Renal (K+ and H+) Flashcards
What is the important of the potassium ion in the body?
K+ = most abundant INTRACELLULAR ion
98% in intracellular fluid, 2% in extracellular fluid
K+ concentration in extracellular fluid → excitable tissues (nerve and muscle, including cardiac muscles)
What are the resting membrane potentials of the excitable tissues related to ?
Directly related to relative intacellular and extracellular K concentrations
What concentrations of K+ are considered to be Hyperkalemia and Hypokalemia?
What do these concentration cause?
Hyperkalemia = high extracellular concentration > 5 mEq/L
Hypokalemia = low extracellular concentration < 3.5 mEq/L
*Very narrow range
Both cause abnormal rhythms of the heart and abnormalities of skeletal muscle contractions
REVIEW SLIDE 4!
How is potassium balance maintained?
(Intake and Excretion)
By Dietary Intake!!
Orange juice, banana, watermelon, pinapple, nuts, potatoes, tomatoes
Excretions = 90% excreted into urine + 10% excreted into faces
How does renal regulation of potassium work?
- K is filtered freely at glomerulus (just a bit, not so much)
- Normally, tubules reabsorb most of the filtered K, so very little is secreted
- But K+ can be secreted at the cortical collecting ducts (can go seen in urine even if almost all reabsorbed)
*Changes in K excretion due to changes in K+ secretion in the CCD (come in the DCT)
*net reabsorption normally around 86% (15-99%)
How is K+ secretion in the CCD done (pump level)?
Coupled with Na+ reabsorption
Counter-transport
Which 2 factors regulate K secretion?
- Dietary intake of potassium
- Aldosterone
What is the process of regulation of K+ secretion by dietary intake and aldosterone?
↑ K+ intake → ↑ Plasma K+ → In the Adrenal Cortex: ↑ Aldosterone secretion → ↑ Plasma aldosterone → In the CCD: ↑ K+ secretion → ↑ K+ excretion
How can the renin-aldosterone system impact the excretion of K+ and Na+?
Na+ and K+ go opposit ways!!!
↓ Plasma volume → ↑ Plasma Angiotensin II → In the Adrenal Cortex: ↑ Aldosterone secretion → ↑ Plasma aldosterone → In the CCD: ↑ K+ secretion → ↑ K+ excretion + ↑ Na+ reabsorption → ↓ Na excretion
What is Hyperaldosteronism?
When adrenal hormone aldosterone is released in excess
Most common cause: adenoma (tumor-like) of adrenal gland → produces aldosterone autonomously
Increased fluid volume, hypertension (bc increases reabsorption of Na+), hypokalemia
Renin is suppressed
Metabolic alkalosis is often seen as well
What is the physiological concentration of H+?
pH of about 7.4 (tightly controlled between 7.35 - 7.45)
H+ concentration = 40 nmol/L
Which reaction is used to control H+ concentration in the body?
Carbonic anhydrase:
CO2 + H2O ←→ H2CO3 ←→ HCO3- + H+
*When body gains a bicarbonate ion = body losing 1 H+
What are different sources of H+ gain for the body?
- Generation of H+ from CO2 (if too much CO2)
- Production of nonvolatile acids from the metabolism fo protein and other organic molecules
- loss of bicarbonate in diarrhea or other nongastric GI fluids
- loss of bicarbonate in urine
What are different sources of H+ loss for the body?
- Utilization of H+ in the metabolism of various organic anions
- loss of H+ in vomitus (only way to lose H+ from the GIT)
- in the urine (physiological or pathological)
- Hyperventilation (loss of CO2 favours the reversed reaction which utilizes H+)
Which are the most important nonvolatile acids?
Phosphoric acid
Sulfuric acid
Lactic acid
*Average net production = 40-80 mmmol of H+/day (rate of use ot these acids)
What is a buffer?
Which are the major extracellular and intracellular buffers?
Any substance that can reversibly bind H+ ions
H+ + buffer ←→ Buffer
Helps maintaining the concentration of H+ ions in a tight range
pH = -log [H+]
Extracellular buffer: CO2 and HCO3-
Intracellular buffer: phosphates and proteins
*Buffering NOT eliminate H+ ions from body, keeps them locked
Which systems are responsible for H+ balance?
Respiratory system (controls CO2)
Kidneys (control HCO3-)
They work together to minimize change in pH
What are the 2 possibilities for renal control of pH via HCO3- control?
Low H+ concentration (high pH: alkalosis) → Kidneys excrete HCO3-
High H+ concentration (low pH: acidosis) → Kidneys produce new HCO3- and add to plasma
What does the HCO3- reabsorption look like in the kidneys?
80% in the Proximal tubule
15% in Thick ascending limb
5% in CCD
0% excreted except in case of alkalosis
How is addition of new HCO3- to plasma achieved?
In case of acidosis
- H+ secretion and excretion on nonbicarbonate buffers (ex: phosphates)
- by glutamine metabolism with NH4+ excretion
*Both can be viewed as H+ excretion by the kidney
Kidneys normally contribute enough new HCO3- to plasma to compensate the 40-80 mmol/day generated by use of nonvolatile acids
What is the process of reabsorption of HCO3-?
*Not that H2O and CO2 are available everywhere
In the tubular epithelial cells:
1. CO2 + H2O → H2CO3 → HCO3- + H+ (Carbonic Anhydrase)
2. HCO3- reabsorbed to interstitial fluid
3. H+ goes into tubular lumen by H+/K+-ATPase and Na+/H+ anti-porter where it is coupled with HCO3-
In thubular lumen: HCO3- + H+ → H2CO3 →CO2 + H2O (reversed rxn)
What is the process by which new HCO3- added to plasma in case of need by H+ secretion and excretion on nonbicarbonate buffers (ex: phosphates)?
*Only after all HCO3- has been reabsorbed and no longer is available in the lumen
What is the process by which new HCO3- added to plasma in case of need by H+ secretion and excretion on nonbicarbonate buffers (ex: phosphates)?
*Only after all HCO3- has been reabsorbed and no longer is available in the lumen
In the tubular epithelial cells:
1. CO2 + H2O → H2CO3 → HCO3- + H+ (Carbonic Anhydrase)
2. HCO3- reabsorbed to interstitial fluid
3. H+ goes into tubular lumen by H+/K+-ATPase and Na+/H+ anti-porter where it is coupled with HCO3- (Up to there, same as HCO3- reabsorption)
4. In tubular lumen:
HPO4 2- (filtered) Acting as buffer + H+ → (H2PO4) - → excreted
What is the process by which new HCO3- added to plasma in case of need by glutamine metabolism with NH4+ excretion ?
*Mainly in the proximal tubule
H+ excretion bound to NH3
- Glutamine from interstitial fluid and from tubular lumen (by Na+ cotransport) enters tubular epithelial cells
- In tubular epithelial cells: Glutamine → HCO3- + NH4+
- HCO3- is reabsorbed
- NH4+ goes into tubular lumen by counter-transport with Na+
- NH4+ is excreted
What is the primary cause of Alkalosis and Acidosis?
Respiratory alkalosis and acidosis
All other causes are classified as metabolic alkalosis and acidosis
What is does the renal response to acidosis look like?
- Sufficient H+ are secreted to reabsorb all filtered HCO3-
- Body still has too much H+ so kidneys have to produce more HCO3- by different ways such as HPO4 2-
- Tubular glutamine metabolism and NH4+ excretion increased (new HCO3- in plasma)
Net result: More new HCO3- in plasma compensates for acidosis + urine highly acidic (lowest attainable pH = 4.4)
What is does the renal response to alkalosis look like?
- Significatn HCO3- excreted in urine
- Little to no H+ secretion on non-HCO3- urinary buffers
- Tubular glutamine metabolism and NH4+ excretion ↓ so little or no new HCO3- added to plasma
Net result: Plasma HCO3- decrease + highly alkaline urine (pH > 7.4)
REVIEW SLIDE 6 OF H+ lecture
What are clinical examples of Respiratory and Metabolic acidosis and alkalosis?
Respiratory acidosis: too much CO2 ex: respiratory failure with CO2 retention
Respiratory alkalosis: not enough CO2, ex: hyperventilation
Metabolic acidosis: diarrhea (loss of HCO3-), renal failure (accumulation of inorganic acids) *when excess of H+ not caused by CO2
Metabolic alkalosis: too much HCO3- base, vomiting (loss of H+), hyperaldosteronism (increase H+ secretion in DCT and CCD)
What are diuretics?
Drugs used clinically to increase the volume of urine excreted
Act on tubules to inhibit reabsorption of Na, along with chloride and/or bicarbonate → increase excretion of these ions
H2O excrtion increases too
What are loop diuretics?
Give an example
Acts on thick ascending limb of the loop of Henle
Inhibits cotransport (reabsorption) of Na+, Cl- and K+ (Na+-K+-2Cl-cotransporter)
*One of the most commonly used diuretics
ex: furosemide
What are Potassium-sparing diuretics?
Give an example
Inhibit Na reabsorption and K+ secretion in the CCD (diffusion across tubular lumen-CCD epithelial cells)
Unlike other diuretics, plasma concentration of K+ does not decrease
*Used for hypokalemic patients
Blocks action of aldosterone or blocks epithelial Na+ channel in CCD (aldosterone-regulated) (aldosterone usually upregulates these pumps)
ex: amiloride, spironolactone
What are clinical uses of diuretics?
- Renal retention of salt and H2O (edema)
ex: congestive heart failure (lowering cardiac output) bc water in the lungs
ex: hypertension caused by renal retention
What are common features of kidney diseases or failures?
- Proteinuria (protein in urine) → problem at level of GFR
- Accumulation of waste products in blood (ex: urea, creatinine, phosphate, sulfate)
- High K+ concentration in blood
- Metabolic acidosis (accumulation of phosphate, sulfate, etc.)
- Anemia (decrease secretion of erythropoietin)
- Decrease secretion of 1,25-VitamineD → hypocalcemia
What are treatments for kidney failures?
When 90% nephrons start working, can’t sustain life → need renal replacement therapy
Renal replacement therapy options:
1. Hemodialysis
2. Peritoneal dialysis
3. Kidney transplantation
What is Hemodialysis?
A form of renal replacement therapy, you connect to a machine and filter the blood
4h, 3x/week
What is Peritoneal dialysis?
A form of renal replacement therapy
Lining of patient’s own abdominal cavity (peritoneum) used as dialysis membrane
Fluid injected into cavity via tube inserted through abdominal wall → Solutes diffuses into fluid from person’s blood → Fluid changes several times/day
*Don’t have to go to hospital
What is the major problem with kidney transplantation?
The shortage of donors
(Donors can function quite normally with one kidney though)
