diabetic nephropathy and its pathophysiology Flashcards
diabetic nephropathy is the leading cause of
end stage renal failure in the developed world
diabetic nephropathy is also known as
kimmelstein-wilson nodules or nodular glomeruloscelrosis
general overview of diabetic nephropathy
progressive kidney disease caused by damage to the capillaries in the kidney glomeruli, characterised by nephrotic syndrome and diffuse scarring of the glomeruli
each kidney has millions of
nephrons each of which are supplied by a tiny capillary bed called a glomeruli
the arteriole approaching the glomeruli is called the
afferent arteriole
the arteriole exiting the glomeruli is called the
efferent arteriole
glomeruli are
tiny cluster of capillaries which are physically supported by messangial cells
when blood is filtered it moves through
the endothelium lining the capillary then through the basement membrane then through the epithelium lining the nephron and then finally into the nephron itself where it is called a filtrate
the endothelium has
pores that keeps cells from entering the filtrate
the basement membrane is
negatively charged which repels other negatively charged molecules and proteins such as albumin preventing it from entering the filtrate
the epithelium has
podocytes which create filtration slits via there foot processes
in diabetes mellitus
there is excess glucose in the blood so when the blood gets filtered through the kidney some of the excess glucose spills into the urine causing glycosuria
also when there is excess glucose in the blood it starts to
stick to proteins in a process called non-enzymatic glycation
because glucose can get through the endothelium
in hyperglycaemic states non-enzymatic glycation can involve the basement membrane of small blood vessels which makes it thicker
the process of non-enzymatic glycation of the basement membrane particularly affects the
efferent arteriole in a process called hyaline arteriosclerosis
hyaline arteriosclerosis causes
narrowing and obstruction making it difficult for blood to leave the glomerulus which increase the pressure in the glomerulus resulting in the dilation of the afferent arteriole
dilation of the afferent arteriole results in
more blood entering the glomerulus and increases the pressure even more
the increased pressure within the glomerulus causes
an increase in the glomerular filtration rate (the blood filtered through the glomerulus in one minute)
the increased glomerular filtration rate
is the first step in diabetic nephropathy and is called HYPERFILTRATION
in response to the hyper filtration the
supporting messangial cells secrete more structural matrix which expands the size of the glomerulus
the expansion in the size of the glomerulus can result in the
formation of nodules called KIMMELSTEIN- WILSON NODULES
thickening of the basement membrane increases its
permeability allowing proteins which would otherwise be filtered out to pass through into the filtrate because the filtration slits of the podocyte foot processes have increased in size
eventually
all these changes damage the glomerulus so much that it is no longer able to filter blood properly and the glomerulus filtration rate decreases
why is diabetic nephropathy so dangerous
because during the hyper filtration stage it is silent and only causes symptoms when it has caused end stage renal failure where there is a massive reduction in the glomeruli filtration rate
whats paramount in monitoring diabetes
urinalysis
microalbunaemia
30-300mg of albumin excreted in one day indicates that diabetic enphropathy has begun
macroalbunaemia
greater than 300mg of albumin ecreteted in one day indicates that the diabetic nephropathy is well established
diabetic nephropathy
is a progressive complication which can be significantly slowed down but never reversed or completely stopped
what is essential in the management of diabetic nephropathy
managing hypertension and hyperglycaemia
management of hypertension in anyone with diabetes
ACE INHIBITORS because not only does it control the hypertension but it also reduces the constriction of the efferent arteriole
if ACE inhibitor are contra-indicated
then use an angiotensin receptor blocker
consequences of diabetic nephropathy
- development of hypertension
- accelerated vascular disease
if untreated diabetic nephropathy causes
a reduction in the glomerular filtration rate of 1ml/min/month
all patients over the age of
12 should be screened for diabetic nephropathy using urinary albumin creatinine ratio (urine ACR)
microalbunaemia values
urine ACR for males: 2.5-25 for females 3.5-35
24hour alumni levels: 30-300mg
macroalbunaemia values
urine ACR greater than 25 for males greater than 35 for females
24hour albumin levels: greater than 300mg
blood pressure should be maintained below
130/80mmHg
