Urinary System Physiology and Pathophysiology

Glance and Buffering Systems

Readings

• Pages 171-172

Learning Objectives

• Objective: List the three major chemical buffer systems of the body and describe how they resist pH changes.

Introduction to Acid-Base Balance

• Definition: Acid-base balance represents the equilibrium between acids, bases, and salts in the body.

• Acidity Measurement: The acidity of a solution is determined by the concentration of hydrogen ions (H+).

  • Higher H+ ions lead to increased acidity.

• Acids: Compounds that donate H+ ions; dissociate in water into H+ and a second ion.

• Bases/Alkalis: Accept H+ ions; typically release hydroxyl ions (OH-) that bond with H+, forming water.

• pH Scale: 0 to 14 scale indicating acidity/alkalinity.

  • 0: Most acidic (more H+ than OH-)

  • 14: Most alkaline (more OH- than H+)

  • 7: Neutral point (equal H+ and OH-).

  • Equation: $H_2O <br>ightleftharpoons H^+ + OH^-$

pH, Acidosis, and Alkalosis

• pH Definition: The pH of a solution is defined as the negative logarithm of the hydrogen ion concentration in moles per liter.

  • Logarithmic scale: Each unit corresponds to a tenfold change in H+ concentration.

• Optimal Extracellular Fluid (ECF) pH: Typically between 7.35-7.45.

• Acidosis/Acidaemia: Abnormal physiological state from low blood pH (< 7.35).

• Alkalosis/Alkalaemia: Abnormal physiological state from high blood pH (> 7.45).

Buffer Systems and pH Control

• Function of Buffers: Buffers stabilize the pH of solutions by removing or replacing hydrogen ions.

  • Weak Acid and Salt: Buffer systems typically consist of a weak acid and its corresponding salt (weak base).

  • Buffers neutralize strong acids and bases.

• Important Buffer: Carbonic acid–bicarbonate buffer system helps maintain pH homeostasis in blood and is the only significant extracellular buffer.

• Blood pH: Can be fatal if outside homeostasis (7.35-7.45).

  • Dissociation Reaction: $H<em>2CO</em>3 <br>ightleftharpoons HCO_3^- + H^+$

  • Components:

  • Carbonic acid (H2CO3): Weak acid, H+ donor

  • Bicarbonate (HCO3-): Weak base, H+ acceptor

• Responses:

  • Increased blood pH: H2CO3 dissociates, increasing H+, making the solution more acidic.

  • Decreased blood pH: HCO3- binds to H+ and reduces acidity, making the solution more alkaline.

Bicarbonate Buffering

• Chemical Buffer Function: Binds H+ when pH drops and releases it when pH rises.

  • Equation: $H^+ ext{ increased } <br>ightarrow ext{ pH decreased (more acidic)}$

• Reaction with Strong Acids:

  • Example Reaction:

  • $HCl + NaHCO<em>3 ightleftharpoons H</em>2CO_3 + NaCl$

  • Process: Strong acid (HCl) + Weak base (NaHCO3) yields weak acid (H2CO3) + salt (NaCl).

  • pH Drop: Minor unless all bicarbonate (alkaline reserve) is consumed.

  • HCO3- concentration is regulated by kidneys.

Buffering with Strong Bases

• When Strong Base is Added:

  • Reaction occurs as follows:

  • Example Reaction:

  • $NaOH + H<em>2CO</em>3 <br>ightleftharpoons NaHCO<em>3 + H</em>2O$

  • Reaction of strong base (NaOH) with weak acid (H2CO3) produces weak base (NaHCO3) and water.

  • Result: pH rises slightly, with H2CO3 supply being almost limitless due to CO2 from respiration.

Phosphate Buffering

• Components:

  • H2PO4- (dihydrogen phosphate): Weak acid that dissociates into H+ and HPO4^2- (monohydrogen phosphate): weak base.

• Functionality:

  • Reaction with strong acid: $HCl + Na<em>2HPO</em>4 <br>ightleftharpoons NaH<em>2PO</em>4 + NaCl$

  • Strong base reaction: $NaOH + NaH<em>2PO</em>4 <br>ightleftharpoons Na<em>2HPO</em>4 + H_2O$

• Role: Minor in ECF but significant in urine and intracellular fluid (ICF) due to higher phosphate concentrations.

Protein Buffering

• Buffer System: Proteins are the largest buffering system in plasma and cells.

• Amphoteric Properties:

  • Can function as either acids or bases.

  • Functionality:

  • Accept and donate H+ ions as needed.

• Influences on pH:

  • Decreased pH: Amino groups (–NH2) accept ions forming NH3+

  • Increased pH: Carboxyl groups (–COOH) release H+ ions, causing dissociation.

• Equilibrium Reaction: $–COOH <br>ightleftharpoons –COO^- + H^+$

Review of Acid-Base Balance

• Understanding Goals:

  • What acid-base balance is and how buffering systems contribute to it.

Chapter 14: Regulation of Acid-Base Balance

Readings

• Page 172

Learning Objectives

• Describe the influence of the respiratory system on acid-base balance.

• Describe how the kidneys regulate hydrogen and bicarbonate ion concentrations in the blood and their role in acid-base balance.

Respiratory Control

• Acidosis Impact: Stimulates respiratory center due to increased CO2.

  • Effects include increased respiratory rate and depth; H+ concentration decreases.

• Alkalosis Impact: Depresses respiratory center due to decreased CO2.

  • Effects include decreased respiratory rate and depth; H+ concentration increases.

• Impairment Effects: Respiratory system impairment can lead to acid-base imbalances:

  • Hypoventilation: Results in respiratory acidosis.

  • Hyperventilation: Results in respiratory alkalosis.

Renal Control

• Mechanisms:

  • Kidney functions: conserving/generating new HCO3-, secreting HCO3-, NH4+ or H+.

• HCO3- Regulation:

  • To reabsorb bicarbonate, kidneys secrete H+.

  • To excrete excess bicarbonate, kidneys retain H+.

Review of Respiratory and Renal Contributions

• Achievement: Understanding how the respiratory and renal systems contribute to acid-base balance.

Acid-Base Disturbances

Learning Objectives

• Distinguish between acidosis and alkalosis resulting from respiratory and metabolic factors.

Readings

• Pages 176-178

pH and Blood

• Blood pH Norm: Normal pH between 7.35 – 7.45.

  • Acidosis: physiological state of low blood pH (< 7.35).

  • Alkalosis: physiological state of high blood pH (> 7.45).

• Sources of H+ in Body:

  • Phosphoric Acid: Breakdown of phosphorous-containing proteins.

  • Lactic Acid: Produced during anaerobic metabolism of glucose.

  • Fatty Acids & Ketone Acids: Produced through metabolism of fats.

  • Transport of CO2: Occurs in the blood as HCO3-.

Respiratory Acidosis and Alkalosis

• Hypercapnia Condition: Hypoventilation leads to elevated PCO2 in the ECF, causing dissociation of H2CO3, resulting in increased H+ and HCO3-, subsequently lowering pH (respiratory acidosis).

• Hypocapnia Condition: Hyperventilation decreases PCO2, H2CO3, and HCO3-, increasing pH (respiratory alkalosis).

Metabolic Acidosis and Alkalosis

• Conditions:

  • Metabolic Acidosis Uncompensated: HCO3 < 22 mEq/L; pH < 7.35.

  • Metabolic Alkalosis Uncompensated: HCO3 > 26 mEq/L; pH > 7.45.

• Possible Causes of Metabolic Acidosis:

  • Severe Diarrhea: Rapid transit of bicarbonate-rich intestinal secretions.

  • Renal Disease: Inability to remove metabolic acids.

  • Diabetes: Ketoacidosis from inability to utilize glucose properly.

  • Starvation: Breakdown of proteins and fats yielding acidic metabolites.

  • Excess Alcohol: Results in increased blood acidity.

  • Vomiting: Leads to loss of stomach HCl.

  • Diuretics: Cause potassium depletion and subsequent H+ secretion.

  • Antacid Ingestion: Increases bicarbonate levels in ECF.

  • Excess Aldosterone: Stimulates reabsorption of Na+, increasing H+ excretion.

Compensation for Acid-Base Imbalances

• Mechanisms: The body's response to maintain normal pH levels is integral when dealing with imbalances.

  • Initial Disturbance: Identify if the disturbance is respiratory or metabolic.

  • Compensatory Response: The body attempts to correct pH by activating the opposite system.

  • Partial Compensation: pH remains outside the normal range but trends towards normal.

  • Full Compensation: pH returns to the normal range.

  • Uncompensated: pH remains abnormal with negligible compensation attempts.

Changes Associated with Common Acid-Base Imbalances

• Table 15.1 Summary: A summary table illustrating parameter changes linked with respiratory and metabolic causes of acidosis and alkalosis.

Review of Respiratory and Metabolic Differences

• Understanding Goals: Distinguish between different types of acidosis and alkalosis.

Chapter 15: Arterial Blood Gas (ABG) Analysis

Readings

• Pages 180-183

Learning Objectives

• Determine acidosis or alkalosis status based on ABG interpretation, distinguishing between respiratory and metabolic origins.

ABG Interpretation

• Parameters:

  • pH is 7.35 (acidic) to 7.45 (alkaline).

  • PCO2: Abnormal above 40 mmHg (respiratory acidosis) and below 35 mmHg (respiratory alkalosis).

  • HCO3-: Abnormal below 24 mmHg (metabolic acidosis) and above 26 mmEq/L (metabolic alkalosis).

Normal vs Abnormal Values in ABG Analysis

• Standards:

  • Normal: pH = 7.35-7.45; PCO2 = 35-45 mmHg; HCO3- = 22-26 mEq/L.

  • Acidosis: pH < 7.35, HCO3- < 22 mEq/L, PCO2 > 45 mmHg.

  • Alkalosis: pH > 7.45, HCO3- > 26 mEq/L, PCO2 < 35 mmHg.

Interpretation Method: Tic-Tac-Toe

• Step-by-Step Procedure:

  1. Reference Normal Values.

  2. Evaluate pH for disorder (low = acidosis; high = alkalosis).

  3. Identify source: abnormal PaCO2 indicates respiratory issue; abnormal HCO3 indicates metabolic issue.

  4. Apply ROME (Respiratory Opposite, Metabolic Equal) rule.

  5. Construct a Tic-Tac-Toe chart for visual aid in interpretation.

  6. Analyze sample values to determine the type and compensation of the disturbance.

  7. Conclude analysis based on associations established in the chart.

Example Scenarios in ABG Analysis

• Confirmed method application in varied scenarios with representative values to demonstrate effective determination of acid-base status.

Review of Acid-Base Disturbances

• Understanding Goals: Achieve competence in recognizing acid-base disturbances through ABG and compensatory checks.

Chapter 16: Urinary Tract Infections (UTIs)

Learning Objectives

• Describe risk factors, clinical manifestations, and management of UTIs.

Path of Urine Flow

• Diagram detailing urine flow from the kidneys to the urethra, including anatomical structures (e.g., papillae, calyces, bladder).

Basics of Urinary Tract Infections

• Normal Flora: Kidneys, ureters, bladder, and proximal urethra are typically sterile.

  • Sterility is upheld by frequent urine flushing and the presence of secretory antibodies (IgA) in bladder lining.

  • Distal Urethra Flora: Usually contains a microbial community (e.g., Staphylococcus epidermis).

Risk Factors for UTIs

• Bacterial Origins: Infection from bowel flora (e.g., Escherichia coli).

• Other Sources: Infection can arise from hematogenous spread from distal infections or breaches via hospital instrumentation (catheterization).

• Gender: Females are significantly more predisposed to UTIs (30 times).

• Age Effects: Issues such as bladder dysfunction or hormonal changes (low estrogen levels) increase risks.

• Obstruction Concerns: Kidney stones can block urine flow causing reflux, and incomplete voiding can promote bacterial growth.

• Metabolic Influences: Diabetes can elevate glucose in urine, potentiating susceptibility to infections.

Clinical Manifestations of UTIs

• Urethritis: E. coli attachment to urethral cells leads to inflammation and symptoms including dysuria, increased urination frequency, and urgency.

• Cystitis: Ascending E. coli infection of the bladder progresses similarly, damaging the epithelial lining leading to cell apoptosis.

• Common symptoms: dysuria, frequency, urgency.

Diagnosis of UTIs

• Urinalysis: Assessing colour, smell, cloudiness, and dipstick tests for blood and nitrites.

• Midstream Urine Sample: Lab tests indicate neutrophils, bacterial concentrations, and sometimes blood.

Management of UTIs

• Catheter Considerations: Removal or optional replacement generally resolves infection.

• Antibiotics: Broad-spectrum therapy during initial treatment while awaiting results (e.g., Co-trimoxazole, Nitrofurantoin, Fluoroquinolones).

• Fluids: Increasing fluid intake to aid in flushing bacteria from the urinary tract.

• Alleviating Symptoms: Urinary alkalisers and warm baths to soothe dysuria, with cranberry derivatives inhibiting bacterial adhesion.

Review of UTI Knowledge

• Understanding Goals: Recognizing risk factors, clinical manifestations, and management of UTIs.

Pyelonephritis

Learning Objectives

• Compare pathophysiology of acute vs chronic pyelonephritis; discuss clinical manifestations and management.

Definitions

• Pyelonephritis:

  • Infection/inflammation beginning in the urinary tract ascending to the kidneys.

  • Primarily associated with E. coli.

Acute Pyelonephritis

• Infection Progression: Microorganisms ascend ureters, causing acute inflammation, obstructing renal function and pus formation.

• Systemic Complications: Potential sepsis can occur due to infection extension.

Chronic Pyelonephritis

• Pathway: Persistent infection leads to gradual damage; often asymptomatic until chronic kidney disease develops.

• Risk Factors: Obstruction (e.g., stones) leads to urinary reflux and stasis.

Clinical Manifestations of Pyelonephritis

• Symptoms: Dysuria, enhanced frequency, flank pain, elevated fever, tachycardia, generalized malaise.

Diagnosis and Treatment of Pyelonephritis

• Diagnosis: Urinalysis and differential blood tests confirm infection presence.

• Treatment: Antibiotics, fluid intake adjustment, obstruction resolution in chronic cases.

Review of Pyelonephritis

• Understanding Goals: Comprehending pathophysiology, manifestations, and treatment modalities for pyelonephritis.

Glomerulonephritis and Glomerulosclerosis

Learning Objectives

• Describe pathophysiology and management of glomerulonephritis.

• Explain glomerulosclerosis pathogenesis and related consequences.

Overview of Glomerulonephritis

• Definition: Group of disorders characterized by glomerular inflammation.

• Functionality Impact: Affects filtration rates, increases chronic kidney injury risk.

Clinical Presentation of Glomerulonephritis

• Proteinuria and Hematuria: Characteristic findings in clinical scenarios.

IgA Nephropathy

• Context: Common type of glomerulonephritis linked to an immune response to IgA.

• Mechanism: Significant immune complex deposition in glomeruli catalyzing inflammation and filtration obstruction.

Membranous Glomerulonephritis

• Triggered often through post-streptococcal infections.

  • Immune Response: Involves type III hypersensitivity reactions mediated by antibodies leading to filtration disruption.

Management Strategies for Glomerulonephritis

• Antibiotics: Infections stemming from streptococcus require treatment.

• Fluid Management: Diuretics and fluid restrictions as necessary.

• Hypertension Control: Managed through antihypertensives.

• Severe Cases: Dialysis as a potential requirement due to oliguria/anuria.

Glomerulosclerosis Definition

• Pathological characteristics: Diffuse scarring against normal glomerular function, leading to progressive renal impairment.

Pathogenesis of Glomerulosclerosis

• Chronic Factors: Hyperglycemia in diabetes causing microvascular injury and subsequent glomerular alterations.

Consequences of Glomerulosclerosis

• Clinical Outcomes: Include susceptibility to infections, edema, and kidney failure.

Acute Tubular Necrosis

Learning Objectives

• Understand and delineate acute tubular necrosis pathophysiology and management protocols.

Definition and Causes

• Acute Tubular Necrosis (ATN): Damage to the nephron’s epithelial cells caused primarily by ischemia or nephro toxins.

Clinical Presentation of ATN

• Variability in Symptoms: Varies based on etiology, frequently demonstrating classic signs such as hypotension, oliguria, elevated blood urea and creatinine levels.

Management of Acute Tubular Necrosis

• Interventions: Focus on correcting underlying causes, potential diuretics use and careful monitoring in severe cases requiring dialysis.

Review of ATN Understanding

• Goals: Mastery of ATN pathophysiology, clinical features, and treatment.