Flashcards in 8 ) Secondary nephropathies: gout, myeloma and diabetic nephropathy Deck (21)
what are the types pf gout nephropathy ?
there is acute and chronic
pathophysiology of acute gout nephropathy ?
deposition of uric acid crystals within the kidney medullary interstitum predominantly in collecting ducts. ALSO renal pelvis, or ureter.
This obstruction is usually bilateral, and patients follow the clinical course of acute kidney failure.
= oliguric and anuric
= most often in tumor lysis syndrome than gout
what is the etiology of hyperurecmia ?
idiopathic - aggregated by poor diet
secondary - decrease - uric acid secretion
by medications such as aspirin and loop diuretics
chronic renal insufficiency
enzyme deficisny in metabolism of purine
Lesch-Nyhan syndrome = X-linked deficit of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
phosphoribosyl pyrophosphate deficiency
diet rich in purine = red , meat and sea food
what is the pathophysiology in chronic gouty nephropathy ?
chronic tubulointerstitial nephritis, induced by deposition of monosodium urate crystals in the distal collecting ducts and the medullary interstitium (loop of henle as well as collecting ducts here)
what is a clinical feature of gouty nephropathy ?
uric acid nephorlithiasis
decrease production of urine
pain in joints
what is the diagnosis of chronic gout nephropathy ?
two of the following criteria :
atleast two attacks of painful joints
clear observation gout in podagra
presence of tophus
rapid response to colchicine within 48hrs of treatment initiation
definitive : presence of monosodium rate crystals seen in synovial fluid or tissues
serum uric acid
uric acid/ creatinine ratio is more than 1
us - renal calculi
kidney biopsy -
Polarized light microscopy: needle-shaped monosodium urate crystals that are negatively birefringent
tophus formation/ granuloma : large aggregations of urate crystals surrounded by an intense inflammatory reaction of macrophages,lymphocytes and large foreign body giant cels engulfing the crystals cortico-medullary junction and deep in the medulla
tubules distended by a collection of needle-like spaces which contained urate crystals
later becomes associated with the findings of
associated with hypertensive kidney disease: advanced arteriosclerosis, glomerulosclerosis,
and interstitial fibrosis.
what is the treatmnet of gouty nephropathy ?
lifestyle modification and dietary changes such as
purine free diet
achieve ideal BMI
nsaids - diclofenac , indomethacin
or cox -2 inhibitors - celecoxib
allopurinol - do not use it if there is an acute gout attack
can add colchicine to reduce the frequency of attacks
increase the urine output - 3l of water a day
increase the urine ph
by giving potassium citrate or sodium bicarbonate
if all above fails hemodialysis
who does multiple myeloma usually affects ?
and mainly they are men
renal failure is the second most frequent cause of death in multiple myeloma
WHAT ARE THE OTHER CLINICAL FEATURES OF mm ?
predominantly those of the myeloma
on bones - bone pain - back pain
cast nephropathy usually presents with acute kidney injury - oliguria due to urinary tract obstruction
the type of kidney disease presented by multiple myeloma can be classified into ?
primary amyloidosis - mesangial deposits
light chain cast nephropathy
distal tubular dysfunction
proximal tube dysfunction - acquired falconi syndrome = wasting of amino acids, glucose, phosphate, uric acid, and various ions
plasma cell infiltration
what is the pathophysiology of cast nephropathy ?
in multiple myelom aproximal tubular cells are overwhelmed and light chains
saturate the reabsorptive capacity
reach distal nephron, where they are directly toxic to epithelial cells; Bence Jones proteins combine with urinary glycoprotein (Tamm-Horsfall) under acidic conditions to form tubular casts that obstruct tubules
myeloma kidney or myeloma cast nephropathy generally refers to renal insufficiency caused by the tubulointerstitial damage that result
what is the diagnosis of MM ?
anemia normochromicand normocytic
proteinurea often light chain protein known as
bence jones protein
casts composed of
protein electrophoresis in urine or immunofixation
monoclonal light chain protein and TAMM horsfall protein secreted by the thick ascending limb of henle
light chains casts located within the distal tubules - ranging from needle shaped crystals to irregular polygonal shapes with sharp edges
several casts engulfed by giant cells
stain very minimal with PAS
mixed red and blue staining with masson trichrome stain
pct show acute tubular injuries - with the loss of apical briush border
IF staining of k light chain in casts
or granular dense material along the basement membrane
what increases the risk of myeloma nephropathy therefor can be used to manage the patients ?
Low urine flow = prevention of volume depletion (eg, using normal saline for volume expansion) to maintain a high urine flow rate
Elevation of luminal sodium chloride concentration (eg, due to a loop diuretic)
Increased intratubular calcium due to the hypercalcemia that often occurs secondary to bone lysis in multiple myeloma
how can we treate myeloma nephropathy ?
Plasma exchange may be tried to remove light chains.
Alkalinization of the urine to help change the net charge of the light chain and reduce charge interaction with Tamm-Horsfall mucoprotein may make the light chains more soluble.
Colchicine may be given to decrease secretion of Tamm-Horsfall mucoprotein into the lumen and to decrease the interaction with light chains, thus decreasing toxicity.
Loop diuretics may be avoided to prevent volume depletion and high distal sodium concentrations that can worsen myeloma-related kidney disease.
what is the characterisation of diabetic nephropathy ?
chronic condition developing over many years
by gradual increase in urinary albumin excretion - nephrotic syndrome
high blood pressure
absence of other renal tract disease
presence of diabetic retinopathy / neuropathy
what is the pathophysiology of diabetic nephrotphathy ?
hypertension which is a common comorbidity with
glycated enzymes - glucose attach to nitrogen molecules such as lysine = easing to schiff base
the shiff base goes into ketone - crosslinks between lysin and arginine - and if the cross linking occur collagen or basement membrane - damages - and get more damaged
increase protein kinase c - because increased
diacyl glycerol - because increase of glycolysis pathway - because increase of glucose
= increase vascular perm
also non enzymatic glycosylation of basement membrane - increasing the perm
vasoconstriction of the efferent arteriole - because of RASS - hyperglycemia causes a an activation of the RASS (maybe because of polyuria there is low fluid volume )
interglomerular hypertension - increase the GFR
the mesangium has extracellular matrix the collagen network which holds the capillary in place = they can cause the capillaries in the glomeruli to
constrict or dilate
and they have the ability to release cytokines in reaction to injury
the mesangium is going to react by releasing cytokines - leading to inflammation
and there is mesangial explanation - due to hypertrophy of the mesangium and proliferation
thickening of the basement membrane
there is increase in the mesangial matrix - firbin and collagen increase - leading to glomerulus atrophy and dysfunction
= leading to hyaline glomerulosclerosis =
which further narrows the vessels - hypertension , decrease in GFR
it affects both efferent and afferent arterioles
1) increase in GFR
2) proteinurea - mesangial expansion and increase in the matrix or the fenestra
because of injury to the tubules due to ischemia - collagen fibrils accumulate in the glomerulus - decrease the blood flow to the efferent arteriole and it supplies the tubules
4) decrease in GFR
what is the difference between hypertensive neproathy and diabetic nephropathy
hypertensive nephropathy is disease of the afferent arteriole
while diabetic nephropathy is more the disease of the mesngium
even though both start with high GFR
but it will not pass through a phase of protein urea because this is due to the contraction of the mesangial cells
however 3-5 is shared in common
hyaline glomeruscleorisis occurs in the afferent and efferent arterioles whilst in diabetic nephropathy while in hypertensive nephropathy it majorly affects the afferent arterioles
what are the clinical features of diabetic nephropathy ?
in type 1 its more severe
onset within 5-10 years
tye 2 - more than 10 years
first symptom is quite frequent urination - increase GFR - polyurea , polydipsia , polyphasgia ,
generally they are asymptomatic until they get to end stage renal disease
ureic polyneuropathy in later stages
diagnosis of diabetic nephropathy ?
first sign you see for diabetic nephropathy : albuminuea
moderate albuminurea = 30-300mg = cannot burin dipstick detected
its important because this is the time we can prevent
it can lead to severe albuminuria / nephrotic syndrome = more than 300mg = which is urine dipstick decade
which will lead to ESRD
GFR - high
then going low
creatinine is also a measure of GFR
it first is low then becomes high
earliest change - diffuse and thickened basement membrane
then mesangial hypercellularity
mesangium nodules or sclerosis - = known as kimmel stein wilson nodule
with time hyaline sclerosis of of glomeruli
risk factors increase DN ?
race - african american , mexican american
diabetic retiinopathy - because it usually occurs BEFRE diabetic nephropathy