Pancreas, exocrine dysfunction

CT may demonstrate an atrophic, fatty pancreas with heterogeneous attenuation. Areas of low attenuation will correspond to cysts, while areas of high attenuation will represent calcifications. Partial or total fatty and fibrous replacement are also commonly seen in these patients. There may be a correlation between the degree of fatty infiltration and the pancreatic exocrine dysfunction (Feigelson et al. 2000). 

Characterised by sideroblastic anaemia and exocrine pancreas dysfunction. Usually fatal in infancy. The few patients who survive into adulthood often develop symptoms of Kearns-Sayre syndrome. It is very rare less than 100 cases have been reported. 

Initially, most of the adverse effects seen with zidovudine use (in particular hematological effects) were attributed to interference with cellular DNA replication. However, DNA replication also occurs in mitochondria. Mitochondrial DNA encodes some of the enzymes used for oxidative phosphorylation. Only recently has it been hjrpothesized that inhibition of this pathway could lead to mitochondrial toxicity and be responsible for most of the toxicity seen with NRTIs, including polyneuropathy, myopathy, cardiomyopathy, steatosis, lactic acidosis, exocrine pancreas failure, bone marrow failure, and proximal tubular dysfunction (11). These adverse effects are also a compilation of the clinical features seen in several genetic mitochondrial cytopathies. 

The pancreas is uniquely susceptible to high concentrations of ethanol, which can induce an acute inflammatory response characterized by release of amylase into the circulation. If severe or if this evolves into chronic pancreatitis it may lead to autodigestion by exocrine enzymes and ultimately to secondary endocrine dysfunction. 

On US, the pancreas with CF is characteristically of an echogenic texture secondary to fatty infiltration (Fig. 4.17). An enlarged pancreas may be seen initially with a subsequent atrophy later in life. Pancreatic duct dilatation and calcifications may be seen. Small cysts (anechoic areas) without vascular communication can be identified. Although a hyperechogenic pancreas is very typical of CF, some other diseases such as Schwachman-Diamond syndrome (exocrine pancreas insufficiency associated with bone marrow dysfunction, cyclic neutropenia, metaphyseal diastasis and growth retardation), hemosiderosis, chronic pancreatitis, and administration of steroids may also reveal this feature (Feigelson et al. 2000). 

To further characterize the toxicity and investigate its possible mechanism, a 14-day time-course study in the rat was conducted to allow for the observation of the lesion development and progression (Brenneman et al., 2014). Light microscopic (i.e., histochemical and IHC with quantification) and ultrastructural (i.e., TEM) examination showed that the injury appeared to originate as degeneration and loss of endothelial cells in the capillaries at the exocrine-endocrine interface. This injury was not associated with any increases in traditional or exploratory serum biomarkers of exocrine injury nor any evidence of endocrine dysfunction as assessed via an OGTT however, it was associated with an increase in EMPs that was not pancreas specific. 

Two diseases causing steatorrhea deserve further attention cystic fibrosis and sprue. Cystic fibrosis is a hereditary dysfunction of the mucous and serous exocrine glands (lung, pancreas, salivary gland, sweat glands, etc.) and is sometimes associated with cirrhosis of the liver. The disease has been described mainly in whites, rarely in Negroes. Cystic fibrosis is probably transmitted by an autosomal recessive mammalian gene. 

The pancreas serves as a secretory- (exocrine) and hormone- (endocrine) producing organ. Exocrine functions are difficult to assess in clinical studies in healthy infants but, as noted above, can be assessed by directly quantifying lumenal concentrations of enzymes and bicarbonate before and after a stimulus. It is only when pancreatic exocrine secretion is dramatically decreased that a deceleration of growth velocity occurs (Huynh and Couper, 2000). Severe pancreatic insufficiency can be monitored by measnring fat or certain enzymes (e.g., trypsin) in stools. Pancreatic endocrine dysfunction is most often manifested as diabetes, which can be assessed by obtaining serum insulin concentrations, blood, and urine glucose (Huynh and Couper, 2000). 

Pigmentary retinopathy Optic atrophy Hepatic failure Tubular dysfunction Diabetes insipidus Delayed puberty Hypothyroidism Hy popa r athy r 0 idis m Diabetes mellilus Exocrine pancreas dysfunction Primary ovarian dysfunction Diarrhoea (villous atrophy)... 

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