Renal Lecture 5 Flashcards
Topic 4 Renal System
Which of the following statements is FALSE?
a. Electrolytes have greater osmotic power than non-electrolytes.
b. Potassium is the major cation found in intracellular fluid.
c. Chloride is the major anion found in plasma.
d. The sodium-potassium ATPase pumps 3 sodium ions out of the cell for every 2 potassium ions into the cell.
e. Bicarbonate ion is the major anion found in interstitial fluid.
The FALSE statement is:
e. Bicarbonate ion is the major anion found in interstitial fluid.
Explanation:
The major anion in interstitial fluid is chloride (Cl⁻), not bicarbonate. Bicarbonate is more prominent in plasma.
Which of the following factors will trigger increased release of ADH?
a. increase in ECF volume
b. decrease in ECF volume
c. decrease in ECF osmolarity
d. increase in ECF osmolarity
e. B and D
e. B and D
Explanation:
Decrease in ECF volume (B) and increase in ECF osmolarity (D) both trigger increased release of ADH.
A decrease in ECF volume signals the body to conserve water, leading to ADH release.
An increase in ECF osmolarity indicates dehydration, which also stimulates ADH to promote water reabsorption.
Sodium’s Role:
Sodium and its anions contribute to 280 mOsm of plasma osmolarity.
Water follows sodium when channels are open.
Sodium Balance Influences:
Aldosterone: Increases sodium reabsorption, raising blood pressure.
ADH: Promotes water reabsorption, maintaining sodium balance.
ANP: Reduces sodium reabsorption, lowering blood pressure.
Other Hormones: Estradiol, progesterone, and cortisol help retain sodium.
Baroreceptors: Regulate sodium and water reabsorption based on blood pressure.
Potassium Balance:
High ECF K+ is toxic, affecting membrane potential, especially in cardiac muscle, and involved in acid-base balance.
K+ Filtration: 10% is lost in filtrate; 65% reabsorbed in PCT, 25% in nephron loop. Tubular secretion occurs to balance excess.
K+ Secretion: Happens in DCT and collecting ducts.
Dietary K+: Essential for maintaining intracellular K+ stores; excess excretion needs to be replaced.
2 factors determine rate & extent of K+ excretion:
(i) plasma [K+]
(ii) [aldosterone]
Calcium and Phosphate Balance:
99% of calcium is in bones.
Calcium is crucial for muscle, nerve function, and bone health.
Hormones:
PTH: Increases blood Ca²⁺.
Calcitonin: Decreases blood Ca²⁺, mainly in children.
Reabsorption: ~98% of filtered Ca²⁺ is reabsorbed.
PTH (Parathyroid Hormone):
Stimulus: Drop in blood Ca²⁺.
Targets:
Bone: Stimulates osteoclasts to release Ca²⁺.
Small intestine: Activates vitamin D to increase Ca²⁺ absorption.
Kidneys: Increases Ca²⁺ reabsorption, but reduces phosphate reabsorption (to balance calcium and phosphate levels).
Phosphate Reabsorption:
No PTH: Phosphate is reabsorbed up to Tm (transport maximum).
High PTH: Reduces phosphate reabsorption in the kidneys.
PTH and Vitamin D:
PTH activates Vitamin D to promote calcium absorption in the GI tract.
Vitamin D becomes active (1,25-dihydroxyvitamin D) after two hydroxylations.
Calcitonin:
Secreted in response to high blood calcium.
Inhibits osteoclasts, reducing bone resorption.
Important in childhood growth but not key for adult bone density regulation or kidney function.
Acid-Base Balance Mechanisms:
Buffer Systems:
Bicarbonate, protein, and hemoglobin buffers neutralize pH changes.
Respiratory Mechanism:
Lungs adjust CO₂ levels to regulate blood acidity by altering ventilation.
Kidney Mechanism:
Excretes H⁺ and reabsorbs HCO₃⁻ to balance pH.
Produces NH₄⁺ to help buffer acidity.
Alkalosis vs. Acidosis:
Alkalosis: pH > 7.45, low H⁺.
Acidosis: pH < 7.35, high H⁺.
Sources of Acid:
Protein breakdown: Phosphoric acid.
Anaerobic metabolism: Lactic acid.
Fat metabolism: Fatty acids and ketones.
CO₂: Forms bicarbonate, releasing H⁺.
CO₂ combines with water to form bicarbonate (HCO₃⁻), which releases H⁺, making the blood more acidic.
Blood [H+] Regulation:
Chemical Buffers: Bicarbonate, phosphate, and protein buffers neutralize H⁺.
Respiratory Center: Adjusts CO₂ to control blood pH.
Renal Mechanisms: Reabsorb/generate or excrete bicarbonate to balance H⁺.
Chemical buffers like bicarbonate, phosphate, and proteins neutralize H⁺ by binding to excess hydrogen ions, preventing pH changes.
Strong vs. Weak Acids:
Strong acids fully dissociate, increasing H⁺.
Weak acids partially dissociate, having a smaller impact on pH.
See diagram
Bicarbonate Reabsorption:
Tubule cells are impermeable to bicarbonate.
Bicarbonate must be replenished as it’s lost during acid buffering.
Bicarbonate is reabsorbed indirectly via bicarbonate formed in tubule cells.
Na⁺ follows bicarbonate into the peritubular capillaries.
see diagram
Bicarbonate is formed in the tubule cells by combining CO₂ with water, creating carbonic acid (H₂CO₃), which quickly dissociates into bicarbonate (HCO₃⁻) and hydrogen ions (H⁺). The bicarbonate is then transported into the blood.
The 3Na⁺ out and 2K⁺ in transport is active transport through the Na⁺/K⁺ ATPase pump.
The 3Na⁺ out and 2K⁺ in transport refers to the Na⁺/K⁺ ATPase pump, which is active transport. It helps maintain the electrochemical gradients of sodium (Na⁺) and potassium (K⁺) across cell membranes, crucial for processes like H⁺ secretion and bicarbonate reabsorption in the kidneys
Cl⁻ and Na⁺ use secondary active transport, relying on the ion gradients created by the Na⁺/K⁺ ATPase pump to move across the membrane with molecules like HCO₃⁻.
Generating New Bicarbonate:
Bicarbonate reabsorption recycles existing bicarbonate.
New H⁺ from metabolism requires generating new bicarbonate via:
Phosphate buffer system
NH₄⁺ excretion
Phosphate Buffer System:
HPO₄²⁻ is the weak base.
75% of phosphate is reabsorbed, except during acidosis.
Type A intercalated cells secrete H⁺, generating new HCO₃⁻ via HCO₃⁻/Cl⁻ antiport.
NH₄⁺ Excretion:
HCO₃⁻ is generated in PCT cells by glutamine metabolism.
HCO₃⁻ moves into the blood, while NH₄⁺ (a weak acid) is excreted in the urine.
Bicarbonate Ion Excretion:
Rare, usually in alkalosis.
Type B intercalated cells: reverse of reabsorption, excrete bicarbonate while reabsorbing H⁺.
Acid-Base Imbalances
Respiratory Acidosis
Hallmark: PCO2 >45mmHg, pH <7.35
Causes: Impaired lung function, paralyzed muscles, narcotics, brain injury.
Respiratory Alkalosis
Hallmark: PCO2 <35mmHg, pH >7.45
Causes: Anxiety, hypoxemia, brain injury.
Metabolic Acidosis
Hallmark: HCO3− <22 mEq/L, pH <7.35
Causes: Diarrhea, renal disease, diabetes (ketoacidosis), starvation, alcohol.
Metabolic Alkalosis
Hallmark: HCO3− >26 mEq/L, pH >7.45
Causes: Vomiting, diuretics, antacid overuse, excess aldosterone.
Problem #1
pH = 7.6: Alkalosis
P(CO2) = 24 mm Hg: Low (respiratory compensation)
HCO3- = 23 mEq/L: Normal
Diagnosis: Respiratory Alkalosis with compensation.
Problem #2
pH = 7.48: Alkalosis
P(CO2) = 46 mm Hg: High (compensating for metabolic alkalosis)
HCO3- = 33 mEq/L: High
Diagnosis: Metabolic Alkalosis with respiratory compensation.
Problem #3
pH = 7.25: Acidosis
P(CO2) = 46 mm Hg: High (respiratory compensation)
HCO3- = 33 mEq/L: High
Diagnosis: Mixed Acid-Base Disorder: Metabolic alkalosis with respiratory compensation.
Respiratory Acidosis: High CO2, low pH.
Respiratory Alkalosis: Low CO2, high pH.
Metabolic Acidosis: Low HCO3-, low pH.
Metabolic Alkalosis: High HCO3-, high pH.
Problems:
Respiratory Alkalosis: High pH, low CO2.
Metabolic Alkalosis: High pH, high CO2.
Mixed Disorder: Low pH, high CO2, high HCO3-.
Direct actions of aldosterone alone include:
The correct answer is: e) c) and d)
Aldosterone is a hormone that primarily acts on the kidneys, promoting the reabsorption of sodium (Na⁺) and the excretion of potassium (K⁺). This helps regulate sodium and potassium balance and contributes to fluid balance. By increasing sodium reabsorption, aldosterone indirectly increases water retention due to osmotic effects, which can lead to increased blood volume and, consequently, higher blood pressure.
To calculate renal clearance, one must know:
The correct answer is: e) a), b) and c)
Renal clearance refers to the volume of plasma that is completely cleared of a substance by the kidneys per unit of time. To calculate it, you need:
a) The concentration of the substance in plasma (to know how much of the substance is present in the blood).
b) The concentration of the substance in urine (to determine how much of the substance is excreted).
c) The glomerular filtration rate (GFR) (which is important to understand the overall kidney filtration capacity).
Glucose is oxidized to carbon dioxide and water via three successive pathways: glycolysis, the citric acid cycle, and oxidative phosphorylation. Small amounts of ATP are harvested in each pathway, but the bulk is captured in oxidative phosphorylation. There is no buildup of acid, thanks to oxygen serving as the final electron acceptor.
Bicarbonate is the form that CO2 is transported in the bloodstream. Using carbonic anhydrase to shift between bicarbonate and carbonic acid, the pH of blood can be quickly regulated back to a normal range of 7.35-7.45.
primary buffer in the plasma
An increase in CO2 results in the formation of more carbonic acid, which leads to an increase in acidity, or a drop in pH.
If the problem is not respiratory, then often carbon dioxide levels are normal. If the kidneys are excreting too much HCO3-, then your pH will decrease.
Which of these combinations of values would help you determine if your patient was suffering from metabolic acidosis?
Excretion of bicarbonate is a long-term mechanism that the kidneys contribute to acid-base regulation.
Excreting bicarbonate helps eliminate H+ by reducing the buffering capacity of the blood. Here’s how:
Bicarbonate acts as a buffer: Normally, bicarbonate (HCO₃⁻) binds to excess H+ ions, neutralizing them and forming carbonic acid (H₂CO₃).
Excretion reduces buffering: If bicarbonate is excreted, less HCO₃⁻ is available to neutralize H+.
Increased H+ elimination: With less buffering, the kidneys can excrete more H+ directly, helping to lower acidity and restore the pH balance.
The phosphate buffer system works similarly to the bicarbonate system, but in cells and the kidneys. It uses weak acids (H₂PO₄⁻) and weak bases (HPO₄²⁻) to maintain pH. When there’s excess H⁺ (acid), HPO₄²⁻ acts as a base, binding with H⁺ to form H₂PO₄⁻. When there’s excess OH⁻ (base), H₂PO₄⁻ releases H⁺ to neutralize it. It’s especially important in the kidneys, helping to regulate blood pH and excrete excess acids.
Respiratory acidosis occurs during periods of hypoventilation. This allows CO2 to build up in the lungs, lowering blood pH and increasing PCO2.
