Gastroenterology Flashcards
1
Q
What is liver cirrhosis?
A
Chronic inflammation and damage
Cells replaced with scar tissue
Nodules of scar tissue form
Affects structure an blood flow through liver, increasing resistance- Portal HTN
2
Q
What are the 4 most common causes of liver cirrhosis?
A
Alcoholic liver disease
Non-alcoholic fatty liver disease (NAFLD)
Hep B
Hep C
3
Q
What are the rarer causes of liver cirrhosis?
A
AI hep
PBC
Haemochromatosis
Wilson’s disease
Alpha-1 antitrypsin deficiency
CF
Amiodarone, methotrexate, sodium valproate
4
Q
List examination findings of liver disease
A
Cachexia- Wasting of body and muscles
Jaundice- Raised bilirubin
Hepatomegaly
Small nodular liver
Splenomegaly- Due to portal HTN
Spider naevi- Telangiectasia with central arteriole and small vessels radiating away
Palmar erythema- Elevated oestrogen
Gynaecomastia and testicular atrophy- Endocrine dysfunction
Bruising- Abnormal clottingExcoriations
Ascites
Caput medusae- Distended paraumbilical veins due to portal HTN
Leukonychia (white fingernails)- associated with hypoalbuminaemia
Asterixis- Flapping tremor- Decompensated liver disease
5
Q
Outline a non-invasive liver screen
A
Done following abnormal LFTs without a clear cause
US liver- Fatty liver
Hep B and C serology
Autoantibodies- AI hep, PBC and PSC
Immunoglobulins- AI hepatitis and PBC
Caeruloplasmin- Wilsons disease
Alpha-1 antitrypsin levels
Ferritin and transferrin (hereditary haemochromatosis)
6
Q
Which autoantibodies are relevant to liver disease?
A
ANA
Smooth muscle antibodies
Antimitochondrial antibodies
Antibodies to liver kidney microsome type 1 (LKM-1)
7
Q
What happens to LFTs in decompensated cirrhosis?
A
(Can be normal if not decompensated)
Deranged bilirubin, ALT, AST, and ALP
8
Q
Which other bloods should be done for liver cirrhosis other than LFTs?
A
Low albumin- Due to reduced synthetic function of liver
Increased prothrombin time- Due to reduced synthetic function of liver (decreased production of clotting factors)
Thrombocytopenia (low platelets)- Indicates more advanced disease
Hyponatremia (low sodium)- Occurs with fluid retention in severe liver disease
Urea and creatinine- Deranged in hepatorenal syndrome
Alpha-fetoprotein- Tumour marker for hepatocellular carcinoma
9
Q
What is the 1st line investigation for assessing fibrosis in non-alcoholic fatty liver disease?
A
Enhanced liver fibrosis (ELF) blood test
Measures HA, PIIINP, TIMP-1
>10.51 - Advanced fibrosis
Recheck every 3y
9
Q
How does liver cirrhosis present on US?
A
Nodularity on surface of liver
Corkscrew appearance to hepatic arteries with increased flow to compensate for reduced portal flow
Enlarged portal vein with reduced flow
Ascites
Splenomegaly
10
Q
What are the screening tools used for hepatocellular carcinoma?
A
US
Alpha-fetoprotein
10
Q
How does non-alcoholic fatty liver disease present on US?
A
Increased echogenicity
11
Q
What is a transient elastography?
A
‘Fibroscan’
Assesses stiffness of liver using high-frequency sound waves
Determines degree of fibrosis to test for liver cirrhosis
12
Q
What can happen to the oesophagus in portal HTN?
A
Oesophageal varices
13
Q
When is the MELD score used?
A
Model for End-Stage Liver Disease
Used every 6 mths in compensated cirrhosis
Bilirubin, creatinine, INR, sodium, and whether they require dialysis
Gives an estimated 3mth mortality %
14
Q
What is the Child-Pugh Score?
A
Assesses severity of liver disease and prognosis
Minimum score 5, maximum 15- Each scored 1-3
A- Albumin
B- Bilirubin
C- Clotting (INR)
D- Dilation (ascites)
E- Encephalopathy
15
Q
Which underlying causes need to be addressed for liver cirrhosis?
A
Stop drinking alcohol
Lifestyle changes for non-alcoholic fatty liver disease
Antiviral drugs for Hep C
Endoscopy every 3y for oesophageal varices
16
Q
How do you monitor for complications of liver cirrhosis?
A
MELD score every 6mths
US and AFP every 6mths for hepatocellular carcinoma
Endoscopy every 3y for oesophageal varices
17
Q
When is a liver transplant considered in liver cirrhosis?
A
In decompensated liver disease
A- Ascites
H- Hepatic encephalopathy
O- Oesophageal varices bleeding
Y- Yellow (jaundice)
18
Q
What is the prognosis of liver cirrhosis?
A
5y survival about 50% once cirrhosis developed
19
Q
List complications of cirrhosis
A
Malnutrition and muscle wasting
Portal HTN, oesophageal varices, bleeding varices
Ascites and spontaneous bacterial peritonitis
Hepatorenal syndrome
Hepatic encephalopathy
Hepatocellular carcinoma
20
Q
Why does cirrhosis lead to malnutrition?
A
Loss of appetite due to reduced intake
Cirrhosis affects protein metabolism in liver and reduces amount of protein liver produces
Disrupts ability of liver to store glucose as glycogen and release it when required
21
Q
What is the management of malnutrition in cirrhosis?
A
Regular meals
High protein and calorie intake
Reduced sodium intake to minimise fluid retention
Avoid alcohol
22
Q
Why does cirrhosis lead to portal HTN and varices?
A
Portal vein comes from Sup. mesenteric and splenic veins and delivers blood to liver
Liver cirrhosis increases resistance to blood flow in liver= Increased back pressure- Results in splenomegaly
Causes swollen and tortuous vessels at sites where collaterals form between portal and systemic venous systems- Distal oesophagus (oesophageal varices) and anterior abdo wall (caput medusae)
23
Outline management of varices in cirrhosis
Asymptomatic until start bleeding
High blood flow= Can exsanguinate quickly
Prophylaxis: Propanolol 1st line, variceal band ligation if BB CI
24
How are bleeding oesophageal varices managed?
Immediate senior help
Consider blood transfusion
Treat coagulopathy- FFP
Vasopressin analogues (terlipressin or somatostatin)- Cause vasoconstriction and slow bleeding
Prophylactic broad-spectrum ABs
Urgent endoscopy with variceal band ligation
Consider intubation and intensive care
Sengstaken-Blakemore tube (inflatable tube in oesophagus to tamponade bleeding varices)
Transjugular intrahepatic portosystemic shunt (TIPS)
25
What is a Sengstaken-Blakemore Tube?
Used to stop oesophageal variceal bleeds
Inflatable tube in oesophagus to tamponade bleeding varices
26
What is Transjugular Intrahepatic Portosystemic Shunt (TIPS)?
Used to stop bleeding oesophageal varices or refractory ascites
Interventional radiologist inserts wire via xray guidance into jugular vein, down vena cava into liver via hepatic vein
Connection made through liver between hepatic vein and portal vein and stent inserted
Allows blood to flow directly from portal vein to hepatic vein, relieving pressure in portal system
27
Why does cirrhosis lead to ascites?
Fluid in peritoneal cavity
Increased pressure in portal system causes fluid to leak out of capillaries in liver and other abdominal organs in peritoneal cavity
Drop in circulating volume caused by fluid loss into peritoneal cavity = Reduced BP in kidneys = Release renin = Increased aldosterone secretion via renin-angiotensin-aldosterone system = Reabsorption of fluid and sodium in kidneys = Fluid and sodium retention
Causes TRANSUDATIVE ascites (low protein)
28
Outline management of ascites in liver cirrhosis
Low sodium diet
Aldosterone antagonists (spironolactone)
Paracentesis (ascitic tap/drain)
Prophylactic ABs (ciprofloxacin) when <15g/l protein in ascitic fluid
TIPS considered in refractory ascites
Liver transplant considered in refractory ascites
29
Why can cirrhosis lead to spontaneous bacterial peritonitis?
Occurs in 10-20% patients with ascites
Mortality 10-20%
Infection in ascitic fluid and peritoneal lining w/o clear source of infection
30
What are the symptoms of spontaneous bacterial peritonitis?
Can be asymptomatic
Fever
Abdo pain
Deranged blood- Raised WBC, CRP, creatinine, or metabolic acidosis
Ileus (reduced movement in intestine)
Hypotension
31
What are the most common causative organisms of spontaneous bacterial peritonitis?
E. coli
Klebsiella pneumoniae
32
Outline management of spontaneous bacterial peritonitis
Sample ascitic fluid or culture before giving ABs
IV broad-spectrum ABs (piperacillin with tazobactam)
33
How can cirrhosis cause hepatorenal syndrome?
Impaired kidney function caused by changes in blood flow to kidneys relating to liver cirrhosis and portal HTN
Portal HTn causes portal vessels to release vasodilators = Significant vasodilation in splanchnic circulation = Reduced BP
Kidneys respond to low BP via RAAS = Vasoconstriction of renal vessels = Kidneys starved of blood
34
What is the prognosis and management of hepatorenal syndrome?
Poor prognosis unless liver transplant
35
How can liver cirrhosis cause hepatic encephalopathy?
Build up of neurotoxic substances that affect the brain
AMMONIA- Produced by intestinal bacteria when break down proteins - Absorbed in intestines and builds up
Ammonia build up due to liver cells functional impairment preventing them from metabolising ammonia into harmless waste products and collateral vessels between portal and systemic circulation means ammonia bypasses liver and enters systemic system directly
36
How does hepatic encephalopathy present?
Reduced consciousness
Confusion
Chronic- Changes to mood/personality and memory
37
List factors which can trigger or worsen hepatic encephalopathy
Constipation
Dehydration
Electrolyte disturbance
Infection
GI bleeding
High protein diet
Meds- Sedatives in particular
38
Outline management of hepatic encephalopathy
Lactulose (need 2-3 soft stools/day)
ABs (eg: Rifaximin)- Reduce number of intestinal bacteria producing producing ammonia
Nutritional support (NG tube)
39
Outline the step-wise progression of alcohol-related liver disease
1. Alcoholic fatty liver- Reversible with abstinence
2. Alcoholic hepatitis- Inflammation in liver cells- Binge drinking associated with same effect- Mild usually reversible with permanent abstinence
3. Cirrhosis- Functional liver tissue replaced with scar tissue- Irreversible- Stop drinking to prevent further damage- Continued drinking has poor prognosis
40
What is the recommended alcohol consumption UK?
Do not regularly drink more than 14 units/wk spread evenly over 3+ days and not more than 5units in a single day
Binge drinking = 6+ units women, 8+ units men in single session
41
What can alcohol in pregnancy lead to?
Miscarriage
Small for dates
Preterm delivery
Fetal alcohol syndrome
42
List complications of alcohol
Alcohol-related liver disease
Cirrhosis and its complications (Hepatocellular carcinoma)
Alcohol dependence and withdrawal
Wernicke-Korsakoff syndrome
Pancreatitis
Alcoholic cardiomyopathy
Alcoholic myopathy, proximal muscle wasting
and weakness
Increased risk CVD
Increased risk cancer- Breast, mouth and throat
43
List examination signs suggestive of excessive alcohol consumption
Smelling of alcohol
Slurred speech
Bloodshot eyes
Dilated capillaries on face (telangiectasia)
Tremor
44
Outline potential blood test results of someone with alcoholic-related liver disease
Raised Mean cell volume (MCV)
Raised ALT and AST
AST:ALS ratio > 1.5
Raised gamma-GT
Raised ALP later in disease
Raised bilirubin in cirrhosis
Low albumin due to reduced synthetic function of liver
Increased PTT due to reduced synthetic function of liver (reduced production of clotting factors)
Deranged U&Es in hepatorenal syndrome
45
Outline investigations of alcoholic related liver disease other than bloods
Liver US- May show early fatty changes with increased echogenicity, then cirrhosis
Transient elastography (FibroScan)- Assess elasticity of liver using high frequency sound waves- Determines degree of fibrosis
Endoscopy- Assess and treat oesophageal varices when Portal HTN suspected
CT and MRI scans- Look for fatty infiltration of liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites
Liver biopsy- Confirms diagnosis (esp. if steroid treatment being considered for alcohol-related hep)
46
Outline the general management of alcohol-related LD
Stop drinking
CBT or motivational interviewing
Detoxication regime
Nutrition- Thiamine (B1) and high protein diet
Corticosteroids- Reduce inflammation in severe alcoholic hepatitis- Improves short-term outcomes
Treat complications
Liver transplant
47
When are corticosteroids considered in liver disease?
Severe alcoholic hepatitis- Improves short term outcomes by reducing inflammation
48
What is a requirement for a liver transplant?
6mths abstinence from alcohol
49
What is alcohol dependence?
Daily alcohol consumption
Strong urges and cravings
Difficulty controlling consumption
Tolerance to effects of alcohol
Withdrawal symptoms when stopping
50
Outline the CAGE questionnaire
C- Cut down? Do you ever think you should cut down?
A- Annoyed? Do you get annoyed at others commenting on your drinking?
G- Guilty? Do you ever feel guilty about drinking?
E- Eye opener? Do you ever drink in the morning to help your hangover or nerves?
51
Outline the timeline of alcohol withdrawal
6-12h: Tremor, sweating, headache, craving, anxiety
12-24h: Hallucinations
24-48h: Seizures
24-72h: Delirium tremens
52
What is the pathophysiology of delirium tremens?
Alcohol is a depressant
Alcohol stimulates GABA receptors in brain which relax brain
Alcohol inhibits glutamate receptors (NMDA receptors) which relaxes brain
Chronic use= GABA system down-regulated, Glutamate system up-regulated- When alcohol removed, GABA system under functions and glutamate system over functions= Extreme excitability of brain and excessive adrenergic activity (adrenaline)
53
Outline the presentation of delirium tremens
Acute confusion
Severe agitation
Delusions and hallucinations
Tremor
Tachycardia
HTN
Hyperthermia
Ataxia (difficulty coordinating movement)
Arrhythmias
54
How is alcohol withdrawal managed?
Chlordiazepoxide (benzo)- Give orally as reducing regime titrated to required dose- Reduce over 5-7d
High dose B vitamins (Pabrinex) given IM/IV followed by long term oral thiamine- Prevents Wernicke-Korsakoff syndrome
55
What causes Wernicke-Korsakoff Syndrome?
Alcohol excess leads to thiamine (B1) deficiency
Thiamine poorly absorbed in presence of alcohol
56
List features of Wernicke's encephalopathy
Confusion
Occulomotor disturbances
Ataxia (difficulty coordinating movement)
57
Outline features of Korsakoff syndrome
Memory impairment (retro and anterograde)
Behavioural changes
58
What is the prognosis of delirium tremens w/o treatment?
35% mortality rate
59
What can non-alcoholic fatty liver disease progress to?
Hepatitis or cirrhosis
60
Outline the stages of NAFLD
1. NAFLD
2. Non-alcoholic steatohepatitis
3. Fibrosis
4. Cirrhosis
61
What are the risk factors for NAFLD?
Middle age
Obesity
Poor diet and low activity levels
T2D
High cholesterol
High BP
Smoking
62
Which syndrome is NAFLD associated with?
Metabolic syndrome
63
What is metabolic syndrome?
Combination of HTN, obesity and diabetes
63
What is often the first indication a patient has NAFLD?
Raised ALT
64
Which markers does the enhanced liver fibrosis (ELF) blood test measure?
HA
PIIINP
TIMP-1
65
What is the NAFLD fibrosis score (NFS) and what is it based on?
Assesses liver fibrosis in NAFLD
Age/BMI/AST and ALT/platelet count, albumin, diabetes
66
What is the fibrosis-4 (FIB-4) score and what does it use?
Assesses liver fibrosis in NAFLD
Age/AST and ALT/platelet count
67
When is transient elastography used in NAFLD?
When ELF test indicates advanced fibrosis
Determines degree of fibrosis and tests for cirrhosis
68
Which ratio of AST:ALT indicates which liver diseases?
Normal ratio <1
> 0.8 in NAFLD = Advanced fibrosis
>1.5 (disproportionately high AST) = Alcohol-related LD
69
How is NAFLD definitively diagnosed?
US findings of fatty liver
Risk factors
Exclude other causes- Alcohol history and full non-invasive liver screen
Liver biopsy- Gold standard
70
Outline management of NAFLD
Weight loss
Mediterranean diet
Exercise
Avoid alcohol
Stop smoking
Control diabetes/BP/cholesterol
Refer if fibrosis
Specialist- Vit E, pioglitazone, bariatric surgery, liver transplant
71
Which hepatitis' are there vaccines for?
Hep A and Hep B
72
Which hepatitis' are RNA?
Hep A, Hep C, Hep D, Hep E
73
Which hepatitis' are DNA?
Hep B
74
How is Hep A transmitted?
Faecal-oral route
75
How is Hep B transmitted?
Body fluids
76
How is Hep C transmitted?
Blood
77
How is Hep D transmitted?
With Hep B
78
How is Hep E transmitted?
Faecal-oral route
79
How is Hep A treated?
Supportive
80
How is Hep B treated?
Supportive/antivirals
81
How is Hep C treated?
Direct-acting antivirals
82
How is Hep D treated?
Pegylated interferon alpha- Over at least 48wks
Has significant SEs and not very effective
83
How is Hep E treated?
Supportive
84
What are the other causes of hepatitis?
Alcoholic hepatitis
Non-alcoholic steatohepatitis (NASH)
AI hepatitis
Drug-induced (eg: Paracetamol overdose)
85
Outline presentation of hepatitis
Viral may be asymptomatic
Abdo pain
Fatigue
Flu-like illness
Pruritis (itching)
Muscle and joint aches
N+V
Jaundice
86
Outline a 'hepatic picture' on LFTs
High transaminases (AST and ALT)
Proportionally less of a rise in ALP
87
Why are transaminases released?
Liver enzymes released into blood due to inflammation of liver cells
88
What other than transaminases also rises as a result of inflammation of liver cells?
Bilirubin
89
How does Hep E present and how is it managed?
Usually produces mild illness
Virus cleared within a month
No treatment required
Rarely progresses to chronic hep and liver failure- Usually in immunocompromised
90
Why does Hep D only survive in patients with Hep B?
Attaches to HBsAg and can't survive w/o this protein
91
What can Hep A lead to?
Cholestasis- Pruritis, significant jaundice, dark urine, pale stools
92
What is cholestasis?
Slowing of bile through biliary system
93
What are the symptoms of cholestasis?
Pruritis
Significant jaundice
Dark urine
Pale stools
94
How is Hep A diagnosed?
IgM antibodies
95
How is Hep A managed?
Usually resolves w/o treatment
Rarely leads to acute liver failure (fulminant hepatitis)
Management- Supportive, basic analgesia
96
What is fulminant hepatitis?
Severe liver function impairment causing hepatic coma and decrease in synthesizing capacity of liver
Develops within 8wks onset of hepatitis
97
Can Hep B be passed to the baby through pregnancy or breastfeeding?
Pregnancy and delivery- Yes (vertical transmission)
Breastfeeding- Low risk
98
What is the progression of Hep B?
Most fully recover within 1-3mths
5-15% become chronic Hep B carriers
99
What does Surface antigen (HBsAg) indicate?
Active Hep B infection
100
What does E antigen (HBeAg) indicate?
Implies high infectivity
101
What do core antibodies (HBcAb) indicate?
Past or current infection
102
What does surface antibody (HBsAb) indicate?
Vaccination/past infection/current infection
103
What is Hepatitis B virus DNA (HBV DNA) used for?
Direct count of viral load
104
What are the initial screening tests for Hep B?
HBcAb (previous infection) and HBsAg (active infection)
If positive- Check HBeAg and HBV DNA
105
What is the purpose of checking HBcAb?
Distinguishes acute/chronic/past infections
IgM- Active infection (high titre)
IgG- Indicates past infection where HBsAg negative
106
Outline management of Hep B
Low threshold for screening
Screen for other viral infections
Refer to gastro/hepatology/infectious diseases
Avoid alcohol
Education about reducing transmission
Contact tracing
Test for cirrhosis and US for hepatocellular carcinoma
Antivirals to slow progression and reduce infectivity
Liver transplant if liver failure
107
How is Hep C managed?
Antivirals- Sofosbuvir, daclatasvir
108
What is the prognosis of Hep C w/o treatment?
25% full recovery
75% chronic Hep C
109
What are the complications of Hep C?
Liver cirrhosis
Hepatocellular carcinoma
110
How is Hep C diagnosed?
Screening- Hep C antibody
Hep C RNA testing- Confirms diagnosis- Calculate viral load and identify genotype
111
Outline type 1 AI hepatitis
Type 1- Women in late 40s, presents after menopause with fatigue and features of liver disease, less acute than type 2
112
Outline type 2 AI hepatitis
Type2- Affects children/young people, more common in girls, acute, high transaminases and jaundice
113
List the autoantibodies in type 1 AI hepatitis
Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (anti-actin)
Anti-soluble liver antigen (anti-SLA/LP)
114
List autoantibodies in type 2 AI hepatitis
Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antigen type 1 (anti-LC1)
115
What are the findings on liver biopsy of AI hepatitis?
Interface hepatitis
Plasma cell infiltration
116
What is shown on bloods in AI hepatitis?
High transaminases (AST and ALT)
Minimal change in ALP
Raised IgG
117
Outline management of AI hepatitis
High-dose steroids (prednisolone)
Azathioprine (immunosuppressant)- To induce remission
Liver transplant- In end-stage LD- Can reoccur in new liver
118
What is haemochromatosis?
Autosomal recessive condition resulting in iron overload
Excessive total body iron and deposition of iron in tissues
119
Outline genetics of haemochromatosis
Autosomal recessive
Human haemochromatosis (HFE) gene on Chr 6
C282Y mutation
120
Outline presentation of haemochromatosis
Chronic tiredness
Joint pain
Pigmentation (bronze skin)
Testicular atrophy
Erectile dysfunction
Amenorrhoea
Memory and mood disturbance
Hepatomegaly
121
When does haemochromatosis present?
After age 40 when overload becomes symptomatic
Later in females due to menstruation eliminating iron from body regularly
122
List causes of raised ferritin
Haemochromatosis
Infections
Chronic alcohol consumption
NAFLD
Hep C
Cancer
123
How is haemochromatosis diagnosed?
Serum ferritin- Raised
Transferrin saturation- High (in other causes of raised serum ferritin= Normal level)
Genetic test- HFE gene
Liver biopsy- Perl's stain establishes iron conc. in liver
MRI- Can quantify iron conc. in liver
124
List complications of haemochromatosis
Secondary diabetes (iron affects pancreas)
Liver cirrhosis
Endocrine and sexual problems (hypogonadism, ED, amenorrhoea, reduced fertility)
Cardiomyopathy (iron deposits in heart)
Hepatocellular carcinoma
Hypothyroidism (iron deposits in thyroid)
Chondrocalcinosis (calcium pyrophosphate deposits in joints) causes arthritis
125
What is the management of haemochromatosis?
Venesection (wkly removal blood to remove excess iron)
Monitor serum transferrin
126
What is Wilson's disease?
Autosomal recessive accumulation of copper, particularly in liver
127
Outline the genetics of Wilson's disease
Autosomal recessive
Mutation in Wilson disease protein gene on Chr 13 (ATP7B copper-binding protein)
This protein helps remove excess copper from body via liver
Copper excreted in bile
128
When does Wilson's disease present?
In teenagers or young adults
Rare for symptoms to start after 40y
129
Outline initial presentation of Wilson's disease
Liver issues arise first
Rarely can present initially with neuro or psychiatric problems
130
Outline presentation of Wilson's disease
Liver- Chronic hepatitis, cirrhosis
CNS- Tremor, dysarthria (speech difficulties), dystonia (abnormal muscle tone)
Copper deposition in basal ganglia- Parkinsonism (tremor, bradykinesia, rigidity
Kayser-Fleischer rings in cornea
Haemolytic anaemia
Osteopenia
Renal tubular damage
131
Outline diagnosis of Wilson's disease
Serum caeruloplasmin- Low (can be falsely elevated in cancer or inflammatory conditions)
24h urine copper assay- High urinary copper
Liver biopsy
Kayser-Fleischer rings
MRI brain- Double panda sign
Low Hb with haemolytic anaemia (negative Coombs test)
Genetic testing
132
What is the characteristic sign on MRI of Wilson's disease?
Double panda sign
133
Outline management of Wilson's disease
Copper chelation- Penicillamine or trientine
Zinc salts (inhibit copper absorption in GI tract)
Liver transplant
134
What is the pathophysiology of Alpha-1 antitrypsin deficiency?
Alpha-1 antitrypsin is a protease inhibitor
A protease enzyme is neutrophil elastase which digests elastin (protein in CT that keeps tissue flexible)- Alpha-1 Antitrypsin (AAT) offers protection by inhibiting neutrophil elastase
In lungs lack of functioning AAT leads to excess protease attacking CT
135
Outline the inheritance of alpha-1 antitrypsin deficiency
Autosomal co-dominant inheritance (both gene copies expressed and contribute to outcome- Neither is dominant or recessive)
136
Outline effect of alpha-1 antitrypsin deficiency on the lungs
Destruction of elastic tissue in lungs = Bronchiectasis and emphysema (smoking accelerates process)
137
Outline effect of alpha-1 antitrypsin deficiency on the liver
AAT is produced in liver
Abnormal mutant version made in certain AAT deficiency and gets trapped/builds up inside liver cells- Toxic to hepatocytes causing inflammation- Progresses to fibrosis/cirrhosis/hepatocellular carcinoma
138
What are the less common associations of AAT deficiency?
Panniculitis- Tender skin nodules caused by inflammation of subcutaneous fat
Granulomatosis with polyangiitis- Small and medium vessel vasculitis
139
How is AAT deficiency diagnosed?
Low serum AAT- Screening test
Genetic testing
140
How is lung damage assessed in AAT deficiency?
Chest xray
High resolution CT thorax
Pulmonary function tests
141
What can a liver biopsy show in AAT deficiency?
Periodic acid-Schiff positive staining globules in hepatocytes, resistant to diastase treatment
142
Outline the management of AAT deficiency
Stop smoking
Symptomatic management- Standard treatment of COPD
Organ transplant for end-stage liver/lung disease
Monitor for hepatocellular carcinoma
Screen family members
143
What is primary biliary cholangitis?
AI condition
Immune system attacks small bile ducts in liver
Results in obstructive jaundice and liver disease
144
Outline pathophysiology of primary biliary cholangitis
Affects small bile ducts (intrahepatic ducts)- Inflammation and damage to epithelial cells of bile ducts (cholangiocytes)
Over time leads to obstruction of bile flow through these ducts= Cholestasis
Back pressure of bile and disease process leads to liver fibrosis/cirrhosis/failure
145
How does primary biliary cholangitis affect bile?
Bile acid/bilirubin/cholesterol excreted through bile ducts into intestines
Obstruction means build up in blood
Raised bile acids in blood- Itching, raised bilirubin, jaundice
Decreased bile acids in GI tract- Abdo symptoms, malabsorption of fat, greasy stools
146
How does primary biliary cholangitis affect cholesterol?
Raised cholesterol
Xanthelasma- Cholesterol deposits in skin
Xanthomas- Larger deposits of cholesterol in skin or tendons
Increased risk atherosclerosis and CVD
147
What colour is stool in cholestasis and why?
Pale
Bilirubin makes stool dark- Lack of bilirubin = Pale stools
Excretion of bilirubin via urine= Dark urine
148
Who is more at risk of getting primary biliary cholangitis?
White women
40-60y
149
How does primary biliary cholangitis present?
Fatigue
Pruritis
GI symptoms and abdo pain
Jaundice
Pale, greasy stools
Dark urine
150
Outline presentation of primary biliary cholangitis on examination
Xanthoma and xanthelasma
Excoriations
Hepatomegaly
Signs of liver cirrhosis and portal HTN in end stage disease- Splenomegaly and ascites
151
What are the key investigation findings of primary biliary cholangitis?
Antimitochondrial antibodies (AMA)
Alkaline phosphatase
152
Middle aged white woman- Itching, positive AMA, raised ALP
Primary biliary cholangitis
153
How is primary biliary cholangitis diagnosed?
LFT- Raised ALP (obstructive pathology), other liver enzymes and bilirubin raised later in disease
Autoantibodies- AMA (most specific), ANA (present in 35%)
Raised IgM (non-specific)
US- Helps exclude other pathology
Liver biopsy- Diagnose and stage disease
154
Outline treatment of primary biliary cholangitis
Ursodeoxycholic acid- Non-toxic, hydrophilic bile acid that protects cholangiocytes from inflammation and damage- Makes bile less harmful to epithelial cells of bile ducts, slows disease progression
Colestyramine for pruritis
Replace fat soluble vitamins
Immunosuppression (steroids)
Liver transplant in end-stage liver disease
155
What is a key complication of primary biliary cholangitis?
Liver cirrhosis
156
What are the other complications of primary biliary cholangitis?
Fat-soluble vit deficiency (A, D, E, K)
Osteoporosis
Hyperlipidaemia (raised cholesterol)
Sjogren's syndrome (dry eyes, dry mouth, vaginal dryness)
Connective tissue disease (systemic sclerosis)
Thyroid disease
157
