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Renal function & dysfunction: a summary
Dr. Madanmohan. MD, DSc, FIAYProf & Head, Dept. of Physiology
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Scheme of my talk
• Functions of kidneys• Renal function in children• Regulation of renal function• Causes of renal dysfunction• Consequences of impaired renal function• Renal function tests: classification description 2
Function(s) of kidneys ?
functions are related to structure
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Functions of kidneys ?Function related to structure
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Juxtaglomerular apparatus
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Defence of milieu interieur and homeostasis:
1. Electrolyte and water balance 2. Acid–base balance: pH: arterial plasma: 7.38–7.42, urine: 4.3–8.0 3. Excrete unwanted toxic substances Metabolites: H+, urea, u.acid, creatinine, bilirubin Drugs: trimethoprim, amoxycillin, erythromycin Heavy metals: Au, Pb, Li, Cd, Hg.
“Death due to renal failure”
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• GFR : 125 ml / min or 180 L/d
• Reabsorption (per day): Fluid: 178.5 L Glucose : 200 g; NaCl: 1kg
• Urine : 1.5 L / d
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Normal urine• 1500 (800 – 2500) ml/d. <500 ml : oliguria
• SG: 1022 – 1030 (1003 – 1032)
• Normal constituents: urea, uric acid, creatine, creatinine
• Abnormal constituents:protein, glucose, ketone bodies, bilirubin, blood 9
Non-excretory functions:
1. Regulation of BP: ECF volume, renin-angiotensin
2. Endocrine function: renin, erythropoietin, 1,25-DHC, natriuretic hormone, PGs
3. Regulation of pH, H2O & electrolyte balance10
Renal function in children
• Infants: nephrons incompletely developed
• Less BP, RBF, GFR, reabsorption, secretion
• Inulin clearance : 25%
• Urine acidic, albumin often present
• Less responsive to hormones11
Contd…
Renal function in children
Urine output:• First 2 days: 20 ml• 12th day : 225 ml• ~10 y: near adult values
• Narrow margin, especially in premature
• Diarrhea, vomiting, fever, hyperthermia: cannot concentrate urine 12
…Contd
Regulation of renal function• Autoregulation
• Neural and reflex regulation:– Rich sympathetic innervation– Exercise, shock: vasoconstriction
• Humoral regulation
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Humoral regulation• ADH: water reabsorption
• Aldosterone: Na reabsorption in DCT
• PTH: Ca reabsorption & PO4 excretion
• Thyroxine: renotropic
• Glucocortocoids: for normal response to ADH
• PGs: modulate effect of other hormones 14
Causes of renal dysfunction1. Acute renal disease : infection, ischemia
2. Chronic renal disease : chronic glomerulonephritis, tuberculosis, obstruction, polycystic kidney
3. Acute on chronic acute renal failure
4. Resection: 1 kidney compatible with life. ½ kidney ?
HT, DM CKD15
Consequences of impaired renal function
1. Retention of waste products in blood: H+, K+, urea, uric acid, creatine, creatinine
2. Abnormal constituents in urine: protein, cells, casts
3. Decreased ability to concentrate/dilute urine
4. End organ damage. Multi system dysfunction
5. Clinical features: edema/dehydration, increase BP, anemia/polycythemia, decreased immunity 16
Renal failure
• Acute: H, K, urea (900 mg%). Disturbed milieu interieur. Death in 5–7 d.
• Chronic: loss of nephrons (>70%) DM, HT, chronic infections, polycystic kidney.
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Classification of RFTs(battery of tests)
Direct measurement is difficult: clearance
Indirect estimation is simple: blood chemistry
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1. Clearance techniques.
2. Measure maximum tubular transport: TmG, TmPAH, TmPO4
3. Assessment of functional state: i) dilution test ii) concentration test iii) acidification test
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Classification of RFTs
Contd…
4. Blood constituents (biochemistry)Plasma concentration is
inversely proportional to clearance
Waste products: urea, uric acid, creatine, creatinine
Electrolytes : H+, K+, Na+, Cl-
5. Urine: macroscopic, microscopic, chemical inexpensive & useful
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Classification of RFTs
Contd…
…Contd
6. Clinical examination
7. Biopsy
8. Experiments: animals
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…Contd
Clearance studies
• Definition• GFR• RPF• Amount reabsorbed• Amount secreted
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Filtered
Secreted
Reabsorbed
GFR by inulin clearance• Amount in urine = amount filtered
Uin x V = Pin x GFR
GFR = Uin x V / Pin
= 120 ml / 1.7 m2
Curea : 75 ml Ccreatinine : ~150 ml 26
RPF by PAH clearance
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PAH: filtered + secreted
UPAH x V / PPAH
Tubular secretion (PAH)
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Amount in urine = amount filtered + amount secreted
Amount secreted = amount in urine - amount filtered
UPAH X V - GFR X PPAH
Tubular reabsorption (glucose)
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Glucose: filtered & reabsorbed
Amount in urine = amount filtered – amount reabsorbed
Amount reabsorb = amount filtered – amount in urine
Dilution test• Excretion of H2O load: hourly samples
• H2O: 2% of body wt in 20 – 30 min, ~ 7 AM
(70 kg x 20 ml = 1400 ml)• Urine at 8, 9, 10 AM• One sample SG <1003 ( N: 1022 – 1030 )• Within 3-6 h, all the input should come out
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Concentration (Addis) test• Dry meals for 18 h, no fluids from 8 PM to 8 AM
• SG: >1025, >700 mOsm/L
• Simple, but crude test
• Early detection of renal disease
• Contra-indications: hot weather, dehydration, diuresis/polyurea (DM), adrenal insufficiency31
Acidification test
• NH3Cl : 0.1 g / kg orally
• Hourly urine samples for 8 h
• About 6 h : pH < 5.3(normal pH : 4.3 – 8)
• > 8 pH : urinary infection32
Imaging• Plain X ray• Ultrasonogram• CT, MRI• IVP• Retrograde pyelography• Renal arteriography (angiography)• Radiorenogram: 125I 131I - hippuran
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Renal biopsy• For exact histological details• Contraindications: i) one kidney ii) bleeding tendency iii) carcinomas iv) renal cyst (large) v) malignant hypertension vi) perinephric abcess 34
• Electrophysiological studies: transtubular, transcellular potentials
• Stop / flow studies
• Micropuncture & microperfusion
• Microcryosopic studies
• Tissue slice experiments35
Experimental studies
Thank you
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