Sonja Benn

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Sonja Benn

• Why Do We Not All Have Proteinuria? An Update of
  Our Current Understanding of the Glomerular
  Barrier
• Borje Haralsson and Jenny Sorensson
• How Does the Kidney Filter Plasma?
• Karl Tryggvason and Jorma Wartiovaara

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Objectives

• Structure of the Glomerulus
• Proteinuria
• Glomeular Disease
• Article Review

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Kidney

• Your kidneys weigh about 0.5 of your total body
  weight
• Each kidney is 4-5 long and about 2 thick
• Blood flows into the kidney at a rate of about
  1,000-1,200 ml per minute
• Represents 20-25 of the cardiac output
• Everyday your kidneys processes 200 quarts of
  blood to sift out about 2 quarts of waste
  products and extra water

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NephronThe Basic Functional and Structural Unit
of the Kidney

• The nephron consists of
• Bowman's capsule-Located at the closed end, the
  wall of the nephron is pushed in forming a
  double-walled chamber which surrounds the
  Glomerulus.
• Glomerulus-A capillary network within the
  Bowman's capsule.
• Proximal convoluted tubule-Coiled and lined with
  cells carpeted with microvilli and stuffed with
  mitochondria.
• Loop of Henle-A U-shaped turn, with a descending
  limb and an ascending limb
• Distal convoluted tubule-highly coiled and
  surrounded by capillaries.
• Collecting tubule-It leads to the pelvis of the
  kidney from where urine flows to the bladder

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Glomerulus-Main Filter of the Nephron

• Capillary Endothelium-contains numerous open
  fenestrations that allow the free filtration of
  substances w/diameters up to 100nm(excludes
  bloods cells and large plasma)
• Glomerular Basement Membrabe(GBM)-made up of
  fibrous proteins which intertwine to form a
  structural meshwork . The crossed fibers act as
  a size barrier and restrict the filtration of
  large molecules. Has been considered to be the
  primary size and charge selective macromolecular
  filter
• Slit Membrane/Diaphragm-located between the foot
  processes of the epithial podocytes. The
  openings are approx 25-60nm wide and are covered
  by a thin diaphragms. The narrow slits combined
  with the negative charge of the podocytes provide
  the final barrier to molecule movement.

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Glomerulus-Main Filter of the Nephron

• 1 million glomeruli in each kidney
• Bundle of capillaries that are highly porous
• Separates particles based on molecular size,
  electrical charge, protein binding,
  configuration, and rigidity
• Small molecules w/less than 7,000 Daltons are
  filtered w/o restriction
• Water, sodium, potassium, magnesium, calcium,
  phosphate
• Larger molecules are filtered to a lesser degree
• Myoglobin-approx 17,000 Daltons
• Very large molecules are restricted
• Plasma proteins-approx 70,000 Dlatons
• The filtration barrier has a net negative
  electrical charge, the movement of large
  negatively charged molecules is restricted more
  than molecules with a positive or neutral charge
• Drugs, ions, or small molecules that are protein
  bound are not filtered easily
• Round molecules do not filter as easily as
  ellipsoid
• The more rigid a molecule the less easily it
  filters

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ProteinuriaThe presence of excess serum proteins
in the urine

• It is often due to increased filtration of
  albumin and other macromolecules across the
  glomerular basement membrane. This occurs because
  of an alteration in both the charge selectivity
  and size selectivity of the glomerular barrier.
• The level and type of proteinuria strongly
  determine the extent of damage and whether you
  are at risk for developing progressive kidney
  failure
• Microalbuminuria-?Full-Fledged Proteinuria
• You may have proteinuria without noticing any
  signs or symptoms. Testing is the only way to
  find out how much protein you have in your urine
• People with diabetes, hypertension, or certain
  family backgrounds are at risk for proteinuria
• If you have diabetes and/or hypertension, the
  first goal of treatment will be to control your
  blood glucose and blood pressure
• ACE inhibitors or ARBs
• Physiologic proteinuria may occur with exercise
  and fever

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Glomerular Diseases

• Allows protein and red blood cells to leak into
  the urine. Sometimes interfering with the
  clearance of waste products, therefore these
  water products begin to build up in the blood
• The signs and symptoms of glomerular disease
  include
• proteinuria large amounts of protein in the
  urine
• Proteinuria may cause foamy urine
• hematuria blood in the urine
• Blood may cause the urine to be pink or
  cola-colored.
• reduced glomerular filtration rate inefficient
  filtering of wastes from the blood
• hypoproteinemia low blood protein
• edema swelling in parts of the body
• Edema may be obvious in hands and ankles,
  especially at the end of the day, or around the
  eyes when awakening in the morning

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Glomerular Diseases

• Autoimmune Diseases
• Systemic Lupus Erythematosus
• Goodpastures Syndrome
• IgA Nephropathy
• Hereditary Nephritis
• Alport Syndrome
• Infection-related
• Acute post-streptoccal glomulonephritis
• Bacterial endocarditis
• HIV
• Sclerotic Diseases
• Glomerulosclerosis
• Diabetic Nephropathy
• Focal Segmental Glomerulosclerosis

• Other
• Membranous Nephropathy
• Minimal Change Disease

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Normal Glomerulos
Diabetic Nephropathy
Post-Streptococcal Glomerulonephritis
Congenital Nephrotic Syndrome of the Finnish Type
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Article Review

• Why Do We Not All Have Proteinuria?
• Is the slit diaphragm the important element for
  restriction of fluid and protein transport?
• What are the true dimensions of the slit
  diaphragm?
• What is the function of the endothelial cell
  surface coat?
• The need for more information and treatment on
  various glomerular disorders..

• How Does the Kidney Filter Plasma?
• Determine the role of GBM proteoglycans in filter
  function?
• Is the slit diaphragm the ultimate size-selective
  macromolecular filter?
• Why does it not clog?
• Rigid possibly cross-linked structure or a
  flexible membrane that can relatively easily open
  to allow free passage of large protein(due to
  increased BP or GF)?
• Zipper-like vs sheet-like for the slit diaphragm?