Week 3 Common Conditions Flashcards
What is jaundice?
Yellow appearance of the skin, sclerae and mucous membranes
An important sign of liver disease, however, not always present
Extra-hepatic disorders can also cause jaundice
Produced by elevated bilirubin (bile pigment and waste product of RBC breakdown)
How is bilirubin metabolised?
Bilirubin is a pigment made during the normal breakdown of senescent RBCs
RBC lifespan: 100-120 days
Engulfed by macrophages in spleen & liver
Haemoglobin broken into heme + globin
Globin chains: broken into constituent AAs
Iron: recycled
Porphyrin ring: converted to unconjugated bilirubin and released into the bloodstream
Unconjugated bilirubin is hydrophobic and must travel bound to albumin in the circulation
In the liver, bilirubin is conjugated with glucuronic acid (enzyme: glucuronyl transferase)
Conjugated bilirubin is water-soluble & released by hepatocytes as a component of bile
Undergoes reduction by intestinal bacteria to urobilinogen
Most urobilinogen: excreted in faeces as stercobilin
A small proportion of urobilinogen enters the portal circulation and is re-excreted by liver
Remaining urobilinogen excreted by kidneys as urobilin
What are the classifications of jaundice?
Based on where bilirubin metabolism is affected:
HAEMOLYTIC JAUNDICE
Due to excessive RBC destruction
Overwhelms liver’s ability to form conjugated bilirubin
E.g. thalassaemia, drug reactions
HEPATIC JAUNDICE
Due to impaired hepatocyte function (various mechanisms)
Impaired uptake or intracellular transport of bilirubin
E.g. viral or alcoholic hepatitis, drug toxicity
Reduced enzymatic activity (glucuronyl transferase)
E.g. newborn with immature enzymes
NEONATAL JAUNDICE
Occurs in ~60% of full-term and 80% of pre-term babies within the first week of life
CHOLESTATIC JAUNDICE
Due to obstruction of intrahepatic or extrahepatic bile ducts.
Intrahepatic bile duct obstruction
E.g. cirrhosis, neoplasia
Extrahepatic bile duct obstruction
E.g. cholelithiasis, neoplasia, cystic fibrosis
What is the aetiology of viral hepatitis?
Most common: Hepatitis virus types A, B, C (pictured), D & E
Hepatitis F & G now known to exist
Other viruses: Epstein Barr virus, cytomegalovirus
What is the pathophysiology of viral hepatitis?
Virus induces an acute inflammatory reaction, leading to widespread hepatocyte necrosis
Usually, liver begins to recover before SSx disappear
Occasionally, severe destruction of whole lobes results in acute hepatic failure
Chronic hepatitis with cirrhosis (pictured) is particularly associated with HBV & HCV
Discuss the types of hepatitis viruses
HAV Transmission: Faecal-oral route Severity: Usually mild, worse in older patients Chronicity: Very rare Vaccination: Yes
HBV
Transmission: Parenteral, sexual contact, perinatal
Severity: Mild to severe (mortality ~10%)
Chronicity: Common
Vaccination: Yes
HCV Transmission: Parenteral, perinatal, possibly sexual Severity: Usually mild Chronicity: Very common Vaccination: Not available
What are the clinical features of acute hepatitis?
Stage 1: Preclinical
Asymptomatic, but virus actively replicating
Spread during this phase a concern
Stage 2: Prodromal/Pre-icteric
Anorexia, nausea, vomiting, malaise, headache
Mild fever, diarrhoea, upper abdominal discomfort
Stage 3: Icteric
Jaundice develops
Possibly tender hepatomegaly +/- splenomegaly
HBV: polyarthralgia affecting small joints, skin rash
Stage 4: Convalescent
Symptoms subside over a course of several weeks
Stage 1: Preclinical
Asymptomatic, but virus actively replicating
Spread during this phase a concern
Stage 2: Prodromal/Pre-icteric
Anorexia, nausea, vomiting, malaise, headache
Mild fever, diarrhoea, upper abdominal discomfort
Stage 3: Icteric
Jaundice develops
Possibly tender hepatomegaly +/- splenomegaly
HBV: polyarthralgia affecting small joints, skin rash
Stage 4: Convalescent
Symptoms subside over a course of several weeks
What are the clinical features of chronic hepatitis?
Persistence of inflammation > 6 months
A wide spectrum of disease exists:
The inflammation may be low-grade (mild, well-contained)
Chronic active hepatitis leads to widespread fibrosis and eventually cirrhosis
What is the management of hepatitis?
There is no specific treatment
Hep A: bed rest is advised
Diet: should be low in fats but relatively high in proteins
Avoid hepatic insults: drugs, esp. alcohol
Advice about reducing spread:
Not sharing needles
Not donating blood or body organs
Advising healthcare workers of health status
Covering wounds appropriately
Carefully disposing of blood stained material
Practising safe sex
What is alcoholic liver disease?
In the liver, it causes the induction of oxidases (these enzymes aid metabolism, but damage hepatocytes with chronic exposure)
Severity of the liver damage is dose related, although individual factors may play a role (? Amount of standard drinks required for hepatic changes to occur)
LIVER RESILIENCE
The liver has excellent potential for hypertrophy & hyperplasia
However, the new growth may not conform to normal cytoarchitecture – this leads to a range of issues
What is the pathophysiology of alcoholic liver disease?
STAGE 1: FATTY LIVER
Destruction of rough ER in hepatocytes reduces the amount of lipoproteins synthesied & secreted – this causes cells to become swollen with lipids
Mild to moderate changes are reversible
Clinical features: +/- hepatomegaly
STAGE 2: ALCOHOLIC HEPATITIS
Usually superimposed on fatty liver
Hepatocyte necrosis induces the infiltration of inflammatory cells
Clinical features: tender hepatomegaly, fever, jaundice, ascites
Severe cases: a heavy drinking bout may induce encephalopathy
STAGE 3: CIRRHOSIS
Irreversible: arises due to chronic inflammation and progressive fibrosis
Regenerating hepatocytes do not conform to normal cytoarchitecture (nodule formation)
The structural change obstructs nutrient flow (impaired hepatocyte function)
Death occurs due to complications (hepatocellular failure, portal hypertension)
What are other causes of cirrhosis? (alcohol ~60-70% of cases)
Non-alcoholic fatty liver disease
Risk factors include: obesity, insulin resistance, hyperlipidaemia
Viral & autoimmune hepatitis
Cholestasis
Metabolic disorders e.g. haemochromatosis
What are the clinical features of cirrhosis?
Jaundice, RUQ pain, hepatomegaly (liver shrinks in advanced stages), foetor hepaticus (late)
Constitutional symptoms: fever, anorexia, nausea, vomiting, weakness, fatigue, weight loss
What are the complications of cirrhosis?
Are related to portal hypertension and hepatocellular failure
What are manifestations of portal hypertension?
Ascites
Accumulation of fluid in peritoneal cavity
Abdominal distension with shifting dullness to percussion
Other causes of ascites: liver carcinoma, cardiac failure
Splenomegaly
Occurs due to passive congestion
Varicose veins
Oesophageal (haemorrhage risk)
Rectal
Caput medusae
