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Renal Function in Disease State

Assessment of Renal Function Renal Tubular Acidosis (RTA)

Glomerular Filtration Rate (GFR) Results from Ineffective Tubular Secretion of H+
(Renal Failure → ↓ GFR) Location of Defect, results in
Estimation of GFR is done from Proximal RTA Distal RTA
Plasma Urea Plasma Creatinine Creatinine Clearance Type II Type I
Measurement Bicarbonate Ion Wasting Failure to Excrete daily metabolic load of acid
Disadvantage – Urea Production rate is “Steady State” depend Associated with other
production rate Proportional to on plasma [Creatinine] proximal tubular defects
affected by Skeletal Mass May be Normal until Phosphaturia
• Protein Intake (Good if muscle mass Creatinine Clearance Glycosuria
• Cell Catabolism is constant) dropped 50% Normal Aminoaciduria
Glomerular Filter (Fanconi syndrome )
(Leakiness of glomerular filter detected by) Distal H+ secretory Able to Reabsorb Bicarbonate Ions in
Proteinuria – Presence & Quality mechanisms is intact, Proximal Tubule
(the ↑ Damage to Glomerular Filter → ↑ Molecular Weight proteins leaked) patients are capable to Cannot Acidify Urine
Haematuria produce urine of ↓ pH Urine pH always > 5.3
Examination of Urinary Deposits (< 5.3) (under any circumstances )
Tubular Function (not performed frequently, but valuable in) (during severe acidosis) (even severe systemic acidosis)
Acute Renal Failure (Acute Tubular Necrosis developed from Pre-Renal ARF) Features
Defects of Renal Con centrating Ability • Urine pH always > 5.3
Renal Tubular Acidosis • Chronic Hyperchloraemic Metabolic
Acidosis Normal Anion gap
Renal Failure • Vitamin D resistant rickets
Definition (caused by Chronic Acid osis)
↓ GFR – Impair Homeostatic Functions of Kidney • Renal Calculi & Nephrocalcin osis
Biochemical Features (Ca2+ salts precipitate out more readily
↑ Plasma Urea, Creatinine in constantly Alkaline urine)
Disturbed Na+, H2O balance (Water Retention → Dilutional HypoNatraemia) • Hypokalaemia (Defective Distal Tubular
Acidosis (Fail to excrete Acid by Kidneys) H+-Na+ ion exchange )
K+ disturbances (Potassium Retention → HyperKalaemia) (↑ Urinary Na+ loss with consequent
Ca2+, Phosphate disturbances 2° Hyperaldosteronism)
• Phosphate Retention
(↑ Phosp hate → Inhibit production of 1,25 -DHCC → ↓ GIT Ca2+ absorb)
• HypoCalcaemia (Acidosis → ↓Protein-b ound Ca2+ in serum)
(In Chronic Renal Failure, if not prevented,
can lead to Metabolic Bone Disease – Renal Osteodystrophy)
Urate Retention
2° Hyperlipidaemia
Magnesium Retention (HyperMagnesaemia)
Plasma Urea
Urea formed in Liver (from Ammonia – released by deamination of amino acid)
75% of Non-Protein Nitrogen is Excreted as Urea (mainly by Kidneys)
Small amounts loss through Skin, GIT
Causes of ↑ Plasma Urea
Pre-Renal Uraemia Renal Uraemia Post-Renal Uraemia
Impaired renal Acute Renal Failure Outflow Obstruction
perfusion Chronic Renal Failure • Ureter
(Hypovolaemia, ↓ BP) (↓ Glomerular Filtration) • Bladder
Renal vasoconstriction Plasma Urea ↑ until • Urethra
↓ GFR new steady state is Caused by
↑ ADH reached • Renal stones
RAAS activation (Urea Production = • Prostatism
(↑ Passive Tubular Excretion) • GU cancer
Reabsorption of Urea)
Shock Plasma Urea continue Back Pressure on
Burns to ↑ in Near-Total Renal Tubules
Haemorrhage Renal Failure (enhances ba ck-
Loss - H2O, Electrolyte diffusion of urea)
(severe diarrhea) (Plasma Urea ↑
Can progress to disproportionately
Intrinsic Renal Failure more than Plasma
[Creatinine])
Can damage Kidney, Can damage Kidney,
cause Renal Uraemia cause Renal Uraemia
↑ Urea Produc#on
↑ Protein Intake
↑ Protein Catabolism
• Trauma
• Major Surgery
• Starvation
Haemorrhage in GIT
(protein-meal blood )
Plasma Urea ↑ more
than Creatinine
(Tubular reabsorption
of Urea is ↑)
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Acute Renal Failure (ARF) Chronic Renal Failure (CRF)

Occur over a short period (hours or days) Develops over a long period of time (months to years)
Associated with Oliguria (urine output < 400ml/day) Destruction of Renal Parenchyma, ↓ Functional Nephron Mass
Causes of Oliguria (Results in Ischae mia, ↓ GFR, Tubular Dysfunction) Dietary load is too ↑ for Failing Kidney to excrete it, results in
Tubular Obstruction (due to cellular debris) Sodium Retention (Hypertension, Edema) (50% Nor mal GFR ↓)
Tubular Back Flow Water Retention (HypoNatraemia)
(Glomerular Filtrate Reabsorption) through damaged tubular epithelium Potassium Retention (HyperKalaemia) (60% Normal GFR ↓)
Alterations in Renal Haemodynamics Anaemia (↓ Erythropoietin produced by Kidney) (60% Normal GFR ↓)
Causes of ARF Progressive Uraemia (80% Normal GFR ↓)
Pre-Renal Renal Post-Renal H+ Total Excretion Impaired (due to ↓ renal capacity to form NH4+)
Hypovolaemia Acute Tubular Necrosis Urinary Tract
(Acute Ischaemic Re nal Failure) Obstruction Metabolic Acidosi s
↓ CO Glomerulonephritis (present but severity remains stable, although urinary H+ excretion ↓)
Nephrotoxins Buffering of H+ by Calcium Salts in Bone
Drug Reactions Demineralization of Bone (often occurs in CRF)
Disorders of Renal Vasculature
Renal Tubule Blockage
Chemical Pathology of ARF
Phases – Oliguric, Diuretic, Recovery
Proteinuria present
Urine dark (Haem pigments from Blood)
Retention of Urea, Creatinine, Phosphate, Sulphate, other waste products in blood
Renal Failure due to Trauma (including Surgical Operations), Plasma Urea ↑ more
rapidly than Renal Failure due to Medical causes (Acute Glomerular Nephritis)
Phases
Oliguric Diuretic
<400 mL urine / day (due to ↓ GFR) ↑ Losses of Electrolytes – Urine
Urine Osmolality similar to Plasma Need to be replaced
↑ Urine [Na] (Orally/ Parenterally)
Plasma Na ↓ due to Assess Urine
Water Intake ↑, Excretion ↓ [Sodium]
↑ Metabolic Water [Potassium]
(from ↑ Tissue Catabolism) Calculate daily output/loss
Na+ Shift from ECF → ICF
Plasma K+ ↑ due to Monitor Plasma
Impaired Renal Output [Creatinine]
↑ Tissue Catabolism [Urea]
Shift of K+ out of cells [Potassium]
(Accompanied Metabolic Acidosis –
developed due to
Failure to excrete H+
↑H+ formed from Tissue Catabolism)

Investigation of ↓ Urinary Output

Simple Hypovolaemia Acute Renal Failure
Urine Osmolality > 500 mmol/kg < 400 mmol/kg
Urine Urea/ Plasma Usually > 10 Usually < 5
Urea Ratio
Urine [Na+] Usually < 20 mmol/L Usually > 40 mmol/L