Renal Diseases Flashcards
Azotemia
Elevation of the blood urea nitrogen (BUN) and creatinine levels, due to decreased filtration of blood through the glomeruli (decreased glomerular filtration rate).
Uremia
Association of azotemia with clinical signs and symptoms, including gastroenteritis, peripheral neuropathy, pericarditis, dermatitis, hyperkalemia, and metabolic acidosis. advanced form of liver disease
Azotemia is due to ________
decrease glomerular filtrate
you get increased levels of ____ and ____ in azotemia
nitrogen and creatinine
Major Clinical Renal Syndromes
Acute nephritic syndrome
Nephrotic syndrome
Acute renal failure (rapidly)
Acute nephritic syndrome
Results from glomerular injury and is characterized by acute onset of hematuria (blood in urine), mild to moderate proteinuria, azotemia, and hypertension.
Nephrotic syndrome
Glomerular syndrome characterized by heavy
proteinuria (> 3.5 grams per day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria.
nephritic associated simply with ____ in urine
blood
nephrotic associated simply with ____ in urine
protein
Acute renal failure
Acute onset of azotemia with oliguria (or anuria). (inability to produce urine)
CONGENITAL CYSTIC KIDNEY DISEASE (2)
Autosomal dominant (adult) polycystic kidney disease Autosomal recessive (childhood) polycystic kidney disease
auto dominant associated with ____ (age group)
adult
auto recessive associated with ____ (age group)
children
Autosomal dominant (adult) polycystic kidney disease clinical presentation
characterized by MULTIPLE EXPANDING CYSTS in BOTH kidneys. Gradual onset of renal failure in adult, urinary tract hemorrhage (hematuria), pain, hypertension, urinary tract infection.
Autosomal dominant (adult) polycystic kidney disease etiology
defective gene is PKD1 (in 90% of families) located on chromosome 16. The gene encodes for polycystin-1
Autosomal dominant (adult) polycystic kidney disease Extrarenal pathology
1/3 of patients have CYSTS IN LIVER; aneurysms
may develop in the circle of Willis (intracranial)
Autosomal dominant (adult) polycystic kidney disease Pathology
very large (up to 4 kg) kidneys with numerous cysts that
arise in every part of the tubular system
BIG KIDNEYS
Autosomal recessive (childhood) polycystic kidney disease clinical presentation
renal failure develops from infancy to several years of age – rare; seen in 1 in 20,000 live births.
Autosomal recessive (childhood) polycystic kidney disease extrarenal pathology
almost all have liver cysts and progressive liver fibrosis
Autosomal recessive (childhood) polycystic kidney disease pathology
numerous small uniform-size cysts from collecting tubules in cortex and medulla
Autosomal recessive (childhood) polycystic kidney disease etiology
Due to mutations in the PKHD1 gene
Mechanisms of glomerular injury
- Immune complex deposits in glomerular basement membrane (GBM)
or mesangium. - Epithelial and endothelial cell injury.
Pathologic evaluation of kidney biopsies
- Light microscopy
- Immunofluorescence
- Electron microscopy
Nephrotic syndrome 4 manifestations
- Minimal change disease
- Focal and segmental glomerulosclerosis
- Membranous nephropathy (glomerulonephritis)
- Glomerular disease in diabetes mellitus
Minimal change disease- nephrotic
- most common nephrotic in KIDS
- normal histology of glomeruli
- good response to treatment (in kids)
Focal and segmental glomerulosclerosis- nephrotic
- one of the most common causes of nephrotic syndrome in ADULTS
- may be primary (idiopathic) or secondary to other glomerular diseases, loss or scarring of other glomeruli, or genetic.
- pathology - partial (segmental) sclerosis of some (focal) glomeruli characterized by increased mesangial matrix collagen with obliteration of capillary loops. The idiopathic form has NO immune complexes.
- poor response to corticosteroid treatment – renal failure in 50% after 10 yrs.
Membranous nephropathy (glomerulonephritis)- nephrotic
a) most common in ADULTS age 30-50
b) may be primary (disease limited to the kidney) or secondary to infection, malignancy, SLE, or drugs.
c) pathology - IMMUNE COMPLEXES in the epithelial side (subepithelial) of the GBM demonstrable by immunofluorescence and electron microscopy
d) poor response to corticosteroid treatment, with 40% developing
renal failure in 2-20 years
Glomerular disease in diabetes mellitus - nephrotic
a) minimal proteinuria progresses, over 10-15 years, to severe proteinuria.
b) thick glomerular basement membranes, diffuse increase in mesangial matrix and formation of mesangial nodules (the latter is nodular glomerulosclerosis or Kimmelstiel-Wilson lesion)
nephrotic typically more chronic or acute?
chronic
nephritic typically more chronic or acute?
acute
basics of nephritic
acute
blood in urine
failure to produce urine
two main causes of nephritic syndrome
- Acute postinfectious (poststreptococcal) glomerulonephritis
- IgA nephropathy
Acute postinfectious (poststreptococcal) glomerulonephritis
a) CHILDREN mostly after strep throat (streptococcal pharyngitis)
b) pathology - proliferation of endothelial and mesangial cells; infiltration of neutrophils and monocytes; immune complexes in GBM and sometimes in the mesangium. basically a immune reaction and INFLMMATORY cells
c) progression to chronic renal disease is more likely in adults.
IgA nephropathy
a) usually occurs in CHILDREN and young adults
b) hematuria is noted 1-2 days after non-specific upper respiratory tract viral infection.
c) pathogenesis may involve increased IgA IMMUNE COMPLEXES production
d) when the glomerular disease is associated with systemic manifestations (purpuric skin rash and arthritis), this is called Henoch-Schönlein purpura.
e) pathology - mesangial deposition of immune complexes containing IgA and variable proliferation of mesangial and endothelial cells. Occasionally there is epithelial cell proliferation with crescents.
affects mainly central core of glomerulus
Crescentic or Rapidly Progressive Glomerulonephritis
antibodies directed against a glomerular basement antigen, deposition of immune complexes, or lack of immune complex deposition (called pauci-immune glomerulonephritis).
characteristic finding is crescentic glomerulonephritis due to proliferation of endothelial cells and histocytes around the edge.
CHRONIC (END-STAGE) RENAL DISEASE
SCAR TISSUE, BECOMES NON FUNCTIONAL. Loss of glomeruli and tubules leads to fibrosis. Damaged glomeruli become completely sclerotic (global sclerosis). With advanced loss of tubules and glomeruli, the remaining glomeruli develop adaptive changes. These changes eventually lead to further injury and progressive renal failure.
IgA nephropathy main points
- children/ young adults
- hematuria after non specific upper resp. viral infection
- IgA immune complexes
Acute postinfectious (poststreptococcal) glomerulonephritis main points
- children after strep
- proliferation of inflammatory cells and immune complexes
- can progress to chronic renal diease in adults
what is ACUTE PYELONEPHRITIS
renal disease affecting tubules, interstitium, and pelvis and is most often secondary to bacterial infection
where does this secondary infection come from?
The infection may spread from the urinary bladder, up the ureters and into the renal pelvis and kidney (ascending) or hematogenous (blood) spread of bacteria..
ACUTE PYELONEPHRITIS clinical presentation
Sudden onset with pain at the costovertebral angle and
systemic evidence of infection. Often there is accompanying dysuria,
frequency and urgency.
ACUTE PYELONEPHRITIS pathology
Patchy interstitial and tubular neutrophilic inflammation.
ACUTE PYELONEPHRITIS etiology
Predisposing conditions, include urinary tract obstruction, instrumentation, vesicoureteral reflux, pregnancy, gender and age, diabetes mellitus and immunosuppression.
Drug-Induced Interstitial Nephritis etiology
some antibiotics, non-steroidal anti-inflammatory drugs and others.
Drug-Induced Interstitial Nephritis pathology
- hypersensitivity reaction to the drugs.
- consists of interstitial infiltration of mononuclear inflammatory cells, often with neutrophils and many eosinophils.
- The glomeruli are not involved in the inflammation
are the glomeruli inovled in drug induced interstitial nephritis
no
rapid onset of renal failure, reduced urine output, electrolyte imbalances. The clinical manifestations are reversible over a period of weeks as the damaged tubular epithelium regenerates.
Acute Tubular Necrosis clinical
injury to tubular epithelial cells from ischemia (ie. shock) or a toxin
Acute Tubular Necrosis
dilation of tubules, interstitial edema, necrosis of epithelium (often very focal and subtle with ischemic injury, more diffuse with injury from a toxin)
Acute Tubular Necrosis
Gross – kidneys are symmetrically atrophic, with
moderate reduction in size. The kidney surface has an even fine
granularity and the cortex is thin.
Arterionephrosclerosis- pathology
Narrowing of the lumens of arterioles and arteries
caused by hyaline type of arteriolosclerosis and fibroelastic hyperplasia of muscular arteries. In addition, there is (1) tubular atrophy and interstitial fibrosis and (2) global sclerosis of glomeruli.
Arterionephrosclerosis- histopathology
Relatively rapid onset of renal failure with increased intracranial pressure leading to headache, nausea, vomiting, and visual impairment.
Arterionephrosclerosis associated with malignant hypertension clinical presentation
Arterioles show hyperplastic arteriolosclerosis, reducing
blood flow and causing necrosis of glomeruli.
Arterionephrosclerosis associated with malignant hypertension pathology
acquired defect in ADAMTS 13, a plasma protease that degrades vWF multimers. The large von Willebrand factor components activate platelets under certain conditions.
Thrombotic thrombocytopenia purpura (TTP)
endothelial cell injury which, in most cases, is due to a Shiga-toxin from E. coli (reason for ground beef recalls in the news) or Shigella. The injury leads to platelet activation.
Hemolytic-uremic syndrome (HUS)
similarities between TTP and HUS
microthrombus formation in capillaries.
which disease has more renal involvement predominates and the disorder most often occurs in children.
Hemolytic-uremic syndrome
which disease is there more widespread involvement of other organs
Thrombotic thrombocytopenia purpura
Stones result in urinary tract obstruction, ulceration of the urothelial lining and bleeding. Small stones may migrate into the ureters and produce intense flank pain. Large stones remain in the pelvis and may be manifested by hematuria and superimposed infection.
Urolithiasis (Renal Stones) clinical
Stones are unilateral in 80% of patients and most
frequent site for their formation is within the calyces and pelvis. Stones
may also develop in the bladder. Large stones are referred to as “staghorn calculi”. These large stones form a cast of the pelvis and calyceal system.
Urolithiasis (Renal Stones) pathology
Types of stones in urolithiasis
- calcium - patients have increased concentration of calcium in the urine
- magnesium ammonium phosphate - patients have persistently alkaline
urine. Infection with Proteus predisposes to these stones. - Uric acid - occur in patients with gout, leukemia (high cell turnover) or
persistently acid urine.
2:1 male:female ratio. Hematuria, mass, pain, fever, polycythemia, paraneoplastic syndromes
renal cell carcinoma
Risk factors include smoking, hypertension, obesity,
cadmium exposure and von Hippel-Lindau syndrome.
renal cell carcinoma
Arise from tubular epithelium, often reach a large size
prior to diagnosis, often invade the renal vein. Most common histologic subtype has cells with very pale or clear cytoplasm (clear cell carcinoma)
renal cell carcinoma
Abdominal mass, risk is greatly increased in some inherited
syndromes, occurs in children ages 2 to 5 years
Wilm’s Tumor
Triphasic pattern with epithelial structures resembling
primitive tubules or glomeruli, stroma (mesenchymal component) and blastema which recapitulates early nephron formation. Thus the tumor illustrates abortive formation of renal structures in various stages of
renal development.
Wilm’s Tumor
