4/13/2016
Pathophysiology of the kidney.
Acute and chronic renal failure
Blagoi Marinov, MD, PhD
Pathophysiology Department
Medical University of Plovdiv
Kidney physiology
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Nephron
anatomy and physiology
Filtration
Reabsorbtion
Secretion
Functional renal syndromes
Hypertension – реноваскуларна, паренхимна, ренопривна
Edema – нефритни, нефрозни
Osteodystrophy
Altered diuresis
Urinary syndrome
Loss of ability to concentrate/dilute urine
Altered homeostasis
Hyper- hypocoagulability
Azotemia
Lithogenesis
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Hypertension
Chronic hypoperfusion
Nephrectomy
Renovascular Renoprival
hypertension hypertension
Low
High
Renin
Renin
Edema
Nephritic (decreased permeability)
Primary Na+ retention (primary hypervolemic)
Sympathetic tone
RAAS
Secondary Na+ retention (membranogenous)
Nephrotic (increased permeability)
Proteinuria
Oncotic pressure
RAAS
Sympathetic tone
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Osteodystrophy
Р-retention
Demineralization
Osteoclasts
Osteopenia
Secondary
Ca2+
PTH
GFR 1, 25 Vit D3
Metabolic acidosis
Osteodystrophy
(Retention)
Diuresis
Increased Normal Decreased Absent
Polyuria Normuria Oliguria<0.5 Anuria
> 2 L/24 h 0.5-2.0 L/24 h L/24 h <0.15 L/24 h
Tubular dysfunction Glomerular hypo- and afunction
Omotic
Hypotonic normotonic
and hypertonic
Hyperhydration
(hypervolemia)
Dehydration
(hypovolemia)
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Proteinuria and hematuria
Microhematuria
(>3 Ers)
Increased
permeability of Overwhelmed (up to 1 g/24 h) Proteinuria
glomerular or (0.5 to 3.5 and
Suppressed >3.5 g/24 h)
basal membrane tubular reabsorbtion
Cilindruria
Proteinuria
Protein is not normally filtered at glomerulus and
only trace amounts should be in urine
Microalbuminuria-20-200 mcg/min (30-
300mg/24hr)
Proteinuria/albuminuria - >200 mcg/min (albumin
is more specific for glomerular disease than
protein)
Consider : Ingestion of high-protein meal and
vigorous exercise -> increase protein in urine
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Anemia
Fe-deficit
Inhibitors
erythropoesis
Suppressed
BONE
ЕРО MARROW
ANEMIA
Microangiopathic
hemolysis
Protoporphyrin
hyposynthesis
Lithogenesis
Hyper- normo-
calciemia
Normocalciuria
Hypercalciuria
Overwhelmed
metastability limit
of the urine Hyper-
oxaluria
solubilizers или
in the urine Spontaneous Hyper-
urikosuria
crystalization
of the urine solution
Hypocytraturia
Lithogenesis
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Nosology of the kidney
Glomerular
Tubulointerstitial
Toxic influences
Neoplastic processes
The kidney is an “innocent bystander” in
many systemic diseases
Hypertension
Hypotension
Vasculitis
Thrombotic diseases/DIC
Systemic Lupus Erythematosis
Sickle cell anemia
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Tubulo-interstitial diseases:
Cluster of abnormalities that, early on,
affects the renal tubules and the interstitium
Spares the glomeruli and the blood vessels
TIDs can be divided into the
following categories:
Ischemic: Acute renal failure, hypotension,
blood loss, shock
Infections: Acute and Chronic pyelonephritis,
viruses, parasites
Toxins: Drugs, analgesics, heavy metals (Pb)
Metabolic: Urate, nephrocalcinosis, Oxalate
Neoplasms: Multiple Myeloma
Immunologic reaction: Transplant rejection
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Urinary Tract Infections
F:M ratio 8:1
Females 15-40 years of age
Infecting organisms from patient’s own flora
Bacteria reaches the kidney by:
Ascending route (more common)
Blood borne (more dangerous)
Urinary Tract infections:
Most common organisms:
Gram negative bacilli (E. Coli is the most
common)
Proteus, Klebsiella, Enterobacter,
Mycobacteria (T.B)
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Predisposing factors for UTI:
Diabetes
Pregnanct
Obstruction (BPH, Tumors..)
Reflux
Immunosuppression
Instrumentation (Catheters, surgery...)
Acute Pyelonephritis
(Microscopic)
Neutrophils in the interstitium
Tubular damage (later)
Microabscesses in the interstitium
May lead to perinephric abscesses (Very
painful)
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Pathogenesis of tubulointerstitial lesions
Bacterial colonisation
(E. coli, Proteus, Clebsiela)
Difficult urine outflow
Reflux (urostatsis)
Inefficient defences
in urinary ducts
Tubulointerstitial Contractile dysfunction
invasion of urinary ducts
Hyperosmolality
Suppressed Resilient (L-form)
macrophages bacteria
Persistent bacterial
inflammation
Glomerulonephritis
Definition:
Renal disease characterized by inflammation of the
glomeruli, or small blood vessels in the kidneys.
Glomerulonephrites are categorised into several
different pathological patterns, which are broadly
grouped into non-proliferative or proliferative types.
Diagnosing the pattern of GN is important because
the outcome and treatment differs in different types.
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Normal glomerulus
Membranoproliferative
glomerulonephritis
Pathogenesis of glomerulonephritis
Immunologic
conflict
Towards own Ag Towards implanted
(autoimmunity) foreign (nonglomerular)
Similar to GBM Ag
Constructed in situ
bacterial Ag bacterial, viral
(on site)
(immune) (immune)
Circulating immune
complexes
Forcefully
“Deposited”
or
Actively captured
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Nephrotoxicity of the complexes
depends on:
Size – small to medium;
Ag-Ab avidity – high;
Clearance– low;
Electrical charge – polycationic;
Valence - mono-, polyvalenticполивалентни;
Ratio – excess of Ag
Immune (autoimmune) inflammation
Ab mediated complement citotoxicity
Ab mediated cellular citotoxicity
Neutrophil and/or monocite attack
Proliferation of cells with growth potential –
monocites, fibroblasts, mesangial cells
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Signs of glomerular damage are :
Increased permeability of glomerular basal
membrane
Drop in overall glomerular filtration rate
Disfunction of JGA (Juxtaglomerular aparatus)
Glomerular-tubular disbalance
Acute glomerulonephritis
Most causes are infectious
Follows a streptococcal infection (when
taking history ask client about recent
infections)
Related to systemic diseases
Lupus
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Signs and Symptoms
Hematuria: dark brown or smoky urine
Oliguria: urine output is < 400 ml/day
Edema: starts in the eye lids and face then the
lower and upper limbs then becomes
generalized; may be migratory
Hypertension: usually mild to moderate
Nephrotic Syndrome
Condition of increased glomerular
permeability that allows larger molecules to
pass through the membrane into the urine
and be removed from the blood
Severe loss of protein into the urine
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Clinical Manifestations Of
Nephrotic Syndrome
Severe proteinuria
Hypoalbuminemia
Hyperlipidemia
Edema
Hyptertension
Renal vein thrombosis may occur
May progress to ESRD without tx
Chronic Glomerulonephritis
A slow, progressive disease that can be caused by primary
( Nephrotic & Nephritic Syndromes) or secondary disorders
( SLE, Good pasture's)
Typically develops asymptomatically over many years
Hypertension, proteinuria and hematuria exhibited with
progression of disease
Late stages display uremic symptoms of azotemia, nausea,
vomiting, dyspnea and pruritis
Leads to chronic renal failure (CRF)
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Renal failure
Failure to excrete nitrogenous waste and
electrolyte imbalance.
Criteria for diagnosis (lab definition):
Cr increase of .5 mg / dl.
Increase in more than 50% over baseline Cr.
Decreased in calculated Cr Clearance by
more than 50%.
Any decrease in renal function that requires
dialysis.
Acute renal failure
Acute renal failure - ARF, now increasingly
called acute kidney injury, is a rapid loss of
kidney function.
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Acute renal failure
Spasm of Dilation of
v. afferens v. efferens
Decreased kidney permeability
Plugs Increased tubular
pressure Cellular tubular edema
detrite, cilinders
Tubullar compression
“glaucoma mechanism”
Tubulorrhexis
(interstitial urine spill)
Chronic renal failure
Definition:
Progressive tissue destruction with
permanent loss of nephrons and renal
function
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Chronic renal failure
Biology – loss of working nephrons
Progress – increasing loss nephrons (%)
Stages – compensated, decompensated, uremic,
comatous
Clinica syndromes – according to the main
disease, complications, stage
Risk factors
Age > 60 years
Race or ethnic background
African-American
Hispanic
American Indian
Asian
History of exposure to chemicals/toxins
Cigarette smoke
Heavy metals
Family history of chronic kidney disease
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Chronic vs. Acute Renal Failure
Acute Renal Failure (ARF):
Abrupt onset
Potentially reversible
Chronic Renal Failure (CRF):
Progresses over at least 3 months
Permanent- non-reversible damage to nephrons
Causes of CRF
Diabetic Nephropathy
Hypertension
Vascular Disease
Polycystic Kidney Disease/Genetics
Chronic Inflammation
Obstruction
Glomerular Disorders/ Glomerulonephritis
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Pathophysiology of CRF
Progressive destruction of nephrons leads to:
Decreased glomerular filtration, tubular
reabsorption & renal hormone regulation
Remaining functional nephrons compensate
Functional and structural changes occur
Inflammatory response triggered
Healthy glomeruli so overburdened they
become stiff, sclerotic and necrotic
Structural Changes of CRF
Epithelial damage
Glomerular and parietal
basement membrane
damage
Vessel wall thickening
Vessel lumen narrowing
leading to stenosis of arteries Healthy Glomerulus
and capillaries
Sclerosis of membranes,
glomeruli and tubules
Reduced glomerular filtration
rate
Nephron destruction
Damaged Glomerulus
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Functional Changes of CRF
The Kidneys are unable to:
Regulate fluids and electrolytes
Balance fluid volume and renin-angiotensin
system
Control blood pressure
Eliminate nitrogen and other wastes
Synthesize erythropoietin
Regulate serum phosphate and calcium
levels
Four Stages of CRF
Reduced Renal Reserve (Silent): no
symptoms evident- GFR up to 50ml/min
Renal Insufficiency: ½ function of both
kidneys lost- GFR 25-50 ml/min
Renal Failure: GFR 5-25 ml/min
End Stage Renal Disease: GFR less than 5
ml/min
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Signs & Symptoms
Peritoneal dialysis
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Hemodialisis
Kidney transplantation
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Thank you
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