypass (TPN) Autoimmune hepatitis Cryptogenic cirrhosis.
List the microscopic features of diverticulitis
The walls of colonic diverticula are comprised of flattened mucosa +/- submucosa, without muscularis.
In the case of infection, inflammatory infiltrate may be present at the base.
Granulomas may begin to form, especially in the case of perforation
Barrett’s oesophagus will develop in every case of GORD - true or false
False
Wont develop in every chronic GORD patient but its not known why some are effected and not others
List the Borrman classifications for gastric cancer
Type I: polypoid
Type II: fungating
Ischemic-> necrotic -> shed off
Type III: ulcerated
Heaped up/everted edges
Type IV: diffusely infiltrating
Thickening of stomach wall
Very firm (leather-bottle stomach/linitis plastica)
What is the pro of the UKMELD
All laboratories in transplant units measure serum bilirubin and creatinine conc. using the same methods - consistent
Which infections can cause acute pancreatitis
Mumps Coxsackievirus Hepatitis Infectious mononucleosis HIV/AIDS parasitic:ascariasis
Describe mixed cirrhosis
Has an equivalent no. of micro- and macro-nodules so cannot be clearly classified as one of the other types
Describe the pathogenesis of peptic ulcer disease
Results from imbalance between defence mechanisms & aggressive factors that cause chronic gastritis
Under normal conditions: a physiologic balance exists between gastric acid secretion & gastroduodenal mucosal defense
Aggressive factors alter mucosal defense by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury
Where does the stomach sit
From the gastroesophegeal junction at T11 to the duodenum at l1-l2
How do hepatocytes regenerate in early stage cirrhosis
Primarily by replication of mature hepatocytes adjacent to those that have died (even with significant confluent necrosis)
Will however reach replicative senescence - can no longer replicate
Describe the path of the oesophagus
Muscular tube that’s normally collapsed
In the neck is within the deep cervical visceral fascia with the trachea and thyroid
Runs behind the aortic arch and to left and descending aorta
Travels behind the left main bronchus and right pulmonary artery
Comes in front of the descending aorta at the oesophageal diaphragmatic hiatus (passes through at T10)
Gastroesophageal junction at T1
The presence of red blood cells in ascites fluid suggests what
possible disseminated intra-abdominal cancer
Describe the brain injury caused by subdural haematomas
Primary brain injury can occur from the haematoma itself or the causative trauma .
Secondary injuries can include oedema, infarction, secondary hemorrhage, and brain herniation (all of which cause further brain damage and potentially death)
List the management options for GORD
Lifestyle modification - stop smoking, wt loss (if obese), avoid provoking factors i.e. certain foods
Antacids and H2 antagonists for symptomatic relief
PPI for symptom relief and healing of the oesophagus – GOLD standard
Nissen Fundoplication – rarely used and only for young patients with severe refractory disease and complications
What is cryptogenic cirrhosis
Where cirrhosis arises without any clear cause.
In which part of the stomach are gastric peptic ulcers most commonly found
along lesser curvature near the interface of the body & antrum
How is quality of life affected in subdural haematoma survivors
Quality of life is often impaired due to loss of function
How does alcohol cause oesophageal varices
Impaired blood flow through the portal system and liver leads to increased pressure in collateral vessels, such as those in the oesophagus.
These vessels become dilated and are at risk of rupture and fatal bleeding
Describe the epidemiology of chronic pancreatitis
According to Robbins, prevalence is 0.04% - 5%
Middle age males most affected
A BAC of between 100-200 mg/100ml is likely to have what effect
Causes confusion, loss of fine motor control and emotional control and slurring of speech
What is the aim of GORD management
To relive symptoms, heal oesophagitis and prevent complications ( mainly BE)
How does alcohol cause malnutrition
Ethanol provides calories but not nutrition.
Chronic drinkers are therefore at risk of many nutritional deficiencies, particularly B vitamins as they often won’t eat properly
Oesophageal cancer is more common in which sex
Men
How does a shunt within the rectum/anal canal veins collaterals present
With haemorrhoids
How might decompensated cirrhosis present
With the signs + symptoms of liver failure
Stigmata of cirrhosis and symptoms of cause may also be present
Describe the pathogenesis of GORD
Reflux of gastric bile and acid into oesophagus irritates the stratified squamous epithelium as it’s not designed to deal with corrosive acids
Leads to irritation and inflammation causing symptoms and if not resolved then chronic pathological changes occur
Describe the natural history of GORD
It’s a chronic rather than acute condition that lasts for many years
Can progress to Barretts and cancer
What is the most common cancer of the pancreas
80% are adenocarcinomas of the ductal epithelium
In which countries is gastric cancers most prevalent
Incidence varies markedly with geography
Japan, Chile, Costa Rica, Eastern Europe: Incidence is up to 20-fold higher than in North America, Northern Europe, Africa and Southeast Asia
Highest death rates are recorded in western Asian countries (Iran, Turkmenistan, Kyrgyzstan)
Mass endoscopic screening programs have been successful in regions where the incidence is high
Describe the acute effects of alcohol on the CNS
Alcohol acts as a depressant and mainly affects subcortical structures and therefore cortical activity
This leads to the common ‘symptoms’ of drunkenness such as loss of motor and cortical functions (e.g., decision making) and decrease in intellectual function.
At higher levels it affects cortical neurones and medullary centers including the respiratory centre = respiratory arrest
How does pancreatic adenocarcinoma spread
Typically, pancreatic cancer first metastasizes to regional lymph nodes, then to the liver and, less commonly, to the lungs.
It can also directly invade surrounding organs such as the duodenum, stomach, and colon, or it can metastasize to any surface in the abdominal cavity via peritoneal spread.
It may spread to the skin as painful nodular metastases.
List causes of bleeding in the small intestine and colon
Diverticulitis
Colonic Angiodysplasia
Infective Colitis Colonic Polyps IBD Colorectal Ca Ischaemic Colitis
What proportion of upper GI bleeds are caused by Mallory-Weiss tears
3-15%
What causes spider nevi in cirrhosis
Impaired oestrogen metabolism
Each spider angioma is a central, pulsating, dilated arteriole from which small vessels radiate
What is the arterial supply to the pancreas
Mainly branches from splenic artery - pancreatic branches
Gastroduodenal artery - superior pancreaticoduodenal
Superior mesenteric artery- inferior pancreaticoduodenal
Close relationship to the duodenum so similarities in blood supply
What is the main function of M cells in Peyer’s patches
for primary defense against mucosal infection
What are the main aims of treatment in PUD
Aimed at H. pylori eradication & neutralization of gastric acid (primarily with proton pump inhibitors)
Describe the end stage of cirrhosis with diffuse scarring
Areas of hepatocyte loss transformed into dense fibrous septa -> encircle surviving hepatocytes.
Prominent feature in most cirrhotic livers: regenerative nodules
How does a shunt within the paraumbilical + abdominal wall collaterals present
Appear as dilated subcutaneous veins extending from the umbilicus toward the rib margins - called caput medusae
It is a clinical hallmark of portal HTN
Describe the process of scar formation and regression in cirrhosis
Hepatic stellate cells differentiate into highly myofibroblasts in response to injury.
Release cytokines, growth factors, chemotactic Kupffer cells or recruited macrophages & lymphocytes.
ECM deposition + scar formation often in space of Disse.
Loss of sinusoidal endothelial cells fenestration (sinusoidal capillarisation).
List the morphological features of cirrhosis
Hepatocyte degeneration
Inflammatory cell infiltration-induced necrosis
Liver fibrous tissue hyperplasia (fibrosis)
Hepatocyte nodular regeneration
What is the risk of sudden abstinence from alcohol
It can cause alcoholics to go into withdrawal
This is a very dangerous state
What is the ligamentum teres hepatis a remnant of
the obliterated umbilical vein
How do patients present with a GI perforation
Usually present with peritonitis and shock
Which genetic variation to alcohol metabolism is common in the Asian population
Some people have very low levels of ADH due to a genetic variant
Approximately 50% of the Asian population have this
Leads to nausea, flushing, tachycardia and hyperventilation after alcohol intake
What is the prevalence of oesophageal varices
Cause 5-10% of UGI bleeds
Present in up to 90% of patients with cirrhosis, more in those with decompensated cirrhosis
Mortality of 15-20%/ haemorrhagic episode, with >50% of patients having a recurrent bleed within the first year
List the potential mechanisms of death from Barretts
Have a lower life expectancy than the average population
May die due to progression to adenocarcinoma
May die from complications of screening and treatment
May die due to comorbidities which are common due to risk factors for the original GORD including obesity, smoking and alcohol
What is a blumer shelf
A palpable metastatic mass in the rectal pouch
Seen in pancreatic cancer
Cervical nodes may be palpable in pancreatic cancer - true or false
True
What is the main carcinogenic agent in laryngeal and oesophageal cancers
Acetaldehyde
What causes pruritis in cirrhosis
Derived from persistent cholestasis
How do you treat diverticulitis
1st line treatment is lifestyle modification +/- oral Abx
In acute bleeding, patients may require stabilisation and resuscitation, followed by endoscopic haemostasis (via clips, powders, stitching)
In the case of perforations, these should be surgically drained and IV Abx prescribed
Alcohol misuse increases your risk of which cancers
Increased risk of cancer of the oral cavity, larynx oesophagus, liver and breast
List pre-hepatic causes of portal hypertension
Obstructive thrombosis of portal vein
Structural abnormalities e.g., narrowing of portal vein before it ramifies in liver.
Massive splenomegaly w/ increased splenic vein blood flow
Describe the pathogenesis of SCC of the oesophagus
The molecular pathogenesis is not well understood but recurrent abnormalities are seen as amplifications of transcription factor SOX1, over expression of the cell cycle regulator cyclin D and LOF mutations in tp53, CDH1 and NOTCH1 tumour suppressors
Generally thought to be linked to inflammation of the squamous epithelium which leads to dysplasia and in situ malignant transformation
How do alcohol and tobacco cause SCC of the oesophagus
Alcohol damages the cellular DNA by decreasing metabolic activity in the cell
This promotes oxidation by blocking detoxification
Tobacco then has the synergistic effect and because alcohol is a solvent it allows the tobacco to penetrate into the oesophageal epithelium with more ease
How do you diagnose portal hypertension
Diagnosis often based on clinical findings
Portal pressure can be measured if required but patency of portal vein should be assessed by Doppler USS before attempting to measure pressure in it
List the potential complications of oesophageal radiofrequency ablation
bleeding and stricture formation
List risk factors for oesophageal SCC
Smoking Alcohol use Caustic oesophageal injury Achalasia Plummer vinson syndrome, Tylosis - rare genetic HPV Consumption of very hot beverages Caustic strictures Use of oral bisphosphonates Poor oral hygiene Prior gastrectomy
How do you manage Hypovolaemic shock in GI bleeds
Patients may require careful management, including fluid resuscitation and blood products
Treat underlying bleed
Where do most pancreatic cancers arise
Approximately 60% arise in the head of pancreas, 15% in the body, 5% in the tail and in 20% the entire pancreas is involved
How do you treat BO with confirmed high grade dysplasia
endoscopic mucosal resection followed by ablation of remaining BE mucosae
Describe the structure of the submucosa in the stomach
Loose connective tissues, larger blood & lymph vessels, lymphoid tissue, Meissner’s plexus, no submucosal glands
List the microscopic features of cirrhosis
Lobular architecture destroyed by dense bands of fibrosis.
Hepatocyte degeneration – fatty, ballooning, eosinophilic, hydropic, etc.
Patterns of necrosis
Damaged/altered vasculature – central vein, bile ducts.
Nodular regeneration.
Specific cell types may be seen – e.g., Mallory bodies in alcoholic hepatitis/cirrhosis, Wilson’s disease
List the potential complications of oesophageal cryo-ablation
pain, bleeding, scarring, dysphagia
List some of the necrosis patterns seen in cirrhosis
Confluent - begins in zone 3 (near CV) w/ hepatocyte dropout (space filled with cellular debris
Bridging -may extend from the central veins to portal tracts, or across adjacent portal tracts
Pan-acinar – entire lobule obliterated
Piecemeal, zonal, spotty, etc.
How are stage T1a gastric cancers treated
T1a - well-differentiated, ≤2 cm, confined to the mucosa, and not ulcerated
May be amenable to endoscopic resection
List liver disease that can be caused alcohol
Alcoholic steatosis
Alcoholic hepatitis
Cirrhosis (with portal hypertension
and hepatocellular carcinoma as a consequence)
What is the most common cause of chronic pancreatitis
Alcohol abuse
Non-linear dose-response relationship
1.2x risk with ~40 g/day alcohol consumption
4x risk with ~100 g/day alcohol consumption
Which factors are included in the Child-Pugh score
Encepathology - which grade Ascites - presence/extent Bilirubin level Bilirubin in those with PBC or PSC Albumin level Prothrombin time or INR
What UKMELD score is needed for a patient to be put on the transplant list
UKELD score ⩾ 49 is the minimum criteria for entry to waiting list under this category.
Unless patient has hepatocellular carcinoma and variant syndromes.
Those with alcoholic liver disease, past IVDU or current methadone use must be assessed individually.
How do you treat a GI obstruction following a GI bleed
The precise treatment depends on the location, but endoscopic dilation is often a first line treatment
Which neoadjuvant and adjuvant therapies are used in the treatment of gastric cancer
Neoadjuvant chemotherapy - pre-op and then post-op too Intraoperative radiotherapy (IORT) Adjuvant chemotherapy (eg, XELOX) Adjuvant radiotherapy - post-op Adjuvant chemoradiotherapy
How does smoking cause peptic ulcer disease
It harms the mucosa
Smoking in the setting of H. pylori infection may increase the risk of relapse of peptic ulcer disease
How can a subdural haematoma resolve
Venous bleeding is typically self-limiting.
The resulting haematoma can be broken down and organised with time
List pre-sinusoidal causes of increased resistance in the portal vein
Compression of hepatic venules
e.g., by regenerative nodules (cirrhosis), cysts (polycystic disease), granulomatous disease or metastases
How do you differentiate between high and low grade dysplasia in Barrett’s oesophagus
High grade is differentiated from low grade as it has more severe architectural and cytological changes
If a mucosal lesion cant be seen but dysplasia is confirmed ( either high or low grade) then radio/cryo ablation can be done - true or false
True
Describe the aetiology of Barrett’s oesophagus
It’s a complications of chronic GORD - not known why some affected and some not
You have intestinal type metaplasia within the oesophageal squamous mucosae due to chronic inflammation by the gastric contents
There are some autosomal dominant familial genetic mutations that will cause it but it’s a minority cause
Describe the structure of H pylori
Gram negative
Spiral-shaped bacterium
Has 4-6 unipolar flagellae
Describe the microscopic appearance of the exocrine pancreas
It actually resembles the parotid gland
Has numerous serous acini and ducts
The cells are very basophilic because they contain large amounts of Rough Endoplasmic R.
What is peptic ulcer disease typically associated with
Is almost always associated with H. pylori infection, NSAIDs, or cigarette smoking
What are the 3 major complications of peptic ulcer treatments
Hemorrhage, Perforation/Penetration, Pyloric stenosis
List the features of the dysplasia seen in Barrett’s
Increased nuclear to cytoplasm ration
Atypical mitoses
Irregularly clumped chromatin
Nuclear hyperchromasia
Failure of epithelial cells to mature as they travel to the surface of the oesophagus
Dysplastic glands show budding, cellular crowding and irregular shapes
What are the hepatic stellate cells
Also called Ito cells
They are modified fibroblasts found in the space of Disse
They produce CT and store vitamin A in fat droplets.
Describe the layers found in the mucosae of the oesophagus
Made of 3 layers - epithelium, lamina propria and mucularis mucosae
Describe the structure of intestinal villi
Lined by columnar epithelial cells with abundant goblet cells
Lymphocytes, plasma cells, eosinophils present in lamina propria
Smooth muscle cells extend from muscularis mucosae – modulate height of villi
Fenestrated blood capillaries & lacteals – for fat absorption
Microvilli – further increase surface area
List early post-op complications seen in gastric cancer treatment
Anastomotic failure Bleeding Ileus Transit failure at the anastomosis Cholecystitis (often occult sepsis without localizing signs) Pancreatitis Pulmonary infections Thromboembolism
Direct mortality after 30 days - 1-2%
which lymph nodes may be dissected in the treatment of gastric cancer
D1: perigastric lymph nodes
D2: hepatic, left gastric, celiac, splenic arteries, in the splenic hilum
D2 recommended
Try to spare pancreas and spleen
List the microscopic features of alcohol cirrhosis
Hepatocytes in moderate-severe fatty degeneration Presence of Mallory bodies Eosinophilic degeneration & bodies Bridging necrosis Bile duct proliferation
Describe the structure of the epithelium of the oesophagus
Non-keratinised stratified squamous epithelium
Also contains melanocytes, Langerhans cells, Merkle cells, endocrine cells and squiggle cells
Which cells in the pancreas secrete digestive enzymes
Acinar cells
How do you treat a GI perforation
Surgery is sometimes necessary but most can be treated in the same way as the underlying pathology
How does alcohol metabolism lead to fatty liver disease
Oxidation cause by alcohol leads to reduction of NAD to NADH which decreases the overall amount of NAD available
As this is required for fatty acid oxidation in the liver it leads to an accumulation of fat in the liver
Describe the pathogenesis of Barrett’s Oesophagus
Get chronic reflux of acidic gastric contents through the LOS into the distal oesophagus
The squamous epithelium is inflamed by the acidic contents and continued exposure leads to persistent inflammation as the squamous cells release Il8 and Il 1b signalling T lymphocytes and neutrophils
A columnar type metaplastic reaction occurs developing an intestinal phenotype characterised by goblet cells
Bile acid in particular up regulates CDX2 and MUC2 and therefore plays a role in the cellular transformation
Clonal abberations of p16 as well as mutations in CDX2 and tp53 are also found in early BE lesions and therefore potentially linked to the disease
Embryonic stem cells at the squamocolumnar junction or stem cells derived from undifferentiated mesenchymal cells in the lamina propria of the oesophagus or bone marrow may be the epithelial cells of origin for BO
How does a low fibre diet lead to formation of diverticular
Caused increased transit time in colon and decreased stool volume
This leads to increased intraluminal pressure then increased colonic segmentation
Causes the formation of diverticular
What are some of the complications of oesophageal biopsy
perforation or bleeding
List non-specific symptoms of a GI bleed
Symptoms of anaemia - fatigue, syncope
Epigastric or wider abdominal pain
Describe the structure of the serosa in the stomach
mesothelium and connective tissue
How does h pylori cause gastric cancer
Long-term presence of inflammatory response leads to increased expression of a single cytokine interleukin-1-beta in stomach of transgenic mice
This results in sporadic gastric inflammation + cancer
(increased cell turnover from ongoing cellular damage -> increase likelihood of cells developing harmful mutations)
Infection with CagA- positive H. pylori was associated with inactivation of tumor suppressor proteins (p53)
List late mechanicophysiologic
complications seen after gastric cancer treatment
Dumping syndrome, vitamin B-12 deficiency, reflux esophagitis, and bone disorders, especially osteoporosis
Which parts of the small intestine have an adventitia and which parts have a serosa
Duodenum: adventitia
Jejunum & ileum: serosa
What is the most common cause of ascites
Caused by cirrhosis in 85% of cases
Goblet cells are found in the epithelium of the fundus and body of the stomach - true or false
False
Which proportion of blood is diverted to collateral vessels in portal hypertension
In portal HTN, portal vein diverts 90% of increased blood flow to collaterals
List causes of oesophageal bleeds
Varices
Oesophagitis
Mallory-Weiss Tears
Boerhaave Syndrome
Oesophageal Cancer
What is the recommended surgical approach for a perforated peptic ulcer
Stable: Laparoscopic approach
Unstable: Open surgery
Which vessels are usually responsible for the bleeding in a subdural haematoma
Bridging veins
They cross the subdural space and drain blood from the brain into the larger dural sinuses
List the macroscopic features of a Mallory-Weiss tear
Single or multiple vertical lacerations at the gastroesophageal junction, measuring anywhere between a few millimeters and several centimeters
The liver has a dual blood supply - true or false
True
Supplied by both the hepatic portal vein and left & right hepatic arteries (come from the hepatic artery proper, a branch of the coeliac trunk).
Describe the specific effect adenocarcinoma has on the pancreas
They recapitulate normal ductal epithelium by forming glands and secreting mucin
The larger the spleen the more severe the other features of portal HTN - true or false
False
Size is not necessarily correlated with other features of portal HTN
Describe the natural history of SCC of the oesophagus
The various underlying causes will result in squamous dysplasia which the progresses into invasive lesion
What are the most common locations for mets in oesophageal cancer
Liver followed by the lung and lymph nodes
What can cause pancreatic adenocarcinoma
Smoking
Diabetes
Chronic inflammation of the pancreas (pancreatitis)
Family history of genetic syndromes that can increase cancer risk, including a BRCA2 gene mutation, Lynch syndrome and familial atypical mole-malignant melanoma (FAMMM) syndrome
Family history of pancreatic cancer
Obesity
Older age, as most people are diagnosed after age 65
Where would you find intestinal crypts
Between villi & in lamina propria of the small intestine
Describe the metabolism of alcohol
The majority of the alcohol is metabolised to acetaldehyde in the liver by 3 enzymes - alcohol dehydrogenase, cytochrome P-450 and catalase
The acetaldehyde will eventually be converted to acetate by alcohol dehydrogenase which can be used in the respiratory chain or lipid synthesis
Describe the natural history of gastric cancer
Normal epithelium can be damaged by chronic gastritis
This can lead to atrophic gastritis
This can progress to intestinal metaplasia, then dysplasia
Finally the cancer forms
Huge number of factors can trigger/influence each step in this progression - including mutations, lifestyle factors etc
How would you investigate suspected oesophageal cancer
CT chest and abdo PET Endoscopic USS Bronchoscopy Barium swallow
How do you manage early stage oesophageal cancer
Endoscopic mucosal resection if small and confined to inner lining of oesophagus
If it has spread out with the inner lining then oesopahgectomy is done
Chemoradiation may be done if cant have/doesn’t want surgery or neoadjuvantly
Describe the aetiology of adenocarcinoma of the oesophagus
Most cases are caused by chronic GORD and its progression to BO
Lesser causes include tobacco smoke and exposure to radiation
What is the third most common cause of death from cancer
Gastric cancer
Describe the natural history of oesophageal adenocarcinoma
Starts as GORD, progresses to BO then adenocarcinoma due to dysplasia
List the layers of the small intestine
Mucosa
Submucosa
Muscularis externa
Adventitia/Serosa
Describe the microscopic features of Barrett’s
Intestinal type metaplasia is characterised by replacement of squamous epithelium with goblet cells
Goblet cells are diagnostic of BE and have distinct mucous vacuoles that stain pale blue and shape the rest of the cytoplasm like a wine glass
Non goblet columnar cells such as gastric type foveolar cells may be seen also – not enough for diagnosis
Why might a patient with oesophageal cancer not notice their dysphagia
Some people inadvertently alter their diet - less solids so problem is less obvious
Describe the structure of the muscularis mucosae of the oesophagus
Longitudinally orientated smooth muscle bindles
Will thicken as the oesophagus descends
What is the most likely cause of gastric metaplasia
Most likely to be a defence response or adaptation to excess acid reaching the duodenum
What stimulates hepatic stellate cells to turn into myofibroblasts in cirrhosis
Cytokines e.g. TNF-alpha (produced by Kupffer cells, macrophages)
Altered interactions with ECM
Toxins
Reactive oxygen species
Describe the mechanism of death from oesophageal cancer
Organ dysfunction due to metastasis
Local invasion resulting in asphyxia, haematemesis or recurrent infection = respiratory failure and sepsis
Invasion of the aorta ( SCC) causing fatal exsanguinations
Sinusoidal capillarisation is a particularly prominent feature of which conditions
NASH
Also a feature of the abnormal sinusoids seen in hepatocellular carcinoma.
What signs on examination may suggest acute pancreatitis
(Rare) signs of haemorrhage on the physical exam include:
Cullen sign: periumbilical bruising
Grey-Turner sign : flank bruising
Which zone of the liver is most affected by paracetamol overdose
Zone 3
List the 2 characteristic features of pancreatic caner
1) highly invasive extending into peripancreatic tissues
2) they elicit a desmoplastic response that results in deposition of dense collagen
Describe the range of pathology seen in acute pancreatitis
The morphology of acute pancreatitis ranges from limited inflammation and oedema to extensive necrosis and haemorrhage
How do NSAIDs cause peptic ulcer disease and bleeding
COX-1 pathway promotes prostaglandin production, which contributes to maintaining the mucus-bicarbonate barrier in the stomach, optimal submucosal blood flow, and improved healing when tissues are damaged
NSAIDs inhibit this pathway, rendering the gastric mucosa more susceptible to damage
Also have anti-platelet action, which increases bleeding risk
When is oesophageal cancer considered advanced
When it has spread to nodes, liver, lungs or stomach
What is the connection between the portal and systemic systems in the abdominal area that allows shunts
Connection between para-umbilical + small epigastric veins
Describe the structure of pyloric glands
Shorter & more branched glands
Deeper pits
Where is gastric juice secreted from and what is its function
The fundus and body of the stomach
It is for digestion - contains water, HCl, mucus, digestive enzymes, electrolytes
What is the role of hepatic stellate cells in both normal health and in the context of chronic liver disease?
Store vitamin A in fat droplets normally
Transform into myofibroblasts in setting of chronic liver injury. Myofibroblasts are fibrogenic and are involved in scar formation.
Describe the macroscopic features of oesophageal SCC
50% of cases will be in the middle 1/3 of the oesophagus and all will start as squamous dysplasia
Early lesions - small plaque thickenings that are gray-white in colour
Over months to years will grow into a tumour mass that is either polypoid or exophytic and protrudes into and obstructs the lumen
Otherwise tumours mat be diffuse infiltrated lesions that will spread in the oesophageal wall and cause rigidity, thickening and narrowing of the lumen or they may also be ulcerated
What is the transplant benefit score used for
It is a national set of rules offering livers to named adult patients on the elective liver waiting list
Livers offered to named patients throughout the UK who are predicted to gain the most survival benefit from receiving the particular liver graft on offer
Describe the pathological timeline of cirrhosis
Starts with hepatocyte degeneration (ballooning, fatty change)
Then hepatocyte necrosis
Then hepatocyte regeneration
Then scar formation and regression
Eventually will have extensive, diffuse scarring with dense fibrous septa surrounding remaining normal hepatocytes (cirrhosis).
What innervates the pancreas
Sympathetic – abdominopelvic splanchnic nerves
Parasympathetic – vagus nerves
Both of these pass through the diaphragm, then follow arteries from the celiac and superior mesenteric plexus to reach the pancreas
List the classic symptoms of GORD
Heartburn Dysphagia and odynophagia Regurgitation of sour tasting gastric contents, usually postprandial Coughing Hoarseness Chest pain that differs from heartburn
What is the most common cause of acute lower GI bleeds in Western countries
The two most common causes of acute LGI bleeding with significant blood loss are diverticulitis and colonic angiodysplasia
What is ascites
The accumulation of fluid in the peritoneal cavity
List the potential adverse outcomes of acute pancreatitis
Acute renal failure Acute respiratory distress syndrome Sterile pancreatic abscesses Pseudocysts In around half of patients with acute necrotizing the debris becomes infected
How is T1 gastric cancer treated if endoscopic treatment isn’t possible - doesnt meet criteria
Lymph node dissection during open surgery (limited to perigastric nodes & local N2 nodes)
What causes coffee-ground vomit and melaena
Gastric acid oxidises the haem in RBCs after a period of time giving these appearances
What nerve system coordinates peristalsis
Myenteric plexus
Found in the muscularis externa
What is contributing to a decrease in gastric cancer cases
Reduced rate of H. pylori infection
Decreased consumption of dietary carcinogens such as N-nitroso compounds and benzo[a]pyrene
Widespread availability of refrigeration -reduced use of salt and smoking for food preservation
How long does it take for alcohol withdrawal to set in
Usually begins 6-12 hours after last drink (can be up to 72hours) and lasts a few days
Describe the aetiology of diverticulitis
Thought to be multifactorial with both genetic and environmental factors contributing
Low fibre diet thought to be main contributing factor in Western countries
May also be due to dysfunction of the colonic wall, changes in colonic motility, and disruptions to the gut microbiome
Other RF – Obesity, smoking, excessive alcohol and caffeine intake, NSAID use
What signs of oesophageal cancer may be seen on physical examination
Usually normal but may show enlargement of laterocervical or supraclavicular nodes or hepatomeagaly
How does COVID affect the pancreas
SARS-CoV-2 has been shown to infects cells of the human exocrine and endocrine pancreas ex vivo and in vivo
Has been detected in pancreas cells PM
Infection is associated with morphological, transcriptional and functional changes
Can affect insulin and contribute to the metabolic dysregulation observed in patients with COVID-19.
Which signs suggest a poor prognosis in gastric cancer
Paraneoplastic syndromes e.g. dermatomyositis, acanthosis nigricans, circinate erythemas
How do upper GI bleeds present
Haematemesis
“coffee-ground” vomit
Melaena
Which palliative therapies are used in the treatment of gastric cancer
Palliative radiotherapy
Palliative-intent procedures (eg, wide local excision, partial gastrectomy, total gastrectomy, simple laparotomy, gastrointestinal anastomosis, bypass)
What are the duct cells within the pancreatic acini called
Centroacinar cells
Commonly called duct cells
List rare cancers that can affect the oesophagus
Unusual adenocarcinoma Undifferentiated carcinoma Neuroendocrine carcinoma Melanoma Lymphoma Sarcoma
What causes fat necrosis
Caused by lipase leads to “saponification”
Fatty acids combine with calcium to form insoluble soaps that impart a granular blue microscopic appearance to surviving fat cells
Which enzymes are secreted by the pancreas
proteases to break down proteins
lipases to break down lipids
nucleases to breakdown DNA/RNA
amylase to break down starch
Describe the microscopic features of oesophageal adenocarcinoa
Form glands and produce mucin - glands tend to have intestinal type morphology
Less commonly the tumours may be made of diffusely infiltrating signet ring cells or rarely small poorly differentiated cells
Its also common to find BO beside the tumour
What causes Wernicke-Korsakoff Syndrome
Thiamine (vitamin B1) deficiency - common in chronic alcoholics
List the 4 layers of the oesophagus
mucosae, submucosae, muscularis propria and adventitia
Subdural haematomas are most common over which part of the brain
The lateral aspects of the cerebral hemispheres
How does alcohol cause hepatitis
By-products of metabolism cause hepatic injury and inflammation though exact mechanism uncertain
What is the UKMELD
UK-specific version of the MELD score which was designed to predict waiting list mortality and improve distribution of liver grafts
Very few pancreatic tumours are benign - true or false
True
Only 2% of tumours in the exocrine pancreas
Which malignancies can cause acute pancreatitis
pancreatic adenocarcinoma
lymphoma
H pylori are present in what proportion of chronic gastritis cases
H. pylori are present in majority of individuals w/ chronic antral gastritis
What is the standard eradication therapy for H pylori
First-line eradication therapy: standard triple therapy i.e. amoxicillin, clarithromycin, PPI
Should be started after 72-96 hours of intravenous proton-pump inhibitor and continued for 14-day duration
Other options: PPI-based triple therapy, clarithromycin-based triple therapy, quadruple therapy
Describe the natural history and progression of PUD
Imbalance between aggressive factors & defensive factors leads to gastric metaplasia (defence adaptation) of duodenum/stomach
This causes duodenitis/gastritis
Further addition of aggressive factors causes a duodenal/gastric ulcer
Ulcer penetrates through muscularis and adventitia (ulcer perforates into peritoneal cavity!) causes peritonitis and eventually death
List the macroscopic features of Barrett’s
Red velvety mucosae extending upwards in tongues from the gastroesophageal junction
The metaplastic mucosae alternates with the squamous epithelium that remains (it is pale) and will interface with the gastric mucosae distally which is a light brown columnar gastric mucosae
Separated into short segment ( <3cm) and long segment ( >/3cm)
Where does the pharynx run
Base of skull to criciod cartilage
List potential mechanisms of death from gastric cancer
Hematogenous spread & lymphatic spread can lead to:
Pathologic peritoneal & pleural effusions
Liver failure
Intrahepatic jaundice caused by hepatomegaly
Extrahepatic jaundice
Obstruction of gastric outlet, gastroesophageal junction, or small bowel
Adenocarcinoma of the oesophagus can cause which specific symptoms
Most will have had symptoms of underlying GORD
The cancer may be diagnosed before symptoms occur if picked up on GORD/BO screening
Describe the structure of the adventitia of the oesophagus
Made of loose connective tissue.
Most of the oesophagus is surrounded by fascia
List the most common causes of cirrhosis
Alcohol NAFLD Hep C and B PBC Autoimmune hepatiti
The activation of the alcohol metabolism pathway can increase susceptibility of other drugs - true or false
True
If the other drug uses the same enzymes in their metabolism then the person is more susceptible - e.g. cocaine
However, when both are present the alcohol competes for the enzyme and may slow drug metabolism (potentiated effect)
What causes the majority of adenocarcinoma cases in the oesophagus
Barrett’s
Each functional segment of the liver contains what structures
Each with a branch of the hepatic artery and portal vein, a bile duct and venous drainage (to IVC).
List the potential complications of oesophagectomy
bleeding, infection, anastomotic leak, change to voice, pneumonia, dysphagia, AF, death
What can cause a Mallory-Weiss tear
Associated with activities which cause a transmural pressure gradient between the abdomen and thorax
Coughing, vomiting, CPR, hiccups, medications (particularly NSAIDS), instrumentation
Hiatus hernias are thought to be a risk factor
Most commonly associated with prolonged retching or vomiting during alcohol intoxication
Which disease can alcohol consumption protect you from?
Coronary heart disease
List the clinical signs of hepatic encephalopathy
Fluctuating rigidity and hyperreflexia.
Asterixis – nonrhythmic, rapid flexion-extension movements of head and extremities
Best seen when arms held in extension with dorsiflexed wrists. Aka. ‘liver flap’.
Describe the aetiology of chronic pancreatitis
Most common cause is alcohol
Also associated with long-standing obstruction of pancreatic duct, autoimmune injury and hereditary factors
Genetics - CFTR
Where is the pancreas located in the body
Transversely orientated retroperitoneal organ extending from the c-loop of the duodenum to the hilum of the spleen
Lies between the duodenum on the right and the spleen on the left, posterior to the stomach
List risk factors for subdural haematomas
Chronic alcohol misuse Epilepsy Coagulopathies Anticoagulant use Diabetes
Describe how duct obstruction can cause acute pancreatitis
Back up of enzymes such as lipase cause extensive damage such as fat necrosis as well as oedema
Common in gallstones and cancer
What are some of the complications of PPI treatment
hypomagnesium, hypocalceamia, c. diff infection, pneumonia
How many lobes does the liver have
2 main lobes - L&R
Also has 8 functional segments
When would you see incomplete septal cirrhosis
If chronic injury is interrupted – e.g., clearance of hepatitis viral infection, EtOH cessation
The stellate cell activation and scarring ceases and the fibrous septae may be broken down by metalloproteinases
Leads to partial resolution
However, vascular remodelling + other architectural changes that occur in cirrhosis may not revert to normal, even with extensive scar resorption – may explain why portal HTN fails to improve in some patients
Describe the path pancreatic juice takes from the pancreas
It is secreted into a branching system ofpancreatic ductsthat extend throughout the gland.
In the majority of individuals, the main pancreatic duct empties into the second part of duodenum at theampulla of Vater.
What is the risk of pruritis in cirrhosis
Patients may scratch their skin raw and risk bouts of potentially life-threatening infection
Relief may only come with transplantation.
List the clinical features of a subdural haematoma
Usually present on a background of head trauma.
Typically the deterioration is slow and progressive but patients can also suddenly decompensate as blood accumulates.
Consciousness may fluctuate.
Focal neurological signs (e.g. unequal pupils, hemiparesis) that are dependant on the location of the haematoma.
Non-focal signs such as headache, unsteadiness, personality change, seizures and confusion.
Symptoms of raised ICP – headache, vomiting, altered GCS etc
