PBL 51 Flashcards
1
Q
Social impacts of alcohol
A
- 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
2
Q
What is the blood supply to the liver?
A
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
3
Q
The venous blood from the GI tract drains into the portal vein, what is this made up of?
A
The superior and inferior mesenteric veins, which are joined by the splenic vein
4
Q
What is cirrhosis?
A
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.
5
Q
Give some causes of liver cirrhosis
A
- 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
6
Q
Explain the pathogenesis of liver cirrhosis
A
- 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
7
Q
Risk factors for liver cirrhosis
A
• 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).
8
Q
Fatty liver that is not caused by alcohol usually occurs in which people?
A
- overweight
- have diabetes or pre-diabetes
- high cholesterol.
9
Q
Signs and symptoms of liver cirrhosis
A
- 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
10
Q
Complications of cirrhosis
A
- 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
11
Q
What is portal hypertension
A
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
12
Q
Where do collateral vessels develop?
A
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.
13
Q
Portal hypertension can cause which organ to increase in size? What is the consequence of this?
A
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)
14
Q
What is portopulmonary hypertension? Give some symptoms
A
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
15
Q
What is spontaneous bacterial peritonitis?
A
When the fluid in the abdomen becomes infected, this is usually in those with ascites
16
Q
Poor absorption of vitamin D leads to what?
A
Osteoporosis
17
Q
Poor absorption of vitamin K leads to what?
A
People bleeding more easily
18
Q
How does liver cirrhosis cause bleeding irregularities?
A
- Less production of Vit K (clotting factor)
2. Splenomegaly which traps blood cells and platelets, so there are less platelets in the bloodstream
19
Q
How does liver cirrhosis increase the risk of infection?
A
- 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.
20
Q
What is hepatorenal syndrome?
A
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
21
Q
How does liver cirrhosis cause deterioration of brain function?
A
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.
22
Q
Symptoms of hepatic encephalopathy?
A
Confusion
Altered level of consciousness
Coma due to ammonia accumulation
23
Q
Vascular spiders are caused by what?
A
Excess levels of oestrogen
24
Q
What are the clinical consequences of hepatic failure?
A
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)
25
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
26
What is the gold standard for diagnosis of liver cirrhosis?
Liver biopsy
27
Why does bilirubin increase in liver impairment?
Less is conjugated by the liver, so it builds up in the bloodstream --> Jaundice
28
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
29
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
30
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
31
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
32
What is the treatment for haemochromatosis?
Phlebotomy
33
How is ascites treated?
Restriction of sodium in the diet because excess sodium can contribute to fluid accumulation.
- Diuretics
34
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
35
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)
36
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
37
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
38
Risk factors for acute pancreatitis
* Obesity
* Diabetes
* Cigarette smoking
* FHx
* Xs alcohol
39
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)
```
40
What is the most common cause of acute pancreatitis?
Gallstones and then alcohol intake
41
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
42
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
43
Acute pancreatitis is a complication that develops after which procedure?
endoscopic retrograde cholangiopancreatography (ERCP) in about 5% of patient
44
Diagnosis of acute pancreatitis?
* Raised serum amylase & lipase (> 3x upper limit)
* Glucose intolerance
* Hypocalcaemia (fat sequestration)
* Raised CRP, WCC etc
* Haemorrhagic peritoneal effusion
45
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
46
Treatment of acute pancreatitis
* Early goal-directed fluid resuscitation: Acute pancreatitis can cause dehydration
* Oxygen
* Analgesia
* Anti-emetics
* Nutritional support
47
Which analgesia are used to treat acute pancreatitis?
Parenteral opioids such as hydromorphone or fentanyl.
48
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.
49
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)
50
Who is the typical chronic pancreatitis-suffering patient?
Middle-aged alcoholic male
51
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
52
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.
2. 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.
3. Neuronal sheath hypertrophy and perineural inflammation occur and may contribute to chronic pain.
53
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.
54
What are clinical manifestations of pancreatic insufficiency?
```
Flatulence
Abdominal distention
Steatorrhea
Undernutrition
Weight loss
Diabetes
Jaundice
Hypoalbuminaemia
Pseudocysts
Splenic vein thrombosis and fatigue
```
55
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
56
Risk factors for chronic pancreatitis
- Heavy alcohol consumption
- Smoking
Less common causes:
- Genetic disorders: cationic trypsinogen gene, CTFR, SPINK1
- Obstructive: pancreatic duct stricture, mass effect due to tumour, sphincter of Oddi dysfunction
- Autoimmune: Type 1, related to IgG4 disease, and type 2 autoimmune pancreatitis
- Idiopathic: Tropical pancreatitis
57
Idiopathic form of chronic pancreatitis occurs in which demographic?
Idiopathic form occurs in children and young adults in tropical regions such as India, Indonesia, and Nigeria.
58
Tropical pancreatitis is characterised by what?
- Early age of onset
- Large ductal calculi
- An accelerated course of the disease
- Increased risk of pancreatic cancer
59
Complications of chronic pancreatitis?
- When lipase and protease secretions are reduced to < 10% of normal, the patient develops malabsorption characterized by steatorrhea, the passing of greasy stools, or even oil droplets that float in water and are difficult to flush.
- In severe cases, undernutrition, weight loss, and malabsorption of fat-soluble vitamins (A, D, E, and K) may also occur
- Glucose intolerance may appear at any time
- Formation of pseudocysts
- Obstruction of the bile duct or duodenum
- Disruption (disconnection) of the pancreatic duct (resulting in ascites or pleural effusion)
- Thrombosis of the splenic vein (can cause gastric varices)
- Pseudoaneurysms of arteries near the pancreas or pseudocyst
- Patients with chronic pancreatitis are at increased risk of pancreatic adenocarcinoma, and this risk seems to be greatest for patients with hereditary and tropical pancreatitis.
60
Diagnosis of chronic pancreatitis
Imaging studies:
- Abdominal CT can be used to detect calcifications and other pancreatic abnormalities (e.g., pseudocyst or dilated ducts) but still may be normal early in the disease.
- MRI coupled with magnetic resonance cholangiopancreatography (MRCP) is now frequently used for diagnosis and can show masses in the pancreas as well as provide more optimal visualization of ductal changes consistent with chronic pancreatitis
Pancreatic function tests:
- Direct pancreatic function tests are most useful in patients who have an earlier stage of chronic pancreatitis in whom imaging studies are not diagnostic. Direct tests involve intravenous infusion of the hormone cholecystokinin to measure the production of digestive enzymes or infusion of the hormone secretin to measure the production of bicarbonate.
- Indirect pancreatic function tests are less accurate in diagnosing earlier stages of chronic pancreatitis. Very low levels of serum trypsinogen (< 20 ng/mL) are highly specific for chronic pancreatitis. The indirect tests are widely available, less invasive, inexpensive, and easier to do than the direct tests.
61
Treatment for chronic pancreatitis
- Pain control
- Pancreatic enzyme supplements
- Management of diabetes
- Management of other complications (stop smoking and alcohol)
- Surgical treatment
62
Which drugs are used as chronic pain control for chronic pancreatitis?
adjunctive pain drugs, such as: tricyclic antidepressants, gabapentin, pregabalin, and selective serotonin reuptake inhibitors, have been used alone or combined with opioids to manage chronic pain
63
How do pancreatic enzyme supplements reduce chronic pain?
Reduce chronic pain by suppressing the release of cholecystokinin from the duodenum, thereby reducing the secretion of pancreatic enzymes (works better in idiopathic rather than alcoholic pancreatitis)
64
Pancreatic enzyme replacement is used to treat which symptom of pancreatitis?
Steatorrhoea
NOTES: In patients with exocrine pancreatic insufficiency, malabsorption of fat is more severe than malabsorption of proteins and carbohydrates. Fat malabsorption also results in a deficit of fat-soluble vitamins (A, D, E, and K).
65
Explain what happens with drug metabolism in patients with liver impairment
Liver dysfunction not only reduces the clearance of a drug metabolized through hepatic enzymes or biliary mechanisms, but also affects plasma protein binding due to reduced synthesis of albumin and other drug-binding proteins.
66
What is the effect of portal-systemic shunting in patients with liver cirrhosis
Portal-systemic shunting present in patients with advanced liver cirrhosis can cause a significant reduction in first-pass metabolism of high-extraction drugs, thus increasing bioavailability as well as the risk of drug overdose and toxicity.
67
Metabolism in the liver is mainly carried out by which enzyme?
Cytochrome p450
68
Drug metabolism has 2 phases, what are they?
* Phase 1 - Reduction, hydrolysis, or oxidation (the resulting metabolise is often chemically active)
* Phase 2 - Conjugation (attaching ionising group makes metabolite more water soluble)
69
Which of the 2 phases of drug metabolism are affected in liver disease?
Although the Phase I reaction involving cytochrome P-450 enzymes may be significantly impaired in liver disease, the Phase II reaction (glucuronidation) seems to be unaffected.
70
Patients with liver disease often suffer from hypoalbuminaemia, what is the consequence of this?
Protein bindings of strongly protein-bound drugs are impaired and cause elevation of pharmacologically active free fraction of the drug
71
What is the most common chronic liver disease?
Non-alcoholic fatty liver disease
- This type of liver disease also affects the activity of drug-metabolizing enzymes in the liver with the potential to produce adverse drug reactions from the standard dosage
72
Why does the liver have to break down fat-soluble drugs? What does the liver do to them?
Most drugs are fat-soluble, meaning that they are difficult to pass in urine.
- The enzymes in the liver work to break down these substances and convert them into water-soluble forms, which can then pass in bile and/or urine
73
Which conditions slow drug metabolism?
* Kidney disease
* Shock
* Heart failure
* Liver disease
74
What is drug-induced liver injury?
Drug induced liver injury (DILI) occurs when the consumption of a substance, such as a drug, nutritional supplement, medicinal herb, or plant, causes direct damage to the liver
75
Which drugs are involved in drug-induced hepatitis?
```
Characterised by inflammation of the liver:
• Acetaminophen
• NSAIDs
• Birth control pills
• Anabolic steroids
```
76
Factors that increase the risk of drug-induced liver injury (DILI)
* Drinking alcohol
* Being 18 or older
* Genes that affect user's response to drugs
* Obesity
* Pregnancy
* Sex
* Diseases such as HIV, liver disease
* Illicit drug abuse
* Taking medications or drugs in excess
* Combining drugs and/or alcohol
77
Drugs that can damage the liver
* Antibiotics - Erythromycin, amoxicillin, tetracyclins
* Antipsychotic drugs
* Statins
* Antifungals
* Antihypertensives - Lisinopril, captopril
* Helothane (anaesthetic)
* Birth control pills
* Antidepressants
* Anticonvulsants
* NSAIDs
* Anabolic steroids
* Recreational drugs
78
Hepatitis commonly results from...
1. A virus - Hepatitis A, B, C, D or E
2. Excessive alcohol intake
3. Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH)
4. Use of certain drugs, such as isoniazid
5. Autoimmune hepatitis
79
Symptoms of acute viral hepatitis
- Loss of appetite
- Fatigue
- Jaundice
- A general feeling of illness (malaise)
- Nausea and vomiting
- Pain in the upper right part of the abdomen (where the liver is located)
- Clay-coloured stool.
- Low-grade fever.
- Dark urine.
- Joint pain.
80
People who smoke that are infected with acute viral hepatitis develop a distaste for cigarettes as a symptom, true or false?
True
81
What is the most common cause of acute viral hepatitis?
Hepatitis A
82
Amongst which demographic is hepatitis A most common?
Children and adults
83
Can hepatitis A become chronic (last >6months)?
NO
84
How is hepatitis A spread?
Faecal-oral route
85
Shellfish taken from waters where raw sewage drains are sometimes contaminated and can cause infection when they are eaten raw, which type of infection is this?
Hepatitis A
86
Which type of hepatitis is spread in day care centres?
Hepatitis A
87
Symptoms of hepatitis A?
Most older children and adults with hepatitis A have typical symptoms of acute hepatitis. These symptoms include:
- Loss of appetite
- Fatigue
- Jaundice
- A general feeling of illness (malaise)
- Nausea and vomiting
- Pain in the upper right part of the abdomen (where the liver is located)
- Clay-coloured stool.
- Low-grade fever.
- Dark urine.
- Joint pain.
88
Does hepatitis A cause severe scarring of the liver?
No
89
Diagnosis of hepatitis A?
- Liver function test: ALT, bilirubin, foecal HAV (increased)
- Blood tests for specific antigens
90
People at high risk of hepatitis A exposure
* Travelers to parts of the world where hepatitis A is widespread
* People who work in diagnostic or research laboratories that handle hepatitis A virus
* People with chronic liver disorders or bleeding disorders
* Men who have sex with men
* People who use illicit drugs (who are often infected for reasons other than drug use)
* People who do not have stable housing or who are homeless
* Pregnant women who are at risk of getting hepatitis A infection during pregnancy
91
Treatment for hepatitis A
- Prevention with hepatitis A vaccine
- Do not drink alcohol
- Cholestyramine for itching
92
Where is hepatitis B most prevalent?
* China
* Korea
* North Africa
* Eastern Europe
93
Signs and symptoms of hepatitis B
- Loss of appetite
- Fatigue
- Jaundice
- A general feeling of illness (malaise)
- Nausea and vomiting
- Pain in the upper right part of the abdomen (where the liver is located)
- Clay-coloured stool.
- Low-grade fever.
- Dark urine.
- Joint pain.
94
How is hepatitis B transmitted?
- Transmission commonly occurs when needles are reused without being first sterilised—as when people share needles to inject drugs or when needles are reused to apply tattoos
• Razors
• Toothbrushes
* Transmission through blood transfusions is possible but is now rare in the United States because blood is screened.
* Hepatitis B is also spread through contact with saliva, tears, breast milk, urine, vaginal fluid, and semen, but such spread is less common than blood-to-blood transmission.
* Transmission may occur between sex partners, both heterosexual and homosexual. Also at increased risk are people living in close quarters (such as prisons and mental health institutions) because contact with another person's body fluid is more likely.
* A pregnant woman infected with hepatitis B can transmit the virus to her baby during birth. The child will have a 90% risk of developing chronic Hepatitis B in life.
95
Where is hepatitis C most prevalent?
Pakistan
96
Is there a vaccine for hepatitis C?
No
97
How is hepatitis C most commonly transmitted?
* Hepatitis C is usually spread through contact with blood of an infected person. Hepatitis C is most commonly transmitted among people who share unsterilized needles to inject illicit drugs. The infection can also be transmitted through unsterilized needles used for tattoos and body piercings.
* Transmission through blood transfusions or organ transplants is possible but is now rare due to screening processes
* Transmission through sexual contact is uncommon, as is transmission from an infected pregnant woman to her baby.
98
Signs and symptoms of hepatitis C
Some people with acute hepatitis C have typical symptoms of viral hepatitis. These symptoms include
- Pruritus
- Loss of appetite
- Fatigue
- Jaundice
- A general feeling of illness (malaise)
- Nausea and vomiting
- Pain in the upper right part of the abdomen (where the liver is located)
- Clay-coloured stool.
- Low-grade fever.
- Dark urine.
- Joint pain
99
Does hepatitis C become chronic?
Yes, in about 75% of people
100
Diagnosis of hepatitis C
- Blood tests for liver enzymes etc...
| - Blood tests for HCV antibody
101
Treatment of hepatitis C
Antiviral drugs
| - DONT DRINK ALCOHOL
102
Hepatitis D can occur on its own, true or false?
False, it occurs as a co-infection with hepatitis B, it makes hepatitis B worse
103
How is hepatitis D transmitted?
- Hepatitis D can be spread by contact with blood and other body fluids.
- Hepatitis D is most often spread when people share unsterilized needles to inject illicit drugs. It can also be spread through sexual activity.
104
Signs and symptoms of hepatitis D
```
• Scarring of the liver (cirrhosis).
• Coinfection with hepatitis B and D can lead to fulminant hepatitis (a very severe form of hepatitis)
- Loss of appetite
- Fatigue
- Jaundice
- A general feeling of illness (malaise)
- Nausea and vomiting
- Pain in the upper right part of the abdomen (where the liver is located)
- Clay-coloured stool.
- Low-grade fever.
- Dark urine.
- Joint pain.
```
105
Treatment for hepatitis D
Antiviral drug - INTERFERON ALPHA
| - Do not drink alcohol
106
What is the most common cause of acute hepatitis worldwide?
Hepatitis E
107
How is hepatitis E transmitted?
Faecal-oral route
108
Where have hepatitis E epidemics occurred?
Epidemics have occurred only in China, India, Mexico, Peru, Russia, Pakistan, and central and northern Africa, not in the United States or Western Europe.
In developed countries, most cases occur in travellers returning home from a country where sanitation is poor and access to safe water is limited
109
Symptoms of hepatitis E
- Loss of appetite
- Fatigue
- Jaundice
- A general feeling of illness (malaise)
- Nausea and vomiting
- Pain in the upper right part of the abdomen (where the liver is located)
- Clay-coloured stool.
- Low-grade fever.
- Dark urine.
- Joint pain.
110
Diagnosis for hepatitis E
- Blood tests
| - Liver function tests
111
Prevention of hepatitis E
Good sanitation and personal hygiene
112
Is there a vaccine for hepatitis E?
YES
113
Treatment for hepatitis E
* General measures
* Possibly ribavirin for chronic hepatitis E
DONT DRINK ALCOHOL
• There is no specific treatment for acute hepatitis E.
• If itching occurs, cholestyramine, taken by mouth, may relieve the itching.
114
What are the most common causes of chronic hepatitis?
- Hepatitis C causes 60-70% of chronic hepatitis
- Hepatitis B (5-10% of cases)
- Non-alcohol steatohepatitis
- Alcohol-related liver disease
Less often, chronic hepatitis results from:
• Autoimmune hepatitis
• Drugs
• Alpha-1 antitrypsin deficiency (a hereditary disorder)
• Coeliac disease
• Hemochromatosis (a hereditary disorder that causes the body to absorb too much iron)
• Primary biliary cholangitis
• A thyroid disorder
115
Signs and symptoms of chronic hepatitis
Chronic hepatitis often causes general symptoms, such as a vague feeling of illness (malaise), poor appetite, and fatigue.
Sometimes affected people also have a low-grade fever and some discomfort in the upper abdomen.
Jaundice is rare unless liver failure develops. Many people with chronic hepatitis have no symptoms.
Often, the first specific symptoms occur when liver disease has progressed and there is evidence of cirrhosis. Symptoms can include:
• An enlarged spleen
• Small spiderlike blood vessels visible in the skin (called spider angiomas)
• Redness of the palms
• Accumulation of fluid within the abdomen (ascites)
• A tendency to bleed (coagulopathy)
• Jaundice
• Deterioration of brain function (hepatic encephalopathy)
116
What is jaundice?
Jaundice is a yellowish discolouration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL
117
Explain the normal pathway of bilirubin formation and excretion
- Most bilirubin is produced when haemoglobin (Hb) is broken down into unconjugated bilirubin (and other substances).
- Unconjugated bilirubin binds to albumin in the blood for transport to the liver, where it is taken up by hepatocytes and conjugated with glucuronic acid to make it water soluble.
- Conjugated bilirubin is excreted in bile into the duodenum. In the intestine, bacteria metabolise bilirubin to form urobilinogen. Some urobilinogen is eliminated in the faeces, and some is reabsorbed, extracted by hepatocytes, reprocessed, and re-excreted in bile
118
Give some examples of how unconjugated hyperbilirubinaemia occurs
Unconjugated hyperbilirubinemia is most often caused by ≥ 1 of the following:
• Increased production
• Decreased hepatic uptake
• Decreased conjugation
119
Give some examples of how conjugated hyperbilirubinaemia occurs?
Conjugated hyperbilirubinemia is most often caused by ≥ 1 of the following:
• Dysfunction of hepatocytes (hepatocellular dysfunction)
• Slowing of bile egress from the liver (intrahepatic cholestasis)
• Obstruction of extrahepatic bile flow (extrahepatic cholestasis)
120
Give examples of hepatobiliary disorders which cause both forms of hyperbilirubinaemia
Many conditions can cause jaundice, but the most common causes overall are:
- Inflammatory hepatitis (viral hepatitis, autoimmune hepatitis, toxic hepatic injury)
- Alcohol-related liver disease
- Biliary obstruction
121
Give examples of pre-hepatic (unconjugated) jaundice causes
- Haemolysis
- Resorption from bleed
- Gilbert syndrome (most common cause)
- Ineffective erythropoiesis
N.B people will get PRURITUS
122
Causes of hepatic jaundice?
```
Liver disease
Drugs
Toxins
Cancer
Primary sclerosing cholangitis
```
123
Causes of post-hepatic jaundice
```
Gallstones
Pancreatic cancer
Colangeal carcinoma of biliary tree
Strictures
Biliaryatresia
Primary sclerosing cholangitis
```
124
Diagnosis for jaundice
1. Blood tests - bilirubin, aminotransferase, alkaline phosphatase
2. Imagine
3. Biopsy
125
Treatment for jaundice
Jaundice requires no treatment in adults, unlike in neonates (phototherapy)
- Itching can be relieved by cholestyramine, but this is ineffective in patients with complete biliary obstruction
126
What are the different types of autoimmune hepatitis?
T1
T2
T3
127
Serum markers for T1 autommune hepatitis
Raised anti-smooth muscle antibodies
128
Serum markers for T2 autoimmune hepatitis
Anti-liver/kidney/microsomal antibodies
129
Serum markers for T3 autoimmune hepatitis
Raised anti-soluble liver antibodies
130
Causes/associations with autoimmune hepatitis
```
Graves disease
Type 1 diabetes
Hashimoto's
Ulcerative colitis
Coeliac diseaes
```
131
Acute vs chronic infection serum antibody markers
IgM is a temporary antibody which represents acute infection
IgG replaces IgM and stays for life, so is sign of previous or chronic infection
132
Risk factors for gallstones?
5F's
1. Female
2. Fat
3. Fourty
4. Fertile
5. Fair
133
Causes of gallstones
- Chronic haemolysis
- Lithogenic bile
- Inflammation/infection
- Rapid weight reduction
- Stasis (e.g. pregnancy or spinal cord injuries)
134
80% of gallstones are which type of stones?
Cholesterol stones
135
What are the symptoms of pancreatic cancer?
Weight loss
Back pain
PAINLESS JAUNDICE
136
All painless jaundice is what until proven otherwise?
Pancreatic cancer
137
Aetiology of pancreatic cancer is unclear but what is said to increase the risk by x1.5?
Heavy smoking
138
What are different endocrine tumours of the pancreas
Most of the cells of the endocrine pancreas are capable of developing tumours:
- Islet cell tumours
- Insulinoma
- Gastrinoma (Zollinger-Ellison syndrome)
- Glucagonoma
- Somatostatinoma
- VIPoma - Watery diarrhoea, hypokalaemia, achlorhydria
139
What are different exocrine pancreatic tumours?
- Pseudocysts - Contain fibrosis, organising blood clot, cholesterol crystals, debris
- Pancreatic abscess
- Cystic tumours - Benign (e.g. mucinouscystadenoma), malignant (e.g. mucinouscystadenocarcinom
