Endocrine Pathology Flashcards
define diabetes mellitus
a chronic disorder of carbohydrates, fat and protein metabolism due to defective insulin secretory response, resulting in impaired carbohydrate, mainly glucose, use
what are the subtypes of primary diabetes?
type 1; insulin dependent diabetes mellitus
type 2; non-insulin dependent diabetes mellitus
what genetic abnormalities is diabetes associated with?
genetic defects of B-cell function;
including maturity onset diabetes of the young (MODY)
chromosomal abnormalities; 2, 7, 12
some mitochondrial DNA abnormalities
what is associated with secondary diabetes?
chronic pancreatitis
haemochromatosis
infectious; congenital rubella, cytomegalovirus
endocrinopathies; adrenal, pituitary tumours
congenital rubella
cytomegalovirus infection
drugs; corticosteroids, pentamidine, vacor
genetic disorders; downs syndrome
gestational diabetes mellitus
what are the clinical features of type 1 diabetes?
<20yrs onset typically has normal weight decreased blood insulin levels anti-islet cell antibodies in the blood ketoacidosis common
what are the clinical features of type 2 diabetes?
onset later in life, >30yrs typically obese insulin levels normal or increased ketoacidosis rare 90-100% concordance in twins no HLA association
what are the pathological features of type 1 diabetes?
frequently HLA-D linked autoimmune immunopathological mechanism inflammation or insulitis in the islet cells early on in the disease marked atrophy and fibrosis severe beta cell depletion
what are the pathological features of type 2 diabetes?
insulin resistance relative deficiency of insulin no inflammation in the islets of langerhans become focally atrophic amyloid proteins may be deposited only mild beta-cell depletion
describe normal insulin production in normal islet cells
glucose results in stimulation of insulin production
increasing levels of glucose in the blood are transported across the cell boundary by the GLUT-2 transport mechanism
increasing production of preproinsulin and proinsulin
insulin is released into the bloodstream
what are the normal effects of insulin on cells?
attaches to the insulin receptors increased production of glucose transport units increase in glucose uptake by the cell increased protein synthesis transfer of glucose into lipids
how does type 1 diabetes develop?
genetic deposition; HLA-linked gene environmental insult; viral infection direct damage to beta cells immune response develops against normal/altered beta cells increased beta cell destruction
what are the autoimmune factors that are associated with type 1 diabetes?
pre-clinical phase of islet destruction; insulitis presence of CD8 and CD9-positive macrophages increase in class 1 major histocompatibility complex molecules aberrant expression of class 2 MCH 70-80%; islet cell autoantibodies in their circulation 10-20%; other autoimmune diseases, SLE, RA
how is obesity a risk factors for type 2 diabetes?
the peripheral tissues; muscle and fat, develop insulin resistance
unable to adequately utilise the glucose present in the blood
combined with deranged insulin secretion
= hyperglycaemia
the beta cells are unable to produce enough insulin to adequately lower the blood glucose and become exhausted
what are the features of deranged insulin secretion?
loss of the normal pulsatile oscillating secretion of insulin within the blood
abnormal response to hyperglycaemia
possibility of a genetic vulnerability to hyperglycaemia
what are the pathological complications of diabetes?
non-enzymatic glycolysation; glucose becomes linked with haemoglobin or becomes linked to collagen and form advanced glycosylation end products (AGE)
intracellular hyperglycaemia; disturbances of the polyol pathways
accumulation of sorbitol and fructose within the cells
what are the clinical complication of diabetes?
brain; disease of small vessels
eyes; cataracts and glaucoma
MI
diseases of the small vessels of the peripheries; gangrene of the feet and toes
describe the complications of diabetes in the pancreas
more common in type 1 diabetes inflammatory cells/leucocytes are present in the islets; insulitis beta cell degranulation reduction in the islet cell mass amyloid deposition may occur
describe atherosclerosis in diabetes
occurs more rapidly in diabetes
atherosclerotic plaques are complicated by ulceration
marked fibrosis and calcification
origin of many of the vessels are occluded
what are the causes of vascular complications in diabetes?
elevated blood lipid levels
low levels of HDL
increased thromboxane A2 activity; increased platelet stickiness
hyaline arteriosclerosis
describe the complications of diabetes in the kidneys
renal artery narrowing; renal ischaemia and hypertension
diabetic microangiopathy
describe diabetic microangiopathy
diffuse thickening of the basement membrane of small capillaries;
glomerular lesions
vascular lesions
pyelonephritis and necrotising papillitis
describe the glomerular lesions of diabetic microangiopathy
basement membrane thickening; the normal structures of an internal lamina densa, with outer laminar rara is lost
uniform thickening
increased deposition of glycjogenated collagen proteins
diffuse glomerulosclerosis; increase in mesangial matrix and narrowing of the capillary loops
nodular glomerulosclerosis; deposition of abnormal collagen fibres, result in a decrease in glomerular blood flow and development of renal failure
describe the vascular lesions of diabetic microangiopathy
hyaline arteriosclerosis; narrowing of the afferent and efferent arterioles due to deposition of hyaline material, replacing the muscle of the media
describe pyelonephritis and necrotising papillitis associated with diabetic microangiopathy
acute pyelonephritis; mottled appearance, hyperaemia, inflammation and necrosis
tubules filled with polymorphs and inflammatory debris
necrotising papillitis; inflammation, associated ischaemia, necrosis of the papilla, passes into the ureter and may cause obstruction
what are the neurological complications associated with diabetes mellitus?
peripheral symmetrical neuropathy may involve the sensory, motor or autonomic nervous system
gangrene; inadequately supply of nerves with blood, resulting in nerve damage and cerebral haemorrhage
cerebral haemorrhage; microangiopathy
cerebral infarction; loss of blood supply, involvement of vessels within the brain, embolism from atherosclerotic neck vessels
what are the skin complications of diabetes?
recurrent infections; bacterial, fungal
necrobiosis lipodica diabeticorum
granuloma annulare
what are the pregnancy complications of diabetes?
increased chance of pre-elcamptic toxaemia
large and immature babies
risk of neonatal hypoglycaemia
describe the thyroid gland
develops embryologically from a down-growth of the pharyngeal epithelium
descends lower in the neck during embryological development
15-20g
very vascular organ
nerve supply; cervical sympathetic nerves
act on blood vessels to influence secretions
describe the histology of the thyroid gland
thyroid follicles lined by thyroid follicular epithelium
the follicles contain colloid; the store for thyroid hormone
describe the physiology of the thyroid gland
TSH released by the pituitary gland
following the action of trophic factors from the hypothalamus in the base of the brain
TSH acts on thyroid tissue to release T4/thyroxine and smaller amounts of T3/triiodothyronine
T3 and T4 are released into the circulation; reversibly bound to thyroxine-binding globulin/TBG
T3 and T4 have a negative effects on TSH and TRH
describe multi nodular goitre formation
a progressive cycle of hyperplasia, degeneration and fibrosis
the gland becomes overall enlarged and nodular
cystic change within the follicles
surrounded by fibrosis
describe hyperthyroidism
a hyper metabolic state characterised by increased levels of thyroid hormones and gland hyperfunction
causes; diffuse hyperplasia thyroiditis hyper-functioning goitre over-ingestion of hormone
what conditions are associated with hyperthyroidism?
diffuse toxic hyperplasia (Grave's) toxic multi nodular goitre toxic adenoma acute.subacute thyroiditis thyroid stimulating hormone secreting pituitary hormone neonatal thyrotoxicosis in maternal struma ovarii; ovarian teratomatous thyroid iatrogenic (exogenous) hyperthyroidism
what are the clinical features of hyperthyroidism?
overactivity of the sympathetic nervous system
cardiac; output increased, tachycardia, palpitations, arrhythmias, congestive heart failure
neuromuscular; atrophy of musculoskeletal tissues, tremor, hyperactivity, emotional lability, anxiety
osteoporosis
skin; warm and moist, increased sweating
GI; increased appetite, weight loss, increased bowel motility
