Lec 20 - Loop of Henle

pH definition

Negative log of hydrogen ion concentration

Neutral pH

7 (equal H+ and OH-)

Acidic solution

pH < 7 (more H+)

Basic/alkaline solution

pH > 7 (more OH-)

Normal arterial pH

~7.40

Normal venous pH

~7.35

Normal interstitial pH

~7.35

Intracellular pH range

6.0–7.4

Urine pH range

4.5–8.0

Lethal pH limits

6.8–8.0

Importance of pH

Affects enzymes, proteins, membranes

Systems affected by pH

Nervous and cardiovascular systems

Acidosis definition

pH < 7.35

Alkalosis definition

pH > 7.45

Volatile acids

Can leave solution (CO2 system)

Example volatile acid

Carbonic acid (H2CO3)

Carbonic acid reaction

CO2 + H2O ⇌ H2CO3 ⇌ H+ + HCO3-

Enzyme involved

Carbonic anhydrase

Fixed acids

Cannot leave solution

Examples fixed acids

Sulfuric acid, phosphoric acid

Organic acids

Lactic acid, ketone bodies

Source of lactic acid

Anaerobic respiration

Source of ketones

Excess lipid metabolism

H+ elimination routes

Kidneys and lungs

Kidney role

Secrete H+

Lung role

Remove CO2

Buffer definition

Resists pH changes

Buffer action

Binds or releases H+

Buffer equation

HY ⇌ H+ + Y-

High H+ effect

Drives reaction left (binds H+)

Low H+ effect

Drives reaction right (releases H+)

Types of buffers

Bicarbonate, phosphate, protein

Bicarbonate buffer system

Main ECF buffer

Components

H2CO3 and NaHCO3

H2CO3 role

Acts in acidic conditions

HCO3- role

Binds H+ (buffer reserve)

Adding acid effect

HCO3- binds H+

Adding base effect

H2CO3 neutralizes OH-

Bicarbonate limitation

Cannot buffer CO2 changes well

Dependence on lungs

Requires normal respiration

Dependence on HCO3-

Limited by availability

Phosphate buffer system

Important in ICF and tubular fluid

Phosphate buffer equation

H2PO4- ⇌ H+ + HPO42-

Weak acid

H2PO4-

Weak base

Na2HPO4

Phosphate reservoir

Bone (~85%)

Other phosphate roles

DNA, ATP, membranes

Hypophosphatemia

Causes hypophosphatemia

Alcoholism, starvation, burns

Symptoms hypophosphatemia

Muscle weakness, heart issues

Hyperphosphatemia

4.5 mg/dL

Causes hyperphosphatemia

Renal failure, acidosis

Effect hyperphosphatemia

Hypocalcemia (tetany)

Protein buffer system

Major intracellular buffer

Mechanism

Amino acid side chains bind/release H+

Contribution

60–70% of total buffering

Respiratory regulation

Controls pH via ventilation

Alveolar ventilation

Controls CO2 levels

↑ ventilation

↓ CO2 → ↑ pH

↓ ventilation

↑ CO2 → ↓ pH

Relationship

H+ ↑ → ventilation ↑

CO2 relationship

CO2 ↓ → H+ ↓

Effectiveness respiratory

50–75% compensation

Capacity respiratory buffer

1–2x extracellular buffers

Respiratory response speed

Fast (minutes)

Most effective condition

Acidosis

Impaired lungs effect

Respiratory acidosis

Renal regulation

Controls pH via H+ and HCO3-

Bicarbonate reabsorption

Requires H+ secretion

Acidosis kidney response

↑ H+ secretion, ↑ HCO3- reabsorption

Additional effect acidosis

New bicarbonate production

Alkalosis kidney response

↓ H+ secretion

Alkalosis effect

↓ HCO3- reabsorption, ↑ excretion

Kidney response speed

Slow (hours to days)

Kidney effectiveness

Most powerful long-term regulator

Concept: What happens if pH decreases?

H+ increases → acidosis

Concept: What happens if pH increases?

H+ decreases → alkalosis

Concept: What happens if CO2 increases?

pH decreases (acidosis)

Concept: What happens if CO2 decreases?

pH increases (alkalosis)

Concept: What happens if ventilation increases?

CO2 decreases → pH increases

Concept: What happens if ventilation decreases?

CO2 increases → pH decreases

Concept: What happens in metabolic acidosis?

Kidneys excrete H+, lungs increase ventilation

Concept: What happens in metabolic alkalosis?

Kidneys excrete HCO3-, lungs decrease ventilation

Concept: Why are buffers important?

Immediate pH stabilization

Concept: Why is bicarbonate main buffer?

Works with respiratory system

Concept: Why is phosphate buffer important?

Works in cells and kidneys

Concept: Why are proteins good buffers?

Many binding sites for H+

Concept: What happens if bicarbonate is low?

Reduced buffering → acidosis risk

Concept: What happens if bicarbonate is high?

Alkalosis

Concept: Why is CO2 important in pH?

Forms carbonic acid

Concept: Why is carbonic anhydrase important?

Speeds reaction

Concept: What happens if lungs fail?

CO2 accumulates → acidosis

Concept: What happens if kidneys fail?

H+ accumulates → acidosis

Concept: Why is renal regulation slow?

Requires transport and synthesis

Concept: Why is respiratory regulation fast?

Direct gas exchange

Concept: What happens in severe acidosis?

Enzyme dysfunction, CNS depression

Concept: What happens in severe alkalosis?

Neuromuscular excitability

Concept: Why is pH tightly controlled?

Essential for enzyme function

Concept: Why is 7.4 optimal?

Optimal protein function

Concept: What happens if buffer systems overwhelmed?

pH imbalance occurs