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Physiology

Renal

Question 14 of 180

Molecules with a molecular weight of less than which of the following are filtered freely at the glomerular filtration barrier:

Answer:

Molecular weight is the main factor in determining whether a substance is filtered or not - molecules < 70oo Da in molecular weight are filtered freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70000 Da, above which filtration is insignificant. Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69000 Da and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma.

Glomerular Filtration Barrier

Structure of the Glomerulus

The glomerulus is a ball of capillaries surrounded by the Bowman's capsule.

The glomerulus is interspersed with mesangial cells which act to:

  • provide structural support for the capillaries
  • exhibit phagocytic activity
  • secrete extracellular matrix
  • secrete prostaglandins
  • help regulate blood flow through the glomerular capillaries through their contractile activity

Structure of the Glomerulus. (Image by OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)])

Glomerular Filtration Barrier

Plasma is selectively filtered through the glomerular capillary wall into the Bowman's capsule. The solution that arrives in the Bowman's capsule is called ultrafiltrate which then passes into the proximal tubule.

Selective filtration is dependent on the filtration barrier, which has three main layers:

  1. The glomerular capillary endothelium
    • Perforated by pores (fenestrations) which allow plasma components with a molecular weight of < 7000 Da to pass freely.
  2. A specialised capillary basement membrane
    • Layer of connective tissue containing negatively charged glycoproteins, thought to be the main site of ultrafiltration.
  3. Modified epithelial lining of the Bowman's capsule
    • Single layer of specialised cells called podocytes which have long extensions that engulf the capillaries and numerous foot-like processes (pedicels) directly contacting the basement membrane. The regular gaps between pedicles are called filtration slits. Across these slits, a protein network forms slit pores in the epithelial lining which prevent the passage of larger molecules through this final layer. Podocytes maintain the basement membrane and, like mesangial cells, may be phagocytic and partially contractile.

Glomerular Filtration Barrier. (Image modified by FRCEM Success. Original image by MKomorniczak [CC BY-SA 3.0 , via Wikimedia Commons)

Glomerular Filtration Barrier. (Image modified by FRCEM Success. Original image by MKomorniczak [CC BY-SA 3.0 , via Wikimedia Commons)

Factors affecting Permeability of the Filtration Barrier

Molecular weight is the main factor in determining whether a substance is filtered or not - molecules < 7000 Da in molecular weight pass freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which filtration is insignificant.

Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69 kDa and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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