Liver lover lol alliteration Flashcards
Major aspects of structure which influence function?
Vascular system
Biliary 🌳-system of ducts 🚌bile out of liver➩small intestine
3D arrangement of liver cells w vascular + biliary systems
Blood supply to liver?
75% from portal vein
25% from hepatic artery
Where do the central veins of liver lobules drain?
➩ hepatic vein ➩ vena cava
1ᵒ cells of liver + function?
Hepatocytes 60%– perform metabolic functions
Kupffer cells 30%– type of tissue macrophage
Others -endothelial cells+stellate cells
What’s the functional unit of the liver?
Hepatic lobule - hexagonal plates of hepatocytes around central hepatic vein – each 6 corners is triad of branches of portal vein, hepatic artery, bile duct
What are sinusoids?
small channels lined w hepatocytes
What’s the biliary system?
hepatocytes⇶bile –> channels between cells-canalinculi –> small ducts –> large ducts–>
anastomose onto common bile duct
How liver’s microstructure supports its roles?
↑ SA for exchange of ∞
Separation of blood from bile
Pumps positioning achieves specific localisation of materials at cellular level
How Kupffer cells act as protective barrier?
Removes gut 🐛 ∴ <1% entering portal blood succeeds in passing via liver➩systemic circulation
What’s bile?
Fluid=water, electrolytes, organic∞-bile acids, cholesterol, bilirubin,phospholipids
How’s bile secreted?
- by hepatocytes-bile salts, cholesterol, other organic constituents
- by epithelial cells lining bile ducts-watery solution of Na+HCO3, stimulated by Secretin∵acid in duodenum
How much bile does a human produce daily?
400-800ml
Diff processes of bile→duodenum?
Bile from hepatic ducts–>common bile duct–>duodenum
OR
diverted via cystic duct–>GALL BLADDER–>conc +stored 30-50ml–>⇶ by cholecystokinin ∵ fat in duodenum
What’s the entry➩ doudenum is controlled by?
Sphincter of Odii
How’s gallstone produced?
Abnormal conditions–>cholesterol ppts in gallbladder–>
Types of stones?
cholesterol 80% + pigment 20%
What causes gallstones?
- ↑fat diet
- ↑synthesis of cholesterol
- Inflammation of GB epithelium changes mucousa absorption
- ⇑ absorption of H2O+bile salts–>cholesterol conc
Risk factors of gallstones?
♀,obesity, ⇑ oestrogen eg 🤰, HRT
Where do gallstones form?
anywhere along biliary tract
What are bile acids?
derivatives of cholesterol, made in hepatocytes
How are bile acids made?
cholesterol→cholic + chenodeoxycholic acids–>conjugated w glycine/taurine–>↑ solubility➩cannaliculi–> the intestinal 🐛converts → 2ᵒ bile acid
What’s the enterohepatic circulation of bile acids?
Bile acids from liver/gall bladder➩ small intestine for fat absorption–> re-absorbed in terminal ileum–>hepatic portal vein–>liver–>taken up in hepatocytes–>re-secreted in new bile
How often bile acids recirculated?
6-8x per day
How much bile acids reabsorbed?
95%.. 5% lost in faeces
Function of bile?
- Emulsification for fat digestion + absorption
- Bile+pancreatic juice neutralises gastric juice as enters small intestine
- Aids digestive 𝔼
- Remove waste from blood -bilirubin +cholesterol
How much cholesterol is eliminated daily?
500g cholesterol→ bile acids
What’s bilirubin?
Yellow pigment from Hb breakdown
Useless+toxic but ~6g/day .. a lot
How’s aged 🔴 destroyed?
Digested by macrophages
Fe- recycled
Globin chains-catabolized
Haem (porphyrin)-eliminated
Where’s 🔴 digested?
mostly in spleen
Formation + removal of bilirubin?
Haem→free bilirubin–>released into plasma carried bound to albumin–>absorbed by hepatocytes –>conjugated w glucoronic acid→bile–>metabolised by intestinal lumen–>faeces/urine
Why’s faces brown + urine yellow?
Stercobilin – metabolite
Yellow urobilin + urobilinogen-metabolite
What’s jaundice?
⇑ of free or conjugated bilirubin accumulate in ECF
∴
Yellow discoloration of the skin, sclera,mucous membranes is observed
Normal plasma [bilirubin] = 0.5mg/dl
discolouration >1.5mg/dl
What’s ‘green jaundice’?
mutation of biliverdin reductase gene ∴biliverdin NOT→ bilirubin∴ built up in plasma
Types of jaundice?
Pre-hepatic (haemolytic)
Hepatic
Post-hepatic (obstructive)
What’s pre-hapatic jaundice?
- ⇑🔴breakdown eg neonatal jaundice
- ⇑unconjugated bilirubin
What’s hepatic jaundice?
- Hepatocyte damage (>80%) eg cirrhosis,💊, hepatitis A,B,C,E, Gilberts Syndrome
- ⇑conjugated +/or unconjugated bilirubi
What’s post-hepatic jaundice?
- ⇑conjugated bilirubin
- Obstruction ➩duodenum
- Enters circulation➩ dark urine eg gallstones, carcinoma of pancreas/bile ducts
What’s Gilbert’s syndrome?
congenital disorder where ↓𝔼 that conjugates bilirubin w glucoronic acid–>↑unconjugated bilirubin
Why does neonatal jaundice occur?
Fetal Hb →adult Hb so ⇑🔴breakdown results –> normal physiological jaundice but liver’s immature- delay in processing
Treatment for neonatal jaundice?
Sunlight includes blue light- filters out (UVA, UVB, UVC, IR etc) ↓ risk of over-heating or sunburn
What’s the Glucose Buffer Function?
Humans (pre-prandial) 4-5.9mmol/L
What’s glycogenesis?
glucose → glycogen (stimulated by insulin). Liver stores glycogen 80g
What’s glycogenolysis
glycogen→glucose stimulated by glucagon + A
What’s gluconeogenesis?
lactate, AA & glycerol (from TGC)→glucose
What’s glycolysis?
glucose → pyruvate releasing E to form ATP + NADH
How’s fat metabolised in liver?
TCG oxidized in hepatocytes
Lipoproteins synthesised in liver
⇑Carb+🐟 → FA + TCGs – stored in adipose
Synthesis of cholesterol + phospholipids- some→lipoproteins
What’s citric cycle?
FA enter it to release E + → ketone bodies
Sources of FA for metabolism?
Dietary source of TCGs
TCGs stored in adipocytes
TCGs synthesised in the liver
How’s 🐟 metabolised in liver?
Deamination + transamination of AA-non-nitrogenous of AA → glucose +lipids
Synthesis of non-essential AA
Synthesis of nearly all plasma proteins (90%) 15-50g/day
Synthesis of urea-removes NH3
Why remove NH3?
Depress cerebral blood flow + cerebral O2 consumption.
Toxic especially to 🧠–>hepatic encephalopathy
Where does NH3 come from?
deamination + gut 🐛
What toxic substances does the liver excrete?
Bilirubin. NH3. Hormones eg all steroid (androgens, oestrogens, cortisol, aldosterone, thyroxine),💊+ exogenous toxins (asprin, paracetamol, ethanol)
What are steroid hormones excreted as?
glucuronide/sulphate conjugates
If ⇑steroid hormones what happens?
gonadal dysfunction ♂
spider angioma in ♀
How does liver metabolise drugs + hormones?
Phase 1 (primarily oxidation/reduction) Phase 2 (conjugation) phase 3 ATPase pumps to eliminate➩blood or bile
What happens in phase 1?
In SER, catalysed by cytochrome P450- substrate → polar compound
What happens in phase 2?
↑solubility by conjugating w Glucuronyl
Features of paracetamol?
Acetaminophen
Has narrow therapeutic index–>overdose
Max dose 4g/day or 1g/dose
❌after 🥤
How’s paracetamol metabolised?
- Glucoronidation (45-55%)
- Sulfation (20-30%)
- N-hydroxylation+dehydration → NAPQI (toxic)–>detoxified by glutathione (GSH) conjugation (<15%) in phase 2
How paracetamol overdose occurs?
Incomplete metabolism∵
𝔼 saturated + glutathione stores depleted–> liver necrosis + kidney damage by toxic metabolites
Treatment for paracetamol overdose?
N-acetylcysteine : the precursor to glutathione ∴ increases it’s levels
Why does paracetamol have 2 phase effect?
feel fine after od∴dont seek help until late
What happens after drinking🥤?
readily absorbed from GI but not stored ∴ oxidized in liver
How’s 🥤oxidised?
ethanol→acetaldehyde by alcohol dehydrogenase containing the coenzyme NAD+ –> ⇑ NADH
How’s ⇑ NADH removed?
- Used in conversion of pyruvic acid→lactic acid
- Reducing agent to synthesise glycerol + FA
- Used in ETC to synthesise ATP
What happens when NADH ❌ gluconeogenesis?
hypoglycaemia ∵ lack of glucose synthesis from pyruvic acid
What happens when NADH used in ETC ∴ ❌fat oxidation?
FA accumulation (alleviated by releasing lipids into the blood stream)--> ❤ attack Acetyl coA accumulation -->ketosis--> hepatatis, cirrosis
What’s 🥤 flush?
Accumulation of acetaldehyde ∵ ALDH2 missense polymorphism mutation
50% of Asians have 1 mutant that encodes inactive mitochondrial isoenzyme
What are 🥤liver probs?
Fatty liver : deposits of fat –>liver enlargement; strict abstinence leads to full recovery
Liver fibrosis : scar tissue; recovery possible but scar remains
Liver cirrhosis : connective tissue growth destroys liver cells; irreversible
Alcoholic hepatitis : acute + chronic hepatitis-inflammation
Alcoholic cirrhosis : injury∵⇑🥤, chronic hepatitis B/C infection,⇑Fe/Cu,💊, obstruction of the bile duct
Why’s alcoholic cirrhosis a degenerative disease?
liver cells damaged + replaced by scar
What can cause Gynecomastia?
alcoholic cirrhosis
What part of cell cycle are adult hepatocytes in?
G0
NO CELL ÷
When do hepatocytes enter cell cycle?
After partial hepatectomy (70% liver removed by by ligation of the blood supply+resection)
Toxic injury
When does proliferation of hepatocytes stop?
when mass of liver established
Pathways of liver regeneration?
- growth-factor mediated pathway →HGF (hepatocyte growth factor) + TGFα(transforming growth factor alpha)
- cytokine signalling pathway using IL-6 via TNFα binding to its receptor on Kuppfer cells
Process of liver regeneration?
- signals initiated simultaneously in the liver
- gut-derived factors- lipopolysaccharide (LPS) unregulated+reach the liver via portal blood supply
- activates hepatic non-parenchymal cells-Kupffer + stellate cells–>↑ tumour necrosis factor (TNF) + interleukin (IL)-6
- insulin, epidermal growth factor (EGF), NA, triodothronine(T3),hepatocyte growth factor (HGF)
- cooperative signals from factors allow hepatocytes to move via cell cycle–> DNA synthesis + proliferation
- transforming growth factor (TGF) signalling❌DNA synthesis during proliferation but restored after regeneration by helping hepatocytes return to quiescent state
What coagulation factors are produced in the liver?
Fibrinogen
Prothrombin
Nearly all the other factors eg V, VI, IX, X, XII
Function of Vit K?
formation of pro-thrombin + factors II,VII, IX & X
What do stellate cells store?
fat-soluble vit D, K, E, A
What vit does liver store?
vitamin B12- last for 2 - 3 yrs
deficiency–> pernicious anemia
What’s folate?
stored in liver vital in early 🤰
What’s Fe stored as in liver?
ferritin
How does liver act as Fe buffer system?
Hepatic cells contain apoferritin -combines reversibly w Fe= ferritin
Ferritin releases Fe when low
What’s LFT?
check liver 𝔼+🐟 in your blood
Screens for hepatitis
Monitor the progression of alcoholic hepatitis,shows if treatment working
Measure the severity-scarring of the liver (cirrhosis)
Monitor side effects of 💊
Common sections of LFT?
- alanine aminotransferase (ALT) - 𝔼 in hepatocytes-in blood when hepatocytes are damaged, high levels in hepatitis and alcohol induced damage
- aspartate aminotransferase (AST) - 𝔼 in hepatocytes, in blood when hepatocytes are damaged, high levels in hepatitis and alcohol induced damage
- alkaline phosphatase (ALP) - 𝔼 in bile duct, indicates obstruction in bile flow
- gamma glutamyl transferase (GGT) – indicates obstruction
- bilirubin - jaundice
- albumin - ↓ in chronic liver disease/malnutrition
- clotting studies, i.e. prothrombin time (PT)-if ↓ then ↓ clotting factors or international normalised ratio (INR)
