Mnu-4 Renal

Front 1

What establishes the K+ gradient across cells?

Where does it move?

Back 1

K+ gradient is established by Na/K ATP-ase pump.

This favours diffusion of K+ out of cells (cell membrane impermeable to Na+). A small amount diffuses out of cells, leaving behind a negative interior. K+ stays in the lumen by electrochemial equilibrium.

Recall: cell membrane potential determined by Nernest equation.

Front 2

What is the role of K+ in action potential in cardiac myocytes?

What effect does hyperkalemia have on the action potential?

Back 2

K+ exits the cell to facilitate repolorization.

Hyperkalemia brings resting potential closer to the threshold. Na+ permeability is decreased, and conduction is slowed. = SLOW DOWN.

Front 3

What effect does hyperkalemia have on the a) heart, b) skeletal muscle, and c) brain?

Hypokalemia on a) heart, b) skeletal muscle, c) kidney, d) brain?

Back 3

Heart: arrhythmia leading to slowing and stop. Tall T wave, lose P wave, broadened QRS to sine wave.
Skeletal muscle: weakness, stiffness.
Brain - no effect.

Heart: arrhythmia - premature ventricular beats, ventricular tachycardia (extra beats!)
SM: weakness, muscle breakdown
Kidney: stimulates bicarbonate production
Brain: nada.

Front 4

Where is most K+ found in the body?

Name 4 factors increasing K+ entry into cells.

Back 4

Found in ICF (98.7%!).

Entry: 1. Na K+ ATP-ase.

2. Insulin (stimulates Na+/H+ exchange bringing Na+ in and H+ out. as Na+ increases, it is pumped out by Na K+ ATP-ase pump, bringing K+ in.

3. Adrenaline (beta-2-stimulation) acting directly on Na K ATPase.

4. Low ECF [H+]

Front 5

Name 5 factors increasing K+ exit from cells.

Back 5

1. Insulin deficiency (no Na+/H+ stimulation...)

2. Hyperglycemia. Osmotically shifts water out of cells, K+ gets lonely.

3. Widespread cell death - chemo, crush injury.

4. Beta blockers (drugs blocking adrenaline).

5. Metabolic acidosis - H+ enters cells, K+ exits, but only when the associated anions do not enter the cell.

Front 6

All potassium excretion occurs via kidneys. What effect does aldosterone have on potassium excretion?

Back 6

Aldosterone acts on cytosolic receptor, changing gene transcription. This leads to insertion of epithelial sodium channels (eNaC). Na+ is reabsorbed faster than Cl- can follow, leaving a net negative charge in lumen. K+ secretion from the cell is favoured. This is washed away via intratubular flow.

This occurs @ collecting duct. KEY - ALDOSTERONE INC K+ SECRETION

Front 7

Name 2 stimuli for aldosterone release.

Outline the acute and chronic responses to increased potassium intake.

Back 7

K+. Angiotensin II

Acute: insulin released in response to food, K+ uptaken into mm cells.

ECF K is left slightly raised. This causes aldosterone release to increase renal excretion.

Front 8

Name 3 causes of hyperkalemia.

Back 8

1. increased intake - rare.
2. shift out of cells:
-insulin deficiency
-hyperglycemia (sucks it out)
-beta-blockers
-widespread cell death
-metabolic acidosis

3. failure of renal excretion
-decreased flow in collecting duct
-decreased secretion

Front 9

Name 2 causes for decreased flow through the cortical collecting duct.

Name 3 causes of decreased secretion of K+ in the cortical collecting duct.

Back 9

1. Renal failure.
2. Reduced osmole excretion (due to low protein, low salt diet = reduced flow).

1. Hypoaldosteronism
2. Aldosterone antagonist
3. Tubular disease.

Front 10

Explain how hypoaldosteronism can occur (2 ways).

Back 10

2. Loss of signal for the aldosterone release. This could be hyporeninemia (no renin) due to NSAIDS or type II diabetes, or ACE inhibitors/angiotensin receptor blockers.

Adrenal Dx (Addison's). Can be autoimmune, infection, metastatic CA, some forms of congenital adrenal hyperplasia.

Front 11

Name 3 antagonists of aldosterone.

Back 11

1. Spironolactone - an aldosterone receptor antagonist.

2. Triameterene, amiloride, which block epithelial sodium channels (ENaC).

3. Trimethoprim - part of a commonly used antibiotic, which acts like amiloride at high doses.

Front 12

Name 4 principles of treating hyperkalemia.

Back 12

4 Principles:
1. antagonize adverse cardiac effects. CALCIUM GLUCONATE, does not affect plasma K+

2. shift K+ into cells. INSULIN, BETA2 AGONISTS, NaHCO3.

3. Increase removal of K+ outski - via urine (furosemide), via gut through powdered resin exchanging Na+ for K+, via dialysis.

4. Reduce K+ intake

Front 13

Name 4 causes of Hypokalemia.

Back 13

1. Decreased intake - rare alone, but can contribute if there are increased losses.

2. Shift into cells: administration, NaH CO3, Beta-2 adrenergic stimulation (e.g. Asthma), tx of perincious anemia can deplete K+ in mad cell assembly!

3. Increased GI losses: diarrhea and vomiting (via kidneys due to bicarbonaturia).

4. Increased renal excretion: increased flow through the cortical collecting duct (CCD) - osmotic diuresis (glucose, phamacogelogic diuretics, bicarbonaturia (vomiting). or by Increased secretion - hyperaldosternism, bicarbonaturia, Liddle's syndrome.

Front 14

How do osmotic diuresis or diuretics affect K+ loss?

Back 14

These increase the flow through CCD as extra particles drag more water, and ECF volume depletion - via increased aldosterone, RAAS, etc.

Front 15

How does vomiting create bicarbonaturia?

Back 15

Vomiting causes addition of new HCO3- to the blood.

There is a sudden rise in ECF HCO3 as H+ and Cl- are lost. This results in increased CCD flow which drags Na+ and H2O with it, and increased K+ secretion because less HCO3 makes the lumen more negatively charged.

Front 16

What are causes of primary, secondary and other hyperaldosteronism?

Back 16

Primary: tumor of adreanal cortex making aldosterone in unregulated way. This leads to uncontrolled Na+ reabsorption, and hypertension, and uncontrolled K+ secretion.

Secondary: most important - renal artery stenosis - incrased renin leads to RAAS....

OTHER: 1. Cortisol binds to mineralocorticoid receptor...CCD has enzyme which catabolises it 11-BDHsteroid denydrogensase. None of this = cortisol acts like a mineralocorticoid. Via licorice or congenital absence. OR...glucocorticoid-sensitive hyperaldosteronism. Or inherited disorder where aldosterone synthase gene becomes connected with ACTH-sensitive promotor of 11-beta-hydroxylase gene.

Front 17

What is Liddle's syndrome?

Back 17

An inherited dx where epithelial sodium channels are abnormally open. Aldo and renin levels are low.

Front 18

What happens to plasma [K+] when aldosterone is stimulated by ECF volume depletion?

What happens to plasma [K+] when aldosterone release is inhibited by a high salt diet?

Back 18

Expect [K+] to fall, but see no change because of reduced CCD flow due to increased proximal reabsorption of Na+ and H2O.

Expect [K+] to rise, but see no change due to increased CCD flow due to reduced proximal absorption of Na+ and H2O.

Front 19

How is hypokalemia treated? (3 ways).

Back 19

Tx underlying cause.

Prevent further loss via K+ sparing diuretic.

Replace KCl (oral, or iv).

Front 20

What determines whether an acid is dissociated?

Back 20

pH < pk = undisociated
pH > pk = dissociated
pH = pk = 1/2 dissociated.

E.g. if Ka = 10-5, at H+ 10-6 acid = 1/10 dissoc., at 10-7 = 1/100 dissoc.

Front 21

What determines the final [H+] in consideration of the bicarbonate buffer system?

Outline the buffer equation.

How do we know that the bicarbonate buffered H+?

Back 21

H+ is proportional to PCO2/HCO3-

The normal ratio for this is 40/25.

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

Look for a decrease in plasma HCO3. The new [H+] can be predicted based on knowledge of the new HCO3 and PCO2.

Front 22

What happens if lung ventilation is increased?

What happens if pH decreases because of metabolic acidosis?

Back 22

More CO2 will be blown off, increasing pH.

Metabolic acidosis: lung ventilation increased by chemoreceptor stimulation, = respiratory compensation...lowering PCO2 but not bringing it back to normal.

Front 23

Define metabolic acidosis and metabolic alkalosis.

Define respiratory acidosis and respiratory alkalosis.

Back 23

MACID: primary effect is to lower plasma bicarbonate concentration and pH.

MALK: primary effect is to increase plasma bicarbonate concentration and pH.

RACID: Increase pCO2 and decrease pH.

RALK: Decrease PCO2 and increase pH.

Front 24

What do low pH and low bicarb signify?
Low pH and high bicarb?
Low pH and normal or low pCO2?
Low pH and normal or high bicarb?

Back 24

metabolic acidosis.
respiratory acidosis.
metabolic acidosis.
respiratory acidosis.

Front 25

What happens when there is a primary acid-base disturbance?

Back 25

A compensatory mechanism is attempted to bring pH back to normal.

This change is in the SAME direction as the primary change by pH is proportional to HCO3/pCO2.

Front 26

Name the compensatory change.

1) Metabolic acidosis with a decreased HCO3.
2) Metabolic alkalosis with an increased HCO3.
3) Respiratory acidosis with increased PCO2.
4)Respiratory alkalosis with decreased PCO2.

Back 26

1) Decreased PCO2.
2) Increased PCO2.
3) Increased HCO3.
4) Decreased HCO3.

Front 27

What is the mechanism of compensation for:

a) respiratory
b) metabolic

Back 27

Respiratory: increase or decrease alveolar ventilation induced by change in pH.

Metabolic: if respiratory acidosis, increase in NH4+ secretion by kidney to increase serum bicarbonate.
For respiratory alkalosis, reduce NH4+ excretion by kidney to decrease bicarbonate.

Front 28

The amount of change in PCO2 can be predicted based on.....?

Back 28

The decrease in serum bicarbonate. The decrease in PCO2 from normal is roughly the same as the decrease in HCO3 from normal.

Front 29

When metabolic acidosis is present......what happens if the PCO2 is too high?

What happens if the PCO2 is too low?

Back 29

A: a respiratory acidosis is also present.

A2: a respiratory alkalosis is also present.

PCO2 compensation should be within +/-3 Compare to 40 for PCO2 and 25 for HCO3.

Front 30

Outline the kidney's role in acid-base balance.

Back 30

Kidney maintains serum bicarbonate. This is done by reabsorbing filtered bicarbonate to prevent loss and by making new bicarbonate by excreting acid to restore bicarbonate to the blood plasma.

Front 31

How is excess acid normally dealt with by the body?

Back 31

Dealt with by excreting this in the urine as ammonium (NH4) and dihydrogen phosphate (H2PO4-).

Kidney recognizes reduced pH and attempts to increase serum bicarbonate and excrete acid as amonium. For every 1 mmol of NH4 excreted, 1 mmol of bicarbonate is added to blood.

Front 32

List signals that would increase acid excretion.

Back 32

Intracellular acidosis in tubular cells of kidney, via. resp or met acidosis, and by hypokalemia. This would be loss of K+ from most cells of the body. Cells replace K+ in cells with H+ and Na+ from ECF. This increases cell H+ concentration, leading to acidosis.

Front 33

Where does bicarbonate reabsorption occur? How?

Back 33

Proximal tubule, via a lumenal sodium-hydrogen exchanger. Sodium crosses into cell down electrochemical gradient, driving H from cell into lumen. This reacts with bicarbonate, generating CO2 which escapes to blood. HCO3 generated in cell diffuses into blood.

Front 34

How is H+ secreted?

Back 34

In the collecting duct via H+ATPase pump. this is buffered by HPO4 or NH3. NH4 excrete in urine. Note this proton pump is not linked to sodium.

Front 35

What are the 3 necessary components for ammonium excretion?

Back 35

1) Ammonium synthesis from glutamine by proximal tubule cells, secretion in to lumen.

2) Ammonium reabsorbed in loop, NH3 diffuses through interstitum.

3) Collecting duct secretes H+, lowers pH in lumen, trapping NH3 and NH4+. H+ is secreted by Hydrogen ion ATPase (proton pump), NH4+ cannot cross cell membranes. NH4+ is excreted in urine (acidic urine is required to excrete this).

Front 36

Would high urine ammonium excretion be expected in either of the following?

Metabolic acidosis in chronic kidney dx due to low GFR?

Metabolic acidosis with urin pH of 8.0?

Back 36

No!

Front 37

What is the anion gap.

What causes the anion gap to be increased in a basic sense?

Back 37

In serum, anions should = cations. However, Na+ and K+ can exceed Cl- and HCO3- by 10-14 due to the effects of albumin (polyanion).

Cations never exceed anions, but Na+ always > Cl- and HCO3-.

Increase represents that a certain amount of bicarbonate was lost, therefore something else increased by x amount to cause x decrease in bicarb.

Front 38

What does an increase in the anion gap mean?

Back 38

Accumulation of anions in serum other than chloride or bicarbonate.

MEANS METABOLIC ACIDOSIS.

Front 39

Name 2 ways metabolic acidosis can occur without an increase in the anion gap?

Back 39

Occurs if bicarbonate is lost with a corresponding decrease in Na+, e.g. diarrhea, kidney dx (mild to moderate kidney failure, renal tubular acidosis).

Note: diarrheal fluid contains Na+, HCO3-, and H2O. Cl- should be increased.

Front 40

What are the 6 cases in which an increased anion gap would be observed in metabolic acidosis?

Back 40

Ketoadicosis
ASA
Renal Failure
Methanol
Ethylene glycol
Lactic acidosis

Front 41

What is ketoacidosis?

Back 41

Occurs in the absence of insulin. Triglycerides are broken into fatty acids and then into ketones.

Occurs in uncontrolled type I diabetes (hyperglycemia, ECF volume depletion) and in fasting (normal or low blood glucose, normal ECFV), or alcoholic ketosis (normal blood glucose, severe ECF volume depltion)

Front 42

What is lactic acidosis?

Mechanism?

Back 42

Inadequate tissue perfusion and cell hypoxia. Hypovolemic shock, cardiogenic shock, septic shock, exercise.

Mechanism: inadequate oxygen increase pyruvate due to reduced activity of the Kreb's cycle. Increased glycolysis occurs to make ATP anaerobically. Increased NADH/NAD results which increases lactic acid/pyruvate.

Front 43

How does kidney failure contribute to metabolic acidosis?

Back 43

Results in retention of organic acids with a low GFR. E.g. sulfuric acid, dihydrogen phosphate, etc.

Front 44

How do salicylate poisoning, methanol poisoning and ethylene glycol contribute to metabolic acidosis?

Back 44

Salicylate: accidental overdose with salicylic acid, will dissociate to salicylate and H+.

Methanol: metabolized to FORMIC ACID which is toxic. Causes severe brain and eye damage, tx with ethanol and hemodialysis.

Ethylene Glycol: metabolized to organic acids (glycolic a and oxalic a), toxic to brain, heart, kidneys. Tx is ethanol and hemodialysis.

Front 45

How does kidney dx contribute to acidosis?

Back 45

Reduced GFR = reduced excretion of NH4+. Dietary protein generates H+ which reduces serum bicarbonate. Failure to excrete NH4 = bicarbonate cannot return to normal. May occur as: proximal renal tubular acidosis (fail to reabsorb bicarbonate filtered), distal RTA = failure to secrete H+ by collecting ducts, or hyperkalemic RTA - low aldosterone or aldosterone antagonism.

Front 46

How is metabolic alkalosis recognized?

What is it often associated with?

How does compensation occur?

Back 46

High serum bicarbonate and alkalema.

Assoc. w. low serum potassium.

Compensate mild increase in PCO2.

Front 47

Outline the pathogensis of metabolic alkalosis.

Outline sources for an increase in bicarbonate.

Back 47

Add bicarbonate to ECF = raise serum bicarbonate. Kidney must reabsorb this to maintain elevated levels in serum.

Sources: hemoconcentration - reduced ECF. Raises the concentration, but not amount. Loss in GI (vomiting or NG suction), increased urine ammonium excretion (hypokalemia, increased aldosterone). Shift H+ into cells = Hypokalemia.

Front 48

How could hydrochlorthizide for hypertension cause metabolic alkalosis?

Back 48

Diuretic induces a source of new bicarbonate as urine NH4+ increases due to hypokalemia and increased aldosterone. This increases bicarbonate reabsorption.

Front 49

How could vomiting induce metabolic acidosis?

Back 49

In vomiting, HCl is lost and there is hemoconcentration of remaining fluid. Bicarbonate reabsorption is increased due to hypokalemia and increased angiontensin II.

Front 50

Can hyperaldosteronism cause metabolic alkalosis?

Back 50

Yes - this is a source of increased bicarbonate as there will be increased urine NH4 due to hypokalemia and high aldosterone. This will increase bicarbonate reabsorption.

Front 51

Give 2 main causes of metabolic alkalosis and hypokalemia.

Back 51

1. High BP - due to primary hyperaldosternism or renal artery stenosis.

2. Normal or low BP: diuretics (thazides or loop diuretics), vomiting, or rare disorders- Bartter's/Gitelman's).

Front 52

What is the osmolar gap?

Back 52

Used in ER to detect toxic alcohol. These are small, and contribute to measured osmolality. These can be compared to serum osmolality.

Actual = measured.
Expected = 2x Na + GLU + UREA
If actual is greater than expected by 10 = alcohol in blood.

Front 53

DO THE CASES!

REMEMBER - METABOLIC ALKALOSIS IS ALMOST ALWAYS SEEN WITH.......

Back 53

HYPOKALEMIA!!!