PBL 2 - Hepatitis C + Cirrhosis

Question 1

Structure of Hepatitis C

Answer 1

Double stranded DNA virus

Question 2

What is secreted by infected cells

Answer 2

HbeAg antigen

marker for active infection

Question 3

What does Anti-HBc suggest

Answer 3

core antibody implies previous/current infection

Question 4

Significance of Anti-HBs

Answer 4

Immunity

Question 5

Symptoms of Hep C

Answer 5

Nausea
Fatigue
RUQ pain –> liver fibrosis/cirrhosis/hepatocellular carcinoma

Question 6

How is hep C transmitted

Answer 6

o Sex, blood (transfusions), vertical (mother –> infant), injecting drugs,

Question 7

Causes of cirrhosis

Answer 7

Viral - HepB, C
Alcohol
Autoimmune disesae
Wilson’s disease

Question 8

Pathogenesis of cirrhosis

Answer 8

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

Question 9

Macronodular cirrhosis

Answer 9

Hepatitis B

Question 10

Micronodular cirrhosis

Answer 10

Alcohol

Question 11

Compensated cirrhosis

Answer 11

 Liver can still undergo its function, may be asymptomatic or have non-specific symptoms such as weight loss, fatigue, weakness

Question 12

Decompensated cirrhosis

Answer 12

 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

Question 13

Diagnosis of cirrhosis

Answer 13

Fibroscan

Liver biopsy

Question 14

What does fibroscan measure

Answer 14

measures how stiff the liver is, non-invasive, no sedation, no pain

Question 15

Downsides of liver biopsy

Answer 15

invasive, sedation needed, requires hospitalisation

Question 16

Why did the pt have high INR and low platelets

Answer 16

Coagulopathy
Clotting factors + platelets produced in liver
Poor blood flow to spleen due to fibrosis –> congestion of platelets in spleen –> retention

Question 17

Why low albumin

Answer 17

Synthesised in liver
fibrosis/necrosis reduces synthesis –> equilibrium between oncotic pressure (maintained by albumin) and hydrostatic pressure –> ascites/oedema

Question 18

High bilirubin why

Answer 18

o Breakdown of RBC removed and conjugated at liver with glucuronic level. Less conjugation –> less removed –> high level –>jaundice

Question 19

ALT significance

Answer 19

more specific to liver cells

Question 20

ALP significance

Answer 20

biliary duct/pagets/pregnancy/bone

Question 21

yGT significance

Answer 21

induced by alcohol

Question 22

AST significance

Answer 22

seen in heart/muscle/brain

Question 23

AST:ALT ratio of 2:1

Answer 23

Alcoholic liver disease

Question 24

What causes reduces ALT

Answer 24

Reduced ALT production in alcoholic due to vit B6 deficienc

Question 25

Why high urea

Answer 25

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

Question 26

Why low blood glucose

Answer 26

Glucose homeostasis impaired due to reduced ability to undergo gluconeogenesis, store glycogen, undergo glycogenolysis

Question 27

Why low haemoglobin

Answer 27

o Alcohol --> macrocytic anaemia o Loosing blood from varices --> haemolytic anaemia o Alcohol --> direct effect damaging the bone marrow ---> low platelet/haemoglobin count

Question 28

What causes ascites

Answer 28

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.

Question 29

Oesophageal Varices

Answer 29

= 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.

Question 30

How do you treat cirrhosis

Answer 30

``` Diuretics High Carb diet Pabrinex Terlipressin Lactulose Gastric Banding Liver transplant Anti virals ```

Question 31

Diuretics

Answer 31

o Clear fluid from interstitium – spironolactone + furosemide

Question 32

High carb diet

Answer 32

o To ensure not malnourished, raise BCAA --> prevent muscle wasting/brain problems

Question 33

Pabrinex

Answer 33

B1, B2, b6 --> Alcoholics have low thiamine, these B vits used in carbohydrate/lipid metabolism

Question 34

Terlipressin

Answer 34

Used as vasoactive drug in managing low BP | --> To counteract the dilation of splanchnic vessels

Question 35

Lactulose

Answer 35

Reduces absorption of ammonia from gut -> Helps with encephalopathy Osmotic laxative --> reduces fluid intake from gut

Question 36

Gastric Banding

Answer 36

Reduces bleeding in the gut

Question 37

NtRTI (Nucleotide Reverse Transcriptase Inhibitor)

Answer 37

Tenofovir, entecavir

Question 38

Antivirals

Answer 38

Antivirals- PEGylated interferon alfa-2a

Question 39

Affect of alcohol on the liver

Answer 39

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

Question 40

Progression of alcoholic disease on liver

Answer 40

1) Hepatic steatosis 2) Alcoholic hepatitis 3) Cirrhosis

Question 41

Hepatic steatosis

Answer 41

- Increased levels of NADH increase f.a. production - Build up of fat in liver - Reversible

Question 42

Alcoholic hepatitis

Answer 42

- ROS and cytokines generated - Inflammation leads to damage of hepatocytes - Neutrophil infiltration - Mallory bodies form (hyperpigmented) - Damaged intermediate filaments in cytoplasm

Question 43

Cirrhosis

Answer 43

- 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.

Question 44

Complications of cirrhosis

Answer 44

``` Congestive splenomegaly Hepatorenal failure Coagulopathy Hepatic encephalopathy Wernike-korsakoff syndrome Hepatocellular carcinoma Spontaneous bacterial periconditis ```

Question 45

Congestive splenomegaly

Answer 45

 Fluid backing up into the spleen due to portal hypertension

Question 46

Hepatorenal failure

Answer 46

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)

Question 47

Hepatic encephalopathy

Answer 47

• 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

Question 48

Spontaneous bacterial periconditis

Answer 48

Weakened immune system, liver contains reticuloendothelial cells which clear bacteria + complement system proteins made by liver as well.

Question 49

A patient like Oliver is showing signs of protein malnutrition (like muscle wasting). Would he be called "kwashiorkor-like" or "marastic"?

Answer 49

"kwashiorkor-like"

Question 50

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.

Answer 50

V B6

Question 51

What concentration of blood insulin would you expect in this patient? & Why? [1

Answer 51

Insulin levels low [1/2] due to low blood glucose [1/2]

Question 52

What would you anticipate to be the main muscle metabolic fuel for this patient? [1 marks]

Answer 52

Fatty Acids

Question 53

Why measure the AST/ALT ratio?

Answer 53

This enables the differentiation of liver disease from other diseases and can also suggest the potential cause of the liver disease

Question 54

Why is the patient at risk of infection?

Answer 54

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

Question 55

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]

Answer 55

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

Question 56

Lactulose is a very useful part of Oliver’s treatment for two reasons, what are they?

Answer 56

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]