Study Notes: Basics of Intensive Care (ICU)

1. What is the ICU?

• ICU = Intensive Care Unit (also called Critical Care Unit or Intensive Therapy Unit).

• Specialized hospital ward for critically ill, unstable patients.

• Main purposes:

  • Treat life-threatening illnesses.

  • Support failing organ systems.

  • Prevent secondary injury.

  • Provide specialized environment with 1:1 care and continuous monitoring.

2. How ICU Differs From General Wards

• Staffing: More staff; typically 1 nurse per patient.

• Expertise: Specialized nurses, intensivists, and allied health staff.

• Monitoring: Continuous and invasive (e.g., arterial lines, ECG, ICP).

• Outcomes: Mortality increases as more organs fail (≥3 organ failures → survival 20–30%).

• Cost: Higher due to staff, equipment, and investigations.

3. ICU Admission Criteria

• Patients with organ failure and a reasonable chance of recovery.

• Types of Admission:

  • Emergency: After sudden deterioration (e.g., pneumonia, asthma, sepsis) or emergency surgery.

  • Elective: Planned monitoring/support after major surgery.

• Common Emergency Triggers:

  • Respiratory: Hypoxia, abnormal respiratory rate.

  • Cardiovascular: Hypotension, arrhythmias.

  • Renal: Oliguria/anuria.

  • Neurological: Reduced consciousness, seizures.

  • Metabolic: Severe derangements (e.g., acidosis).

4. Common Conditions Requiring ICU Care

• ARDS (Acute Respiratory Distress Syndrome): Severe lung inflammation, hypoxemia.

• Sepsis: Systemic infection → inflammatory response → multi-organ failure.

  • Diagnosed by abnormal temp, HR, RR, WBC.

  • Treated with “Sepsis Bundles” (e.g., Surviving Sepsis Campaign).

• Acute Kidney Injury (AKI): Sudden decline in kidney function (oliguria/anuria, ↑ creatinine).

5. Specialized ICU Equipment & Monitoring

• Bedside monitor: HR, BP, SpO₂, temp, etc.

• Arterial lines: Continuous BP, blood sampling.

• Ventilator: Provides oxygen & ventilation via endotracheal tube.

• IV access: Central lines for drugs, fluids, nutrition.

• Chest drains, NG tubes, urinary catheters.

• Airway suction: Removes secretions.

6. Organ Support in ICU

Respiratory Failure

• Cause: Inability to oxygenate or ventilate.

• Treatment: Mechanical ventilation (intubation + ventilator).

• Modes: From full control to pressure support as recovery begins.

Cardiovascular Failure

• Definition: Inadequate blood flow to organs.

• Equation: MAP = CO × SVR.

  • CO low → due to ↓ HR or ↓ stroke volume (e.g., heart block, myocardial damage).

  • SVR low → sepsis, anaphylaxis (vasodilation).

• Support: Vasopressors, inotropes, fluids, pacing.

Renal Failure

• Cause: Inability to excrete waste and maintain electrolytes.

• Diagnosis: Oliguria/anuria, abnormal urine studies, ↑ creatinine/urea.

• Treatment: Renal replacement therapy (hemofiltration, dialysis).

Neurological Failure

• Cause: Trauma, stroke, hypoxia, infection, metabolic derangements.

• Manifestation: Reduced consciousness, coma.

• Management:

  • Prevent secondary brain injury (reduce swelling, maintain perfusion & oxygenation).

  • Monitoring: ICP measurement when needed.

  • Ventilation if consciousness is impaired.

7. Discharge from ICU

• Once organ support can be withdrawn and patient is stable:

  • Transfer to High Dependency Unit (HDU) or regular ward.

• Recovery influenced by:

  • Severity of illness.

  • Number of organs affected.

  • Pre-existing health/fitness.

• Post-ICU complications:

  • Persistent organ dysfunction.

  • ICU-acquired weakness.

  • Psychological sequelae: depression, delirium, anxiety, PTSD.

8. Key Takeaway

ICU provides the highest level of care in the hospital:

• Specialized staff, equipment, and organ support.

• Admission for patients with critical illness but a potential for recovery.

• Focus on treating organ failure while preventing secondary injury.

• Recovery continues long after discharge, with both physical and psychological challenges.

Acid–Base Balance and Buffer Systems

Study Notes Acidosis 

1. Major Chemical Buffers in the Body

• Phosphate buffer

  • Works mainly inside cells and at the kidneys (renal tubules).

• Protein buffer

  • Found inside cells.

  • Most abundant buffer in the body.

• Bicarbonate buffer

  • Most important clinically.

  • Primary extracellular buffer system.

2. Bicarbonate Buffer System

• Buffers resist changes in pH.

• pH depends on hydrogen ion concentration:

  • ↑ H⁺ → acidic.

  • ↓ H⁺ → basic/alkaline.

Reaction:
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

• H₂CO₃ = carbonic acid (weak acid).

• Splits into H⁺ (acid) and HCO₃⁻ (bicarbonate, conjugate base).

• Reversible process allows buffering in both directions.

3. Metabolism and CO₂ Production

• Food (proteins, fats, carbs) → ATP via mitochondria + electron transport chain.

• Nutrients mainly contain C, H, O (proteins also have N, but nitrogen not used for ATP).

• Hydrogens removed → carried by NADH and FADH₂ → donated to ETC → ATP formed.

• Leftover C + O → CO₂ (waste product).

• CO₂ = body’s “exhaust fumes.”

• Every tissue produces CO₂ → must be eliminated via lungs.

4. CO₂, Carbonic Acid, and Acidity

• CO₂ mixes with water in blood → forms carbonic acid.

• Carbonic acid dissociates → H⁺ ions → lowers pH.

• More CO₂ = more H⁺ = more acidic.

• Lungs excrete CO₂ → prevents buildup.

• Called a volatile acid (easily exhaled).

5. Independent H⁺ Production

• Not all H⁺ comes from CO₂.

• Example: lactic acid (exercise).

• Excess H⁺ binds to HCO₃⁻ → forms H₂CO₃ → converted to CO₂ + H₂O → exhaled.

6. Chemoreceptor Control

• Peripheral chemoreceptors:

  • Located in aortic bodies (aortic arch) + carotid bodies (carotid bifurcation).

  • Detect ↑ H⁺ and ↑ CO₂.

  • Send signals → brainstem → increase ventilation.

• Central chemoreceptors:

  • Located in brainstem.

  • Directly sense CO₂ and H⁺ in CSF.

• Response: ↑ ventilation → ↓ CO₂ → ↓ H⁺ → restores pH.

7. Respiratory Control of pH

• Holding breath → ↑ CO₂ → ↑ H⁺ → acidosis.

• Hyperventilation → ↓ CO₂ → ↓ H⁺ → alkalosis.

• Respiratory regulation = short-term pH control.

8. Respiratory Disorders

• Respiratory alkalosis

  • Cause: hyperventilation (e.g., anxiety).

  • Mechanism: ↓ CO₂ → ↓ H⁺ → blood becomes alkaline.

• Respiratory acidosis

  • Cause: inadequate ventilation (↓ CO₂ excretion).

  • Examples:

    • COPD (emphysema, chronic bronchitis).

    • Neuromuscular disease (e.g., polio).

    • Rib fractures (restrict lung expansion).

    • Pulmonary scarring or obstruction.

  • Mechanism: ↑ CO₂ → ↑ H⁺ → blood becomes acidic.

9. Renal Control of pH

• Kidneys regulate H⁺ excretion and HCO₃⁻ reabsorption/production.

• Slower than lungs → long-term control of pH.

• Compensation:

  • Acidosis → kidneys excrete more H⁺, reabsorb HCO₃⁻.

  • Alkalosis → kidneys retain H⁺, excrete HCO₃⁻.

Summary:

• Bicarbonate buffer is the most clinically important.

• Lungs = fast regulation (CO₂ control).

• Kidneys = slow regulation (H⁺ and HCO₃⁻ control).

• Disorders:

  • Respiratory alkalosis = hyperventilation.

  • Respiratory acidosis = hypoventilation/CO₂ retention.

How to Identify Organic Compounds

Organic compounds are carbon-based molecules (C–H backbone, often with O, N, S, P, halogens). They’re classified mainly by their functional groups. Each group gives the compound its chemical properties.

1. Hydrocarbons (C + H only)

• Simplest organic compounds.

• Subgroups:

  • Alkanes (single bonds) – C–C, C–H only.

    • Example: Methane (CH₄), Ethane (C₂H₆), Propane (C₃H₈).

    • Structure: CH₃–CH₃

  • Alkenes (double bonds) – contain C=C.

    • Example: Ethene (C₂H₄), Propene (C₃H₆).

    • Structure: CH₂=CH₂

  • Alkynes (triple bonds) – contain C≡C.

    • Example: Ethyne (acetylene, C₂H₂).

    • Structure: HC≡CH

  • Aromatic hydrocarbons (benzene ring)

    • Example: Benzene (C₆H₆), Toluene (C₆H₅CH₃).

2. Alcohols (–OH group)

• Contain hydroxyl group bonded to carbon.

• Examples:

  • Methanol (CH₃OH) – toxic, solvent.

  • Ethanol (C₂H₅OH) – drinking alcohol.

  • Isopropanol (C₃H₇OH) – rubbing alcohol.

• Structure: R–OH

3. Phenols (–OH attached to aromatic ring)

• Examples:

  • Phenol (C₆H₅OH) – antiseptic.

  • Thymol – in mouthwash.

4. Ethers (R–O–R)

• Oxygen linking two carbons.

• Examples:

  • Diethyl ether (CH₃CH₂–O–CH₂CH₃) – early anesthetic.

  • MTBE – fuel additive.

5. Amines (–NH₂, –NHR, –NR₂)

• Derived from ammonia (NH₃).

• Examples:

  • Methylamine (CH₃NH₂).

  • Aniline (C₆H₅NH₂).

  • Epinephrine (neurotransmitter).

6. Aldehydes (–CHO)

• Carbonyl group at end of chain.

• Examples:

  • Formaldehyde (H–CHO) – preservative.

  • Acetaldehyde (CH₃CHO) – alcohol metabolism intermediate.

7. Ketones (C=O in middle of chain)

• Examples:

  • Acetone (CH₃COCH₃) – nail polish remover.

  • Butanone (CH₃COCH₂CH₃).

8. Carboxylic Acids (–COOH)

• Acidic organic group.

• Examples:

  • Formic acid (HCOOH) – ant stings.

  • Acetic acid (CH₃COOH) – vinegar.

  • Citric acid (C₆H₈O₇) – citrus fruits.

9. Esters (R–COO–R)

• Formed from acid + alcohol. Sweet/fruity smells.

• Examples:

  • Ethyl acetate (CH₃COOCH₂CH₃) – solvent.

  • Isoamyl acetate – banana smell

10. Amides (R–CONH₂, R–CONHR, R–CONR₂)

• Found in proteins (peptide bonds).

• Examples:

  • Acetamide (CH₃CONH₂).

  • Urea – major component in urine.

11. Nitriles (–C≡N)

• Carbon triple-bonded to nitrogen.

• Examples:

  • Acetonitrile (CH₃CN) – solvent.

  • Benzonitrile (C₆H₅CN).

12. Halogenated Compounds (R–X, X = F, Cl, Br, I)

• Examples:

  • Chloroform (CHCl₃) – anesthetic.

  • Dichloromethane (CH₂Cl₂) – solvent.

  • Freons (CFCs).

13. Biological Macromolecules

• Built from organic groups above.

  • Carbohydrates – glucose (C₆H₁₂O₆), sucrose.

  • Lipids – triglycerides (glycerol + 3 fatty acids).

  • Proteins – polymers of amino acids (amines + carboxylic acids).

  • Nucleic Acids – DNA/RNA (sugars, bases, phosphate).

Tips for Identifying Compounds

1. Look for functional groups: OH, COOH, NH₂, C=O, C≡N.

2. Name based on parent chain + suffix:

   • –ane (alkane), –ene (alkene), –yne (alkyne).

   • –ol (alcohol), –al (aldehyde), –one (ketone), –oic acid (carboxylic acid).

3. Examples in real life: Medicines, fuels, plastics, food molecules.

Mr. Critical ICU Nursing: Comprehensive Study Notes

1) Quick Critical Values & Must-Act Triggers

Airway & Breathing

• SpO₂ < 90% (or drop >4% from baseline) despite O₂ → escalate, check airway, consider ABG.

• pH < 7.20 with rising PaCO₂ or refractory hypoxemia → consider ventilatory support.

Circulation

• MAP < 65 mmHg (or below patient-specific goal) after fluids → start/adjust vasopressors.

• Lactate ≥ 4 mmol/L or rising trend → search for shock/sepsis, optimize perfusion.

• Urine output < 0.5 mL/kg/hr for >2 hours → assess volume, perfusion, obstruction.

Electrolytes (action thresholds; follow local protocols)

• K⁺ < 3.0 or > 6.0 mEq/L

• Mg²⁺ < 1.6 mg/dL

• Ionized Ca²⁺ < 0.9 mmol/L

• Na⁺ change > 10–12 mEq/L in 24 h → risk of osmotic injury

Bleeding/Coagulation

• Hgb < 7 g/dL (individualize for ACS, neuro, active bleed).

• INR > 2.0 or platelets < 50k with planned procedures → correct per protocol.

Neuro

• Sudden GCS drop ≥ 2, new focal deficit, or pupil asymmetry > 1 mm → emergent eval.

• ICP > 22 mmHg sustained, CPP < ordered goal (often 60–70 mmHg).

2) Core ICU Labs: What They Mean & What To Do

Arterial/Venous Blood Gases

• ABG: pH, PaCO₂, PaO₂, HCO₃⁻, SaO₂

  • Respiratory acidosis: ↑PaCO₂ → ↑ventilation (rate/VT), fix obstruction, sedation PRN.

  • Respiratory alkalosis: ↓PaCO₂ → reduce ventilation or treat pain/anxiety.

  • Metabolic acidosis: ↓HCO₃⁻ → check lactate, ketoacids, renal failure, toxins.

  • Metabolic alkalosis: ↑HCO₃⁻ → assess chloride, volume status, diuretics.

• VBG: good for pH/CO₂ trends (not oxygenation).

Key Formulas

• Anion Gap (AG) = Na – (Cl + HCO₃). Normal ~8–12.

• Winter’s Formula (expected PaCO₂ in metabolic acidosis) = 1.5 × HCO₃ + 8 ± 2.

• A–a Gradient = [FiO₂ × (Pb – PH₂O) – PaCO₂/R] – PaO₂.

Lactate

• Shock marker.

• Clearance (>10–20% at 2–4 h) = improving perfusion.

• Elevated from: tissue hypoxia, seizures, β-agonists, liver dysfunction, thiamine deficiency.

Electrolytes & Action Pearls

• K⁺: target 4–5 in arrhythmia risk. ~10 mEq KCl ↑ serum K⁺ by 0.1 (variable). Monitor on cardiac monitor.

• Mg²⁺: keep ≥ 2.0 mg/dL with arrhythmia risk; treat torsades aggressively.

• Ca²⁺: check ionized. Replace in massive transfusion or hyperK⁺ ECG changes.

• Phosphate: low Phos (<2.0) → diaphragm weakness. Replace carefully.

• Na⁺: correct chronic changes slowly.

  • Hyponatremia: check serum/urine osmolality & urine Na.

  • Hypernatremia: free-water deficit, correct gradually.

Renal & Urine Studies

• BUN/Cr: trends > absolute values.

• FENa/FEUrea: differentiate pre-renal vs intrinsic (FEUrea <35% → pre-renal).

Cardiac Markers

• Troponin: trend + ECG + symptoms; distinguish type 1 vs type 2 MI.

• BNP/NT-proBNP: assess volume/pressure overload; integrate with exam/echo.

Coagulation

• PT/INR, aPTT, anti-Xa, fibrinogen, D-dimer.

• Anti-Xa preferred for heparin titration where adopted.

Inflammatory/Infectious

• Procalcitonin/CRP = trends only.

• Draw cultures (blood before antibiotics).

• Don’t anchor on one biomarker.

Medication Levels

• Vancomycin (AUC/trough), aminoglycosides, digoxin, phenytoin, lithium.

• Time draws correctly; adjust for renal function.

Metabolic/Endocrine

• Glucose: target 140–180 mg/dL (avoid hypoglycemia).

• Triglycerides: monitor on propofol.

• TSH/Free T4: if myxedema concern.

• Cortisol: if adrenal insufficiency suspected.

3) Hemodynamic Monitoring & “The Notches”

Arterial Line (A-line)

• Radial site most common. Level at phlebostatic axis. Zero to air.

• Waveform: systolic upstroke → dicrotic notch (aortic closure) → diastolic runoff.

• Damping:

  • Underdamped: exaggerated systolic.

  • Overdamped: blunted waveform.

• Square-wave test: 1–2 oscillations optimal.

• PPV/SVV: preload markers in controlled ventilation (not reliable with arrhythmia, low TV, high PEEP, or spontaneous breaths).

Central Venous Pressure (CVP)

• Normal: 2–8 mmHg (use trends).

• Waveform:

  • a wave = atrial contraction

  • c wave = tricuspid bulge

  • v wave = venous filling

  • x/y descents = relaxation/filling

• Giant v waves: TR. Prominent a waves: pulm HTN or ↓RV compliance.

Pulmonary Artery Catheter (PAC)

• Normal pressures: RA 2–8, RV 15–30/2–8, PA 15–30/5–15, PAOP 6–12.

• RV waveform = tall systolic, near-zero diastolic.

• PA waveform = dicrotic notch.

• PAOP = atrial-type waveform when wedged.

• Derived metrics: CO/CI, SV, SVR, PVR.

• SvO₂ vs ScvO₂ = O₂ delivery/consumption balance.

Noninvasive/Advanced

• POCUS Echo: LV/RV function, IVC, effusions, tamponade.

• Pulse contour devices: PiCCO, FloTrac.

4) Cardiac Monitoring (ECG) Essentials

Rapid Review

1. Rate & rhythm

2. PR/QRS/QT

3. Axis

4. Ischemia (ST/T)

5. Blocks

6. Compare to prior

Key Pearls

• ST elevation/depression: correlate with baseline, symptoms, troponins.

• QTc: use Fridericia in tachy. Check meds/electrolytes.

• BBB: STEMI can hide in LBBB (Sgarbossa criteria).

• Pacers: verify capture on ECG + perfusion on A-line.

Arrhythmia Quick Guide

• Unstable tachy: synchronized cardioversion.

• Stable narrow tachy: vagal → adenosine → meds.

• A-fib RVR: rate control, anticoagulation, treat triggers.

• VT/VF arrest: defibrillate, CPR, epi, fix H’s & T’s.

• Torsades: IV Mg, overdrive pacing.

5) Mechanical Ventilation & Oxygenation

Initial Settings

• ARDS: VT 4–6 mL/kg IBW, RR 16–24, PEEP per FiO₂, keep plateau ≤30.

• Obstructive: longer expiratory time, lower RR.

Troubleshooting

• Double trigger = low VT/set RR.

• Shark fin flow = obstruction.

• Scooped flow = air trapping.

• Auto-PEEP = incomplete exhalation → allow more time, bronchodilate.

Oxygenation/Ventilation Targets

• SpO₂ 92–96%. Avoid hyperoxia.

• Correct acidosis only if clinically significant.

Liberation

• Daily SAT/SBT, minimal sedation, adequate cough, stable hemodynamics, cuff leak if prolonged intubation.

VAP Prevention Bundle

• HOB 30–45°, oral care with CHG, subglottic suction, sedation holiday, DVT/GI prophylaxis, early mobility.

6) Shock: Types, Profiles, First Moves

• Distributive (sepsis): warm, low SVR, high CO → early antibiotics, fluids, norepinephrine.

• Cardiogenic: cool, high filling pressures, low CO → gentle fluids, dobutamine ± vasopressors.

• Hypovolemic: flat veins, tachy, narrow PP → stop bleed, MTP, TXA, calcium.

• Obstructive: tension pneumo (needle decompression), tamponade (pericardiocentesis), PE (lysis/embolectomy).

Monitor: lactate, ScvO₂/SvO₂, UO, mentation, skin perfusion.

7) Medication Titration: Principles & Common Drips

Vasopressors

• Norepinephrine: first-line; titrate to MAP.

• Vasopressin: fixed dose, adjunct.

• Epinephrine: refractory shock; ↑lactate risk.

• Phenylephrine: use if tachy with hypotension.

• Dopamine: high arrhythmia risk → rarely used.

Inotropes

• Dobutamine: ↑CO, may ↓BP.

• Milrinone: PDE-3 inhibitor, long half-life, avoid in AKI.

DKA Study Notes 2025

 Definition:

• Acute, life-threatening complication of diabetes (mostly type 1, but can occur in type 2).

• Characterized by:

  1. Hyperglycemia

  2. Ketosis

  3. Metabolic acidosis

Pathophysiology

• Absolute or relative insulin deficiency + ↑ counterregulatory hormones (glucagon, cortisol, catecholamines, growth hormone).

• ↓ Glucose uptake → hyperglycemia → osmotic diuresis → dehydration & electrolyte loss.

• ↑ Lipolysis → free fatty acids → hepatic ketogenesis → ketone bodies (acetoacetate, β-hydroxybutyrate).

• Accumulation of ketones → anion gap metabolic acidosis.

Precipitating Factors

• Infection (most common).

• Missed insulin doses.

• Myocardial infarction, stroke.

• Pancreatitis.

• Medications: steroids, thiazides, sympathomimetics, SGLT2 inhibitors (can also cause euglycemic DKA).

Clinical Features

Symptoms

• Polyuria, polydipsia, polyphagia.

• Nausea, vomiting, abdominal pain.

• Fatigue, weakness.

Signs

• Dehydration (dry mucous membranes, poor skin turgor, hypotension, tachycardia).

• Kussmaul respirations (deep, rapid breathing → respiratory compensation for acidosis).

• Fruity/acetone breath odor.

• Altered mental status (confusion, drowsiness, coma in severe cases).

Laboratory Findings

• Glucose: > 250 mg/dL (though lower in euglycemic DKA).

• Arterial pH: < 7.3.

• Serum bicarbonate (HCO₃⁻): < 18 mEq/L.

• Anion gap: elevated.

• Ketones: positive in serum and urine (β-hydroxybutyrate most specific).

• Electrolytes:

  • Total body K⁺ is low, but serum K⁺ may be normal or elevated initially due to acidosis/insulin deficiency.

  • Na⁺ may appear low due to hyperglycemia (pseudohyponatremia).

Management (ABCDE approach)

1. Airway/Breathing/Circulation – stabilize first.

2. Fluid replacement:

   • Isotonic saline (0.9% NaCl) initially.

   • Replace deficits gradually (6–9 L over 24 hrs).

3. Insulin therapy:

   • IV regular insulin after fluids started.

   • Corrects hyperglycemia & suppresses ketogenesis.

4. Potassium management:

   • If K⁺ < 3.3 → replace K⁺ before insulin.

   • If 3.3–5.0 → replace K⁺ with insulin therapy.

   • If > 5.0 → monitor, no replacement initially.

5. Bicarbonate therapy:

   • Only if pH < 6.9.

6. Monitor closely:

   • Vitals, neuro status, glucose, electrolytes, urine output, anion gap.

Complications

• Cerebral edema (especially in children).

• Hypoglycemia (from treatment).

• Hypokalemia (from insulin + correction).

• ARDS, shock if severe.

Prognosis

• Good with prompt treatment.

• Mortality higher in elderly, comorbidities, delayed diagnosis.

Key Takeaways:

• DKA = hyperglycemia + ketosis + acidosis.

• Always correct fluids first, then insulin, while managing potassium.

• Search for precipitating cause (infection, MI, missed insulin).

Acute Kidney Injury (AKI) / Acute Renal Failure

Definition: Rapid decline in renal function. Classified into pre-renal, intra-renal, post-renal.

1. Pre-Renal AKI

• Cause: ↓ renal blood flow → ↓ GFR, ↓ Na⁺ filtration.

• Pathophysiology:

  • Less Na⁺ reabsorption (main O₂ consumer) → ↓ renal O₂ demand.

  • Results in oliguria.

• Reversible if blood flow restored before ischemic damage.

• Common causes:

  • Volume depletion: hemorrhage, diarrhea, vomiting, burns.

  • ↓ Cardiac output: MI, valvular disease.

  • Vasodilation: sepsis, anaphylaxis, anesthesia.

  • Renal artery stenosis, embolism, thrombosis.

2. Intra-Renal AKI

• Glomerular damage:

  • Vasculitis, malignant HTN, cholesterol emboli.

  • Post-strep glomerulonephritis (1–3 wks after Group A strep) → immune complex deposits.

• Tubular injury:

  • Ischemia or toxins → acute tubular necrosis (ATN).

• Interstitial injury:

  • Acute pyelonephritis.

  • Interstitial nephritis.

3. Post-Renal AKI

• Cause: Urinary tract obstruction.

• Sites:

  • Bilateral ureteral obstruction (stones, clots).

  • Bladder outlet obstruction.

  • Urethral obstruction.

  • Foley catheter obstruction.

Clinical Features of AKI

• Retention of: water, electrolytes, wastes.

• Complications: edema, HTN, hyperkalemia, metabolic acidosis.

• Anuria → death within weeks unless treated (restored function or dialysis).

Chronic Kidney Disease (CKD)

Definition: Loss of ~75% of nephrons; usually irreversible.

Causes

• Metabolic: diabetes, obesity, amyloidosis.

• Hypertension.

• Renovascular disease: atherosclerosis, nephrosclerosis.

• Immune: chronic glomerulonephritis, lupus.

• Infections.

• Nephrotoxins.

• Obstruction: post-renal.

• Congenital disorders.

Pathophysiology

• Remaining nephrons hyperfunction → rapid tubular flow.

• Kidneys can still make urine, but it is dilute (poorly concentrated).

• Progression → end-stage renal disease (ESRD).

Common U.S. Causes of ESRD

• Diabetes.

• Hypertension.

Manifestations of CKD

• Fluid & electrolytes: edema, HTN, acidosis, hyperkalemia.

• Nitrogenous waste: uremia (↑ urea, creatinine, uric acid).

  • Uremic platelet dysfunction → bleeding.

• Other retained toxins: phenols, sulfates, phosphates, potassium, guanidine.

• Endocrine/metabolic:

  • ↓ Erythropoietin → anemia.

  • ↓ Vitamin D activation → osteomalacia.

  • ↑ Phosphate retention → ↓ Ca²⁺ → ↑ PTH → secondary hyperparathyroidism → bone demineralization.

• Hypertension: both cause and consequence (salt/water retention, ↑ renin/Ang II).

Dialysis and Renal Replacement Therapy

Indications (Mnemonic: AEIOU)

• A: Acidosis.

• E: Electrolyte disturbances (K⁺, Na⁺, Ca²⁺).

• I: Intoxication (methanol, ethylene glycol, lithium, aspirin, drugs).

• O: Overload (volume).

• U: Uremia (symptoms: nausea, seizures, pericarditis, bleeding).

Hemodialysis

• Blood removed, passed across a semipermeable membrane against dialysate → solutes/water exchange.

• Typical schedule: 4–6 hrs, 3x/week.

• Access types:

  • Fistula: artery–vein connection; best option but needs months to mature.

  • Graft: synthetic tubing connecting artery–vein; usable immediately.

  • Central dialysis catheter: temporary, immediate use.

Peritoneal Dialysis

• Catheter placed in peritoneal cavity → dialysate instilled.

• Solutes diffuse across peritoneum.

• Types:

  • Continuous ambulatory (manual exchanges).

  • Automated (cycler overnight).

• Advantages: better tolerated fluid shifts, useful when vascular access is difficult.

• Risks: peritonitis (abdominal pain, fever).

Anesthesia Considerations in CKD/ESRD

• Pre-op:

  • Check serum creatinine for renal function.

  • Check serum potassium, often required on day of surgery.

  • Assess comorbidities (diabetes, HTN).

• Medications:

  • Avoid drugs heavily dependent on renal clearance (dose-adjust).

  • Succinylcholine hyperkalemia not exaggerated in CKD.

• Hematology:

  • May have anemia (↓ EPO).

  • Uremic platelet dysfunction → may respond to desmopressin.

• Hemodynamics:

  • Impaired vasoconstriction → hypotension risk (hypovolemia, PPV, anesthesia).

• Vascular access precautions:

  • Avoid BP cuff, IV, arterial line on arm/leg with dialysis access.

  • Monitor fistula/graft thrill during surgery.

• Fluid management:

  • Avoid K⁺-containing fluids (e.g., LR).

  • NS may cause acidosis.

  • Fluids used sparingly—balance risk.

• Volume assessment:

  • Compare weight to dry weight (post-dialysis baseline).

  • Recently dialyzed → may behave hypovolemic → sensitive to anesthetics.

• Monitoring:

  • Consider arterial line or central line for closer hemodynamic control.

 Takeaways

• AKI = reversible, classified into pre-renal, intra-renal, post-renal.

• CKD = progressive, irreversible nephron loss → ESRD.

• Dialysis indicated by AEIOU.

• Anesthesia in CKD requires careful attention to electrolytes, fluid status, vascular access, and drug dosing.

Renal Physiology – Acid-Base and Diuretics Study Notes (Part 5)

1. Definitions

• Acidosis: A primary physiologic process causing acidemia (low pH)

  • Respiratory acidosis: Elevated pCO2 due to hypoventilation → ↑ hydrogen ions → ↓ pH

  • Metabolic acidosis: ↑ hydrogen ions or ↓ bicarbonate → ↓ pH

• Alkalosis: A primary physiologic process causing alkalemia (high pH)

  • Respiratory alkalosis: ↓ pCO2 due to hyperventilation → ↓ hydrogen ions → ↑ pH

  • Metabolic alkalosis: ↑ bicarbonate or ↓ hydrogen ions → ↑ pH

2. Respiratory Acidosis

Causes:

• CNS damage affecting breathing centers

• Respiratory tract obstruction

• Decreased gas exchange (e.g., COPD, pneumonia)

Compensation:

• Acute: pH ↓ 0.07 per 10 mmHg ↑ pCO2, HCO3⁻ ↑ ~1 mEq/L per 10 mmHg pCO2

• Chronic: pH ↓ 0.03, HCO3⁻ ↑ 3–4 mEq/L per 10 mmHg pCO2

• Renal compensation takes ~4 days, never fully normalizes pH

• Red flag: HCO3⁻ > 30 mEq/L → possible second process (e.g., metabolic alkalosis)

3. Metabolic Acidosis

Causes:

• Increased anion gap: Formation of excess acid (DKA, lactic acidosis, uremia, aspirin, methanol)

• Normal anion gap (hyperchloremic): Loss of bicarbonate (diarrhea, RTA, renal failure)

Compensation:

• Respiratory: ↑ ventilation → ↓ pCO2

• Takes 12–24 hours

• Winter’s formula: Expected pCO2 = 1.5 × [HCO3⁻] + 8 ± 2

• Approximation: Expected pCO2 ≈ last two digits of pH ± 2

• Deviation:

  • pCO2 lower than expected → concomitant respiratory alkalosis

  • pCO2 higher than expected → concomitant respiratory acidosis

4. Respiratory Alkalosis

Causes:

• Hyperventilation: altitude, drugs, pregnancy, cirrhosis, sepsis

Compensation:

• Acute: pH ↑ 0.08 per 10 mmHg ↓ pCO2, HCO3⁻ ↓ ~2 mEq/L

• Chronic: pH ↑ 0.03, HCO3⁻ ↓ ~5 mEq/L per 10 mmHg pCO2

• Renal compensation can fully normalize pH

Red flag: HCO3⁻ ↓ > 2–4 mEq/L → possible superimposed metabolic acidosis

5. Metabolic Alkalosis

Causes:

• Retention of bicarbonate or loss of hydrogen ions

  • Vomiting, gastric suctioning

  • Diuretics → increased Na⁺ reabsorption → H⁺ secretion

  • Excess corticosteroids or aldosterone

  • Ingestion of alkaline substances

Compensation:

• Hypoventilation → ↑ pCO2

• Approximate: ↑ pCO2 ~5 mmHg per 10 mEq/L HCO3⁻

• Rarely exceeds pCO2 > 50 mmHg unless concomitant respiratory acidosis

6. Anion Gap

• Equation: Na⁺ – (Cl⁻ + HCO3⁻) = 12 ± 4 (8–16)

• Unmeasured anions: albumin, phosphate, sulfate, lactate, keto acids, Ca²⁺, Mg²⁺, K⁺

• Albumin effect: ↓1 g/dL → anion gap ↓ 2.5

• High pH effect: albumin more negative → ↑ anion gap

Mnemonics for high anion gap metabolic acidosis:

• MULE-PACK: Methanol, Uremia, Lactic acidosis, Ethylene glycol, Propylene glycol, Aspirin, Ketoacidosis

• MUD-PILES: Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Iron/Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates

Non-anion gap metabolic acidosis:

• Hyperchloremic acidosis → diarrhea, RTA, carbonic anhydrase inhibitors, Addison’s disease

Delta Delta (ΔΔ):

• Ratio of Δ anion gap / Δ bicarbonate

• ΔΔ < 1 → mixed metabolic acidosis (non-anion gap)

• ΔΔ > 2 → metabolic alkalosis or bicarbonate retention

7. Base Excess

• Represents excess or deficit of base (mainly bicarbonate)

• Normal: –2 to +2 mEq/L

• Negative → metabolic acidosis

• Positive → metabolic alkalosis

8. Approach to Acid-Base Disorders

1. Assess clinical picture

2. Measure pH, pCO2, HCO3⁻

3. Identify primary disturbance:

   • pH ↓ & pCO2 ↑ → respiratory acidosis

   • pH ↓ & HCO3⁻ ↓ → metabolic acidosis

   • pH ↑ & pCO2 ↓ → respiratory alkalosis

   • pH ↑ & HCO3⁻ ↑ → metabolic alkalosis

4. Determine acute vs chronic (respiratory)

5. Check anion gap (metabolic acidosis)

6. Assess expected compensation

7. Identify mixed disorders if compensation deviates

Note: Normal pH does not always mean normal acid-base status

9. Expected Compensation Summary (Simplified)

Respiratory Acidosis:

• Acute: ΔHCO3⁻ ≈ +1 mEq/L per 10 mmHg ↑ pCO2

• Chronic: ΔHCO3⁻ ≈ +4 mEq/L per 10 mmHg ↑ pCO2

Respiratory Alkalosis:

• Acute: ΔHCO3⁻ ≈ –2 mEq/L per 10 mmHg ↓ pCO2

• Chronic: ΔHCO3⁻ ≈ –5 mEq/L per 10 mmHg ↓ pCO2

Metabolic Acidosis:

• Expected pCO2 ≈ 1.5 × [HCO3⁻] + 8 ± 2 or last two digits of pH

Metabolic Alkalosis:

• Expected pCO2 ≈ 0.7 × [HCO3⁻] + 20 ± 5

10. Examples

• Acute respiratory acidosis: OR patient hypoventilating → pH ↓, pCO2 ↑, HCO3⁻ slightly ↑

• Chronic respiratory acidosis: COPD patient → pH mildly ↓, pCO2 ↑, HCO3⁻ significantly ↑ (renal compensation)

• Mixed disorders: Cardiac arrest + lactic acidosis → combined respiratory and metabolic acidosis

11. Diuretics Overview

• Increase urine output → ↓ renal sodium absorption → water follows → increased excretion

• Often cause potassium, chloride, magnesium, calcium loss

• Potassium-sparing diuretics: aldosterone antagonists, sodium channel blockers

• Goal: reduce extracellular fluid volume in edema or hypertension

• Effect over time: increased sodium excretion → gradual reduction in extracellular fluid volume

These notes summarize the main points for renal acid-base physiology and diuretic therapy. They are structured for quick review and exam prep.

Renal Physiology – Acid-Base Regulation (Part 4)

Basic Definitions

• Acid: Molecule that can release a hydrogen ion (HCl, H₂CO₃).

• Base: Molecule that can accept a hydrogen ion (HCO₃⁻, phosphate, hemoglobin).

• Normal arterial blood pH: 7.4
  → corresponds to [H⁺] = 40 nEq/L.

Acid-Base Regulation

• The body maintains precise pH via three mechanisms:

  1. Buffer systems – act within seconds.

  2. Lungs – act within minutes, eliminate CO₂ (carbonic acid).

  3. Kidneys – act within hours to days, excrete acid and regulate bicarbonate.

Bicarbonate Buffer System

• Equation:
  CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻

• Excess acid → buffered by HCO₃⁻ → forms H₂CO₃ → breaks into CO₂ + H₂O → CO₂ exhaled.

• Excess base (e.g., NaOH) → reacts with H₂CO₃ → forms Na⁺ + HCO₃⁻ + H₂O.

Henderson-Hasselbalch Equation

• pH depends on:

  • Directly proportional to [HCO₃⁻]

  • Inversely proportional to PCO₂

• Clinical principle:

  • Lungs control PCO₂ → respiratory disorders.

  • Kidneys control [HCO₃⁻] → metabolic disorders.

Phosphate Buffer System

• Components: H₂PO₄⁻ / HPO₄²⁻.

• pKa ~ 6.8 (less effective at plasma pH 7.4).

• Works mainly in:

  • Renal tubules

  • Intracellular fluid (more acidic environment, higher phosphate concentration).

Respiratory Regulation

• Normal PCO₂ = 40 mmHg (≈ 1.2 mmol/L CO₂).

• Ventilation ↔ pH relationship:

  • ↑ Ventilation → ↓ PCO₂ → ↑ pH (alkalosis).

  • ↓ Ventilation → ↑ PCO₂ → ↓ pH (acidosis).

• Negative feedback:

  • Acidosis (↑ H⁺) → ↑ ventilation.

  • Alkalosis (↓ H⁺) → ↓ ventilation.

• Dysfunction → respiratory acidosis (CO₂ retention).

Renal Regulation

Bicarbonate Handling

• Normal serum HCO₃⁻: 24 mEq/L.

• Daily filtered load:

  • GFR = 180 L/day → 4320 mEq HCO₃⁻ filtered daily.

• To prevent loss:

  • Each HCO₃⁻ must pair with an H⁺ → forms H₂CO₃ → CO₂ + H₂O.

  • Requires 4320 mEq H⁺ secretion/day.

Non-Volatile Acids

• Produced from metabolism (cannot be exhaled as CO₂).

• Must be excreted by kidneys.

• CTotal H⁺ excretion ≈ 4400 mEq/day.

Renal Response to Disorders

• Acidosis:

  • ↑ H⁺ secretion.

  • ↑ HCO₃⁻ reabsorption.

  • Additional HCO₃⁻ generation.

  • Na⁺/H⁺ exchange & ATP-dependent H⁺ secretion.

• Alkalosis:

  • ↓ H⁺ secretion.

  • ↓ HCO₃⁻ reabsorption → more bicarbonate excreted in urine.

Limits of Urine Acidification

• Lowest urine pH ≈ 4.5.

• This corresponds to only 0.03 mEq/L free H⁺ → insufficient.

• Most H⁺ excreted is buffered by:

  • Phosphate

  • Ammonia (NH₃/NH₄⁺)

Factors Affecting Renal H⁺ Secretion & HCO₃⁻ Reabsorption

• ↑ PCO₂ → ↑ H⁺ secretion, ↑ HCO₃⁻ retention.

• ↑ H⁺ or ↓ HCO₃⁻ → same response.

• ↓ ECF volume → ↑ H⁺ secretion (to retain Na⁺/water).

• ↑ Angiotensin II / Aldosterone → ↑ H⁺ secretion.

• Hypokalemia → promotes H⁺ secretion and HCO₃⁻ retention.

• Opposite conditions → opposite effects.

Key Takeaway:

• Lungs regulate CO₂ → respiratory component.

• Kidneys regulate HCO₃⁻ → metabolic component.

• Acid-base balance depends on tight coordination of both systems with buffer support.

Renal Physiology – Electrolyte Disorders

Hypokalemia

Definition (serum K⁺):

• Normal: 3.5–5 mEq/L

• Mild: 3.0–3.5

• Moderate: 2.5–3.0

• Severe: <2.5

Causes:

• ↓ Intake

• ↑ Excretion: diarrhea, diuretics, hyperaldosteronism, hypomagnesemia

• Shifts into cells: alkalosis, insulin, β2-agonists

Signs/Symptoms:

• Nonspecific: weakness, cramps

• ECG: flattened/inverted T-waves, U-waves

• Chronic hypokalemia tolerated better than acute

Treatment:

• Oral or IV K⁺ supplementation

• Oral preferred (safer, slower rise)

• IV guidelines:

  • Max: 10 mEq/hr (0.5 mEq/kg/hr)

  • Limit: 250 mEq/day

  • Central line preferred (peripheral causes burning)

  • Continuous ECG monitoring

• Rule of thumb: 10 mEq KCl → ↑ serum K⁺ by ~0.1 mEq/L (slow redistribution)

• Correct hypomagnesemia concurrently

Perioperative Considerations:

• No universal cutoff for canceling surgery

• Risk ↑ when K⁺ <3.5, especially in cardiac surgery (AFib, atrial flutter)

• 1 mEq/L drop in serum K⁺ = ~200–400 mEq total body deficit

Calcium & Phosphate (brief renal overview)

Calcium:

• Reabsorbed in proximal tubule (via Ca²⁺ ATPase & Na⁺/Ca²⁺ counter-transport)

• Regulated by PTH → ↑ renal Ca²⁺ reabsorption, ↑ bone resorption

• Follows Na⁺ and water

• Alkalosis → ↑ Ca²⁺ reabsorption

Phosphate:

• Normal: 2.5–4.5 mg/dL (0.81–1.45 mmol/L)

• Reabsorbed in proximal tubule (~0.1 mmol/min max)

• PTH: ↓ renal phosphate reabsorption → ↑ phosphate excretion

Hyperphosphatemia Causes:

• Kidney disease, hypoparathyroidism, acidosis, DKA, phosphate enemas

• Symptoms similar to hypocalcemia

• Treatment: phosphate binders

Hypophosphatemia Causes:

• Alcoholism, burns, starvation, diuretics, alkalosis, aluminum antacids

• Symptoms: weakness → respiratory failure, heart failure

• Treatment: oral or IV phosphate (0.5 mmol/kg KPhos over 6 hrs)

Magnesium

Normal: 1.8–2.6 mg/dL

• 50% intracellular, 50% bone, tiny fraction extracellular (half protein-bound)

Hypomagnesemia:

• Causes: GI losses (diarrhea), poor intake, diuretics

• Symptoms: anorexia, nausea, weakness, tremors, fasciculations, seizures

• Often with hypokalemia & hypocalcemia

• Treatment: MgSO₄ 2 g IV (15 min, can be faster if urgent)

Hypermagnesemia:

• Causes: renal failure, ingestion (antacids), medical therapy

• Symptoms by level:

  • 4–6 mEq/dL (4.8–7.2 mg/dL): ↓ reflexes

  • 10 mEq/dL (12 mg/dL): hypotension, paralysis, respiratory depression, cardiac arrest

• Treatment:

  • IV calcium (cardiac protection)

  • Diuretics (excretion)

  • Dialysis if severe

Clear takeaway: 

Always correct Mg²⁺ with K⁺/Ca²⁺ disturbances, watch cardiac effects, and consider chronic vs. acute context.

Gorgeous Day At Work

 

Renal Physiology – Study Notes (Part 2)

Urine Osmolarity

• Range: 50–1400 mOsm/L

• Determined by how much free water the body must excrete.

• Maintains plasma volume without altering solute concentration.

Antidiuretic Hormone (ADH, Vasopressin)

• Secreted by: Posterior pituitary.

• Stimulus: ↑ plasma osmolarity (↑ solute concentration).

• Action:

  • Acts on distal tubule & collecting duct.

  • Increases free water reabsorption → concentrates urine.

• Obligatory urine volume:

  • Solute excretion ≈ 600 mOsm/day.

  • Max urine concentration ≈ 1200 mOsm/L.

  • Minimum urine volume ≈ 0.5 L/day (to excrete solutes).

• Clinical example: Seawater ingestion → too much salt intake → requires excessive urine output → worsens dehydration.

Disorders of ADH Regulation

SIADH (Syndrome of Inappropriate ADH Secretion)

• Pathophysiology: Too much ADH → water retention → dilutional hyponatremia.

• Causes:

  • CNS issues: head injury, hemorrhage, tumors.

  • Cancers: e.g., small-cell lung carcinoma.

  • Drugs: carbamazepine, antipsychotics.

• Findings:

  • Hyponatremia (Na < 110 mEq/L = CNS toxicity risk).

  • Concentrated urine.

• Treatment:

  • Fluid restriction.

  • Hypertonic saline (if severe).

  • Diuretics.

  • Correct Na < 0.5 mEq/L per hour to avoid central pontine myelinolysis (CPM).

Diabetes Insipidus (DI)

• Pathophysiology: Lack of ADH activity → impaired water reabsorption → excessive dilute urine.

• Types:

  1. Central (Neurogenic):

     • ↓ ADH secretion (pituitary damage: trauma, tumors, surgery, SAH).

     • Onset: 4–24 hrs after pituitary surgery.

     • Symptoms: polyuria, polydipsia, hypernatremia.

     • Treatment: Desmopressin (DDAVP), carbamazepine.

  2. Nephrogenic:

     • Normal ADH secretion, but kidney unresponsive.

     • ADH analogs ineffective → different treatments required.

• Findings:

  • Very dilute urine (low specific gravity, low urine osmolarity).

  • High serum osmolarity & sodium.

  • Large urine volumes (several 100s of mL/hr).

ADH Regulation

• Stimuli that ↑ ADH:

  • ↑ plasma osmolarity (Na+).

  • Hypovolemia, hypotension.

  • Nausea, hypoxia.

• ↓ ADH: Alcohol (→ diuresis).

• Contrast:

  • ADH: Retains free water only → changes osmolarity & Na+.

  • Aldosterone/Angiotensin II: Retain Na+ + water → minimal effect on osmolarity.

Potassium Physiology

• Normal plasma [K+]: 3.5–5.0 mEq/L.

• Distribution: 98% intracellular, 2% extracellular.

• Daily intake: ~100 mEq → mostly excreted renally, some in feces.

Regulation of K+ between ICF & ECF

• Shift K+ into cells: Insulin, aldosterone, β-stimulation, alkalosis.

• Shift K+ out of cells: Insulin deficiency, aldosterone deficiency, β-blockade, acidosis, cell lysis, strenuous exercise.

Renal Handling of K+

• Aldosterone: ↑ Na+ reabsorption, ↑ K+ secretion (via Na+/K+ ATPase).

• Increased tubular flow: ↑ K+ excretion.

• Acidosis:

  • Acute: ↓ K+ secretion (retention).

  • Chronic: ↑ K+ loss (via ↓ Na+ reabsorption).

Disorders of Potassium

Hyperkalemia

• Defined as: K+ > 5.5 mEq/L.

• Severity:

  • Mild: 5.5–6.0

  • Moderate: 6–7

  • Severe: >7 (life-threatening >8.5).

• Causes:

  • Renal failure.

  • ↓ Aldosterone.

  • Medications (K+-sparing diuretics).

  • Acidosis (H+ moves in, K+ moves out).

  • Cell destruction (lysis, trauma, exercise).

• Symptoms: Palpitations, muscle weakness.

• ECG changes:

  • Peaked T waves → widened QRS → sine wave → VFib/asystole.

Treatment of Hyperkalemia (Mnemonic: C BIG K Drop)

• C – Calcium gluconate (10 mL 10% IV over 10 min): cardiac protection.

• B – Beta agonists (albuterol); Bicarbonate (NaHCO₃): shift K+ into cells.

• I – Insulin (10 units IV) + G – Glucose (D50 IV): drive K+ into cells.

• K – Kayexalate (polystyrene resin): removes K+ via GI tract.

• D – Diuretics or Dialysis: excretion of K+.

✅ That closes out Part 2: ADH physiology, SIADH, Diabetes Insipidus, and Potassium balance.

Renal Physiology – Part 1 Study Notes

Functions of the Kidney

• Excretion of metabolic waste/toxins:

  • Urea (amino acid metabolism)

  • Creatinine (muscle breakdown)

  • Uric acid (nucleic acid breakdown)

  • Bilirubin (hemoglobin breakdown)

• Water & electrolyte balance (adjusts to intake changes)

• Arterial pressure regulation:

  • Short-term: Renin–angiotensin system

  • Long-term: Sodium & water balance

• Acid–base balance: excretes acids, regulates buffers

• Erythropoiesis regulation: secretes erythropoietin → RBC production

• Hormones & glucose: Vitamin D activation, gluconeogenesis

Anatomy & Filtration

• Glomerulus: capillary network at start of nephron → filtrate enters Bowman’s capsule

• Filtrate = water + solutes (no proteins, protein-bound solutes, cells, or most negatively charged molecules)

• Blood supply: Afferent arteriole → glomerulus → efferent arteriole (unlike typical venules)

• ~1 million nephrons per kidney (non-regenerative if destroyed)

Excretion = Filtration + Secretion – Reabsorption

• Filtration: glomerular capillaries → Bowman’s capsule

• Reabsorption: nephron → blood

• Secretion: peritubular capillaries → renal tubules

Urinary Tract

• Bladder: smooth muscle storage chamber

• Ureters: drain urine into bladder

• Urethra: exits bladder; innervated by sympathetic & parasympathetic nerves

Glomerular Filtration Rate (GFR)

• Definition: Flow rate of filtered fluid through kidneys; indicator of renal function (important for drug dosing)

• Normal: 125 mL/min (~180 L/day)

• Renal blood flow (RBF): ~1100 mL/min (~22% CO)

• Renal plasma flow: RBF × (1 – hematocrit) ≈ 660 mL/min

• Filtration fraction: GFR / RPF ≈ 20%

• Reabsorption: ~124 mL/min → net urine output ≈ 1 mL/min

Determinants of GFR

• Hydrostatic pressure

• Oncotic pressure

• Causes of ↓ GFR:

  • Renal disease/diabetes (membrane damage)

  • Hypotension (↓ hydrostatic pressure)

  • ↑ resistance in afferent arteriole (↓ flow in; e.g., vasopressors, sympathetic tone)

  • ↓ resistance in efferent arteriole (blood leaves too quickly; low Ang II)

  • ↑ plasma oncotic pressure (opposes filtration)

  • ↑ Bowman’s capsule pressure (e.g., obstruction/stone)

Autoregulation

• Maintains constant RBF & GFR despite MAP changes (70–170 mmHg)

• Mechanisms:

  • Tubuloglomerular feedback (macula densa senses NaCl in distal tubule)

  • Adjusts afferent/efferent resistance

  • Renin release from juxtaglomerular cells

• Net effect: as MAP ↑ → urine output ↑ (RBF & GFR constant)

Clearance

• Definition: volume of plasma completely cleared of a substance per unit time

• Theoretical concept → substance passes repeatedly until cleared

• Example: If [substance] = 1 mg/mL in plasma & 1 mg/min excreted → clearance = 1 mL/min

Creatinine & GFR

• Creatinine: freely filtered, slight secretion → good approximation of GFR

• Methods:

  • 24-hour urine collection → precise Cr clearance

  • Serum creatinine (inverse relationship with GFR)

• Equations:

  • Cockcroft–Gault (older, still used for drug dosing)

  • MDRD & CKD-EPI (preferred in modern practice)

Clinical note: Drugs with renal clearance require dose adjustment if creatinine clearance is low.