Pathophysiology Chapter 22 Renal Disorder
Kidneys
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Organs of filtration and secretion
Also plays a role in
o Acid/base balance, BP regulation
o RBC formation, drug metabolism
o Hormone metabolism, VD synthesis
o Glucose homeostasis
Alterations in kidney function can impair all of these processes
Incidence of kidney disease growing in US
Diabetes mellitus, hypertension, autoimmune conditions play a role
End-stage renal disease (ESRD) has significantly increased
Basic Concepts Renal Function
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Kidneys receive ~1/5 of cardiac output
Glomerular filtration rate (GFR)
o Renal blood filtered per unit of time
o Directly related to renal perfusion
o Decrease renal perfusion= decrease GFR
GFR reduction with aging
Nephron and Excretory Function
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Nephron
o Basic functional unit of kidney
o Processes filtered fluid
o End product: urine
Glomerular capillaries
o Specialized capillaries
o High hydrostatic pressure favors filtration
Filtrate moves into Bowman’s capsule (initial portion of nephron)
Nephron Overview
o Proximal tubule
 Segment following Bowman’s capsule
 Reabsorbs majority of filtrate
o Loop of Henle
 Begins to concentrate filtered fluid
 Urea: a waste product enters Loop of Henle
o Distal tubule
 Under influence of aldosterone, absorbs water and sodium
o Collecting ducts
 Under influence of ADH, additional water reabsorbed
Kidney Functions
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Acid-base balance
o Excrete/reabsorb H+ and bicarbonate as needed
Waste elimination
o Urea, uric acid, creatinine (Cr), drug metabolits
Secretory function
o Erythropoietin (EPO)
 Increase RBCs in response to hypoxia
o Renin
 Released in response to low BP or perfusion
 Activate RAAS
Vitamin D synthesis and calcium balance
o Kidney activates VD
o VD important in calcium absorption
Glucose homeostasis
o Renal threshold to reabsorb glucose (BG of 180 mg/dL)
 If exceeded, glucose appears in urine
o Kidneys degrade insulin
o Gluconeogenesis
Kidney Dysfunction Consequences
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Insufficient filtration
o Waste product buildup
Urine not concentrated
Toxin buildup leading to destruction of blood cells
Neurological
o Confusion, stupor, encephalopathy
Excess renin secreted, raising BP
Decreased erythropoietin, decreasing RBCs
Acid-base balance not maintained
Excess K+ not secreted
Decreased Ca+ absorption (renal osteodystrophy)
Basic Pathophysiology
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Kidneys susceptible to ischemic injury
High pressure required to push fluid through kidneys and urinary system
Nephrons can be harmed by toxins
Urine outflow must be maintained
Uropathy
o Obstruction of urine flow
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Can cause fluid backup which damages renal pelvis
Categories of Renal Dysfunction
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Prerenal
o Decreased BF and perfusion to the kidney
Intrarenal
o Actual injuries to the kidney
Postrenal
o Obstruction of urine outflow from the kidneys
Prerenal Dysfunction
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Any condition that directly or indirectly decreases renal perfusion
o Hypovolemia, heart failure, shock
Injury results from ischemia
Sufficient BP also needed to maintain glomerular filtration and urine output
Intrarenal Dysfunction
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Direct damage to kidney
o Trauma to kidney
 Pyelonephritis, autoimmune conditions (lupus)
o Infection of kidney
 Post-streptococcal glomerulonephritis
o Nephrotoxic drugs
 NSAIDs, ACE inhibitors, angiotensin-receptor blockers, statins, some antibiotics
Postrenal Dysfunction
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Obstructive uropathy
o prevents urine outflow from the kidney
Hydronephrosis
o Urine back up into kidney
Examples:
Kidney stone
o Slowed urinary excretion, urinary stasis, and precipitation of calcium,
which leads to kidney stones
o Nephrolithiasis is the formation of stones, also called calculi, in the kidney.
o Kidney stones can vary from the size of the head of a pin to the size of a piece of gravel
or larger
o Prostated gland hyperplasia
Acute Tubular Necrosis (ATN)
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Ischemia and hypoxia damage to nephron
o Ischemia causes sloughing of nephron tubule cells into nephron lumen
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o Lumen becomes blocked, preventing fluid flow and urine formation
Common cause of acute kidney injury (AKI)
May lead to renal failure
Assessment of Renal Disorders
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Determine medicines
o Specifically nephrotoxic drugs
Assess illness
o Diabetes, HTN, Heart failure,
o Autoimmune conditions, recent streptococcal infections
Ask patient about pattern of urine excretion and character or urine
Signs and symptoms
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May be multisystemic depending on severity
Abdominal pain, confusion
Costovertebral angle (CVA) tenderness
Hematuria (blood in urine)
o Urine looks pink or red
o May be a sign of renal calculi or infection
Proteinuria (aka microalbuminuria)
o Protein in urine, urine looks foamy
Tea-colored urine
o Bilirubin in urine
Diagnosis: Urinalysis
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Urinalysis is a basic examination of urine that includes a description of the character of
o the urine, as well as biochemical and microscopic analysis.
Normally, urine is odorless and clear or slightly hazy with a color ranging
o from yellow to amber.
The color varies according to the concentration of solutes and water content of the
urine.
For example, a dehydrated person has an amber-colored urine,
a well-hydrated person has a light yellow urine, though
urine color can vary with some medications or certain disorders
pH
specific gravity
glucose
ketones
leukocyte esterase
nitrite
Blood Urea Nitrogen (BUN)
* protein
* bilirubin
* urobilinogen
* crystals
* casts
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The normal level for BUN is 5 to 20 mg/dL.
 An elevated BUN can occur when there is a decrease in the GFR, which leads to
accumulation of nitrogenous waste products in the blood.
 a high BUN level is not always an indicator of kidney dysfunction; it can result from
dehydration, which highly concentrates the urea in the urine.
 A high BUN level can also occur in any condition that elevates the amount of
nitrogen waste in the bloodstream
 increase BUN
o Decreases GFR
o Dehydration
o Extremely muscular persons
o High protein diet
Should not use BUN measurement alone for kidney function indicator
Creatinine (Cr)
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Serum creatinine
o Indicator of kidney function
Breakdown product of muscle filtered and excreted by kidney
Indicator of GFR
o Increasing serum Cr indicated decreasing GFR
Clearance
o Cr clearance used to assess GFR
o Measurement of blood and urine Cr with 24-hour urine volume
o Total amount of Cr in urine= amount filtered at glomerulus
o Decreased Cr clearance indicates decreased GFR and impaired renal function
Diagnosis: Imaging Studies
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Renal ultrasound
Intravenous pyelography
CT scans
MRI
Note: IV contrast-enhanced imaging studies avoided in patients with renal impairment because
radiopaque dye can cause renal failure
Treatment
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Must attempt to maintain renal function
Medication option
o Sodium bicarbonate, beta blocker, epogen, diuretics
Dialysis may be needed if renal failure can not be reversed
o Indications: persistent hyperkalemia, metabolic acidosis, fluid volume excess
unresponsive to diuretics
Peritoneal Dialysis (PD)
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Peritoneum filled with a dialysis solution (dialysate)
Waste and extra fluid pulled from blood into abdominal cavity by dialysate
Dwell time
o Time fluid sits in peritoneal cavity
o ~4 hours
After dwell time, solution is drained
Hemodialysis
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Patient’s blood drawn out of the body (200-400 mL/min)
Blood passes through dialyzer
o Removes excess solutes and fluid from the blood
o Entire blood volume circulates through machine every 15 minutes
Commonly, arterial-venous fistula created in the arm
o Blood drained from the brachiocephalic artery, pumped into dialyzer, returned via the
cephalic vein
Continuous Renal Replacement Therapy (CRRT)
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Similar to hemodialysis
Slower process
Used for patients who are hemodynamically unstable and fluid overloaded
Continuous process
Smaller volumes of blood from the patient
o Filters it through a dialyzer over 24 hours
Acute Glomerulonephritis (AGN)
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Immunological mechanism
Triggers inflammation that damages the membranes of the glomerulus
Autoimmune or post-streptococcal disorder
o PGSN: post-streptococcal glomerulonephritis
Can progress to ESRD
Antigen-antibody reaction damages glomeruli leading to hyperpermeability
Damaged glomeruli leads to:
o Protein loss
o Edema(periorbital)
o Oliguria
o Hypervolemia (HTN)
o PGSN: 7-21 days post-strep infection
o Dark urine: RBCs
Diagnosis
o Elevated serum Cr and BUN; low serum albumin
o Urinalysis: protein, WBCs, blood
o Antibodies to streptococcal bacteria may be present
Treatment
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Antibiotics, dietary modifications, diuretics
Nephrotic Syndrome
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Glomerular damage resulting in proteinuria and edema
Most commonly caused by diabetes, amyloidosis and lupus
Massive albuminuria (with facial edema), hematuria, HTN, oliguria
Hyperlipidemia may develop
o Lipid synthesis by liver increases, as liver increases albumin synthesis to compensate for
urinary loss
Treatment
o Adequate fluid, dietary modification, may progress to renal failure
Nephrolithiasis
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Stones (calculi) in kidneys
Urolithiasis
o Stone travels to ureter
Presentation based on stone’s location
Stones
o Calcium (most common), struvite, uric acid, cystine
Kidneys secrete stone-inhibitors
Risk factors
o Genetic susceptibility
o Dehydration
o Hypercalcemia
 Excessive calcium intake
o Hyperparathyroidism
o Gout
o Hyperuricemia
o Urinary tract infection
o Immobility
Symptoms
o Severe abdominal, flank pain
o Colicky pain caused by ureter spasms
o Hematuria
o Crystalluria
o Hydronephrosis may develop
o Diagnosis requires stone analysis
Treatment
o Pain relief
o Prevent recurrence and UTI
o Strain urine to catch stone for analysis
o High fluid intake: greater than 3 liters/day
o Lithotripsy
o Surgery, if no relief
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Dietary changes to keep urine acidic or alkaline, depending on stone composition
Pyelonephritis
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Infection of renal pelvis
o Ascending UTI
o Stasis of urine plays a role
Other factors
o Obstructive uropathy
o Vesicoureteral reflux
 Anatomical abnormality (urine refluxes from bladder into ureters)
o Neurogenic bladder
o Urological instrumentation
o Pregnancy
Signs and symptoms
o Fever (uncommon in lower UTI)
* dysuria
o Abdominal or CVA tenderness
*urinary frequency
o Flank pain
*microscopic hematuria
o Nausea and vomiting
* pyuria (WBCs in urine)
o Chills
* Leukocyte esterase test of urine
Diagnosis
o Urine cultures
 E.coli (most common cause), S. saprophyticus, P. mirabilis
o Dipstick urinalysis
 Pyuria, positive leukocyte esterase
o Contrast-enhanced helical/spiral computed tomography (CECT)
o CT scan
 Kidney, ureters, bladder (KUB)
o Ultrasound
Treatment
o Antibiotics
o Analgesics, if needed
o Fluid intake greater than 3 L/day
o Remove urological obstruction, if present
Polycystic Kidney Disease (PKD)
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Genetic disorder
Kidney and other organs (liver, pancreas)
Cysts formation impairs renal function
Most common form
o Autosomal dominant PKD (ADAPKD)
o Recessive form also exists
Decrease account for 6%-8% of patients on dialysis in US
Fluid filled cysts in kidneys
Patients present with
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o Pain
o Renal calculi
o CVA
o Increased BP (if cysts place pressure on kidney BV, activating RAAS)
Diagnosis
o Ultrasound and CT scan
Treatment
o Control HTN, decreases infection risk, tolvaptan (decreases cyst formation)
Goodpasture’s Syndrome
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Immunological disease of kidney (and alveoli)
o Aka: antiglomerular basement membrane (anti-GBM) disease
Antibodies attack glomerular basement membrane
o Rapidly progressive of unknown etiology
o Can lead to renal failure
The disorder is an acute, rapidly progressive type of glomerulonephritis caused by circulating
antibodies
Transplant may be needed
Patient may present with nonspecific symptoms(fever, malaise) and renal manifestations
(hematuria, edema)
Blood test
o Detect antibodies
Treatment
o Plasmapheresis(remove antibodies), immunosuppressant, dialysis, and/or kidney
transplant
Acute Kidney Injury (AKI) (Acute Renal Failure)
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Abrupt insult to the kidney
o Rapid decrease kidney function (with intervention, normal function restored)
Azotemia, elevated Cr, fluid retention are common signs
Classification
o Prerenal (most common): decreased perfusion
o Intrinsic: medications, infections
o Postrenal: obstruction
Cause
o Prerenal
 Renal ischemia, hemorrhage, shock
o Intrarenal
 Nephrotoxic drugs (NSAIDs, aminoglycosides, radiopaque dyes)
 Infections
 Excess hemoglobin, myoglobin, purine breakdown
o Postrenal
 Nephrolithiasis, prostatic hyperplasia
o Treatment
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 Must address underlying cause
Can be divided into 4 phases
o Initial insult
 Prerenal, inrarenal, or postrenal condition that disrupts kidney function
o Oliguria
 Low GFR, lack of urine output, fluid overload
o Diuresis
 Large unconcentrated urine outflow; kidney is not concentrating urine properly
o Recovery
 Healthy nephrons take over function of damaged nephrons; kidney function
resumes
Chronic Renal Failure (CRF)
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Irreversible and progressive, with gradual onset
90% to 95% of the nephrons affected
Usually progresses to ESRD
Hemodialysis or kidney transplant needed
DM, HTN, glomerulonephritis and PKD are leading causes
5 stages of the progression of CRF
o Stage 1
 Kidney damage with normal or increased GFR (greater that 90 mL/min)
o Stage 2
 Mild reduction in GFR (60 to 89 mL/min)
o Stage 3
 Moderate reduction of GFR (30 to 59 mL/min)
 Symptoms normally become apparent
 Serum Cr and BUN increase
o Stage 4
 Severe reduction if GFR (15-29 mL/min)
o Stage 5
 Kidney failure (GFR lower than 15 mL/min)
Complications
o Uremic encephalopathy
* decreased vitamin D
o Proteinuria
* hypertension
o Hypoalbuminemia
*metabolic acidosis
o Edema
* hyperkalemia
o Fluid overload
* hypocalcemia
o Oliguria
* hyperphosphatemia
o Electrolyte imbalances
* hyperparathyroidism
o Hemolysis
(due to Ca+ loss, leads to renal osteodystrphy)
o Thrombocytopenia
o Anemia
Lower UTIs
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account for 1% to 3% of all visits to family clinicians.
The patient commonly presents with pain and burning on urination, as well as
urinary frequency and urgency.
If the infection persists, the symptoms can progress to cloudy, strong-smelling urine &
Hematuria
An untreated lower UTI can put the patient at risk for an ascending UTI that can result
In pyelonephritis, which is kidney infection.
Factors that increase susceptibility to UTI in women:
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Improper perineal hygiene
wearing tight restrictive clothing
use of irritating bath products.
Sexual intercourse increases a woman’s risk of UTI
use of contraceptive diaphragms and spermicides are also known to increase
susceptibility
Pyelonephritis | Infection of the upper urinary tract, commonly caused by an ascending lower UTI.