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275 Cards in this Set
- Front
- Back
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Give an overview of renal function
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A. Excretes harmful waste products
B. Maintains acid-base homeostasis C. Reabsorbes essential substances D. Regulates water and sodium metabolism E. Maintains vascular tone 1. Angiotensin II a. Vasoconstricts peripheral resistance arterioles and efferent arterioles b. Stimulates the synthesis and release of aldosterone 2. Renal-derived prostaglandin (PGE2) -Vasodilates the afferent arterioles F. Produces erythropoietin -Synthesized in the renal cortex by interstitial cells in peritubular capillary bed G. Maintains calcium homeostasis 1. Second hydroxylation of vitamin D a. 1-α-Hydroxylase is synthesized in the proximal renal tubule cells b. Converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol 2. Functions of vitamin D a. Increases GI reabsorption of Ca and phosphorus b. Promotes bone mineralization; maintains serum Ca level c. Increases monocytic stem cells to become osteoclasts |
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Describe vitamin D
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Promotes bone mineralization by stimulating the release of alkaline phosphatase from osteoblasts. Alkaline phosphatase hydrolyzes pyrophosphate and other inhibitors of calcium-phosphate crystallization
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Describe the causes of hematuria
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1. Upper urinary tract (kidneys, ureter) causes of hematuria
a. Renal stone b. Glomerulonephritis -Characterized by dysmorphic RBCs (irregular membrane) 2. Lower urinary tract (bladder, urethra, prostate) causes hematruia a. Infection b. Transitional cell carcinoma -Most common cause of gross hematuria in the absence of infection c. Benign prostatic hyperplasia -Most common cause of microscopic hematuria in adult males 3. Drugs associated with hematuria a. Anticoagulants b. Cyclophosphamide (1) Hemorrhagic cystitis (2) Risk factor for transitional cell carcinoma |
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Describe the causes of proteinuria
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1. General
a. Protein >150mg/24 hours or >30 mg/dL (dipstick) b. Persistent proteinuria usually indicates renal disease c. Qualitative tests include dipsticks and sulfosalicylic acid (SSA) (1) Dipsticks are specific for albumin (2) SSA detects albumin and globulins d. Quantitative test is a 24-hour urine collection 2. Know types of proteinuria |
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Describe the serum blood urea nitrogen (BUN)
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-Normal serum BUN is 7 to 18 mg/dL
1. End-product of amino acid and pyrimidine metabolism -Produced by the liver urea cycle a. Filtered in the kidneys (1) Partly reabsorbed in the proximal tubule (2) Amount reabsorbed is flow dependent (a) Decreased GFR, more reabsorbed (b) Increased GFR, less reabsorbed b. Extrarenal loss with very high serum concentration c. Serum levels depend on the following (1) GFR (2) Protein content in the diet (3) Proximal tubule reabsorption (4) Functional status of the urea cycle 2. Know cDauses of increased and decreased serum BUN |
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Describe the serum creatinine
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-Normal serum creatinine is 0.6 to 1.2 mg/dL
1. Metabolic end-product of creatine is muscle -Creatine binds phosphate in muscle for ATP synthesis 2. Creatinine is filtered in the kidneys and not reabsorbed or secreted -Excellent metabolite for renal clearance testing 3. Serum concentration varies with age and muscle mass -Increased with age, decreased in muscle wasting 4. Increase in serum BUN and creatinine is called azotemia 5. Causes of increased and decreased serum creatinine -Similar to those for serum BUN |
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Describe the serum BUN:creatinine ratio
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1. Using normal values, the normal ratio is 15
a. Creatinine is filtered and is neither reabsorbed nor secreted b. Urea is filtered and partly reabsorbed in the proximal tubule c. BUN:Cr ratio depends on changes at several times: (1) Before the kidneys (prerenal) (2) Within the kidney parenchyma (renal) (3) After the kidneys (postrenal) 2. Prerenal, renal, and postrenal azotemia a. Azotemia refers to an increase in serum BUN and creatinine |
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Describe the serum BUN:creatinine ratio in prerenal azotemia
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1. Caused by a decrease in cardiac output
a. Hypoperfusion of the kidneys decreases GFR b. There is no intrinsic renal parenchymal disease 2. Examples - blood loss, congestive heart failure 3. Serum BUN:Cr ratio >15 a. Decreased GFR causes creatinine and urea to back up in blood -Ratio remains unchanged, because of proportionate increase b. After filtration, proportionately more urea is reabsorbed back into the blood due to the decreased flow rate (Po>PH) -All of the creatinine is excreted in the urine c. Addition of proportionately more urea to blood increases the ratio to >15 |
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Describe the serum BUN:creatinine ratio in renal azotemia (uremia)
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1. Caused by parenchymal damage to the kidneys
2. Examples- acute tubular necrosis, chronic renal failure 3. Serum BUN:Cr ratio<15 a. Decreased GFR causes creatinine and urea to back up in blood; increased extrarenal loss of urea -Ratio is already <15 due to extrarenal loss of urea b. After filtration, both urea and creatinine are lost in the urine -Proximal tubule cells are sloughed off in renal failure c. Serum BUN:Cr ratio remains <15 d. Example - serum BUN 80 mg/dL, serum creatinine 8 mg/dL -BUN:Cr ratio is 10 |
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Describe the serum BUN:creatinine ratio in postrenal azotemia
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1. Caused by urinary tract obstruction below the kidneys
-No intrinsic parenchymal disease 2. Examples-prostate hyperplasia; blockage of ureters by stones/cancer 3. Serum BUN:Cr ratio >15 a. Obstruction to urine flow decreases the GFR b. Backup of urea and creatinine in the blood -Proportionate increase at the point; ratio unchanged c. Increased tubular pressure causes back-diffusion of urea (not creatinine) into blood -Disproportionate increase in urea increases ratio to >15 4. Persistent obstruction damaged tubular epithelium causing renal azotemia (ratio <15) |
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Describe functional proteinuria
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Def: Protein <2g/24hr, Not associated with renal disease
Causes: Fever, exercise, congestive heart failure Orthostatic (postural): occurs with standing and is absent in the recumbent state; urine protein is absent in the first morning void; no progression to renal disease |
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Describe overflow proteinuria
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Def: Protein loss is variable, LMW proteinuria, Amount filtered > tubular reabsorption
Causes: Multiple myeloma with BJ poritenuria Hemoglobinuria: eg, intravascular hemolysis Myoglobinuria: crush injuries, McArdles glycogenosis (deficient muscle phosphorylase); increase in serum creatinine kinase |
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Describe glomerular proteinuria
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Def: Nephritic syndrome: protein >150mg/24hr, but <3.5g/24hr
Nephrotic syndrome: protein 3.5g/24hr Causes: Damage of GBM: nonselective proteinuria with loss of albumin and globulins; example is post-streptococcal glomerulonephritis; example is minimal change disease (lipoid nephrosis) |
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Describe tubular proteinuria
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Def: Protein <2 g/24hr, Defect in proximal tubule reabsorption of LMW proteins (eg, amino acids at normal filtered loads)
Causes: Heavy metal poisoning: eg, lead and mercury poisoning Fanconi syndrome, Hartnup disease |
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Describe Fanconi syndrome
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Inability to reabsorb glucose, amino acids, uric acid, phosphate, and bicarbonate
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Describe Hartnup disease
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Defect in reabsorption of neutral amino acids (eg, tryptophan) in the GI tract and kidneys
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Describe the causes of increased serum BUN
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-Decreased CO
-Increased protein intake -Increased tissue catabolism -Acute glomerulonephritis -Acute or chronic renal failure -Postrenal disease |
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Describe the causes of decreased serum BUN
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-Increased plasma volume
-Decreased urea synthesis -Decreased protein intake |
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Describe how decreased cardiac output leads to increased serum BUN
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-CHF, shock (eg, hemorrahge)
-Result in decreased CO -Causes decreased GFR -Leads to increased proximal tubule reabsorption of urea -Increases serum BUN |
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Describe how increased protein intake leads to increased serum BUN
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-High protein diet
-Blood in GI tract leads to increased amino acid degradation -Increases serum BUN |
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Describe how increased tissue catabolism leads to increased serum BUN
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-Third-degree burns, postoperative state
-Increased amino acid degradation -Increased serum BUN |
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Describe how acute glomerulonephritis leads to increased serum BUN
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-Poststreptococcal glomerulonephritis
-Decreases GFR -Increased BUN |
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Describe how acute or chronic renal failure leads to increased serum BUN
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-Acute tubular necrosis, diabetic glomerulopathy
-Leads to decreases GFR -Increases BUN |
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Describe how postrenal disease leads to increased serum BUN
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-Urinary tract obstruction (eg, urinary stone, BPH)
-Decreases GFR back-diffusion or urea -Increased serum BUN |
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Describe how increases plasma volume leads to decreased serum BUN
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-Occurs in normal pregnancy, SIADH
-Increases plasma volume -Increased GFR -Decreases serum BUN |
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Describe how decreased urea synthesis leads to decreased serum BUN
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-Occurs in cirrhosis, Reye syndrome, fulminant liver failure
-Dysfunctional urea cycle -Decreased serum BUN |
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Describe how decreased protein intake leads to decreased serum BUN
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-Occurs in Kwashiokor (Increased CHO is protein sparer), starvation gluconeogenesis in kidneys
-Decreases amino acid degradation -Decreases serum BUN |
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Describe creatinine clearance
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1. Correlates with GFR
a. Annual decrease in CCr of 1 mL/minute after age 50 years b. Useful in detecting renal dysfunction 2. Creatinine clearance (CCr) formula a. Measured CCr=UCr (mg/dL) x V (mL/min)/PCr(mg/dL) (1) V= volume of a 24-hr urine collection in mL/minute, and UCr and PCr are the creatinine concentration of urine and plasma, respectively (2) CCr results are dependent on a correct 24hr urine collection b. Normal adult CCr is 97-137 mL/minute (1) In general, CCr<100 mL/minute is abnormal (2) CCr <10mL/minute indicates renal failure 3. Know causes of increased and decreased CCr |
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Describe urinalysis
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Gold standard test in the initial workup of renal disease
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Describe the causes of increased CCr
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-Normal pregnancy
-Early diabetic glomerulopathy |
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Describe the causes of decreased CCr
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-Elderly people
-Acute and chronic renal disease |
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Describe the increased CCr from normal pregnancy
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Normal increase in plasma volume causes an increase in the GFR leading to an increase in CCr; highest at the end of the first trimester
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Describe the increased CCr from early diabetic glomerulopathy
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-Efferent arteriole becomes constricted due to hyaline arteriolosclerosis causing an increase in the GFR and CCr
-Increased GFR damages the glomerulus (hyperfiltration injury) |
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Describe the decreased CCr in elderly people
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GFR normally decreases with age causing a corresponding decrease in the CCr, danger when using nephrotoxic drugs
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Describe the decreased CCr in acute and chronic renal disease
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ARF due to acute tubular necrosis, CRF due to diabetic glomerulopathy
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Describe the significance of dark yellow urine in urinalysis
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-Dark yellow: concentrated urine, bilirubinuria, increased UBG, vitamins
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Describe the significance of red or pink urine in urinalysis
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Red or pink: hematuria, hemaglobinuria, myoglobinuria, drugs (eg phenazopyridine, a urinary anesthetic), porphyria
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Describe the significance of smoky-colored urine in urinalysis
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Acid pH urine converts Hb to hematin, common finding in nephritis type of glomerulonephritis
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Describe the significance of black urine in urinalysis
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-Black urine after exposure to light: alkaptonuria (AR disease with deficiency of homogentisate oxidase) with an increase in homogentisic acid in urine
-Turns black when exposed to light |
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Describe the significance of cloudy urine with alkaline pH
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Normal finding most often due to phosphates
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Describe the significance of cloudy urine with acidosis pH
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Normal finding most often due to uric acid
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Describe microalbuminuria dipsticks
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-More sensitive than standard dipstick
-Sensitive to 1.5-8 mg/dL -Microalbuminuria is the first sign of diabetic nephropathy |
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Describe ketone urinalysis
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-Detects acetone, acetoacetic acid (not β-OHB)
-Nitroprusside in the test system only reacts with AcAC and acetone, not β-OHB |
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Describe the causes of ketonuria
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-DKA
-Starvation -Ketogenic diets -Pregnancy (normal finding) -Isopropyl alcohol poisoning |
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Describe bilirubin urinalysis
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Detects conjugated (water-soluble) bilirubin
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Describe the causes of bilirubinuria
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-Viral hepatitis
-Obstructive jaundice |
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Describe the cause of cloudy urine independent of pH
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-Bacteria
-WBCs -Hb -Myoglobin |
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Describe the specific gravity of urine
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Evaluates urine concentration and dilution
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Describe the importance of high urine specific gravity
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-Specific gravity > 1.023 (UOsm 900 mOsm/kg)
-Indicates urine concentration and excludes intrinsic renal disease |
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Describe the importance of low urine specific gravity
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-Specific gravity < 1.015 (UOsm 220 mOsm/kg)
-Hypotonic urine |
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Describe fixed specific gravity urine
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-1.008-1.010
-Correlates with UOsm -Lack of concentration and dilution (eg chronic renal failure) |
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Describe the pH of urine
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-Determined by diet and acid-base status of the patient
-Pure vegan usually has alkaline pH (citrate converted into bicarbonate) -Meat eater usually has acid pH (organic acids in meat) -Alkaline pH + smell of ammonia: urease-producing pathogen (eg Proteus) |
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Describe urinalysis for protein
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-Detects albumin (not globulins)
-SSA: Detects albumin and globulins (eg BJ protein) -Albuminuria: reagent strip and SSA have the same results -BJ protein: SSA greater than reagent strip result; always confirm BJ protein with urine immunoelectrophoresis |
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Describe urinalysis for glucose
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-Specific for glucose; will not detect fructose or other sugars
-Detect glucose in urine as low as 30 mg/dL |
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Describe the causes of increased serum glucose and glucosuria
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Diabetes mellitus
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Describe the causes of normal serum glucose + glucosuria
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-Normal pregnancy (normally have a low renal threshold for glucose)
-Benign glucosuria (low renal threshold for glucose) |
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Describe urobilinogen
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Normal to have trace amounts (normal urine color is due to urobilin)
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Describe the cause of increased urine bilirubin and absent urine UBG
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Obstructive jaundice
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Describe the cause of increased urine UBG and absent urine bilirubin
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Extravascular hemolytic anemia (eg, hereditary spherocytosis)
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Describe the cause of increased urine UBC and increased urine bilirubin
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Hepatitis
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Describe blood urinalysis
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Detects RBCs, Hb, and myoglobin
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What causes hematuria?
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Renal stones
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What causes hemoglobinuria?
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Intravascular hemolytic anemia
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What causes myoglobinuria?
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Crush injuries, increased serum creatinine
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Describe nitrate urinalysis
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-Detects nitrites produced by nitrate reducing uropathogens (eg E coli)
-Test sensitivity and specificity is 30% and 90%, respectively -Requires ~4hr for nitrate reducing uropathogens to convert nitrates to nitrites and patients with UTI frequently have increased frequency of urination, which explains the tests poor sensitivity |
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Describe leukocyte esterase urinalysis
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-Detects esterase in neutrophils (pyuria)
-~80% sensitivity |
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What do infections of the urinary system cause?
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-Urethritis
-Cystitis -Pyelonephritis |
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What are the causes of sterile pyuria?
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-Neutrophils present but negative standard urine culture
-Caused by Chlamydia trachomatis urethritis, tuberculosis, drug-induced interstitial nephritis |
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Describe the importance of bacteria in urinary sediment
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Usually a sign of a urinary tract infection
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Describe the importance of RBCs in urinary sediment (hematuria)
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-Renal stone
-Cancer (bladder, renal) -Glomerulonephritis -Hematuria is >2-3 RBCs per HPF |
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Describe the importance of dysmorphic RBCs in urinary sediment
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Indicates hematuria of glomerular origin
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Describe the importance of neutrophils in urinary sediment
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-Pyuria
-From urinary tract infection, sterile pyuria, oyuria refers to >10 WBCs/HPF in a centrifuged specimen of >5 WBCs/HPF in an uncentrifuged specimen |
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Describe the importance of oval fat bodies in the urinary sediment
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Renal tubular cells with lipid (nephrotic syndrome)
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Describe urinary casts
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-Casts are formed in tubular lumens in the kidney
-They are composed of a protein matrix (Tamm-Horsfall protein) within which are entrapped cells, debris, or protein leaking through the glomeruli -Their presence proves a renal origin of disease |
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Describe the presence of hyaline casts in urinary sediment
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-Acellular
-Ghost-like cast containing protein -No significance in the absence of proteinuria |
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Describe the presence of RBC casts in urinary sediment
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Nephritic type of glomerulonephritis (eg, post-streptococcal glomerulonephritis)
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Describe the presence of WBC casts in urinary sediment
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From acute pyelonephritis, acute tubulointerstitial nephritis
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Describe the presence of renal tubular cell casts in urinary sediment
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Indicates acute tubular necrosis
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Describe the presence of fatty casts in urinary sediments
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-Contains lipid
-Sign of nephrotic syndrome (eg, lipoid nephrosis) |
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Describe the presence of waxy (broad) casts in urinary sediments
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-Refractile, acellular cast
-Sign of chronic renal failure |
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Describe the presence of calcium oxalate crystals in the urinary sediment
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From pure vegan diet, ethylene glycol poisoning, calcium oxalate stone
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Describe the presence of uric acid crystals in the urinary sediment
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Hyperuricemia associated with gout or massive destruction of cells after chemotherapy
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Describe the presence of triple phosphate crystals in the urinary sediment
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May be a sign of urinary tract infection due to urease producing uropathogens (eg Proteus species)
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Describe the presence of cystine crystals in the urinary sediment
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Hexagonal crystal seen in cystinuria
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Describe the distribution of blood in the kidney
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-Renal cortex receives ~90% of the blood supply
-Renal medulla is relatively ischemic due to reduced blood supply |
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Describe the arteries of the kidney
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1. Renal vessels are end-arteries
a. No collateral circulation b. Occlusion of any branch of a renal artery produces infarction 2. Afferent arterioles a. contain the juxtaglomerular apparatus -Produces renin b. Blood flow is controlled by renal-derived PGE2 (vasodilator) c. Direct blood into the glomerular capillaries 3. Efferent arterioles a. Drain the glomerular capillaries b. Blood flow controlled by ATH (vasoconstrictor) c. Eventually become the peritubular capillaries |
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Describe the cells of the glomerulus
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1. Glomerular capillaries contain fenestrated epithelium
-Holes in the endothelial surface are important in the filtration process 2. Glomerular basement membrane 3. Visceral epithelial cells (VEC) 4. Mesangial cells 5. Parietal epithelial cells |
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Describe the glomerular basement membrane
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1. Composed of type IV collagen
2. Size and charge are the primary determinants of protein filtration a. Heparan sulfate produces the negative charge of the GBM b. Cationic proteins of low molecular weight (LMW) are permeable c. Albumin has a strong negative charge and is not permeable i. Loss of the negative charge causes loss of albumin in the urine ii. Called selective proteinuria (eg minimal change disease) d. GBM is permeable to water and LMW (<70k daltons) proteins (eg amino acids) |
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What are some causes of GBM thickening?
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1. Deposition of immunocomplexes
-Examples: membranous glomerulopathy 2. Increased synthesis of type IV collagen -Example: diabetes mellitus |
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Describe Visceral epithelial cells
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1. Primary responsible for production of the GBM
2. Contain podocytes and slit pores between the podocytes -Serve as a distal barrier for preventing protein loss in the urine 3. Fusion of the podocytes is present in any cause of the nephrotic syndrome |
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Describe Mesangial cells
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1. Support the glomerular capillaries
2. Can release inflammatory mediators and proliferate -Example: IgA glomerulopathy has mesangial immunocomplex deposits |
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Describe Parietal epithelial cells
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1. Lining cells of the Bowman's capsule
2. Proliferation causes "crescents" that encroach upon and destroy the glomerulus |
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Describe horseshoe kidney
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1. Most common congenital kidney disorder
2. Majority (90% of cases) are fused at the lower pole -Kidney is trapped behind the root of the inferior mesenteric artery 3. Clinical findings a. Increased incidence with Turner's syndrome b. Danger of infection and stone formation |
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What are the cystic disorders of the kidney?
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-Renal dysplasia
-Juvenile polycystic kidney disease -Adult polycystic kidney disease -Medullary sponge kidney -Acquired polycystic kidney disease -Simple retention cysts |
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Describe renal dysplasia
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-Most common cystic disease in children
-No inheritance pattern -Abnormal development of one or both kidneys; abnormal structures persist in the kidneys (eg, cartilage, immature collecting ductules) -Present as an enlarged, irregular, cystic, unilateral (bilateral) flank mass -Bilateral dysplastic kidneys may lead to renal failure; accounts for ~20% of cases of CRF in children |
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Describe Juvenile polycystic kidney disease
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-AR inheritance
-Bilateral cystic disease; cysts in the cortex and medulla -Cysts also occur in the liver -Association with congenital hepatic fibrosis leading to portal hypertension -Enlarged kidneys at birth; most serious types are incompatible with life -Maternal oligohydramnios (decreased amniotic fluid); newborns have Potter's facies, a deformation due to oligohydramnios; findings include low-set ears, parrot beak nose, and lung hypoplasia |
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Describe Adult polycystic kidney disease
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-AD inheritance; defect on chromosome 16
-Bilateral cystic disease develops by 20-25 years of age; bilaterally palpable kidneys; cysts involve all parts of the nephron in the cortex and medulla -Cysts are present in the liver (50%), pancreas (10%), spleen (5%) -Hypertension (>80% of cases); associated with stroke due to rupture of intracranial berry aneurysms (aneurysms in 10-30% of cases), intracerebral hemorrhage, lacunar infarcts -CRF begins at age 40-60; due to destruction of kidneys by slowly expanding cysts; accounts for ~10% of cases of CRF; it is the most common cause of death -Other associations: sigmoid diverticulosis, hematuria, mitral valve prolapse, slight risk for developing renal cell carcinoma -Treatment: renal transplantation |
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Describe Medullary sponge kidney
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-No inheritance pattern
-Most commonly discovered with an IVP; striations are present in the papillary ducts of the medulla ("Swiss-chesse" appearance); multiple cysts of the collecting ducts are present in the medulla -Recurrent UTIs, hematuria, and renal stones |
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Describe Acquired polycystic kidney disease
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-Most common cause in renal dialysis; occurs in ~50% of patients on long-term dialysis
-Tubules are obstructed by interstitial fibrosis or oxalate crystals -Small risk for developing renal cell carcinoma |
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Describe Simple retention cysts
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-Most common adult renal cyst
-Derived from tubular obstruction -May produce hematuria -Requires needle aspiration to distinguish it from renal cell carcinoma |
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Describe the mechanisms for producing glomerular disease
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1. Immunocomplexes (type III hypersensitivity)
a. Circulate and deposit in glomeruli or they develop in situ -Example: DNA-anti-DNA complexes in SLE b. ICs activate the complement system i. C5a is produced, which is chemotactic to neutrophils ii. Neutrophiles damage the glomeruli by neutrophiles, which occurs in nephritis types of glomerulonephritis 2. Antibodies directed against GBM antigens -Example: Goodpasture syndrome 3. T-cell production of cytokines a. Cytokines cause the GBM to lose its negative charge b. Cytokines damage podocytes causing them to fuse c. Example- minimal change disease in nephrotic syndrome |
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What are the clinical manifestations of glomerular disease?
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1. Nephritic syndrome
2. Nephrotic syndrome 3. Chronic glomerulonephritis |
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Describe the clinical and laboratory findings in nephritic syndrome
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1. Hypertension
-Due to salt retention 2. Periorbital puffiness a. Due to salt retention in the loose skin in that area b. In some cases, edema can be more generalized -Na retention increases plasma hydrostatic pressure 3. Oliguria (~400mL urine/day) a. Due to decreased GFR from inflamed glomeruli b. Tubular function is intact 4. Hematuria a. Dysmorphic RBCs with irregular membranes b. Due to inflamed glomeruli from IC deposition 5. Neutrophils in the sediment -Particularly in IC types 6. RBC casts are a key finding -Occasionally, WBC casts are also present 7. Proteinuria >150 mg/day, but <3.5g 8. Azotemia with a BUN:Cr >15 -Tubular function is intact in acute glomerulonephritis |
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What are the primary nephritic types of glomerular disease?
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-IgA glomerulopathy (Berger's disease)
-Post-streptococcal glomerulonephritis -Diffuse proliferative glomerulonephritis (SLE) -Rapidly progressive crescentic glomerulonephritis |
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Describe IgA glomerulopathy (Berger's disease)
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-Overlapping features with HSP may occur
-Episodic bouts of hematuria (mircroscopic or gross) usually following an upper respiratory infection; hypertension -Slow progression to CRF (40-50%) |
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Describe the treatment for IgA glomerulopathy
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-Slow progression to CRF (40-50%)
-Corticosteroids decrease proteinuria -Treat hypertension |
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Who gets IgA glomerulopathy?
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-Most common nephropathy; majority are nephritic (5% nephrotic)
-Affects children and adults |
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Describe who gets post-streptococcal glomerulonephritis
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-Most common type of postinfectious GN
-Usually follows group A streptococcal infection of skin (eg scarlet fever) or pharynx |
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Describe the histology of post-streptococcal glomerulonephritis
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-Subepithelial IC deposits with granular IF
-ICs activate alternative complement pathway -Diffuse proliferative pattern with neutrophil infiltration |
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Describe the clinical symptoms of post-streptococcal glomerulonephritis
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-Hematuria 1-3 weeks following group A streptococcal infection by a nephritogenic strain (never produces acute rheumatic fever)
-Periorbital edema (Na retention) -Edema can occasionally be more extensive but is related to Na retention not hypoalbuminemia -Hypertension (usually transient; sometimes severe) |
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Describe the histology of IgA glomerulopathy
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-Focal proliferative glomerulopathy
-Mesangial IgA IC deposits with granular IF -ICs activate alternative complement pathway -Overlapping featiures if HSP may occur |
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Describe the blood work in Post-streptoccal glomerulonephritis
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-Increased anti-DNase B titers
-ASO is degraded by oil in the skin and is not increased -Streptozyme test is positive (can detect anti-DNase B, ASO, anti-AH, and anti-NAD antibodies) |
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Describe the treatment of Post-streptoccal glomerulonephritis
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-Usually resolves; CRF is uncommon
-Treatment: Supportive; penicillin G or V if cultures are positive from Streptococcus pyogenes; treat hypertension |
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Describe the blood work in IgA nephropathy
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Increased mucosal synthesis and decreased clearance of IgA; increased serum IgA (50%)
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Describe diffuse proliferative glomerulonephritis (SLE)
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-Diffuse proliferative GN is most common subtype of glomerular disease in SLE
-Other types can have a nephrotic presentation -Evolves into CRF in most cases -Common cause of death in SLE |
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Describe the histology of diffuse proliferative glomerulonephritis
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-Subendothelial IC deposits with granular IF
-DNA-Anti-DNA ICs activate classical complement pathway -"Wire looping" of capillaries (Corresponds with subendothelial ICs) -Neutrophil infiltration with hyaline thrombi in capillary limens |
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What is the major target organ in SLE?
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Kidneys (~90%)
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Describe the blood test for diffuse proliferative glomerulonephritis
|
-Serum ANA test usually has a rim pattern, which corresponds with the presence of anti-dsDNA antibodies
|
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|
Describe treatment for diffuse proliferative glomerulonephritis
|
Corticosteroids and Cyclophosphamide
|
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Describe rapidly progressive crescentic glomerulonephritis
|
-Clinical syndrome that may be primary or secondary type of glomerlar disease
-Rapid loss of renal function progresses to ARF over days to weeks -Very poor prognosis -May or may not be associated with crescent formation (crescentic GN) |
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Describe the clinical associations of rapidly progressive crescentic glomerulonephritis
|
-Goodpasture’s syndrome
-Microscopic polyarteritis (p-ANCA) -Wegener’s granulomatoris (c-ANCA) |
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|
Describe Goodpasture syndrome
|
-Male dominant disease
-80% HLA-BR2 positive -Crescentic GN (accounts for 5% of all cases) -Begins with hemoptysis and ends with renal failure |
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Describe the histology of Goodpasture syndrome
|
-Anti-basement membrane antibodies against collagen in glomerular and pulmonary capillaries
-Linear IF -EM has no electron-dense deposits |
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Describe the treatment of Goodpasture syndrome
|
-Plasma exchange
-Immunosuppressive therapy with corticosteroids and cyclophosphamide -Renal transplantation |
|
|
What causes the damage in Nephrotic syndrome?
|
Glomerular injury is due to cytokines not neutrophils
a. Cytokines damage podocytes causing them to fuse together b. Cytokines destroy the negative charge of the GBM |
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Describe the clinical and laboratory findings of nephrotic syndrome
|
a. Key finding is proteinuria >3.5g/24hr
b. Generalized pitting edema and ascites 1. Due to hypoalbuminemia -Pitting edema is nephritic syndrome is due to Na retention 2. Increased risk for developing spontaneous peritonitis -Due to S. pneumonia c. Hypertension in some types -Due to Na retention d. Hypercoagulable state due to loss of antithrombin IUII -Potential for renal vein thrombosis e. Hypercholesterolemia -Hypoalbuminemia increases synthesis of cholesterol f. Hypogammaglobulinemia -Due to the loss of gamma-globulins in the urine g. Fatty casts with maltese crosses and oval fat bodies -Key finding of the nephrotic syndrome |
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|
Describe minimal change disease
|
-Lipoid nephrosis
-Most common cause of nephrotic syndrome in children -More common in girls than boys -Occurs in ~15% of adults with nephrotic syndrome -T-cells cytokines cause the GBM to lose its negative charge; selective proteinuria (albumin not globulins) -Often preceded by respiratory infection or routine immunization -Usually normotensive (90%), unlike other types of nephrotic syndrome |
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|
What are the secondary causes of minimal change disease?
|
Hodgkin’s lymphoma
|
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Describe the histology of minimal change disease
|
-Structurally normal glomeruli
-Positive fat stains in glomerulus and tubules -Negative IF -EM shows fusion of podocytes and no deposits |
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Describe the treatment for minimal change disease
|
-Children respond well to steroid therapy
-CRF is rare |
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|
Describe focal segmental glomerulosclerosis
|
-Primary or secondary disease
-Secondary causes include HIV (most common glomerular disease), and IV heroin abuse -Nonselective proteinuria, microscopic hematuria (60-80%) -Hypertension early (20%) -Poor prognosis, commonly progresses to CRF |
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|
Describe treatment of focal segmental glomerulosclerosis
|
Corticosteroids (only 15-20% response)
|
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|
Describe membranous glomerulosclerosis
|
-Most common cause of nephrotic syndrome
-Primary and secondary types -Secondary causes -Drugs: captopril, gold therapy -Infections: HBV, Plasmodium malariae, syphilis -Malignancy: carcinomas, Hodgkin’s lymphoma -Autoimmune disease: SLE (nephrotic presentation) |
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Describe the histology of membranous glomerulosclerosis
|
-Diffuse thickening of membranes
-Silver stains show “spike and dome” pattern beneath VECs (subepithelial deposits) -Subepithelial ICs with granular IF |
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Describe the treatment of membranous glomerulosclerosis
|
Corticosteroids may slow progression
|
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|
Describe Type I Membranoproliferative Glomeruloenephropathy
|
-Most common type of MPGN
-Nephrotic presentation (60%) -Some causes have a nephritic presentation -Associated with HBV, HCV (more common), or cryoglombulinemia -Hypertension (35%) -Majority have hematuria -Majority progress to CRF |
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|
Describe the histology of Type I Membranoproliferative Glomeruloenephropathy
|
-Subendothelial ICs with granular ICs
-ICs activate classical and alternative complement pathways -EM shows tram tracks caused by splitting of the GBM by an ingrowth of mesangium |
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|
Describe the treatment of Type I Membranoproliferative Glomeruloenephropathy
|
Response to corticosteroids NOT established
|
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|
Describe Type II Membranoproliferative Glomeruloenephropathy
|
-Associated with the C3 nephritic factor (C3NEF)
-An autoantibody that binds to C3 convertase (C3bBb) -Prevents degradation of C3 convertase causing sustained activation of C3 resulting in very low levels of C3 -Hypertension (35%) -Majority have hematuria -Majority progress to CRF |
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|
Describe the histology of Describe Type II Membranoproliferative Glomeruloenephropathy
|
-Diffuse intramembranous deposits (“dense deposit disease”
-EM shows tram tracks |
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|
Describe the treatment of Type II Membranoproliferative Glomeruloenephropathy
|
Response to corticosteroids NOT established
|
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|
Describe diabetic glomerulopathy
|
-Nodular glomerulosclerosis (Kimmelstiel-Wilson disease)
|
|
|
Describe the epidemiology of diabetic glomerulopathy
|
1. Glomerulopathy occurs in type 1 and type 2 diabetes
-Occurs more often in type 1 (35-45%) than type 2 diabetes (20%) 2. Most common cause of chronic renal failure in the US -Type 1>Type 2 diabetes mellitus |
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|
Describe the risk factors for diabetic glomerulopathy
|
1. Poor glycemic control
2. Hypertension 3. Diabetic retinopathy -High correlation with coexisting glomerulopathy |
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|
Describe the pathogenesis of diabetic nephropathy
|
1. Nonenzymatic glycosilization of the GBM
-Also affects tubular basement membranes a. Glycosylation refers to glucose attaching to amino acids b. Increases vessel and tubular cell permeability to protein 2. NEG of the afferent and efferent arterioles a. Produces hyaline arteriolosclerosis b. Involves efferent arterioles before afferent arterioles 3. Osmotic damage to glomerular capillary endothelial cells a. Glucose is converted by aldose reductase into sorbitol b. Sorbitol is osmotically active c. Water enters the cells causing damage 4. Hyperfiltration damage to the mesangium a. Selective hyaline arteriolosclerosis of efferent arterioles b. Increase the GFR, which damages mesangial cells 5. Diabetic microangiopathy; increased deposition of type IV collagen -GBM, tubular cell basement membranes, mesangium |
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|
Describe the histology of diabetic nephropathy
|
-Nonspecific immunofluorescence
-EM shows fusion of podocytes -Afferent and efferent hyaline arteriolosclerosis -When the afferent arteriole becomes hyalinized, the GBM decreases -Nodular masses develop in the mesangial matrix -Due to increased type IV collagen synthesis and trapped proteins |
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|
Describe the clinical and laboratory findings of diabetic nephropathy
|
1. Microalbuminuria
a. Initial laboratory manifestations of diabetic glomerulopathy -Usually begins after ~10 years of poor glycemic control b. Microalbuminuria dipsticks detect albumin levels in the range of 1.5-1.8 mg/dL 2. Other renal diseases associated with diabetes mellitus -Renal papillary necrosis, acute and chronic pyelonephrotis |
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|
Describe renal amyloidosis
|
Associated with primary and secondary amyloidosis
|
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|
Describe the use of ACEi in diabetic glomerulopathy
|
-Prescribed when microalbuminuria is first detected
-Slows progression of diabetic glomerulopathy and retinopathy in both types of DM -One possible mechanism is by reducing pressure in the glomerular capillaries by decreasing ATII vasoconstriction of the hyalinzied efferent arterioles -Angiotensin receptor blockers are also useful, particularly in type 2 DM. These changes are independent of the BP lowering capabilities of both drugs |
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|
Describe Alport’s syndrome
|
1. Autosomal dominant disease, perhaps X-linked recessive
-Autoantibodies to type IV collagen in GBM 2. No specific IF or EM findings 3. Microscopic findings -Lipid accumulation in VECs producing foam cells 4. Sensorineural hearing loss and ocular abnormalities |
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|
Describe Thin basement membrane disease
|
-“Benign familial hematuria”
1. Autosomal dominant disorder 2. Extremely thin GBMs -Normal renal function 3. Mild proteinuria, persistent microscopic hematuria |
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|
Describe the causes of glomerulonephritis
|
a. Rapidly progressive glomerulonephritis (PRGN, 90%)
b. Focal segmental glomerulosclerosis (80%) c. Type I membranoproliferative glomerulonephritis (40%) d. Membranous glomerulopathy (20-30%) e. Type IV diffuse proliferative glomerulonephritis in SLE (20%) f. IgA glomerulopathy (10%) |
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|
Describe the gross and microscopic findings in Chronic glomerulunephritis
|
a. Shrunken kidneys
b. Glomerular sclerosis and tubular atrophy |
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|
Describe the epidemiology of acute renal failure
|
1. Greater than 10% of ICU patients develop acutre renal failure
2. Greater than 40% of hospital ARF is iatrogenic 3. ARF occurs in 20% of patients with sepsis 4. ARF develops in >50% of patients with septic shock |
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|
Describe acute renal failure
|
a. Acute suppression of renal function developing in 24 hours
b. Accompanies by anuria or oliguria (~400 mL/24hr) c. ATN is the most common cause of ARF -Subdivided into ischemic nad nephrotoxic types d. Other causes of ARF i. Postrenal obstruction (prostate hyperplasia, invasive cervical cancer) ii. Vascular disease (malignant hypertension) iii. RPGN, drugs, DIC, urate nephropathy |
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|
Describe ischemic ATN
|
Most often caused by prerenal azotemia due to hypovolemia
|
|
|
Describe how ischemia damages endothelial cells in ischemic ATN
|
1. Causes a decrease in vasodilators
-Examples: NO, PGI2 2. Increase in vasoconstrictors -Example: Endothelin 3. Net effect is vasoconstriction of afferent arterioles, which decreases GFR |
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|
Describe how ischemia damages tubule cells in ischemic ATN
|
1. Causes detachment of tubular cells into the lumen causing obstruction
-Produces pigmented renal tubular cell casts 2. Casts obstruct the lumen causing an increase in intratubular pressure a. Decreases GFR b. Pushes fluid into the interstitium c. Net effect is oliguria |
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|
Describe the sites of tubular damage in ischemic ATN
|
1. Straight segment of proximal tubule
-Part of the nephron most susceptible to hypoxia 2. Medullary segment of the thich ascending limb (TAL) -Location of the NaK2Cl cotransporter 3. Tubular basement membranes are disrupted at these sites -Interferes with renal tubular cell regeneration |
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|
Describe the causes of nephrotoxic ATN
|
1. Aminoglucosides are the most common cause (eg, gentamicin)
2. Radiocontrast agents 3. Heavy metals (eg, lead and Mg) |
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|
Describe the microscopic findings in ATN
|
1. Primmary damages to the proximal tubule cells
2. Tubular basement membrane is intact |
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|
Describe the clinical and laboratory findings in ATN
|
a. Oliguria, in most cases
-Some cases have puluria (~800mL/24hrs) b. Pigmented renal tubular cell casts c. Hyperkalemia, increased anion gap metabolic acidosis d. Increased serum BUN and creatinine (ratio<15) e. Hypokalemia (dieresis phase) and infection are common problems |
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|
Describe the treatment of ATN
|
a. Treat prerenal azotemia
-Volume expansion if hypovolemic; increase renal blood flow b. Low dose dopamine c. Fenoldopam (dopamine alpha-1-receptor agonist) d. Dialysis |
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|
Describe the epidemiology of acute pyelonephritis
|
1. More common in women than men
-Women have a shorter urethra 2. Escherichia coli most common cause -Enterococcus is second in frequency 3. Risk factors a. Indwelling urinary catheter b. Urinary tract obstruction c. Medullary sponge kidney d. Diabetes mellitus, pregnancy e. Sickle cell trait/disease |
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|
What are the possible pathogeneses of acute pyelonephritis
|
1. Vesicoureteral reflux (VUR) with ascending infection (most common)
2. Ascending infection 3. Hematogenous spread to kidneys |
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|
Describe Vesicoureteral reflux with ascending infection as a cause for acute pyelonephritis
|
1. Intravesicular portion of the ureter is normally compressed with micturition
-Prevents reflux of urine into the ureters 2. In VUR, the intravesicular portion of the ureter is not compressed during micturition -Urine refluxes into the ureters 3. Should be corrected by reimplantation of the ureters/stents |
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|
Describe ascending infection as a cause for acute pyelonephritis
|
1. Most common mechanism for lower and upper UTIs in females
2. Distal urethra and vaginal introitus are normally colonized by E. coli 3. Organisms ascend into the urethra nad bladder -Causes urethritis and cystitis 4. If VUR is present, infected urine ascends to the renal pelvis and renal parenchyma -Causes APN |
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|
Describe hematogenous spread to kidneys as a cause of acute pyelonephritis
|
1. Uncommom cause of APN
2. Suspect if S. aureus is cultured in urine |
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|
Describe the gross and microscopic findings in acute pyelonephritis
|
1. Grayish white areas of abscess formation are in the cortex and medulla
2. Microabscess formation occurs in the tubular lumens and interstitium |
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|
Describe the clinical findings in acute pyelonephritis
|
1. Spiking fever, flank pain
2. Increased frequency of urination 3. Painful urination (dysuria) |
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|
Describe the laboratory findings in acute pyelonephritis
|
1. WBC casts
2. Pyuria, bacteriuria (usually E. coli) 3. Hematuria |
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|
Describe the complications of acute pyelonephritis
|
1. Chronic pyelonephritis
2. Perinephric abscess 3. Renal papillary necrosis 4. Septicemia with endotoxic shock |
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|
Describe the treatment for acute pyelonephritis
|
1. Ciprofloxacin given orally if uncomplicated
2. Ciprofloxacin IV if hospitalized 3. Repair VUR |
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|
What are the major causes of oliguria?
|
1. Prerenal azotemia (most common cause)
2. Acute glomerulonephritis (nephritic type) 3. Acute tubular necrosis (renal azotemia) 4. Postrenal azotemia |
|
|
What laboratory tests are commonly used to differentiate the cause of oliguria?
|
1. Urine osmolality (UOSm)
2. Fractional excretion of Na (FENa) 3. Random urine Na (UNa) 4. Serum BUN:Cr ratio |
|
|
What does a high UOsm (>500 mOsm/kg) indicate?
|
Good concentrating ability and intact tubular function
|
|
|
What does a low UOsm (<350 mOsm/kg) indicate?Poor concentrating ability and tubular dysfunction
|
Poor concentrating ability and tubular dysfunction
|
|
|
Describe FENa
|
-The amount of Na excreted in the urine divided by the amount of Na that is filtered by the kidneys
-FENa=[(UNa*PCr)/(PNa*UCr)]*100 |
|
|
What does a low FENa (<1%) indicate?
|
-Good tubular function
-Excludes acute tubular necrosis (ATN) as a cause of oliguria |
|
|
What does a high FENa (>2%) indicate?
|
-Tubular dysfunction
-Highly predictive of ATN as a cause of oliguria |
|
|
What does a low UNa (<20 mEq/L) indicate?
|
Intact tubular function
|
|
|
What does a high UNa (>40 mEq/L) indicate?
|
Tubular dysfunction
|
|
|
What does a BUN/Cr ration>15 indicate?
|
Intact tubular function
|
|
|
What does a BUN/Cr ration <15 indicate?
|
Tubular dysfunction
|
|
|
What is the differential for oliguria with preservation of tubular function?
|
-Prerenal azotemia
-Acute glomerulonephritis |
|
|
Describe the urine sediment in prerenal azotemia
|
Has no abnormal findings or may have a few hyaline casts
|
|
|
Describe the urine sediment of acute glomerulonephritis
|
Hematuria and RBC casts
|
|
|
What is the differential for oliguria with tubular dysfunction?
|
-Acute tubular necrosis
-Post renal azotemia (long-standing obstruction) |
|
|
Describe the urine sediment of actue tubular necrosis
|
Pigmented renal tubular cell casts
|
|
|
Describe the urine sediment In post renal azotemia
|
Normal, patient will likely have a history of a renal stones, benign prostatic hyperplasia or cervical cancer
|
|
|
Describe the FENa, BUN:Cr, UNa, UOsm, and Urinalysis of Prerenal Azotemia
|
FENa: <1
BUN:Cr: >15 UNa: <20 UOsm: >500 Urinalysis: Normal sediment or hyaline casts |
|
|
Describe the FENa, BUN:Cr, UNa, UOsm, and Urinalysis of Acute Glomerulonephritis
|
FENa: <1
BUN:Cr: >15 UNa: <20 UOsm: >500 Urinalysis: RBC casts, hematuria |
|
|
Describe the FENa, BUN:Cr, UNa, UOsm, and Urinalysis of Acute tubular necrosis
|
FENa: >2
BUN:Cr: <15 UNa: >40 UOsm: <350 Urinalysis: Renal tubular cell casts |
|
|
Describe the FENa, BUN:Cr, UNa, UOsm, and Urinalysis of Postrenal azotemia
|
FENa: >2
BUN:Cr: <15 UNa:>40 UOsm: <350 Urinalysis: Normal sediment |
|
|
Describe the pathogenesis of chronic pyelonephritis
|
1. VUR starting in young girls
2. Lower urinary tract obstruction a. Produces hydronephrosis b. Examples: prostate hyperplasia, renal stones |
|
|
Describe the gross findings in chronic pyelonephritis
|
1. Reflux type of CPN
a. U-shaped cortical scares overlying a blunt calyx b. Visible with an intravenous pyelogram (IVP) 2. Obstructive type CPN a. Uniform dilation of the calyces b. Diffuse thinning of the cortical tissue |
|
|
Describe the microscopic findings of chronic pyelonephritis
|
1. Chronic inflammation
-Secondary to scarring of the glomeruli 2. Tubular atrophy -Tubules contain eosinophilic material resembling thyroid tissue (“thyroidization”) |
|
|
Describe the clinical and laboratory findings in chronic pyelonephritis
|
1. Usually a history of recurrent APN
2. May cause hypertension -Reflux nephropathy is a cause of hypertension in children 3. May cause chronic renal failure (CRF) |
|
|
Describe the common drug associations in acute drug-induced TIN
|
1. Penicillin, particularly methicillin
2. Rifampin, sulfonamides 3. NSAIDs, diuretics |
|
|
Describe the pathogenesis of acute drug-induced TIN
|
1. Combination of type I and type IV hypersensitivity
2. Occurs ~2 weeks after beginning a drug |
|
|
Describe the clinical and laboratory findings in acute drug-induced TIN
|
1. Abrupt onset of fever, oliguria, and rash
-Withdrawal of the drug cause reversal of the disease 2. Laboratory findings a. BUN/Cr <15 b. Eosinophilia and eosinophiluria (highly predictive) |
|
|
Describe the treatment for acute drug-induced TIN
|
Withdraw the drug
|
|
|
Describe the epidemiology of analgesic nephropathy
|
1. Common cause of chronic drug induced TIN
2. More common in women than men 3. Usually occurs in patients with chronic pain |
|
|
Describe the pathogenesis of analgesic nephropathy
|
1. Chronic use of acetaminophen plus aspirin for 3 or more years
2. Acetaminophen free radicals damage renal tubules in medulla 3. Aspirin inhibits renal synthesis of PGE2, leading ATII unopposed -Decreased blood flow to the renal medulla |
|
|
Describe the complications of analgesic nephropathy
|
1. Renal papillary necrosis
a. Sloughing of renal papillae -Produces gross hematuria, proteinuria, and colicky flank pain b. An IVP shows a “ring defect” where one or more papillae used to reside c. Other causes of renal papillary necrosis -Diabetes, sickle cell trait/disease, APN 2. Hypertension, CRF 3. Renal pelvic and bladder transitional cell carcinomas |
|
|
Describe urate nephropathy
|
a. Deposition of urate crystals in the tubules and interstitium
b. Causes i. Massive release of purines (precursor of uric acid) -Usually following aggressive treatment of disseminated cancer (eg leukemia) ii. Lead poisoning, gout c. May produce ARF |
|
|
Describe chronic lead poisoning
|
1. Decreases excretion of uric acid (urate nephropathy)
-Can also decrease uric acid secretion producing gout 2. Direct toxic effect produces TIN 3. Proximal tubule cells contain characteristic nuclear acid-fast inclusions |
|
|
Describe Bence-Jones proteinuria
|
1. BJ protein produces tubular casts
-Light chains are toxic to renal tubular epithelium 2. Casts obstruct the lumen and incite a foreign body giant cell reaction -Reaction involves tubules and interstitium leading to renal failure |
|
|
Describe Nephrocalcinosis
|
1. Due to hypercalcemia
-Metastatic calcification of the basement membrane of collecting tubules 2. Causes polyuria and renal failure |
|
|
Describe primary amyloidosis producing nephrotic syndrome
|
Light chains are converted to amyloid
|
|
|
Describe chronic renal failure
|
1. Progressive irreversible azotemia that develops over months to years
2. Culminates in end-stage renal disease a. Kidneys no longer function well enough to sustain life b. GFR<10mL/minute |
|
|
What are the primary causes of chronic renal failure?
|
1. Diabetic mellitus (37%)
2. Hypertension (30%) 3. Chronic glomerulonephritis (12%) -Particularly due to RPGN and focal segmental glomerulosclerosis 4. Cystic renal disease -Renal dysplasia in children, adult polycystic kidney disease |
|
|
Describe the gorss appearance of chonric renal failure kidneys
|
Bilateral, small shrunken kidneys
|
|
|
Describe the hematological findings in Chronic renal failure
|
1. Normocytic anemia with corrected reticulocyte count <3%
-Primarily due to decreased erythropoietin 2. Qualitative platelet defects |
|
|
Describe osteitis fibrosis cystic
|
1. Due to hypovitaminosis D
a. Causes hypocalcemia, which stimulates production of PTH b. Called secondary hyperparathyroidism (HPTH) 2. Secondary HPTH increased bone resoprtion a. Causes cystic lesions in bone (e.g, jaw) b. Hemorrhage into cysts causes a brown discoloration |
|
|
Describe osteomalacia
|
1. Decreased mineralization of the organic bone matrix (osteoid)
2. In CRF, it id due to hypovitaminosis D -Causes hypocalcemia, leading to decreased bone mineralization 3. Produces fractures and bone pain |
|
|
Describe osteoporosis
|
1. Loss of organic bone matrix and minerals
-causes an overall reduction in bone mass 2. IN CRF, it is due to chronic metabolic acidosis -Excess H+ ions are buffered by bone 3. Produces fractures and bone pain |
|
|
Describe the cardiovascular findings of chronic renal failure
|
1. Hypertension from salt retention
2. Hemorrhagic fibrinous pericarditis 3. CHF, accelerated atherosclerosis |
|
|
Describe the GI findings of chronic renal failure
|
Hemorragic gastritis
|
|
|
Describe the dermatological findings of chronic renal failure
|
Uremic frost (urea crystals deposit on skin)
|
|
|
Describe the acid-base and electrolyte abnormalities in chronic renal failure
|
1 .Hyperkalemia and increased anion gap metabolic acidosis
2. Na is usually normal except in salt-losing types of CRF |
|
|
What are the results of hypocalcemia from chronic renal failure?
|
1. Hypovitaminosis D
a. Due to decreased synthesis of 1-alpha-hydroxylase b. Decreased reabsorption of calcium from the small intestine 2. Hyperphosphatemia a. Due to decreased renal excretion b. Drives calcium into bone nad soft tissue -Metastatic calcification |
|
|
What are the results of hypocalcemia from chronic renal failure?
|
1. Hypovitaminosis D
a. Due to decreased synthesis of 1-alpha-hydroxylase b. Decreased reabsorption of calcium from the small intestine 2. Hyperphosphatemia a. Due to decreased renal excretion b. Drives calcium into bone nad soft tissue -Metastatic calcification |
|
|
Summarize the laboratory findings in chronic renal failure
|
1. Acid-base and electrolyte abnormalities
2. Hypocalcemia 3. Normocytic anemia-prolonged bleeding time 4. Increased serum cystatin C 5. Urinanalysis findings |
|
|
Describe the increased serum cystatin C in Chronic renal failure
|
1. Cystine protease inhibitor produced by all nucleated cells
2. Filtered by glomerulus but not secreted 3. Less dependent on age, sex, race, and muscle mass than creatinine 4. May be superior to creatinine in assessing severity of renal function -Biomarker of kidney function |
|
|
Describe the urinalysis findings in chronic renal failure
|
1. Fixed specific gravity
a. Tubular dysfunction causes lack of concentration and dilution b. Free water clearance is zero 2. Waxy/broad casts |
|
|
Describe the nonpharmacologic treatment of Chronic renal failure
|
1. Restrict Na
2. Low-protein diet 3. Adjust drug doses to renal clearance 4. Kidney transplantation |
|
|
Describe the general treatment of chronic renal failure
|
1. ACEi
a. Reduced proteinruia and disease progression b. Treat hypertension 2. Dialysis 3. Erythrpoiesis stimulating agents 4. Ca supplementation and vitamin D (calcitriol) -Treat renal osteodystrophy 5. Phosphate binder (eg sevelamer) |
|
|
Describe benign nephrosclerosis
|
1. Most common renal disease in essential hypertension
2. Pathogenesis a. Hyaline arteriolosclerosis of arterioles in the renal cortex b. Causes tubular atrophy, interstitial fibrosis, glomerular sclerosis 3. Small kidneys with a finely granular cortical surface |
|
|
Describe the laboratory findings of benign nephrosclerosis
|
1. Mild proteinuria
2. Hematuria (no RBC casts) 3. Renal azotemia |
|
|
Describe the epidemiology of malignant hypertension
|
1. Sudden onset of accelerated hypertension
a. May occur in normotensive individuals b. May occur in those with BNS (most common) c. May occur as a complication of various disorders 2. Risk factors a. Pre-existing BNS (most common) b. Hemolytic-uremic syndrome c. Thrombotic thrombocytopenic purpura d. Systemic sclerosis |
|
|
Describe the pathogenesis of malignant hypertension
|
1. Vascular damage to arterioles and small arteries
2. Gross and microscopic changes a. Fibrinoid necrosis and necrotizing arteriolitis and glomerulitis -Pinpoint hemorrhages on the cortical surface (“flea-bitten” kidneys) b. Hyperplastic arteriolosclerosis (“onion-skin” lesion) -Smooth muscle hyperplasia and reduplication of basement membrane |
|
|
Describe the clinical findings in malignany hypertension
|
1. Rapid increased in BP to >210/120
2. Hypertensive encephalopathy a. Cerebral edema b. Papilledema -Loss of the normal optic nerve disk margin c. Retinopathy -Flame hemorrhages, exudates d. Potential for an intracerebral bleed 3. Oliguric acute renal failure |
|
|
Describe the laboratory findings in malignant hypertension
|
1. Azotemia with BUN/Cr <15
2. Hematuria with RBC casts 3. Proteinuria |
|
|
Describe the initial treatment for malignant hypertension
|
IV Sodium nitroprusside
|
|
|
Describe the causes of renal infarction
|
1. Embolization from thrombi in the left side of the heart (most common)
2. Atheroembolic renal disease 3. Vasculitis, particularly polyarteritis nodosa |
|
|
Describe the gross and microscopic appearance of renal infarction
|
1. Irregular, wedge-shaped pale infarctions in the cortex
2. Old infarcts have a V-shaped appearance due to scar tissue |
|
|
Describe the clinical presentation of renal infarction
|
Sudden onset of flank pain and hematuria
|
|
|
Describe Sickle Cell nephropathy
|
1. Occurs with sickle cell trait or disease
2. Clinical presentations a. Asymptomatic hematuria (most common) -Due to infarctions in the medulla b. Loss of concentrating ability c. Renal papillary necrosis d. Pyelonephritis |
|
|
Describe Diffuse cortical necrosis
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1. Complications of an obstetric emergency
-Examples: Preeclampsia, abruption placentae 2. Due to DIC limited to the renal cortex a. Fibrin clots in arterioles and glomerular capillaries b. Bilateral, diffuse, pale infarct of the renal cortex 3. Anuria (no urine ) in a pregnant woman followed by ARF |
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Describe the epidemiology of hydronephrosis
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1. Children usually have congenital malformation
-Examples: Bladder neck obstruction, urethral valve 2. Adults usually have acquired disease -Examples: stone (most common), prostate hyperplasia |
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Describe the causes of hydronephrosis
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1. Renal stone (most common)
2. Retroperitoneal fibrosis 3. Cervical cancer, benign prostatic hyperplasia |
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Describe the gross findings in hydronephrosis
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1. Dilated ureter and renal pelvis
2. Compression atrophy of the renal medulla and cortex |
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Describe the consequences of hypdronephrosis
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May produce postrenal azotemia
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Describe the treatment of hydronephrosis
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-Treatment is to relieve the obstruction
-Catheter (most often) -Nephrostomy tube -Cystoscopy |
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Describe the epidemiology of renal stones
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1. Stones occur in males more often than females
2. Incidence is greater during the summer -Insufficient fluid intake |
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Describe the causes of renal stones
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1. Hypercalciuria in the absence of hypercalcemia
a. Most common metabolic abnormality b. Due to increased GI reabsoption of Ca -Called absorptive hypercalciuria 2. Decreased urine volume concentrates the urine -Hydration is essential in preventing stone formation 3. Reduced urine citrate -Citrate normally chelates Ca 4. Primary HPTH (10% of cases) 5. Diets high in dairy products (contains phosphate) or oxalates 6. Urinary infections due to urease producers (eg Proteus) |
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Describe the types of renal stones
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1. Calcium stones (~80%)
2. Magnesium ammonium phosphate 3. Uric acid (8%) 4. Cystine (3%) |
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Describe Calcium renal stones
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1. Calcium oxalate stone (>50%) is the most common type in adults
-Increased incidence in pure vegans and those with Crohn’s disease 2. Calcium phosphate stones (10-20%) are the most common type in children -Associated with dairy products and distal renal tubular acidosis |
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Describe magnesium ammonium phosphate stones
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1. “Staghorm calculus” or struvite stone (15%)
2. Associated with urease produces (eg Proteus) 3. Urine is alkaline and smells like ammonia |
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Describe the clinical findings in renal stones
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1. Sudden onset of flank tenderness
2. Nausea and vomiting 3. Colicky pain radiation into groin 4. Patient constantly moving to try and relieve pain 5. Gross hematuria may be evident |
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Describe the laboratory findings in renal stones
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1. Hematuria
2. May find crystals in urine 3. Hypercalcemia -Consider primary HPTH |
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Describe the diagnosis of renal stones
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1. Plain film (kidney-ureter-bladder [KUB])
-Approx. 80% of stones are radiopaque 2. Unenhanced spiral CT -Sensitivity 96%, Specificity 100% 3. Ultrasound -Sensitivity 15%, specificity 90% 4. Strain urine to collect sones a. Always send for dialysis b. Greater than 50% pass stone within 48 hours c. Recurrence occurs in ~50% of patients |
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Describe treatment of calcium stones
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1. Hydrochlorothiazide
-Increases renal tubule reabsorption of calcium 2. Callulose phosphate -Binds calcium in intestines |
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Describe treatment of uric acid stones
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1. Allopurinol
2. Increase urinary pH -Makes uric acid soluble in urine |
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Describe treatment of struvite stones
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1. Surgical removal because of size
2. Antibiotic to eliminate urease producer |
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Describe surgical removal of renal stones
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1. Extracorporeal shock wave lithotripsy
2. Ureteroscopic stone extraction |
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Describe angiomyolipomas
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1. Hamartoma composed of blood vessels, smooth muscle, and adipose cells
2. Associated with tuberous sclerosis -Mental retardation -Multisystem hamartomas |
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What are the other names from renal cell carcinoma
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-Grawitz tumor
-Clear cell carcinoma -Hypernephroma |
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Describe the epidemiology for renal cell carcinoma
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1. Sporadic (most common) and hereditary types
2. Occur sin men more frequently than women -Occurs in 6th or 7th decade |
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Describe the Risk factors for renal cell carcinoma
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1. Smoking (most common)
2. Von Hippel-Lindau diease (VHL) i. Autosomal dominant ii. Chromosome 3 relationship iii. Hemangioblastomas of cerebellum and retina iv. Bilateral renal cell carcinoma (50-60%) 3. Adult polycystic kidney disease 4. Obesity, asbestos exposure, exposure to lead 5. Exposure to gasoline and petroleum products |
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Describe the pathogenesis of renal cell carcinoma
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1. Cytogenic abnormalities occur in sporadic hand hereditary cancers
-Translocations with loss of von Hippel-Lindau suppressor gene 2. Cancer derives from proximal tubule cells |
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Describe the gross and microscopic findings of clear cell carcinoma
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1. Most common type (70-80%)
2. Most are sporadic -Remainder are associated with VHL 3. Upper pole mass with cysts and hemorrhage -Tumor is a bright yellow mass larger than 3cm (75-80%) 4. Composed of clear cells that contain lipid nad glycogen 5. Tendency for renal vein invasion (15-20%) -Yellow tumor may invade inferior vena cava and extend to right side of heart |
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Describe the metastasis of clear cell carcinoma
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1. Lungs are the most common site (50-60%)
-Often hemorrhagic, “cannonball” appearance on radiographs 2. Bone (lytic lesions; 30-40%) 3. Regional nodes (15-30%) 4. Hemorrhagic nodules in the skin -Due to increased vascularity in the tumor |
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Describe the clinical findings of clear cell carcinoma
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a. Hematuria (50-60%)
b. Abdominal mass (25-45%) c. Flank pain (35-40%) d. Hypertension (20-40%) e. Triad-hematuria, abdominal mass, flank pain (5-10%) f. Weight loss (30-35%) g. Fever (5-15%) h. Left-sided varicocele (2-3%) -Related to invasion of left renal vein blocking left spermatic vein drainage |
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Describe the laboratory findings of clear cell carcinoma
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a. Elevated erythrocyte sedimentation rate (50-60%)
b. Normocytic anemia (20-40%) c. Extopic secretion of hormones i. Erythropoietin (EPO) -Produces secondary polycythemia (4%) ii. PTH-related protein -Produces hypercalcemia (3-6%) |
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Describe how to diagnose clear cell carcinoma
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US, abdominal CT, MRI
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Describe the treatment for clear cell carcinoma
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Nephrectomy
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Describe the prognosis of clear cell carcinoma
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a. Characteristically has late metastases
-May recure 10-20 years after the tumor has been removed b. Average 5-yr survival rate is 45% with metastasis -Up to 70% of cases do not have metastasis c. Extension into the renal vein or through the renal capsule has a poor prognosis -10-15% 5yr survival rate |
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Describe transitional cell carcinoma (TCC)
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a. Most common type of renal pelvic cancer
-Appox. 50% have similar tumors elsewhere in the urinary tract b. Risk factors i. Smoking (most common) ii. Phenacetin abuse iii. Aromatic amines (aniline dyes) iv. Cyclophosphamide |
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Describe Squamous cell carcinoma of the renal pelvis
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Risk factors include renal stones and chronic infection
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Describe the epidemiology of Wilm’s tumor
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a. Accounts for ~5% of childhood cancer
b. Most common primary renal tumor in children c. Occurs between 2-5yr of age d. Sporadic type (most common) e. Genetic type i. Autosomal dominant inheritance (chromosome 11) ii. WAGR syndrome -Wilm’s tumor, aniridia (absent iris) , genital abnormalities, retardation iii. Beckwith-Wiedmann syndrome -Wilm’s tumor, enlarged body organs, hemihypertrophy of extremities |
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Describe the tumor in Wilm’s tumor
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-Large, necrotic gray-tan tumor
-Derived from mesonephric mesoderm -Contains abortive glomeruli and tubules, primitive blastemal cells and rhabdomyoblasts |
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Describe the clinical findings in Wilm’s tumor
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1. Unilateral palpable mass in a child with hypertension
-Hypertension due to rennin secretion 2. Lungs are the most common site of metastasis 3. With combined therapies 2-yr survival rate is >90% |
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Describe the clinical findings in Wilm’s tumor
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1. Unilateral palpable mass in a child with hypertension
-Hypertension due to rennin secretion 2. Lungs are the most common site of metastasis 3. With combined therapies 2-yr survival rate is >90% |
