27glomerular and tubular dysfunctions
DESCRIPTION
variations in glomerular filtration and tubular reabsorption, common abnoralities.TRANSCRIPT
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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
filtration koefficient (Kf)surface area
permeability
GFR = Kf x NFP
NFP = PGC – PT – GC
24 = 60 - 15 - 21 mmHg
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Disturbances of glomerular function (1)
A. Decrease of glomerular filtration
• renal blood flow stenosis of renal artery
• glomerular capillary hydrostatic pressure (PGC)hypovolemia, circulatory shock
• hydrostatic pressure in Bowman´s 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, creatinín2.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 limbof 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
A. Disturbances of water reabsorption- diabetes insipidus
B. 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:1. Hypovolemia and R-A-A activity
- small glomerular abnormalities
2. 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