WEEK 7: Intro to the Renal System

1. Gross Anatomy and Functions of the Kidney

• Location: Retroperitoneal, near the level of the lower ribs.

• Structure: Outer cortex, inner medulla (with renal pyramids), renal pelvis (drains urine to the ureter).

• Major Functions:

  • Homeostasis: Regulates blood volume, pressure, osmolarity, pH, and ion balance.

  • Excretion: Removes waste; filters ~180 L/day but excretes only ~1.5 L as urine.

  • Hormones: Produces erythropoietin (RBC production) and renin (blood pressure).

2. Structure of the Nephron and Vasculature

• Renal Corpuscle: Composed of glomerulus (capillary network) and Bowman’s capsule.

• Renal Tubule:

  • Proximal Tubule: Reabsorbs water, ions, and nutrients.

  • Loop of Henle: Concentrates filtrate, extending into the medulla.

  • Distal Tubule: Regulates ion balance and pH.

  • Collecting Duct: Collects filtrate from multiple nephrons, adjusts water reabsorption.

• Vasculature:

  • Afferent and Efferent Arterioles: Control blood flow to and from the glomerulus.

  • Peritubular Capillaries & Vasa Recta: Surround the tubules, aiding in reabsorption and secretion.

3. Filtration Barriers

• Layers:

  • Endothelial Cells: Fenestrated, allowing selective passage.

  • Basement Membrane: Repels large proteins.

  • Podocytes: Foot processes form filtration slits.

• Modulation: Mesangial cells alter blood flow; arteriolar dilation/constriction adjusts filtration rate.

4. Forces Regulating Glomerular Filtration Rate (GFR)

• Pressures:

  • Glomerular Capillary Hydrostatic Pressure (GHP): Primary force driving filtration.

  • Bowman’s Capsule Hydrostatic Pressure (CHP): Opposes filtration.

  • Blood Colloid Osmotic Pressure (BCOP): Pulls water back, opposing filtration.

• Modifications:

  • Afferent/Efferent Arteriole Constriction: Affects GHP and, consequently, GFR.

5. Regulation of GFR

• Intrinsic Mechanisms:

  • Myogenic Mechanism: Responds to blood pressure changes; constriction/dilation of arterioles.

  • Tubuloglomerular Feedback: Macula densa cells detect NaCl; adjust GFR via afferent arteriole constriction.

• Extrinsic Mechanisms:

  • Sympathetic Nervous System: Constricts afferent arterioles during stress.

  • RAAS (Renin-Angiotensin-Aldosterone System): Elevates blood pressure and GFR.

  • Atrial Natriuretic Peptide (ANP): Increases GFR, promoting Na+ excretion.

1. Functions of the Respiratory System

   • Gas Exchange: Facilitates O₂ and CO₂ exchange between the atmosphere and the blood.

   • pH Regulation: Maintains homeostasis by balancing blood pH.

   • Protection: Filters out pathogens and irritants through airway mechanisms.

   • Vocalization: Air movement through the vocal cords enables sound production.

2. Definitions of Respiration

   • Cellular Respiration: Production of ATP by converting oxygen to carbon dioxide within cells.

   • External Respiration: Includes four main processes:

     • Ventilation: Air movement between the atmosphere and lungs.

     • Gas Exchange (Lungs-Blood): O₂ and CO₂ exchange across alveoli.

     • Transport of Gases: O₂ and CO₂ transported by the blood.

     • Gas Exchange (Blood-Cells): Movement of gases between blood and body cells.

3. Structure of the Respiratory System

   • Upper Respiratory System: Includes the nasal cavity, pharynx, and larynx. Warms, humidifies, and filters incoming air.

   • Lower Respiratory System: Composed of the trachea, bronchi, bronchioles, and alveoli.

   • Alveolar Structure:

     • Type I Alveolar Cells: Thin cells for gas exchange.

     • Type II Alveolar Cells: Produce surfactant to reduce surface tension and prevent alveolar collapse.

     • Capillaries: Surround alveoli for efficient gas exchange.

4. Mechanics of Ventilation

   • Boyle’s Law: Pressure inversely related to volume; drives air movement.

   • Inspiration:

     • Active Process: Diaphragm and intercostal muscles contract.

     • Pressure Change: Thoracic volume increases, reducing alveolar pressure to draw air in.

   • Expiration:

     • Passive Process: Muscles relax; elastic recoil of lungs and thoracic cage.

     • Pressure Change: Alveolar pressure rises, expelling air.

     • Active Expiration: Uses abdominal and internal intercostal muscles during forced breathing.

5. Factors Influencing Ventilation

   • Lung Compliance: The ability of the lungs to stretch. High compliance means easier stretching; low compliance requires more effort.

   • Elastance: The ability of the lungs to return to their original shape. High elastance supports expiration.

   • Surface Tension: Managed by surfactant produced by type II alveolar cells to reduce effort needed for lung expansion.

   • Airway Resistance:

     • Bronchoconstriction: Increases resistance, decreasing airflow (e.g., asthma).

     • Bronchodilation: Decreases resistance, increasing airflow (stimulated by CO₂ and adrenaline).

6. Lung Volumes and Capacities

   • Tidal Volume (VT): Air moved during normal breath (~500 mL).

   • Expiratory Reserve Volume (ERV): Extra air exhaled after normal exhalation.

   • Inspiratory Reserve Volume (IRV): Additional air inhaled after a normal inspiration.

   • Residual Volume (RV): Air remaining in lungs after maximum exhalation.

   • Total Lung Capacity (TLC): VT + IRV + ERV + RV; the maximum volume of air the lungs can hold.

   • Vital Capacity (VC): VT + IRV + ERV; maximum exchangeable air volume

WEEK 8: renal system 2

1. Describe How Sodium Is Reabsorbed and Drives Reabsorption of Other Molecules

• Sodium Reabsorption: Occurs primarily in the proximal tubule and is an active process.Mechanism:

  • Sodium enters tubule cells via specific channels (e.g., ENaC) or cotransporters (e.g., Na⁺-H⁺ exchanger) and is actively transported into the interstitial fluid via Na⁺/K⁺ ATPase pumps.

  • This creates a low intracellular Na⁺ concentration, enabling passive sodium entry from the tubule lumen.

• Driving Reabsorption of Other Molecules:

  • Glucose and Amino Acids: Reabsorbed via secondary active transport with Na⁺ using cotransporters like SGLT.

  • Water: Follows sodium osmotically, moving into the blood as Na⁺ reabsorption creates an osmotic gradient.

  • Chloride and Other Ions: Follow the electrochemical gradient set up by Na⁺ reabsorption.

2. Explain and Give Examples of the Importance of Tubular Reabsorption and Secretion in Renal Function

• Tubular Reabsorption: Reclaims essential solutes and water, conserving nutrients and maintaining homeostasis.Example: Nearly all filtered glucose and amino acids are reabsorbed to prevent loss in urine.

  • ~99% of filtered water and ions like Na⁺ and Cl⁻ are reabsorbed to regulate fluid and electrolyte balance.

• Tubular Secretion: Moves waste and excess substances from blood to filtrate, aiding excretion and pH regulation.Example: K⁺ and H⁺ ions are secreted to regulate electrolyte balance and blood pH.

  • Drug Clearance: Compounds like penicillin are secreted to enhance their removal from the body.

3. Explain How the Counter-Current Multiplier System in the Loop of Henle Regulates Urine Concentration

• Mechanism:

  • Descending Limb: Permeable to water but not solutes; water exits to the hyperosmotic medulla, concentrating the filtrate.

  • Ascending Limb: Impermeable to water; actively transports Na⁺, K⁺, and Cl⁻ out, reducing filtrate osmolarity.

• Counter-Current Multiplier:

  • Creates a high osmolarity gradient in the medulla, maintained by the vasa recta.

  • The collecting duct can reabsorb water depending on ADH levels, which uses the osmotic gradient to concentrate urine.

4. Describe the Involuntary Micturition Reflex and Voluntary Control Pathway by Higher Brain Centers

• Involuntary Micturition Reflex:

  • Stretch Receptors: When the bladder fills, stretch receptors send signals to the spinal cord.

  • Parasympathetic Activation: Triggers bladder smooth muscle contraction and relaxes the internal sphincter, initiating urination.

• Voluntary Control:

  • Higher Brain Centers: Brainstem and cortex can inhibit or facilitate the reflex by controlling the external urethral sphincter.

  • External Sphincter Control: The somatic nervous system allows voluntary relaxation when socially appropriate.

WEEK 9: Learning Objectives

1. Describe the Role of the Renin-Angiotensin-Aldosterone System (RAAS) in Blood Pressure Regulation

   • RAAS Activation: Triggered by low blood pressure, low sodium, or sympathetic nervous system activation, the kidneys release renin.

   • Angiotensin II Effects:

     • Vasoconstriction: Increases total peripheral resistance (TPR), elevating mean arterial pressure (MAP).

     • ADH Secretion: Promotes water retention.

     • Aldosterone Release: Stimulates Na⁺ reabsorption in the distal nephron, aiding water retention if ADH is present.

     • Na⁺/H⁺ Exchanger Activation: Enhances Na⁺ reabsorption in the proximal tubule.

   • Clinical Target: Drugs like ACE inhibitors and AT1 receptor blockers are used to manage hypertension by interfering with RAAS.

2. Explain How Natriuretic Peptides Regulate Na⁺ and Water Balance

   • ANP and BNP: Released by the heart’s atria and ventricles in response to increased blood volume and pressure.

   • Effects:

     • Inhibition of RAAS: Suppresses renin release, reducing angiotensin II and aldosterone effects.

     • Increased Na⁺ and Water Excretion: Promotes natriuresis (Na⁺ excretion) and diuresis (water excretion), reducing blood volume and pressure.

     • Vasodilation: Lowers blood pressure by widening blood vessels.

3. Importance of Regulating Body K⁺ Levels

   • Maintaining Resting Membrane Potential: K⁺ is critical for resting membrane potential in nerve and muscle cells.

   • Prevention of Arrhythmias: Both hyperkalemia and hypokalemia can cause dangerous cardiac arrhythmias.

   • Hormonal Regulation: Aldosterone plays a key role by increasing K⁺ secretion when levels are high, thus balancing K⁺ and Na⁺.

4. Kidney’s Role in Long-term Blood Pressure Regulation

   • Volume Regulation via RAAS: Adjusts Na⁺ and water reabsorption in response to blood pressure changes, thus controlling blood volume.

   • Na⁺ and Water Excretion: The kidneys excrete excess Na⁺ and water when blood pressure is elevated.

   • Slow but Lasting Effect: The kidney’s adjustments occur over hours to days and are critical for long-term blood pressure stability.

5. Causes and Effects of Kidney Disease on Renal Function

   • Causes:

     • Chronic Conditions: Hypertension, diabetes, glomerulonephritis, and polycystic kidney disease.

     • Acute Conditions: Infections, toxins, obstructions (e.g., kidney stones), and ischemia.

   • Effects:

     • Impaired Filtration: Leads to waste buildup and electrolyte imbalances.

     • Symptoms of Dysfunction: Proteinuria, hematuria, glucosuria, and abnormal electrolyte levels.

     • Chronic Kidney Disease (CKD): GFR below 60 mL/min/1.73 m² over 3+ months; can progress to end-stage renal disease requiring dialysis or transplant.

     • Systemic Impacts: Hypertension, metabolic acidosis, anemia, bone disorders, and fluid overload.

WEEK 10: Intro to the Respiratory System

WEEK 11: Learning Objectives

1. Dalton’s Law and Gas Exchange

   • Dalton’s Law: Each gas in a mixture exerts its own partial pressure (P_gas). The total pressure is the sum of all partial pressures in the mixture.

   • Example: At sea level (760 mmHg):

     • P_N2 = 593 mmHg (78%)

     • P_O2 = 160 mmHg (21%)

   • Humidity Impact: Water vapor (47 mmHg at 37 °C) dilutes the contribution of gases. P_O2 in humidified air = (P_ATM – P_H2O) × %O2.

2. Gas Exchange and Partial Pressure Gradients

   • External Respiration: O2 diffuses from areas of high to low partial pressure.

     • Blood entering the lungs has P_O2 of 40 mmHg; after gas exchange, blood leaves with P_O2 of 100 mmHg.

   • Internal Respiration: Tissues consume O2, lowering P_O2 to 40 mmHg.

     • O2 diffuses from arterial blood (P_O2 100 mmHg) to tissues until equilibrium.

3. Alveolar Ventilation and Gas Exchange Efficiency

   • Hypoventilation: Decreases alveolar ventilation, resulting in lower P_O2 and higher P_CO2.

   • Hyperventilation: Increases alveolar P_O2 and decreases P_CO2.

   • Factors Influencing Gas Exchange:

     • Surface Area: More area enhances gas diffusion.

     • Barrier Thickness: Thicker barriers reduce diffusion.

     • Concentration Gradient: Steeper gradients increase diffusion rates.

4. CO2 Transport and Blood pH Regulation

   • CO2 Transport:

     • Dissolved in Plasma: 7%

     • Bound to Hemoglobin: 23% (carbaminohemoglobin)

     • Converted to Bicarbonate (HCO3−): 70% via carbonic anhydrase.

   • Buffering and pH:

     • Bicarbonate Buffer System: H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3−. Helps maintain pH around 7.4.

   • Ventilation Effects:

     • Hypoventilation: Leads to respiratory acidosis (low pH, high P_CO2).

     • Hyperventilation: Leads to respiratory alkalosis (high pH, low P_CO2).

1. Functions of the Respiratory System

   • Gas Exchange: Facilitates O₂ and CO₂ exchange between the atmosphere and the blood.

   • pH Regulation: Maintains homeostasis by balancing blood pH.

   • Protection: Filters out pathogens and irritants through airway mechanisms.

   • Vocalization: Air movement through the vocal cords enables sound production.

2. Definitions of Respiration

   • Cellular Respiration: Production of ATP by converting oxygen to carbon dioxide within cells.

   • External Respiration: Includes four main processes:

     • Ventilation: Air movement between the atmosphere and lungs.

     • Gas Exchange (Lungs-Blood): O₂ and CO₂ exchange across alveoli.

     • Transport of Gases: O₂ and CO₂ transported by the blood.

     • Gas Exchange (Blood-Cells): Movement of gases between blood and body cells.

3. Structure of the Respiratory System

   • Upper Respiratory System: Includes the nasal cavity, pharynx, and larynx. Warms, humidifies, and filters incoming air.

   • Lower Respiratory System: Composed of the trachea, bronchi, bronchioles, and alveoli.

   • Alveolar Structure:

     • Type I Alveolar Cells: Thin cells for gas exchange.

     • Type II Alveolar Cells: Produce surfactant to reduce surface tension and prevent alveolar collapse.

     • Capillaries: Surround alveoli for efficient gas exchange.

4. Mechanics of Ventilation

   • Boyle’s Law: Pressure inversely related to volume; drives air movement.

   • Inspiration:

     • Active Process: Diaphragm and intercostal muscles contract.

     • Pressure Change: Thoracic volume increases, reducing alveolar pressure to draw air in.

   • Expiration:

     • Passive Process: Muscles relax; elastic recoil of lungs and thoracic cage.

     • Pressure Change: Alveolar pressure rises, expelling air.

     • Active Expiration: Uses abdominal and internal intercostal muscles during forced breathing.

5. Factors Influencing Ventilation

   • Lung Compliance: The ability of the lungs to stretch. High compliance means easier stretching; low compliance requires more effort.

   • Elastance: The ability of the lungs to return to their original shape. High elastance supports expiration.

   • Surface Tension: Managed by surfactant produced by type II alveolar cells to reduce effort needed for lung expansion.

   • Airway Resistance:

     • Bronchoconstriction: Increases resistance, decreasing airflow (e.g., asthma).

     • Bronchodilation: Decreases resistance, increasing airflow (stimulated by CO₂ and adrenaline).

6. Lung Volumes and Capacities

   • Tidal Volume (VT): Air moved during normal breath (~500 mL).

   • Expiratory Reserve Volume (ERV): Extra air exhaled after normal exhalation.

   • Inspiratory Reserve Volume (IRV): Additional air inhaled after a normal inspiration.

   • Residual Volume (RV): Air remaining in lungs after maximum exhalation.

   • Total Lung Capacity (TLC): VT + IRV + ERV + RV; the maximum volume of air the lungs can hold.

   • Vital Capacity (VC): VT + IRV + ERV; maximum exchangeable air volume.

Notes for WEEK 12 Learning Objectives

1. Regulation of Breathing

• Automatic Nature: Breathing is usually an unconscious process initiated by the contraction of skeletal muscles.

• Neuronal Control:

  • Brainstem Involvement: The respiratory rhythm is set by the brainstem, involving:

    • Dorsal Respiratory Group (DRG): Controls muscles of inspiration via the phrenic and intercostal nerves.

    • Ventral Respiratory Group (VRG): Active during forced breathing; controls muscles involved in active expiration and greater inspiration.

    • Pre-Bötzinger Complex: Potential pacemaker of respiratory rhythm.

    • Pontine Respiratory Group (PRG): Modulates rhythm for smooth breathing.

• Feedback Mechanisms: Adjustments based on O22​, CO22​, and H++ levels in blood and extracellular fluid.

2. Chemoreceptor Function and Regulation of Ventilation

• Types of Chemoreceptors:

  • Peripheral Chemoreceptors:

    • Location: Carotid and aortic bodies.

    • Function: Detect changes in PO22​, PCO22​, and pH. Activated significantly when PO22​ drops below 60 mmHg or when PCO22​ and H++ rise.

    • Pathway: Signals sent to the DRG via cranial nerves IX (glossopharyngeal) and X (vagus).

  • Central Chemoreceptors:

    • Location: Surface of the medulla.

    • Function: Detect changes in PCO22​ indirectly by monitoring pH changes in cerebrospinal fluid (CSF).

    • Role: Continuously influence breathing rate to maintain CO22​ balance.

• Primary Stimulus for Altered Ventilation: CO22​ levels are the main drivers for modifying ventilation.

3. Acid-Base Balance and Regulation

• pH Maintenance:

  • Normal Range: Plasma pH must remain between 7.35 and 7.45.

  • Acidosis: pH < 7.35; causes CNS depression, potential coma, and respiratory failure.

  • Alkalosis: pH > 7.45; causes hyperexcitability, muscle spasms, and possible respiratory paralysis.

• Regulatory Mechanisms:

  • Chemical Buffers: Fast-acting, but only buffer small pH changes.

    • Key Buffer: Carbonic acid-bicarbonate system.

  • Respiratory Response:

    • Rapid: Adjusts CO22​ levels to regulate pH.

    • Acidosis Response: Increased ventilation expels CO22​, raising pH.

    • Alkalosis Response: Decreased ventilation retains CO22​, lowering pH.

  • Renal Response:

    • Slow but Powerful: Alters excretion/reabsorption of H++ and HCO3−3−​ to correct long-term pH changes.

    • Type A Intercalated Cells: Active during acidosis; secrete H++ and reabsorb HCO3−3−​.

    • Type B Intercalated Cells: Active during alkalosis; secrete HCO3−3−​ and reabsorb H++.