Transcript Hematurie - Univerzita Karlova v Praze

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
Haematuria
• 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 haematuria (IgA GN, thin basement memrane
disease, Alport, other GN)
– Renal non-glomerular haematuria (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/posttraumatic 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),
Diagnosis + Treatment of
haematuria
• Urinalysis
• Urine microscopy (sediment, phase-contrast)
• PSA
• Imaging (US, IVU,CT, angiography)
• Cystoscopy
• Urine cytology
• Renal biopsy (in glomerular hematuria)
• Early diagnosis is essential
• Treatment 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 "casts" 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
= clinical complex consisting of:
•
•
•
•
•
•
Proteinuria of >3.5g / 1.73m2 / 24 hours
Hypoalbuminaemia
Oedema
Hyperlipidaemia
Lipiduria
Hypercoagulability
Patophysiology of the nephrotic syndrome. Primary insultincreased 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,
hypovolemia
(caused
by
hypoalbumine
mia
and
decreased
oncotic
plasma
pressure) is
the
main
cause of renal
Na+ a H20
retention.
??
The “overfill” mechanism of edema formation. In this
theory, abnormal renal Na+ and H20 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, H20 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
• haematuria (red cell casts).
Typical example: Poststreptococcal
glomerulonephritis in children
Differences between nephrotic and nephritic
syndromes
Typical features
Nephrotic syndrome
Nephritic syndrome
onset
slow
acute
swelling
++++
++
arterial blood pressure
normal
increased
central venous pressure
normal/low
increased
proteinuria
++++
++
hematuria
present/not present
+++
red cell casts
not present
present
glomerular filtration
normal
normal/low
serum albumin
low
normal/slightly
decreased
Histology (light microscopy) of acute poststreptococcal GN
(marked invasion of polymorphonuclear cells)
Histology of acute poststreptococcal GN (subepithelial humplike deposits (strait arrows), subendothelial (arched arrows) and
mesangial deposits). Endocapillary 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.
Continuous
alterations
of
structural
changes
caused by
glomerular
inflammati
on (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 monocytes). 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
Risk.. Injury…Failure.. Loss…End-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, preexisting renal disease, surgery, volume depletion, cardiac
disease, cirrhosis, drugs – NSA, ACEI, ARB), myeloma
Chronic kidney disease
→ Renal insufficiency → Renal failure
* exocrine dysfunction (ions – K, Na, P, H.., fluid,
and other catabolites – uremic toxins retention)
• endocrine dysfunction (erythropoietin, 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
1. Asymptomatic urinary abnormalities:
GFR > 90 ml/min (> 1,5 ml/s)
2
Mild CRF:
GFR 60-89 ml/min (1-1,5 ml/s)
3
Moderate CRF:
GFR 30-59 ml/min (0,5-1 ml/s)
4
Severe CRF:
GFR 15-29% (0,25-0,5 ml/s)
5
Approaching ESRD: GFR < 15 ml/min (< 0,25 ml/s)
Uremic syndrome - clinical features 1
• Gastrointestinal
– Anorexia, nausea, vomiting
• Neurological
– Central: uremic encefalopathy (daytime
drowsiness, disorientation, myoclonus, coma)
– Peripheral: uremic polyneuropathy (restless legs
syndrome)
• Respiratory
– pulmonary edema
Uremic syndrome - clinical
features 2
• Cardiac
– uremic pericarditis
• Dermatological
– pruritus
• Hematological
– fatigue due to anemia
• Endocrinological
– secondary hyperparathyreoidism (bone pain),
dysmenorrhea
Uremia
* in 3 different clinical situations → different clinical
features
– acute renal failure – exocrine dysfunction, 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.).
Treatment of uremia
•
-
Conservative:
diet: Na, K, PO3 and protein restriction
control of hypertension
NaHC03 treatment to reduce metabolic acidosis
anemia management (erythropoietin)
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