Liver & Friends Flashcards
1
Q
Describe the drug metabolism of aspirin
A
Phase I: - Hydrolysis reaction: Aspirin + H2O —> Salcylic acid + Ethanoic acid Phase II: - Conjugated with glycine or glucuronic acid - Forms a range of ionised products which can be excreted
2
Q
What is the metabolism reaction of alcohol
A
ADH = alcohol dehydrogenase ALDH = aldehyde dehydrogenase
3
Q
Treatment for paracetamol overdose
A
- Activated charcoal within 1 hour of ingestion - Sticks to paracetmol to ensure it’s not absorbed (adsorption), decreases all intestinal absorption - Followed by IV N-Acetyl Cysteine - Increases availability of glutathione to get rid of excess NAPQI
4
Q
Paracetamol metabolism
A
- 95%: Phase II conjugation -> excreted - 5%: Phase I conjugation -> NAPQI (hepatotoxic) -> Phase II conjugation -> glutathione (antioxidant) -> excreted
5
Q
How does paracetamol overdose work?
A
- Shunting phase 1 pathway as phase 2 is too saturated - Glutathione depleted - Hypertoxicity of NAPQI in liver and inflammation
6
Q
Functions of the liver (ADMIReS)
A
Albumin Detoxification Metabolism of carbs and billirubin Immunity (Kuppfer cells) Regulation of oestrogen levels e Storage (vitamins ADEK, Fe, Cu, fat)
7
Q
Liver function tests (LFTs) - markers of liver function
A
- Bilirubin (mainly unconjugated) - Albumin - Prothrombin time (PT/INR)
8
Q
Direct markers of liver damage
A
High Bilirubin - Low Albumin - High PT/INR
9
Q
Enzymes that show liver damage is likely
A
- AST and ALT - AST:ALT usually around 1
10
Q
Aetiology of acute liver failure
A
- Viral: Viral hepatitis, CMV, EBV - Autoimmune hep (more chronic) - Drugs: paracetamol overdose, alcohol, ecstasy - HCC - Metabolic: Wilson’s, haemochromatosis, A1ATD - Budd Chiari syndrome
11
Q
Aetiology of chronic liver failure
A
- ALD (Most common) - NAFLD - Viral: Hep B, C, D - Budd Chiari syndrome - Drugs - Autoimmine - PBC + PSC
12
Q
Risk factors for chronic liver failure
A
alcohol - Obesity - T2DM - Drugs - Inherited Metabolic diseases/existing autoimmunity
13
Q
Fulminant liver failure
A
- Rare syndrome of massive multiacinar necrosis - Rapid - Caused by paracetamol overdose in 50% of cases in the UK
14
Q
Types of fulminant liver failure
A
Hyperacute - Hepatic encephalopathy within 7 days of jaundice Acute - Hepatic encephalopathy within 8-28 days of jaundice Subacute - Hepatic encephalopathy within 5-26 weeks of jaundice
15
Q
Pathophysiology of acute liver failure
A
- Declined liver function - Liver loses regeneration/repair ability -> irreversibly damaged - In patient with previously normal liver
16
Q
West Haven criteria grades 1-4 of hepatic encephalopathy
A
- Altered mood, sleep problems 2. Lethargy, mild confusion, asterixis, jaundice 3. Marked confusion, solmonence, ataxia 4. Comatose
17
Q
Presentation of acute liver failure and their diagnosis
A
- Jaundice - hyperbilirubinaemia - Coagulopathy - raised PT/INR over 1.5 - Hepatic encephalopathy - EEG - Extent of liver damage: biopsy GOLD STANDARD Top 3 are main characteristics
18
Q
Diagnosis of acute liver failure
A
Bloods - Imaging - Microbiology
19
Q
Bloods for acute liver failure
A
- LFTs show liver damage (High bilirubin, low albumin, high PT/INR) - High serum AST + ALT - High NH3 - Low glucose
20
Q
Imaging for acute liver failure
A
EEG to grade HE - Abdominal ultrasound to check for Budd Chiari syndrome
21
Q
Microbiology for acute liver failure
A
to rule out infections - Blood culture, urine cultire, ascitic tap
22
Q
Treatment of acute liver failure
A
ITU, ABCDE, fluid, analgesia - Treat underlying cause and complications
23
Q
Treatments for complications of liver failure
A
- High ICP: IV mannitol - HE: Lactulose (increases NH3 excretion) - Coagulopathy: Vit K - Ascites: Diuretics, esp spironolactone - Sepsis: Sepsis 6 pathway
24
Q
Assessing prognosis and requierd treatment for chronic liver disease
A
✨Child-Pugh score✨ - Considers bilirubin, ascites presence, serum albumin, PT/INR, hepatic encephalopathy A: 100% 1 year survival B: 80% 1 year survival C: 45% 1 year survival
25
End stage liver failure
Decompensated cirrhosis - A High risk factor for developing hepatocellular carcinoma
26
Presentation of chronic liver failure
- Same as acute + - Portal hypertension - Oesophageal varices - Caput medusae - Spider naevi (Fig.1) - Palmar erythema - Gynecomastia - Clubbing 🕺 - Fetor hepaticus - Dupuytren contracture
27
Diagnosis of chronic liver failure
liver biopsy to determine extent (fibrosis vs cirrhosis) - LFT, Imaging, ultrasound, ascitic tap culture
28
Treatment of chronic liver failure
Prevent progression (decrease alcohol and BMI, avoid Drugs) - Consider liver transplant if Decompensated liver failure - Manage complications
29
Bilirubin metabolism
img
30
Alcohol units
- 1 unit = 8g/10ml pure alcohol - Recommended no more than 14 units a week for both men and women Equation: strength (ABV) x volume (ml) --------------------------------------- 1000
31
Risk factors for alcoholic liver disease
chronic alcohol - Obesity - Smoking - Female gender - Genetic
32
Stages of alcoholic liver disease
img
33
Symptoms of alcoholic liver disease
- Early stages may be asymptomatic Later: - Chronic liver failure symptoms - Alcohol dependency - Hepatomegaly
34
Assessing alcohol dependency
1. Alcohol use disorder ID test: 10 questions 2. Questionnaire with CAGE questions (>2 = dependent!) - Should you cut down? - Are people annoyed by your drinking? - Do you feel guilty about drinking? - Do you drink in the morning? (eye opening)
35
Diagnosis of alcoholic liver disease
Bloods - LFT shows liver damage - High GGT - AST:ALT > 2 - Macrocytic and megaloblastic anaemia Biopsy to confirm extent: - Mallory cytoplasmic inclusion bodies - Inflammation and necrosis in alcoholic hepatitis
36
Conservative treatment for alcoholic liver disease
Healthy diet, lower BMI - Stop alcohol
37
Pharmacological treatment for alcoholic liver disease
- Consider steroids short term (Maddrey's discriminant value of 32) - IV thiamine (Vit B1) so you don’t develop Wernicke Korsakoff syndrome - Could also give folate
38
Surgical treatment for alcoholic liver disease
- Consider liver transplant for ESLF cases - Must have abstained from alcohol for 3+ months
39
Complications of alcoholic liver disease
Pancreatitis - HE - Ascites - HCC - Mallory-weiss tear - Wernicke Korsakoff syndrome
40
What is a hernia?
Protrusion of an organ through a defect in its containing cavity. Typically bowel
41
Reducible vs irreducible hernias
Reducible - can be pushed back into place Irreducible: - Obstructed - intestinal obstruction - Strangulation - intestinal ischaemia - Incarcerated - contents fixed in sac due to size or adhesions
42
Rolling hiatal hernias
20% - LOS stays in the abdomen - Part of fundis rolls into thorax
43
Sliding hiatal hernias
80% - LOS slides into abdomen
44
What is a hiatal hernia?
- Stomach herniates through diaphragm aperture - Obese women and 50+ year olds
45
Symptoms of hiatal hernias
GORD - Dysphagia
46
Diagnosis of hiatal hernias
Barium swallow (diagnostic) - Oesophago gastro duodenoscopy - Chest x-ray
47
Curative treatment for hernias
Surgery
48
What is a femoral hernia?
Bowel herniates through femoral cord - Female, mid-old age - Very likely to strangulate due to rigid femoral canal borders
49
Symptom of femoral hernia
Swelling in upper thigh pointing down
50
Diagnosis of femoral hernia
Abdo/pelvic ultrasound if unsure - BUT usually clinical (based on symptoms)
51
Borders of the femoral TRIANGLE
Sartorius laterally Adductor longus medially Inguinal Ligament superiorly ⛵️
52
Borders of the femoral CANAL (within the femoral triangle
Femoral vein laterally Lacunar ligament medially Inguinal ligament anteriorly Pectineal ligament posteriorly
53
What is an inguinal hernia?
- Spermatic cord herniates through inguinal canal - In males (obviously - History of heavy lifting/abdopressure
54
Direct inguinal hernias
- 20% - In Hesselbach's triangle - Medial to inferior epigastrics
55
Hesselbach's triangle
Rectus abdominis medially Inferior epigastric vessels superiorly/laterally Poupart's (inguinal) ligament inferiorly 🪦
56
Indirect inguinal hernias
- 80% - Not in Hesselbach's triangle - Lateral to inferior epigastrics
57
Symptoms of inguinal hernias
Painful swelling in groin - Points along groin margin
58
Diagnosis of inguinal hernias
- Usually clinical - Unsure = AUSS (CT/MRI)
59
Other types of hernias
- Umbilical (in neonates) - Incisional (surgical scars) - Epigastric - Obturator (Howship-Romberg sign) - Diastasis recti - Spigelian
60
Risk factors for NAFLD
Obesity - T2DM - hypertension - Hyperlipidaemia - Middle aged onwards - Family History - Drugs (NSAIDs, amiodarone)
61
Stages of NFALD
1. Hepatosteatosis (NAFLD) 2. Non-alcoholic steatohapatitis (NASH) 3. Fibrosis 4. Cirrhosis
62
Symptoms of NAFLD
Typically asymptomatic, findings are incidental - if v.severe, present with signs of liver failure
63
Diagnosis of NAFLD
- first line Deranged LFTs (High PT/INR, low albumin, high bilirubin) high everything else - AST:ALT < 1 - FBC: thrombocytopaenia, hyperglycaemia - Enhanced liver fibrosis blood tests if fibrosis suspected (comes under lft) ELF - Abdominal ultrasound to confirm Fib 4 score (second line) - Assess risk of fibrosis using non-invasive method
64
Enhanced liver fibrosis blood test for assessing fibrosis
- Measure three markers - HA, PIIINP and TIMP-1 - <7.7 = none-mild fibrosis - ≥7.7 - 9.8 = moderate fibrosis - ≥9.8 = severe fibrosis
65
FIB-4 score for assessing fibrosis
>2.67 = advanced -> refer to hepatology specialist
66
Management of NAFLD
Weight loss - Exercise - Control diabetes, Blood pressure and cholesterol - Stop Smoking - avoid alcohol - Vitamin E to improve liver function - Pioglitazone to decrease insulin resistance
67
Complications of NAFLD
HE - Ascites - HCC - Portal hypertension - Oesophageal varices
68
Pathophysiology of viral hepatitis
Inflammation of the liver as a result of viral replication within hepatocytes
69
Virus types of Hepatitis
All are single-strand RNA - Apart from hep B, which is double-strand DNA
70
Which hepatitis needs to be notified to Public Health England?
All
71
Spread of Hep A
Faeco-oral spread - Fly vectors - Picornavirus
72
Which types of hepatitis have 100% immunity after infection?
A & E
73
Risk factors for Hep A
Overcrowding - Poor sanitation - Shellfish - Travel - endemic in Africa, Asia, South America, Middle East
74
Pathophysiology of Hep A
- Incubation for 2 weeks - Replicates in liver, excreted in bile - Self limiting within 6 weeks (having it/vaccine gives 100% immunity) - Acute, mild
75
Symptoms of Hep A
Prodromal phase (1-2 weeks): - Malaise - Nausea and vomiting - Fever Then: - Jaundice - dark urine + pale stools - Hepatosplenomegaly - Skin rash
76
Diagnosis of Hep A
Bloods: High ESR + leukopenia - LFT: Bilirubin High when there is Jaundice - Serology: HAV IgM = acutely infected HAV IgG = chronically infected
77
Treatment of Hep A
Supportive (treatment often Not required) - Travellers vaccine available
78
Complications of Hep A (Rare)
Fulminant liver failure😶🌫️
79
Spread of Hep C
Blood-borne and bodily fluids - IVDU - Flavivirus - IVDU more than vertical/sexual transmission - More common in the UK, again common in Africa
80
Symptoms of Hep C
often acutely asymptomatic, allowing it to become chronic Later on - Few patients with flu-like symptoms - chronic causes A sow progressive fibrosis over years + hepatosplenomegaly
81
Diagnosis of Hep C
- LFTs - Serology: HCVRNA = current infection/diagnoses acute infection HCVAb = presents within 4-6 weeks of infection, if present after 6 months then it's chronic
82
Treatment of Hep C
Direct acting antivirals, expensive 💸 - NS5A-inhibitor (acivir) - NS5B-inhibitor (buvir) - Previr
83
Complications of Hep C
30% cases progress to chronic liver failure (cirrhosis and HCC risk)
84
Spread of Hep E
Faeco-oral (undercooked pork) - Water - Dogs - Calicivirus
85
More on Hep E
- Usually self limiting acute hepatitis (95% are asymptomatic) - Commoner than Hep A in the UK (endemic) - Common in Indo-China
86
Complications of Hep E
- Can cause chronic disease in immunosuppressed - Can cause fulminant liver failure: Normal mortality 1-2%Pregnant ladies 10-20% !!!
87
Diagnosis of Hep E
Serology: HEV IgM = acute infection HEV IgG = recovery, only chronic in immunocompromised patients
88
Treatment of Hep E
Supportive, self limiting - vaccine only in China!🇨🇳
89
Spread of Hep D
Intravenous drug use - Sexually transmitted
90
Pathophysiology of Hep D
acute + chronic (like hep B) - Dependant on surface antigen of hep B to replicate, makes hep B more likely to progress to cirrhosis/HCC - Clinically indistinguishable from acute hep B
91
Diagnosis of Hep D
Manifests as co-infection IgM HDV + IgM HBV
92
Treatment and complications of Hep D
Treat hep B - Can also use inteferons BUT Not that good lol
93
Spread of Hep B
- Needles (needlestick injury, tattoo, IVDU) - Sexual - Vertical (mother -> child) - Horizontal (between children) Blood borne and found in semen and saliva
94
Risk factors for Hep B
IVDU - MSM - Dialysis patients - Healthcare workers - present worldwide
95
Symptoms of Hep B
- Similar to Hep A - 1-2 weeks prodrome - Then jaundice (dark urine + pale stools), hepatomegaly, uticaria, arthralgia
96
Pathophysiology of Hep B
- Acute infection infects hepatocyte, cellular response usually clears it - Incubation 1-6 months
97
Serology chart for Hep B
img
98
Hepatitis B antigens and antibodies diagram
img
99
What do all types of hepatitis show?
Interface necrosis "Piecemeal necrosis" on histology (don't ask wjhat it looks like bc idk)
100
Pathophysiology of autoimune hepatitis
chronic inflammation of the liver - aka: lupoid hepatitis, Very Rare - T helper cell mediated response vs hepatocytes
101
Risk factors for autoimmune hepatitis
Female:male, 1:4 - Nitrofurantoin use - Other Autoimmune diseases - Viral hepatitis - HLA DR3 or DR4
102
Type 1 autoimmune hepatitis
- Adult females - 80% of cases - ANA - antinuclear antibody (found in many other autoimmune diseases but very specific for Type 1 autoimmune hep) - ASMA - antismooth muscle antibody
103
Type 2 autoimmune hepatitis
- Young females - Rarer - ALC-1 (antiliver cystosol) - ALKM-1 (antiliver-kidney microsome)
104
Presentation of autoimmune hepatitis
- 25% asymptomatic - Many = jaundice, fever, hepatosplenomegaly - Anorexia - Lupus-like rash
105
Treatment for autoimmune hepatitis
Corticosteroids - prednisolone - Immunosuppressants - azathioprine - hep A+B vaccination (depending on cause) - Last resort - Consider transplant
106
Treatment for Hep B
- Peginterferon alfa-2a - Antiviral therapy - IV Igs for neonates
107
Complications of Hep B
- 5-10% of cases progress to chronic liver failure + HCC risk - HBV-associated decompensation with HCC has the worst prognosis - 90% cases in children become decompested and associated with poor prognosis. TRANSPLANT
108
Progress of chronic liver failure
img
109
Pathophysiology of liver cirrhosis
the result of chronic inflammation and damage to liver cells - when liver cells are damaged, they are replaced with scar tissue, fibrosis, and nodules within the liver - Increased resistance leading to Portal hypertension
110
Aetiology of liver cirrhosis
- Alcoholic liver disease (most common cause in developed world) - Non-alcoholic fatty liver disease - Hepatitis B - Hepatitis C
111
Complications of liver cirrhosis
- Ascites - Portal hypertension - Varices - Jaundice - Spider naevi + caput medusae - Coagulopathy - Hypoalbuminaemia -> oedema - Portosystemic encephalopathy - Hepatorenal and hepatopulmonary syndromes
112
Diagnosis of liver cirrhosis
LFTs show liver damage (Most accurate) - FBC: thrombocytopaenia - ALT, AST, ALP are All Deranged - Definitive = liver biopsy
113
Treatment for liver cirrhosis
Definitive = liver transplant - Conservative: fluids, analgesia, alcohol abstinence, good nutrition - Treat complications
114
Pathophysiology of ascites
Accumulation of fluid in the peritoneal cavity
115
How can liver cirrhosis cause ascites?
- Hypoalbuminaemia (reduced plasma oncotic pressure) - Portal hypertension (increased hydrostatic pressure) - Renal water retention Cirrhosis is the most common cause of ascites (50% of patients develop ascites within 10 years
116
Aetiology of ascites
- Cirrhosis (70%) - Malignancy - Heart failure - TB - Pancreatitis
117
Symptoms of ascites
- Abdominal distension (severe = risk of SBP!) - Pain/discomfort = malignant - Signs of liver disease - May have jaundice and puritis - Shifting dullness
118
Treatment of ascites
Treat underlying cause - Diuretic to increase Na+ excretion (spironolactone) + socium restriction - Paracentesis (or indwelling drain for smaller volume) - Peritoneovenkus Shunting
119
Diagnosis of ascites
- Shifting dullness on exam Imaging: x-ray, uss, CT abdomen Ascitic tap: - Cytology (WCC counts) + MC+S - Protein measurement: transudate + exudate
120
Transudate testing for ascites
- <30g/L protein (low) - Serum albumin ascitic gradient is <11g/L - Clear fluid - Fluid due to high hydrostatic pressure - portal htn, budd chiari, constructive pericarditis, CHF, nephrotic syndrome
121
Exudate testing for ascites
- ≥30g/L protein (high) - Serum albumin ascitic gradient is ≥11g/L - Cloudy fluid - Fluid due to inflammation mediated exudation, or low oncotic pressure - malignancy, peritonitis, pancreatitis
122
Prehepatic jaundice
unconjugated hyperbilirubinaemia due to Increased RBC breakdown - mainly Caused by haemolytic anaemias - urine Bilirubin negative and urobilinogen High
123
Intrahepatic jaundice
Conj/unconj hyperbilirubinaemia, may be mixed - Dark urine - raised Bilirubin in urine and raised bile salts, decrease in urobilinogen - Parenchymal disease: HCC, ALD/NAFLD, hep, hepatotoxic Drugs (eg: rifampicin), Gilbert syndrome, Crigler-Najjar syndrome
124
Post hepatic jaundice
- Conjugated hyperbilirubinaemia due to biliary obstruction - Pale stools + dark urine as bilirubin can't reach GI tract and builds up in urine - Caused by biliary tree pathologies (eg: choledocholelithiasis, cancers) - High bilirubin and low urobilinogen in urine
125
Biliary tree pathology
- Choledocholithiasis - Pancreatic cancer - Cholangiocarcinoma - Mirizzi syndrome - Drug induced cholestasis - Autoimmune (PBC+PSC) - GALLSTONES
126
What is jaundice?
aka: icterus - Yellowing of skin/eyes/mucous membranes due to accumulation of Conjugated or unconjugated Bilirubin - sign of liver dysfunction
127
Four signs to look for when a patient presents with jaundice
- Courvoisier sign - Charcot triad - Reynold's pentad - Murphy sign
128
Murphy sign
RUQ tenderness, ask patient to take A breath in while pressing RUQ - Will wince or Stop inspiring normally in cholecystitis
129
What is pancreatic cancer?
Adenocarcinoma (in Most cases) of the exocrine pancreas - of ductal origin - Typically affects the head of the pancreas
130
Risk factors for pancreatic cancer
- Males - 60+ - Smoking - Alcohol - DM - Family history/genetics (PRSS-1 gene mutation) - Chronic pancreatitis
131
What parts of the pancreas does pancreatic cancer usually target?
head - 60% - Body - 25% - Tail - 15%
132
Presentation of pancreatic cancer of the head
Courvoisier sign - Painless jaundice - Pale stools + dark urine - Palpable gall bladder
133
General presentation of pancreatic cancer
Epigastric pain radiating to the back, worse at night (relieved sitting forward) - Trousseau sign - migratory thrombophlebitis - Weight loss and anorexia - Recent diagnosis of DM - Nausea - Vomiting - Constipation
134
Referral for pancreatic cancer
- Over 40 + jaundice - 2 week wait referral for suspected cancer pathway - Over 60 + weight loss + one other symptom - direct access CT scan within 2 weeks
135
Management of pancreatic cancer
- Mainly palliative due to very poor prognosis, 5 year survival rate of 3% - Surgery (Whipple's procedure) + post-op chemo if no mets
136
Diagnosis of pancreatic cancer
- CT scan and histology from a biopsy - CA19-9 tumour marker (non-specific) - CT TAP scan (thorax, abdomen pelvis) for staging
137
Primary vs secondary liver cancer
Primary - Less common - Cancer that originates in the liver - Hepatocellular carcinoma (90%) and cholangiocarcinoma (10%) - There are also benign primary tumours Secondary - More common - Cancer that originates outside of the liver and metastasises to the liver
138
What does hepatocellular carcinoma (HCC) arise from?
Liver parenchyma
139
Risk factors of HCC
- Chronic hepatitis virus - C and B - Decompensated liver cirrhosis
140
What does HCC metastasise to?
- Lymph nodes, bones, lungs - Via haematogenous spread (hepatic/portal veins)
141
Symptoms of HCC
signs of Decompensated liver failure (Jaundice, Ascites, HE...) - signs of cancer (TATT, unexplained Weight loss, Nausea, vomiting...) - may have irregular hepatomegaly
142
Diagnosis of HCC
High serum AFP - Imagine: first line ultrasound, CT for confirmation - biopsy is diagnostic BUT often avoided to Prevent seeding of tumour elsewhere
143
Treatment for HCC
- Surgical resection of tumour - In decompensative cirrhosis -> liver transplant - Prevantative: Hep B vaccine
144
Types of benign primary tumours
- Hepatic adenoma - Focal nodular hyperplasia - Haemangioma - most common, seen in infants as "strawberry mark" on skin within first few weeks of life 🍓
145
What does cholangiocarcinoma arise from
the biliary tree - Typically adenocarcinomas
146
Risk factors for cholangiocarcinoma
Parasitic flukeworms - biliary cysts - IBD - Primary sclerosing cholangitis
147
Symptoms of cholangiocarcinoma
Abdominal pain - Weight loss - Puritis - Fevers - COURVOISER sign (BUT Pancreatic cancer is usually more comon) 🌌late constellation of symptoms as tumour is slow growing🌌
148
Diagnosis of cholangiocarcinoma
LFT: High Bilirubin, High ALP - High CEA and CA19-9 - first line = Imaging: Abdominal ultrasound + CT - ERCP (Imaging of biliary tree) - invasive BUT Can be therapeutic and diagnostic
149
Treatment of cholangiocarcinoma
Majority of cases inoperable as patients present very late
150
Gilbert's syndrome
Most common in males - T1DM - Autosomal recessive - Most common cause of hereditary Jaundice
151
Pathophysiology of Gilbert's syndrome and Crigler Najjar syndrome
Autosomal recessive - Deficient or abnormal UGT (UDP101), reducing UGT activity - causes an excess in unconjugated hyperbilirubinaemia (in Crigler Najjar, UGT is completely gone)
152
Presentation of Gilbert's syndrome
- 30% asymptomatic - Typically males around 20 - May present with painless jaundice at a young age
153
Symptoms of Crigler Najjar syndrome
- More severe than Gilbert's - Jaundice - Nausea and vomiting - Lethargy
154
Treatment of Gilbert's and Crigler Najjar syndrome
- Gilbert's: Usually no need - CN: Phototherapy to break down unconjugated bilirubim
155
Complications of Crigler Najjar syndrome
more severe progression chances - Can die from kernicterus in childhood - kernicterus is accumulation of Bilirubin in the basal ganglia, causing severe neurological deficits
156
What are gall stones made from?
- Cholestrol (80%) - Pigment - Or mixed
157
Risk factors for biliary tract disease
- Female - Fat (BMI 30+) - Forty (+) - Fertile (pregnant or many children) - Fair also: - Family history - Fatty liver disease (non-alcoholic) - T2DM - Haemolytic conditions
158
Symptoms of gallstones
Colicky or sharp pain - Fever - Jaundice - Dietary upset worse after A fatty meal, may come in episodes
159
Diagnosis of gall stones
Bloods: - Alanine transaminase - Bilirubin - Amylase Then: First line: Abdominal ultrasound to identify gallstones Or: MRCP (MRI scan) or CT abdomen & pelvis
160
Treatment of gallstones
Symptomatic OR asymptomatic and stone blocks CBD: Elective laproscopic cholecystectomy Radiological drain (cholesystostomy) ERCP (endoscopy)
161
Complications of gallstones that may also be signs
acute cholecystitis - acute cholangitis - Obstructive Jaundice - Pancreatitis
162
Symptoms of cholecystitis
RUQ pain - Fever - Tender gallbladder - Referred pain to tip of right shoulder (phrenic) - Murphy sign positive
163
Diagnosis of cholesystitis
- FBC: leukocytosis + neutrophilia - LFT: normal - Abdo ultrasound shows thickened gallbladder wall 3mm≤ and stones/sludge in and fluid around gallbladder
164
Treatment for cholecystitis
- Surgery within 1 week, typically done within 72 hours - via laproscopic cholecystectomy - Until then: IV fluids, analgesia, antibiotics if necessary, nothing by mouth
165
Complications of cholecystitis
Sepsis - gallbladder empyema - Gangrenous gallbladder - Perforation
166
Symptoms of ascending cholangitis
Charcot's triad: - RUQ pain - High fever - Jaundice Reynold's pentad: - Charcot's triad + altered mental state + hypotension
167
Diagnosis of ascending cholangitis
FBC: leukocytosis - LFT: High Conjugated hyperbilirubinaemia - Abdo ultrasound for CBD dilation and gallstones - MRCP: diagnostic
168
Treatment of ascending cholangitis
ERCP (bile duct clearance) - Laproscopic cholecystectomy once stable to Prevent recurrence - Consider risk of Sepsis - Empiricle while waiting Abx - co-amoxiclav
169
MRCP and ERCP
MRCP = Magnetic resonance cholangio-pancreatography ERCP = Endoscopic retrogade cholangio-pancreatography
170
Pathophysiology of primary biliary cholangitis
- Intrahepatic autoimmune jaundice affecting intralobular bile ducts - Autoantibodies cause intralobular bile duct damage; chronic autoimmune granulomatous inflammation - Resulting in cholestasis -> Fibrosis, cirrhosis, portal hypertension, infection
171
Risk factors for primary biliary cholangitis
- Female - 40-50 years old - Other autoimmune disease - Smoking
172
Complications of primary biliary cholangitis
- Malabsorption of fats + vit ADEK (=steatorrhoea) - Ostemalacia - Coagulopathy
173
Symptoms of primary biliary cholestasis
- Initially often asymptomatic - Routine test shows high anti-mitochondrial antibodies - Pruritis + fatigue earliest, then jaundice, then hepatosplenomegaly, + xanthelasma
174
Diagnosis of primary biliary cholangitis
LFT - rule out acute hepatitis by testing for HepBsAg and HVCAb - Serology - rule out extrahepatic cholestasis Via ultrasound - liver biopsy
175
LFT and serology results for primary biliary cholangitis
LFT: - High ALP - High conjugated bilirubin - High albumin Serology: 95% have anti-mitochondrial antibodies (especially M2)
176
Liver biopsy results for primary biliary cholangitis
- Portal tract infiltrate (lymphocyte + plasma cell) - 40% granulamatous - Portal tract fibrosis
177
Treatment for primary biliary cholangitis
Ursodeoxycholic acid (reduces intestinal absorption of cholesterol) - Colestyramine to Treat pruritus - Consider Vitamin ADEK supplements - may ultimately need liver transplant
178
Pathophysiology of primary sclerosis cholangitis
Autoimmune destruction of intra + extralobular hepatic duct - Blocks the flow of bile out of the liver into the intestines - chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis
179
Risk factors for primary sclerosing cholangitis
male - 40-50 - Strong link to IBD (especially ulcerative cholitis)
180
Presentation of primary sclerosis cholangitis
- 50% asymptomatic until disease advances - Charcot's sign - Pruritis - Fatigue - Hepatosplenomegaly - IBD
181
Diagnosis of primary sclerosing cholangitis
- Cholestatic LFT - GS imaging: MRCP - Biopsy same as PBC Serology: - HBVsAg/HCVAb -ve - AMA -ve - Coelic screen anti tTG -ve - pANCA +ve in 33-88%
182
Treatment of primary sclerosing cholangitis
Conservative: - Colestyramine for pruritis - Fat soluble ADEK - ERCP to dilate and stent structures - Consider liver transplant
183
Causes of acute pancreatitis
Idiopathic Gallstones Ethanol🍾🍷🍻 Trauma Steroids Mumps/malignancy Autoimmune Scorpion stings Hypercalcaemia/hyperlipidaemia ERCP Drugs (azathiprine, NSAIDs, ACE inhibitors, tobacco, thiazides)
184
Pathophysiology of acute pancreatitis
- Gall stones obstruct pancreatic secretions - Accumulated digestive enzymes in pancreas - Host defences soon overwhelmed - Causes autodigestion -> inflammation + enzymes leak in blood
185
Symptoms of acute pancreatitis
Sudden severe Epigastric pain radiating to the back (DDx: Abdominal aortic aneurysm) - Nausea and Vomiting - Jaundice - Pyrexia - Steatorrhoea - Grey Turner sign and Cullen sign
186
Diagnosis of acute pancreatitis
- Blood test first line: High serum amylase/lipase - Cxr to eclude gastroduodenal perforation - Abdo ultrasound -> diagnostic for gall stones; CT/MRI for extent of damage
187
Glasgow score for severity of acute pancreatitis
PaO2 < 8KPa Age > 55 Neutrophils (WBC > 15x109/L) Calcium > 2mmol/L Renal urea > 16mmol/L Enzymes (LDH > 600iu/L or AST > 200iu/L) Albumin < 32g/L Sugar, glucose > 10mmol/L 0-1 - mild pancreatitis 2 - moderate pancreatitis 3+ - severe pancreatitis
188
Treatment for acute pancreatitis
- Rescuscitation if required - IV fluid - IV analgesia - IV antibiotics for infection/associated cholangitis - Nil by mouth - ERCP within 72 hours of pain onset if required
189
Main complication of acute pancreatitis
Systemic inflammatory response syndrome (SIRS) 2 ≤ out of: - Tachycardia (90+ bpm) - Tachypnoea (20+ RR) - Pyrexia (38°c <) - High WCC
190
Acute vs chronic pancreatitis
Acute - Reversible acute inflammation of the pancreas Chronic - 3+ month history of pancreatic deterioration - Irreversible pancreatic inflammation + fibrosis
191
Causes of chronic pancreatitis
- Alcohol (mc) Also: - CKD - CF - Trauma - Recurrent acute pancreatitis - Cancer - Autoimmune
192
Symptoms of chronic pancreatitis
Epigastric pain radiating to back - exacerbated by alcohol - exocrine (eg: Steatorrhoea) and endocrine (eg: T2DM) dysfunction - Pseudocysts or abscesses DDx: Pancreatic cancer, especially of Body and Tail
193
Diagnosis of chronic pancreatitis
Faecal elastase Low (indicator of exocrine function) - Abdo ultrasound and CCT to detect Pancreatic calcification and dilated Pancreatic duct (diagnostic)
194
Treatment of chronic pancreatitis
alcohol cessation - Dietary modification - analgesia for Abdo pain, first line = NSAIDs - Pancreatic supplements (eg: enzymes, insulin for DM) - ERCP or Surgery if required
195
Pathophysiology of portal hypertension
- Normal pressure in portal vein = 5-8mmHg - Cirrhosis = increased resistance to flow, leads to splanchnic dilation and compensatory increased CO - Fluid overload in portal vein (10+ = bad, 12+ = very bad)
196
Causes of portal hypertension
Prehepatic: Portal vein thrombosis Intrahepatic: Cirrhosis (mc in UK), schistomiasis (mc worldwide) Post hepatic: Budd chiari, RHS heart failure, constrictive pericarditis
197
Symptoms of portal hypertension
- Mostly asymptomatic - Present when oesophageal varices rupture - (90% of portal hypertension cases develop oesophageal varices, 1/3 of these rupture)
198
Pathophysiology of oesophageal varices
Portal hypertension results in collateral Blood Shunting to gastroesophageal veins - Typically small, become Oesophageal varices at the cardia and lower oesophagus
199
Presentation of haemorrhage of oesophageal varices
Haematemesis (vomiting blood) DDx: Mallory-Weiss tear - Tear in oesophageal mucosa - Very acute history - Increased abdominal pressure
200
Diagnosis of oesophageal varices
Oesophagogastroduodenoscopy
201
Acute treatment for oesophageal varices
Acutely: - Resus until haemodynamically stable - Consider blood trasfusion (Hb < 70g/L or <80g/L w cardiac comorbidity)
202
Stopping bleeding of oesophageal varices
1. IV terupressin (SST is CI) 2. Variceal banding 3. Transjugular intrahepatic portosystemic shunt - decreases portal pressure by diverting blood to other larger veins, SE = hepatoencelopathy
203
Preventing bleeding of oesophageal varices
Non-selective beta blocker (eg: propanolol) + nitrates - Repeat variceal banding - Last resort: liver transplant (decompensate cirrhosis)
204
Primary and secondary peritonitis
Primary - Ascites - Spontaneus bacterial peritonitis (infection) (mc) Secondary - Underlying cause, eg: bile, malignancy Peritonitis can also be classified as acute or chronic
205
Bacterial causes of SBP
Gram -ve = e.coli + klebsiella (colliform rods) - Gram +ve = stap.aureus (cocci)
206
Chemical causes of SBP
bile - old clotted Blood - Ruptured ectopic pregnancy - intestinal Perforation (which get ultimately infected)
207
Presentation of SBP
Sudden onset severe abdo pain (and shoulder tip pain) then collapse + septic shock, fever - Rigidity helps pain (DDx: renal colic) - Poorly localised -> more localised + ascities usually Symptoms and signs of underlying conditions
208
Diagnosis of SBP
- Ascitic tap shows neutrophilia - Cultures (mc+s) show causative organism - High ESP and CRP - Exclude pregnancy as cause (b-hCG test) and bowel obstruction (abdo xR) - Cxr shows air under diaphragm -> indicates perforated colon
209
Treatment of SBP
- Treat underlying cause; IV fluid + IV antibiotics - Urinary catheterisation + GI decompression - IV Broad spectrum antibiotic therapy - Analgaesia - Surgery = peritoneal lavage
210
Complications of SBP
Septicaemia if Not treated Early - Subphrenic/pelvic abscesses - Paralytic ulcers
211
Pathophysiology of haemachromatosis
- Autosomal recessive mutation of HFE gene (chromosome 6) - Excess Fe uptake by transferrin-1 and low hepcidin synthesis (hepcidin regulates Fe homeostasis) - Fe accumulation and fibrosis of liver (+ pancreas, kidney, heart, skin, ant. pituitary)
212
Normal Fe vs Fe in haemochromatosis
- Normal: 3-4g - Haemochromatosis: 20-30g
213
Risk factors for haemochromatosis
- Male - 50s - Genetics - Can be due to excess transfusions (secondary)
214
Symptoms of haemochromatosis
fatigue - Joint pain - Hypogonadism (due to anterior pituitary damage) - Slate Grey/bronze skin - liver cirrhosis symptoms - Osteoporosis - Heart failure
215
Gross Fe overload triad
bronze statue skin - hepatomegaly - T2DM
216
Diagnosis of haemochromatosis
- Fe studies - Genetic test - Liver biopsy (assess degree of damage with Perl's Prussian blue stain)
217
Fe studies results in haemochromatosis
High serum Fe - High ferritin - High transferrin saturation - Low total iron-binding capacity
218
Treatment of haemochomatosis
- First line: Venesection 3-4 times a year for life - If contraindicated; desfernoxamine (chelation therapy) - Lifestyle, decrease Fe in diet, avoid fruits
219
Pathophysiology of Wilson's disease
- Autosomal recessive mutation of ATP7B gene on chromosome 13 - Impaired biliary copper excretion and transport bound to caeruloplasmin - Excess Cu accumulation in liver, basal ganglia and cornea
220
The three features of Wilson's disease
Hepatic - Chronic hepatitis - Liver cirrhosis Neurological - Assymetrical parkinsonism - Memory issues - Dysarthria and dystonia - Depression - Full psychosis Opthamological - Kayser-Fleischer rings - Cu deposits in in cornea, greenish brown ringed appearance
221
Diagnosis of Wilson's disease
- 24 hour urine Cu tests: low serum copper and caeruloplasmin - AST:ALT >4.5 - Liver biopsy - High Cu, hepatitis - MRI brain: cerebellar + basal ganglia degeneration
222
Management of Wilson's disease
- 1st line - D-Penicillinamine (Cu chelation, lifelong) - Diet change: avoid food high in Cu, shellfish, mushroom - Last resort -> liver transplant
223
Pathophysiology of alpha 1 antitrypsin (A1AT) deficiency
- Autosomal recessive muttion of serdina-1 gene (protease inhibitor) on chromosome 14 causes deficiency of A1AT - A1AT normally inhibits NE, NE degrades elastic tissue Lungs: - Degrades elastic tissue - Alveolar duct collapse - Air trapping - Characteristic panacinar emphysema Liver: - Soon becomes fibrotic; cirrhosis + HCC risk - A1AT is made by the liver so fibrotic will make synthetic liver function even worse - catch 22
224
Presentation of A1AT deficiency
- Young/mid aged man with little to no smoking history but COPD-like symptoms Lung symptoms: - Dyspnoea - Chronic cough - Sputum production - Barrel chest - Pink puffer Liver symptoms: - Jaundice
225
Diagnosis of A1AT deficiency
- Serum A1AT < 20mmol/L - Barrel chest on exam, cxr shows hyperinflated lungs - CT = panacinar emphysema - LFT shows obstruction (FEV1:FVC < 0.7) - Genetic testing
226
Treatment for A1AT deficiency
if Smoking, Stop - Manage ephysema, eg: inhalers (SABAs and LABAs) - Consider hepatic decompensation patients for liver transplant
227
What is SAAG?
- Serum albumin ascites gradien - SAAG >1.1g/dL = portal hypertension, suggesting nonperitoneal cause of ascites
228
Acute vs chronic hepatitis
- Acute: First 6 months of liver inflammation - Chronic: Any inflammation beyond 6 months
229
Aetiology of gall stones
- Cholesterol supersaturation (diet, hormones) - Genetic (gallbladder motility) - Haemoglobin turnover (haemolytic anaemia, cirrhosis, sickle cell) 10% of people have gallstones And they acount for 30% of all acute presentations
230
Management of gall stones if not treating directly/straight away
NSAIDs for mild pain - IM diclofenac for severe pain - Change lifestyle - decrease Fat in diet
231
Functions of the peritoneum
In health: - Visceral lubrication - Fluid and particulate absorption In disease: - Pain perception - Inflammatory and immune response - Fibrinolytic activity
232
What is spontaneous bacterial peritonitis?
Peritonitis (infection of the peritoneum), that happens without a hole or a tear. Ascitic fluid is affected
233
Classification of ascites
Stage 1: Detectable only after careful examination/uss Stage 2: Easy detectable but relatively small volume Stage 3: Obvious, not tense ascites Stage 4: Tense ascites (large)
234
Cause of failure with lung pathology
Alpha 1 antitrypsin deficiency
235
Compensated vs decompensated cirrhosis
Compensated - liver is able to override ability to function
236
Ammonia
Neurotoxic - causes irreversible brain damage - Because it stops the Krebs cycle
237
Symptoms of liver failure
RUQ pain - hepatomegaly - Jaundice - Nausea and Vomiting - Ascites - Bruising or muscle wasting
238
What is it called when a gall stone is trapped in the common bile duct?
Choledocholelithiasis
239
Investigations for jaundice
- Bloods - LFTs - First line imaging - ultrasound Normally:- No bilirubin in urine - Urobilinogen in urine
240
Pathophysiology of ALD
- Alcohol dehydrogenase enzymes and cytochromes (2 ways of metabolism) - Risk of forming reactive O2 species, more overload = more O2 species - Eventual scar tissue around central veins, adding to portal hypertension
241
Alcohol withdrawal
6-12 hours: tremours, sweating, headaches 12-24 hours: hallucination 24-48 hours: seizures 24-72 hours: delirium tremens (medical emergency)
242
Delirium tremens
alcohol stimulates GABA receptors and inhibits glutamate receptors - chronic alcohol leads to upregulation of glutamate receptors and downregulation of GABA receptors - Treat wirh IV Chlordiaepoxide or diazepam
243
What is the name of the cells responsible for fibrosis?
Stellate
