Gastro Flashcards
What is the primary factor leading to accumulation of ascities in patients with cirrhosis?
Splanchnic dilatation
What is the pathophysiology of ascites in cirrhosis?
Cirrhosis -> portal hypertension (sinusoidal pressure > 12 mmHg)-> splanchnic dilatation-> increase splanchnic pressure -> formation of ascities
Splanchnic dilatation also results in arterial underfilling -> activation of vasoconstriction and antinatriuretic factors -> sodium retention -> plasma volume expansion -> ascites
what is the serum to ascites albumin gradient (SAAG)? What is it used to identify?
SAAG = serum albumin - ascites albumin
Used to identify the presence of portal hypertension
> 11 = portal HT (cirrhosis, HF, bud chiari, alcholic hepatitis)
what does the appearance of the following ascitic fluid suggest: clear yellow brown turbid milky pink or bloody
Clear yellow = normal bili and protein
brown = high bili
turbid = infection
milky = elevated triglyceride concentration usually secondary to lymphoma
Pink or bloody = traumatic tap, malignancy, cirrhosis, punctured vessel
What Ix do you order for an ascitic fluid?
MCS
Protein; if >=2.5 or 3 gldL then exudate, if 1.0 = malignancy
Amylase, lipase- elevated if due to pancreatitis or gut perforation
Tb- Tb PCR
Cytology - malignant cells
what is the treatment for ascites due to cirrhosis?
- Spironolactone50-100 mg PO OD, increase by 100 mg q 4 days up to 400 mg OD.
2, Can add Frusemide40 mg PO. Increase by 40 mg q 4 days up to 160 mg OD - Amiloride 10-20 mg OD if pt cannot tolerate spironolactone
what is the Tx fro severe and refractory ascites sue to liver cirrhosis?
- Transplant only definitive therapeutic option
2. TIPS to shunt between hepatic and portal veins
what does B12 deficiency lead to?
Pernicious anaemia identified by macrocytosis, intramedullary haemolysis and peripheral neuropathy
Where is our source of Vit B12?
Where is Vitamin B12 stored?
How is Vitamin B12 absorbed?
Meat and dairy is the only source of Vit B12
Total body stores are 2-5 mg with half of stores in the liver
Cobalamin is liberated from food by acid and pepsin. Binds to R-factors in the saliva and gastric juice.
In the duodenum, cobalmin freed from R-proteins due to actions of PANCREATIC proteases. Then binds to intrinsic factor.
The IF-Cbl complex binds to ileal receptors in the terminal ileum.
MOA Azathioprine?
Immunosuppressive drug.
A purine anti-metabolite.
Metabolised via mercaptopurine to thioguinine metabolites which interfere with purine synthesis imparing with lymphocyte proliferation, celluluar immunity and anti-body responses.
Indications for Azathioprine
Prevention of post transplant rejection
immune and inflammatory diseases
What is the significance of TMPT testing when starting azathioprine?
1 in 300 ppl have low or no TPMT activity and are at severe risk of myelosuppresion. Avoid use or reduce dose to 1/10.
What is the interaction of azathioprine and allopurinol?
Allopurinol reduces azathioprine metabolism increasing the risk of severe bone marrow toxicity
What results would you expect in a pt with azathioprine resistance?
high 6MMP, low 6-TGN
Describe the pathway of azathioprine metabolism
AZA -> 6-MP -> 6 - MMP via TPMT
AZA -> 6-MP -> 6-TIMP -> 6-TXMP -> 6- TGN
What is the recommended treatment for Hepatitis C Genotype 1?
Sofosbuvir (Nucleotide polymerase inhibitor) + ribavirin + PEG for 12 weeks or
Olysio for 12 weeks + ribavirin + PEG for 24 weeks
If not elgible to receive interferon:
Solvadi + Olysio +/- ribavirin for 12 weeks or
Solvadi + ribavirin for 24 weeks
How many Hep C genotypes are there?
6
What is the treatment for Hep C Genotype 2?
Solvadi + ribavirin for 12 weeks
What is the treatment for Hep C Genotype 3?
Solvadi + ribavirin for 24 weeks
What is the treatment for Hep C Genetoype 4?
Solvadi + ribavirin + PEG for 12 weeks or
Olysio fro 12 weeks + ribavirin + PEG for 24-28 weeks
If not eligible for interferon:
Solvadi + ribavirin for 24 weeks
what is the treatment for Hep C genotype 5 or 6?
Solvadi + ribavirin + PEG for 12 weeks or
Ribavirin + PEG for 48 weeks
If not eligible to receive Interferon there are no recommended treatment options
What are the American Gastro Association guidelines for a pt with Barrett’s oesophagus:
without dysplasia
low grade dysplasia
High-grade dysplasia in the absence of eradication therapy
No dysplasia : 3-5 years
Low grade: 6-12 months
High grade dysplasia in the absence of eradication therapy: 3 months
What is the treatment for recurrent C. diff infection?
Duodenal infusion of faeces.
Sig more effective than the use of vancomycin
What is the recommended guidelines for colorectal ca screening for average or slightly increased risk (Asymptomatic or one first or second degree relative with CRC diagnosed at 55 years or older)
FOBT every 2 years from age 50 years
What is the recommended guidelines for colorectal ca screening for moderately increased risk (1-2% of population) (asymptomatic with 1 first degree relative with CRC diagnosed before 55 years or 2 first degree or 1 first degree and one second degree on the same side of the family with CRC diagnosed at any age without high risk features)?
Colonoscopy
Sigmoidoscopy plus double contrast barium enema or CT colonography if colonoscopy CI.
Every 5 years from age 50 years or at an age 10 years younger than the age of 1st diagnosis of CRC in the family. Whichever comes first.
Consider offerring FOBT in intervening years.
What is the recommended guidelines for colorectal ca screening for high risk (=3 1st degree or second degree relatives on the same side of the family diagnosed with CRC (suspected Lynch syndrome, also known as HNPCC) or other Lynch syndrome related cancers or
- > =2 first or second degree relatives on the same side of the family Dx with CRC, including any of the following high risk features: multiple CRC in one person, CRC before 50 y, family member who has or had Lynch syndrome related cancer or
- 1 fist degree or second degree relative with CRC, with suspected FAP or
- somebody in the family whom the presence of a high risk mutation in the adenomatous polyposis coli (APC) or one of the mismatch repair genes has been identified
- refer to genrtic screening of affected relatives.
- FAP: flexible sigmoidoscopy or
- Colonoscopy in attentuated FAP
Those at risk for FAP
what do the following mean? Autocrine Endocrine Neurocrine Paracrine
Autocrine - self communicating e.g. NO, IGF
Endocrine - hormones
Neurocrine - Vagus nerve e.g. Ach, VIP
Paracrine - parallel, talking next door e.g. somatostatin
Where are the following peptide hormones produced? Function? Gastrin CCK Secretin Glucagon Gastric inhibitory peptide VIP Serotonin Substance P
Gastrin - Antral G cells. Regulates gastric H+.
CCK - Intestinal I cells. Regulates pancreatic enzyme regulation.
Secretin - Intestinal S cells. Regulation of HCO3.
Glucagon - Intestinal L cells. Regulation of Insulin.
Gastric inhibitory peptide - Intestinal K cells. Reg of insulin release. Inhibitor of H+.
VIP - Myenteric inhibitory motorneurons/submucosal neurons. Neural inhibitor of of motility/stimulant of fluid secretion.
Serotonin - EC cell of digestive tract. Stimulus of peristalsis.
Substance P - Neurotransmitter.
what is the rate limiting step in acid production?
H/K/ATPase pump
What are some of the AE of PPIs in studies?
Increased risk of Pneumonia, Gastroenteritris e.g. Campylobacter, Salmonella, OP.
Significant risk of C. diff in meta analysis.
What are the causes of Hypergastrinaemia?
Atrophic gastritis - pericious anaemia, H. pylori
Renal failure
Hypercalcaemia
Hyperlipidaemia
Vagotomy/SB resection
Gastrin secreting tumour
Prolonged acid inhibition e.g. PPI, H2RAs
What is Zollinger-Ellison Syndrome?
Gastrin secreting tumour -> ulcer disease.
1/3 of pts have MEN1
How do you Dx ZES?
Gastrinoma triangle - bound by junction of cystic and CBD, junction of 2nd-3rd parts of duodenum and junction of neck and body of pancreas.
Step 1 - Fasting gastrin > 1000 pg/mL in absence of PPI.
If eelvated gastrin, confirm with basal acid output test.
Step 2 - BAO = acid output > 10 mEq/ hr.
Secretin provocation
Step 3 - secretin provocation test to confirm Dx.
Should expect increase of gastrin>200pg/ml above baseline within 15 minutes of infusion.
Which cells control persitalsis?
Interstitial cells of Cajal in myenteric plexus. Serves as pacemaker cells leading to slow waves potential -> contraction of smooth muscle
Which motility disorders are associated with loss of interstitial cells of Cajal?
Slow transit constipatiomn/chronic idiopathic constipation Internal anal sphincter achalasia Gastroparesis (idiopathic and diabetic) Afferent loop syndrome Megacolon and megaduodenum Paraneoplastic dysmotlity Crohn's disease Achalasia of LES
What are the acute causes of pancreatitis?
Alcohol Gallstones Drugs Infection metabolic ERCP, post Ischaemia - rare, after prolonged Sx in prone position
Causes of chronic pancreatitis?
EtOH Genetic Duct obstruction Tropical Systemic disease AI Idiopathic
Have studies shown statins reduce risk of pancreatitis?
Yes.
Fibrates no.
How do you treat post ERCP pancreatitis?
NSAIDs
Acute Mesenteric ischaemia. Cause, Presentation, Ix, Tx?
Causes:
occlusive (85-95%) or non occlusive (20-30%) obstruction of arterial or venous flow.
SMA embolism in 50%
SMA thrombosis 15-25%
Non occlusive - usually due to splanchnic vasoconstriction
Mesenteric venous occlusion 5%
Focal segmental inschaemia
SMA embolism from LA or ventricular mural thrombus is the most common cause
Presentation: >50 y Underlying cardiac disease Acute onset of severe ado pain AS, tender, pain out of proportion to examination
Ix:
Gold standard is mesenteric angiography
Tx:
Papaverine- phosphodiesterase inhibitor can be used at the time of angiography to relieve mesenteric vasoconstriction in pts with embolic and non embolic arterial occlusion as well as nonexclusive ischaemia.
Laparotomy and embolectomy
Mesenteric artery thrombus - Surgical revascularisation
Mesenteric venous thrombus - anitcoag and resection of infarcted bowel
Non- occlusive - Tx cause, resection is ischaemia present
Chronic Mesenteric Ischaemia. Cause, Presentation, Ix, Tx?
Intestinal angina.
Manifestation of mesenteric arthersclerosis.
Presentation:
Abdo pain 30 minutes after eating - due to diversion of small bowel blood flow to gut after eating.
Leads to sitophobia - fear of eating
Ix:
Splanchnic angiography - occlusion of at least 2 of the major splanchnic arteries
Doppler US a screening test but cannot confirm Dx
MR and CT angiography useful but abnormal study still warrants a splanchnic angiography.
Tx:
Surgical revascularisation is the definitive Tx
Percutaneous angioplasty with or without stunting can be attempted in pts who are poor surgical candidates for bypass Sx.
Primary Biliary Cirrhosis: What, Presentation, Ix, Tx?
Chronic cholestatic liver disease of unknown cause. Ongoing immunologic attack on interlobular bile ducts eventually lead to cirrhosis and liver failure.
Affects middle aged F, median onset 50y.
Presentation: Fatigue Dry eyes Dry mouth Pruritis Jaundice and cutaneous hyperpigmentation rarely observed.
Ix:
High Bili
ALP 1.5 x ULN
AST and ALT 5xULN
Mitochondrial antibody present in 90-95% at titres > 1:40
Liver bx if ab -ve
Histo - focal duct obliteration with granuloma formation known as florid duct lesion is pathognomonic.
Tx:
Ursodeoxycholic acid , offers survival benefit
Symptomatic Tx of dry eyes, dry mouth and pruritis
Liver transplant highly effective for end stage PBC
What test has the most NPV in coeliac disease?
HLA DQ2/8 negative
Very unlikely to have disease
Consider testing in non dx histo or negative serology
PUD: most common cause? Common site? Dx?
H. pylori and NSAIDs cause > 90%
Duodenum most common, 95% in bulb or pyloric channel.
In the stomach most are in the antrum.
Duodenal ulcers have increased acid secretion compared with gastric.
Dx confimed by upper endoscopy with rapid urease test and histo.
If Bx not taken, then urea breath test or faecal antigen test
PPIs can casue false negatives and should be stopped 7-14 days prior
Where are the following absorbed in the GIT? Iron, folate, B12/bile salts
iron - duodenum
folate - jejunum
absorption > in proximal then distal jejunum
B12/bile salts - ileum
Tx of alcoholic hepatitis?
Based on Maddrey discriminant function score (MDF)
MDF ≥32 = severe alcoholic hepatitis. Tx with prednisone or pentoxifylline.
Pentoxyfylline used when pt has fever (SBP), bleeding, RF as prednisone CI.
Cease EtOH
Supportive care
How do you calculate the Maddrey discriminant function score (MDF)?
4.6 [PT (s) - control PT (s)] + total bilirubin.
>= 32 suggest severe alcoholic hepatitis with short term mortality risk of 50%
What is the MELD score? How do you calculate it?
Prognostic Index to assess mortality in pts with ALD
MELD score: Total Bilirubin Serum albumin INR Ascites Hepatic encephalopathy
MELD 5-6 = 100% 1 y survival
MELD 7-9 = 81% 1 y survival
MELD 10-15 = 45% 1 yr survival
Biggest predictor of varices?
Portal pressure (hepatic venous portal pressure)
> 10 suggest high risk of bleeding
HVPG is the only measurable factor
Child Pugh score C = 70% risk of bleed
NAFLD. What, Dx, Tx?
Usually results fro insulin resistance and metabolic syndrome.
Inflammation and fibrosis associated with NAFLD is referred to as NASH.
10% progress to cirrhosis.
Dx: US, VT, MRI can confirm heaptic steatosis but cannot indetify inflammtion and fibrosis. Liver Bx confirms NASH
Tx:
Weight loss and managment of co-morbidities
What is the criteria for liver transplantation in fulminant hepatic failure?
PT > 100 sec irrespective of grade of encephalotpathy OR
any 3 of the following
- Age 40 y
- non A-B hepatitis, halaothane of drug reaction
- Jaundice to encephalopathy > 7 d
- PT > 50 s
- serum bilirubin > 300
What is the criteria for liver transplantation in fulminant hepatic failure in paracetamol overdose?
pH 100 and
serum Cr > 300
in pts with grade III or IV encephalopathy
CI to liver transplant?
Ongoing smoking and EtOH
Indications for liver transplant?
MELD score> 15 in adult Small HCC Liver disease that would result in a 2 year mortality rate of >50% without liver tranplantation Diuretic resistnat ascites recurrent HE recurrent SBP recurrent or persistent GI haem Intractable cholangitis HPS Portopulmonary HT Metabolic syndromes curable with lvier tranplant e.g. falilial amyloidosis, urea cycle disorders, oxalosis
Most common indication for liver transplant?
Hepatoma
