PBL 51 Flashcards
Social impacts of alcohol
- Crime and disorder
- Domestic violence - Workplace
- Poor productivity
- Absences/sick leave for alcohol-related reasons - Family
- Arguments, violence, debt, relationship problems - Alcohol-related harms
- Deaths
- Alcohol-related hospital admissions
- Crime and public disorder
What is the blood supply to the liver?
The liver has a double blood supply:
1. The right and left hepatic arteries - Carry oxygenated blood to the liver
- Portal vein - Receives deoxygenated blood from the GI tract containing newly absorbed nutrients, drugs, microbes and toxins and carries it to the liver
The venous blood from the GI tract drains into the portal vein, what is this made up of?
The superior and inferior mesenteric veins, which are joined by the splenic vein
What is cirrhosis?
Cirrhosis is distortion of the liver’s internal structure that occurs when a large amount of normal liver tissue is permanently replaced with non-functioning scar tissue.
The scar tissue develops when the liver is damaged repeatedly or continuously.
Give some causes of liver cirrhosis
- Infection - Most common types are hepatitis viruses
- Autoimmunity - Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis
- Genetics - Haemochromatosis, hyperoxaluria and oxalosis, Wilson’s disease
- Cancer - Liver cancer, bile duct cancer, liver adenoma
- Chronic alcohol abuse
- Non-alcoholic fatty liver disease
Explain the pathogenesis of liver cirrhosis
- Development of fibrosis
- Scarring
- As scar tissue begins to lay down, the previous ability to adapt to high pressures of the hepatic artery and portal vein diminishes, so you get nodules and back pressure out of the liver.
- This means the blood can’t find its way out through the sinusoids, so needs another way out. This is the reason why patients with cirrhosis may have splenomegaly and varices. - Formation of nodules
- Loss of hepatocyte microvilli
- Activated stellate cells
- Deposition of scar matrix
- Loss of fenestrae
- Kupffer cell activation
Risk factors for liver cirrhosis
• Alcohol (1/3 most common causes)
- One way that chronic alcohol abuse damages the liver is by causing fat to accumulate (fatty liver).
- Chronic viral hepatitis B, B+D, C (1/3 most common causes)
- Non-alcoholic steatohepatitis (1/3 most common causes)
- Drugs
- Autoimmune liver disease
- Cholestatic liver disease
- Metabolic liver disease
- Hepatic venous congestion
- ‘Cryptogenic’
- Some specific causes include certain hereditary metabolic disorders, such as iron overload (hemochromatosis), copper overload (Wilson disease), and alpha-1 antitrypsin deficiency, and disorders that damage the bile ducts, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).
Fatty liver that is not caused by alcohol usually occurs in which people?
- overweight
- have diabetes or pre-diabetes
- high cholesterol.
Signs and symptoms of liver cirrhosis
- About 1/3 of people have no symptoms
1. Ascites
2. Abdominal discomfort, often with fever
3. Calf pain or swelling
4. Confusion and drowsiness
5. Difficulty breathing
6. Fatigue and pale skin
7. Reduced urination
8. Symptoms of infection
9. Jaundice
10. Bruising, petechiae
11. Pruritus
12. Splenomegaly
13. Rectal bleeding
14. Steatorrhoea
15. Vomiting blood
16. Malnourishment
17. Palmar erythema
18. Spider angioma
19. Peripheral neuropathy
20. Gynecomastia
21. Testicular atrophy
22. Clubbing
Complications of cirrhosis
- Portal hypertension
- Portopulmonary hypertension
- Ascites
- Poor absorption of fats and vitamins
- Bleeding irregularities
- Increased risk of infection
- Kidney failure - hepatorenal syndrome
- Brain function deterioration - hepatic encephalopathy
- Liver cancer - hepatocellular carcinoma
- Spider angioma - Xs oestrogen
- Hepatic failure
What is portal hypertension
Back up of blood down portal venous system leads to portal hypertension. High blood pressure in the portal vein is the most serious complication. When it causes blood to back up in the veins connected to it, these veins may enlarge and twist (called varicose veins).
Portal hypertension leads to the development of new veins (called collateral vessels) that bypass the liver. These veins directly connect the portal blood vessels to veins that take blood away from the liver into the general circulation, they can be seen on the skin of the abdomen or around the rectum
Where do collateral vessels develop?
The most important are located at the lower end of the oesophagus and at the upper part of the stomach. Here, the vessels enlarge and become full of twists and turns—that is, they become varicose veins in the oesophagus (oesophageal varices) or stomach (gastric varices).
These enlarged vessels are fragile and prone to bleeding, sometimes seriously and occasionally with fatal results. Other collateral vessels may develop on the abdominal wall and at the rectum.
Portal hypertension can cause which organ to increase in size? What is the consequence of this?
Spleen, because the pressure interferes with blood flow from the spleen into the portal blood vessels.
When the spleen enlarges, the number (count) of white blood cells can decrease (increasing the risk of infections), and the number (count) of platelets can decrease (increasing the risk of bleeding)
What is portopulmonary hypertension? Give some symptoms
portal hypertension can cause high pressure in the arteries in the lungs. This can cause symptoms of heart failure, such as difficulty breathing, particularly when lying down, and fatigue
What is spontaneous bacterial peritonitis?
When the fluid in the abdomen becomes infected, this is usually in those with ascites
Poor absorption of vitamin D leads to what?
Osteoporosis
Poor absorption of vitamin K leads to what?
People bleeding more easily
How does liver cirrhosis cause bleeding irregularities?
- Less production of Vit K (clotting factor)
2. Splenomegaly which traps blood cells and platelets, so there are less platelets in the bloodstream
How does liver cirrhosis increase the risk of infection?
- The number of white blood cells may be reduced (called leukopenia) because the enlarged spleen traps them.
- When the number of white blood cells is low and the liver’s synthesis of proteins that fight infections decreases, the risk of infections increases.
What is hepatorenal syndrome?
In this syndrome, less urine is produced and excreted from the body, resulting in the build-up of toxic substances in the blood. Eventually, people with hepatorenal syndrome have difficulty breathing. This kidney problem can become severe enough to require dialysis
How does liver cirrhosis cause deterioration of brain function?
Liver failure can also cause brain function to deteriorate (called hepatic encephalopathy) because the damaged liver can no longer remove toxic substances from the blood. These toxic substances then travel through the bloodstream and build up in the brain.
Symptoms of hepatic encephalopathy?
Confusion
Altered level of consciousness
Coma due to ammonia accumulation
Vascular spiders are caused by what?
Excess levels of oestrogen
What are the clinical consequences of hepatic failure?
Prevents the normal functions of the liver:
- Unable to filter toxins
- Metabolism of nutrients reduced
- Reduced immunity: unable to fight infection by removing bacteria from blood
- Reduced production of clotting factors
- Unable to store nutrients so body may experience shortage
- Reduced protein production e.g., albumin
- Reduced bile production (reduced absorption of vit A,D,E,K)
Signs and symptoms of hepatic failure
- Cerebral oedema
- Bleeding and bleeding disorders
- Infections
- Kidney failure
- Jaundice
- Ascites
- Melena – Upper GI bleeding in poo
- Hypotension and tachycardia – due to reduced systemic vascular resistance
What is the gold standard for diagnosis of liver cirrhosis?
Liver biopsy
Why does bilirubin increase in liver impairment?
Less is conjugated by the liver, so it builds up in the bloodstream –> Jaundice
Why do blood ALT and AST rise during liver impairment?
The liver releases ALT and AST into the blood when it is damaged or inflamed
What does blood ALP reflect?
Does NOT reflect liver damage or inflammation.
- It occurs when there is a blockage of flow in the biliary tract or a buildup of pressure in the liver–often caused by a gallstone or scarring in the bile ducts
What happens to pro-thrombin time (PTT) and APTT in liver impairment?
The time increases as their are fewer clotting factors produced by the liver
Treatment for liver cirrhosis
- Correcting or treating the cause, such as alcohol abuse, use of a drug, exposure to a toxin, hemochromatosis, or chronic hepatitis
- Treating complications as they develop
- Sometimes transplanting a liver
What is the treatment for haemochromatosis?
Phlebotomy
How is ascites treated?
Restriction of sodium in the diet because excess sodium can contribute to fluid accumulation.
- Diuretics
How is hepatic encephalopathy treated?
Drugs to help bind toxins in the bowel (in the stool) and antibiotics to reduce the number of bacteria in the gastrointestinal tract that produce these toxins
How is bleeding from digestive tract varices treated?
Beta-blockers to lower blood pressure in the liver’s blood vessels and/or surgical application of elastic bands to tie off the bleeding blood vessels (called endoscopic banding, or ligation)
Explain the pathophysiology of acute pancreatitis
Acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas.
- Intra-acinar activation of pancreatic enzymes (including trypsin, phospholipase A2, and elastase), leading to the auto-digestive injury of the gland itself.
- The enzymes can damage tissue and activate the complement system and the inflammatory cascade, producing cytokines and causing inflammation and oedema
Signs and symptoms of acute pancreatitis
- Acute abdominal pain in the epigastric region
- Central, severe pain, and often radiates to the back
- Fever
- Nausea & vomiting
- Pain relieved by sitting forwards
- Pain worsened by coughing, vigorous movement, deep breathing
- Pulse rate is usually elevated and blood pressure may be transiently high or low
Risk factors for acute pancreatitis
- Obesity
- Diabetes
- Cigarette smoking
- FHx
- Xs alcohol
Causes of acute pancreatitis?
Causes (I GET SMASHED): I - Idiopathic G - Gallstones E - Ethanol T - Trauma S - Steroids or surgery M - Mumps/malignancy A - Autoimmune S - Scorpion sting H - Hypertriglycerides or hypercalcemia E - ERCP (endoscopic retrograde cholangio-pancreatography) D - Drugs (valproic acid, sulfonamides, azathioprine, oestrogen preparations)
What is the most common cause of acute pancreatitis?
Gallstones and then alcohol intake
How do gallstones cause acute pancreatitis?
The precise mechanism of gallstone pancreatitis is unknown but likely involves increased pressure in the pancreatic duct caused by obstruction at the ampulla secondary to a stone or oedema caused by the passage of a stone.
- Ductal hypertension results in aberrant activation of digestive enzymes from acinar cells
How does alcohol cause acute pancreatitis?
Pancreatic acinar cells metabolize alcohol into toxic metabolites via both oxidative and nonoxidative pathways and exhibit effects that predispose the cells to autodigestive injury and predispose the pancreas to necrosis, inflammation, and cell death
Acute pancreatitis is a complication that develops after which procedure?
endoscopic retrograde cholangiopancreatography (ERCP) in about 5% of patient
Diagnosis of acute pancreatitis?
- Raised serum amylase & lipase (> 3x upper limit)
- Glucose intolerance
- Hypocalcaemia (fat sequestration)
- Raised CRP, WCC etc
- Haemorrhagic peritoneal effusion
What are some differential diagnoses of acute pancreatitis symptoms
- Perforated gastric or duodenal ulcer
- Mesenteric infarction
- Strangulating intestinal obstruction
- Aortic aneurysm
- Biliary colic
- Appendicitis
- Diverticulitis
- Inferior wall MI
- Haematoma of abdominal muscles or spleen
Treatment of acute pancreatitis
- Early goal-directed fluid resuscitation: Acute pancreatitis can cause dehydration
- Oxygen
- Analgesia
- Anti-emetics
- Nutritional support
Which analgesia are used to treat acute pancreatitis?
Parenteral opioids such as hydromorphone or fentanyl.
Why is hydromorphone preferred over morphine in the treatment of acute pancreatitis?
Morphine can increase pressure of sphincter of Oddi which is why hydromorphone is preferred.
What is chronic pancreatitis?
persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine function (pancreatic insufficiency)
Who is the typical chronic pancreatitis-suffering patient?
Middle-aged alcoholic male
What is the hallmark of chronic pancreatitis?
Fibrosis caused by inflammation and recurrent pancreatic injury is the hallmark of chronic pancreatitis but needs to be distinguished from fibrosis caused by the ageing process and diabetic pancreatopathy
Explain the pathophysiology of chronic pancreatitis
Several mechanisms have been proposed:
1. The stone and duct obstruction theory proposes that disease is due to ductal obstruction caused by formation of protein-rich plugs as a result of protein–bicarbonate imbalance for unknown reasons. These plugs may calcify and eventually form stones within the pancreatic ducts. If obstruction is chronic, persistent inflammation leads to fibrosis, pancreatic ductal distortion, strictures, and atrophy. After several years, progressive fibrosis and atrophy lead to loss of exocrine and endocrine function.
- The necrosis–fibrosis hypothesis posits that repeated attacks of acute pancreatitis with necrosis are key to the pathogenesis of chronic pancreatitis. Over years, the healing process replaces the necrotic tissue with fibrotic tissue, leading to the development of chronic pancreatitis.
- Neuronal sheath hypertrophy and perineural inflammation occur and may contribute to chronic pain.
Signs and symptoms of chronic pancreatitis
Abdominal pain and pancreatic insufficiency are the primary manifestations of chronic pancreatitis.
Pain is often the dominant symptom in chronic pancreatitis and is present in most patients.
Pain is usually postprandial, located in the epigastric area, and partially relieved by sitting up or leaning forward. The pain attacks are initially episodic but later tend to become continuous.
What are clinical manifestations of pancreatic insufficiency?
Flatulence Abdominal distention Steatorrhea Undernutrition Weight loss Diabetes Jaundice Hypoalbuminaemia Pseudocysts Splenic vein thrombosis and fatigue
Why does jaundice appear in those with chronic pancreatitis?
Jaundice (fibrosis causes biliary obstruction)
- In chronic pancreatitis, the jaundice is caused by tube-like, long stenosis of the choledochal duct or its compression by a cyst within the head of the pancreas
