Hepatitis C and pancreatitis

Question 1

What is hepatitis C?

Answer 1

-Inflammation that disrupts hepatocytes and small bile ductules caused by the hepatitis C virus via parenteral transmission

Question 2

What is the hepatitis C virus?

Answer 2

-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

Question 3

What are the leading causes of chronic liver failure worldwide?

Answer 3

-Hep B
-Hep C
-NAFLD
-ALD

Question 4

What is the pathological sequence in HCV?

Answer 4

1. Acute hepatitis
2. Chronic hepatitis
3. Cirrhosis
4. LIver cell failure
5. HCC

Question 5

What are the most common risk factors for hepatitis C?

Answer 5

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

Question 6

What is cirrhosis?

Answer 6

-End stage liver failure
-Characterised by disruption of normal liver parenchyma with bands of fibrosis and regenerative nodules of hepatocytes

Question 7

What are the clinical features and pathological sequence of cirrhosis?

Answer 7

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

Question 8

What is the most common cause of cirrhosis in the UK?

Answer 8

Chronic alcoholism

Question 9

Describe the relationship between alcoholism, hepatic steatosis, hepatitis and cirrhosis

Answer 9

Question 10

Describe the mechanism of fibrosis

Answer 10

1. Persistent tissue injury leads to chronic inflammation and loss of normal tissue architecture
2. 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
3. The net result is the replacement of normal tissue with fibrosis

Question 11

What causes the different types of necrosis?

Answer 11

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

Question 12

What is the type of necrosis in hepatitis?

Answer 12

Coagulative

Question 13

What are the different types of candida?

Answer 13

-Oral
-Vaginal
-Cutaneous
-Invasive

Question 14

Describe candida albicans

Answer 14

-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

Question 15

Describe candida microscopic appearance and staining

Answer 15

-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

Question 16

What are the stages and classification of venous leg ulcers?

Answer 16

Question 17

What is the differential diagnosis for inguinal lymphadenopathy

Answer 17

Systemic causes

neoplastic
—> leukaemia
—> lymphoma

Inflammatory
—> sarcoid
—> TB

Local causes

Infective
—> infection in groin or lower limb

Malignant:
—> Metastatic disease from lower limb/external genitalia/perineal/perianal area
—> malignant melanoma

Question 18

Scenario: 55 yr old lady IVDU with left lower limb venous ulcer

What will you see microscopically on a cut inguinal lymph node section in this patient?

Answer 18

Chronic non-specific lymphadenopathy (one of 3 patterns depending on the causative agents)
–> Follicular hyperplasia (B cell compartment)
–> Paracortical (interfollicular) hyperplasia (T cell compartment)
–> Sinus histiocytosis (reticular hyperplasia) (macrophage compartment)

https://en.wikipedia.org/wiki/Lymphoid_hyperplasia

Question 19

Describe follicular hyperplasia

Answer 19

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

-
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.

Question 20

Describe paracortical (interfollicular) hyperplasia

Answer 20

Reactive changes in the T cell region of the lymph node with paracortical expansion caused by:
–> EBV
–> certain vaccinations (e.g. smallpox)

-

T cells
-CD4 cells (helper cells: recruit other inflammatory cells)
-CD 8 cells: cytotoxic cells. Kill virus infected/cancer cells

Question 21

What is sinus histiocytosis (reticular hyperplasia)? When would it occur?

Answer 21

-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

Question 22

What is amylase and what is its function?

Answer 22

-Group of proteins (digestive enzymes) found in saliva and pancreatic juice
-All are glycoside hydrolases and act on alpha 1,4 glycoside bond to convert starch into smaller carbohydrate molecules (oligosaccharides and disaccharides)

Question 23

What is CRP and from where is it produced?

Answer 23

-Protein produced by the liver in response to inflammation (acute phase protein)
-Non specific
-Can be used to monitor disease progress and flares

Question 24

What blood tests would you do in pancreatitis?

Answer 24

-FBC
-U + E
-CRP
-Amylase/lipase (higher sensitivity)

For glasgow score:
-ABG
-Calcium
-Albumin
-LDH
-Blood glucose

Question 25

Scenario: patient complaining of epigastric pain. Recent hospitalisation for acute pancreatitis 3 weeks ago. Patient is having compression on his stomach. What is the cause?

Answer 25

Pseudocyst

Question 26

What organisms can cause pancreatitis?

Answer 26

VIrus: mumps, cocksackie b, hepatitis Parasites: hydatid Bacteria: mycoplasma pneumoniae, leptospirosis

Question 27

Scenario: patient complaining of epigastric pain. Recent hospitalisation for acute pancreatitis 3 weeks ago. Patients haemoglobin drops, what is the cause?

Answer 27

-Rupture of splenic artery/PDA/GDA pseudoaneurysm

Question 28

Scenario: patient complaining of epigastric pain. Recent hospitalisation for acute pancreatitis 3 weeks ago. What non surgical option is available to stop the bleeding of the pseudoaneurysm?

Answer 28

Interventional radiology

Question 29

How does interventional radiology work for embolysation?

Answer 29

Using real time imaging, catheter is inserted into the artery and clotting agents are released (coils, particles, gel or foam) into the blood vessel slowing the blood flow and causing an internal injury to activate the coagulation cascade

Question 30

Which part of the coagulation cascade will be activated in IR?

Answer 30

Intrinsic pathway

Question 31

Which clotting factors are involved in the intrinsic pathway?

Answer 31

12,11,9,8

Question 32

Describe the extrinsic pathway of the coagulation cascade

Answer 32

1. Damage to endothelium means that factor 7 escapes from circulation into the surrounding tissue 2. Activated by tissue factor (3) which is released by damaged cells--> TFVIIa complex 3. TFVIIa activates factor X 4. With factor Va this triggers production of thrombin Note extrinsic pathway is responsible for initial production of Xa, whereas intrinsic pathway amplifies its production

Question 33

Describe the intrinsic pathway of the coagulation cascade

Answer 33

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.

Question 34

Describe common pathway clotting

Answer 34

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.

Question 35

Describe regulation of clotting

Answer 35

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.

Question 36

How to remember clotting cascade

Answer 36

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