Glomerular and tubular dysfunctions

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Glomerular and tubular dysfunctions

• Tatár M.

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Basic kidney functions

• Water and electrolyte homeostasis
• Acid base balance
• Elimination of waste products and ingested
  chemicals
• Hormone production

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Mechanisms of renal excretion

• 180 l glomerular filtrate per day (2 ml/s)
• 99 - back reabsoption
• Renal perfusion at rest 20 of cardiac output
  (this is higher than in heart, brain and liver

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Glomerular filtration rate

• Balance of hydrostatic and osmotic pressures
  acting across diffusion barrier (endotelium
  fenestrae, basement nenbrane, slit diaphragms
  betweens the podocytes)
• Factors determining GFR
• Surface area (1 milion nephrons within each
  kidney)
• Permeability
• Net filtration pressure (NFP) across diffusion
  barrier

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Factors determining GFR
surface area permeability
filtration koefficient (Kf)
GFR Kf x NFP
NFP PGC PT ?GC
24 60 - 15 - 21 mmHg
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Disturbances of glomerular function (1)

• Decrease of glomerular filtration
• ? renal blood flow
• stenosis of renal artery
• ? glomerular capillary hydrostatic pressure (PGC)
• hypovolemia, circulatory shock
• ? hydrostatic pressure in Bowmans capsule (PT)
• block of fluid flow ( intra- and extrarenal)
• ? concentration of plasma proteins (?GC)
• ? Kf
• ? effective filtration surface area

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Disturbances of glomerular function (2)

• B. Increase of glomerular permeability
• Proteinuria
• Glomerular proteinuria
• Size-selective properties of the glomerulus
• Charge-selective propeties of the glomerulus
• Hamodynamic forces operating across the
  glomerulus

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Glomerular proteinuria

• Selective proteinuria
• Albumin
• Small amount of low-molecular globulins
• Non-selective proteinuria
• Albumin
• Globulins of various molecular weight

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Tubular reabsorption of proteins
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Tubular proteinuria

• ? excretion of low molecular proteins
• ?1-microglobulin, ?2-microglobulin

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Overload (prerenal) proteinuria

• Small molecular weight proteins can rise when are
  synthetised in excess
• Tissue degraded products
• Proteins of acute phase (pyretic proteinuria)
• Myoglobin (rhabdomyolysis)
• Ligfht immunoglobulin chains (myeloma)

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Proteinuria

• Healthy adult subject
• No more than 150 mg/day
• Small proteinuria
• 1 g/day
• Haevy proteinuria
• 3,5 g/day and more
• Nephrotic syndrome (10 30 g/day)

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Renal hematuria

• Glomerular
• Abnormally increased permeability
• Non-glomerular
• Rupture of tumor or cyst vessels
• Bleading from urinary tract

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Relation between the reduction of GFR and
excretion function of kidneys

• ? GF ? ? retention of substrates
• 1. urea, creatinín
• 2. phosphates, K, H
• 3. NaCl

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Tubular reabsorption and secretion
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Active transport
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Reabsorption of glucose, amino acids, Na, K, Cl,
H2O
Proximal tubule
Thick ascending limb of loop of Henle
Distale tubule
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Disturbances of tubular functions

• Tubular proteinuria
• Glucosuria
• Aminoaciduria
• Diabetes insipidus
• Neurogenic (? ADH)
• Nephrogenic (insensitivity of the renal tubule to
  ADH)
• Osmotic diuresis
• Pressure of large quantities of unreabsorbed
  solutes in the renal tubules ? increase in urine
  volume
• Unreabsorbed solutes in the proximal tubules
  hold water in the next tubules

Transport maximum
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Hydrogen ion secretion and bicarbonate
reabsorption
Renal tubular acidosis - impairment of the
ability to make the urine acidic - chronic
renal disease reduction of secreted hydrogen
ion because of impaired renal tubular
production of NH4
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Loop of Henle and production of concentrated urine
- Permeability for water and NaCl - ADH
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Counter-current exchange in the vasa recta
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Disturbances of kidney ability to concentrate
urine

• Disturbances of water reabsorption
• - diabetes insipidus
• Disturbances of the production of medullar
  hyperosmolarity
• - osmotic diuresis
• - ? blood flow in vasa recta
• - morphologic deformations of medulla

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Nephrotic syndrome

• Proteinuria 3.5 g or more of protein in the
  urine per day
• Minimal changes of glomerular membrane 90
  albumin (selective proteinuria)
• Hypoproteinemia (hypoalbuminemia)
• Mechanisms proteinuria
• Protein loss by stool
• Plasma proteins are shifted to extravascular
  space
• Increased albumin katabolism
• Inadequately increase albumin synthesis in liver
• Hyperlipidemia
• Incresed lipoprotein synthesis in liver
• Generalised edema

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Mechanisms of edema in nephrotic syndrome (NS)

• Classis theory
• Hypoalbuminemia ? ? plasma oncotic pressure ?
  hypovolemia ? R-A-A ADH ? Na water retention
• !!! But hypovolemia is present only in 30 of
  patients suffering from NS plasma renin activity
  and aldosteron are decreased
• Two groups of patients with NS
• Hypovolemia and ? R-A-A activity
• - small glomerular abnormalities
• Hypervolemia without R-A-A activation
• - more serious morphological abnormalities

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Pathophysiology of edema formation

• Extracellular fluid volume is determined by the
  balance between Na intake and its renal excretion
• Common feature renal salt retention despite
  progressive expaansion of ECF volume
• Primary abnormality of the kidney
• Secondary response to some disturbances in the
  circulation

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Primary edema (overfill)

• Primary defect in renal sodium excretion
• Hyperevolemia leads to high cardiac output
• ? R-A-A, ? ADH, ? sympathetic activity
• Examples blomerulonephritis, renal failure

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Secondary edema (underfill)

• Response of normal kidnay to actual or sensed
  underfilling of the circulation
• Primary disturbances within the circulation
  secondary triggers renal sodium retention
• ? R-A-A, ? ADH, ? sympathetic activity
• Effective arterial blood volume