Case 3 Flashcards
Dependence syndrome
3 or more of the following symptoms:
withdrawal state evidence of tolerance lack of control strong desire neglect of alternative interests persist despite harmful consequences
Negative reinforcement behaviours
Relief of bad symptoms - starting to drink alcohol again due to unpleasant withdrawal symptoms
Positive reinforcement behaviours
Bring about good symptoms - drinking alcohol for euphoric feeling of being intoxicated
How does smoking bring about release of dopamine?
Nicotine binds to nicotinic (ACh) receptors in mesolimbic reward system. Activation of dopamine cells = release of dopamine.
Dopamine pathway is involved in…
Reward, pleasure and euphoria
Serotonin pathway is involved in…
Mood
Memory
Sleep
Cognition
Mallory Weis Syndrome
Gastro-oesophageal laceration due to alcoholism, bulimia or any other condition causing violent vomiting.
Causes painful haematemesis.
Korsakoff’s Syndrome
Persistent amnesia due to chronic alcoholism
Transmission of Hep A
Faeco oral
Risk factors for Hep A
Poor sanitation
Gay men
Travellers
Prevention of Hep A
Vaccination
Hand washing
Food/water hygiene
Hepatitis E
Very similar to Hep A but very rare.
Associated with animal contact.
Treatment for Hep A
No specific treatment - spontaneous clearance by immune system.
Signs/Symptoms of Hep A
Fever
Malaise
Jaundice
Transmission of Hep B
Blood (assoc with needle stick injury and IV drug use)
Sexual (semen)
Vertical
Acute Hep B can become chronic, what is the chance of HBV becoming chronic?
95% in neonates
<5% in adults
Definition of chronic HBV
Failure to clear after 6 months
Effects of chronic HBV
End stage liver disease - portal hypertension/ascites, bleeding oesophageal varices, liver failure
Vaccination is available for which forms of hepatitis
A and B
Transmission of Hep C
Blood and vertical
Acute Hep C can become chronic. What is the chance of Hep C becoming chronic?
85% (15% will recover)
What is the risk of liver cirrhosis in Hep C?
20%/year of individuals with Hep C will get cirrhosis of the liver
Hepatitis D
Only presents WITH Hep B
Very high incidence of cirrhosis development
Features of liver cirrhosis
Ascites and oedema Impaired immunity Oesophageal Varices Splenomegaly Testicular atrophy Gynaecomastia Spider Naevi
Why does liver cirrhosis cause oedema?
Low albumin
Increased hydrostatic pressure of blood
Why does liver cirrhosis cause ascites?
Low albumin
Portal hypertension
Why does liver cirrhosis cause oesophageal varices and splenomegaly?
Portal hypertension
Why does liver cirrhosis cause Testicular atrophy and Gynaecomastia
Impaired metabolism of oestrogen
HBcAg
Core antigen
Present during acute infection
HBsAg
Surface antigen
Present during active infection
HBsAb
Surface antibody
Present in an immune person
HBcAb
Core antibody
Present in someone who has had the infection in the past.
Does not provide immunity
How is vertical transmission of HBV prevented?
Antiviral therapy to mother during pregnancy.
Passive immunisation of mother (eAg)
Vaccination of infant (3 dose schedule, started at birth)
Oesophageal varices
Dilated submucosal veins at anastomosis between systemic and portal drainage of oesophagus.
Usually caused by portal hypertension.
Risk of bleeding - causing haematemesis
High risk in alcoholics
Symptoms of GORD
Heartburn
Dysphagia
Sour taste in mouth
Causes of GORD
Dysfunction of lower oesophageal sphincter
Hiatus Hernia
Delayed gastric emptying (functional dyspepsia)
Sliding hiatus hernia
Diaphragm no longer supporting lower oesophageal sphincter.
Upper part of stomach can slide through.
Rolling hiatus hernia
Part of stomach herniates into chest next to normal oesophagus.
Looks like a balloon next to oesophagus.
Barrett’s Oesophagus
Metaplasia of lower oesophageal squamous epithelium to gastric columnar due to chronic acid exposure.
Can lead to adenocarcinoma
How is cholesterol converted to bile salts?
Cholesterol converted to bile acids by Cytochrome P450.
Bile acids are conjugated to glycine or taurine by liver cells to form bile salts.
Primary vs secondary bile salts
Primary - formed by hepatocytes
Secondary - formed by bacteria in the intestine
How are bile salts recycled?
Absorbed in GI tract and enter portal circulation.
Active reuptake of bile salts from blood into liver cells via sodium dependent transporters
HMG CoA Reductase
Enzyme responsible for cholesterol synthesis.
Inhibited by statins.
Bilirubin Metabolism
Haem from Hb split into Fe2+ and Porphyrin ring.
P ring converted to biliverdin which is converted to bilirubin.
Bilirubin is conjugated by the liver and converted to urobilinogen.
Urobilinogen is excreted in urine or converted to stercobilin to be removed in faeces.
Conjugation of bilirubin
UDP-glucuronic acid supplies glucuronic acid, leaving UDP remaining.
Bilirubin also loses albumin
Signs/Symptoms of jaundice
Dark urine - excretion of bilirubin via kidneys
Pale stools with fatty streaks (absence of bilirubin and poor fat digestion)
Itching (accumulation of bile acids)
Conjugated bilirubin converted to urobilinogen by…
Bacterial flora of the colon.
Function of LDL
Carries cholesterol from liver to tissues
Function of HDL
Carries cholesterol from tissues to liver
Length of thoracic oesophagus
23cm
Length of abdominal oesophagus
2cm
Muscle distribution in oesophagus
Superior 1/3 = Voluntary striated
Middle 1/3 = mixture
Inferior 1/3 = smooth muscle
Vertebral level of oesophageal hiatus
T10
Greater curvature of stomach is supplied by
Short gastric arteries
Right and left omental arteries
Lesser curvature of the stomach is supplied by
Left gastric artery
Right gastric branch of hepatic artery
Epiploic foramen
Allows communication between greater and lesser sac
Lesser omentum
Connects stomach to duodenum and liver
Function of Greater omentum
Involved in combating GI infection - contains many lymph nodes with macrophages
Parasympathetic innervation of stomach
Vagus nerve
Increased stomach motility, gastric juice secretion and relaxation of sphincter
Sympathetic innervation of stomach
Coeliac plexus
Reduced stomach motility and gastric juice secretion. Constriction of sphincters
Transition from foregut to midgut occurs at…
Major Duodenal Papilla in superior duodenum
Distinguishing features of jejunum
Red
Thick walled
Long vasa recta (straight arteries)
Less arcades (arterial loops)
Distinguishing features of ileum
Pink
Thin walled
Short vasa recta
More arcades
Primary site of lipid absorption
Jejunum
Primary site of bile salt absorption
Ileum
Primary site of cobalamin (Vit B12) absorption
Ileum
LFTs: Elevated ALP - Alkaline Phosphatase
When bile flow is obstructed or biliary tree is damaged
When canaliculi or hepatocytes are damaged
LFTs Elevated AST - Aspartate Transaminase
When hepatocellular necrosis occurs BUT also in heart, muscle, kidney and brain injury
LFTs: Elevated ALT
A more specific measure than AST. Only increased with liver failure
LFTs: Low albumin indicates…
Chronic liver disease - reduced synthetic capability of liver.
OR
Inflammation - redistribution of albumin into extracellular space of plasma compartment
LFTs: Prothombin time
More sensitive indicator than albumin since clotting factors have a shorter half life.
Elevated PT in chronic liver dysfunction
Causes of prehepatic unconjugated hyperbilirubinaemia
Haemolytic anaemia Defects in RBC membranes Defects in Hb production Sickle cell anaemia Defect in RBC metabolism
Mechanism for prehepatic unconjugated hyperbilirubinaemia
Bilirubin is produced at a greater rate than the capacity of the liver to conjugate it.
i.e. excessive breakdown of RBCs
Lab results for prehepatic unconjugated hyperbilirubinaemia
Raised plasma unconjugated bilirubin. Normal conjugated bilirubin (since liver is functioning normally) Raised reticulocytes (immature RBCs) Low Hb Normal LFTs
Mechanism for Hepatic unconjugated hyperbilirubinaemia
Reduced conjugated and excretion of bilirubin
Causes of Hepatic unconjugated hyperbilirubinaemia
Crigler Najjar Syndrome - lack of conjugating enzyme
Gilbert’s - mild deficiency of conjugating enzyme
Newborns with immature liver.
Lab results for hepatic unconjugated hyperbilirubinaemia
Raised plasma unconjugated bilirubin
No urinary conjugated bilirubin
Raised AST, ALP and GGT
LFTs: Gamma-Glutamyl Transferase
Found almost exclusively in the liver
Increased during cholestasis or hepatocellular disease
Mechanism for hepatic conjugated hyperbilirubinaemia
Liver damage leading to reduced uptake of unconjugated bilirubin from plasma
Causes of hepatic conjugated hyperbilirubinaemia
Viral or toxic hepatitis or cirrhosis causing leakage of bilirubin from hepatocytes.
Dubin-Johnson Disease (deficiency in conjugated bilirubin transport into canaliculi)
Lab results in hepatic conjugated hyperbilirubinaemia
Raised plasma conjugated bilirubin (leaking out of hepatocytes)
Raised urine conjugated bilirubin and urobilinogen
Raised ALT and AST
Causes of post-hepatic conjugated hyperbilirubinaemia
Gall stones Biliary stricture Cancer Biliary cirrhosis Drugs Acute hepatocellular damage e.g. infection
Lab results for post-hepatic conjugated hyperbilirubinaemia
Elevated plasma and urine conjugated bilirubin
No urobilinogen (since bilirubin cannot leave liver)
Raised ALP, AST, ALT and GGT
Cholesterol based gall stones
80% of cases
Occur when bile contains too much cholesterol and too little bile salts
Less calcium
Green/Brown in colour
Pigment gall stones
20% of cases
Composed of bilirubin pigment and calcium salts.
Small and dark
Risk factors for cholesterol gall stones
Increased cholesterol - female, increased age, obesity
Increased bile salts - high oestrogen, malabsorption
Risk factors for pigment gall stones
Increased RBC breakdown (e.g. sickle cell anaemia) - causing increased unconjugated bilirubin.
Chronic biliary infected - causing glucuronidase production by epithelium or bacteria.
Hartmann’s Pouch
Mucosal fold at neck of gallbladder
Common site for gallstones to become lodged.
Symptoms of gallstone lodged in common hepatic bile duct
Post-hepatic Conjugate Hyperbilirubinaemia
Dark urine, pale stools, yellow skin, fatty streaks in stool.
Symptoms of gallstone lodged in Ampulla of Vater
Post-hepatic Conjugate Hyperbilirubinaemia
Dark urine, pale stools, yellow skin, fatty streaks in stool
Plus pain in abdomen and back due to pancreatitis.
Acute Pancreatitis
Blockage of duct causing injury to acini cells since activated digestive enzymes are trapped in pancreas.
Symptoms of Chronic Pancreatitis
Steatorrhoea
Flatulence and fowl smelling stools (inability to digest proteins, bacterial growth in intestines)
Acinar cells of pancreas release…
In response to…
Pancreatic enzymes (protease, amylase and lipase) Cl- rich secretions
In response to CCK
Ductal cells of acini of pancreas release…
In response to…
HCO3- (exchanged for Cl- released by acinar cells)
In response to secretin and ACh
How does Secretin bring about alkaline secretions from pancreatic acinus?
Activates Gs (GPCR) PKA activated PKA phosphorylates Cl- channels (cAMP mediated CFTR). Stimulates HCO3-/Cl- exchange by ductal cells. Cl- in lumen exchanged for HCO3- in ductal cells
CFTR Channel
Cystic Fibrosis Transmembrane Conductance Regulator (encoded by CFTR gene)
Transport of Cl- across apical membrane of acini.
Regulated by cAMP
Ca2+ dependent.
Hormonal and neural control mechanisms involved in CEPHALIC phase of digestion
Cephalic phase accounts for 30% digestion.
Sight, taste and smell of food stimulates output of gastric glands (via parasympathetic afferents)
Stimulates output of gastric glands.
Increased watery saliva production, containing amylase and mucins (stimulated by bradykinin and kallikrein)
Release of zymogen granules from acinar cells in pancreas.
Hormonal and neural control mechanisms involved in GASTRIC phase of digestion
Gastric phase accounts for 60% of digestion.
Distension of stomach and chemical content of food results in gastrin production from G cells.
Also stimulates vago-vagal gastropancreatic reflex i.e. Pancreatic acini release digestive enzymes and alkaline fluid.
Gastrin also stimulates acinar cells.
Hormonal and neural control mechanisms involved in INTESTINAL phase of digestion
Intestinal phase accounts for 5% of digestion.
pH of 2-3 in duodenum due to stomach acid stimulates S cells to secrete secretin.
Secretin (and H+ and GIP) stimulates D cells to produce somatostatin.
Somatostatin inhibits G cells (therefore, less Gastrin)
Secretin causes duct cells in pancreatic acini to secrete bicarbonate.
CCK released from duodenal cells in response to products of protein and fat digestion. CCK stimulates acinar cells of pancreas to secrete enzyme rich fluid.
Proteolytic component of pancreatic secretions
Trypsin, chymotrypsin and elastase (endopeptidases)
Carboxypeptidases (attack terminal bond)
Liplytic component of pancreatic secretions
Colipase, cholesterol esterase and PLA2 secreted as zymogens.
What is the significance of trypsin in exocrine pancreatic secretions?
Activates zymogen granules of all proteolytic and lipolytic pancreatic secretions.
Activated by enteropeptidase.
Cholagogue
Promotes discharge of bile
Orexin is released from…
In response to …
Released from lateral and posterior hypothalamus
In response to low blood glucose and high ghrelin.
Ghrelin is released from…
In response to…
Released from gastric mucosa of stomach and small intestine.
In response to empty stomach, hypoglycaemia
Leptin is released from…
In response to…
Released from adipocytes
In response to distension of stomach and presence of glucocorticoids (insulin)
Leptin is responsible for…
Suppression of appetite
Brown fat metabolism
Maintenance of baseline weight
CCK is released from…
In response to…
released from I cells in duodenal mucosa.
In response to products of protein and fat digestion in duodenum
CCK is responsible for…
Suppression of appetite
Slowing of gastric emptying
Contraction of gallbladder
PYY is released from…
In response to…
Released from L cells in colon and ileum.
In response to calorie intake
PYY is responsible for..
Suppression of appetite
Slowing of peristalsis to maximise absorption.
Cause of fatty change in the liver
White droplets
Metabolic stress
Alcohol
Pregnancy
Liver change which occurs as a result of cholestatic obstruction
Proliferation of bile ducts
Also occurs as a result of autoimmune disease, viral hepatitis, pregnancy and some drugs.
Hepatocyte necrosis
Affects individual cells, usually in zone 3 of liver acini (poorer blood supply)
Cells have a shrunken nucleus
How does liver fibrosis differ from cirrhosis?
Fibrosis results from inflammation and is reversible.
Cirrhosis results from repetitive injury and is irreversible.
Why is liver at a high risk of metastatic cancer?
Dual blood supply
Drugs which can cause dose-dependent liver damage
Paracetamol (in over dose) - zone 3 necrosis
Methotrexate - fibrosis
Glisson’s Capsule
Fibrous layer coating the liver
Falciform ligament
Attaches anterior surface of liver to anterior abdominal wall
Free edge contains ligamentum teres (remnant of umbilical vein)
Lobes of the liver
Left
Right
Quadrate (anterior)
Caudate (posterior)
Morrison’s Pouch
Hepatorenal recess - most likely place for fluid collection in a bed-ridden px
Blood supply to the liver:
Hepatic artery proper - branch of coeliac trunk carrying oxygenated blood.
Hepatic portal vein - carries deoxygenated blood containing nutrients absorbed from small intestine (Dominant blood supply to parenchyma
Autonomic nerve supply to liver
Parasympathetic - vagus nerve
Sympathetic - coeliac plexus
Sphincter of Oddi
Opening of hepatopancreatic Ampulla of Vater into duodenum.
Vasculature of gallbladder
Arterial supply - cystic artery (branch of common hepatic)
Venous drainage - cystic vein (drains into portal vein)
Autonomic innervation of gallbladder
Sympathetic - coeliac plexus
Parasympathetic - vagus nerve
Epithelium which lines the gall bladder
Simple columnar
Connective tissue on the outer surface of the gallbladder
Adventitia - where GB attaches to liver
Serosa - at free edge
Serosa
Encloses body cavities. Consists of a thin layer of connective tissue and a layer of cells secreting serous fluid.
Adventitia
Thin layer of connective tissue
Function of myenteric plexus
Motor innervation of GI tract.
Function of submucosal plexus
Carries sensory information from stretch receptors
Regulates secretory activity of the GI tract.
Effects of perforation of oesophagus
Contents extravasates into mediastinum.
Causes breathing difficulties and lung infection.
Epithelium found in the stomach
Simple columnar
Distribution of mucosa in the stomach
Cardiac mucosa - mucus secreting glands
Body mucosa - Many gastric pits, parietal cells (eosinophilic) and peptic cells (Haematoxyphilic)
Pyloric mucosa - deeper pits, shorter glands, mostly mucus secreting cells. Fewer parietal cells.
Gastric pits
Indentations in mucosa lined with foveolar cells. Secrete mucus to protect mucosa from HCl.
Found abundantly in cardiac and pyloric mucosa of stomach.
Rugae
Longitudinal folds in stomach mucosa. Allow distension of stomach.
Epithelium found in the small intestine
Simple columnar with microvilli
Plicae circularis
Circular folds in small intestine wall
Peyer’s Patches
Small masses of lymphatic tissue found in ileum. Generate antibodies to protect against infection.
Sinusoids
Small, irregular shaped vessel which receives nutrient rich blood from portal vein and oxygen rich blood from hepatic artery.
Carry blood from edges of lobule to central vein.
Kupffer Cell
Macrophages found in the liver
How does blood plasma move from liver sinusoids to hepatocytes?
Endothelial cells have pores and fenestrations.
Basement membrane is discontinuous and non obstructing.
Therefore, plasma can enter Space of Disse (gap between hepatocytes and sinusoid).
Hepatocytes have many microvilli which increase absorption from plasma.
Bile is synthesised by…
Hepatocytes
Canals of Hering
Canals into which Bile canaliculi drain bile into after it has been synthesised by hepatocytes.
Effect of parasympathetic innervation on salivary secretion
Vasodilation - increased blood supply to salivary glands. Watery saliva secreted, containing high HCO3- and Na+ but low K+
(Activates exchange of Cl- for HCO3-, deactivates exchange of Na+ for K+)
Effect of sympathetic innervation on salivary secretion
Vasoconstriction - reduced blood supply to salivary glands. Dry mouth in response to fear/stress.
Function of Intrinsic factor
Binds to B12 in duodenum - protecting it from digestion so that it can be absorbed in ileum.
Parietal cells in the stomach release…
When stimulated by…
Release: Intrinsic Factor and HCl
When stimulated by Gastrin and Histamine
Chief Cells in the stomach release…
When stimulated by…
Pepsinogen
When stimulated by Gastrin
Effects of Gastrin
Intrinsic factor and HCl secretion by Parietal cells.
Pepsinogen release by chief cells.
D cells in the stomach release…
In response to…
Release somatostatin
In response to low pH in stomach (acidity) and secretin
Effects of somatostatin
Inhibits gastrin release from G cells
S cells release…
In response to…
Secretin
In response to pH 2-3 in duodenum
CCK is released in response to…
Products of protein and fat digestion in duodenum.
Inhibitors of gastrin secretion
CCK
GIP
Somatostatin
Deglutition Apnoea
Epiglottis covers opening of nasopharynx during swallowing.
Prevents food from entering airway AND inhibits breathing briefly.
Mechanism for swallowing
Voluntary Phase 1: Tip of tongue pushes against hard palate and contracts.
Involuntary phase 2: Food stimulates mechanoreceptors in pharynx. Contraction of superior constrictor to prevent food entering nasopharynx. Wave of peristaltic contraction propels bolus through upper oesophagus. Relaxation of upper oesophageal sphincter.
Involuntary Phase 3: wave of contraction continues down length of oesophagus (7-10s)
Mechanism for HCl secretion from parietal cells
Binding of the ligand to cholinergic and gastrin receptors causes activation of PKA and therefore increased Ca2+ (Gq)
Binding of histamine to its receptor causes activation of PKA and therefore increases the effects of gastrin (Gs)
Results in acid secretion
Mechanism for inhibition of HCl secretion from parietal cells
Somatostatin and prostaglandins bind to their receptors (Gi) causing deactivation of PKA and therefore switching of HCl secretion.
Excitatory neurotransmitters in enteric nervous system
ACh
Substance P
Neurokinin A
Inhibitory neurotransmitters in enteric nervous system
NO
ATP
GABA
Neuropeptide Y
Composition of saliva
Salivary amylase - starch digestion
IgA
Lysozyme
Alkaline fluid
How does flow rate affect composition of saliva?
Increased flow rate, increases concentration of solutes in saliva (Na+, HCO3- and Cl- BUT NOT K+)
Therefore, increased pH.
Phase I of drug metabolism
Expose or create a chemically reactive group on the drug to facilitate phase II
e.g. oxidation, de-esterification, reduction or isomerisation
Phase II of drug metabolism
Deactivate/switch off biochemical or pharmaceutical activity.
Make water soluble by replacing reactive regions with a sugar or sulphate group.
Therefore, prepared for renal/hepatobiliary excretion
Cytochrome P450
Most significant family in phase I drug metabolism. Oxidative modification of drug molecule.
UDP-glucuronyl transferase
Phase II drug metabolism.
Conjugates a water soluble Glucuronide to the drug/metabolite (e.g. unconjugated Bilirubin)
CYP2E1
Metabolism of ethanol
CYP1A2
Metabolism of caffeine and theophylline
CYP1A1
Metabolism of theophylline
CYP3A4
Responsible for half of all phase I metabolism
Toxic paracetamol dose
4-6g
Lethal paracetamol dose
> 12g
Normal paracetamol dose
0.5g
Treatment of paracetanol overdose
N-Acetyl Cysteine
Toxic species generated by phase I metabolism of paracetamol….
How is this removed?
N-acetyl P-benzoquinone imine
Deactivated by conjugation to glutathion (phase II metabolism)
Metabolism of paracetamol
CYP1A2 and CYP2E1 pathway - oxidation of drug which generates NAPBQI. NAPBQI is deactivated by conjugation to glutathione.
UGT pathway - glucuronidation, making it soluble, inactive and easy to excrete.
Why does paracetamol overdose cause hepatotoxicity?
UGT pathway is overwhelmed. More paracetamol is metabolised via the CYP pathway.
More NAPBQI generated which must be deactivated -
quickly depletes glutathione reserves.
NAPBQI causes significant damage to hepatocytes.
Risk factors for dyspepsia
Pregnancy Alcohol Hiatus hernia Lactose intolerance Peptic or duodenal ulceration Stomach cancer NSAID use Anxiety/depression
Effect of alcohol on lining of GI tract
Alcohol inhibits formation of a protective gel via combination of water with mucins from surface of mucosal cells.
Symptoms of dyspepsia
Bloating Belching Retrosternal pain Epigastric pain/burning Nausea Reflux (acid taste in mouth) Heartburn Fullness/Early satiety
What is functional dyspepsia?
Most common form of dyspepsia
Delayed gastric emptying - can be caused by diet, stress, H.Pylori
Stage I treatment of dyspepsia
Antacids - weak bases which react with gastric acid
Stage II treatment of dyspepsia
H2 Receptor Antagonists - Ranitidine
Competitive inhibition of H2 (histamine) receptors - reduced gastic acid secretion stimulated by histamine (and gastrin)
MOA of Ranitidine
H2 Receptor Antagonists
Competitive inhibition of H2 (histamine) receptors - reduced gastic acid secretion stimulated by histamine (and gastrin)
ADRs of ranitidine
Impotence
Gynaecomastia (anti androgen)
Stage III treatment of dyspepsia
Proton Pump Inhibitors e.g. Omeprazole
Irreversible inhibition of H+K+ATPase
MOA of Omeprazole
PPI - Irreversible inhibition of H+K+ATPase
ADRs of omeprazole
Diarrhoea, Nausea, dizziness, headaches, confusion, impotence, gynaecomastia (anti androgen)
Causes of gastric ulcers
Helicobacter Pylori infection (60%)
NSAIDs (30%)
Carcinoma (5%)
Other (5%)- Crohn’s, neoplasia, stress, 2E syndrome
Causes of duodenal ulcers
Helicobacter Pylori infection (85%)
NSAIDs (10-14%)
Other (1%)- Crohn’s, neoplasia, stress, 2E syndrome
Diagnosis of H.Pylori infection
Endoscopy
Urea breath test - 95% sensitive/specific
Stool antigen - 92% sensitive/specific
Serology - 80% sensitive/specific
Treatment of H.Pylori infection causing gastric ulceration
3, 2, 1 Treatment
3 drugs:
PPI, Amoxicillin + Clarithromycin/Metronidazole
2x per day
For 1 week
(If allergic to penicillin, C+M Abx)
HMG CoA Reductase
Reduces HMG CoA to Mevalonate which can then be converted to cholesterol
St John’s Wart and Oral Contraceptive Pill
St John’s Wart induces CYP3A4, increasing the breakdown of the oral contraceptive pill - therefore reducing its efficacy
Erythromycin and Oral Contraceptive Pill
Erythromycin inhibits CYP3A4, decreasing metabolism of oral contraceptive pill - increased risk of thromboembolic events and other ADRs
Fat soluble vitamins
ADEK
Water soluble vitamins
B (B1,2,3,6,9,12) and C
Koilonychia
Nail spooning - iron deficiency
Leukonychia
White nails caused by hypoalbuminaemia
Dupuytren’s Contracture
Contracture of the hand due to palmar fibromatosis - fingers bend towards palm and cannot be fully extended.
Associated with chronic liver disease.
Palmar erythema
Redness of palms due to chronic liver disease or pregnancy
Anything which causes hyperdynamic circulation
Beau’s Lines
Deep grooved lines running from side to side on the finger or toenail.
Caused by any illness that interrupts growth of nail bed.
Spider naevi
Swollen blood vessels slightly beneath the skins surface, often contain a red central spot.
Caused by chronic liver disease, pregnancy or oestrogenic hormones
Asterixis Sign
Rapid relaxation of dorsiflexion of the wrist - fingers are observed to flap.
Caused by hepatic encephalopathy - imbalance between agonist and antagonist muscle
Acanthosis nigricans
Darkened, thickened patches of skin in the arm pit.
Associated with carcinoma of stomach and diabetes
Causes of abdominal distension
Fat Flatus Faeces Foetus Fluid
Caput Medusae
Multiple dilated superficial veins associated with portal hypertension
Contraindications for PPIs
Osteoporosis
C.Diff infection
Risk associated with PPIs and H2 receptor antagonists
May mask some symptoms of gastric cancer
ADRs of antacids
Eructation (burping - due to liberation of CO2 when acid is neutralised)
Diarrhoea
Contraindications of antacids
Hypophosphataemic
Renal impairment
Hepatic coma (can lead to renal impairment)
Why can antacids and PPIs not be given at the same time?
PPIs are prodrugs
They rely on the acidity of the stomach to activate them
Neutralisation of stomach acid by antacids will prevent activation of PPI
