Renal Physiology Part 2

98% of K is in the

ICF

ECF K+ has a range of

3.5-5.5 mEq/L

K has a strong influence on what aspect of the cells?

Resting membrane potential

__________ is central hormone controlling K balance

Aldosterone

What two factors affect plasma potassium levels?

→ Shifts between ICF and ECF (internal balance)

→ Ingestion vs. excretion (external balance)

What happens when ECF K⁺ increases?

1. Stimulates aldosterone secretion

→ Renal K⁺ excretion

2. Increases cellular K⁺ uptake in skeletal muscles cells

Which hormones promote potassium movement from ECF to ICF?

1. Insulin

2. Epinephrine

Acidosis is buffered by

ICF

How does acidosis affect plasma K+?

Acidosis → H⁺ enters cells → K⁺ exits cells → ↑ plasma K⁺ (hyperkalemia)

→ H⁺/K⁺ ATPase pumps

How does alkalosis affect plasma K+?

Alkalosis → H⁺ leaves cells → K⁺ enters cells → ↓ plasma K⁺ (hypokalemia)

→ H⁺/K⁺ ATPase pumps

What percentage of filtered K⁺ is reabsorbed in the proximal tubule?

70%

What percentage of filtered K⁺ is reabsorbed in the thick ascending limb?

25%

What is the usual fractional excretion of K⁺?

10-20%

How low can fractional K⁺ excretion be in K⁺ deficiency?

0%

How high can fractional K⁺ excretion go in states of K⁺ excess?

150-200%

What parts of the nephron are the most important determinant of urinary K⁺ output?

Secretion of K⁺ from:

→ Late distal tubule

→ Cortical collecting duct

Aldosterone stimulates ____ secretion while promoting ____ uptake

1. K⁺ and H+ secretion

2. Na⁺ uptake (water follows)

How is K⁺ reabsorbed in the collecting duct during K⁺ depletion?

α-intercalated cells reabsorb K⁺

→ H⁺/K⁺-ATPase

Which drugs can cause hyperkalemia?

1. Alpha inhibitors

→ No aldosterone = K+ in ECF

2. Beta blockers

Which drugs/hormones cause hypokalemia?

1. Aldosterone

2. Beta agonist

3. Insuline

Do the following cause hyperkalemia or hypokalemia?

1. Metabolic acidosis

2. Metabolic alkalosis

3. Diarrhea

4. Cell lysis

5. ↑ECF osmolarity

1. Hyperkalemia

2. Hypokalemia

3. Hypokalemia

4. Hyperkalemia

5. Hyperkalemia

Which diuretics cause loss of K+? How?

→ Thiazides

→ Loop diuretics

→ Prevent Na reabsorption

→ Increased delivery of Na to the cortical collecting duct

→ Increased Na reabsorption and K secretion

How does metabolic alkalosis promote renal K⁺ loss?

Metabolic alkalosis → ↑ HCO₃⁻ in tubule → ↑ K⁺ secretion → ↓ ECF K⁺

How is pH regulated in the body?

1. CO₂ excretion in the lungs

2. H⁺ excretion in the kidneys

3. HCO₃⁻ production in the kidneys

True or false: Most acids and bases in physiology are weak

True

3 components for defense against pH disturbances

1. Buffers

2. Ventilation

3. Renal H⁺ excretion and HCO₃⁻ production

What defense against pH is limited but immediate?

Buffers

What defense against pH occurs over seconds to minutes

Ventilation

What defense against pH occurs over a period of hours to days to prevent sustained pH changes

Renal H⁺ excretion and HCO₃⁻ production

First, second, and third line of defense against pH disturbances

1. Buffers

2. Ventilation

3. Renal H⁺ excretion and HCO₃⁻ production

Most important buffer in ECF is

Bicarbonate buffer system

How do changes in ventilation affect blood pH?

Hypoventilation → High PCO₂ → Respiratory acidosis

Hyperventilation → Low PCO₂ → Respiratory alkalosis

True or false: Changes in CO2 excretion can help compensate for metabolic acid-base disturbance

True

What is a potent stimulus to increase ventilation?

Low plasma pH

Why does an increase in plasma pH cause only a slight change in alveolar ventilation?

Because low ventilation rates can compromise blood oxygenation

True or false: Renal regulation can excrete and generate bicarbonate

True

Where are most acidic ions (like phosphate and bicarbonate) initially filtered?

Glomerulus

Which part of the nephron secretes most of the H⁺?

Proximal tubule

Under normal circumstances, which has more bicarbonate ions: renal venous or renal arterial blood?

Renal venous blood (because kidneys add new HCO₃⁻)

What type of acids are excreted by the kidneys during renal regulation?

Fixed metabolic acids

Acid in urine is mainly in the form of

1. Ammonium (NH₄⁺)

2. Phosphoric acid (H₂PO₄⁻)

What happens to the bicarbonate filtered in the kidneys?

Almost all of it is reabsorbed

Most reabsorption of bicarbonate occurs in the

Early proximal tubule

_______ bicarbonate ions are exchanged for 1 Na ion in the proximal tubule cell

3

Renal _______ production accounts for ~ 75% of H+ excretion

Ammonia

Renal _______ production accounts for ~ 25% of H+ excretion

Phosphate ion

When ammonia is filtered into the lumen, more ________ ions are released in the blood

Bicarbonate

→ Titrating (losing acid and creating base)

When phosphate ion is filtered into the lumen, more ________ ions are released in the blood

Bicarbonate

True or false: Acidification of urine occurs along the entire renal tubule

True

Why doesn’t tubular pH drop below 6.8 even though the proximal tubule secretes most H⁺?

Because of large amounts of HCO₃⁻ and phosphate buffers

Cells in the Loop of Henle, distal tubule, and the principal cells in CCD all secrete H+ via

Na/H exchanger

α-intercalated cells in CCD use primary active H+ secretion via

1. H⁺-ATPase

2. H⁺/K⁺-ATPase pumps

In which part of the nephron is there often a reciprocal relationship between H⁺ and K⁺ secretion?

Cortical collecting duct

CCD secretes large ______ to combat primary acidosis, as a result, less _____ is excreted and ______ may develop

1. H+

2. K+

3. Hyperkalemia

CCD secretes large ______ to combat primary alkalosis, as a result, less _____ is excreted and ______ may develop

1. K+

2. H+

3. Hypokalemia

What does increased Na⁺ delivery to the CCD from diuretic use cause?

More H⁺ and K⁺ secretion (alkalosis and hypokalemia)

Respiratory acid-base disorders are based on

PCO₂

Metabolic acid-base disorders are based on

HCO₃⁻ concentration

What PaCO₂ levels define respiratory acidosis and respiratory alkalosis?

> 45 mmHg → Respiratory acidosis

< 35 mmHg → Respiratory alkalosis

What HCO₃⁻ levels define metabolic acidosis and metabolic alkalosis?

< 22 mEq/L → Metabolic acidosis

> 28 mEq/L → Metabolic alkalosis

Excess production or ingestion of fixed acids can cause

Metabolic acidosis

What are some causes of metabolic acidosis?

1. Ketoacid accumulation

→ Diabetes

2. Lactic acid accumulation

→ Hypoxia

3. Failure to excrete acids

→ CRF

4. Ingestion of toxins

→ Methanol

→ Ethylene glycol

→ Aspirin

What type of compensation is usually present in metabolic acidosis?

Compensatory respiratory alkalosis

Resolution of metabolic acidosis w/o treatment requires

1. ↑HCO₃⁻

2. ↑H⁺ excretion via NH₄⁺

Diarrhea can lead to metabolic acidosis due to

Loss of HCO₃⁻ ions

Anion gap is usually

8-16 mEq/L

Most common cause of metabolic alkalosis

Vomiting

A state of metabolic alkalosis characterized by a net gain of bicarbonate, often due to ECF volume contraction

Contraction alkalosis

What happens to aldosterone and H⁺ secretion when the effective circulating volume is low?

Aldosterone levels increase

→ More H⁺ secretion by the distal nephron

What is the compensatory response to metabolic alkalosis?

Respiratory acidosis

→ Hypoventilation

ROME

→ Acidosis and alkalosis

→ Respiratory Opposite

→ Metabolic Equal

pH ↓ + CO₂ ↑ = Respiratory acidosis

pH ↑ + CO₂ ↓ = Respiratory alkalosis

pH ↓ + HCO₃⁻ ↓ = Metabolic acidosis

pH ↑ + HCO₃⁻ ↑ = Metabolic alkalosis

Inadequate ventilation can cause

Respiratory acidosis

If respiratory acidosis is acute, inadequate time for

Renal compensation

Chronic respiratory acidosis, renal system normalizes pH by

1. Excreting more acid

2. Producing more HCO3-

Respiratory acidosis with no metabolic component (normal HCO3-) can cause

Severe acidemia

If respiratory alkalosis is acute, inadequate time for

Renal compensation

Psychogenic hyperventilation can cause

Respiratory alkalosis

Chronic respiratory alkalosis, renal system normalizes pH by

1. Excreting less acid

2. Producing less HCO3-

Refers to responses that normalize plasma pH

Compensation

True or false: Compensation is usually not complete, which allows the primary acid-base disorder to be recognized

True

pH = 7.32 - Acidic

PCO2 = 55 - Acidic

HCO3 = 31 - Alkalosis

Diagnosis?

Respiratory acidosis with kidneys compensating

pH = 7.48 - Alkalosis

PCO2 = 50 - Acidic

HCO3 = 35 - Alkalosis

Diagnosis?

Metabolic alkalosis with lungs compensating

Prevents involuntary emptying of the bladder

Guarding reflex

How do stretch receptors in the bladder signal to initiate urination?

Bladder stretch receptors → Visceral afferent nerves → S2–S4 spinal cord → Pons micturition center

What happens after the pons micturition center processes information about bladder stretch?

Internal urethral sphincter opening

→ Inhibits sympathetic innervation (L2, inferior hypogastric plexus)

→ The internal urethral sphincter relaxes/opens

Bladder contraction

→ Parasympathetic pelvic splanchnic nerves (S2–S4) release acetylcholine (ACh)

→ ACh binds to M3 muscarinic receptors

→ Detrusor muscle contracts

Which nervous system controls voiding (bladder contraction)?

PNS

Which nervous system inhibits voiding, and through which receptors?

Sympathetic neurons

→ α₁ and β₃ receptors

The person can control urination voluntarily by relaxing the

External urethral sphincter

Which nerve controls the external urethral sphincter?

Pudendal nerve (S2–S4)

How does the pudendal nerve control the external urethral sphincter?

Active pudendal nerve → ACh → Nicotinic receptors → Sphincter closed

Inhibition of the pudendal nerve → No ACh → No contraction →Sphincter opens

Internal urethral sphincter:

1. Muscle type

2. Voluntary or involuntary

3. Innervation

1. Smooth muscle

2. Involuntary

3. Sympathetic (L2 - inferior hypogastric plexus)

External urethral sphincter:

1. Muscle type

2. Voluntary or involuntary

3. Innervation

1. Skeletal muscle

2. Voluntary

3. Pudendal nerve