S4C5 Flashcards
What are the 8 principles of Confidentiality?
Use the minimum necessary personal information.
Manage and protect information.
Be aware of your responsibilities.
Comply with the law.
Share relevant information for direct care in line with the principles in this guidance unless the patient has objected.
Ask for explicit consent to disclose identifiable information about patients for purposes other than their care or local clinical audit, unless the disclosure is required by law or can be justified in the public interest.
Tell patients about disclosures of personal information you make that they would not reasonably expect, or check they have received information about such disclosures, unless that is not practicable or would undermine the purpose of the disclosure.
Support patients to access their information.
What does Hep B screening involve?
HBV has three antigens (surface, core, and e), some of which can be detected in the blood.
What does Hep B surface antigens suggest?
Determines whether a person currently has the infection
Detectable 4-10 weeks after exposure
After 6 months, if still present, infection considered chronic
What does Hep B core antibodies suggest?
Determines whether a person has ever been infected
Appears within a few weeks
Has or is infected
What does Hep B surface antibodies suggest?
Determines whether a person has cleared the virus after infection, or has been vaccinated and is now immune to future infections
Detects presence of the antibodies
A positive hepatitis B surface antibody screening test means the person has lifetime immunity from hepatitis B.
What does a positive HCV antibody test mean?
The person is a chronic carrier of HCV - 75-85%
Has been infected but has resolved infection 15-25%
Recently (acutely) infected
Takes 6-8 weeks
What does a qualitative HCV RNA test measure?
RNA is the genetic material of the virus, and the qualitative test determines whether the virus is present.
A quantitative RNA test—or quantitative viral load test—measures how much of the virus is present
If HCV RNA is present for at least 6 months, the HCV infection is considered chronic.
What is the pathology of the liver in viral hepatitis?
Hepatitis viruses: Non-cytopathic
Hepatocyte damage is immune-mediated
Antigen recognition by Cytotoxic T cells: Apoptosis
Chemokine driven recruitment of Ag-nonspecific cells
Depending on strength of immune response
Mild inflammation to massive necrosis of liver
What is hepatic encephalopathy?
A syndrome observed in patients with cirrhosis. Hepatic encephalopathy is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of brain disease
What are the mild symptoms of hepatic encephalopathy?
confusion forgetfulness personality or mood changes stale or sweet odour on the breath poor judgement poor concentration change in sleep patterns worsening of handwriting or small hand movements.
What are the severe symptoms of hepatic encephalopathy?
unusual movements or shaking of hands or arms extreme anxiety seizures severe confusion sleepiness or fatigue severe personality changes jumbled and slurred speech slow movement
What viral family is Hep A from?
Picornavirus
Non-enveloped
+ sense single-stranded linear RNA
What transmission route and incubation period for Hep A?
Fecal-Oral
15-50
What are the signs and symptoms for Hep A?
Acute hepatitis Fever Malaise Loss of appetite Nausea Abdominal pain Jaundice Increased AST/ALT
What test do you do to serological diagnose Hep A?
Anti-HAV IgM
What treatment is required for Hep A?
Supportive
How can you prevent Hep A?
Food and water hygiene
Immunisation
What is the prognosis of Hep A?
Full recovery with ~3 months
Does not become chronic
What viral family is Hep B from?
Hepadnavirus
Enveloped virus
Partially double-stranded circular DNA
What transmission route and incubation period for Hep B?
Parenteral
Sexual
Perinatal
30-180
What are the signs and symptoms for Hep B?
Often asymptomatic
Serum sickness-like reaction in prodome phase
Acute hepatitis
Stigmata of cirrhosis in chronic case
What test do you do to serological diagnose Hep B?
HBsAg
Anti-HBc
HbeAg
What treatment is required for Hep B?
Acute - supportive
Chronic - interferon-α or tenofovir
How can you prevent Hep B?
Safe sex; screening of blood products
HBV vaccination post-exposure prophylaxis
What is the prognosis of Hep B?
Fulminant hepatitis
Chronic disease
What viral family is Hep C from?
Flavivirus
Enveloped virus
Partially double-stranded circular DNA
What transmission route and incubation period for Hep C?
Parenteral
14-180
What are the signs and symptoms for Hep C?
Often asymptomatic
Acute hepatitis
Stigmata of cirrhosis in chronic cases
What test do you do to serological diagnose Hep C?
Anti-HCV IgM
HCV RNA
What treatment is required for Hep C?
Acute: interferon-α or peginterferon-α
Chronic: interferon-α plus ribavirin or DAAs
Liver transplantation
How can you prevent Hep C?
Use of sterile instruments and needles
Safe sex
There is no vaccination available
What is the prognosis of Hep C?
Chronic disease
What viral family is Hep D from?
Deltavirus
Enveloped virus
Negative sense, single-stranded, circular RNA
What transmission route and incubation period for Hep D?
Co-infection with HBV Requires HBsAg for entry into hepatocytes Parenteral Coinfection: 45-160 Superinfection: 14-56
What are the signs and symptoms for Hep D?
Acute hepatitis
What test do you do to serological diagnose Hep D?
HDV-RNA
Anti-HDV IgM
What treatment is required for Hep D?
peginterferon-α
How can you prevent Hep D?
Prevention of HBV infection
What is the prognosis of Hep D?
Fulminant hepatisis
High risk of severe chronic lover disease
What viral family is Hep E from?
Hepevirus
Non-enveloped virus
Positive sense, single-stranded linear RNA
What transmission route and incubation period for Hep E?
Fecal-Oral
15-64
What are the signs and symptoms for Hep E?
Similar to Hep A, milder
What test do you do to serological diagnose Hep E?
Anti-HEV IgM
What treatment is required for Hep E?
Supportive
How can you prevent Hep E?
Food and water hygiene
What is the prognosis of Hep E?
Fulminant hepatitis
High mortality rate in pregnant women
What are the causes of prehepatic jaundice?
Haemolysis
Ineffective erythropoiesis
What type hyperbilirubinemia is prehepatic jaundice?
Unconjugated
What are the colours of the stool and urine prehepatic jaundice? What about urinary urobilinogen?
Stool - Dark
Urine - Normal
Urinary urobilinogen - very increased
What are the causes of intrahepatic jaundice?
Nonobstructive biliary disease
Mechanical biliary obstruction (within liver)
What type hyperbilirubinemia is intrahepatic jaundice?
Conjugated
What are the colours of the stool and urine intrahepatic jaundice? What about urinary urobilinogen?
Stool - Pale, clay coloured
Urine - Dark
Urinary urobilinogen - normal/ slightly increased
What are the causes of posthepatic jaundice?
Mechanical biliary obstruction (outside liver)
What type hyperbilirubinemia is posthepatic jaundice?
Conjugated
What are the colours of the stool and urine intrahepatic jaundice? What about urinary urobilinogen?
Stool - Pale, clay coloured
Urine - Very dark
Urinary urobilinogen - low
What are the causes of unconjugated hyperbilirubinemia?
Increased haemoglobin breakdown
Defective hepatic uptake
Defective conjugation of unconjugated bilirubin
What are the causes of conjugated hyperbilirubinemia?
Reduced drainage via biliary tract
Decreased reuptake
Explain Bilirubin metabolism
Haemoglobin is broken down into Haem and globin in the spleen (80%) and bone marrow (20%)
Macrophages break down haem to unconjugated bilirubin.
Unconjugated bilirubin binds to albumin and reaches the liver
Bilirubin is conjugated in the liver and secreted in bile
In order to be secreted, conjugated bilirubin enters the blood to reach the hepatocytes with direct connection to the bile canaliculi
Bilirubin reaches the intestine via the bile
Intestinal bacteria coverts bilirubin into urobilinogen
Describe urobilinogen break down
Most urobilinogen is converted into stercobilinogen and then stercobilin
The rest of the urobilinogen is reabsorbed and follows 2 pathways; most of it undergoes hepatobiliary recirculation, while the rest is filtered in the kidney
In urine, urobilinogen oxidates to urobilin, which is responsible for its characteristic yellow colour
What gives stool is characteristic colour?
Stercobilin
What is Vd? (pharmokinetics)
the fluid volume that would be required to contain the total amount of absorbed drug in the body at a uniform concentration equivalent to that in the plasma at steady state
Dose/ conc in blood
What characteristic makes drugs highly distributed?
High lipid solubility
What is drug metabolism?
the enzyme-mediated conversion of a lipid-soluble compound into a more water-soluble one
Where does drug metabolism mainly occur?
Liver
In the SER and cytosol and mitochondria
What happens in phase 1 reactions?
Produce/uncover chemically reactive functional groups → ‘FUNCTIONALISATION’
Help with excretion
Oxidation, e.g. alcohol dehydrogenase, MAO, CYP450 (most important)
products slightly more polar → water-soluble
preparation for phase 2
pro-drugs > ‘pharmacological activation’
What happens in phase 2 reactions?
Conjugation reactions
What are the conjugation reactions?
Glucuronidation * – most widespread Sulphation * Methylation Acetylation Amino acid (Damage to hepatocytes can restrict this) Glutathione Fatty acid
What are the products of phase 2 reactions?
Water-soluble and easily excreted
Increased MW
Inactive (Decrease receptor affinity and
Enhance excretion)
What are the outcomes of drug metabolism?
Pharmacological activation (pro-drugs) Pharmacological inactivation Change in type of pharmacological response No change in pharmacological response Change in drug distribution
What internal factors affect metabolism?
Age Gender Pregnancy Disease Genetic
How does age affect metabolism?
Reduced as liver mass and blood flow decrease
Drug inactivation is slower - mostly in phase 1 oxidation
Decrease first-pass metabolism
How does pregnancy affect metabolism?
Increased hepatic metabolism
Increased blood flow to liver and kidney
What external factors affect metabolism?
Drug induced Lifestyle Environment Diet Inducers Inhibitors
What drugs can affect metabolism?
Licensed e.g. Co-amoxiclav, isoniazid, methyldopa, halothane, rifampicin, paracetamol Unlicensed herbal remedies: Comfrey Black cohosh Kava
What drugs does smoking increase the metabolism of?
Theophylline Caffeine Tacrine Imipramine Haloperidol Pentazocine Propranolol Flecainide Estradiol
What in the environment can affect metabolism?
Arsenic
Toluene
Fluorine
What foods can affect metabolism?
BBQ meat
brussel sprouts increase metabolism
grapefruit juice decrease metabolism
What are some inducers of metabolism?
Carbamazepine
Alcohol
St Johns wort
What are some inhibitors of metabolism?
Fluoxetine
Erythromycin
Ketoconazole
Grapefruit juice
How does grapefruit juice affect metabolism?
Inhibits CYPA4
Metabolises ~30% of all drugs
Increase in plasma levels - prolonged effect
What genetic type makes up a poor metaboliser?
Homozygous for defective CYP gene
Increased [drug}, decreased [metabolites]
What genetic type makes up a intermediate metaboliser?
Heterozygous for defective CYP gene
Increased [drug}, decreased [metabolites]
What genetic type makes up a extensive metaboliser?
Homozygous for functional CYP gene
decreased [drug}, increased [metabolites]
What genetic type makes up a ultra-rapid metaboliser?
Extra copies of functional CYP gene
decreased [drug}, increased [metabolites]
How does paracetamol normally metabolise?
Paracetamol gets glucuronide and sulphate conjugates of -OH group
This produces an inactive metabolite which undergoes urinary excretion
How does an small increased dose of paracetamol metabolise?
Undergoes N-hydroxylation (CYP450)
This causes rearrangement N-acetyl-p-benzoquinone-imine
This undergoes Glutathione conjugation
This produces an inactive metabolite which undergoes urinary excretion
What happens if too much paracetamol is consumed?
Undergoes N-hydroxylation (CYP450)
This causes rearrangement N-acetyl-p-benzoquinone-imine
This leads hepatotoxicity and cell death
What are type A ADRs?
augmented reactions, exaggerated response to drugs normal actions, dose dependent
Causes 80% of hospital admissions
What are type B ADRs?
bizarre reaction, novel response to drug that was not expected based upon known pharmacological actions of the drug
What are type C ADRs?
Dose and time chronic reaction
What are type D ADRs?
delayed chronic reaction
What are type E ADRs?
Withdrawal reaction
What are type F ADRs?
Unexpected failure of therapy
How many hospital admissions are due to ADR (p.a.)? What are the death rates and cost of them?
1 in 16 admissions
>2% die
>£1 billion
What are the signs of hepatocellular injury?
Hepatocyte necrosis and inflammations
V increased ALT and AST
Increased γ-glutamyl transpeptidase
What are the signs of cholestatic injury?
Resembles bile duct obstruction
V increased ALP and γ-glutamyl transpeptidase
Increased AST and ALT
What are the signs of mixed hepatocellular-cholestatic injury?
Most characteristic pattern
Increased ALP and ALT
