03-10 Liver Structure and Fxn Flashcards
• Describe the gross and microscopic anatomy of the liver • Discuss the normal physiologic functions of the liver including: Bilirubin production and excretion; the metabolism of drugs and toxins; the metabolism of carbohydrate, lipid and protein; and the synthesis of albumin and clotting factors • List the different laboratory tests used to assess liver function, discuss their significance in assessing patients with liver disease • Describe the different imaging modalities and invasi
<p>Major cell types (+ function) in the liver</p>
<p>Three major cell categories:</p>
<ol>
<li>– Hepatocytes PRODUCTION
<ul>
<li>Organized in lamina of cell plates</li>
<li>metab fxns involving CHOs, fats and prots</li>
<li>bile production</li>
<li>biotransform Rx & toxins (make hydro<u>philic</u>)</li>
<li>gets rid of bilirubin</li>
<li>storage</li>
</ul>
</li>
<li>– Cholangiocytes EXCRETION
<ul>
<li>Intercellular channels > bile canaliculi</li>
</ul>
</li>
<li>– Non-parenchymal cells FILTRATION
<ol>
<li>Kuppfer cells</li>
<li>Sinusoidal epithelial cells (leaky)</li>
<li>Hepatic stellate cells, a.k.a. Ito cells (collagen synth)</li>
</ol>
</li>
</ol>
<p>Describe the gross anatomy of the liver</p>
<ul>
<li>Gross</li>
<li>Blood Supply</li>
<li>Biliary Tree</li>
<li>Lymphatics</li>
</ul>
<p>GROSS:</p>
<ul>
<li>Capsule (peritoneal): surrounds liver except “bare spot” of posterior aspect - continuity w/ retro-peritoneum</li>
<li>organ divided into segments by blood supply</li>
</ul>
<p>BLOOD SUPPLY: Dual hepatic a. + portal vein</p>
<ul>
<li>aorta→ celiac artery→ common hepatic a.→ r & L hep a.
<ul>
<li>OR</li>
</ul>
</li>
<li>aorta→SMA→RHA +</li>
<li>left gastric→LHA
<ul>
<li>R hep art→ cystic aa. to G.B.</li>
</ul>
</li>
<li>L, mid, and R hepatic vv.</li>
</ul>
<p>BILIARY TREE</p>
<ul>
<li>Canals of Hering→ bile ductules→ terminal bile ducts→ segmental bile ducts→ R + L lobar ducts→ common hepatic bile duct (see image)</li>
</ul>
<p>LYMPHATICS</p>
<ul>
<li>lymph forms in space of Disse</li>
<li>
<p>Pleural effusion in the presence of massive ascites may be explained by lymph flow in trans-diaphragmatic lymphatics</p>
</li>
</ul>
<p></p>
<p>Describe the microscopic anatomy of the liver.</p>
<ul>
<li>Divided into ~hexagonal "classic lobules with CV at center and 6 peripheral hepatic triads OR</li>
<li>Divided into acina, the area surrounding a portal "triad" which contains:
<ul>
<li>proper hepatic artery</li>
<li>hepatic portal vein</li>
<li>common bile duct</li>
<li>lymphatic vessels</li>
<li>branch of thevagus nerve</li>
</ul>
</li>
<li>Blood supply diminishes as you go to outside of acinus</li>
</ul>
<p>Hepatocyte arrangement</p>
<ul>
<li>
<p>Basal surface faces sinusoidal space, microvilli</p>
<p>Apical face adjacent cells, enclose bile canaliculi</p>
</li>
<li>
<p>Lateral from bile canaliculi > Disse’s space</p>
</li>
</ul>
<p>Kartagener's syndrome involves what findings?</p>
<ol>
<li>situs inversus</li>
<li>Bronchiectasis
<ul>
<li> </li>
</ul>
</li>
<li>chronic sinusitis</li>
</ol>
<p>Describe bilirubin production and excretion.</p>
<ol>
<li>RBC breakdown: Hgb →Heme →<strong>Biliverdin</strong> →Bilirubin</li>
<li>Bilirubin transported in blood bound to albumin (unconjugated, lipidsoluble)</li>
<li>Bili taken up by hepatocytes</li>
<li>Bound to glutathione-s-transferase and then conjugated by <strong>bilirubinUDP-glucuronosyltransferase</strong></li>
<li>conj bili (water soluble) →bile ducts via MRP2 transporter (or some back to blood)
<ul>
<li>some: bili—intest. bacteria→ urobilinogen→ reabsorb'd = <strong>eneterohepatic circulation</strong> (99%)
<ul>
<li>will be secreted by kidney</li>
<li>or urobilinogen —reduction→ stercobilin (gives poop brown color)</li>
</ul>
</li>
</ul>
</li>
</ol>
<p>DDx for jaundice</p>
<ul>
<li>framework for thinking</li>
<li>DDx for unconjugated hyperbilirubinemia</li>
<li>DDx for conjugated hyperbilirubinemia</li>
</ul>
<ul>
<li>Pre-Hepatic
<ul>
<li>e.g. hemolysis</li>
</ul>
</li>
<li>Hepatic
<ul>
<li>viral/toxic hepatic impairment</li>
</ul>
</li>
<li>Post-Hepatic
<ul>
<li>bile duct obstruction</li>
</ul>
</li>
</ul>
<p>UNCONJUGATED</p>
<ul>
<li>↑ production (hemolysis)</li>
<li>Liver cell damage (no uptake)</li>
<li>↓<span> conjugation (</span>↓<span> UDP-glucuronosyltransferase)</span></li>
<li><span>Congenital</span>
<ul>
<li>Gilbert’s (5% of people)</li>
<li><span>» Crigler-Najjar</span></li>
</ul>
</li>
<li><span>Acquired: drug effect</span></li>
</ul>
<p>CONJUGATED</p>
<ul>
<li>Liver cell damage (<span>limited MRP2 activity)</span></li>
<li>Obstruction (stone or tumor)</li>
<li>Decreased excretion (limited MRP2 activity)</li>
<li>Congenital:
<ul>
<li>» Dubin-Johnson</li>
<li>» Rotor</li>
</ul>
</li>
</ul>
<p>Describe liver metab of Rx</p>
<ul>
<li><span>Phase I: cytochrome P-450 monooxygenase system (many) – Oxidation, Reduction, Hydrolysis, Hydration, Decarboxylation,</span>
<ul>
<li>Isomerization</li>
<li>Variability: drug-drug, host factors, environmental factors</li>
</ul>
</li>
<li><span>Phase II: other enzymes</span>
<ul>
<li>Glucuronidation, Sulfation, Methylation, Acetylation, Glutathoine conjugation</li>
</ul>
</li>
</ul>
<p>Describe liver metab of carbs</p>
<p>Carbs</p>
<ul>
<li>Recall that G-6-P has 3 fates→
<ul>
<li>glycogen (2 days supply)</li>
<li>breakdown→ TCA</li>
<li>Pentose-Phosphate shunt</li>
</ul>
</li>
</ul>
<p>Liver Makes Glucose via Gluconeogenesis</p>
<ul>
<li>
<p>glycogenolysis → glucose(liver has enough glycogen for two days' energy needs)</p>
</li>
<li>
<p>pyruvate, AAs, and FAs→ glucose</p>
</li>
<li>
<p>Lactatefrom muscle, intestine, liver, or RBCs→<strong>Cori cycle </strong>(see image here)</p>
</li>
<li>
<p><strong>Alanine Cycle</strong>:</p>
<ul>
<li>
<p><span>Ala made by catab of muscle (muscle wasting during prolonged fasting)→ liver→ glucose→ back to muscle</span></p>
</li>
</ul>
</li>
</ul>
<p>Describe liver metab of fats</p>
<ul>
<li>the liver is the main site of fatty acid synthesis from excess glucose (mammary gland and to a lesser extense adipose do this, too [Wiki])</li>
<li>
<p>the liver synthesizes and extracts a large number of apolipoproteins* to transport these lipids</p>
<ul>
<li>
<p>*contain TGs, phospholipids, cholesterol and its esters, and lecithins</p>
</li>
</ul>
</li>
<li>
<p>Recall that Cholesterol from food or made by liver is not a fuel source but a structural component of membranes and a steroid hormone precursor</p>
</li>
</ul>
<p>Describe liver synthesis of albumin and clotting factors</p>
<ul>
<li>What proteins are synthesized in the liver</li>
</ul>
<ul>
<li>Coagulation</li>
<li>Transport, such as albumin and iron binding</li>
<li>Protease inhibitors</li>
<li>Acute-phase reactants
<ul>
<li>group of proteins expressed during acute and chronic systemic inflammation</li>
<li>These proteins are assumed to play an important role in the host defense against tissue damage and infection.</li>
<li>Example: <span>Fibrinogen aids in clot formation</span></li>
<li><span>Anti-proteases serve to protect normal cells from proteases that are released from </span><span>necrotic tissues.</span></li>
</ul>
</li>
</ul>
<p>Interpret elevated AST (SGOT) and ALT (SGPT)</p>
<ul>
<li>Ref Range</li>
<li>Basis</li>
<li>Assoc Dzs</li>
<li>Extrahep sources</li>
</ul>
<p>Both Aminotransferaseselevated in "hepatic pattern"</p>
<p><strong>Ref Ranges</strong></p>
<ul>
<li>ALT/SGPT <strong>10-55</strong> U/L</li>
<li>AST/SGOT <strong>10-40</strong> U/L</li>
<li>part of gluconeogenic pathway</li>
</ul>
<p><strong>Basis</strong></p>
<ul>
<li>
<p>Leakage from damaged tissue into circulation (hepatocellular necrosis)</p>
</li>
</ul>
<p><strong>Assoc Dzs</strong></p>
<ul>
<li>
<p>Viral, autoimmune, toxic, Wilsons, ischemia, acohol, NASH etc.</p>
</li>
</ul>
<p><strong>Extrahepatic Sources</strong></p>
<ul>
<li>ALT, relatively specific for hepatocyte necrosis AST: muscle (skeletal and cardiac), kidney, brain, pancreas, RBC</li>
</ul>
<p>Interpret alk phos (AP, AF) findings.</p>
<p>High alk phos + GGT is a<strong> biliary pattern</strong></p>
<p><strong>Ref Ranges</strong></p>
<ul>
<li>(ALP, AF 45-115 U/L: Catalyze hydrolysis of phosphate esters</li>
<li><span>3x higher in children due to bone growth</span></li>
</ul>
<p><strong>Basis</strong></p>
<ul>
<li>
<p>Overproduction and leakage into serum (rise is delayed due to need for induction of enzyme)</p>
</li>
</ul>
<p><strong>Assoc Dzs</strong></p>
<ul>
<li>
<p>Marked elevations: extra- and intrahepatic cholestasis, infiltrating disease (e.g., tumor, MAC), occasionally alcoholic hepatitis</p>
</li>
</ul>
<p><strong>Extrahepatic Sources</strong></p>
<ul>
<li>
<p>Bone growth or disease (e.g., tumor, fracture, Paget's disease), placenta, intestine, tumors</p>
</li>
</ul>
<p>Interpret bilirubin labs</p>
<p><strong>Ref Ranges</strong></p>
<ul>
<li>
<p>Total Bilirubin (0.0-1.0 mg/dL, 0,)</p>
</li>
</ul>
<p><strong>Basis of elevation</strong></p>
<ul>
<li>
<p>Decreased hepatic clearance</p>
</li>
</ul>
<p><strong>Assoc Dzs</strong></p>
<ul>
<li>
<p><u>Unconjugated</u>: liver cell damage (no uptake, e.g. viral/drug/EtOH hepatitis), increase production (hemolysis), decreased conjugation (congenital: Gilbert's and Crigler-Najjar or acquired: drug effect), vascular (decreased flow to liver), or starvation</p>
</li>
<li>
<p><u>Conjugated</u>: liver cell damage, obstruction (stone or tumor), or congenital (Dubin-Johnson and Rotor)</p>
</li>
</ul>
<p><strong>Extrahepatic Sources</strong></p>
<ul>
<li>
<p>Increased breakdown of hemoglobin (hemolysis, ineffective erythropoiesis, resorption of hematoma) or myoglobin (resulting from muscle injury)</p>
</li>
</ul>
<p>Interpret elevated GGT</p>
<p>High alk phos + GGT is a<strong> biliary pattern</strong></p>
<p><strong>Ref Ranges</strong></p>
<ul>
<li>
<p>Gammaglutamyl transpeptidase (gamma-GT 0-30 U/L):</p>
</li>
</ul>
<p><strong>Enzyme Fxn</strong></p>
<ul>
<li>
<p>catalyzes the transfer of gamma glutamyl groups of peptides such as glutathione to other amino acids</p>
</li>
</ul>
<p><strong>Basis for Elevation</strong></p>
<ul>
<li>
<p>Overproduction and leakage into serum (inducible by alcohol and dilatin)</p>
</li>
</ul>
<p><strong>Assoc Dzs</strong></p>
<ul>
<li>
<p>Same as for high Alk P (Marked elevations: extra- and intrahepatic cholestasis, infiltrating disease (e.g., tumor, MAC), occasionally alcoholic hepatitis)</p>
</li>
</ul>
<p><strong>Extrahepatic Sources</strong></p>
<ul>
<li>
<p>Kidney, spleen, pancreas, heart, lung, brain</p>
</li>
</ul>
<p>Interpret <strong>low</strong> albumin labs.</p>
<p><strong>Ref Ranges</strong></p>
<ul>
<li>
<p>(4.0-6.0 g/dL = 40-60 g/L)</p>
</li>
</ul>
<p><strong>Basis for Low Alb</strong></p>
<ul>
<li>Decreased synthesis</li>
<li>?Increased catabolism</li>
<li><u>poor nutrition</u><u></u> (in that case, you'd expect INR to be normal or correctable with vit k supp; if not, likely liver dz)</li>
</ul>
<p><strong>Assoc Dzs</strong></p>
<ul>
<li>
<p>chronic liver failure</p>
</li>
</ul>
<p><strong>Extrahepatic Cause</strong></p>
<ul>
<li>
<p>Malnutrition Nephrotic syndrome, Protein-losing enteropathy, vascular leak, , malignancy, and inflammatory states</p>
</li>
</ul>