Acute & Chronic Pancreatitis

Question 1

What is pancreatitis?

What are the 2 different types?

Answer 1

a condition involving inflammation of the pancreas

pancreatitis can be acute or chronic

acute pancreatitis can return to normal after resolution of the episode

chronic pancreatitis involves continuing inflammation, often with irreversible structural changes

Question 2

What 2 factors account for the vast majority of cases of acute pancreatitis?

Answer 2

gallstones and alcohol

Question 3

How does the severity of acute pancreatitis vary?

What is the mortality in the more severe form and why?

Answer 3

severity varies from mild self-limiting to extremely severe with extensive pancreatic and peripancreatic necrosis as well as haemorrhage

mortality is 40-50% in the more severe form as damage can result in the release of lytic enzymes into the blood

this contributes to severe shock and digestion of surrounding tissue

Question 4

What does the acronym GET SMASHED stand for?

Answer 4

GET SMASHED are the causes of acute pancreatitis

G - gallstones

E - ethanol (alcohol)

T - trauma

S - steroids

M - mumps

A - autoimmune (e.g. SLE)

S - scorpion bites

H - hypercalcaemia, hypothermia, hyperlipidaemia

E - ERCP

D - drugs - e.g. azathiaprin

Question 5

What element is suggested to be raised in the final common pathway for pancreatitis?

What does this lead to?

What lifestyle factor can also influence this process?

Answer 5

the final common pathway has a marked rise in intracellular calcium

this leads to activation of intracellular proteases

there is evidence that alcohol interferes with calcium homeostasis in pancreatic acinar cells

Question 6

What is the result of activation of intracellular proteases following an increase in intracellular calcium?

Answer 6

proteases digest the walls of blood vessels, leading to blood extravasation

amylase is released into the blood

(this is a non-specific diagnostic marker)

Question 7

As well as amylase, what is released into the blood following blood extravasation?

What “sign” can this lead to?

Answer 7

released lipases are a better diagnostic marker than amylase

they cause fat necrosis within the abdomen and subcutaneous tissue

this can lead to discolouration of the skin - Grey Turner’s sign

Question 8

What is Grey Turner’s sign?

Answer 8

this refers to discolouration of the skin / bruising of the flanks

it appears as a blue discolouration

this is a sign of retroperitoneal haemorrhage or bleeding behind the peritoneum

Question 9

How can levels of calcium and glucose be affected in pancreatitis and why does this happen?

Answer 9

• fatty acids are released into the blood following extravasation and lipase release

these can bind to Ca²⁺ and lead to hypocalcaemia

• concomitant destruction of adjacent islets can lead to hyperglycaemia

this can then cause Type II diabetes

Question 10

What can occur following necrosis and destruction of pancreatic tissue in pancreatitis?

Answer 10

• formation of abscesses or cysts within the pancreas or adjacent tissues can occur
• infection secondary to pancreatic tissue damage does not always occur, but can
• not all cases of infection lead to cyst / pseudocyst formation

Question 11

Why can pulmonary failure occur in acute pancreatitis?

What does this eventually lead to?

Answer 11

pulmonary failure in acute pancreatitis is caused by circulating activated digestive enzymes

(e.g. phospholipase A2, trypsin)

this leads to a loss of surfactant, atelectasis and irritation

this eventually leads to ARDS and pleural effusion

Question 12

What else can occur in acute pancreatitis as a result of circulating activated digestive enzymes?

Answer 12

• cardiac depression
• breakdown of the blood brain barrier

Question 13

What is the main clinical feature of acute pancreatitis?

How does this change as inflammation spreads?

Answer 13

upper abdominal pain that usually starts in the epigastrium and is accompanied by nausea and vomiting

as inflammation spreads in the peritoneal cavity, the pain becomes more intense

involvement of the retroperitoneum frequently leads to back pain

Question 14

What clinical features may be present in severe cases of acute pancreatitis?

Answer 14

• tachycardia
• hypotension
• oliguria (reduced urine output)

Question 15

What might be seen on abdominal examination in acute pancreatitis?

Answer 15

• widespread tenderness with guarding
• reduced / absent bowel sounds
• periumbilical bruising (Cullen’s sign) and flank bruising (Grey Turner’s sign)

Question 16

What is Cullen’s sign?

Answer 16

haemorrhagic discolouration of the umbilical area due to intraperitoneal haemorrhage of any cause

Question 17

What does it mean if Cullen’s sign and Grey Turner’s sign are present?

Answer 17

if these signs are present they show severe necrotising pancreatitis

Question 18

What sign, if present, is indicative of poor prognosis in acute pancreatitis?

Answer 18

left-sided pleural effusion

Question 19

What will blood tests show in acute pancreatitis?

Answer 19

• raised serum amylase
• raised serum lipase

amylase is not prognostic and the level is not related to the degree of tissue damage

lipase levels are more specific and relate to the level of tissue damage, but levels do not rise until up to 8 hours after the onset of symptoms

Question 20

What does raised amylase suggest?

Answer 20

raised amylase, many times above the normal level, is an important indication of pancreatic inflammation

Question 21

Why might a chest X-ray be performed when diagnosing acute pancreatitis?

Answer 21

• CXR excludes gastroduodenal perforation, which also causes raised serum amylase
• CXR may show gallstones or pancreatic calcification

Question 22

Why might an USS be performed in suspected acute pancreatitis?

What might this show?

Answer 22

USS is performed to look for gallstones which may cause pancreatitis

It may also show pancreatitic swelling and necrosis

Question 23

Why might a contrast-enhanced spiral CT be performed in acute pancreatitis?

Answer 23

• to assess the extent of pancreatic necrosis
• to detect complications such as abscesses, fluid collection and pseudocyst formation

Question 24

What is the purpose of performing an MRI in acute pancreatitis?

Answer 24

MRI (MRCP) assesses the degree of pancreas damage

it can be used to locate gallstones

it can also differentiate between fluid and solid inflammation

Question 25

What is ERCP? Why might it be used?

Answer 25

**_endoscopic retrograde cholangiopancreatography_** this is used to look at the pancreatic duct for inflammatory fibrosis or tumours pancreatic juice can be collected and biochemically examined

Question 26

What is APACHE and what does a score \>8 suggest?

Answer 26

**a**cute **p**hysiology **a**nd **c**hronic **h**ealth **e**valulation score it assesses the **_severity_ of a _wide spectrum_ of illness** it is adjusted for **age + obesity** and other health problems it has a **_high sensitivity_** as early as **24 hours after symptom onset** a score **_\>8_** indicates **_severe disease_**

Question 27

What scoring system is used to assess the severity and prognosis of pancreatitis? What acronym does this use?

Answer 27

the **_Glasgow scoring system_** can be used to assess the **prognosis** and **severity** of pancreatitis it can be remebered with the acronym **_PANCREAS_**

Question 28

What does PANCREAS stand for in the Glasgow scoring system?

Answer 28

**_P - PO₂:_** * oxygen \< 60 mmHg or 7.9 kPa **_A - Age:_** * age \> 55 **_N - Neutrophilia:_** * white blood cells \> 15 **_C - Calcium:_** * calcium \< 2 mmol/L **_R - Renal urea:_** * urea \> 16 mmol/L **_E - Enzymes:_** * lactate dehydrogenase (LDH) \> 600 iu/L * aspartate transaminase (AST) \> 200 iu/L **_A - Albumin:_** * albumin \< 32 g/L **_S - Sugar:_** * glucose \> 10 mmol/L

Question 29

What are the initial supportive treatments for acute pancreatitis?

Answer 29

* **_replace lost fluids (IV)_** and a **urinary catheter** might be necessary * **_nasogastric suction_** to prevent **abdominal distension** and **vomitus**, lowering risk of **_aspiration pneumonia_** * **_continuous oxygen_** administration may be necessary depending on sats

Question 30

What types of medication might be prescribed for acute pancreatitis?

Answer 30

**_Prophylactic antibiotics:_** * these should ***broad spectrum*** - e.g. ***_cefuroxime_*** or ***_aztreonam_*** * reduces risk of infection complications **_Analgesia:_** * ***_pethidine_*** and ***_tramadol_*** administered under patient control system

Question 31

What other treatment may be given to a patient in hospital with acute pancreatitis?

Answer 31

enteral nutrition via nasojejunal tubes

Question 32

What treatment is given to patients with multiorgan failure?

Answer 32

ventilation and renal support this has a mortality rate \> 80%

Question 33

What do mortality and morbidity reflect in the first week of acute pancreatitis and after this?

Answer 33

* within the first week, mortality and morbidity reflect the **_systemic inflammatory response_**, which in turn results in **multiple organ failure** * after this, prognosis is related to the extent of **_pancreatic necrosis_**

Question 34

What is extensive pancreatic necrosis associated with? What happens if the necrotic pancreas becomes infected?

Answer 34

extensive necrosis (**\>50%**) is associated with **higher risk of further complications** these frequently need **_surgical intervention_** **infection** of the necrotic pancreas can lead to **_sepsis_** and **resection** of infected areas of pancreas may be needed

Question 35

Why might surgical intervention be needed in an infected necrotic pancreas?

Answer 35

* some **fluid collections** are surrounded by **_granulation tissue_** (**_pseudocysts_**) * larger ones (**_\>6cm_**) may become **infected** or lead to **intraperitoneal bleeding** * these need to be **_drained surgically_**

Question 36

What is the prognosis like overall for acute pancreatitis? What happens in people with severe acute pancreatitis?

Answer 36

* vast majority with mild or moderate acute pancreatitis will make a **full recovery** * **severe** acute pancreatitis patients may become **_pancreatically insufficient_** with respect to **exocrine (_malabsorption_)** and **endocrine function (_diabetes_)**

Question 37

What is the most common cause of chronic pancreatitis?

Answer 37

**_alcohol_** accounts for the vast majority of cases (60-80%) this may either be **_chronic_** pancreatitis or **_repeated episodes of acute_** pancreatitis

Question 38

What are rarer inherited causes of chronic pancreatitis?

Answer 38

* rare autosomal dominant trait associated with **aminoaciduria** or **hyperparathyroidism** * **_cystic fibrosis_** due to **CFTR** problems, which causes mucus problems * **benign or malignant _obstruction_** of the pancreatic duct * **congenital abnormalities**, such as **_pancreas divisum_**

Question 39

What is thought to be involved in the pathogenesis of chronic pancreatitis that is hereditary?

Answer 39

* due to **_inappropriate activation of enzymes_** within the pancreas * genetic abnormalities of **cationic trypsinogen** and its **inhibitory proteins** lead to **_unopposed trypsin activity_** within the pancreas

Question 40

What lifestyle factor can also influence trypsin activity within the pancreas? Why is trypsin thought to be the main enzyme involved in chronic pancreatitis?

Answer 40

* **_chronic alcohol intake_** raises the level of **trypsinogen relative to its inhibitor** * human trypsinogen also has a tendency to **_auto-activate_** * this leads to more **unopposed activity** and **damage to the pancreas**

Question 41

What is the result of intrapancreatic protein activity? How can this lead to further pancreatic damage?

Answer 41

* intrapancreatic protein activity leads to **_precipitation_ of proteins** within the **_pancreatic duct lumen_** in the form of **_plugs_** * plugs form a starting point for **_calcification_** and lead to **_ductal hypertension_** * this causes further pancreatic damage

Question 42

What factors can perpetuate the formation of pancreatic plugs?

Answer 42

**_cytokine activation_** and **_oxygen stress_** perpetuate the process via **inflammation**

Question 43

What is the pain like in chronic pancreatitis? What can make it worse and what symptom usually accompanies it?

Answer 43

* pain is usually **_epigastric_** and radiates through **into the back** * pain may be **_episodic_** * **exacerbations** may follow further **_alcohol excess_** * during periods of abdominal pain, **_weight loss_** may be severe

Question 44

What are other clinical features of chronic pancreatitis?

Answer 44

* **_malabsorption_** develops due to **exocrine insufficiency** * **_diabetes_** develops due to **endocrine insufficiency** * **_jaundice_** secondary to **common bile duct obstruction** is a feature in a small number of patients

Question 45

What will ERCP show in someone with chronic pancreatitis?

Answer 45

* **_distorted pancreatic ducts_** due to **scar tissue** resulting from a chronic inflammatory process

Question 46

What would an X-ray of the upper abdomen show in someone with chronic pancreatitis?

Answer 46

flecks of **_calcification_** due to **previous fat necrosis**

Question 47

What tests might be abnormal in chronic pancreatitis?

Answer 47

* serum **_amylase_** and **_lipase_** levels are elevated * **_faecal elastase_** levels are abnormal in the majority of patients

Question 48

Why is a faecal elastase test done?

Answer 48

**elastase** is produced by **_exocrine tissue_** in the pancreas the test measures the amount of **_elastase within the stool_** to evaluate whether the pancreas is functioning properly

Question 49

What is prescribed for pain relief in chronic pancreatitis?

Answer 49

* a combination of **_NSAIDs and opiate_** (**tramadol**) used for pain relief * **_tricyclic antidepressant_** (e.g. **amitriptyline**) used for chronic pain

Question 50

How can pancreatic enzyme supplements improve pain in chronic pancreatitis?

Answer 50

pancreatic enzyme supplements **_reduce pancreatic stimulation_** by a **negative feedback** mechanism this reduces the intensity of the pain

Question 51

How does pain change over time in chronic pancreatitis? What option is available for patients with debilitating pain?

Answer 51

pain **_improves_** over time after 6 to 10 years, 60% of patients are pain free for patients with debilitating pain, **surgical intervention** is an option **_duct drainage_** and **_limited resection_** can relieve pain in 80% of patients, but has a 5% mortality

Question 52

What is the purpose of endoscopic techniques in treatment of chronic pancreatitis?

Answer 52

endoscopic techniques can **_improve pancreatic drainage_**

Question 53

What other group of medication is given in chronic pancreatitis and why?

Answer 53

an acid suppressor - **_H₂-receptor antagonist_** or **_PPI_** this compensates for **decreased bicarbonate secretion**

Question 54

How effective is treatment for chronic pancreatitis?

Answer 54

a proportion of patients still continue to **_malabsorb_** due to inadequate mixing of pancreatic supplements with the food as well as the low pH in the duodenum

Question 55

What is pancreatin?

Answer 55

a pancreatic enzyme supplement consisting of **_protease, lipase and amylase_**

Question 56

How must supplements like pancreatin be taken and why?

Answer 56

protease, lipase and amylase are **inactivated** by **_gastric acid_** and **_heat_** supplements must be taken **_with food_** (but not mixed with very hot food) and either concurrently with **gastric acid suppression therapy** or as **enteric-coated formulations**

Question 57

What drug tends to be used as gastric acid suppression therapy alongside pancreatin?

Answer 57

**_cimetidine_** this is a H2 receptor antagonist a PPI could also be used

Question 58

How is dosage of pancreatin adjusted?

Answer 58

dosage is adjusted according to **_size_**, **_frequency_** and **_consistency_** of stools

Question 59

What are the unwanted effects of pancreatin?

Answer 59

* **irritation** of the **mouth** and **perianal skin** * nausea and vomiting * abdominal discomfort

Question 60

How is the amount of pancreatin given balanced with side effects?

Answer 60

* to **reduce side effects**, the amount of pancreatin given has to be **reduced** * this means that the amount of **_total dietary fat_** consumed also has to be **reduced** * otherwise it could result in **_steatorrhoea_**

Question 61

What are the complications of chronic pancreatitis?

Answer 61

* same as acute pancreatitis (e.g. pseudocyst formation) * formation of **_ascites_** * **accumulation of serous fluid** in the peritoneal cavity * occasionally **_pleural effusions_**

Question 62

What is steatorrhoea?

Answer 62

the **_passage of fat_** in large amounts in the **_faeces_** (up to 30 mmol per 24 hours) due to **failure to digest and absorb** the fat it is associated with **_pancreatic insufficiency_**

Question 63

What usually improves steatorrhoea?

Answer 63

pancreatic enzyme supplements (e.g. pancreatin) and a low fat diet