Transcript Altered Renal Function

Altered Renal Function
Overview of Kidney
Diseases
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Classified by site or cause of disease
Organization by site:
– Prerenal
– Intrarenal (Renal)
– Postrenal
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Prerenal disease
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Results from inadequate blood flow to the
kidney
– Decreased intravascular volume
– Lesions in the renal arteries
– Hypotension
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Renal diseases
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Result from direct damage to nephron
Glomerular disorders
Tubulointerstitial disorders – disorders
of the medullary tubules and
interstitial cells
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Postrenal diseases
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Commonly due to urinary tract
obstruction
– Kidney stones
– Tumors of bladder, ureters or prostate
gland
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Obstructive Disorders
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Interference with urine flow at any point
Anatomic or functional
Impedes flow proximal to blockage
Dilates urinary system
Increases risk for infection
Compromises renal function
Anatomic changes are called obstructive
uropathy
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Causes of obstruction
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Congenital malformations
Stones
Abdominal tumor or inflammation and
scarring
Tumor of urinary system or prostate
Severe pelvic organ prolapse in women
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Consequences depend on:
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Location of lesion
Whether one or both upper urinary tracts
are involved
Severity and completeness of blockage
Duration of blockage
Nature of the lesion
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Obstruction causes dilation:
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Of ureters – hydroureter
Of renal pelvis and calyces –hydronephrosis
Of both - ureterohydronephrosis
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There was a large renal calculus (stone) that
obstructed the calyces of the lower pole of this
kidney, leading to a focal hydronephrosis
(dilation of the collecting system).
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Here is a kidney with much more advanced
hydronephrosis in which there is only a thin rim of
remaining renal cortex
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Initial tubular damage decreases the
ability to concentrate urine, causing an
increase in urine volume, decrease
concentration
Affected kidney cannot conserve water,
sodium, or bicarb, or excrete potassium,
or hydrogen ions.
Leads to metabolic acidosis and
dehydration.
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Recovery depends on Completeness of
blockage and duration.
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Body can partially compensate if one
kidney is affected by compensatory
hypertrophy of other kidney
– No increase in number of nephrons
– Increase in size of glomerulus and
tubules
– Ability decreases with age
– Is reversible if other kidney recovers
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Relief of obstruction of partial
obstruction of both kidneys
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Usually mild
Restores fluid and electrolyte balance
Occasionally, can result in output of 10L/day
Can cause dehydration and electrolyte
imbalance
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Obstruction of bladder outlet or urethra
affects upper and lower tracts.
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Partial obstruction can lead to over active bladder and urine
retention
Can back up and cause hydroureter, hydronephrosis and
impaired kidney function
Urine can be a microbiological growth medium – infection of
obstructed kidney can cause further damage and scarring
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Could lead to Hypertension
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Renin-angiotensin pathway in acute
unilateral obstruction
– Increased renin  angiotensin I 
angiotensin II  increased aldosterone
 increased Na and water retention
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Due to water and sodium and urea
retention in chronic bilateral partial
obstruction
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Kidney stones or renal
calculi
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Masses of crystals, protein or other
substances
Common cause of obstruction in adults
2-3 % of U.S. population
Recurrence within 10 years is 50 %
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Influenced by age, gender, race,
geographic location, season, fluid intake,
diet and occupation.
Seen in more men than women
Less risk if physically active and drink
adequate water
Other risk factors
– Overweight, Caucasian, previous stones,
infections
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Type of Stone
Frequency
Calcium oxalate (or phosphate)
- more in men
Magnesium ammonium phosphate
(struvite, or "triple phosphate")
- more in women
Uric acid
(Gout)
75%
Cystine
1%
Other
6%
12%
6%
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Increased renal excretion of these
molecules
Decreased urine volume
Change in pH of urine
– Alkaline urine increases risk of calcium
phosphate stones
– Acid urine increases risk of uric acid stones
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Size of stone determines
likelihood it will be passed.
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< 0.5 cm 50 % chance
1 cm almost no chance ( unless ureter
dilated by previous passage)
Develop in renal tubules, calyces,
ureter or bladder
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Clinical manifestations
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Pain (renal colic) – can determine
location
Nausea / vomiting
Chills, fever
hematuria
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Treatment
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Urinalysis and analysis of stones
Removal by surgery/ percutaneous
lithotripsy
Drugs to dissolve stones
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Prevention of future
stones
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Treat underlying metabolic disorders
Water intake = urine output of 2 -3 L /day
Reduction in dietary oxalates (chocolate, nuts,
soybeans, rhubarb and spinach) and animal protein
for uric acid stones
Increased dietary fiber
Do NOT decrease calcium intake – increases risk of
stones
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Urinary Tract infections
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Bacteria most common cause
Can also be due to viruses, fungi or
parasites
Classified by location in system or by
complicating factors
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Cystitis – inflammation of the bladder
– Urinary frequency
– Dysuria – painful or difficult urination
– Urgency
– Lower abdominal, lower back or suprapubic
pain
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May be uncomplicated in otherwise
healthy individual
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Incidence
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Young adult women – 0.2/month
Lifetime risk in women 50%
Young adult men prevalence < 1%
High risk groups:
– Premature infants
– Sexually active women
– Women using a diaphragm or spermicide
– Diabetics
– HIV or immunosuppressive disorders
– Obstruction of lower urinary tract
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Most UTIs are caused by:
gram negative bacteria of the intestinal tract
Escherichia coli – 80% of all uncomplicated
infections. Can form pili allowing bacterium to
adhere to bladder epithelium
Cranberry juice decreases bacterial adhesions by
epicatechin
Staphylococcus saprophyticus 10-20%
Other entreobacter species (Klebsiella, Proteus)
remaining 5%
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Treatment
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Antibiotics
Drink normal amounts of water, but
avoid bladder irritants, such as
caffeine
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Nonbacterial cystitis
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Same symptoms but without infection
Dysfunction of external sphincter,
urethritis, or inflammation of glands near
vagina
– antibiotics, drugs to relax urethral sphincter,
retraining of voiding habits
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Interstitial cystitis – may be due to an
autoimmune reaction, mucus deficiency or
abnormal mast cells.
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Tubulointerstitial disorders
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Acute pyelonephritis (pyelo – pelvis)
– Urinary obstruction and reflux of urine most
common risk factors
– One or both kidneys may be involved
– Most common in women
– Usually E. coli, Proteus or Pseudomonas
– Usually By ascending microorganisms, but can
be carried in blood.
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Acute pyelonephritis
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Inflammation is usually focal, affecting
pelvis, calyces, and medulla but glomeruli
not usually involved.
Kidney is infiltrated with wbc’s – pyuria
Healing involves scarring and atrophy of
affected tubules
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Acute pyelonephritis
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Clinical manifestations:
– Acute onset
– Fever or chills
– Flank or groin pain
– Frequency and dysuria
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May be difficult to distinguish from cystitis
– look for white cell casts
Treatment:
– Microorganism specific antibiotics
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Chronic Pyelonephritis
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Cause is more difficult to determine
More likely in patients with reflux or renal
stones
Scarring can lead to impaired urineconcentrating ability, leading to chronic renal
failure
May be due to drug toxicity from analgesics,
such as phenacetin, aspirin, acetaminophen
Ischemia, radiation, immune-complex disease
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Chronic Pyelonephritis
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Manifestations are often minimal– Hypertension
– Frequency and Dysuria
– Flank pain
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Diagnosis
– Urinalysis
– Intravenous pyelography, ultrasound
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Treatment
– Relieve obstruction
– antibiotics
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Normal glomerulus
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Acute pyelonephritis
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At high magnification, many neutrophils are seen in the tubules and interstitium
in
a case of acute pyelonephritis.
Ascending bacterial infection
This is an ascending bacterial infection leading to acute
pyelonephritis.
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Chronic pyelonephritis
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Chronic pyelonephritis
The large collection of chronic inflammatory cells here is in a patient
with a history of multiple recurrent urinary tract infections. This is
chronic pyelonephritis.
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Glomerular disorders
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Due to a change or dysfunction of the
glomerular capillaries
– Changes in membrane permeability
– Change in GFR
– Protein or blood cells in the urine
– Systemic changes – hypertension;
edema; acid-base and electrolyte
imbalances
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Glomerulonephritis
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Caused by a number of factors, most commonly
abnormal immune response
– Infection
– Toxins
– Vascular diseases
– Systemic diseases (diabetes mellitus)
Can be diffuse, focal or segmental
Can be membranous, proliferative, sclerotic, or crecentic
Often divided into acute, rapidly progressive and chronic
forms.
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Acute Glomerulonephritis
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Often associated with streptococcal infection
Abrupt onset 7-10 days after strept throat or skin
infection (impetigo)
– Also staphylococcus or viruses
Strept antigens deposit in glomerular basement
membrane and attract neutrophils and macrophages,
initiating phagocytosis and release of inflammatory
mediators that damage cells on both side of the
basement membrane.
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Poststreptococcal GN
Post-streptococcal glomerulonephritis is immunologically mediated, and the
immune deposits are distributed in the capillary loops in a granular, bumpy
pattern because of the focal nature of the deposition process.
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Acute Glomerulonephritis
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Symptoms occur 10-21 days after infection
– Hematuria
– Proteinuria
– Decreased GFR, oliguria
– Hypertension
– Edema around eyes, feet and ankles
– Ascites or pleural effusion
Biopsy – immune complexes and proliferation
Most recover without significant loss of renal function or
recurrence
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Rapidly Progressive GN
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Develops over a period of days or weeks
Primarily adults in 50’s and 60’s
May be idiopathic or assoc. with a proliferative disease
By the time of diagnosis patient has renal insufficiency
Proliferation of cells in Bowman’s space with crescent
formation
Progresses to renal failure in a few weeks or months
Hematuria is common, may see proteinuria, edema or
hypertension
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RPGN
This immunofluorescence micrograph of a glomerulus demonstrates positivity with
antibody to fibrinogen. With a rapidly progressive GN, the glomerular damage is so
severe that fibrinogen leaks into Bowman's space, leading to proliferation of the 51
epithelial cells and formation of a crescent.
Goodpasture Syndrome
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Antibody formation against pulmonary and glomerular
capillary basement membranes
Activation of complement and neutrophils damage
glomerular basement membrane
Men 20 - 30 years of age
Pulmonary hemorrhage and renal failure
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Goodpasture Syndrome
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Treatment must begin early or prognosis
is poor
– Anticoagulants reduce fibrin content of
crescents
– Plasmapheresis with steroids and
immunosuppression therapy
– Dialysis or transplant if kidneys fail
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Goodpasture’s syndrome
This immunofluorescence micrograph shows positivity with antibody to IgG has
a smooth, diffuse, linear pattern that is characteristic for glomerular basement
membrane antibody with Goodpasture's syndrome.
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Chronic Glomerulonephritis
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Several diseases with a progressive course
leading to chronic renal failure
Two patterns – deposition of antigen-antibody
complexes, or antigens specific for GBM.
Complement activation and phagocyte activity
damage wall of capillary and cause proliferation
of extracellular matrix, affecting GFR
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Chronic Glomerulonephritis
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At first see increased membrane
permeability and lose cells (hematuria) or
protein into urine (proteinuria)
Fibrin is deposited into Bowman’s space –
crescent formation
Renal blood flow and GFR is reduced
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Chronic Glomerulonephritis
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Clinical manifestations:
– Hematuria – smoky brown-tinged urine as
opposed to pink or red
– Proteinuria > 3-5 g/day mostly albumin
– ↓ GFR leads to fluid retention and
hypertension
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After 10 – 20 years, renal insufficiency
develops and progresses to renal failure
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Chronic Glomerulonephritis
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Treatment:
– Treat underlying disease
– Steroids do not change the course of the
disease
– Correct accompanying problems such as
volume disorders, blood pressure
– Ultimately dialysis or transplant
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Nephrotic Syndrome
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Defined as excretion of 3.5 or more grams of
protein / day
Characteristic of glomerular injury
Also see hypoalbuminemia, edema,
hyperlipidemia
Loss of immunoglobulins can increase
susceptibility to infections
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Nephrotic Syndrome
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Treatment:
– Diet – normal protein, low-fat, salt restricted
– Diuretics
– Immunosuppression
– Protein supplements
– Removal of glomerular membrane toxic factor
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Renal Failure
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Acute renal failure – abrupt decrease in renal function
– Increase in BUN and creatinine
– Usually oliguria (output < 30 ml/hour or 400 ml/day)
– Most cases are reversible if diagnosed and treated early
 Prerenal most common cause – failure to restore blood
volume or pressure and oxygen can lead to acute
tubular necrosis or acute cortical necrosis
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Acute Renal Failure
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Intrarenal acute renal failure
– Usually due to acute tubular necrosis
 Usually caused by ischemia most often
after surgery (40 -50 %)
 Also sepsis, burns, obstetrical
complications, antibiotics, radiocontrast
media, other toxic substances
– Whatever the cause, decreased GFR and
oliguria
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Acute Renal Failure
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Postrenal acute renal failure
– Usually due to urinary tract obstruction that
affects both kidneys
– Characterized by several hours of anuria
with flank pain, followed by polyuria
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Acute Renal Failure
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Clinical symptoms of ARF are divided into
three stages:
Stage1 Oliguria:
↓urine vol about 25 % of normal to anuria
can last 1-3 weeks
↑BUN, plasma creatinine
↑ K+ (hyperkalemia) and electrolyte imbalance
fluid retention and edema
congestive heart failure
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Stage 2 Diuresis:
3-4 L/day of urine
Tubules still damaged, but recovering
Can lose too much Na+ and K+
May see extracellular volume depletion
Stage 3 Recovery
May take 3-12 months for plasma
creatinine to return to normal
About 30 % never regain normal kidney
function.
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Acute Renal Failure
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Treatment
– Prevention if possible
– Maintain individual’s life until renal function is
recovered
 Correct fluid and electrolyte imbalances
 Treat infections
 Maintain nutrition and cardiac function
 Remember drugs and/or medications are
not excreted!
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Chronic Renal Failure
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Progressive and irreversible loss of nephrons
Slow development (years)
Alterations in salt and water balance not apparent until
renal function is less than 25% of normal.
Common causes:
– Chronic glomerulonephritis
– Chronic pyelonephritis
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Chronic Renal Failure
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Clinical manifestations are often described using the
term uremia –symptoms due to accumulation of
toxins in plasma.
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hypertension
Anorexia
Nausea
Vomiting
Diarrhea
Weight loss
Pruritis (itching)
Edema
Anemia
Neurologic changes
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Chronic Renal Failure
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Diagnosis is by increased BUN and serum
creatinine; imaging will show small
kidneys, and can be confirmed by biopsy
Management includes:
– Diet control – restrict proteins, potassium
– Evaluate fluid and sodium levels
– Treat with erythropoietin as needed.
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