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Basic Examination of Urine Physical Examination Chemical Examination Microscopic Examination 尿常规 Blood 潜血 Bilirubin 胆红素 Urobilinogen 尿胆原 Ketones 酮体 Protein 蛋白质 Nitrite 亚硝酸盐 Glucose 葡萄糖 PH PH值 Specific Gravity 比重 Leucocytes 白细胞 Ascorbic Acid 抗坏血酸 BLD BIL URO KET PRO NIT GLU PH S.G LEU VTC Case I Urine sample obtained during normal voiding from a 7-year-old spayed yellow Labrador Retriever. Color Protein Turbidity – RBC Specific gravity WBCpH Casts Glucose – Epithelial cells – Acetone – Bacteria – Bilirubin – Crystals – Occult blood - light yellow 4+ clear 1 - 2 /hpf 1.025 0 - 1 /hpf 6.0 occasional hyaline/lpf. negative occasional negative none negative none negative The best interpretation of the results of this urinalysis is that the patient: a. Is normal. b. Has generalized glomerular disease. c. Has an inflammatory process somewhere along the urinary tract. d. Has generalized tubular disease. e. Has findings indicative of congestive heart failure or fever. Case II A voided urine sample obtained from a 5-year-old neutered male Persian cat: Color – yellow Protein -trace Turbidity - clear RBC - 1 - 3 / hpf Specific gravity - 1.045 WBC- 0 - 1/ hpf pH - 7.0 Casts - none Glucose - negative Epithelial cells - occasional Acetone - negative Bacteria - none Bilirubin - 1+ Crystals - few amorphous phosphates Occult blood - negative The best interpretation of the results of this urinalysis is that this feline patient: a. Has significant bilirubinuria. b. Has inflammatory disease syndrome along the urinary tract. c. Is normal. d. Has acute renal failure. e. Has lower urinary tract disease. Physical Examination Color Appearance (Clarity) Specific Gravity Chemical Examination pH Protein Glucose Ketones Blood Bilirubin Urobilinogen[ˌjuərəbaiˈlinədʒin] 尿胆原 Nitrite [ˈnaɪˌtraɪt]亚硝酸盐 Microscopic Examination Urinary Sediments Renal Tubular Cast Red Blood Cells White Blood Cells Squamous Epithelial Cells Transitional Epithelial Cells Renal Tubular Cells Oval[ˈəuvəl ] Fat Bodies Granular Cast颗粒 Fatty Cast Waxy Cast Broad Cast Hyaline[ˈhaɪəlɪn ]透明的 Cast RBC Cast WBC Casts accumulate Normal Urine Crystals(略) Acid pH Uric acid Amorphous urates Calcium oxalate Alkaline pH Amorphous phosphates Calcium phosphate Triple phosphate Ammonium biurate Calcium carbonates Color Normal random urine specimens pale yellow straw light yellow yellow dark yellow amber Yellow-brown, yellow orange, yellow green bilirubin胆红素, biliverdin胆绿素[ˌbiliˈvə:dn] , Red and cloudy red blood cells (hematuria), menstrual contamination, beets甜菜 Red and clear, pink red or red-brown hemoglobin or myoglobin is present (hemoglobinuria) Dark brown, black urine rhabdomyolysis横纹肌溶解, melanin Appearance (Clarity)略 Normal random urine specimen clear hazy slightly cloudy cloudy Turbidity white blood cells red blood cells epithelial cells bacteria White cloudiness Alkaline urine precipitated amorphous phosphates carbonates Acidic urine precipitated amorphous urates calcium oxalate Specific Gravity A measure of the density of the dissolved [diˈzɔlv ]chemicals in the urine urea尿素 sodium chloride [ˈklɔrˌaɪd] Normal random urine specimen SG range from 1.015 to 1.025 Specific Gravity The specific gravity is a convenient index of urine concentration. It measures density and is only an approximate guide to true concentration. Specific gravity between 1.002 and 1.035 on a random sample should be considered normal if kidney function is normal. Clinical Significance of Urine Specific Gravity is related to Patient hydration(Drink so much water )and dehydration Loss of renal tubular concentrating ability Determination of unsatisfactory specimens due to low concentration 测定 pH value of urine Normal random specimen pH range is 4.5 to 8.0 Ability of the kidneys to maintain normal hydrogen ion[ˈhaɪdrədʒən ˈaɪən ] concentration in plasma and extracellular fluid (Reflect) Aids in determining the existence of systemic acid-base (帮助确定身体的酸碱度) Aids in the management of urinary conditions that require the urine to be maintained at a specific pH Acid urine 酸性尿 1 High protein diet, 2 Pharmacologic agents like ammonium[əˈmoniəm] chloride, methionine蛋氨酸 [meˈθaiəni:n ], 3 Metabolic/respiratory acidosis, diuretics, prolonged vomiting, diabetic ketoacidosis Alkaline [ˈælkəlaɪn] urine 1 diet high in fruits and vegetables 2 sodium bicarbonate, potassium citrate, metabolic/respiratory alkalosis(causes of metabolic alkalosis : 1. loss of hydrogen ion;2. Excessive intake of alkaline substances; 3. potassium deficiency) Measurement of urine protein Specimen Timed 24-h is best Normal protein excretion is <150 mg/24h 50-60% albumin Smaller proteins (1-, 2-microglobulins) Tamm-Horsfall (uromucoid尿粘蛋白, secreted by tubules) IgA, tubular epithelial enzymes肾小管上皮细胞酶 Dipstick method for urine protein(略) Method is based on protein association with pH indicator Test pad contains dye tetrabromphenol blue at pH=3 If protein binds to the pH indicator, H+ is displaced and the color changes from yellow to green (or blue) Most sensitive to albumin (poor method for detecting tubular proteinuria) What causes excess protein? [ˈɛkˌsɛs] urinary Overload proteinuria Bence-Jones (multiple myeloma) Myoglobin (crush injury, rhabdomyolysis[ræbdoʊmaɪ‘oʊlɪsɪs 肌溶解) Hemoglobin Tubular proteinuria Mostly low molecular weight (MW) proteins (not albumin) pyelonephritis[paɪələʊnɪ‘fraɪtɪs]肾盂肾炎 Glomerular [ɡ'lɒmrjʊlə]proteinuria Mostly albumin at first, but larger proteins appear as glomerular membrane selectivity is lost. Clinical Significance of Urine Protein Glomerular membrane damage systemic lupus erythematosus(SLE) Amyloidosis[ˌæmilɔiˈdəusis] 淀粉样变 Toxic agents(gentamycin,amphotericin B, streptomycin) Impaired renal tubular re-absorption Multiple myeloma[ˌmaɪəˈlomə]骨髓瘤 Diabetic nephropathy Orthostatic or postural proteinuria 直立 Severe Proteinuria :Nephrotic syndrome is defined as >3.5g/d of proteinuria Glucose In general the presence of glucose in urine indicates that the filtered load of glucose exceeds the maximal tubular reabsorptive capacity Glycosuria is usually occurs when the blood level is more than 100 to 200 mg/dL Less than 0.1% of glucose normally filtered by the glomerulus appears in urine (< 130 mg/24 hr).. Clinical Significance of Urine Glucose Diabetes mellitus Impaired tubular re-absorption Central nervous system damage (glucocorticoid ) Thyroid disorders(hyperthyreosis[haɪpəθaɪr'ɪəʊsɪs]) Pregnancy with possible latent diabetes mellitus [ˌglu:koʊ‘kɔ:tɪˌkɔɪd]糖皮质H Ketones Formation of urine ketones occurs when the use of carbohydrates as the major source of energy becomes compromised and the body fat metabolism is increase to supply energy Ketones (acetone, aceotacetic acid, betahydroxybutyric acid) results from either diabetic ketoacidosis or some other form of calorie deprivation (starvation) Clinical Significance of Urine Ketones Diabetic acidosis Insulin dosage monitoring Starvation Excessive carbohydrate loss Blood > 5 red blood cells/microliter of urine – is clinically significant Chemical tests for hemoglobin – accurate means of detecting presence of blood Microscopic examination – can differentiate between hematuria and hemoglobinuria Clinical Significance of Urine Blood Hematuria [ˌhi:məˈtjuriə] Renal calculi[ˈkælkjəˌlaɪ]结石 Glomerulonephritis/pyelonephritis Tumors Trauma Exposure to toxic chemicals or drugs Strenuous exercise Hemoglobinuria Transfusion reactions Hemolytic anemia Severe burns Infections Strenuous exercise/RBC trauma Bilirubin胆红素 Bilirubin in urine can provide early indication of liver disease Conjugated bilirubin appear in the urine when the normal degradation cycle is disrupted by the obstruction of the bile[baɪl ] duct and or when the integrity of the liver is damaged. Clinical Significance of Urine Bilirubin Hepatitis Cirrhosis Other liver disorders Biliary [ˈbiljəri ]胆汁obstruction (bile duct obstruction) [sɪˈrosɪs ] Urobilinogen[ˌjuərəbaiˈlinədʒin]尿胆素原 Appears in the urine because as it circulates into the blood to the liver, it may pass through the kidney and filtered by glomerulus Normal – 0.5 to 2.5 mg or units/24 hrs. Urine urobilinogen is increased in any condition that causes an increase in production (hemolytic disorders) or retention of bilirubin (liver disease). Clinical Significance of Urine Urobilinogen Early detection of liver diseases Hemolytic disorders Nitrite A positive nitrite test indicates that bacteria may be present in significant numbers in urine. Gram negative rods such as E. coli are more likely to give a positive test. If nitrite test is positive, a culture should be considered provided that the specimen was properly collected and stored prior to testing. Clinical Significance of Urine Nitrite Cystitis[sɪˈstaɪtɪs] 膀胱炎 Pyelonephritis Evaluation of antibiotic therapy Monitoring of patients at high risk for urinary tract infection Screening of urine culture specimens Leucocyte Esterase(略) A positive test results from the presence of white blood cells either as whole cells or as lysed cells. Pyuria can be detected even if the urine sample contains damaged or lysed WBC's. A negative test means that an infection is unlikely and that, without additional evidence of urinary tract infection, microscopic exam and/or urine culture need not be done to rule out significant bacteriuria. Red Blood Cells Normal = 0 to 2 rbc/hpf (high power field) Presence of dysmorphic [dɪs'mɔ:fɪk]RBC's in urine suggests a glomerular disease(Glomerular Basement Membrane ) Increased RBC - hemorrhage, inflammation, necrosis, trauma or neoplasia somewhere along the urinary tract (or urogenital[ˌjʊroˈdʒɛnɪtl Phase contrast microscopy (PCM) (Glomerular Basement Membrane ) dysmorphic RBCs< 30-50 % non-glomerular hematuria dysmorphic RBCs≥30-50% glomerular hematuria case 1 One 9 years old gril, with the complaint that burning urination for 3 days associated with abnormal urine routine test,no fever, no cough, no diarrhea . PE: T: 37 。 R: 28 /min HR : 89/min BP: 110/70 mmHg The throat was a little red, no significant findings in the chest and abdominal examination , urethral orifice is red laboratory tests: URT :RBC 20-25/HPF, WBC 1015/HPF,PRO 1+ BRT is normal Phase contrast microscopy: dysmorphic RBCs< 30 % Hypertension diagnosis standard age BP(mmHg) <7 years >120/80 >7years >130/90 Step 1 hematuria burning urination for 3 days urethral orifice is red BRT is normal renal causes PCM: dysmorphic RBCs< 30 % non-glomerular burning urination for 3 days urethral orifice is red URT: WBC 10-15/HPF Step 2 suspected diagnosis of UTI urine culture to confrim the diagnosis of UTI URI:urinary tract infection antibiotics case 2 One 8 years old boy, with the complaint that gross hematuria for 3 days, no fever, no cough, no diarrhea .he got cold 2 weeks ago and has recovered now. PE: T: 36.9。 R: 34 /min HR : 94/min BP: 140/90 mmHg The throat was a little red, no significant findings in the chest and abdominal examination , mild edema around the eyes. laboratory tests: URT :RBC >50/HPF, WBC 3- 5/HPF, PRO 1+ BRT is normal Phase contrast microscopy: dysmorphic RBCs 90 % Step 1 Haematuria gross haematuria for 3 days mild edema around the eyes BRT is normal Renal causes PCM: dysmorphic RBCs 90 % glomerular Step 2 catched cold 2 weeks ago mild edema around the eyes URT: RBC>50/HPF, PRO 1+ suspected diagnosis of PSAGN Serum C3 etc, to confrim the diagnosis of PSAGN rest, poststreptococcal acute glomerulonephritis is one self-limited disease antibiotics, etc grupa A streptococcal infection formation of IC(immune complex) Glomerular local immune reaction endocapillary proliferation GFR↓ hematuria oliguria output of fulid↓ blood volume↑ GBM injury edema hypertension proteinuria The total plasma volume filtered by the glomeruli per unit time is called Glomerular filtration rate (GFR) laboratory tests ● urinalysis: hematuria and proteinuria ● blood test:C3 ↓ ASO(antistreptolysin O)↑ ● kidney biopsy: not necessary ASO normal C3 1 2 3 4 5 6 7 8 16 time (weeks) ASO: begin to raise in the 10-14th day,climb to the peak in 3-5th week,and recover normal in 3-6th month C3: decrese within 2weeks after the onset of disease and recover normal within 8 weeks HEMATURIA Important questions to ask in patients History •Has there been any signs of a UTI such as dysuria and frequency? Any suprapubic pain? •Has there been any recent URI symptoms or sore throat? •Has there been any type of skin rashes or sores? •Any abdominal pain or colicky pain绞痛? •Are the stools loose or bloody? •Has there been any recent trauma? •Has there been any joint pains or swellings? •Is there any history of sickle cell disease or trait? •Is there any family history of renal disease, transplants, or dialysis? •What medications does the child take? HEMATURIA Important areas to check on the physical examination •Blood Pressure •Check for edema, especially around the eyes •Careful inspection of the external genitalia •Look for any rashes, evidence of trauma and bruising, petechiae •Exam all joints for signs of arthritis-red, warm, or swollen •Feel the abdomen carefully for any masses or tenderness. Try to feel for enlarged kidneys. •Check for evidence of paleness or jaundice (hemolytic?) --Approaching to the patient– HEMATURIA (Harrison’s Principle of Internal Medicine,14th Ed) proteinuria (>500mg/24h) Dysmorphic RBC or RBC casts (-) Pyuria,WBC casts (-) (+) urine culture eosinophils Hb electrophoresis, urine cytology, UA of family member, 24h urinary calcium/uric acid (-) IVP+/-renal ultrasound (+) (-) cystoscopy (-) CT scan (-) follow (+) As indicated: retrograde pyelography or arteriogram of cyst aspiration (+) serologic and hematologic evaluation: blood culture, anti-GBM Ab, ANCA, complement, cryoglobulin HBV,HCV,VDRL,HIV, ASO renal biopsy biopsy (+) open renal biopsy ANCA:antineutrophil cytoplasmic antibody, VDRL:venereal dis. research laboratory, ASO: antisteptolysin O, IVP: intravenous pyelography question 1. In the case 1, why does the patient have the proteinuria? 2. In the case 2, the URT indicate WBC 3-5/HPF, what is the reason? White Blood Cells Normal <5 wbc/hpf Greater numbers (pyuria[paiˈjuəriə ]) generally indicate the presence of an inflammatory process somewhere along the course of the 1、Nephropyelitis 肾盂肾炎 urinary tract. 2、tuberculosis of kidney 3、cystitis [sɪˈstaɪtɪs] 膀胱炎 4、urethritis[ˌjʊrɪˈθraɪtɪs] 尿道炎 Cells in UA WBC : number seen per high power field (HPF) none seen; <5, 5-20, 20100, or >100. WBC are normal in urine in low numbers Up to 5 WBC/HPF nucleus RBC : number seen per high power field (HPF): none seen; <5, 5-20, 20-100, or >100. RBC are normal in urine in low numbers Up to 5 RBC/HPF The patient,female,34 years, was hospitalized with edema of the lower limb for one month. Urinalysis and microscopy: Pro 300mg/dl +++ (Nomal<150 mg/24h) BLD (urine occult blood) 250 /ul ++++ 24h urinary protein:3.4g urinary sediments:ERY 25-30 /HPF, irregular shape 90% What is the primary diagnosis? Nephrotic syndrome Nephropyelitis?肾盂肾炎 Transitional Epithelial Cells(略) Originate from the renal pelvis, ureters, bladder and/or urethra. Seldom pathologically important unless with unusual morphology Renal Tubular Cells Most significant – increased number indicate tubular necrosis and renal graft rejection Hyaline ['haɪəlɪn] Cast Normal = 0-2/lpf Physiologic - strenuous[ˈstrɛnjuəs ] exercise, heat exposure, dehydration脱水, emotional stress Pathologic – acute glomerulonephritis[gloʊˌmerjəloʊnə'fraɪtɪs] (GN) , acute pyelonephritis chronic renal disease, congestive heart disease Casts in UA B Casts : A: Hyaline cast; B: Fatty cast; C: Hyaline to finely granular cast; D: Cellular cast; E: Cellular to coarsely granular cast; F: Coarsely granular cast; G: Finely granular cast; H: Granular to waxy cast, I: Waxy cast. Casts in UA Cylinduria Significance of RBC casts in urine Indicative of blood crossing the GBM (glomerular basement membrane) Casts form in the distal tubules Stasis produces brown, granular casts RBC casts almost always reflect glomerular disease WBC Casts Signifies infection or inflammation within the nephron Most frequently seen in pyelonephritis[pailonfraitis] and acute interstitial[ˌɪntɚˈstɪʃəl ] nephritis. Renal Tubular Cast Tubular cells usually seen in cast are from collecting tubules A very few hyaline RTC casts or RTC casts can occasionally be encountered in a healthy person's urinary sediment Among the disorders associated with the presence of increase of this cast are: acute interstitial nephritis acute transplant rejection tubular necrosis. Granular Cast Rare finding is physiologically due to stress and exercise Pathologically due to GN and pyelonephritis, Waxy[ˈwæksi] Cast Found especially in chronic renal diseases, and are associated with chronic renal failure; they occur in diabetic nephropathy, malignant hypertension and glomerulonephritis. Broad Cast Formation in collecting ducts or distended renal tubules The finding of many broad waxy casts suggests a serious prognosis Referred to as “renal failure casts” Uric Acid Crystals pH -- acidic Color -- colorless, yellow brown or reddish brown; highly birefrigent Shape -- variety (rhombic plates, spears, wedges, needles) May indicate increased nucleoprotein metabolism when found in freshly voided urine Calcium Oxalate Crystals pH -- acid, neutral Color -- colorless Shape -- octahedral, dumbbell, oval “envelop” High potential for forming renal stones Abnormal Urine Crystals Cystine Cholesterol Leucine Tyrosine Bilirubin Sulfonamides Radiographic dyes Ampicillin Cystine Crystals pH -- Color -- colorless (cannot polarize) acidic Shape -- thin hexagonal plates Significance -- metabolic defect; cystinuria Leucine Crystals pH -- acid, neutral Color -- yellow brown bodies Shape -- spheroids with concentric striations and radial structures; dense, highly refractive (Maltese-cross pattern under polarize light) Significance -- severe liver disease Tyrosine Crystals pH -- acid, neutral Color -- colorless, yellow brown Shape -- needle shaped, single or arranged in sheaves or rosettes, with fine silky appearance. Significance -- severe liver disease Bilirubin Crystals pH -- Color -- Shape -- acid bright yellow clumped needles or spheres Significance -- liver disease Cholesterol Crystals pH -- Color -- acid colorless, polarized Shape -- irregular transparent to rectangular plate with notch or one or more curve (“stair step crystals”). Significance -- always considered pathological and can be found in various renal diseases. Sulfadiazine crystals pH -- Color - Shape acid, neutral variable -- rosettes, fan Significance -- tend to form renal calculi that may damage renal tubules. Sulfonamide Crystals pH -- acid Color -- Shape -- resemble uric acid crystals yellow Other Urine Elements Fungal elements Trichomonas vaginalis Bacteria Spermatozoa Mucus Starch or Talc powder Fiber Fungal elements(略) The presence of yeast in the urine sediment may indicate an infection. A frequently seen yeast in urine is Candida. Yeast containing casts have a very high clinical value; these are pathognomonic of pyelonephritis. Trichomonas vaginalis(略) usually comes from genital secretions contaminating the specimen. Identification of the living cell is quite easy owing to its spectacular motility. Bacteria Bacteria associated with urinary tract infection are mostly bacillus (E. Coli) (E. Coli) summary preservation of urine specimen Toluene Formaldehyde Concentrated hydrochloric acid Acetic acid glacial Thyme camphor summary Routine Urinalysis physical characteristics volume -polyuria -oliguria -anuria color -hematuria -hemoglobinuria -bilirubinria -chyluria summary Appearance and turbidity - urate - phosphate and carbonate - pyuria pH Specific gravity summary Chemical examination 1. protein 2. glucose summary Microscopy examination Cellular Red cell White cell Epithelium Cast hyaline cast cellular cast granular cast fatty cast renal failure cast waxy cast paracylinder Crystals summary Other Urine Test 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. ketone bodies bilirubin urobilinogen nitrite lysozym β2-microglobin fibrin degradation product Ig、C3 amylase hemosiderin Tamm-Horsfall Case III A voided urine sample obtained from a 10-year-old domestic neutered shorthair cat. Color yellow Protein negative Turbidity clear RBC negative Specific gravity 1.010 WBC negative pH 6.0 Casts negative Glucose negative Epithelial cells negative Acetone negative Bacteria negative Occult blood negative Crystals negative Bilirubinnegative The best interpretation of the specific-gravity value of this urinalysis is that: a. The patient's kidneys have lost the ability to concentrate and dilute urine. b. The patient's kidneys have lost the ability to concentrate urine. c. The patient's kidneys have lost the ability to dilute urine. d. No conclusions can be established about the ability of the patient's kidneys to concentrate and dilute urine. e. The patient has a fixed urine specific gravity, probably as a result of primary renal failure. A fresh urine sample obtained by cystocentesis from a 10-year-old spayed Pomeranian dog. Color yellow Protein 2+ Turbidity cloudy RBC numerous / hpf Specific gravity - 1.035 WBC numerous / hpf pH 8.0 Casts none Glucose negative Epithelial cells many Acetone negative Bacteria many cocci Bilirubin negative Crystals moderate struvite Occult blood - 4+ The best interpretation of the results of this urinalysis is that the patient: Case IV a. Has an inflammatory process somewhere along the urinary tract caused by bacterial infection. b. Has an inflammatory process somewhere along the genitourinary tract caused by bacterial infection. c. Has an inflammatory process somewhere along the urinary tract caused or complicated by bacterial infection. d. Is normal, and the sample was contaminated during the process of analysis. e. Has struvite uroliths associated with urinary-tract infection. The patient,female,34 years, was hospitalized with edema of the lower limb for one month. Urinalysis and microscopy: Pro 300mg/dl +++ (Nomal<150 mg/24h) BLD (urine occult blood) 250 /ul ++++ 24h urinary protein:3.4g (Nomal<150 mg/24h) urinary sediments:ERY 25-30 /HPF, irregular shape 90% What is the primary diagnosis? Nephrotic syndrome Nephropyelitis?肾盂肾炎