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Renal function & dysfunction:
a summary
Dr. Madanmohan. MD, DSc, FIAY
Prof & Head, Dept. of Physiology
1
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
3
Functions of kidneys ?
Function related to structure
4
5
Juxtaglomerular apparatus
6
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”
7
• 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
8
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 balance
10
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 hormones 11
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
13
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 dysfunction
1. 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  CKD
15
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.
17
Classification of RFTs
(battery of tests)
Direct measurement is difficult: clearance
Indirect estimation is simple: blood chemistry
21
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
22
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
23
Classification of RFTs
Contd…
…Contd
6. Clinical examination
7. Biopsy
8. Experiments: animals
24
…Contd
Clearance studies
• Definition
• GFR
• RPF
• Amount reabsorbed
• Amount secreted
25
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
27
PAH: filtered + secreted
UPAH x V / PPAH
Tubular secretion (PAH)
28
Amount in urine = amount filtered + amount
secreted
Amount secreted = amount in urine - amount
filtered
UPAH X V - GFR X PPAH
Tubular reabsorption (glucose)
29
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
30
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 infection
32
Imaging
• Plain X ray
• Ultrasonogram
• CT, MRI
• IVP
• Retrograde pyelography
• Renal arteriography (angiography)
• Radiorenogram: 125
I 131
I - hippuran 33
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 experiments 35
Experimental studies
Thank you
36

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Renal func &amp; dysfunc may 2016

  • 1. Renal function & dysfunction: a summary Dr. Madanmohan. MD, DSc, FIAY Prof & Head, Dept. of Physiology 1
  • 2. 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
  • 3. Function(s) of kidneys ? functions are related to structure 3
  • 4. Functions of kidneys ? Function related to structure 4
  • 5. 5
  • 7. 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” 7
  • 8. • 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 8
  • 9. 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
  • 10. 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 balance 10
  • 11. 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 hormones 11 Contd…
  • 12. 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
  • 13. Regulation of renal function • Autoregulation • Neural and reflex regulation: – Rich sympathetic innervation – Exercise, shock: vasoconstriction • Humoral regulation 13
  • 14. 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
  • 15. Causes of renal dysfunction 1. 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  CKD 15
  • 16. 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
  • 17. 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. 17
  • 18.
  • 19.
  • 20.
  • 21. Classification of RFTs (battery of tests) Direct measurement is difficult: clearance Indirect estimation is simple: blood chemistry 21
  • 22. 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 22 Classification of RFTs Contd…
  • 23. 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 23 Classification of RFTs Contd… …Contd
  • 24. 6. Clinical examination 7. Biopsy 8. Experiments: animals 24 …Contd
  • 25. Clearance studies • Definition • GFR • RPF • Amount reabsorbed • Amount secreted 25 Filtered Secreted Reabsorbed
  • 26. 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
  • 27. RPF by PAH clearance 27 PAH: filtered + secreted UPAH x V / PPAH
  • 28. Tubular secretion (PAH) 28 Amount in urine = amount filtered + amount secreted Amount secreted = amount in urine - amount filtered UPAH X V - GFR X PPAH
  • 29. Tubular reabsorption (glucose) 29 Glucose: filtered & reabsorbed Amount in urine = amount filtered – amount reabsorbed Amount reabsorb = amount filtered – amount in urine
  • 30. 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 30
  • 31. 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
  • 32. 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 infection 32
  • 33. Imaging • Plain X ray • Ultrasonogram • CT, MRI • IVP • Retrograde pyelography • Renal arteriography (angiography) • Radiorenogram: 125 I 131 I - hippuran 33
  • 34. 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
  • 35. • Electrophysiological studies: transtubular, transcellular potentials • Stop / flow studies • Micropuncture & microperfusion • Microcryosopic studies • Tissue slice experiments 35 Experimental studies