Liver Flashcards
What is Jaundice?
↑ Serum bilirubin
(visible at >35umol/L)
Ix Jaundice
- Dark urine, pale stools, itching?
- Look for symptoms
Biliary pain, rigors, abdomen swelling, weight loss - Past history
Biliary disease, malignancy, HF, blood products, autoimmune disease - Drugs history
If started drugs/herbs recently - Social history
Alcohol?
Family history?
Potential hepatitis contact? - Irregular sex, IVDU, exotic travel, certain foods
–
Liver enzymes - if high AST/ALT suggests liver disease
Biliary obstruction
Imaging - CT, MRCP, ERCP
Types of Jaundice
Describe
1. Pre-hepatic - XS breakdown of Hb (∴ ↑ unconjugated bilirubin)
2. Hepatic - hepatocytes fail to take up, metabolise or excrete bilirubin
3. Post-hepatic - Obstruction in biliary system
Unconjugated or conjugated bilirubin?
What’s the stool & urine look like?
in Pre-hepatic Jaundice
↑Unconjugated bilirubin
Normal stool and urine
Unconjugated or conjugated bilirubin?
What’s the stool & urine look like?
in Hepatic Jaundice
↑Unconjugated and conjugated bilirubin
Dark urine
Normal/pale stools
Unconjugated or conjugated bilirubin?
What’s the stool & urine look like?
in Post-hepatic Jaundice
↑Conjugated bilirubin
Dark urine
Pale stools
Causes of Pre-hepatic jaundice
More haemolysis
e.g. malaria, sickle cell anaemia, foetal Hb in newborns
Causes of Hepatic Jaundice
Viral hepatitis, drugs, alcohol, cirrhosis
Causes of Post-hepatic jaundice
Gallstones
Pancreatitis - head of pancreas blocks CBD
Describe urine, stools, itching and Liver tests in Pre-hepatic Jaundice
Describe urine, stools, itching and Liver tests in Hepatic/Post-hepatic Jaundice
What is fulminant hepatic failure?
Clinical syndrome
Results from massive necrosis of liver cells
∴ severe impairment of liver function
What is compensated liver failure?
When liver can still function effectively
No/Few noticeable clinical symptoms
Causes Liver Failure
Infections - Viral Hep (B, C, CMV), yellow fever, leptospirosis
Drugs - Paracetamol ovedose, halothane, isoniazid
Toxins - carbon tetrachloride, amanita phalloide mushroom
Vascular - Budd-Chiari
–
OTHER - Alcohol, Non-alcoholic steatohepatitis
Immune - autoimmune hepatitis, 1° biliary cholangitis, sclerosing cholangitis
Metabolic - haemochromatosis, Wilson’s, alpha-1-antitrypsin deficiency
History for Liver Failure
- Dark urine, pale stools, itching?
- Look for symptoms
Biliary pain, rigors, abdomen swelling, weight loss - Past history
Biliary disease, malignancy, HF, blood products, autoimmune disease - Drugs history
If started drugs/herbs recently - Social history
Alcohol?
Family history?
Potential hepatitis contact? - Irregular sex, IVDU, exotic travel, certain foods
Ix Liver Failure
Viral serology - Hep B surface Ag, hep C Ab, EBV, CMV etc
Immunology - Autoantibodies (ANA, AMA, ASMA, coeliac Abs) & immunoglobulins
Bloods - LFTs, FBC, U&E, clotting (↑PT/INR), glucose
Iron/Copper studies
Alpha-1-antitrypsin level
USS/CT/MRI/Doppler flow studies of portal vein
Microscopy - blood/urine culture, if neutrophils > 250/mm3 could be spontaneous bacterial peritonitis
IF ascites, peritoneal tap w/ microscopy & culture
Tx Liver Failure
TREAT CAUSE!
Conservative - analgesia, fluids
–
Protect airway! - intubate
Also, NG tube (avoid aspiration) & remove blood from stomach
Urinary/Central vein catheters to assess fluid state
LIVER TRANSPLANT!!!
–
TREAT COMPS!
Describe the progression of Acute and Chronic Liver Failure
Comps Liver Failure
& How would you treat?
Seizures - phenytoin
Encephalopathy - lactulose
Ascites - diuretics
Cerebral oedema - mannitol
Sepsis - Abx
Hypoglycaemia - dextrose
Bleeding - VitK + blood
What is decompensated liver disease?
How does it present?
List some causes
When liver is so damaged, cannot function adequately
Presents with overt clinical complications - jaundice, ascites, variceal haemorrhage
AKA chronic liver failure
Causes : infection, portal vein thrombosis, surgery
What is leukonychia?
White discolouration on nails (due to hypoalbuminaemia)
What is Xanthelasma?
Yellow fat deposits under skin
Around eyelids usually
Causes Portal HTN
Pre-hepatic - due to blockage of portal vein before liver
Portal vein thrombosis
Intra-Hepatic - distortion of hepatic architecture
Cirrhosis
Schistosomiasis
Sarcoidosis
Congenital hepatic fibrosis
Post-Hepatic - venous blockage outside of liver
RHF
Constrictive pericarditis
IVC obstruction
Budd-Chiari
Pathophysiology of Portal HTN
After liver injury and fibrogenesis (e.g. bc of cirrhosis), contraction of activated myofibroblasts occurs
(Mediated by endothelin, NO + prostaglandins)
∴ ↑ resistance to blood flow
∴ PORTAL HTN
∴ splanchnic vasodilation
∴ ↓ BP
To compensate, ↑cardiac output
Also, ↑salt+water retention to ↑blood vol
∴↑Hyperdynamic circulation (↑portal flow)
∴ formation of collateral vessels! between portal + systemic systems
Signs / Symptoms Portal HTN
Usually asymptomatic!
High SAAG?
Ascites
Splenomegaly
Formation of collateral vessels ∴ variceal bleeding!
Hepatic encephalopathy - bc toxins in general circulation
Tx Portal HTN
General : Alcohol abstinence, good nutrition
To manage ascites : Fluid restriction, low-salt diet
Manage variceal bleeding
Surgery - reroute blood flow (Portosystemic shunting)
Liver transplant
What are the 3 key histological characteristics of Cirrhosis?
- Loss of normal hepatic architecture
- Nodular regeneration
- Bridging fibrosis
Causes Cirrhosis
COMMON :
Chronic alcohol abuse
Non-alcoholic fatty liver
Hep B +/- D
Hep C
Less common :
1° biliary cirrhosis
Autoimmune hepatitis - presents w ↑ALT
Hereditary haemochromatosis
Wilson’s
Alpha-1-antitrypsin deficiency
Drugs e.g. amiodarone, methotrexate
RF Cirrhosis
Chronic alcohol abuse
Obesity
T2DM
Hep B +/- C
Signs / Symptoms Cirrhosis
Compensated - asymptomatic obvs
General, non-specific e.g. malaise
Decompensated -
Jaundice!
Pruritus
Abdo pain - bc of ascites
Bruising
White discolouration on nail - Leukonychia
Clubbing
Xanthelasma
Palmar erythema
Dupuytren’s contractures
Ascites
Oedema
Why do oesophageal varices form?
PORTAL HYPERTENSION
Cirrhosis
Thrombosis
Schistosomiasis
Signs / Symptoms Varices
Only symptomatic if they rupture + bleed!
Haematemesis
Melaena
Rectal bleeding
Bloody stool
Pallor
Light-headedness
LoC if severe
Signs of chronic liver damage (+ splenomegaly, ascites)
Ix Varices
UPPER GI ENDOSCOPY
Tx Oesophageal varices
Urgent endoscopy!
Fluid resus - bleeding can be huge
Blood transfusion if very anaemic
BB - reduce CO ∴ ↓ Portal pressure
Nitrate - cause vasodilation ∴ ↓ Portal pressure
Terlipressin (ADH analogue) - ↓ Portal pressure
Correct clotting abnormalities - VitK and platelet transfusion
GS!! ENDOSCOPIC THERAPY - band ligation or scleropathy
Prophylaxis Oesophageal Varices
Trans-jugular intrahepatic portoclaval shunt (TIPS)
Propanolol
Don’t drink alcohol
Healthy diet + weight
Reduce risk of hepatitis - no sharing of needles or unprotected sex
Gallstones RF
5 Fs
Fat
Fair
Female
Fertile
Forty
Signs / Symptoms Gallstones
Asymptomatic!
Can be temporary - stone could dislodge from cystic duct!
Severe colicky RUQ pain
May radiate to epigastric or back
Triggered by meals (esp fatty meals)
Lasts 30 mins - 8 hours
N+V
Can present with comps
Why does eating fatty meals trigger RUQ pain with gallstones?
Bc when eating fatty foods, cholecystokinin (CCK) is secreted from duodenum
CCK triggers gallbladder contractions
∴ causes biliary colic (RUQ pain)
∴ Patient advised to avoid fatty foods!!
↑ Bilirubin presents as?
Jaundice
What does ↑Bilirubin indicate?
Bilirubin = waste product of haemoglobin breakdown!
∴ indicates : Blockage in bile excretion pathway (cholestatic jaundice)
Esp with Pale stools + dark urine
& XS bilirubin breakdown (pre-hepatic jaundice)
& Breakdown in bilirubin metabolism (hepatocellular jaundice)
What is ALP associated with?
Liver
Biliary system
Bones
Placenta (∴pregnant women may have ↑ALP)
What does ↑ALP indicate?
OBSTRUCTION of biliary system (esp with RUQ pain +/- Jaundice)
ALSO : 1° biliary cirrhosis, liver/bone malignancy, Paget’s
AST & ALT are enzymes produced in the ?
And therefore … ?
Liver
∴ markers of hepatocellular injury
What would you expect AST/ALT and ALP levels to be like in Gallstones?
(↑) AST/ALT
↑↑ALP
= OBSTRUCTIVE PICTURE
What would you expect AST/ALT and ALP levels to be like in a Hepatitic Picture?
↑↑ AST/ALT
(↑) ALP
= HEPATOCELLULAR INJURY
i.e. problem within liver
Ix Gallstones
LFTs - ↑ALP
(Bilirubin and ALT is usually normal)
FBC, CRP - look for inflammatory response (which suggests cholecystitis)
Amylase - Check for pancreatitis
GS - US!
Duct dilation, stones, gallbladder wall thickness
CT would not provide results so don’t say that at all in exams
Limitations of US to diagnose gallstones
If ↑weight/obese
Gas obstructs view
Discomfort of Px
Tx Gallstones
NSAIDs/Analgesia Cholecystectomy (usually laparascopic)
What is acute cholecystis?
When gallstone blocks cystic duct or GB neck
Pathophysiology Acute cholecystitis
When CCK signals (after fatty meal), gallbladder walls contract
Causes gallstones to get lodged in cystic duct
∴ BILE STASIS
Chemical irritant
∴ can stimulate mucosa in wall to stimulate inflammatory responses + mucus release
∴ inflammation
∴ Pressure builds up + distention of gallbladder causes symptoms
Signs / Symptoms Acute cholecystitis
RUQ pain - may radiate to right arm
Muscle guarding, tenderness
Murphy’s sign
N+V
Fever, fatigue (inflammation)
What is Murphy’s sign?
Tenderness that is worse upon inspiration
Ix Acute Cholecystitis
Abdo US - stones, thick GB walls, fluid around GB, shrunken GB
FBC - ↑WBC (∴not biliary colic bc = inflammation)
LFTs - to exclude liver/bile duct pathology
Tx Acute Cholecystitis
Laparoscopic Cholecystomy
Conservative before surgery - aggressive analgesia, IV fluids, IV abx
Comps Acute Cholecystitis
Peritonitis
Bc bacteria can start to grow (e.g. E.Coli) & invade GB wall
What is Ascending Cholangitis?
Inflammation of biliary tree
Pathophysiology of Ascending Cholangitis
Normally bacteria cannot travel up common bile duct bc flow of bile + pancreatic juices
BUT if obstruction occurs = bile stasis
∴ becomes infected and inflamed
Causes Ascending Cholangitis
> Infection of biliary tree -
Most commonly bc 2° to CBD obstruction (gallstones)
> Benign biliary structures -
Following biliary surgery, malignancy, chronic pancreatitis
> 1° sclerosing cholangitis
Signs / Symptoms Ascending Cholangitis
Charcot’s triad / Reynold’s pentad
Rigors
What is Charcot’s triad?
- Jaundice
- Fever
- RUQ pain
What is Reynold’s pentad?
- Jaundice
- Fever
- RUQ pain
- Shock - hypotension, tachycardia
- Confusion
Ix Ascending Cholangitis
US abdo +/- ERCP
> FBC - ↑WBC, ↑ESR/CRP, ↑bilirubin, ↑ALP
(Bilirubin v high if bile duct obstruction)
> Blood cultures - to see which bacteria
> MRCP - to locate stones
> LFTs
> CT
What is ERCP?
Endoscopic Retrograde Cholangiopancreatography
(Biliary tree contrast XR)
What is MRCP?
Basically more detailed US
Tx Ascending Cholangitis
NBM
Treat sepsis - IV Abx, aggressive fluid resus
ERCP & stenting - clear blockage
Shockwave lithotripsy first! if fails, then laparoscopic cholecystectomy
Causes Acute Pancreatitis
I GET SMASHED
Idiopathic
Gallstones
Ethanol (alcohol!)
Trauma
Steroids
Mumps/Malignancy
Autoimmune e.g. SLE
Scorpion stings
Hyperglycaemia/Hypertriglyridaemia
ERCP
Drugs/Meds
Signs / Symptoms Acute Pancreatitis
Sudden, epigastric pain radiating to back
Relieved by sitting forwards
N+V
Cullen’s sign
Grey Turner’s sign
Tachycardia
Abdo guarding & tenderness
Distention
Anorexia
Hyperdynamic instability
Fever, chills
Pathophysiology of Acute Pancreatitis
(Alcohol, Gallstones)
Alcohol - directly toxic to pancreatic cells ∴ causes inflammation !
Also - creates pancreatic juice to become thick + viscous which obstructs pancreatic duct
∴ ↑ Pressure
∴ ducts distend
INFLAMMATION
–
Gallstones - become lodged in sphincter of Oddi
∴ blocks release of pancreatic juices into duodenum
∴ causes INFLAMMATION
Ix Acute pancreatitis
↑ Serum amylase
↑ Serum lipase - more sens than amylase
Urinalysis - ↑urine amylase
Routine bloods, ↑CRP
Abdo US/CT/MRI/XR
XR - no psoas shadow
CT - shows inflammation
–
If lipase:amylase >2 - suggest alcohol cause
If ↑ALT >150 - suggests gallstones
Tx Acute pancreatitis
NG Tube
NBM - ↓pancreatic stimulation
Analgesics
Treat gallstones if present - ERCP/Cholecystectomy
Tx Comps
MONITOR CAREFULLY!
Monitoring Acute Pancreatitis
Why?
Bc repeated acute pancreatitis can cause chronic pancreatitis??
Carefully & regularly
Hourly pulse, BP, urine output
Daily FBC, U&E, glucose amylase
Comps Acute Pancreatitis
Early and Late
Early - Shock, Renal failure, Sepsis
Late - Pancreatic necrosis, Thrombosis in splenic arteries (causes bowel necrosis)
What is the scoring system for Pancreatitis?
APACHE 2
&
GLASGOW scoring system
PaO2 < 8kPa
Age > 55
Neutrophils (WBC >15)
Calcium < 2
uRea > 16
Enzymes (LDH >600 or AST/ALT >200)
Albumin < 32
Sugar (glucose > 10)
0 or 1 - mild pancreatitis
2 - moderate pancreatitis
3 or more - severe pancreatitis
Is chronic pancreatitis reversible or irreversible?
Usually irreversible
Signs / Symptoms Chronic Pancreatitis
Similar to acute but less intense + longer lasting
Epigastric pain - through back, worsens after alcohol, better when leaving forward, might be related to eating
N+V
Steathorroea
Weight loss (malabsorption)
Insulin dependent DM
Causes Chronic Pancreatitis
Repeated bouts of acute
Alcohol abuse
Cystic tumours - main cause in children
Tumours
Pancreatic trauma - knife wounds
What is chronic pancreatitis?
Healthy pancreatic tissue replaced by misshapen ducts, calcium deposits and fibrosis
Ix Acute Pancreatitis
Abdo CT/US/XR
ERCP, MRCP
Bloods - serum amylase/lipase
Might be raised if enough healthy cells to produce
OR might be low bc no healthy cells
Faecal elastase
Tx Chronic Pancreatitis
Lifestyle management - STOP alcohol!
Also, healthy diet, more exercise
Pain control - analgesia
Replace pancreatic enzymes + PPI
Give nutritional supplements
ERCP/Surgery as required - pancreatectomy for unremitting for unremitting pain/weight loss
Insulin
Comps Chronic Pancreatitis
DM
Biliary obstruction
Local arterial aneurysm
Gastric varices
Symptoms of Acute Hepatitis
Can be asymptomatic
General malaise
Myalgia
Abdo pain
GI upset
Jaundice
Tender hepatomegaly
↑AST, ↑ALT, ↑Bilirubin
Signs / Symptoms Chronic Hepatitis
Can be Asx / Non-specific symptoms
+ Chronic Liver Disease
LFTs can be normal
Hepatitis A big stuff
ACUTE
RNA virus
MC acute viral hepatitis
Transmission of Hep A
Faeco-Oral
Contaminated food or water e.g. shellfish
Overcrowding / Poor sanitation facilitate spread
RF Hep A
Shellfish
Travellers
Food handlers
Where is Hep A found?
Africa & S. America
How long is the incubation period of Hep A?
Short incubation period (15-50 days)
Mean = 28 days
Immunity after infection?
Hep A
100% Immunity after infection
Presentation Hepatitis A
Usually symptomatic in adults
PRE-ICTERIC - constitutional Sx + abdo pain
ICTERIC (days to 1week later) - Jaundice! + hepatosplenomegaly
Serology Hep A
First, anti-HAV IgM (non-spec)
Then, replaced by longer lasting HAV-IgM
Ix Hep A
Antibody tests - HAV Abs
Liver biochemistry:
Prodromal - normal serum bilirubin, ↑serum AST/ALT
Icteric - ↑Bilirubin (reflects jaundice)
Bloods :
FBC - ↓WBC
↑ESR
Tx Hep A
Supportive - anti-emetics, rest
Monitoring Hep A
Monitor Liver function (INR, albumin, bilirubin)
Monitoring of close contacts
1° Prevention Hep A
Hep A vaccine
6-12 months after first
e.g. travellers, MSMs, IDU
Comps Hep A
Fulminant Hepatic failure
Acute liver failure
Hepatitis E Big stuff
RNA virus
ACUTE
Can be chronic in immunosuppressed
MC in older men
Where is Hepatitis E common?
Hep E > Hep A IN THE UK
↑Mortality in?
Hep E
Pregnancy
Transmission Hep E
Faeco-Oral route
Water or food borne
Undercooked pork!
Presentation Hep E
> 95% cases asymptomatic
Usually self-limiting
Which Hepatitis are faeco-oral transmitted?
A & E
fAEco-oral
Mortality Hep E
Acute-on-chronic - ↑Mortality
What increases risk of chronic infection with Hep E?
Immunosuppressed
- transplant recipients, HIV Px
- rapid progression to cirrhosis & fibrosis
Ix Hep E
Serology - HEV Abs
Nucleic acid amplification test
What types of Hepatitis virus are notifiable?
ALL TYPES OF VIRAL HEP
What is Acute Liver Failure?
Coagulopathy (INR>1.5) and encephalopathy in an otherwise healthy liver
If only HE, then acute liver injury - not failure
Types of Drug induced Liver injury
Hepatocellular
Cholestatic
Mixed
Value for Hepatocellular DILI
ALT > 2 x normal
or
ALT/ALP > 5
Value for Cholestatic DILI
ALP > 2x normal
or ratio < 2
Value for Mixed DILI
Ratio > 2
but < 5
DILI onset?
Usually between 1 - 12 weeks!
Not less than 1 week usually
Can be several weeks after stopping
DILI - causes
ABX !! - fluclocacillin, TB drugs !
CNS drugs - chlorpromazepine, cabamazepin, valproate
Immunosuppresants
Analgesics/MSK - diclofenac
GI drugs - PPI
What drugs are not rlly involved in DILI?
NSAIDs other than Diclofenac
BB
HRT
ACEi
Thiazides
CCBs
Paracetamol drug name
Acetaminophen
Paracetamol Overdose Pathophysiology
95% of paracetamol :
Undergoes glucuronidation -> Paracetamol conjugate forms -
Tx Paracetamol Overdose
N Acetyl Cysteine (NAC)
Supportive - correst coag defects, electrolytes, renal failure, hypoglycaemia, encephalopathy
What clinical indicators are there that an accidental paracetamol overdose is severe?
Late presentation! - NAC less effective after 24 hours
Acidosis
Prothrombin time > 70 seconds
Serum creatinine > 300 micromol/L
Consider liver transplant!!!!