Liver + Kidneys + Urinary Tract Flashcards
What do abnormalities in the different LFTs signify
ALT (3-40) / AST (3-30), liver enzymes, raised in pathologies that cause liver cell inflammation or damage; hepatitis, liver cirrhosis, drug / toxin induced liver injury, malignancy. Alcoholic liver disease AST:ALT >2:1 (L = less)
ALP (30-100), biliary epithelial cells and in bones, cholestasis or bone disease
GGT (8-60), hepatocytes and biliary epithelial cells, non specific but highly sensitive marker of liver damage and cholestasis. Isolated GGT in alcoholics
Bilirubin (3-17), haemoglobin breakdown, jaundice >50, unconjugated = prehepatic, conjugated = hepatic / post. Post has dark urine and pale stools (not metabolised in gut)
Albumin (35-50), nonspecific marker of function, also malnutrition / nephrotic syndrome
Hepatocellular injury = >ALT 10 + <ALP3, cholestasis >ALT10 + <ALP3, bone isolated ALP without GGT, albumin and coagulation studies for synthetic function and severity
Describe the pathogenesis of liver failure
Range of causes: hepatitis viruses, EBV, herpes simplex, paracetamol, alcohol, hepatocellular carcinoma, alpha-1 antitrypsin deficiency
Fulminant hepatic failure: syndrome resulting in rapid massive necrosis of liver cells leading to severe impairment of liver function and hepatic encephalopathy
Hepatic encephalopathy: as liver fails ammonia builds up in circulation and passes to brain, neurotoxic (halts krebs cycle), resulting in irreparable cell damage and neuronal death
What is the presentation, investigations and treatment for liver failure
Jaundice, small liver, bruising, clubbing, fever, vomiting. Ascites is rare
Bloods (LFTs, clotting screen, albumin, FBC, U+Es, ammonia), ultrasound +/- elastography, EEG useful for encephalopathy, microbiology to rule out infection
Non invasive liver screen: US, hep B+C serology, autoantibodies + immunoglobulins, ceruloplasmin (wilson’s), alpha-1 AT levels, ferritin + transferrin (haemochromatosis)
Treat cause (paracetamol poisoning - N-acetly-cysteine), IV glucose if necessary, mannitol for raised ICP, IV vitamin K + blood / platelets, lansoprazole to reduce GI bleeds
Liver transplant
What is the difference between cholecystitis, acute / biliary / sclerosing cholangitis
Acute cholecystitis (obstruction of gallbladder emptying): increased secretions - progressive distension (may compromise vascular supply), inflammatory response due to retained bile, increases risk of infection. Complication of cholelithiasis
Acute / ascending cholangitis (bile duct inflammation): infection of biliary tree most commonly secondary to a gallstone obstructing the common bile duct, infection often from bacteria rising from duodenum, causes entire biliary stasis and dilated ducts. Risk of sepsis
Biliary: progressive intrahepatic bile duct damage and loss, autoimmune with PBC-specific antibodies
Sclerosing: associated with IBD, inflammation and fibrosis of intra / extra hepatic bile ducts, diffuse stricture formation
Describe cholelithiasis
Cholesterol gallstones (80%): cholesterol crystallisation in bile due to high concentrations, deficiency in bile salts / phospholipids (cirrhosis, Crohn’s, ileal disease), excess cholesterol (diabetes, diet, obesity), also stasis (pregnancy, age)
Bile pigment stones (mostly calcium): mostly due to haemolysis (anaemia, sickle cell, thalassaemia), stasis
Majority of gallstones are asymptomatic, once symptomatic recurrence common. Biliary colic, related to eating fatty food
Biliary colic / gallstones - abdominal ultrasound (thin walls, non dilated ducts), normal lab results
All symptomatic gallbladder stones - laparoscopic cholecystectomy, paracetamol +/- hyoscine (antispasmodic). Asymptomatic: avoid fatty foods, statins. No evidence for ursodeoxycholic
5 Fs: fair, female, fat, fourty, fertile
pathogenesis and presentation of cholecystitis
Acute cholecystitis (obstruction of gallbladder emptying): increased secretions - progressive distension (may compromise vascular supply), inflammatory response due to retained bile, increases risk of infection. Complication of cholelithiasis
Initially continuous epigastric pain that develops into localised RUQ pain, associated with tenderness / guarding / rigidity, signs of inflammation, palpable mass
Investigations and treatment of cholecystitis
Imaging - abdo US or CT / MRCP if sepsis is suspected, bloods (FBC - raised WCC, raised CRP, elevated bilirubin, ALP, ALT, GGT), culture to rule out sepsis
US: pericholecystic fluid, distended, thickened wall (>3mm), sonographic murphy’s sign
(Organ dysfunction - ICU admission)
IV fluids, paracetamol / diclofenac, IV abx if sepsis suspected, if required cholecystectomy / cholecystostomy (drain fluid) / lithotripsy / ursodeoxycholic acid
Describe the pathogenesis and presentation of acute cholangitis
Acute / ascending cholangitis (bile duct inflammation): infection of biliary tree most commonly secondary to a gallstone obstructing the common bile duct, infection often from bacteria rising from duodenum, causes entire biliary stasis and dilated ducts. Risk of sepsis
Rare causes: strictures following surgery, pancreatic cancer, parasites
Cholangitis: biliary colic, fever, rigours, jaundice, right upper quadrant pain
Jaundice is cholestatic - dark urine, pale stools, itchy skin
Investigations and treatment for acute cholangitis
Ascending cholangitis: bloods, transabdominal ultrasound / MRCP (dilatation of CBD)
Raised WCC, blood culture / lactate / urine (sepsis), LFTs (bilirubin, AST, ALT, ALP), CRP
Cholangitis: IV antibiotics for all suspected (cefotaxime / metronidazole, piperacillin / tazobactam), removal of stones with ERCP or lithotripsy if large (non invasive preferred), analgesia (morphine, oxycodone, paracetamol)
Describe the pathogenesis and presentation of biliary and sclerosing cholangitis
Biliary: progressive intrahepatic bile duct damage and loss, autoimmune with PBC-specific antibodies
Sclerosing: associated with IBD, inflammation and fibrosis of intra / extra hepatic bile ducts, diffuse stricture formation
Fatigue, xanthelasma, dry eyes + mouth, abdo discomfort, pruritus
Pathogenesis of pancreatitis
Acute - syndrome of inflammation initiated by any acute injury, in most severe form there is extensive pancreatic / peripancreatic necrosis and haemorrhage
Gallstones (60%), alcohol (30%), trauma, idiopathic, autoimmune, drugs
Destructive effect of premature activation of pancreatic enzymes - enzyme autodigestion
Gallstones - obstruction of pancreatic duct so enzyme fluid builds up. Alcohol - interferes with calcium homeostasis - increased enzyme secretion due to contraction of ampulla of vater
Chronic: reduction in bicarbonate secretion, alkaline pH, activation of trypsinogen - necrosis and fibrosis. Protein plugs form and become calcified (obstruction and further damage)
Long term alcohol (75%), idiopathic, chronic kidney disease, genetic (CF), recurrent acute, autoimmune
What is the presentation of pancreatitis
Upper abdominal pain (severe that radiates to back), anorexia, N+V, fever, jaundice, shock + hypotension
Exocrine dysfunction in chronic: malabsorption, steatorrhoea, jaundice. Endocrine - diabetes
Investigations and scoring for pancreatitis
History + elevated lipase / amylase diagnostic
Bloods: clearly raised amylase + lipase (more specific), CRP (severity), FBC, LFTs, calcium (hypercalcaemia rare cause); urine amylase can be diagnostic if levels remain elevated
Abdo US (gallstones, pancreatic inflammation), CXR (pleural effusion, basal atelectasis, exclude others)
Pancreatic Glasgow scoring system (PANCREAS): PaO2 <8 kPa, Age >55, Neutrophils (WCC) >15*109, Calcium <2, Renal (urea) >16, Enzymes LDH >600 AST >200, Albumin <32, Sugar >10
3+ severe
What is the management for acute and chronic pancreatitis
Acute: IV fluids, analgesia, IV abx if infection; if required: oxygen, ondansetron
severity assessment + appropriate dietary supplements (nasogastric tube, nil by mouth), urinary catheter
Abx: carbapenem (imipenem / cilastatin) FL, fluoroquinolone (ciprofloxacin), metronidazole
Chronic: cessation of alcohol / smoking, dietary intervention, analgesia (paracetamol / ibuprofen / opiates), surgical duct drainage if required
Dietary: address malabsorption of fat, fat soluble vitamins (A, D, E, K), protein. Enzyme replacement
Gallstones - shockwave lithotripsy, steatorrhoea - enzyme supplements + PPI, diabetes - insulin
What is the pathogenesis of alcoholic liver disease
When alcohol is metabolised Acetyl-CoA is the final product (fatty acid), NADH is produced, increasing NADH/NAD+ ratio (decreased FA oxidation), converted to triglycerides in hepatocytes
Steatosis (worst in zone 3 with least O2) - hepatocellular ballooning blocking ducts
Changes in oxidation / reduction also impair carbohydrate and protein metabolism → necrosis of hepatic acinus
Acetaldehyde is toxic in high quantities, alcohol increases effects of toxic metabolites of drugs
Infiltration of leucocytes, necrosis (also TNF-alpha from kupffer), leads to cirrhosis
Investigations and treatment for alcoholic liver disease
Alcoholic liver disease: raised AST and ALT, AST:ALT >2:1, raised ALP + GGT. Function impaired disease: elevated bilirubin, decreased albumin, hyponatraemia, elevated prothrombin time. US
Cessation of alcohol + weight loss, fatty liver will heal, hepatitis requires nutrition supplementation and prednisolone (if bilirubin falls continue, if no change after 7 days stop)
Influenza and pneumococcal vaccines, hep A and hep B
Cirrhosis may require transplant
Symptomatic: diazepam for withdrawal (delirium tremens), thiamine to prevent encephalopathy, fluid and sodium restriction for ascites
What is the pathogenesis of cirrhosis, portal hypertension and varices
Cirrhosis (irreversible damage): inflammation, matrix deposition, necrosis, angiogenesis → fibrosis
Injury: necrosis, apoptosis, reactive oxygen species. Stellate: neutrophils, macrophages - inflammation. Kupffer cells: phagocytose and inflammatory mediators. Myofibroblasts deposit collagen
Alcohol abuse, NA fatty liver, hepatitis viruses. Also primary biliary cirrhosis, autoimmune
Portal hypertension (hepatic venous pressure > 5mmHg): 80% cirrhosis - contraction of myofibroblasts, portal vein thrombosis, schistosomiasis (most common global), sarcoidosis, right heart failure, IVC obstruction
Reduced venous flow to liver, splanchnic vasodilation, salt and water retention, formation of collaterals / varices, fluid leaks - ascites. drop in BP, compensating increase in cardiac output
Varices: compensating venous dilation (oesophageal, gastric, rectum, left renal, umbilical), potential to rupture (especially oesophageal)
Describe the presentation of cirrhosis
Ascites (distention), hepatic jaundice + pruritus, haematemesis / melaena (blood in stool); general: fatigue, weakness, weight loss, peripheral oedema
Physical signs:
Hands: leukonychia (white nails), palmar erythema, spider naevi, clubbing, cholesterol deposits, dupuytren’s in alcoholics
Facial: telangiectasia (red lesions) / spider naevi, jaundiced sclera, xanthelasma (lipid plaques on eyelids)
Abdo: caput medusae (swollen veins around umbilicus), hepatosplenomegaly, shifting dullness, hepatic bruit
Investigations and score for cirrhosis
Liver biopsy gold standard but often not required, LFTs, US + US elastography, CT / MRI if indicated, most sensitive and specific indicator is thrombocytopenia (platelets < 150,000 / micL)
Elastography assesses the stiffness of organs
LFTs: raised AST, ALT, ALP + GGT. Decreased albumin, bilirubin can be compensated, prolonged prothrombin time
Other blood tests: FBC, albumin, clotting screen, hepatitis serology
Child-Pugh classification: ascites, encephalopathy, high bilirubin, low albumin, long prothrombin
1y survival rates of cirrhosis patients
Fibrosis-4 score: age, AST, platelets, ALT
Management for cirrhosis
Treatment of underlying liver disease, monitor complications, support and palliative care
Good nutrition vital, alcohol abstinence, screening for cancer, hep A+B vaccinations, no NSAIDs
Transjugular intrahepatic portosystemic shunts (TIPSS) - for ascites. Transplant only cure
Ruptured varices: resuscitation, blood transfusion if anaemic, vitamin K + platelet transfusion, terlipressin to vasoconstrict, prophylactic antibiotics
Variceal banding, balloon tamponade, transjugular intrahepatic portocaval shunt
Describe the pathogenesis of the different types f hepatitis
Viral: infection of liver cells activates immune system, inflammation and cell death, chronic - fibrosis
Hep A: faecal-oro (a=anus), always acute and usually symptomatic
Hep B: blood-borne (sex, mother to child, IV drugs), ~70% asymptomatic in acute, risk of becoming chronic largely dependent on age (90% infants, 2-6% adults), chronic risk of cirrhosis and HCC
Hep C: blood borne (often iatrogenic), 30% spontaneous resolution, 70% chronic (30% will develop cirrhosis)
Hep D: is only simultaneous with or following B, also blood borne, secondary acute and increased rate of progression, increased risk of fulminant and carcinoma
Hep E: acute only, faecal-oro (usually water or food), self limiting but can cause fulminant
(A+E, the two ends are transmitted faecal - orally, end to end)
What is the presentation of hepatitis
Acute: fever, malaise, N+V, jaundice later (light stools), RUQ pain. Hepatomegaly.
Chronic (B+C) often asymptomatic until they develop: cirrhosis, liver failure, cancer. Jaundice, RUQ pain, hepatomegaly, ascites, fever, fatigue
95% of E are asymptomatic
Investigations and treatment for hepatitis
Serology tests for diagnosis and progression - surface antigens, antibodies for surface antigens, viral DNA / RNA (C)
Other bloods: LFTs, FBCs, clotting screen, U+Es (hyponatraemia), alpha-fetoprotein (HCC)
All acute, supportive treatment, monitor liver function. E can only be affected once. 95% of immunocompetent will clear B
Supportive: analgesia, metoclopramide, ursodeoxycholic acid / steroids if required
B (+D): acute - at 6 months measure for full clearance; chronic - pegylated interferon alpha 2a (weekly sc injection for 48 weeks), nucleotide analogues (daily tablet, may be life long)
Risk of autoimmune and lifelong immunosuppression
C: observe for viral clearance, pegylated interferon alpha 2a + oral ribavirin. Alternatively triple therapy direct acting antivirals
We have vaccines for A and B. antivirals (entecavir, tenofovir) and transplant if required
Describe haemochromatosis
Haemochromatosis: disorder of iron metabolism, deposited in liver, joints, heart, pancreas, pituitary, adrenals, skin. Iron precipitates fibrosis, late feature - cirrhosis
Increased iron absorption, stored in hepatocytes, oxidative stress and tissue damage
Classic triad of bronze skin, hepatomegaly, diabetes. Early - tiredness, weakness and arthralgia; hypogonadism (impotence / amenorrhoea); later - chronic liver, osteoporosis, cardiomyopathy
Serum iron + ferritin, genetic testing, MRI (iron overload), liver biopsy
Lifelong venesection (removal of blood), treat diabetes, testosterone replacement, low iron diet
Describe Wilson’s
Wilson’s: failure of biliary copper excretion, too much copper in liver and CNS, cirrhosis and damage to basal ganglia. Also kidney tubular degeneration and bone erosion
Hepatitis / liver failure, kayser-fleischer rings, behaviour changes, tremor, dysarthria, dystonia
LFTs, 24h urinary copper, slit-lamp exam, serum ceruloplasmin
24h copper excretion high, liver biopsy, haemolysis and anaemia, MRI shows degeneration
Slit lamp: see kayser-fleischer rings (gold-brown copper rings in cornea)
Lifelong chelating agent (penicillamine), avoid high copper foods, liver transplant if severe
Describe Alpha1 antitrypsin
Alpha1 antitrypsin deficiency: lack of inhibition of neutrophil elastase (protease enzyme to kill pathogens) in liver and lung; results in emphysema, liver cirrhosis, hepatocellular carcinoma
In lungs lack of elastin (they lose stretch): bronchiectasis, emphysema and potential of COPD
In liver toxic proteins are made: cirrhosis, fibrosis, hepatocellular carcinoma in adults, cholestasis in children
Emphysema and obstructive lung disease are the most common, bronchiectasis; liver: hepatitis, jaundice, ascites. Obstructive: dyspnoea, wheeze, cough, chest tightness
Plasma AAT, spirometry, CXR / CT, LFTs. Spiro: reduced FEV1, FVC, FEV1/FVC, increased TLC
no smoking, supportive (bronchodilators, physio), IV A1AT protein concentrates, lung reduction surgery + transplant
Describe the pathogenesis of liver cancer
Primary tumours - hepatocellular carcinoma, cholangiocarcinoma. Most common is actually secondary, often from GI / breast / lung. Hemangioma and hepatic adenoma are both benign tumours, HA only surgery if symptomatic and > 5cm.
HCC: cells resemble hepatocytes, can be multiple nodules in liver, can metastasise via hepatic or portal veins to lymph nodes / bone / lungs
Cholangiocarcinoma - cancer of biliary tree (biliary endothelium), usually slow growing
Presentation and investigations for liver cancer
Weight loss, fever, fatigue, jaundice, ache in right hypochondrium, ascites, varices (+ haemorrhage)
Rapid development of features in cirrhotic patients
Examination - large, irregular, tender liver
Raised alpha-fetoprotein, ultrasound (filling defects), enhanced CT (lesion > 1cm), liver biopsy (used less due to risk of spread)
FBC, metabolic panel, LFTs, clotting screen
Cholangocarcinoma: often asymptomatic
Raised but unspecific: CA 19-9, CA 125, carcinoembryonic antigen (CEA)
How is liver cancer managed
Isolated lesion - surgical resection / thermal ablation / radiofrequency ablation / transarterial chemoembolization, liver transplant only cure
Biologics: atezolizumab / bevacizumab
Describe the pathogenesis and presentation of pancreatic cancer
Adenocarcinoma, 99% occurs in exocrine component, ductal epithelium, progresses to fully invasive, most metastasise early so present late
5 year survival rate is 3%
PRESENTATION
Weight loss, diabetes, acute pancreatitis (obstructive jaundice, upper abdo discomfort). Many present minor - back / abdo pain, bowel habit change
Head of pancreas: painless obstructive jaundice (pale stools and dark urine)
Body and tail: epigastric pain, radiated to back and relieved by sitting forwards
What are the investigations and treatment for pancreatic cancer
Transabdominal ultrasound + CT - mass and dilated biliary tree, biopsy to stage
LFTs (obstructive jaundice): raised bilirubin, ALP, GGT. raised CA 19-9, staging laparoscopy, biopsy
Resectable disease: Whipple procedure (pancreaticoduodenectomy) for head of pancreas, extended resections if required
Resectable = no involvement of superior mesenteric artery, coeliac axis, common hepatic artery
Palliative: biliary stenting for jaundice, opiates, nutrition - pancreatic enzymes
Chemo: gemcitabine, FOLFIRINOX regimen
What are the causes of ascites
Local inflammation - peritonitis, intra abdominal surgery, infection (TB)
Low protein - hypoalbuminaemia, nephrotic syndrome, malnutrition
Low flow of fluid (fluid leaks out of vessels) - clot, cirrhosis (portal hypertension), cardiac failure, constrictive pericarditis
