LIVER let die - Alcoholic Liver Disease and LFTs

We have a guest author this week, a Mr Philip Nelson from the University of Glasgow who has been working with the medical education department for the past 5 weeks.

 Scots have an unenviable reputation for alcohol consumption. Unfortunately this means that there are a lot of admissions to hospital due to alcohol abuse. It seems as though it is going to be a big problem in the future as compared with 30 years ago there are 4 times as many people dying of alcoholic liver disease(ALD) now.

Last week we had a tutorial on ALD, talking a bit about the functions of the liver and what to look for in LFTs. In this post we will go over ALD and have a few questions at the end you can mull over. You can view the presentation here.


The liver is a complicated organ, so it's helpful to simplify its functions into three main groups:

• Storage - glycogen, vitamins A, D, B12, K, iron, copper
• Metabolism - drugs, carbohydrates (gluconeogenesis, glycogenolysis), lipids, proteins 
• Production - bile, albumin, clotting factors, hormones (inslulin like growth factor 1, thrombopoeitin)

With that in mind we will focus on how alcohol effects the liver. In chronic alcohol abuse the liver is damaged and some of these functions become impaired. There are three main pathologies that constitute ALD: 

• Steatosis: Fatty liver is a reversible condition that occurs in nearly all people who are chronic alcohol abusers. Excess fatty acids accumulate in hepatocytes. Ususally asymptomatic. 

• Hepatitis: Again reversible, affecting about 1 in 4 alcoholics. Hepatocyte inflammation and necrosis. Signs and symptoms include jaundice, weight loss, tender hepatomegaly, fevers.

• Cirrhosis: Usually irreversible, affecting 10-20% of alcoholics. The liver becomes inflamed, fibrosed and undergoes micronodular regeneration.  

Patients who have cirrhosis will exhibit some of the signs of chronic liver disease, including:

- Hepatomegaly +/- Splenomegaly

- Jaundice, pruritis 

- Gynaecomastia

- Spider naevi

- Palmar erythema

- Finger Clubbing 

- Dupytrens contracture

- Asterixis

- Ascites

- Encephalopathy

When you're assessing a patient with ALD, its important to take a thorough history and examination to get an idea of the effects of the disease on the individual. Blood tests are also an important part of the assessment. The main ones to look in ALD at are: 

• Albumin, INR - Synthetic function of the liver. Albumin decreases and INR increases in cirrhosis.
• AST/ALT - Hepatic enzymes. Both raised, if ratio AST:ALT = >2:1 it is due to alcohol
• ALP, GGT - Cholestatic enzymes. ALP mildly raised, GGT significantly raised.
• Bilirubin - Conjugated by liver. Raised in cirrhosis, higher in acute hepatitis. 

Three complications of ALD that patients may present with are ascites, encephalopathy and varices. We talked about these in the presentation and the links provide another good introduction to each topic.These complications all have an effect on the prognosis of the disease, which can be estimated using the Child-Pugh score.

Measure	1 point	2 points	3 points
Total bilirubin, μmol/l	<34	34-50	>50
Serum albumin, g/l	>35	28-35	<28
PT INR	<1.7	1.71-2.30	> 2.30
Ascites	None	Mild	Moderate to Severe
Hepatic encephalopathy	None	Grade I-II (or suppressed with medication)	Grade III-IV (or refractory)

Points	Class	One year survival	Two year survival
5-6	A	100%	85%
7-9	B	81%	57%
10-15	C	45%	35%

Here are some sample LFTs for you to think about. Try to come up with differential diagnoses for each. The information on the slides might give you some help.  

Danger! - Blood Gas Interpretation

After a long Christmas break I'm back to teaching and what a better way to start the year with some blood gas interpretation.

The first thing to think about before doing the gas is "will a venous sample suffice?".  This is often over looked due to habit or requests from a old school consultant.  The H+, Bicarbonate and Lactate are accepted to be the same between arterial and venous samples and the correlation with pCO2 for hypercarbia is regularly debated.  The pO2 is obviously not present in venous samples and the sample should be compared with the patients current oxygen saturation.  A good summary article of these issues can be found here.

There are 5 key questions to ask when interpreting an ABG.

1. What is the oxygenation like?  Is there respiratory failure?

Type 1 - pO2 <8    pCO2<6
Type 2 - pO2 <8    pCO2 >6

2.  Look at the H+, is there acidosis (H+ >45) or alkalosis (H+<45)?

3.  Look at the CO2, is it raised (respiratory acidosis) or lowered (respiratory alkalosis)?   Does this fit?

4.  Look at the Bicarb, is it raised (metabolic alkalosis) or lowered (metabolic acidosis)?  Does this fit?

5.  Is there any compensation? Either Full, Partial or None


Remember there only 4 broad answers to blood gas interpretation and you should know a handful of causes for each.


Respiratory Acidosis - These people have a high CO2 and are hypoventilating.  Using a top down approach the causes are:

Respiratory centre - Drugs i.e. opoids
Peripheral nerves - Guillain-Barré syndrome
Neuromuscular junction - Myaesthenia gravis
Chest Wall - Obesity, severe kyphoscoliosis
Airways - COPD, Severe asthma

Respiratory Alkalosis - These people are the opposite and are hyperventilating.  People hyperventilate commonly due to anxiety and pain, however, more serious conditions such as P.E. and Subarachnoid Haemorrhage need to be remembered

Metabolic Acidosis - These people have extra acid or have lost base.  You can calculate their anion gap to see if there are extra acids by :

(Na⁺ + K⁺) - (Cl^- - HCO₃^-).  

The normal range is 12 - 18. 

(The reason it is not 0 is due to the weak acid affects of albumin and lactate)

If it is raised then it is due to one of the following: MUDPILES. 


Methanol intoxication
Uremia
Diabetic or alcoholic ketoacidosis
Propolyene Glycol
Isoniazid
Lactic acid
Ethylene glycol intoxication
Salicylate intoxication


If the gap is normal then it is likely due to Renal tubular acidosis, Diarrhea or Gastrointestinal fistula



Metabolic Alkalosis - This is more likely from the loss of acid rather than gaining base as even with infusing bicarbonate the pH barely moves.  Acid is lost through vomiting or through the kidney with diuretics or Conn's syndrome.

It is possible to have a mix of two i.e. respiratory and metabolic acidosis by combining two diagnosis' from above.  I appreciate that some people out there may prefer using the strong ion difference rather than the traditional Henderson Hasselbalch approach outlined above.  For undergraduates the traditional method is more than adequate and exams will feature this approach.  For those keen for a deeper understanding see Scott Weingarts brilliant acid base series here,

Here are 5 examples and I want you to work them through using the 5 questions and tell me the acid base disturbance and a possible cause.

		1	2	3	4	5
H+	(35-45)	62	29	27	84	103
pCO2	(4.6- 6)	10.3	2.7	5.8	2.5	7.8
pO2	(10.5 - 13)	6.5	18.1	11.4	16.3	8.8
Bic	(22-26)	32	25	35	9	6

Scroll down for the answers.













1.Type 2 Respiratory Failure with a partialy compensated respiratory acidosis COPD.  2. Uncompensated Respiratory Alkalosis Anxiety attack.  3.  Uncompensated compensated metabolic alkalosis  Vomiting.  4.  Partially compensated metabolic acidosis DKA.  5. Mixed respiratory and metabolic acidosis Obese Sepsis