The upper pole of each kidney is near the level of which vertebra?
12th thoracic
The kidneys process how much blood per minute?
Per day?
1 Liter (20% of total cardiac output)
1500L
What functions do the kidneys perform?
- Excrete metabolic waste
- Regulate electrolytes
- Buffer acid-base in blood
- Activate vitamin D
- Secrete renin
- Secrete erythropoietin
Structural and functional unit of the kidney:
consists of:
Nephron
- glomerular capsule
- proximal convoluted tubule
- loop of Henle
- distal convoluted tubule
- collecting duct
Capillary tuft surrounded by Bowman’s capsule:
Blood supply in and out:
Glomerulus
Blood IN via Afferent arteriole
Blood OUT via Efferent arteriole
What is the GFR?
Glomerulur filtration rate
blood filtration rate, utilizing pressure gradient btw afferent and efferent arterioles to drive filtration
Risk of CAKUT:
CAKUT - congenital abn of kidneys and urinary tract
1/3 of anomalies noted on prenatal US
predisposed adult HTN & CVD
40% of childhood end-stage renal failure
Failure of kidney(s) to develop to normal size/weight:
Renal hypoplasia
unilateral MC than bilateral
smaller kidney prone to infx & scarring
Kidneys fused at the upper or lower pole:
Horseshoe kidney
lower pole MC
often asx
infx may occur d/t urinary stasis
Abnormal location of one/both kidney(s):
Ectopic kidney
MC locations - lower abdomen, pelvis
Cystic lesions of the kidneys are (common/rare) and most are (asx/severe).
common
asx - found incidentally on imaging or post-mortem
T/F: Simple cysts predispose an individual to developing chronic renal failure and/or neoplasia.
False
mb multiple, but never as numerous as polycystic kidney dz
Autosomal recessive form of PKD:
ARPKD
childhood PKD
autosomal dominant - adult (ADPKD)
Histopathology of childhood PKD:
multiple large cysts
lined by flattened cuboidal epithelium
fibrotic intervening parenchyma
islands of bluish cartilage
T/F: The adult form of PKD is more commonly associated with concurrent liver cysts than is childhood PKD.
True
cysts not usu present at birth, develop slowly over time
assoc w/oxalate crystals in urine and cysts
Presumed mechanism for adult PKD:
Abnormal collagen and elastin that results in diminished integrity
Familial recurrence rate of ADPKD:
50%
Patients on ________ commonly form kidney cysts, and are at increased risk for _________________.
dialysis
renal cell carcinoma
Most forms of glomerular injury are found to be __________ mediated. Histo findings include:
immunologically
WBC infiltration
inflammatory cell infiltration
Proliferation of mesangial, endothelial and epithelial cells is (common/uncommon) in glomerular dz.
Common
In glomerular dz, thickening of the ___________ is a common and important finding.
basement membrane
usu d/t deposition of immune complexes on epithelial side of the membrane
Immune complexes are often the result of specific antibodies to the glomerular basement membrane aka:
anti-GBM antibodies
Glomerular dz’s presenting as nephrotic syndrome:
Lipoid nephrosis
Membranous glomerulopathy
Focal-segmental glomerulosclerosis
Nodular and diffuse glomerulosclerosis
Characteristic findings of nephrotic syndrome (4):
Proteinuria (>3 gm per 24 hrs.)
Decreased serum proteins
Increased serum lipid levels
Generalized edema
MC cause of nephrotic syndrome in children:
Peak incidence at ____ years.
lipoid nephrosis - 90% of cases
2-3 y.o.
Lipoid nephrosis accounts for ___% of adult nephrotic syndrome.
20-30%
Lipoid nephrosis exhibits _______________, in that _______ is the only protein commonly in the urine.
selective proteinuria
albumin
Minimal change dz (MCD) is characterized by:
effacement of the epithelial cell foot process (podocyte) and loss of the normal charge barrier
albumin selectively leaks out
proteinuria ensues
MC cause of adult nephrotic syndrome:
Membranous glomerulopathy (aka membranous glomerulosclerosis)
Etiology of most cases of membranous glomerulopathy:
unknown (idiopathic)
can develop via response to antigenic stimulation to infectious agent/toxin
Membranous glomerulopathy is known to follow infx, such as:
or drug therapy, such as:
Hep B Hep C Syphilis Malaria Schistosomiasis
gold therapy
Captopril
Tumors have been known to lead to membranous glomerulopathy, such as:
lung cancer
colon cancer
melanoma
lymphoma
In membranous glomerulopathy, the (capillary loops/loops of Henle) are usually (atrophied/thickened) and prominent.
capillary loops
thickened
Light microscopy findings in membranous glomerulopathy:
- diffuse thickening of basement membrane
* spiked appearance w/silver or Jones stain
Membranous glomerulopathy is generally a ____________ mediated disease in which deposits of __________ and _________ collect in the basement membrane.
immunologically
IgG and/or IgM
complement (usually C3)
_________________ is the MC cause of nephrotic syndrome in African-Americans.
Focal segmental glomerulosclerosis (FSGS)
and accts for 15% of nephrotic syndrome cases in adults and children (1/6 of cases)
T/F: Immune complexes are always in FSGS, pointing to the cause of dz.
False.
Immune complexes are not always seen and focal sclerosis appears to be idiopathic.
commonly seen in AIDS pts [d/t dz or drug toxicity; drugs like NSAIDs, lithium, interferon implicated]
T/F: In contrast to minimal change disease, patients with focal segmental glomerulosclerosis are far more likely to present with non-selective proteinuria.
True
clinical outcome often poor
inevitable renal failure
The hypercellularity of post-infectious glomerulonephritis is due to increased numbers of:
- epithelial, endothelial, and mesangial cells
* presence of neutrophils in/around the glomerular capillary loops
T/F: Rapidly progressive glomerulonephritis (RPGN) is a description, not a specific disease.
True
it can be seen d/t a variety of causes
only rarely seen as result streptococcal infx
MC cause of chronic renal failure in the US:
Thus it’s called:
DM
Diabetic nephropathy
In many diabetics, renal sx are (sudden/insidious) and findings include:
insidious - over 10-20 years
proteinuria
glycosuria
progressive decrease of renal function
Possible renal complications due to diabetes:
arteriosclerosis
glomerulosclerosis
pyelonephritis
renal failure
A commonly noted histologic change seen in patients who develop diabetic nephropathy:
glomerulosclerosis - generally appears several years after onset of DM
described as: nodular, diffuse, or mixed
Nodular glomerulosclerosis related to diabetes is referred to as:
Kimmelstiel-Wilson disease
The first abN lab in diabetic nephropathy is:
microalbuminuria
may also show glucose
late findings - elev serum creatinine and BUN
Etiology of primary amyloidosis:
Characterized by:
idiopathic
amyloid depositions in one or more organs
Histologically, amyloid appears:
Light microscopy:
pink
eosinophilic
acellular
homogenous
highly refractive
affinity for Congo red
With renal involvement, amyloid is first deposited in:
mesangium and capillary walls
eventually in glomerular & tubular BM
Pt undergoes a procedure, and starts to develop spontaneous periorbital ecchymosis without trauma to the face. What should be in your ddx?
Amyloidosis
UA of pts with amyloid dz shows:
protein
fatty casts
fat bodies
Characteristic amyloidosis finding w/electron microscopy:
fibrils within the amyloid deposition
non-branching filaments, 8-12nm wide, perpendicular to BM
Acute nephritis is characterized by the presence of:
- hematuria with red blood casts
- oliguria
- uremia
- varying degree of HTN
- minimal (no) proteinuria
MC cause worldwide of glomerulonephritis:
IgA nephropathy (aka Berger’s dz)
d/t marked hyper secretion of IgA in response to an antigenic stimulus)
T/F: Edema is most usually associated with nephritic syndrome.
False - not usually, if present it is mild.
Findings of nephritic syndrome:
PHAROH
- proteinuria
- hematuria
- azotemia (elev blood N)
- RBC casts (KEYNOTE)
- oliguria
- HTN (KEYNOTE)
IgA nephropathy is more common in pts with ________.
celiac dz
IgA nephropathy pts generally present with new onset hematuria within days of:
a respiratory, gastrointestinal or genitourinary infx
usu disappears in days, my recur for mos/yrs
50% renal failure @20yrs
Another dz state of IgA over-secretion, a hypersensitivity vasculitis involving blood vessel walls in the skin, kidneys and/or G.I. tract:
Henoch-Schonlein purpura
Exam findings in H-S purpura:
PE: skin lesions, jt tenderness
UA: hematuria
Skin bx: vasculitis
H-S purpura may occur at any age, but peak incidence is:
3-8 yrs
more severe sx/sequelae in adults
Mesangial deposits - if IgA could be:
If IgG:
IgA - H-S purpura OR IgA nephropathy
IgG - lupus nephritis
Primary or secondary immune-mediated renal disease characterized by inflammation of the glomeruli:
Glomerulonephritis
Glomerulonephritis may present with:
- isolated hematuria and/or proteinuria
- nephrotic syndrome,
- nephritic syndrome
- acute renal failure
- chronic renal failure
Non-proliferative glomerulonephritis is characterized by:
Frequently present with (nephritic/nephrotic) syndrome.
low numbers of cells (lack of hypercellularity) in glomeruli.
nephrOtic
(e.g. MCD, FSGS)
Proliferative glomerulonephritis is characterized by:
Often present with (nephritic/nephrotic) syndrome and can progress to end-stage renal failure in:
increased number of cells (hypercellularity) in the glomerulus.
Nephritic
weeks to years
MC cause of acute nephritic syndrome:
PSGN (post-streptococcal glomerulonephritis)
T/F: PSGN can follow strep throat or impetigo.
True
nephrogenic strain of group A beta-hemolytic strep
[compare to Rheumatic Heart Dz - pharynx strain only]
PSGN ssx:
1-2 wk latency after infx RBCs on UA possible casts fever chills HTN usu develops
T/F: Early abx intervention appears to significantly alter the course of PSGN.
False
this suggests genetic disposition to certain strains
Light microscopy of the glomeruli affected by PSGN usually reveal infiltration by:
PMNs and mononuclear macrophages
Endothelial and mesangial proliferation
Immunofluorescent studies of PSGN demonstrate a granular deposition of:
Electron microscopy characteristically shows:
IgG, C3 and mesangial fibrin
“lumpy” appearance w/ dx finding of sub-endothelial “clumps of humps”
Broad term for the type of glomerular destruction and renal dz that may be d/t several different etiologic agents:
RPGN (rapidly progressing)
must often begin dialysis and/or await renal transplantation in order to survive.
Initial symptoms of RPGN:
hematuria
oliguria
HTN
Conditions known to cause or increase the risk for RPGN:
vasculitis polyarteritis SLE Goodpasture's syndrome H-S purpura IgA nephropathy membranoproliferative GN internal organ abcess (any) Hx of malignant tumor blood/lymph system d/o hydrocarbon solvent exposure
RPGN is also called __________ GN, for the characteristic bands of ________ that form around _________________.
Crescentic
fibrin
glomerular capillaries throughout capillary tufts
With RPGN, immunofluorescent staining reveals:
deposition of IgM, IgG and fibrin:
- 1/3 granular
- 1/3 linear
- 1/3 non-specific
Goodpasture’s often presents with RPGN and is characterized by _________________.
It is MC seen in___________ in their 20s and 30s.
___________ is common.
IgG deposition in a _______ pattern.
Circulating anti-basement membrane antibodies
Caucasian males
Pulmonary hemorrhage
linear
Goodpasture’s is usu treated aggressively with:
Cause of death is usu:
steroids, chemo, plasma exchange
pulmonary hemorrhage
Form of vasculitis that commonly involves kidneys, with potential for multi-organ involvement:
Presenting sxs may be:
Wegener’s granulomatosis
- mucosal surface inflammation & ulceration
- purulent otitis media
- severe sinusitis.
- hemoptysis
- pleuritis
Wegener’s granulomatosis findings:
- lung nodules/infiltrates
- conjunctivitis
- scleritis/episcleritis
- swelling/hemorrhage/ulceration of the gums
The classic renal pathology in Wegener’s is ______________________ accompanied by ___________ of renal vessels.
the combination of focal & segmental glomerulonephritis
granulomatous vasculitis
T/F: In Wegener’s, serology is often positive for P-ANCA.
False - C-ANCA
P-ANCA is seen in polyarteritis nodosum, another vasculitis.
Acute tubular necrosis is characterized by _____________ and is usu classified as being either ______ or ________.
proximal tubular epithelium necrosis
toxic or ischemic
Necrotic cells fall into the tubule lumen, obliterating it and eventually resulting in acute renal failure.
In toxic ATN, the affected tubular cells characteristically reveal an (absence/abundance) of nuclei and a (heterogenous/homogenous) cytoplasm which stains (mildly/intensely) eosinophilic and preserves it’s normal shape.
absence
homogenous
intensely
T/F: full recovery of renal function is possible if the underlying ATN cause is removed.
True
Because tubular cells normally undergo continual replacement
Ischemic ATN causes ________ through the tubules due to differences in ________ within the kidney
skip lesions
perfusion
Acute interstitial nephritis (AIN) is MC a result of:
It may also be linked to ___________ and may result in ___________.
an allergic response to a drug
infectious agents (CMV, streptococcus, legionella) acute rejection of a renal transplant
AIN may be in the ddx when acute renal dz begins after ___________ or the start of a ______________.
recent infx new medication * ibuprofen/NSAIDs * acetaminophen * penicillin * cephalosporin * cimetidine * thiazide diuretics * cyclosporin
AIN refers to:
presence of edema, inflammatory cell infiltration in renal parechyma, and often tubular injury
drug/infx agent acts as hapten, binds to membrane binding site, w/ 2° immune-mediated injury (type I or IV).
Dx findings of AIN:
Eosinophilia (serum, urine)
definitive - kidney bx
Chronic interstitial nephritis (CIN) is caused by disorders that ultimately lead to _________ of the _________.
Causes include:
progressive scarring
interstitium
- persisting AIN
- hematologic malignancies (lymphoma, mult myeloma)
- chronic exposure to toxin (lead)
T/F: CIN has no cure.
True
some pts will require dialysis
mb eventual transplanation
Histopathology of CIN:
- interstitium expanded by fibrosis
- distortion of tubules
- peri-glomerular fibrosis
- glomerulus unchanged
Dz of the proximal renal tubules in which glucose, amino acids, uric acid, phosphate & bicarbonate are passed into the urine instead of being reabsorbed:
Fanconi’s syndrome
hereditary
drugs
heavy metals
T/F: The term renal tubular acidosis (RTA) refers to individuals with poor urinary acidification d/t poor-functioning kidneys.
False
RTA refers to poor acidification in otherwise healthy kidneys, and several types exist (1, 2, 4)
Compare types 1, 2, and 4 of RTA.
Consider location, acidosis, potassium, & pathophys.
Type 1 - distal tubules
severe acidosis
hypOkalemia
no H+ secretion by intercalated cells
Type 2 - proximal tubules
mod. acidosis
hypOkalemia
too little HCO3 reabsorption
Type 4 - adrenal
mild acidosis
hypErkalemia
resistance to/low aldosterone
Light microscopy of Fanconi’s:
atrophic and hyalinized glomeruli
seen in end-stage kidney dz
Analgesic nephropathy occurs after ingestion of (small/large) amounts of analgesics over a (short/long) period of time.
large long (vs. AIN which mb 1 dose/short course)
leads to papillary necrosis, spares cortex
Two of the MC drugs responsible for analgesic nephropathy:
acetaminophen [covalent bond to papilla, 2° oxid. dmg]
aspirin [inhibits prostaglandin synthesis]
Atherosclerotic changes in the renal blood vessels:
benign nephrosclerosis
occurs as a renal complication of HTN (seen on bx in diabetics w/HTN)
The surface of the benign nephrosclerotic kidney has a characteristic granular appearance due to:
Microscopically:
patchy ischemic atrophy w/in the kidney
focal loss of parenchyma
hyaline thickening of walls of small arteries/arterioles
Malignant nephrosclerosis:
- severe changes in renal architecture d/t malignant HTN
- focal small hemorrhages
- small arteries/arterioles become hyperplastic, “onion ring” appearance
Narrowing or blockage of a renal artery is called __________ and mb d/t
renal artery stenosis (RAS)
- atherosclerosis
- fibromuscular dysplasia of renal a.
- atheroembolic renal dz
- scar formation
T/F: Renal artery stenosis often causes mild HTN that responds well to treatment.
False
often causes HTN that may be severe and resistant to tx
How is RAS typically found?
on work up for difficult to control HTN
in some cases bruits mb heard in mid-back
among the MC causes of 2° HTN
Systemic dz that results in widespread thrombosis in capillaries & arterioles, and may have a significant effect on the kidneys and renal function.
Thrombotic microangiopathy
hallmark: widespread formation of hyaline thrombi in microcirculation (dense platelet accumulations surrounding fibrin)
The 2 MC conditions with thrombotic microangiopathy:
HUS and TTP
[or mb better HUS/TTP syndrome d/t overlap]
Hemolytic uremic syndrome
thrombotic thrombocytopenic purpura
What appears to be the initiating event in thrombotic microangiopathy?
Endothelial injury resulting in thrombus formation triggers: * bacterial endotoxins * cytotoxins * cytokines * viruses * drugs * endothelial abs * septicemia and in many cases is unknown
Classic triad of HUS:
- acute renal failure
- microangiopathic hemolytic anemia
- thrombocytopenia
MC causes of acute renal failure in children:
which involved bacteria is MC?
HUS
E coli 0157:H7
verocytotoxin releasing bacteria
How does HUS work?
- Endothelium shows inc. adhesion of leucocytes.
- Inc endothelin production.
- Loss of endothelial nitric acid production.
- Cytokines (eg TNF) involved in lysis of endothelial cells.
- Resultant vasoconstriction & thrombosis causing classis microangiopathy.
Hx finding in HUS:
- recent gastroenteritis (83%)
- fever (56%)
- bloody diarrhea (50%)
- seizures
- acute renal failure
- anuria
Histopathology of HUS:
- capillary lumens often occluded by debris/thrombi
- patchy or diffuse microangiopathy
- swelling of endothelium
- cortical necrosis
- thick capillary walls in glomeruli
HUS/TTP syndrome in adults follows/correlates with:
- viral infx
- septicemia
- typhoid, shigella, E coli
- SLE, scleroderma
- antiphospholipid ab
- malignant HTN
- chemo/immunosuppressive drugs
- pregnancy/post-partum
Source of most renal artery emboli?
a cardiac source (i.e. enlarged left atrium)
MC non-cardiac source - ruptured aortic atheromatous plaque (spontaneous or post-sx/angioplasty)
incidence increases with age
Biopsy of renal tissue affected by embolic disease often reveals
cholesterol laden emboli w/in involved arteries
cholesterol usu dissolves leaving cleft-like spaces on slides
T/F: Renal ischemia of any kind will show poor uptake of “vital” stain, which are taken up by metabolically active cells.
True
A gross specimen of ischemic renal tissue may appear normal but anoxic tissue to the degree of infarction will have a classic wedge-shape to the infarcted tissue
Kidney stones (renal calculi) are:
crystalline accumulations that precipitate out of urine they would normally be dissolved in.
Does dehydration contribute to stone formation?
Yes, because the resulting supersaturation by one or more substances will precipitate out of solution.
Kidney stones most often develop in the ________ of the kidney and are usu composed of ___________________.
pelvis
- oxalates
- phosphates
- uric acid
- carbonates
Approx 75% of kidney stones are:
calcium oxalate stones
Remaining 25% of kidney stones are:
15% - triple phosphate (struvite) stones
6% - uric acid
1% - cystine
T/F: Most calcium oxalate stones are assoc w/ hypercalcemia & hypercalciuria.
False! only 5%
abN renal absorption of Ca+ is found in 55%
risk factor: inc serum oxalate
many pts w/stones have NO risk factors
Triple phosphate stones (magnesium ammonium phosphate) are seen most commonly in association with:
UTIs by bacteria which are urea-splitting:
- proteus spp.
- staphylococcus (some)
these convert ammonia to urea => increase pH
Staghorn crystals are:
triple phosphate stones
some of the largest!
Uric acid crystals are seen in:
- normal pts (esp w/acidic urine
Cystine stones are caused by:
genetic defects in the renal reabsorption of amino acids, including cystine, leading to cystinuria.
Precipitate more readily out of acidic urine.
Benign tumors of the kidneys are generally (severe/moderate/asx) and are usually noted ______________.
asx
incidentally on autopsy
malignant tumors of the kidney cause considerable morbidity and mortality.
Benign renal tumors:
- Renal papillary adenoma (fronds)
- Renal fibroma or hamartoma
- Angiomyolipoma
- Oncocytoma
Renal adenomas are often called ______________ because they are MC found in the __________. Most are __mm or (less/more)
papillary adenomas
papilla
5mm or less
Epithelial tumor composed of oncocytes, large eosinophilic cells that are round to polygonal shaped cells with benign-appearing nuclei with large nucleoli:
oncocytoma
Characteristic histopathology of oncocytoma:
Electron microscopy:
- large polygonal cells
- round nuclei
- uniform appearance
- numerous prominent mitochondria, “stacked”
Primary renal malignancies include:
- renal cell carcinoma
- transitional cell carcinoma
- papillary & non
- Wilm’s tumor (nephroblastoma)
- renal sarcoma
- lymphoma
MC kidney malignancy:
Renal cell carcinoma (85%)
2nd - mets
2nd primary renal malignancy - TCC
RCCA is (asx/painful) in early stage, sx are (specific/nonspecific) and mb:
asx - until advanced stage (25% have distant mets on dx)
fever
malaise
weakness
wt loss
Class triad of RCCA that suggests advanced dz:
flank pain
hematuria
palpable abd mass
Major risk factors for RCCA:
TOBACCO cadmium/asbestos exposure FHx obesity HTN unopposed estrogen therapy radiation therapy to kidney area
RCCA tumors range from _______ cm.
2-25cm!
What are the 5 types of RCCA? Which is most prevalent?
Clear cell carcinoma (75-85%) chromophilic carcinoma chromophobic carcinoma oncocytic carcinoma collecting duct carcinoma
Histologic appearance of RCCA:
neoplastic cells
clear cytoplasm
nest of tumor cells w/intervening vessels
Common sites of mets for RCCA:
lungs lymph nodes bone liver brain ipsilateral adrenal gland contralateral kidney renal vein -> vena cava
Risk factors for urothelial (transitional cell) carcinoma:
Cigarette smoking (lower risk w/pipes, etc) chemical exposure - petroleum - paint - pigments * aniline dyes - agrochemicals
MC primary renal tumor in children:
Age of dx:
Related to defects in:
Wilm’s tumor
2-5 y.o.
chromosome 11
Pt’s with Wilm’s tumor have a noted propensity for:
developing other kinds of primary tumors
- genito-urinary tumors
- bone tumors
- soft tissue sarcoma
- leukemia
MC cause of hydronephrosis in infants/children:
ureteropelvic junction obstruction
Abnormal movement of urine from the bladder into the ureters and potentially to the kidneys:
vesicoureteral reflux
Obstructive lesions of the ureter:
- calculi - usu
Bilateral ureteral obstruction generally occurs as a result of __________, where unilateral obstruction is typically ________.
ascending pathology from (near) the bladder - BPH, tumor
descending pathology from the kidney
MC ureteral malignancies:
Transitional cell carcinoma (TCC)
Failure of normal development of the anterior wall of the abdomen and bladder:
exstropy - repairable with surgery
inc risk of bladder adenocarcinoma later in life
Embryological canal connecting the urinary bladder with the allantoids, which is normally obliterated during development, but leads to risk of cysts when persisting:
urachus
bladder adenocarcinoma can arise in cysts
Inflammation or infection of the urinary bladder:
cystitis
Microscopically, the urothelial mucosa of the bladder in chronic cystitis show inflammatory cells in the _____________.
lamina propria - mostly lymphocytes
Pattern of bladder change as a result of chronic inflammation:
malakoplakia
Malakoplakia, microscopic findings:
foamy histiocytes
round basophilic inclusions
* Michaelis-Gutmann bodies (pathognomonic)
Urinary bladder dz of unknown origin characterized by dysuria, frequency, urgency, and pressure:
interstitial cystitis
Definitive dx of IC requires:
cystoscopy
The pathognomonic lesion of IC:
Hunner’s ulcer
Non-infectious causes of IC:
cytotoxic anti tumor drugs
* methotrexate
* cyclophosphamide
radiation to the bladder
MC bladder cancer:
TCC
M:F 3:1
Bladder cancer risk factors:
cigarette smoking long term use of analgesics radiation to the bladder aryl amine exposure (industrial) schistosomiasis infx
What are the 2 distinctive precursor bladder cancer lesions:
- noninvasive papillary tumors - MC
* urothelial carcinoma in situ (CIS) - worse prognosis
