STUDY - Technical - New Dacian's Medicine
The Main
Manifestations of Kidney Disease (1)
Translation Draft
Patients with kidney disease may present themselves to the doctor in different ways, depending on the nature of the disease and the time of presentation. Some patients with advanced renal disease may have signs and symptoms of uremia with unremarkable urinary tests, while others have urinary abnormalities, but disorders of kidney function little or no. After a complete anamnesis and physical examination, urine tests and the chemical composition of serum are essential aids in differentiating the various etiologies of renal disease.
The characteristics of urine, including volume, specific weight, electrolyte composition and sediment (cells, cylinders and crystals), can help define the specific process affecting the kidneys. In this group of posts we will focus on patients with a reduced glomerular filtration rate (RFG) and/ or urine abnormalities.
I'm going to start with the introductions on nitrogenemia, based on the evaluation of the glomerular filtration rate. A reduction in RFG leads to the retention of excretion nitrogen products (nitrogenemia), such as blood urea nitrogen (NUS) and creatinine. Nitrogenemia may be the result of reduced renal infusion, intrinsic kidney disease or a postrenal process (ureteral obstruction). Precise determination of RFG is problematic, since commonly used markers (urea and creatinine) are partially subject to tubular transport.
An ideal endogenous marker for RFG should be produced at a constant rate, freely filtered at the level of the glomerum, unbound by protein and excreted without tubular changes (without reabsorption, secretion or catabolism). NUS varies directly with protein intake, and urea is easily resorbed by the collector tube in the medullary. The permeability of the tube to urea is linked to water reabsorption, it is low in diuresis conditions and low levels of vasopressin aginin (AVP), but is increased under conditions of low intravascular volume, a low rate of tubular fluid flow and increased levels of AVP.
Gastrointestinal bleeding, glucocorticoids and tetracycline may also increase NUS, while low levels may be seen in patients with malnutrition and muscle depletion occurring in starvation or chronic liver disease. Urea clearance is generally an underestimation of RFG due to tubular urea resorption and can only be half of RFG measured by other techniques. Creatinine is a small, freely filtered solvent, whose production varies little from day to day (since it is derived from the metabolism of muscle creatinine).
However, serum creatinine can increase acutely through the ingestion of cooked meat. Creatinine can be secreted by the proximal tube on the path of an organic cation, which is saturable and can be blocked by some commonly used drugs including cimetidine, trimetoprim, pyrimethamine and dapsone.
The secreted component of creatinine alters RFG measurements, as it may vary in an individual over time, moreover, the proportion of secreted creatinine increases as RFG decreases. Extrarenal clearance of creatinine through gastrointestinal metabolism using bacterial flora may affect RFG measurements when RFG is reduced. Most serum creatinine autoanalyzers avoid contributions from non-creating chromogenics, but high levels of bilirubin can cause falselow levels of creatinine. Despite these shortcomings, creatinine clearance remains the most common clinical measure of RFG.
Progressive loss of muscle tissue due to chronic disease, glucocorticoids and malnutrition may mask significant changes in RFG through small or imperceptible changes in serum creatinine. Higher accuracy determinations of RFG are available using inulin clearance or radioisotope markers such as I125 (iotalamat) or Cr51 ethylendiaminatetraacetic acid (EDTA).
With regard to the approach of the nitrogen patient, once it has been established that RFG is reduced, the doctor must decide whether it represents an acute or chronic renal failure. Clinical condition, history and laboratory data often make this distinction easy. Anomalies of laboratory data characteristic of chronic renal failure include anemia, hypocalcemia, hyperphosphatemia and radiographic signs of renal osteodystrophy.
Urinary tests and renal ultrasound may also facilitate differentiation between acute and chronic renal failure. Patients with advanced chronic renal impairment often have some proteinuria, unconcentrated urine (isostenuria) and small kidneys on ultrasound, characterized by increased ecogenicity and cortical thinning.
Treatment should be directed towards slowing the progression of kidney disease and symptomatic improvement of edema, acidosis, anemia and hypophosphatemia. Acute renal failure may be the result of processes affecting renal blood flow (prerenal nitrogenemia), intrinsic kidney diseases (affecting vessels, glomerules or tubules) or postrenal processes (obstruction of urinary flow in the ureters, bladder or urethra).
As for prerenal insufficiency, low renal infusion is responsible for 40-80% of cases of acute renal failure and if treated properly, is easily reversible. Prerenal nitrogen etiologies include any cause of decrease in circulating blood volume, including loss of volume (gastrointestinal haemorrhages, burns, diarrhea, diuretics), volume sequestrations (pancreatitis, peritonitis, rhabdomyolysis) or effectively low circulating volume (cardiogenic shock, septicaemia). Renal infusion may also be adversely affected by reduced cardiac output through peripheral vasodilation (septicemia, medicines) or deep renal vasoconstriction (severe heart failure, hepatorenal syndrome, drugs - e.g. non-steroidal anti-inflammatory or NSAIDs).
True or "effective" hypovolemia leads to a decrease in average arterial pressure, which in turn triggers a number of nerve and hormonal responses that include activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and release of AVP. RFG is maintained by relaxing the related prostaglandin-mediated arterioles and by constricting the efferent arterioles mediated by angiotensin II. Once the average blood pressure drops below 80 mmHg, there is a steep decline in RFG.
Blocking the production of prostaglandins by NSAID may result in severe vasoconstriction and acute renal failure in the presence of hypotension. Angiotensin conversion enzyme (ECA) inhibitors decrease the tone of efferent arterioles and thus reduce infusion pressure in glomerular capillaries.
Patients receiving NSAID and/ or ACE inhibitors are most likely to develop hemodynamically mediated acute renal failure when blood volume is low. Patients with renal artery stenosis are dependent on the vasoconstriction of efferent arteriole in order to maintain the pressure of glomerular filtration and are particularly susceptible to a precipitated decline in RFG when given ACE inhibitors. Prolonged renal hypoperfusion can lead to acute tubular necrosis (NAT), an intrinsic renal disease.
Urinary analyses and urinary electrolytes can be useful in distinguishing prerenal nitrogenemia from NTA. In prerenal insufficiency the tubes are intact, leading to the formation of concentrated urine, avid sodium retention and fractional sodium excretion, and a plasma creatinine/creatinine ratio greater than 40. Urinary sediment in prerenal insufficiency is usually normal or has hyalini cylinders and occasional granulars, while the NTA sediment is usually full of cellular detritus and dark brown granular cylinders.
Let's "talk" now about intrinsic kidney disease! When prerenal and postrenal nitrogenemia have been excluded as etiologies of renal failure, intrinsic parenchymal renal disease is present. Intrinsic renal disease can come from processes involving large renal vessels, microvascularization and glomerules or tubular interstitial. Ischemic and toxic NTA is responsible for about 90% of intrinsic acute renal failure. Clinical picture and urinary analyses are helpful in separating possible etiologies of intrinsic acute renal failure.
Prerenal nitrogenemia and NTA are part of the renal hypoperfusion spectrum: signs of structural tubular injury are present in THE NTA, while prerenal nitrogenemia is promptly reversible after the restoration of an adequate renal infusion. Thus, NTA can often be distinguished from prerenal nitrogenemia by analysis of urine and electrolyte composition of urine.
Ischemic NTA is most commonly observed in patients who have undergone major surgery, trauma, severe hypovolemia, overwhelming septicaemia or extensive burns. Nephrotoxic NTA complicates the administration of many common medicines, usually by inducing a combination of intrarenal vasoconstriction, direct tubular toxicity and/ or tubular obstruction. The kidney is vulnerable to toxic injuries due to its rich vascularity (25% of cardiac output) and its ability to concentrate and metabolize toxins.
A careful search of hypotension and nephrotoxins will usually reveal the specific etiology of NTA. Processes involving tubus and interstitial can lead to acute renal failure. These include drug-induced interstitial nephritis (especially antibiotics, NSAIDs and diuretics), severe infections (both bacterial and viral), systemic diseases (such as systemic lupus erythematosus) or infiltrating diseases (such as sarcoidosis, lymphomas or leukaemia).
Urinary tests usually show mild or moderate proteinuria, hematuria and piuria and occasionally leukocyte cylinders. The presence of erythrocyte cylinders has been described in interstitial nephritis, but it should guide the search for glomerular disease. Finding eosinophils in urine is suggestive for allergic interstitial nephritis or atheroemboli. Occlusion of large renal arteries and veins is an unusual cause of acute renal failure. A significant reduction in RFG through this mechanism suggests bilateral processes or a unilateral process in a patient with a single functional kidney.
Kidney arteries may be obstructed by atheroemboli, thromboembolisms, thromboses in situ, dissection of the aorta or vasculitis. Atheroembolic renal failure may occur spontaneously, but most often it is associated with recent surgical maneuvers on the aorta. Embols are high in cholesterol and are implemented in the middle and small renal arteries, leading to an inflammatory reaction rich in eosinophils. Urinary analyses in acute atheroembolic renal failure are usually normal, but may contain eosinophils and cylinders.
Diagnosis can be confirmed by renal biopsy, but often this is not necessary when other stigmas of atheroembolism (livedo reticularis, peripheral distal infarctions, eosinophilia) are present. Renal artery thrombosis can lead to mild proteinuria and hematuria, while renal vein thrombosis usually induces intense proteinuria and hematuria (these vascular catastrophes often require angiography for confirmation). Diseases of glomerules (glomerulonephritis or vasculitis) and renal microvascularization (hemolytic uremic syndrome, thrombocytopenic purpura or malignant hypertension) usually occur with various manifestations of glomerular injury: proteinuria, hematuria, low RFG and alterations in sodium excretion leading to hypertension, edema and circulatory congestion (acute nephritis syndrome).
These characteristics may occur as primary kidney disease or as renal manifestations of a systemic disease. Finding erythrocytic cylinders in urine is an indication for immediate renal biopsy, since the pathological paternal has important applications in diagnosis, prognosis and treatment. Hematuria without erythrocytic cylinders can also be an indicator of glomerular disease.
That's it for today! Tomorrow I'll continue "discussing" postrenal nitrogenemia. But I'm still going to run to the sea with my family tomorrow and stop postings until July 7. Anyway, I'm going to recover because I want to finish the signs of disease as soon as possible.
Patients with kidney disease may present themselves to the doctor in different ways, depending on the nature of the disease and the time of presentation. Some patients with advanced renal disease may have signs and symptoms of uremia with unremarkable urinary tests, while others have urinary abnormalities, but disorders of kidney function little or no. After a complete anamnesis and physical examination, urine tests and the chemical composition of serum are essential aids in differentiating the various etiologies of renal disease.
The characteristics of urine, including volume, specific weight, electrolyte composition and sediment (cells, cylinders and crystals), can help define the specific process affecting the kidneys. In this group of posts we will focus on patients with a reduced glomerular filtration rate (RFG) and/ or urine abnormalities.
I'm going to start with the introductions on nitrogenemia, based on the evaluation of the glomerular filtration rate. A reduction in RFG leads to the retention of excretion nitrogen products (nitrogenemia), such as blood urea nitrogen (NUS) and creatinine. Nitrogenemia may be the result of reduced renal infusion, intrinsic kidney disease or a postrenal process (ureteral obstruction). Precise determination of RFG is problematic, since commonly used markers (urea and creatinine) are partially subject to tubular transport.
An ideal endogenous marker for RFG should be produced at a constant rate, freely filtered at the level of the glomerum, unbound by protein and excreted without tubular changes (without reabsorption, secretion or catabolism). NUS varies directly with protein intake, and urea is easily resorbed by the collector tube in the medullary. The permeability of the tube to urea is linked to water reabsorption, it is low in diuresis conditions and low levels of vasopressin aginin (AVP), but is increased under conditions of low intravascular volume, a low rate of tubular fluid flow and increased levels of AVP.
Gastrointestinal bleeding, glucocorticoids and tetracycline may also increase NUS, while low levels may be seen in patients with malnutrition and muscle depletion occurring in starvation or chronic liver disease. Urea clearance is generally an underestimation of RFG due to tubular urea resorption and can only be half of RFG measured by other techniques. Creatinine is a small, freely filtered solvent, whose production varies little from day to day (since it is derived from the metabolism of muscle creatinine).
However, serum creatinine can increase acutely through the ingestion of cooked meat. Creatinine can be secreted by the proximal tube on the path of an organic cation, which is saturable and can be blocked by some commonly used drugs including cimetidine, trimetoprim, pyrimethamine and dapsone.
The secreted component of creatinine alters RFG measurements, as it may vary in an individual over time, moreover, the proportion of secreted creatinine increases as RFG decreases. Extrarenal clearance of creatinine through gastrointestinal metabolism using bacterial flora may affect RFG measurements when RFG is reduced. Most serum creatinine autoanalyzers avoid contributions from non-creating chromogenics, but high levels of bilirubin can cause falselow levels of creatinine. Despite these shortcomings, creatinine clearance remains the most common clinical measure of RFG.
Progressive loss of muscle tissue due to chronic disease, glucocorticoids and malnutrition may mask significant changes in RFG through small or imperceptible changes in serum creatinine. Higher accuracy determinations of RFG are available using inulin clearance or radioisotope markers such as I125 (iotalamat) or Cr51 ethylendiaminatetraacetic acid (EDTA).
With regard to the approach of the nitrogen patient, once it has been established that RFG is reduced, the doctor must decide whether it represents an acute or chronic renal failure. Clinical condition, history and laboratory data often make this distinction easy. Anomalies of laboratory data characteristic of chronic renal failure include anemia, hypocalcemia, hyperphosphatemia and radiographic signs of renal osteodystrophy.
Urinary tests and renal ultrasound may also facilitate differentiation between acute and chronic renal failure. Patients with advanced chronic renal impairment often have some proteinuria, unconcentrated urine (isostenuria) and small kidneys on ultrasound, characterized by increased ecogenicity and cortical thinning.
Treatment should be directed towards slowing the progression of kidney disease and symptomatic improvement of edema, acidosis, anemia and hypophosphatemia. Acute renal failure may be the result of processes affecting renal blood flow (prerenal nitrogenemia), intrinsic kidney diseases (affecting vessels, glomerules or tubules) or postrenal processes (obstruction of urinary flow in the ureters, bladder or urethra).
As for prerenal insufficiency, low renal infusion is responsible for 40-80% of cases of acute renal failure and if treated properly, is easily reversible. Prerenal nitrogen etiologies include any cause of decrease in circulating blood volume, including loss of volume (gastrointestinal haemorrhages, burns, diarrhea, diuretics), volume sequestrations (pancreatitis, peritonitis, rhabdomyolysis) or effectively low circulating volume (cardiogenic shock, septicaemia). Renal infusion may also be adversely affected by reduced cardiac output through peripheral vasodilation (septicemia, medicines) or deep renal vasoconstriction (severe heart failure, hepatorenal syndrome, drugs - e.g. non-steroidal anti-inflammatory or NSAIDs).
True or "effective" hypovolemia leads to a decrease in average arterial pressure, which in turn triggers a number of nerve and hormonal responses that include activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and release of AVP. RFG is maintained by relaxing the related prostaglandin-mediated arterioles and by constricting the efferent arterioles mediated by angiotensin II. Once the average blood pressure drops below 80 mmHg, there is a steep decline in RFG.
Blocking the production of prostaglandins by NSAID may result in severe vasoconstriction and acute renal failure in the presence of hypotension. Angiotensin conversion enzyme (ECA) inhibitors decrease the tone of efferent arterioles and thus reduce infusion pressure in glomerular capillaries.
Patients receiving NSAID and/ or ACE inhibitors are most likely to develop hemodynamically mediated acute renal failure when blood volume is low. Patients with renal artery stenosis are dependent on the vasoconstriction of efferent arteriole in order to maintain the pressure of glomerular filtration and are particularly susceptible to a precipitated decline in RFG when given ACE inhibitors. Prolonged renal hypoperfusion can lead to acute tubular necrosis (NAT), an intrinsic renal disease.
Urinary analyses and urinary electrolytes can be useful in distinguishing prerenal nitrogenemia from NTA. In prerenal insufficiency the tubes are intact, leading to the formation of concentrated urine, avid sodium retention and fractional sodium excretion, and a plasma creatinine/creatinine ratio greater than 40. Urinary sediment in prerenal insufficiency is usually normal or has hyalini cylinders and occasional granulars, while the NTA sediment is usually full of cellular detritus and dark brown granular cylinders.
Let's "talk" now about intrinsic kidney disease! When prerenal and postrenal nitrogenemia have been excluded as etiologies of renal failure, intrinsic parenchymal renal disease is present. Intrinsic renal disease can come from processes involving large renal vessels, microvascularization and glomerules or tubular interstitial. Ischemic and toxic NTA is responsible for about 90% of intrinsic acute renal failure. Clinical picture and urinary analyses are helpful in separating possible etiologies of intrinsic acute renal failure.
Prerenal nitrogenemia and NTA are part of the renal hypoperfusion spectrum: signs of structural tubular injury are present in THE NTA, while prerenal nitrogenemia is promptly reversible after the restoration of an adequate renal infusion. Thus, NTA can often be distinguished from prerenal nitrogenemia by analysis of urine and electrolyte composition of urine.
Ischemic NTA is most commonly observed in patients who have undergone major surgery, trauma, severe hypovolemia, overwhelming septicaemia or extensive burns. Nephrotoxic NTA complicates the administration of many common medicines, usually by inducing a combination of intrarenal vasoconstriction, direct tubular toxicity and/ or tubular obstruction. The kidney is vulnerable to toxic injuries due to its rich vascularity (25% of cardiac output) and its ability to concentrate and metabolize toxins.
A careful search of hypotension and nephrotoxins will usually reveal the specific etiology of NTA. Processes involving tubus and interstitial can lead to acute renal failure. These include drug-induced interstitial nephritis (especially antibiotics, NSAIDs and diuretics), severe infections (both bacterial and viral), systemic diseases (such as systemic lupus erythematosus) or infiltrating diseases (such as sarcoidosis, lymphomas or leukaemia).
Urinary tests usually show mild or moderate proteinuria, hematuria and piuria and occasionally leukocyte cylinders. The presence of erythrocyte cylinders has been described in interstitial nephritis, but it should guide the search for glomerular disease. Finding eosinophils in urine is suggestive for allergic interstitial nephritis or atheroemboli. Occlusion of large renal arteries and veins is an unusual cause of acute renal failure. A significant reduction in RFG through this mechanism suggests bilateral processes or a unilateral process in a patient with a single functional kidney.
Kidney arteries may be obstructed by atheroemboli, thromboembolisms, thromboses in situ, dissection of the aorta or vasculitis. Atheroembolic renal failure may occur spontaneously, but most often it is associated with recent surgical maneuvers on the aorta. Embols are high in cholesterol and are implemented in the middle and small renal arteries, leading to an inflammatory reaction rich in eosinophils. Urinary analyses in acute atheroembolic renal failure are usually normal, but may contain eosinophils and cylinders.
Diagnosis can be confirmed by renal biopsy, but often this is not necessary when other stigmas of atheroembolism (livedo reticularis, peripheral distal infarctions, eosinophilia) are present. Renal artery thrombosis can lead to mild proteinuria and hematuria, while renal vein thrombosis usually induces intense proteinuria and hematuria (these vascular catastrophes often require angiography for confirmation). Diseases of glomerules (glomerulonephritis or vasculitis) and renal microvascularization (hemolytic uremic syndrome, thrombocytopenic purpura or malignant hypertension) usually occur with various manifestations of glomerular injury: proteinuria, hematuria, low RFG and alterations in sodium excretion leading to hypertension, edema and circulatory congestion (acute nephritis syndrome).
These characteristics may occur as primary kidney disease or as renal manifestations of a systemic disease. Finding erythrocytic cylinders in urine is an indication for immediate renal biopsy, since the pathological paternal has important applications in diagnosis, prognosis and treatment. Hematuria without erythrocytic cylinders can also be an indicator of glomerular disease.
That's it for today! Tomorrow I'll continue "discussing" postrenal nitrogenemia. But I'm still going to run to the sea with my family tomorrow and stop postings until July 7. Anyway, I'm going to recover because I want to finish the signs of disease as soon as possible.
Have a wonderful weekend
(and I "along" with you) and, don't forget understanding, love
and gratitude!
Dorin, Merticaru