Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/66

Click to flip

66 Cards in this Set

  • Front
  • Back
What is the effect of excess Na in the ECF? Low Na?

What is hyponatremia? Hypernatremia?
High: Increased ECF volume, edema.
Low: Decreased ECF volume, low blood volume.

Hyponatremia:[Na] in plasma is too low, excess water in cells (ICFV).

Hypernatremia: [Na] in plasma too high, decreased ICFV.
Outline blood supply in the kidney.

Outline flow through the nephron.
Blood: renal artery branches into afferent arteriole to glomerulus to efferent arteriole to peritubular capillary to renal vein.

Nephron: Bowman's capsule to proximal convoluted tubule to loop of Henle (descending, ascending), then distal convoluted tubule to collecting duct.
What is the main factor controlling renal blood flow?

What effect does high blood pressure have on afferent arteriole? Low?

Name 2 other factors important at low bp.
-Myogenic reflex in afferent arteriole.

-High constricts afferent arteriole, low dilates.

Low bp: vasodilatory prostglandins, angiotensin II (acts on efferent arteriole).
Name 3 renal vasoconstrictors.

Name 3 dilators.
Constrictors:
1. angiotensin II (efferent a).
2. catecholamines
3. sepsis, liver failure

Dilators:
1. Prostaglandins, ANP
2. Pregnancy, high protein diets
3. Diabetes mellitus.
Name 2 factors that determine renal blood flow.

What are the effects of afferent arteriolar constriction? Efferent?
Renal blood flow: 1. mean arterial pressure, 2. renal vascular resistance.

A Constriction: reduces glomerular capillary pressure, renal blood flow and GFR.

E Constriction: increases capillary blood pressure, reduces renal blood flow, variable effect of GFR.
What is the filtration fraction?

What does afferent constriction do to filtration fraction? GRF?

What does efferent constriction do to filtration fraction?
The ratio of GFR (volume of fluid filtered into Bowman's capsule from glomerular capillaries/unit of time) to RPF (renal plasma flow)

Afferent constriction: does not affect filtration fraction, reduces GFR.

Efferent constriction: increases filtration fraction (less opportunity to go into efferent blood pathway, more is filtered).
How does angiotensin II affect filtration fraction?
Angiotensin II is made in presence of low blood pressure, causing efferent constriction.

Efferent constriction increases filtration fraction (GFR/RPF), preventing GFR from dropping.

If not, there would be a huge drop in GFR. Ace inhibitors do not affect GFR @ notmal b.p, but if this is low, it could result in a catastrophic drop.

KEY: preserve GFR by increasing FF.
What affect does diabetes mellitus have on kidney?

Tx?
-Causes afferent dilation and increased glomerular capillary pressure.
-Increased pressure can cause injury

Tx: drugs blocking angiotensin II cause efferent dilatation, reducing glomerular capillary pressure.
How is GFR measured? What substance is used?

Formula?
By a solute that is freely filtered and neither secreted nor reabsorbed. When this occurs, filtration = excretion. Creatine (produced from muscles at a constant rate).

Filtration = GFR x Pc ([plasma])
Excretion = Urine flow rate x Uc

GFR x Pc = UFR x Uc

And solve!
What is the relationship between plasma creatinine an GFR?
GFR is inversely proportional to Pcreatinine.

E.g. baseline level of creatinine is 100, and GRF is 100 ml/min, creatine is is 50 if serum doubles, 100 if it quadruples, etc.

CREATINE EXCRETION REMAINS CONSTANT. MUST BE IN STEADY STATE TO APPLY RULE.
what are the 3 things which affect baseline creatinine?

What 2 equations are applied to more accurately estimate GRF from Pcreatinine?
Age, gender, bodyweight.

Equations:
Cockcroft;Gault equation: uses weight
MDRD: uses age and gender.
Where is Na+ restricted to?

What effect does high Na+ have?
What effect does low Na+ have?
ECF

High Na+ makes water cross cell membranes to equalize osmolality., leading to increased ECF volume and edema.

Low Na+ reduces ECF volume and results in low blood volume.
What effect does water excess have on fluid volumes? Water deficit?
Excess: hyponatrema = increased ICFV.

Deficit: Hypernatremia = decreased ICFV.
How is ECF volume assessed?

How is ICF volume assessed?
ECF volume assessed by clinical exam.
ICF volume assessed by serum [Na+] and serum osmolality. If both are low, the ICFV is increased. If both are high, ICFV is decreased. If Na is low and osmolality is high, it depends upon the extra solute.
What are the 3 ways GFR is regulated?
1. Afferent arteriolar tone
2. Prostaglandins
3. Angiotensin II.
Outline how tubular reabsorption and secretion occurs in a general sense.
Driven by Na/K+ATPase on the basolateral membrane (next to peritubular capillaries).

Sodium transport proteins on the lumenal membrane move Na into tubule down electro-chemical gradient.

ATPase pump moves it out.

Reabsorption or secretion of other solutes is linked via sodium-coupled transport proteins on the lumenal side.

TIght junctions exist between cells.
Structurally speaking, what determines how much Na+ is reabsorbed?
Determined by the Na-K-ATPase pump presence - more - more absorbed.

Leakiness of tubules to water and solutes, presence of transporters and presence of hormone receptors on basolateral membrane also play a role.
The proximal tubule is the site of bulk reabsorption for 5 things. What are they?

What substances are co-transported across the proximal tubule?

What is the main lumenal Na+ transporter?
Na+, Cl-, H2O, K+, bicarbonate.

Cotransport: glucose, phosphate, aa, lactate.

Lumenal transporter: Na-H+ countertransporter secretes H+ to reabsorb bicarbonate (NHE) (sodium hydrogen exchanger).

Note: if a solute escapes reabsorption in the proximal tubule, it cannot be picked up later.
What lumenal transport proteins are present in the thick ascending limb of the loop of Henle?

What inhibits this?

The fluid leaving the ascending limb is ________ concentrated than plasma.
Na-K-2Cl.

Inhibited by furosemide.

Fluid leaving is less concentrated than plasma (hypotonic). Thick ascending limb is very impermeable to water, making medulla hypertonic.

KEY: dilute lumen fluid, concentrated interstitial fluid.
What is the main lumenal Na+ transporter in the distal convoluted tubule?

What inhibits this transporter?

What hormone acts here?
Na+-Cl- co-transporter.

Thiazides inhibit reabsorption.

ADH acts here to increase water reabsorption.
What lumenal Na+ transporter acts in the cortical collecting duct?

Which drugs inhibits this?
ENaC (epithelial sodium channel).

Inhibited by amiloride directly and spironolactone weakly (by inhibiting ALD). These are K+ sparing diuretics.
Which hormone receptors are present in the cortical collecting duct?

What ion is secreted here?
Aldosterone receptors, which stimulate the number of open sodium channels to increase sodium reabsorption.

ADH receptors: increase water reabsorption.

K+ is secreted here. The lumen is negative and less permeable to chloride. THis facilitates K+ movement out of the cell. ALD means more Na channels, making the lumen more negative because more Na+ has left and more Cl- is left, drawing K+ out.
Outline the leakiness (and therefore ability to generate gradients) of the: proximal tubule? collecting duct?

How is water reabsorbed?
Proximal tubule: leaky, no large gradients established.
Collecting duct: tight, larger gradients established.

PASSIVELY: follows Na+ isotonically in the proximal tubule, and depends on ADH in DCT and collecting duct.
What happens when Na+ is added to body and not excreted?

Where is the H2O derived from?
Stays in ECF, and ECF volume rises as water goes where particles are by osmosis.

H2O comes from thirst, water exiting cells, and reabsorbing Na+ in the kidney (water reabsorbed by following kidney).
What is extracellular fluid-volume composed of?

Name 4 effects due to a decreased ECFV?

What can occur as result of an increased ECFV?
Plasma and ISF.

4 effects: 1) plasma volume decreased, 2) blood volume decreased, 3) cardiac output decreased, 4) blood pressure down.

Edema, risk of pulmonary edema.
Outline what will occur if NaCl and H2O are added to plasma?
Increased plasma volume will dilute albumin in plasma. The increased plasma volume will increase intravascular hydrostatic pressure, and dilution of albumin will decrease oncotic pressure. This will result in addition of fluid to interstitial space and plasma in a ration of 1:3 (plasma to interstitium). Key - will not stay in plasma, some will move to ISF.
OUtline how loss of NaCl and H2O from plasma and interstitial space an affect volumes?
Loss of NaCl and H2O will decrease the plasma hydrostatic pressure and increase oncotic pressure. This will move fluid from interstital space to plasma, resulting in a final loss ratio of 1:3 from plasma to interstitum.
How is ECF volume regulated?
Changes in effective arterial volume, the volume of blood perfusing tissues and stimulating atrial barorceptors. NOT by plasma [Na+], but by effective circulating volume.
Where are baroreceptors located?
Central arteries (carotid sinus, aortic arch), renal afferent arteries, cardiac atria, ventricles.
What are the 3 key responses to effective arterial blood volume depletion?
1. Sympathetic nervous system.
2. Renin-angiotensin-aldosterone system
3. Antidiuretic hormone
What effect does the SNS have on the heart, blood vessels, and kidneys?
Heart: increased rate and contractility.
Vessels: increased arteriolar resistance, venous constriction to increase preload.
Kidney: increase Na+ reabsorption in proximal convoluted tubule and increase renin secretion.
Outline the Renin-Angiotensin-Aldosterone System (RAAS).
-Decrease in BP at the renal afferent arteriole or increased sympathetic stimulation.

-Increased renin secretion acting on angiotensinogen in the lver to convert it to angiontensin I.

-Angiotensin I converted to angiotensin II by ACE in lungs.

-Angiotensin II induces arteriolar constriciton of all tissues and the renal efferent arterioles. It increases Na+ reabsorption at the PCT via aldosterone, and increases thirst and ADH.
How does angiotensin II induce effects via efferent arteriolar constriction?
Constriction increases glomerular capillary pressure and increases the filtration fraction to maintain GFR. THis decreases hydrostaic pressure in the peritubular capillary, and increases oncotic pressure. These favour reabsorption of Na+ in the PCT, and water follows.

KEY: filtration fraction increased.
Name 3 pathologic effects of activated RAAS.
1. Atherosclerosis.
2. Cardiac scarring and remodelling (after MI, due to hypertension).
3. Renal scarring after injury.
How can negative Na+ balance occur?
Intake less than output, or excessive loss from skin, GI, kidney, third space, and bleeding.

Burns in particular: needs in first 24 hours: 4cc x wt(kg) x %BSA

GI losses occur due to diarrhea, and volume. Vomiting is not s large of a loss, but has urinary losses due to excretion of NaHCO3. May also occur in ileus if bowel is obstructed or paralyzed.

Overuse of dieuretics, osmotic diuresis, or tubular dx where renal absorption fails.
Outline how glucose-induced osmotic diuresis can occur in uncontrolled diabetes mellitus.
Renal tubule can only absorb 1800 mmol of glucose/day. Once plasma glucose > 10 mmol/L, all transporters can be saturated and excess is excreted. THis osmotically holds water, and leads to diuresis.

This also causes excess loss of Na+ as the concentration gradient at the proximal tubule reduces reabsorption.
Outline the renal responses to hypovolemia.
Hypotension leads to renal vasconstriction decreasing blood flow and thereby GFR.

This increases tubular reabsorption of Na+ in the proximal tubule by Ang-II, SNS and peritubular factors, cortical collecting duct due to aldosterone, and increased reabsorption of H2O at collecting duct by ADH.

Final urine volume is smaller, and [Na+] is low, and osmolarity is high (mainly urea).
Name 7 manifestations of Na+ loss.
1. hypotension, including postural.
2. tachycardia, including postural.
3. dizzy when standing
4. fatigue
5. cold, sweaty skin
6. low urine output
7. circulatory shock.
How is volume depletion treated?

How is hypovolemia treated by iv?
Treat underlying cause or problem. Give fluid (need Na+ and H2O) orally if possible, iv if necessary.

Need to give fluid that will expand ECF volume. Can't give H2O, Give NaCl solution with Na+ normal saline. NaCl stays in ECF, keeps water in ECF and expands plasma and ISF. Can also give colloids, not effective and $.
What normally occurs in response to increased sodium intake?
Initially, Na intake exceeds excretion and a positive balance exists. After a few days, Na excretion in urine is increased and steady state is restored, but ECF volume is expanded.

ECF volume is sensed by receptors in carotid atria. As response:
Na-retaining hormone (Ang-II, Aldo, SNS) secretion decreased; Natriuretic peptides - atrial natriuretic peptide and brain natriuretic peptide and others lead to increased renal Na+ excretion.
What is pressure natriuresis?
Rate of urinary excretion sodium excretion increases with mean arterial blood pressure. Intrarenal pressure is up via hydrostatic pressure in medullary capillaries, decreased tubular fluid reabsorption.
What happens if Na+ intake remains high?
ECF volume is not restored. Kidneys need signals (natriuretic peptide) to excrete excess Na+. This is triggered by ECF. If Na+ is retained in the first few days, intake would fall toward normal. But excretion would drop toward normal and if intake remained high, Na+ balance would be positive again.
What disease states contribute to a positive Na+ balance? How?
Renal failure, heart failure, cirrhosis, nephrotic syndrome. These cause inhibited excretion of Na+.
How does renal failure create a positive Na+ balance?

How does heart failure create a positive Na+ balance?
Low GFR reduces ability to excrete sodium load. Can be acute or chronic.

Low cardiac output activates signals for low ECF. Volume gets caught up in veins, and is not part of effective arterial blood volume, leading to renal retention of Na+ and H2O despite expanded blood volume.
How does cirrhosis contribute to positive Na+ balance?
Scarring leads to portal hypertension, which leads to pooling of blood in gut vasculature. This increases toxin absorption from gut leading to arteriolar vasodilation. This decreases effective arteriolar volume despite increased total blood volume and increased CO. Activates Na+ and H2O retaining properties.
How does nephrotic syndrome disrupt ECF fluid volumes?
Glomerular dx disrupts normal glomerular capillary wall, resulting in +++ protein filtration. This leads to heavy proteinurea, to hyopalbumineria, leading to liver: hypercholsterlemia and edema via increased ISF volume.
What must occur for edema to occur?
Must be rental retention of ingested sodium and water. Need > 3 L of extra ISF.
What are the 2 theories for renal retention of Na+ and H2O in nephrotic syndrome?
1) hypoalbuminea leads to loss of fluid from plasma to ISF leading to intravascular volume contraction and baroreceptor-mediated hormone release and renal retention of Na+ and H2O.

2) Renal dx leads to glomerular leak of protein and increased tubular sodium reabsorption leading to renal retention of sodium and H2O.
What occurs when there is a positive Na+ balance?
Edema (a detectable ISF volume), (swelling of ankles, sacral edema, pulmonary edema or plural effusion, ascites), Possibly high BP.
How is positive Na+ balance treated?
1) Decrease Na+ intake.
2) Increase excretion o Na+ and H2O with diuretics.
Where do each of the following drugs act and with what mechanism?

Acetazolamide
Furosemide and Ethacrynic Acid
Hydrochlorothiazide
Spironolactone
Amiloride and Triamterene
Acetazolamide: proximal convoluted tubule, carbonic anhydrase inhibitor.

Ethacrynic acid: thick ascending limb of loop, inhibit Na K 2Cl transporter.

Thiazides: distal convoluted tubule, inhibit NaCl transporter.

Spironolactone: cortical collecting duct, direct aldosterone antagonist.

Amiloride and Triamterene: block Na+ channel of cortical collecting duct.
When would an antagonist of the RAAS system be used?
Hypertension, congestive heart failure, progressive renal dxx, after MI.

Action sites: direct renin inhibitor, ACE inhibitor, direct angiotensin receptor blocker, aldosterone antagonist.

RAAS activated in all states of effective low blood volume.
Which particles change a lot in size? Which cells are most vulnerable?

How is this sensed? What effect does it have?
ECF particles (ICF are largely fixed). Cells in brain are most vulnerable.

Sensed by osmoreceptor in hypothalamus (OVLT), near 3rd ventricle. This acts as a mechanoreceptor in cell membrane senses a decrease in cell stretch, leading to an inward decrease in Ca++.

Effect: stimulates thirst and synthesis and release of ADH.
Where is ADH synthesized? Stored?
What does it activate?
Supraoptic and paraventricular nucleii of hypothalamus. Stored in posterior pituitary.

Activates: vasopressin receptors: V1 for vasoconstriction, V2 for ADH response in renal collecting duct. Early response makes it hold onto the water already present in body.
Name 2 stimuli for ADH release.

What are the effects of ADH?

What effect does this have on urine volume and concentration?
1) ECF osmolarity up (due to hypernatremia).
2) ECF arterial volume down (hypovolemia, but also in heart failure, cirrhosis).

Effects: results in insertion of water channels into the lumenal membrane of cortical and medullary collecting duct. Water is reabsorbed from lumen to hyperosmotic interstitial space of kidney.

Urine volume: small and highly concentrated.
Free water - define.
Amount of water to be removed from a solution before it is isotonic.
What are the causes of hypernatremia?
Anything that increases the number of mol of Na+ in ECF, (drink seawater, improperly prepared infant formula, large volumes of iv fluid and loss of water) or decreasing the ECF water...may be due to:

-reduced intake of water (coma, stroke, dementia, swallowing difficulty, infants).
-Increased loss - sweating, GI, urine.
What does lack of ADH cause?
Diabetes insipidus - may be central (dx of pituitary/hypothalamus), impairs production and release of ADH, may be due to trauma or infiltrative dx), or nephrogenic - where kidney fails to respond to ADH (e.g. congenital or with lithium tx).
What occurs in diabetes insipidus? Tx?

What impact does this have on ECF volume>
Large volume of dilute urine, responds to exogenous vasporessin if central.

E.g. if 3L of H20 are lost in urine, this would have come from the ECF. This would increase [Na+], drawing water out of cells. Overall, volume is maintains such that 2L would come from ICF and 1 L from ECF.
Define osmolarity.

Name 2 consequences of hypernatremia in brain.
# particles/volume. If the number of particles is constant, then size will shrink in hypernatremia.

Hypernatremia: 1. cells shrink - brain cells don't work properly. 2. Adaptation - brain imports new particles to restore cell size. Hence, overly rapid correction leads to brain cells being larger than normal = cerebral edema.
How is hypernatremia managed?

How is free H2O given?
Treat the underlying cause
Give free H2O
May also provide isontonic fluid to correct defects
Monitor to ensure correct is not too fast.
Replace ongoing losses of fluid.

Give free H20 - by os, NG, subdermal, or iv. Cannot give water directly iv - give with a solute to make an iso-osmotic solution...e.g. D5W: 5% dextrose. Other option is half-normal saline.
What causes hyponatremia?

What response is expected?
Extra water in ECF. The amount of Na may be decreased, normal, or increased, as [Na+] is the ratio of Na+ to water.

Expected response: suppression of ADH release via osmoreceptor, therefore expect increase in excretion of free water in urine.
Name 3 possible scenarios in persistant hyponatremia.
If persistent, water is not being excreted fast enough.

1. Very high intake (e.g. psychogenic polydipsia).
2. Severe renal failure (very low GFR).
3. ADH present when it should be suppressed by hyponatremia. What?:

-Effective arterial volume may be depleted - true hypovolemia, or heart failure or severe liver dx (vasodilation). This would cause baroreceptor-mediated ADH release. OR....non-volume stimuli...lung dx, CNS, drugs, ectopic production by CA, hypothyroidism, cortisol deficiency, stress.
What are the 2 main consequences of hyponatremia?
1. Cells swell - cerebral edema. Confusion, seizures, coma, death.

2. Cells adapt if hyponatremia develops slowly...cells export intracellular particles. If corrected rapidly = rapid brain shrinkage...neurons can lose myelin coating!
How is hyponatremia treated?
SEVERE SYMPTOMS: Rapidly increase plasma [Na+] by giving hypertonic (3%) NaCl by iv to suck water out of cells, tx the underlying cause and restrict H2O intake.

If there are few or no symptoms, adaptation occurred. Tx underlying cause, restrict water, consider oral NaCl, monitor to ensure [Na+] is not rising too quickly.
By volume = # particles/osmolarity, what would cause volume to increase due to number of particles? By decreased osmolarity?
Glucose, urea, NaCl.

Diabetes insipidus, excess intake.

KEY: polyurea is due to excessive urinary excretion of solutes and/or a reduced urine osmolarity.