Kidney Block Review Questions

Front 1

What are the body's normal responses to reduced effective circulatory volume?

Back 1

Reduction in volume is sensed by vascular receptors (in atria, great veins = volume, in arteries, wall tone and pressure sensed by baroreceptors (including JGA)) which then activate mechanisms to retain water and sodium. Water retained due to release of ADH, Sodium reabsorbed by sympathetic activity (catecholamines) and other pressor systems activating the Renin Angiotensin System which activates aldosterone.

Front 2

What is the main trigger for ADH release? What is the main ADH action/

Back 2

hyperosmolality sensed in hypothalamus. Increases water retention by increasing aquaporin water channels in collecting tubule. Can also be activated in cases of significant reduction in circulatory volume. ADH has no significant effect on Na+ handling.

Front 3

What is tubuloglomerular feedback (TGF)?

Back 3

Mechanism of controlling filtered load by lowering GFR in response to high solute (likely Cl-) to the distal nephron. It is not entirely understood. Some believe it is a mechanism to prevent excess Na+ loss when tubular reabsorption is reduced.

Front 4

Will increasing the GFR by autoregulatory constriction of the efferent arteriole increase or decrease Na+ reabsorption from proximal tubule? What is the mechanism?

Back 4

YES, Na+ reabsorption increases. Increased filtration/GFR leaves the peritubular capillary with reduced hydrostatic pressure and increased osmotic pressure (more volume removed, greater protein concentration), both of which improve Starling forces that favor reabsorption of Na+ (and other solutes) and water in PT. This effect (greater filtered load of Na+ = greater % proximal reabs) is called Glomerulotubular Balance. Remember this means REDUCED Na+ delivery to distal nephron.

90-95% of Na+ can be reabsorbed in PT under such conditions.

Front 5

What is the major determinant of the kidney's ability to excrete free water?

Back 5

Solute (Na+, K+, Cl-) delivery to thick ascending limb, where conditions prevent water reabsorption and favor active transport of solute out of the filtrate, leaving behind a hypotonic filtrate which includes free water.

This process is hindered when a large % of solute is reabsorbed proximally, ie by autoregulation. Inability to excrete free water can lead to hyponatremia.

Front 6

What is the role of aldosterone? when would it be expected to be high or low?

Back 6

Aldosterone acts in the distal tubule to increase sodium reabsorption. Na+ is exchanged via ENaC channels which reabsorb 1 Na+ in return for 1 K+ or H+ excreted (high aldosterone can -> hypokalemia, hypernatremia, metabolic alkalosis).

Expected to be high in cases of volume depletion, CHF (can lower Na+ FE to <0.1%). Low during volume expansion -> natriuresis.

Front 7

Derive (or just state if you are lazy) the equation for fractional excretion of Na+ (or another solute for that matter) (FENa)

Back 7

FENa = (Na+ excretion in urine) / (Na+ filtered) = ([Na+]urine * urine flow rate (V)) / ([Na+]plasma * GFR) where GFR estimated by CL(Cr) = ([Cr]urine * V) / [Cr]plasma so

FENa = ([Na+]urine * V) / ([Na+]plasma * ([Cr]urine * V) / [Cr] plasma) -> cross out V and cross multiply ->

FENa = ([Na+]urine * [Cr]plasma) / ([Na+]plasma * [Cr]urine)

multiply by 100 to get percentage(%)
** Don't need timed urine collection to estimate FENa!

Front 8

What are natriuretic peptides? What do they accomplish and what is the mechanism?

Back 8

As the name implies, these are peptide hormones that promote natriuresis(Na+ excretion) in response to volume overload (hypervolemia) sensed in the atria (ANP) and ventricles (BNP).

MOA:
(1) dilate afferent glomerular arteriole -> incr RBF -> increased filtration of Na+
(2) Inhibit tubular reabsorption of Na+

Clinical tidbit: BNP is easily assayed and is therefore used diagnostically in evaluating CHF pts.

Resistance to NPs has been implicated as a possible cause of hypervolemic/Na+ overload disease.

Front 9

What are the clinical manifestations of sodium depletion?

When might it occur?

Back 9

They relate to LOSS OF ECV.
Mild volume depletion -> thirst, weakness, dizziness.

Severe volume depletion -> hypotension, reflex tachycardia, orthostatic hypotension, shock

Since kidneys are so good at reabsorbing Na+, usually caused by kidney disease, severely deficient Na+ dietary intake, severe loss via GI or skin (dysentery or heat exhaustion).

Front 10

What does renal disease usually not present with symptoms of sodium depletion ie hypovolemia?

Back 10

Typically renal disease causes reductions in GFR. Reduced filtration of Na+ means Na+ retention even if the kidney is unable to reabsorb as much Na+ as normal. This disorders that do affect Na+ reabsorption more so than GFR are called salt-wasting nephropathies (eg acute tubular necrosis)

More commonly caused by diuretics which work by inhibiting reabsorption of Na+.

Front 11

what are clinical manifestations of sodium overload?

Back 11

sodium overload -> expanded ECF volume, volume overload.
May present as weight gain, hypertension, vascular congestion (eg EDEMA).

This rarely occurs in a normal pt as the kidney is very good at sodium dumping (natriuresis) when necessary. Usually caused by some clinical disorder.

Front 12

What is edema? what is it comprised of?

Back 12

Edema is abnormal accumulation of fluid in the interstitial space. Remember interstitial space is the extravascular portion of the extracellular compartment.

Edema is an ultrafiltrate of plasma, so it is identical to plasma minus the cells and protein which cannot transude.

Think of edema and clinical syndromes that cause it by the changes in STARLING FORCES (most importantly the hydrostatic and oncotic pressures in the vascular compartment and the permeability of capillaries).

Front 13

What can cause localized edema (localized to one area of body) in terms of starling force changes (and a clinical disorder that may cause the change).

Back 13

Increased K (capillary permeability) due to local inflammation or vascular damage. Allergies, insect bites, burns.

Increased hydrostatic pressure locally. vessel obstruction in veins or lympatics (clot, tumor, swelling of contiguous tissue). Colonization of lymphatics by tropical microfilaria leads to massive local edema called elephantiasis.

reduced osmotic pressure. Does not occur locally but can be caused systemically by hypoalbuminemia

Front 14

What causes generalized/diffuse edema?

Back 14

This is caused by a state of significant total-body Na+ overload. A number of important clinical disorders can cause it, they are typicall characterized by:
(1) Starling forces deranged in capillaries
(2) kidney persistently in state of sodium-retention due to hemodynamic alterations.

Examples include CHF, cirrhosis, nephrotic syndrome, nephritic syndrome/renal failure.

Front 15

Name the starling force alteration and the stimulus for Na+ retention in the following causes of generalized edema:
CHF, Cirrhosis, Nephrotic syndrome, Nephritic syndrome/renal failure

Back 15

CHF: Increased hydrostatic pressure in capillaries and veins. Stimulus for Na+ retention = decr effective circulatory vol

Cirrhosis: Increased hydrostatic pressure and decreased oncotic pressure. Stim for Na+ retention is decr effective circulatory vol.

Nephrotic syndrome: definitely reduced oncotic pressure, perhaps hydrostatic also. Na+ retention due to decreased plasma vol

Nephritic syndrome/RF: increased hydrostatic pressure, decr filtered load of Na+ causes Na+ retention.

Front 16

Difference between underfill and overflow edema?

Back 16

Overflow: edema caused by increased hydrostatic pressure (typically plasma volume increased despite decrease in effective circulatory volume)

Underfill: edema due to decreased oncotic pressure, at the expense of low plasma volume.

Front 17

What is anasarca?

Back 17

Generalized edema affecting entire body. Usually begins in higher likelihood sites like feet and ankles (due to gravity), periorbital spaces (loose interstitium and space to accomodate transudate),

body cavities can accomodate large amount of transudate, when this occurs it is called an effusion (into pleural space, peritoneum (ie ascites), etc)

Front 18

What are diuretics?

Back 18

Technically the term refers to removal of water, however pharmacological diuretics are actually natriuretics, removing sodium (and along with sodium, water).

Front 19

How do loop diuretics work? What are some common loop drugs? What effects do they have (good and bad)?

Back 19

MOA: Block Na-K-2Cl co-transporter in the ascending limb of the loop of Henle which under normal circumstances accounts for 25% of Na+ reabsorption. They reach this site as part of the filtrate and are excreted in urine.

Common drugs: Furosemide (Lasix), torsemide, bumetanide (Bumex). Orally bioavailable, rapid onset, 6 hr duration.

Require a 2nd dose to get a net Na+ loss as when they are wearing off the kidney becomes very Na+ retentive.

Good effects: Natriuresis and diuresis.
Bad effects: hypokalemia, ototoxic in large doses

Front 20

How do thiazide diuretics work? What are some common thiazide drugs? What effects do they have (good and bad)?

Back 20

MOA: Inhibit Na-Cl symporter in distal convoluted tubule

Common drugs: Hydrochlorothiazide (HCTZ) , chlorothiazide (Diuril), metolazone, chlorthalidone. Dosed once daily, longer acting than loops.

Good effects: volume reduction (useful for HTN, not as strong as loop diuretics for treating edema)

Bad effects: hypokalemia (incr Na+ delivery downstream), hypercalcemia, hyperuricemia (trigger gout), glucose intolerance (hypokalemic effect on betal islets),, increased serum cholesterol, hyponatremia (reduce free water clearance), allergy

Front 21

MOA, drug names, and adverse effects of potassium sparing diuretics?

Back 21

MOA: Blockage of Na+ reabsorption in the collecting tubule, thereby preventing Na+/K+ exchange which accounts for K+ loss in potassium wasting diuretics. However not much of Na+ reabsorbed here so not very potent diuretics. Block ENaCs or antagonize aldosterone.

Usually used anti-kaliuretic adjunct therapy to loop or thiazide diuretics.

ENaC antagonist Drugs: Triamterene, Amiloride. Maxide and Dyazide are combinations of triamterene and HCTZ.

Aldosterone antagonists: Spironolactone and Epleronone, at basolateral collecting tubule. Not widely used except in cirrhosis where secondary aldosteronism is thought to contribute to edema/ascites. Also may be useful in CHF.

adverse effects: hyperkalemia? metabolic acidemia?

Front 22

What is Mannitol?

Back 22

an osmotic diuretic, i.e., a non-reabsorbable, osmotically active agent whose presence in the nephron opposes sodium and water reabsorption. It must be given by continuous intravenous infusion and it is hard to regulate. Its main clinical application is in treating cerebral edema.

Front 23

What is Acetazolamide?

Back 23

This agent inhibits carbonic anhydrase, the enzyme system that plays a central role in proximal tubular bicarbonate reuptake. This process is linked to sodium reabsorption, so acetazolamide has some natriuretic properties, albeit mild. Because of its negative effects on bicarbonate balance, it may induce a
hyperchloremic metabolic acidosis.

Front 24

What is the physiologic basis for diuretic resistance?

Back 24

The physiologic basis for diuretic resistance is probably as follows:
1. After treatment with diuretics, the fraction of filtered sodium reabsorbed proximally may increase to the point that little sodium is left
in the distal nephron where most diuretics work. In other words,
everything has already been reabsorbed upstream.
2. The volume depletion induced by diuretics causes activation of anti-
natriuretic mechanisms, such as aldosterone.
3. The condition for which the diuretic was used may have gotten sufficiently worse that the patient no longer responds.

Front 25

What equation estimates plasma osmolality?

Back 25

Posm = 2([Na+]serum) (mEq/L) + [glucose]serum/18 (mg/dL) + BUN/2.8 (mg/dL)

the divided numbers are to convert from mg/dL to mmol/L. Na+ multiplied by 2 to account for accompanying anions.

Front 26

What are the kidney's normal responses to an increased water load (decreased osmotic pressure)?

Back 26

Increased volume -> increased GFR (and to some degree suppressed ADH) -> increased production of Free Water

decreased osmotic pressure -> decreased thirst and decreased ADH secretion -> decreased H2O reabsorption in CT

Front 27

What are the kidney's normal responses to an decreased water load (increased osmotic pressure)?

Back 27

decreased volume -> decreased GFR and delivery of H2O to ascending limb (and ADH release to some extent) -> decreased free water production

increased osmotic pressure -> thirst and ADH release -> increased water reabsorption in CT

Front 28

what % change in osmolarity or volume is required to elicit an ADH release response?

Back 28

Only about 2% increase in osmolarity to get ADH release (increases linearly as osm increases).

Need 10% decrease in plasma volume to get ADH release (increases exponentially as plasma vol further decreases).

Front 29

What is the target of ADH? What is the effect it has on the kidney?

Back 29

ADH binds V2 receptor on the basal surface of principal cells in the collecting tubule. cAMP in the principal cell stimulates production of aquaporin proteins which are water channels. Water is passively reabsorbed from nephron lumen into medullary interstitial space and then capillaries due to the hypertonic medullary environment of the kidney.

This mechanism also drives further dfevelopment of the hyperosmotic medullary gradient via urea absorption/diffusion.

Front 30

What are the bottom line key concepts for excreting water or solute normally? What conditions must be true?

Back 30

1. To excrete water normally,
a. You must be able to suppress ADH release appropriately.
b. You must be able deliver adequate amounts of filtrate to the diluting
segment of the nephron (the ascending limb of the Loop), so as to make free water.
c. Your ascending limb cells must make free water by reabsorbing solute
molecules from the filtrate.
2. To conserve water, you must concentrate the urine through the
effects of ADH on the collecting tubule.

Front 31

What are the clinical symptoms of hypoosmolality?

Back 31

neurological symptoms! hypoosmolar plasma leads to brain swelling, however the brain neurons have adaptive mechanisms to limit swelling (after 5-7 days). Nonspecific symptoms like lethargy, irritability, nausea, seizures, and in extreme cases coma and death.

Front 32

Will ADH be released in a patient who is hypovolemic and hypoosmolar?

Back 32

YES, despite hypoosmolality that would suppress ADH release, humans defend ECF volume at the expense of exacerbating osmolality disturbance.

Front 33

Contrast the expected symptoms of hypovolemia (eg blood loss) and diminished effective circulatory volume (eg CHF).

Back 33

Hypovolemia: decreased skin turgor, dry mucous membranes, orthostatic hypotension.

decreased effective circulatory volume: extracellular volume expansion and generalized edema.

Front 34

List the major causes of Hypoosmolar hyponatremia in the following categories: Reduced ECV, Normal ECV, Expanded ECV (edema).

Back 34

Reduced ECV: GI fluid loss, hemorrhage, transcutaneous fluid loss, renal fluid loss

Normal ECV: SIADH, hypocortisolism, primary polydipsia, hypothyroidism

Expanded ECV: Cardiac failure, hepatic cirrhosis/ascites, nephrotic syndrome, renal failure

Front 35

What does dipsogenic mean? Which hormones are dipsogenic?

Back 35

Dipsogenic means to stimulate thirst. ADH and angiotensin are dipsogenic.

Front 36

How can diuretics cause hypoosmolality?

Back 36

All diuretics have effects that impair ability to excrete water; these include
(a) they cause electrolytes to be excreted that otherwise would have been reabsorbed. This reduces free water formation;
(b) they induce some degree of hypovolemia, stimulating ADH release, and thus reducing free water excretion.
(c) With enough volume reduction, the changes in peritubular Starling forces may occur which increase the fractional reabsorption of filtrate in the proximal tubule. This means less filtrate will be delivered to the free water formation site in the ascending limb.
Together, these three actions could cause a patient receiving diuretics to develop water retention.

Front 37

Are thiazides or loop diuretics more likely to cause hypoosmolality?

Back 37

In practice, it is chiefly the thiazide diuretics that are frequent causes of hyponatremia. These agents work specifically in the distal tubule. Thiazide diuretics cause cause considerable sodium wasting and potassium loss. The loss of potassium, chiefly an intracellular cation, obligates the movement of sodium from the extracellular to the intracellular compartment. The loop diuretics (furosemide, ethacrynic acid, bumetanide) operate at both the cortical and medullary thick ascending limb. The action of the loop diuretics at the medullary portion of the TALreduces sodium and chloride transfer to the medullary interstitium, thereby reducing the medullary hydroosmotic gradient and urinary concentrating ability. Hence, although the loop diuretics may disturb urinary dilution, they also impair urinary concentration and are thereby less likely to cause hypoosmolality.

Front 38

NSAIDs can interfere with the actions of ADH. How does that work?

Back 38

NSAIDs, like aspirin, block formation of prostaglandins among other members of the arachidonic acid pathway. Normally prostaglandins work to blunt the effects of ADH, therefore in the absence of prostaglandins due to NSAIDs, ADH activity is augmented, increasing water retention and potentially causing hypoosmolality.

Front 39

What patients are at high risk of inadequate solute intake relative to water, causing hyponatremia?

Back 39

Chronic psychosis patients with primary polydipsia can drink so much water as to overwhelm the body's ability to dilute urine, leading to solute loss and hypoosmolality.

Also patients with very low salt intake such as those on a tea-and-toast diet (eg, Grandma) or alcoholics (beer drinker's potomania).

Front 40

What can cause hyperosmolal hyponatremia?

Back 40

diabetes! High serum glucose causes hyperosmolality which draws water out of cells, diluting the ECF Na+, causing hyponatremia.

Front 41

Major causes of hyperosmolal hypernatremia?

Back 41

Typically due to WATER LOSS

Renal water loss (diabetes insipidus, osmotic diuresis), polyuria

Insensible water loss (sweating, burns, respiratory loss ie pneumonia)

GI water loss (diarrhea particularly from osmotic agents eg lactulose).

Hypertonic saline administration

Front 42

what factors influence K+ handling in the distal nephron?

Back 42

-Aldosterone and Na+/K+ ATPase of principal cells (basolateral) (in response to ECV depletion or K+ overload)
-Acid-base status
-Na+ delivery and reuptake (potassium wasting diuretics)
-urine flow rate (incr volume decreases [K+] in filtrate, favoring K+ excretion
-accompanying anions (can cause K+ wasting because anions require + charge escort)

Front 43

discuss how the following affect K+ balance:
-Plasma pH
-beta-adrenergic agonists/antagonists
-alpha-arenergics
-hyperosmolar states
-insulin
-cell membrane defects

Back 43

-Plasma pH: In an acidosis, H+ is traded into cells for K+, leading to hyperkalemia (0.5mEq/L per 0.1 pH). alkalosis is opposite
-beta-adrenergic agonists/antagonists: agonists favor K+ uptake by cells, MOA not understood. blockers block this effect.
-alpha-arenergics: mitigate cell uptake of K+.
-hyperosmolar states: sudden onset drags water out of cells and K+ goes along ("solvent drag").
-insulin: makes cell membranes more permeable to K+.
-cell membrane defects: K+ can be taken up more easily "kalemic paralyses" can cause spontaneous hypo or hyper kalemia.

Front 44

Difference between internal and external potassium balance?

Back 44

external: total body potassium content , balance between K+ entering body and that being excreted.

internal: changes in distribution of K+ between intracellular and extracellular space, nothing to do with total potassium content.

Front 45

What are symptoms of hypokalemia and hyperkalemia?

Back 45

hypokalemia: muscle weakness, rhabdomyolysis can occur. kidney loses ability to concentrate urine leading to polyuria ie nephrogenic diabetes insipidus. ileus, orthostatic hypotension, EKG abnormalities, increased renin release.

hyperkalemia: potentially most lethal of electrolyte imbalances. hyperkalemic paralysis, myocardial irritability and EKG abnormalities, stimulation of aldosterone release.

Front 46

How do you calculate serum and urine anion gap?

Back 46

Serum anion gap = [Na+]serum - ([Cl-]serum + [HCO3-)serum)

Urine anion gap = ([Na+]urine + [K+]urine) - [Cl-]urine

Front 47

how can an acidosis cause an anion gap? how could you have an acidosis WITHOUT an anion gap?

Back 47

presence of a new source of protons decreases the bicarbonate concentration, increasing the anion gap which is calculated by subtracting the Cl- + HCO3- from Na+.

When bicarb is simply lost or hydrogen ions retained, Cl- concentration is increased and compensates for drop in HCO3-.

Front 48

What are the forms of metabolic acidosis without an anion gap?

Back 48

Bicarbonate Loss caused by:
-Non-Renal causes: diarrhea, laxatives, percutaneous drainage of upper GI fluids
-Renal: Type 2 RTA, acetazolamide or other CA inhibitors

H+ Retention caused by:
-Type 1 (distal) RTA
-Type 4 RTA and related conditions

Dilutional
-Expansion acidosis
-Exogenous chloride loading

Front 49

What is a type 1 renal tubular acidosis?

Back 49

acidosis caused by failure of proton-pumps in the collecting tubule to secrete H+ ions adequately.

Can be congenital or autoimmune or caused by drugs/toxins.

Diagnosis is made by normal anion gap metabolic acidosis with urine pH > 5, often accompanied by hypokalemia.

Front 50

What is a type 4 renal tubular acidosis?

Back 50

acidosis caused by failure to deliver enough ammonia buffer to distal nephron to enable secretion of H+. Caused by K+ retention due to urinary obstruction, hypoaldosteronism, drugs (eg ACE inhibitors).

Diagnosis made by a normal anion gap metabolic acidosis with hyperkalemia, urine pH can be 5 or greater.

Front 51

What is a type 2 renal tubular acidosis?

Back 51

Proximal tubular defect reducing reabsorptive capacity for HCO3-. Manifests as a metabolic acidosis with normal anion gap.

Causes include congenital, and acquired: CA inhibitors and other drugs, infiltrative disease (amyloidosis, myeloma), wilson's disease, heavy metals, others.

Diagnosis made by metabolic acidosis with normal anion gap. Pt CAN maximally acidify urine (unlike type 1,4). Occassionally hypokalemia. Can present with other proximal reabsorption problems, dumping of glycogen, amino acids, phosphate... ("Fanconi Complex")

Front 52

What are expansion acidosis and contraction alkalosis? What causes them?

Back 52

Contraction acidemia is caused by dilution of bicarbonate by saline or other fluid replacement therapy in severely hypovolemic patients. Usually self-limited and not serious.

Contraction alkalosis is caused by diuretics that increase chloride and sodium loss but have no effect on bicarbonate. Increased bicarbonate can cause an alkalosis.

Front 53

metabolic acidosis with normal anion gap in a patient with a urine pH > 5. What is the most likely cause?

Back 53

Type 1 (distal) RTA. Pt should be acidifying the urine, so we know it is a kidney problem, and type 2, 4 are better able to acidify urine.

Front 54

What notable urinary cation is absent from the urinary anion gap equation that should always be considered when contemplating the urine anion gap result?

Back 54

Ammonium NH4+, which should increase in an acidosis (making the anion gap more negative), or more positive in alkalotic pt.

Front 55

How do a type 1 or 4 RTA contribute to diminished ammonium secretion?

Back 55

in type 1 there is insufficient proton pump activity, so fewer protons to protonate ammonia.

in type 4, ammonia production is impaired, so although protons are available in distal nephron/collecting tubule, there is insufficient ammonia to buffer H+, so it can reenter renal tubule cells.

Front 56

What can cause a metabolic acidosis with anion gap?

Back 56

lactic acidosis (many causes including ischemia, shock, sepsis, hypoxia, metabolic dysreg)

ketoacidosis (DM type 1, starvation, alcoholism)

uremic acidosis (chronic kidney disease, acute kidney injury) ie renal failure acidosis

exogenous (toluene, methanol, ethylene glycol, isopropranol)

ACRONYM: MUDPILES (methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, lactic acidosis, ethylene glycol, salicylates)

Front 57

what systemic clinical effects can long term chronic acidosis have on patients?

Back 57

metabolic bone disease, anemia, hypercalciuria, among others.

Front 58

is metabolic alkalosis typically caused by a loss of protons or a gain of bicarbonate?

Back 58

Almost always proton loss. There is a maximal set point for kidney bicarb concentration, ~24, anything above that the kidney dumps.

Front 59

how can mineralocorticoid excess cause metabolic acidosis?

Back 59

hyperaldosteronism -> ongoing loss of K+ due to Na+ swapping -> hypokalemia -> H+ moves intracellular to replace lost K+ -> high H+ in collecting tubule enhances H+ secretion -> alkalosis

K+ deficiency also causes ammoniagenesis, further assisting H+ secretion

Front 60

What are the renal and non-renal causes of metabolic alkalosis?

Back 60

Renal: Hypermineralocorticoid (Bartter's, Gitelman's, primary hyperaldosteronism), hypokalemia, diuretics

Non-Renal: Vomiting, nasogastric suction

Front 61

Although hypokalemia can cause metabolic alkalosis, metabolic alkalosis without hypokalemia can lead to hypokalemia. what is the mechanism?

Back 61

Decreased pH in ECF draws H+ out of cells, which is replaced by more K+ to maintain membrane potential, increasing intracellular K+ concentration but causing hypokalemia. This also favors secretion of K+ in distal nephron.

Front 62

how can urine chemistries contribute to metabolic alkalosis diagnosis?

Back 62

If the kidney is not involved in the pathogenesis of metabolic alkalosis, it should be trying to correct it. In other words, if the alkalosis is due to hydrogen chloride loss from the stomach, the urine chemistries should reveal very low chloride and high pH, reflecting the kidney’s attempt to correct the alkalosis by conserving chloride and dumping bicarbonate. On the other hand, if the alkalosis is diuretic-induced, the urine chemistry will reveal no evidence of chloride conservation, and may even manifest an acid pH.

Front 63

Are patients with metabolic alkalosis chloride depleted?

Back 63

YES, all are chloride depleted. Cation replacement should be with chloride, not bicarbonate.

alkaloses can be either chloride sensitive or insensitive based on whether they respond to chloride replacement therapy. renally mediated alkalosis is typically chloride insensitive and referred to as chloride resistant.

Front 64

general treatment of metabolic alkalosis.

Back 64

Replace what is being lost, which is typically potassium, chloride, water/Na+ (vomiting, diuretics)

Front 65

Causes of respiratory acidosis?

Back 65

hypoventilation caused by obstructive airway disease, chest wall dysfunction or paralysis of respiratory muscles, suppression of CNS respiratory drive

kidneys respond by bicarb retention to offset acidosis.

Front 66

causes of respiratory alkalosis?

Back 66

Hyperventilation -> usually centrally mediated. can be caused by anxiety, hypoxia, stimulatory agents, sepsis, liver disease

Front 67

what common scenarios can cause metabolic acidosis with respiratory alkalosis mixed?

Back 67

due to diseases simultaneously causing hypoxia and hyperventilation. Lactic acidosis, or salicylate overdose leading to lactic acidosis. Uncouples oxidative phosphorylation.

Front 68

What can cause a mixed metabolic acidosis and metabolic alkalosis?

Back 68

diabetic has been vomiting (alkalosis) and chooses not to take insulin (acidosis)

Front 69

why is serum creatinine generally not a good marker for GFR?

Back 69

The relationship is nonlinear. For large drops in GFR there is only a small rise in serum creatinine, however as you decrease from a low to a very low GFR the serum creatinine increases exponentially.

Front 70

What is the cutoff level for oliguria, nonoliguria, and anuria in acute kidney injury?

Back 70

oliguria is <400 ml/day of urine output.
nonoliguria > 400ml/day urine output
anuria <50ml/day urine output

oliguria confers a worse prognosis for survival and recovery of renal function.

Front 71

What are the RIFLE criteria used for and what are they?

Back 71

RIFLE criteria are a classification scheme created to standardize the definition of AKI. the acronym is Risk, Injury, Failure, Loss, End stage renal disease.

Risk
1.5-fold increase in the serum creatinine or GFR decrease by 25 percent or urine output <0.5 mL/kg per hour for six hours

Injury
Twofold increase in the serum creatinine or GFR decrease by 50 percent or urine output <0.5 mL/kg per hour for 12 hours

Failure
Threefold increase in the serum creatinine or GFR decrease by 75 percent or urine output of <0.5 mL/kg per hour for 24 hours, or anuria for 12 hours

Loss
Renal replacement therapy for more than four weeks

End Stage Renal Disease (ESRD)
Renal replacement therapy for more than three months

Front 72

What are the 3 disease categories of AKI?

Back 72

1. Prerenal Azotemia
2. Parenchymal (or intrinsic) kidney damage
3. Obstructive uropathy (postrenal AKI)

Front 73

Describe prerenal azotemia

Back 73

purely a pathophysiologic condition, no pathologic changes. It is caused by a physiologic response to hypoperfusion of the kidney.

Autoregulation attempts to maintain GFR by dilating afferent arteriole (incr RBF) and constricting efferent arteriole (incr FF). However the effects are mitigated as increasing GFR in this fashion leads to increased proximal reabsorption due to Starling forces.

Therefore since this is a normal physiological response, PA is clinically REVERSIBLE.

Common causes include volume depletion (from GI tract, dehydration, diuretics, injury, burns, renal stenosis (bilateral), medications, etc), cardiomyopathy (CHF, other causes of low CO), systemic vasodilation/vascular redistribution (septic shock, cirrhosis), increased vascular permeability (capillary leak syndrome), autoregulatory failure (vessels decrease responsiveness after long period of HTN when treated)

Front 74

Describe parenchymal AKI

Back 74

Kidney is significantly injured, in contrast to prerenal azotemia, and cell damage has occurred, typically to the tubules. Kidney is highly vulnerable to ischemia, especially medulla, despite being well vascularized. High energy demand for active transport of solutes.

Common form is Acute Tubular Necrosis. Ischemia leading to endothelial injury activates an inflammatory cascade (express adhesion molecule ICAM-1, leukocyte activation and attraction, cytokine release). In tubule epithelium ATN causes cytoskeleton disruption, loss of brush border, membrane integrity compromised. These cells can then slough off and form casts which can obstruct the tubule.
ATN commonly caused by ischemia (hypotension, renal artery occlusion/embolus), toxin exposure (aminoglycoside ABs, amophotericin, radiographic contrast), endogenous "toxins" like myoglobin in rhabdomyolysis, hemoglobin (rarely). Prerenal azotemia can also progress to ATN. Acute interstitial nephritis and glomerular injury can also lead to parenchymal AKI.