Year 2: Substance Use

What are the two major branches of the hepatic portal vein?

• Superior mesenteric vein

• Splenic vein

Which vein drains the transverse colon?

Middle colic vein

Which vein drains the ascending colon?

Right colic vein

Which vein drains the descending colon?

Left colic vein

Which vein drains the sigmoid colon?

Sigmoid vein

When vein drains the rectum?

Sigmoid-rectal vein

Which vein drains the ileum, caecum, appendix?

Ileocaecal vein

Where does the abdominal portion of the oesophagus drain into?

Left gastric vein→ portal circulation

Where does the thoracic portion of the oesophagus drain into?

Azygous veins→ systemic circulation

Which veins drain the pancreas and duodenum?

Pancreaticoduodenal veins

Which veins drain the fundus of the stomach?

Short gastric veins

Which vein drains the greater curve of the stomach?

Left gastroepiploic vein

Which vein drains the lesser curve of the stomach?

Left gastric vein

Which vein does the splenic vein branch from?

Inferior mesenteric vein

Para-oesophageal anastomosis→ Varices

• Left gastric vein

• Azygous vein

Para-rectal anastamosis→ Piles

• Superior rectal vein

• Middle/inferior rectal vein

Para-umbilical anastomosis→ caput medusae

• Para-umbilical vein

• Superficial epigastric vein

How can portal hypertension be treated via TIPS?

Transjugular intrahepatic portosystemic shunting:

1. insert a catheter into the jugular vein to access the hepatic vein

2. needle puncture the portal vein to insert a stent

3. this stent keeps the portal vein open to allow blood flow with more ease!

What are the pre-hepatic causes of portal hypertension?

• Congenital atresia/stenosis

• Thrombosis

What are the hepatic causes of portal hypertension?

• Cirrhosis

• Hepatitis

• Schistosomiasis→ (LFT will be normal)

• Idiopathic

What are some post-hepatic causes of portal hypertension?

• Pericarditis

• Heart failure

• Budd-chiari syndrome

Which two lines seperate the coinaud segments of the liver?

1. portal line (horizontal)

2. cantile line (vertical)

How are the coinaud segments organised?

7 8 2

6 5 4 3

Which structures are involved in the pringle manouver?

• Hepatic artery

• Common bile duct

• Hepatic portal vein

If the bleeding does not stop after performing the pringle manouver, what is the likely origin of the bleeding?

• IVC

• Hepatic veins

What is the structure of the liver in regards to lobes and ligaments?

Anterior:

• Right and Left lobes

• Falciform ligament

Posterior:

• Caudate lobe

• Quadrate lobe

• Gallbladder

What is pancreatitis and hallmarks of diagnosis?

• Inflammation of pancreas

• Left upper quadrant

• Epigastric pain

• Negative murphy’s sign

• Raised amylase and lipases

Which procedure is used to treat pancreatic cancer?

Whipple procedure→ removal of the head of the pancreas, the duodenum, the gallbladder, and part of the bile duct

Describe the billary tree

right/left hepatic ducts→ common hepatic duct→ common bile duct→ common hepatopancreatic duct→ main pancreatic duct

What are the exocrine functions of the pancreas?

digestion via:

• HCO3

• amylase

• protease

• lipase

What are the endocrine functions of the pancreas?

Production of insulin and glucagon

What type of structure is the pancreas?

Endocrine organ, foregut

Pancreatic lypmh nodes

• Pancreaticosplenic

• Celiac

• Superior mesenteric

In which artery does pancreatic haemorrhage typically occur?

SMA

What is grey turner’s sign?

Bruising on flank (side)

What is cullen’s sign?

Bruising around belly button via falciform ligament

What is murphy’s sign?

It's performed by pressing on the patient's upper right abdomen while they inhale deeply. If the patient experiences pain and stops breathing in, the test is positive→ acute cholecystitis (gallbladder inflammation)

What is the pressure in the hepatic portal system?

5-10mmHg

What are the extra-ocular muscles of the eyes?

• Superior rectus + Superior oblique

• Medial rectus

• Inferior rectus

• Lateral rectus

What are the intra-occular muscles of the eye?

• Cilliary muscles

• Pupillary constrictor muscle

Which cranial nerve controls the superior oblique muscle?

Trochlear (CN VI)

Which cranial nerve controls the lateral rectus muscle?

Abducens (CN IV)

Which cranial nerve controls all other muscles of the eye?

Occulomotor (CN III)

What is the most common cause of bleeding at the back of the eye?

Diabetes

What is the medical term for tunnel vision?

• Retina pigmentosa

• Macula degeneration

What is the medical term to describe a blurry vision, painful eye and colour loss?

Optic neuritis

What is vertical diplopia?

• Double vision

• Upwards

What is diplopia?

• Double vision

• Laterally

Which structures are found is cavernous sinus?

• Carotid artery

• Nerves

What can a fistula cause?

Eye swelling

What is mydriasis?

Widened pupil

Where is McBurney’s point?

One of third of the way from ASIS to umbillicus

Where is Roving’s sign?

Apply left lower quadrant pressure→ pain is a positive sign for appendicitis

What does retrocaecal appendicitis cause?

Flank pain

What does retroileal appendicitis cause?

Testicular pain

What kind of structure is the appendix? Which arteries supply the appendix?

Midgut:

• SMA

• Appendicular artery

What is the arterial supply to the small intestine?

1. ileocolic artery (right-side)

2. right colic artery (right-side)

3. middle colic artery (right-side)

4. marginal artery (left-side)

5. left colic artery (left-side)

What are the nine quadrant regions of the stomach?

• Right hypochondriac→ Epigastric ← Left hypochondriac

• Right lumbar→ Umbillical ← Left lumbar

• Right iliac→ Hypogastric ← Left iliac

What overall effects do sedatives, hypnotics and anxiolytics have?

1. Sedatives→ relaxants

2. Hypnotics→ sleep

3. Anxiolytics→ anxiety-relief

What is the difference between persistent and episodic anxiety?

• Persistent→ general

• Episodic→ trigger-induced

Overstimulation of which structure causes anxiety?

Amygdala

Why can benziodiazepines be used to treat anxiety?

Benzodiazepines + Z-drugs; they increase Cl- influx and increase GABA release

Which benzodiazepene is both an anxiolytic AND a hypnotic?

Zalpidem→ due to short half life (2 hours)

Diazepam is a benzodiazepine. What is the a) half life? b) overdose treatment?

a) 20-40 hours

b) Flumazenil to treat overdose (GABA antagonist)

SSRI’s are anxiogenic. How do they work?

SSRI’s downregulate the 5HT2 receptor and increase the action of GABA in the amygdala

However, it takes 3-4 weeks for this to take action

Fluxoetine and citalopram are example of which class of anxiolytic drugs?

SSR’s

SARI’s are a class of anxiolytic drugs. What does SARI stand for and name a drug?

“Seretonin-receptor antagonist and reuptake inhibitor”:

e.g. Trazadone→ at low doses it is hypnotic, at high doses it is antidepressant

Buspirone is an anxiolytic drug. How does it work?

5HT1A receptor partial agonist

How do beta-blockers work? Who cannot take beta-blockers?

• Peripheral beta-adrenoreceptor antagonists

• Blocks salbutamol so do not give to asthmatics!!!

What is phase 1 drug metabolism?

Polar metabolites via P450 enzymes in SER of hepatocytes

What is phase 2 drug metabolism?

Oxidation of metabolites→ water soluble via taurine, glycine and sulfate

What are the four principles of pharmacokinetics?

1. Absorption

2. Distribution

3. Metabolism

4. Excretion

Which CYP protein metabolises the most drugs?

CYP 3A4

Which CYP protein inhibits enzyme induction?

CYP 2D6

Which CYP protein mutation results in poor warfarin clearance?

CYP 2C9→ warfarin will have a lower therapeutic index so can become toxic quickly.

Why can you not take medications with grapefruit juice?

1. Grapefruit juice inhibits the CYP 3A4 protein in the enterocytes of small intestine

2. This reduces the drugs first-pass metabolism

3. Therefore, the concentration of drug in the blood remains high

4. This can reduce blood pressure and cause issues

Which BNF appendix is used to search for drug interactions?

BNF-Appendix 1

Which BNF-appendix is used for patients with liver disease?

BNF-Appendix 2

Which BNF-Appendix is used for patients with renal disease?

BNF-Appendix 3

Which BNF-Appendix is used for maternal and fetal health?

BNF-Appendix 4

What are the functions of the liver?

• Protein synthesis

• Bilirubin clearance

• Ammonia conversion to urea

• Iron metabolism

• Vitamin storage

What is acute-on-chronic liver failure?

Sudden inability of liver to perform metabolic function but due to underlying pathology

What are some signs and symptoms of liver disease?

• Jaundice

• Abdo pain

• Peripheral oedema

• Priutus (itchy)

• Dark urine and stools

• Lose of appetite

• Bruising

What is hepatic encephalopathy?

When excess neurotoxins are in the blood and cause you to be awake at night but sleep during the day

What is portosystemic shunting?

Abnormal connection between portal vascular system and systemic circulation→ leaking of toxins

What is steatosis?

fatty liver disease due to alcohol (reversible via cessation)

What is the pathophysiology alcohol-induced liver cirrhosis?

1. Alcohol to acetaldehyde via alcohol dehydrogenase

2. Acetalydehyde to acetate via aldehyde dehydrogenase

3. These by-products stimulate kupffer cells to release TNF-alpha, IL-1, IL-6 and ROS→ inflammation!

4. Stellate cells are also activated to produce ECM and extra collagen→ fibrosis!

How do you investigate for liver disease?

• Bilirubin

• Alanine aminotransferase (ALT)→ hepatocellular damage

• Alkaline phosphotase (ALP)→ colestasis or billary obstruction

• Biopsy at 7th or 8th intercostal space at midaxillary line

Which gene mutation causes haemochromatosis?

C282Y gene mutation → excess iron in blood

Which recreational drug is most commonly used in the UK?

Cannabis

From which plant is heroin derived?

Poppy plants→ depressant

From which plant is cocaine derived?

Coca plants→ stimulant

What is the mechanism of action of stimulant drugs?

1. opiods ENHANCE the release and re-uptake of neurotransmitters at the pre-synapse

2. Ca2+ and Na+ channels open and depolarise

3. More neurotransmitter is released so:

• dopamine released→ happy!

• seretonin released→ arousal, mood, pain!

• noradrenaline released→ fight or flight!

What is the mechanism of action of depressant drugs?

1. drugs REDUCE neurotransmitter activity

2. adenylyl cyclase and cAMP is inhibited

3. this reduces Ca2+ and Na+ influx whilst K+ eflux increases leading to hyperpolarisation

4. more GABA-agonist stimulated to inhibit the CNS

Overdose of barbiruates can cause what? Overdose of benzodiazepenes can cause what?

• Barbiurates→ death

• Benzodiazepenes→ coma

What is drug tolerance?

Increasing a dose of drug to obtain the same effect

What is the difference between dependence and addiction?

• Dependence→ physiological

• Addiction→ psycological

Which drugs are commonly used in the UK in order from highest to least?

1. Cannabis

2. Cocaine

3. NO

4. Ecstasy

5. Hallucinogens

6. Ketamines

What are class A drugs? Legal consequences?

• Possession→ 7 years

• Supply→ Lifetime

• e.g. cocaine, heroine, ecstasy

What are class B drugs? Legal consequences?

• Possession→ 5 years

• Supply→ 14 years

• e.g. amphetamines, cannabis, mephedrone