GI Flashcards
What are the causes of hepatomegaly?
…
What are the management plans for Gastro-Oesophageal Reflux Disease (GORD)?
What are the drugs to avoid?
Lifestyle changes
No alcohol
No fizzy drinks, tomatoes, citrus fruits,
- Medications*
1. Antacids: magnesium trisilicate mixture etc. 10ml/8h or Alginates: Gaviscon 10-20ml/8h
2. PPI: Lansoprazole 30mg/24h or Omeprazole
3. If either PPI doesn’t work, swap to the other one. Try not to give dual PPI at this stage
4. If both don’t work, add ranitidine.
Drugs to avoid
Avoid drugs that affect oesophageal motility like anticholinergic drugs, CCB,
Avoid drugs that disturb mucous lining (NSIADS, bisphosphates, K+ drugs)
What is the MOA of omeprazole?
It irreversibly binds (via covalent bonding) to H+/K+ proton pump channels on gastric parietal cells to inhibit H+ release into the stomach. Omeprazole also inhibits both basal and stimulated acid secretion irrespective of the stimulus.
It is completely metabolised by the P450 cytochrome system, mainly in the liver. Main metabolites are sulfone and hydroxy-omeprazole. Both exert no significant impact on acid secretion.
Effects of inhibition start 1h after administration, reaches a maximum after 2h, wear off after 72h.
What is the MOA of Azathioprine?
Inhibits purine synthesis. Purines are needed to produce DNA and RNA. By inhibiting purine synthesis, less DNA and RNA are produced for the synthesis of white blood cells, thus causing immunosuppression.
Azathioprine is in the purine analogue and antimetabolite family of medication. It works via 6-thioguanine to disrupt the making of RNA and DNA by cells.
Azathioprine converted within tissues to 6-mercaptopurine => add amino acid group => thioguanine => 6-MP and 6-thioguanine are conjugated with ribose => phosphorylated to form the nucleotides thioinosinic acid and thioguanylic acid respectively => masquerade, respectively, as inosinic acid (starting point for purine biosynthesis) and guanylic acid (impt for DNA and RNA biosynthesis) => nucleotides are incorporated into newly synthesized but non-functional DNA => inhibition of the glutamine phosphoribosyl pyrophosphate transaminase (GPAT) aka product inhibition (i.e negative feefback)
A portion of the nucleotides is additionally phosphorylated to the triphosphate forms => bind to GTP-binding protein Rac1 +> block synthesis of the protein Bcl-xL => send activated T cells and mononuclear cells into apoptosis. Increased apoptosis of mononuclear cells is seen in IBS patients treated with azathioprine.
What are the effects of anti-cholinergic drugs on oesophagus motility and the lower oesophageal sphincter (LES)?
Oesophageal motility
Anti-cholinergics, in particular anti-muscurinic drugs, reduce oesophageal motility.
In man, atropine sulfate administered intravenously in doses of 6 and 12 µg/kg decreases the amplitude of the peristaltic contraction waves by about 50 p. cent for about one hour. The speed of propagation is slowed at the transition zone between the smooth and striated muscle. The incidence of primary complete peristaltic sequences provoked by swallowing is reduced to only 60 p. cent, compared with a rate of almost 100 p. cent after administration of isotonic saline
LES
Atropine provokes a 42 p. cent fall in basal pressure of the LES over about an hour.
The relaxation, which is the second essential property of the LES, is not affected by atropine during its activation by swallowing or esophageal distension. Indeed, relaxation is under the influence of putative, noncholinergic nonadrenergic neurotransmitter(s).
What is the MOA of ranitidine?
Competitive and reversible blocker of H2 histamine receptors, which are commonly found in gastric parietal cells. This results in decreased gastric acid secretion and gastric volume, and reduced hydrogen ion concentration.
What are the drugs to avoid in patients with GORD?
Drugs that affect oesophageal motility: anticholinergic drugs, CCB, nitrates
Drugs that disturb mucous lining: NSIADS, bisphosphates, K+ drugs
What are the causes of hepatomegaly?
- Chronic parenchymal liver disease (Cirrhosis)
a. Alcoholic liver disease
b. Fatty liver disease
c. Autoimmune hepatitis
d. Viral hepatitis
e. Primary biliary cirrhosis/primary biliary cholangitis - Malignancy (Cancer)
a. Primary Hepatocellular carcinoma
b. Secondary metastatic cancer - Congestion/Cardiac
a. Congestive heart failure
b. Constrictive pericarditis - Haematological disorders
a. Lymphoma
b. Leukaemia
c. Polycythaemia
d. Myelofibrosis - Rare issues
a. Sarcoidosis
b. Amyloidosis
c. Budd-Chiari Syndrome (narrowing and obstruction of the hepatic veins)
d. Glycogen storage disorders
e. Haemochromotosis
What are the causes of splenomegaly?
- Portal Hypertention
- Haematological issues
a. Lymphoma and lymphatic leukaemia
b. Myeloproliferative disorders, myelofibrosis and polycythaemia rubra vera
c. Haemolytic anaemia
d. Congenital spherocytosis - Infections
a. Salmonellosis, tuberculosis, brucellosis
b. Glandular fever
c. Malaria, kala-azar (leishmaniasis)
d. Bacterial endocarditis - Inflammation
a. Amyloidosis
b. Sarcoidosis
c. Glycogen storage disorders - Andersen disease - Rheumatoid issues
a. Rheumatoid arthritis (Felty’s syndrome)
b. SLE
What do the following terms mean?
Cholangitis Cholecystitis Calculous cholecystitis Cholelithiasis Choledocholithiasis Cholestasis
Cholangitis = obstruction of the biliary tree, which may lead to bile stasis and subsequent bacterial infection.
Cholecystitis = Inflammation of the gall bladder
Calculous cholecystitis = inflammation of the gall bladder resulting from gallstones obstructing the cystic duct
Choletithiasis = Gallstones in gall bladder
Choledocholithiasis = Gallstones in common bile duct
Cholestasis = Reduction or stoppage of bile flow
What is the triad of symptoms typical of cholangitis called? What does it consist of?
Charcot’s triad. Abdominal pain, fever, jaundice
If patient has Primary Sclerosing Cholangitis (PSC) and has IBD such as UC, what is he/she at risk of?
Colorectal malignancy
What are the top causes of liver cirrhosis?
Most common causes:
- Alcohol
- Hep B/C
- Non-alcoholic liver disease (NASH)
Genetic:
* Haemochromatosis - Iron dependent
* Wilson’s disease - Copper deposition in the brain which causes extra-pyramidal symptoms
Alpha-1 anti-trypsin deficiency (A1AT deficiency)
Autoimmune hepatitis
Respiratory:
Emphysema of the lung
Inflammatory: * PBC * PSC TB Schistosomiasis
Drugs:
Methotrexate
*Amiodarone
Rare causes:
Andersen Disease - glycogen storage disorder
Lympho-proliferative disease
What are the risk factors of metabolic syndrome? What are the investigations to do next?
Risk factors:
Fatty liver
Hyperlipidaemia
Diabetes
Ix:
LFTs
What is a common cause of deranged LFTs?
Non-alcoholic fatty liver disease (NASH)
