Hepatic Flashcards
why is liver disease relevant to dentistry
liver is main production site for clotting factors 2, 7, 9, 10 = reduced clotting = more bleeding
chronic liver disease often accompanies hep B and C blood borne disease
where does the main blood flow come from to the liver
hepatic portal venous system
all blood from gut goes to liver
where does the main blood flow come from to the liver
hepatic portal venous system
all blood from gut goes to liver
what organ will be enlarged in haemolytic anaemia and why and what is a possible side effect of this
the spleen
splenomegaly
The RBC’s are stored and broken down in the spleen so it gets enlarged
pre-hepatic jaundice, yellow eyes and skin
what is the main cause of ‘too little liver’
cirrhosis
end stage liver disease
how would cirrhosis present histologically
regenerating cells seperated by bands of fibrosis
what causes cirrhosis (3) and give the process (2)
constant liver abuse, viruses such as hepatitis, alcohol
usually after liver cells are damaged = inflammation = regeneration
under constant, prolonged abuse, the cells will heal by fibrosis (scarring)
name 6 viruses that cause cirrhosis
Hep B, C, D, E
Cytomegalovirus
Epstein Barr Virus
why does Hep A not cause cirrhosis
this is an acute attack on the liver, not chronic (unline B, C, D, E, EBV,)
may kill patient but if recover, the virus is cleared completely from the liver and doesn’t cause chronic damage and fibrosis
what are the consequences of cirrhosis (4)
liver failure = jaundice
Portal hypertension = raised BP in portal venous system
Ascites =
Hepatocellular cancer =
what are varices and what causes them
Varices are dilated veins in the distal oesophagus or proximal stomach caused by elevated pressure in the portal venous system, typically from cirrhosis.
what is a treatment for varices
Varices are dilated veins in the distal oesophagus or proximal stomach caused by elevated pressure in the portal venous system, typically from cirrhosis.
inject sclerosing agent or place rubber band over it
what is the only symptom of varices and how would we diagnose
massive bleeding and being sick with blood
endoscopy
explain the blood flow through the liver
from the gut, the portal vein takes blood to the liver and this goes to capillary level
blood then leaves via the hepatic vein
give 2 reasons why fibrosis from cirrhosis causes problems in the liver and what does this lead to
fibrosis may disrupt blood supply = death of tissue and difficulty pushing blood through liver
hepatocytes are aligned along blood vessels in health but under cirrhosis, the cells form in nodules leading to th cells being harder to get to for the blood
This leads to portal vein hypertension
what is ascites and what causes this (explain mechanism (2))
a build up of fluid in the abdomen causing bloating and swollen abdomen
cirrhosis
Reduced albumin production = reduced fluid absorption into blood = increased external fluid
portal hypertension = high pressures in the gut = swelling
how would ascites present and what is its cause
large swollen abdomen which is dull to tap and would show up as high volume liquid under a scan
what is albumin and where is it produced
most abundant serum protein helping regulate osmosis and blood content and also helps carry proteins and hromones
absorbs fluid back into the blood at venous end of capillaries
produced in the liver
how might we vaccinate against hepatocellular carcinomas
vaccine against hepatitis B
stops hep B infection
stops cirrhosis therefor no fibrosis
reduces turnover of hepatocytes
reduces risk of hepatocellular carcinomas
what is the major cause of bile flow blockage
gall stones
what are the main signs and symptoms of jaundice
yellow skin
yellow eyes
itchiness
pale stool
dark urine
high Bilirubin levels in blood
what affects does gall bladder blockage have on the skin
this can cause jaundice = yellow skin
if a patient never drinks alcohol or doesn’t have hepatitis but suddenly gets pain and jaundice, what is the likely cause?
gall stone in bile duct
if a patient rarely drinks alcohol, doesnt have hepatitis and has no pain but comes in with jaundice, what is the liekly cause
a cancer in the bile duct or pancreatic/duodenal cancer that is blocking the bile duct
why does bile blockage cause jaundice
if the bile cannot exit the gall bladder/liver, this causes a build up of bile in the liver
causes overflow into the blood
what is hepatitis
inflammation of the liver
what can cause hepatitis
infections e.g. viral, bacterial, fungal
non infectious = alcohol, drugs, autoimmunity, metabolic problems
what is the general pathway of drestuction of the liver (3)
hepatitis (inflammation
Cirrhosis = permanent damage
hepatocellular carcinoma - HCC - with cirrhoisis
what is HCC
hepatocellular carcinoma
symptoms of hepatitis
jaundice
pale fatty stools
dark urine
malaise
serum biochemical tests/ serological tetss
how do we diagnose hepatitis
symptoms
serum biochemistry and serological tests
what is a virion
complete virus
what are the major types of hepatitis virus
A-E
what are the two main ways of classifying hepatitis viruses
Genome = All RNA apart from Hep B - DNA (vaccine)
Route of transmission = A and E oro-faecal route
BCD are all parental route e.g. saliva, blood, needles
which types of hepatitis virus are oral facieses route
A and E
spread through food contamination
whcih hepatitis virus is DNA and RNA
B = DNA
ACDE = RNA
how many types of Hep A are there, which ones are relevent (3)
I-VII
I-III and VII are human viruses
I is 80% relevant and III is very common too
how does Hep A and E get into the faeces (3)
enters through stomach and intestine
absorbed in the blood and makes way to liver causes hepatitis
secreted from liver in bile into the intestine = faeces
what type of vaccine do we have for hep A
whole formalin killed virus
what is the infection and serum levels rates for Hep A (3)
2 week incubation (no serum antibodies)
4-10 day prodrome period (symptoms but general also Ig start showing)
resolves in a few weeks
what age group is often asymptomatic for Hep A
3-5 year olds
risk as they are not very hygienic and add to spread
would we see antibodies in the blood, or pathogen in the faeces first and why is this relevent for Hep A
pathogen in faeces first
this is a problem as the patient is shedding and contagious before we can detect disease and prevent
why is Hep B more dangerous than Hep A
most Hep A patients recover in 2 weeks
2.5% of Hep B patients go into chronic hepatitis
either persistant (‘health’) hepatitis or active hepatitis which is very damaging
what happens to 2.5 percent of hepatitis B surfferers
they develop chronic carrier state, being either
Chronic persistent hepatitis (‘healthy carrier’) - just spread
Chronic active hepatitis (damaging and spread)
how does Hep B become chronic in some patients
HBV integrates into hepatocyte DNA so constantly produces antigens
compare chronic persistant hepatitis and chronic active hepatitis
both 2.5% of Hep B patients, both very infective, both HBV integrated DNA
CPH - non symptomatic and no damage
CAH - symptomatic, cirrhosis, very damaging, very infecitious
describe the structure of Hepatitis B virus dane particle (4)
full particle = ‘dane particle’
DNA with DNA polymerase
plasmid with HBcAg (core antigen)
Capsule with HBsAg (surface antigen)
what 3 forms does Hep B come in
Dane particle = whole = infectious
Filamentous = non infectious
sphere = non infectious
what is the hep B core made up of (3)
dsDNA
DNA polymerase
HBcAg core antigen
what would we see in a serology of acute hep B (2)
HBsAg
and IgM of HBcAg
what 4 genes are in HBV
S protein = surface antigen
C protein = core antigen
P = polymerase antigen
X = unknown, reguatory
which antigen is causing illness in Hep B
E antigen
HBeAg - breakdown of HBcAg core protein
what is HBeAg and when is it seen in serology
a breakdown molecule of HBcAg - hepatitis B core antigen
seen when there are high levels of antigen and very infectious
what would be a serological diagnosis of Chronic Hep B infection
characterized by the persistence of HBsAg for at least 6 months (with or without concurrent HBeAg). Persistence of HBsAg is the principal marker of risk for developing chronic liver disease and liver cancer (hepatocellular carcinoma) later in life.
how much chronic hep B leads to chronic liver disease
10%
what increases chances of getting chronic hep B
getting it earlier in life
what antigen is genetically engineered for vaccine for Hepatitis B
HbsAg surface antigen
what do we need before we can get Hepatitis D
Hepatitis B
which hepatitis viruses are related
hepatitis D needs hepatitis B
what percent of Hep B carriers also carry HepD
5%
why can a pt not be ONLY infected by Hepatitis D (3)
Hep D is caused by a ‘defective’ RNA virus which coexists with HBV
Outer coat derived from HBsAg – cannot survive without HBV.
~5% HBV carriers are HDV positive.
what is the structure of hep D
RNA surrounded by Delta antigen
Surface formed from HBsAg
what do we use to detect HDV
hep D virus
Delta antigen found at the core of Hep D
what is the effect if having Hep D
rarely progressive
‘supervirus’ makes Hep B more likely to be chronic and destructive
what percent of IV drug users are infected by Hepatitis C
80%
what hepatitis virus is very common in IV drug users
hep C
how is Hepatitis C transferred
IV drug abuse needle sticks, tattoos, ear piercing
80% iv drug users infected
Previously
blood products, haemodialysis, transplantation
minor routes - saliva; sexual; vertical
when does the Hep C antigen show up
6 weeks to 6 months (97% by 6 month)
is acute Hep C serious
very mild acute infection
1% get jaundice
describe Hepatitis C chronicity
50 - 85% become chronic
50% fatigue (10y); 25% cirrhosis (20y); 5% HCC(30y)
350 000 to 500 000 people die each year from hepatitis C-related liver diseases.
what percent of HCV get cirrhosis after chronicity
25% after 10 years
what percent of HCV get HCC after chronicity
5%
if a patient is on interferon alpha and Ribavirin
hep C (outdated)
what drugs have historically been used for Hep C
Ribavirin and Alpha Interferon
which hep virus has there been recent cures and targets for elimination by
hep C
how can we reduce Hep C (4)
safe IV drug use with good hygeien control
cures
more screening and protection
find a vaccine
which hep virus has a large 10 gene genome
Hep C
which antigen is responsible for Hep C attachment to host cells
E2
which hepatitis virus causes epidemics in middle aged patients
Hep E
whats the incubation period for Hep E
6 weeks
which group has particularly high mortality/chronicity with hep E
pregnancy and immunocomprimsied
which hepatitis virus has high mortality with pregnancy
hep E
how is Hep E mainly spread
food contamination epidemics
how do we diagnose Hep E
PCR or IgM or IgG serology
how do we reduce Hep E
good hygiene, cooking food thouroughly, no vaccine, observe for liver problems
where is the liver positioned
mid right abdomen to upper left abdomen
Infront of stomach and bile duct
what vessels provide oxygenated and non-oxygenated blood to the liver
proper hepatic artery = oxygenated
hepatic portal vein = deoxygenated
what does the portal vein carry and from where
deoxygenated blood from
SI, LI, pancreas and spleen
oxygen been used in these organs and blood travels through liver
how does fat stimulate biliary secretion
fat detected in liver = release of CCK
CCK causes gall bladder constriction
presses out bile into the small intestine
what shape are hepatocytes
hexagonal
what is the structure of liver tissue
haxagonal hepatocytes
surrounded by portal triads in the corner
with branch of bile duct, portal vein and portal artery
what are portal triads
triad of hepatic portal vein, hepatic artery and bile duct
found in corners of hepatocytes
the liver have ~500 functions, give the main ones
Detoxification: Filters & cleans blood of waste products (drugs, hormones) - ammonia (excess = swelling brain = confusion, first function that goes with liver disease)
Immune functions: Fights infections and diseases (RE system)
Involved in Synthesis of clotting factors, proteins, enzymes, glycogen and fats
Production of bile & breakdown of bilirubin
Energy storage (glycogen and fats)
Regulation of fat metabolism
Ability to regenerate
how might liver failure result in confusion
liver is responsible for detoxification of ammonia
if not occurring, ammonia builds up
causes swelling of the brain
presses on parts of the brain = confusion
what is one of the first signs of liver failure
build-up of ammonia = confusion
give 2 ways that liver failure means a pt is more prone to bleeding
1: cirrhosis = portal hypertension = splenomegaly = increased platelet destruction = less platelets = reduced primary haemoastasis
2: liver is site of vitamin K dependant clotting factor production = reduced this = reduced clotting factors = reduced Extrinisc and intrinsic pathways of secondary haemostasia
give 4 ways liver disease is classified
By time line: Acute vs chronic
By pattern: Hepatic vs cholestatic (more to do with bile ducts) vs mixed
By presentation: asymptomatic vs symptoms
By severity: cirrhotic vs non-cirrhotic
compare hepatic and cholestatic liver disease
h = liver tissue
c = more to do with bile ducts
most are mixed
give 4 ways we might get acute liver injury
Hepatitis A, B or E
Epstein Barr Virus
drug overdose = paracetamol
vascular problems e.g., hepatic thrombosis
compare acute liver damage and acute liver failure
damage = recovery is likely
failure = complete lack of function = need transplant
give some causes of chronic liver damage, and what might this lead to
alcohol
viral (hep B,C)
autoimmune
Vascular
metabolic = NAFLD, iron, copper
leads to cirrhosis and chronic liver failure
give some examples of presenting factors of acute liver injury
Asymptomatic (mainly)
abnormal LFTs &coagulopathy
Malaise, nausea, anorexia
Jaundice
Confusion – think ALF !
Bleeding - rare
Upper right Liver pain - rare
give some signs and symptoms of chronic liver damage
abnormal LFTs
hepatomegaly,
malaise, abdo discomfort
itching
Ascites, oedema
Haematemesis (varices)
Easy bruising (coagulopathy)
Jaundice
Confusion
Anorexia, wasting
give some important markers tested in LFTs (5)
LFT = liver function tests
Albumin
ALT – Alanine Aminotransferase
AST – Aspartate Aminotransferase
Bilirubin
Globulin
what is indicative of ALT and AST increase to 1000’s from blood tests
liver failure
what two proteins found in the blood would be in the thousands with liver failure
ALT and AST
what two liver enzymes are increased when drinking alcohol
ALT and AST
what 2 blood tests can be done, other than enzyme/protein markers, to test for ALF
platelet count
INR
what is jaundice (2)
yellow pigmented sclera and skin
due to build of unconjugated bilirubin in the blood
what 2 things can be the cause of jaundice
increased breakdown on RBC = increased bilirubin
liver failure = reduced conjugation of bilirubin
what does pale faces and dark urine mean
reduced steroicobilogen
reduced bilirubin conjugation = liver failure
briefly explain the breakdown of haemoglobin and metabolism of bilirubin
haemoglobin = haem and globin (in spleen)
haem = iron and bilirubin (liver or spleen)
unconjugated biliburin attached to albumin is conjugated in liver
travels down intestine, 10% reabsorbed, most is converted to sterocobiligen = brown pigment in feces
of the re-absorbed 10%, half is metabolised in kidney as urobiligen (yellow pigment in urine)
why does dark urine and pale feces indicate liver disease
post-hepatic jaundice
reduced conjugated bilirubin = reduced sterocobiligen= brown pigment in faeces
reduced liver metabolism of bilirubin = increased renal metabolism = increased urobiligen = darker urine
what is and what causes pre-hepatic jaundice
jaundice caused by things other than liver
increased substrate = more RBC breakdown
splenomegaly, thallasaemia, sickle cell
Haemolytic anaemia
Gilbert’s syndrome
Criggler-Najjar syndrome
what causes hepatic jaundice
Cirrhosis
Infiltration of the liver by tumours
Acute hepatitis
(viral, alcoholic, autoimmune, drug-induced)
what causes post-hepatic jaundice
Post-hepatic, or obstructive jaundice, happens when bilirubin can’t be drained properly into the bile ducts or digestive tract because of a blockage therefor overflows into blood (and gets metabolised in kidneys more = dark urine)
give some causes of post-hepatic jaundice
Gallstones
External compression:
-pancreatitis
-pancreatic tumour
-ampullary tumour
what are the most common causes of chronic liver disease
NAFLD & NASH
Alcohol
Viral hepatitis (B, C - cause chronic)
what are NAFLD and NASH
NAFLD = non-alcoholic fatty liver disease
NASH = nonalcoholic steatohepatitis
compare NAFLD and NASH
both caused by fatty diets and have fatty liver
NAFLD = little, no inflammation
NASH = inflamationa and pre-cirrhotic hepatitis
what is wilsons disease involved with
copper deposits on the liver = chronic liver damage
give some risk factors of NAFLD
Hypertension, diabetes, high alcohol, obesity
what autoimmune disease can affect the liver and who is more likely to get this
autoimmune hepatitis - affect more women ~ middle-aged 10:1
what can an ultrasound of the liver look at
bile duct blockage
cirrhosis
big spleen
portal hypertension
Metastasis
how many units of alcohol class as binge drinking, safe limit, hazerdous drinking
> 10 in one sitting = binge
<14 over three days = safe
28 = hazardous
how many units of alcohol class as binge drinking, safe limit, hazerdous drinking
> 10 in one sitting = binge
<14 over three days = safe
28 = hazardous
what is the commonest, and rising commonest cause of liver disease
alcoholic liver disease
NAFLD is on the rise and is often un-recognised
why does fat cause liver damage
fat deposits on the liver = more likely to get blood clots
enlarged liver = need more blood supply
hypertension
cirrhosis
what hepatitis viruses cause chronic liver damage and how many people worldwide have this
Only hepatitis B and C generally can cause chronic hepatitis = 500 million people worldwide are infected with Hepatitis B or C
how can we reduce HCV
PREVENTION = screening blood donations, no IV drug use, wear gloves and cross contamination control
treat = 90% of pts within 8-12 weeks
no vaccine
how can we reduce HCV
PREVENTION = screening blood donations, no IV drug use, wear gloves and cross contamination control
treat = 90% of pts within 8-12 weeks
no vaccine
what year did blood donations start getting screened for e.g. hep C
1991
what are the three stages of scarring of the liver
NCPH = non-cirrhotic portal hypertension
Often due to vascular problems in the liver
Tolerating bleeding well and clotting generally intact;
Relatively rare (patients generally aware)
Pre-cirrhotic
No effect on dental work
May be asymptomatic
Liver cirrhosis
Compensated & decompensated
compare compensated and uncompensated cirrhosis
compensated= Invisible
Blood can be normal
Risk low
uncompensated= Visible
Big belly, thin limbs
Jaundice
high alcohol take
Abnormal blood tests
Risks high
what is ascites
bloating and swollen tummy (liver cirrhosis)
as time goes on, what changes with liver disease and how do we use these to score liver disease
bilirubin increases
albumin decreases
risk of ascites and encephalopathy increase
INR increases
used in child pugh scoring
what is the child pugh score
bilirubin
albumin
INR
Ascites
Encephalopathy
use of all these factors to classify grade of cirrhosis
what is the implication of a child-pugh score of C
mortality increases to 50% in two years if child-pugh C
what is the major cancer found in liver
hepatocellular carcinoma
what is palmer erythema and what is it related to
red palms of hands
many diseases - liver disease
what are and what causes spider navaei
red marks on skin = small clumps of blood vessels which appear on the surface of the skin
found in many diseases, late cirrhosis
what are and what causes spider navaei
red marks on skin = small clumps of blood vessels which appear on the surface of the skin
found in many diseases, late cirrhosis
what does >10 spider naevi above the chest =?
high risk of hypertension
why might liver damage cause Gynaecomastia
liver is involved in testosterone production
testosterone inhibits oestrogen
if testorone reduces and oestrogen increases, breatss may form
Gynecomastia is men growing breasts
what is gynaecomastia
men growing breasts due to low testosterone and high oestrogen
what does hypoalbuminemia cause
white nail beds
sign of liver disease
what is a cause of white nail beds
hypoalbuminaemia
could be due to liver disease
how might we tests for decompensation liver failure encephalopathy
pt will be confused
Pt may struggle with sleep cycle, change in personality, not able to concentrate, worse with infection = confusion
ask to count back from 100 in 7sor draw 5 sided star
OR test for albumin levels
how do we treat the symptoms of liver disease (3)
Diuretics = removes ascites
Nutrition support
Supplements
Propranolol = reduced portal hypertension
how does liver disease effect us as dentists
possible contamination of hep B
prescribing drugs metabolised in the liver
increased toxicity of drugs metabolised in the liver
what drugs must we avoid with liver failure patients
NSAIDs, anticoagulants or antiplatelets - any drug that cause coagulopathies
increased DILI with Flucloxacillin and Co-Amoxyclav
what two antibiotics ahve increased DILI
drug induced liver injury
Flucloxacillin and Co-Amoxyclav
how much paracetamol is safe for patient siwht liver disease
3g a day, not 4
