W30 Pathophysiology and risk factors for hepatic disorders Flashcards
1
Q
What is liver disease?
A
- Build-up of scar tissue (fibrosis)
- Scar tissue is formed when your liver is damaged (inflamed) from one of many different causes:
- Metabolic associated fatty liver disease,
- Alcohol FLD,
- Viral infections
- Autoimmune liver disease
- The scarring in the liver forms irregular bumps (nodules) that replace the smooth liver tissue and the liver becomes harder
- The scar tissue changes the liver’s shape (which affects the blood flow through the Liver) and also changes how the liver works
2
Q
What are the functions of the liver?
A
- Helps break down food and convert it into
energy, storing carbohydrates and maintaining a good balance of glucose levels in the blood - Processes waste products produced by the body (e.g. ammonia»_space; urea)
- Helps you fight infections
- Creates proteins that are responsible for blood clotting
- Helps the body process medication and alcohol
- Dysfunction with liver disease
3
Q
What is Steatosis?
A
Steatosis causes fat droplets to form within hepatocytes
↑ synthesis & uptake FFA
↓ FA oxidation
↓ secretion of FA for lipoproteins
4
Q
Main causes of FLD- Alcoholic
A
- Globally 3 million deaths annually
- Chronic heavy alcohol ingestion. About 40 to 80 g/day in men and 20 to 40 g/day in women for 10 to 12 years is sufficient to cause liver damage in the absence of other liver diseases
- Clinical presentations are highly variable
- No specific laboratory test to identify alcohol as a cause of liver damage
- Liver biopsy, in the context of a history of alcohol abuse, is diagnostic but is not absolutely indicated in all patients
- Alcohol abstinence is the first line of treatment, with periodic liver enzyme tests to monitor ongoing liver damage
- Abstinence is also the key to prevention of alcoholic liver diseases
5
Q
Main causes of FLD- Non-Alcoholic
A
- NAFLD, is one of the most common causes of chronic liver disease in the developed world
- Considered the hepatic manifestation of metabolic syndrome and is associated with obesity, dyslipidaemia, and type 2 diabetes mellitus
- Diagnosis of NAFLD is based on exclusion of other aetiologies of hepatic steatosis, such as alcohol use, and supportive laboratory tests and imaging. Liver biopsy and histology is the gold standard for diagnosis, and is performed for patients at higher risk of fibrosis or steatohepatitis
- Lifestyle modification, including weight loss, physical activity, and dietary changes, is the first-line therapy
- There are no licensed drug treatments, although use of pioglitazone or vitamin e may be considered for selected patients
6
Q
Main causes of FLD- imbalances
A
- ↑ Acetyl CoA = ↑ FA
- ↑ NADH = ↓ metabolism ↑ FA
- ↓ NAD+ = ↓ FA oxidation
- ↓ synthesis of lipoproteins
- ↑ peripheral lipolysis
7
Q
Main causes of FLD- Non-alcoholic
A
- ↑ dietary fats, ↑ fructose intake
- ↑hepatic lipase uptake FFA
- ↑storage of FFA as TG
- ↓secretion of lipoproteins
- ↓FA secretion
8
Q
The liver metabolizes ethanol: enzymes (3)
A
- Alcohol dehydrogenase (ADH)
- Cytochrome p450
- Catalase in peroxisomes
9
Q
What is Cirrhosis?
A
- Cirrhosis develops progressively as a result of damage to the liver (which can be due to a number of causes), usually over a number of years
- The normal smooth liver structure becomes distorted, with nodules surrounded by fibrosis. This affects the liver’s synthetic, metabolic and excretory actions.
10
Q
How can cirrhosis be categorised? (2)
A
- Compensated — when the liver can still function effectively and there are no, or few, noticeable clinical symptoms [Muir, 2015]
- Decompensated — when the liver is damaged to the point that it cannot function adequately and overt clinical complications (such as jaundice, ascites, variceal haemorrhage, and hepatic encephalopathy) are present.
11
Q
Prevalence of Cirrhosis:
A
- It is difficult to assess the true prevalence of cirrhosis because the initial stages are often
asymptomatic, meaning it remains undiagnosed in many people with the condition [Tsochatzis et al, 2014] - In England and Wales, liver disease affects 600,000 people, of whom 60,000 have
cirrhosis [Williams et al, 2014]. Cirrhosis more commonly affects people living in urban
areas and those who are experiencing social deprivation [Keane et al, 2016] - Liver disease has been identified as the only major cause of mortality and morbidity that
is increasing for chronic, non-communicable diseases [NICE, 2016; RCGP, 2017] - Over the decade 2005–2015, there was a 49% increase in the number of admissions with
a primary diagnosis of cirrhosis in England [NICE, 2016] - A UK cohort study also found an increase in the incidence of cirrhosis of just over 50%
during the 12 years between 1998 and 2009 [Ratib et al, 2014a]
12
Q
What are the risk factors for liver disease?
A
- Alcohol misuse — decreased in the 1990’s but numbers have risen over the last decade.
- Hepatitis B and C infection
- Obesity or type 2 diabetes — but only if they have NAFLD
- However, not everyone with risk factors will develop cirrhosis
Less common causes:
* Autoimmune liver disease (for example, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis).
* Genetic conditions (for example, haemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cystic fibrosis)
* Medication use, usually over a long period of time (for example, methotrexate)
* Budd-Chiari syndrome or veno-occlusive disease
* Sarcoidosis and glycogen storage disease
13
Q
Prognosis of liver disease:
A
- Irreversible – people are generally well, no clinical symptoms or signs
- Eventually, compensated»_space; decompensated cirrhosis complications such as jaundice, ascites,
variceal haemorrhage, or hepatic encephalopathy arise, due to portal hypertension and/or hepatocellular failure - The prognosis of cirrhosis is influenced by a number of factors, including:
- Underlying cause — successful treatment of the cause may prevent additional liver injury (for example antiviral treatment for hepatitis C
- Lifestyle changes — obesity and alcohol use have prognostic relevance in people with cirrhosis, regardless of the underlying cause [Garcia-Tsao et al, 2017]
- Development of complications
- Median survival compensated stage >12 years; decompensated stage two years [D’Amico et al, 2006]
- UK population-based cohort study of people with cirrhosis (n = 5118) found average survival
probabilities at 1 and 5 years were better for the ambulatory group (0.84 and 0.66) than for people who had required admission to hospital (0.55 and 0.31)
14
Q
What are the complications of Cirrhosis?
A
Infection
Portal hypertension
Hepatic encepalopathy
Ascites
Haemorrhage from oesophageal varices
Hepatorenal syndrome
Infection
15
Q
Portal hypertension:
What is portal hypertension?
What is it caused by?
What is it determined by?
What are the obvious signs of portal HTN? (5)
A
- Portal hypertension is defined as the pathological increase of portal venous pressure, mainly due to chronic end-stage liver disease, leading to augmented hepatic vascular resistance and congestion of the blood in the portal venous system
- Caused by ↑pressure within the portal venous system
- It is determined by the increased portal pressure gradient (the difference in pressures between the portal venous pressure and the pressure within the inferior vena cava or the hepatic vein
- > 5 mmHg – portal HTN
- > 10 mmHg – significant portal HTN
Obvious signs of portal HTN:
- Blood in vomit
- Blood in poop
- Bloated stomach with rapid weight gain (from fluid)
- Swelling in your legs and feet (Oedema)
- Mental confusion or disorientation
