Week 18 Pathology

Pancreas

  • Retroperitoneal organ
  • Secretes 2-2.5L per day
  • Endocrine function by Islet cells which secrete
    • Insulin – B – 68%
    • Glucagon – a – 20%
    • Somatostatin  – d – 10% (inhibit other 2)
    • 1-2% of pancreas
  • Exocrine Function
    • Proenzymes
      • Tryprsinogen
      • Chymotrypsinogen
      • Procarboxypeptidase
      • Proelastase
      • Kallikreinogen
      • Phospholipase A
    • Conversion of proenzymes requires conversion of trypsinogen to tripsin by duodenal enteropeptidase.
    • Enzymes released in active form
      • Lipase
      • amylase

 

Acute pancreatitis

A group of reversible lesions characterised by inflammation of the pancreas ranging in severity.

  • In its most severe form the mortality rises to between 40-50%.
  • In more severe disease the patient may have a tachycardia, hypotension and be oliguric.
  • Abdominal examination may show widespread tenderness with guarding as well as reduced or absent bowel sounds.
  • Specific clinical signs that support a diagnosis of severe necrotizing pancreatitis include periumbilical (Cullen’s sign) and flank bruising (Grey Turner’s sign).
  • In patients with a gallstone aetiology the clinical picture may also include the features of cholangitis.

Aetiology.

  • Incidence yearly of 10-20/100 000
  • 80% due to Gallstones(present in 35-60%, only 5% of all ppl with GS develop pancreatitis) or EtOH
  • Causes (GET SMASHED)
    • G- gallstones
    • E-tOH
    • T-raumatic, tumour
    • S-teroids
    • M-umps
    • A-utoimmune
    • S-corpion bite
    • H-ypercalcaemia, hyperlipidaemia, hyper PTH
    • E-RCP and emboli
    • D-rugs – thiazide diuretics, sufonamides, frusemide, methyldopa.
    • Pancreatic tract obstruction – papillary tumours, parasites, divisum.
    • Infections – mumps, cocksakie, mycoplasma pneumoniae
    • Genetic.

Pathogenesis.

  • Autodigestion of pancreatic substance by inappropriately activated enzymes(especially trypsin) due to
  • Pancreatic duct obstruction
  • Primary acinar cell injury – viruses, drugs, trauma, iscahemia
    Faulty transport of intracellular proenzymes to ducts – delivery of proenzymes to lysosomal compartment leads to activation within the cell.

Morphology

  • Ranges from trivial inflammation and oedema to severe extensive necrosis and haemorrhage
  • Microvasc leak–> oedema
  • Necrosis of fat by lipolytic enzymes
  • Acute inflammatory reaction
  • Proteolytic destruction of pancreatic parenchyma
  • Destruction of blood vessels (elastase)–> intersitial haemorrhage.
  • Acute necrotizing pancreatitis – red-black haemorrhage with white chalky fat necrosis interspersed.

 

Complications / sequelae.

  • Early:
    • Renal failure
    • HypoCa
    • ARDS
    • Shock
    • Sepsis
    • DIC
    • Transient hyperglucose
  • Late- week 2-4
    • Pancreatic necrosis- lack of IV contrast enhancement in CT
    • Haemorrhage – from pancreatitis eroding nearby arteries–> GI bleed, intra abdominal bleed–>angiography + embolisation.
    • Pancreatic ascites – high amylase
    • Pancreatic pseudocyst and abscess
    • Fistula
    • Pleural effusion high in amylase
  • 6 weeks
    • Pseudocyst
  • Long-term outcome
    • The vast majority of patients with a mild to moderate episode of acute pancreatitis will make a full recovery with no long-term sequelae. Recurrent episodes of pancreatitis may occur, particularly if there has been any long-term pancreatic ductular damage. Patients with more severe acute pancreatitis may become pancreatic insufficient both with respect to exocrine (malabsorption) and endocrine function (diabetes).

Ranson’s criteria

Form a clinical prediction rule for predicting the severity of acute pancreatitis.

For non-gallstone pancreatitis, the parameters are.

  • At admission:
    • Age in years > 55 years
    • White blood cell count > 16000 cells/mm3
    • Blood glucose > 10 mmol/L (> 200 mg/dL)
    • Serum AST > 250 IU/L
    • Serum LDH > 350 IU/L
  • Within 48 hours:
    • Serum calcium < 2.0 mmol/L (< 8.0 mg/dL)
    • Hematocrit fall > 10%
    • Oxygen (hypoxemia PaO2 < 60 mmHg)
    • BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration
    • Base deficit (negative base excess) > 4 mEq/L
    • Sequestration of fluids > 6 L
  • The criterion for point assignment is that a certain breakpoint be met at anytime during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to non-gallstone pancreatitis.

For gallstone pancreatitis, the parameters are:

  • At admission:
    • Age in years > 70 years
    • White blood cell count > 18000 cells/mm3
    • Blood glucose > 12.2 mmol/L (> 220 mg/dL)
    • Serum AST > 250 IU/L
    • Serum LDH > 400 IU/L
  • Within 48 hours:
    • Serum calcium < 2.0 mmol/L (< 8.0 mg/dL)
    • Hematocrit fall > 10%
    • Oxygen (hypoxemia PaO2 < 60 mmHg)
    • BUN increased by 0.7 or more mmol/L (2 or more mg/dL) after IV fluid hydration
    • Base deficit (negative base excess) > 5 mEq/L
    • Sequestration of fluids > 4 L
  • If the score ≥ 3, severe pancreatitis likely.
    If the score < 3, severe pancreatitis is unlikely
    Or

    • Score 0 to 2 : 2% mortality
    • Score 3 to 4 : 15% mortality
    • Score 5 to 6 : 40% mortality
    • Score 7 to 8 : 100% mortality
  • At admission “GA LAW” (GA is abbreviation for the U.S. state of Georgia): Glucose >200, AST >250, LDH >350, Age >55 y.o., WBC >16000
  • initial 48 hours “C & HOBBS” (Calvin and Hobbes):
    Calcium < 8 , Hct drop > 10% , Oxygen < 60 mm , BUN > 5 , Base deficit > 4 , Sequestration of fluid > 6L

 

Chronic pancreatitis:

  • Alcohol(60-80%), hereditary(trypsin defect, cystic fibrosis), idiopathic(40%), trauma

Pathogenesis.

  • Ductal obstruction by concretions – calcification of ductal plugs.
  • Toxic metabolic – toxin–> lipid acumulation in acinar cell–> acinar cell death–> fibrosis
  • Oxidative stress – alcohol and toxins –> lipid oxidation –> chemokines –> inflammation and fibrosis, fusion of zymogens with lysosomes, acinar cell necrosis.
  • Necrosis – fibrosis. Repeat episodes of acute panceratitis leading to loss of parenchyma and fibrosis

Complications.

  • Steatorrhoea:  Enzyme supplements + low fat diet.
  • DM: Usually difficult to control. Quick progress from OHA to insulin.
  • Pseudocyst(fluid collection with granulation tissue surrounding it)- can arise during the attack or silently. Can expand and block CBD or duodenum, can rupture, bleed or get infected. If more than 6cm diameter and present for >6wks, usually can drain endoscopically using a plastic stent. Otherwise surgical drainage.
  • Ascites, occasional pleural effusion: the fluid will have high amylase content.

 

Diabetes mellitus

Type 1 Type 2
Pathogenesis. Islet B cell destruction by T lymphocytes and autoantibodies are also present, prone to other autoimmune disorder Insulin resistance followed by insulin insufficiency
Complications Acute: Hypoglycaemia, ketoacidosis.Long Term: Micro and macro vascular complications Long Term: Micro and macro vascular complications
  • Polyuria, polydipsia, unexplained weightloss, visual blurring, genital thrush, lethargy AND raised venous blood glucose(>7mmol/L fasting or >11.1 random) detected once. OR raised BSL twice under same criteria or impaired oral glucose tolerance test(2hr value>11.1)
  • Type 1 vs 2: Do C peptide, antiGAD, anti islet Ab. Check for ketones in urine(more sinister than glucose)
  • Complications
    • Microvascular
      • Peripheral neuropathy
      • Nephropathy
      • Retinopathy, cataracts
      • Autonomic neuropathy – gastroparesis, postural hypotension, erectile dysfunction
    • Macrovascular/atherosclerosis
      • Happens earlier, more extensive than normal population.
      • IHD
      • PVD
      • Cerebrovascular- Stroke
      • Qs- previous MI, stroke, TIA(visual loss, weakness), angina, SOBOE, stents, bypass, lipid levels, BP,