GEP (Life Maintenance) Week 2 Flashcards
Name the anatomical structures
Falciform ligament attaches to the diaphragm.
What are the ligaments associated with the liver.
- Ligamentum teres -> embryological remnant of foetal umbilical vein.
- Falciform ligament -> remnant of embryonic ventral mesentery.
- Coronary ligament -> attaches superior surface of liver to inferior surface of diaphragm
- Triangular ligaments -> left and right attach respective lobes to diaphragm.
- Lesser omentum -> attach liver to lesser omentum of stomach and first part of duodenum. Consists of hepatoduodenal and hepatogastric ligaments.
What is the artery supply to the liver
- Abdominal aorta -> coeliac trunk -> common hepatic artery -> proper hepatic artery -> left and right hepatic artery
- N.B. left and right hepatic arteries mainly supply bile ducts, liver supply comes from proper hepatic artery
What is the venous supply and drainage for the liver
- Superior mesenteric + splenic vein -> hepatic portal vein
- Hepatic portal vein carries most of blood that enters the liver. Brings nutrient rich blood from GI tract.
- Central vein -> collecting vein -> hepatic veins -> IVC
What innervates the liver
Innervation -> hepatic plexus. Sympathetic fibres from coeliac plexus and parasympathetic fibres from anterior and posterior vagal trunks.
What are hepatic lobules and the portal triad
What are the roles of the liver
Liver functions:
*People - Protective Barrier
*Partially - Plasma protein synthesis
*Believe - Bile synthesis & metabolism
*Bilirubin - Bilirubin synthesis & metabolism
*Can - Coagulation/clotting factors
*Cause - Carbohydrate metabolism
*Nasty - Nitrogen metabolism
*Dark - Detoxification
*Dank - Drug Metabolism
*Smelly - Storage
*Faeces - Fat metabolism
Describe further the protective barrier role of the liver
Describe further the plasma protien synthesis and clotting factor
Plasma proteins
Transport nutrients like glucose, amino acids, lipids, & vitamins absorbed from the digestive tract to different parts of the body → carry substances poorly water soluble
Key plasma protein: Albumin - Marker of liver synthesising function
Clotting factor:
*Fibrinogen
*Prothrombin
*Nearly all the other factors e.g. V, VI, IX, X, XII
*DISCO 1972
What is bile and how is it secreted
Fluid composed of water, electrolytes + mix of organic molecules
Organic molecules: bile acids, cholesterol, bilirubin and phospholipids
Secreted via:
Hepatocytes: Bile salts, cholesterol & other organic constituents
Epithelial cells lining bile ducts: Large quantity of watery solution: Na+ & HCO3-
What are the roles of bile
- Emulsification: fat digestion & absorption of fat soluble vitamins (Vitamins ADEK)
- Bile + pancreatic juice neutralises gastric juice as it enters the small intestine - aids digestive enzymes & regulation of digestion
- Eliminates waste products from blood, particularly bilirubin & cholesterol - 500mg of cholesterol converted to bile acids per day
How is bile synthesied and metabolised
1)Cholesterol synthesised to primary bile acids (By enzyme 7 α- hydroxylase)
->Presence of -COOH and -OH groups makes bile acids water soluble than cholesterol
2) Primary acids conjugate with glycine or taurine to form bile salts
3)Conjugated bile salts in sinusoidal blood transported to bile canaliculi
4)Bile acids are reabsorbed in the intestine by passive diffusion or active transport in terminal ileum
5)Enterohepatic circulation raises the bile salt concentration in the portal vein -> inhibits the hepatic synthesis of bile salts via negative feedback
Bile is released by cholecystokinin in response to the presence of fat in the duodenum
Gallstones Can form anywhere along this tract
2 types:
Cholesterol (80%)
Pigment (20%)
Describe the synthesis and metabolism of bilirubin
Haem converted into free bilirubin via 2 enzymes:
Heme Oxygenase
Biliverdin reductase
Released into plasma – carried around bound to Albumin
Free bilirubin absorbed by hepatocytes → conjugated with glucuronic acid by UDP-Glucuronosyltransferase
Conjugated bilirubin secreted into bile → metabolised by bacteria in intestines & eliminated into faeces/urine
Major metabolite in faeces is Stercobilin – brown colour
In urine – Yellow urobilin & urobilinogen
What are the causes of Jaundice
- Normal urine + normal stools = pre-hepatic cause
- Dark urine + normal stools = hepatic cause
- Dark urine + pale stools = post-hepatic cause (obstructive – i.e. biliary obstruction)
How is Carbohydrates metabolised and transported
Pathway Produces Fresh Glucose
Pyruvate carboxylase
-Pyruvate → oxaloacetate
-Mitochondria
-Activator: acetyl-CoA
-Inhibitor: ADP
PEP carboyxlase
-Oxaloacetate → phosphoenolpyruvate
-Cytosol
Fructose-1,6-biphosphatase
-Fructose-1,6-biphosphate → fructose-6-phosphate
-Cytosol
Glucose-6-phosphatase
-Glucose-6-phosphate → glucose
-Endoplasmic reticulum
Not present in muscle (why muscles cannot generate glucose)
Extra follow up notes
Describe fat metabolism
1.Triglycerides oxidized in hepatocytes to produce energy
2.Lipoproteins synthesised in liver (e.g., LDL, HDL)
3.Excess carbohydrates & proteins converted into FA & TGs – stored in adipose
4.Synthesis of large quantities of cholesterol & phospholipids – some packaged as lipoproteins
Describe nitrogen metabolsim
- Most nitrogen enter body as amino acids from protein diet
- Most nitrogen excreted from body as urea in urine
- Liver regulates blood level of A.As based on tissues need for protein synthesis
- Transamination: Amino acid converted from one type to another i.e. essential A.A -> non-essential A.A
- Oxidative Deamination: Break down of amino acid via removal of amino acid group -> urea
How does the liver detoxify
Liver detoxifies all the rubbish from the blood received from the gut via excretion & metabolism:
* Bilirubin
* Ammonia
* Hormones (steroid hormones e.g, androgens, oestrogens, cortisol)
* Drugs & exogenous toxins
What is the key enzyme for detoxification for the liver
Cytochrome P450 enzyme: key enzymes in detoxification & metabolism -> induction or inhibition can be affected by drug-drug interactions
Cytochrome P450 enzyme: controls metabolism regulation of waste products
Describe the 2 step detoxification and metabolism steps that occurs in the liver for drug and hormones.
What are the cytochrome p450 inducers and inhibitors
Inducers:
-St Johns wort
-Carbamazepine
-Rifampicin
-Alcohol (chronically)
-Phenytoin
Inhibitors:
-Grapefruit juice
-Isoniazid
-Valproate
-Erythromycin
-Ritonavir
SCRAP GIVER IS A GOOD WAY TO REMEBER
What are the presentation of acute liver failure
Signs and symptoms:
* Hypotension
* Altered mental state
* Fever
* RUQ discomfort
* Pain
* Tenderness
* Nausea
* Jaundice
* Fluid overload
* Hepatomegaly
* Malaise
Remember - in patients with overdose, you must always consider that more than one substance has been taken, so symptoms and signs are often not cut-and-dry.
What is the pathophysiology of paracetamol overdose part 1
When the non-toxic metabolite pathway get overloaded it goes to the other pathway that produces NAPQI.
What is the pathophysiology of paracetamol overdose part 2
What are the bedside, 1st line, further tests would you consider for overdose
What is the management of single time overdose
What is the management of unknown or staggered overdose
N-Acetyl Cystine
What is part of an LFT (liver function test) screen
- Alanine aminotransferase -> ALT
- Aspartate aminotransferase -> AST
- Alkaline phosphatase -> ALP
- Gamma-glutamyltransferase -> GGT
- Bilirubin
- Albumin
And also clotting factors to check issues with the liver as it prooduces clotting factor
what does ALT and AST in a LFT indicate
What does ALP and GGT in LFT indicate
What does Bilirubin and Albumin in LFT indicate
What is the systematic approach to interpreting LFTs part 1
First Look at INR
What is the systematic approach to interpreting LFTs part 2
Second compare ALP and GGT
What is the systematic approach to interpreting LFTs part 3
Thirdly compare ALP and ALT
What is the systematic approach to interpreting LFTs part 4
Fourthly compare ALT and AST
Knowing that abnormalities in AST shows either biliary tree or bone pathology.
What is the MICRA of Paracetamol