Liver Disease Flashcards
What is meant by Acute on chronic inflammation?
Where chronic liver disease often presents with acute exacerbation plus evidence of underlying chronicity - i.e fibrosis
What the most common “target” of inflammation in the liver, and how does this impact other structures?
Liver Parenchyma (hepatocytes, bile apparatus and blood vessels) - specifically the hepatocytes are usually the key target
the problems is - when one part of the parenchyma is targeted - usually the rest will also become damaged
Define end stage liver cirrhosis:
Diffuse
Nodular
Fibrotic
*to avoid this is the aim of treatment
Outline the very basic clinical approaches to liver damage:
LFTs
- AST
- ALT
- ALK Phos
- GGT
Haematology
- haemolysis
- Iron levels
Viral serology
Autoimmune serology
- Anti - mitochondrial (PBC)
- Anti ANA (auto Hep)
Radiology
- ultrasound
Histologically: what does acute hepatitis look like?
Diffuse cellular swelling
with areas of necrosis
- spotty necrosis
with inflammatory infiltrate in all places
If there is paracetamol overdose, what is the AST/ALT levels going to be?
> 1000s
- very high
What colour does bile turn in histology staining?
Brown
Histologically, what does the hep B virus in the liver look like?
Ground glass cytoplasm
- due to accumulation of surface antigen
What may co-amoxiclav cause?
Acute Cholestatic hepatitis
Name a biliary Hamartoma:
Von Meyenberg complex
If there is haemochromatosis and you take a biopsy - how do you differentiate between Lipofucin (a normal wear and tear deposit within the liver) and Iron?
Prussian Blue stain
- stains Iron blue
What are the most common causes of Abnormal Liver blood tests?
Fatty Liver
- alcohol
- non alcohol
Chronic viral Hepatitis
Autoimmune
- primary Biliary Cholangitis
- Autoimmune Hepatitis
Haemochromatosis
What is non- alcoholic fatty liver disease often associated with, and what may it become?
Metabolic syndrome:
- obesity
- insulin resistance
- Hyperlipidaemia
there severity of the steatohepatitis increases the metabolic risk factors
NASH
- non alcoholic Steatohepatitis
Outline the pathological changes that occur in alcoholic and nonalcoholic liver fatty liver disease
Alcohol:
Alcoholic Steatosis > Alcoholic Hepatitis > Alcoholic Cirrhosis
Non - Alcoholic:
Steatosis > NASH ?
NAFLD Cirrhosis
Name some key lab findings that differentiate between Fatty liver disease and non fatty liver disease:
AST:
Higher in Alcoholic
AST:ALT ratio:
much higher in alcoholics
GGT:
Much higher in alcoholics
Outline some classical clinical features of newly jaundiced ALD patient:
Hepatomegaly
Fever
Leukocytosis
Hepatic Bruit
In liver fibrosis - where does the fibrosis start?
Portal tract then moves into the septa and spreads diffusely
What non-invassive scan can be done for Liver fibrosis?
Fibroscan
- measures the firmness of the liver.
Blood based Assessment:
- ELF test
- Fib-4 score
- NAFLD Fibrosis Score
What assessment is used to asses the degree of liver damage?
Child’s Turcotte- Pugh Score
Grade A: 5-6
- mild
Grade B: 7-9
- moderat e
Grade C: 10-15
- Severe
What is the model for End staged liver failure, and what is it also used for?
Model for End stage Liver Disease
Used to allocate donor organs
What are the two main alcohol metabolic pathways within the liver?
Alcohol Dehydrogenase
- cytosol
Microsomal Ethanol Oxidase System
- Smooth endoplasmic
Where does fibrosis first start in alcohol disease?
Perivenular area
- zone 3
When assessing Ascites what things must you assess?
Cell count
- high white blood cell count (>250) suggests: Spontaneous Bacterial Peritonitis
Albumin:
- Serum ascites albumin Gradient
What is the Serum Ascites Albumin gradient?
Is it important to understand where the fluid within the peritoneum has come from:
- portal hypertension (transudate)
- Infection within the peritoneum (exudate) (Spontaneous bacterial peritonitis)
This is worked out by assessing the amount of albumin in the ascites.
[Serum Ascites Albumin Gradient]
it involves:
- Serum Albumin MINUS Ascites Albumin
> 11g/l = Portal hypertension
Since portal hypertension produced transudate - you would expect a greater difference between the plasma and peritoneal fluid.
- thus an increase of over >11g/L is suggestive of transudate
If there is a high Lymphocytes within the ascites - what does this suggest?
TB
or
Peritoneal Carcinomatosis
What is the management of Ascites?
Low salt diet
Spironolactone
Furosemide
paracentesis
Transjugular intrahepatic portosystemic shunt (TIPSS)
List some precipitating factors to hepatic encephalopathy and name some key things not to make it worse:
Encephalopathy comes about due to the build up of waste products in the blood namely - ammonia NH3.
anything that will increase the level of this will make it worse.
Gastrointestinal bleeding
- direct spillage of NH3
Infections
- production of NH3
Constipation
- increased break down of Urea to NH3 by bacteria
electrolyte imbalance
- hyponatremia makes it worse
Excess protein
- more substance for bacteria
Alkalosis
- holds the NH3 - as there is a reduction in H+ ions to bind with it
Things to avoid:
Avoid sedation
- opiates
Avoid Hyponatremia
What score is used to assess Mental state in Hepatic Encephalopathy?
Conn Score
score 0 = no changes
Score I = lack of awareness
Score II = Lethargy or apathy
Score III = Somnolence
Score IV = coma
List the common things Cirrhosis is associated with:
Ascites
Encephalopathy
Variceal bleeding
Hepatocellular carcinoma
List some investigation you would carry out in suspected Liver disease:
LFTs
FBC
- clotting factors
- Vitamin K
Bilirubin
autoimmune antibodies
- ANA
- Anti - mitochondrial
Conn Score
Liver ultrasound
Name an important benign tumour of the liver that shouldn’t be biopsied due to the risk of bleeding.
Haemangioma
What serum marker can be seen in Hepatocellular carcinoma?
Alpha fetal Protein
What is a high Alpha Fetal protein indicative off?
Hepatocellular carcinoma
If IgG levels are elevated in liver disease, what is this suggestive off?
Autoimmune hepatitis
If the IgM levels are elevated in liver disease, what is this suggestive off?
Primary biliary cholangitis
In someone with chronic liver disease, what viruses would you check for?
Hep B
Hep C *this is the most common
these are the only ones that lead to chronic states.
In chronic liver disease - what investigations would you do?
Ultrasound
Autoimmune test
Viral tests
- HCV
- HBV
Metabolic functions
- ferritin levels
- Ceruloplasmin - Wilson’s
- Alpha -1 - antitrypsin
List some Stigmata (obviously) chronic liver failure signs:
Encephalopathy
Foetor on the breath - smells like rich tea biscuits
Prolonged prothrombin
Hypoalbuminemia
Portal hypertension
What are the combined pathologies that lead to increased Encephalopathy?
Inflammation induced by liver failure
Increased levels of ammonia - which is leaking out from the shunting portal veins.
**important not to give benzodiazepines and opioids
What is the classical diagnostic sign seen in hepatic encephalopathy?
1Hz flapping tremor
Treatment of Hepatic encephalopathy?
increase bowel Movements
- lactulose
Antibiotics
In the context of liver disease, itchy skin can be indicative of what?
Primary Biliary cholangitis
What blood test can help diagnose Wilson’s disease?
Ceruloplasmin
Copper and protein bind to make ceruloplasmin. In the presence of kidney disease or wilson’s disease the protein won’t be made, lead to free copper. as such if there is LOW ceruloplasmin then it is suggestive of wilson’s
What is the screening marker for Hepatocellular carcinoma?
Alpha Fetal protein
What tests would you do to assess the functioning of the liver?
Prothrombin time
Albumin levels
Bilirubin levels
*these demonstrate the functioning of the liver much more over the LFTs
Name come clinical signs that may be seen in chronic hepatic failure:
Spider navei
- above the SVC
Palmer erythema
Axthanomas
Gynecomastia in males
What are some key lab findings for auto immune hepatitis, and what is the treatment?
Anti smooth muscle antibodies
Anti nuclear antibodies
Treatment:
- steroids
+/- Azathioprine
In suspicion of colorectal cancer, what blood tests would you carry out?
FBC
U&Es
LFTs
- often metastasis from the liver can arrive there.
What is used to stage colorectal cancers:
CT
MRI - very useful for pelvis
What is the treatment of colorectal cancer:
Neo Adjunctive therapy (for some patients)
Surgical resection
- this is primary choice.
- abdominal peri- anal resection may need to be done and results in need for colostomy bag
What stage is used for Colorectal cancer?
Dukes
A - tumour confined to mucosa
B1 - Growth into muscular propia
B2 - Full thickness - through mucosa
**Through the muscular propia
C1 - Tumour spread to 1-4 lymph nodes
C2 - > 4 lymph nodes
**local lymph nodes
D - Distant metastasis - liver, bone
Where would you expect to see obstruction from a colon cancer and why?
Left sided colon involvement
- this is because the bowel is narrower here resulting in decreased space.
What polyps are usually stalked, and why is this, and name one that isn’t:
Adenomatous Polyps
Tubulovillous Polyps
these are stalked due to the waves of peristalsis which drag the polyp along into the shape of it.
there is also extreme pressures within the colon which may lead to bleeding
Villous adenoma
What kind of epithelial, lines the serosa?
Non keratinised squamous epithelium
What is the stages that cause the Adenomatous polyps to become malignant:
APC mutation development (either sporadic or Familial poly polyposis adenoma)
this leads to KRAS mutations - which causes the mutation
this then leads to p53 mutation = cancer
What medication protects against polyps forming cancer?
Aspirin
What is the management of Ascites?
*Spironolactone +/- Furosemide
What is refractory ascites? and what is the management?
Sodium restriction
Spironlactone
furosemide
Paracentesis
- drainage of the fluid
for every 3L drained albumin needs to be given. this is because there can be massive fluid shifts that occur as fluid from the extravascular space come into the space that was the ascites.
What is the destruction that occurs in primary biliary cholangitis?
Granulomatous destruction of the intrahepatic bile ducts