Session 7 Flashcards

Question

Describe the functions of the liver in relation to blood proteins

Answer 1

[\*] Functions of the liver * Bile production * Carbohydrate, protein and lipid metabolism * Protein synthesis * Vitamin D synthesis * Detoxification * Vitamin and mineral storage * Phagocytosis [\*] Albumin: Albumin is the most abundant plasma protein. Albumin is essential in maintaining the oncotic pressure needed for proper distribution of body fluids [\*] Coagulation Factors: The liver produces several coagulation factors * I – Fibrinogen * II – Prothrombin * V * VII * IX * X * XI * As well as Protein C, Protein S and Antithrombin [\*] Thrombopoietin: a glycoprotein hormone that regulates the production of platelets by bone marrow [\*] Amino acid synthesis: transamination

Answer 2

[\*] Hepatocellular damage: if hepatocytes are damaged, their ruptured membranes will allow Aminotransferases into the blood stream. Their presence there is indicative of liver damage (ALT/AST) * Aminotransferases (ALT/AST) * γ-Glutamyl transpeptidase (γ-GT) [\*] Cholestasis (bile ducts) * Bilirubin – unable to secrete bilirubin, plasma concentration rises * Alkaline phosphatase – enzyme in cells lining the liver’s biliary ducts. Plasma levels rise with an obstruction [\*] Synthetic function * Albumin (levels reduced in chronic liver disease) * Prothrombin time (clotting) (measures the clotting tendency of blood)

Answer 3

[\*] Damaged hepatocytes have a reduced capacity to excrete bilirubin. This leads to bilirubin accumulating in the blood, giving jaundice. [\*] The increased levels of bilirubin (Hyperbilirubinaemia) results in a yellowish pigmentation of the skin, conjunctival membranes over the scleae and other mucus membranes [\*] Yellow pigmentation of the skin and eyes * Clinically detectable at \>40 μmol/L * Normal range \<22 μmol/L

Answer 4

Inherited: * Red cell membrane defects * Haemoglobin abnormalities * Metabolic defects Congenital hyperbilirubinaemias * Gilbert’s syndrome (~10% of the population; too little glucuronyltransferase – unable to conjugate as much bilirubin for excretion, no clinical significance) * Crigler-Najjar syndrome (rare) * Dublin-Johnson syndrome (rare) Acquired * Immune * Mechanical e.g. RBCs running across metal heart valves * Acquired membrane defects * Infections * Drugs * Burns

Answer 5

[\*] Hepatic / hepatocellular jaundice causes Congenital: * Gilbert’s syndrome * Crigler-Najjar syndrome Hepatic inflammation * Viruses (Hepatitis A, B, C and E; Epstein Barr virus) * Autoimmune hepatitis * Alcohol * Haemochromotosis * Wilson’s disease * Drugs e.g. paracetamol * Cirrhosis Alcohol Chronic hepatitis Metabolic disorders * Hepatic tumours Hepatocellular carcinoma Metastases

Answer 6

Intrahepatic (hepatocyte swelling) * Hepatitis * Drugs * Cirrhosis * Primary biliary cirrhosis Extrahepatic (obstruction distal to bile canaliculi) * Gallstones * Biliary stricture * Carcinoma of the head of pancreas, ampulla, cholangiocarcinoma (bile duct), porta hepatis lymph nodes, liver metastases * Pancreatitis * Sclerosing cholangitis

Answer 7

Excessive haemolysis (increased breakdown of red blood cells) =\> excessive bilirubin production Liver unable to cope with excess bilirubin Lab findings * Unconjugated hyperbilirubinaemia * Reticulocytosis (excess of immature RBCS) * Anaemia * Increased LDH (lactate dehydrogenase; product contained inside RBC =\> released in breakdown) * Decreased Haptoglobin (protein that binds free haemoglobin released from erythrocytes with high affinity and thereby inhibits its oxidative activity. Then the haptoglobin-haemoglobin complex will be removed by the spleen).

Answer 8

* Deranged hepatocyte function =\> reduced capacity of liver cells to secrete conjugated bilirubin into the blood * Element of cholestasis **Lab findings** * Mixed unconjugated and conjugated hyperbilirubinaemia * Increased liver enzymes (AST/ALT) reflecting liver damage * Normal or raised ALP – alkaline phosphatase - (cholestasis – swollen cells – liver can’t get rid of its excretions as well) * Abnormal clotting

Answer 9

Obstruction of biliary system (obstruction to drainage of bile) * Intrahepatic * Extrahepatic Passage of conjugated bilirubin blocked, causing a backup of bile acids into the liver. Lab findings * Conjugated hyperbilirubinaemia (water soluble) * Bilirubin in urine (dark) * No urobiliongen in urine (no bilirubin enters bowel) * Increased canalicular enzymes (ALP) * Normal or raised liver enzymes (ALT and AST) due to mild hepatocyte damage caused by the pressure

Answer 10

[\*] Pathology Fatty change * Alcohol metabolism generates NADH from NAD+ * Increased NADH induces fatty acid synthesis * Decreased NAD+ results in decreased fatty acid oxidation * Accumulation of fatty acids in the liver (glycerol =\> TAGs) Alcoholic hepatitis: inflammation of hepatocytes Cirrhosis: liver cell necrosis followed by nodular regeneration and fibrosis, resulting in increased resistance to blood flow and deranged liver function [\*] Complications Hepatocellular carcinoma Liver failure Wernicke-Korsakoff syndrome (neuropsychiatric problem) Encephalopathy (neuropsychiatric problem) Dementia (gross atrophy of brain parenchyma leads to dementia) Epilepsy [\*] Causes of Cirrhosis Alcohol Biliary cirrhosis Haemochromotosis Wilson’s disease Alpha1-antitrypsin deficiency Autoimmune hepatitis Hepatitis B or C

Answer 11

[\*] Clinical features: * Liver dysfunction * Jaundice * Anaemia * Bruising * Palmar erythema * Dupuytren’s contracture * Flapping tremor due to buildup of metabolites which liver can’t get rid of. * Portal hypertension * Spontaneous bacterial peritonitis [\*] Lab investigations * Normal or raised ALT/AST * Raised Alkaline Phosphate * Raised Bilirubin * Decreased Albumin * Deranged clotting * Decreased Na2+

Answer 12

* Stop drinking (even if cirrhosis is not alcohol related, stop drinking to avoid stressing the liver) * Treat complications * Transplantation (strict criteria

Answer 13

**Primary biliary cirrhosis** * Chronic destruction of bile ducts * Clinical: Jaundice, pruritis, xanthelasma, hepatosplenomegaly * Supportive treatment then liver transplant **Hereditary Haemochromotosis** * Autosomal recessive. * Believed to be IgG mediated disease (autoimmune disease) * Abnormal iron transport =\> iron deposition within the tissues leading to sclerosis and fibrosis * Clinical: Heart (Cardiomyopathy); Pancreas (Diabetes – due to lack of insulin production – sufferers are known as ‘Bronze diabetics’); Pituitary (hypogonadism); Liver (Hepatitis/cirrhosis); Skin (Hyperpigmentation) * Treatment: Venesection **Wilson’s Disease** * Autosomal recessive * Disordered copper transport =\> deposition in issues e.g. in basal ganglia * Clinical: Liver (Hepatitis =\> cirrhosis); Basal ganglia (Tremor, dysarthria, dementia – symptoms of Parkinson’s); Kidney (tubular degeneration); Eyes (Kayser-Fleischer rings) * Treatment: Penecillamine (chelation) **Alpha1-antitrypsin deficiency** * Autosomal recessive * Deficient alpha1-antitrypsin * Clinical: Liver cirrhosis, emphysema (happens at the bases in young people. In smoking emphysema occurs in the apices of lungs) * Treatment: Transplant (of both lungs and liver)

Answer 14

[\*] Portal venous pressure in excess of 20 mmHg, resulting from intrahepatic or extrahepatic portal venous compression or occlusion. The portal system has no valves therefore increased resistance =\> retrograde blood flow [\*] Causes: Obstruction of portal vein * Congenital * Thrombosis * Extrinsic compression Obstruction of flow within liver * Cirrhosis * Hepatoportal sclerosis * Schistosomiasis (a type of trematode (fluke) infection) * Sarcoidosis

Answer 15

[\*] Porto-systemic anastomoses: there are several anastomoses between the hepatic portal and systemic veins. As such when the pressure is increased in the portal venous system, blood is backed up through these anastomoses. The increased blood pressure causes the vessels to dilate, protrude into the lumen, rupture/ulcerate and haemorrhage * Oesophageal branch of left gastric vein (portal) and oesophageal tributaries of azygous system (systemic) [oesophageal varices] * Superior rectal branch of IMV (portal) and inferior rectal veins (systemic) [rectal varices] * Portal tributaries of mesentery (portal) and retroperitoneal veins – small epigastric of abdominal wall (systemic) * Portal veins in liver and veins of anterior abdominal wall (systemic) * Portal branches (colic/splenic/portal) in liver and retroperitoneal veins of posterior abdominal wall or diaphragm (bare area of liver)

Answer 16

* Splenomegaly: due to subsequent increased blood pressure in the spleen * Ascites: the high pressure in the portal venous system means blood is backed up into the abdomen. The increase in hydrostatic pressure in the abdomen means less fluid is reabsorbed into blood vessels at the end of capillary beds. If the liver is damaged, reduced oncotic pressure inside the vessels, due to lack of plasma proteins may also contribute. * Spider naevi (oestrogen dependent) * Caput medusa (patent umbilical vein is recanalized due to the pressure; paraumbilical veins anastomose with small epigastric of abdominal wall) * Oesophageal/rectal varices (portal pressure \> systemic venous pressure) Venous dilatations Protrude into lumen Rupture/ulceration =\> haemorrhage NB: venous bleeding is difficult to treat

Answer 17

[\*] Post-hepatic jaundice: Courvoisier’s Law * Gallstones formed over a long period of time result in a shrunken fibrotic gallbladder * Gallbladder more often enlarged by pathologies that cause biliary obstruction over a shorter period of time (malignancy) * A tender gallbladder may be seen with acute cholecystitis and may be tender and distended with a mucocele or empyema related to gallstones [\*] Bile acids return to the liver in between meals and are secreted by canaliculi cell walls a long time before they are next needed. The gallbladder and biliary tree is responsible for the storage and passage of bile from liver to duodenum. To reduce the volume that needs to be stored, bile acids are concentrated by the transport of salt and water across the gallbladder epithelium. However the concentration process increases the risk of precipitation leading to Gall stones. [\*] Pathological processes * Obstruction * Infection * Inflammation * Neoplasia

Answer 18

[\*] Cholelithiasis (gallstones) 10-20% of the population Aetiology/risk factors * Female * Increasing age * Obesity (rapid weight loss) * Multiparity * Diet * Developed countries * Drugs e.g. oral contraceptive pill * Ileal disease / resection * Haemolytic disease e.g. sickle cell disease

Answer 19

[\*] Gallstones are often asymptomatic but they can move into the neck of the gallbladder or biliary tree, causing very painful biliary colic or even obstruction. This is often followed by inflammation (cholecystitis) and infection of the Gallbladder [\*] Biliary colic * Impaction of stone * Gallbladder contraction * Intermittent pain Post prandial (can be worse after eating as the secretion of Cholecystokinin (CCK) will cause the gallbladder to contract). Severe pain felt in the right upper quadrant, which is made worse by inspiration. It generally lasts a small number of hours, ending when the stone returns to the body of the gallbladder or into the intestines.

Answer 20

[\*] Cholecystitis due to irritation of the biliary tree during obstruction Stones – maybe acalculus (ischaemia/infection) Oedema =\> mucosa ulceration =\> fibropurulent exudate Pain, SIRS, pyrexia, sepsis Pain is similar to biliary colic but longer lasting, and there may well aslo be fever. Can be life threatening and may need surgery.

Answer 21

**Mucocoele** * Impaction of stone * No superadded infection * Mucus secretion * Painful distension **Empyema** * As above with superadded infection * Pus * *Obstructive jaundice** * *Ascending cholangitis** (LIFE-THREATENING – bacterial infection with biliary obstruction) * Life threatening * Charcot’s triad: RUQ pain, jaundice, fever * *Acute pancreatitis** * *Biliary-enteric fistula / gallstone ileus** * Fistula between gallbladder and duodenum * Large stone obstructs ileum **Gallbladder carcinoma** - 2% of all cancers - As with gallstones **Gallbladder perforation**

Answer 22

[\*] Functions * Endocrine: insulin, glucagon, somatostatin * Exocrine: alkaline juice (HCO3- in fluid), enzymes (proteolytic, amylase, lipolytic) [\*] Close anatomical relations * Duodenum * Common bile duct * Portal vein * Coeliac trunk [\*] Pancreatitis: inflammatory process caused by effects of enzymes released from pancreatic acini

Answer 23

[\*] Acute Pancreatitis * Oedema * Haemorrhage * Necrosis [\*] Chronic Pancreatitis * Fibrosis * Calcification

Answer 24

GET SMASHED Gallstones Ethanol ( =\> hyperstimulation of pancreatic secretions is most common cause) Trauma Steroids Mumps Autoimmune Scorpion Bite Hyperlipidaemia ERCP/Iatrogenic Drugs

Answer 25

* Duct obstruction – juice and bile reflux * Acinar damage – from reflux or drugs * Protease =\> tissue destruction * Lipase =\> fat necrosis * Elastase =\> blood vessel destruction **Biochemical Changes:** * Increased amylase * Decreased Ca2+ * Increased glycaemia * Increased ALP/bilirubin **Clinical manifestations** * Severe constant upper abdominal pain which commonly radiates to the back. * Vomiting * Dehydration * Shock/SIRS * Ecchymosis * Ileus Prognostic Classification: Glasgow/Ranson - Mild/Severe Treatment: supportive Mortality: Overall 10% * Severe = 30% * Haemorrhagic = 50%

Answer 26

* Chronic inflammatory condition * Parenchyma destruction, fibrosis, calcification loss of acini and duct stenosis (fibrosis is due to repeated inflammation) * Causes: chronic alcoholism, CF, inherited, biliary disease * Clinical: pain, malabsorption (=\> steatorrhoea, decreased albumin, weight loss) * Diabetes mellitus * Jaundice

Answer 27

[\*] 90% ductal adenocarcinoma [\*] Often patients present with advanced disease – too late [\*] Accounts for 5% of cancer deaths [\*] Aetiological factors * Smoking * Beta napthylamine * Benzidine * Familial pancreatitis [\*] Clinical features * Initially symptomless * Obstructive jaundice (=\> palpable gallbladder) – the cancer wraps around and blocks the bile duct * Pain * Vomiting * Carcinomatosis (cancer has eroded into nerves – extremely painful) * Malabsorption (cancer erodes into duodenum =\> gastric outflow obstruction) * Diabetes [\*] Prognosis * 5th cause of cancer death in UK * Resective surgery best current treatment * Only 5-15% suitable for curative treatment * Considerable morbidity and mortality * 15-35% 5-year survival rate * Overall 1-year survival ~12% (the carcinoma invades locally very quickly but normally asymptomatic)

Answer 28

[\*] The term Caput Medusae describes the appearance of distended and engorged umbilical veins which are seen radiating from the umbilicus across the abdomen to join systemic veins. It is a sign of severe portal hypertension with portal-systemic shunting through the umbilical veins. [\*] Caput Medusae is distinguished from inferior vena cava obstruction by determining the direction of flow in the veins below the umbilicus; it is towards the legs in the former, and towards the head in the latter (as abdominal collaterals develop to bypass the blocked inferior vena cava and permit venous return from the legs).

Session 7 Flashcards

(52 cards)