Term
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Definition
| Chronic renal disease is rising in the US and in other parts of the world; In the year 2000, in which we have the most reliable available estimates, nearly 400,000 people had to be dialyzed or transplanted due to chronic renal disease; That same year, approximately 20 million adults in the US had chronic renal disease that was not yet diagnosed (11.7% of the population); The most common risk factors for developing chronic renal disease are diabetes, chronic HTN, cardiovascular disease, family history of chronic renal disease, and age greater than 60 |
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Term
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Definition
| The GFR is the sum of the filtration rates of all the nephrons total; The GFR is the best measure of overall renal function; Estimating the GFR (along with other tests, such as measuring protein in the urine) can find chronic renal disease in its earliest stages when it is more amenable to therapies. |
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Term
| Stages of Chronic Renal Disease |
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Definition
| Chronic Renal Insufficiency (CRI) is the preferred term for patients with mild-to-moderate renal impairment, whose GFR falls in the range of 30-60ml/min; Chronic Renal Failure (CRF) is usually reserved to describe patients whose GFR is between 15 and 30 ml/min; End-Stage Renal Disease (ESRD), usually associated with signs and symptoms of uremia, is the term reserved for patients whose GFR has declined to levels of less than 10 to 15 ml/min |
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Term
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Definition
| Normal subjects excrete approximately 40-80mg of total protein a day into the urine (upper range of normal being about 150mg total in 24h); Albumin usually accounts for less than 20mg of the total daily urinary excretion, while Tamm-Horsfall protein amounts to about 30-50mg/ day; The gold standard for assessing daily protein excretion in the urine is by measuring protein in a 24h urine collection |
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Term
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Definition
| Early detection of small amounts of albumin in the urine is important in identifying diabetic and hypertensive patients who are at high risk for progressing to end-stage renal disease (ESRD); The dipstick is relatively insensitive to detecting early increases in glomerular filtration of albumin (not positive until 24h excretion >300-500mg). Advanced glomerular disease can already be present when albumin excretion is this high; Direct, sensitive measurement of urinary albumin should be done in diabetic/ hypertensive patients on a consistent basis (using specialized assays), to detect these early small increases in albumin excretion into the urine (persistent albumin excretion between 30 and 300mg/ day is microalbuminuria, and is indicative of onset of nephropathy) |
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Term
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Definition
| The afferent arteriole brings arterial blood into Bowman's capsule and is the beginning of the formation of the glomerular capillaries; The glomerular capillaries exit Bowman's capsule as the efferent arteriole |
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Term
| Glomerular Capillary Membrane Structure |
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Definition
| The glomerular capillary membrane consists of: 1) Fenestrated endothelium, 2) Glomerular basement membrane, 3) Interdigitated foot processes (podocytes), and 4) Slit diaphragms that span the podocytes |
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Term
| Definition of Nephrotic Syndromes |
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Definition
| Major clinical finding is heavy proteinuria (>3.5g/day) with a urine sediment that is relatively inactive (contains few cells or casts). Hypoalbuminemia - due to urinary losses not matched by increased hepatic protein synthesis. Edema is present, mostly due to retention of sodium as opposed to loss of albumin into the urine. |
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Term
| Definition of Nephritic Syndromes |
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Definition
| Heavy proteinuria may or may not occur. Urine sediment is active, containing red and white cells and cellular and granular casts. These urine abnormalities reflect influx of circulating inflammatory cells into the glomerular capillaries and mesangium. Decreased GFR in this setting is due to decreased glomerular surface area, often due to partial or complete closure of the glomerular capillary lumen by inflammatory cells. |
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Term
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Definition
| The structure of the slit diaphragm has become a major area of interest in terms of the proteinuria seen in many chronic renal diseases, including nephrotic syndromes; The slit diaphragm proteins, composed of the nephrin and podocin families, are now known to be adversely affected in people with Type II diabetes, and may be responsible for the proteinuria seen in those patients that marks the onset of many renal diseases |
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Term
| Inflammation Mechanisms in Nephritic States |
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Definition
1) Immune complex formation and complement activation in the subendothelial space or mesangium (as occurs in post-streptococal glomerulonephritis).
2) Circulating antibodies directed against the GBM as in antiGBM antibody disease.
3) Circulating antibodies directed against neutrophil cytoplasmic antigens (ANCA), as seen in most polyangiitides. |
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Term
| Typical GFR in Healthy Young People |
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Definition
MEN - 115-125 ml/min per 1.73 m2;
WOMEN - 90-110 ml/min per 1.73 m2;
NOTE - if a male is filtering 125 ml of plasma per minute, this amounts to a total filtration of 180L/ day, however we produce an average of only 1.5 L of urine each day. Therefore, the vast majority of filtered plasma is being reabsorbed downstream in the nephron, long before it reaches the collecting system to shunt it off to the bladder. |
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Term
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Definition
When we talk about the GFR in medicine, we are referring to the TOTAL amount of plasma being filtered across the glomerular capillaries by ALL the nephrons in both kidneys (if you have 2) each minute;
Another concept is the "single nephron glomerular filtration rate" (SNGFR) - this comes into play when discussing disease states and loss of functional nephrons |
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Term
| Dynamics of Ultrafiltration |
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Definition
| Starling's forces apply to glomerular capillaries just as they do to other capillaries; There are 2 forces opposing filtration (Pressure in Bowman's Space, and Glomerular Capillary oncotic pressure)and two forces promoting filtration (Glomerular Capillary Pressure, and Bowman's Space Oncotic pressure); Subtracting the pressure exerted by the opposing forces from the pressures promoting filtration gives you the NET ultrafiltration pressure. |
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Term
| What are the 2 Major Mechanisms that Could Alter the GFR? |
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Definition
| Alterations in Net ultrafiltration pressure, and changes in glomerular capillary surface area and intrinsic permeability |
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Term
| Initiation of Renin Release by the Juxtaglomerular Apparatus |
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Definition
| A decrease in NaCl delivery to macula densa cells in the thick ascending limb will also provoke a signal to the granular cells (also called juxtaglomerular cells) to stimulate renin release. This renin will then activate the renin-angiotensin-aldosterone cascade. Increased sympathetic input to the afferent arterioles and decreased perfusion pressure that causes vasoconstriction of afferent arterioles (both of which occur when arterial pressure declines) will directly enhance renin release from granular cells that are present in the afferent arterioles. |
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Term
| Ideal Characteristics of a Clearance Compound Used to Estimate GFR |
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Definition
| The substance should only enter the nephron via glomerular filtration (NO secretion of the substance should occur); Once the substance has been filtered in, the substance is NOT reabsorbed anywhere in the nephron; If those 2 requirements are met, it means the amount filtered in each day is equal to the amount excreted into the urine each day. |
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Term
| 24 Hour Creatinine Clearance to Measure GFR |
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Definition
Creatinine is produced by metabolism of creatine in muscle, and is present in the plasma in relatively constant amounts;
Creatinine is freely filtered at the glomerulus, but unfortunately around 15% of the creatinine appearing in the urine was SECRETED into the nephron;
Creatinine is not reabsorbed once it enters the nephron |
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Term
| Drawbacks to Creatinine Clearance |
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Definition
In normal people, around 15% of creatinine appearing in the urine was secreted, thus overestimating true GFR. This is offset, however, by an overestimation of plasma creatinine when assayed by the alkalin picrate colorimetric assay;
In patients who already have significant renal impairment (true GFR is less than 60 ml/min), the amount of creatinine being secreted is much greater (up to 35% of the urinary creatinine was secreted), resulting in a significant overestimation of the true GFR;
24 hour urine collections are often incomplete (non-compliance by patients), which results in an UNDERestimation of the true GFR |
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Term
| Short Urine Collection Using Cimetidine |
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Definition
| A loading dose of 1200 to 2000 mg of cimetidine is given (with doses adjusted for renal insufficiency) is given on day 1. This is followed by 400mg/day for 3 to 4 days. A 1.5 hour urine collection is then obtained. This has been shown to be about as accurate as a 24 hour collection. |
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Term
| Plasma Creatinine and GFR |
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Definition
Plasma creatinines and GFR are inversely related. If GFR falls by 50% for some reason, filtered load of creatinine (and therefore, urinary excretion) will intially be reduced. The decline in filtered load will cause plasma creatinine levels to increase;
Early declines in GFR (up to 40-50% of initial GFR) do NOT cause large increases in plasma creatinine. Excessive creatinine secretion by surviving nephrons enables the patient to keep increases in plasma creatinine minimal until disease is advanced;
Put another way: The GFR can fall up to 50% before the plasma creatinine starts to rise into the "red flag" area; After this, the rise in plasma creatinine for any given drop in GFR is more linear; Because the rise in plasma creatinine is fairly linear to a given decline in GFR in people with known, advanced renal disease (GFR <30ml/min), plasma creatinine can be used to assess therapeutic effectiveness in these patients |
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Term
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Definition
| A glycosylated protein produced at a constant rate by all nucleated body cells; Measuring the clearance of cystatin C is now being evaluated as an improved method of measuring GFR in children |
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Term
| Methods for Imaging the Kidney |
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Definition
IVP (IV pyelograms) are traditionally the workhorse of renal imaging - IV iodinated contrast is injected and multiple x-ray images are taken at varying coronal depths through the kidneys, Typically IVP is not used much anymore;
Ultrasound is the preferred initial method for most conditions - hydronephrosis, ? mass, pyelo, abscess, simple cyst, renal stones (require a CT);
3 Phase CT with contrast is the best method for mass evaluation - it is able to fully characterize masses other than cysts, and shows vascular invasion and metastasis, MRIs should be used in place of CT if there is an allergy to the contrast or if the patient has renal failure;
VCUG (voiding cystourethrogram) is used for evaluation of patients with suspected urinary reflux - a catheter is placed in the bladder and contrast is instilled, the path of the dye is then watched under fluoroscopy for reflux into the ureters and kidneys |
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Term
| Appearance of Normal Kidneys on CT |
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Definition
| The kidney should appear homogeneous, with no striations or lesions |
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Term
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Definition
| A congenital anomaly; Associated with genital anomalies in females; 10% of cases are unilateral, and the remaining kidney hypertrophies; Bilateral agenesis is incompatible with life (known as Potter's disease) |
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Term
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Definition
| A Congenital anomaly of the kidneys; Most common fusion anomaly; The lower poles of the kidneys are joined by a fibrous or renal parenchymal band (malrotated kidneys result); The kidneys are located BELOW the level of the inferior mesenteric artery because the fused kidney can't ascend past that level during fetal development, and the kidney gets "stuck" (Kloda mentioned this as a good pimp question for Boards and Rounds); The kidney may have multiple ectopic renal arteries; There is an increased incidence of trauma and urinary stasis in these patients (stasis = prone to infection, so the patients get recurrent pyelonephritis, recurrent infections can sometimes lead to cancer down the road) - the stasis occurs with horseshoe kidneys because they're oriented in such a way that the urine is unable to get out. |
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Term
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Definition
| A congenital anomaly of the kidney; Both kidneys are fused on one side of the abdomen; May present as an abdominal mass; Abberant renal arteries; Normal ureteral insertion at the bladder trigone (the kidneys retain their individual ureters - if the bladder doesn't have 2 ureters going into it the patient DOESN'T have Cross Fused Ectopia); If the kidneys aren't fused, one kidney may be located in the pelvis |
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Term
| Renal Cell Carcinoma (General) |
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Definition
| Renal Cell Carcinoma (RCC) accounts for 85% of solid renal masses; Male > Female, 3:1; Occurs more commonly in smokers; 2% of cases are bilateral; Treatment = radical nephrectomy with fascial removal and excision of adrenal, perirenal fat, and nodes (now they do percutaneous ablation); Hemorrhage and necrosis are common (because the tumors outgrow their blood supply); ANY solid renal mass should be suspected for RCC; Tumors are hypervascular and may extend into renal veins or the IVC; 40% of cases are metastatic at the time of diagnosis (metastasizes commonly to lung, nodes, liver, bone, adrenals or the other kidney); Patients present with gross hematuria and weight loss as common sxs |
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Term
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Definition
| An Uncommon (1-3% of renal neoplasms) mesenchymal tumor; Fat, smooth muscle, abnormal vessels; Most common in middle aged women; Prone to hemorrhage (especially in tumors >3-5cm) because the tumors contain thin walled vessels that are very friable; Fat density within the kidney is seen on CT; If large and solitary it may be excised surgically; Followed by CT or MRI; Multiple Bilateral AML are seen in patients with Tuberous Sclerosis (Common question on Boards/ Rounds) |
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Term
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Definition
| Metastatic Lymphoma is more common than a primary renal lymphoma; Most cases are non-Hodgkins; May have varied appearance - diffuse enlargement of kidneys, multiple bilateral masses, may have a solitary bulky tumor, invasion into renal sinus, or a perirenal tumor surrounding the kidneys |
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Term
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Definition
| Simple cysts are the most common renal mass overall (including solid renal masses); Most are asymptomatic (those >4cm may cause pain, obstruction and/or hematuria); Can be definitively diagnosed by ultrasound, CT or MRI (they should not enhance with contrast); Complicated cysts may have septations, calcifications, or irregular walls; When <1cm, they are hard to characterize and should be watched for a few months to see if they grow/ change at all (even if the mass turns out to be a tumor, not a cyst, it won't hurt to wait a few months) |
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Term
| Appearance of a Simple Cyst on Imaging |
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Definition
Ultrasound - Uniformly anechoic (black);
CT - uniformly low density, no calcification or septations |
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Term
| CT Appearance of a Complicated Cyst |
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Definition
| Irregular, thickened peripheral calcification surrounding a dark area |
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Term
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Definition
| Ascending gram negative infection (E.Coli is the most common); Uncomplicated infection requires no imaging; CT or US if severely ill or not responding to tx in order to look for abscesses (intra- or perirenal); Diabetes, drug abuse, and immunocompromise all predispose the patient to pyelonephritis as does inadequate tx of a lower UTI; CHARACTERISTIC SXS - Fever, positive UA, flank pain; EMPHYSEMATOUS PYELO: severe form, gas in the renal parenchyma, usually seen in critically ill diabetics, rapidly fatal despite adequate tx |
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Term
| Imaging of Pyelonephritis |
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Definition
| Appears as a "striated nephrogram" (dark areas are areas of edema, separated by light areas which are normal kidney) |
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Term
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Definition
| Usually due to cholesterol emboli; Could be due to trauma (ex: dissection of the renal artery); Appears as areas of non-enhancement on CT |
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Term
| Methods for Imaging the Collecting System, Ureters, Bladder and Urethra |
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Definition
| IVP (IV Pyelogram) has been the traditional imaging method of choice, but CT scan is replacing it (non-contrast to detect stones, Contrast enhanced phase for renal parenchyma, and delayed images as contrast is excreted into the ureters and bladder); CYSTOGRAM - through a catheter they instill contrast into the bladder and take an image (used to detect bladder rupture due to trauma, and to detect tumors); CT CYSTOGRAM - same as the cystogram, but image them with CT instead of x-ray (gives better detail of adjacent structures); VCUG (Voiding cystourethrogram) - like a cystogram, but watch for reflux backwards toward the kidneys with voiding |
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Term
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Definition
| A Congenital anomaly of the kidney in which the renal pelvis is located outside of the kidney (instead of within the kidney as usual) |
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Term
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Definition
| A congenital anomaly of the ureter; Occurs in 1-2% of the population; Unilateral occurrence is more common than bilateral; UTI, reflux and obstruction are common with ureteral duplication; Chronic reflux leads to scarring and renal failure |
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Term
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Definition
| A mainstay of imaging non-contrast CT scan (contrast obscures the stones); 10% of all people will have a stone in their lifetime; Most commonly composed of calcium oxalate; Others caused by Struvite (15%) and Cystine (1-2%); COMPLICATIONS - obstruction, stricture, infection, renal failure; SIGNS/ SYMPTOMS - flank pain, microscopic hematuria (the patient won't see the blood, but you can see it under microscope); On imaging, stones are high density (white) due to the large amount of calcium they contain; Stones that are less than 5mm should be able to pass on their own |
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Term
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Definition
| A very large calcification (stone) within most, if not all, of the renal collecting system so that on x-ray it looks like a stag horn; Must be surgically removed; Patients get recurrent infections and are more prone to transitional cell carcinoma |
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Term
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Definition
| Dilation of the upper urinary tract; Not synonymous with obstruction; US is a great screening exam for hydro (cheap, readily available, no radiation); May be caused by obstruction (stone, stricture, tumor, extrinsic compression); Hydronephrosis is when the collecting system is filled with urine, Pyonephrosis is when it is filled with pus; Interventional radiology can place percutaneous nephrostomy tubes (a drainage catheter into the renal pelvis through the flank); Vesicoureteral reflux can cause hydronephrosis in children |
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Term
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Definition
| Very common in children; CAUSE IN FEMALE CHILDREN - Abnormal ureteral tunnel into the bladder (they usually outgrow the problem, but may require ureter reimplantation); CAUSE IN MALE CHILDREN - posterior urethral valve (requires surgical correction); CAUSE IN ADULTS - neurogenic bladder or bladder outlet obstruction; Leads to renal scarring and renal failure (may require transplantation by early adulthood if not treated properly); Prophylactic abx; Voiding cystourethrogram (VCUG) is the imaging test of choice |
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Term
| Grading of Vesicoureteral Reflux |
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Definition
| Based on VCUG; Each side is graded separately (you may have different grades on each side); GRADE I - Reflux only into ureter; GRADE II - into ureter and kidney; GRADE III - grade II with mild blunting of the calyces; GRADE IV - ureter mildly dilated, collecting system slightly more dilated; GRADE V - more dilation of ureter and collecting system |
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Term
| Transitional Cell Carcinoma (TCC) |
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Definition
| Accounts for 85-90% of uroepithelial tumors; Exophytic, polypoid, attached to the mucosa by a stalk; Filling defects are seen in the collecting system; IVP used to be the gold standard, but now it's CT with contrast and delayed excretory images; M >F (ratio is 4:1); Age > 60; Smoking, chemical exposures (especially to aniline dye) and chronic urinary stasis predispose patients to getting TCC; Treatment is radical surgery - resection of the kidney, ureter, insertion at bladder |
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Term
| Congenital Anomalies of the Bladder |
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Definition
BLADDER EXSTROPHY - deficiency of the lower abdominal wall such that the bladder is open to the skin, Accompanied by a diastasis of the pubic symphysis (the pubic symphysis is gapped);
URACHAL REMNANT - many forms, including draining sinus at the umbilicus, Remnant of the allantois and urogenital sinus, Most common associated malignancy is Adenocarcinoma (know this), You can get a cyst anywhere along the urachal remnant |
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Term
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Definition
| Bladder wall is normally <5-6mm thick; There are many causes of bladder wall thickening - BPH, urethral stricture, posterior urethral valve, neurogenic bladder (these patients are prone to stasis, stones and infection), Chronic Infection |
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Term
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Definition
Many Causes - infection (bacterial, TB, adenovirus, shistosomiasis which also causes calcification), Drugs (cyclophosphamide which causes a hemorrhagic cystitis), Radiation, Autoimmune; May become hemorrhagic in bacterial infections and with chemotherapeutics; Patients will have Nonspecific findings radiographically (bladder wall thickening and irregularity are the most common findings radiographically);
EMPHYSEMATOUS CYSTITS - gas in the bladder wall, the patient will probably die even if you give them aggressive treatment, Can be distinguished on imaging from air seen with a bladder perforation by the fact that air from a perforation will only be at the top of the bladder whereas gas forms a ring all the way around the inside bladder wall;
SCHISTOSOMIASIS will cause bladder wall calcification |
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Term
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Definition
| TCC is the most common malignancy (due to smoking, chemical exposure or chronic infection); Imaging includes IVP, CT, MRI, and all will show irregular filling defects; 4% of bladder masses are Squamous cell carcinomas; <1% are adenocarcinoma (related to urachal remnants); Benign tumors will show up as a smooth filling defect on imaging and include leiomyomas and hemangiomas |
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Term
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Definition
| Rupture can be seen when trauma occurs with a full bladder (especially blunt force trauma); Pelvic fractures are also a common cause of bladder trauma; Cystograms or CT cystograms are perforemed through a Foley catheter to assess for bladder trauma; Two types of rupture - Intraperitoneal (20%) and Extraperitoneal (80%); INTRAPERITONEAL RUPTURE - occurs at bladder apex (where the peritoneum drapes over the bladder) and requires surgery, upon imaging contrast will be seen around loops of bowel; EXTRAPERITONEAL RUPTURE - from pelvic fracture, treatment is a Foley Catheter for 4-6 weeks, Contrast will be seen in the perineum |
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Term
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Definition
| Occurs more frequently in males than females and is usually the result of a straddle injury; Problems usually occur in the bulbous or penile urethra; NOTE - on imaging, a narrowing near the bulbourethra is normal |
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Term
| Methods for Imaging the Urethra |
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Definition
| Retrograde Urethrogram (RUG) - the preferred method of imaging, Usually performed in the setting of trauma (indication for a RUG is blood at the urethral meatus); A syringe or catheter occludes meatus and contrast is injected, Plain x-rays are then taken to detect a leak; A RUG can also be used to evaluate stricture of the urethra (ex: in someone who's had recurrent infection and is now having dribbling and signs of obstruction) |
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Term
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Definition
| Abnormal narrowing caused by fibrous scar tissue; Variable involvement - part or all; Abrupt, short segment strictures are usually due to trauma; Long segments are either traumatic or inflammatory; Traumatic Causes of Stricture - instrumentation, indwelling catheters, prostatectomy, straddle injury, pelvic fracture; Inflammatory Causes - usually gonorrhea (causes multiple short segment strictures) |
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Term
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Definition
| Smooth saccular outpouchings (just like a bladder diverticula); Can be congenital, or caused by trauma or infection; Infection within the diverticula is common (as a result of urinary stasis); May be seen by urethrogram, CT, US, MRI or IVP (and is usually an incidental finding) |
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Term
| Imaging of Urethral Transection via a Retrograde Urethrogram (RUG) |
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Definition
| Contrast stops abruptly and fills collateral channels |
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Term
| Urinalysis Reagent Test Strips |
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Definition
Test for: Protein, blood, leukocytes, nitrites, glucose, ketones, pH, specific gravity, bilirubin, and urobilinogen;
The test strips are designed to assist in the diagnosis of: Kidney function, UTIs, Carbohydrate Metabolism (Diabetes Mellitus), and Liver Function |
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Term
| Normal Range for Glucose in a Urinalysis |
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Definition
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Term
| Normal Range for Bilirubin in a Urinalysis |
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Definition
Negative;
NOTE - Normal adult urine contains 0.02mg/dl of bilirubin, which is not detectable. Reported trace amounts are abnormal and require further investigation. 0.1mg/dl or greater may be found in early liver disease. Test strips begin detection at 0.4mg/dl. If early hepatitis or liver disease is suspected, ICTOTEST reagent tablets may be used to detect the smaller amounts |
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Term
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Definition
| Good for confirming positive reactions of bilirubin urinalysis test strips that may be due to urine color or for early liver disease; Purple is Positive |
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Term
| Normal Range for Ketones in a Urinalysis |
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Definition
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Term
| Conditions in Which Ketones Might Be Detected on Urinalysis |
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Definition
| Ketoacidosis, Starvation, Abnormalities of carbohydrate or lipid metabolism; Trace results are a sign of physiologically stressful conditions (fasting, pregnancy, frequent exercise); Urine must reach levels of 10 mg/dl or higher before serum ketones are elevated |
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Term
| Specific Gravity of Urine (General) |
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Definition
Principle of the Test - based on pKa changes of certain pretreated polyelectrolytes in relation to ionic concentration; Presence of an Indicator - deep blue-green = urine of low ionic concentration, Green and yellow-green = urines of increasing ionic concentration;
Specific Gravity is directly proportional to urine osmolality, which measures solute concentration (ie specific gravity measures urine density and the ability of the kidney to concentrate or dilute the urine over that of plasma) |
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Term
| Normal Range of Specific Gravity of Urine |
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Definition
| 1.001 to 1.035; NOTE - The values above are for the test strip method and they correltate within 0.005 with values obtained wtih the refractive index method; The test strips are not affected by the presence of radio-opaque dyes, unlike the refractive index, urinometer and osmolality methods |
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Term
| Normal Range of Blood in a Urinalysis |
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Definition
| Color Range - orange (negative) to green (positive) - note that very high levels of blood may cause the color development to continue to blue; The Normal rage extends from negative to trace in females, and should always be negative in males; OCCULT BLOOD OCCURS in urological, nephrological and bleeding disorders; NOTE - small amounts of blood are sufficiently abnormal to require further investigation (you often want to do a repeat test). Clinical Judgement is based on the case. |
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Term
| Normal Range of Urinary pH |
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Definition
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Term
| Normal Range of Protein on Urinalysis |
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Definition
Negative;
NOTE - <150mg of total protein is excreted per day (<15mg/dl). Clinical proteinuria is indicated at >500mg protein/ day (strip results of >30mg/dl). Clinical judgement is required to evaluate the significance of trace results.;
TRACE positive results (slightly hazy urine) are equivalent to 10mg/100ml or about 150mg/ 24 hours (the upper limit of normal);
GRADING: 1+ = 200-500mg/day, 2+ = 0.5-1.5gm/day, 3+ = 2-5gm/day, 4+ = 7gm/ day |
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Term
| Significance of Protein in Urine |
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Definition
| Occurs with Urological and Nephrological disorders; Indicative of tubular or overflow proteinuria in the absence of any glomerular abnormality; Proteins of renal origin may be excreted during infection, strenuous exercise, dehydration, UTIs or Acute illness with fever |
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Term
| Normal Range of Urobilinogen in a Urinalysis |
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Definition
0.2-1.0mg/dl;
NOTE - A result of 2.0mg/dl represents the transition from normal to abnormal and these patients need to be evaluated further for hemolytic and hepatic disease; You should evaluate bilirubin and urobilinogen results for differential diagnosis of jaundice, liver and biliary disorders |
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Term
| Normal Range of Nitrites in a Urinalysis |
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Definition
| Negative; NOTE - normally no nitrite is detectible in the urine, Many enteric gram-negative organisms will give a positive result |
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Term
| Normal Range of Leukocytes in a Urinalysis |
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Definition
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Term
| Positive Result of Leukocytes in a Urinalysis |
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Definition
| Indication of pyuria; Found in nearly all diseases of the kidney and urinary tract; Pyuria may often be present in non-infective conditions as well; A strip result of a small (or greater) leukocyte level is a useful indicator of infection; Observation of repeated trace results may be clinically significant |
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Term
| Urine Microscopic Evaluation |
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Definition
| RBCs/ High Power Field (HPF) = normal range of 0-4; WBCs/ HPF = normal range of 0-4; NOTE - if you see RBCs or WBCs in EVERY field (even if it's less than 4 of them) this is still significant); Epithelial Cells (Squamous)/ Low Power Field (LPF) = can be none, rare or few; Bactreria/ HPF = normal is none or rare; Crystals/ LPF = may be present but few have clinical significance; Casts/ LPF = normal amount is none; Amorphous - normal amount is none or few |
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Term
| Things that Would Cause you to Do a Microscopic Evaluation of the Urine |
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Definition
If, on visual exam of the urine, the urine is found to have a clarity of anything by clear or slightly cloudy/ turbid, a microscopic evaluation should be performed;
If the dipstick test gives a positive result for any of the following: leukocytes, nitrites, protein, Blood (1+ or > in females, Trace or > in males), a microscopic evaluation should be done |
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Term
| Things That Would Cause You To Culture the Urine |
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Definition
| Positive leukocytes - 1+ or greater on dipstick with microscopic evaluation showing > 5-10 WBC/ high power field; Any positive Leukocytes 2+ or greater; Any positive nitrites; 3+ or greater bacteria seen on urine sediment; 5-10 WBCs seen on urine sediment |
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Term
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Definition
Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct (distal nephron). The proximal convoluted tubule (PCT) and loop of Henle are NOT locations for cast formation. If you see a lab report come back with a report of "casts" this is always a significant finding;
When cellular casts remain in the nephron for some time before they are flushed into the bladder urine, the cells may degenerate to become a coarsely granular cast, and ultimately, a waxy cast. Granular and waxy casts are believed to be derived from renal tubular cell casts |
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Term
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Definition
Proteinuria occurs; Hyaline Casts are composed primarily of a mucoprotein called Tamm-Horsfall protein, which acts as a glue that cements the urinary casts together (albumin and some globulins are also incorporated). Tamm-Horsfall is secreted by tubule cells.
Variations in the size, shape and texture of the hyaline casts are of no clinical value. Hyaline casts are the least significant kind of cast, they are considered physiological casts and can be seen after strenuous exercise or dehydration |
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Term
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Definition
| RBCs may stick together and form RBC casts; RBC Casts are indicative of: glomerulonephritis with leakage of RBCs from the glomeruli, and of severe tubular damage |
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Term
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Definition
| Indicative of: Acute pyelonephritis (most often), Glomerulonephritis, and/ or Inflammation of the kidney (only form in the kidney) |
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Term
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Definition
| Renal tubular cell casts suggest injury to the tubular epithelium |
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Term
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Definition
| Composed of Opaque, wax-like Material; Related to long periods of urinary stasis; Usually without inclusions or slightly granular; May be short, normal or long (length is of no clinical value) |
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Term
| What Can Cuase Hematuria? |
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Definition
| Glomerular damage, Tumors that erode the urinary tract anywhere along its length, Kidney trauma, Urinary tract stones, Renal infarcts, Acute tubular necrosis, Upper and Lower UTIs, Nephrotoxins, Physical stress, Menstruation, Trauma produced by bladder catheterization |
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Term
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Definition
| NO RBCs should be found in urine; If One or more RBCs can be found in every high powered field the specimen is probably abnormal (assuming contamination can be ruled out); RBCs may appear normally shaped, swollen by dilute urine (in fact, only cell ghosts and free hemoglobin may remain), crenated by concentrated urine or dysmorphic due to glomerular disease (dysmorphic RBCs have odd shapes as a consequence of being distorted via passage through the abnormal glomerular structure) |
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Term
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Definition
Refers to the presence of abnormal numbers of leukocytes in the urine; May appear with infection in either the upper or lower urinary tract or with acute glomerulonephritis; Usually the WBCs are granulocytes. White cells from the vagina, especially in the presence of vaginal and cervical infections, or the external urethral meatus in men and women, may contaiminate the urine;
TWO or more leukocytes per each high power field (in non-contaminated urine) is abnormal; Leukocytes have lobed nuclei and granular cytoplasm |
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Term
| Renal Tubular Epithelial Cells |
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Definition
| Larger than granulocytes; Contain a larger round or oval nucleus; Normally slough into the urine in small numbers; In nephrotic syndrome or conditions leading to tubular degeneration, LIPIDURIA occurs because these cells contain endogenous fats. When filled with numerous fat droplets, such cells are called "oval fat bodies" - oval fat bodies exhibit a "Maltese cross" configuration under polarized light microscopy |
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Term
| Transitional Epithelial Cells |
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Definition
| From the renal pelvis, ureter, or bladder; Have more regular cell borders, larger nuclei and smaller overall size than squamous epithelium; Renal tubular epithelial cells are smaller and rounder than transitional epithelium, and their nucleus occupies more of the total cell volume |
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Term
| Squamous Epithelial Cells |
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Definition
| From the skin surface and outer urethra; The significance of these cells in a urinalysis is that they represent possible contamination of the specimen with skin flora |
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Term
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Definition
| Microbial organisms can be found in all but the most scrupulously collected urine samples and should be interpreted in view of clinical symptoms (abundant normal microbial flora of the vagina or external urethral meatus rapidly multiply in urine standing at room temperature); Suspected UTI requires culture; A colony count may also be done to see if significant numbers of bacteria are present - generally, more than 100,000/ml of one organism reflects significant bacteriuria; Multiple organisms reflect contamination; Presence of any organism in a catheterized or subrapubic tap specimen should be considered significant |
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Term
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Definition
| May be due to Contaminants or a true yeast infection; It is difficult to distinguish yeast from RBCs and amorphous crystals but they may be distinguished by the tendency of yeast to bud. Most often the yeasts found in urine specimens are candida, which may colonize the bladder, urethra or vagina |
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Term
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Definition
COMMON CRYSTALS seen even in healthy patients (not clinically significant) - calcium oxalate, triple phosphate crystals, amorphous phosphates;
VERY UNCOMMON CRYSTALS - Cystine Crystals (in the urine of neonates with congenital cystinuria or severe liver disease), Tyrosine Crystals (with congenital tyrosinosis or marked liver impairment), Leucine Crystals (in patients with severe liver disease or with maple syrup urine disease), Cholesterol Crystals (look like plates of glass and are present in renal tubular disease), Bilirubin Crystals (appear when the bilirubin level is high) |
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Term
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Definition
| Renal Papillary Adenoma, Angiomyolipoma (AML), Oncocytoma |
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Term
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Definition
| Renal Cell Carcinoma (RCC) - subtypes include: clear cell carcinoma, papillary carcinoma, chromophobe renal carcinoma, collecting duct (bellini duct) carcinoma, and medullary-type renal cell carcinoma |
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Term
| Pediatric Renal Neoplasms |
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Definition
| Wilm's tumor (nephroblastoma, nonanaplastic) - 80%; Wilm's tumor (nephroblastoma, anaplastic) - 5%; Mesoblastic nephroma - 5%; Clear cell sarcoma - 4%; Rhabdoid tumor - 2% (associated with Xp11.2 translocation/ TFE3 gene fusion) |
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Term
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Definition
| WHO DEFINITION - tumors with papillary or tubular architecture of low nuclear grade and 5mm in diameter or smaller; Composed of renal tubular epithelium; Commonly found at autopsy (7-22%); 10% of cases are seen in patients <40y/o; 40% are seen in patients >70y/o; 33% in acquired renal cystic disease; Long-term hemodialysis patients; GROSS PATHOLOGICAL FEATURES - small, <5mm in diameter, pale yellow-gray, discrete, well-circumscribed nodules; MICROSCOPIC PATHOLOGICAL FEATURES - complex, branching, papillomatous structures with numerous complex fronds, Tubules, glands, cords, sheets, Cuboidal-to-polygonal in shape, regular, small central nuclei, scanty cytoplasm, no atypia |
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Term
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Definition
| WHO DEFINITION - benign mesenchymal tumor composed of a variable proportion of adipose tissue, spindle and epitheliod smooth muscle cells, and abnormal thick-wall blood vessels; 25-50% of patients with tuberous sclerosis also have an AML (RECALL - tuberous sclerosis is an autosomal dominant condition that causes lesions of the cerebral cortex which may result in seizures, patients may also have mental retardation and skin abnormalities) |
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Term
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Definition
| WHO DEFINITION - benign renal epithelial neoplasm composed of large cells with mitochondria-rich eosinophilic cytoplasm thought to arise from intercalated cells of collecting ducts; Account for 5-15% of surgically resected renal neoplasms; Electron microscopy reveals numerous mitochondria; GROSS PATHOLOGICAL FEATURES - well-circumscribed, non-encapsulated neoplasms that are clasically mahogany-brown to tan/pale yellow and a Central Stellate Scare is seen in up to 33% of cases; MICROSCOPIC PATHOLOGICAL FEATURES - solid compact nests, lots of mitochondria, Oncocytes (round-to-polygonal cells with densely granular eosinophilic cytoplasm); These tumors have benign behavior, although anecdotal cases of metastases have been reported |
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Term
| Epidemiology of Renal Cell Carcinoma (RCC) |
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Definition
| Accounts for 1-3% of all visceral cancers; In men it is the 12th most common cancer, in women it is the 17th most common; Accounts for 85% of renal cancers in adults; There are 30,000 new cases/ year and 12,000 deaths from the disease; Occurs in older patients (60s-70s) but also has a bimodal distribution; Male to Female Ratio is 2-3:1 |
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Term
| Risk Factors for Renal Cell Carcinoma (RCC) |
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Definition
| Tobacco (cigarette smokers have 2X the incidence of RCC than non-smokers, 39% of cases); Obesity in women (A BMI of >29 yields a 2-fold increase in risk, and a BMI between 25 and 30 yields a 50% increase in risk); HTN; Unopposed estrogen therapy; Exposure to asbestos, petroleum products and heavy metals; Arsenic exposure imposes a 30% increase in risk; There is an increased incidence of RCC in patients with chronic renal failure, acquired cystic disease and tuberous sclerosis |
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Term
| Heredity of Renal Cell Carcinoma (RCC) |
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Definition
| Most renal cell cancers are sporadic (not familial); Autosomal Dominant familial cancers usually occur in younger people; Familial variants account for only 4% of renal cancers; von Hippal-Lindau (VHL) results in familial and sporadic forms of clear cell carcinoma; There are hereditary (familial) forms of clear cell carcinoma and papillary carcinoma |
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Term
| 3 Classic Diagnostic Features of Renal Cell Carcinoma |
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Definition
| Costovertebral pain, Palpable mass, Hematuria (this is the most reliable symptom, may be intermittent, the blood may be only seen microscopically); Only 10% of patients exhibit all 3 symptoms (and 40% of cases lack all 3) |
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Term
| Clinical Presentation of Renal Cell Carcinoma |
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Definition
| 3 Classic Symptoms - costovertebral pain, palpable mass, hematuria; Asymptomatic growth; Paraneoplastic Syndromes - Polycythemia (66% of patients have increased EPO but <4% have erythrocytosis), Hypercalcemia (without bone mets, 10%), HTN (33% of patients have increased renin), Hepatic Dysfunction, Feminization (gynecomastia) or masculinization, Cushing's syndrome, Eosinophilia, Leukemoid Reaction, Amyloidosis (3%) |
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Term
| Clinical Course of Renal Cell Carcinoma (RCC) |
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Definition
| Often Metastasizes widely before showing local signs or symptoms (a result of asymptomatic growth of the tumors); 25% of patients have metastasis at the time of presentation - Lungs (>50%, via the IVC), Bone (33%), Regional lymph nodes, Liver, Adrenals, Brain; For staging purposes, you want to know if the tumor has extended to/ beyond Gerota's fascia, as this has a poor prognosis; Fuhrman Nuclear Grading System - the higher the grade, the higher the nuclear size and the larger/ more conspicuous the nucleoli, The higher the grade, the lower the 10 year survival rate |
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Term
| Subtypes of Renal Cell Carcinoma (RCC) |
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Definition
| Clear cell carcinoma, Papillary carcinoma, Chromophobe renal carcinoma, Collecting duct (Bellini duct) carcinoma, Medullary type renal cell carcinoma |
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Term
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Definition
| A subtype of Renal Cell Carcinoma (RCC); WHO DEFINITION - malignant neoplasm composed of cells with clear or eosinophilic cytoplasm within a delicate vascular meshwork; This is the most common type of RCC, accounting for 70-80% of renal cell cancers; Familal or associated with von Hippal-Lindau (VHL) in 5% of cases, sporadic in 95% of cases; 98% (familial or sporadic) are associated wtih loss of the short arm of chr 3 (harbors the VHL gene 3p25.3); A second nondeleted allele of VHL via somatic mutation inactivation or hypermethylation occurs in 80% of all clear cell carcinomas; Tumors arise from the proximal tubules |
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Term
| Gross Pathological Findings in Clear Cell Carcinoma |
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Definition
| Solitary unilateral lesions (multicentricity or bilaterality, <5%); Spherical masses, vary in size (typically circumscribed, pushing border); Bright yellow (lipid)-gray-white tissue; Necrosis, hemorrhage, calcifications |
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Term
| Microscopic Pathological Findings in Clear Cell Carcinoma |
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Definition
| Varies from solid to trabecular (cordlike) or tubular; Rounded or polygonal shape; Abundant clear (rich lipid (predominant) and glycogen content) or granular cytoplasm |
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Term
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Definition
| A Subtype of Renal Cell Carcinoma (RCC); WHO DEFINITION - malignant renal parenchymal tumor with a papillary or tubulopapillary architecture; Accounts for 10-15% of RCC; Most common cytogenic abnormalities are trisomies 7,16,17, and loss of Y in male patients in the sporadic form, and trisomy 7 in the familial form; Most common type of renal cancer in patients who develop dialysis-associated cystic disease; Arise from the distal convoluted tubules |
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Term
| Gross Pathological Findings of Papillary Carcinoma |
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Definition
| Multifocal, bilateral (more common compared to other parenchymal malignancies); Hemorrhagic and cystic components |
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Term
| Microscopic Pathological Findings of Papillary Carcinoma |
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Definition
| Cuboidal or low columnar cells arranged in papillary formations; Interstitial foam cells are common papillary cores; Psammoma bodies (calcifications) may be present (they are NOT specific for papillary carcinoma); Scanty stroma, highly vascular |
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Term
| Chromophobe Renal Carcinoma |
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Definition
| A Subtype of Renal Cell Carcinoma (RCC); WHO DEFINITION - Characterized by large pale cells with prominent cell membranes; Accounts for 5% of renal cell cancers; Occurs in patients 27-86 years old (with a mean incidence in the 6th decade); M=F; Multiple chromosome losses, extreme hypodiploidy; Thought to grow from intercalated cells of collecting ducts; Excellent prognosis compared with clear cell and papillary carcinomas; Mortality <10% |
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Term
| Gross Pathological Findings in Chromophobe Renal Carcinoma |
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Definition
| Solid circumscribed tumors wtih slightly lobulated surfaces; Light brown or tan; Sometimes can see a central scar (like with oncocytomas - can be difficult to distinguish the two based on gross appearance alone) in 15% of cases |
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Term
| Microscopic Pathological Findings in Chromophobe Renal Carcinoma |
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Definition
| Prominent cell membranes, pale eosinophilic cytoplasm, halo around the nucleus (helps to distinguish it from oncocytoma cells, which don't have a halo); Solid sheets, around blood vessels; Diffuse cytoplasmic staining with Hale's colloidal iron stain (also helpful in distinguishing this from oncocytoma) |
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Term
| Collecting Duct (Bellini Duct) Carcinoma |
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Definition
| A Subtype of Renal Cell Carcinoma (RCC); WHO DEFINITION - malignant epithelial tumor thought to be derived from the principal cells of the collecting duct of Bellini; RARE (accounts for <1% of renal malignancies); Wide age range; male to female ratio is 2:1; Poor prognosis with many being metastatic at the time of presentation; 2/3 of patients die of their disease within 2 years of diagnosis |
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Term
| Medullary-Type Renal Cell Carcinoma |
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Definition
| A Subtype of Renal Cell Carcinoma (RCC); Rapidly growing tumor of the renal medulla associated almost exclusively with SICKLE CELL TRAIT; Occur almost exclusively in young black patients (10-40 y/o) with sickle cell trait; Male predominance - male to female ratio is 2:1; RARE (in 22 years, the AFIP collected only 34 cases); Believed to originate in the renal collecting ducts; Benign, spontaneous, unilateral hematuria has long been recognized in sickle cell patients; Poor prognosis - mean duration of life after surgery is about 15 months; Metastasizes to lung, liver and lymph nodes |
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Term
| Wilm's Tumor (Nephroblastoma) - General |
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Definition
| WHO DEFINITION - malignant embryonal neoplasm derived from nephrogenic blastemal cells that both replicates the histology of developing kidneys and often shows divergent patterns of differentiation; Most common primary renal tumor of childhood; 4th most common pediatric malignancy in the US; Approximately 10 children per million under age 15 are affected; Usually diagnosed between the ages of 2 and 5; Approximately 5-10% of Wilm's tumors involve both kidneys, either simultaneously (synchronous) or one after the other (metachronus); Bilateral Wilm's tumors have a median age of onset approximately 10 months earlier than tumors restricted to one kidney |
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Term
| Clinical Features of Wilm's Tumor (Nephroblastoma) |
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Definition
| Present with a large abdominal mass when very large, may extend across the midline and down into the pelvis; Hematuria, pain in the abdomen after some traumatic incident, intestinal obstruction, and appearance of HTN are other patterns of presentation; Pulmonary metastases can be present at the time of primary diagnosis |
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Term
| Genetics of Wilm's Tumor (Nephroblastoma) |
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Definition
| The risk of Wilm's Tumor is increased in association with at least 3 recognizable groups of congenital malformations associated wtih distinct chromosomal loci; Account for no more than 10% of cases; WAGR SYNDROME - 33% chance of developing Wilm's Tumor, Aniridia, Genital anomalies, Mental Retardation, Carry constitutional (germline) deletions of 11p13, Studies on these patients led to the identification of the first Wilm's Tumor-associated gene: WT1; DENYS-DRASH SYNDROME - Gonadal dysgenesis (male psuedohermaphroditism), early-onset nephropathy (diffuse mesangial sclerosis) leading to renal failure, higher risk for Wilm's tumor (approximately 90%), Also deminstrate germline abnormalities in WT1; BECKWITH-WIEDEMANN SYNDROME - organomegaly, Macroglossia, Hemihypertrophy, Omphalocele, Abnormal large cells in the adrenal cortex (adrenal cytomegaly), Increased risk of developing Wilm's tumor, Genetic Locus that is involved in these patients is in band p15.5 of chromosome 11 distal to the WT1 loss and is called "WT2" for the Second Wilm's Tumor Locus |
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Term
| Gross Pathological Findings in Wilm's Tumors (Nephroblastomas) |
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Definition
| Large, solitary, well-circumscribed mass, although 10% are either bilateral or multicentric at the time of diagnosis; Soft, homogeneous, and tan to gray with occasional foci of hemorrhage, cyst formation and necrosis |
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Term
| Microscopic Pathological Findings in Wilm's Tumors (Nephroblastomas) |
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Definition
Characterized by recognizable attempts to recapitulate different stages of nephrogenesis; The classic triphasic combinaton of blastemal, stromal and epithelial cell types - Blastemal (sheets of small blue cells, primative), Epithelial Differentiation (abortive tubules or glomeruli, ie not fully formed), Stromal Cells (fibrocytic or myxoid in nature);
Skeletal muscle differentiation is not uncommon; Rarely, other heterologous elements are identified, including: squamous or mucinous epithelium, smooth muscle, adipose tissue, cartilage, and osteoid and neurogenic tissue;
Approximately 5% of tumors reveal anaplasia, defined as the presnce of cells with large (3x larger than other tumor cells), hyperchromatic, pleomorphic nuclei and abnormal mitoses - the presence of anaplasia correlates with underlying p53 mutations and the emergence of resistance to chemotherapy |
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Term
| Staging of Pediatric Renal Tumors (According to the National Wilm's Tumor Study Group) |
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Definition
| STAGE I - limited to kidney and completely resected; STAGE II - tumor infiltrates beyond the kidney, but is completely resected; STAGE III - residual nonhematogenous tumor confined to the abdomen; STAGE IV - hematogenous metastases; STAGE V - bilateral renal involvement at diagnosis |
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Term
| Prognosis of Wilm'S Tumor (Nephroblastoma) |
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Definition
| Currently very good, and excellent results are obtained with a combination of nephrectomy and chemotherapy in most cases; 2-year survival rates are as high as 90%, even for tumors that have spread beyond the kidney; Survival for 2 years usually implies a cure; Even recurrences can be successfully treated; Tumors with diffuse anaplasia, especially those with extrarenal spread, have the least favorable outcome; Along with increased survival of patients with Wilm's Tumor have come reports of an increased relative risk of developing second primary tumors (they're not sure if this is due to the patient having received chemo as a kid or because they have some underlying genetic abnormality) |
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Term
| Congenital Mesoblastic Nephroma |
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Definition
| WHO DEFINITION - low grade fibroblastic sarcoma of the infantile kidney and renal sinus; Confined to infancy; Median age 2 months (90% of cases are in the 1st year of life); Ultrasound studies during pregnancy have allowed this condition to be recognized prior to birth; Associated with t(12;15); Hypercalcemia due to excessive prostaglandin E; Solitary, unilateral mass with cysts, hemorrhage, and necrosis; Monomorphic spindled mesenchymal cells of fibroblastic or myofibroblastic lineage; Treatment is Complete surgical excision without chemo; Recurrence and mets occur about 5-10% of the time |
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Term
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Definition
| WHO DEFINITION - rare pediatric renal sarcoma with a propensity to metastasize to bone; Mean age is 36 months; Male to female ratio is 2:1; GROSS PATHOLOGICAL FINDINGS - typically large (mean diameter of 11cm) and centered in the renal medulla, always unicentric; MICROSCOPIC PATHOLOGICAL FINDINGS - nests or cords of cells separated by arborizing fibrovascular septa (looks like chickenwire), cord cells are epithelioid or spindle; PROGNOSIS - increased from 20% to 70% due to addition of adriamycin (doxorubicin) to chemo protocols, Lymph node involvement is common (29%), Bone metastasis are common, Also metastasizes to brain, soft tissue and the orbit |
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Term
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Definition
| WHO DEFINITION - highly invasive and highly lethal neoplasm of young children composed of cells with vesicular chromatin, prominent nucleoli and hyaline intracytoplasmic inclusions; Mean age is 1 year old (80% are diagnosed by age 2); Hematuria and disseminated disease at time of diagnosis; 15% of patients have a tumor in the posterior fossa of the brain that resembles primative neuroectodermal tumor (PNET); GROSS APPEARANCE - large, hemorrhagic and necrotic, Highly invasive; MICROSCOPIC APPEARANCE - sheets of tumor cells overrunning native nephrons and vascular invasion, Triad Of: vesicular chromatin, cherry red nucleoli and hyaline pink inclusions; PROGNOSIS - dismal, over 80% of patients will die of the tumor within 2 years of diagnosis |
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Term
| Xp11.2 Translocations/ TFE3 Gene Fusion |
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Definition
| WHO DEFINITION - defined by several different translocations involving chromosome Xp11.2, all resulting in gene fusions involving the TFE3 gene; t(X;1) - fusion of PRCC and TFE3 (most common; t(X;17) - fusion of ASPL and TFE3 (rare); Children in young adults; Characteristically present at an advanced stage; GROSS APPEARANCE - tan-yellow, often necrotic and hemorrhagic; MICROSCOPIC APPEARANCE - papillary architecture comprised of clear cells; ? Clinical behavior - appears indolent |
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Term
| Reasons for a Percutaneous Renal Biopsy |
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Definition
| Establish diagnosis, Ascertain active and chronic changes, Aid to determine therapy |
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Term
| Complications of a Percutaneous Renal Biopsy |
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Definition
| Bleeding - Gross hematuria occurs 3-10% of the time; Pain lasting >12 hours (4%); Mortality (0.2%, but currently thought to be substantially lower); AV Fistula (4-18%, clinically silent, and most resolve over 1-2 years); Chronic HTN (rare); Perirenal soft tissue infection (0.2%, most often in patients with active renal infections); Puncture of adjacent organs (rare) |
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Term
| Definition of "Focal" with Respect to The Kidneys |
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Definition
| Some (<50%) of the glomeruli involved |
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Term
| Definition of "Diffuse" with Respect to The Kidneys |
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Definition
| Most (>50%) of the glomeruli involved |
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Term
| Definition of "Segmental" with Respect to The Kidneys |
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Definition
| Involving PART of a glomerular tuft |
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Term
| Definition of "Global" with Respect to The Kidneys |
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Definition
| Involving ALL of a glomerular tuft |
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Term
| Nephrotic Syndrome Characteristics |
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Definition
| Massive proteinuria (>3.5g of protein, less in children); Hypoalbuminemia (plasma albumin levels <3g/dL); Generalized edema; Hyperlipidemia and lipiduria |
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Term
| Causes of Nephrotic Syndrome |
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Definition
PRIMARY GLOMERULAR DISEASE CAUSES - membranous glomerulonephropathy (according to Dr. Fong this causes 30% of nephrotic syndromes in adults), Minimal Change Disease (according to Dr. Fong, this causes 65% of nephrotic syndromes in children), Focal Segmental glomerulosclerosis (FSGS, according to Dr. Fong this causes 35% of nephrotic syndromes in adults), Others such as IgA nephropathy;
SYSTEMIC DISEASE CAUSES - diabetes mellitus, Amyloidosis, Systemic lupus erhythematosus, Drugs (NSAIDs, penicillamine, "street heroin"), Infections (malaria, sypilis, hepatitis B and C, AIDS), Malignant disease (carcinoma and lymphoma), Others |
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Term
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Definition
| Relatively benign disorder is the most frequent cause of nephrotic syndrome in children, but is less common in adults; Characterized by diffuse effacement of foot processes of epithelial cells in glomeruli that appear virtually normal by light microscopy; Peak incidence is between 2 and 6 years of age; Disease sometimes follows a respiratory infection or routine prophylactic immunization; Most characteristic feature is its usually dramatic response to corticosteroid therapy |
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Term
| Morphology of Minimal Change Disease |
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Definition
| Light Microscope - glomeruli are normal; Immunofluorescence - no immunoglobulin or complement deposits; Electron Microscopy - basement membrane appears normal, and no electron-dense material is deposited, Diffuse effacement of foot processes (electron microscopy is the KEY to making the dx of this disease) |
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Term
| Etiology and Pathogenesis of Minimal Change Disease |
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Definition
| Absence of immune deposits in the glomerulus excludes classic immune complex mechanisms; Features of the disease point to an immunologic basis including: clinical association with respiratory infections and prophylactic immunization, response to corticosteroids and/or other immunosuppressive therapy, association with other atopic disorders (eg eczema, rhinitis), There is an Increased incidence of minimal change disease in patients with Hodgkin's disease in whom defects in T cell-mediated immunity are well recognized; The Current leading hypothesis involves some immune dysfunction, eventually resulting in the elaboration of a cytokine that damages visceral epithelial cells and causes proteinuria |
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Term
| Morphology of Minimal Change Disease |
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Definition
| Light Microscope - glomeruli are normal; Immunofluorescence - no immunoglobulin or complement deposits; Electron Microscopy - basement membrane appears normal, and no electron-dense material is deposited, Diffuse effacement of foot processes (electron microscopy is the KEY to making the dx of this disease) |
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Term
| Clinical Course of Minimal Change Disease |
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Definition
| Despite massive proteinuria, renal function remains good, and there is commonly no HTN or hematuria - proteinuria usually is highly selective, with most of the protein consisting of albumin; Most children (>90%) with minimal change disease respond rapidly to corticosteroid therapy; Nephrotic phase may recur, and some patients may become steroid dependent or resistant; Long-term prognosis for patients is excellent, and even steroid-dependent disease resolves when children reach puberty; Adults are slower to respond, the long-term prognosis is also excellent - minimal change disease in adults can be associated with Hodgkin disease and, less frequently, other non-Hodgkin lymphomas and leukemias; Secondary minimal change disease may follow NSAID therapy, usually in association with acute interstitial nephritis |
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Term
| Focal Segmental Glomerulosclerosis (FSFS) |
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Definition
| Characterized by: Sclerosis of some,but not all, glomeruli ("focal") and, in the affected glomeruli, only a portion of the capillary tuft is involved ("segmental"); Frequently accompanied clinically by the nephrotic syndrome or heavy proteinuria; Classification and Types (Examples) - primary disease (idiopathic focal segmental glomeruloscelerosis) - 10-35% of cases, Association with other known conditions such as HIV infection (HIV nephropathy), heroin addiction (heroin nephropathy), sickle cell disease, and massive obesity; Secondary event, reflecting glomerular scarring, in cases of focal glomerulonephritis (eg IgA nephropathy); FSGS (both primary and secondary forms) has increased in incidence - most common cause of nephrotic syndrome in adults in the U.S.; Common cause of nephrotic syndrome in Hispanic and African American patients |
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Term
| Morphology of Focal Segmental Glomerulosclerosis (FSGS) |
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Definition
| Light Microscopy - segmental sclerosis, atrophy of tubules; Immunofluorescence - no immune deposition, "Hyalinosis material"/ proteinaceous material IgM/ C3, but no IgG/IgA staining; Electron Microscopy - foot process loss +/- segmental sclerosis |
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Term
| Pathogenesis of Idiopathologic Focal Segmental Glomerulosclerosis (FSGS) |
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Definition
| Distinct disease or evolution of subset of minimal change disease; Epithelial damage is the hallmark of focal segmental glomerulosclerosis: protein nephrin, podocin and alpha-actinin 4, Specific functions and interactions are incompletely understood, but it is clear that the integrity of each is necessary to maintain the normal glomerular filtration barrier; Recurrence of proteinuria, sometimes within 24 hours after transplantation, suggests that a circulating factor, perhaps a cytokine, may be the cause of the epithelial damage |
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Term
| Clinical Course of Fogcal Segmental Glomerulosclerosis (FSGS) |
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Definition
| Little tendency for spontaneous remission in idiopathic focal segmental glomerulosclerosis, and responses to corticosteroid therapy are variable - children have a better prognosis than adults; Progression of renal failure occurs at variable rates - 20% of patients follow an unusually rapid course, with intractable massive proteinuria ending in renal failure within 2 years, Recurrences are seen in 25-50% of patients receiving allografts |
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Term
| HIV-Associated Nephropathy |
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Definition
| HIV Infection - acute renal failure and/or acute interstitial nephritis induced by drugs or infection, thrombotic microangiopathies (TTP), Postinfectious glomerulonephritis, and, focal segmental glomerulosclerosis; FSGS occurs in 5-10% of HIV-infected patients in some series, more frequently in blacks than whites; In rare cases, the nephrotic syndrome may precede the development of acquired immunodeficiency syndrome |
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Term
| Morphologic Features of HIV-Associated Nephropathy |
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Definition
| Collapsing variant of focal segmental glomerulosclerosis (FSGS) - most common, particularly poor prognosis; Presence of large numbers of tubuloreticular inclusions in endothelial cells, detected by electron microscopy: also present in SLE, shown to be induced by circulating interferon-alpha, Not present in idiopathic FSGS |
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Term
| Membranous Glomerulopathy |
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Definition
| AKA Membranous Nephropathy; Another common cause of nephrotic syndrome in adults; CHARACTERIZED BY - Diffuse thickening of the glomerular capillary wall, and accumulation of electron-dense, immunoglobulin-containing deposits along the subepithelial side of the basement membrane; Secondary membranous glomerulopathy may be caused by - drugs (penacillamine, captopril, gold, NSAIDs), SLE (15% of glomerulonephritis in SLE is of the membranous type), Infections (chronic hepatitis B, hepatitis C, syphilis, schistosomiasis, malaria), and Other autoimmune disorders such as thyroiditis; In 85% of patients, no associated condition can be uncovered, and these cases are considered idiopathic |
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Term
| Morphology of Membranous Glomerulopathy |
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Definition
| LIGHT MICROSCOPY - Normal to thick capillary loops, Spikes; IMMUNOFLUORESCENCE - diffuse granular capillary loop IgG & C3; ELECTRON MICROSCOPY - diffuse subepithelial deposits |
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Term
| Etiology and Pathogenesis of Membranous Glomerulopathy |
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Definition
| A form of chronic immune complex-mediated disease; In Secondary membranous glomerulopathy, particular antigens can sometimes be identified in the immune complexes: Membranous glomerulopathy in SLE is associated with deposition of autoantigen-antibody complexes, Exogenous (hepatitis B, Treponema) antigens or endogenous (thyroglobulin) antigens have been identified within deposits in some patients |
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Term
| Clinical Course of Membranous Glomerulopathy |
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Definition
| In Healthy Individuals it usually begins with the insidious onset of the nephrotic syndrome - 15% of patients, with non-nephrotic proteinuria; Hematuria and mild HTN (15-35%); Need to rule out the secondary causes in the work-up; Course of the disease is variable, but generally indolent; Proteinuria is nonselective; Doesn't usually respond well to corticosteroid therapy; Progression is associated with - increasing sclerosis of the glomeruli, Rising BUN reflecting renal insufficiency, Development of HTN |
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Term
| Membranoproliferative Glomerulonephritis (MPGN) |
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Definition
| Characterized histologically by alterations in the basement membrane, proliferation of glomerular cells, and leukocyte infiltration - proliferation is predominantly in the mesangium; Accounts for 10-20% of cases of nephrotic syndrome in children and young adults; Hematuria or proteinuria in the non-nephrotic range (combined nephrotic-nephritic picture); MPGN can either be associated with other systemic disorders and known etiologic agents (secondary MPGN) or it may be idiopathic (primary MPGN); Primary MPGN is divided into 2 major types on the basis of distinct ultrastructural, immunofluorescent, and pathologic findings: Type I, and Type II (dense-deposit disease, Rare) |
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Term
| Morphology of Type I Membranoproliferative Glomerulonephritis (MPGN) |
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Definition
| LIGHT MICROSCOPY - Diffuse glomeruli hypercellularity with Glomerular basement membrane (GBM) hypertrophy, Diffuse proliferative disease (increased mesangial matrix), "Double contours" or "tram-track" appearance of the GBM; IMMUNOFLUORESCENCE - Subendothelial (capillary loop) and mesangial deposis, C3 deposited in a granular pattern; ELECTRON MICROSCOPY - subendothelial and mesangial deposits with GBM duplication, Look for new GBM formation |
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Term
| Morphology of Type II Membranoproliferative Glomerulonephritis (MPGN) |
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Definition
| LIGHT MICROSCOPY - Diffuse glomeruli hypercellularity with Glomerular basement membrane (GBM) hypertrophy, Diffuse proliferative disease (increased mesangial matrix), "Double contours" or "tram-track" appearance of the GBM; IMMUNOFLUORESCENCE - "Linear" C3 with mesangial rings, IgG and IgA negative; ELECTRON MICROSCOPY - Electron dense transformation of the GBM lamina densa |
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Term
| Pathogenesis of Membranoproliferative Glomerulonephritis (MPGN) |
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Definition
| Most cases of Type I MPGN have evidence of immune complexes in the glomerulus and activation of both the classical and alternative complement pathways - the antigens involved in idiopathic MPGN are unknown, Proteins derived from infectious agents such as Hep C and B viruses can presumably behave as either "planted" antigens after first binding to or becoming trapped within glomerular structures, OR contained in preformed immune complexes deposited from the circulation; Most patients with dense-deposit disease (Type II MPGN) have abnormalities that suggest activation of the alternative complement pathway (these patients have a consistently decreased serum C3, but normal C1 and C4) |
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Term
| Clinical Course of Membranoproliferative Glomerulonephritis (MPGN) |
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Definition
| The principal mode of presentation is the nephrotic syndrome occurring in older children or young adults (idiopathic MPGN Type I and cases of type II); Few remissions occur spontaneously in either type - the disease follows a slowly progressive but unremitting course; Some patients develop numerous crescents and a clinical picture of Rapidly Progressive Glomerulonephritis (RPGN); About 50% of patients develop chronic renal failure within 10 years; Treatments with steroids and immunosuppressive agents have not been proved to be effective; High incidence of recurrence in transplant recipients, particularly in dense-deposit disease (type II MPGN) - dense deposits may recur in 90% of such patients |
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Term
| Secondary Membranoproliferative Glomerulonephritis (MPGN) |
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Definition
| Always a Type I MPGN; More common in adults and arises in the following settings: Chronic Immune Complex Disorders (SLE, Hep B, Hep C usually with cryoglobulinemia, Endocarditis, Infected ventriculoatrial shunts, Chronic visceral abscesses, HIV infection, Schistosomiasis), Alpha-1 Antitrypsin Deficiency, Malignant diseases (chronic lymphocytic leukemia and lymphoma), Hereditary deficiencies of compliment regulatory proteins |
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Term
| Diabetic Glomerulosclerosis |
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Definition
| Major cause of renal morbidity and mortality; Advanced or end-stage kidney disease occurs in as many as 40% of both insulin-dependent type 1 and type 2 diabetics; Most common lesions involve the glomeruli and are associated clinically with 3 glomerular syndromes: Non-nephrotic proteinuria, Nephrotic syndrome (Common cause of nephrotic syndrome), Chronic renal failure; "Diabetic Neuropathy" is applied to the conglomerate of lesions that often occur concurrently in the diabetic kidney; Proteinuria, sometimes in the nephrotic range, occur in about 50% of both type 1 and type 2 diabetics (12-22 years after the clinical appearance of diabetes, Progressive development of chronic renal failure ending in death or end-stage renal disease within a period of 4-5 years); Morphologic changes in the glomeruli include: Capillary basement membrane thickening, Diffuse mesangial sclerosis, Nodular glomerulosclerosis |
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Term
| Morphology of Diabetic Glomerulosclerosis |
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Definition
LIGHT MICROSCOPY - capillary basement membrane thickening, Diffuse mesangial sclerosis, Nodular glomerulosclerosis or Kimmelstiel-Wilson disease; IMMUNOFLUORESCENCE - Negative (non-specific linear IgG);
ELECTRON MICROSCOPY - severe thickening of the glomerular basement membrane, Mesangial Sclerosis |
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Term
| Clinical Course of Diabetic Glomerulosclerosis |
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Definition
| Clinical manifestations of diabetic glomerulosclerosis are linked to those of diabetes: increased GFR typical of early-onset type 1 diabetes is associated with microalbuminuria (urinary albumin excretion of 30-300mg/day), Microalbuminuria and increased GFR are important predictors of future overt diabetic nephropathy in these patients; Overt proteinuria then gradually increases to nephrotic levels (in some patients); Progressive loss of GFR, leading to end-stage renal failure within a period of 5 years; Systemic HTN may precede the development of proteinuria and renal insufficiency; Most patients with end-stage diabetic nephropathy are maintained on long-term dialysis, and many undergo renal transplantation - diabetic lesions may recur in the renal allografts, ACE-Inhibitors or angiotensin receptor blockers are indicated |
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Term
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Definition
| Most types of disseminated amyloidosis may be associated with deposits of amyloid within the glomeruli - Most commonly renal amyoid is of light-chain (AL) or AA type, Amyloidosis-associated lymphoproliferative disorder; CONGO RED amyloid-positive fibrillary deposits are present within the mesangium and capillary walls - rarely localized to the subepithelial space; Eventually, they obliterate the glomerulus completely - deposits of amyloid also appear in blood vessel walls and in the kidney interstitium; Patients with glomerular amyloid may present with the nephrotic syndrome - later, owing to destruction of the glomeruli, the patients die of uremia; Characteristically, kidney size tends to be either normal or increased |
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Term
| Morphology of Amyloidosis |
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Definition
| LIGHT MICROSCOPY - Glomeruli looks like Diabetes mellitus - thickened capillary loops, Tubules - "out of kidney"; IMMUNOFLUORESCENCE - Light chains; ELECTRON MICROSCOPY - "delicate fibers" |
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Term
| S/S of Nephritic Syndromes |
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Definition
| Hematuria with RBC casts, Azotemia (abnormal levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood), Variable proteinuria, Oliguria, Edema, HTN |
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Term
| Types of Nephritic Syndromes |
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Definition
| Acute Proliferative (Poststreptococcal, Postinfectious/ Nonstreptococcal) Glomerulonephritis, Rapidly Progressive (Crescentic) Glomerulonephritis - inluding Goodpasture's Syndrome, Henoch-Schonlein purpura (IgA), Wegener's Granulomatosis, and Microscopic polyarteritis nodosa/ microscopic polyangiitis |
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Term
| Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis |
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Definition
| A cluster of diseases characterized histologically by: diffuse proliferation of glomerular cells, Associated wtih influx of leukocytes; Typically caused by immune complexes; The inciting antigen may be exogenous or endogenous: Exogenous antigen-induced pattern of disease - postinfectious glomerulonephritis (the most common infections are streptococcal, but the disorder has also been associated with other infections), Endogenous antigen-induced disease pattern - systemic lupus erythematosus (SLE) |
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Term
| Poststreptococcal Glomerulonephritis |
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Definition
| Decreasing in frequency in the US, but continues to be a fairly common disorder worldwide; Usually appears 1-4 weeks after a streptococcal infection of the pharynz or skin (impetigo); Occurs most frequently in children 6-10 years of age, but adults of any age can be affected |
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Term
| Etiology and Pathogenesis of Acute Proliferative (Poststreptococcal) Glomerulonephritis |
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Definition
| Only certain strains of group A beta-hemolytic streptococci are nephritogenic - more than 90% of cases are traced to types 12, 4, and 1 (M protein of the cell wall); Immunologically mediated Disease - latent period between infection and onset of nephritis, Elevated titers of antibodies against one or more streptococcal antigens, Serum complement levels are low, Presence of granular immune deposits and electron-dense deposits in the glomeruli demonstrates an immune-complex-mediated mechanism; ? Streptococcal antigenic component |
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Term
| Complement Levels in Glomerulonephritides |
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Definition
WITH LOW COMPLEMENT LEVELS - Acute post-streptococcal (postinfectious) - nephritic, Membranoproliferative glomerulonephritis, types 1 and 2 - nephrotic/ nephritic, Hepatitis C/ Cryoglobulinemic glomerulonephritis, Diffuse Proliferative lupus nephritis (WHO Class IV);
WITHOUT LOW COMPLEMENT LEVELS - Diffuse proliferative IgA Nephropathy (Berger's Ds) |
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Term
| Morphology of Acute Proliferative (Poststreptococcal/ Postinfectious) Glomerulonephritis |
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Definition
| LIGHT MICROSCOPY - Diffuse glomeruli hypercellularity, PMNs in glomeruli favors post-infectious, No basement membrane abnormalities, Capillary loops are normal, In severe cases there is crescent formation; IMMUNOFLUORESCENCE - Capillary loop +/- mesangial IgG/C3, Large coarse granular deposits, Granular deposits of IgG, IgM and C3 in the mesangium and along the basement membrane; ELECTRON MICROSCOPY - Large infrequent "hump-like" subepithelial deposits (usually not numerous), Deposits much larger than those seen in Membranoproliferative glomerulonephritis |
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Term
| Clinical Course of Acute Proliferative (Poststreptococcal/ Postinfectious) Glomerulonephritis in Children |
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Definition
| The Child will Abruptly develop malaise, fever, anusea, oliguria and hematuria 1-2 weeks after recovery from a sore throat; Exhibit red cell casts in the urine, mild proteinuria (usually less than 1g/ day), periorbital edema, and mild-to-moderate HTN; Important LAB FINDINGS - elevations in antistreptococcal antibody (ASO) titers, Decline in the serum concentration of C3 and other components of the complement cascade, Presence of cryoglobulins in the serum |
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Term
| Clinical Course of Acute Proliferative (Poststreptococcal/ Postinfectious) Glomerulonephritis in Adults |
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Definition
| Onset is more likely to be atypical with the sudden appearance of HTN or edema, frequently with elevation of BUN; Important LAB FINDINGS - elevations in antistreptococcal antibody (ASO) titers, Decline in the serum concentration of C3 and other components of the complement cascade, Presence of cryoglobulins in the serum |
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Term
| Prognosis of Acute Proliferative (Poststreptococcal) Glomerulonephritis in Children |
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Definition
| >95% of affected children eventually recover totally; <1% do not improve, become severely oliguric, and develop a rapidly progressive form of glomerulonephritis; Remaining patients may undergo slow progression to chronic glomerulonephritis; Prolonged and persistent heavy proteinuria and abnormal GFR mark patients with an unfavorable prognosis |
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Term
| Prognosis of Acute Proliferative (Poststreptococcal) Glomerulonephritis in Adults |
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Definition
| Less benign than in children; Only in about 60% of sporadic cases do the patients recover promptly; The remaining patients fail to resolve quickly, as manifested by persistent proteinuria, hematuria, and HTN; In Some of these patients, the lesions eventually clear totally, but others develop chronic glomerulonephritis; Some patients will develop a syndrome of rapidly progressive glomerulonephritis |
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Term
| Nonstreptococcal Acute Proliferative Glomerulonephritis (Postinfectious Glomerulonephritis) |
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Definition
| A similar form of glomerulonephritis (to the poststreptococcal form) that occurs sporadiccaly in association with: Other bacterial infections (eg staphylococcal endocarditis, pneumococcal pneumonia, and meningococcemia), Viral diseases (eg Hep B, Hep C, mumps, HIV, varicella, and infectious mono), and Parasitic infections (malaria, toxoplasmosis); In this setting, granular immunofluorescent deposits and subepithelial humps characteristic of immune complex nephritis are present |
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Term
| Rapidly Progressive (Crescentic) Glomerulonephritis |
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Definition
| A Syndrome associated with severe glomerular injury - doesn't denote a specific etiologic form of glomerulonephritis; Characterized clinicaly by rapid and progressive loss of renal function associated with severe oliguria and death (if untreated) from renal failure within weeks to months; The Classic histologic picture is characterized by the presence of crescents in most of the glomeruli (hence the name) - produced in part by proliferation of the parietal epithelial cells lining Bowman's capsule and in part by infiltration of monocytes and macrophages |
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Term
| Classification and Pathogenesis of Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) |
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Definition
| May be caused by a number of different diseases, some restricted to the kidney and others systemic; No single mechanism can explain all cases; Glomerular injury is immunologically mediated; Three groups, distinguished on the basis of immunologic findings - Type I RPGN - idiopathic, Goodpasture Syndrome; Type II RPGN - Idiopathic, postinfectious, SLE, Henoch-Schonlein purpura (IgA), others; Type III RPGN - ANCA associated, idiopathic, Wegener's granulomatosis, Microscopic polyarteritis nodosa/ microscopic polyangiitis |
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Term
| Type I (Anti-GBM Antibody) Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) |
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Definition
| Accounts for 20% of RPGNs; Characterized by linear deposits of IgG and C3 (in many cases) in the GBM - in some patients, the anti-GBM antibodies cross-react with pulmonary alveolar basement membranes to produce the clinical picture of pulmonary hemorrhage associated wtih renal failure (Goodpasture's Syndrome); Immunosuppression and plasmapheresis(used to remove the pathogenic circulating antibodies) are usually part of the treatment; Goodpasture antigen is a peptide within the noncollagenous portion of the alpha 3- chain of type IV collagen; It is unclear what triggers the formation of these antibodies in most patients |
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Term
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Definition
| One of the Type I (Anti-GBM antibody) Rapidly Progressive (Crescentic) Glomerulonephritides (RPGN); Occurs in older children and adults of all ages; In younger patients (<30 years) it is more likely to present with the full constellation of symptoms (renal and respiratory) and to have a slight male predominance; In older patients (>50 years) it is usually isolated glomerulonephritis (ie no respiratory syndromes) and has a female predominance; Most cases begin with respiratory symptoms (hemoptysis and radiographic evidence of focal pulmonary consolidation) and glomerulonephritis that results in rapid progressive renal disease; The Most common cause of death in patients wtih Goodpasture's Syndrome is uremia; Treatment includes plasma exchange and immunosuppression |
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Term
| Type II (Immune complex-mediated disease) Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) |
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Definition
| Accounts for 25% of all Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN); Complication of any of the immune complex nephritides - postinfectious glomerulonephritis, SLE, IgA nephropathy, Henoch-Schonlein purpura; Immunofluorescence reveals the granular pattern of staining characteristic of immune complex deposition; Cannot usually be helped by plasmapheresis - treatment requires treatment for the underlying disease |
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Term
| Type III (Pauci-Immune Type) Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) |
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Definition
| Accounts for 55% of Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN); Defined by the lack of anti-GBM antibodies or immune complexes by immunofluorescence and electron microscopy; Most patients with this type of RPGN have antineutrophil cytoplasmic antibodies (ANCAs) in the serum, which play a role in some vasculitides; In some cases, this type of RPGN is a component of a systemic vasculitis such as Wegener's Granulomatosis or microscopic polyarteritis; In many cases, however, pauci-immune crescentic glomerulonephritis is isolated and hence idiopathic; More than 90% of such idiopathic cases have c-ANCA or p-ANCA in the serum - ?direct cause of RPGN |
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Term
| Morphology of Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) |
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Definition
| LIGHT MICROSCOPY - Crescents, Glomeruli may show focal necrosis, diffuse or focal endothelial proliferation, and mesangial proliferation, Neutrophils and lymphocytes may be present; IMMUNOFLUORESCENCE (IF) - Type I - linear IF, Type II - Granular IF, Type III - Pauci-immune IF (ie nothing is seen on IF); ELECTRON MICROSCOPY - subepithelial deposits in some cases, but in many cases, it shows distinct ruptures in the GBM |
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Term
| Pathogenesis of Crescents |
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Definition
| Capillary loop necrosis --> Fibrin extravasation into Bowman's Space --> Activation of the inflammatory cascade --> Fibroblasts/ epithelial cells lay down matrix --> Crescent Formation |
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Term
| Clinical Course of Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) |
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Definition
| Renal manifestations of all forms include: hematuria with red cell casts in the urine, Moderate proteinuria (occasionally reaching the nephrotic range), Variable HTN and edema; Serum analysis for anti-GBM antibodies, antinuclear antibodies, and ANCA are helpful in the diagnosis of specific subtypes; Renal involvement is usually progressive over a matter of weeks and culminates in severe oliguria; Recovery of renal function may follow early intensive plasmapheresis (plasma exchange) combined with steroids and cytotoxic agents in Goodpasture Syndrome; Other forms of RPGN also respond well to steroids and cytotoxic agents; Despite therapy, patients may eventually require chronic dialysis or transplantation |
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Term
| Antineutrophilic Cytoplasmic Antibody (ANCA) |
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Definition
C-ANCA (CYTOPLASMIC) - anti-proteinase 3, 90% of Wegener's Patients are c-anca positive, Rarely microscopic polyangiitis, anti-GBM, or immune complex glomerulonephritis patients are c-anca positive as well;
P-ANCA (PERINUCLEAR) - anti-myeloperoxidase, 80% of patients with microscopic polyangiitis are p-anca positive, 75% of patients with Churg-Strauss Disease are positive, Rarely patients with Wegener's granulomatosis, anti-GBM, immune complex glomerulonephritis are positive |
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Term
| Wegener's Granulomatosis (Type III/ Pauci-Immune Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN)) |
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Definition
| TRIAD OF - (1) acute necrotizing granulomas of the upper respiratory tract (ear, nose, sinuses, throat), the lower respiratory tract (lung) or both; (2) Necrotizing or granulomatous vasculitis affecting small to medium-sized vessels (eg capillaries, venules, arterioles, and arteries), most prominent in the lungs and upper airways but affecting other sites as well; (3) Renal disease in the form of focal necrotizing, often crescentic, glomerulitis |
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Term
| IgA Nephropathy (Berger's Disease) |
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Definition
| Characterized by the presence of prominent IgA deposits in the measngial regions, detected by immunofluorescence microscopy; Can be suspected by light microscopic examination, but diagnosis is made only by ummunocytochemical techniques; Probably the most common type of glomerulonephritis worldwide: Adults - US(20%), Mid East/ Northern Europe (20-25%), Asian (50%), Children - uncommon; Frequent cause of recurrent gross or microscopic hematuria; Mild proteinuria is usually present - nephrotic syndrome may occasionally develop; Rarely, patients may present with rapidly progressive crescentic glomerulonephritis |
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Term
| Morphology of IgA Nephropathy (Berger's Disease) |
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Definition
| LIGHT MICROSCOPY - Variable proliferation +/- sclerosis, Focal mesangial cellularity, Segmental proliferative lesion, Focal Segmental Glomerulosclerosis (FSGS) appearance (requires Immunofluorescence), +/- crescent, Presence of leukocytes within glomerular capillaries is variable; IMMUNOFLUORESCENCE - IgA deposits, Primarily mesangial, "Branching arborizing pattern" (burning bush); ELECTRON MICROSCOPY - Mesangial Deposits |
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Term
| Pathogenesis of IgA Nephropathy (Berger's Disease) |
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Definition
| IgA - main Ig in mucosal secretions, Low levels in normal serum; In patients with IgA Nephropathy - Serum IgA is increased, In some patients the circulating IgA-containing immune complexes are present; Increased production of IgA cannot itself cause this disease; ? Genetic Influence; ? Immune regulation dysfunction; ? Increased mucosal IgA synthesis in response to respiratory or gastrointestinal exposure to environmental agents (eg viruses, bacteria, food proteins); Qualitative alterations in the IgA1 molecule |
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Term
| Clinical Course of IgA Nephropathy (Berger's Disease) |
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Definition
| Can occur at any age, but older children and young adults are most commonly affected; Presents with gross hematuria after respiratory infection or (less commonly) gastrointestinal or urinary tract infections; Subsequent course is highly variable: Many patients maintain normal renal function for decades, 15-40% have a slow progression to chronic renal failure over a period of 20 years; There is an increased risk of progression when the onset is in old age, when there is heavy proteinura, HTN, and depends on the extent of glomeruloscerosis on biopsy; Recurrence of IgA deposits in transplanted kidneys is frequent - approximately 15% of those with recurrent IgA deposits |
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Term
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Definition
| Involves the deposition of immune complexes within the glomeruli; The International society of nephrology/ Renal Pathology Society Classification of Lupus involves 6 classes of the disease; CLASS I (Minimal Mesangial Lupus Nephritis) - normal glomeruli by light microscopy, but mesangial immune deposits by immunofluorescence; CLASS II (Mesangial Proliverative Lupus Nephritis) - accounts for 10-25% of cases, Most have minimal clinical manifestations, such as mild hematuria or transient proteinuria; CLASS III (Focal Lupus Nephritis) - Accounts for 20-30% of cases, Focal Lesion that affects fewer than 50% of the glomeruli and generally only parts of each glomerulus, Associated with hematuria and proteinuria; CLASS IV (Diffuse Lupus Nephritis) - accounts for 35-60% of cases; CLASS V (Membranous Lupus Nephritis) - accounts for 10-15% of cases, Consists of widespread thickening of the capillary walls (diffuse capillary loop thickening), Almost always accompanied by severe proteinuria with the nephrotic syndrome; CLASS VI (Advanced Sclerosing Lupus Nephritis) - Greater than or equal to 90% of the glomeruli are globally sclerosed without residual activity |
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Term
| Class IV (Diffuse) Lupus Nephritis |
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Definition
| Accounts for 35-60% of cases of lupus nephritis; Most serious of the renal lesions in patients with SLE; Most or all glomeruli are involved in both kidneys, and the entire glomerulus is frequently affected; Patients with diffuse lesions are usually overtly symptomatic, showing microscopic or gross hematuria, proteinuria (nephrotic syndrome in more than 50% of patients); HTN and mild to severe renal insufficiency are also common; LIGHT MICROSCOPY - "wire loop lesions"; IMMUNOFLUORESCENCE - Deposits are numerous and can be anywhere(mesangial, capillary loops, interstitial, tubules, vessels), no other disease does this; ELECTRON MICROSCOPY - Massive subendothelial deposits, Endothelial reticulotubular inclusions (also seen in HIV) |
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Term
| Hereditary Syndromes of Isolated Hematuria |
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Definition
| A group of heterogeneous familial renal diseases associated primarily with glomerular injury; Includes - Alport Syndrome and Thin Basement Membrane Disease (the most common cause of benign familial hematuria) |
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Term
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Definition
| A hereditary syndrome of isolated hematuria; Manifests as nephritis progressing to chronic renal failure, accompanied by nerve deafness and various eye disorders, including lens dislocation, posterior cataracts and corneal dystrophy; Defective GBM synthesis due to the production of abnormal collagen type IV; Most common form is the X-linked form - males express the full syndrome, while females are carriers in whom manifestations of disease are typically limited to hematuria; There are rare cases that are autosomal recessive, and autosomal-dominant pedigrees also exist; Involves the alpha 5-chain of type IV collagen; LIGHT MICROSCOPY - normal or segmental/global sclerosis, foam cells; IMMUNOFLUORESCENCE - negative; ELECTRON MICROSCOPY - GBM +/- lamellation or "basket weave" (splitting); The most common presenting sign is gross or microscopic hematuria, frequently accompanied by erythrocyte casts; Proteinuria may occur; Nephrotic syndromes are rare; Symptoms appear at ages 5-20 and the onset of overt renal failure is between 20-50 years in men; Auditory defects may be subtle, requiring sensitive testing |
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Term
| Thin Basement Membrane Disease |
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Definition
| A hereditary syndrome of isolated hematuria; Fairly common entity, manifested clinically by familial asymptomatic hematuria usually uncovered on routine urinalysis and morphologically by diffuse thinning of the GBM; The Anomaly in thin basement membrane disease is traced to genes for Type IV collagen; Most patients are heterozygous for the defective gene, but homozygotes are reported; Involves the alpha 3 or alpha 4 chains of type IV collagen; LIGHT MICROSCOPY - normal; IMMUNOFLUORESCENCE - Negative; ELECTRON MICROSCOPY - GBM thickness is 150-250 nm (compared with 300-400nm in normal adult individuals); S/S - hematuria, Mild or moderate proteinuria may be present, Renal function is normal; Prognosis is excellent; Homozygotes resemble autosomal-recessive Alport disease, and many progress to renal failure, even in women; Differential diagnosis includes IgA nephropathy |
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Term
| Diseases Affecting Tubules and Interstitium |
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Definition
| Acute Tubular Necrosis (ATN), Tubulointerstitial Nephritis, Acute Pyelonephritis, Renal Papillary Necrosis, Acute Drug-Induced Interstitial Nephritis, and Multiple Myeloma |
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Term
| Acute Tubular Necrosis (ATN) |
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Definition
| Characterized morphologically by destruction of tubular epithelial cells and clinically by acute diminution or loss of renal funciton; Most common cause of acute renal failure - rapid reduction of renal function and urine flow, falling within 24 hours to less than 400mL per day; Caused by a variety of conditions, including: ischemia, direct toxic injury, acute tubulointerstitial nephritis, disseminated intravascular coagulation, and urinary obstruction; Accounts for some 50% of cases of acute renal failure in hospitalized patients; Reversible renal lesion that arises in a variety of clinical settings |
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Term
| Nephrotoxins Leading to Acute Tubular Necrosis (ATN) |
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Definition
ENDOGENOUS/ TISSUE TOXINS - Excessive light chains of immunoglobulins (as in multiple myeloma), Myoglobin (skeletal muscle injuries with rhabdomyolysis), Hemoglobin (mismatch blood transfusion reaction), Heme pigments (hemolysis, blood transfusions);
EXOGENOUS/ DRUGS - Aminoglycosides, Radiocontrast agents, Chemo agents (eg cisplatin), Heavy metals (ie mercury), Organic solvents (ie carbon tetrachloride) |
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Term
| Morphology of Acute Tubular Necrosis (ATN) |
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Definition
ISCHEMIC ATN - focal tubular epithelial necrosis, Rupture of basement membranes (tubulorrhexis), Occlusion of tubular lumens by casts, Straight portion of the proximal tubule and the ascending thick limb in the renal medulla are especially vulnerable;
TOXIC ATN - Most obvious in the proximal convoluted tubules, Tubular necrosis may be entirely nonspecific, but it is somewhat distinctive in poisoning with certain agents |
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Term
| Clinical Course of Acute Tubular Necrosis (ATN) |
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Definition
| INITIATION PHASE - Lasting for about 36 hours, is dominated by the inciting event (ischemic form), Slight decline in urine output, but rise in BUN; MAINTENANCE PHASE - Sustained decreases in urine output to between 40 and 400mL/day (oliguria), Salt and water overload, Rising BUN, Hyperkalemia, Metabolic acidosis, and other manifestations of uremia, With appropriate attention to the balance of water and blood electrolytes, including dialysis, the patient can be carried over this oliguric crisis; RECOVERY PHASE - Steady increase in urine volume that may reach up to 3L/day, Tubules are still damaged - large amounts of water, sodium and potassium are lost in the urinary flood, Hypokalemia (verus the hyperkalemia in the maintenance phase), Increased vulnerability to infection at this stage |
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Term
| Prognosis of Acute Tubular Necrosis (ATN) |
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Definition
| Depends on the clinical setting surrounding its development - Recovery (95%) is expected with nephrotoxic ATN when the toxin has not caused serious damage to other organs; Shock related to sepsis, extensive burns, or other causes of multiorgan failure (mortality rate up to 50%); Up to 50% of patients with ATN might not have oliguria and might in fact have increased urine volumes - "nonoliguric ATN" occurs particularly often with nephrotoxins, and generally tends to follow a more benign clinical course |
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Term
| Tubulointerstitial Nephritis |
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Definition
| A group of renal diseases characterized by histologic and functional alterations that involve predominantly the tubules and interstitium; Can be acute or chronic; ACUTE - Rapid clinical onset, Edema, Eosinophils and neutrophils, and focal tubular necrosis; CHRONIC - Infiltration with predominantly mononuclear leukocytes, prominent interstitial fibrosis, and widespread tubular atrophy; Can be differentiated by glomerular disease by the fact that these patients can't concentrate their urine, but the patients with glomerular disease can, because their tubules are intact; Secondary Tubulointerstitial Nephritis is Present in: vascular, cystic (polycystic kidney disease), Metabolic (diabetes) and Renal disorders |
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Term
| Causes of Tubulointerstitial Nephritis |
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Definition
| INFECTIOUS - Acute bacterial pyelonephritis, Chronic pyelonephritis (including reflux nephropathy), Other infections (eg viruses, parasites); TOXINS - drugs, acute hypersensitivity interstitial nephritis, Analgesic nephropathy, heavy metals, Lead, cadmium; METABOLIC DISEASES - urate nephropathy, nephrocalciunosis (hypercalcemic nephropathy), Hypokalemic nephropathy, Oxalate nephropathy; PHYSICAL FACTORS - chronic urinary tract obstruction, radiation nephropathy; NEOPLASMS - multiple myeloma (cast nephropathy); IMMUNOLOGIC REACTIONS - transplant rejection, Sjogren syndrome, Sarcoidosis; VASCULAR DISEASES; MISCELLANEOUS - Balkan nephropathy, Nephronophthsis - medullary cystic disease complex, "Idiopathic" interstitial nephritis |
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Term
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Definition
| Acute suppurative inflammation of the kidney - bacterial, sometimes viral (eg polyoma virus) infection; Hematogenous and induced by septicemic spread; Ascending and associated with vesicoureteral reflux; Three Complications of Acute Pyelonephritis are encountered in special circumstance - Papillary Necrosis (diabetics, urinary tract obstruction, Papillary necrosis may lead to acute renal failure), Pyonephrosis (pus/ inflammatory infiltration, Seen with total or almost complete obstructions in which suppurative exudate is unable to drain), Perinpehric Abscess (extension of suppurative inflammation through the renal capsule into the perinephric tissue) |
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Term
| Causes of Renal Papillary Necrosis |
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Definition
| Diabetes mellitus, Analgesic Nephropathy, Sickle Cell Disease, Obstruction, Renal Tuberculosis (focal) |
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Term
| Tubulointerstitial Nephritis Induced By Drugs and Toxins |
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Definition
| Toxins and drugs can produce renal injury in at least 3 ways: (1) Trigger an interstitial immunologic reaction - acute hypersensitivity nephritis induced by such drugs as methicillin, (2) Acute renal failure - a direct result of the drug, (3) Cause subtle byt cumulative injury to tubules that takes years to become manifest, resulting in chronic renal insufficiency - analgesic abuse nephropathy, which is usually detected only after the onset of chronic renal insufficiency |
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Term
| Acute Drug-Induced Interstitial Nephritis |
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Definition
| Well-recognized adverse reaction to a constantly increasing number of drugs: sulfonamides, synthetic penicillins (methicillin, ampicllin), other synthetic antibiotics (rifampin), NSAIDs, Miscellaneous drugs (allopurinol, cimetidine); Begins about 15 days (rage 2-40) after exposure to the drugs and is characterized by: Fever, Eosinophilia (which may be transient), Rash (in about 25% of patients), Renal abnormalities (hematuria, mild proteinuria, leukocyturia - often including eosinophils, rising serum creatinine level or acute renal failure with oliguria in about 50% of cases, particularly in older patients); MORPHOLOGY - abnormalities are in the interstitium, Pronounced edema, Infiltration by mononuclear cells, principally lymphocytes and macrophages (eosinophils and neutrophils may be present, often in large number), Variable degrees of tubular necrosis and regeneration are present, Glomeruli are normal except in some cases caused by NSAIDs when minimal change disease and the nephrotic syndrome develop concurrently; PATHOGENESIS - suggest an immune mechanism, Immune response idiosyncratic and not dose-related |
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Term
| Clinical Features of Acute Drug-Induced Interstitial Nephritis |
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Definition
| It's Important to recognize drug-induced renal failure because withdrawal of the offending drug is followed by recovery; It may take several months for renal function to return to normal, and irreversible damage may occur occasionally in older subjects; Drugs are the leading identifiable cause of acute interstitial nephritis - in approximately 30-40% of patients with acute interstitial nephritis, an offending drug or mechanism for nephritis can't be identified |
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Term
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Definition
| A Form of chronic renal disease caused by excessive intake of analgesic mixtures and characterized morphologically by chronic tubulointerstitial nephritis with renal papillary necrosis; The Incidence of analgesic nephropathy reflects to consumption of analgesics in various populations throughout the world - overall, it accounted for 9%, 3% and 1% of patients undergoing dialysis in Australia, Europe and the US respectively (before the recent surge in end-stage renal disease attributable to diabetes reduced these rellative percentages); MORPHOLOGY - Papillae show various stages of necrosis, calcification, fragmentation and sloughing, Papillary changes may take one of several forms: early cases - patchy necrosis, Advanced cases - entire papilla is necrotic with ghosts of tubules and foci of dystrophic calcification |
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Term
| Clinical Course of Analgesic Nephropathy |
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Definition
| F>M; Recurrent headaches and muscle pain, in psychoneurotic patients and in factory workers; Early renal findings include inability to concentrate the urine; Acquired distal renal tubular acidosis contributes to the development of renal stones; Headache, anemia, GI sxs, and HTN are common - anemia is out of proportion to the renal insufficiency; UTIs in 50% of cases; Gross hematuria; Renal colic due to obstruction of the ureter; May lead to chronic renal failure, but with drug withdrawal, renal function may either stabilize or actually improve; A small percentage of patients with analgesic nephropathy develop transitional papillary carcinoma of the renal pelvis |
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Term
| Nephropathy Associated with NSAIDs |
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Definition
| NSAIDs are one of the most common classes of drugs currently in use and produce several forms of renal injury. NSAID-associated renal syndromes include: Hemodynamically induced acute renal failure due to the inhibition of vasodilatory prostaglandin synthesis by NSAIDs, Acute hypersensitivity interstitial nephritis resulting in acute renal failure, Acute interstitial nephritis and minimal change disease, Membranous glomerulonephritis with nephrotic syndrome (unclear etiology) |
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Term
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Definition
| Overt renal insufficiency occurs in 50% of patients; Several factors contribute to renal damamge: Bence-Jones proteinuria and cast nephropahty (direct toxicity to epithelial cells, Combine with urinary glycoprotein - tamm-horsfall prtine - under acidic conditions causing tubular cast nephropathy), Amyloidosis, Light-chain deposition disease, Hypercalcemia and hyperuricemia; MORPHOLOGY - Bence-Jones tubular casts (pink to blue amorphous masses, Some of the casts are surrounded by multinucleated giant cells, Adjacent interstitial tissue shows a nonspecific inflammatory response and fibrosis); Clinical Course; Chronic Renal Failure (most common); Acute renal failure with oliguria - precipitating factors include dehydration, hypercalcemia, acute infection, and treatment with nephrotoxic antibiotics |
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Term
| Renal Disease Caused by Blood Vessel Disease |
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Definition
| Benign Nephrosclerosis, Renal Artery Stenosis, Thrombotic Microangiopathies, Classic (Childhood) Hemolytic-Uremic Syndrome, Idiopathic TTP |
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Term
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Definition
| Associated with sclerosis of renal arterioles and small arteries; 2 Processes participate in inducing the arterial lesions: medial and intimal thickening, and Hyaline deposition in arterioles; MORPHOLOGY - Kidneys are either normal in size or moderately reduced (loss of mass is due to cortical scarring and shrinking), Cortical surfaces have a fine even granularity that resembles grain leather, Narrowing of the lumens of arterioles and small arteries caused by thickening and hyalinization of the walls (hyaline arteriolosclerosis), Fibroelastic hyperplasia, Foci of tubular atrophy and interstitial fibrosis, Sclerosis of glomeruli |
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Term
| Clinical Features of Benign Nephrosclerosis |
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Definition
| It's Unusual for uncomplicated benign nephrosclerosis alone to cause renal insufficiency or uremia; Usually moderate reductions in renal plasma flow, but the GFR is normal or only slightly reduced; On occasion, there is mild proteinuria; 3 Groups of hypertensives with benign nephrosclerosis are at increased risk of developing renal failure: blacks, Patients with more severe blood pressure elevations, Patients with a second underlying disease, especially diabetes |
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Term
| Malignant HTN and Accelerated Nephrosclerosis |
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Definition
| Can Develop In - Previously normotensive individuals; Superimposed on - Pre-existing essential benign HTN, Secondary form of HTN, Underlying chronic renal Disease, Particularly glomerulonephritis or reflux nephropathy; It is also a frequent cause of death from uremia in patients with scleroderma; Occurs in 1-5% of all patients with elevated blood pressure; Usually affects younger individuals, with a high preponderance in men and blacks; Small, pinpoint petechial hemorrhages may appear on the cortical surface from rupture of arterioles or glomerular capillaries, giving he kidney a peculiar "flea-bitten" appearance; Fibrinoid necrosis of arterioles; In the interlobular arteries and arterioles there is "onion-skinning"; CHARACTERIZED BY - diastolic pressures >130mmHg, Papilledema retinopathy, Encephalopathy, Cardiovascular abnormalities, Renal Failure; Early Symptoms are related to increased intracranial pressure; "Hypertensive Crises" - Characterized by episodes of loss of consciousness or even convulsions; At the onset of rapidly mounting BP there is marked proteinuria and microscopic/ macroscopic hematuria, but no significant alteration in renal funciton; True Medical Emergency; Previously associated with a 50% mortality rate within 3 months of onset, progressing to 90% within a year; Currently 75% of patients will surive 5 years, and 50% survive with pre-crisis renal function |
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Term
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Definition
| Unilateral renal artery stenosis is a relatively uncommon cause of HTN (2-5% of cases); Potentially curable form of HTN - surgial treatment is successful in 70-80% of cases; Patients resemble those presenting with essential HTN; On occasion, a bruit can be heard on auscultation of the kidneys; Elevated plasma or renal vein renin; Arteriography is required to localize the stenotic lesion; Most common cause of renal artery stenosis (70%) is occlusion by an atheromatous plaque at the origin of the renal artery; Ischemic kidney is usually reduced in size and shows signs of diffuse ischemic atropy; Fibromuscular Dysplasia (FMD) - heterogeneous group of lesions characterized by fibrous or fibromuscular thickening and may involve the intima, the media or the adventitia of the artery, More common in women and occcur in younger age groups (ie in the 3rd and 4th decades), Can be a Single well-defined constriction or a series of narrowings, usually in the middle or distal portion of the renal artery |
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Term
| Thrombotic Microangiopathies |
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Definition
| Charcterized morphologically by thrombosis in capillaries and arterioles throughout the body and clinically by microangiopathic hemolytic anemia, thrombocytopenia, and, in certain conditions, renal failure; Renal failure is associated with platelet or platelet-fibrin thrombi in the interlobular renal arteries, arterioles, and glomeruli together with necrosis and thickening of the vessel walls; Includes - Hemolytic-Uremic Syndrome (HUS) and Thrombotic thrombocytopenic purpura (TTP); Adult HUS is associated with - infection, antiphospholipid antibodies, complications of pregnancy and contraceptives, vascular renal diseases such as scleroderma and HTN, chemotherapeutic and immunosuppressive drugs, and Radiation; Familial HUS; Idiopathic TTP |
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Term
| Classic (Childhood) Hemolytic-Uremic Syndrome (HUS) |
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Definition
| 75% of cases occur in children after intestinal infection with verocytotoxin-producing E.Coli (eg type O157:H7) - some epidemics have been traced to ingestion of infected ground meat (ie hamburgers); One of the main cases of acute renal failure in children; Characterized by sudden onset (usually after a GI or influenza-like prodromal episode) of - bleeding manifestations (especially hematemesis and melena), severe oliguria, hematuria, microangiopathic hemolytic anemia, Prominent neurologic changes (in some patients), HTN (50%); If the renal failure is managed properly with dialysis, most patients recover in a matter of weeks; Long-term (15-25 year) prognosis is not uniformly favorable |
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Term
| Idiopathic Thrombotic Thrombocytopenic Purpura (TTP) |
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Definition
| MANIFESTED BY - fever, neuro symptoms, hemolytic anemia, thrombocytopenic purpura, presence of thrombi in glomerular capillaries and afferent arterioles; Caused by an acquired or genetic defect in ADAMTS-13, the protease that cleaves large vonWillebrand Factor (vWF) multimers - abnormal (noncleaved) forms of vWF promote platelet aggregation; More common in women and most patients are <40 years; In CLASSIC TTP - CNS involvement is the dominant feature, Renal involvement occurs in only about 50% of patients; Eosinophilic granular thrombi are present in the interlobular arteries, afferent arterioles, and glomerular capillaries; Untreated, the disease was once highly fatal, but exchange transfusions and corticosteroid therapy have reduced mortality to less than 50% |
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Term
| Urinary Tract Obstruction (Obstructive Uropathy) |
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Definition
| COMMON CAUSES - congenital anomalies (posterior urethral valves and urethral strictures, meatal stenosis, bladder neck obstruction, ureteropelvic junction narrowing or obstruction, severe vesicoureteral reflux), Urinary Cacluli, Benign Prostatic Hypertrophy, Tumors (carcinoma of the prostate, bladder tumors, contiguous malignant disease, carcinoma of the cervix or uterus), Inflammation (prostatitis, ureteritis, urethritis, retroperitoneal fibrosis), Sloughed papillae or blood clots, Normal Pregnancy, Uterine Prolapse and Cystocele, Functional Disorders (neurogenic - spinal cord damage or diabetic nephropathy, and other functional abnormalities of the ureter or bladder - often termed dysfunctional obstruction); When the obstruction is sudden and complete, the reduction of glomerular filtration usually leads to mild dilation of the pelvis and calyces, but sometimes to atrophy of the renal parenchyma; When the obstruction is subtotal or intermittent, glomerular filtration is not suppressed, and progressive dilation ensues; Acute obstruction may provoke pain attributed to distention of the collecting system or renal capsule; Unilateral, complete or partial hydronephrosis - may remain silent for long periods, since the unaffected kidney can maintain adequate renal funciton; Bilateral partial obstruction - earliest manifestation is inability to concentrate the urine, reflected by polyuria and nocturia, Acquired distal tubular acidosis, renal salt wasting, secondary renal calculi and a typical picture of tubulointerstitial nephritis with scarring and atrophy of the papilla and medulla, HTN is common in such patients; Complete Bilateral Obstruction - results in oliguria or anuria, Incompatible with long survival unless the obstruction is relieved, After relief of complete urinary tract obstruction, postobstructive diuresis occurs (can often be massive, with the kidney excreting large amounts of urine that is rich in sodium chloride) |
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Term
| Congenital Anomalies of the Ureters |
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Definition
| Occur in about 2% or 3% of all autopsies; Double ureters; Ureteropelvic junction obstruction - a congenital disorder that results in hydronephrosis; Usually presents in infants or children, much more commonly in boys, usually in the left ureter; Bilateral in 20% of cases and may be associated with other congenital anomalies; Most common cause of hydronephrosis in infants and children |
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Term
| Tumors and Tumor-Like Lesions of the Ureters |
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Definition
| Primary neoplasia of the ureter is rare - Small benign tumors of the ureter are generally of mesenchymal origin; The Two most common are fibroepithelial polyps and leiomyomas; Primary malignant tumors of the ureter - Majority are transitional cell carcinomas, They Cause obstruction of the ureteral lumen and are found most frequently during the sixth and seventh decades of life, Sometimes multiple and occasionally occur concurrently with similar neoplasms in the bladder or renal pelvis |
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Term
| Obstructive Lesions of the Ureters |
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Definition
| COMPLICATIONS – Hydroureter, Hydronephrosis, Pyelonephritis; Can be on Intrinsic or extrinsic origin; INTRINSIC – Calculi (Of renal origin, rarely more than 5 mm in diameter, Larger renal stones cannot enter ureters, Impact at loci of ureteral narrowing-ureteropelvic junction, where ureters cross iliac vessels, and where they enter bladder-and cause excruciating "renal colic"), Strictures (Congenital or acquired due to inflammations), Tumors (Transitional cell carcinomas arising in ureters, Rarely, benign tumors or fibroepithelial polyps), Blood Clots (Massive hematuria from renal calculi, tumors or papillary necrosis), Nerogenic (Interruption of the neural pathways to the bladder); EXTRINSIC - Pregnancy (Physiologic relaxation of smooth muscle or pressure on ureters at pelvic brim from enlarging fundus), Periureteral inflammation (Salpingitis, diverticulitis, peritonitis, sclerosing retroperitoneal fibrosis), Endometriosis (With pelvic lesions, followed by scarring); Unilateral obstruction typically results from proximal causes; Bilateral obstruction arises from distal causes, such as nodular hyperplasia of the prostate |
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Term
| Sclerosing Retroperitoneal Fibrosis |
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Definition
| An Uncommon cause of ureteral narrowing or obstruction characterized by a fibrous proliferative inflammatory process encasing the retroperitoneal structures and causing hydronephrosis; Occurs in middle to late age; RADIOLOGY - Medial deviation of ureters; ETIOLOGY - Drugs (ergot derivatives, β-adrenergic blockers), Adjacent inflammatory conditions (vasculitis, diverticulitis, Crohn disease), Malignant disease (lymphomas, urinary tract carcinomas), 70% of cases have no obvious cause and are considered primary or idiopathic (Ormond disease); Several cases have been reported with similar fibrotic changes in other sites (referred to as mediastinal fibrosis, sclerosing cholangitis, and Riedel fibrosing thyroiditis); ? autoimmune reaction; MICROSCOPY - Inflammatory fibrosis is marked by a prominent inflammatory infiltrate of lymphocytes, often with germinal centers, plasma cells, and eosinophils; Sometimes, foci of fat necrosis and granulomatous inflammation are seen in and about the fibrosis. |
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Term
| Diseases/ Disorders of the Bladder |
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Definition
| Disorders are more disabling than lethal; Cystitis, particularly common in young women of reproductive age and in older age groups of both sexes; Tumors of the bladder are an important source of both morbidity and mortality. |
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Term
| Congenital Anomalies of the Bladder |
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Definition
| DIVERTICULA - Congenital versus acquired, Most diverticula are small and asymptomatic; MISCELLANEOUS - Urachus may remain patent in part or in whole (persistent urachus) - Central region of the urachus persists, giving rise to urachal cysts, Carcinomas, (resembles colonic adenocarcinomas), Minority of all bladder cancers (0.1% to 0.3%) but 20% to 40% of bladder adenocarcinomas |
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Term
| Inflammation of the Bladder |
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Definition
| CLINICAL TRIAD: Frequency, Lower abdomen pain, Dysuria; May be antecedent to pyelonephritis, prostate enlargement, cystocele, calculi, tumor; INCLUDES - infectious cystitis, Radiation cystitis, Hemorrhagic cystitis, Interstitial cystitis (Hunner ulcer), Polypoid cystitis, Malacoplakia, and Metaplasic Lesions |
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Term
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Definition
| ETIOLOGIES - Escherichia coli, Proteus, Klebsiella, Enterobacter , Chlamydia and Mycoplasma; Women more common than men to develop cystitis secondary to shorter urethras; Immunosuppressed patients and on long-term antibiotics (Candida albicans, Cryptococcal); Middle East countries (Egypt) - Schistosoma haematobium; Viruses; PREDISPOSING FACTORS - Bladder calculi, Urinary obstruction, Diabetes mellitus, Instrumentation, Immune deficiency, and Inflammation |
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Term
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Definition
| DUE TO - Cytotoxic antitumor drugs or Adenovirus |
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Term
| Interstitial Cystitis (Hunner Ulcer) |
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Definition
| A Persistent, painful form of chronic cystitis occurring most frequently in women and associated with inflammation and fibrosis of all layers of the bladder wall; Chronic ulcers --> Hunner ulcer --> late (classic, ulcerative) phase (Inflammatory cells, granulation tissue, mast cells (characteristics of disease)); Biopsy to rule out CIS (flat urothelial carcinoma/ carcinoma-in-situ); ? etiology --> autoimmune, i.e. SLE |
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Term
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Definition
| Irritation to the bladder mucosa such as Indwelling catheters; May be confused with papillary urothelial CA |
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Term
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Definition
| An Unusual but distinctive type of inflammatory reaction of unknown etiology; ? Related to chronic bacterial infections; Occurs with increased frequency in immunosuppressed transplant recipients; Urinary tract most common site of involvement (described in other GU and non-GU sites); Solitary or confluent yellow nodules or plaques of various size; Large, foamy macrophages, occasional multinucleated giant cells and interspersed lymphocytes; Michaelis-Gutmann bodies --> laminated mineralized concretions resulting from deposition --> present within macrophages and between cells; Cystoscopy may be confused with carcinoma |
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Term
| Metaplastic Lesions of the Bladder |
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Definition
| Includes Cystitis glandularis and cystitis cystic; Not associated with an increased risk for the development of adenocarcinoma; Squamous metaplasia in Response to injury; Nephogenic metaplasia (nephrogenic adenoma) – a Reaction of the urothelium to inflammation and/or injury |
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Term
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Definition
| Continue to exact a high toll in morbidity and mortality; Incidence of bladder epithelial tumors in the United States has been steadily increasing during the past years (>57,000 new cases annually); Despite improvements in detection and management of these neoplasms, the death toll remains at about 12,000 annually because the increased prevalence; About 95% of bladder tumors are of epithelial origin, the remainder being mesenchymal tumors; INCLUDES - Urothelial/ Transitional Cell Tumors (Flat urothelial carcinoma/ carcinoma-in-situ, Papillomas, etc.) |
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Term
| Urothelial (Transitional Cell) Tumors (General) |
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Definition
| Account for 90% of all bladder tumors - Varies in behavior --> benign to highly aggressive, Most are multifocal at presentation; 2 distinct precursor lesion to invasive urothelial carcinoma - Noninvasive papillary tumor, More common, Arise from papillary urothelial hyperplasia, Demonstrate range of atypia |
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Term
| Flat urothelial carcinoma/ Carcinoma-in-Situ (CIS) |
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Definition
| WHO Definition: “Non-papillary, i.e. flat lesion in which the surface epithelium contains cells that are cytologically malignant”; By definition, high grade; About 50% of pt. have invasive CA at time of presentation; Major decrease in survival related to tumor invading the muscularis propria (detrusor muscle) --> 50% 5-year mortality rate; CIS may range from full-thickness cytologic atypia to scattered malignant cells in an otherwise normal urothelium; Lack of cohesiveness which leads to the shedding of malignant cells into the urine; Denuded urothelium with only a few CIS cells clinging to the basement membrane; Usually appears as an area of mucosal reddening, granularity, or thickening without an intraluminal mass; Commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra; Most often found in bladders harboring other patterns of transitional cell carcinoma; If untreated, 50% to 75% of CIS cases progress to muscle-invasive cancer. |
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Term
| Epidemiology and Pathogenesis of Urothelial (Transitional Cell) Tumors |
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Definition
| More common in men than in women; M:F ratio is 3:1; More common in industrialized than in developing nations; More common in urban than in rural dwellers; About 80% of patients are between the ages of 50 and 80 years; Bladder cancer, with rare exception, is not familial; RISK FACTORS - Cigarette smoking (increases the risk 3-7X), Industrial exposure to arylamines, Schistosoma haematobium infections in endemic (Egypt, Sudan) areas, Long-term use of analgesics (Phenacetin), Heavy long-term exposure to cyclophosphamide an Immunosuppressive agent that induces hemorrhagic cystitis, Prior exposure of the bladder to radiation; A Number of genetic alterations have been observed in urothelial cell carcinoma - Cytogenetic and molecular alterations are heterogeneous, Particularly common (occurring in 30% to 60% of tumors studied) are - Chromosome 9 monosomy, Deletions of 9p and 9q, 17p, 13q, and 14q, and Others include deletion of 11p, increased expression of RAS and epidermal growth factor receptors |
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Term
| Pathologic findings in Urothelial (Transitional Cell) Tumors |
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Definition
| Gross pattern - papillary to nodular to flat; Invasive and non-invasive; Papillary lesions; Can be multicentric; Most arise from lateral or posterior walls of the bladder base |
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Term
| Classification System for Papillary Urothelial Neoplasm |
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Definition
| 2004 WHO and 1998 WHO/ISUP – Papilloma, Exophytic, Inverted, Papillary urothelial neoplasm of low malignant potential (PUNLMP), Papillary carcinoma (Low grade or High grade) |
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Term
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Definition
| WHO DEFINITION - “Composed of a delicate fibrovascular core covered by urothelium indistinguishable from that of normal urothelium”; Inverted papillomas; 1% or fewer of bladder tumor; Younger patients; Usually single, small, 0.5-2.0 cm, delicate structures, superficially attached to the mucosa by a stalk; Recurrence is rare |
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Term
| Papillary Urothelial Neoplasm Of Low Malignant Potential (PUNLMP) |
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Definition
| WHO DEFINITION - “Resemble exophytic urothelial papilloma but shows increased cellular proliferation exceeding the thickness of normal urothelium”; May show diffuse nuclear enlargement; Mitotic figures are rare; AT CYSTOSCOPY - Tend to be larger than papillomas, May be indistinguishable from low- and high-grade papillary cancers; Not associated with invasion; May recur with the same morphology; Only rarely recur as higher-grade tumors associated with invasion and progression |
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Term
| Low-grade Papillary Urothelial Carcinomas |
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Definition
| WHO DEFINITION - “Neoplasm of urothelium lining papillary fronds which shows orderly appearance but easily recognizable variations in architecture and cytologic features”; Cells are evenly spaced and cohesive; Minimal but definite evidence of nuclear atypia; Can recur and, although infrequent, can invade; Only rarely do these tumors pose a threat to the patient's life |
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Term
| High-grade Papillary Urothelial Carcinomas |
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Definition
| WHO DEFINITION - “Neoplasm of urothelial lining papillary fronds which shows a predominant pattern of disorder with moderate-to-marked architectural and cytologic atypia”; Cells that may be discohesive and have large hyperchromatic nuclei; Some of the tumor cells show frank anaplasia; Mitotic figures, including atypical ones, are frequent; Architecturally, there is disarray with loss of polarity; Tumors have a much higher incidence of invasion into the muscular layer, a higher risk of progression than low-grade lesions, and significant metastatic potential |
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Term
| Invasive Urothelial Carcinoma |
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Definition
| If detected early, may be superficial in the lamina propria and can be associated with either papillary urothelial cancer, usually high grade, or with CIS (Carcinoma-in-Situ); Extent of the invasion is of prognostic significance; Extent of spread at the time of initial diagnosis is the most important factor in determining the outlook for a patient |
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Term
| Squamous Cell Carcinomas of the Bladder |
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Definition
| WHO DEFINITION - “Malignant neoplasm derived from the urothelium showing pure squamous cell phenotype.”; Represent about 3% to 7% of bladder cancers in the United States, but in countries endemic for urinary schistosomiasis, they occur much more frequently; Pure squamous cell carcinomas are nearly always associated with chronic bladder irritation and infection; Mixed urothelial cell carcinomas with areas of squamous carcinoma are more frequent than pure squamous cell carcinomas; Most are invasive, fungating tumors or infiltrative and ulcerative; Often cover large areas of the bladder and are deeply invasive by the time of discovery. |
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Term
| Adenocarcinomas of the Bladder |
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Definition
| WHO DEFINITION - “Malignant neoplasm derived from urothelium showing histologically pure glandular phenotype.”; Rare and histologically identical to adenocarcinomas seen in the gastrointestinal tract; Rare variants of adenocarcinoma are the highly malignant signet-ring cell carcinoma, and mixed adenocarcinoma and urothelial cell carcinomas; Some arise from urachal remnants or in association with extensive intestinal metaplasia; Urachal tumors occur in the dome or anterior wall, arise within the wall rather than from the mucosa, and extend out of the bladder towards the umbilicus. |
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Term
| Clinical Course of Bladder Neoplasms |
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Definition
| Bladder tumors classically produce painless hematuria - Sometimes this is the only clinical manifestation of the cancer; Frequency, urgency, and dysuria occasionally accompany the hematuria; When the ureteral orifice is involved, pyelonephritis or hydronephrosis may follow; About 60% of neoplasms, when first discovered, are single, and 70% are localized to the bladder; Patients with urothelial tumors, whatever the grade, have a tendency to develop new tumors after excision, and recurrences may exhibit a higher grade; Risk of recurrence and progression is related to several factors - Tumor size, Stage, Grade, Multifocality, Prior recurrence rate, Associated dysplasia and/or carcinoma in situ in the surrounding mucosa; The most important factors for progression-free survival are – Grade, Presence of lamina propria invasion, Associated carcinoma in situ; Papillomas, papillary urothelial neoplasms of low malignant potential, and low-grade papillary urothelial cancer yield a 98% 10-year survival rate regardless of the number of recurrences - Few patients (<10%) experience progression of their disease to higher-grade lesions; About 40% of individuals with a high-grade cancer survive 10 years; the tumor is progressive in 65%; Approximately 70% of patients with squamous cell carcinomas are dead within the year. |
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Term
| Treatment of Bladder Cancers |
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Definition
| FOR SMALL, LOCALIZED PAPILLARY TUMORS THAT ARE NOT HIGH GRADE – Initially patients undergo a diagnostic transurethral resection, This is Followed with periodic cystoscopies and urine cytology for tumor recurrence; FOR MULTIFOCAL BLADDER TUMORS - Instillation of topical chemotherapy into the bladder, There is a High risk of recurrence and/or progression with Attenuated strain of Mycobacterium tuberculosis called Bacillus Calmette-Guérin (BCG); RADICAL CYSTECTOMY IS TYPICALLY PERFORMED FOR - Tumor invading the muscularis propria, CIS or high-grade papillary cancer refractory to BCG, CIS extending into the prostatic urethra and extending down the prostatic ducts beyond the reach of BCG; Advanced bladder cancer is treated by chemotherapy (in addition to the other interventions above) |
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Term
| Inflammation of the Urethra |
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Definition
| Urethritis is classically divided into gonococcal and nongonococcal urethritis; GONOCOCCAL URETHRITIS is one of the earliest manifestations of this venereal infection; NONGONOCCOCAL URETHRITIS is common and can be caused by a variety of bacteria, among which E. coli and other enteric organisms predominate; Often accompanied by cystitis in women and by prostatitis in men; In many instances, bacteria cannot be isolated; Various strains of Chlamydia (e.g., C. trachomatis) are the cause of 25% to 60% of nongonococcal urethritis in men and about 20% in women; Mycoplasma (Ureaplasma urealyticum) also accounts for the symptoms of urethritis in many cases; Urethritis is also one component of Reiter syndrome, which comprises the clinical triad of arthritis, conjunctivitis, and urethritis |
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Term
| Tumors and tumor-like lesions of the Urethra |
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Definition
| Urethral caruncle is an inflammatory lesion presenting as a small, red, painful mass about the external urethral meatus in the female patient; Benign epithelial tumors of the urethra include squamous and transitional cell papillomas, inverted papillomas, and condylomas; Primary carcinoma of the urethra is an uncommon lesion; Cancers can arise within the prostatic urethra |
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Term
| Regulation of Plasma Osmolality |
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Definition
| The osmolality of plasma (Posm) is tightly regulated between 270 mOsm/kg and around 300 mOsm/kg – generally 285 mOsm/kg is quoted as “median” normal plasma osmolality; The Posm is equal to the sum of the osmolalities of the individual solutes in the plasma. Most of the plasma osmoles are Na+ salts, with lesser contributions of other ions, plus the non-ions glucose and urea; Since cell membranes are generally permeable to water, intracellular osmolality is essentially the same as plasma and ECF osmolality |
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Term
| Calculating Plasma Osmolality |
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Definition
The following equation gives a good estimate of the total plasma osmolality:
Posm = (2 X Na+) + (glucose ÷ 18) + (urea ÷ 2.8); (This formula assumes glucose and urea are provided as mg/dl) |
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Term
| “Effective” Plasma Osmolality (Tonicity) |
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Definition
The effective Posm is determined by those osmoles that can effectively exert osmotic pressure across cell membranes.; Urea is an ineffective osmole; so effective osmolality is best calculated as:
Effective Posm = 2 X plasma [Na+] + ([glucose] / 18) |
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Term
| Common Measure of Plasma Osmolality |
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Definition
Under normal circumstances, glucose accounts for only about 5 mOsm/kg of the total Posm. Therefore, a common estimate of effective Posm is simply:
Posm = 2 X plasma [Na+]; However, in conditions such as uncontrolled diabetes mellitus, glucose can be a large contributor to the overall effective Posm. |
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Term
| Normal Urine Osmolalities |
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Definition
| The osmolality of urine (Uosm) normally varies in the range of 500-800 mOsm/kg, and around 1.0 to 1.5 L of urine is produced in 24 hours in the average person; During situations of excessive water entering the ECF, the kidneys can produce a urine as dilute as 50 mOsm/kg in attempting to normalize ECF osmolarity, with up to 15 to 20 L of urine produced a day; When excessive water loss from the ECF occurs, the Uosm can become as concentrated as 1400 mOsm/kg, with less than 0.5 L/day being excreted. |
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Term
| How sensitive is ADH to changes in Plasma Osmolality? |
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Definition
| Very sensitive - it only takes very small increases in plasma osmolality (1-2%) to cause plasma ADH levels to begin to maximize |
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Term
| ADH Response to Volume Changes |
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Definition
| ADH levels increase after a 10% or greater decline in volume and/ or BP; Increases in ADH response to a decline in volume will take precedent over a decrease in osmolality, due to the risk of rapid death that can occur from a decline in perfusion pressures; What this means is that AHD levels will stay high in severe volume depletion, even if plasma becomes hypoosmotic |
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Term
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Definition
| Changes in Posm affect the perception of thirst. When Posm Increases, the individual affected perceives thirst; Similar to ADH, an increase in Posm of only 1-2% will produce a strong desire to drink, while decreases in blood volume or pressure of 10-15% or so are required to produce the sensation of thirst |
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Term
| Can Increases in Plasma ADH "Correct" Hyperosmolality |
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Definition
| No - water loss doesn't occur exclusively through the urine (it's lost in sweat, etc. as well), so ADH (which is only acting to preserve water lost from urine) is just a hormone that "buys time" during times of water deprivation, until the person can find water to drink |
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Term
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Definition
| Defined as a serum sodium concentration exceeding 145 mEq/L. Hypernatremia almost alway results from excessive water loss for some reason. Rarely, it can be caused by excessive sodium retention (eg administration of hypertonic sodium bicarb during CPR); ALWAYS occurs with hyperosmolality; People with a normal thirst mechanism correct this by drinking water; As with hyponatremia, hypernatremia can be rapidly fatal if it occurs in a short period of time (< 24-36 hours); In this case, mortality is caused by an acute decrease in brain volume (water flows out of neurons and into ECF) that can then cause rupture of cerebral veins, resulting in focal intracerebral and subarachnoid hemorrhage; Neurons protect themselves from slow onset hypernatremia by making organically active solutes so that the water is drawn back in/ held in the cells |
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Term
| Hypernatremic Water Disorders |
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Definition
| Hypernatremic water disorders are almost always due to excessive loss of free water from the ECF compartment for some reason; ALL hypernatremic water disorders are accompanied by plasma hyperosmolality. |
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Term
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Definition
| Central diabetes insipidus (CDI) is caused by a partial or total lack of ADH (which is made in the hypothalamus and released from the posterior pituitary, so damage to either place will cause decreased ADH levels); Nephrogenic DI (NDI) is caused by failure of the kidneys to respond to appropriate levels of plasma ADH (Lithium can cause this); The effect of DI on urine osmolality and volume is that patients will have an increased volume of hypoosmolar urine (ie dilute) |
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Term
| What would a patient with Nephrogenic Diabetes Insipidus Show With a Water Deprivation Test? |
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Definition
| In these patients excess water drinking is caused by excess urination and ADH is made appropriately, but doesn't work on the kidney - following water deprivation, they will have low Uosm and will not have an increase in osmolality after administration of synthetic ADH |
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Term
| What would a patient with Central Diabetes Insipidus Show With a Water Deprivation Test? |
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Definition
| In these patients excess water drinking is caused by excess urination and while their kidneys respond normally to ADH, they aren't making enough of it - following water deprivation they will have low Uosm but after administration of a synthetic ADH Uosm will increase |
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Term
| What would a Normal, Healthy Patient Show With a Water Deprivation Test? |
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Definition
| Following water deprivation, their urine will be appropriately concentrated - normal Uosm following a 10 hour water deprivation is >800 mOsm/ kg; If you give such a patient synthetic ADH at this point, their Uosm will increase a little bit because synthetic ADH is more potent than endogenous ADH |
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Term
| Distinguishing Diabetes Insipidus (DI) from Psychogenic Polydipsia (PP) |
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Definition
| When you see patients presenting with polydipsia and polyuria, try to answer this question when you take their history: Is the patient peeing so much because he drinks so much (PP), or is he drinking so much because he pees so much (DI)? |
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Term
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Definition
| Defined as a serum sodium concentration of less than 135 mEq/L. Hyponatremia is usually caused by excessive retention of water for some reason. Much less commonly, hyponatremia can be caused by excessive sodium loss exceeding isotonic water loss (eg, thiazide-induced hyponatremia); Hyponatremia is physiologically significant when symptoms appear, due to a tendency for free water to shift from the vascular space to the intracellular space; Although cellular edema is well tolerated by most tissues, it is not well tolerated within the rigid confines of the skull. Therefore, clinical manifestations of hyponatremia are related primarily to cerebral edema - If dilution of ECF occurs rapidly, water will flow down its concentration gradient and into neurons, causing neuronal swelling and cerebral edema; If ECF dilution occurs slowly, this gives neurons a chance to dump organic solutes OUT of the cell, decreasing the concentration gradient between ECF and ICF, resulting in less movement of water into neurons. |
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Term
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Definition
| Total body water (TBW) decreases and total body sodium (Na+) decreases to a greater extent. The extracellular fluid (ECF) volume is decreased; This type of hyponatremia is often seen in patients who are volume-depleted secondary to diuretic use, GI loss through vomiting, diarrhea or gastric tube drainage, or skin loss through burns or cystic fibrosis; Both aldosterone and ADH levels are elevated (due to volume depletion), leading to net dilution of the ECF (often compounded by the patient drinking water or other hypotonic liquids to replace lost fluid). |
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Term
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Definition
| Total Body Water (TBW) increases somewhat while total sodium remains normal. Although it is classified as ‘euvolemic hyponatremia, the ECF volume is increased minimally to moderately, but edema is not present; This type of hyponatremia is often seen in patients who have an excess of total body water due to a state of inappropriate ADH secretion (ADH levels stay inappropriately high in the presence of plasma hypoosmolality. |
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Term
| Common Etiologies of SIADH |
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Definition
| 1 - Tumors, 2 - Central nervous system disorders, 3 - Drugs, 4 - Pulmonary diseases |
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Term
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Definition
| Decreased effective osmolality of the plasma (< 275 mOsm/kg) combined with an inappropriately concentrated urine (>150 to 200 mOsm/kg); If Plasma osmolality is <275 mOsm/ kg, urine should be maximally dilute (50mOsm/ kg) – but the inappropriate ADH in SIADH prevents this; Clinical euvolemia is present, as defined by the absence of clinical signs of hypervolemia or hypovolemia |
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Term
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Definition
| A subset of patients diagnosed with SIADH have a ‘reset osmostat’ - They respond appropriately to a water load by shutting off ADH release, and They respond appropriately to solute load (hyperosmolality) by increasing ADH release; Thus, these patients behave similarly to normal subjects except that the threshold for ADH release is reduced (occurring at a plasma [Na+] somewhat lower than 140 - 142 mEq/L) – ie their “set-point” is lower than normal. |
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Term
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Definition
| The vast majority of hyponatremias are accompanied by hypoosmolality (unlike hypernatremias, where ALL of them are accompanied by hyperosmolality); When a hyponatremia is present with either normal, or hyperosmolality, it is referred to as a pseudohyponatremia. |
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Term
| Common Causes of Pseudohyponatremias |
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Definition
| 1. Abnormally high plasma levels of proteins or triglycerides (produces a hyponatremia with predominantly normal plasma osmolality); 2. Abnormally high levels of glucose (produces a hyponatremia with a predominantly hyperosmotic plasma osmolality); 3. The presence of high levels of some exogenous, osmotically active compound in the plasma. |
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Term
| Hospital Acquired Hyponatremias in Children |
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Definition
| Prevention of Hospital-Acquired Hyponatremia - A Case for Using Isotonic Saline. Pediatrics. 2003. Vol. 111 (2):227-230; This paper overviews the risks of producing acute hyponatremia in sick, hospitalized children by maintaining them on parenteral flujds that are hypotonic; This risk is predominately due to the fact that many of these children have illnesses that elevate plasma ADH in a non-physiologic manner, which will then cause retention of free water from the administered hypotonic fluids, and acute hyponatremia (SIADH); This is especially dangerous in children, as they have a higher brain to skull size ratio, increasing the risk of death in the face of cerebral edema. |
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Term
| Oligohydramnios and Neonatal Renal Disorders |
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Definition
| Oligohydramnios could indicate a kidney problem in the fetus, since the amniotic fluid is mostly urine (ie if there isn't enough amniotic fluid, then the fetus' kidneys aren't putting out enough urine); This is especially seen with bilateral renal agenesis (Potter's Disease) - babies with Potter's disease have a characteristic facial appearance at birth due to the fact that their face was squished in utero since there wasn't enough room due to the oligohydramnios; Oligohydramnios is also a problem because the fetal lungs need amniotic fluid to develop, and the babies get pulmonary hypoplasia if there's oligohydramnios |
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Term
| What Does a Palpable Abdominal Mass in a Neonate Mean? |
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Definition
| It is usually the kidney(s) or bladder; Hydronephrosis is the most common cause; Other causes include cyts, Renal Vein Thrombosis (RVT); RVTs should be considered if the palpable mass is hard - blood goes slowly through the renal veins, The kidney will swell as a result of a RVT; The most common time you'll feel a bladder on a baby is in a boy with posterior urethral valves (this is the #1 or 2 cause of kidney disease in kids) |
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Term
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Definition
| Associated with Congenital Nephrotic Syndrome |
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Term
| What Should be your First Thought in a Baby with HTN? |
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Definition
| Kidneys; Baby hearts don't tolerate HTN well |
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Term
| Creatinine Levels in Neonates |
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Definition
| Creatinine levels will reflect the mother's creatinine levels for 24-48 hours after birth; Normal Creatinine levels are difficult to assess in neonates because they don't make very much (since they don't have much muscle mass) |
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Term
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Definition
| AKA Triad Syndrome; Babies have poor abdominal musculature, Cryptorchidism (undescended testes), and Hydronephrosis; Their ureters are very dilated; The patient's belly looks like a prune because you can see their intestines under the skin (because there is no muscle covering it) |
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Term
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Definition
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Term
| What Does "Foamy" Urine Indicate? |
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Definition
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Term
| Why is it Important to Draw a Complement (C3, C4) Level ASAP? |
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Definition
| Because if you miss the period of time when the complement level is low, you might think that a condition is normocomplementemic when it is really hypocomplementemic and the two categories have different differential diagnoses and different prognoses |
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Term
| Hypocomplementemic Renal Disorders |
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Definition
| (1) Post-infectious glomerulonephritis (GN) - this is the 2nd most common cause of nephritis in kids, The complement level is low initially and then goes back up as the disease progresses (C3 low, C4 normal); (2) Membranoproliferative GN - complement level stays down (it never goes back up), C3 low, C4 normal, Very rare under age 6; (3) SLE - C3 and C4 are both low; (4) SBE; (5) VA shunt |
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Term
| Normocomplementemic Renal Disorders |
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Definition
| (1) IgA Nephropathy - the most common cause of gross hematuria, 30% of patients end up with long-term kidney disease, common in white's and Asians; (2) Henoch-Schonlein Purpura (HSP) - rash on the legs, joint pain, abdominal pain, and renal issues that may cause long term renal disease; (3) ANCA positive vasculitis; (4) Goodpasture's,etc.; NOTE - you might think that a disease is normocomplementemic because the C3 is normal, when in fact it is just that you missed the window of time when complement is low in Post-Infectious Glomerulonephritis |
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Term
| Hemolytic Uremic Syndrome (HUS) |
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Definition
| HUS describes the syndrome, not the disease; SYNDROME - microangiopathic hemolytic anemia of very rapid onset, Renal insufficiency, and Thrombocytopenia; May be diarrhea associated or not; DIARRHEA ASSOCIATED (Clasic) - Associated wtih enteral infection, E.coli O157:H7, Shiga-Like Toxin (Verotoxin), Can be associated with other enteral pathogens, Causes a microangiopathic hemolytic anemia with thrombocytopenia and renal failure, More common in small children (if you get it when you're older the prognosis is much worse), Primarily small vessel/ glomerulous involved, Can be very aggressive with multiple medical issues (renal failure, seizures, bowel perforation, brain abscess, death, etc.), Typically seen in spring and summer, Treatment - primarily supportive, Outcome - usually good but a signficant chance of longstanding renal disease; NONDIARRHEA ASSOCIATED (Atypical) - typically seen in adults, May be associated with a respiratory illness, May be familial (this is the type of non-diarrhea associated HUS that kids get and it's very bad), May be associated with the post-partum period or be medication induced, Affects Larger vessels (arterioles), More likely to have a worse outcome |
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Term
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Definition
Microangiopathic hemolytic anemia, Renal Insufficiency, and Thrombocytopenia;
NOTE - This is likely to be an exam question from Dr. Hand |
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Term
| Clinical Presentation of IgA Nephropathy |
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Definition
| Hematuria (gross/ microscopic), Proteinuria, HTN, Renal failure, Nephritis (decreased urine output, edema) |
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Term
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Definition
| Hematuria, Proteinuria, Decreased Urine Output, HTN, Edema |
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Term
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Definition
| Massive Proteinuria (>3-4g/day), Low Serum Albumin (Hypoalbuminemia), Edema, High Lipid Levels (Hyperlipidemia) |
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Term
| What is the Most Common Cause of Hypocomplementemic Glomerulonephritis? |
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Definition
| Post-infectious Glomerulonephritis |
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Term
| What is the Most Common Cause of Normocomplementemic Glomerulonephritis? |
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Definition
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Term
| Chronic Renal Failure in Kids |
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Definition
| Non-specific Clinical Picture - anemia, growth failure, anorexia, bed-wetting, fever, GI sxs; No cures, only therapies; Most Common ETIOLOGIES - dysplasia, hypoplasia and obstruction, Focal Segmental Glomerulosclerosis (FSGS) is also a cause; EVALUATION - BP (!!!), Electrolytes (hyperkalemia, Sodium disturbance, hypocalcemia (they can't hydroxylate vitamin D without functioning kidneys, so they get renal rickets), Hyperphosphatemia, Increased PTH), Acidosis, Anemia, Growth |
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Term
| What are the Most Common Causes of Chronic Renal Failure In Kids? |
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Definition
| Dysplasia, Hypoplasia, Obstruction, and Focal Segmental Glomerulosclerosis (FSGS) |
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Term
| Recapturing Filtered HCO3- |
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Definition
HCO3- is readily filtered into Bowman’s space, but normally very little escapes into the urine; Around 85% of the HCO3- filtered load of is reabsorbed in the proximal tubules, 10-15% in Henle’s loop, and only 3-5% at more distal sites; Note the mechanism utilized: secreted protons combine with the filtered HCO3-; It is important to recognize that the loss of any free HCO3- into the urine is equivalent to the addition of free H+ ions to the ECF:
C02 + H2O <--> H+ + HCO3-;
The loss of HCO3- from the ECF lowers the ratio of base (HCO3-) to acid (CO2) in the ECF, and will therefore result in an increase the free H+ ion concentration (and thus a decrease the pH!) |
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Term
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Definition
| During a metabolic acidemia, free H+ ions are added to the ECF for some reason, which “uses up” HCO3- in the buffering process; The equation (CO2 + H20 <- -> H+ + HCO3-) shifts to the LEFT, generating CO2; This HCO3- that buffered the excess H+ ions is lost for good, and MUST BE REPLACED to bring plasma HCO3- levels back up to approximately 24 mMol/ L |
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Term
| HCO3- Generation in the Proximal Tubules using Titratable Acids |
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Definition
| PROXIMAL TUBULE: Similar to what happens for HCO3- REABSORBTION, except now a H+ is excreted into the urine, generating a new HCO3- - In this scenerio, filtered sodium monohydrogen phosphate (Na2HPO4) serves as a proton acceptor (base), and is converted to the acid, Na2H2PO4 |
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Term
| HCO3- Generation in Distal Tubules and Collecting Ducts using Titratable Acids |
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Definition
| DISTAL TUBULE AND COLLECTING DUCTS: Similar to what happens here for HCO3- REABSORBTION, except now a H+ is excreted into the urine, generating a new HCO3- ; A filtered Na2HPO4 serves as the proton acceptor, and is converted to Na2H2PO4 |
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Term
| What is Titratable Acidity? |
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Definition
The amount of strong base (such as NaOH) that it takes to titrate a patient’s urine that is acidic back to normal pH (~7.42) is approximately equal to the amount of titratable acids that were in the urine (ie, if 45 mMol of NaOH were required to titrate urine pH up to 7.42, the assumption can be made that 45 mMol of H+ ion were buffered by titratable acids, and 45 mMol of ‘new’ HCO3- were generated);
Dihydrogen phosphate is the major titratable acid measured in urine;
A healthy individual can easily generate some 50 to 100 mEq’s of H+ ions daily, However, titratable acidity normally can account for the excretion of only about 10 to 40 mEq of H+ ion per day. |
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Term
| Limitations of Titratable Acids |
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Definition
| As the filtrate passes from Bowman’s space to the collecting tubules, the pH can drop all the way to about 4.50. This is an important concept, because urinary pH cannot drop below approximately 4.50; Unfortunately almost all titratable acids will be fully protonated when the urine pH reaches about 5.20. |
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Term
| Importance of Urinary Acid Buffering |
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Definition
| Assumption: individual has to excrete 100 mEq (mMol) of H+ ion a day to stay in acid / base balance (this is about average); The minimum pH that can be achieved by the urine is about 4.50. Although urine with a pH of 4.50 has a H+ concentration about 1000 times greater than healthy plasma (7.42 vs 4.50…..about 3 log units), the H+ ion concentration of this urine with a pH of 4.5 is still only about 40 uMol/L (normal plasma is 40 nMol/L); Thus, to get 100 mMol’s of unbuffered H+ ion into the urine each day you would have to produce about 2500 liters of this urine !! (2500 L x 40 uMol H+ ion/L = 100,000 uMol H+ ion = 100 mMol of H+ ion ) |
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Term
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Definition
Many years ago, it was observed that in those patients experiencing metabolic acidemia, there was not only a rise in urinary titratable acid’s, but also in urinary ammonium ion (NH4+); We now know that ammonia is a very important renal buffer, because the amount available is not directly dependant on diet or filtration, like titratable acids such as monohydrogen phosphate;
Ammonium ion can actually be produced in the cells lining the nephron, predominately in the proximal tubule, mostly (but not exclusively) from the deamination of of the amino acid glutamine. The stimulus to start doing this is acidificaiton of the renal tubular cells; The synthesis of ammonium ion in the proximal tubule occurs as follows: Glutamine --> 2NH4+ + alpha-ketoglutarate; The subsequent metabolism of alpha-ketoglutarate in the proximal tubular cell results in the CONSUMPTION OF TWO H+ ions. Removal of two H+ ions is equivalent to the GENERATION OF TWO NEW HCO3- ions in these cells. These two new HCO3- ions are transported across the basolateral membrane of the cell via a Na+/ HCO3- symporter, and returned to the general circulation; The ammonium ion (NH4+) is transported into the luminal fluid, mostly by substituting for H+ on the Na+/H+ antiporter, and passed out into the urine. Once in the tubule, it cannot diffuse back in due to it’s large charge, and is thus lost in the urine; The urinary excretion of NH4+ plays NO DIRECT ROLE in removing protons: NH4+ is merely a side product - or marker - of the formation of alpha-ketoglutarate in renal proximal tubular cells;
Therefore, proximal tubular secretion and subsequent urinary excretion of each NH4+ ion is linked to the generation of a new HCO3- ion in proximal tubular cells, which will then be returned to the circulation to replace HCO3- lost buffering excess plasma H+ ions. |
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Term
| Definition of "Respiratory Disorder" (Respiratory as in Respiratory vs Metabolic) |
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Definition
| A respiratory disorder is by definition an acid/base disorder that is due to a primary disturbance (increase or decrease) in pCO2 |
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Term
| Definition of "Metabolic Disorder" (Metabolic as in Metabolic vs Respiratory) |
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Definition
| A metabolic disorder is by definition an acid/base disorder that is due to a primary disturbance (increase or decrease) in HCO3-. |
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Term
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Definition
| A respiratory acid/base disorder is always compensated by an appropriate change in NaHCO3 ; A metabolic acid/base disorder is always compensated by an appropriate change in pCO2 ; The ‘appropriate change’ will always go in the same direction as the primary disturbance!; If the primary disturbance is in plasma HCO3- (i.e., a metabolic disorder), then the compensator will be PCO2 ; If the primary disturbance is in PCO2 (i.e., a respiratory disorder), then the compensator will be HCO3-. |
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Term
| Acute Vs Chronic Respiratory Acid/ Base Disorders |
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Definition
| We refer to respiratory acid/base disorders as “acute” (less than one day in duration) or “chronic” (more than three or four days in duration). That’s because it can take the kidneys three to four days before they are fully compensating a respiratory acid/base disorder; These terms are generally not applied to metabolic disorders. That’s because the lungs can begin to compensate metabolic disorders within minutes or hours, by alterations in respiration rate. |
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Term
| Method for Evaluating Blood Gasses |
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Definition
| STEP 1: Assess the pH. Low pH (< 7.35) is acidemia, high pH (>7.45) is alkalemia; STEP 2: Determine the cause of the alkalemia or acidemia. Acidemia can only be caused by acidosis, and therefore implies the presence of an acidosis. Similarly, alkalemia can only be caused by alkalosis, and therefore implies the presence of an alkalosis; STEP 3: Determine which of the constituents in your buffer (conjugate acid or conjugate base) can explain the change in pH (Ex if you have an acidemia – this could be explained either by an increase in the acid or a decrease in the base); LOW pH EXAMPLE - An acidemia may either be respiratory or metabolic (remember, HCO3- is the conjugate base, and pCO2 is the conjugate acid in this buffering pair) - Therefore, either a DECLINE IN HCO3- or AN INCREASE IN PCO2 can explain the presence of an acidemia: (1) If a high PCO2 is the primary disturbance, it’s a respiratory acidemia, (2) If a low HCO3- is the primary disturbance, it’s a metabolic acidemia (if both the HCO3- is low and the pCO2 is high then this is a mixed acid-base disorder); HIGH pH EXAMPLE -An alkalemia may either be respiratory or metabolic, Therefore, either a DECLINE IN PCO2 - or AN INCREASE IN HCO3- can produce an alkalemia – (1) If a low PCO2 can explain the alkalemia, it’s a respiratory alkalemia, (2) If high HCO3- can explain the alkalemia, it’s a metabolic alkalemia (if both a high HCO3- and a low pCO2 can account for the alkalemia then this is a mixed acid-base disorder) |
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Term
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Definition
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Term
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Definition
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Term
| What Type of Acid Base Disorder Does This Patient Have? pH = 7.30, HCO3- = 14, and pCO2 = 30 |
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Definition
| The pH is 7.3, so this is an acidemia. An acidemia could be explained by a high pCO2 or by a low HCO3-. In this case, the HCO3- is low, meaning this is a metabolic acidosis. The pCO2 is also low, so this is a Compensated metabolic acidosis |
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Term
| What Type of Acid Base Disorder Does This Patient Have? pH = 7.57, HCO3- = 42, pCO2 = 47 |
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Definition
| The pH is 7.57, so this is an Alkalemia. An alkalemia could be explained by a high HCO3- or a low pCO2. In this case the HCO3- is high, so this is a Metabolic alkalemia. The pCO2 is also high, so it is a Compensated Metabolic Alkalemia. |
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Term
| What Type of Acid Base Disorder Does This Patient Have? pH = 7.57, HCO3- = 18, pCO2 = 18 |
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Definition
| The pH is 7.57, so this is an Alkalemia. An Alkalemia could be explained by a high HCO3- or by a low pCO2. In this case the pCO2 is low, so this is a Respiratory alkalemia. The HCO3- is also low, so it is a Compensated respiratory alkalemia |
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Term
| Acute vs Chronic Appearance of Renal Disease on Ultrasound |
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Definition
CHRONIC: small, echogenic kidneys;
ACUTE: normal looking kidneys |
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Term
| Urine Output Classifications |
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Definition
Non-Oliguric: >500cc urine output/ 24 hrs;
Oliguric: <500cc urine output/ 24hrs;
Anuric: No urine output |
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Term
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Definition
| DEFINITION - decreased renal perfusion; CAUSES - Hypovolemia, Hypotension, CHF, Renal artery stenosis, Sepsis (you vasodilate, which shunts the blood away from the kidney and other organs); DIAGNOSIS - history/ chart review, Physical Exam (looking at the oral mucosa to see if it's moist or not and look for axillary sweat - both help determine if the patient is well-hydrated or not), Verify that there's been no nephrotoxic drugs (look in the patient's medication administration record), or IV contrast (look for radiologic studies, cardiac catheterizations, etc.) |
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Term
| Pre-Renal vs. Renal Oliguria |
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Definition
PRE-RENAL: oliguria with normal kidneys, Elevated BUN:Creatinine ration, Normal Urinary sodium, Normal urine osmolality, Normal Urinary creatinine: Plasma creatinine ratio, Normal FENa;
RENAL: oliguria with damaged kidneys, Normal BUN: Creatinine ratio, High Urinary sodium, Low urine osmolality, Low Urinary creatinine/ Plasma creatinine ratio, High FENa |
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Term
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Definition
| Usually about 10 in an average, healthy person; BUN represents nitrogen waste from the protein in your diet; Creatinine is related to muscle mass; Ratio is normal in Renal oliguria and elevated with Pre-renal oliguria |
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Term
| Urinary Sodium in the Oliguric Patient |
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Definition
| Normal is <10 in Oliguric patients; The kidneys should hold on to sodium and water if you're oliguric, so in patients with pre-renal oliguria the kidneys are normal and so is the level of Urinary sodium, In patients with renal oliguria, the kidneys are abnormal so the level of urinary sodium is too high (there is salt wasting because the kidneys can't reabsorb it) |
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Term
| Urine Osmolality in the Oliguric Patient |
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Definition
| Want Uosm to be concentrated (>500) in an oliguric patient; This is the case in patients with pre-renal olguria because their kidneys are functioning normally; In a patient with renal oliguria, however, the Uosm is about 300, which is too dilute (it's about the same as plasma osmolality, because the kidneys can't concentrate the urine) |
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Term
| Urinary Creatinine/ Plasma Creatinine Ratio |
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Definition
| If you're oliguric, you should be able to put a lot of creatinine into your urine; Patients with pre-renal oliguria are able to do this since their kidneys are normal, But patients with renal oliguria have abnormal kidneys and have a Ucreat/ Pcreat ratio that is too low |
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Term
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Definition
| If this is low (<1%), it means that you filtered a lot of sodium, and the rest (99%) got reabsorbed (ie only 1% got peed out), and this is what healthy kidneys should be able to do; Patients with pre-renal oliguria have a normal FENa of <1%, While those with renal oliguria have a FENa of >1%; FENa is calculated by the equation: FENa = (UNa/ PNa X100)/ (Ucreat/ Pcreat); Diuretics can mess up the FENa value because they make you pee out sodium |
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|
Term
| Complete vs Incomplete Obstructive Uropathy |
|
Definition
COMPLETE - The patient is anuric;
INCOMPLETE - the patient has some urine output (usually accompanied by overflow incontinence in which the patient pees a small amount of urine frequently) |
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Term
| Locations of Obstruction in Obstructive Uropathy |
|
Definition
| URETHRA - stricture (ex from gonorrhea), posterior urethral valves (pediatrics); BLADDER OUTLET - men with prostatic enlargement, Women with advanced cervical cancer; URETERS, URETEROVESICAL JUNCTION - stones, tumors |
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Term
|
Definition
| DIAGNOSIS - History ("I can't pee!"), Physical (smooth, symmetrical subrapubic mass which is the distended bladder), Labs (urine indices are not helpful, they're really only helpful in differentiating between pre-renal and renal problems, and obstructive uropathy is a post-renal issue), Imaging studies (Ultrasound is the best choice since it's cheap and non-invasive, but IVPs are also done sometimes) |
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Term
| Approach to Renal Disease |
|
Definition
| Rule out pre-renal azotemia and obstruction (post-renal issue), Then identify the site of the lesion within the kidney - glomerular, tubulointerstitial and/ or vascular |
|
|
Term
| What is the Basement Membrane Made of? |
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Definition
| It is a gel made up of type IV collagen |
|
|
Term
| What is the Mesangium Made Up Of? |
|
Definition
| Macrophage-like phagocytic cells, and actin/ myosin contractile proteins |
|
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Term
|
Definition
| Made of Tamm-Horsfall protein, a normal mucoprotein secreted by tubular cells; Tamm-Horsfall protein precipitates out in concentrated urine, forming a "hyaline cast" inside of the tubule (NOT pathologic); Cells (ex RBCs and WBCs) coming from the glomerulus or tubules can be suspended in the cast; The main importance is confirming the upper tract source of cells seen in the urinalysis - RBC casts can only have come from the glomerulus, while free RBC hematuria could have come from anywhere |
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Term
| Clinical Presentations of Glomerular Disease |
|
Definition
ASYMPTOMATIC - Some people have nephritic range proteinuria or hematuria, but don't present with edema or nephritic syndrome, Usually it is an incidental finding of proteinuria or blood on routine urinalysis; ACUTE NEPHRITIC SYNDROME - Hematuria/ RBC casts, Proteinuria, Oliguria, Volume Overload (HTN, CHF, Edema); NEPHROTIC SYNDROME - >3.5g protein/ day (normal is <150 mg/day), Hypoalbuminemia, Hypercholesterolemia (nobody really knows why - the current theory is that inhibitors of cholesterol synthesis get peed out, so the liver goes crazy making cholesterol), Edema;
Unfortunately the clinical presentation of glomerular disease doesn't tell you what the tissue diagnosis is, Most glomerular diseases can only be diagnosed by biopsy |
|
|
Term
| Sites of Glomerular Injury |
|
Definition
| Epithelium (podocytes), Basement Membrane, Endothelium, Mesangium |
|
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Term
|
Definition
| Minimal Change Disease, Focal Segmental Glomerulosclerosis (FSGS) |
|
|
Term
| Basement Membrane Diseases |
|
Definition
| Alport's Nephritis, Thin Basement Membrane Disease (TBMD); Involve an Inherited defect in type IV collagen that makes up the basement membrane (also affects the inner ear and cornea because they also have type IV collagen); Alport's Nephritis is X-linked and has abnormal type IV collagen; TBMD also has abnormal type IV collagen, but not the the extent of Alport's; Both present with hematuria, but Alport's eventuates in renal failure, and TBMD has a benign prognosis; TBMD accounts for 50% of patients with "benign microscopic hematuria" |
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Term
|
Definition
| AKA Thrombotic/ Microangiopathic Diseases; Hemolytic-Uremic Syndrome (HUS), Thrombotic Thrombocytopenia Purpura (TTP), Eclampsia (Toxemia of pregnancy), Anti-Phospholipid Antiobody Syndrome |
|
|
Term
| Minimal Change Disease (Friedenberg) |
|
Definition
| AKA Lipoid Nephrosis or Nil Disease; There is a Loss of negative charge on epithelial foot processes and the foot processes get squished together; Presents as nephrotic syndrome with a benign urine sediment; Most frequent cause of nephrotic syndrome in children; Responds to steroids 90% of the time; Occasionally associated with Hodgkin's Disease; Frequent Relapses; Poorly understood - don't really know what causes it; You see proteinuria despite the fact that the foot processes appear fused because in some places they are really squished together, but in other areas the foot processes are really thin or absent |
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Term
| Focal Segmental Glomerulosclerosis (FSGS) |
|
Definition
| Damage to and loss of podocytes; A common pattern of glomerular injury - damage, then healing with fibrosis/ sclerosis; CAUSES - idiopathic, persistent high intraglomerular pressures, Obesity/ Sleep apnea, Heroin nephropathy, HIV Nephropathy (viral particles in the podocytes), Hereditary, Unilateral Renal Agenesis (decreased nephron mass = higher pressures in the remaining nephrons, damaging those nephrons) |
|
|
Term
| What is the most Frequent Cause of Nephrotic Syndrome in Children? |
|
Definition
|
|
Term
| Immune Complexes and the Glomerulus |
|
Definition
| Circulating immune complexes can end up in different sites in the glomerulus based on their size and charge characteristics; The size of immune complexes is determined by the relative concentration of the antigen to the antibody: A large excess of either = small complexes, Equimolar concentrations = large complexes; Large immune complexes tend to be Subendothelial and mesangial because they can't get that far through the capillary wall; Smaller immune complexes tend to be subepithelial or intramembranous |
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|
Term
| Post-Streptococcal or Post-Infectious Glomerulonephritis (Friedenberg) |
|
Definition
| A generalized ACUTE inflammatory reaction; Immune complexes throughout the glomerulus; Caused by an immune response to bacterial or viral antigens; Prototype is "nephritogenic" strep; Occurs weeks after the infection; Treatment is supportive; Usually resolves with some residual fibrosis or scarring |
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Term
| Membranoproliferative Glomerulonephritis (Friedenberg) |
|
Definition
| A CHRONIC immune reaction; Can be idiopathic or due to low grade chronic antigenemia (ex Hep C, lupus, etc.); Involves a continuing cycle of inflammatory damage, then repair, which leads to a thick basement membrane; TRAM TRACK APPEARANCE - There's The original layer of basement membrane, then a layer of inflammatory cells, then another new layer of basement membrane |
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|
Term
| Immune Complexes in the Mesangium |
|
Definition
| Occurs in IgA Nephropathy - On light microscopy it looks like the mesangium is expanded and those are the areas that "light up" under immunofluorescence for IgA; IgA nephropathy was first described in the early 1960s by Berger (Berger's Disease) and he diagnosed it by immunofluorescence; Accounts for 50% of patients wtih "benign microscopic hematuria" (the other 50% is accounted for by Thin Basement Membrane Disease); Some patients with IgA nephropathy develop proteinuria, HTN and kidney failure |
|
|
Term
| Causes of "Benign Microscopic Hematuria" |
|
Definition
| Thin Basement Membrane Diseae (TMBD) - 50%, IgA Nephropathy - 50% |
|
|
Term
| Immune Complexes Within The Basement Membrane |
|
Definition
| Occurs in Membranous Glomerulopathy; Filtered CATIONIC antigens localize SUBEPITHELIALLY and can form in situ immune complexes as antibodies bind to it (ie these are not circulating immune complexes, they form right in the basement membrane); Presents with nephrotic syndrome, benign urinalysis; The antigen can be a drug, viral antigen, or tumor antigen, Usually it's an unknown antigen; Usually the disease is a long, indolent course to renal failure |
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|
Term
| Rapidly Progressive or Crescentic Glomerulonephritis (Friedenberg) |
|
Definition
| Any injury so severe that it causes rupture of the basement membrane; Usually kills kidneys within 6 months; Can occur with lupus or ANCA positive vasculitis; Can have immune complexes (~25%); Can have antibodies to the glomerular basement membrane (~25%, Goodpasture's Syndrome); Can be pauci-immune with no immune complexes (~50%) |
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|
Term
|
Definition
| A secondary glomerulopathy; Accounts for 25-33% of all dialysis patients in the USA; Occurs in 40% of type I diabetics, 20-30% of type II diabetics (probably an underestimate); 50% mortality by 3 years on dialysis (related to vascular diseae and sepsis); The first clinical signs begin after 15-20 years of diabetes: Supernormal GFR (creatinine would be low), Microalbuminuria (doesn't show up on a regular dipstick in early stages, so you have to order a microalbumin level specifically), Increasing proteinuria to nephrotic rage as the GFR is dropping to normal and below, Rising creatinine to end-stage renal disease; PATHOGENESIS - role of glycemic control - tight control may help prevent diabetic nephropathy, but once nephropathy is established it doesn't seem to help; Glycosylation of the basement membrane proteins (just like glycosylation of Hg that allows you to measure HbA1C), Thickening of basement membranes, Glomerular hemodynamics (high intraglomerular pressures cause damage); DIAGNOSIS - microalbuminuria (PCP should screen diabetics annually), presence of proliferative retinopathy, Duration of diabetes, Normal-sized to large kidneys on ultrasound (normally with chronic disease the kidneys shrink, but in diabetics the insulin-like growth factor keeps them a normal size or even large), Nephrotic range proteinuria, Varying degrees of azotemia (depending on the phase of the disease), Biopsy (nodular glomerulosclerosis/ Kimmelstiel-Wilson disease); TREATMENT - try to prevent it in the first place with tight glycemic control, Aggressive BP control (125/75 or as low as the patient will tolerate), ACE Inhibitors and Angitensin II receptor blockers, Spironolactone (block the RAAS - aldosterone especially because it is profibrotic), Low protien diet (controversial) |
|
|
Term
|
Definition
| Circulating "junk" gets caught in the glomeruli and gloms them up; Amyloidosis, Fibrillary glomerulonephritis, Immunoglobulin light or heavy chains |
|
|
Term
| Acute Tubular Necrosis (Friedenberg) |
|
Definition
| Damage to cells of the proximal tubule; Can involve cells of the thick ascending limb of Henle's loop; Can be due to an Ischemic insult to the kidney: Hypovolemia, Hypotension, Anoxia, Sepsis, Iodinated IV contrast (causes diuresis - vasodilation to the kidney initially, followed by vasoconstriction a few hours later. The vasoconstriction and the volume depletion from the diuresis causes ATN); Can be due to a Toxic insult to the kidney: Drugs (aminoglycosides like gentamycin and tobramycin, Cisplatinum, Iodinated IV contrast), Heavy metals (uranium), Organic solvents (toluene, carbon tetrachloride), Pigments; Can be caused by hemoglobin (due to hemolysis) and myoglobin ("crush injury," myoglobin released from damaged muscle. Intravascular volume depletion as fluid "3rd spaces" into damaged muscles. Urine is now concentrated. The kidneys suffer an ischemic insult due to intravascular volume loss and a toxic insult as concentrated urinary myoglobin poisons tubular cells, resulting in ATN); DIAGNOSIS - clinical setting, urine sediment ("muddy brown casts"), urinary indices; Non-oliguric ATN has a better prognosis than oliguric ATN; Use of a loop diuretic or osmotic diuretic in early ATN to convert from oliguric to non-oliguric state seems like it might work, but you're probably not discovering the ATN until the patient is already oliguric |
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|
Term
|
Definition
| Afferent Arteriole Constriction (decreases glomerular pressure; one cause of constriction is tubuloglomerular feedback); Diminished permeability (has a small effect); Tubular obstruction; Backleak of filtrate (free reabsorption of filtrate) |
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|
Term
|
Definition
| Usually lasts an average of 2-4 weeks, then enters a diuretic recovery phase; The longer oliguria persists, the less likely recovery is (start getting nervous after 6-8 weeks); TREATMENT - restrict fluid, potassium and magnesium, Nutritional support, Follow patient's electrolytes, BUN, Creatinine, Volume Status and urine output, Dialysis may be necessary but not always; PREVENTION - Keep patients well hydrated, especially before an IV contrast study, Administer acetylcysteine (a sulfhydryl/ reducing agent that increases glutathione stores) as prophylaxis against the toxic effects of IV contrast (which can create free-radicals) in high risk patients; HIGH RISK PATIENTS - those with a creatinine >1.5, Diabetes, Myeloma, Hepatic or Biliary tract disease; Follow peak and trough aminoglycoside levels (mainly for the lawyers), but the toxicity is mainly a function of the Cumulative Dose (this is really what makes a difference, the peak and trough levels don't really matter); PROGNOSIS - hasn't changed in 50 years, Mortality is 15% in obstetric patients, 30% in medical patients, and 60% in surgical patients |
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|
Term
|
Definition
| Precipitation of substances in the renal tubules, causing acute renal failure by obstruction; EXAMPLES - uric acid (ex following tumor lysis by chemo - can prevent this by prophylaxing with allopurinol), Sulfonamides, Acyclovir (especially in patients with herpes encephalitis because you need such high doses), Methotrexate, Myeloma proteins (they make heavy and light chains, and those can form casts), Phospho soda (colonoscopy prep, You absorb the phosphates and you poop so much that you're volume depleted and then the phosphates precipitate out) |
|
|
Term
|
Definition
| An inflammatory process primarily involving the interstitium; Can be acute or chronic; Can be caused by drug/ toxin exposure or infection |
|
|
Term
| Acute Drug-Induced Interstitial Nephritis (Friedenberg) |
|
Definition
| AKA Allergic Interstitial Nephritis; Typical offending agents - Sulfonamides, penicillins, diuretics (they have a sulfur group on them), Allopurinol, and NSAIDs; Acute onset; CLASSIC PRESENTATION - fever, rash, eosinophilia, renal failure; URINE SEDIMENT - pyuria (ie WBCs in the cast) - you see WBCs and you think infection, but in this case the cultures come back negative, WBC casts, Eosinophiluria (use Hansel's stain to see it); TREATMENT - Discontinue the offending agent, Steroids (knock out the inflammation and you're less likely to get scarring) |
|
|
Term
| Acute Bacterial Interstitial Nehpritis |
|
Definition
| AKA Acute pyelonephritis; Bacterial UTI that involves the renal pelvis, papillae, and surrounding interstitium; TREATMENT - antibiotics |
|
|
Term
| Chronic Interstitial Nephritis |
|
Definition
| ETIOLOGY - Auto-immune diseases, Analgesic abuse (analgesic nephropathy), Long-term lithium use, Lead, cadmim, other heavy metals, Cyclosporine, Chronic infection (chronic pyelonephritis); DIAGNOSIS - mainly by history, urine sediment is benign because renal inflammation is very low grade, May see a few WBCs, Sub-nephrotic proteinuria, Atrophic echogenic kidneys on ultrasound, Renal biopsy is rarely necessary; CLINICAL COURSE - slowly progressive renal failure; TREATMENT - identify and discontinue the offending agent |
|
|
Term
| Polycystic Kidney Disease (PKD) |
|
Definition
| Autosomal Dominant Inheritance (pediatric patients can have an autosomal recessive form); Several types, each of which is a different mutation of the gene for the protein called polycystin (a signalling protein in the cell wall which regulates/ controls cell growth); Gene is located on chromosome 16 (or, less commonly, on chromosome 4); Molecular diagnostic testing is starting to become available (very expensive, not covered by insurance); CLINICAL PRESENTATION - very large, palpable kidneys loaded with cyts of varying sizes and originating from different tubular segments, Cysts in other organs (liver, pancreas, ovaries), Flank pain (caused by: pressure from a cyst into adjacent structures, bleeding into a cyst - usually accompanied by gross hematuria, rupture of a cyst, infection of a cyst), HTN (almost all patients with PKD have HTN); Associated wtih intracranial berry aneurysms (which can rupture) and colonic diverticuli; Slow progression to end-stage renal disease (ESRD); Age at reaching ESRD is fairly constant within a give family; ADH stimulates cyst growth; DIAGNOSIS - Family History, Any renal imaging study (IVP, US, CT); TREATMENT - Treat HTN (CCBs work best), Treat UTIs, Drink lots of water to suppress ADH; Cyst Aspiration and a low protein diet do NOT work |
|
|
Term
| Vascular Disease of the Kidney |
|
Definition
| Based on What's Blocked Up; LARGE VESSELS - Renal Artery (atherosclerotic plaque, embolus, fibromuscular dysplasia), Renal Vein (thrombus); SMALL VESSELS - Atherosclerotic occlusion of the small vessels of the kidney (AKA Nephrosclerosis, Hypertensive nephrosclerosis, Arteriolonephrosclerosis); MICROEMBOLIC DISEASE - microscopic cholesterol atheroemboli shower off the wall of the aorta and occlude the microvessels of the kidney, often hitting the intestine causing ischemic bowel and the feet causing blue toe syndrome |
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|
Term
|
Definition
| If you're born with a decreased number of nephrons, you may be predisposed to developing renal failure on a hemodynamic basis; With loss of nephron mass, the afferent arteriole vasodilates (mediated by PGE2 and PGI2) and the efferent arteriole vasoconstricts (mediated by angiotensin II) in order to increase the SNGFR in the remaining nephrons, but it results in high intraglomerular pressures, which ultimately destroy the glomeruli; ACE Inhibitors allow for increased SNGFR, but normal net filtration pressures, by increasing the surface area of the glomerular capillary available for filtration. It does this by relaxing the actin/ myosin fibrils in the mesangium |
|
|
Term
| Things That Lower Intraglomerular Pressure |
|
Definition
| Lower systemic pressure; Use of ACE Inhibitors or Angiotensin Receptor Blockers (block angiotensin II-mediated vasoconstriction of the efferent arteriole and also relaxes the mesangium which increases the glomerular capillary surface area); Dietary protein restriction (most people with Chronic renal failure are "turned off" by protein anyway) |
|
|
Term
|
Definition
| The increment in GFR after being given a protein meal; The renal reserve represents recruitment of cortical nephrons; With kidney disease/ damage, we lose a substantial amount of our renal reserve before we see a rise in serum creatinine; There is less renal reserve in patients with chronic renal failure |
|
|
Term
| Renal Effects of Dietary Protein |
|
Definition
| A protein meal increases GFR by causing renal vasodilatation, sending blood to the cortical as well as the juxtamedullary nephrons; In patients with chronic renal failure, who have less nephrons to recruit, the renal vasodilatation from a protein mean causes increased intra-glomerular pressures in the remaining nephrons (instead of the increased bloodflow recruiting more nephrons, it just increases the pressure in the nephrons that are already working) |
|
|
Term
| Current Thinking About Dietary Protein Restriction in Patients with Chronic Renal Failure (CRF) |
|
Definition
| The worse your kidney funciton is, the more protein restriction seems to help slow disease progression; It doesn't seem to help patients with polycystic kidney disease; Protein restriction is difficult for patients to do, and they should see a dietician if they're going to do it; Can result in patients starting dialysis with established malnutrition |
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|
Term
| Hormones Which Dispose of Potassium Extra-Renally |
|
Definition
| Aldosterone - via the colon and sweat glands; Insulin - pushes potassium into cells by glucose-linked transport; Beta-2 Agonists - pushes potassium into cells |
|
|
Term
| Hyperkalemia and Renal Failure |
|
Definition
| Hyperkalemia can be a big problem with Acute renal failure because the body has no time for an adaptive response; Not usually a problem in chronic renal failure because patients are able to adapt over time by increasing aldosterone-mediated secretion of potassium in the sweat glands and the colon; Can become a problem with ACE inhibitors |
|
|
Term
| Strategies to Manage Chronic Hyperkalemia |
|
Definition
| Increase distal sodium delivery (because it makes the lumen more negative, and this draws potassium out of the renal tubule cell); Give non-resorable anion (soidum bicarb, works by the same mechanism as increasing distal sodium delivery); Increase urine flow rate (diuretics, Give them more volume and potassium gets washed out of the lumen and the potassium in the cells goes out into the lumen); Give aldosterone (Fluorinef, increases the number of sodium/potassium ATPases on the cell membrane facing the blood so that potassium goes out of the blood and into the cell and then can go out of the cell into the lumen and get peed out); Kayexalate (a resin that has sodium as a part of it - potassium goes into the molecule in the place of the sodium and then gets pooped out) |
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|
Term
| Chronic Renal Failure (CRF) and Bone Metabolism |
|
Definition
| CRF can involve both acidosis and PTH release which combine to cause calcium to come out of bones; High serum calcium can result in: arterial calcification, calcification of heart valves and soft tissues, Pruritis (itching), and conjunctivitis (calcium-phosphate crystals accumulate in the conjunctiva and irritate the eye) |
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|
Term
| Treatment of Uremic Bone Disease |
|
Definition
| Low Phosphate diet; Phosphate binders with meals - Calcium carbonate (tums), Calcium acetate (phoslo), Sevelamer (renagel, renvela), Lanthanum carbonate (Fosrenol); Get serum calcium to a normal range; Monitor PTH levels, if elevated give a vitamin D analog (calcintriol, zemplar, hectorol) or a calcimimetic (cinacalcet); Correct acidosis with alkali therapy |
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|
Term
| Main Causes of Anemia in Chronic Renal Failure (CRF) |
|
Definition
| Decreased EPO production (recall that EPO is produced in the proximal tubule cells); Resistance to EPO action in the uremic state; Decreased RBC survival time (life-span is about half of what it normally is) |
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|
Term
| Treatment of Anemia in Chronic Renal Failure |
|
Definition
| Recombinant EPO (epogen, procrit, aranesp); Iron supplementation; Adequate B12 and folate; RBC transfusion when necessary; Treat infections/ inflammatory conditions (because it makes EPO not work) |
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|
Term
| Vascular Disease and Chronic Renal Failure (CRF) |
|
Definition
| Vascular disease and sepsis are the leading causes of death (by far) in patients with CRF or end-stage renal disease (ESRD). Be aggressive in treating Hyperlipidemia, Hyperhomocysteinemia and HTN in patients with CRF and ESRD, and get them to Stop Smoking! |
|
|
Term
| Vascular Disease and Chronic Renal Failure (CRF) |
|
Definition
| Vascular disease and sepsis are the leading causes of death (by far) in patients with CRF or end-stage renal disease (ESRD). Be aggressive in treating Hyperlipidemia, Hyperhomocysteinemia and HTN in patients with CRF and ESRD, and get them to Stop Smoking! |
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|
Term
| Drug Dosing in Patients with Chronic Renal Failure (CRF) |
|
Definition
| Hepatic Excretion - little or no change in dosage; Highly protein bound - small dosage adjustment; Avoid NSAIDs (they decrease prostoglandin-mediated vasodilatation of the afferent arteriole, so it's vasoconstricted and you get decreased blood flow thorugh the glomeruli); After starting an ACE Inhibitor or ARB, check potassium and creatinine to be sure they're not going up; Don't forget renally excreted active metabolites (ex procainamide); Use creatinine clearance rather than serum creatinine to make dosage adjustments; When in doubt, look up dosages in the PDR |
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|
Term
| When Do You Start Dialysis? |
|
Definition
| It's a judgement call; Start at the earliest signs of Uremic Syndrome - GI sxs (nausea, vomiting, dry heaves, anorexia) which lead to decreasing serum albumin, Refractory CHF, Malaise and fatigue which interfere with the patient's lifestyle; Start based on symptoms, not lab values (unless the patient is lying and saying that they're not having sxs, when their lab values clearly indicate that they must be) |
|
|
Term
| Epidemiology of Renal Cell Carcinoma (Hirschhorn) |
|
Definition
| New Cases - 36,000/yr; Deaths - 10-12,000/yr; M:F ratio = 3:2; Age = 50-70yrs |
|
|
Term
| General Info about Renal Cell Carcinoma |
|
Definition
| It's an adenocarcinoma; Involves the proximal convoluted tubule; Associated with a mutation in the VHL gene (3p25) |
|
|
Term
| Risk Factors for Renal Cell Cancer (Hirschhorn) |
|
Definition
Environment - Tobacco, Analgesic abuse (Phenacetin), Cadmium, Leather Tanning;
Acquired Cystic Disease (hemodialysis);
Von Hippel Lindau;
Tuberous Sclerosis |
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|
Term
Presentation of Renal Cell Carcinoma Environment
Tobacco
Analgesic abuse (Phenacetin)
Cadmium
Leather Tanning
Acquired Cystic Disease (hemodialysis)
Von Hippel Lindau
Tuberous Sclerosis |
|
Definition
| Incidental finding (70%); “Classic Triad” (10-15%) - Flank pain, mass, hematuria; Paraneoplastic Syndrome (Hypercalcemia); Hypertension (40%); Stauffer’s Syndrome - Non-neoplastic hepatic dysfunction |
|
|
Term
| Metastatic Disease with Renal Cell Carcinoma (Hirschhorn) |
|
Definition
| Local Extension into Gerota’s Fat, the Adrenals, Renal Vein, IVC; Lung; Bone |
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|
Term
|
Definition
| A constellation of signs and symptoms of liver dysfunction that arise due to presence of renal cell carcinoma but are not due to tumour inflitration into the liver and/or intrinsic liver disease; it is a paraneoplastic syndrome. (NOTE - this info was from wikipedia) |
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|
Term
| What is Renal Cell Carcinoma Best Treated By? |
|
Definition
| Surgery; Small tumors can be followed with observation; Surgery could be laproscopic or open, could be partial or radical nephrectomy; Cryotherapy can be used to freeze tumors |
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|
Term
|
Definition
| Transitional Cell Cancer (85%), Squamous Cell Cancer (15%), Rarely - adenocarcinoma, small cell carcinoma, metastatic deposits |
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|
Term
| Microscopic Hematuria is What Until Proven Otherwise? |
|
Definition
| A uroepithelial carcinoma |
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|
Term
| Treatment of Bladder Cancer |
|
Definition
| OBSERVATION - Cystoscopy and Cytology/FISH every 3 months; If 1st surveillance cysto (+), then risk of additional recurrences is approximately 80%; INTRAVESICAL AGENTS - Mitomycin C (chemo therapy), Bacillus Calmette Guerin (BCG, tumorcidal via T-cell mediated killing, Used the most out of all 3 of the treatments listed on this slide), Interferon alpha 2b (Intron A, Enhances T, B & NK-cell response, Enhances efficacy of BCG); RADICAL CYSTECTOMY - Males (Removal of - Bladder, Prostate (45 – 60 % incidental CaP), ? Urethra), Females (Removal of - Bladder, Uterus, tubes, ovaries, ? Urethra); CHEMOTHERAPY - Cis-Platinum (MVAC), Carboplatinum, Gemcitabine, Taxol, Generally agreed that postop MVAC will prolong progression free survival in T3 disease. Increase in survival benefit in T4 and N+ disease is controversial |
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|
Term
| Staging & Treatment of Bladder Cancer |
|
Definition
TA - Mucosal (superficial), observation or intravesical therapy; T1 - lamina propria (superficially invasive), intravesical therapy or cystectomy; T2 - Muscle invasive, Cystectomy, TURBT/ Radiation/ Chemo;
SURVIVAL RATES - T2 (65%), T3 (30%), + Nodes (20%) |
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|
Term
| Risk Factors for Bladder Cancer |
|
Definition
| TOBACCO; Petroleum; Benzene; Dry Cleaners, textile workers; Cyclophosphamide (Cytoxan) - acrolein |
|
|
Term
| Types of Testicular Cancer |
|
Definition
Germ Cell Neoplasia (95%);
Gonadal Stromal Neoplasia (5%) |
|
|
Term
| Epidemiology of Testicular Cancer |
|
Definition
| Relatively rare (1% of Ca in Males); Most common Neoplasm in young adult men; Overall Prevalence: 2-3/100,000; Prevalence (ages15-34): 62/100,000; Highest in Scandanavians; Rare in African Americans |
|
|
Term
| Risk Factors for Testicular Cancer |
|
Definition
| Cryptorchidism (undescended testicle); Contralateral Tumor; Testicular Intraepithelial Neoplasia (TIN/CIS); Testicular Microlithiasis; 70% concordance in monozygotic twins |
|
|
Term
| Histology of Testicular Cancer |
|
Definition
| 95% of tumors are Germ Cell; Tumors often comprised of mixed cell lines (40% Mixed, 60% Pure); Seminoma 60% of tumors; Nonseminoma (NSGCT) 65% of tumors – Embryonal, Teratoma, Choriocarcinoma, Yolk Sac Carcinoma |
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|
Term
| Presentation of Testicular Cancer |
|
Definition
| Painless lump on the testis; Often noticed incidental to mild trauma or by sexual partner; “Heaviness” – up to 65%; Up to 9 month delay in seeking medical attention; Systemic Symptoms (15%) - Weight loss, fatigue, abdominal/back pain raise concern for metastatic disease; Lymphadenopathy – testicular cancer usually metastasizes via lymphatics – first to retroperitoneum, then mediastinal, then cervical…if it goes very late, then it can end up in the groin; Lymph node removal isn’t just diagnostic, it’s also curative; Inguinal nodes are palpable only with diffuse metastatic disease (rare, unless prior testicular surgery) |
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|
Term
| Lymphatic Drainage of the Testes |
|
Definition
| Spermatic Cord; Retroperitoneal Lymph Nodes - Right Testis (tend to cross midline, Interaortocaval, Precaval, Preaortic), Left Testis (Para-aortic, Preaortic) |
|
|
Term
| Lab Studies for Testicular Cancer |
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Definition
| Tumor Markers - Alphafetoprotein (AFP), Beta – Human Chorionic Gonadotropin (b-HCG), Lactate Dehydrogenase (LDH), Placental Alkaline Phosphatase (PLAP); Ultrasound (hypoechoic lesion); Chest Xray; Abdominal/Pelvic CT scan – for staging; Do it before surgery because the gonadal artery can bleed during surgery and obscure the retroperitoneum so that you can’t see the lymph nodes, and it takes 3-6 months to resolve |
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Term
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Definition
| A Tumor Marker for Testicular Cancer; T ½ = 5-7 days ( Normal <5); Oncofetal Protein made by Yolk Sac Elements; Not produced by pure Seminoma or Choriocarcinoma; Elevated in upper GI tumors – Hepatoma, Hepatic Ca, Gastric Ca, Panreatic Ca |
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Term
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Definition
| T ½ = 24-36 hours (Normal<2); Heterodimeric Protein; Syncitiotrophoblast – Choriocarcinoma (100%), Embryonal Cell (60%), Seminoma (10%); False Positive Elevation – Marijuana, and the alpha subunit of LH, FSH, TSH |
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Term
| What Does Persistent Elevation of Tumor Markers After an Orchiectomy Suggest? |
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Definition
| Metastatic disease secondary to testicular cancer |
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Term
| Why is a Trans-Scrotal Biopsy Contraindicated? |
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Definition
| The testicle drains to the peritoneum, while the scrotum drains to the groin – so if you do a trans-scrotal needle biopsy, you just changed the place that the testicle drains to and you might never make the diagnosis |
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Term
| Staging of the Primary Tumor in Testicular Cancer (Based on Where the Tumor is in the Testicle) |
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Definition
| T1 - Testis,Epididymis,Tunica Albuginea (without lymphovascular invasion); T2 - T1 with lymphovascular invasion or Tunica Vaginalis; T3 - Spermatic Cord; T4 - Scrotum (very rare) |
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Term
| Systemic Staging of Testicular Cancer (Is the Tumor Anywhere Outside of the Testicle?) |
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Definition
| I - Negative CT and Markers; II - Low Volume Adenopathy (N1-N2); III - Bulky Adenopathy and Mets |
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Term
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Definition
| STAGE I - Observation or Radiation (RT); STAGE II - RT; STAGE III -Chemo (cisplatinum); In all stages – remove the testicle |
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Term
| Treatment of NSGCT (Non-Seminoma Germ Cell Tumor) |
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Definition
| STAGE I - Observation, Chemo (short cycle) or Retroperitoneal Lymph Node Dissection (RPLND), STAGE II –RPLND; STAGE III - Chemotherapy (full cycle); NO Radiation – it doesn’t work! |
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Term
| Prognosis of Testicular Cancer |
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Definition
| 90-95% Cure; Cure of Relapse - Minimal 90-98%, Moderate 85-90%, Advanced 60-85% |
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Term
| Incidence of Prostate Cancer |
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Definition
| 1986 - White Men 86/100,000, African American Men 124/100,00; 1993 - White Men 179/100,000, African American Men 250/100,000; Apparent increase in incidence wasn’t actually due to an increase in the ## of cases, but to advances in detection – 1989 saw the beginnings of PSA screening, and around the same time, ultrasound began to be used more |
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Term
| Risk Factors for Prostate Cancer |
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Definition
| Age; Family History - Risk depends upon the age at which a relative was diagnosed and the number of affected relatives:Father @ 70 – Son Relative Risk (RR) = 1.0, Father @ 50 – Son RR=2.0, Father @50 and Uncle has CaP – Son RR=7.0; Genetics - Isolation of specific genes has proven challenging, Possible increased risk with BRCA1 & BRCA2 (BRCA1+ confers 1.8 RR, BRCA2+ confers 4.7 RR); Race/ Ethnicity - Asian - Lowest Incidence/Mortality, Scandinavian - Highest Incidence/Mortality, African American - Higher incidence/mortality at all ages (than white American), Higher stage of disease at diagnosis, Lower survival rates; Dietary (Protective Factors) - Low fat, Lycopenes (cooked tomatoes, watermelon, guava), Flaxseed, Soy (Vitamin E and Selenium do NOT prevent prostate Cancer) |
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Term
| How Can Men Decrease Their Risk of Prostate Cancer? |
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Definition
| Daily Vitamin (may decrease rate x 25%), 5 servings of fruits and veggies/day, Lycopene, flaxseed, Selenium, soy, Low saturated fat, Exercise, Finasteride (Proscar); All of these may decrease rate of cancer by 25%???? |
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Term
| Prostate Specific Antigen(PSA) |
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Definition
| The most clinically useful tumor marker for early detection and staging of CaP; 237aa serine protease; Secreted by prostatic epithelium; Seminal anticoagulant; t ½ = 4 days; Serum PSA levels are determined by the amount of PSA that “leaks” out of the prostate |
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Term
| Conditions That Can Give You a False Positive PSA Level |
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Definition
| Prostate Cancer, BPH, Infection (ex prostatitis), Urinary Retention, Sexual activity (within 48 hours prior to the PSA level being drawn); IMPORTANT NOTES !! - Acute prostatitis can result in both a significant rise in PSA and an abnormal DRE.If either PSA or DRE remain abnormal after a proper course of antibiotics, the patient should undergo Trans-rectal Ultrasound (TRUS)/Biopsy; If your patient’s PSA remains normal, but it is progressively rising (PSAvelocity) abnormally, he should undergo TRUS/Bx; If your patient’s PSA remains normal, but his DRE is abnormal, he should undergo TRUS/Bx |
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Term
| What is a "Normal" PSA Level? |
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Definition
| Standard 0-4.0 ng/ml; Age Specific PSA - 40’s- 2.5, 50’s-3.5, 60’s-4.5, 70+-6.5; PSA Velocity (>0.35 ng/ml/yr); % Free PSA (the more free PSA there is, the greater chance that the elevated PSA indicates something benign; Bound PSA is Bad) - use after negative biopsy (not for screening purposes) - >25% = < 10% Cancer risk, <10% = >40% Cancer risk; PSA Doubling Time (3 months or less – metastatic disease; 2 Years or more – local recurrence/ single site) |
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Term
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Definition
| Change in PSA over time; 3 readings over 12-24 months; NCCN Guidelines: Biopsy patients with a PSA velocity of >0.35 ng/ml/yr; >0.35 ng/ml/yr 10-15 years prior to dx confers increased mortality 25 yrs; >2.0 ng/ml/yr within 1 yr prior to dx - Shorter time to death after Surgery or Radiation |
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Term
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Definition
| WHAT - Yearly digital rectal exam (DRE) and PSA level; WHO - Men < 75 yrs with a > 10yr life expectancy, Men > 50 yrs, Men > 45yrs who are at high risk for Prostate cancer (ie Prostate cancer in a 1st degree relative, or the patient is African American) |
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Term
| Indications for a Prostate Biopsy |
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Definition
| Elevated PSA; Abnormal digital rectal exam (DRE); Abnormal PSA Velocity |
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Term
| Histologic Grading of Prostate Cancer |
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Definition
| Gleason’s Grade (1 – 5); Gleason’s Score = most common pattern + 2nd most common pattern: 2+3 = 5/10 – low grade, 3+3 = 6/10 – low grade, 3+4 = 7/10 – intermittent grade, 4+3 = 7/10 (total score is the same as a 3+4, but a 4+3 is more serious; Intermittent grade) |
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Term
| Treatment Options for Prostate Cancer |
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Definition
| Observation; Active Surveillance; Hormonal Deprivation – ex: overdrive suppress LH production (Lupron) or Removal of the testes; Radiation - External Beam or Brachytherapy (Seed Implant); Surgery |
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Term
| Prostate Cancer (General Summary) |
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Definition
| Most common male cancer USA (25%); 2nd most common cause of male cancer death USA (Prostate Cancer 10%; Lung 31% in 2008); Screening permits early diagnosis - Early diagnosis doesn’t necessarily decrease mortality though; Multiple treatments available for localized disease; Prognosis is variable (depends on PSA, pTNM, Grade) |
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Term
| Renal Sequelae of Obstruction |
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Definition
| Hypertrophy of renal pelvis smooth muscle; Decreased GFR (to “accommodate” obstruction); Dilatation; Parenchymal damage, atrophy (Complete Obstruction can lead to Irreversible damage in 6 weeks, Partial Obstruction can lead to Dilatation with variable renal insult) |
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Term
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Definition
| KUB (Kidney Ureter Bladder) – shows stones; Ultrasound - hydronephrosis, large mass; IVP (Intravenous Pyelogram) - dynamic and functional study, shows obstruction; CT Scan - w/ contrast shows mass or obstruction, w/o contrast shows stones or hydronephrosis; MRI |
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Term
| Ureteropelvic Junction (UPJ) Obstruction |
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Definition
| Congenital (kids) or acquired (adults) narrowing of the ureter joining the renal pelvis and proximal ureter; This creates resistance to urinary flow across this region and results in dilation of the intrarenal collecting system; Intervene if: stone in pelvis, recurrent infection, pain, or dilating renal pelvis |
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Term
| Etiology of Ureteropelvic Junction (UPJ) Obstruction |
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Definition
| Disordered collagen bundles that prevent normal propagation of peristalsis – often Associated with an anomalous lower pole crossing vessel (? cause & effect); Extrinsic compression from renal or retroperitoneal mass (e.g., renal cyst) |
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Term
| Presentation of a Ureteropelvic Junction (UPJ) Obstruction |
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Definition
| Infant – prenatal ultrasound, congenital; Young Adult – acute onset of flank pain, nausea, vomiting during a major diuresis, congenital; Mature Adult – same sxs as young adult, acquired |
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Term
| Diagnosis of Ureteropelvic Junction (UPJ) Obstruction |
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Definition
| Ultrasound - Hydronephrosis, thinning of renal cortex; IVP - Dilated intrarenal collecting system, delayed excretion of contrast with normal ureter; Nuclear Renogram / Lasix Washout - Accumulation of radioactivity within renal pelvis with delayed washout after Lasix administration |
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Term
| Treatment of Ureteropelvic Junction (UPJ) Obstruction |
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Definition
| Dismembered Pyeloplasty - Open (flank incision) or Laparoscopic – done more than the open version now; Endopyelotomy - Antegrade (via percutaneous access) or Retrograde (via ureter); Both the dismembered pyeloplasty and the endopyelotomy open up the obstructed area and then put in a stent |
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Term
| Presentation of Ureteral Stones |
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Definition
| Acute onset flank pain; Waves of increasing intensity (Colic); No comfortable position; Radiation to abdomen, groin, scrotum/labia; Nausea/Vomiting; Patients look pale/green/diaphoretic |
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Term
| Spontaneous Passage Rates of Ureteral Stones Based on the Size of the Stone |
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Definition
| 1-4 mm – >90%; 5-6 mm – 50-60%; >= 7 mm - <10% |
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Term
| Extrinsic Ureteral Compression |
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Definition
| DUE TO: Retroperitoneal Inflammation - Retroperitoneal Fibrosis, Lymphadenopathy, Neoplasm, Diverticulitis; Pelvic Malignancy - Ovarian, Uterine, Bladder, Prostate |
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Term
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Definition
| In the Risk Group of Men over the age of 50 = 29 million; Clinical BPH = 7 million (30% treated, 70% untreated); Histologic BPH predates symptoms by approximately 20 years |
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Term
| Types of Obstruction Seen with BPH |
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Definition
| DYNAMIC OBSTRUCTION: Alpha-adrenergic receptor rich smooth muscle (bladder neck and prostatic capsule/stroma); STATIC OBSTRUCTION: Bulky prostatic lobar enlargement |
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Term
| Symptoms of Prostatism (BPH) |
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Definition
OBSTRUCTIVE – Hesitancy, Straining, Slow Stream, Intermittent Stream, Double Voiding, Prolonged Micturition;
IRRITATIVE – Frequency, Urgency, Urgent Incontinence, Nocturia;
Irritative sxs occur because as the bladder fights against the obstruction from the prostate it hypertrophies, and as a result it isn’t as compliant and can’t hold as much urine as before, so you pee more often, etc. |
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Term
| What is the Most Common Cause of Bilateral Hydronephrosis? |
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Definition
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Term
| International Prostate Symptom Score (IPSS or I PiSS) |
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Definition
| A Patient administered questionnaire regarding symptoms of Prostatism; 7 symptom questions, 1 quality of life question; Valid for evaluating symptoms in a given patient over time (can’t be used to compare between patients) |
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Term
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Definition
| ALPHA-1 BLOCKERS – these drugs relax the tight prostate, Takes about 1 week to work; Includes - Flomax (Tamsulosin) - 0.4 mg qd pc, Uroxatrol (Alfuzosin), Cardura (Doxazosin) - 1-8 mg qhs, Hytrin (Terazosin) - 1-10 mg qhs; 5-ALPHA REDUCTASE INHIBITORS – block the transformation of testosterone to 5-DHT which causes prostate enlargement; These drugs reverse the disease process; Take a while to work; Includes - Proscar (Finasteride) - 5 mg qd, and Avodart (Dutasteride) - 0.5 mg qd |
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Term
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Definition
| Cause Relaxation of smooth muscle tone; Side Effects - Orthostatic Hypotension, Non-hypotensive dizziness and fatigue; Effective anti-hypertensive agent |
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Term
| 5-Alpha Reductase Inhibitors for BPH |
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Definition
| Sustained reduction in prostate volume; Reduction in PSA (50% at 6 months); Reduction in risk of acute retention and BPH-related surgery; Clinical benefits of 5ARI are seen only in men with LARGE glands (lemon-sized or greater); NOTE - If your patient is on Proscar/Avodart, you need to double his PSA result when evaluating his risk of Prosate Cancer; Pregnant women should NOT handle Proscar/ Avodart because it can cause genital ambiguity in the fetus; Patients on these drugs also can’t donate blood |
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Term
| Surgical Treatments for BPH |
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Definition
| TURP- Gold Standard – shave it; TUIP – cut it; TUNA – heat it with Radio Frequency; TUMT – nuke it with microwaves; TUVP – vaporize (bipolar); PVP – vaporize (Greenlight Laser); HoLRP – enucleate (Holmium Laser); Open Prostatectomy |
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