Lecture 21 Flashcards
67 year old cook island man presents to his GP after his wife commented that he had “gone yellow”. He has recently been feeling fatigues and suffers from bouts of abdominal pain. The GP asks if you can take a history before they see the patient. You speak to him and he tells you that his stool is pale and urine is dark/
Anatomy of the liver and its functions; include microscopic detail of lobules and the relationship between the portal and hepatic blood supplies and bile ductules
Pathophysiology of portal hypertension
Normal Liver
1400-1600g
Porta hepatis- portal vein, bile duct, hepatic artery
Lobules- anatomical (based around terminal hepatic vein + portal triads)
Acini- functional- 3x zones- pathologies- areas of changes(inflammatory changes around portal triad/vein)
-relevance around “cause” of disease
-3x zones of 1.periportal 2.mid-zonal 3.Centrilobular. Prianchimal
-Blood flows through sinusoids –> to hepatic vein
What are the 3x zones of the liver’s Functional acini?
Portal Triad ---> 1. Peri-portal 2. Mid-zonal 3. Centri-lobular Terminal Central Vein
4x General features of Hepatic Disease
- Patterns of Hepatic injury
- Hepatic Failure
- Cirrhosis (chronic inflammatory change distinct to liver)
- Portal Hypertension
Patterns of Hepatic Injury
Limited repertoire of responses to injury: 5 general responses
- Degeneration(of hepatocytes) and intercellular accumulation
- fat steatosis (alcohol or metabolic syndrome)
- bilirubin-cholestasis (biliary system obstruction) - Necrosis and Apoptosis (toxic/drug insults)
- Inflammation
- hepatitis (viral/autoimmune) - Regeneration
- Fibrosis (part of repair. can lead to chirrosis. which can also lead to portal hypertension)
Hepatic Failure
Failure/Decompensation
Sudden and massive destruction or endpoint of chronic damage
-needs to be overwhelming damage - drug toxicity/significant insult
Apparent only with loss of 80-90% capacity (liver has extra capacity/can have a lobule removed (for tumour or donation) and be fine- require considerable loss to get symptoms of hepatic failure)
Decompensation associated with increased demand
-associated co-morbidity (when have more hepatic reserve. decreased ability for patient/liver to compensate. E.g. ongoing sepsis, may trigger hepatic failure)
-infection, GI bleeding (huge protein/nitrogen load into gut,), anaemia, hypotension
High mortality
-liver normally has huge synthetic organ (body proteins- albumin and coagulation factors) + detoxification. Symptoms related to failure of these activities
Clinical features include:
-Hypoalbuminaemia -Peripheral Oedema - low albumin level, decreased oncotic pressure,
-jaundice -failure to metabolise bilirubin appropriately
-Bleeding- loss of coagulation factors
-Neurological dysfunction/ decreased alertness - (elevated) ammonia buildup (and other compounds) due to decreased detoxification by liver
Clinical features of Hepatic Failure
-liver normally has huge synthetic organ (body proteins- albumin and coagulation factors) + detoxification. Symptoms related to failure of these activities
Clinical features include:
- Hypoalbuminaemia -Peripheral Oedema - low albumin level, decreased oncotic pressure,
- jaundice -failure to metabolise bilirubin appropriately
- Bleeding- loss of coagulation factors
- Neurological dysfunction/ decreased alertness - (elevated) ammonia buildup (and other compounds) due to decreased detoxification by liver
Hepatocellular Necrosis (histology)
Paracetamol overdose (hepatotoxic) with confluent necrosis near hepatic vein (loss of normal hepatocytes) Residual normal tissue present (around portal triad)
A 45 yr old Korean man present to the General Medical clinic after being told he had abnormal blood tests. He has been feeling “run down” for some time. He thinks he has some lost some weight and his friends remark that he is “yellow”. Recently his legs and abdomen become swollen and he seems to bruise easily.
Histopathology of cirrhosis
Microbiology of the hepatitis viruses, especially hepatitis B and C viruses
Differential diagnosis of chronic liver disease
Complication of acute and chronic liver disease
yellow-jaundice
liver disease acites - abdominal + legs (low albumin levels)
easy bruising- coagulopathy-failure to produce normal clotting factors (esp. vit K dependant clotting factors produced by liver)
Cirrhosis
Cause:
-Drug/alcohol toxicity
-hepatitis
-immunologically mediated
–> dmaage to normal liver architecture/hepatocyte
Bridging fibrosis Septae
-link portal tracts
-smaller
Parenchymal nodules
-proliferating hepatocytes encircled by fibrosis (response to damage, increasing fibrosis around lobules and extending b/w portal triads, with proliferating hepatocytes inside)
-micronodules ( venous); PV(especially) and HA blood bypasses function liver cells
-Progressive fibrosis
-can lead to Portal hypertension (complication of)
Cirrhosis Cellularily
All Mediated by number of enflammatory cytokines:
Stellate cell activation and liver fibrosis
Kupffer cell (macrophage) activation leads to secretion of multiple (inflammatory) cytokines (induce fibrosis, Bv changes, release of fibrogenic growth factors)
-all results in damage to normal hepatocytes (necrosis and apoptosis), inflammatory response (increased fibrosis), progresses to cirrhosis
Stellate cells activated by Platelet derived growth factor (PDGF) and TNF-a (tumour necrosis factor alpha)
Activated Stellate cell contraction stimulated by Endothelin-1 (ET-1)
Fibrosis is stimulated by TGF-B (Transforming growth factor B)
Chemotaxis of activated stellate cells to areas of injury is promoted by PDGF and MCP-1 (monocyte chemotactic protein 1)
Monocyte macrophage family/Lineage
Body chronic inflammatory cell
Kupffer cell - in liver
Alveolar macrohphage cell - in lung
Langham cells- in skin
Alcoholic Cirrhosis Histology
Thick bands of collagen (fibrosis) separating cirrhotic nodules (of proliferating hepatocytes)
- loss of normal architecture
- profound effects on:
1. Normal hepatic function (synthetic and detoxifation)
2. Normal Bile flow and BV pressure (Can lead to complication of portal hypertension- -> reversal of normal flow in portal vein)
Portal Hypertension
Increased resistance to portal blood flow
Prehepatic (obstructive thrombosis/clot in portal vein. rare. (patients with cocagulopathy/ increased clotting tendancy)
Posthepatic (severe R sided heart failure- raised right vascular pressures)
Intrahepatic (cirrhosis)- most common cause (chronic liver disease complicated by portal hypertension)
Consequences:
1. Ascites (abdominal fluid accumulation, increased portal vein pressure, often + decreased serum albumin levels, decreased venous oncotic pressure (increased portal venous pressure-resulting in fluid accumulation into abdomianl cavity) - legs as well.
2. Portosystemic shunts- bypasses developing where systemic and portal circulation share capillary beds (varices
3. Congestive splenomegaly (raised pressure –> elargement of spleen due to congestion)
4. Hepatic Encephalopathy (failure of liver to remove toxins/detox, neurological deterioration of patients with acute hepatic injury)
Potential explanation for a patient who is bruising easily (and has other liver disease symptoms)
easy bruising- coagulopathy-failure to produce normal clotting factors (esp. vit K dependant clotting factors produced by liver)
