PBL ILO’s

Question 1

Complications of untreated coeliac disease

Answer 1

• Vitamin deficiency
• Anaemia
• Osteoporosis
• Ulcerative jejunitis
• Enteropathy-associated T-cell lymphoma (EATL) of the intestine
• Non-Hodgkin lymphoma (NHL)
• Small bowel adenocarcinoma (rare)

Question 2

Management of coeliac disease

Answer 2

• Lifelong gluten-free diet: foods containing gluten include rye, wheat, barley and oats. Dietetic input may be required and should be considered case by case.
• Immunisation: individuals with coeliac disease often have functional hyposplenism (defective immune response) and therefore require pneumococcal vaccines every 5 years. Yearly influenza vaccines may be given to patients, however, this is on a case by case basis.

Question 3

Vitamin A deficiency

Answer 3

Vitamin A
• Obtained from food sources such as carrots, spinach, milk, egg, liver and fish.
• Required for normal vision, reproduction, growth and healthy immune system of an individual
• Most children below 5 years of age will suffer from xeropthalmia, a serious eye disorder, in which the child is at risk of becoming blind
• Vit A deficiency in pregnant woman can lead to complications during pregnancy and childbirth

Question 4

Vitamin B deficiency

Answer 4

Vitamin B
• Vit B1: Deficiency of vit B1 causes beriberi, which results in weak muscles and severe weight loss. Acute deficiency can lead to paralysis and cardiac failure
• Vit B6: Lack of vit B6 causes anaemia and certain skin disorders such as cracks around the mouth. It can also lead to depression and nervous breakdowns.
• Vitamin B12: Lack of vitamin B12 causes pernicious anaemia. Other diseases related to B12 deficiency are muscle and nerve paralysis, extreme fatigue, dementia and depression.

Question 5

Vitamin C deficiency

Answer 5

Vitamin C
• Deficiency of vit C can cause scurvy, a disease that is characterised by bleeding gums, skin spots and swelling in joints. It also affects the immune system and can even be fatal in acute conditions.

Question 6

Vitamin D deficiency

Answer 6

Vitamin D
• Rickets, which leads to weakening of bones, especially near the joints. It can also lead to the decay of teeth

Question 7

Vitamin K deficiency

Answer 7

Vitamin K
• It is important for blood coagulation. Its deficiency is common in infants and leads to excessive bleeding due to the inability to form blood clots

Question 8

Short term symptoms of coeliac disease

Answer 8

Eating foods that contain gluten can trigger a range of gut symptoms, such as:
• diarrhoea, which may smell particularly unpleasant
• stomach aches
• bloating and farting (flatulence)
• indigestion
• constipation

Coeliac disease can also cause more general symptoms, including:
○ tiredness (fatigue) as a result of not getting enough nutrients from food (malnutrition)
○ unintentional weight loss
○ an itchy rash (dermatitis herpetiformis)
○ problems getting pregnant (infertility)
○ nerve damage (peripheral neuropathy)
○ disorders that affect co-ordination, balance and speech (ataxia)
Children with coeliac disease may not grow at the expected rate and may have delayed puberty.

Question 9

Complications of untreated coeliac disease

Answer 9

Complications of Untreated Coeliac Disease
• Vitamin deficiency
• Anaemia
• Osteoporosis
• Ulcerative jejunitis
• Enteropathy-associated T-cell lymphoma (EATL) of the intestine
• Non-Hodgkin lymphoma (NHL)
• Small bowel adenocarcinoma (rare)

Question 10

Decreased duodenal ph

Answer 10

Zollinger-Ellinson syndrome - Lowers pH through the destruction of pancreatic enzymes by secreting gastric stomach acids

Question 11

What bowel symptoms should be assessed in a presenting compliant?

Answer 11

1. Character
   2. Stool consistency
   3. Blood? - mixed with stool or just around the sides of toilet or on toilet paper
   4. Dysentery? - watery and bloody - infections
   5. Steatorrhoea? - loose, greasy, pale, foul smelling stools - malabsorption
   6. Offensive smell?
   7. Easy to flush? - steatorrhoea
   8. Melena? - dark, tarry, sticky, offensive smelling - upper GI bleed

Question 12

How are carbohydrates digested and absorbed?

Answer 12

Carbohydrates
1. Mouth
• Begin to digest carbohydrate in the mouth
• Saliva secreted from salivary glands moistens food
• Saliva releases amylase → begins breakdown process of sugars in carbohydrates

2. Stomach
   • Food is chewed into smaller pieces and chewed
   • Carbohydrates travel through oesophagus to stomach
   • At this stage, food is referred to as chyme
   • Stomach makes acid to kill bacteria in chyme
3. Small intestine, pancreas and liver
   • Chyme goes from stomach to duodenum → causes pancreas to release pancreatic amylase
   • Enzyme breaks chyme into dextrin and maltose
   • Wall of small intestine begins to make lactase, sucrase and maltase → breakdown sugar into monosaccharides or single sugars
   • Sugars are absorbed into the small intestine
   • Once absorbed → processed by liver and stored as glycogen
   • Hormone insulin is released from pancreas and allows the glucose to be used as energy
4. Colon
   • Anything left over goes to colon
   • Then broken down by intestinal bacteria
   • Fibre in many carbohydrates cannot be digested by body
   • It reaches colon and is then eliminated with stools

Question 13

How are fats absorbed and digested?

Answer 13

Fats

1. Mouth
   • Saliva moistens food → easier to move down oesophagus and into the stomach
   • Saliva also contains enzymes that begin breaking down fat in food → enzyme lingual lipase initiates process of digestion
2. Oesophagus
   • A series of muscle contractions → peristalsis, moves food through the oesophagus and into the stomach
3. Stomach
   • Lining produces acid and enzymes that break down food further so food can pass to the small intestine
   • Gastric lipase starts to break down triacylglycerols into diglycerides and fatty acids
4. Small intestine
   • Bile is released from the liver to the small intestine
   • Bile contains bile salts, lecithin and substances derived from cholesterol so it acts as an emulsifier
   • Pancreatic lipase is released from the pancreas and breaks down the fats into free fatty acids and monoglycerides
   • Bile salts envelop the fatty acid and monoglycerides to form micelles → allow efficient transportation to the intestinal microvillus
5. Into the bloodstream
   • Inside intestinal cells, monoglycerides and fatty acid reassemble into triacylglycerols
   • Triacylglycerol’s, cholesterol and phospholipids all form a chylomicron → a large lipoprotein that enters the lymphatic system and will be released into the bloodstream

Question 14

How are proteins digested and absorbed?

Answer 14

Proteins
1. Mouth to stomach
• Food is first chewed and broken down into smaller pieces for swallowing
• Saliva aids swallowing and passage through the oesophagus
• Food pieces enter the stomach
• Stomach releases gastric juices containing hydrochloric acid and the enzyme, pepsin, which initiate breakdown of the protein
• Pepsin → dismantles protein chains into smaller fragments
• Partially digested protein forms a chyme in the stomach

2. Stomach to small intestine
   • Two major enzymes released from the pancreas for protein digestion are chymotrypsin and trypsin
   • The goal of the digestive process is to break the protein into dipeptides and amino acids for absorption
3. Protein absorption
   • Essentially all protein is absorbed as tripeptides, dipeptides or amino acids → process occurs in the duodenum or proximal jejunum
   • Peptides and/or amino acids pass through the interstitial brush border by facilitative diffusion or active transport
   • Active transport sodium and ATP to actively transport the molecule through the cell membrane
   • Once passed through membrane, amino acids or peptides are released into the intestinal blood stream and are transport to the liver by the hepatic portal vein

Question 15

Describe Chron’s disease

Answer 15

• Chronic inflammatory disorder characterised by patchy, transmural inflammation of intestinal mucosa
• Can affect any part of the gastrointestinal tract from mouth to anus
• Skip lesions are the main identifier
• Inflammation is found in all layers from mucosa to serosa, with increased goblet cells and granulomas

C - Cobblestone appearance
R - Rosethorn ulcers
O - Obstruction
H - Hyperplasia of lymph nodes
N - Narrowing of lumen
S - Skip lesions

Question 16

Blood tests for suspected Crohn’s disease

Answer 16

Blood
• FBC
• LFTs
• U&Es
• CRP - indicated inflammation and active disease
• Magnesium
• Haematinics
• Bone profile
• Clotting

Question 17

Complications of Crohn’s disease

Answer 17

Complications

• Bowel obstruction (stricture)
○ Thickened wall of intestines causes narrowing of the bowel
○ This is more common in Crohn’s than UC

• Fistula
○ Inflammation goes through the wall and creates tunnels
○ Abnormal passage between 2 organs or an organ and the outside of your body
○ Can become infected

• Abscesses
○ Swollen, pus-filled pockets of infection in intestinal walls

• Anal fissures
○ Small tears in the anus that may cause itching, pain or bleeding

• Ulcers

• Malnutrition

• Inflammation in other areas of the body

• Colorectal cancer

Question 18

Presentation of Crohn’s disease

Answer 18

Symptoms
Nausea & vomiting
Fatigue
Low-grade fever
Weight loss
Abdominal pain
Diarrhoea (+/- blood)
Rectal bleeding
Perianal disease
Signs
Pyrexia
Dehydration
Angular stomatitis
Aphthous ulcers
Pallor
Tachycardia
Hypotension
Abdominal pain, mass and distension

Question 19

Management of Crohn’s disease inducing remission

Answer 19

Inducing Remission
• First line: Steroids (e.g. oral prednisolone or IV hydrocortisone)
• If steroids alone don’t work, consider adding immunosuppressant medication under specialist guidance:
○ Azathioprine
○ Mercaptopurine
○ Methotrexate
○ Infliximab
○ Adalimumab
• Apply nutritional alterations
○ Exclusive enteral nutrition (EEN) is a liquid diet that excludes all food + drink expect water.
○ Supplement drink at 25kcal/kg/day
○ 1g/kg/day of protein

Question 20

Management of Crohn’s maintaining remission

Answer 20

Maintaining Remission
• Tailored to individual patients based on risks, side effects, nature of the disease and patient’s wishes. It is reasonable not to take any medications whilst well.
• First line = thiopurines:
○ Work through purine synthesis inhibition in lymphocytes -> immunosuppressive properties
○ E.g.Mercaptopurine + Azathioprine
○ SE: pancreatitis + hepatotoxicty
• Alternatives:
○ Methotrexate
▪ Inhibits dihydrofolate reductase
▪ Immunomodulatory + anti-inflammatory properties
▪ SE: bone marrow suppression, hepatotoxicity + pulmonary toxicity
○ Monoclonal antibodies
▪ E.g. Infliximab + Adalimumab
▪ SE: numbness/tingling, vision problems, leg weakness, chest pain, SOB, new joint pain, hives/itching

Question 21

Surgery options for Crohn’s disease patients

Answer 21

Maintaining Remission
• Tailored to individual patients based on risks, side effects, nature of the disease and patient’s wishes. It is reasonable not to take any medications whilst well.
• First line = thiopurines:
○ Work through purine synthesis inhibition in lymphocytes -> immunosuppressive properties
○ E.g.Mercaptopurine + Azathioprine
○ SE: pancreatitis + hepatotoxicty
• Alternatives:
○ Methotrexate
▪ Inhibits dihydrofolate reductase
▪ Immunomodulatory + anti-inflammatory properties
▪ SE: bone marrow suppression, hepatotoxicity + pulmonary toxicity
○ Monoclonal antibodies
▪ E.g. Infliximab + Adalimumab
▪ SE: numbness/tingling, vision problems, leg weakness, chest pain, SOB, new joint pain, hives/itching

Question 22

Describe ulcerative colitis

Answer 22

Ulcerative colitis is a chronic, inflammatory disease characterised by a relapsing-remitting course affecting the gastrointestinal tract.

UC is a disease of the colonic mucosa, which has a relapsing-remitting course. It is characterised by inflammation of the mucosa, affecting the rectum (rectal sparing occurs but is rare) and may progress proximally through the colon.

The terminal ileum may be affected (‘backwash ileitis’) in those with extensive colitis.

Question 23

How is ulcerative colitis diagnosed?

Answer 23

Diagnosis is based on macroscopic assessment (e.g. endoscopy) and histological evidence (e.g. biopsy) of colonic inflammation.

Question 24

What bloods should be done for suspected UC?

Answer 24

Bloods
○ Full blood count
○ Liver function tests
○ Urea & electrolytes
○ CRP
○ Arterial/venous blood gas
○ Haematinics
○ Magnesium
○ Clotting
○ Autoantibodies (e.g. p-ANCA)

Question 25

Imaging and endoscopy for suspected UC?

Answer 25

Imaging
Abdominal X-rays are useful for looking at dilatation of the bowel and perforations. Dilatation is said to be present if:
• Small bowel: diameter > 3cm
• Large bowel: diameter > 6cm
• Caecum: diameter > 9cm
Computed tomography may be organised where there is concern regarding complications (e.g. toxic megacolon) and prior to surgery.

Endoscopy
Colonoscopy is considered the diagnostic investigation of choice as it allows assessment of the whole colon.
Biopsies can be taken for histological assessment of the mucosa.
Caution should be taken during acute flares due to the increased risk of perforation.
Sigmoidoscopy may be used as an alternative endoscopic test.

Question 26

Presentation of UC

Answer 26

Presentation:
The hallmark of UC is bloody diarrhoea / rectal bleeding.
Patients with UC may become acutely unwell with features of hypovolaemic shock, so it is important to resuscitate patients with respect to airway, breathing and circulation.

Symptoms
• Weight loss
• Fatigue
• Abdominal pain
• Loose stools
• Rectal bleeding
• Tenesmus (incomplete emptying)
• Urgency

Signs
• Febrile
• Pale
• Dehydrated
• Abdominal tenderness
• Abdominal distension/mass
• Tachycardic, hypotensive

Question 27

Extra colonic manifestations of UC

Answer 27

Extra-colonic manifestations
Approximately 25% of patients will develop extra-colonic manifestations during their lifetime.

Musculoskeletal
Arthritis is the most common extracolonic manifestation, which may be a simple peripheral arthritis or more complex spondyloarthropathy (e.g. ankylosing spondylitis).

Eyes, mouth & skin
Uveitis (inflammation of the uvea) is strongly associated with UC.
Extracolonic manifestations of the mouth commonly include aphthous ulcers. The skin is another organ widely affected by UC, leading to erythema nodosum, which is a type of panniculitis that classically results in multiple, painful, purple nodules on the anterior aspect of the shins

Hepatobiliary
Numerous hepatobiliary pathologies are associated with UC including fatty liver disease and autoimmune liver disease.

Haematological
Two common haematological problems associated with UC are anaemia and thromboembolism.

Question 28

Management of UC to induce remission

Answer 28

Induce remission:

In patients presenting with UC for the first time, or those who develop a flare of UC, the principal aim is to induce remission with aminosalicylates (5-ASA) and/or steroids.

Assess severity of UC using true love and witts classification

Moderate: Topical 5-ASA +/- Oral 5-ASA +/- Oral Steroids -> Treat as severe if no better in 2 weeks Severe: Admit, IV Hydrocortisone, IV Fluids -> Step-down to oral when well

Question 29

What is the true love and witts classification of UC?

Answer 29

Bowel movements (number per day):
Mild - Fewer than 4
Moderate - 4-6
Severe - 6 or more plus at least 1 of the features of systemic upset (marked with * below)

Blood in stools:
Mild - No more than small amounts of blood
Moderate - Between mild and severe
Severe - Visible blood

Pyrexia (temperature greater than 37.8oC) *
Mild - No
Mild - No
Severe - Yes

Pulse rate greater than 90 bpm*
Mild - No
Severe - Yes

Anaemia
Mild - No
Severe - Yes (<105mg/l)

Erythrocyte sedimentation rate (mm/hour)*
Mild - 30 or below
Moderate - Above 30

Question 30

Common differentials of diarrhoea

Answer 30

· Coeliac Disease
· Inflammatory bowel disease
· Crohn’s and Ulcerative Colitis
· Irritable bowel syndrome
· Colorectal Cancer
· Infective gastroenteritis
· Drugs

Question 31

Drugs that cause diarrhoea

Answer 31

Osmotic

· Citrates
· Osmotic laxatives
· Magnesium containing antacids
· Sugar alcohols

Secretory

· Quinine
· Augmentin
· Metformin
· Calcitonin
· Digoxin
· Colchicine
· NSAIDs
· Prostaglandins (Misoprostol)

Motility

· Macrolides E.g. Erythromycin
· Metoclopramide
· Stimulant laxatives

Malabsorption

· Acarbose
· Aminoglycosides
· Orlistat
· Levothyroxine

Pseudomembranous Colitis

· Antibiotics- especially Ciprofloxacin, Cephalosporins, Clindamycin, Amoxicillin

Question 32

Important clinical features of diarrhoea

Answer 32

Important clinical features of diarrhoea
• Abdominal cramps or pain
• Abdominal tenderness
• Bloating
• Nausea
• Vomiting
• Weight loss
• Fevers
• Fatigue
• Mucous in stool
• Blood in stool
• Steatorrhea → increase in fat excretion in stools

Question 33

Causes of diarrhoea

Answer 33

Causes of diarrhoea

• Viruses → including norovirus, enteric adenoviruses, astrovirus, cytomegalovirus and viral hepatitis
○ Rotavirus is common cause of acute childhood diarrhoea

• Bacteria & parasites → exposure to pathogenic bacteria e.g. E. Coli or parasites through contaminated food or water leads to diarrhoea
○ Traveller’s diarrhoea → from travelling to different countries. Caused by bacteria & parasites.
○ Clostridioides difficle (C. diff) → bacterium that causes diarrhoea.

• Medications → such as antibiotics can cause diarrhoea.
○ Antibiotics kill good bacteria as well as the bad, this disturbs the natural balance of bacteria in the intestines.

• Lactose intolerance → difficulty digesting lactose can cause diarrhoea after eating dairy.

• Fructose → can cause diarrhoea in those that struggle to digest it.

• Artificial sweeteners → sorbitol, erythritol and mannitol → can cause diarrhoea.

• Surgery → partial intestine or gallbladder removal surgery can cause diarrhoea.

• Other digestive disorders → IBS, Crohn’s disease, Ulcerative colitis, Coeliac disease, Microscopic colitis and small intestinal bacterial overgrowth

Question 34

Features of dehydration caused by diarrhoea

Answer 34

Complications of diarrhoea → dehydration
• Features of dehydration include:
○ Increased pulse rate
○ Reduced skin turgor
○ Dryness of mucous membranes
○ Delayed capillary refill time
○ Decreased urine output
○ Hypotension
○ Altered mental status

Question 35

Hypovolaemia treatment

Answer 35

Hypovolaemia → Geeky Medics

• Hypovolaemic patients require fluid resuscitation:
○ Administer a 500ml bolus Hartmann’s solution or 0.9% sodium chloride over 15 mins
○ Administer 250ml boluses in patients at increased risk of fluid overload (e.g. heart failure)

• After each fluid bolus, reassess for clinical evidence of fluid overload (e.g. auscultation of the lungs, JVP assessment)

• Repeat administration of boluses up to four times (e.g. 2L or 1L in patients at increased risk of fluid overload), reassessing the patient each time

• Seek senior input if the patient has a negative response (e.g. increased chest crackles) or if the patient isn’t responding adequately to repeated boluses (e.g. persistent hypotension)

Question 36

Red flag symptoms and referral criteria for endoscopy

Answer 36

Red flag symptoms of acute diarrhoea:
• Blood in stool
• Recent hospital treatment or antibiotic treatment
• Weight loss
• Evidence of dehydration
• Nocturnal symptoms

Refer for further assessment and management if:
History, examination and blood test results suggest any of the following:
○ Coeliac disease
○ Crohn’s disease
○ Ulcerative colitis
○ Bile acid diarrhoea
○ Microscopic colitis
○ Malabsorption

Question 37

Describe the pathophysiological steps of hepatitis

Answer 37

Hepatitis describes inflammation in the liver. This can vary from a chronic low level inflammation to acute and severe inflammation that leads to large areas of necrosis and liver failure.
1) Viruses enter the blood stream and spread to the liver.
2) They infect the hepatocytes and multiply.
3) They change the antigen structure on the virus site.
4) The body begins to use self-mediated immune response attempting to damage the hepatocytes.
5) In Hep B and C, they can continue this process over and over for years increasing the risk of cirrhosis
6) Liver cirrhosis is the result of chronic inflammation and damage to liver cells. The functional liver cells are replaced with scar tissue (fibrosis). Nodules of scar tissue form within the liver.

Question 38

Causes of hepatitis

Answer 38

Causes

• Alcoholic hepatitis
• Non alcoholic fatty liver disease
• Viral hepatitis - most common cause 
• Autoimmune hepatitis
• Drug induced hepatitis (e.g. paracetamol overdose)

Question 39

Presentation of hepatitis

Answer 39

Presentation

Hepatitis may be asymptomatic or could present with non-specific symptoms:
• Abdominal pain
• Fatigue
• Pruritis (itching)
• Muscle and joint aches
• Nausea and vomiting
• > 5 Spider naevi
• Jaundice
• Fever (viral hepatitis)

Typical biochemical findings are that liver function tests become deranged with high transaminases (AST / ALT) with proportionally less of a rise in ALP.
• This is referred to as a “hepatitic picture”.
○ Transaminases are liver enzymes that are released into the blood as a result of inflammation of the liver cells. Bilirubin can also rise as a result of inflammation of the liver cells. High bilirubin causes jaundice.

Question 40

Biochemical findings of hepatitis

Answer 40

Typical biochemical findings are that liver function tests become deranged with high transaminases (AST / ALT) with proportionally less of a rise in ALP.
• This is referred to as a “hepatitic picture”.
○ Transaminases are liver enzymes that are released into the blood as a result of inflammation of the liver cells. Bilirubin can also rise as a result of inflammation of the liver cells. High bilirubin causes jaundice.

Question 41

Hepatitis A

Answer 41

Hepatitis A

Pathophysiology
Often found in communities with overcrowding, water, raw shellfish.
It is very contagious and spreads due to oro-faecal transmission.

Risk Factors
Travelling or living in a country with high infection rates
Eating raw foods, drinking tap water while travelling

Presentation
May be asymptomatic, but can present with the following: Jaundice, malaise, abdominal pain, nausea & fever – usually lasting around 2 weeks.

Investigation
Anti-HAV test
(you will see IgM in blood in first 6 weeks then IgG after)
ALT > AST

Management
Usually self limiting.
Does not usually require hospital admission in uncomplicated cases!
In most people, the severity of the virus peaks 4 weeks after infection, and symptoms will be virtually gone 2 weeks.

Complications
Not associated with chronic liver disease

Question 42

Hepatitis B

Answer 42

Pathophysiology
Spread through contact with the blood or body fluids of an infected person. Often through unprotected sex. Mother can pass to the baby during childbirth.

10 % of cases of infection will go on to develop chronic hepatitis B.

The risk of developing chronic disease depends on the age at which the infection is acquired.

The risk in neonates from maternal transmission >90 %, whilst in adults, it is around 10 %

Risk factors
Multiple sexual partners
IV drug use
Occupational exposure

Presentation
May be asymptomatic, or have minor flu-like symptoms.
Symptomatic individuals: fever, malaise, fatigue, joint pains, pale stools/dark urine/ jaundice.

Investigation:
Deranged LFTs (raised bilirubin, ALT/AST, ALP)
+
HBsAg, Anti-HBs imply immunity (also seen in vaccinated individuals).

Also check for HepC and HIV.

Management:
If acutely unwell would need hospital admission.
Otherwise non-urgent gastro referral.
Antiviral therapy for those with chronic infection.
Lifestyle advice about alcohol and safe sex advice

Complications:
Chronic Hepatitis, cirrhosis, Hepatocellular carcinoma

Question 43

Hepatitis C

Answer 43

Pathophysiology
Transmission is usually via blood products or vertical transmission from mother to foetus.

Sexual transmission is possible.

Risk factors
Needle sharing
Tattoos or body piercing
UPSI
IV Drug Use
Haemodialysis

Presentation:
Majority of patients asymptomatic.
10-15% may have jaundice and other symptoms suggestive of hepatitis.

Investigations:
Raised ALT, low albumin, raised bilirubin, raised INR, positive anti-HCV (perform PCR to check viral load).
FBC to check for anaemia.
Consider gastroscopy in chronic HCV.

Management:
Antiviral therapy treatment with Interferon which would also require monitoring (FBC, LFTs and U&Es every 4 weeks and 12 weeks after the end of treatment)

Question 44

Hepatitis D

Answer 44

You can only contract this if you are also suffering from Hepatitis B.

Risk factor:
The most common mode of transmission is IV drug use

Investigation:
Anti-HDV test

Complications:
Fulminant liver disease

Question 45

What is liver impairment and what would clinical findings present like?

Answer 45

Liver impairment: inflammation and damage to liver cells. Diseases include cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease, hepatitis etc

Clinical findings on examination
· Jaundice
· Hepatomegaly
· Spider naevi (5 is normal)
· Palmar erythema
· Gynaecomastia – increased oestrogen
· Bruising – due to abnormal clotting
· Abdominal distension
· Ascites
· Caput Medusae – engorged superficial epigastric veins
· Asterixis – ‘flapping tremor’ in decompensated liver disease

Question 46

What is hepatic encephalopathy?

Answer 46

Hepatic encephalopathy
· Build up of toxins that affect brain cells – ammonia is key
· Ammonia produced by intestinal bacteria when they break down proteins and is absorbed in the gut
· Ammonia build up common in liver cirrhosis due to:
○ Functional impairment of hepatocytes – ammonia unable to metabolise into urea (harmless waste product)
○ Collateral vessels between portal and systemic circulation means that the ammonia bypasses liver, enter systemic system directly

Question 47

Management of hepatic encephalopathy

Answer 47

· Management:
○ Laxatives (lactulose) – promote excretion of ammonia from gut before it is absorbed. Aim: 2-3 soft motions daily. May require enemas initially
○ Antibiotics (rifaximin) – reduces number of intestinal bacteria producing ammonia, poorly absorbed = stay in GI tract decreasing ammonia production
○ Nutritional support – nasogastric feeding if required

Question 48

Autoimmune hepatitis.
What is it?
Clinical features
Investigations
Treatment

Answer 48

• Autoimmune hepatitis is a rare cause of chronic hepatitis a chronic inflammatory liver disorder.
• Not sure of the exact cause - could be associated with a genetic predisposition and triggered by environmental factors such as a viral infection or environmental factors that cause a T cell-mediated response against the liver cells.
Type 1- adults
Type 2- children

Clinical Features
• Asymptomatic
• Acute hepatitis
○ Anorexia
○ Nausea
○ Jaundice
○ Right upper quadrant pain
○ Hepatomegaly
• Chronic liver disease (cirrhosis)
• Acute liver failure
○ Jaundice
○ Confusion
○ coagulopathy

Investigations
Investigations will show raised transaminases (ALT and AST), IgG levels and it is associated with many autoantibodies.
Diagnosis can be confirmed using a liver biopsy.

Treatment
• High dose steroids (prednisolone) that are tapered over time as other immunosuppressants, particularly azathioprine, are introduced. Immunosuppressant treatment is usually successful in inducing remission however it is usually required life long.
Liver transplant may be required in end stage liver disease, however the autoimmune hepatitis can recur in transplanted livers.

Question 49

Alpha -1-antitrypsin deficiency
What is it?
Clinical features
Investigations
Treatment

Answer 49

• Alpha-1-antitrypsin deficiency is a condition caused by an abnormality in the gene for a protease inhibitor called alpha-1-antitrypsin.
• Two main organs are affected by alpha-1-antitrypsin deficiency, the liver and the lungs. It leads to:
○ Liver cirrhosis after 50 years old - build up of hepatocytes leading to cirrhosis
○ Bronchiectasis and emphysema in the lungs after 30 years old - absent inhibition of neutrophil elastase causes lung damage leading to COPD

Clinical Features
• The clinical features of AATD depends on the underlying genotype. Patients may have features of both COPD and chronic liver disease.
• Pulmonary clinical features
○ Dyspnoea
○ Cough
○ Wheeze
○ Ankle swelling (right-sided heart failure from chronic lung disease)
• Hepatic clinical features
○ Jaundice
○ Bruising
○ Spider naevi
○ Palmar erythema
○ Hepatomegaly
○ Ascites
○ Leuconychia
○ Confusion
○ Asterixis: flapping tremor (suggests encephalopathy)
○ Cachexia

Diagnosis
• Low serum-alpha 1-antitrypsin (screening test of choice)
○ Normal AAT levels = 0.9-1.9g/L
○ Minimum required to protect against lung damage ~0.8g/L
• Liver biopsy shows cirrhosis and acid-Schiff-positive staining globules (this stain highlights the mutant alpha-1-antitrypsin proteins) in hepatocytes
• Genetic testing for the A1AT gene
○ Rarer alleles may not be detected by routine testing, a whole genetic sequencing would have to be carried out
• High resolution CT thorax diagnoses bronchiectasis and emphysema

Management
• Stop smoking (smoking dramatically accelerates emphysema)
• Decrease alcohol intake
• Nutritional support
• Pulmonary rehab (if needed)
• Seasonal vaccination (to prevent respiratory infections)
• Symptomatic management
• NICE recommend against the use of replacement alpha-1-antitrypsin, however the research and debate is ongoing regarding the possible benefits
• Organ transplant for end-stage liver or lung disease
• Monitoring for complications (e.g. hepatocellular carcinoma)

Question 50

Hereditary Haemochromotosis
What is it?
Clinical features
Investigations
Management

Answer 50

Haemochromatosis is an iron storage disorder that results in excessive total body iron and deposition of iron in tissues.

Symptoms
• Haemochromatosis usually present after the age of 40 when the iron overload becomes symptomatic. It presents later in females due to menstruation acting to regularly eliminate iron from the body.
○ Chronic tiredness
○ Joint pain
○ Pigmentation (bronze / slate-grey discolouration)
○ Hair loss
○ Erectile dysfunction
○ Amenorrhoea
○ Cognitive symptoms (memory and mood disturbance)

Diagnosis
• The main diagnostic method is to perform a serum ferritin level.
○ Ferritin is an acute phase reactant, meaning that it goes up with inflammatory conditions such as infection.
• Performing a transferrin saturation is helpful in distinguishing between a high ferritin caused by iron overload (in which case transferrin saturation is high) from a high ferritin due to other causes such as inflammation or non alcoholic fatty liver disease.
• If serum ferritin and transferrin saturation is high and there is no other reason then genetic testing can be performed to confirm haemochromatosis.
• Liver biopsy with Perl’s stain can be used to establish the iron concentration in the parenchymal cells used to be the gold standard but has been surpassed by genetic testing.
• A CT abdomen scan can show a non-specific increase in attenuation of the liver.
• MRI can give a more detailed picture of liver deposits of iron. It can also be used to look at iron deposits in the heart.

Management
• Venesection = a weekly protocol of removing blood to decrease total iron
• Iron chelation therapy
• Monitoring serum ferritin
• Avoid alcohol
• Genetic counselling
• Monitoring and treatment of complications

Question 51

Primary hepatocellular carcinoma
What is it?
Signs and symptoms
Diagnosis
Management

Answer 51

• A primary liver cancer that occurs most commonly in patients with cirrhosis
• Often diagnosed late and has a poor prognosis

Signs and symptoms
• Asymptomatic
• Fever
• Anorexia
• Night sweats
• Weight loss
• Fatigue

Diagnosis
• The diagnosis of HCC may be based on imaging criteria alone in the context of cirrhosis.
• There are two ways to make a formal diagnosis of HCC:
○ Imaging: specific criteria for HCC can be used in patients with cirrhosis.
§ Nodules are >1cm with typical vascular features
○ Histology: required in patients without cirrhosis. May be needed in equivocal cases with cirrhosis.

Management
• Locoregional therapies: liver resection, percutaneous ablation, transarterial therapies
• Liver transplantation
• Systemic therapy: multikinase inhibitors (e.g. Sorafenib), others.
• Other therapies: radiotherapy, brachytherapy, immunotherapy
• Best supportive care

Question 52

What blood tests are used to assess liver function?

Answer 52

LFT’s:
• Alanine transaminase (ALT)
• Aspartate aminotransferase (AST)
• Alkaline phosphatase (ALP)
• Gamma-glutamyltransferase (GGT)
• Bilirubin
• Albumin
• Prothrombin time (PT)
Hint: ALT, AST, ALP and GGT are used to distinguish between hepatocellular damage and cholestasis. Bilirubin, albumin and PT are used to assess the liver’s synthetic function.

Question 53

ALT

Answer 53

Alanine transaminase (ALT)

This is an enzyme that catalyses a reaction between an amino acid and a keto-acid. Ultimately, they are important in producing various amino acids.

During liver damage, ALT is released into serum causing raised levels that may remain high for weeks or months. Levels will be raised before jaundice appears.

• More specific for liver damage than AST.
• Levels of ALT and AST both raised above 2x normal then this is significant.
• If the transferases are very high (greater than 1000 U/L then the diagnosis is almost certainly hepatitis
• Alcoholic liver disease is unlikely cause an AST of >1000 u/L

Question 54

AST

Answer 54

Aspartate aminotransferase (AST)

These type of enzymes have a similar function to ALT enzymes. These enzymes are found in the liver, RBC’s, cardiac and skeletal muscle, kidney and brain tissue. As a result, damage to any of these areas can result in an increased level on test result.

Remember, high levels are likely to be liver OR heart problems OR muscle damage (use other tests, namely ALT to help you decide)

• Levels can go as high as 20x normal. This would normally indicate something like viral hepatitis, sever skeletal muscle trauma, extensive surgery, drug induced hepatic trauma,
• Levels from 10-20x normal may suggest MI, and alcoholic cirrhosis.
• 5-10x normal may suggest chronic cirrhosis
• Mildly raised levels are often found it fatty liver (steatosis), liver metastasis and PE.

Question 55

ALP

Answer 55

Alkaline phosphatase (ALP)

• These enzymes work best in an alkaline environment are involved in hydrolysis reactions – i.e. they remove a phosphate group from a molecule.
• It is found in large concentrations in cells lining the bile duct and in bone. So when levels are raised in the plasma, it normally means damage to one of these areas. Levels can be physiologically elevated in times of high bone turnover, such as adolescence and in the third trimester of pregnancy.
• ALP is likely to be largely elevated in bile duct blockage, and slightly raised in liver disease (e.g. hepatitis or liver cancer)

Question 56

GGT

Answer 56

Gamma-glutamyltransferase (GGT)

• Commonly raised in increased alcohol intake
• Also, very commonly a “false positive”
• Raised levels are common in obstruction of the bile ducts.
• GGT is often used to confirm that ALP readings are due to liver damage and not another cause.
• If ↑ALP but normal GGT – likely bone – consider checking calcium
• If ↑ALP and ↑GGT – likely liver cause
• GGT is used to particularly monitor cirrhosis caused by alcoholism.
• In patients with known liver disease GGT is a strong predictor of mortality

Question 57

ALT vs ALP

Answer 57

Key facts about ALT and ALP
ALT is found in high concentrations within hepatocytes and enters the blood following hepatocellular injury. It is, therefore, a useful marker of hepatocellular injury.

ALP is particularly concentrated in the liver, bile duct and bone tissues. ALP is often raised in liver pathology due to increased synthesis in response to cholestasis. As a result, ALP is a useful indirect marker of cholestasis.

How do we compare the rise in ALT and ALP?
• A greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular injury.
• A less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis.
• It is possible to have a mixed picture involving both hepatocellular injury and cholestasis.

Question 58

What if the patient is jaundiced but ALT and ALP levels are normal?

Answer 58

An isolated rise in bilirubin is suggestive of a pre-hepatic cause of jaundice.
Causes of an isolated rise in bilirubin include:
• Gilbert’s syndrome: the most common cause.
• Haemolysis: check a blood film, full blood count, reticulocyte count, haptoglobin and LDH levels to confirm.

Question 59

What are the livers main synthetic functions and what investigations can be used to measure these?

Answer 59

The liver’s main synthetic functions include:
• Conjugation and elimination of bilirubin
• Synthesis of albumin
• Synthesis of clotting factors
• Gluconeogenesis

Investigations that can be used to assess synthetic liver function include:
• Serum bilirubin
• Serum albumin
• Prothrombin time (PT)
• Serum blood glucose

Question 60

Bilirubin

Answer 60

Bilirubin is a breakdown product of haemoglobin. Unconjugated bilirubin is taken up by the liver and then conjugated.

Most commonly used to asses for obstructive jaundice. Levels also likely to be raised in liver damage and in cases of severe RBC damage. Test for urobilinogen can be useful in determining whether it is due to RBC’s or a problem with the liver / bile system.

Question 61

Albumin

Answer 61

This is the major protein constituent of plasma, and accounts for over 50% of all plasma proteins. It is manufactured in the liver from ingested amino-acids. It helps to regulate osmotic pressure as well as transport nutrients and waste products.

Question 62

Reasons for albumin levels to fall

Answer 62

Albumin levels can fall due to:
• Liver disease resulting in a decreased production of albumin (e.g. cirrhosis).
• Inflammation triggering an acute phase response which temporarily decreases the liver’s production of albumin.
Excessive loss of albumin due to protein-losing enteropathies or nephrotic syndrome.

Question 63

Common causes of acute hepatocellular injury

Answer 63

Common causes of acute hepatocellular injury include:
• Poisoning (paracetamol overdose)
• Infection (Hepatitis A and B)
• Liver ischaemia

Question 64

Causes of chronic hepatocellular injury

Answer 64

Common causes of chronic hepatocellular injury include:
• Alcoholic fatty liver disease
• Non-alcoholic fatty liver disease
• Chronic infection (Hepatitis B or C)
• Primary biliary cirrhosis

Less common causes of chronic hepatocellular injury include:
• Alpha-1 antitrypsin deficiency
• Wilson’s disease
• Haemochromatosis

Question 65

Increase INR
Decrease albumin
Decrease platelets

Answer 65

Synthetic failure
• Urgent Referral to hospital
• In hospital – likely will have full “liver screen” of autoantibodies, ferritin, hepatitis serology

Question 66

Role of the liver in glucose metabolism

Answer 66

Gluconeogenesis
• → synthesis of glucose from non-carbohydrate substrates
• Occurs after around 8 hours of fasting when liver glycogen stores start to deplete

Glycogen metabolism
Liver maintains steady blood glucose levels by converting excess glucose into glycogen → glycogenesis
When there is demand for glucose, glycogen is converted back into glucose → glycogenolysis

Glycogenesis
• Glucose is delivered to hepatocytes by the portal vein
• Once in the liver, the following occurs:
(Glucose made into glycogen following several steps)

Question 67

Role of liver in protein metabolism

Answer 67

Liver is important in protein metabolism for following reasons:
• Stores more proteins than other tissues
• Can rapidly synthesise or degrade proteins
• Can quickly synthesise and degrade amino acids

Liver proteins:
Protein synthesis is stimulated by insulin and growth hormone
Plasma proteins:
• Albumin
• Globulin
• Fibrinogen
• CRP (an infection marker)
• Clotting factors
• Thrombopoietin
• Angiotensinogen
In times of amino acids depletion, these proteins can be degraded and released back into the blood as amino acids

Clotting factors
• Almost all are synthesised by the liver

Amino acid catabolism
Transamination
• Amino acids → keto acids

Deamination
• Glutamate → ammonia → ammonium (NH4+) + a-ketoglutarate
• Ammonium is highly toxic → removed through urea cycle

Urea cycle
• Occurs both in mitochondria & cytoplasm of hepatocytes

Question 68

Role of liver in bilirubin metabolism

Answer 68

Bilirubin → yellow bile pigment produced through breakdown of red blood cells

Forms of bilirubin
• Unconjugated → insoluble in water. Can only travel in bloodstream bound to albumin. Cannot be directly excreted.
• Conjugated → water soluble. Can travel through bloodstream without requiring proteins.

Bilirubin metabolism

1. Creation
   ○ Heamoglobin → haem and globin (by reticuloendothelial cells)
   ○ Haem → iron and viliverdin. Catalysed by haem oxygenase
   ○ Iron is recycled
   ○ Biliverdin is reduced → unconjugated bilirubin
2. Conjugation
   ○ Unconjugated bilirubin binds to albumin in blood stream to facilitate transport to liver
   ○ In liver, glucuronic acid is added to unconjugated bilirubin by enzyme glucuronyl transferase → conjugated bilirubin
   ○ Conjugated bilirubin can be excreted into the duodenum in bile
3. Excretion
   ○ In colon, colonic bacteria deconjugate bilirubin → urobilinogen
   ○ ~80% urobilinogen is oxidised by intestinal bacteria → stercobilin → excreted through faeces
   ○ ~20% urobilinogen is reabsorbeed into bloodstream as part of enterohepatic circulation
   § Carried to liver → recycled for bile production
   § Small percentage goes to kidneys → oxidised further into urobilin → excreted into urine

Question 69

Primary sclerosing cholangitis

Answer 69

Primary sclerosing cholangitis is a condition where the intrahepatic or extrahepatic ducts become strictured and fibrotic. This causes an obstruction to the flow of bile out of the liver and into the intestines.

Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts. Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.

The cause is mostly unclear although there is likely to be a combination of genetic, autoimmune, intestinal microbiome and environmental factors.
There is an established association with ulcerative colitis.

Question 70

Alcoholic liver disease

Answer 70

Alcoholic liver disease
There is a stepwise process of progression of alcoholic liver disease:

1. Alcohol related fatty liver
   Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks.
   The hepatocytes have to divert resources away from metabolising fats to metabolising alcohol. As a result, fat metabolism is altered resulting in fat deposits inside the cells. There are more fats released into the blood stream (fatty acids) and within the hepatocytes, there is increased synthesis of triglycerides and fatty acids.
2. Alcoholic hepatitis
   Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.
   The hepatocytes, there is increased synthesis of triglycerides and fatty acids.
   Acetaldehyde is a product of alcohol metabolism. It binds to liver cell proteins, and causes hepatocytes injury, leading to inflammation. This inflammation can be a causatory factor in cirrhosis. It is likely that this produces Mallory’s sign.

Alcohol stimulates collagen synthesis by fibroblasts as well as fibroblast proliferation.

3. Cirrhosis
   This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
   Ultimately, the fibrosing process will end up linking hepatic veins to portal veins, and in these places, cell regeneration occurs, and nodules form – this is the start of the process of cirrhosis.

Question 71

Causes of hepatocellular jaundice

Answer 71

Hepatitis
The inflammation of the liver which causes liver damage is called hepatitis. Hepatitis is characterized by swelling and improper liver function. It can be caused due to viral infection. Hepatitis may be acute and chronic.

Medication
Paracetamol toxicity, Halothane, herbal remedies, and antituberculosis drugs can potentially cause acute liver failure.

Acute Liver Injury
Acute liver failure, or ALF, is a serious condition characterized by a rapidly progressive decline in liver function. ALF is defined as the onset of clinical features within eight weeks without pre-existing liver disease.

Chronic Liver Injury
Chronic liver injury refers to liver inflammation persisting for more than six months. Patients may remain asymptomatic in the early stages of chronic liver injury.

Haemochromatosis
The condition in which excess iron accumulates in the body.

Infection
Infection caused by a virus resulting in viral hepatitis (an inflammation of the liver).

Alcoholic Hepatitis
Alcoholic liver disease is caused by the misuse of alcohol, resulting in liver fibrosis.

Exposure to Toxic Materials
Food poisoning or allergies can also alter the function of the liver, causing jaundice.

Question 72

Functions of the liver

Answer 72

Carbohydrate metabolism:
Glycogen storage
Conversion of galactose and fructose to glucose
Gluconeogenesis
Glucose buffer

Fat metabolism:
High rate of oxidation of fatty acids
Conversion of AA and CH fragments to fats
Synthesis of lipoproteins, cholesterol and phospholipids
Synthesis of bile acids

Protein metabolism
Deamination of AA
Formation of urea

Synthesis of blood proteins
Detoxification
Waste disposal