Hepatitis C and pancreatitis Flashcards
What is hepatitis C?
-Inflammation that disrupts hepatocytes and small bile ductules caused by the hepatitis C virus via parenteral transmission
What is the hepatitis C virus?
-Single stranded RNA virus from the family of flaviviruses.
-Can cause acute hepatitis or chronic hepatitis
Acute hepatitis
–> Presents with jaundice (mixture of CB and UCB) with dark urine (CB), fever, malaise and elevated enzymes (ALT>AST)
–>Chronic hepatitis characterised by symptoms that last >6 months. Risk of progression to cirrhosis and HCC
What are the leading causes of chronic liver failure worldwide?
-Hep B
-Hep C
-NAFLD
-ALD
What is the pathological sequence in HCV?
- Acute hepatitis
- Chronic hepatitis
- Cirrhosis
- LIver cell failure
- HCC
What are the most common risk factors for hepatitis C?
IV drug use
Multiple sexual partners
Surgery in last 6 months
Needle stick
Multiple contacts with HCV infected individuals
Working in medical or dental field
What is cirrhosis?
-End stage liver failure
-Characterised by disruption of normal liver parenchyma with bands of fibrosis and regenerative nodules of hepatocytes
What are the clinical features and pathological sequence of cirrhosis?
Portal hypertension
–> Ascites
–> congestive splenomegaly/hypersplenism
–> portosystemic shunt (oesophageal varices, haemorrhoids, caput medusae)
–> hepatorenal syndrome (rapidly developing renal failure secondary to cirrhosis
Decreased detoxification
–> Mental state changes, asterixis and eventual coma (due to rising serum ammonia)
–> Gynaecomastia, spider naevi and palmar erythema due to hyperestrinism
–> jaundice
Decreased protein synthesis
–> Hypoalbuminaemia and oedema
–> Coagulopathy: reduced production of clotting factors
Hepatocellular carcinoma
What is the most common cause of cirrhosis in the UK?
Chronic alcoholism
Describe the relationship between alcoholism, hepatic steatosis, hepatitis and cirrhosis
Describe the mechanism of fibrosis
- Persistent tissue injury leads to chronic inflammation and loss of normal tissue architecture
- Cytokines produced by macrophages and other leucocytes stimulate migration and proliferation of fibroblasts and myofibroblasts and the deposition of collagen and other extracellular matrix proteins
- The net result is the replacement of normal tissue with fibrosis
What causes the different types of necrosis?
Coagulative
–> ischaemic infarction of any organ except the brain
Liquefactive
–> brain infarction/abscess/pancreatitis
Caseous
–> TB
Fat necrosis
–> Traumatic breast injury
Fibrinoid necrosis
–> HTN
Gangrenous
–> wet and dry gangrene
What is the type of necrosis in hepatitis?
Coagulative
What are the different types of candida?
-Oral
-Vaginal
-Cutaneous
-Invasive
Describe candida albicans
-Most common disease causing fungus
-Normal inhabitant of GI tract, mouth and vagina in some individuals
-Systemic candidiasis with associated pneumonia is a disease restricted to immunocompromised individuals
Describe candida microscopic appearance and staining
-In tissue sections c albicans demonstrates yeast like forms (blastoconidia), pseudohyphae and true hyphae
-Pseudohyphae–> represent budding yeast cells which join end to end at constrictions resembling true hyphae
-May be visible on normal H and E staining but ‘fungal’ staining e.g. gomori methenamine silver, periodic acid-schiff can be used to better highlight the pathogens
What are the stages and classification of venous leg ulcers?
Describe follicular hyperplasia
Predominantly B cell response with germinal centre hyperplasia which may be associated with marginal zone hyperplasia. Follicles vary in size and shape
Caused by stimuli that activate b cell follicles e.g. sjogren’s, RA, syphilis
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Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer’s patches, and the spleen[1] – where mature B cells are activated, proliferate, differentiate, and mutate their antibody genes (through somatic hypermutation aimed at achieving higher affinity) during a normal immune response; most of the germinal center B cells (BGC) are removed by tingible body macrophages
B lymphocytes, also called B cells, create a type of protein called an antibody. These antibodies bind to pathogens or to foreign substances, such as toxins, to neutralize them.
In the periphery of a lymph node is the paracortical region where lymphoid follicles are located. A follicle is a loosely arranged structure with an outer mantle of small T lymphocytes and a germinal center composed of B lymphocytes, follicular dendritic cells, and macrophages.
Describe paracortical (interfollicular) hyperplasia
Reactive changes in the T cell region of the lymph node with paracortical expansion caused by:
–> EBV
–> certain vaccinations (e.g. smallpox)
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T cells
-CD4 cells (helper cells: recruit other inflammatory cells)
-CD 8 cells: cytotoxic cells. Kill virus infected/cancer cells
What is sinus histiocytosis (reticular hyperplasia)? When would it occur?
-Distension and prominence of lymphatic sinusoids, due to marked hypertrophy of lining endothelial cells and an infiltrate of macrophages (histiocytes). Non specific but often encountered in lymph node draining cancers
Describe the extrinsic pathway of the coagulation cascade
- Damage to endothelium means that factor 7 escapes from circulation into the surrounding tissue
- Activated by tissue factor (3) which is released by damaged cells–> TFVIIa complex
- TFVIIa activates factor X
- With factor Va this triggers production of thrombin
Note extrinsic pathway is responsible for initial production of Xa, whereas intrinsic pathway amplifies its production
Describe the intrinsic pathway of the coagulation cascade
factor 12 (damaged collagen)–> factor 11–>factor 9–>8 (released by platelets)–> 10–>5 –> thrombin
-Factor XII activated when it comes into contact with damaged collagen on damaged endothelium–> activates factor XI–> activates factor IX
-Along with clotting factors, platelets form a cellular ‘plug’ at the site of injury. These platelets also release mediators that facilitate further clotting, including Factor VIII.
-Factor IX combines with Factor VIII to form an enzyme complex that activates factor X, which along with factor Va, stimulates the production of thrombin.
Describe common pathway clotting
1 X 2 X 5 =10
Factor10 –> (prothrombin to thrombin by prothrombinase-5 and 10) –> (fibrinogen to fibrin). FIbrin stabilised by factor 13
The intrinsic and extrinsic pathways converge to give rise to the common pathway. The activated factor X causes a set of reactions resulting in the inactive enzyme prothrombin (also called factor II) being converted to its active form thrombin (factor IIa) by Prothrombinase (factor 5 and factor 10).
The thrombin then converts soluble fibrinogen (also referred to as factor I) into insoluble fibrin strands. The fibrin strands which comprise the clot are stabilised by factor XIII.
Describe regulation of clotting
Protein s, protein c and antithrombin provide negative feedback
To prevent excessive clotting and subsequent disease, mediators including Protein C and Protein S provide negative feedback on the clotting cascade.
Protein C is activated following contact by thrombomodulin, which is itself activated by thrombin. Along with co-factors including protein S, activated protein C degrades factor Va and factor VIIIa, thus slowing the rate of clotting.
Calcium ions play a role through their interaction with the activation of several clotting factors. Low levels of calcium are therefore inhibitory to the clotting cascade.
Antithrombin is a protease inhibitor that degrades thrombin, factor IXa, factor Xa, factor XIa and factor XIIa. It is constantly active but can be activated further by a group of common anticoagulants known as heparins.
How to remember clotting cascade
Common pathway:
–> 1 X 2 X 5 = 10
Extrinsic:
–> Extrinsic starts with 7: 7 has two e’s
–> factor 7 (activated by tissue factor) makes up extrinsic pathway and helps activate factor 10
Intrinsic:
–> count back from 12 but skip 10 because we already have it
