Rossi Flashcards

1
Q

Go through the circle of events that occur in diabetes mellitus with respect to: ketone bodies, pH changes, buffering, and compensatory mechanisms

A

decreased insulin sensitivity to glucose (or no insulin) causes hyperglycemia leading to hyperinsulemia; acts like glucagon thus stimulating lipolysis which leads to increased plasma ketones; increased KB causes a decrease in pH

the decrease in pH is buffered by:

  1. ICF: proteins (Hb) and organic phosphates
  2. ECF: bicarb, proteins, inorganic phosphates

Compensation: since the body is in METABOLIC acidosis (because their is an accumulation of non-volatile acids), compensate by hyperventilating to increase alveolar respiration and decrease pCO2 thus decreasing [H+] bringing the pH back towards normal (**doesn’t exceed normal)
also there is an increase in urinary acid excretion (as NH4+ increase)

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2
Q

what is the effect of diabetes related hyperglycemia on the reabsorption of water/Na?

A

hyperglycemia leads to excess glucose that is SECRETED (because it surpasses Tm and tubules can’t resorb anymore) this leads to an osmotic diuresis in which water and Na+ aren’t resorbed as much because they normally resorption is iso-osmotic and Na+ is staying to balance the high osmolality of the urine;

** so although the Na+ concentration may be lower in TF, the absolute amount of Na+ left behind in the TF is GREATER; thus hyperglycemia increases BOTH Na+ and H2O excretion (more brought downstream)

leads to polyuria; leads to a decrease in ECF volume because a lot of water is leaving to balance out glucose

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3
Q

How are ketoacids (weak acids) buffered in the cell?

A

conjugate base of the ketoacid has transporters that can pump it into the cell along with H+ (THUS ELECTRONEUTRALITY IS MAINTAINED); there is no need for K+ to shift out of cell (like what happens with a strong acid buffering)

**Thus the acidosis in uncontrolled diabetes mellitus is NOT the cause of high plasma (or ECF) K+ seen in diabetic patients**

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4
Q

What is the cause of high plasma K+ seen in untreated diabetic patients?

A

NOT DUE TO ACIDOSIS (BECAUSE KETOACIDS ARE WEAK ACIDS)

due to high plasma osmolality that occurs when insulin is not present;

when insulin IS present, glucose in the ECF can enter the cells and be metabolized to CO2 and H2O. Thus the contribution of ECF glucose to the osmolality is minimal ~ 5mosm/kgH20 and STAYS CONSTANT. (blood glucose does not vary that much in normal individuals)

In the absence of insulin (as in diabetes) glucose cannot enter the cell (ignore brain for now), and the ECF osmolality rises; this causes a shift of gluid from the ICF to the ECF until the osmolalities are equalized AT A HIGHER OVERALL OSMOLALITY!

As fluid leaves the cell, the cell shrinks and K+ in the ICF increases (due to this decrease in fluid; not due to an increase in K+) leading to K+ leaving the cell (high to low) and entering the ECF causing ECF [K+] to increase and the AMOUNT of K+ in ICF to decrease (even though the CONCENTRATION is elevated from what it was originally) … thus a K+ (ICF) deficit that will lead to an H+ deficit and high K+ in plasma

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5
Q

What happens as a result of the high plasma K+ in diabetes mellitus?

A

trigers secretion of aldosterone (to decrease K+ and increase Na+) ** while the adernals respond to Na/K ratio, the ratio is most sensitive to K+ concentrations;

Aldosterone acts on the principal cell of the distal nephron to increase K+ secretion (and Na+ reabsorption) in order to mitigate the high K+ concentration;;
So now we have HYPER aldosteronism triggered by hyperglycemia

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6
Q

What are the factors that affect Distal Na+ reabsorption and K+ secretion?

A

Increase Na+ resorption and increase K+secretion:

  1. Aldosterone (due to high plasma [K+] from the glucose that is impermeable and K+ trying to balance it)
  2. Increased Na+ load to the distal tubule (Na+ not reabsorbed proximally due to osmotic diuresis)

Decrease Na+ resorption and Increase K+ secretion

  1. Non-resorbable anions (from ketoacids that exceed the Tm and are left in the lumen)
  2. High tubular fluid flow rate (due to osmotic diuresis and high fluid flow from upstream)

So plasma [K+] is high and:

  • in the presence of aldosterone (due to low ECF volume and blood pressure) K+ will be secreted
  • the high Na load (from osmotic diuresis upstream) will also increase K+ losses
  • the presense of non-reabsorbed ketoacids makes the tubular potential more negative and more K+ secreted
  • high tubular fluid flow rate will increase K+ losses in urine

NET RESULT: THE BODY BECOMES K+ DEPLETED, even though the PLASMA K+ is HIGH;
ICF K which cannot be measure directly is in deficit (big time)

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7
Q

What happens to the Na+ in diabetes mellitus?

A

hyperglycemia causes and increase in osmotic diuresis and less Na+ is resorbed; thus more Na+ gets to the distal tubule, and the increased Na+ load causes increase Na+ resorbption and increased K+ secretion; But the transporters Tm is exceeded and not all of the Na+ that now available (due to diuresis) can be resorbed;

Also the increase in ketoacids brings an overall negative charge in the urine (non-resorbable anions) as they exceed their Tm. Causes more Na+ to be secreted to balance the charge;

Even though aldosterone is triggered by the increase in plasma K+, and causes and increase in H2O and Na+ reabsorption, the Tm is exceeded. as more and more Na+ is not being reabsorbed, there is a net decrease in plasma volume, increasing even more aldosterone and causing more K+ secretion

NET RESULT: Na+ is excreted into the urine despite the ECF volume depletion

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8
Q

Thus, hyperglycemia due to diabetes mellitus (insulin insensitivity/absence) results in:

A
ketoacidosis
ketoaciduria
glycosuria
osmotic diuresis (loss of Na+ and H2O) 
hyperkalemia (high blood [K+]) with total body K+ deficit 
Hyperaldosteronism (secondary to high plasma [K+] ) which induces distal K+ secretion 
limited distal Na+ resorbption despite aldosterone due to nonreabsorbed anions
Increased distal K+ secretion (due to the effect of high aldosterone (from high plasma [K+] and ECF volume depletion), unresorbable anions, and increased Na+ load and flow
Total body Na+ and K+ deficit WORSENS!!
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9
Q

Why does aldosterone increase in diabetes mellitus?

A
  1. high plasam K+ concentration
  2. Low ECF volume (due to loss of Na and water leading to lower blood pressure and renin secretion, thereby stimulating the renin-angiotensin-aldosterone cascade)

Although the increased Na load to the principal cell AND aldosterone would increase Na reabsorption, the increased nonreabsorbed anions (ketoacids) will limit the ability of the distal nephron to make up for the na+ tat was not reabsorbed in the prox tubule due to osmotic diuresis

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10
Q

How does osmotic diuresis contribute to the corticomedullary gradient?

A
osmotic diuresis (due to high glucose in diabetes) causes an increase in flow of fluid though the loop of Henle since less Na+ and water are reabsorbed upstream in the Prox tubule; 
The delivery of solute at this speed exceeds the rate at which the thick ascending limb of Henle can reabsorb solute, resulting in less solute reabsorbed and then the gradient in the interrstitium will not be as steep.
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11
Q

How does the corticomedullary gradient effect water resorption and diabetes meillitus?

A

the CM gradient is less steep (due to the high flow rate of filtrate through the PT due to decreased resorption because of osmotic diuresis)

This causes a smaller gradient in the CD/DT for water resorption and thus less water is reabsorbed (more excreted); Result is that PLASMA osmolality increases (less water in to dilute it) and thus ADH expression is increased; but DESPITE THE PRESENCE OF ADH, the person with uncontrolled diabetes will not be able to resorb water optimally; thus POLY uria occurs.
due to polyuria, polydipsia (increased thirst) also occurs. if you don’t drink water to compensate for the loss of water, then increased [Na+] in plasma will cause further K+ secretion because the [K+] will also increase!

Also polyuria results in increased water and Na+ deficits that result in decreased ECF volume and decreased venous return and decreased blood pressure

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12
Q

What happens as a result of decreased ECV in diabetes?

A

hypotension and tachycardia (to compensate)

The decrease in ECV causes:

  1. DIRECT RENIN secretion (due to less Cl- seen at distal tubule/macula densa)
  2. INDIRECT RENIN secretion via a decrease in stretch = baroreflex to increase renal sympathetic nerve activity and increase plasma catecholamine concentration resulting in increased renin secretion
  3. INHIBITION OF RENIN due to increased Na+ load at JG cells, but blood pressure is a more powerful stimuli, so this is overwritten

Increased renin = increased angiotensin II = increased aldosterone (which is already stimulated by high plasma [K+])

* even eating a high Na+ sodium diet cannot compensate for the large fluid/Na+ loss in uncontrolled DM

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13
Q

What SHOULD happen when renal nerve activity and plasma catecholamines are high??

A

Decrease in ECV = decreased blood volume = decrease venous return to heart = decreased cardiac output = decreased blood pressure = baroreceptor reflex = increased renal sympathetic nerve activity and increased plasma catecholamines = 1. increased proximal Na+/H20 reabsorptions 2.afferent arteriole VASOCONSTRICTION = decreased GFR = decreased filtered Na/H2O = DECREASED urinary excretion of Na+ and decreased URINE FLOW

** this doesn’t happen in diabetic patients (person exhibits polyurea, even if DM is controlled due to osmotic diuresis)

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14
Q

What are some of the actions of Angiotensin II?

A
  1. increased vasoconstriction to increase BP
  2. increased aldosterone synth and secretion to decrease Na+ excretion and increase K+ excretion
  3. Increased thirst and increased ADH secretion
  4. increased efferent constriction (to maintain GFR), increased proximal Na+ reabsorption, decreased renin secretion (negative feedback)

most of these actions are not possible in diabetes because:

  1. decreased blood volume = decreased venous return = decreased cardiac output = decreased BP (even though vasoconstriction occurs)
  2. Na+ increased due to osmotic diuresis and nonreabsorbable anions so it can’t be reabsorbed well (it is excreted a lot)
  3. sometimes drinking water is not possible (ie: coma, vomitting etc)

*** that’s why if a pt has severe volume loss and is on an ACE inhibitors (that prevent angiotensin II) it is super dangerous (even though a lot of times ACE inhibitors are good for preventing diabetic kidney disease or diabetic heart failure)

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15
Q

What are the GENERAL effects of diabetes?

A

hyperglycemia (hyperosmolality) = metabolic acidosis = profound K+ depletion with high K+ concentration = Na and water depletion = cause high plasma osmolality = ECF volume depletion and hypotension = baroreflex activation of RAAS, ADH, sympathetic nervous system (catecholamines) and increased HR

PROBLEM = HIGH GLUCOSE
TREATMENT  = INSULIN (and replace lost Na+ K+ and H2O)
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16
Q

What happens in heart failure with respect to the kidney? (generally)

A

heart failure = kidney increases Na+ and H2O reabsorption because it receives ‘signals’ that the ECF volume is decreased; resulting in EXCESS NA+ and H2O in the body and the patient presents with edema, shortness of breath, low plasma [Na+] and osmolality

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17
Q

How much of total body water is in each compartment? what solutes are in ECF/ICF?

A
TBW = 0.6 * LEAN BODY WT
ECV = 1/3 TBW
ISV = 3/4 ECV
PV = 1/4 ECV

ICV = 2/3 TBW

Solutes:
Na, Cl, bicarb = ECF
K, organophos, protein = ICF

Osmolality = 300 osm

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18
Q

How does Fick’s principle relate to Na/Water balance?

A

Na in = Na out
water in = water out
IN NORMAL PATIENTS

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19
Q

How is water balanced in the body?

A

osmolality (tonicity) is regulated within +/- 1%; because the solutions are electroneutral, in ECF,
Na = Cl + HCO3- + proteins etc.

THUS PLASMA OSMOLALITY = 2* PLASMA [Na+]

if water is lost then:
there is an increase in osmolality which stimulates increased ADH and thirst = increased drinking and decreased water excretion = decreased osmolality back to normal

THUS REGULATING OSMOLALITY = REGULATES [Na+]
**abnormal plasma osmolality or plasma [Na+] is due to disturbed H2O balance

** Na CONCENTRATION does not tell you the Na content in the body, rather it is directly proportional to plasma osmolality and therefore the PLASMA Na+ CONCENTRATION tell us the AMOUNT OF WATER in the body

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20
Q

How is Na balanced in the body?

A

the AMOUNT of Na determines the size of ECV (because Na is confined to ECV)

ECV * plasma osmolality = TOTAL amount of solute in ECF and the major solute = Na so the Posm = Pna;

if the amount of Na is constant then the size of ECV = constant

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21
Q

What does a physical exam say about the amount of Na? What does the plasma concentration of Na tell you about?

A

if the interstitial compartment of ECV is Na high = edema in legs, pulmonary edema

if the plasma compartment of ECV is high = hypertension

Plasma concentration of Na tells you about the water content in the body:
high plasma Na = body water deficit
low plasma Na = body water excess

22
Q

What happens if you increase dietary Na?

A

increase in Na intake = increase in water retention proportionally (in order to maintain osmolality); causes gain of “water weight” that is not seen as swelling yet;increased volume is detected by body and causes a decrease in RAAS and decreased SS activity, to cause increased urinary excretion of Na+ (but this does not occur immediately, normally takes 2-3 days to come to a new equilibrium)

if you decrease Na+ intake then the Na+/water balance occurs at a lower level

23
Q

What does the excretion of Na+ depend on?

A
  1. amount of Na filtered (= Na filtered load) = GFR* Amount Na
  2. amount of Na+ reabsorbed (RNa)

But on a day to day basis, the GFR doesn’t really change but the resorption of Na does with different pathophysiological states (ie: diarrhea, hemorrhage etc)

24
Q

How is ISV/PV maintained in non-glomerular capillaries?

A

STARLING FORCES;
if you assume the amount of protein solutes is the same. then an increase in PV (by adding Na+ or water to ECF) causes a decreased in capillary oncotic pressure (due to dilution) ;
an increase in PV also results in an increased venous return = increase cardiac output = increased BP
So, the increase in PV = increase in capillary hydrostatic pressure, which in combination with decreased capillary oncotic pressure causes an increased filtration of fluid into the ISV and a decreased PV toward normal

** THUS A RISE IN ECV distributes into the INTERSTITIAL compartment, ISV

That’s why a high sodium meal does NOT cause an increase in blood pressure but does cause an increase in swelling/edema in legs

BUT: if the ISV expands enough (it can’t expand forever due to skin) then the tissue hydorostatic pressure will increase and oppose filtrations such that any further increase in ECV = both an increase in ISV AND AN INCREASE IN PV; the increased PV leads to an increase in urinary excretion (in attempt to decrease it back to normal)

^^ occurs only really is the volume increase is >2L (2kg Na)

25
Q

What is the normal response to increased PV?

A

increased PV = stretching of the aortic arch and carotid sinus baroreceptors (small changes in arterial pressure) which causes a decreased sympathetic output (decreased vasoconstriction.. increased vasodilation)

increased stretch also occurs at the justaglomerular cells of the kidney, leading to decrease in renin secretion and suppression of the renin-ang II-aldosterone pathway

when the increased volume makes its way to the venous side, the stretch of the pulmonary and atrial barorecpetors also suppresses the sympathetic output, and decreased ADH, leading to release of atrial natruretic hormone (ANH aka ANP)

ANP works on the kidney to INHIBIT Na reabsorption in the proximal tubule leading to more Na+ excretion and establishment of normal ECF and plasma volume (increased urinary excretion)

** BASICALLY: inhibition of a ton of hormones/mechanisms that usually cause reabsorption of Na+/H2O, and stimulation of ANP to cause increased Na+ excretion

26
Q

How does the kidney respond to hemorrhage?

A

hemorrhage = decreased blood volume translated to decreased PV :
causes decreased venous return, decreased CO and thus decreased BP

decreased BP = decreased stretch at aortic arch, carotid sinus, and JG cells and decreased stretch at pulm veins and atria

decreased aortic/carotid sinus = increased sympathetic stimulation (increased vasoconstriction) ,increased ADH, increased RAAS etc. all in attempt to increase BP

decreased JG cells stretch = same thing: stimulate RAAS to increase BP/restore ECF volume

decreased pulm veins/atria stretch = decreased ANP (not losing Na/water then)

OVERALL GOAL: maintain Na/water in ECV (includes PV) to maintain BP

27
Q

How does the kidney respond to heart failure? What is the initiating factor for the response to heart failure?

A

initiating factor = DECREASED CARDIAC OUTPUT;
leads to:
decreased blood pressure with decreased stretch at arterial and JG baroreceptors which leads to increased sympathetic and ADH and RAAS (like in hemorrhage), the difference is the the blood volume is NOT ACTUALLY LOW, the heart just can’t pump it out efficiently resulting in a decreased cardiac output that is sensed as low volume;

sets in motion the systems for Na/water reabsorption by the kidney (increased sympathetic activity, ang II, aldosterone, ADH) causing an increase in plasma volume which results in an increased venous return and and increased stretch in the pulmonary veins and atria (OPPOSITE OF HEMORRAGE) cause ANP TO INCREASE!! (increase Na+ excretion) WHICH SHOULD TURN OFF ADH (due to increased atrial pressure) but in SEVERE heart failure the venous side becomes INSENSITIVE TO STRETCH and since the pressures are chronically high and the barorecpetors are chronically stretched, they become desensitized so ADH is NOT turned off by the high atrial pressure

So despite the stimulation for ANP, there is a DECREASE IN water excretion and thus there is an increase in PV and a decrease in osmolality that does NOT result in decreased sympathetic or ADH

28
Q

Where is the the site of treatment for heart failure? (what types of drugs should you use)

A

Goal: want to stop Na+ reabsorbtion/SS function so that you can excrete Na+/water and reduce the blood pressure associated with heart failure (perceived decrease in cardiac output)

ACE INHIBIT (renin to angiontensin II)
antagonists to aldosterone,
beta blockers that inhibit catecholamine actions
diuretics that block Na reabsorption at thick ascending limb and distal tubules

*drugs that increase cardiac output can be dangerous, but can also work

29
Q

What is the role of ADH in heart failure t

A

ADH is high despite the increased stretch in pulmonary veins and atria so that water excretion is decreased; leads to a dissociate of the normal relationship between Na and water in the body;

Plasma Na concentrations are normally very stable; when you eat more Na your osmolality goes up, thirst is stimulated, and ADH is released to resorb water and thus the plasma Na concentration and osmolality remain stable

In heart failure, ADH is secreted due to lack of inhibition by the stretch receptors in the atria and pulmonary veins; decreased arterial pressures due to the low cardiac output (high pressure baroreceptors) will also disinhibit ADH and potentiate its release. As a result, water may be reabsorbed even when the plasma osmolality is normal or low and lead to very low plasma osmolality and plasma [Na].

30
Q

How does the kidney respond to hyperaldosteronism?

A

primary hyperaldosteronism = due to a tumor in the adrenal cortex that secretes constant aldosterone (increases) regardless of feedback

Increased aldosterone stimulates Na+ resorption and K+ secretion, which decreases Urinary excretion of Na; the resorption of Na leads to an increase venous return (increased stretch at the atria and pulmonary veins) and an increase in PV (and ISV). This increased stretch at the atria will increase ANP which will try to counteract the renal resorption of Na+.

The increase in PV will increase stretch at arterial and JG thereby decreasing catecholamines, renin, and ang II. High ANP and low catecholamines, renin, and ang iI cause a rise in PV and results in HYPERTENTENSION

because of the high aldosterone, they will also have low [K+] and metabolic alkalosis

    • normally if you increase PV, that would cause a decrease in aldosterone, but since its a tumor, you can’t. so this constant unsuppressable aldosterone at DT causes Na reabsorption (but all other hormones decrease.. so PT reabsorption is decreased, causing a new Na+ excretion balance at a high amount of Na+) similar to increased Na+ diet but now can’t decrease the blood pressure sooooo primary hyperaldosteronism =
      1. increased Na+
      2. increased BP
      3. decreased K+
31
Q

What is escape from aldosterone?

A

when a person with primary hyperaldosteronism comes into balance at a new level of blood pressure (high) at which Na+ intake will be again matched by Na+ excretion.
(Na + coming back into balance but with a HIGHER BP)

Primary hyperaldosteronism: =
decreased urinary excretion of sodium (Na+ highly resorbed); causes increased ECV and increased BP

As a result of increased ECV and increased BP, GFR increases, renin/ang II decreases, ANP increases, and urinary excretion returns to a new stable baseline BUT AT THE EXPENSE OF HYPERTENSION.

32
Q

What is congestive heart failure?

A

a clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood;

Heart failure is defined by the clinical symptoms and signs secondary to abnormal ventricular function

HF is caused by primary pathologic condition of the heart (MI due to coronary artery disease, etc) OR it can be secondary to systemic alterations placing undue demands on the heart or altering its function (hypertension, cardiac tamponade, respiratory and/or metabolic acidosis, electrolyte imbalances etc.)

33
Q

What are the different classifications of heart failure?

A

systolic (forward) HF or diastolic (backward) HF
Left sided HF or right sided HF or both
acute HF or chronic HF

*types of HF can occur concurrently

34
Q

What are the causes of systolic dysfunction (systolic, forward HF)

A
  1. Decreased contractility:
    acute = coronary occlusion
    chronic = cardiomyopathy (viral, autoimmune, drug induced)
  2. Afterload mismatch; malignant hypertension
  3. valvular disease and other forms of cardiac overload
    ie: mitral regurgitation, acute aortic regurgitation

**can’t push enough blood out, but you are properly filling the heart with blood

35
Q

What is diastolic HF?

A

heart failure PLUS: PRESERVED EJECTION FRACTION and with abnormal diastolic distensibility, filling pressures, or relaxation

36
Q

What are the causes of diastolic dysfunction (HF)

A
  1. impaired myocardial relaxation (ie: hypertrophic heart disease)
  2. increased resistance to ventricular inflow (ie: restrictive cardiomyopathies, constrictive pericarditis)
  3. Diastolic calcium overload (ie: conditions where SERVA2 activity/levels are decreased –> incomplete relaxation)

**problem with heart not filling completely, but you are contracting all that you can (all that comes in, but just decreased coming in)

37
Q

What are some of the clinical signs and symptoms of CHF? (ie: left vs right, respiratory, cardiovascular)

A

decreased cardiac output

left ventricular dysfunction leading to congestive LUNGS and PULMONARY edema while right ventricular dysfunction (without or with left ventricular dysfunction) results in SYSTEMIC venous congestion, peripheral edema, and ascites

with the increased venous pressure, starling forces favor filtration which results in fluid accumulation in the interstitial space;

Respiratory signs and symptoms:
crackles/wheezes, labored breathing, orthopnea (can’t breathe), non-productive cough, acute pulmonary edema leading to tachypnea, use of respiratory muscles, cyanosis, cold extremities

Cardiovascular signs and symptoms: palpitations, resting tachycardia, asucultation to reveal 3rd heart sound, increased central venous pressure, peripheral edema, low CO, HYPOtension which leads to low urine output

38
Q

How does systolic dysfunctional heart failure effect cardiac mechanics?

A

Starling curve shifts DOWN and to the RIGHT;

Heart becomes insensitive to changes in preload and more sensitive to changes in afterload

so systolic HF therapies try to improve contractility and reduce the load on the heart (because an increased preload doesn’t have much of an effect on the SV but an increase afterload has a HUGE effect on SV in the systolic HF heart)

39
Q

What is the relationship between end diastolic pressure and cardiac output in the normal, systolic, and diastolic HF hearts? What does decreasing preload do? what does decreasing afterload do?

A

Normal: increase in End Diastolic P (preload) should cause an increase in Stroke Volume (SV)
Systolic HF: (trouble with ejection); increased end diastolic pressure = doesn’t change the stroke volume much

If you DECREASE the preload (EDP) WITH A DIURETIC:
causes relief of pulmonary congestion by decreasing LV EDP (so more blood/fluid can get into LV), but you cause a little change in CO (need to be careful not to decrease the CO by using a diuretic!)

If you decrease the AFTERLOAD with an ACE INHIBITOR (NITROPRUSSIDE)
you increase the cardiac output by relieving the aortic pressure against which the ventricles need to work (therefore can eject more)

also cause a decreased LV EDP

40
Q

What does systolic HF look like on a pressure volume graph?

A

shifted to the right (higher Left Ventricular pressure since you are ejecting less) and the area of the loop = smaller (lower stroke volume)

the elastance (slope of the line passing through the end-systolic points of the loops and indicates the contractile state of the ventricle) is also decreased

41
Q

What do systolic HF therapies try to do?

A
  1. improve the myocardial contractility (but this can incrase the cardiac work, and the heart is already tired.. so maybe its not a good idea.. need to consider the trade off .. ie digitalis)
  2. Reduce the load on the heart
42
Q

What does diastolic HF look like in the pressure volume graph?

A

diastolic HF may or may not accompany systolic dysfunction diastolic HF = due to DECREASED relaxation and/or decreased ventricular compliance

three graphs:
1. abnormal relaxation (muscle is too thick; can’t fill as much so decreased SV); graph shows difference in inner left

  1. pericardial restraint (decreased relaxation because you meet resistance of pericardium and decreased filling) graph shows higher pressure (change is above the normal graph)
  2. increased diastolic stiffness (therefore can’t relax as much so cant fill) graph shows difference in inner right
43
Q

What is aortic stenosis? What does the PV loop look like?

A

= impaired left ventricular emptying due to high resistance by the stenotic aortic valve; result of high outflow resistance is: large pressure gradient across the aortic valve, and increased peak systolic pressure within the ventricle;

Stroke volume is decreased (width of PV loop) because the velocity of fiber shortening is decreased because of the high afterload; end systolic volume is elevated resulting in excess residual volume which, when added to the incoming venous return, results in increased end diastolic volume; pre-load increases and activates the frank-starling mechanism to increase the force of contraction to overcome the resistance of the valve;

If severe, the stroke volume falls substantially and leads to low arterial pressure

GRAPH:
smaller width; steep peak from top right to top left (top right = aortic valve opening) because a larger pressure gradient is required to push the blood through the valve, raising the peak (end-systolic pressure)

44
Q

What is mitral stenosis? What does the PV loop look like?

A

= mitral valve stiffens so it can’t open very well = impaired left ventricular filling; thus end diastolic volume is decreased (preload decreases). As a result, stroke volume decreases (Frank-Starling again);
Final result = decreased cardiac output an decreased systemic arterial pressure

GRAPH:
shifts to the left (over the edges of normal PV loop) because of EDP decreasing (preload decreased) and SV decreased (narrower)

45
Q

What is Mitral Regurgitation? what does the PV loop look like?

A

valve is basically constantly open (so blood is not only ejected into aorta from LV but also back into the LA) ;

NO ISOVOLUMETRIC PHASES!!! (graph is curved, no straight verticals) because blood flows back into LA before aortic valve opens and also back into the atrium when the ventricle is supposed to be filling ;

during systole, blood also flows in to the LA when LVP > LAP such that:
LAP and LAV increase during systole, thus the LV preload also increases; LV afterload decreases, so ESV also decreases (so the ventricular volume is decreased)

**Even though the LV and SV increase, the LV ejection (into the aorta) decreases

note: the SV is increased because the LAP is increased (due to increased blood coming back from LV during systole) and the increase in LAP/V causes a greater LV EDV/P

PV GRAPH: wider than the normal PV graph, and no isovolumetric phases (curved)

46
Q

What is aortic regurgitation? How does it look on the PV graph

A

= aortic valve doesn’t close completely at the end of systole;

as the ventricle relaxes during diastole, the blood travels from the aorta back into the ventricle and as a result the ventricle begins to fill from the aorta (rather than from the atrium) so there is no isovolumetric RELAXATION phase since ventricular volume is increasing even before the mitral valve opens

Once the mitral valve opens, filling also occurs from the left atrium but blood continues to go from the aorta into the ventricle throughout diastole because aortic pressure is greater than ventricular pressure during diastole; end diastolic volume is increased as a result. (SO GRAPH SHIFTS RIGHT)

No isovolumetric CONTRACTION (CURVED GRAPH ON RIGHT SIDE) because volume is increasing throughout. when ventricular pressure finally exceeds aortic pressure, the blood is ejected into the aorta.

THUS: increased EDV = increased preload = increased force of contraction = increased LVPP and increased SV;
diastolic arterial pressure is low (because during filling/diastole, blood is leaving the aorta back into the LV so less blood = lower pressure)

47
Q

What are some of the compensatory mechanisms of heart failure? what do they try to do?

A

1 adrenergic mechanism

  1. renal mechanism
  2. ventricular remodeling

try to compensate the decrease in cardiac output via modifying: HR, preload, afterload, and contractility

48
Q

How does ventricular remodeling act as a compensatory mechanism for heart failure?

A

hopes to decrease wall stress;

wall stress = pressure * radius/thickness
**chamber dilation and elevated transmural pressure = increase myocardial stress
increased myocardial thickening = decreases wall stress

49
Q

What are the types of ventricular remodeling (ie: hypertrophy)

A
  1. concentric hypertrophy = due to wall stress; result in sarcomere replication in PARALLEL, leading to an increase in ventricular wall thickness in attempt to increase the force of contraction to overcome the rise in afterload (uniform hypertrophy in all directions); results in a decreased ventricuar volume and increased wall thicness which reduces stress but cardiac work is maintained at increased level (because more sarcomeres = more energy requirement)
    SUPER THICK = bad because you can’t perfuse all of the tissue leading to ischemia
  2. Eccentric Hypertrophy = due to volume overload;
    replication of sarcomeres IN SERIES causes fiber elongation and ventricular enlargement; causes ventricular dilation (increased ventricular volume) which INCREASES myocardial stress (bad)
50
Q

Why isnt the body’s compensatory mechanisms for heart failure chronically effective

A

because even if you can increase the wall thickness to decrease the wall stress, the increased tissue mass requires increased oxygen and ATP (increased myocardial work) and eventually ischemia could happen;

catecholamines + ang II induce myocardial remodeling and apoptosis; but increased na+/water retention also leads to increased venous pressure (leading to edema); the increased total peripheral resistance (TPR) causes an increased afterload; and increased afterload and increased HR lead to increase in myocardial oxygen demand + reduced myocardial perfuction; which leads to increased ventricular dysfunction………