73: Renal Disease Flashcards
Nephrotic syndrome = The _____ manifestion of a kidney disease. So, by definition, I will not be talking about kidney disease but rather about the systemic manifestation of a heterogenous group of kidney diseases and the extra-renal complications associated with it.
This 18 year old sailor was relatively healthy until about a month before his presentation when he began to experience progressive edema (_____).
His history was rather unremarkable, he had a benign physical other than anasarca and a slightly elevated blood pressure. His urine was notable only for lipid droplets and his labs revealed profound _____ albuminemia, _____ lipidemia, and nephrotic range proteinuria. We biopsied him and found minimal change disease and began a course of oral _____.
Two days later he was found in his bunk by a roomate very dead. The autopsy demonstrated unilateral renal vein thrombosis and bilateral pulmonary emboli. In retrospect, these events must have occured after the biopsy when a little hematuria was not felt to be of great significance.
This highlights that these complications are often a major source of both morbidity and mortality with nephrotic syndrome rather than the primary renal disease itself. In fact, it is often odd that the life of this patient was lost even when he had a _____ creatinine clearance.
Hypoalbuminemia probably plays at least some part in this whole process since we usually see _____ with albumins less than about 2.5. The party line is that lowering the colloid _____ pressure in the intravascular system allows egress of fluid into the interstitium: _____ volemia then propogates the process by activating a number of intrarenal and etxtrarenal hemodynamic and neurohormal mechanisms. So, one would surmise that this is an appropriate _____ conserving maneuver by the body to optimize circulatory volume.
Nephrotic syndrome = The systemic manifestion of a kidney disease. So, by definition, I will not be talking about kidney disease but rather about the systemic manifestation of a heterogenous group of kidney diseases and the extra-renal complications associated with it.
This 18 year old sailor was relatively healthy until about a month before his presentation when he began to experience progressive edema (Anasarca).
His history was rather unremarkable, he had a benign physical other than anasarca and a slightly elevated blood pressure. His urine was notable only for lipid droplets and his labs revealed profound hypoalbuminemia, hyperlipidemia, and nephrotic range proteinuria. We biopsied him and found minimal change disease and began a course of oral steroids.
Two days later he was found in his bunk by a roomate very dead. The autopsy demonstrated unilateral renal vein thrombosis and bilateral pulmonary emboli. In retrospect, these events must have occured after the biopsy when a little hematuria was not felt to be of great significance.
This highlights that these complications are often a major source of both morbidity and mortality with nephrotic syndrome rather than the primary renal disease itself. In fact, it is often odd that the life of this patient was lost even when he had a normal creatinine clearance.
Hypoalbuminemia probably plays at least some part in this whole process since we usually see edema with albumins less than about 2.5. The party line is that lowering the colloid oncotic pressure in the intravascular system allows egress of fluid into the interstitium: Hypovolemia then propogates the process by activating a number of intrarenal and etxtrarenal hemodynamic and neurohormal mechanisms. So, one would surmise that this is an appropriate sodium conserving maneuver by the body to optimize circulatory volume.
Normally, plasma COP (colloid osmotic pressure) is about 24 mmHg and interstitial COP is about 12 mmHg. So the transcapillary gradient is about ____ mmHg.
The funny thing is that the fall in interstitial COP falls in ____ with the fall in plasma COP as ____ albuminia occurs.
Thus, the net transcapillary COP gradient is maintained in the ____ range. Since these studies it has become apparent that the compensatory mechansim fails when plasma albumin falls below about ____ and the COP gradient does fall and fluid moves into the ____.
Normally, plasma COP (colloid osmotic pressure) is about 24 mmHg and interstitial COP is about 12 mmHg. So the transcapillary gradient is about 12 mmHg.
The funny thing is that the fall in interstitial COP falls in parallel with the fall in plasma COP as hypoalbuminia occurs.
Thus, the net transcapillary COP gradient is maintained in the normal range. Since these studies it has become apparent that the compensatory mechansim fails when plasma albumin falls below about 2 and the COP gradient does fall and fluid moves into the interstium.
So, there is more to the story than simple hypoalbuminemia, hypovolemia, loss of colloid osmotic pressure and edema. It turns out that 2/3 of nephrotic patients actually have a ____ or ____ plasma volume.
Despite substantial volume expansion with hyperonctotic plasma, only about 50% will achieve an adequate ____ or ____. Sodium is retained in the proteinuric kidney of animals made unilaterally nephrotic.
____ occurs in children recovering from minimal change disease (disease of the kidney that causes nephrotic syndrome) with an increase in this filtration fraction.
We have seen cases of edema resolution ____ albumin improvement.
And children with congenital analbuminemia (albumin levels that are undetectable) have ____ edema. It should also be noted that plasma renin and aldosterone concentrations are only high in fewer than 50% of patients with nephrotic syndrome.
So, there is more to the story than simple hypoalbuminemia, hypovolemia, loss of colloid osmotic pressure and edema. It turns out that 2/3 of nephrotic patients actually have a normal or increased plasma volume.
Despite substantial volume expansion with hyperonctotic plasma, only about 50% will achieve an adequate diuresis (increased or excessive production of urine) or natriuresis (excretion of sodium in the urine). Sodium is retained in the proteinuric kidney of animals made unilaterally nephrotic.
Natriuresis occurs in children recovering from minimal change disease (disease of the kidney that causes nephrotic syndrome) with an increase in this filtration fraction.
We have seen cases of edema resolution without albumin improvement.
And children with congenital analbuminemia (albumin levels that are undetectable) have no edema. It should also be noted that plasma renin and aldosterone concentrations are only high in fewer than 50% of patients with nephrotic syndrome.
Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of signs of disease: protein ____, ____ albuminemia and edema.
It is characterized by an ____ in permeability of the capillary walls of the ____ leading to the presence of high levels of protein passing from the blood into the urine, low levels of protein in the blood (hypoalbuminemia), ascites and in some cases, edema; high cholesterol (hyperlipemia) and a predisposition for coagulation.
The cause of NS is damage to the ____, which can be the cause of the syndrome or caused by it, that alters their capacity to filter the substances transported in the blood. The severity of the damage caused to the kidneys can vary and can lead to complications in other organs and systems. However, patients suffering from the syndrome have a good prognosis under suitable treatment.
Kidneys affected by nephrotic syndrome have small pores in the ____, large enough to permit ____ uria (and subsequently hypoalbuminemia due to the protein albumin that has gone from the blood to the urine) but not large enough to allow red blood cells through (hence no hematuria).
Nephrotic Syndrome Edema: The reflex action should _____ be to give diuretics
Nephrotic syndrome is a nonspecific kidney disorder characterised by a number of signs of disease: proteinuria, hypoalbuminemia and edema.
It is characterized by an increase in permeability of the capillary walls of the glomerulus leading to the presence of high levels of protein passing from the blood into the urine, low levels of protein in the blood (hypoalbuminemia), ascites and in some cases, edema; high cholesterol (hyperlipemia) and a predisposition for coagulation.
The cause of NS is damage to the glomeruli, which can be the cause of the syndrome or caused by it, that alters their capacity to filter the substances transported in the blood. The severity of the damage caused to the kidneys can vary and can lead to complications in other organs and systems. However, patients suffering from the syndrome have a good prognosis under suitable treatment.
Kidneys affected by nephrotic syndrome have small pores in the podocytes, large enough to permit proteinuria (and subsequently hypoalbuminemia due to the protein albumin that has gone from the blood to the urine) but not large enough to allow red blood cells through (hence no hematuria).
Nephrotic Syndrome Edema: The reflex action should NOT be to give diuretics
There may even be two distinct groups of edematous patients.
Patients who fulfill the classical underfill theory are ____ albuminemic with secondary ____ of the renin-angiotensin system and subsequent salt and water retention.
Other patients have a component of primary renal salt and water retention, but rather an ____ with expanded plasma volume, ____ of the renin-aldosterone system, and leak into the interstitium.
Both mechanims may even exist within the same patient. If patients have the ____ state, they may be safely and aggressively diuresed (the act of effecting diuresis)..
There may even be two distinct groups of edematous patients.
Patients who fulfill the classical underfill theory are hypoalbuminemic with secondary activation of the renin-angiotensin system and subsequent salt and water retention.
Other patients have a component of primary renal salt and water retention, but rather an overflow with expanded plasma volume, suppression of the renin-aldosterone system, and leak into the interstitium.
Both mechanims may even exist within the same patient. If patients have the overflow state, they may be safely and aggressively diuresed (the act of effecting diuresis)..
Proteinuria ultimately leads to ____ albuminemia and ____ formation by several mechanisms. Along the way there is a loss of hormones, vitamins, minerals and immunoglobulins as well as factors involved in the coagulation cascade.
Compensatory hepatic synthesis as well as reduced lipoprotein lipase (hydrolyzes Triglycerides) activty contribute to ____ lipidemia and an increase in the rate of renal catbolism in the setting of a decreased overall albumin pool aggravates the process and contributes to malnutrition.
Proteinuria ultimately leads to hypoalbuminemia and edema formation by several mechanisms. Along the way there is a loss of hormones, vitamins, minerals and immunoglobulins as well as factors involved in the coagulation cascade.
Compensatory hepatic synthesis as well as reduced lipoprotein lipase (hydrolyzes Triglycerides) activty contribute to hyperlipidemia and an increase in the rate of renal catbolism in the setting of a decreased overall albumin pool aggravates the process and contributes to malnutrition.
ADH action in the kidney is mediated by its binding to V2 receptors, coupled to ____ cyclase and ____ production.
cAMP activates protein kinase ____ which prompts the insertion of water ____ into the apical membrane of the cell.
When ADH is removed, the water channels ____ from the membrane and the apical surface of the cell becomes ____ to water once again.
ADH action in the kidney is mediated by its binding to V2 receptors, coupled to adenylate cyclase and cAMP production.
cAMP activates protein kinase A which prompts the insertion of water channels into the apical membrane of the cell.
When ADH is removed, the water channels withdraw from the membrane and the apical surface of the cell becomes impermeable to water once again.
Osmotic Factors that influence ADH release = plasma ____
\_\_\_\_-Osmotic Factors that influence ADH release: • Volume or blood pressure • Nausea • Pain • Physical stress • Hypoglycemia • Narcotics/ SSRIs • Angiotensin II • Ethanol • Prostaglandins • ANP
Osmotic Factors that influence ADH release = plasma osmolality
Non-Osmotic Factors that influence ADH release: • Volume or blood pressure • Nausea • Pain • Physical stress • Hypoglycemia • Narcotics/ SSRIs • Angiotensin II • Ethanol • Prostaglandins • ANP
The syndrome of inappropriate antidiuretic hormone secretion or SIADH is characterized by excessive release of antidiuretic hormone from the ____ pituitary gland or another source.
The result is often dilutional ____natremia in which the sodium remains normal but total body fluid ____. The treatment may consist of fluid intake restriction, various medicines, and management of the underlying cause.
**Clinical criteria for the ____ of SIADH:
• POsm ____ 275
• Inappropriately ____ urine
• ____ volemia
• Urine Na ____ 40
• No diuretic ____ or renal / adrenal / thyroid disease
Relatively common and mild in the ____.
The syndrome of inappropriate antidiuretic hormone secretion or SIADH is characterized by excessive release of antidiuretic hormone from the posterior pituitary gland or another source.
The result is often dilutional hyponatremia in which the sodium remains normal but total body fluid increases. The treatment may consist of fluid intake restriction, various medicines, and management of the underlying cause.
Clinical criteria for the diagnosis of SIADH:
• POsm 40
• No diuretic use or renal / adrenal / thyroid disease
Relatively common and mild in the elderly.
ACE inhibitors ____ blood pressure by inhibiting conversion of angiotensin 1 to angiotensin 2.
Angiotensin 2 is a potent vaso ____ that preferentially constricts the ____ arteriole.
Normal subjects have ____ renal blood flow and GFR with ACE inhibition.
Pts with underlying vascular disease or CHF are at increased risk of a ____ in GFR.
ACE inhibitors lower blood pressure by inhibiting conversion of angiotensin 1 to angiotensin 2.
Angiotensin 2 is a potent vasoconstrictor that preferentially constricts the efferent arteriole.
Normal subjects have increased renal blood flow and GFR with ACE inhibition.
Pts with underlying vascular disease or CHF are at increased risk of a decrease in GFR.
Acute renal failure occurs in patients with underlying abnormalities of ____:
– CHF on diuretics
– Severe bilateral renal artery stenosis
– Renal artery stenosis of 1 functioning kidney or transplant
Acute renal failure occurs in patients with underlying abnormalities of vasculature/circulation:
– CHF on diuretics
– Severe bilateral renal artery stenosis
– Renal artery stenosis of 1 functioning kidney or transplant
Renin Secretion by the Macula Densa ____:
– Baroreceptors/myogenic reflexes in AFFerent arteriole
– SNS
– Catecholamines
– Cl delivery Macula Densa
Renin Secretion by the Macula Densa ____:
– ADH
– ANP
– Perhaps BNP, CNP
Renin Secretion by the Macula Densa stimulates:
– Baroreceptors/myogenic reflexes in AFFerent arteriole
– SNS
– Catecholamines
– Cl delivery Macula Densa
Renin Secretion by the Macula Densa inhibits:
– ADH
– ANP
– Perhaps BNP, CNP
NSAIDS can induce acute renal ____. Afferent arteriole is regulated by vasodilator ____ & disruption can produces sudden, ____ (low output of urine) acute renal failure.
- Acute Kidney Injury (AKI) occurs with preexisting compromise of renal perfusion-volume depletion, CHF, Cirrhosis, diuretics and advanced age.
- NSAIDs inhibit cyclooxygenase enzymes that produce vasodilator prostaglandins PGE2 and PGI2
- In normals, renal prostaglandin production is low and NSAIDs have little effect.
NSAIDS can induce acute renal failure.
- Acute Kidney Injury (AKI) occurs with preexisting compromise of renal perfusion-volume depletion, CHF, Cirrhosis, diuretics and advanced age.
- NSAIDs inhibit cyclooxygenase enzymes that produce vasodilator prostaglandins PGE2 and PGI2
- In normals, renal prostaglandin production is low and NSAIDs have little effect.
NSAID + ACE inhibitos + Intravascular Volume Depletion = “dys-autoregulation” & leads to acute renal ____.
NSAID + ACE inhibitos + Intravascular Volume Depletion = “dys-autoregulation” & leads to acute renal failure.
