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.
