Physiology Flashcards - Week 7 Concepts on Acid-Base Balance and Renal Regulation

How do the kidneys control extracellular fluid?

Regulate balance of intake and output of water and salt

What is sodium excretion controlled by?

1. Altering GFR

2. Altering tubular Na+ reabsorption

If intake increases, so will pressure diuresis and natriuresis

Describe what would occur in the kidney as a result of increased intake of sodium and water.

Increased intake = increase in blood volume --> will increase CO and BP

Increased arterial pressure will increase urine output by stimulating pressure diuresis

Increased fluid excretion will balance the increased intake

What are 4 factors for edema?

1. Increased capillary hydrostatic pressure

2. Decreased plasma colloid osmotic pressure

3. Increased capillary permeability

4. Obstruction of lymphatic vessels

Caused by an inability to accommodate increase in fluid volume

How does the sympathetic nervous system control extracellular fluid through the kidneys?

Works to decrease Na+ and H2O excretion

- Constriction of renal arterioles (will decrease GFR if activity is severe)

- Increased tubular reabsorption of Na+ and H2O

- Stimulation of renin release (which will trigger AngII and aldosterone)

How do baroreceptors in the carotid sinus and aortic arch control ECF through the kidneys?

With significant change/activation --> will activate and respond to increased pressure

How does angiotensin II control ECF?

Will primarily stimulate thirst centers

Vasoconstrictor --> promotes Na+ and H2O retention

How does aldosterone control ECF?

Reabsorbs Na+ in response to low Na+ intake

How does ADH control ECF?

Responds to osmolarity

Increased osmolarity (typically due to H2O deprivation), increased reabsorption of H2O

How does ANP control ECF?

Released from the R side of the heart in response to overstretch --> will cause secretion and excretion of Na+ (and H2O along with it)

Will compensate for excess blood volume

What are the responses to increased sodium intake?

High Na+ intake will:

- Suppress antinatriuretic system

- Suppress angiotensin II formation (increased Na+ intake, increased BP, decreased Ang II)

- Activate natriuretic system (stimulation of ANP and pressure natriuresis to further excrete Na+)

How does increased Na+ intake suppress the antinatriuretic system?

Will activate low-pressure receptor reflexes which inhibit the sympathetic nerve activity (in an attempt to decrease Na+ reabsorption)

What are some diseased states of volume overload?

- Heart failure (causes blood vol. to increase 15-20%)

- Increased vascular capacity in pregnancy and varicose veins

- Nephrotic syndrome (accumulation of H2O in extracellular tissues --> H2O will move into interstitial space)

- Liver cirrhosis (will lead to non-dependent edema (loose tissues) --> in eyes, scrotum in men)

What is an acid?

Proton donor

What is a base?

Proton acceptor

What is the concentration of H+ in the cell and why is this significant?

0.00004 mEq/L (super low!)

Compared to 142 (Na) and 4 (K)

Describe the pH in different parts of the body.

Arterial pH 7.4

Venous pH 7.35

Interstitial fluid pH 7.35

Intracellular pH 6.0-7.4

Urine pH 4.5-8.0 (can be low/high depending on body's needs)

Gastric pH 0.8 (super low because of HCl in stomach for digestion)

What are 3 systems in the body that prevent acidosis or alkalosis?

1. Acid-base buffer system (fastest)

2. Respiratory centers (removal of CO2 as we breathe)

3. Kidneys (excrete acidic or alkalinic urine as needed)

Describe what would happen to the pH of the blood in a person experiencing a panic attack and hyperventilating.

Hyperventilation --> expelling a lot more CO2 than normal --> blood CO2 goes down

Decrease in CO2 will shift equation to the R to compensate and try to form more CO2 --> H+ will be used up more and will also deplete

Decrease in H+ will result in respiratory alkalosis

Describe what would happen to the pH of the blood in a person with sleep apnea during an apneic episode.

Temporary cessation of breathing --> CO2 will accumulate --> equation shifted to the L --> accumulation of H+

Increase in H+ will lead to respiratory acidosis

What is a buffer?

A substance that reversibly binds H+ in an attempt to minimize changes in PH

What is the most important buffer in the body?

Bicarbonate --> HCO3-

(formed from carbonic acid H2CO3)

What is the phosphate buffer system and where do we usually see its effects?

Utilizes H2PO4- and HPO4(2-)

Main buffer in the kidneys/tubules, also done intracellularly

What is the protein buffer system and how does it work?

Uses hemoglobin to bind or release H+

How is carbonic acid formed?

CO2 + H2O --> H2CO3 --> HCO3- + H+

H2CO3 is a weak acid --> will dissociate into H+ and HCO3-, Na+ will quickly neutralize the bicarb

Must use carbonic anhydrase to catalyze reaction of CO2 + H2O

Where is carbonic acid found?

Lungs and renal epithelial cells

If a strong base is added to carbonic acid, what happens?

It becomes neutralized and produces H2O

If a strong acid is added in the presence of bicarb, what happens?

Increase in H+ will be buffered by HCO3 to form CO2 and H2O (will send the reaction in the reverse direction)

How does the respiratory system regulate acid-base balance?

By exhaling CO2

We measure the partial pressure of CO2 (PCo2), which is usually around 40 mmHg in the arteries

How would the respiratory system respond to an increase in ventilation?

Increased ventilation --> exhaling more CO2 --> decrease in extracellular H+ --> increase in PH

This will stimulate ventilation centers to hypoventilate and get PCo2 back to normal level --> will be negative feedback

Can the respiratory system fully compensate for acid-base regulation?

No! Only about 50-75% effective

EX: If there is metabolic acidosis, balance can be created by respiratory alkalosis --> will not completely return it to normal

If there is an impairment in lung function, how can acid-base balance be affected?

Impairment in lung function --> respiratory acidosis

EX. Severe emphysema --> impaired ability of lungs to eliminate CO2 --> buildup of CO2 in the blood --> acidosis

How do the kidneys regulate acid-base balance?

Through bicarb levels, will excrete acidic or basic urine to balance

Elevated bicarb = metabolic alkalosis

Decreased bicarb = metabolic acidosis

H+ is regulated by __________.

Bicarb is regulated by __________.

H+ is regulated by secretion.

Bicarb is regulated by filtration.

What are the mechanisms through which the kidney regulates acid-base balance?

1. Secretion of H+ by Na/H countertransporter

2. Reabsorption of HCO3-

3. Production of new HCO3-

In the presence of H+ will bicarb be reabsorbed or secreted? In the absence of H+?

Presence of H+ = reabsorption of bicarb

Absence of H+ = secretion/excretion of bicarb

Describe the secretion of H+ at different tubular segments.

Secretion of H+ via Na/H counter transporter

- Proximal tubule, thick ascending limb, early distal tubule

Secretion of H+ via active transport

- Intercalated cells in late distal and collecting tubules

Where is bicarb reabsorbed most?

Proximal tubule (about 85%)

Describe the mechanism of H+ secretion and HCO3- reabsorption in the proximal tubule, thick ascending limb, and early distal tubules.

1. CO2 either diffuses into the tubular cells or is formed by metabolism in the cells

2. CO2 will combine with H2O and form H2CO3 via carbonic anhydrase.

3. H2CO3 will dissociate into HCO3- and H+

4. H+ secreted into tubular lumen by Na/H countertransporter

5. HCO3- reabsorbed into blood via basolateral membrane co-transport with Na+

For every H+ secreted, one bicarb enters the blood

Describe the mechanism of H+ secretion and HCO3- reabsorption in the late distal and collecting tubules.

Occurs in type A intercalated cells.

1. CO2 diffuses into the cell and combines with H2O to form H2CO3

2. H2CO3 will diffuse into HCO3- and H+

3. HCO3- will be reabsorbed into the blood via Cl-/HCO3- countertransporter

4. H+ will be secreted into the lumen via 2 active transport pumps

What are the two active transport pumps for H+ located on the luminal membrane of the late distal and collecting tubule cells?

H+ ATPase and H+/K+ ATPase

Why is maximally acidic urine formed in the late distal and collecting tubule cells?

Can have higher [H+] than proximal tubule --> will be more acidic

Once all HCO3- is reabsorbed, what happens to the excess H+ in tubular cells?

Will be buffered by phosphate and excreted as a sodium salt

About 30-40 mEq of H+ can be buffered by phosphate each day

Will result in a net gain of HCO3

Describe the ammonia buffer system in the proximal tubular cells and how it excretes excess H+.

1. Glutamine enters the cell and is converted to 2 HCO3- and 2 NH4+

2. Bicarb will be reabsorbed

3. NH4+ ion will be transported out of the tubular cell into the lumen where it is neutralized with Cl- and excreted in the urine

Describe the ammonia buffer system in the collecting tubular cells and how it excretes excess H+.

1. CO2 will diffuse into the cell and form H2CO3 with water, which dissociates into HCO3- and H+

2. The HCO3- molecule will be absorbed into the blood, while the H+ is secreted via H+ ATPase

3. NH3 is in the cell and will diffuse out into tubule through luminal side

4. In the lumen, NH3 will combine with H+ that was secreted to form NH4+

5. NH4+ will bind to Cl- and be neutralized and excreted into urine

Why is there NH3? Acidosis gives ability of tubular cell to produce ammonia

Describe what would lead to increased H+ secretion and HCO3 reabsorption.

Increase in PCo2 due to hypoventilation --> increase in H+, decrease in bicarb --> body will want to excrete excess H+ and reabsorb bicarb to bring pH back down

Will cause decreased ECF volume which stimulates Na+ reabsorption (counter transported with H+ so will cause H+ secretion)

Increased angiotensin II will also stimulate Na+ reabsorption through increased aldosterone

Hypokalemia will also result (will affect proximal tubule where K+ and H+ are interchanged)

Describe what would lead to decreased H+ secretion and HCO3 reabsorption.

Decrease in PCo2 due to hyperventilation --> decrease in H+, and increase in bicarb --> body will want to conserve H+ to bring pH back up, wants to decrease H+ secretion and HCO3- reabs.

Will cause increased ECF volume which will stimulate Na+ excretion, decreased angiotensin II and aldosterone in response

Hyperkalemia will also result

What are the 4 primary acid-base disturbances?

- Respiratory acidosis

- Respiratory alkalosis

- Metabolic acidosis

- Metabolic alkalosis

Describe pH, [HCO3-], and PCo2 for respiratory acidosis.

pH < 7.4

HCO3- >24 (increased due to compensation by kidneys)

PCo2 >40 (increased)

Describe pH, [HCO3-], and PCo2 for respiratory alkalosis.

pH > 7.4

HCO3- <24 (decreased due to compensation by kidneys)

PCo2 <40 (decreased)

Describe pH, [HCO3-], and PCo2 for metabolic acidosis.

pH < 7.4

HCO3- <24 (decreased)

PCo2 <40 (decreased due to compensation of respiratory system)

Describe pH, [HCO3-], and PCo2 for metabolic alkalosis.

pH > 7.4

HCO3- > 24 (increased)

PCo2 >40 (increased due to compensation of respiratory system)

What are some causes of respiratory acidosis?

- Damage to respiratory center

- Obstruction (emphysema, pneumonia, sleep apnea)

What are some causes of respiratory alkalosis?

- Hyperventilation

- High altitude (O2 will drop enough to trigger hyperventilation)

What are some causes of metabolic acidosis?

- Renal tubular acidosis

- Diarrhea

- Vomiting of intestinal contents

- Diabetes

- Ingestion of acids

- Chronic renal failure

What are some causes of metabolic alkalosis?

- Diuretics

- Excess aldosterone

- Vomiting

- Ingestion of alkali drugs (ex. tums)