endocrine pancreas Flashcards
4 main types of islands of langerhans cells
Beta cells - insulin
alpha cells - glucagon
delta cells - somatostatin
PP cells - secretes pancreatic polypeptide
2 minor cell types of the normal endocrine pancreas
D1 - vasoactive intestinal polypeptide (VIP), induces glycogenolyss and hyperglycaemia
enterochromaffin cells - serotonin
types of diabetes
dibetes type 1 diabetes type 2 hypoglycaemia diabetic ketaacidosis hyperglycaemic hyperosmolar state
diabetes mellitus
common disease
family of metabolic disease - common feature is hyperglycaemia
type 1 diabetets
autoimmune
B cell destruction - total or near insulin deficiency
usually ages <20 at onset
type 2 diabetes
peripheral resistance to insulin and subsequent inadequate insulin secretion
90-95% of cases
usually adult onset but occasionally seen in younger people
impaired glucose tolerance
precursor to T2DM
may be reversible with diet/lifestyle change
elevated plasma glucose but not in diagnostic range
25% develop T2DM within 5 years
other causes of diabetes
- drugs - glucoocorticoids, thyroid hormone, interferon, pancreatitis, pancreatomy, trauma, neoplasia, cystic fibrosis, haemochromatosis
- gestational DM
- endocrinopathies - acromegaly, cushings, hyperthyroidism, phaeochromocytoma, glucagonoma
- genetic defects in B cell function
- infections - rubella, CMV, coxsackie B
- genetic syndromes - downs, klinefelters, turner, prayer willi, others
latent autoimmune diabetes
maturity onset diabetes of the young
have islet autoantibodies
clinical presentation of type 1
indolent but silent onset over years, often sudden presentation with acute severe hyperglycaemia (decompensation)
- polyuria, polydipsia, polyphagia, subsequently DKA
clinical presentation of type 1
indolent but silent onset over years, often sudden presentation with acute severe hyperglycaemia (decompensation)
- polyuria, polydipsia, polyphagia, subsequently DKA
clinical presentation of type 1
indolent but silent onset over years, often sudden presentation with acute severe hyperglycaemia (decompensation)
- polyuria, polydipsia, polyphagia, subsequently DKA
clinical presentation of type 1
indolent but silent onset over years, often sudden presentation with acute severe hyperglycaemia (decompensation)
- polyuria, polydipsia, polyphagia, subsequently DKA
clinical presentation of type 2
unexplained fatigue, dizziness, blurred vision, symptoms often mild and come/go depending on BSL
often asymptomatic. may becomes hyperosmolar non-ketonic state if BSL very high
pathogenesis of type 1
develops in childhood and manifest around puberty
without exogenous insulin they becomes ketotic causing coma and death
interplay of genetics and environment
B cell destruction follows loss of self tolerance for T cells specific islet antigens - insulin receptor, GAD, others - auto active T cells are not removed, are able to attack islets
pathogenesis of type 2
interplay of genetics and environment
develops in adulthood, slow progression initially high insulin but peripheral insulin resistance, later low insulin due to B cell dysfunction
insulin sensitivity decreases in T2DM because
free fatty acids
adipokines - secreted by adipocytes
inflammation (pro-inflammatory cytokines secreted in response to nutrient excess)
gestational diabetes pathogenesis
- patients with pre existing DM
- pregnancy may result in impaired glucose tolerance
- higher rates in obese women
- associated with increased risk of stillbirth, congenital malformations in the foetus, especially macrosomia (high birth weight)
- laos associated with increased risk of obesity and diabetes later in life (for mother and baby)
- typically resolves following delivery
acute diabetic ketacidosis
usually T1DM
insufficient insulin - initial presentation or under administration of exogenous insulin (ie. patient not taking enough insulin)
- increased needs due to infection, illness, drugs etc. increased adrenaline secretion blocks insulin and stimulates glucagon
acute ketoacidosis causes
hyperglycaemia
osmotic diuresis and dehydration
activates ketogenic pathway, increased fat breakdown, which leads to increase ketone bodies as a byproduct
if urinary excretion is composed, systemic ketoacidosis
symptoms of acute diabetic ketoacidosis
fatigue, nausea, vomiting, abdominal pain, ketotic breath, laboured breathing (kussmaul), eventually loss of consciousness and coma
treating acute diabetic ketoacidosis
correct insulin deficiency, correct metabolic acidosis and treat precipitating factors
rare in T2DM
cosequences of acute diabetic ketoacidosis
hyperosmolar hyper osmotic state
usually in T2DM
severe dehydration due to severe osmotic diuresis due to hyperglycaemia
absence of ketosis, mild or no metabolic acidosis
hypoglycaemia
- over treatment of hyperglycaemia
- dizziness, tachycardia, confusion, palpitations, potentially loss of consciousness and death
- always consider hypo and hyperglycaemia in an unconscious or drowsy patient
chronic consequences of diabetes
- impaired immunity
- CVD
- cerebrovascular disease
- eye issues
- peripheral nervous system neuropathy
- diabetic nephropathy, glomerulosclerosis, pyelonephritis and papillary necrosis, arteriosclerosis, nephrosclerosis
- gangrene and ulceration
macroangiopathy
atherosclerosis
ischaemic heart disease
cerebrovascular disease
peripheral vascular disease (esp. lower limb ischaemia)
microangiopathy
retinopathy, nephropathy and neuropathy
diffuse thickening of basement membranes of capillaries
- skin, muscle, retina, renal glomeruli and medullar as well as non-vascular structures and nerves
- vessels are leaky, plasma proteins escape
microangiopathy underlies many of more serious complications including diabetic neuropathy, retinopathy and some neuropathies
poor wound healing
predisposition to infection in diabetes
bacterial and fungal infections of skin, mucosal surfaces and urinary tract most common
impaired neutrophil function
abnormalities in chemotaxis, adhesion to endothelium , phagocytic capacity and microbicidal activity
impaired cytokine production by macrophages
impaired blood supply
glomerular leions in diabetic nephropathy
nodular glomerulosclerosis, diffused mesangial sclerosis, glomerular capillary basement membrane thickening
renal vascular lesions in diabetic nephropathy
diabetic microanggiopathy
renal artery atherosclerosis
tubular/parenchymal lesions in diabetic nephropathy
pyelonephritis and necrotising papillitis
glycogen/lipid vacuoles in tubules
