liver middle tier Flashcards
acute vs chronic hepatitis time-wise
acute = <6m chronic = 6m +
signs and symptoms of acute hepatitis
- none/few
- malaise
- lethargy
- myalgia
- GU/ abdom pain - RUQ
- jaundice (pale stool, dark urine, itch)
- ascites
- tender hepatosplenomegaly
- bleeding
- encephalopathy
- high bilirubin
- high ALT/AST
signs and symptoms of chronic hepatitis
- none/few
- clubbing
- palmar erythema
- spide naevi
- signs of decompensated liver
- – coagulopathy, jaundice, low albumin, ascites, encephalopathy
causes of hepatitis
- split into acute and chronic
ACUTE
infectious
- hepatitis A,B,C,D,E (c= less so, more chronic)
- herpes, EBV, CMV, VZV
- non viral - toxoplasmosis, coxiella, leptospirosis
non infectious
- alcohol, drugs
- toxins / poisons
- pregnancy
- autoimmune
- metabolic, heridatry - Wilsons, A1AT def
CHRONIC infectious - hepatitis B,C,D (A+ E= acute only) non infectious - alcohol, drugs - autoimmune - metabolic, heridatry - Wilsons, A1AT def
hepatitis LFTs
hepatitis complications
may be normal! may be high in acute
hepatocellular carcinoma
portal hypertension
– varices, bleeding, ascites
hep A epidemiology
- where
- commonness
LIC, poor sanitation (Africa, S america)
most common Hep worldwide
hep A risk factors
travel food handler sexual shellfish poor sanitation, overcrowding drug use, lick needle first household contacts of infected
hep A pathophysiology
- spread
- incubation
- virus
- acute/ chronic
- other features
- faeco-oral spread
- short incubation period - 2-6w
- RNA
- self limiting, ONLY acute. + 100% immune once had
- rarely results in liver failure
hep A diagnosis
anti HAV antibodies IgM - acute marker I gG = marker of past infection / vaccine + immunity \+ billirubinuria \+ nausea \+ fever
hep A management / prevention
- good prognosis
- supportive treatment
- – close contacts –> vaccine, immunoglobulins
- – avoid alcohol
- – monitor liver function
- notify public health
- hygiene inc boil water
- vaccine
hep E epidemiology
- age
- gender
- where
- mortality
indonesia
endemic in UK
older men
mortality high in preg
hep E pathophysiology
- spread
- incubation
- virus
- acute/ chronic
- other features
- two strands. GT1/2 spread in contaminated food/water (faecooral). GT3/4 spread in undercooked meat, pigs, rodents, dogs
- RNA virus
- self limiting - only chronic in immunosuppressed and GT3/4. 100% immune after infection
hep E diagnosis
anti HEV antibodies
IgM - acute marker
I gG = marker of past infection / vaccine + immunity
+ neurological manifestations
hep E management/ prevention
- supportive treatment
- – close contacts –> vaccine, immunoglobulins
- – avoid alcohol
- – monitor liver function
- notify public health
vaccine
thorough meat cooking, sanitation/hygiene
dont be immunocomprimised
hep B epidemiology
worldwide - esp Africa, mediterranean, Far East, common
hep B pathophysiology
- spread
- incubation
- virus
- acute/ chronic
- other features
- very infectious
- blood
— sex esp MSM
— needle (needle stick , IV drug use, dialysis, tattoos)
— vertical (mum to baby)
+ semen/saliva - incubation period 1-6m
- DNA!! only one not rna
- can cause acute + chronic (most resolves alone though)
hep B AND D risk factors
healthcare/ emergency proffesion dialysis - CKD travellesrs tattoo lads MSM IV drug use
Hep B diagnosis
anti HBV antibodies
IgM - acute marker
I gG = marker of chronic infection/ previous infection (may not be resolved)
+ HBsAG (hep B surface antigen - produced by hepatocytes)
+ rashes
+ anorexia
hep B AND D management/ prevention
- supportive treatment
— close contacts –> vaccine, immunoglobulins
vaccine for hep B. (NO vaccine for hep D)
— sex contacts/ preg mum –> vaccine
— avoid alcohol
— monitor liver function - notify public health
pegylated interferon subcut if chronic
nucleotide analogues - inhibit viral replication
hep D epidemiology
where
E europe, N africa
hep D pathophysiology
- spread
- incubation
- virus
- acute/ chronic
- other features
- blood borne (sex, needles, vertical)
- RNA (but incomplete)
- needs hep B to be present to exist (activation, assembly, replication)- so acquired with hep b
- can be acute or chronic
hep B and D - coinfection/ superinfection
coinfection = hep b acute + hep D
- indistinguishable from hep b acute
- igM present got anti HBV and HDV
superinfection = hep B chronic + hep D
- severe - risk of fulmiant hepatitis –> liver failure
- fibrosis
- high AST/ALT
- secondary acute hep
hep C epidemiology
-where
Egypt
hep c risk factors (inc transmission type)
- blood : IV drug users, blood transfusion before 1991 (before blood product screening),
- limited sex transfusion but MSM more severe infection
- alcohol –> more severe infection
hep c pathophysiology
- spread
- virus
- acute/ chronic
- other features
- blood transmission,
limited sex transmission
rare vertical transmission - RNA
- majoirty = chronic –> cirrhosis, hepatocellular carcinoma, liver failure
minority= acute , resolves alone - doesn’t stimulate v good immune response
hep c diagnosis
acute – HCV RNA
chronic / was infected – HCV IgG
hep c treatment / prevention
prevention
- no vaccine! (C, D don’t have)
- reduce risk factors (needles, blood screening etc)
destroy virus :
- pegylated interferon subcut if chronic
nucleotide analogues - inhibit viral replication
- antiviral
diarrhea red flags
blood in stool family history of cancer chronic weight loss old
diarrhea onset if cause is worms
slower
what is the most common cause of infective diarrhea in uk
viral
norovirus - anyone, epidemics as v contagious
rotavirus - childen, vaccine given to baby
travellers diarrhea
- relation to travel
- main cause
- symtoms
- from trip start up to 10 days after return
- bacteria mainly - ecoli
- diarrhea
- naus/vom
- fever
- cramps
- bloody stool
enterotoxin mediated bacteria diarrhea
- affects where
- pathophys
- effect
- eg
- upper bowel
- bacteria –> enterotoxins –> increase intracellular AMP–> cells secrete fluid–> watery, voluminous diarrhoea
- dehydration
- cholera, c.diff
invasive bacteria diarrhea
- affects where
- pathophys
- effect
- eg
- large bowel
- penetrate intestinal mucosa
- bloody stool
- shigella, salmonella
infective diarrhea risk factors
- travel
- low hygiene person/ workplace etc
- children who attend preschool
- health workers
- immunocomprimised
- hobbies/ occupation (fresh water swimming, chef)
- food/drink (street foot, sea food)
- contact with animals
- taken antibiotics (wipe gut flora out so bad bacteria more able to flourish)
infective diarrhea investigation
history inc pain where
Stool sampleS
- Microscope
- Culture
- blood/pus/eggs (ova)
- Toxin detection -toxin positive = infectious
Bloods
- Inflammatory markers
- Blood cultures
what is faecal transplant used to treat
C.diff
to replenish bacteria
cholera treatment
doxycycline
infective diarrhea general treatment
- Hydrate inc electrolytes
- Wait - normally self limiting
- Sometimes antibiotics
- Sometimes need to notify public health
- Sometimes barrier – + their family etc
non-infective causes of diarrhea
hormonal neoplasm inflammatory irritable bowel chemical radiation anatomical
bristol stool chart- which end is which
1 (hard) -7 (liquid)
dys/meta/neoplastic
meta –> dys –> neo
meta= reversible replacement of one differentiated cell type with another dys= appear abnormal but not cancer neo = tumour (benign/malignant)
enteric fever aka typhoid fever
- where in world
- cause
- spread
- symptoms
- treatment
- complications
- S Asia, poor sanitation
- salmonella typhoid
- faeco-oral
- high fever
- general/ RLQ pain
- headache
- myalgia
- bradycardia
- rose spots
- constipation
- antibiotics
- surgery - emergency
- vaccine
- GI bleed,
- abscesses
- myocarditis
haemochromatosis causes
Genetic:
- C282Y mutation and H63D mutation on the HFE gene, recessive (low penetrance so screening not advised)
- this causes deficiency of iron regulation hormone = hepcidin
- rarely not genetic, but guess these thing may precipitate/ worsen:
- high iron intake (ascrobic acid, )
- blood transfusion needs iron chelation
- alcoholic
haemochromatosis
- race
- gender
m>f (menstruation protective)
C282Y mutation more common if white
wilsons cause/ risk factor
mutation in ATP7B (needed to remove excess copper) , recessive
consanginuity
wilsons
- commonness
- age
- rare
- 20-30
A1AT deficiency more common in what race
cause
white populations
genetic
haemochromatosis pathophysioogy
- low levels of hepcidin (regulating hormone)
- high iron uptake due to increased intestinal uptake
- exceeds binding capacity of transferring
- iron is deposited in liver, heart, pancreas –> fibrosis
A1AT deficiency pathophysiology
- alpha-1-antitrypsin deficiency
heamochromatosis symptoms
- Not many
- Fatigue , weakness
- Weight loss
- Joint pain- arthropathy from psuedogout
- Heart problems
- Erectile dysfunction (hypogonadism)
- absent/irregular periods (hypogonadism)
- Bronzed/grey skin
- Diabetes (iron deposited in pancreas :/ )
- splenomegaly/ hepatomegaly
- cirrhosis –> failure due to deposition here
haemochromatosis investigations
- Screening not advised as v low penetrance
- Genotyping (look at genetic make up of them)
- Liver biopsy
- Bloods
- – Raised serum ferritin/iron
- – transferrin saturation ratio raised (total iron binding capacity reduced)
- MRI - can detect iron overload
- ECHO/ECG if cardiomyoptahy is suspected
haemochromatosis treatment
- Phlebotomy / venesection- removing blood regularly for a lifetime - excess iron then used to make new rbc, reducing excess . and can monitor levels during that time
- Chelation if they cant tolerate that - desferrioxamine
- Testosterone replacement
- Diet: Iron low diet (high in tea,coffee, red wine) and avoid fruit juice, avoid alcohol and uncooked seafood
- Liver transplant if severe
- Insulin (treat diabetes)
- Screen first degree relatives (or not as it is low penetrance)
wilsons pathophysiology
- disorder of copper billiary excretion. unable to move it across out of hepatocyte membranes so it accumulates
- so copper builds up in the liver and CNS
normal copper physiology
- copper absorbed from diet
- transported by albumin
- incorporated into ceruloplasmin glycoprotein
- rest is excreted in bile
wilsons signs/symptoms
- Kayser fleischer ring on eyes = bronze/greenish brown ring on cornea
- Sunflower cataracts
- These are able to be seen with a slit lamp
- acute liver disease / hepatitis/ asterixis
- CNS problems:
- Reduced memory
- Low mood
- Behavioural problems
- Tremor
- Slowed speech = dysarthria
- involuntary movements
- dementia
wilson investgations
- Slit lamp - to detect kayser-fleischer rings and sunflower catarcats
- Low serum caeruloplasmin (what copper is supposed to be converted into without pathology)
- Serum copper can be low/ normal
- High copper in urine
- Liver biopsy
- MRI can see CNS degeneration
wilsons management
- Avoid alcohol, reduce copper intake
- Prevent copper absorption in gut
- – Zinc / penicillamine used as a chelating agent
- – Zinc salts - inhibits copper absorption
- Liver transplant mebs
- Neuro - deep brain stimulation
A1AT deficiency pathophsyiology
- A1AT deficiency = Can’t export alpha1 antitrypsin from liver, so it accumulates in hepatocutes and is low in serum
- A1AT role = inhibits the proteolytic enzyme neutrophil elastase
- neutrophil elastase enzymes lose their inhibition from A1AT. so can break down elastase excessively in liver (cirrhosis, hepatocellular cancer ) and lungs (emphysema)
A1AT def management
No treatment cure
Liver
- stop drinking
- Treat liver disease
- possible liver transplant - if decompensation
Lungs
- Manage emphysema : Bronchodilators for lung
- treat infection
- No smoking
ATA1 def investigations
Serum levels of A1AT
Liver biopsy
A1AT def symptoms
liver:
- Neonatal jaundice
- Liver disease presentation esp in children
- Possible cirrhosis/ failure
lungs:
- COPD-like symptoms, emphysema esp in adults
- Dysnopea, cough, wheeze
hepatocellular carcinoma
- gender
- commonnes
- where
men>women
Common
China
secondary liver tumour
- commonness
common, even more common than hepatocellular carcinoma
pancreatic adenocarcinoma
- gender
- age
males>females
Increase with age (rare below 40, typically 60+)
risk factors for hepatocellular carcinoma
HBV, HCV carriers- high likelihood
Cirrhosis
- Alcohol
- Haemochromatosis
cholangiocarcinoma risk factors
Parasitic worms
Biliary cysts
Inflammatory bowel disease - UC (ulcerative colitis) and Crohns
haemangioma risk factors
Oral contraceptives
Anabolic steroids
Pregnancy
pancreatic adenocarcinoma risk factors
Smoking Excess alcohol/coffee/aspirin Diabetes Pancreatitis Family history Genetic predisposition
what cancers are esp likely to spread to liver
GI tract, bronchus, breast
hepatocellular carcinoma
- what type of cancer
- single or mutliple nodes
- cells resemble?
- metastases?
- primary liver tumour
- single/ multiple nodules in liver
- Cells resemble hepatocytes
- Can metastasize to lymph, bones, lungs via hepatic/portal veins
secondary liver tumour
- single or multiple nodes
normally multiple (As with all secondary tumours)
cholangiocarcinoma
= cancer of where?
- fast/slow
= biliary tree cancer
Slow growing
pancreatic adenocarcinoma
- where
- metasases?
- when does is present
- In epithelium, most in pancreatic head. Majority in exocrine part (releases pancreatic juice)
- Metastasise early
- Present late
hemiangioma
- where
- benign/malignant
- size
- single/ multiple nodes
- liver
- benign
- small and singular normally (but can be multiple /large ones)
symptoms and signs of hepatocellular carcinoma
- jaundice
- Fever
- Enlarged, irregular, tender liver
- Ascites
- Liver disease decompensation
- Weight loss, anorexia
- R hypochondrium ache
- Abdominal pain
- Fatigue
symptoms and signs of secondary liver tumour
- Hepatomegaly
- Jaundice sometimes
- Malaise
- Upper abdom pain
symptoms and signs of pancreatic adencarcinoma
- Anorexia, weight loss
- Change in bowel habit
- Pain if body/tail and radiates to back . No pain if head
- Acute pancreatitis
- Jaundice - if head of pancreas (+stool, urine etc). No jaundice if body/tail
symptoms and signs of cholangiocarcinoma
- Fever
- Malaise
- Abdominal pain
- jaundice
- ascites
hepatocellular carcinoma investigations
- Examination of liver
- Biopsy confirms diagnosis
- CT/ultrasound
- bloods - bilirubin (jaundice), raised LFTs -alkaline phosphate
pancreatic adencarcinoma investgations
- bloods - jaundice,
- CT/MRI/ ultrasound
- biopsy
cholangiocarcinoma investigations
- bloods - bilirubin (jaundice), raised alkaline phosphate
-
secondary liver cancer investigations
- CT/MRI/ultrasound
- alkaline phosphate is raised
hepatocellular carcinoma treatment
Chemo
Transplant
Surgical Resection /local ablation
secondary liver cancer treatment
Depends on where primary is
Sometimes chemo
Sometimes surgery
cholangiocarcinoma treatment
Surgical resection and transplant are NOT good ideas
haemangioma treatment
Need no treatment
Surgery only if symptomatic (intraperitoneal bleeding , abdominal pain)
pancreatic adenocarcinoma treatment
- Low prognosis
- Surgery -pancreatoduodectomy
- – If fit
- – High post - op morbidity
- – Post-op chemo good idea
- Palliative care
- – Jaundice stenting
- – Opiates
- – Nutritional supplements
