Anatomy of the nephron
- The basic structural and functional unit of the kidney
- Filters and cleanses the blood and produces urine
- Each kidney contains > 1 million nephrons.
Parts of nephron:
- Afferent arteriole: renal artery arteriole that enters the glomerulus
- Efferent arteriole: renal artery arteriole that exits the glomerulus
- Glomerulus: capillary tuft that receives its blood supply from an afferent arteriole of the renal circulation
- Bowman capsule: surrounds the glomerulus
- Renal tubule: coiled tube that converts blood filtrate into urine.
- Proximal convoluted tubule (PCT): portion close to the glomerulus in the renal cortex
- Loop of Henle: forms a loop (with descending and ascending limbs) that goes through the renal medulla
- Distal convoluted tubule (DCT): portion of the tubule restricted to the renal cortex
Physiology of urine production
Urine is a waste by-product composed of excess water and metabolic waste filtered out of the bloodstream by nephrons. Urine formation is a stepwise process.
- Glomerular filtration:
- The kidneys filter about 180 L of plasma per day (125 mL/min).
- Takes place inside glomerulus
- Water and nitrogenous waste are filtered out of the blood and form glomerular filtrate.
- Nonfilterable components exit the glomerulus via the efferent arteriole.
- Tubular reabsorption:
- Reabsorption of nutrients shed by glomerulus
- Occurs in the PCT
- Can be passive (along gradients) or active (using ATP-generated energy)
- Water and electrolyte reabsorption hormonally regulated
- Tubular secretion:
- Undesirable products like metabolic wastes, urea, uric acid, and certain drugs
- Most of the tubular secretion happens in the DCT.
Serologic Parameters of Renal Function
Creatinine and estimated glomerular filtration rate (eGFR)
The most commonly used marker to assess kidney function is the measurement of excreted creatinine, based on which the eGFR can be calculated.
- Creatinine: by-product of creatine phosphate metabolism in muscle:
- Produced at a constant rate by the body
- Amount produced per day depends on muscle bulk and meat consumption
- Cleared from the blood entirely by the kidney
- Commonly used endogenous marker for assessment of glomerular function: calculated clearance of creatinine → eGFR
- Mean serum values:
- Dependent on sex and ethnicity
- 1.13 mg/dL for men (higher muscle mass and creatinine excretion)
- 0.93 mg/dL for women (lower muscle mass and creatinine excretion)
- Mean values have been shown to be higher in non-Hispanic Black Americans → considered when calculating the eGFR
- Creatinine clearance should be corrected for body surface area.
- Creatinine clearance overestimates GFR by around 10%–20% because of tubular secretion.
Glomerular filtration rate (GFR)
- The most exact overall indicator of glomerular function
- Rate (in milliliters per minute) at which a substance in plasma is filtered through the glomeruli
- Commonly measured by administering inulin:
- Polysaccharide that cannot be broken down and is completely filtered
- Used as a marker by measuring rate at which it appears in the urine
- Time-consuming and expensive to measure → performed only in specialized centers
Blood urea nitrogen (BUN)
- Normal metabolic processes (including the urea cycle) result in the production of nitrogen-rich ammonia in the liver.
- Ammonia is further refined to urea and excreted primarily (85%) by the kidneys.
- Measurement of urea excretion as a marker of kidney function is less accurate than creatinine but increases earlier in renal disease.
- Other pathological states may lead to elevated urea excretion:
- Upper GI bleeding
- Catabolic states
- High protein diets
Ratio of BUN:creatinine
Provides more useful information than either tests alone:
- Distinguish prerenal from renal causes of kidney failure
- In prerenal disease, ratio is close to 20:1
- In intrinsic renal disease, ratio is closer to 10:1
- Low-molecular-weight protein, functions as a protease inhibitor
- Cystatin C is measured in serum and urine: normally not found in urine.
- Serum levels of cystatin C are inversely correlated with the glomerular filtration rate (GFR).
- Formed at a constant rate→filtered by the kidneys→ reabsorbed and metabolized by proximal renal tubules
- Less dependent on age, gender, ethnicity, diet, and muscle mass compared to creatinine
- May be more specific than creatinine for estimation of GFR
There are 3 basic components to urinalysis:
- Gross examination
- Chemical evaluation (usually done using urine dipstick)
- Microscopic examination
- Turbidity: a visual evaluation of how cloudy the urine appears
- Yellow-amber: normal
- Yellow-cloudy: infectious causes (pyuria)
- Orange: dehydration
- Red: hemolysis
- Dark brown: myoglobinuria (due to rhabdomyolysis)
- Brownish black to black: alkaptonuria
- Green, or dark with a greenish hue: jaundice (bilirubinuria)
- Nitrite: indicates the presence of coliform bacteria
- Leukocyte esterase: indicates the presence of WBCs
- Albuminuria: increased permeability of glomerulus, usually secondary to chronic diseases such as diabetes mellitus
- hCG: appears during pregnancy in females and testicular cancer in males
- pH: Normal range is 4.5–8; elevated or decreased urine pH levels are associated with kidney stones or infections.
- Specific gravity:
- Detects the ion concentration of urine
- Value < 1.010 indicates diluted urine.
- Value > 1.020 indicates concentrated urine.
- Glucose (glucosuria), seen in diabetes mellitus
- Ketone bodies, seen in diabetic ketoacidosis
- Bilirubin: increased due to RBC hemolysis and liver damage
- Urobilinogen: Increased levels are seen in liver damage.
- RBCs (hematuria): various renal, bladder, or urethral etiologies
- Acanthocytes: dysmorphic RBCs seen in glomerular disease
- RBC casts: seen in glomerulonephritis or hypertensive emergency
- WBCs: infectious causes (pyuria)
- Urinary casts:
- Microscopic cylindrical structures formed in the DCT and collecting ducts of the kidneys
- Present in the urine in certain disease states
|Epithelial cell casts|
|Fatty casts||Nephrotic syndrome|
|Granular, muddy brown casts||Acute tubular necrosis (ATN)|
The following conditions are associated with abnormal kidney function tests:
- Acute renal failure: classified into prerenal, intrinsic, and postrenal categories, depending on the etiology. Acute renal failure is marked by decreased urine output, metabolic acidosis, fatigue, confusion, and nausea. Laboratory test shows elevated creatinine levels.
- Chronic kidney disease: characterized by progressive deterioration of renal function. Associated symptoms and findings of CKD include fatigue, water retention, pruritus, muscle weakness, confusion, and peripheral neuropathy. Treatment includes hemodialysis or peritoneal dialysis and renal transplantation in combination with supportive measures.
- Tumor lysis syndrome: complication of cancer treatment when large amounts of cells are suddenly lysed as a result of chemotherapy. Tumor lysis syndrome usually occurs with acute leukemias and non-Hodgkin’s lymphomas but can also occur with other hematologic malignancies or solid tumors. The syndrome can lead to AKI in association with a number of metabolic abnormalities (hypocalcemia, hyperphosphatemia, hypokalemia, elevated uric acid). Uric acid–lowering medications can prevent the syndrome and should be initiated prior to chemotherapy.
The following conditions are associated with abnormal urinalysis:
- Glomerulonephritis: Acute glomerulonephritis is defined as glomerular injury that is accompanied by inflammation of the glomeruli. Acute glomerulonephritis is a clinical constellation of sudden onset of hematuria and proteinuria, edema, and hypertension with or without RBC casts and can be due to a number of underlying pathologies, such as infection, connective tissue disorders, drug toxicity, hematologic dyscrasias, glomerular basement membrane diseases, and hereditary disorders.
- Rhabdomyolysis: clinical syndrome characterized by the breakdown of skeletal muscle. The acute release of muscle protein (myoglobin) into the circulation is followed by myoglobinuria, which can lead to AKI. Rhabdomyolysis can follow trauma, sepsis, or exposure to drugs. The diagnosis is established by history and the finding of elevated CK in the serum.
- Diabetic ketoacidosis: acute metabolic complication of diabetes characterized by hyperglycemia (> 11 mmol/L), ketonemia (> 31 mg/mL)/ ketonuria (3+), and metabolic acidosis (pH < 7.3). Diabetic ketoacidosis occurs mostly with type 1 diabetes mellitus. Treatment involves insulin, IV fluids, and prevention of hypokalemia.
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