The pancreas has both endocrine and exocrine functions. The islets of Lang-erhans secrete several hormones directly into the blood stream (endocrine effect) of which insulin and glucagon play a crucial role in the regulation of blood sugar. The pancreatic acinar cells produce pancreatic enzymes (lipase, colipase, amylase and proteases), which pass via the main pancreatic duct into the duodenum and are involved in the digestion of fat, carbohydrate and protein in the small intestine.
Pancreatitis is divided into acute and chronic. Acute pancreatitis occurs on the background of a previously normal pancreas and the pancreas returns functionally and structurally to normal after the episode. It occurs as isolated or recurrent attacks. In chronic pancreatitis, there is continuing inflammation with irreversible structural changes. In practice, it is not always possible to clearly separate acute from chronic forms because the acute causes (if untreated) may eventually lead to chronic pancreatitis and there may be relapses of the chronic condition - ‘acute-on-chronic pancreatitis'.
Acute pancreatitis is a disease of increasing incidence and associated with significant morbidity and mortality. Most patients will recover from the attack with only general supportive care, but 25% will develop severe acute pan-creatitis with multiorgan failure and about 20% of these patients may die. The causes of acute pancreatitis are given in Table 4.13.
It is thought that the final common pathway, whatever the initiating cause, is a marked elevation in intracellular calcium leading to activation of intra-cellular proteases and the release of pancreatic enzymes. Acinar cell injury and necrosis follows, which promotes migration of inflammatory cells from the microcirculation into the interstitium. Release of a variety of mediators and cytokines leads to a local inflammatory response and sometimes a systemic inflammatory response that can result in single or multiple organ failure.
There is usually epigastric or upper abdominal pain radiating through to the back, associated with nausea and vomiting. On examination there is epigas-tric or general abdominal tenderness, guarding and rigidity. However, other symptoms (coma, multiorgan failure) may dominate the clinical picture leading to a delay in diagnosis. Ecchymoses around the umbilicus (Cullen's sign) or in the flanks (Grey Turner's sign) indicate severe necrotizing pancreatitis.
Table 4.13 Causes of pancreatitis
Infections (e.g. mumps, Coxsackie B)
Drugs: azathioprine, oestrogens, corticosteroids, didanosine
Hereditary: Trypsinogen and inhibitory protein defects, cystic Abrosis
latrogenic: post-surgical, post-ERCP
Metabolic: hypercalcaemia, hypertriglyceridaemia
Miscellaneous: trauma, scorpion bite, cardiac surgery
Idiopathic (unknown cause)
*Commonest causes in the Western worỉd.
ERCP, endoscopic retrograde choỉangiopancreatography.
The purpose of investigation is to make the diagnosis, assess the severity and determine the aetiology.
■ Blood tests. A raised serum amylase or lipase, in conjunction with an appropriate history and clinical signs, strongly indicates a diagnosis of acute pancreatitis. Normal levels of serum amylase occur if the patient presents late when urinary amylase or serum lipase levels may still be raised. Serum amylase may also be moderately raised in other abdominal conditions, such as acute cholecystitis, perforated peptic ulcer and intes-tinal ischaemia, although very high levels (>3 times normal) are diagnos-tic of pancreatitis. Full blood count, C-reactive protein (CRP), urea and electrolytes, liver biochemistry, plasma calcium, and arterial blood gases are also measured on admission and at 24 and 48 hours, and used to assess the severity of pancreatitis (Table 4.14).
■ Radiology. An erect chest X-ray is performed to exclude perforated peptic ulcer as the cause of the pain and raised amylase. Abdominal US is performed as a screening test to look for gallstones as a cause of pan-creatitis and may show swelling of the inflamed pancreas. Contrast-enhanced spiral CT scanning or MRI is performed in all but the mildest attack of pancreatitis to confirm the diagnosis, identify the presence and
Table 4.14 Glasgow criteria for severity. Three or more factors present during the first 48 hours predict a severe episode and a poor prognosis
White blood cell count
>15 X 109/L
<8.0 KPa (60 mmHg)
Liver, biliary tract and pancreatic disease
extent of pancreatic necrosis (associated with organ failure and higher mortality) and identify peripancreatic fluid collections. It is performed after 72 days as early CT may underestimate the severity of pancreatitis.
The management of acute pancreatitis is summarized in Fig. 4.9. Assessment of severity is essential; those predicted to have severe pancreatitis with a protracted course can then be managed in a high-dependency or intensive care unit with vigorous fluid resuscitation, correction of metabolic abnormali-ties and administration of therapies to improve outcome. Most attacks of pancreatitis are mild with none or only minimal pancreatic necrosis and without systemic complications; these patients usually recover within 5-7 days and need general supportive care only. In contrast, severe pancreatitis is associated with failure of one or more organ systems, such as renal or respiratory failure, and impaired coagulation with disseminated intravascular coagulation. Severe attacks are usually associated with pancreatic necrosis on CT scanning. Several scoring systems are in use to predict those patients with severe pancreatitis: Glasgow criteria (Table 4.14), Ranson's criteria and the acute physiology and chronic health evaluation score, APACHE). Obesity and a C-reactive protein >200 mg/L in the first 4 days are also associated with a worse outcome.
General supportive care
Early fluid replacement is essential and in severe pancreatitis 5 L or more of crystalloid daily may be required to maintain adequate urine output (>0.5 mL/ kg body weight/hour). Supplemental oxygen is given and requirements are guided by pulse oximetry and arterial blood gases. Low molecular weight heparin is given for deep vein thrombosis prophylaxis. Electrolyte and
Fig. 4.9 The management of acute pancreatitis. HDU, high-dependency unit; ITU, intensive care unit; TPN, total parenteral nutrition; ERCP, endoscopic retrograde cholangiopancreatography; NG, nasogastric.
metabolic abnormalities are corrected and a sliding scale of insulin may be necessary for good control of blood sugar levels. Pain is controlled by pethi-dine and tramadol and a patient-controlled system of administration is neces-sary if there is persistent pain. Morphine is avoided because it increases sphincter of Oddi pressure and may aggravate pancreatitis. In patients with a predicted severe episode, there is little likelihood of oral nutrition for a number of weeks. Nutrition is provided via a nasogastric tube or a naso-jejunal tube (placed endoscopically) for patients who are intolerant of nasogastric feeding due to exacerbation of pain or nausea and vomiting. Therapies to reduce the severity or frequency of complications Broad-spectrum antibiotics, e.g. cefuroxime or aztreonam, reduce the risk of infection of the necrotic pancreas and are given from the outset. Early ERCP (within 48-72 hours) and sphincterotomy improves the outcome in patients with biliary pancreatitis and evidence of cholangitis or a high suspicion of a CBD stone (dilated CBD or CBD stone seen on US or jaundice) or when pancreatitis is predicted to be severe. Surgical treatment is sometimes required for very severe necrotizing pancreatitis, particularly if it is infected, or if complications such as pancreatic abscesses or pseudocysts occur.
Acute complications include hyperglycaemia, hypocalcaemia, renal failure and shock.
Inappropriate activation of enzymes within the pancreas leads to precipitation of protein plugs within the duct lumen, forming a nidus for calcification. Subsequent duct blockage leads to ductal hypertension and further pan-creatic damage. This together with cytokine activation leads to pancreatic inflammation, irreversible morphological change and/or permanent impair-ment of function. The commonest cause of chronic pancreatitis in most developed countries is excess alcohol. Other causes are tropical chronic pancreatitis, and hereditary, autoimmune and cystic fibrosis.
Epigastric abdominal pain, either intermittent or constant, and radiating through to the back is the commonest symptom. There may be severe weight loss as a result of anorexia. Diabetes and steatorrhoea may develop due to endocrine (insulin) and exocrine (lipase) insufficiency. Occasionally jaundice is the presenting symptom due to obstruction of the CBD during its course through the fibrosed head of pancreas. The differential diagnosis is from pancreatic carcinoma, which also presents with pain and weight loss and may develop on a background of chronic pancreatitis. Carcinoma should be considered when there is a short history and localized ductular abnormalities on imaging.
The diagnosis of chronic pancreatitis is made by imaging (to demonstrate structural changes in the gland), and metabolic studies, which demonstrate functional abnormalities.
■ Radiology. A plain abdominal X-ray will show pancreatic calcification in some cases. US and CT scanning may show calcifications, ductal dilata-tion, irregular consistency and outline of the gland, and fluid collections. CT is a more sensitive test than US. MRCP and endoscopic US are some-times used if the diagnosis is not confirmed with other imaging tests. ERCP is usually reserved for therapeutic e.g. pancreatic stent placement, rather than diagnostic purposes.
■ Functional assessment. These tests are insensitive in early pancreatic insufficiency. Faecal elastase, measured on a single random stool sample, is reduced. Other tests rely on measuring decreased concentra-tions of the products of synthetic compounds, e.g. fluorescein dilaurate (pancreolauryl) or W-benzoyl-L-tryosyl-p-amino benzoic acid (NBT-PABA), which appear in the urine after oral administration and intraluminal hydrolysis by pancreatic esterases and gut absorption. Serum amylase is not of use in the diagnosis of chronic pancreatitis, but may be raised during an acute episode of pain. A raised blood sugar indicates diabetes mellitus.
The patient should be advised to stop drinking alcohol. The pain may require opiates for control, with the attendant risk of addiction. Surgical resection combined with drainage of the pancreatic duct into the small bowel (pancreaticojejunostomy) is of value for severe disease with intractable pain. Pancreatic strictures or stones are sometimes amenable to endoscopic treat-ment with ERCP. Persistent pseudocysts are drained endoscopically into the stomach or by surgical drainage. Pancreatic enzyme supplements are useful for those with steatorrhoea and may reduce the frequency of attacks of pain in those with recurrent symptoms. Diabetes requires appropriate treatment with diet, oral hypoglycaemics or insulin.
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER DISEASE IN PREGNANCY
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS
5. Haematological disease
Assessment and treatment of suspected neutropenic sepsis
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
6. Malignant disease
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
8. Water, electrolytes and acid–base balance
WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
9. Renal disease
INVESTIGATION OF RENAL DISEASE
URINARY TRACT INFECTION
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
10. Cardiovascular disease
COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
ISCHAEMIC HEART DISEASE
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
ARTERIAL AND VENOUS DISEASE
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS
11. Respiratory disease
12. Intensive care medicine
13. Drug therapy, poisoning, and alcohol misuse
14. Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
15. Diabetes mellitus and other disorders of metabolism
16. The special senses
COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES