10a Syndromology in nephrology.ppt
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10a Syndromology in nephrology.ppt 10a Syndromology in nephrology.ppt Presentation Transcript

  • Syndromology in nephrology Martina Peiskerová 1.LF UK Praha Klinika nefrologie 9/2007
  • Syndromology in nephrology - outline
    • Haematuria
    • Proteinuria
    • Leucocyturia
    • Polyuria, oliguria, anuria
    • Nephrotic syndrome
    • Nephritic syndrome
    • Acute glomerulonephritis
    • Rapidly progressive glomerulonephritis
    • Pulmonary-renal syndromes
    • Chronic glomerulonephritis ??
    • Acute renal failure
    • Chronic kidney disease
    • (Chronic renal failure)
    • Uraemia
    • Tubular syndromes
    • Hypertension
    • Pain
    • Obstruction
  • Ha ematuria
    • Definition > 2 red cells / hpf ,
    • Hamburger’s sediment (3 hours) > 2000/min.
    • microscopic x macroscopic
    • persitent x transient (exercise, menstruation, trauma, infection)
    • glomerular x non-glomerular x uncertain origin (exercise, over-anticoagulation, factitious)
    • Source: kidney x urinary tract
      • Renal glomerular h a ematuria ( IgA GN, thin basement memrane disease, Alport, other GN)
      • Renal non-glomerular h a ematuria ( tumours, cysts, calculs, pyelonephritis, papillary necrosis, renal vein thrombosis)
      • Urinary tract bleeding ( cystitis, prostate, tumours, stricture, Schistosoma haematobium)
  • Clinical importance of haematuria
    • Cause dependent
    • The most frequent causes:
    • - inflammation or infection of the prostate or urinary bladder
      • urinary calculi
      • malignant neoplasms
      • glomerular disorders
    • Risk of malignity: age > 40, smoking, NSA, pelvic irradiation, CFA treatment)
    • Glomerular disorder more likely if:
      • proteinuria > 0.5 g/24h
      • dysmorphic erythrocytes present and red blood cells casts on phase-contrast microscopy
      • ↑ BP
  • Diagnosis of haematuria - history and physical examination
    • Pyuria or dysuria  urinary tract infection
    • Respiratory tract infection  postinfectious GN, IgA nephropathy
    • Family history  polycystic kidney disease, hereditary nephritides
    • Low back pain  ureteral obstruction
    • Physical exercise, injury  post-exercise/post-traumatic hematuria
    • Micturition disorders in older men  prostatic obstruction
    • History of bleeding from multiple sources  coagulation disorder
  • Phase-contrast microscopy
    • A-dysmorphic erythrocytes
    • B-isomorphic erythrocytes
    • C-acanthocytes
    • (spur / spiny / star cells)
    • D- neutrophils
    • E-lymphocytes
    • F-eosinophils (arrow),
  • Diagnos is + Treatment of h a ematuria
    • Urinalysis
    • Urine microscopy (sediment, phase-contrast)
    • PSA
    • I maging ( US, IVU,CT, angiography)
    • Cystoscopy
    • Urine cytology
    • Renal biopsy (in glomerular hematuria )
    • E arly diagnosis is essential
    • T reatment of the causing disorder
  • Proteinuria
    • benign ( < 1g/day, age < 30, fever, cold, exercise, CCF, seizures, postural), vs. pathological
    • importance of abnormal proteinuria:
    • marker of intrinsic renal disease, prognostic factor for progression of renal insufficiency, risk factor for CV mortality, treatment target in CKD
    • normally < 150 mg/day (albumine < 30 mg/ day)
    • microalbuminuria 30-300 mg/day
  • Proteinuria 2
    • Pathophysiology
    • glomerular (mostly albumin),
    • tubular (beta2microglobulin),
    • overflow (light chains in myeloma),
    • secretory (tumour, inflammation)
    • Quantity
    • Mild < 1,0 g/day
    • Significant 1,0 – 3,5 g/day (probably glomerular)
    • Nephrotic range > 3,5 g/day (probably glomerular)
  • Leucocyturia
    • neutrophiles – infection, GN, TIN
    • sterile pyuria (treated UTI, Chlamydia, calculi, prostatitis, bladder tumor, papillary necrosis, TIN, TB)
    • lymphocytes – TIN
    • Active urinary sediment
    • red blood cells, proteinuria, white blood cells, and &quot;casts&quot; of cells
  • Urinary sediment abnormalities „Mixed urinary findings“
    • isolated haematuria or haematuria + mild proteinuria ( < 1g/day) … good prognosis
    • isolated proteinuria ( < 3,5g/day) .. worse prognosis
    • nephrotic proteinuria + haematuria … the worst prognosis
  • Nephrotic syndrome = c linical complex consisting of:
    • Proteinuria of > 3.5g / 1.73m 2 / 24 hours
    • Hypoalbuminaemia
    • Oedema
    • Hyperlipidaemia
    • Lipiduria
    • Hypercoagulability
  • Patophysiology of the nephrotic syndrome . Primary insult- increased glomerular permeability, causing plasma protein leakage into urine. Hypoalbuminemia is the cause of the main clinical features.
  • Metabolic albumin turnover in healthy subjects vs. subjects with nephrotic syndrome .
  • ?? The “ underfill ” mechanism of edema formation. In this theory, hypovol e mi a ( caused b y hypoalbuminemia and decreased oncotic plasma pressure) is the main cause of renal Na + a H 2 0 retention.
  • ?? The “ overfill ” mechanism of edema formation. In this theor y , a bnorm a l renal Na + a nd H 2 0 retention is the main cause of Starling forces alteration at local tissue level.
  • (Possible) consequences of proteinuria and lipid spectrum abnormalities.
  • Diagram showing pathogenetic factors leading to hypercoagulability , tromboembolism and renal vein thrombosis.
  • Causes of nephrotic syndrome
  • Treatment of nephrotic syndrome
    • Symptomatic
      • NaCl, H 2 0 restriction
      • diuretic therapy
      • ultrafiltration
      • nephrectomy
    • Specific (depending on the causative disease)
      • immunosuppressive therapy
      • in amyloidosis, treatment of the causative process
    • Treatment and prevention of complications
      • thromboembolism
      • lipid metabolism disturbances
      • immunoglobulin deficiency
      • Ineffective: high protein diets, albumin supplementation.
  • Nephritic syndrome
    • Glomerular inflammatory changes leading to
    • ↓ GFR
    • moderate proteinuria
    • oedema
    • hypertension
    • h a ematuria (red cell casts).
    • Typical example: Poststreptococcal glomerulonephritis in children
  • Differences between nephrotic and nephritic syndromes normal/low normal glomerular filtration normal/slightly decreased low serum albumin present not present red cell casts +++ present/not present hematuria ++ ++++ proteinuria increased normal/low central venous pressure increased normal arterial blood pressure ++ ++++ swelling acute slow onset Nephritic syndrome Nephrotic syndrome Typical features
  • Histology (light micros c opy) of acute poststreptococcal GN (marked invasion of polymorphonuclear cells)
    • Histology of acute poststreptococcal GN (subepithelial hump-like deposits (strait arrows), sube ndothelial (arched arrows) and mesangial deposits) . E ndocapillary hypercellularity caused by neutrophil infiltration, endothelial and mesangial proliferation .
  • Immunological findings in poststreptococcal GN
    • 1. The serial estimation of complement -
    • Early in the acute phase, the levels of hemolytic complement activity (CH50 and C3) reduced .
    • Within 8 weeks return to normal
    • 2. Serial ASO titer measurements - twofold or greater rise in titer are highly indicative of a recent infection.
  • C ontinu ous alterations of structural changes caused by glomerular inflammation (upper part), clinical syndromes (middle part) and specific nosologic units (lower part).
  • Rapidly progressive GN (RPGN)
    • Severe glomerular disorder -> ↓ glomerular filtration in days or weeks.
    • Clinical features: acute uremic or nephritic syndrome with renal insufficiency rapidly -> renal failure
    • Histology: negative IF (pauci-immune), crescentic GN (crescent = half-moon-shaped lesion in Bowman ’s space composed of proliferating parietal epithelial cells and infiltrating monoc ytes). Crescentic GN: > 70% glomeruli are involved.
    • Typical diseases : WG, GP and SLE.
    • + Extrarenal symptoms: pulmonary, skin, ORL, CNS..
  • Large cellular crescent filling the Bowman’s space and compressing the glomerular tuft in WG.
  • Acute renal failure 1
    • due to rapid ↓ GFR (hours, days)
    • retention of urea, creatinine, disorders in electrolytes, acid-base, fluid homeostasis
    • oliguric x non-oliguric
    • anuria < 100 ml/day, oliguria < 400 ml/day, polyuria > 3l/day
    • RIFLE classification
    • R isk.. I njury… F ailure.. L oss… E nd-stage)
    • Acute kidney injury classification :
    • 1. s-creat to 1,5-2x baseline / oliguria > 6 hours
    • 2. s-creat to 2-3x baseline / oliguria > 12 hours
    • 3. s-creat above 3x baseline / anuria
    • * the highest risk – pulmonary edema, hyperkalemia
  • Acute renal failure 2 - causes
    • Prerenal (from ↓ BP -> ↓ GFR, or arterial stenosis or NSA, ACEI)
    • Intrinsic
    • - ATN (ischemic – e.g.myoglobinuria, myeloma
    • casts, nephrotoxic – radiocontrast, drugs – gentamicin,
    • vancocin, cisplatin)
    • - vascular
    • - acute GN
    • - acute TIN
    • Postrenal (obstructive)
    • Patients at risk of developping ARF: ↑age, DM, pre-existing renal disease, surgery, volume depletion, cardiac disease, cirrhosis, drugs – NSA, ACEI, ARB), myeloma
  • Chronic kidney disease -> Renal insufficiency -> Renal failure
    • * exocrine dys function (ion s – K, Na, P, H.. , fluid, and other catabolite s – uremic toxins retention )
    • endocrine dys function (erythropo i etin, 1,25 vitamin D metabolism, renin-angiotensin system)
    • -> laboratory: GF < 1,0 ml/s, hyperkalemia, hypocalcemia, hyperphosphatemia, metabolic acidosis, anemia
  • Stages of kidney disease NKF/ KDOQI
    • Asymptomatic urinary abnormalities:
    • GFR > 90 ml/min ( > 1,5 ml/s)
    • Mild CRF: GFR 60-89 ml/min (1-1,5 ml/s)
    • Moderate CRF: GFR 30-59 ml/min (0,5-1 ml/s)
    • Severe CRF: GFR 15-29% (0,25-0,5 ml/s)
    • 5 Approaching ESRD : GFR < 15 ml/min ( < 0,25 ml/s)
    • Gastrointestinal
      • Anorexia, nausea, vomiting
    • Neurological
      • Central: u remic encefalopathy (daytime drowsiness, disorientation, myoclonus, coma)
      • Peripheral: u remic polyneuropathy (restless legs syndrome)
    • Respiratory
      • pulmonary edema
    Uremic syndrome - c linical features 1
  • Uremic syndrome - c linical features 2
    • Cardiac
      • u remic pericarditis
    • Dermatologic al
      • pruritus
    • Hematologic al
      • f atigue due to anemia
    • Endo c rinologic al
      • s econdary hyperparathyreoidism (bone pain), dysmenorrhea
    • U remia
    • * in 3 different clinical situations -> different clinical
    • features
      • acute renal failure – exocrine dys function, no time for endocrine dysfunction development
      • chronic renal failure – endocrine and exocrine renal dysfunction (fluid excretion usually preserved until late stages)
      • dialysis treated CRF – caused by insufficient dialysis treatment and/or insufficient substitution of the decreased renal endocrine production (EPO, vitamin D, etc.).
  • Urea Pyridine derivatives Phenols Guanidino compounds Indoles b2-Microglobulin Skatoles Aliphatic amines Hormones Hippurate esters Polyamines Trace elements (Mg) Aromatic amines Serum proteineases Potentially Toxic Compounds That Accumulate in Renal Failure
  • Toxic Sequelae of Metabolic Acidosis Organ Mechanism -> Sequelae Muscle Proteolysis -> Loss of lean body mass Bone Inhibition of osteoblasts -> Dissolution of bone matrix Stimulation of osteoclasts -> Dissolution of bone mineral Hormonal  PTH level -> Osteopenia  Vitamin D3 -> Osteomalacia  Cortisol -> Activation of catabolism  Thyroxine -> Hypometabolism  Growth hormone -> Stunted growth ↑ Insulin resistance -> Activation of catabolism
  • Treatment of uremia
    • Conservative:
    • diet: Na, K, PO3 and protein restriction
    • control of hypertension
    • NaHC03 treatment to reduce metabolic acidosis
    • anemia management (erythropoi e tin)
    • secondary hyperparathyroidism management (vitamin D, phosphate binders)
    • Renal replacement therapy: hemodialysis, peritoneal dialysis, renal transplantation
  • Pulmonary-renal syndromes
    • Acute kidney disease (ARF or RPGN) + Pulmonary haemmorhage
    • Features: cough, anaemia, dyspnoea, haemoptysis, hypoxaemia, alveolar shadowing on CXR (df.dg. pulmonary oedema) + features of systemic disease: skin rush, sinusitis, artritis, fever, fatigue
    • Main causes: ANCA vasculitis, antiGBM nephritis, SLE, Henoch-Schonlein purpura
    • Other causes: pulmonary oedema, infection (pneumonia – Pneumocystis, viruses..), hantavirus, pulmonary emboli, acute respiratory distress syndrome
  • Hypertension
    • Primary hypertension – kidney is victim –
    • - vascular nephrosclerosis..
    • Secondary hypertension – kidney is vilain
    • - glomerular and vascular diseases
    • Control of hypertension is crucial in slowing progression of kidney disease -> aim BP 120/75 mm Hg
  • Tubular syndromes
    • Tubular dysfunction may occur in any renal injury
    • Tubular syndromes in the context of normal GFR:
    • Generalised – Fanconi syndrome : multiple tubular defects caus in variable degree
    • -> phosphaturia -> rickets, osteomalacia, osteoporosis
    • -> aminoaciduria – no clinical sequelae
    • -> glycosuria – rarely hypoglycemia
    • -> defective bicarbonate reabsorption – renal tubular acidosis
    • -> Na loss -> rarely ↓BP or metabolic alcalosis
    • -> K loss -> hypokalaemia -> muscle weakness, constipation, arrhytmias
    • -> proteinuria – LMW, no clinical sequelae
    • -> polyuria – dehydration
    • -> hypercalciuria -> rarely nephrolitihiasis/calcinosis
    • Isolated – genetic mechanisms involved
    • - glycosuria - to distinguish from DM
    • - aminoaciduria - e.g. cystinuria -> recurrent cystin stone formation (AR inheritance)
    • - phosphaturia – e.g. vitamin D resistant rickets (XR inheritance)
  • Pain
    • An agressive and destructive renal disease may be painless !!
    • Loin pain - constant dull ache, may irradiate to abdomen, genitalia
    • cause: distension of the renal capsule
    • differential: nerve root irritation (T10-12)
    • Ureteric colic - sudden onset, extremely sever, pale, distressed patient
    • localisation: loin, iliac fossa, genitalia, upper thigh
    • cause: passage of the stone, blood clot or necrotic papillae
    • Suprapubic pain
    • causes: over-distension of the bladder, cystitis, bladder cancer
    • Bladder irritability - dysuria, frequency, urgency
    • causes: over-distension of the bladder, cystitis
  • Bladder outflow obstruction
    • Symptoms
    • Obstructive – voiding: hesitancy, impaired force of stream, incomplete emptying
    • Storage – filling : frequency, dysuria, urgency
    • Causes
    • Structural – prostatic hyperplasia, carcinoma, urethral stricture
    • Functional – bladder neck dyssynergia, DM, multiple sclerosis, spinal corde lesions, drugs - antidepressants