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Case 9: Chemical Pathology - Coggle Diagram
Case 9: Chemical Pathology
Functions of the Liver
Outline the Functions of the Liver
Liver has the following functions:
Production
Liver produces:
Bile acids
Plasma proteins
Lipoproteins
Coagulation Factors
Metabolic
Liver metabolizes:
Carbohydrates
Amino acids
Lipids
Storage
Liver stores:
Glycogen
Lipid
Iron
Vitamin B12
Clearance
Liver exports:
Bilirubin
Ammonia
Xenobiotics
Lipids and Lipoproteins
Hormones
Bilirubin Metabolism
Describe the process of metabolism of Bilirubin
Haemolysis of Erythrocytes results in the release of Heme.
In the Reticuloendothelial System, Heme is converted into Biliverdin in the presence of the Heme Oxygenase enzyme
This conversion releases Fe+ and Carbon Monoxide
The Biliverdin is then reduced into Bilirubin by the Biliverdin Reductase enzyme.
Bilirubin is then released into he blood
Unconjugated Bilirubin
Unconjugated Bilirubin is the main form of Bilirubin found in the plasma
Unconjugated Bilirubin is hydrophobic and is carried bound to Albumin
It can be displaced from Albumin by drugs
Unconjugated Bilirubin cannot be filtered by Glomerulus therefore, it is NOT found in the Urine
Free or Unbound form of Unconjugated Bilirubin is neurotoxic.
If it crosses the Blood-Brain Barrier it causes Kernicterus, which is a risk in neonatal Hyperalbuminemia
Unconjugated Bilirubin is delivered to the Liver and dissociates from Albumin at the Hepatocyte membrane
Conjugation of Unconjugated Bilirubin
Unconjugated Bilirubin is taken up at the hepatocyte membrane by a carrier-mediated process
Unconjugated Bilirubin is conjugated with Glucuronic acid:
By UDP-Glucuronyl Transferase (UDPGT-1) to form Bilirubin Monoglucuronide (BMG)
By UDP-Glucuronyl Transferase (UDPGT-2) to form Bilirubin Diglucuronide (BDG)
Conjugated Bilirubin
Conjugated Bilirubin is water soluble and can be excreted into Bile or Urine
Conjugated Bilirubin is transported out of the Liver Cells into the Bile canaliculi by an energy-dependent, carrier-mediated process
Bile flows through the canaliculi, into the bile ducts and finally into the Duodenum
Urobilinogen and Enterohepatic Circulation
In the GIT, Conjugated Bilirubin is converted into Urobilinogen (colourless), then Urobilin (yellow) and then to Stercobilin (brown)
20% of Urobilinogen in the Small Intestine is reabsorbed into the portal circulation, taken up by the liver again and re-excreted
This is known as the Enterohepatic Circulation
Urobilinogen is therefore normally present in the blood, and is filtered into Urine
Some Urobilinogen and Urobilin (yellow) appear in the urine
Re-uptake of urobilinogen by the Liver is sensitive to the Liver damage
Bile Acid Production
Describe the production of Bile Acids
Bile Acids are formed from the breakdown of cholesterol
Bile acids are produced in the Liver and in the GIT
Liver
Liver produced Primary Bile Acids such as Cholic acid, and Chenodeoxycholic acid
Liver then conjugates the Primary bile acids (Cholic acids and Chenodeoxycholic acid) with Glycine or Taurine to increase their solubility
Liver then transports the Primary Bile Acids in the Bile
GIT
GIT produces Secondary Bile acids such as Lithocholic acid and Deoxycholic acid
In the Enterohepatic circulation of bile acids results in 75% of the bile acids being reabsorbed
Describe the Structure and Function of the Bile Acids
Structure
Bile acids are Amphipathic
Function of Bile acids:
Bile acids solubilise cholesterol for excretion
Bile acids stimulate bile formation and flow
Bile acids solubilise dietary fat for absorption in Micelles
Circulating Bile Acids
Normally
Normally, Bile acids are secreted into the GIT
Bile acids are re-absorbed from the GIT and appear in the blood
Bile acids are transferred back to the Liver with Enterohepatic Circulation and are gradually removed from the blood
Obstruction
Obstruction in the biliary with reflux into circulation
Liver damage with impaired re-absorption of bile acids from the portal circulation
Ileal disease when bile acids are not re-absorbed
Protein production
Outline Protein Production
Liver synthesises practically all circulating plasma proteins except immunoglobulin and Coagulation Factor VIII
Total Protein in the plasma is 60-80 g/L
The Total Protein int he plasma is made up of:
Mainly Albumin of 35-50 g/L, and is synthesized in the liver
Immunoglobulins of approximately 15 g/L, and is synthesized by Plasma cells
A variety of other protein in low concentrations, synthesized by the Liver
List the function of some Plasma Proteins
Albumin
Albumin is responsible for maintaining Oncotic pressure and Buffering
It is a general binding and transporting protein
Immunoglobulins
Immunoglobulins play a role in the immune response
C-Reactive protein
CRP activates Complement Cascade
CRP binds to damaged tissues and pathogens.
RCP plays a role in innate immunity
Coagulation factors and Fibrinogen
Coagulation factors are responsible for coagulation
Fibrinogen is responsible for clot formation
Transferrin and Ferritin
Transferrin is responsible for transporting iron
Ferritin is responsible for iron storage
Caeruloplasmin
Caeruloplasmin is responsible for copper and iron metabolism
Detoxification
Outline the function of Liver Detoxification
In the process of detoxification, Liver detoxifies Ammonia and Xenobiotics
Ammonia is produced from the amino acid metabolism
Ammonia is toxic to the Central nervous system
Ammonia is converted to Urea in the Urea cycle, in the Liver
Xenobiotics are foreign compounds such as drugs
Liver deals with hydrophobic compounds by making them more water soluble for excretion in urine and bile
There are three phases in the detoxification of Xenobiotics:
Phase I
Modification which involves Oxidation, Reduction, Hydrolysis and Hydration is chiefly conducted by Cytochrome P450 enzymes
Phase II
Xenobiotics are then conjugated to add polar groups
Glucuronide, Glutathione, Sulphate and Glycine are the main conjugates
Phase III
Phase III involves excretion
The hydrophilic compound is moved from the liver into the bile by transporters
Biochemical Tests of Liver Function and Liver Damage
List the Biochemical Tests of Liver Function and Liver Damage
Tests that indicated Liver Damage
Enzymes, AST, ALT, LDH, ALP and GGT
Tests of Liver Function
Excretory Function: Bilirubin, Urobilinogen and Bile salts
Detoxification Function: Blood ammonia
Synthetic Function: Total Protein, and Albumin, Prothrombin Time
Metabolic Functions: Blood glucose
Test that determine Cause:
Red cell parameters
Viral Serology
Specific proteins
Auto-immune markers
Typical "LFT" panel:
Total protein
Albumin
Total Bilirubin
Conjugated Bilirubin
AST
ALT
ALP
GGT
Laboratory Tests
Outline the Laboratory tests for Bilirubin and Urobilinogen
Measurement of Bilirubin
Conjugated Bilirubin is "Direct Reacting"
Total Bilirubin: Reaction includes an extra step so that all Bilirubin reacts
Unconjugated Bilirubin - by reference: "Indirect-Reacting"
Levels in plasma:
Total Bilirubin: Less than 21 umol/L
Conjugated Bilirubin: Less than 3 umol/L
Unconjugated Bilirubin is the predominantly found Bilirubin in plasma
Normal levels in Urine:
No Bilirubin is found in urine, since Unconjugated Bilirubin is hydrophobic and not filtered
Measurement of Urine Urobilinogen
Urine Urobilinogen is measured qualitatively using a dipstick.
This means that the Urine Urobilinogen is present or absent
Normal urine contains some urobilinogen and Urobilin (yellow)
Measurement of Enzymes indicating Liver Cell Damage
List the Enzymes indicating Liver Cell Damage
Aspartate Transaminase (AST)
Alanine Transaminase (ALT)
Lactate Dehydrogenase (LDH)
Outline the characteristics of the Enzymes indicating Liver Cell Damage
Aspartate Transaminase (AST)
AST is widespread, It is located in the Liver, Red blood cells, Skeletal Muscle and Cardiac Muscle
There are no tissue-specific isoenzymes of AST
AST are found in the Liver Cytosol and Mitochondria
The greater the liver damage the greater the likelihood of Mitochondrial damage and the more the AST enzyme is increased
Alanine Transaminase (ALT)
ALT is more Liver specific
ALT is located in the Liver Cytosol
Lactate Dehydrogenase (LD)
LDH is widespread, it is located in the Liver, Red blood cells Skeletal Muscle and Cardiac Muscle
Tissue-specific isoenzymes of LDH are separated by electrophoresis
LDH5 isoenzyme is found in the Liver and Skeletal muscles only
Measurement of Liver Enzymes indicating Cholestasis
List the Liver Enzymes indicating Cholestasis
Alkaline Phosphatase (AP)
Gamma-Glutamyl Transferase (GGT)
Outline the characteristics of Liver Enzymes indicating Cholestasis
Alkaline Phosphatase (ALP)
ALP is produced by the Liver, Bone, Placenta and GIT
The Liver Isoenzyme of ALP can be identified by electrophoresis or heat inactivation (rarely performed)
ALP is an Ecto-enzyme and is located on the outside of the cell membrane (Canalicular Side of the Liver)
Alkaline Phosphatase is released into the plasma in Cholestasis
Gamma-Glutamyl Transferase (GGT)
Gamma-Glutamyl Transferase is more Liver specific
It is located int he Liver Cytosol only
GGT is involved in the transport of Amino acids across the Liver Cell Plasma membrane
Serum level of GGT is increased by Cholestasis or Chronic ingestion of alcohol, Barbiturates, Phenytoin and other drugs which induce the enzyme
Protein Measurements
Outline the types of Protein Measurements
Total Protein (TP) and Albumin
Total protein and Albumin are the most commonly measured
If the TP is decreased and Albumin is decreased, then there is a
Decrease in the synthesis of Albumin
Increase in the loss of Albumin
If the TP is increased and Albumin is decreased, there there is a:
Increase in Immunoglobulins
Individual Proteins
Individual Proteins are measured for specific indications, depending on their function
Example: Transferrin and Ferritin to check the Iron status
In Liver Disease
The main indicator of Liver Disease is Albumin
Individuals proteins can be measured to investigate if they are implicated in the cause of the liver disease (Decreased Caeruloplasmin in Wilson disease) or as a result of the liver disease (Polyclonal immunoglobulin increase)
Ammonia
Outline the measurement of Ammonia and the Precautions used in the Ammonia Blood Test
A healthy Liver maintains very low blood of Ammonia levels of less than 40 umol/L
Mild to moderately reduced Liver function still maintains low Ammonia blood levels
ONLY with severely reduced Liver function of Liver Failure can there be increased Ammonia blood levels resulting in Hyper-ammonaemia
After taking blood, Glutaminase activity causes in vitro rise in ammonia
To get an accurate result, precautions taken during Ammonia Blood Test:
Pre-arrange
Place on ice
Deliver to lab immediately
Test must be done within 20 minutes
International Normalised Ratio (INR)
The Liver produces all Coagulation Factors except for Coagulation Factor VIII
Coagulation Factor VIII has a particularly short half-life of 3.5 hours
Coagulation Factor VII is the earliest to be reduced in Liver Disease
To assess the extrinsic coagulation cascade measure INR
INR is the measurement of how long it takes blood to clot, it is used to asses the effects of Oral Anti-coagulants on the Clotting System
Laboratory Tests: Patterns of Liver Disease
Outline the Patterns of Liver disease seen in Hepatocellular damage
Hepatocellular damage
Unconjugated Bilirubin is Increased due to the the reduced rate of Conjugation
Conjugated Bilirubin is not increased since there is no Obstruction
Urine Bilirubin is Negative
Urine Urobilinogen is Increased due to the reduced re-uptake by the Liver
AST and ALT are Increased
Outline the Patterns of Liver disease seen in Obstruction
Obstruction (Cholestasis)
Conjugated Bilirubin is Increased due to obstruction
Urine Bilirubin is Positive
Urine Urobilinogen is Decreased, as the Conjugated Bilirubin is not reaching the GIT
ALP and GGT are Elevated
INR may be prolonged but it can be corrected by Vitamin K
Liver Failure
Hypo-albuminaemia
Hyper-ammonaemia
Hypoglycaemia
Prolonged INR
Laboratory Tests: Guidelines
Describe the Liver Enzyme Pattern and Cause
Liver Enzyme Pattern and Cause
Predominant Increase in Transaminases (AST and ALT) more than Alkaline Phosphatase (ALP) is seen in Primarily Hepatocellular pathology
Increase in Transaminase of less than 8 x ULN is seen in either Hepatocellular Disease or Cholestatic Disease
Increase in Transaminase more than 25 x ULN is seen in mainly in Hepatocellular Disease
Describe the interpretation of the AST:ALT Ratio
AST:ALT ratio is usually Less that 1
AST:ALT ratio Greater than 1, indicated more severe acute disease (Greater cell injury affecting mitochondria)
AST:ALT ratio Greater than 1, also more common in Cirrhosis
AST:ALT ratio Greater than 2, suggests alcoholic liver disease
Outline the Levels of Transaminase in various Hepatocellular Disease
Transaminase levels of Less than 15 x ULN is usually seen in chronic liver disease or milder forms of liver disease
Transaminase levels of Greater than 15 x ULN is seen in more severe forms of Acute Liver Disease
Transaminase levels of Greater than 25 x ULN are seen in Acute Viral hepatitis or Toxin-induced Injury
Transaminase levels of Greater than 50 x ULN are seen in Acute Ischaemic Hepatitis
Jaundice
Define Jaundice
Jaundice or icterus is the yellow appearance of the skin and sclera due to increased Bilirubin
Classification of the causes of jaundice:
Pre-Hepatic causes (Before the Liver)
Excess Bilirubin production
Intra-hepatic (In the Liver)
Decreased uptake, metabolism or excretion of Biliruibin
Post-Hepatic (After the Liver)
Obstruction to Bile flow
Pre-Hepatic Jaundice
List the Causes of Pre-Hepatic Jaundice
There are two types of Causes of Pre-Hepatic Jaundice:
Haemolytic Disorders
Abnormal haemoglobins (eg: Sickle cell anaemia)
Red blood cell (RBC) membrane defects (eg: Hereditary Spherocytosis)
RBC enzyme defect
Autoimmune Haemolytic Anaemias
Mechanical RBC damage (eg: Prosthetic Heart valves)
Blood Group incompatibility
Malaria
Ineffective Erythropoiesis
Megaloblastic Anaemias
A. Pre-Hepatic Jaundice
Describe the Laboratory Results of Pre-Hepatic Jaundice
Results of the Laboratory Tests:
Increased Unconjugated Bilirubin, this is because the production of Bilirubin exceeds the maximum rate of Conjugation
Normal Conjugated Bilirubin, as there is NO obstruction
Urine Bilirubin is Negative
Urine Urobilinogen is Increased due to the Increased flux through the pathway
Lactate Dehydrogenase (LDH) enzyme is Elevated
Other enzymes (AST, ALT, ALP and GGT) is normal
Perform Haematological Tests
Outline the results from the Haematological Tests
Results from the Haematological Tests in Pre-Hepatic Jaundice:
Low Haemoglobin, Heamatocrit and Red cell count
Increased reticulocyte count
Perform tests to identify the cause of Haemolysis
Post-Hepatic Jaundice
Outline the diseases causing Post-hepatic Jaundice
Disease causing Post-hepatic Jaundice as a result of Cholestasis:
In the lumen such as Gallstones, and Worms
In the wall such as the Bile Duct Carcinoma, Stricture, Atresia
Outside the wall such as Carcinoma of the Head of the Pancreas, Lymph nodes enlargement at Porta Hepatis
List the Biochemical Features of Post-Hepatic Jaundice
Biochemical Features of Post-Hepatic Jaundice:
Jaundice, Dark urine, Pale stools
Increased Conjugated Bilirubin in the Serum and Urine
Decreased urobilinogen/Urobilin in the stools because the Bilirubin is unable to reach the GIT
Increased obstructive enzymes such as ALP and GGT
If the obstruction is partial then obstructive enzymes will be elevated but the Bilirubin is normal or only mildly increased
Intra-Hepatic Jaundice
Outline the Biochemical Features of Intra-Hepatic Jaundice
Unconjugated Bilirubin is increased due to the reduced rate of conjugation of Bilirubin
Increased Urobilinogen due to non-obstructive Hepatocellular disease
Due to the decreased re-uptake of Urobilinogen by the liver
AST and ALT enzymes are elevated
Inherited Defects causing Intra-hepatic Jaundice
Describe the Inherited Defects causing Intra-Hepatic Jaundice
Defects in Bilirubin Uptake/Conjugation
Gilbert's Syndrome:
Gilbert's Syndrome is an AR Inherited Disorder due to a decrease in the expression of UDP-Glucuronyl Transferase I (UDPGT I)
This results in a mildly increased Unconjugated Bilirubin. Worsened by Viral infection and Fasting
Criggler-Najjar Syndrome:
Type 1 Criggler-Najjar syndrome is an AR Inherited Disorder due to ABSENT UDPGT I activity
This results in severely increased Unconjugated Bilirubin
Type 2 Criggler-Najjar Syndrome is an AD Inherited Disorder due to REDUCED UPGT I activity
This is results in a moderately increased unconjugated Bilirubin
Defects in the excretion of Bilirubin into the Bile Canaliculi
Dubin-Johnson and Rotor Syndrome
Dubin-Johnson and Rotor Syndrome are benign inherited disorders
They result in mildly increased Conjugated Bilirubin
List some hepatocellular conditions that can cause Intra-hepatic Jaundice
Viral Hepatitis and Alcohol are Hepatocellular conditions that can cause Jaundice
Acute Viral Hepatitis
Outline Acute Viral Hepatitis
Acute Viral hepatitis is a common infection worldwide especially Hepatitis B
Risk factors of Hepatitis B Virus (HBV) are as follows:
Living in or travelling to areas of high prevalence
Contact through household or institutional facilities
Multiple sexual partners or STDs
MSM
Use of injected drugs
Clinical Features of Acute Viral hepatitis
Outline the Clinical Features of Acute Viral Hepatitis
The Clinical features of Acute Viral Hepatitis have 3 Phases:
Pre-icteric Phase
Flu-like illness, Nausea, Vomiting, Diarrhoea or Abdominal Pain
2/3 cases of Pre-Icteric Phase never develop Jaundice
This is known as Anicteric or Subclinical Hepatitis
Icteric Phase
Tender Hepatomegaly
Jaundice
Dark Urine containing Bilirubin during later obstructive phase
If Intra-Hepatic Cholestasis is severe: Pruritus, Pale stool and Steatorrhea
Recovery Phase
Prolonged lassitude
Depression
Outline the Development of the Types of Acute Viral Hepatitis
Pre-Icteric Acute Hepatitis may resolve itself or it may develop into Icteric Acute Hepatitis
Icteric Acute Hepatitis may resolve or it may develop into:
Massive Hepatic Necrosis
Massive Hepatic Necrosis may
Resolve
Result in Cirrhosis and then Hepatocellular carcinoma
Or may result in Death
Chronic hepatitis especially in Hepatitis B and C
Chronic Hepatitis may result in Cirrhosis
Cirrhosis may result in Hepatocellular carcinoma
Laboratory Results of Acute Viral Hepatitis
Outline the Laboratory Results of Acute Viral Hepatitis
In the early phase of Acute Viral hepatitis we have a Hepatocellular injury pattern
In the late phase of Acute Viral hepatitis we have an Obstructive pattern due to cellular swelling
Laboratory Results of Acute Viral Hepatitis are as follows:
Bilirubin
Unconjugated Bilirubin is increased throughout
Conjugated Bilirubin is increased during the late obstructive phase of Acute Viral Hepatitis
Urine
Urobilinogen is increased during the early phase of Acute Viral Hepatitis due to a reduced re-uptake of urobilinogen by the damaged hepatocytes
During the late obstructive phase of Acute Viral Hepatitis, Urobilinogen is decreased
BUT Urine is still positive for Bilirubin
Enzymes
Transaminases such as AST and ALT will have an early rise indicating hepatocyte damage
Transaminases may start to rise before the onset of Jaundice
The more severe the liver damage, the greater the likelihood of mitochondrial damage and the more AST is increased
During the late obstructive phase of Acute Viral Hepatitis ALP and GGT enzyme are increased
Plasma Proteins
Albumin is only slightly decreased
Increase in Acute Phase Proteins
Immunoglobulins: IgM will increase early and IgG will increase later
Alcohol Liver Disease
Describe the Alcohol Liver Disease
There are various types of Alcohol Liver Disease such as:
Fatty Liver
Alcohol Hepatitis
Alcohol Cirrhosis
Outline the the Biochemical Features of Alcohol Liver Disease
GGT enzyme is raised due to enzyme induction and Cholestasis
GGT is used as a monitor for alcohol intake
Mild Alcohol Disease: Nothing specific
In the Severe Alcohol liver Disease: Transaminases are elevated, especially AST enzyme
As a result the AST:ALT Ratio is Greater then 2
Non-Alcohol Fatty Liver Disease (NAFLD)
Outline Non-Alcoholic Fatty Liver Disease
Non-Alcoholic Fatty Liver Disease refers to Hepatic Steatosis after excluding alcohol and other causes
Types:
There are Two Types of NAFLD:
Non-Alcoholic Fatty Liver (NAFL) which is when Hepatic Steatosis is present without inflammation
Non-Alcoholic Steatohepatitis (NASH) is when Hepatic Steatosis is present with inflammation
Causes and Risk Factors:
Causes of Non-Alcoholic Fatty Liver Disease (NAFLD) are unknown
Main Risk Factors of Non-Alcoholic Fatty Liver Disease (NAFLD) are as follows:
Central Obesity
Type 2 Diabetes mellitus
Dyslipidaemia
Metabolic Syndrome
Pathogenesis:
Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD) is not known.
It may result from Insulin resistance and oxidation damage
Biochemical Features of Non-Alcoholic Fatty Liver Disease (NAFLD):
Biochemical features of NAFLD is mildly elevated AST, ALT or GGT
Diagnosis:
Diagnosis of Non-Alcoholic Fatty Liver Disease is made by Non-invasive imaging, primarily liver ultrasound in at risk individuals
Treatment:
Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) includes: Lifestyle changes including diets, exercise and gradual weight loss
Cirrhosis
Outline the characteristics of Cirrhosis
Cirrhosis is the common final pathway for many chronic liver diseases
Histologically Cirrhosis presents with:
Fibrosis
Regenerating nodules
Alcohol, Cholestatic Cirrhosis and Congestive Cirrhosis are Micronodular
Post-Viral Hepatitis Cirrhosis is Macronodular
Derangement of the microvasculature leads to Portal Hypertension and Shunting of portal blood to systemic circulation
List the Most Common causes of Cirrhosis
The most common causes of Cirrhosis are:
Chronic Viral Hepatitis (Hep B and C)
Alcohol Liver Disease
Non-Alcoholic Fatty Liver Disease (NAFLD)
Haemochromatosis
Metabolic: Alpha-1 anti-trypsin deficiency
Infection: Syphilis
Vasculatures: Right-sided heart failure
Clinical Presentation of Cirrhosis
Describe the Clinical Presentation of Cirrhosis
Symptoms of Cirrhosis are grouped into:
Symptoms of Compensated (Early) Cirrhosis
Non-specific weakness, Fatigue, and Fever
Loss appetite
Loss of weight and muscle mass
Nausea
Symptoms of Decompensated Cirrhosis
Jaundice
Pruritus
Dark Urine
Bruising (Inability to clot as a result of Vitamin K deficiency)
Upper GIT bleeding resulting in Melena
Fluid Build-Up: Oedema or Abdominal ascites
Diarrhoea
Abdominal pain
Palmar eythema
Spider Naevi
Finger clubbing
Pathophysiology of the Features and Complications of Cirrhosis
Outline the Pathophysiology of the Features and Complications of Cirrhosis
Jaundice
Jaundice is due to the:
Shunting of Blood past the Liver
Impaired conjugation ability due Hepatocellular dysfunction
Obstruction
Mixed picture of hepatocellular dysfunction and obstruction: Increased unconjugated and conjugated Bilirubin
Liver Enzymes mildly to moderately increased without characteristic pattern
Ascites (Major)
Ascites is due to:
Portal Hypertension
Low plasma Albumin due to hepatocellular dysfunction
Secondary Hyperaldosteronism due to low "effective arterial volume"
Varices
Varices are due to Portal Hypertension causing thin walled varices at the Systemic portal anastomotic sites
Can bleed if traumatised
Bleeding Tendency
Bleeding Tendency are due to:
Impaired synthesis of clotting factors due to Hepatocellular dysfunction
Vitamin K Deficiency due to fat malabsorption
Thrombocytopaenia due to portal Hypertension
Oesophageal varices are the most common site for bleeding
Anaemia
Anemia are is due to:
Disturbances in Vitamin B12 and Folate Metabolism
Bleeding
Hypersplenism
Endocrine Changes
Endocrine changes are due to failure to conjugate oestrogens
Malnutrition, Vitamin Deficiencies and Loss of Muscle Mass
Malnutrition, Vitamin Deficiencies and Loss of Muscle Mass is due to:
Alcoholism
Loss of appetite
Malabsorption
Decreased protein synthesis especially Albumin
Possibly increased protein breakdown
Has a negative impact on survival
Infection
Immune dysfunction is due to: Lack of Liver clearance, Reduced White Cell Number and Function reduced synthesis of complement
Ascites can lead to spontaneous bacterial peritonitis
Hospitalisation associated with increased risk of Hospital-acquired infection
Course of Cirrhosis
Describe the Course of Cirrhosis
With early Cirrhosis, Liver reserve can maintain liver function, this is known as Compensated Cirrhosis
Compensated Cirrhosis is asymptomatic, or has mild non-specific symptoms
Cirrhosis is progressive and irreversible
Patients with major complications such as Ascites, Variceal Haemorrhage, Hepatic Encephalopathy or Renal Impairment have Decompensated cirrhosis
Decompensated Cirrhosis is also known as End-Stage Liver Disease or Liver failure
Laboratory Results in Liver Cirrhosis
Outline the Laboratory Results of Liver Cirrhosis
Bilirubin may be normal but rises with decompensation
Level of Bilirubin correlates with severity of cirrhosis
AST and ALT enzymes are moderately raised with the AST:ALT Ratio greater than 1
Normal levels of the transaminases do not exclude Cirrhosis
ALP is moderately elevated, usually no more than 2-3 x ULN
Albumin levels are reduced, and Albumin levels correlate with the severity of cirrhosis
INR is prolonged
INR level correlated with Liver cirrhosis
Hyponatraemia (Reduced Sodium levels)
Increased Creatine if Hepatorenal Syndrome has developed
Polyclonal Hypergammaglobulinaemia
Thrombocytopaenia and Anaemia
Thrombocytopaenia occurs when your blood platelet count is low. Platelets are also called thrombocytes.
Laboratory Results of Liver Failure
Outline the Laboratory results of Liver Failure
Bilirubin is elevated
AST and ALT enzymes are elevated but may decrease with worsening of Liver failure
Albumin is Low
INR prolonged
Creatine is elevated
Ammonia is elevated
Glucose is low
