tbl 5 patholgy- liver failure Flashcards
Review of normal liver structure
- Hepatocytes – principal cells of the liver, in cords, separated by cords of intervening sinusoids
o Conventional hepatic lobule – central vein in centre and portal triad at periphery
o Acinar model – functional unit with portal triad at centre
- Portal triad – portal vein carries _________ blood from the GI tract and hepatic arteriole carries _________ blood, eventually draining into central vein
o Bile drains in opposite direction to the bile duct at the portal triad
- Zones of hepatic lobule and acinus o Periportal (zone 1) – nearest to portal triad, receives most oxygenated blood o Midzonal (zone 2) o Centrilobular (zone 3) – nearest to central vein
nutrient-rich; oxygenated
Overview of liver pathology
- Inflammatory – infections e.g.viral hepatitis, autoimmune e.g. autoimmune hepatitis or cholangitis
- Metabolic – acquired e.g. non-alcoholic fatty liver disease (NAFLD), congenital e.g. Wilson’s disease, ____________, α1-antitrypsin deficiency
- Toxic – alcohol (common aetiology for chronic liver disease), drugs
- Cholestasis – primary excretion of hepatocytes is bile, commonest common cause of accumulation of bile pigment in liver is obstruction along the biliary duct
- Vascular – circulatory disturbances
- Neoplasia – liver can be site for primary or secondary tumours
Patterns of response to liver injury
- Inflammation – can be chronic or acute
o Commonly, liver cell death leads to inflammatory reactions
o __________ are important in liver cell apoptosis and immune response to antigens e.g. viral or autoimmune diseases - Necrosis – stimulates regeneration
- Regeneration – hepatocytes are stable cells with marked regenerative capacity
o Hepatocyte proliferation of adjoining cells to replace dead cells
o If the ___________ is preserved, hepatocytes are replaced with preservation in architecture - Fibrosis – in connective tissue is damaged and/or injury persists e.g. chronic viral hepatitis
o Increased fibrosis leads to cirrhosis
o If there is continued cell loss, surviving cells proliferate too
hemochromatosis;
T cells; reticular network
Patterns of liver cell injury
- Reversible injury (commonly due to alcohol, infections)
o Ballooning degeneration
o _______ - Necrosis (ischemia , toxic)
o Zonal – different agents lead to predominant injury in a zone
o Massive or submassive – extent of damage
o Focal – fewer cells involved - Apoptosis (viral, autoimmune, drug and toxins)
o ____________ body – apoptotic hepatocytes
Liver failure
- Caused by 2 reasons –
o Not enough _______ to support normal liver function
o Hepatocytes not being able to function efficiently due to architectural design
- Massive hepatocyte necrosis is typically an acute process due to rapid loss of liver cells
- ______________ is the main cause of chronic liver failure – necrosis is present but is a slow process leading to fibrosis and regenerative nodules
Steatosis;
Acidophil;
hepatocytes;
Architectural disruption
Acute liver failure – fulminant hepatic failure
- Rare, severe and life-threatening condition – marked hepatic dysfunction leading to jaundice, encephalopathy and __________ in the absence of prior liver disease
- Massive hepatocyte necrosis
o In rare cases, there is no necrosis – e.g. in fatty liver of pregnancy, marked hepatic dysfunction is due to mitochondrial dysfunction (thought to be caused by a disordered metabolism of fatty acids by mitochondria in the mother)
- Aetiology o Hepatitis A, B, E o Drugs – e.g. paracetamol o Autoimmune hepatitis o Wilson disease o Reye’s syndrome
- Gross features – small shrunken liver with ___________ due to massive hepatocyte loss
o Decrease in weight from 1400 – 1600g to >800g - Microscopy – massive hepatocyte necrosis
- Certain agents have predilection for injury at certain
zones
o Centrilobular – __________
o Midzonal – ____________________
o Periportal – ______________
coagulopathy;
capsular wrinkling;
paracetamol;
yellow fever, dengue;
phosphorus
Cirrhosis – represents the end stage of most chronic liver diseases (especially decompensated)
- Irreversible _______________ condition – loss of architecture with replacement of normal liver by nodules of proliferating hepatocytes separated by bands of fibrosis
- Diffuse transformation of the liver into regenerative parenchymal nodules surrounded by ____________
o Results in chronic destruction of cells and chronic inflammation leading to fibrosis
o Nodular regeneration of hepatocytes leads to distorted vascular architecture
– compromises liver function - Gross appearance – normal liver has a smooth surface
o Cirrhotic liver – diffused nodular surface (nodules
indicate distorted hepatocyte regeneration)
o Commonly presents as a mixed pattern (macro- and micronodular) - It is rare for cirrhosis to be focal lesions – however, focal lesions can occur on the background of cirrhosis e.g. micronodular cirrhosis
- Micronodular cirrhosis: Nodules of <3mm – seen in _______________
- Macronodular cirrhosisa: Larger nodules
- Microscopy – in very advanced cirrhosis, underlying histopathological features may not be seen
o Inflammation and cell death – indicates active cirrhosis, suggesting disease progression
o ____________ is used to assess extent of fibrosis in diagnosis of cirrhosis
diffuse (widespread);
fibrous bands;
alcoholic cirrhosis;
Mallory trichrome stain
Classification of aetiology of cirrhosis
- Common – alcohol, chronic hepatitis B, C, _________ (unknown cause)
- Less common causes – autoimmune hepatitis, chronic biliary obstruction, primary biliary cirrhosis, NFLD
- Congenital – haemochromatosis, Wilson disease, α1-antitrypsin deficiency, galactosemia
Complications of cirrhosis
- Chronic liver failure
- Portal hypertension
- Hepatic encephalopathy
- Hepatorenal and hepatopulmonary syndrome
- Increased risk of hepatocellular carcinoma
Clinical features on chronic liver failure due to cirrhosis
- Portal hypertension: _________, shunts e.g. oesophageal varices, splenomegaly, hepatorenal syndrome
- Decreased synthetic function: Hypoalbuminemia – leads to oedema, ___________
- Decreased detoxification (of GI toxins): Mental changes, coma, Hypoestrogenism – leads to palmar erythema, gynaecomastia, _________, Jaundice
Portal hypertension – increased resistance to portal blood flow
cryptogenic;
Ascites;
coagulopathy;
angiomas;
Portal Hypertension
Can be classified as prehepatic, intrahepatic and post hepatic
- 4 major clinical consequences o Ascites o Portosystemic venous shunts o \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ o Hepatic encephalopathy
Prehaptic
- ________________
Intrahepatic (most important)
- cirrhosis: forms majority of cases
- primarily biliary cirrhosis
- schistosomiasis
- massive fatty changes, sarcoidosis
- nodular regenerative hyperplasia
- malignancy: infiltrative, and involving portal veins
- amyloidosis
Posthepatic
- severe _____ failure
- constrictive pericarditis
- __________ outflow obstruction
Congestive splenomegaly;
Portal vein thrombosis;
right sided heart;
hepatic vein
Ascites – excess fluid in peritoneal cavity, 85% of cases due to cirrhosis
- Pathogenesis – portal hypertension leads to increased _______________ (sinusoidal hypertension)
o Hypoalbuminemia – decreased plasma oncotic pressure
o These 2 factors lead to extravasation of fluid into the peritoneal cavity
- Increased hepatic lymph
- ____________- vasodilatation and hyperdynamic circulation – activation of renin-angiotensin-aldosterone system, resulting in further Na+ and H2O retention
o Further increase in capillary hydrostatic pressure leads to extravasation of more fluid into the peritoneal cavity - Sinusoidal hypertension – increased __________ of portal flow at the level of sinusoids
o Vascular smooth muscle and myofibroblast contraction
o Disruption of vascular flow by abnormal regenerative nodules and fibrosis - Sinusoidal remodelling with arterial-portal anastomoses in fibrous septa – change of low pressure portal systems to high pressure (arterial) systems
o Increased portal venous flow (hyperdynamic circulation) – leads to splanchnic vasodilatation
capillary hydrostatic pressures;
Splanchnic;
resistance;
- Portosystemic venous shunts
- Rise in portal pressure leads to ______________ (portal to systemic)
- In addition, there is dilatation of collateral vessels and new vessel formation
- Venous bypass at sites of anastomosis – rectum (piles), oesophago-gastric junction (varices), retroperitoneum and _______________ of liver (caput medusa)
o Some portal venous blood bypasses the liver to enter the systemic circulation
- Oesophageal varices are seen in 40% of cirrhosis cases – fatal hematemesis in half of them
- Varices – distorted, torturous and engorged collateral veins
o Lower oesophagus and proximal stomach, periumbilical (caput medusae), rectum (haemorrhoids)
o Submucosal vessels can be visible as they protrude into the lumen – increased risk of bleeding with increased size of varices
reversal of flow;
falciform ligament;
- Splenomegaly – enlarged, congested and heavy spleen
- Long standing congestion commonly due to cirrhosis – leading to congestive splenomegaly
o Spleen can enlarge up to 1000g
- Hypersplenism – haematologic abnormalities e.g. ____________ (deficient platelet count)
o As the transit time of blood in the spleen increases, there are destruction of certain blood cells
o Anaemia or leukopenia may also be seen
thrombocytopenia;
- Hepatopulmonary syndrome – 30% with cirrhosis and portal hypertension
- Lung – capillary and precapillary dilatations, increases the rate of blood flow leading to _________________ and hypoxia
- Mainly in ______________ (further accentuated by gravity)
- Unclear pathogenesis
- Poor prognosis
- Hepatopulmonary syndrome presents with a triad of Low oxygenation, especially on standing up (_____________)
o Some form of underlying liver disease (e.g. liver cirrhosis)
§ Usually, if patients develop hepatopulmonary syndrome, they usually have some form of chronic liver disease
o Intrapulmonary venous abnormalities – usually intrapulmonary venous dilatation which presents with increased breathlessness on standing.
- Diagnosis is ___________ on standing up and lying down, and bubble echo (contrast enhanced transthoracic echocardio-cardiography)
o Normally, there will be no bubbles in the left heart in normal patients – presence of such bubbles show intrapulmonary vascular abnormalities - Treatment is a liver transplant within the window – if patients are too sick with severe HPS, then transplant has a very high mortality risk
ventilation-perfusion mismatch;
upright posture;
platypnoea- orthodeoxia;
arterial blood gas;
- Porto-pulmonary hypertension
- Pulmonary arterial hypertension in liver cirrhosis with portal hypertension
o Excessive pulmonary vasoconstriction and remodelling
o Dyspnoea on exertion and ___________
- Poorly understood - Hepatorenal syndrome
- Renal failure secondary to liver failure
o __________ leading to acute renal failure
- Poorly understood – thought to be due to vasoactive substances produced by the liver
- Renal failure can be reversed after a liver transplant
finger clubbing;
Renal hypoperfusion;
- Hepatic encephalopathy – neurological symptoms due to chronic or acute liver failure, ranges from mild symptoms to coma
- Ammonia hypothesis – ammonia from the gut is detoxified in the liver
o Can be converted to urea or used in the production of ___________ (glutamine synthetase) - Decreased liver mass and by pass shunts especially in chronic liver failure – leads to increased ammonia concentration in blood
- Neurotoxic effects and interference with neurotransmission
o Damage to astrocytes (astrocytosis) and nuclear swelling of astrocytes – worse with associated inflammation - ______________ – characteristic breath in hepatic encephalopathy
o Thought to be due to due to mercaptans (thiols) – breakdown products of ______-containing amino acids in saliva
o Portosystemic shunting allows thiols to pass directly into the lungs – late sign in liver failure
glutamine;
Fetor hepaticus;
sulfur;
Acute on chronic liver failure
- In acute liver failure, __________ can occur with
herniation – can be a cause of death
- Acute on chronic liver failure – ALF developing in a stable, compensated CLF patient
o Due to precipitation effects such as excessive alcohol intake
o High short term mortality of about 50%
cerebral oedema
