Renal Pathophysiology III :

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Renal Pathophysiology III

• Diseases that affect the kidney and urinary tract
• Acute and chronic renal failure

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Plumbing Problems

• Kidney Stones
• Calcium
• Cystine
• Struvite
• Vesicoureteral Reflux

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Struvite Bladder Stones from a Dog
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Acute Renal Failure

• Defined by increases in serum creatinine and
  urea, reflecting decreased GFR
• Creatinine is used as an indicator of GFR
• Urea is passively reabsorbed in the renal
  tubules. More urea in the blood indicates less
  urea is being filtered.
• Normal Values
• plasma creatinine 1 mg/dl
• plasma urea (BUN) 8-25 mg/dl

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Causes of Acute Renal Failure

• Pre-renal kidneys ok, but blood flow/suppy is
  reduced, resulting in decreased GFR.
• Intrarenal usually result of acute tubular
  necrosis
• Post-renal results from obstruction of urinary
  tract (eg kidney stone).

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Risk Factors for CKD

• Hypertension
• Diabetes
• Autoimmune diseases
• Low birthweight
• Exposure to certain drugs,
• Genetic factors eg polycystic kidney disease
• Socioeconomic risk factors include
• Older age
• African American, Native American or Hispanic
  ethnicity,
• Low income/education.

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Polycystic Kidney Disease
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Autoimmune Disease Example Lupus (SLE)

• Cause of SLE is unknown, genetic and immune
  factors involved.
• Autoantibodies against many cellular components,
  including DNA, and other molecules in the nucleus
  and cytoplasm of cells are produced
• Characterized by flares followed by periods of
  remission.
• 90 of cases are in women of childbearing age.

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Renal Damage from Lupus

• In the renal system, damage results largely from
  deposition of antigen-antibody immune complexes
  in the glomeruli.
• This leads to the appearance of protein in the
  urine, and can cause acute renal failure.

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Antigen-Antibody Complex
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Deposition in Tissues Leads to Inflammation
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Diabetic Nephropathy

• Diabetics have abnormal thickening of the
  mesangial matrix, the material that surrounds and
  supports the glomerular capillaries.
• Diabetics also tend to have atherosclerosis.
  When it affects the renal artery, it can decrease
  renal blood flow, further lowering the GFR.

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Normal Protein Handling by Kidney
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Proteinuria

• Glomerular proteinuria altered size and change
  function of glomerular barrier
• Tubular proteinuria altered reaborption
• Overload proteinuria excessive filtered load

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Nephrotic syndrome

• protein in urine greater than 3g/day
• decreased protein concentrations in the plasma
• edema
• excess lipids in the plasma
• Characteristic of SLE and diabetic nephropathy.

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Edema in Nephrotic Syndrome
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Chronic Renal Failure

• Results from irreversible, progressive injury to
  the kidney.
• Characterized by increased plasma creatinine and
  urea, indicating decreased GFR, as well as loss
  of hormonal functions of the kidney.

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Consequences of Kidney FailureProblems with Na
and Water Balance

• Na handling can lead to hypo- or hypernatremia
• If GFR is low, and salt intake is high, the
  kidneys cannot excrete enough salt and salt is
  retained.
• But, if the salt intake is very low, the
  diminished capacity of the tubule to reabsorb
  sodium can lead to excessive sodium loss and
  hyponatremia.
• Water handling
• The ability of the kidney to generate the osmolar
  gradient that allows for excretion of
  concentrated or dilute urine is compromised.
• Problems of osmolarity (hypo or hypernatremia)
  occur if the patients drink too much or too
  little water.
• Consequences
• Hypertension
• Edema

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Other Consequences of Renal Failure

• Uric Acid retention
• may result in gout or arthritis, also causes
  itchiness and rash.
• Potassium Handling
• Potassium excretion increases with GFR. Big
  reductions in GFR result in inability to excrete
  K, and increased plasma potassium results.
• This can result in cardiac arrthymias.
• Acid Base Status
• Normal metabolism results in the formation of
  acid, which is normally excreted in the urine.
• When the GFR gets low enough, acids cannot be
  excreted and plasma pH drops (i.e. the
  concentration of H ions increases).
• Buildup of Drugs and Toxins
• The kidney is a major site of excretion of many
  drugs.
• Patients with reduced kidney function have a
  reduced ability to excrete these and they may
  build up in the blood.

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Still Other Consequences of Renal Failure

• Calcium metabolism
• Failure to activate vitamin D decreases calcium
  absorption in the gut
• Causes breakdown of bone
• Also, failure to excrete phosphate leads to
  formation of calcium phosphate salts in soft
  tissues, which further lowers plasma calcium
  levels.
• Hormonal abnormalities
• The kidneys help clear the body of insulin, so
  patient with renal failure often have
  hyperinsulinemia.
• Sex steroid levels are low, often causing
  amenorrhea in women and impotence in men.
• Anemia
• The kidney is the site of production of
  erythropoetin, a hormone necessary to the
  formation of red blood cells.
• Neurologic effects
• Build up of toxins can cause seizures, and other
  neurologic problems
• Gastrointestinal consequences
• Nausea and vomiting resulting from electrolyte
  disturbances.

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Treatment of Chronic Renal Failure Dialysis

• Hemodialysis must go to a clinic about 3 times
  per week for about 4 hours
• Peritoneal Dialysis more frequent, but can be
  done at home
• Also Transplantation

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Hemodialysis
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Peritoneal Dialysis