Week 3 Flashcards
Where does protein digestion begin?
In stomach with pepsin
Where is protein digestion completed?
In small intestine with pancreatic & brush-border proteases
What is the main pancreatic protease secreted as inactive precursor in the small intestine?
Trypsinogen
What mechanism helps absorption of amino acids in the small intestine?
Na+- dependant cotransport
What mechanism helps absorption of Dipeptides in the small intestine?
H+- dipeptide cotransport
What mechanism helps absorption of Tripeptides in the small intestine?
H+- tripeptide cotransport
Dietary lipids are _____?
Hydrophobic
insoluble in water
What % of ingested triglycerides do lingual & gastric lipase hydrolyse?
Hydrolyse 10% into glycerol & free fatty acids
What is the key role of gastric lipase?
Slow the rate of gastric emptying so that pancreatic enzymes are able to digest lipid
What 3 things emulsify dietary lipids?
- Bile salts
- Lysolecithin
- Products of lipid digestion
What are secreted to complete the digestion of lipids in the small intestine?
- Pancreatic enzymes (pancreatic lipase, cholesterol ester hydrolase & phospholipase A2)
- Colipase
What are the 6 steps to digestion and absorption of lipids in the small intestine?
- 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
Describe the structure of a Chylomicron?
- 100nm diameter
- Core of triglycerides & cholesterol ester
- Outside of phospholipids & apoproteins
Where are chylomicrons packaged and where do they go?
Into secretory vesicles on Golgi membrane & exocytose across basolateral membrane
Where does the lymphatic circulation take the chylomicrons?
Thoracic duct which empties into blood stream
What are the differences between tight junctions of the colon & small intestine?
- Small intestine are “leaky” (permeable via paracellular route)
- Colon are “tight” (impermeable via paracellular route)
What 2 different structures absorb & secrete fluids in the small intestine?
- Villi- absorption
2. Crypts of Lieberkuhn- secretion
What 2 different structure absorb & secrete fluids in the large intestine?
- Suface epithelial cells- absorption
2. Colonic glands- secretion
How much H20 is absorbed in the small intestine?
6.5L
How are electrolytes absorbed in the intestine?
Na+, Cl-, HCO-3, K+ absorbed isosmotically with water by villi (as in the renal proximal tube)
What happens at the epithelial cells lining the crypts of Lieberkuhn?
- 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
What regulates diffusion of Cl- at the apical membrane in the intestine?
Secretagogues
What are the 5 different Hormonal/neurotransmitter Secretagogues?
- VIP
- Guanylin
- Acetylcholine
- Bradykinin
- Serotonin (5HT)
What is a Secretagogue?
Substance which promotes secretion
Name some bacterial enterotoxins?
- Cholera toxin
- E coli toxins
- Yersinia toxin
- Clostridium difficile
Where are fat soluble vitamins absorbed?
What is the mechanism?
- Small intestine
- Bile salts form micelles, diffusion into intestinal cells
Where are water soluble vitamins absorbed?
What is the mechanism?
- Small intestine
- Na+ dependant cotransport
Where is Vitamin B12 absorbed?
What is the mechanism?
- Ileum
- Intrinsic factor
Where are bile salts absorbed?
What is the mechanism?
- Ileum
- Na+ bile salt cotransport
Where is Ca2+ absorbed?
What is the mechanism,?
- Small intestine
- Vitamin D- dependant Ca2+ binding protein (Calbindin)
Where is Fe2+ absorbed?
What is the mechanism,?
- Small intestine
- Binds to apoferritin in intestinal cell, binds to transferrin in blood
What are the ordered steps for examination?
“IIPPA”
- Introduction/explanation
- Inspection
- Palpation
- Percussion
- Auscultation
What does “MILC” stand for in causes of GI clubbing?
- Malabsorption (coeliac)
- Inflammatory bowel disease (UC & Crohn’s)
- Lymphoma
- Cirrhosis
When does Asterixis/flapping tremor occur?
With hepatic encephalopathy (severe liver failure)
What is Leuconychia?
White discolouration appearing on nails
What is Koilonychia?
Spoon nails, can be a sign of iron-deficiency anemia
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
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
What is Angular Stomatitis?
- Inflammation of one/both corners of the mouth
- Caused by infection, irritation, or allergies
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
What is Telangiectasia?
Dilatation of capillaries causing them to appear as small red or purple clusters, often spidery in appearance
What is Gynaecomastia?
Enlargement of male breasts, usually due to hormone imbalance/hormone therapy
What are the “5 F’s” for abdominal distension?
- Fat
- Fluid
- Faeces
- Flatus
- Foetus
What are you palpating for when examining the abdomen?
- Tenderness (guarding or re-bound tenderness)
- Masses
- Organomegaly
- Abdominal aorta
What can Palmar erythema be a sign of?
Chronic liver disease, or be normal in pregnancy
Does the liver & spleen move during respiration?
YES
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
What are the 5 different things to note when palpating the liver?
- Size
- Surface & edge (smooth/irregular)
- Consistency (soft/hard)
- Tenderness
- Pulsatility
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
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
What is Courvoisier’s Sign?
- Painless Jaundice & a palpable gallbladder
- Likely due to extra hepatic obstruction ie. Pancreatic cancer
What is Courvoisier’s Sign UNLIKELY to be?
Gallstones
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
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
How do you palpate the bladder during abdominal examination?
- Palpate upper border
- In midline
- Lower border not palpable
What are the possible causes of renal enlargement?
- Hydronephrosis
- Polycystic kidney disease
- Renal cell carcinoma
- In children, nephroblastoma (Wilm’s tumour)
- Solitary cysts
What is the most common aortic aneurysm?
Abdominal
What is percussion ascites?
Abnormal collection of fluid in peritoneal cavity
What are the possible causes for percussion ascites?
- Hepatic cirrhosis
- Intra-abdominal malignancy
- Nephrotic syndrome
- Cardiac failure
- Pancreatitis
- Constrictive pericarditis
Where may tumours of the upper GI tract metastasise?
Lower part of left posterior cervical triangle (cervical lymph nodes)
What other areas can you offer in an abdominal examination?
- Examine groin
- Examine genitalia
- Requests to do digital rectal examination (DRE)
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
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
What is the possible female pelvic pathology?
- Ovarian cyst, malignancy
- Uterine prolapse, fibroids, cervical carcinoma
- Vaginitis, prolapse
- Pelvic infection
- Ectopic pregnancy
What is the possible male reproductive pathology?
- Epididymitis
- Testicular torsion
- Epididymal cysts
- Testicular tumours
- Indirect inguinal hernia
What are the causes of acute oesophagitis?
usually in immunocompromised patients
- Herpes simplex viruses
- Candida
- Cytomegalovirus (CMV)
- Corrosives
What are the causes of chronic oesophagitis?
- Tuberculosis
- Bullous pemphigoid & Epidermolysis bullosa
- Crohn’s disease
- Reflux oesophagitis
What does “GORD” stand for?
Gastro-oesophageal reflux disease
What are predisposing factors for “incompetent” gastro-oesophageal junction?
- Alcohol & tobacco
- Obesity
- Drugs ie. caffeine
- Hiatus hernia
- Motility disorders
What can severe oesophagitis reflux lead to?
Ulceration (complete loss of epithelia)
What is Barrett’s Oesophagus?
- Longstanding reflux oesophagitis
- Lower oesophagus becomes lined by columnar epithelium (metaplasia)
- Premalignant, risk of adenocarcinoma of distal oesophagus 100x
What are the causes for acute gastritis?
- Usually due to chemical injury
- H pylori-associated
What are the causes for chronic gastritis?
- Active chronic (H pylori-associated)
- Autoimmune
- Chemical (reflux)
What chemical injury can cause acute gastritis?
- Drugs ie. NSAIDS
- Alcohol
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
What are the 2 distribution patterns of H pylori-associated gastritis?
- Diffuse involvement of antrum and body
2. Antral but not body
How can you detect H pylori-associated Gastritis?
- Faecal bacterial
- Urea breath test
- Gastric biopsy rapid urease test
What causes chemical (reflux) gastritis?
Regurgitation of bile & alkaline duodenal secretion
What is chemical (reflux) gastritis associated with?
- Defective pylorus
- Motility disorders
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
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
What are risk factors for peptic ulceration?
- Hyperacidity
- H pylori gastritis
- Duodenal reflux
- NSAID’s
- Smoking
- Genetic factors
- Zollinger-Ellison syndrome
What are the complications of peptic ulceration?
- Haemorrhage
- Penetration of adjacent organs ie. pancreas
- Perforation
- Anaemia
- Obstruction
- Malignancy
What 3 things are acute peptic ulcers related to?
- Acute Gastritis
- Stress response
- Extreme hyperacidity
Where do chronic peptic ulcers tend to occur?
Mucosal junctions ie. antrum-body
What is the pathogenesis of a chronic peptic ulcer?
- Hyperacidity
- Mucosal defence defects
What are the mucosal defences?
- Mucus-bicarbonate barrier (dissolved by biliary reflux)
- Surface epithelium (damage by NSAIDs, injured by H pylori)
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
What can the complications of chronic duodenal ulcers be?
- “Bleed, burst or block”
- Penetration of adjacent organs ie. pancreas
- Malignant change
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
What are the 4 layers typical of gastric ulcers?
superficial to deep
- Necrotic debris
- Nonspecific acute inflammation
- Granulation tissue
- Fibrosis
What can an untreated ulcer causing epithelial perforation result in?
Leading of food & gastric juices to peritoneal / abdominal cavities
What 2 pathogens can cause bloody stools?
- Campylobacter
- Shigella
What 2 pathogens can cause watery stools?
- EPEC
- Cholera
Name 5 gram negative bacterial diarrhoeal pathogens?
- Vibrio cholerae
- Escherichia coli
- Campylobacter jejuni
- Salmonella spp.
- Shingella spp.
Name a gram positive bacterial diarrhoeal pathogen?
Listeria monocytogenes
Describe the characteristics of V. cholerae?
- Flagellated
- Epidemics & Pandemics
- Human-only pathogen
- Flourishes with no clean drinking water/sewage disposal
What antigens are V. cholerae serotypes based on?
O antigens
What are the 2 different routes for V. cholerae vaccines and what are they particularly good for?
- Parenteral vaccine: low protective efficiency
2. Oral vaccine: effective & suitable for travellers
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
Describe the oligomeric complex (6 protein subunits) of Cholera Toxin?
- 1 copy of A subunit (enzymatic)
- 5 copies of B subunit (receptor binding)
What are the consequences of Cholera infection?
- Fluid loss of upto 1L/hr
- Electrolyte imbalance leading to dehydration, metabolic acidosis & hypokalemia
- Hypovolaemic shock
What is the mortality difference between an ORT treated cholera infection and an untreated?
- 40-60% untreated
- <1% ORT treated
Describe the characteristics of E. coli?
- Bacillus
- Member of normal GI microbiota
- Some strains possess virulence factors enabling them to cause disease
Name 2 types of E. coli that cause GI infections?
EPEC= enteropathogenic ETEC= enterotoxigenic
What kind of E. coli infections are EPEC involved in?
Sporadic cases & outbreaks of infection in under 5’s
What kind of E. coli infections are ETEC involved in?
“Travellers’ diarrhoea” occurs in 20-50%
What are the 2 main enterotoxins secreted by the bacteria?
- LT= heat labile toxin
2. STa= heat stable toxin
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
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
Describe the characteristics of Salmonella spp.
- Bacilli
- Food-associated diarrhoea
- Through computation of raw/undercooked meat, contaminated eggs & milk
- Secondary spread human-human
What are the 3 important species of Salmonella spp.?
- S. typhi
- S. paratyphi
- S. enteritidis
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
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
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