Week 3 Flashcards
(142 cards)
1
Q
What is ERCP?
A
Endoscopic retrograde cholangio-pancreatography
Technique using endoscopy and fluoroscopy used to diagnose pancreatic/biliary duct disease
2
Q
How are patients prepared for endoscopy?
A
Local oral anaesthetic, benzodiazepine injection, laxative
3
Q
In the GI tract, what is the Z-line?
A
Line of transition from oesophageal to gastric mucosa (pinker)
4
Q
How are x-rays used for the GI tract?
A
Secondary role
Show accumulation of gas, occlusion and perforation
5
Q
How is fluoroscopy used for the GI tract?
A
Radiation, contrast and distension with gas/air required
Used for patients who refuse/cannot tolerate endoscopy
6
Q
How is ultrasound used for the GI tract?
A
Investigation of abdominal pain/gallstones (thickened gallbladder wall, tenderness, bloating, visible stones)
Limited by habitus and gas
7
Q
How is CT used for the GI tract?
A
High dose of radiation, dye used, poor tissue differentiation
Diagnosis of disease, staging of malignancy, assessing response to treatment, percutaneous biopsy
CT enterography - SI, fill with fluid for better visualisation
CT colonoscopy - LI
PET-CT - combined functional imaging of tracer (fluorodeoxyglucose) uptake with anatomical image; sensitive for metastases
CT angiography - identification of bleeding points
8
Q
How is MRI used for the GI tract?
A
No radiation, good tissue differentiation, slow
Biliary tree/small intestine imaging, staging of rectal cancer, diagnosis of liver lesions
9
Q
What is MRCP?
A
Magnetic resonance cholangio-pancreatography
Visualisation of gallbladder and bile duct (e.g. stones)
10
Q
How are gastric ulcers classified?
A
Risk of re-bleeding
Blood vessel erosion, blocked by clot, spasm of vessel
11
Q
What percentage of upper GI bleeding do gastric ulcers account for?
A
20-50%
12
Q
Who is at highest risk of gastric ulcers?
A
Middle aged/elderly men
13
Q
What are the major causes of gastric ulcers?
A
H.pylori infection, excessive alcohol consumption, NSAID overuse
14
Q
What are Klean-prep iso-osmotic bowel cleansing sachets used for?
A
Preparation of patients for colonoscopy
Care must be taken with renal patients
15
Q
What is a minimal prep stool tagged CT and who is it suitable for?
A
Small amount of contrast ingested and homogenised in stool so that anything not uniformly tagged is abnormal (e.g. poly, tumour)
Less invasive, used in frail elderly patients
16
Q
What is CT colonography used for?
A
Patients who refuse/cannot tolerate colonoscopy
Diagnosis/staging
Laxative preparation, contrast tagging, air distension
17
Q
Who does the bowel screening program target and how often is it sent out?
A
Elderly men and women between 50-74 years old
Every 2 years
18
Q
How is rectal cancer managed?
A
Radiotherapy/chemotherapy used before surgical removal, MRI defines margins
Mesorectal excision of tumour and surrounding mesenteric fat
19
Q
What is familial adenomatous polyposis?
A
Genetic condition characterised by a carpet of small adenomatous polyps in the colon/rectum
High risk of developing into adenocarcinoma - total colectomy carried out at a young age
20
Q
What is the total iron content of the body and where is this distributed?
A
4g
Bone marrow/RBCs (3g), reticuloendothelial system (200-500mg), myoglobin (200-300mg), enzymes (100mg)
21
Q
In what 2 ways is iron stored in the body?
A
Ferritin - soluble, safe, readily available from RES
Haemosiderin - insoluble, aggregates of ferritin, slowly available
22
Q
Why is serum ferritin clinically useful?
A
Very small amount present but levels directly relate to whole body stores of iron
Decreased in deficiency/anaemia, increased in overload/haemochromatosis
Ferritin is an acute phase protein - increased in tissue inflammation
23
Q
What is the plasma iron transport protein?
A
Transferrin
Glycoprotein, synthesisted in hepatocytes, 3 iron binding domains, 30% normal saturation
24
Q
What is the relationship between iron and transferrin?
A
Increased transferrin = decreased iron
Decreased transferrin = increased iron
25
What is the normal daily iron requirement?
1-2mg/day
| Also equates to menstrual loss
26
How much iron does a typical Western diet provide?
15-20mg/day
| Nutritional deficiency is rare
27
What is hepcidin?
Regulator
Reduces levels of iron in plasma by binding and degrading ferroportin (decreased enterocyte absorption and macrophage release of iron)
28
Where in the diet is haem and non-haem iron obtained?
Haem - red meat
| Non-haem - white meat, green vegetables, cereals
29
What is the only mechanism for maintaining iron balance?
Regulation of dietary iron absorption - no excretory mechanism for excess
30
Where and how is iron predominantly absorbed?
Duodenum
Haem - easy
Non-haem - needs to be digested by acid/enzymes (reduced from ferric to ferrous form by duodenal cytochrome b1, influenced by vitamin C)
31
How is non-haem iron taken up from the gut lumen into enterocytes?
Through divalent metal transporter 1 (DMT1) - electrogenic pump upregulated in iron deficiency
32
How is iron exported from enterocytes into plasma?
```
Through ferroportin (transmembrane protein) and hepcidin
Most important regulators of absorption
```
33
What roles does ferroportin have in iron transport?
Exports iron from enterocytes to plasma
| Essential for release of iron from macrophages
34
What is the RES?
Reticuloendothelial system
The aggregate of the phagocytic cells that have reticular and endothelial characteristics and function in the immune system's defense against foreign bodies
35
Outline iron release from the RES
RES macrophages acquire iron from weak/ineffective RBCs → iron stored as ferritin/haemosiderin → iron released into plasma (to transferrin) by ferroportin and hepcidin → transferrin-iron is taken up by RBCs/hepatocytes etc.
36
How many molecules of iron can transferrin bind?
2
37
What is the distribution of transferrin receptors in the body?
80% RBC precursors
| 20% liver etc.
38
What happens to iron inside erythroblasts?
Most iron is transported to the mitochondria where ALA-synthase enzyme uses it to produce haem
Some iron is stored as ferritin
39
What is the golden rule of IDA?
IDA in males and post-menopausal women is due to GI blood loss until proven otherwise
40
Haematologically, how would IDA RBCs be described?
Hypochromic (pale) and microcytic (small)
41
What might cause IDA in young women?
Menstrual blood (1-2mg loss) and pregnancy (500mg of loss)
42
What is a main cause of iron malabsorption?
Haematinic deficiency in coeliac disease
43
What are the 3 main haematinic deficiencies in coeliac disease?
Folate - most likely, found in green vegetables/liver/citrus fruit, daily requirements are high but body stores are low
Iron
Vitamin B12 - unlikely, found in meat/dairy, body stores vast
44
How is coeliac mucosa characterised?
Villus atrophy, enlarged hyperplastic crypts, increased infiltration of lymphoid cells in lamina propria and epithelium
45
What are the haematological features of a patient who is hyposplenic due to coeliac disease?
Target RBCs
Howell-Jolly bodies (DNA fragments)
Irregularly contracted RBCs
46
What is the consequence of a loss of hepcidin?
Increased enterocyte absorption and macrophage release of iron → increased transferrin saturation → parenchymal iron overload (e.g. haemochromatosis)
47
Where is hepcidin synthesised?
Liver
48
What is hereditary haemochromatosis?
Autosomal recessive disorder of iron metabolism causing iron overload usually due to HFE gene abnormalities (needed to produce hepcidin)
More severe in males; females protected by menstruation/child birth
49
What is the most common HFE gene mutation?
Homozygous C282Y mutation - H63D
| <50% have HH
50
What is the iron saturation of transferrin in normal, IDA and HH?
Normal - 30%
IDA - <15%
HH - 100%
51
What are the effects on tissues/organs of excess iron?
```
Liver - cirrhosis
Pancreas - diabetes
Skin - bronzing/pigmentation
Joints - arthritis
Heart - restrictive cardiomyopathy
```
52
How is HH treated?
Venesection - removal of blood until iron levels are normalised
500ml blood = 150mg iron
Monitor ferritin and transferrin saturation
Prevent/limit organ damage
53
What is sideroblastic anaemia?
Erythroblasts take in iron but do not convert it into haem and instead lock it away in haemosiderin in mitochondria which become paralysed
54
What is the difference between actute and chronic hepatitis?
Acute - short-term inflammation of the liver
| Chronic - hepatitis virus present for > 6 months
55
What are the main causes of acute hepatitis?
Infections - hepatitis A/B/C/D/E, Epstein Barr, cytomegalovirus, toxoplasmosis, malaria, syphilis, haemorrhagic fever
Toxins - drugs, alcohol
Autoimmune
Secondary to - Wilson's, haemochromatosis
56
Which of the hepatitis viruses are not blood bourne?
Hepatitis A and E
57
Which of the hepatitis viruses are blood bourne?
Hepatitis B, C and D
58
What are the main features of hepatitis A?
RNA virus
Faecal-oral transmission (contaminated water/food)
Incubation period - 30 days
Symptoms - fever, abdominal pain, diarrhoea, jaundice, itching, muscle pain
Asymptomatic in children, low mortality in elderly
Diagnosis - IgM positive or RNA in blood/stool; IgG positive means previous exposure
Treatment - self-limiting/non-specific; hydration
Vaccination - excellent, pre- or post-exposure, 2nd dose gives protection for life
Immunoglobulin - if allergic to vaccine, 3-6 months protection
59
What are the main features of hepatitis E?
RNA virus
Faecal-oral transmission (pork products)
Incubation period - 40 days
4 genotypes; type 3 neurological (encephalitis, myopathy)
Similar to hepatitis A, plus neurological effects
Treatment - supportive; no vaccine or immunity
Chronic infection seen in immunosuppressed
60
What are the main features of hepatitis B?
DNA virus
Most common worldwide
Transmission - transfusion, fluids, transplantation, maternal, contaminated needles, children
Incubation - 2-6 months
Symptoms - fever, fatigue, jaundice, myalgia, joint pain, weight loss, abdominal pain, bloody ascites
Age at infection determines severity and risk of chronic
Diagnosis - HBs antigen positive, sAg (surface antigen), DNA
Serology - sAg, sAb, cAb, eAg, eAb, HBV DNA
25% of chronic infection leads to chronic liver disease
Treatment (chronic only) - treat inflammation and suppress viral replication via immunological and antiviral drugs; no cure
61
What are the following serological indicators and what do they mean in relation to hepatitis B?
sAg, sAb, cAb, eAg, eAb
```
sAg - surface antigen; infection marker
sAb - surface antibody; immunity marker
cAb - core antibody; past infection, now cleared
eAg - e antigen; high infectivity
eAb - e antibody; low infectivity
```
62
How is hepatitis B infection diagnosed using serology?
If sAg or HBV DNA detectable
63
How are carriers of hepatitis B virus divided by stage of disease?
1. eAg +ve (early disease) - high viral load, high risk of chronic liver disease and hepatocellular carcinoma, highly infectious
2. eAg -ve (late disease) - low viral load, low risk of chronic liver disease and hepatocellular carcinoma, less infectious
64
What drugs are used to treat chronic hepatitis B?
Immunological - pegylated interferon α; increases cellular immune response, many side-effects
Antiviral - tenofovir, entecavir; suppress viral replication
65
How can hepatitis B infection be prevented?
Education - safe sex and injecting
Screening - pregnant women, doctors
Blood products - protection of supplies
Immunisation - active for high risk groups, passive for babies born to positive mothers
66
What 3 pregnancy interventions are in place regarding hepatitis B infection?
HBV vaccination to all newborns
HBV immunoglobulin if eAg+ or high viral load
Tenofovir in last trimester if viral load exceeds 106 IU/ml
Pegylated interferon is contraindicated in pregnancy
67
What are the main features of hepatitis D?
RNA virus
Requires hepatitis B to replicate - co-infection/super-infection
Increased risk of chronic liver disease
Treatment - pegylated interferon
68
What are the main features of hepatitis C?
Most common hepatitis virus in the UK
Transmission - contaminated needles, transfusion, transplant, sexual and vertical (rare)
No vaccine, post-exposure prophylaxis or reliable immunity
Multiple genotypes
Incubation period - 6-7 weeks
Diagnosis - screening of high risk groups
Treatment - over 24-48 weeks; pegylated interferon and ribavirin, direct acting antivirals; PCR negative 12 weeks after treatment = cured (40-60%)
69
How is the treatment for hepatitis C currently decided?
Direct acting antiviral regimen decided according to genotype and degree of fibrosis/cirrhosis
70
What hepatitis viruses can lead to chronic infection?
Hepatitis B, C and D
71
What is coeliac disease?
Gluten sensitive enteropathy characterised by small intestinal villous atrophy caused by inappropriate T cell-mediated immune response
72
What is the most toxic moiety in coeliac disease?
α-gliadin
Digestion produces stable peptide which is absorbed into the lamina propria
Exposure to tissue transglutaminase from the damaged epithelium leads to deamination of glutamine residues and allows bonding to HLA-DQ2 and activation of pro-inflammatory T-cell responses
73
What is the epidemiology of coeliac disease?
More women affected than men
Affects all ages
Rare in Africa/Asia, 1% prevalence in UK
95% are HLA-DQ2; 5% HLA-DQ8
74
What is the infection hypothesis in coeliac disease?
Infection with adenovirus 12 in genetically susceptible individuals → peptide on α-gliadin similar to that within the E1b portion of the virus → cross-reactivity with α-gliadin → development of coeliac disease
75
How does coeliac disease present?
Children - at 4-24 months old; impaired growth, diarrhoea, vomiting, abdominal distension
Older children - anaemia, short stature, pubertal delay, abdominal pain, behavioural disturbance
Adults - diarrhoea, bloating, flatulence, constipation, IDA, nutritional deficiency, reduced fertility, amenorrhoea, osteoporosis, unexplained elevated AST/ALT, peripheral neuropathy, epilepsy
76
How long is the small intestine?
3-7m
| Duodenum (26cm), jejunum (3.5m), ileum (1.5m)
77
What effects does coeliac disease have on the bowel?
Reduced villous height (atrophy), surface area and absorptive capacity - inflammation, increased plasma cells and intraepithelial lymphocytes
78
How is gastric acid involved in iron absorption?
Gastric acid lowers pH in the duodenum → increased solubility and uptake of ferric iron (enhanced by vitamin C, inhibited by phytates/tannins)
79
How is coeliac disease diagnosed?
Serology - IgA tissue transglutaminase antibody; IgA antiendomysial antibody
Endoscopy - scalloping and paucity of folds, mosaic pattern, prominent submucosal blood vessels, nodular mucosal pattern
Biopsy - distal duodenum, 4 (patchy), gluten-rich diet beforehand
Marsh classification used - 0, 1, 2, 3a-3c
80
What other conditions may cause villous atrophy?
Giardiasis, common variable immune deficiency, Crohn's disease, lymphoma, Whipple's disease, HIV, NSAIDs
81
What conditions are associated with coeliac disease?
```
Dermatitis herpetiformis (itchy rash on extensor surfaces)
Other autoimmune disorders - type 1 diabetes, thyrotoxicosis, Addison's disease
```
82
What is a gluten free diet?
Avoid - wheat, barley, rye
Can eat - oats, rice, maize
Symptomatic improvement in 70%
83
What are the complications of coeliac disease?
Infection - hyposplenism increasing susceptibility to meningococcus, haemophilus influenzae etc.
Osteoporosis - low BMI/calcium/vitamin D
Refractory coeliac disease - persistence of symptoms and villous atrophy at 6-12 months despite gluten free diet
Malignancy - enteropathy associated T-cell lymphoma (advanced and incurable, fatal), small bowel adenocarcinoma (rare, fatal)
84
Outline refractory coeliac disease types I and II
RCD I - villous atrophy with normal immunophenotype; 95% survival at 5 years, steroid treatment
RCD II - villous atrophy with abnormal immunophenotype (CD3/8 -ve) - ulcerative jejunitis, 58% survival at 5 year, progression to EATL
85
Where is the foregut?
From the mouth to the duodenum
86
What is the mesentery?
Continuous set of tissues formed by the double fold of peritoneum which attaches the intestines to the wall of the abdomen
87
What is the anatomical position of the appendix?
Retro-caecal
88
What is the ileo-caecal valve?
Where the caecum meets the ascending colon
89
What is another name for the right colic flexure?
Hepatic flexure
90
What is another name for the left colic flexure?
Splenic flexure
91
Which parts of the colon are attached to mesenteries?
Transverse and sigmoid colon
92
What is the importance of paracolic gutters?
Fluid from an inflamed appendix may collect in the right paracolic gutter when the patient is lying down
93
Where is the midgut?
From the duodenum to 2/3rd along the transverse colon
94
What artery supplies the midgut?
Superior mesenteric artery
95
What are arterial arcades and what is their function?
Network of anastomoses between blood vessels of the gut which are more complex in the ileum than the jejunum
Allows partial resection of the bowel without compromising blood supply
96
What does the marginal artery do?
Joins branches of various arteries in the gut
97
Where is the hindgut?
From 2/3rds along the transverse colon to the rectum
98
What arteries supply the hindgut?
Inferior mesenteric and superior rectal arteries
99
What external features of the small and large intestines are notable?
Small - smooth surface with no particular identifying features
Large - unequal width due to haustrations, fatty tags covered in peritoneum (appendices epiploicae), 3 thick bundles of longitudinal muscle running along the length (taeniae coli)
100
What is Meckel's diverticulum?
An abnormal sac/pouch develops at at weak point in the intestinal wall, usually at 5-7 weeks of foetal development (remnant of the vitelline duct/yolk stalk)
101
What are plicae circulares?
Circular folds/valves of Kerckring - large valvular flaps projecting into the lumen of the small intestine
102
What is the definition of infectious diarrhoea?
3 or more loose/watery stools per day
103
What are the pathogenic mechanisms of infectious diarrhoea?
Toxin mediated damage to intestinal epithelial surface and invasion across barrier
104
What are the differences between diarrhoea manifesting from the small intestine and large intestine?
Small - fluid and enzyme secretion and nutrient absorption; large volume of watery diarrhoea; cramps, bloating, wind, weight loss
Large - absorption of fluid and salt; potassium excretion; frequent small volumes of painful stool; fever and blood in stool
105
What are the main causes of infectious diarrhoea?
Bacteria - campylobacter, salmonella, shigella, clostridium, staphylococcus
Viruses - rotavirus, norovirus, adenovirus
Parasites - cryptosporidium, cyclospora
106
How should a patient with suspected infectious diarrhoea be approached?
History (food, travel, onset, residence, occupation, hospitalisation) → faecal leukocyte (inflammation)/occult (bacteria) blood → stool examination (parasites)/culture → endoscopy
107
How is infectious diarrhoea treated?
Oral rehydration solution (e.g. dioralyte) - water absorbed in presence of glucose and sodium
IV fluids - replacement of lost fluids (e.g. vomiting)
Antibiotics - reduce duration by 1 day and can worsen outcomes (e.g. E.coli 0157), only for sepsis or bacteraemia or some extenuating circumstance
108
What pathogens can cause bacterial gastroenteritis and what are their main features?
Campylobacter - sensitive to stomach acidity, 3 day incubation; frequent large volume diarrhoea, severe abdominal pain, fever; vomiting rare; self-limiting (7 days), antibiotics not indicated; complications (reactive arthritis, Guillain-Barre)
Salmonella - increased risk with low acid and gut flora; illness within 72 hours, rapid onset; nausea, diarrhoea, cramps, fever; invasive (bacteraemia, endocarditis, osteomyelitis); self-limiting (10 days), antibiotics not indicated; negative stool cultures needed to clear (asymptomatic shedding common)
E.coli 0157 - shiga toxin kills enterocytes and enters circulation; low infectious dose; 3-4 day incubation; bloody diarrhoea, abdominal tenderness; complications (haemolytic uraemic syndrome - microangiopathic haemolytic anaemia, acure renal failure and thrombocytopenia)
Clostridium difficile - antibiotic exposure, old age, hospitalisation; decreased resistance leads to colonisation and toxin production; loose stool, colic, fever; narrow spectrum antibiotics (e.g. vancomycin, metronidazole)
109
What pathogen can cause viral gastroenteritis and what are its main features?
Norovirus - faecal-oral transmission, low infectious dose, very stable, peak in winter, explosive diarrhoea and vomiting for 24-48 hours, no lasting immunity
110
How are oral water soluble drugs usually excreted by the body?
Poorly absorbed
| Excreted by kidneys into urine
111
How are oral lipid soluble drugs usually excreted by the body?
By the kidneys
| Filtered by the glomerulus and reabsorbed in the PCT
112
What is the role of the liver in excretion of lipid soluble drugs?
Conversion of lipid to water soluble drug (metabolite) which can then be excreted by the kidneys in the urine
113
What is phase I metabolism in the liver?
Dependent on cytochrome P450
Oxidation, reduction and hydrolysis
Produces polar metabolite
114
What is phase II metabolism in the liver?
Conjugation
Addition of glycine/glutamine/sulphate/acetyl/methyl
Converts metabolite to more polar form
115
What is the therapeutic range of a drug?
The difference between the concentration which achieves a therapeutic response and that which produces an adverse toxic effect
E.g. penicillin wide, theophylline narrow
116
What is the volume of distribution of a drug?
The apparent volume throughout which the drug would be evenly distributed to obtain the measured serum/plasma concentration
Proportionality constant relating to the amount of drug in the body to the concentration measured in blood
Volume of distribution (L) = dose (mg)/concentration (mg/L)
117
What would the volume of distribution be if a drug was bound highly to plasma proteins compared to tissue proteins?
Plasma proteins - distribution to tissues restricted; plasma concentration high, volume of distribution low
Tissue proteins - plasma concentration low, volume of distribution high
118
Is volume of distribution high or low for water soluble and lipid soluble drugs?
Water - low
| Lipid - high
119
What is the equation for the initial drug concentration achieved after a single intravenous bolus injection?
C0 = dose/volume
120
What is the equation for the loading dose?
Loading dose = target concentration (mg/L)/volume (L)
121
What is the equation for a top up dose?
Top-up dose = (target concentration - measured concentration) x volume
122
What is clearance?
The volume of blood/serum/plasma cleared of a drug per unit time
Depends on rate of drug delivery (blood flow) and efficiency (extraction ratio) of drug removed
123
What is the equation for average steady state concentration?
Cssav = infusion rate/clearance
124
What is the equation for infusion rate?
Infusion rate = target steady state concentration/clearance
125
When is the average steady state concentration useful?
Oral administration, when the concentration peaks and troughs; dose and dose interval also required
126
What is bioavailability?
Fraction of an oral administered dose which reaches the systemic circulation
127
What is the equation for oral maintenance dose?
Oral maintenance dose = target average steady state concentration x clearance x dosage interval
128
What is the equation for the elimination rate constant?
Elimination rate constant (k) = clearance/volume of distribution
129
What is the elimination rate constant?
The constant proportion per unit time in which drugs are eliminated from the body
130
What is the elimination half-life?
Time taken for a drug concentration to fall to half; can be used to estimate time taken for the drug to be eliminated from the body and steady state
131
Approximately how many half-lives does it take a drug to clear the body?
4-5
132
How is bioavailability affected in those with liver disease?
Reduction in first-pass metabolism cause an increase in drug concentration
Doses of drugs which are extensively metabolised by the liver will need to be reduced in patients with severe hepatic disease
133
How is volume of distribution affected in those with liver disease?
Oedema and ascites with reduced albumin synthesis will increase volume of distribution of water soluble drugs
134
What adjustments need to be made to drug dosage in hypoalbuminaemia?
Hypoalbuminaemia decreases the percentage of drug which is bound to plasma proteins - bound concentraion falls
Dose adjustments only required if unbound concentration also changes due to altered clearance
Measurement of total concentration way cause misinterpretation
135
What is the equation for elimination half-life?
Elimination half-life (T1/2) = 0.693 x volume x clearance
136
How is clearance of drugs affected in those with liver disease?
Clearance of drugs with a high extraction ratio (>0.7) depends on liver blood flow - factors affecting blood flow will require dose adjustment
137
What does the clearance of drugs with a high extraction ratio (>0.7) depend on?
Liver blood flow
138
What does the clearance of drugs with a low extraction ratio depend on?
Capacity of metabolising enzymes
| Highly susceptible to drug interactions
139
What is gallbladder relaxation and closure of the sphincter of Oddi mediated by?
VIP - vasoactive intestinal polypeptide
140
With which ion are amino acids co-transported into enterocytes?
Na+
141
With which ion are di-peptides and tri-peptides co-transported into enterocytes?
H+
142
What is the consequence of a deficiency of pancreatic protease enzymes which help break down of proteins in the small intestine?
Increased risk of intestinal infections
