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
What are manifestations of hepatocellular failure?
Hepatic encephalopathy
Failure to metabolise neurotoxic nitrogenous wastes from gut bacteria
Changes in intellect, mood, alertness
Asterixis (flapping tremor), hyper-reflexia, Babinksi
Coagulation defects
Failure to produce coagulation factors
Endocrine changes
Failure to deactivate hormones
Peripheral oedema
Failure to produce albumin
What is the management of alcoholic liver disease?
Cease alcohol
Improve nutrition
Carefully monitor medications
Treat the complications: ascites, encephalopathy, varices
There is no treatment to reverse the cirrhosis
What is the prognosis of alcoholic liver disease?
Poor overall - most people present in the later stages of the disease (5-year survival - 25%)
If liver function is good, 50% of patients survive for 5 years and 25% for 10 years
What are the three types of liver tumours?
Benign tumours
Haemangiomas, adenomas
Focal nodular hyperplasia
Primary malignant liver tumours
Hepatocellular carcinoma – most common
Cholangiocarcinoma
Secondary malignant liver tumours
Are relatively common
Primary usually in lung, breast, GIT, skin (melanoma)
50% of cases: primary tumour is asymptomatic
What is hepatocellular carcinoma? (hepatoma)
primary malignant tumour arising from liver epithelial cells (hepatocytes)
What are the risk factors of hepatocellular carcinoma?
Cirrhosis, viral hepatitis (HBV & HCV)
Exposure to aflatoxins
More common in men
What are the clinical features of hepatocellular carcinoma?
Irregular hepatomegaly, RUQ pain, jaundice
Symptoms of cirrhosis e.g. ascites
Constitutional symptoms e.g. anorexia, weight loss, fever
Can appear as a single mass or as multiple nodules
50% of cases: metastasis to regional lymph nodes, lungs, bone
What is the management of hepatocellular carcinoma
Radiofrequency ablation and chemotherapy are the most common treatments
Partial hepatectomy is considered in some patients, dependent on tumour size, number and location
What is the prognosis of hepatocellular carcinoma?
In Australia, the 5-year survival is 16%
What is cholelithiasis?
Gallstones
Most common GB disorder of the Western world
Estimated to affect 11% of the population
What are the risk factors of cholelithiasis?
In adults <40 years, stones are more common in women (no difference in elderly)
Obesity, increased age, multi-parity, diabetes, diets high in refined sugar, ileal disease
What are the types of cholelithisasis?
Cholesterol variety
Most common type in Western countries
Linked to disturbed cholesterol balance
Pigment variety
More common in developing countries
Correlation with infection
What is the pathophysiology of cholesterol stones?
The solubility of cholesterol in bile is determined by the ratio:
Cholesterol : Bile salts : Phospholipids
Many factors can alter this ratio
Crystals begin to form when bile is supersaturated with cholesterol - “lithogenic bile”
What are the clinical features of cholesterol stones?
Most gallstones are asymptomatic, especially if the stone remains in the GB
Only 25% of stones have enough calcium to be radio-opaque
Pure cholesterol stones: often solitary
May be more than 3cm in length
More likely for a patient to present with a complication
What are complications of cholelithiasis? (7)
Acute Cholecystitis
Impaction in the cystic duct results in biliary stasis
Acute inflammation arises from chemical irritation
Clinical features:
Sudden onset RUQ pain, +/- Rt shoulder referral
+/- fever or chills
Murphy’s sign: tenderness on RUQ palp., worse w. inspiration
Chronic cholecystitis
GB walls become fibrotic & shrunken following repeated bouts of acute inflammation
Clinical features: similar acute cholecystitis, but milder
Mucocele development
GB becomes distended with mucoid watery fluid
Due to cholestasis (bile pigments are reabsorbed through GB wall)
Infection
Increased risk of bacterial infection (especially E. coli)
Persistent inflammation and infection can result in empyema
Increased risk for carcinoma
Gallstones are seen in 80% of GB malignancies
Suggest that gallstones may play a role in neoplasia
Choledocholithiasis
Impaction of gallstone in the bile duct
Often results in inflammation of bile duct - cholangitis
Clinical features:
Biliary colic
Charcot’s triad of RUQ pain, jaundice, fever
Acute pancreatitis
Obstruction at hepatopancreatic ampulla generates back-pressure
Causes secretions to flow back up the pancreatic duct
Clinical features:
Severe abdominal pain (LUQ Lt scapula)
Bloating, fever, sweating, nausea, vomiting
What is the management of gallstones?
Surgery (Cholecystectomy)
For symptomatic cases
Open or laparoscopic
Oral bile acid therapy
Ursodeoxycholic acid
Chemical dissolution of stones
Not suitable for all patients
Extra-corporeal shockwave lithotripsy
Application of high frequency sound waves to fracture the stones
Followed by a course of bile salts to dissolve the fragments
What is cystic fibrosis?
A disorder of exocrine glands, in which the secretions of the lungs, pancreas, bile ducts and reproductive tract have increased viscosity
What is the pathophysiology of cystic fibrosis?
The gene responsible (CFTR) is located on chromosome 7 and codes for a membrane-bound chloride channel
There are nearly 2000 possible mutations
Affected chloride channels are non-responsive to intra-cellular signalling (cAMP second messenger system) that would normally open the channel
Secretions of affected cells contain inadequate amounts of chloride and water
The abnormal secretions are viscid and are retained by the affected gland
Secretions that may be affected: Pulmonary mucous* Pancreatic enzymes* Sweat Bile Reproductive secretions
What are the clinical features of cystic fibrosis?
PULMONARY FEATURES
Mucous plugging & impaired mucociliary function
Recurrent infections & chronic inflammation (fibrosis)
PANCREATIC FEATURES
Reduced or absent pancreatic enzymes
Malabsorption occurs due to impaired digestion
Failure to thrive/growth retardation
Steatorrhoea
Recurrent pancreatitis leads to extensive fibrosis
Exocrine portion: permanent pancreatic insufficiency
Endocrine portion: CF-induced diabetes
BILIARY FEATURES
Cholestasis can result in secondary biliary cirrhosis & cholelithiasis
REPRODUCTIVE FEATURES
Sub-fertility or infertility
98% affected men: Congenital bilateral absence of the vas deferens
What is the management of cystic fibrosis?
PULMONARY SUPPORT
Chest physiotherapy
Inhalation of agents to reduce sputum viscosity (deoxyribonuclease)
or assist in mucus clearance (hypertonic saline)
Antibiotics for infections; Bronchodilator therapy
Lung transplantation: advanced CF
PANCREATIC SUPPORT
Pancreatic enzyme replacement – pancrelipase (Creon)
Vitamin therapy to correct any deficiencies
Insulin for CF diabetes
