GI problem III - Ow

Question 1

Give some signs that are stigmata of chronic liver disease

Answer 1

Yellowing of the sclera - Jaundice
Palmar erythema
Spider naevi - often in chest, upper arms and back

Question 2

what are the two main patterns of liver test abnormality?

Answer 2

Cholestaysis: when the GGT and ALP together rise
Hepatitis or hepatocellular pattern: AST and ALT go up.
Mixed picture: both transaminases and GGT are up.

Question 3

What are some causes of high GGT

Answer 3

If obstruction expect to see the ALP go up with it

Question 4

What tests mark synthetic function of the liver?

Answer 4

Albumin and prothrombin

Question 5

Causes that lead to a fall in albumin

Answer 5

Inflammation (dec)

Question 6

Low albumin in the contest of liver disease suggests?

Answer 6

They’ve had liver dysfunction for some time (chronic)

Question 7

what is a good indicator of acute liver failure?

Answer 7

Raised prothrombin ratio in the context of liver disease

Question 8

GGT up alone

Answer 8

Usually indicates steatosis i.e fat deposited into liver cells (either from alcohol or non-alcoholic fatty liver disease)

Question 9

GGT and ALP

Answer 9

Think of cholestasis i.e obstruction to biliary drainage e.g. bile duct obstruction

Question 10

AST and ALT

Answer 10

Think of hepatitis i.e. hepatocellular drainage

Question 11

Steatosis - causes

Answer 11

Alcohol 
Non-alcoholic fatty liver disease 
- metabolic syndrome 
i.e: diabetes 
Dyslipidaemia 
Hypertension 
Increased BMI

Question 12

Hepatitis - causes of hepatocellular damage

Answer 12

• viral hepatitis
• Alcoholic hepatitis (separate to alcoholic steatosis)
• Non-alcoholic hepatitis (what you get from the inflammation caused by non-alcoholic steatosis)
• Autoimmune hepaitis
• Ischaemic hepatitis (e.g. in severe blood loss or dehydration)
• Haemochormatosis(iron overload)
• Drugs/ herbal or natural supplements

Question 13

What do drugs do to the liver?

Answer 13

Cholestasis
Hepatitis
Mixed

Not just new drugs, sometimes drugs that people have been on for a long time can cause abnormal liver tests

Question 14

Liver tumors

• can present with?
• Types?

Answer 14

Cholestasis
mixed pattern

primary: hepatocellular carcinoma (above) only really develops in people with cirrhosis or chronic liver diseases
Secondary: liver mets (right)

Question 15

lets talk about alcoholic liver disease

Answer 15

spectrum between steatosis and hepatitis
As the normal liver becomes exposed to alcohol you get fatty change e.g. fatty deposits in the liver, this is reversible so if you abstain from alcohol steatosis can improve and may disappear.
If people are binge drinkers they may get episodes of hepatitis with sudden or large volume exposure e.g. binge drinking
If you have chronic progressive steatosis, the liver doesn’t like to have fat in it, so over time will contribute to hepatitis and you will get inflammation from that. similarly if you abstain the hepatitis will go away and you’ll be left with steatosis.
And over time (usually with episodes of binge drinking) get cirrhosis, irreversible scarring of the liver (when fibrosis isn’t given time to repair itself)

Question 16

Lets talk about Non-alcoholic fatty liver disease

Answer 16

instead of alcohol the cause is metabolic syndrome (encompasses a number of conditions including insulin resistance and risk factors for that e.g. diabetes, obesity, high lipids, hypertension)
Normal liver –> steatosis –> fat cells –> fibrosis/cirrhosis

Question 17

Diagnosis of ALD and NAFLD?

Answer 17

Usually clinically

Question 18

Transmission Hep A, B and C

Answer 18

A: fecal oral, contaminated food or water
B: Body fluids and blood - sex, transfusion and IDU
C: Blood: IDU
Problems with blood transfusions in underdeveloped contruies

Question 19

Hepatitis D can only cause infection of you have?

Answer 19

Hep B, co infection. or superinfection. Cant have D alone

Question 20

Hep E

Answer 20

Very much like Hep A also fecal oral

Question 21

EBV and CMV

Answer 21

mostly asymptomatic in healthy adults
EBV –> infectious mono / glandular fever
CMV –> similar mono like syndrome

Question 22

autoimmune hepatitis

Answer 22

Chronic autoimmune disease
Unknown aetiology
Autoantibodies attack the liver causing inflammation and damage
Episodic (flares), recurrent
More common in females than males
bimodal age distribution: young groups: 10-20 years, older group 45-70 years
Diagnosis:
- Autoimmune screen for certain liver antibodies
- Liver biopsies

Question 23

Islamic hepatitis

Answer 23

results form severe haemodynamic compromise

• cariogenic
• severe dehydration
• severe sepsis
• blood clot to hepatic artery

Question 24

Haemochromatosis

Answer 24

Hereditary 
- Autosomal recessive 
- Mutation of HFE gene 
- Most common: homozygous for C282Y 
- Europeans at highest risk 
- Low hepcidin levels --> increased iron absorption in GI tract 
Secondary 
- blood disorders 
- repeated blood transfusions 
Diagnosis: ferritin and iron saturation

Question 25

Drugs and what they can do to the liver?

Answer 25

Paracetamol overdose - antidote is NAC (N-acetylcysteine) - narrow window period to give antidote - History: at risk of self harm? - Paracetamol - need to know time of ingestion - Or give empirically if high risk many drugs can affect liver function tests and present as - Cholestasis - Mixed - predominantly hepatitis

Question 26

Risk factors for liver tumours?

Answer 26

``` for heptocellular carcinoma - underlying liver cirrhosis - chronic hepatitis B with or without cirrhosis --> oncogenic virus for liver mets - known cancer elsewhere ```

Question 27

If AST and ALP are in the thousands, typically 3 possibilities

Answer 27

- viral - Ischemia - paracetamol ... if AST and ALP in the hundreds no so helpful as it can be anything AST >2x ALT usually suggests alcoholic hepatitis

Question 28

How to work up a patient with abnormal LFTs

Answer 28

Is there jaundice? - indicates severity of disease (bilirubin) Is synthetic function impaired? - low albumin suggests possible cirrhosis - Normal prothrombin ratio suggests no acute liver failure

Question 29

Investigations

Answer 29

``` US - Gallstones, normal looking gall bladder - Bile ducts not obstructed - check echogenicity of liver, nodules? Hep A, B and C serology Iron studies Auto antibodies ```

Question 30

Treatment of portal hypertension

Answer 30

Started on diuretics to treat ascites Protein supplements to improved nutrition and albumin Advised must stop alcohol

Question 31

How canyon have no alcohol for years but liver failure?

Answer 31

brought on by infection

Question 32

How can you treat hepatic encepalopthy?

Answer 32

Lactulose and fleet enema

Question 33

What happens after decompensation

Answer 33

``` cant fix, liver gets worse medical emergency Code red for large volume haematemesis BP low, HR inc Peripheries cold IV fluid started for ressus Urgent full blood count Blood transfusion commenced ```

Question 34

Spontaneous bacterial peritonitis

Answer 34

A complication that can occur in patients with cirrhosis and ascites - Translocation of bacteria and endotoxins from the gastrointestinal tract to peritoneal fluid Facilitated by: impaired defensive mechanisms in cirrhotic patients. Spontaneous infection in peritoneal cavity i.e. peritonitis Diagnosis: ascitic tap - neutrophils 250x10^6/L Treatment: - identify organism on culture - treat with appropriate antibiotic

Question 35

Acute versus chronic hepatitis B, the different types of transmission

Answer 35

Acute hep B - adult transmission - Parenteral (IV drug use/ contaminated blood transfusion) and sexual Because your immune system will clear hep B as an adult Chronic Hep B - Neonate or childhood transmission - perinatal / vertical and horizontal (child to child) comm

Question 36

The different stages of HBV infections and the antigens / antibodies present

Answer 36

HBsAg - when initially infected Shortly after this you develop symptoms Start to develop immune response Core antibodies: IgM is initial immune response to virus, when these rise the surface antigen levels start to fall. This is an acute antibody that doesnt stay in the system forever. Over time the IgM core antibodies are replaced by the more permanent anti HB surface antibodies

Question 37

Window period

Answer 37

if you do a blood test at a particular point in time it may not show you that the person has actually been exposed e.g. time between when the surface antigen disappears and when the surface antigen appears, so you need to request a core IgM antibody

Question 38

if you've been successfully vaccinated, but not exposed to HBV what will show up on the antigen / antibody test?

Answer 38

Anti-HBs

Question 39

The stages of chronic Hep B from childhood onwards

Answer 39

Phase 1: when baby / child infected, because their immune system is underdeveloped they are tolerant to the hep B so they don't develop an immune response and therefore don't have inflammation, typically they have very high levels of virus and the ALT is usually normal Phase 2: as the child matures and enters adulthood in their 20's and 30's, the body tries to clear the virus, in this phase you're most at risk of inflammation and fibrosis caused by the immune system attacking infected hepatocytes. Viral load will start to drop, get fluctuating levels of ALT, from inflam. Chronic Hep B is one of the leading causes of cirrhosis. Phase 3: The body controls the virus, inflammation gone. this can last for many years Phase 4: in some people the virus escapes from the immune regulation and reactivates --> ongoing liver damage So chronic Hep B patients need regular blood tests to check for immune activation and inflammation.

Question 40

briefly describe the progression of symptoms of hepatic encephalopathy

Answer 40

1. mild confusion, limited attention span, irritability, inverted sleep, incoordination, tremor, impaired handwriting 2. drowsiness, personality changes, intermittent dterioirdation, asterixis, ataxia, dysarthria 3. somnolent, gross disporietaiton, marked confusion, slurred speech, hyperreflexia, muscle rigidity, babinski sign 4. coma, no response to pain, decrebarte posture

Question 41

Liver functions summary

Answer 41

- removes toxins - metabolises glucose, produces energy - removes bacteria from blood, helps body fight infection - produces bile so we can absorb fats - stores vitamins, minerals and sugar - Produces most of the proteins needed by the body - Produces most of the substances that regulate blood clotting

Question 42

What is the Child-pugh score?

Answer 42

classifies the severity of cirrhosis and predicts mortality without transplantation (uses, billlirubin, albumin, PR ratio, degree of ascites and encephalopathy)

Question 43

Complication of cirrhosis result from?

Answer 43

``` portal hypertension (variceal haemorrhage, ascites) of liver insufficiency (jaundice) both give encephalopathy ```

Question 44

Manifestations of portal hypertension

Answer 44

arteriovenous shunting and or mechanical obstruction hypersplenisim - moderate anaemia - neutropenia - thrombocytopenia oesophageal varices caput medusae Haemorrhoids

Question 45

Pathogenesis of ascites

Answer 45

``` cirrhosis Inc resistance to portal flow Portal hypertension Two pathways: 1. Inc hydrostatic pressure + decreased albumin 2. Splanchnic vasodilation systemic arterial underfilling Activation of ADH and RAAs Renal Na and H20 retention ```

Question 46

What is hepatic encephalopathy

Answer 46

the inability to get rid of the ammonia in the circulation, which we all form through breakdown of proteins in the gut. It passes through the BBB

Question 47

Mechanism of action of lactulose

Answer 47

- a non-absorbable daiassachride produces osmosis of water - Diarrhoea Reduces pH of colonic content and thereby prevents absorption of NH3 Converts NH3-NH4 that can be excreted

Question 48

Some causes of portal hypertension other than cirrhosis

Answer 48

Right heart failure Portal vein thrombosis Budd chiari syndrome

Question 49

how does portal hypertension lead to ascites?

Answer 49

``` PH splanchnic vasodilation Decreased effective circulatory volume Activation of RAAs 1. Renal sodium retention --> ascites 2. Renal vasoconstriction --> heptorenal syndrome ```

Question 50

Definition of hepatorenal syndrome: types 1 and 2

Answer 50

Type 1: doubling of serine creatinine over 24 hours frequently follows a precipitating event such as infection Survival without treatment in the order of weeks Type 2: less rapid renal functional deterioration than type 1 Mainly presents with refractory ascites Survival without treatment in order of months

Question 51

HCC treatment

Answer 51

if detected early can be cured all patients with cirrhosis need HCC surveillance - liver ultrasound and alpha fetoprotein every 6 months