PROTEINURIA AND THE NEPHROTIC SYNDROME · Heavy proteinuria > 3.5 g/day/1.73 m2 highly or poorly...
Transcript of PROTEINURIA AND THE NEPHROTIC SYNDROME · Heavy proteinuria > 3.5 g/day/1.73 m2 highly or poorly...
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PROTEINURIA, NEPHROTIC AND NEPHRITIC SYNDROME
Beata Mladosievičová
Institute of Pathophysiology
Medical Faculty, Bratislava
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The kidneys play a major role
in regulating
fluids, electrolytes, acids and bases,
osmolality
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Imbalances occur as the kidneys
• increase the ability to excrete proteins
or
• decrease the ability to excrete (water,
electrolytes, wastes and acid-base
products) .
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The daily excretion of protein into the urine of normal subjects rarely exceeds 150 mg... the small quantity of protein: High molecular weight glycoproteins from the distal tubular epithelium
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PROTEINURIA
daily urinary excretion of
protein>150 mg/ day
Unrelated to renal disease
Pathological
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Pathological proteinuria
1. Overflow of plasma proteins in excessive concentration – Ig light chains
2. Increased glomerular permeability – abnormalities of GFB 1-40 g of protein/d
3. Tubular damage < 2 g/d
4. Disease of the lower urinary tract
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Glomerular permeability to proteins:
the nature of the glomerular filter – Endo, GBM, Epi
(pores in layers,
charge-selective filter,
blood flow)
the properties of the proteins (size, shape, charge)
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Bacterial, viral Ag(Ab)
components of complement
attraction of the Leu
lysosomal enzymes, free oxygen radicals
filter damage
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Increased glomerular permeability:
congenital NS
minimal change disease (most common in children)
glomerulosclerosis (hypertension, diabetes mellitus)
glomerulonephritis (membranous common in adults)
IK deposits*
postinfectious – bacterial endocarditis, hepatitis, TBC
malignancy – Ca lung, breast, cervix. colon, kidney,
ovary, leukaemias, lymphomas
renal transplant rejection
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Glomerulosclerosis
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THE NEPHROTIC SYNDROME
Heavy proteinuria > 3.5 g/day/1.73 m2 highly or poorly selective increased glomerular permeability*
decreased tubular reabsorbtion
Hypoproteinaemia (esp.hypoalbuminaemia)
Edema (increased ECF in the interstitium)
decreased oncotic pressure,
increased aldosterone and ADH, sodium and water retention
Hyperlipidaemia increased hepatic synthesis of
lipoproteins
Lipiduria - oval fat bodies, granular casts
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Oval fat bodies
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Complications of NS
• Infection – skin, lungs, peritoneum
• Premature atherosclerosis
• Impaired coagulation – increased circulating
levels fibrinogen, factors V and VIII, decreased
antithrombin III, haemoconcentration
• Disorders in vitamins, hormones and elements
bound to plasma proteins
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Clinical presentation of the NS:
•anorexia
•edema - ankles, periorbital region, anasarca, pleural effusion
• may be hypertension
• thrombotic complications (renal vein!)
• frothy urine (proteinuria), nocturia
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Laboratory findings:
Urine: heavy proteinuria, protein ++ or greater in
the urine for 2 consecutive days
casts: granular, hyaline, epithelial
Blood: hypoalbuminemia
globulines, hormones adrenocortical or
thyroid may be low
lipemia (elevated cholesterol, Tg)
anemia (loss of transferrin, poor
production of erythropoetin)
increased levels of fVIII, fibrinogen, Tr, Er
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Hematuria
Generally, hematuria is defined as the presence of 5 or more red blood cells (RBCs) per high-power field in 3 of 3 consecutive centrifuged specimens obtained at least 1 week apart.
Hematuria can be either gross - visible(ie, overtly bloody, smoky, or tea-colored urine) or
microscopic.
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Hematuria
• Renal
• Postrenal - cystitis, stone, tumor,
accident
• Other – drugs, infections
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Hematuria – renal causes
Renal GLOMERULAR
-postinf. GN, RPGN,
glomerulosclerosis...
Renal NONGLOMERULAR–
interstitial, Tu, accident, cystic,
hydronephrosis...
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PHARAOH Nephritic sy
Proteinuria
Hematuria
Azotemia
RBC casts
Antistreptolysin O titres
Oliguria
Hypertension
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Nephritic sy in adults
Abdominal abscess
Hepatitis B or C
Infective endocarditis
Membranoproliferative GN
Rapidly progressive glomerulonephritis
SLE
Vasculitis
Viral diseases: measles, mononucleosis,
mumps
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Case
• 40 yrs old patient. 5 months ago both leg
edema slowly progressive, phlebography
without thrombosis, fatigue 3 months, no
drugs, general practitioner found
hypoproteinemia
• History: alcohol abusus successfully treated
3 yrs ago
• Physical exam: leg edema, back edema, soft
pitting edema
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Causes of generalized edema?
• Hypoproteinemia (low intake, enteropathies,
liver damage, nephrotic sy)
• Heart failure (RAA)
• Electrolyte and water dysbalance (primary
hyperaldosteronism, renal failure,...
• Acute GN
• Hypothyreosis
• Drugs
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Causes of localized edema?
• Flebotrombosis
• Leg ischemia
• Trauma
• Inflammation
• Lymphedema
• Allergy
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Case II cont
• Clinical signs and symptoms of heart
failure, liver damage, myxedema and GIT
damage are not present
• Drugs potentially associated with edema,
such as corticoids, calcium antagonist and
others were not given
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Which examinations are
suggested?
• complete blood count,
• proteins,
• electrolytes (Na, K, Cl, Ca),
• creatinín, urea,
• glycemia,
• lipids,
• markers of inflammation
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Which next exams?
• Liver test (AST,ALT, bilirubín...),
• urine test,
• X ray chest (pulmonary edema),
• Sonography (ascites, kidneys, liver),
• EKG
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Results
• ERY a Hb decreased,
• FW a CRP mild increase,
• Total proteins in blood and albumins
decreased
• cholesterol and TG increased
• liver test normal
• creatinin, urea normal
• EKG, X ray, abdominal and heart
sonography normal
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Conclusion
• Low probability of heart, liver and
kidney failure
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Next exams?
• Quantitative and qualitative exam of
proteins during 24 hours, electrophoresis
• Systemic disorders (ASLO, RF, antinuclear
faktors)
• Renal biopsy
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Results
• IgG low (excluded myeloma and systemic
diseases),
• ASLO,RF, antinuclear ff negat. excluded
systemic disorders
• Proteinuria 36g/day • Histology on biopsy: focal segmental
glomerulosclerosis
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Therapy
• Diuretics,
• Corticoids
• ACE inhibitors
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Later after 6 months- worsening
• Dialysis and planned transplantation
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Hematuria could also be
attributed to
- non-nephrologic bleeding (e.g. menstruation),
• But many are false positive findings due to the
use of certain drugs or consumption of certain
foods (e.g. mangold).
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• Transient hematuria is common (40% in the
general population)
• Persistent hematuria (defined as urine
positive in two out of three consecutive
dipsticks, e.g. over a one to two weeks
period) in just 2.5–4.3%