Transcript Renal Diseases

Chapter 11
Pathophysiology of Renal
disorders.
By
Dr. Uche Amaefuna-Obasi (MD)
THERE ARE MORE
TO LECTURES
THAN JUST
SLIDES   
Renal Diseases
Introduction:
• 150gm: each kidney
• 1700 liters of blood filtered  180 L of G.
filtrate  1.5 L of urine / day.
• Kidney is a retro-peritoneal organ
• Blood supply: Renal Artery & Vein
• One half of kidney is sufficient – reserve
• kidney function: Filtration, Excretion,
Secretion, Hormone synthesis.
Kidney
Location:
Kidney Anatomy:
Renal Pathology Outline
• Glomerular diseases:
Glomerulonephritis
• Tubular diseases: Acute tubular necrosis
• interstitial diseases: Pyelonephritis
• Diseases involving blood vessels:
Nephrosclerosis
• Cystic diseases
• Tumors
Clinical Syndromes:
• Nephritic syndrome.
 Oliguria, Haematuria, Proteinuria, Oedema.
• Nephrotic syndrome.
 Gross proteinuria, hyperlipidemia,
• Acute renal failure
 Oliguria, loss of Kidney function - within weeks
• Chronic renal failure.
 Over months and years - Uremia
Introduction
• Functions of the kidney:
 excretion of waste products
 regulation of water/salt
 maintenance of acid/base balance
 secretion of hormones
• Diseases of the kidney
 glomeruli
 tubules
 interstitium
 vessels
Kidneys
• Nephron
Working unit of the kidney
Consists of
• Glomerulus: works like a sieve
• Tubules: fluid reabsorbed or
sent to bladder
Kidney Functions
• Regulates
extracellular fluid
& osmolarity,
electrolyte
concentrations, &
acid-base balance
• Excretes wastes
• Secretes renin
• Produces
erythropoietin
• Converts vitamin
D to active form
Abnormal findings
• Azotemia:  BUN (A blood urea nitrogen (BUN) test measures the
amount of nitrogen in your blood that comes from the waste product urea. Urea is
made when protein is broken down in your body. Urea is made in the liver and passed
out of your body in the urine. A BUN test is done to see how well your kidneys are
working),
creatinine
• Uremia: azotemia + more problems
• Acute renal failure: oliguria
• Chronic renal failure: prolonged uremia
Nephrotic syndrome
Nephritic syndrome
• Massive proteinuria
• Hematuria
• Hypoalbuminemia
• Oliguria
• Edema
• Azotemia
• Hyperlipidemia/-uria
• Hypertension
Glomerular diseases
Nephrotic syndrome
•Minimal change disease
•Focal segmental glomerulosclerosis
•Membranous nephropathy
Nephritic syndrome
•Post-infectious GN
•IgA (immune) nephropathy
Nephrotic Syndrome
• Massive proteinuria
• Hypoalbuminemia
• Edema
• Hyperlipidemia
Causes
• Adults: systemic disease (diabetes)
• Children: minimal change disease
• Characterized by loss of foot
processes
• Good prognosis
Nephrotic Syndrome
• Any kidney disorder that results in
proteinuria exceeding 3.5 g/day
• Cause
Any damage to glomeruli increasing
their permeability to plasma proteins
Nephrotic Syndrome
• Possible causes
 Infections
 Chemical damage
 Immunological &
hereditary
disorders
 Diabetes mellitus
• Clinical findings
 Proteinuria
 Low serum albumin
 Edema
 Elevated blood
lipids
 Blood coagulation
disorders
Consequences
• Disturbances in
protein metabolism
• Edema
 Loss of albumin
 Sodium retention
• Risk of CVD
 Elevated LDL, VLDL
& lipoprotein(a)
 Loss of blood
clotting proteins
• Loss of antibodies
• Decreased
vitamin D-binding
protein
 Lower D & calcium
levels
• Protein energy
malnutrition
(PEM)
Consequences
of Protein Loss
© 2007 Thomson - Wadsworth
Treatment
• Medications
• Fat
 Anti-inflammatory
 Low saturated fat,
drugs, ACE inhibitors,
cholesterol, &
antihypertensives,
refined sugars
immunosuppressants, • Sodium
lipid-lowering drugs,
 2-3 g/day
diuretics
• Protein & energy
 0.8-1.0 grams/day
 35 kcalories/kg
• Vitamin D & calcium
• Multivitamin
Nephritic Syndrome
• Hematuria
• Oliguria, azotemia
• Hypertension
Causes
• Post-infectious GN, IgA nephropathy
• Immunologically-mediated
• Characterized by proliferative changes
and inflammation
Post-Infectious
Glomerulonephritis
• Child after streptococcal throat infection
• Immune complexes
• Hypercellular glomeruli
• Subepithelial humps
IgA Nephropathy
• Common!
• Child with hematuria after (URI) Upper
Respiratory Infection
• IgA in mesangium
• Variable prognosis
• Tubular and interstitial diseases
Inflammatory lesions
• pyelonephritis
Pyelonephritis
• Invasive kidney infection
• Usually ascends from UTI
• Fever, flank pain
• Organisms: E. coli, Proteus
Urinary Tract Infection
• Women, elderly
• Patients with catheters or mal-formations
• Dysuria, frequency
• Organisms: E. coli, Proteus
Acute pyelonephritis with abscesses
Chronic pyelonephritis
Drug-Induced Interstitial
Nephritis
• Antibiotics, NSAIDS
• IgE and T-cell-mediated immune reaction
• Fever, eosinophilia, hematuria
• Patient usually recovers
• Analgesic nephritis is different (bad)
Acute Tubular Necrosis
• The most common cause of ARF!
• Reversible tubular injury
• Many causes: ischemic (shock), toxic
(drugs)
• Most patients recover
Benign Nephrosclerosis
• Found in patients with benign
hypertension
• Hyaline thickening of arterial walls
• Leads to mild functional impairment
• Rarely fatal
Malignant nephrosclerosis
• Arises in malignant hypertension
• Hyperplastic vessels
• Ischemia of kidney
• Medical emergency
Malignant Hypertension
• 5% of cases of hypertension
• Super-high blood pressure, encephalopathy,
heart abnormalities
• First sign often headache, scotomas
• Decreased blood flow to kidney leads to
increased renin, which leads to increased BP!
• 5y survival: 50%
Adult Polycystic Kidney Disease
• Autosomal dominant
• Huge kidneys full of cysts
• Usually no symptoms until 30 years
• Associated with brain aneurysms.
Adult polycystic kidney disease
Childhood Polycystic Kidney
Disease
• Autosomal recessive
• Numerous small cortical cysts
• Associated with liver cysts
• Patients often die in infancy
Childhood polycystic kidney disease
Medullary Cystic Kidney Disease
• Chronic renal failure in children
• Complex inheritance
• Kidneys contracted, with many cysts
• Progresses to end-stage renal disease
• Tumors
Renal cell carcinoma
Bladder carcinoma
Renal Cell Carcinoma
• Derived from tubular epithelium
• Smoking, hypertension, cadmium
exposure
• Hematuria, abdominal mass, flank pain
• If metastatic, 5y survival = 5%
Renal cell carcinoma
Bladder Carcinoma
• Derived from transitional epithelium
• Present with painless hematuria
• Prognosis depends on grade and depth of
invasion
• Overall 5y survival = 50%
Acute renal failure
Acute renal failure represents a rapid decline in
renal function leading to increased blood levels
of nitrogenous wastes and impaired water and
electrolyte balance, and manifesting water
intoxication, azotemia, hyperkalemia, and
metabolic acidosis.
Acute Renal Failure
• Function rapidly deteriorates
Reduced urine output
Build up of nitrogenous wastes
• Mortality rates are high
Acute renal failure is reversible if the cause
can be identified and corrected before
permanent kidney damage has occurred.
The most common indicator is azotemia, which
is an accumulation of nitrogenous wastes
(urea nitrogen, uric acid and creatinine)
Etiology and classification
Prerenal failure
Intrarenal failure
Postrenal failure
Causes
• Prerenal
 Heart failure
 Shock
 Blood loss
• Intrarenal
 Infections
 Toxins
 Drugs
 Direct trauma
• Postrenal
 Factors preventing
excretion of urine
 Urinary tract
obstructions
Prerenal failure- functional failure
Prerenal failure is the most common form of acute
renal failure. It is caused by a marked decrease in
renal blood flow.
Causes
•Hypovolemia
•Heart failure
•Intrarenal vasoconstriction
•Increased blood vessel bed
Intrarenal failure- parenchymal renal failure
Intrarenal failure results from conditions that
can cause damage to structures within the
kidney, glomerular, tubular and interstitial.
Causes
Acute tubular necrosis (ATN)
Prolonged renal ischemia (ischemic ATN)
or ischemia-reperfusion injury
Toxic insult of tubules by drugs, heavy metals
(nephrotoxic ATN)
Intratubular obstruction
hemoglobin and myoglobin
severe hypokalemia, hypercalcemia
Acute glomerulonephritis and acute
pyelonephritis
Postrenal failure – obstructive renal failure
Obstruction of urine outflow from the kidneys.
(ureter, bladder and urethra)
Prostatic hypertrophy (most common)
Consequences
• Oliguria < than
• Uremia
400 mL urine/day
 BUN, creatinine & uric
acid accumulate in
• Sodium retention
blood
• Elevated
 Fatigue, lethargy,
potassium,
confusion, headache,
phosphate, &
anorexia, metallic
taste, N & V, diarrhea
magnesium
• Edema
Treatment
• Drug therapy
 Diuretics
 Potassium exchange
resins
 Insulin, glucose
 Bicarbonate
• Protein
 Depends on kidney
function, degree of
catabolism, use of
dialysis
• Fluids
 Measure output and
add 500 mL
 Can increase if on
dialysis
• Electrolytes
 Restrict potassium,
phosphorus, sodium
Chronic Renal Failure
• Is a gradual &
• Causes
irreversible
 Diabetes mellitus
43%
deterioration
 Hypertension 26%
• Usually not
 Inflammatory,
diagnosed until
immunological, or
75% of function is
hereditary
lost
diseases
 May follow acute
failure
Consequences
• Nephrons enlarge to compensate
• Overburdened nephrons
degenerate
• End-stage renal disease occurs
• Evaluation
Glomerular filtration rate (GFR)
Rate at which kidneys form filtrate
Consequences
• Electrolyte imbalances
occur when
 GFR becomes extremely
low
 Hormonal adaptations are
inadequate
 Intake of water &
electrolytes are very
restrictive or excessive
• Renal osteodystrophy
 Increased parathyroid
hormone contributes to
bone loss
• Acidosis may develop
• Uremic syndrome
 Mental dysfunctions
 Neuromuscular changes
 Muscle cramping, twitching,
restless leg syndrome
• Protein energy
malnutrition
Complications of
Uremic Syndrome
• Impaired hormone
synthesis
• Impaired hormone
degradation
• Bleeding
abnormalities
• Increased
cardiovascular
disease risk
• Reduced
immunity
Treatment
• Goal
Slow disease
progression
Prevent or
alleviate
symptoms
• Drugs
Antihypertensives
Erythropoietin
Phosphate binders
Sodium bicarbonate
Cholesterol-lowering
medications
Active vitamin D
supplements
Dialysis
• Removes excess
fluid & wastes from
blood
• Blood is circulated
though a dialyzer
• Blood is bathed by
dialysate
• Hemodialysis &
peritoneal dialysis
Medical Nutrition Therapy
• Energy
 Enough to maintain
healthy weight &
prevent wasting
• Low-protein diet
 Can increase when
on dialysis
• Lipids
 Restrict saturated fat
& cholesterol
• Fluids
 Not restricted until
output decreases
• Sodium
 Mild restriction
• Potassium
 May need to
restrict highpotassium foods
Medical Nutrition Therapy
• Calcium & vitamin
D needs increase
• May need
phosphorus
restrictions
 Restrict protein
 Restrict milk &
milk products
• Dietary supplements
 Generous folate and B6
 Recommended
amounts of watersoluble vitamins except
vitamin C
 IV iron administration
• Intradialytic
parenteral nutrition
Kidney Transplants
• Restores function
• Allows a more liberal
diet
• Frees patient from
dialysis
• Immunosuppressive
drug therapy
 Many side effects
affecting nutrition
• Protein & energy
requirements increase
• Control CHO & lipids
• Sodium, potassium, &
phosphorus intakes
liberalized
• Calcium supplementation
• Be alert for potential food
borne infection
Kidney Stones
• Affects 12% of
men & 5% of
women
• Crystalline mass
in urinary tract
 Severe pain
 Can obstruct tract
• Formation is
promoted by:
 Reduced urine
volume
 Blocked urine flow
 Increased
concentrations of
stone-forming
substances
Types of Stones
• Calcium oxalate
stones
 Most common
 Reduce intake of
oxalate
 Avoid vitamin C
supplements
• Uric acid stones
 Abnormally acidic urine
 Associated with gout
 Low-purine diet
• Cystine stones
 Inherited disorder
cystinuria
• Struvite stones
 Form in alkaline urine
Calcium Oxalate Stone
Consequences
• Renal colic
 Severe,
continuous pain
 Begins in the back
& travels toward
bladder
 Nausea &
vomiting
• Urinary tract
complications
 Urgency
 Frequency
 Inability to urinate
 Obstruction
 Infection
Prevention & Treatment
• Drink 12-16
cups of
fluids/day
• Tea, coffee,
wine, beer
• No apple or
grapefruit
juices
Other Dietary Measures
• Consume enough calcium to control
oxalate absorption
• Restrict dietary oxalate & purine
• Moderate protein intake
• Sodium restriction
Dialysis
How Does Dialysis Work?
• Employs diffusion, • If substance is
osmosis, &
higher in the
ultrafiltration
dialysate,
substance will
• If a substance is
diffuse into the
lower in dialysate,
blood
substance will
diffuse out of the
• Ultrafiltration
blood
removes fluid
from the blood
Dialysis
• Hemodialysis
 Lasts 3-4 hours
 3 times/week
 Complications
•
•
•
•
•
•
•
Infections
Blood clotting
Hypotension
Muscle cramping
Headaches, weakness
Nausea & vomiting
Agitation
• Peritoneal dialysis
 Vascular access not
required
 Fewer dietary
restrictions
 Can be scheduled
when convenient
• Acute failure
 Continuous renal
replacement
therapy (CRRT)