liver Flashcards
Liver Failure: define acute and chronic hepatic failure
acute
- Acute live injury
- with encephalopathy and deranged coagulation (INR > 1.5)
- in a patient with a previously normal liver
- <26 weeks in normal healthy person
chronic
on background of cirrhosis
Liver Failure: aetiology?
- Infection e.g. viral hepatitis B, C.
- Induced e.g. alcohol, drug toxicity,
- Paracetamol - COMMON CAUSE
- Alcohol
- Anti-depressant - Amitriptyline
- NSAIDs
- Ecstasy or cocaine
- Antibiotics - Ciprofloxacin, doxycycline or erythromycin - Inherited e.g. autoimmune.
- Hepatocellular carcinoma
One big complication of liver failure?
and why?
Hepatic Encephalopathy ]
The liver can’t get rid of ammonia and so ammonia crosses the BBB -> cerebral oedema.
Liver Failure: Complications>
- Hepatic encephalopathy.
- Abnormal bleeding.
- Jaundice.
- Ascites.
Liver Failure: management>
- Treat cause
eg paracetamol poisoning - give N-acetyl cysteine
2. Treat complications (Ascites – diuretics, cerebral oedema – mannitol, bleeding – vit K + fresh frozen plasma, encephalopathy – lactulose, sepsis – sepsis 6,antibiotics, hypoglycaemia - dextrose)
- . Mineral supplements e.g. calcium, potassium, phosphate etc.
- Liver transplant.
Liver Failure: signs and symptoms?
Hepatic encephalopathy: so also (altered mood/dyspraxia, liver flap/asterixis)
- Abnormal bleeding (coagulopathy)
- Ascites
- Jaundice
- small liver
- fetor hepaticus (sweet/pear drops and musty breath/urine)
- cerebral oedema
Symptoms:
- Same as acute presentation (malaise, myalgia, fever), restless, altered personality
Alcoholic Liver Disease: Stepwise progression of alcoholic liver disease?
and the Pathophysiology?
- Alcohol related fatty liver: hepatocytes contain triglycerides.
- Alcohol hepatitis.
- Alcoholic cirrhosis: destruction of liver architecture and fibrosis.
healthy liver → simple steatosis (beginning of fatty liver disease) → steatohepatitis (fatty liver disease) → cirrhosis
Alcoholic Liver Disease: histological signs?
Signs and symptoms?
HISTOLOGY
Neutrophils and fat accumulation within hepatocytes.
- Perivenular fibrosis - scar tissue forms around central veins
- Dense cytoplasmic inclusions called Mallory bodies are sometimes seen in hepatocytes and giant mitochondria are also a feature
SIGNS:
vague abdominal signs —> n+v, diarrhoea
- signs: mild jaundice, ascites, hepatomegaly, iron overload
MACROCYTIC ANAEMIA - symptoms: fatigue, malaise, dull RUQ pain
Alcoholic Liver Disease: investigations?
- GGT very raised (gamma-glutamyl transferase)
- AST and ALT may be mildly raised
- ALP (alkaline phosphate) raised
- prothrombin time raised
- low platelet count
- low blood sugar
- FBC – Macrocytic anaemia!!!!
- Liver Biopsy !!!
- Perivenular fibrosis - scar tissue forms around central veins
- Dense cytoplasmic inclusions called Mallory bodies are sometimes seen in hepatocytes and giant mitochondria are also a feature
- ultrasound or CT = fatty infiltration as will liver histology
Alcoholic Liver Disease: management?
- Drinking cessation
- Treat delirium tremens* (withdrawal symptom) **with DIAZEPAM
- IV Thiamine. - to prevent Wernicke-Korsakoff encephalopathy (presents with ataxia, confusion and nystagmus) which occurs from alcohol withdrawal, occurs 6-24 hours after last drink and lasts up to a week
- Diet changes (high in vitamins and proteins) and consider *corticosteroids** for inflammation/to suppress immune system
- Avoid aspirin and NSAIDs
- Liver transplant if very severe
For fatty liver - if pt stops alcohol = fat will disappear and return to normal
Non-alcoholic Liver Disease: define and progression?
Disease due to fat accumulation in the liver and associated with inflammation AND associated w
“metabolic syndromes”
- Steatosis
- Steatohepatitis - baso when you have steatosis and inflammation (NASH) in the absence of alcohol
- Fibrosis
- Cirrhosis - non reversible end stage of progressive chronic liver disease
Non-alcoholic liver disease: aetiology?
Risk factors?
Usually affects individuals with metabolic syndrome: (3/5)
- Type 2 diabetes mellitus.
- Hypertension.
- Obesity.
- Hyperlipidaemia
- Hypertriglyceridaemia
Overweight diabetics with high cholesterol!
RISK FACTORS: inc >50, high BMI, DM, HYN, hyperlipidaemia, excessive soft drinks
Non-alcoholic Liver disease: Pathophysiology w ref to insulin resistance and the diff diseases:
(insulin resistance) = play a role → insulin receptors become less responsive to insulin THUS liver increases fatty acid storage and decreases fatty acid oxidation THUS also decreased secretion of fatty acids into bloodstream and increased synthesis and uptake of fatty acids = steatosis = liver = large, yellow, soft and greasy
= Steatosis!!!!!
Steatohepatitis!!!!
When you have steatosis and inflammation - damage attracts neutrophils to liver (inflammation) = MALLORY bodies!!
Fibrosis:!!
Steatosis and inflammation and fibrosis - baso when stellate cells lay down fibrotic tissue = fibrosis
Baso the stellate cells release cytokines which attract neutrophils and macrophages SO inflammation -> necrosis -> eventual fibrosis
Cirrhosis: see cirrhosis cards
non-alcoholic liver disease: signs and symptoms ?
- even at advanced stages = may be no symptoms
- Often vague symptoms - fatigue, malaise, RUQ discomfort (‘gnawing’)
Once there is significant damage:
- hepatomegaly
- Pain
- Jaundice
- Accumulation of fluid in the peritoneal cavity = ascites
non-alcoholic liver disease: investigations?
Increase in:
- ALT (alanine transaminase)
- AST (aspartate transaminase) SOMETIMES
(In alcoholic - its opp so big rise in AST and less of a rise in ALT)
- ultrasound, MRI, CT scan = look for fatty infiltration
- Biopsy = to diagnose disease - >5% fat content = abnormal
- (raised IgM)
Cirrhosis: define?
Non-reversible
end stage of all progressive chronic liver diseases; which once fully developed is irreversible and may be associated clinically with symptoms and signs of liver failure and portal hypertension
Or
A chronic disease of the liver resulting from necrosis of liver cells followed by fibrosis. The end result is impairment of hepatocyte function and distortion of liver architecture.
Cirrhosis: aetiology
- Alcohol!
- Hepatitis B and C.
- Any chronic liver disease e.g. autoimmune, metabolic, vascular etc.
Cirrhosis: management?
- Deal with the underlying cause e.g. stop drinking alcohol.
- Screening for HCC.
- Consider transplant.
Cirrhosis: complications?
Commonest serious infection in those w cirrhosis = spontaneous bacterial peritonitis!!!!!!!
(can also affect immunocompromised people and those undergoing peritoneal dialysis)
- neoplasia
- ascites
- HCC
- coagulopathy (fall in clotting factors 2,7,9,10)
Cirrhosis: Pathophysiology?
Liver injury causes necrosis and apoptosis, releasing cell contents and reactive oxygen species (ROS)
- This activates hepatic stellate cells and tissue macrophages (Kupffer cells)
- Stellate cells release cytokines that attract neutrophils and macrophages to the liver which results in further inflammation and thus necrosis and eventual fibrosis
- Kupffer cells phagocytose necrotic and apoptotic cells and secrete pro- inflammatory mediators: TGF-beta and PDGF
- → Increased myofibroblasts leads to progressive collagen matrix deposition resulting in fibrosis and scar accumulation in the liver
Chronic Hepatitis: aetiology?
Acute Hepatitis: aetiology?
Non-infective causes of acute and chronic hepatitis??
CHRONIC Infective causes: - 1. Hepatitis B (+/-D). 2. Hepatits C. 3. Hepatitis E.
Non-infective causes:
- Alcohol
- Drugs
- Autoimmune
- Hereditary metabolic
ACUTE: Viral: - Hepatitis A and E • Herpes viruses e.g. EBV (Epstein Barr Virus), CMV (Cytomegalovirus), VZV (Varicella Zoster Virus) Non-viral: • Leptospirosis • Toxoplasmosis • Coxiella (Q fever)
Non-infective causes:
- Alcohol
- Drugs
- Toxins/poisoning
- Pregnancy
- Autoimmune
- Hereditary metabolic
Non-infective causes are baso:
- Alcohol.
- Drugs.
- Toxins.
- Autoimmune.
Acute vs Chronic Hepatitis: define?
Acute:
Acute hepatitis is defined as hepatitis within 6 months of onset
Chronic:
Chronic hepatitis is defined an any hepatitis lasting for 6 months or longer
Acute Hepatitis: symptoms and signs?
- General malaise.
- Myalgia.
- GI upset.
- Abdominal pain.
- Raised AST, ALT.
- +/- jaundice.
- Tender hepatomegaly
- Abdominal pain - particularly in right upper quadrant
Viraemia causes patient to feel unwell, with non-specific symptoms that include nausea, fever, malaise
Hepatitis: (general) causes?
- Viral e.g. A, B, C, D, E.
- Drug induced.
- Alcohol induced.
- Autoimmune.
HAV: define and features?
incubation period?
risk factors?
RNA virus & ACUTE ONLY
Spread via the faeco-oral route
eg contaminated food/water, shellfish
INCUBATION PERIOD
Short incubation period of 2-6 weeks
RISK FACTORS
travellers and food handlers
HAV: investigations?
HAV IgM antibody = ACTIVE INFECTION(non-specific) production is in acute stage
HAV IgG antibody = RECOVERY OR VACCINATION
Raised serum AST or ALT
HAV: management?
- Supportive.
- Monitor liver function to ensure no fulminant hepatic failure.
- Manage close contacts.
HEV: define?
RNA virus
ACUTE HEPATITIS only
Usually self-limiting acute hepatitis: Can cause fulminant hepatitis
FAECAL-ORAL ROUTE (via seafood)
HEV: investigations?
Viral serology: Initially anti-HEV IgM and then anti-HEV IgG.
Serology is similar to Hepatitis A (HEV IgM = ACTIVE INECTION,
HEV IgG = RECOVERY)
Use HEV RNA to detect chronic infection
HEV: management?
- Good food hygiene.
- A vaccine is in development.
NO Vaccine available (only available in china!!!)
Prevention via good sanitation and hygiene
Once you’ve had Hep E then you cannot get infected again - 100% immunity
HBV: define?
DNA virus (it replicates in hepatocytes)!!
& ACUTE + CHRONIC HEPATITIS (chronic in 20% of cases)
HBV: aetiology / transmission?
Blood-borne transmission e.g. IVDU, needle-stick, sexual, MTCT.
HBV is highly infectious!
HBV: investigations?
Viral serology: HBV surface antigen can be detected from 6w - 3m or anti-HBV core IgM after 3 months.
HBV: management?
A - How would you know if an individual had been vaccinated against hepatitis B?
B - How long after infection with hepatitis B virus is anti-HBV core (IgM) present in the serum for?
C = How long after infection with hepatitis B virus is HBsAg present in the serum for?
D = How would you know if someone had acute or chronic HBV infection?
- Supportive.
- Monitor liver function.
- Manage contacts.
- Follow up at 6 months to see if HBV surface Ag has cleared. If present -> chronic hepatitis.
two treatment options for HBV infection.
- Alpha interferon - boosts immune system.
- Antivirals e.g. tenofovir. They inhibit viral replications.
A = If vacced —> They would have anti-HBVs IgG in their serum.
B = Anti-HBV core (IgM) slowly rises from 6 weeks after infection and its serum level peaks at about 4 months.
C = HBsAg will be present in the serum from 6 weeks - 3 months after infection.
D = You would do a follow up appointment at 6 months to see if HBV surface Ag had cleared. If it was still present then the person would have chronic hepatitis.
HDV: define?
Can’t exist wo?
I NCOMPLETE RNA VIRUS & ACUTE + CHRONIC HEPATITIS
-
REQUIRES HBV for assembly
Needs the HBV Sa to protect it
(Can result in HCC!!!!)
HDV: aetiology/transmission?
Blood-borne transmission, particularly IVDU.
HCV: define?
Aetiology/transmission?
- RNA FLAVIVIRUS
- & ACUTE + CHRONIC HEPATITIS
Blood-borne
HCV: risk factors?
- IVDU.
- People who have required blood products e.g. blood transfusion.
- Needle-stick injuries.
- Unprotected sexual intercourse.
- Materno-foetal transmission.
HCV: investigations?
You want to find out if someone has previously been infected with HCV. How could you do this?
Viral serology - HCV RNA tells you if the infection is still present.
HCV RNA:
• Indicates current infection
• Diagnoses acute infection GOLD STANDARD
HCV IgG = NOT DIAGNOSTIC
Ans——> Viral serology - anti-HCV IgM/IgG indicates that someone has either a current infection or a previous infection.
HCV: management?
And prevention?
Lots of new drugs have been developed recently for HCV infection. Direct acting antivirals (DAA) are currently in use e.g. NS5A and NS5B.
Prevention:
- Screen blood products.
- Lifestyle modification.
- Needle exchange.
There is currently no vaccination and previous infection does not confer immunity.
HCV: What percentage of people with acute HCV infection will progress onto chronic infection?
Approximately 70%.
Jaundice: urine/stools/itching/liver tests
in someone w pre-hepatic VS cholestatic (hepatic or post-hepatic) jaundice?
Pre-hepatic: Normal urine Normal stools NO itching Normal liver tests
BUT IN CHOLESTATIC (hepatic/post-hepatic) jaundice: Dark urine Pale stools MAYBE itching ABNORMAL liver tests
Pre-hepatic vs hepatic/post-hepatic jaundice:
Aetiology?
Pre-hepatic:
- Gilberts (deficiency in UDP Glucuronyl Transferase)
- Haemolysis
Hepatic: = baso LIVER DISEASE (see below) 1. Viral hepatitis. 2. Alcoholic hepatitis. 3. Drugs. (Hepatitis) 4. Cirrhosis. Ischaemia Neoplasm Congestion
Post-hepatic: baso BILE DUCT OBSTRUCTION:
- - Gall-stone:
- Bile duct
- Mirizzi syndrome (stone in gallbladder/cystic duct presses on
the common bile duct = jaundice)
- Stricture
- Blocked stent
Jaundice: symptoms?
- Biliary pain.
- Rigors - indicate an obstructive cause.
- Abdomen swelling.
- Weight loss.
Jaundice: define?
Yellow discolouration of the skin due to RAISED SERUM BILIRUBIN
Gallstones: risk factors?
- Female.
- Obese
- Fertile.
smoking
Gallstones: management?
Laproscopic cholecystectomy. - gallbladder removal
For pure or near-pure cholesterol stones = stone dissolution (these can be solubilised by increasing bile salt content of bile)
- Give ORAL URSODEOXYCHOLIC ACID (however these tend to reoccur so surgery is still preferred)
- Can also give cholesterol lowering agents such as statins e.g.
SIMVASTATIN
Shock wave lithotripsy:
- Shock wave directed on to gallbladder stones to turn them into
fragments so that they can be passed
- However the cystic duct requires patency for the fragments to pass
