PBL 2 - Hepatitis C + Cirrhosis Flashcards
Structure of Hepatitis C
Double stranded DNA virus
What is secreted by infected cells
HbeAg antigen
marker for active infection
What does Anti-HBc suggest
core antibody implies previous/current infection
Significance of Anti-HBs
Immunity
Symptoms of Hep C
Nausea
Fatigue
RUQ pain –> liver fibrosis/cirrhosis/hepatocellular carcinoma
How is hep C transmitted
o Sex, blood (transfusions), vertical (mother –> infant), injecting drugs,
Causes of cirrhosis
Viral - HepB, C
Alcohol
Autoimmune disesae
Wilson’s disease
Pathogenesis of cirrhosis
Alcohol or virus –> constant stress on liver –> inflammation and destruction of hepatocytes –> necrosis –> stellate cell activation producing TGF-beta –> increase collagen –> fibrosis –> macronodular or micronodular
Macronodular cirrhosis
Hepatitis B
Micronodular cirrhosis
Alcohol
Compensated cirrhosis
Liver can still undergo its function, may be asymptomatic or have non-specific symptoms such as weight loss, fatigue, weakness
Decompensated cirrhosis
Liver can’t function and do its normal jobs leading to a degree of liver failure(jaundice, pruritus, ascites, hepatic encephalopathy, easy bruising , leads to cancer
Diagnosis of cirrhosis
Fibroscan
Liver biopsy
What does fibroscan measure
measures how stiff the liver is, non-invasive, no sedation, no pain
Downsides of liver biopsy
invasive, sedation needed, requires hospitalisation
Why did the pt have high INR and low platelets
Coagulopathy
Clotting factors + platelets produced in liver
Poor blood flow to spleen due to fibrosis –> congestion of platelets in spleen –> retention
Why low albumin
Synthesised in liver
fibrosis/necrosis reduces synthesis –> equilibrium between oncotic pressure (maintained by albumin) and hydrostatic pressure –> ascites/oedema
High bilirubin why
o Breakdown of RBC removed and conjugated at liver with glucuronic level. Less conjugation –> less removed –> high level –>jaundice
ALT significance
more specific to liver cells
ALP significance
biliary duct/pagets/pregnancy/bone
yGT significance
induced by alcohol
AST significance
seen in heart/muscle/brain
AST:ALT ratio of 2:1
Alcoholic liver disease
What causes reduces ALT
Reduced ALT production in alcoholic due to vit B6 deficienc
Why high urea
o High GI bleeding due to oesophageal varices –> digested as a protein rich meal.
o Hepatorenal syndrome causing kidney failure –> reduces ability to produce urine hence a build-up of urea
Why low blood glucose
Glucose homeostasis impaired due to reduced ability to undergo gluconeogenesis, store glycogen, undergo glycogenolysis
Why low haemoglobin
o Alcohol –> macrocytic anaemia
o Loosing blood from varices –> haemolytic anaemia
o Alcohol –> direct effect damaging the bone marrow —> low platelet/haemoglobin count
What causes ascites
1) albumin –> fluid shifts from intravascular compartment –>peritoneum
2) Less fluid in blood –> renal hypotension –> ADH/RAAS –> even more fluid retention
Non-osmotic secretion of ADH due to kidney impairment –> hyponatremia
3) Portal hypertension caused by scar tissue (fibrosis) blocks the flow of blood through liver (narrows sinusoids)–> raised capillary hydrostatic pressure
Hepatic portal vein (splenic + SMV) normal pressure 5-10, in hypertension above 14 mmHg.
Oesophageal Varices
= Portal hypertension –> Blood diverted to area with least resistance –> directed away from portal system to systemic system
= At the point of anastomosis –> dilation of vessels –> when it happens at lower oesophagus it is called varices and they can bleed.
How do you treat cirrhosis
Diuretics High Carb diet Pabrinex Terlipressin Lactulose Gastric Banding Liver transplant Anti virals
Diuretics
o Clear fluid from interstitium – spironolactone + furosemide
High carb diet
o To ensure not malnourished, raise BCAA –> prevent muscle wasting/brain problems
Pabrinex
B1, B2, b6 –> Alcoholics have low thiamine, these B vits used in carbohydrate/lipid metabolism
Terlipressin
Used as vasoactive drug in managing low BP
–> To counteract the dilation of splanchnic vessels
Lactulose
Reduces absorption of ammonia from gut -> Helps with encephalopathy
Osmotic laxative –> reduces fluid intake from gut
Gastric Banding
Reduces bleeding in the gut
NtRTI (Nucleotide Reverse Transcriptase Inhibitor)
Tenofovir, entecavir
Antivirals
Antivirals- PEGylated interferon alfa-2a
Affect of alcohol on the liver
Alcohol becomes acetaldehyde
1) Oxidised by CYP, ROS is produced and damages proteins and DNA
2) Acetaldehyde –> acetate using NAD+, NADH:NAD ration is high –> increased synthesis of FA
Progression of alcoholic disease on liver
1) Hepatic steatosis
2) Alcoholic hepatitis
3) Cirrhosis
Hepatic steatosis
- Increased levels of NADH increase f.a. production
- Build up of fat in liver
- Reversible
Alcoholic hepatitis
- ROS and cytokines generated
- Inflammation leads to damage of hepatocytes
- Neutrophil infiltration
- Mallory bodies form (hyperpigmented)
- Damaged intermediate filaments in cytoplasm
Cirrhosis
- Damaged hepatocytes are replaced by scar tissue forming regenerative nodules (micronodular)
- Ultrasound can detect a fatty liver, and viral serology should be performed to look for hepA, B, C, EBV and CMV.
Complications of cirrhosis
Congestive splenomegaly Hepatorenal failure Coagulopathy Hepatic encephalopathy Wernike-korsakoff syndrome Hepatocellular carcinoma Spontaneous bacterial periconditis
Congestive splenomegaly
Fluid backing up into the spleen due to portal hypertension
Hepatorenal failure
NO released causing vasodilation in splanchnic circulation (supply intestines)
Effective circulatory volume of blood detected by JGA decreased –> Constriction of renal vessels –> renal hypoperfusion –> activation of RAAS –> further vasoconstriction of renal vessels –> reduced GFR (Hyperaldosteronism retaining water)
Hepatic encephalopathy
• Due to decreased liver function→ metabolites which usually are supposed to be detoxified are unable to e.g. ammonia –> BBB
o Confusion, lethargic, asterixis, coma
o AAA –> imbalance in neurotransmitters
Spontaneous bacterial periconditis
Weakened immune system, liver contains reticuloendothelial cells which clear bacteria + complement system proteins made by liver as well.
A patient like Oliver is showing signs of protein malnutrition (like muscle
wasting). Would he be called “kwashiorkor-like” or “marastic”?
“kwashiorkor-like”
As a prototypical transaminase, AST relies on which vitamin as cofactor to
transfer the amino group from aspartate (or glutamate) to the corresponding
ketoacid? This vitamin is also found in Pabrinex.
V B6
What concentration of blood insulin would you expect in this patient? & Why? [1
Insulin levels low [1/2] due to low blood glucose [1/2]
What would you anticipate to be the main muscle metabolic fuel for this patient?
[1 marks]
Fatty Acids
Why measure the AST/ALT ratio?
This enables the differentiation of liver disease from other diseases and can also
suggest the potential cause of the liver disease
Why is the patient at risk of infection?
Weakened immune system due to reduction in energy metabolism [1]. Build up of
fluid also increases risk (provides a perfect niche for bacterial growth) [1
Which tissue is the main source of creatinine in the body? [1] What is the
rational behind testing this and how could the result change the treatment? [1
marks]
Byproduct of muscle metabolism [1]. Tested to check kidney function. If creatinine
is high this suggests kidney function is impaired so may change the prescription of
diuretics
Lactulose is a very useful part of Oliver’s treatment for two reasons, what are
they?
i) It is an osmotic laxative (will help remove fluids via the gut) [1].
(ii) By acidifying the contents of the gut, lactulose reduces the absorption of
ammonia from the gut, thereby helping to prevent encephalopathy [1]
