Renal 4a Flashcards
renal anatomy
highly vascularized tissue surrounded by adipose and connective tissue capsule
functional unit =
nephron
_____nephrons per kidney
1 million
nephron anatomy
glomerulus + tubule, and associated capillaries
nephrons create ___ from blood
filtrate
useful substances are____ and returned to blood
reabsorbed
other substances (toxins, drug metabolites selectively ____
into tubule to exit the body as urine
porous membrane with large surface area allows for____
water/ solutes to be filtered
what anatomy allows for glomerular filtration
- fenestrasted endothelium (gaps)
- basment membrane
- podocytes with foot processes and filtration silts
(only capillary bed fed AND drained by arterioles)
filtrate =
plasma- proteins
(entire plasma volume filtered 60 times each day! )
Glomerular filtration is a passive process driven by
hydrostatic pressure
-higher than other capillaries (55mmHg)
intrinsic control (autoregulation)
maintains constant GFR when MAP fluctuates (mean arterial pressure)
-Anything that affects BP or blood volume can impact GFR
-healthy kidneys maintain GFR; diseased kidneys cannot
extrinsic control )nervous system, endocrine)
Epi/ NE (neural), renin-angiotensin-aldosterone system (hormonal) indirectly regulates GFR by maintaining systemic BP, drives filtration to kidneys
increase in BP leads to ____
constriction of afferent arterioles which decreases flow to glomerulus
-GFR constant, protect glomeruli from damaging high BP
Decrease in BP leads to
dilation of afferent arterioles which increases flow of glomerulus
-helps maintain normal GFR when BP
Juxtaglomerular apparatus (JGA)
made up of :
-macula densa cells- of ascending limb of nephron loop
-extraglomerular mesangial cells
-granular cells
importance in regulation of filtrate formation and blood pressure
granular (jextaglomerular cells)
smooth muscle cells of afferent arteriole
mechanoreception: sense BP
secrete renin
macula densa
chemoreception: sense NaCl content of filtrate (indicate whether flow rate is too high or too low)
mesangial cells
modified SM cells, can contract to reduce surface area for filtration
allow communication between other 2 cell types
If GFR too high
macula densa cells sense increased NaCl in filtrate
signal to granular cells to constrict afferent arteriole
if GFR too low
too little NaCl sense by macular densa cells
signal granular cells to relax afferent arteriole
acute kidney injury
-sudden onset. may resolve or progress to chronic
chronic kidney injury
progressive damage, leads to kidney failure
kidney injury determined by
imaging
urinalysis
renal clearance
biopsy
Normal urine
-95% water and 5% solutes
-nitrogenous wastes: urea, uric acid and creatinine
-other norrmla solutes: Na, K, PO4, SO4, Ca, Mg, HCO
-pH 6.0 (range 4.6- 8.0 )
abnormal urine- albuminuria
damage to filtration membrane - too much albumin
glucosuria:
hyperglycemia, too much sugar in blood
hematuria
damage to filtration membrane; bleeding in urinary tract, blood in urine
renal clearance
volume of plasma cleared of a particular substance in a given time (1 min)
RC= GFR= 125 mL/ min
renal clearance test used to :
determine GFR
Detect glomerular damage
follow the progress of renal disease
general mechanisms of acute kidney injury
-vascular basis or tubular basis
vascular basis
afferent arteriole constriction OR efferent arteriole dilation
-decrease in renal perfusion
-decrease GFR
caused by ischemia, hypoxia in renal medulla
tubular basis
damaged cells –> cellular debris
genereal mechanisms of acute kidnety of tubule
incr intratubular pressure affects filtration upstream
decr GFR
damaged cells -> filtrate leaks out of tubule
manifestation of acute kidney injury
all result from decreased GFR
Fatigue, malaise - from impaired waste clearance
dyspnea, orthopnea
peripheral edema
-altered mental status -prolonged impairment of excretory fxn
-azotemia
Azotemia
build up of nitrogenous wastes in blood
-elevated ratio BUN (blood urine nitrogen level: creatinine
tx for acute kidney injury
tx underlying reason for kidney damage
tubular cells regenerate ->
nephron fxn return to normal
chronic kidney dx progresses to
renal failure
renal failure
-irreversible loss of nephrons
-greater burden on remaining nephrons -> hyperfiltration (local htn)
-glomerular sclerosis
-increase rate of nephron loss, glomerular scarring
uremia
inadequate renal fxn
-functional reserve of nephrons lost
-s &S of chronic kidney dx
functional reserve
kidneys can lose about 50% of nephrons before impairment
(reason why healthy ppl can donate a kidney)
mechanism of uremia
- retention of products that are normally exerted ( nitrogenous wastes)
- normal renal hormones over-secreted (compensation for low GFR)
- Loss of normal kidney products (vit D, erythropoietin)
hypernatremia and water retention
decr ability to excrete water and Na+
-made worse by dietary Na+
-htn, edema, hrt failure worsened
hyperkalemia
decr GFR leads to incr aldosterone -> K+ retention
metabolic acidosis
decr ability to excrete acid (H+, NH4+)
-put pt at risk of crisis in case of vommiting/ diarrhea)
mineral and bone tissue (uremia)
decr vit D production, decr Ca2+ absorbed in gut
retention of phosphate
-inadequate bone mineralization=
osteomalacia; cant rebuild bone but can break it down normally
CV and pulmonary manifestations of uremia
htn, pulmonary edema
decr GFR -> increases secretion of renin which incr blood volume and BP
Neuromuscular effects of uremia
mild: impaired concentration, memory loss
sever: asterixis (jerking of hands/wrists), seizures, coma
-altered nerve conduction (from abnormal K+ and Na+ levels)
endocrine effects of uremia
females: low estrogen, amenorrhea (absence of menstruation), infertility
men: low testosterone, impotence (inability for a man to achieve erection of orgasm), low sperm count
-metabolism of insulin impaired (good for dm)
derm manifestation of uremia
pallor (anemia)
-hyperpigmentation (accumulated pigmented metabolites)
-hematomas (clotting abnormalities)
Causes of chronic kidney dx
-DM
-HTN
-Glomerulonephritis
-pyelonephritis
-polycystic kidney dx
-toxic nephropathy
-SLE
Diabetes and kidney dx=
diabetic nephropathy
Diabetic nephropathy characteristic changes
glomerulus enlarges
-alter filtration directly:
basement membrane thickens
loss of podocytes
-affect blood flow-> alters filtration:
mesangial cells proliferate
arteriole vasoconstriction
htn and kidney dx
prolonged constriction of afferent arterioles (to regulate GFR)
-Hypertrophy of VSM cells in affernt arteriole
-narrowed vessel -> ischemia
injury to endothelial cells
-enhances vascontriction
-promotes VSM hypertrophy
glomerular sclerosis (scarring)
-decr GFR
htn ____ kidney damage and kidney damage______ htn
promotes, promotes
Glomerulonephritis
damage to glomerular capillary wall. altering filtration
-infiltration of inflamm cells
contraction of mesengial cells
decr GFR
Na+ and water retention
edema, htn, hematuria, proteinuria
acute gn
abrupt onset on hematuria, proteinuria, decr GFR, Na+ and water retention
-infectious dx, often involves autoantbodies, deposition of immune complexes in glomerulus
chronic gn
persistent urinary abnormalities with progressive decline in renal fxn
nephrotic syndrome
proteinuria, hyperlipidemia, edema
-target podocytes
pyelonephritis
inflammation due to bacterial infection
-ascedning UTI
-inflammation
-tubular obstruction and damage
-interstitial edema
more common in females (bc shorter ureters)
pyelonephritis pathogens
KEEPS
Klebsiella, E. coli, enterococcus, pseudomonas, staphylococcus
urine findings:
WBC in urine (incr blood count in blood)
-hematuria (maybe)
-foul-smell
-bacterial culture (+)
polycystic kidney dx
-genetic condition:
95% inherited (autosomal dominant)
PKD1, PKD2, PKD3 mutation
-dysfunctional Ca 2+ channels on epithelial cells:
abnormal Ca2+ entry disrupts signaling
_____develops cysts and abundance of cysyts ____tubules and organ architecture
nephrons, distorts
polycystic kidney dx affecting other epithelial cells
brain-> berry aneurysms (death)
liver-> cyst formation
heart-> valvular dysfxn
seminal vesicles -> decreased sperm motility, infertility
(severity depends on mutation)
manifestation of polycystic kidney dx
proteinuria: damages filtration membrane leaks protein
htn: compressed renal vasculature activates RAAS
Hematuria: altered renal vasculature + damages filtration
pain: inflammation if cysts begin harboring bacteria
polycystic kidney dx diagnosed by
Imaging CT, MRI, ultrasounds
Genetic testing (less common)
toxic nephropathy
=nephrotoxicity
damage induced by chemicals or drugs
-distal tubular cell injury
-impaired mitochondrial fxn -> incr oxidative stress and free radicals
-impaired ability to concentrate urine
-hematuria, pain
-damage resolved if drug stopped
kidneys are vulnerable to drugs bc:
- they receive 25% of cardiac output, exposed to large amounts of chemical in blood
- hyperosmotic medulla allows concentration of drugs in kidney interstitium
- kidneys are common site of exertion; any renal insufficiency leads to the accumulation of the drug
common classes of drugs that cause nephropathy
-pain relievers (naproxen)
-antimicrobials (pcn)
-psychiatric drugs
-cancer tx (methotrexate)
-cholesterol lowering drugs (statins)
SLE and kidney dx - lupus nephritis
development of autoantibodies targeting glomerulus or tubule
-glomerular sclerosis
can occur with other autoimmune conditions: goodpasture syndrome (antibodies attack lungs and kidneys) or
progressive systemic sclerosis (of vasculature)
progressive kidney damage , loss of functional nephrons=
renal failure
med treatments for kidney dx
-treat underlying condition
htn, hrt failure= diuretics
autoimmune= immunosuppressors
infection= antimicrobials
lifestyle tx
dietary regulation of
protein
k+ and na+
fluids
transplant
better tissue matching and immunosuppresent tx, prevent rejection
-limited by donor avalibility
dialysis
main tx
cannot replace hormone fxn of kidney
