Renal Pathophysiology III :

Diseases that affect the kidney and urinary tract

Acute and chronic renal failure

Plumbing Problems

• Kidney Stones– Calcium– Cystine– Struvite

• Vesicoureteral Reflux

Struvite Bladder Stones from a Dog

Stages of Vesicoureteral Reflux

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

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).

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.

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.

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.

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.

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

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.

DAMAGE TO GLOMERULUS

LOSS OF PROTEIN IN URINE

PLASMA ONCOTIC PRESSURE (edema)

BLOOD VOLUME

BLOOD PRESSURESTIMULATION OF ATRIAL/VENOUS VOLUME RECEPTORS

STIMULATION OF CAROTID/AORTIC BARORECEPTORS

RENIN RELEASE

ANGIOTENSIN II

SALT AND WATER RETENTION (more edema)

ADH RELEASE

SYMPATHETIC ACTIVATION

Edema in Nephrotic Syndrome

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.

Consequences of Kidney Failure:Problems with Na+ and Water Balance

• Na+ handling – can lead to hypo- or hypernatremia– If GFR is low, and salt intake is high, the kidney’s 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

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.

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.

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