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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