 - Nephron count : ~1 million per kidney Normal Kidney Functions - Maintain extracellular fluid constancy Excrete dietary surpluses and metabolic waste (urea, creatinine, urate, H+) - Retain necessary substances (proteins, glucose, amino acids, HCO3-) - Endocrine functions Erythropoietin production - Renin secretion - 1-alpha-hydroxylation of Vitamin D → calcitriol --- GLOMERULAR FUNCTION Structure - Three barrier layers : Capillary endothelial → Basement membrane → Visceral epithelium - Primary barrier : Basement membrane - Charge barrier : Negative charge (sialic acid) prevents protein crossing - Pressure : Hydrostatic pressure ~1 kPa Clinical Significance - Oliguria in shock : When BP drops, oncotic pressure stops filtration - Definitions :Polyuria: normal urine output - Oliguria: 18 years) - Variables : Serum creatinine, age, gender, ethnicity - Formula : GFR = 175 × [creatinine × 0.011312]^-1.154 × [age]^-0.203 × [1.212 if black] × [0.742 if female] - Children : Use Schwartz equation (includes height) 5. Abnormal Urea:Creatinine Ratio Increased : High protein intake, GI bleeding, hypercatabolic states, dehydration, urinary stasis Decreased : Low protein intake, dialysis, severe liver disease Tubular Function Tests - Urinary Na+ concentration : Normally low unless high salt intake - Concentration/dilution tests : After pitressin/water load - Osmolality ratio : Urine/plasma osmolality - Acidification tests : After NH4Cl administration Miscellaneous Tests - Microscopy : Casts, cells, crystals - Proteinuria : 2.5 g/day = nephrotic syndrome - Bence-Jones protein : Indicates myeloma - β2-microglobulin : Sensitive tubular function test --- MAJOR RENAL DISORDERS Nephrotic Syndrome - Definition : Glomerular protein permeability increase - Criteria : Proteinuria 2.5 g/day + edema + hypoproteinemia + hyperlipidemia - Selectivity Index : (UIgG/PIgG)/(Ualb/Palb) × 100 - Laboratory findings : ↑α2 globulins, hypercholesterolemia Acute Renal Failure (ARF) - Definition : Urine 50 mMol/L, HCO3- 7.0 mMol/L Chronic Renal Failure (CRF) - Common causes : Glomerulonephritis, diabetes, hypertension - Key feature : Polyuria (opposite of ARF) Early Features (↓Glomerular function) - ↑Urea (chronic uremia/azotemia) - ↑Creatinine, ↓creatinine clearance - ↑Urate, phosphate, sulfate Later Features (↓Tubular function) - Fixed urine output - Loss of concentrating/diluting ability - Metabolic acidosis with ↑anion gap - Sodium instability Management - Water intake controlled by thirst - Careful Na+, K+, protein control - Erythropoietin for anemia - Oral bicarbonate for acidosis - End-stage: Dialysis or transplant --- POLYURIA CLASSIFICATION Water Diuresis (Osmolality 300) - Na+ : Dietary, diuretics, salt-losing nephritis - Urea : CRF, recovery phase of ATN - Glucose : Diabetes mellitus - Mannitol : Therapeutic agents --- RENAL STONES (NEPHROLITHIASIS) Causes - High concentration : Low urine volume, high excretion rate - pH changes : Alkaline → Ca deposition, Acid → uric acid - Stagnation : Usually due to obstruction Types - Calcium oxalate (+ phosphate) - most common - Phosphate stones - Uric acid - 10% of gout cases - Rare forms : Cystine, xanthine, 2,8-dihydroxyadenine Treatment - Fluids : Keep urine dilute (all cases) - Potassium citrate + thiazides : Prevent Ca stones - Alkalinization : Prevent uric acid stones --- RENAL ACIDOSIS Uremic Acidosis - Seen in : Acute/chronic renal failure - Mechanism : ↓H+ excretion (glomerular + tubular failure) - Features : ↑Anion gap, hyperkalemia - Develops when : GFR 350 μMol) Renal Tubular Acidosis (RTA) - Characteristic : Normal anion gap (hyperchloremic) metabolic acidosis - Glomerular function : Normal or slightly decreased Type 1 (Distal) RTA - Defect : Cannot excrete H+ in distal nephron - Urine pH : 5.5 (inappropriately high) - Associated : Hypokalemia, nephrocalcinosis, rickets Type 2 (Proximal) RTA - Defect : ↓Bicarbonate reabsorption - Renal threshold : Decreased (normal 24 mmol/L) - Features : Bicarbonate wasting, hypokalemia - May be part of : Fanconi syndrome Type 4 RTA - Cause : Mineralocorticoid deficiency/resistance - Feature : Hyperkalemia --- RARE INHERITED TUBULAR DISORDERS Liddle's Syndrome - Features : Hypertension, hypokalemia, low renin/aldosterone - Mechanism : ↑ENaC channels in distal tubule - Inheritance : Autosomal dominant Pseudohypoaldosteronism Type 1 - Features : FTT, hyponatremia, hyperkalemia - Mechanism : ENaC gene mutations - Lab : ↑Renin & aldosterone Bartter's Syndrome - Features : FTT, polyuria, hypokalemia, alkalosis - Mechanism : Defective mTAL transport (NKCCT, ROMK1, CLCKB) - Effect : Like furosemide Gitelman's Syndrome - Features : Like Bartter's + hypocalciuria + hypomagnesemia - Mechanism : Defective DCT NCCT - Effect : Like thiazide diuretics --- GASTRIC FUNCTION TESTS Pentagastrin Stimulation Test - Procedure : Basal collection → Pentagastrin (5 μg/kg) → Maximum collection - Normal values :BAO (Basal Acid Output): 4-10 mmol/hr - MAO (Maximal Acid Output): 20-50 mmol/hr - Measurement : Titrate with N/10 NaOH to pH 7.4 Histamine Test - Stimulant : Histamine (powerful gastric stimulant) - Procedure : Basal collection → Subcutaneous histamine → Collection Insulin Test (Hollander's Test) - Purpose : Assess vagotomy completeness - Procedure : IV insulin (0.1 unit/kg) → causes hypoglycemia - Interpretation : No acid increase = successful vagotomy Tubeless Gastric Analysis - Principle : Cation exchange resin exchanges with H+ ions - Advantage : No tube required - Use : Preliminary screening Abnormalities - Increased HCl : Zollinger-Ellison syndrome, duodenal ulcer, hyperplasia - Decreased HCl : Gastritis, gastric carcinoma, pernicious anemia --- PANCREATIC FUNCTION TESTS Secretin Test - Measures : Pancreatic response to secretin - Normal : Secretin → pancreas secretes high bicarbonate fluid - Abnormal in : Chronic pancreatitis, cystic fibrosis, pancreatic cancer Fecal Elastase Test - Measures : Elastase enzyme in stool - Elastase function : Digests proteins Imaging Tests - CT with contrast : Rule out other causes, detect inflammation - Abdominal ultrasound : Detect gallstones, ascites, enlarged bile duct - ERCP : Visualize bile ducts and pancreatic duct - Endoscopic ultrasound : Images abdominal organs - MRCP : MRI of bile ducts and pancreatic duct --- EXAM TIPS High-Yield Facts - Creatinine clearance formula and normal values - ARF diagnostic criteria and urine tests - RTA types and their characteristics - Nephrotic syndrome criteria - Inherited tubular disorders and their mechanisms - Gastric function test procedures and normal values Common Exam Questions - Differentiate pre-renal vs intra-renal failure - Calculate creatinine clearance - Classify types of RTA - Interpret gastric function test results - Recognize inherited tubular disorders Memory Aids - ARF types : Pre-renal (before), Intra-renal (in), Post-renal (after) - RTA : Type 1 (distal, high pH), Type 2 (proximal, bicarbonate waste) - Nephrotic syndrome : 2.5g protein + edema + low albumin + high lipids LIVER FUNCTION TESTS - STUDY NOTES LIVER BASICS - Location : Under right rib cage - Weight : ~3 pounds - Shape : Football-like, flat on one side - Functions :Processes food/drink into energy and nutrients - Removes harmful substances from blood - Synthesizes proteins and enzymes LIVER FUNCTION TESTS (LFTs) Purpose - Check liver health and detect damage - Measure proteins and enzymes in blood - Used for: routine checkups, screening high-risk patients, monitoring treatment --- A. LIVER ENZYME TESTS 1. Alanine Transaminase (ALT) - Source : Mainly liver (liver-specific) - Function : Cytosolic only