1
Q
Where does protein digestion begin?
A
In stomach with pepsin
2
Q
Where is protein digestion completed?
A
In small intestine with pancreatic & brush-border proteases
3
Q
What is the main pancreatic protease secreted as inactive precursor in the small intestine?
A
Trypsinogen
4
Q
What mechanism helps absorption of amino acids in the small intestine?
A
Na+- dependant cotransport
5
Q
What mechanism helps absorption of Dipeptides in the small intestine?
A
H+- dipeptide cotransport
6
Q
What mechanism helps absorption of Tripeptides in the small intestine?
A
H+- tripeptide cotransport
7
Q
Dietary lipids are _____?
A
Hydrophobic
insoluble in water
8
Q
What % of ingested triglycerides do lingual & gastric lipase hydrolyse?
A
Hydrolyse 10% into glycerol & free fatty acids
9
Q
What is the key role of gastric lipase?
A
Slow the rate of gastric emptying so that pancreatic enzymes are able to digest lipid
10
Q
What 3 things emulsify dietary lipids?
A
- Bile salts
- Lysolecithin
- Products of lipid digestion
11
Q
What are secreted to complete the digestion of lipids in the small intestine?
A
- Pancreatic enzymes (pancreatic lipase, cholesterol ester hydrolase & phospholipase A2)
- Colipase
12
Q
What are the 6 steps to digestion and absorption of lipids in the small intestine?
A
- Bile salts from liver coat fat droplets
- Pancreatic lipase & colipase break down fats into monoglycerides & fatty acids stored in micelles
- Monoglycerides & fatty acids move out of micelles & enter cells by diffusion
- Cholesterol is transported into cells by membrane transporter
- Absorbed fats combine with cholesterol & proteins in the intestinal cells to form chylomicrons
- Chylomicrons are released into lymphatic system
13
Q
Describe the structure of a Chylomicron?
A
- 100nm diameter
- Core of triglycerides & cholesterol ester
- Outside of phospholipids & apoproteins
14
Q
Where are chylomicrons packaged and where do they go?
A
Into secretory vesicles on Golgi membrane & exocytose across basolateral membrane
15
Q
Where does the lymphatic circulation take the chylomicrons?
A
Thoracic duct which empties into blood stream
16
Q
What are the differences between tight junctions of the colon & small intestine?
A
- Small intestine are “leaky” (permeable via paracellular route)
- Colon are “tight” (impermeable via paracellular route)
17
Q
What 2 different structures absorb & secrete fluids in the small intestine?
A
- Villi- absorption
2. Crypts of Lieberkuhn- secretion
18
Q
What 2 different structure absorb & secrete fluids in the large intestine?
A
- Suface epithelial cells- absorption
2. Colonic glands- secretion
19
Q
How much H20 is absorbed in the small intestine?
A
6.5L
20
Q
How are electrolytes absorbed in the intestine?
A
Na+, Cl-, HCO-3, K+ absorbed isosmotically with water by villi (as in the renal proximal tube)
21
Q
What happens at the epithelial cells lining the crypts of Lieberkuhn?
A
- Cl- enters cell via Na+ K+ 2Cl- basal transporter
- Cl- diffuses across apical membrane through apical Cl- channels
- Na+ follows Cl- secretion passively via paracellular pathway
- H2O follows NaCl secretion
22
Q
What regulates diffusion of Cl- at the apical membrane in the intestine?
A
Secretagogues
23
Q
What are the 5 different Hormonal/neurotransmitter Secretagogues?
A
- VIP
- Guanylin
- Acetylcholine
- Bradykinin
- Serotonin (5HT)
24
Q
What is a Secretagogue?
A
Substance which promotes secretion
25
Name some bacterial enterotoxins?
- Cholera toxin
- E coli toxins
- Yersinia toxin
- Clostridium difficile
26
Where are fat soluble vitamins absorbed?
| What is the mechanism?
- Small intestine
| - Bile salts form micelles, diffusion into intestinal cells
27
Where are water soluble vitamins absorbed?
| What is the mechanism?
- Small intestine
| - Na+ dependant cotransport
28
Where is Vitamin B12 absorbed?
| What is the mechanism?
- Ileum
| - Intrinsic factor
29
Where are bile salts absorbed?
| What is the mechanism?
- Ileum
| - Na+ bile salt cotransport
30
Where is Ca2+ absorbed?
| What is the mechanism,?
- Small intestine
| - Vitamin D- dependant Ca2+ binding protein (Calbindin)
31
Where is Fe2+ absorbed?
| What is the mechanism,?
- Small intestine
| - Binds to apoferritin in intestinal cell, binds to transferrin in blood
32
What are the ordered steps for examination?
"IIPPA"
- Introduction/explanation
- Inspection
- Palpation
- Percussion
- Auscultation
33
What does "MILC" stand for in causes of GI clubbing?
- Malabsorption (coeliac)
- Inflammatory bowel disease (UC & Crohn's)
- Lymphoma
- Cirrhosis
34
When does Asterixis/flapping tremor occur?
With hepatic encephalopathy (severe liver failure)
35
What is Leuconychia?
White discolouration appearing on nails
36
What is Koilonychia?
Spoon nails, can be a sign of iron-deficiency anemia
37
What is Dupuytrens contracture?
- Fixed forward curvature of one or more fingers
| - Caused by fibrous connection between the finger tendons and the skin of the palm
38
What is Purpura?
- Red/purple discolored spots on skin that do NOT blanch on applying pressure.
- Caused by bleeding underneath the skin usually secondary to vasculitis or dietary deficiency of vitamin C
39
What is Angular Stomatitis?
- Inflammation of one/both corners of the mouth
| - Caused by infection, irritation, or allergies
40
What is Peutz-Jegers Syndrome?
Autosomal dominant genetic disorder characterised by development of benign polyps in the GI tract & hyperpigmented macules on the lips and oral mucosa
41
What is Telangiectasia?
Dilatation of capillaries causing them to appear as small red or purple clusters, often spidery in appearance
42
What is Gynaecomastia?
Enlargement of male breasts, usually due to hormone imbalance/hormone therapy
43
What are the "5 F's" for abdominal distension?
- Fat
- Fluid
- Faeces
- Flatus
- Foetus
44
What are you palpating for when examining the abdomen?
- Tenderness (guarding or re-bound tenderness)
- Masses
- Organomegaly
- Abdominal aorta
45
What can Palmar erythema be a sign of?
Chronic liver disease, or be normal in pregnancy
46
Does the liver & spleen move during respiration?
YES
47
How do you palpate for the liver in an abdominal examination?
- Begin in right iliac fossa
- Ask patient to breathe in and out
- Palpate upwards to right costal margin
- Feel for liver edge as it descends on inspiration & move hand between each breath
48
What are the 5 different things to note when palpating the liver?
1. Size
2. Surface & edge (smooth/irregular)
3. Consistency (soft/hard)
4. Tenderness
5. Pulsatility
49
List the potential different causes for Hepatomegaly (enlarged liver)?
- Hepatitis
- Alcoholic liver disease
- Right heart failure
- Fatty infiltration
- Biliary tract obstruction
- Malignancy (metastatic/primary)
- Haematological disorders
50
What is Murphy's Sign?
- Feel for gall bladder tenderness (acute cholecystitis)
- Patient breathes in whilst you gently palpate RUQ in midclavicular line
- On liver descent contact with inflamed gallbladder causes tenderness and sudden arrest of inspiration
51
What is Courvoisier's Sign?
- Painless Jaundice & a palpable gallbladder
| - Likely due to extra hepatic obstruction ie. Pancreatic cancer
52
What is Courvoisier's Sign UNLIKELY to be?
Gallstones
53
How do you palpate the spleen during abdominal examination?
- Ask patient to breathe in & out deeply
- Palpate upwards to left hypochondrium
- Feel for edge of enlarged spleen as it descends on inspiration
- Characteristic notch may be palpable
- Move hand between each breath
54
What are the possible causes of Splenomegaly?
- HAEMATOLOGICAL: haemolytic anaemias, leukaemias, lymphoma
- INFECTIVE: infective endocarditis, TB, malaria
- Portal hypertension
- RHEUMATOLOGICAL: rheumatoid arthritis, SLE
- RARE: sarcoidosis, amyloidosis, glycogen storage diseases
55
How do you palpate the bladder during abdominal examination?
- Palpate upper border
- In midline
- Lower border not palpable
56
What are the possible causes of renal enlargement?
- Hydronephrosis
- Polycystic kidney disease
- Renal cell carcinoma
- In children, nephroblastoma (Wilm's tumour)
- Solitary cysts
57
What is the most common aortic aneurysm?
Abdominal
58
What is percussion ascites?
Abnormal collection of fluid in peritoneal cavity
59
What are the possible causes for percussion ascites?
- Hepatic cirrhosis
- Intra-abdominal malignancy
- Nephrotic syndrome
- Cardiac failure
- Pancreatitis
- Constrictive pericarditis
60
Where may tumours of the upper GI tract metastasise?
Lower part of left posterior cervical triangle (cervical lymph nodes)
61
What other areas can you offer in an abdominal examination?
- Examine groin
- Examine genitalia
- Requests to do digital rectal examination (DRE)
62
What are the possible reasons for requesting to do a rectal examination on a patient?
- Rectal bleeding
- Prostatic symptoms
- Change in bowel habits
- Possible spinal cord injury
63
What are the possible reasons for requesting to do a female reproductive examination on a patient?
- Pelvic pain
- Abnormal vaginal bleeding
- Abnormal vaginal discharge
- If considering vaginal / uterine prolapse
64
What is the possible female pelvic pathology?
- Ovarian cyst, malignancy
- Uterine prolapse, fibroids, cervical carcinoma
- Vaginitis, prolapse
- Pelvic infection
- Ectopic pregnancy
65
What is the possible male reproductive pathology?
- Epididymitis
- Testicular torsion
- Epididymal cysts
- Testicular tumours
- Indirect inguinal hernia
66
What are the causes of acute oesophagitis?
| usually in immunocompromised patients
- Herpes simplex viruses
- Candida
- Cytomegalovirus (CMV)
- Corrosives
67
What are the causes of chronic oesophagitis?
- Tuberculosis
- Bullous pemphigoid & Epidermolysis bullosa
- Crohn's disease
- Reflux oesophagitis
68
What does "GORD" stand for?
Gastro-oesophageal reflux disease
69
What are predisposing factors for "incompetent" gastro-oesophageal junction?
- Alcohol & tobacco
- Obesity
- Drugs ie. caffeine
- Hiatus hernia
- Motility disorders
70
What can severe oesophagitis reflux lead to?
Ulceration (complete loss of epithelia)
71
What is Barrett's Oesophagus?
- Longstanding reflux oesophagitis
- Lower oesophagus becomes lined by columnar epithelium (metaplasia)
- Premalignant, risk of adenocarcinoma of distal oesophagus 100x
72
What are the causes for acute gastritis?
- Usually due to chemical injury
| - H pylori-associated
73
What are the causes for chronic gastritis?
- Active chronic (H pylori-associated)
- Autoimmune
- Chemical (reflux)
74
What chemical injury can cause acute gastritis?
- Drugs ie. NSAIDS
| - Alcohol
75
Describe Helicobacter pylori-associated acute gastritis?
- Usually transient phase
- Often becomes chronic
- Does not colonise intestinal type epithelium
- Found in 90% of active chronic gastritis
76
What are the 2 distribution patterns of H pylori-associated gastritis?
1. Diffuse involvement of antrum and body
| 2. Antral but not body
77
How can you detect H pylori-associated Gastritis?
- Faecal bacterial
- Urea breath test
- Gastric biopsy rapid urease test
78
What causes chemical (reflux) gastritis?
Regurgitation of bile & alkaline duodenal secretion
79
What is chemical (reflux) gastritis associated with?
- Defective pylorus
| - Motility disorders
80
What is autoimmune chronic gastritis?
- Autoimmune reaction to gastric parietal cells
- Loss of acid secretion (hypochlorhydria/achlorhydria)
- Loss of intrinsic factor (vitamin B12 deficiency, pernicious anaemia)
- Marked gastric atrophy and intestinal metapasia
- Increased risk of gastric cancer
81
What are the major sites of peptic ulceration?
- 1st part of duodenum (most common)
- Junction of antral & body mucosa in stomach
- Distal oesophagus
- Gastro-enterostomy stoma
82
What are risk factors for peptic ulceration?
- Hyperacidity
- H pylori gastritis
- Duodenal reflux
- NSAID's
- Smoking
- Genetic factors
- Zollinger-Ellison syndrome
83
What are the complications of peptic ulceration?
- Haemorrhage
- Penetration of adjacent organs ie. pancreas
- Perforation
- Anaemia
- Obstruction
- Malignancy
84
What 3 things are acute peptic ulcers related to?
- Acute Gastritis
- Stress response
- Extreme hyperacidity
85
Where do chronic peptic ulcers tend to occur?
Mucosal junctions ie. antrum-body
86
What is the pathogenesis of a chronic peptic ulcer?
- Hyperacidity
| - Mucosal defence defects
87
What are the mucosal defences?
- Mucus-bicarbonate barrier (dissolved by biliary reflux)
| - Surface epithelium (damage by NSAIDs, injured by H pylori)
88
What is the pathology of Chronic duodenal ulcers?
- Small
- "Punched out" with defined edges
- Granulation tissue at base
- Underlying inflammation & fibrosis
- Loss of muscular propria
89
What can the complications of chronic duodenal ulcers be?
- "Bleed, burst or block"
- Penetration of adjacent organs ie. pancreas
- Malignant change
90
What happens at the small intestine to activate all the pancreatic proteases?
Inactive Trypsinogen is activated to Trypsin by enterokinase (brush border) to active all the other inactive pancreatic proteases
91
What are the 4 layers typical of gastric ulcers?
| superficial to deep
1. Necrotic debris
2. Nonspecific acute inflammation
3. Granulation tissue
4. Fibrosis
92
What can an untreated ulcer causing epithelial perforation result in?
Leading of food & gastric juices to peritoneal / abdominal cavities
93
What 2 pathogens can cause bloody stools?
- Campylobacter
| - Shigella
94
What 2 pathogens can cause watery stools?
- EPEC
| - Cholera
95
Name 5 gram negative bacterial diarrhoeal pathogens?
- Vibrio cholerae
- Escherichia coli
- Campylobacter jejuni
- Salmonella spp.
- Shingella spp.
96
Name a gram positive bacterial diarrhoeal pathogen?
Listeria monocytogenes
97
Describe the characteristics of V. cholerae?
- Flagellated
- Epidemics & Pandemics
- Human-only pathogen
- Flourishes with no clean drinking water/sewage disposal
98
What antigens are V. cholerae serotypes based on?
O antigens
99
What are the 2 different routes for V. cholerae vaccines and what are they particularly good for?
1. Parenteral vaccine: low protective efficiency
| 2. Oral vaccine: effective & suitable for travellers
100
What is the pathogenesis of V. cholerae?
- Only infective in large doses
- Colonisation of small intestine involving flagellar motion, mucinase, attachment to specific receptors
- Production of multicomponent toxin
- Loss of fluid & electrolytes without damage to enterocytes
101
Describe the oligomeric complex (6 protein subunits) of Cholera Toxin?
- 1 copy of A subunit (enzymatic)
| - 5 copies of B subunit (receptor binding)
102
What are the consequences of Cholera infection?
- Fluid loss of upto 1L/hr
- Electrolyte imbalance leading to dehydration, metabolic acidosis & hypokalemia
- Hypovolaemic shock
103
What is the mortality difference between an ORT treated cholera infection and an untreated?
- 40-60% untreated
| - <1% ORT treated
104
Describe the characteristics of E. coli?
- Bacillus
- Member of normal GI microbiota
- Some strains possess virulence factors enabling them to cause disease
105
Name 2 types of E. coli that cause GI infections?
```
EPEC= enteropathogenic
ETEC= enterotoxigenic
```
106
What kind of E. coli infections are EPEC involved in?
Sporadic cases & outbreaks of infection in under 5's
107
What kind of E. coli infections are ETEC involved in?
"Travellers' diarrhoea" occurs in 20-50%
108
What are the 2 main enterotoxins secreted by the bacteria?
1. LT= heat labile toxin
| 2. STa= heat stable toxin
109
Describe the characteristics of C. jejuni?
- Helical bacillus
- Large animal reservoir
- Food-associated diarrhoea
- Commonest cause
- Through consumption of raw/undercooked meat, contaminated milk
- Mucosal inflammation & fluid secretion
110
What is the histological appearance resulting from a Campylobacter jejuni infection?
- Inflammation involves entire mucosa
- Villous atrophy
- Necrotic debris in crypts
- Thickening of basement membrane
111
Describe the characteristics of Salmonella spp.
- Bacilli
- Food-associated diarrhoea
- Through computation of raw/undercooked meat, contaminated eggs & milk
- Secondary spread human-human
112
What are the 3 important species of Salmonella spp.?
1. S. typhi
2. S. paratyphi
3. S. enteritidis
113
What is the pathogenesis of Salmonella infection?
- Absorption to epithelial cells in terminal section of small intestine
- Penetration of cells & migration to lamina propria
- Multiplication in lymphoid follicles
- Inflammatory response mediates release of prostaglandins
- Stimulation of cAMP
- Release of fluid & electrolytes causing diarrhoea
114
What resuts form a S. typhi or S. paratyphi infection?
- Enteric fevers: typhoid & paratyphoid
- Systemic infections intiated in GI tract
- Multiply within & transported around body in macrophages
115
What are the 2 different routes/types of Typhoid vaccines?
| When do you get the booster?
- Oral, Live attenuated: booster after 5yrs
| - Parenteral, Capsular polysaccharide: booster after 2yrs
116
Describe the characteristics of Shigella spp.?
- Bacillus
- Cause shingellosis
- Human-only pathogen
117
What are the 4 species of Shigella spp. differing in severity?
1. S. dysenteriae: most serious
2. S. flexneri: severe disease
3. S. boydii: severe disease
4. S. sonnei: mild infections
118
What is the pathogenesis of Shingella infection?
- Attaches to mucosal epithelium of distal ileum & colon
- Inflammation & ulceration
- Produces Shiga toxin
- Diarrhoea watery initially, then blood & mucus
119
Describe the characteristics of L. monocytogenes?
- Coccobacillus
- Causes listeriosis
- Associated with pate, soft cheese, unpasteurised milk
- Immunocompromised & pregnant women at risk
120
What infection usually presents as meningitis?
L. monocytogenes
121
What are the 3 Viral diarrhoea pathogens?
1. Rotavirus
2. Norovirus
3. Enteric Adenovirus
122
Describe the characteristics of Rotavirus?
- 11 separate segments of double-stranded RNA
- Common in children <2yr
- 10 ingested particles can cause disease
- Seasonal occurrence (cooler months)
- Faeco-oral, faeco-respiratory
123
What is the pathogenesis of Rotavirus infection?
- Replication of virus in tips of villi in small intestine epithelial cells
- Results in villous atrophy
- Leaving immature cells with reduced absorptive capacity for sugar, water & electrolytes
- Vomiting, diarrhoea
124
What are the Rotavirus Vaccines?
RotaRix & RotaTeq
- Oral (2-3 doses)
- Live, attenuated virus
125
Describe the characteristics of Norovirus?
- "Winter vomiting disease"
| - Faeco-oral, contaminated water/shellfish, fomites
126
Is there a vaccine for Norovirus?
NO
127
Describe the characteristics of Enteric Adenovirus?
- 10% of community-acquired diarrhoea in children
- Asymptomatic
- Mild, prolonged diarrhoea
128
What is Antibiotic-associated Diarrhoea?
- NOT involve ingestion of pathogen/toxin
| - Disruption of gut microbiota following antibiotic therapy
129
What could antibiotic tetracycline lead to?
Colonisation by Staphylococcus aureus & Candida spp.
130
What could antibiotic Clindamycin lead to?
Suppresses gut microbiota & allows Clostridium difficile to multiply
131
What infection in now associated with resistance to Vancomycin?
C. difficile infection
132
What 4 diseases are associated with H. pylori?
- Duodenal ulcers
- Gastric ulcers
- Gastro-oesophageal reflux disease
- Non-ulcer dyspepsia
133
What are the 5 key features of H. pylori?
1. Acid-inhibitng protein: survival in stomach
2. Urease: neutralisation of acid pH
3. Adhesins: binding to gastric epithelium
4. Cytotoxins: damage to gastric epithelium
5. Flagellum: movement through gastric mucus layer
134
What is the 2 different treatments for H. pylori-associated Gastritis?
(1 week triple therapy)
1. Proton pump inhibitor (PPI) + Clarithromycin + Amoxycillin
2. Proton pump inhibitor (PPI) + Clarithromycin + Metronidazole
135
Give 3 examples of toxins causing food poisoning?
1. Emetic toxins of Bacillus cereus
2. Enterotoxin of Staphylococcus aureus
3. Neurotoxin of Clostridium botulinum
136
What is Oral Rehydration Therapy (ORT)?
Involves replacement of fluids & electrolytes lost during ACUTE diarrhoea
- Contains glucose, sodium chloride, potassium chloride, trisodium citrate dihydrate
137
Deep to peritoneal covering, what is the lover completely surrounded by?
Glisson's capsule
138
What does the Hepatic Portal vein bring in?
Absorbed nutrients from stomach & intestine
139
What supplied the liver (hepatocytes) with oxygen?
Hepatic Artery
140
How is bile drained from the liver?
Via canaliculi that lie between hepatocytes into bile ductules & eventually into bile ducts
141
What is the venous drainage of the liver?
Hepatic veins which enter the IVC
142
How are bile pigments derived?
As breakdown products of haemoglobin, Kupffer cells play a role
143
What do bile salts do?
Detergent & emulsify fat increasing absorption by the small intestine
144
What does the liver store?
- Glucose
- Glycogen
- Proteins
- Vitamins
- Fats
145
The liver causes synthesis of _______ and _______ factors?
- Blood clotting
| - Anticoagulant
146
What 2 anticoagulant/ clotting factors does the liver produce?
1. Fibrinogen
| 2. Prothrombin
147
What are the components of the portal triad?
1. Portal vein
2. Hepatic artery
3. Bile ductule
148
What are/what is the purpose of sinusoids?
Lie between sheets of hepatocytes & carry blood from hepatic artery & portal vein to central vein
149
What is another name for the hepatorenal space?
Morison's pouch
150
The visceral surface is covered by peritoneum, except at the _____ & and at the _______?
- Fossa for gall bladder
| - Porta hepatis
151
What is the name given to the peritoneal reflections from the liver to the diaphragm?
Coronary & Triangular ligaments
152
How is the liver divided functionally?
Caudate & quadrate lobes are functionally & vascularly part of the left lobe
153
What are the Liver "ligaments"?
Reflections of peritoneum that surround the bare area
154
How much lymph does the liver produce?
1/3 - 1/2 of all body lymph
155
Where does the lymph from the liver go?
Enter several lymph nodes in the porta hepatis which pass to the coeliac nodes
156
Where does the lymph from the bare area of the liver go?
Through diaphragm to posterior mediastinal lymph nodes
157
What is the sympathetic nerve supply of the liver?
Coeliac plexus (foregut, greater splanchnic nerve T5-9)
158
What is the parasympathetic nerve supply of the liver?
Anterior vagal trunk giving rise to large parasympathetic hepatic branch
159
What is the name of the duct coming from the gall bladder?
Cystic duct
160
What is Hartmann's pouch?
Dilatation of the neck of the gall bladder
161
Is storing and concentrating bile in the gall bladder essential?
NO
162
What does the joining of the cystic duct & common hepatic duct form?
Bile duct
163
What is the function of the "Spiral valve of Heister" in the mucous membrane of cystic duct?
Keep the lumen constantly open
164
What is the blood supply of the gallbladder?
Cystic artery, a branch of right hepatic artery
165
What is the venous drainage of the gallbladder?
Cystic vein directly into portal vein
166
What is the lymph drainage of the gallbladder?
Cystic lymph node --> hepatic nodes --> coeliac nodes
167
What is the nerve supply of the gallbladder?
- Sympathetic (foregut T5-9)
| - Parasympathetic vagal fibres from coeliac plexus
168
What happens to the gallbladder in response to hormone cholecystokinin?
Contracts
169
What are the boundaries of Calot's cystohepatic triangle?
- Edge of right lobe of liver
- Common hepatic duct
- Cystic duct
170
What is the Calot's cystohepatic triangle used to surgically locate?
Cystic artery
171
Where does referred pain from the gallbladder go?
Usually epigastrium (T7-9), but irritation of adjacent peritoneum may involve phrenic nerve going to right shoulder tip
172
What are the 4 different locations of the common bile duct as it descends?
1. Free margin of lesser omentum infront of opening of lesser sac
2. Behind 1st part of duodenum to the right of gastroduodenal artery
3. Groove on posterior surface of head of pancreas where bile duct joins main pancreatic duct
4. Combined ducts open into duodenum at major duodenal papilla
173
What can a carcinoma of the head of pancreas cause?
Obstruct bile duct causing painless, continuous jaundice
174
What does ERCP stand for?
Endoscopic retrograde cholangio pancreaticogram
175
List the structures which lie on the Transpyloric plane (at L1)?
- Fundus of gallbladder
- Pylorus
- Neck of pancreas
- Formation of portal vein
- Hilum of kidney
- Spinal cord ends at L1/2
- Aorta & origin of SMA
- IVC
- 2nd part of duodenum
176
What does the pancreas produce?
- Digestive proenzymes, secreted via pancreatic duct
| - Insuin and glucagon from islets of Langerhans
177
The pancreas is secondarily retroperitoneal except for its ____?
Tail
178
Describe the pancreatic duct?
- Begins at tail of pancreas
| - Joins bile duct at hepatopancreatic ampulla of Vater that opens as the major duodenal papilla
179
What are the 3 components of the Sphincter of Oddi?
1. Around the end of the pancreatic duct
2. Around the end of the bile duct
3. Around the combined ducts
180
Where does the blood supply of the pancreas originate from (2)?
- Coeliac trunk
| - Superior Mesenteric artery
181
What does the Coeliac Trunk give off to supply the pancreas?
1. Gastroduodenal (direct to pancreas) --> superior pancreaticoduodenal --> ant & post branches
2. Splenic --> Greater & Dorsal pancreatic branches
182
What does the Superior Mesenteric Artery give off to supply the pancreas?
Inferior pancreaticoduodenal --> ant & post branches
183
What is the nerve supply of the pancreas?
Vagus (parasympathetic) + T7-9 & T10-11
184
What are 2 examples of Protozoal infections of the small intestine?
- Giardia lamblia
| - Cryptosporidium parvum
185
What is an example of Protozoal infection of the large intestine?
Entamoeba histolytica
186
Describe the characteristics of G. lamblia?
- Traveller's diarrhoea globally
- Drinking & recreational water
- Person-person
- Diagnosis by microscopy of stool samples
187
What are the 2 stages in the life cycle of G. lamblia?
1. Trophozoite
| 2. Cyst
188
Describe the Trophozoite stage in G. lamblia?
- Flagellated & bi-nucleated
- Lives in upper part of small intestine
- Adheres to brush border of epithelial cells
189
Describe the Cyst stage in G. lamblia?
- Formed when trophozoite forms resistant wall
- Passes out in stools
- Survive for several weeks
190
Describe the pathogenesis of G. lamblia?
- Duodenum & upper ileum
- Attaches to mucosa via ventral sucker
- Damage to mucosa & villous atrophy
- Leads to malabsorption of food
- May swim up the bile duct to gallbladder
- Stools loose, foul-smelling & fatty
191
What is the transmission of Cryptospordium parvum?
Faecally-contaminated drinking water
192
Describe the life style of C. parvum?
- Asexual & sexual development within host
- Ingestion of resistant oocysts
- Release of infective sporozoites in small intestine
- Division to form merozoites which re-infect cells
- After sexual phase, oocytes released
193
Describe the pathogenesis of C. parvum?
- Enters cells of the microvillus border of small intestine
- Remains within vacuole of epithelial cell
- May multiply to give large numbers esp. in immunocompromised
194
What are the clinical manifestations of C. parvum?
- Mod-severe profuse diarrhoea
- 25L of watery faeces/day
- HIV + diarrhoea can be prolonged & irreversible
195
Describe the characteristics of E. histolytica?
- Tropical & sub-tropical countries
- Contaminated food/water & Anal sex
- Cysts pass through stomach & excyst in small intestine giving rise to progeny
- After mucosal invasion, cysts invade RBC's increasing amoebic colitis
- Trophozoite stages live in large intestine
196
What is the pathogenesis of E. histolytica?
- Adheres of epithelium & acute inflammatory cells
- Resists host humoral & cell mediated immune defence
- Produces hydrolytic enzymes, proteinases, collagenase, elastase
197
What are the clinical manifestations of E. histolytica?
- Small localised superficial ulcers leading to mild diarrhoea
- Entire colonic mucosa may become deeply ulcerated --> severe amoebic dysentery
- Intestinal perforation
- Rarely, abscesses spread to overlying skin
198
What is the causative agent of Bacillary dysentery?
Shingella sp.
| many PMN, no eosinophils, blood/mucus
199
What is the causative agent of Amoebic dysentery?
Entamoeba
| few PMN, eosinophils, blood/mucus
200
What is the treatment for G. lamblia protozoal infection?
- Mepacrine hydrochloride
- Metronidazole
- Tinidazole
201
What is the treatment for C. parvum protozoal infection?
- Nitazoxanide
| - Spiramycin
202
What is the treatment for E. histolytica protozoal infection?
- Metronidazole
| - Oral rehydration therapy
203
What are some prevention methods of protozoal infection in the GI tract?
- Improve hygiene & water
- Eating freshly prepared food served hot
- No unpeeled salads & fruits
- No tap water & ice cubes
204
What are the 3 different groups of Helminths (worms)?
1. Roundworms (Nematodes)
2. Tapeworms (Cestodes)
3. Flukes (Trematodes)
205
Give examples of Roundworms (nematodes)?
- Strongyloides stercoralis (pinworm/threadworm)
- Trichuris trichiura (whipworm)
- Ascaris lumbricoides (giant roundworm)
- Enterobius vermicularis (pinworm/threadworm)
- Ancylostoma duodenale (hookworm)
206
Give an example of a Tapeworm (cestodes)?
Taenia solium
207
How does a Nematode intestinal infection occur?
- Soil-transmitted
- Swallowing infective eggs
- Active skin penetration by larvae & systemic migration through lung to intestine
208
How is Nematode intestinal infections diagnosed?
Stool microscopy
209
Describe the characteristics of S. stercoralis?
- Pinworm
- Disruption of small intestinal mucosa
- Villous atrophy
- Loss of intestinal wall elasticity
210
What are the clinical manifestations of S. stercoralis?
- Dysentery
- Dehydration
- Malabsorption syndrome
- Anal pruritis (itch)
- Association with appendicitis
211
Describe the characteristics of T. trichiura?
- Whipworm
- Ingesting eggs on vegetables
- Can live in gut for 3 years
212
Describe the characteristics of A. lumbricoides?
- Giant roundworm (20-30cm)
| - Adults live in gut for 2 years
213
What are the clinical manifestations of A. lumbricoides?
- Allergies
- Digestive upset
- Protein/energy malnutrition
- Intestinal blockages
- May invade mouth, nose etc.
214
Describe the characteristics of E. vermicularis?
- Threadworm
- Small cylindrical nematodes <1cm
- Migrates to anus at night to lay eggs
215
What are the clinical manifestations of E. vermicularis?
- Intense itching
| - Secondary bacterial infection: mild catarrhal inflammation & diarrhoea, slight eosinophilia
216
Describe the characteristics of A. duodenale?
- Hookworm
- Walking barefoot in infected areas
- Attaches to small intestine, suck blood & protein
217
What can A. duodenale cause?
Hypochromic anaemia
218
Describe the characteristic of T. solium?
- Ingesting worms/eggs in undercooked pork
- Reside in large intestine
- Scolex for attachment
219
What do particular problems of Antiprotozoal & Antihelminthic agents pose?
- Large variety of species
- Complexities of life cycles
- Differences in metabolic pathways
- Drugs active against protozoa are inactive against helminths
220
What does FAP stand for?
Familial Adenomatous Polyposis
221
What is Lynch syndrome also known as?
Hereditary nonpolyposis colon cancer (HNPCC)
222
What are the features of familial adenomatous polyposis coli?
- Autosomal dominant
- Large number of polyps
- 90% patients also have pigmented lesion in retina (CHRPE)
223
What is the gene defect for familial adenomatous polyposis coli?
- Adenomatous polyposis coli (APC)
| - Chromosome 5 q21-22
224
What are the most common mutations affecting the APC gene?
Nonsense / frameshift mutations
225
How do you test for APC gene defect?
- Protein truncation test
| - Direct sequencing
226
What is the APC gene?
Tumour suppressing gene
227
What does APC do?
- Binds beta-catenin and degrades it stoping cell division
| - Binds microtubules
228
What is a beta-catenin?
- Transcription factor
- Intracellular signal transducer in Wnt signaling pathway
- Binds to TCF in nucleus which stimulates transcription of genes which specifically promote cell division
229
What is the consequence of APC mutation in terms of Wnt signalling?
- Inactive APC doesn't bind to beta-catenin
- Stable Beta-catenin goes on to bind to TCF
- Transcription of Wnt-responsive genes leading to proliferation of gut stem cells
230
How does a APC defect lead to chromosomal instability?
APC forms part of the spindle in mitosis, in mutant, chromosomes may not attach properly to the spindle, leading to hall marks of cancerous cells
231
Why does APC cause cancer in the colon specifically?
- Cells at bottom of crypt are stem cells and are constantly dividing
- Wnt pathway usually inactive at top parts of crypts, in mutant, proliferation occurs abnormally here
232
Is mutation of APC alone enough to cause cancer?
NO
233
What is the name of the extraintestinal involvement of APC defect?
Gardner Syndrome
234
What are the features of gardner syndrome?
- Rare
- Variant of FAP
- Masses of benign tumours
- Jaw cysts
- Sebaceous cysts
- Osteomata
- Pigmented lesions of the retina (CHRPE)
235
What are the features of Hereditary Nonpolyposis coli (Lynch syndrome)?
- Autosomal dominant
- Mutations in mismatch repair genes
- High risk of colon tumours
- Underlying cause of other tumour types
- Low number of polyps
- DNA repair gene defects
236
Which regions of DNA are particularly susceptible to problems from DNA mismatch repair problems?
Microsatelite instability (MIN)
237
Compare FAP and HNPCC?
1. FAP- large number of polyps, low mutation rate, high cancer risk
2. HNPCC- low number of polyps, high mutation rate, high cancer risk
238
What is the average age of onset for FAP & HNPCC?
Approx 40
239
What is the definition of high to moderate risk of colon cancer?
- 3+ affected relatives in 1st degree kinship with eachother
| - 2 affected relatives less than 60yrs/mean age less than 60yrs in 1st degree kinship with eachtoher
240
What happens who EGFR is overproduced?
- Activates signal-transduction cascades
| - Increases cell proliferation, invasion & metastasis, angiogenesis and decreases apoptosis
241
When is the only time you would prescribe Cetuximab for colorectal cancer?
Only used where wild type Kras (not mutated)
242
What factors reduce risk of colorectal cancer?
- High fibre diet
- Low intake of red/processed meats
- High fish diet
- Antioxidants & folate in fruit & veg
- Low alcohol intake
- Aspirin
- Obesity increases risk
243
Why are specific food groups shown to reduce risk of colorectal cancer?
- Less time in bowel
| - Bile salts pass through more quickly
244
How does aspirin reduce risk of colon cancer?
COX-2 is increased in early stage of colorectal cancer, aspirin INHIBITS COX-2
245
What does COX-2 do?
- Increases prostaglandin synthesis (regulate BP)
- Stimulates proliferation & angiogenesis
- Inhibits apoptosis
246
What does Cetuximab do?
Prevents ligand from binding to EGFR
247
What would the % be for obese woman and men by 2050 if no action is taken?
60% men & 40% women will be obese
248
What does McKinsey Report 2014 say regarding global economic impact from obesity?
$2.0 trillion ~ equivalent to global impact from smoking or armed violence...
249
What are the NHS SIGN & NICE guidelines for obesity and primary care medicine?
Doctors regularly screen for obesity & recommend interventions to overweight & obese patients within primary care
250
What is obesity?
- Excess adiposity
251
How do we test for obesity?
Body mass index (BMI)= Wt (kg) / ht (m)2
252
What is a normal BMI?
18.5-24.9 kg/m2
253
What is BMI is obesity classified as?
> 30kg/m2
254
List some of the co-morbidities of obesity?
- Stroke
- Heart disease
- Abnormal periods
- Infertile
- Arthritis
- Inflamed veins
- Gout
- Cancer
- Gallstones
- Liver disease
- Lung disease
- Sleep apnea
255
What did the prevalence of self-reported obesity among US adults by state and territory, BRFSS (2014) conclude?
In 2014, no state had a prevalence of obesity <20%
256
What is the measurement of centines for obesity in children?
- BMI centiles are the child equivalent to adult BMI cut off's
- Underweight: ≤2nd centile
- Healthy weight: >2 - <85th centile
- Overweight: ≥ 85th centile
- Obese: ≥95th centile
257
What is the definition of overweight in children?
Centiles for overweight by sex passing through BMI of 25kg/m2 at age 18
258
What is the definition of obesity in children?
Centiles for obesity by sex, passing through BMI of 30kg/m2 at age 18
259
What are the endocrine & cardiovascular consequences of childhood obesity?
- Insulin resistance/impaired glucose tolerance (type 2 diabetes)
- Polycystic ovary symptom
- Hypertension
- Fatty streaks
- Left ventricular hypertrophy
260
What is the relation between TV watching and child obesity?
- Increased TV watching associated with increased risk of child obesity
- Snack more when watching TV
261
What is the relation between food variety and energy balance?
Increased variety of sensorially distinct foods, virtually identical in composition, can increase food & energy intake and in the short/medium term can alter energy balance
262
What are monogenic forms of obesity?
- Rare (<5%)
- Single gene disorders
- Gene mutations ie. LEP, LEPR, MC4R
263
What are polygenic/common forms of obesity?
- Complex interactions between genes & environment
- Gene-gene
- Gene-environment
- GENES MODIFY!
264
What is the relationship between the Pima in Sierra Madre Mountains of Mexico & the Pima in Arizona?
- Sierra Madre Mountains of Mexico: farming, cooking, fetching water, unaffected by labour saving devices, lower BMI, lower incidence of diabetes
- Arizona: typical american lifestyle, american diet, higher BMI, higher incidence of diabetes
265
What is hyperphagia?
Abnormally high appetite
266
Describe the FTO gene and polygenic obesity?
- Chromosome 16
- Role in fatty acid metabolism, DNA repair, post-translational changes
- Expressed in brain, pancreatic islet, adipose tissue, adrenal glands
267
What are increased hypothalamic expression of FTO associated with?
Regulation of energy intake and satiety regulation
268
What is satiety?
The sensation of feeling full
269
What are the 4 WHO Global strategy on diet, physical activity (PA) and health (2004)?
1. Reduce risk factors for chronic diseases that stem from unhealthy diets & PA through public health actions
2. Increase awareness & understanding of the influences of diet & PA on health & the positive impact of preventive interventions
3. Develop, strengthen and implement global, regional, national policies and action plans to improve diets & increase PA that are sustainable, comprehensive & actively engage all sectors
4. Monitor science & promote research on diet and physical activity
270
According to WHO, 2015 what is the biggest cause of death globally?
Ischaemic heart disease
271
According to WHO, 2015 what is the biggest cause of death in low income economies?
Lower respiratory infections
272
0.8 million children die every year from ____ caused by _______ & _______ ?
- Diarrhoea
- Unclear water
- Poor sanitation
273
What % of water in the world is saltwater?
97.5%
274
What % of water in the world is freshwater?
2.5%
275
Where does the freshwater come from & what is the percentage?
- Glaciers & Snowcover 68.9%
| - Groundwater 30.8%
276
How much fresh water is accessible to humanity?
0.3%
277
What is the different daily water usage in Africa, UK and USA?
- Africa= 10L
- UK= 160L
- USA= 400L
278
How many people in the world don't have access to safe water?
- 884 million
| - 1/8th of world's population
279
How many people in the world don't have access to adequate sanitation?
- 2.5 billion
| - 2/5th of world's population
280
What are the top 5 main causes for diarrhoeal disease in children in developing countries?
1. Rotavirus (20%)
2. Unknown (20%)
3. E. coli (17.5%)
4. Campylobacter spp. (12.5%)
5. Cryptosporidium (10%)
281
What is the definition of Incidence?
Number of new cases in a population over a fixed period of time
282
What is the definition of Period Prevalence?
Total number of existing cases in a population over a fixed period of time
283
What is the definition of Point Prevalence?
Total number of existing cases in a population at a specific time
284
What are the WHO measures to prevent diarrhoea?
- Access to safe drinking water
- Use of improved sanitation
- Hand washing with soap
- Exclusive breastfeeding (for 6 months)
- Good personal & food hygiene
- Health education
- Rotavirus vaccination
285
What is the Millennium Development Goals (MDG) for 2015 agreed by U.N member states?
1. Eradicate extreme poverty & hunger
2. Achieve universal primary education
3. Promote gender equality & empower women
4. Reduce child mortality
5. Improve maternal health
6. Combat HIV/AIDS, malaria and other diseases
7. Ensure environmental sustainability
8. Global partnershop for development
286
What is the aim of Millennium Development Goal (MDG) 7c?
1/2 the proportion of people without sustainable access to safe drinking water & basic sanitation
287
What are the 3 reasons why global health important?
1. Greatest burden on the greatest number of people
2. In a global context we are the exception, not the rule
3. World is becoming a much smaller place every day
288
What is the water footprint?
Total volume of freshwater used to produce goods & services consumed by the individual/community or produced by the businesses both directly and indirectly
MD3002
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