Liver

List commonly used liver function tests

• Bilirubin
• Albumin
• Prothrombin time (PT/INR)
• Alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Alkaline phosphatase (Alk Phos)
• GGT

Complete the table below:

Liver Enzymes Type of Liver Pathology

ALT and AST increased more than ALP and GGT

ALP and GGT increased more than ALT and AST

Biliary tract disease produces a relatively greater increase in ALP than in ALT and AST. ALP is
associated with the plasma membrane of the hepatocyte adjacent to the biliary canaliculus.
Combined elevation of GGT and ALP are compatible with biliary tract disease.
Sources of ALP = Liver, Bone, GIT and placenta. So just elevated ALP on its own is not specific to
biliary tract disease but combining in with GGT increases the specificity for biliary tract disease

Using this information presented, one can interpret the liver enzyme elevations in patients with
suspected liver disease:
ALT and AST increased more than ALP and GGT = Hepatocellular disease
ALP and GGT increased more than ALT and AST = Biliary tract disease

Liver Disease Pathophysiology Biochemical Features

Hepatocellular disease ALT and AST increased more than ALP and GGT
• Viral hepatitis
• Autoimmune
• Drug and toxin induced
hepatitis

Alcoholic and Nonalcoholic AST > ALT (both ↑ ALT and ↑ AST)
Fatty Liver Disease ↑ GGT
• Alcoholic Liver Disease GGT is a very good indicator of excessive alcohol
consumption that has occurred over several weeks. It
may, however, be normal in up to 70% of patients
who abuse alcohol and therefore lacks sensitivity.
GGT is also not particularly helpful in distinguishing
between acute alcohol abuse and established
hepatitis.
↑ Serum ferritin
Macrocytic anemia

• Nonalcoholic Fatty Liver
Disease (NAFLD)
Cholestatic Liver Diseases
Inherited Metabolic Diseases
• Hemochromatosis
• Wilson Disease
While alcohol-induced toxicity to RBC precursors in
the bone marrow may cause nonmegaloblastic
macrocytosis, megaloblastic anemia may result from
malnutrition (vitamin B12 deficiency and/or folate
deficiency).
↑ CDT (carbohydrate-deficient transferrin) -
Most specific biomarker of heavy alcohol use
regardless of the presence of liver disease
Levels elevated up to 6 weeks after abuse
↑ Transaminases (AST/ALT ratio < 1): The reversal of
the AST/ALT ratio to values > 1 may indicate
progression to cirrhosis.
Rule out other causes of chronic hepatitis (e.g., heavy
alcohol use, hepatitis B, hepatitis C, Wilson disease,
autoimmune hepatitis, hemochromatosis, α1-
antitrypsin deficiency)
Cholestasis typically leads to an increase in direct
(conjugated) bilirubin and induces the production of
ALP and γ-GT.
In cholestasis, the retention of bile salts can
additionally lead to hepatocyte damage, resulting in
the release of various enzymes.
Diagnosis of iron overload
↑ Serum ferritin
↑ Transferrin saturation (≥ 45%)
↑ Serum iron
↓ Total iron-binding capacity
Genetic testing (HFE gene)
Indications: unexplained iron overload and/or first-
degree relative with hereditary hemochromatosis
Findings: Homozygous C282Y, homozygous H63D, or
heterozygous C282Y/H63D mutation in the HFE gene
confirms the diagnosis.
Additional studies
↑ Hepatocellular enzymes (e.g., AST, ALT)
CBC may identify iron-loading anemia (e.g.,
sideroblastic anemia).
Elevated serum ferritin in conjunction with elevated
transferrin saturation is highly suggestive of iron
overload.
Slit lamp examination: Kayser-Fleischer rings (best
initial test)
Blood tests
↑ Transaminases
CBC: Coombs-negative hemolytic anemia,
thrombocytopenia
↓ Serum ceruloplasmin (normal value > 20 mg/dL)
↑ Free serum copper, but ↓ total serum copper

• α1-Antitrypsin Deficiency
Tumors
• Hepatocellular Carcinomas
Clinical Syndromes
• Hepatic Failure
• Jaundice and Cholestasis
• Hepatic Encephalopathy
Urine tests: ↑ Urine copper excretion (over 24
hours)
Liver biopsy: if other tests are inconclusive
Hepatic copper concentration (> 250 μg/g dry weight)
Histology: copper staining
Genetic testing: can be performed for confirmation;
consider also testing family members
Serum: decreased antitrypsin protein levels
Electrophoresis: decreased alpha-1 peak
All patients
FBC: may show thrombocytopenia or paraneoplastic
erythrocytosis
Liver chemistries: may be abnormal in preexisting
liver disease or advanced malignancy
Coagulation screen: may be abnormal in severe
preexisting liver disease or advanced malignancy
Serum AFP: typically elevated
Suspected paraneoplastic syndromes: depending on
clinical presentation
Blood glucose: hypoglycemia
Assumed to be caused by the production of insulin
precursor hormones and/or glucose consumption by
the tumor
Serum calcium: hypercalcemia
Due to the tumor secreting parathyroid hormone-like
proteins
Lipid panel: hypercholesterolemia
Due to autonomous cholesterol production by the
tumor
Common findings include:
FBC: typically, platelet count ≤ 150,000/mm3; other
findings are variable and depend on the underlying
etiology.
LFT
Significantly elevated aminotransferases
Hyperbilirubinemia
Chemistry
Hypoglycemia (common)
Electrolyte disturbances (e.g., hyponatremia,
hypokalemia, hypophosphatemia)
↑ BUN and creatinine if acute kidney injury or
hepatorenal syndrome is present
Coagulation panel
Prolonged prothrombin time (INR ≥ 1.5)
The presence of other derangements (e.g.,
hypofibrinogenemia) is variable.
Serum ammonia (preferably arterial): frequently
elevated
Laboratory studies: elevated serum ammonia levels
 • Cirrhosis FBC
Anemia
Microcytic: due to chronic blood loss
Macrocytic: due to vitamin B12 deficiency or folic acid
deficiency
Thrombocytopenia
Caused by the following factors:
↑ Hepatic and splenic sequestration of thrombocytes
(portal hypertension leads to splenomegaly with
hypersplenism)
↓ Thrombopoietin production by the liver
Liver function tests
Parameters of hepatocyte damage
↑ Transaminases (AST, ALT)
ALT > AST: present in most liver diseases
AST > ALT: indicative of alcoholic liver disease
In alcoholic hepatitis, AST generally does not exceed
500 U/L.
AST elevation in nonalcoholic liver disease suggests
progression towards cirrhosis.
If the reference range is > 1,000 U/L, consider
differential diagnoses (e.g., acetaminophen toxicity,
viral hepatitis, autoimmune hepatitis).
Initially normal/↑ bilirubin
↑ Gamma‑glutamyl transpeptidase (GGT)
↑ Alkaline phosphatase
↑ Glutamate dehydrogenase (GDH)
↑ Ammonia
Parameters of impaired hepatic synthesis
↑ Prothrombin time (↑ INR): due to decreased
production of coagulation factors
↓ Total protein (↓ albumin)
↓ Plasma cholinesterase (CHE)
A circulating enzyme produced by the liver that can
hydrolyze several choline-based esters
Involved in the breakdown of muscle relaxants (e.g.,
succinylcholine)
Decreased serum levels can result from cirrhosis or
organophosphate pesticide exposure (occupational or
accidental).

Alcoholic Liver Disease

Alcoholic liver disease (ALD) refers to a range of progressive liver conditions caused by chronic and
excessive alcohol consumption. There are three stages of ALD, which may or may not occur
sequentially. The first stage is typically asymptomatic and involves the development of (potentially)
reversible alcoholic fatty liver. Continued alcohol consumption will lead to alcoholic hepatitis, the
second stage, which often becomes chronic. Clinical findings in this stage include jaundice, fatigue,
and fever. In the third and final stage, the patient develops alcoholic cirrhosis. Patient history,
transaminase levels, and imaging studies are crucial for diagnosis and show different patterns of
hepatic injury.

Hepatic degradation of ethanol to acetyl-CoA by alcohol dehydrogenase results in NADH excess (see
breakdown of ethanol for more details) → ↑ NADH drives the formation of glycerol 3-phosphate
(G3P) from dihydroxyacetone phosphate (DHAP) → ↑ in both G3P and fatty acids causes increased
triglyceride synthesis in the liver and accompanying inflammation → steatohepatitis → chronic
inflammation leads to hepatic fibrosis and sclerosis → portal hypertension and eventually cirrhosis

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)

Descriptions

NAFLD: non-alcohol related accumulation of fat in the liver cells

NASH: NAFLD with chronic inflammation and damage of liver cells

Etiology

• Obesity and/or type 2 diabetes (metabolic syndrome)

• Medication (amiodarone, glucocorticoids, estrogen, antiretroviral drugs)
• Parenteral nutrition, after resection of the small intestine and other gastrointestinal
interventions

Pathophysiology: ↑ Insulin resistance

There is a strong association between NASH and metabolic syndrome. For these conditions, insulin
resistance seems to be the pathophysiological starting point.

↑ Hepatic uptake of fatty acids

↑ Triglyceride synthesis

↑ Peripheral lipolysis

Clinical features

Often asymptomatic

Hepatomegaly

May progress to cirrhosis

Diagnostics

↑ Transaminases (AST/ALT ratio < 1): The reversal of the AST/ALT ratio to values > 1 may indicate
progression to cirrhosis.

Rule out other causes of chronic hepatitis (e.g., heavy alcohol use, hepatitis B, hepatitis C, Wilson
disease, autoimmune hepatitis, hemochromatosis, α1-antitrypsin deficiency)

Pathology

Hepatocellular lipid accumulation, mostly macrovesicular

Ballooning degeneration and necrosis

Inflammatory infiltrates, with scattered lymphocytes, neutrophils, and Kupffer cells

Complications: cirrhosis, hepatocellular carcinoma

Cholestasis

A condition that impairs bile production or secretion (nonobstructive intrahepatic cholestasis),

causes biliary obstruction within the liver (obstructive intrahepatic cholestasis), or causes biliary
obstruction between the liver and the duodenum (obstructive extrahepatic or posthepatic
cholestasis). Manifestations include jaundice, pale stools, dark urine, pruritus, and symptoms of fat
malabsorption (e.g., steatorrhea, weight loss). Diagnostic workup includes liver function tests
(particularly alkaline phosphatase, gamma-glutamyltransferase, and bilirubin) and imaging.

Cholestasis typically leads to an increase in direct (conjugated) bilirubin and induces the production
of ALP and γ-GT.

Fractionating bilirubin (i.e., determining total bilirubin and direct bilirubin) can help to differentiate
between cholestasis and other causes of hyperbilirubinemia.

In cholestasis, the retention of bile salts can additionally lead to hepatocyte damage, resulting in the
release of various enzymes.

Hemochromatosis

Hemochromatosis refers to a group of conditions characterized by excess iron deposition (or

increased risk of excess deposition) in the body as a result of increased iron absorption. Increased
iron absorption leads to iron overload as there is no physiologic method for iron excretion (except
through menstrual bleeding). Primary iron overload (primary/hereditary hemochromatosis) is
caused by mutations in genes involved in regulating gastrointestinal iron absorption, resulting in iron
over-absorption. Secondary iron overload (sometimes referred to as secondary hemochromatosis) is
caused by conditions affecting iron metabolism (e.g., chronic liver disease) or excessive iron
ingestion or infusion (e.g., from repeated transfusions to treat beta-thalassemia major). Patients
with primary iron overload often only become symptomatic after irreversible damage has occurred,
commonly in the third to fifth decades of life. Early clinical features are often nonspecific (e.g.,
fatigue, decreased libido, hyperpigmentation, symptoms of diabetes mellitus, arthralgia). Laboratory
findings of elevated serum ferritin combined with elevated transferrin saturation are highly
suggestive of iron overload.

Wilson Disease

Wilson disease (hepatolenticular degeneration) is an autosomal recessive metabolic disorder in

which impaired copper excretion causes copper to accumulate in the body. In its initial stages,
Wilson disease leads to copper deposits in the liver. As the disease progresses, copper also
accumulates in other organs, most importantly in the brain and cornea. The disease often goes
undiagnosed until the typical combination of hepatitis (or even cirrhosis), dementia, and
parkinsonism raises clinical suspicion. Kayser-Fleischer rings, brownish copper deposits visible
around the iris, are a further indication of Wilson disease. Low serum ceruloplasmin (copper
transport protein) concentrations and increased urinary copper excretion confirm the diagnosis.
Genetic testing or liver biopsies with quantitative copper assays can provide further information if
the diagnosis is indeterminate. Primary management consists of maintaining a low-copper diet and
administration of a chelating agent such as penicillamine. Patients with Wilson disease have a good
prognosis if the condition is diagnosed and treated early

Alpha-1 antitrypsin deficiency

Definition: inherited genetic disorder characterized by the accumulation of defective alpha-1

antitrypsin enzyme

Etiology: mutations in SERPINA1 gene

M is the normal allele.

S mutation causes a moderate decrease in AAT production.

Z mutation causes a significant decrease in AAT production.

The severity of disease depends on the specific genotypic expression, which correlates with the
amount of α1-antitrypsin protein synthesis

PiMM: 100% expression of normal protein and therefore normal serum levels of AAT

PiMS: 80% of normal serum levels of AAT

PiSS, PiMZ, PiSZ: 40–60% of normal serum levels of AAT

PiZZ: 10–15% of normal serum levels of AAT (severe AAT deficiency) [4]

Inheritance: autosomal codominant

Pathophysiology

Alpha-1 antitrypsin: a protease inhibitor that is synthesized in the liver and protects cells from
breakdown by neutrophil elastase

Gene mutation induces a conformational change in the structure of AAT protein → dysfunctional (or
absent) AAT

Effect on the liver: accumulation of AAT in hepatocellular endoplasmic reticulum → hepatocyte

destruction → hepatitis and liver cirrhosis

Effect on the lungs: deficient AAT → uninhibited neutrophil elastase activity → destruction of the
pulmonary parenchyma → panacinar emphysema

Clinical features: The age of onset and the severity of the symptoms depend on the type of mutation
(see “Etiology” above).

Pulmonary manifestations
Cough, wheezing

Dyspnea

Diminished breath sounds

Barrel chest

Hepatic manifestations

Prolonged neonatal jaundice

Hepatitis

Cirrhosis

Increased risk of hepatocellular carcinoma (HCC)

Diagnostics

Serum: decreased antitrypsin protein levels

Electrophoresis: decreased alpha-1 peak

Chest x-ray

Low and flat diaphragm

Widened intercostal spaces

Hyperinflation and increased basilar radiolucency of both lungs with rarification of peripheral
pulmonary vessels

Chest CT

Panacinar emphysema (in contrast to centriacinar emphysema in smoking-related emphysema)

Bronchiectasis

Bullae

Liver biopsy

PAS-positive, spherical inclusion bodies in periportal hepatocytes

Signs of cirrhosis

Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults and one of
the leading causes of cancer-related mortality worldwide. It primarily affects patients with
preexisting liver disease (e.g., liver cirrhosis, chronic hepatitis) and often manifests as a solitary
tumor. HCC is commonly asymptomatic in the early stage. Patients typically present with features of
the underlying liver disease (e.g., ascites, jaundice). Advanced HCC can manifest with nonspecific
features of abdominal pain, weight loss, and anorexia. Regular (6-monthly) surveillance with
abdominal ultrasound, with or without serum AFP levels, is recommended for individuals at risk of
developing HCC. If screening is suggestive of HCC (i..e, liver lesion ≥10 mm or AFP ≥ 20 ng/mL), the
diagnosis should be confirmed with multiphase imaging and, if needed, a liver biopsy. Management
is based on tumor burden, the patient's performance status, and the severity of liver dysfunction.
Potentially curative treatment options include tumor resection, liver transplantation, and ablative
therapy, most commonly radiofrequency ablation (RFA). Patients with advanced tumors may be
treated with noncurative locoregional therapy (LRT) such as transarterial chemoembolization (TACE),
or systemic chemotherapy. As HCC mostly occurs in patients with advanced underlying liver disease,
the prognosis is generally poor.

Hepatic encephalopathy

Definition

Fluctuations in mental status and cognitive function in the presence of severe liver disease (e.g.,
cirrhosis)

Pathophysiology

Cirrhosis → ↓ hepatic metabolism and portosystemic shunt → accumulation of neurotoxic

metabolites, especially ammonia (NH3) → excess glutamine and swelling produced by astrocytes →
cerebral edema and ↑ intracranial pressure → neurological deterioration

• Hypokalemia → shift of K+ ions out of the cells → shift of H+ ions into the cells to maintain
electroneutrality → intracellular acidosis → tubular cells produce more ammonia →
neurological deterioration
• Metabolic alkalosis → decreased H+ ion availability → decreased conversion of ammonia to
ammonium (NH4+)→ increased levels of ammonia → diffuses freely through the blood-brain
barrier → neurological deterioration

Precipitant factors

Increased absorption or production of ammonia

Infections (e.g., spontaneous bacterial peritonitis, SIRS)

Gastrointestinal bleeding

Constipation

Increased dietary protein intake

Hypokalemia

Decreased metabolism and clearance of ammonia

Renal failure

Portal vein thrombosis

Portosystemic shunts (e.g., after TIPS placement)

Hypovolemia (dehydration, diarrhea, vomit)

Metabolic alkalosis
Diuretic use(hypokalemia, hyponatremia)

Clinical features

Symptoms are usually reversible.

Fatigue, lethargy, apathy

Altered levels of consciousness, ranging from mild confusion to stupor or coma

Disoriented

Irritability

Memory loss

Impaired sleeping patterns

Multiple neurological and psychiatric disturbances

Socially aberrant behavior (e.g., urinating/defecating in public, shouting at strangers)

Slurred speech

Asterixis

Muscle rigidity

Diagnostics

Based on the patient's medical history and clinical presentation

Assessment of mental status

Number connection test: test in which patients are timed while connecting numbers in order that
are randomly distributed over a piece of paper (in hepatic encephalopathy it is completed slower
than the age-normalized standard or not completed)

Psychometry‑based diagnostic method (e.g., Mini-Mental State Examination) [

Laboratory studies: elevated serum ammonia levels

Cirrhosis

Cirrhosis is a condition caused by chronic damage to the liver, most commonly due to excessive
alcohol consumption, nonalcoholic fatty liver disease, or hepatitis C infection. Other causes may
include inflammatory or metabolic diseases, such as primary biliary cirrhosis or hemochromatosis.
Cirrhosis is characterized by hepatic parenchymal necrosis and an inflammatory response to the
underlying cause. Subsequent hepatic repair mechanisms lead to fibrosis and abnormal tissue
architecture, which impair liver function. Patients can present with a range of symptoms, including
ascites, hepatosplenomegaly; and skin manifestations of cirrhosis, such as jaundice, spider angioma,
and/or palmar erythema. Men may further display signs of feminization (e.g., gynecomastia,
hypogonadism). In severe cases, accumulation of toxic metabolites or involvement of further organs
can lead to complications such as hepatic encephalopathy or hepatorenal syndrome. Laboratory
tests show signs of hepatocyte damage (e.g., elevated liver enzymes, hyperbilirubinemia) or
impaired hepatic synthetic function (e.g., prolonged prothrombin time, low albumin). Abdominal
ultrasonography typically shows shrunken, heterogeneous liver parenchyma with a nodular surface.
A biopsy is the method of choice for confirming the diagnosis. However, it is usually only performed
if previous diagnostic modalities were inconclusive. Management consists of treatment of the
underlying disease (e.g., avoiding toxic substances, antiviral drugs), adequate caloric intake, and
medication for treating complications (e.g., spironolactone for ascites). In cases of decompensated
cirrhosis, interventional procedures (e.g., paracentesis to drain ascites) may be used to alleviate
symptoms or bridge the time until liver transplantation is possible.

Jaundice

Jaundice: yellowish discoloration of the skin, sclerae, and mucous membranes due to the deposition
of bilirubin

Cholestasis: impaired production, secretion, or outflow of bile

Hyperbilirubinemia: an increased serum concentration of bilirubin (See “Unconjugated

hyperbilirubinemia” and “Conjugated hyperbilirubinemia” for details.)

Etiology
Pathophysiology

Jaundice is due to an elevated level of serum bilirubin, which may be caused by prehepatic,
intrahepatic, or posthepatic defects.

Serum bilirubin concentration depends on the rate of formation and hepatobiliary elimination of
bilirubin.

Any pathology that impairs the process could increase serum bilirubin level: See “Unconjugated
hyperbilirubinemia” and “Conjugated hyperbilirubinemia” for details.

Diagnostic workup
 Complete the following table regarding laboratory differential diagnosis of jaundice

Pre-hepatic Hepatic Post-hepatic

Bilirubin
Urine Bilirubin
RBC
Hb
Haptoglobin
ALT and AST
ALP and GGT
Causes
 MEMO

Liver

List commonly used liver function tests

Complete the table below:

Liver Enzymes Type of Liver Pathology

ALT and AST increased more than ALP and GGT

ALP and GGT increased more than ALT and AST

Liver Disease Pathophysiology Biochemical Features

Hepatocellular disease
• Viral hepatitis
• Autoimmune
• Drug and toxin induced
hepatitis

Alcoholic and Nonalcoholic

Fatty Liver Disease
• Alcoholic Liver Disease
• Nonalcoholic Fatty Liver
Disease (NAFLD)

Cholestatic Liver Diseases

Inherited Metabolic Diseases

• Hemochromatosis
• Wilson Disease
• α1-Antitrypsin Deficiency

Tumors
• Hepatocellular Carcinomas
Clinical Syndromes
• Hepatic Failure
• Hepatic Encephalopathy
• Cirrhosis
 Jaundice

Pre-hepatic Hepatic Post-hepatic

Bilirubin
Urine Bilirubin
RBC
Hb
Haptoglobin
ALT and AST
ALP and GGT
Causes
Case 01

A 53-year-old man is seen by a hepatologist due to abnormal LFT. He admits to drinking no more
than two units of alcohol per day. He has no risk factors for blood borne viruses, has no travel history
abroad. O/E: BMI = 22 kg/m^2. He has spider nevi

Bloods

Parameter Results Reference

Interval
Bilirubin 25 umol/L < 21
ALT 126 U/L 5-40
AST 243 U/L 5-40
GGT 987 U/L 5-45
ALP 180 U/L 40-120
Albumin 37 g/L 32-52
Ethanol 70 mmol/L <4

1. What pattern of LFTs is present?

2. What is the most likely cause?
3. How do other results support this diagnosis?
Case 02

A 20-year-ols old presented with ‘flu-like symptoms, loss of appetite, nausea, and pain in the right
hypochondrium. On examination, the liver was just palpable and tender. Two days later he
developed jaundice, dark urine and pale stools.

Parameter On One week Reference

admission later Interval
Total 38 umol/L 230 <17
Bilirubin
Conj. 25 umol/L 200 <4
Bilirubin
Albumin 40 g/L 38 35-50
ALT 950 U/L 760 1-41
AST 624 U/L 580 1-38
ALP 79 U/L 230 39-117
GGT 20 U/L 215 7-49
Urine dipstick
Bilirubin + +++
Urobilinogen +++ +

1. Suggest the most likely diagnosis. Explain the changes in biochemical profile during the
course of the illness.
Case 03

A 23-year-old woman, who is 34 weeks pregnant with her first child, is seen in the Emergency
Department after taking 28 paracetamol (500 mg) tablets 2 h ago. She is 62 kg in weight. She did not
co-ingest any other drug or alcohol. She complains of nausea and intermittent vomiting, but this has
been consistent throughout her pregnancy.

What would your differential diagnosis include before examining the patient?

There is no real diagnostic difficulty in this case. The issue of greatest concern is that she has
probably ingested 225 mg/kg of paracetamol, i.e. more than 150 mg paracetamol per kg of body
weight. Hence, she is at risk of developing hepatotoxicity and/or (more rarely) nephrotoxicity. The
additional risk is that paracetamol can cross the placenta and this places the baby at risk. The
onset of vomiting in this case is too early to be due to paracetamol-induced liver damage if, as she
states, the timing of ingestion was only 2 h ago. Paracetamol overdose per se , as well as
pregnancy itself, can cause early-onset vomiting.

Physical Examination

All her clinical observations (heart rate, blood pressure, etc.) are within normal limits. She has no
renal angle tenderness and no right upper quadrant tenderness. (Such signs might occur if she had
taken the overdose at an earlier time than stated, or in a staggered way, and was beginning to
develop signs of renal or hepatic injury, respectively.) Her uterus is of a size that is in-keeping with
her stated gestation. She has a very low mood and odd affect.

Has examination narrowed down your differential diagnosis?

Examination of the patient reveals no evidence of current hepatotoxicity or nephrotoxicity, in-

keeping with the patient's history of recent ingestion of paracetamol. However, if left untreated,
she would be expected to develop liver damage from paracetamol within the next 24–36 h. Her
low mood indicates the need to apply the Beck's depression scale (or to undertake some other
form of immediate mood assessment), in order to determine her risk on the ward and the
appropriate degree of nursing/psychiatric support. In view of the fact that she is pregnant, she
may also have obstetric needs.

INITIAL INVESTIGATIONS

Paracetamol levels in the blood are checked 4 h after ingestion and the concentration plotted on a
paracetamol treatment normogram ( Fig. 16.1 ). Prothrombin ratio, liver function tests and venous
bicarbonate concentrations are normal ( Box 16.1 ). Serum paracetamol concentrations should be
measured in any patient who admits to taking excess paracetamol, anyone who has ingested
white tablets and any patient with unexplained coma. Blood paracetamol concentrations taken
within 4 h of ingestion are not interpretable. Prothrombin ratio (PTR) is the most sensitive marker
of ensuing liver dysfunction in paracetamol poisoning; it becomes elevated at 18–24 h after
significant ingestion, with ensuing hepatotoxicity. Prothrombin ratio is checked in this case,
because of the need to be certain that ingestion has not taken place earlier than the patient
states, i.e. to establish that there is no evidence of liver damage from paracetamol at her time of
presentation. Plasma venous bicarbonate is a useful early screening test for metabolic acidosis and
can warn of impending liver damage from paracetamol.

Paracetamol treatment graph. Patients whose plasma paracetamol concentration is above the
normal treatment line should receive antidote. The high-risk treatment line is used in individuals
who may develop paracetamol toxicity at lower levels (see text). After 15 h (dotted lines) the
prognostic accuracy is uncertain.( Source : University of Wales College of Medicine Therapeutics and
Toxicology Centre).

Paracetamol level at 4 h after ingestion 350 mg/L

Urea and electrolytes (U&Es) Normal
Liver function tests (LFTs) Normal
Prothrombin time/ratio Normal
Plasma venous bicarbonate Normal