Nephrology Introduction (Systematic Pathology II) PDF

Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II NEPHROLOGY INTRODUCTION 1. Notes of kidney’s anatomy -The image displays the distinct vascular pattern of the organ, along with its internal struct...

Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II NEPHROLOGY INTRODUCTION 1. Notes of kidney’s anatomy -The image displays the distinct vascular pattern of the organ, along with its internal structure comprising the renal cortex and medulla. -In the picture it’s visible the descending aorta and inferior vena cava, and then ureters. -The constitution of the kidney, following the functional course, is made by in series minor calyx, renal sinus, interlobular vein, renal pyramid and so on.. 1 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II -The most important site of the kidney is the cortex, and this is an important area for nephropathies that will concern next lessons. Specifically, a very important area is the glomerulus, followed by proximal tubule and distal tubule. -Another important aspect is the position of the kidney in the human body; the right kidney is under the liver, and it’s an important aspect that explains why renal biopsy is performed in the left kidney (that is positioned lower with respect to the right kidney). -Important is the constitution of the fat external to the kidney, with a perineal fat,renal fascia, pararenal fat that have relevance in the procedure of kidney biopsy. -And then this picture shows the path of urine from the glomerulus, then it drains in 1. Minor calyx, 2. Major calyx, 3. Renal pelvis 4. Urinary bladder. 2 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II -In kidney surgery, a crucial consideration is the vascularization, as it's common to encounter multiple arteries supplying the kidney. Here, we observe the primary renal artery, an aberrant artery, and a significant artery crucial for transplant procedures involving living donors, known as the accessory artery. -In the picture below it’s visible the structure of glomerulus, it’s important that it receives the blood by afferent arteriole and outflow with efferent arteriole. It’s encircled by Bowman’s capsule and after there is the structure of the tubular system, to produce the urine that goes towards the ureter. -The glomerulus is present here with efferent arteriole and afferent arteriole, and the right slide shows glomerulus in biopsy. 3 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II -The renal corpuscle is constituted by glomerulus capillaries, that are sites of several nephropathy. We can also see Bowman’s space, proximal tubule and distal convoluted tubular, with the presence of macula densa on the left, next to the mesangium-extraglomerular cell. -In this biopsy it’s clearly visible in Bowman's space, Ductal Collector Tubules (DCT), Proximal Collector Tubules (PCT). -This is another section of the constitution of glomerulus. In representation from the top it’s visible the distal convoluted tubule, juxtaglomerular cells, afferent and efferent arteriole, and the glomerulus. 4 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II -Within the glomerulus, there are podocytes located in the visceral layer, and the glomerular capsule is also present internally. 2. Function of kidney -The renal artery serves as the point of entry for blood, waste, and water into the kidney. -The renal vein carries filtered blood, acting as the pathway for the removal of excess water. -Subsequently, the ureters serves as the passage for expelling excess water and toxic waste in the form of urine. -The crucial role of the vein lies in maintaining the balance between hemodynamics and oxygenation to preserve renal function. Various conditions such as hypovolemia, diarrhea, hepatorenal syndrome, and cardiac issues are linked to disruptions in this relationship. -Hemodynamic reach extends to a lower level in the medulla, but higher levels are essential for oxygenating the cortical kidney. Simultaneously, various partial pressures of oxygen play a significant role. These pathophysiological aspects justify the occurrence of several problems observed afterward. 5 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II SEMEIOTICS IN NEPHROLOGY -During a medical examination, it is crucial to gather information on both family medical history (including hereditary nephropathies, cancer, diabetes, and hypertension) and the patient's personal medical history. -For pediatric cases, evaluating ureteral vesical reflux is important, while in adults, considerations include analyzing the work environment, drug abuse, dietary habits, diuresis patterns, infections, headaches, visual disturbances (indicative of hypertension), and symptoms like vomiting, nausea, and pruritus (suggestive of chronic renal disease). -Diuresis can manifest as 1. Polyuria, found in conditions like diabetes, diabetes insipidus, and pyelonephritis, 2. Oliguria in the presence of hypovolemia, nephrotic syndrome, acute renal failure, and chronic renal disease. 3. Anuria and urinary retention are also conditions related to diuresis. 4. Dysuria, characterized by urinary burning, strangury causing urinary pain, pollakiuria indicating repeated urination, nocturia associated with nighttime urination, and vesical tenesmus linked to bladder pressure are additional conditions connected to diuresis. 1.Urinalysis The final aspect to consider is the urine's characteristics. “Urinalysis is a test that examines the visual, chemical and microscopic aspect of your urine.” Healthcare providers often use urinalysis to screen for or monitor certain common health conditions, such as liver disease, kidney disease and diabetes, and to diagnose urinary tract infections. Urinalysis examine urine sample for the following broad aspects: Color and appearance. Normal urine color is usually some shade of yellow and can range from colorless or pale yellow to deep amber, depending on how concentrated or diluted. Many things can affect the color of urine, including certain medications and supplements and certain foods you eat, such as beets. However, an unusual urine color can also be a sign of diease, indicating several different medical conditions, including: Dehydration Kidney stones STIs Urinary tract infection Diabetes 6 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II Chemical findings: Protein urine test: Higher-than-normal urine protein levels may indicate several different health conditions, such as heart failure, kidney issues and dehydration Urine pH level test: A urine pH test measures the acid-base (pH) level in urine. A high urine pH may indicate conditions including kidney issues and UTI. A low urine pH may indicate conditions including diabetes-related ketoacidosis and diarrhea. Ketones urine test: Ketones build up when body has to break down fats and fatty acid to use as fuel for energy. This is most likely to happen if your body does not get enough sugar or carbohydrates as fuel. Healthcare providers most often use ketone urine tests to check for diabetes-related ketoacidosis. Glucose urine test: Under regular circumstances, there shouldn’t be glucose in urine, so the presence of glucose could be a sign of diabetes or gestational diabetes. Bilirubine urine test: if there is bilirubin in your urine, it may indicate liver or bile duct issues. Nitrite urine test: A positive nitrite test result can indicate a UTI. However, not all bacteria are capable of converting nitrate (a substance that’s normally in urine) to nitrite, so you can still have a UTI despite a negative nitrite test. Leukocyte esterase urine test: Leukocyte esterase is an enzyme that’s present in most white blood cells. When this test is positive, it may indicate that there’s inflammation in the urinary tract or kidneys. The most common cause for white blood cells in urine is a bacterial urinary tract infection (UTIs). Urine specific gravity test: A specific gravity test shows the concentration of all chemical particles in urine. Abnormal results may indicate several different health condition 7 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II Also microscopic findings are a very important part of the test to detect presence of pathological conditions of kidneys, such as described on slide. Test related to are: Red blood cell (RBC) urine test: An elevated number of RBCs indicates that there’s blood in urine; however, this test can’t identify where the blood is coming from. For example, contamination with blood from hemorrhoids or vaginal bleeding can’t be distinguished from a bleed somewhere in the urinary system. In some cases, higher than normal levels of red blood cells in your urine may indicate bladder, kidney or urinary tract issues. WBC urine test: An increased number of WBCs and/or a positive test for leukocyte esterase may indicate an infection or inflammation somewhere in the urinary tract. Epithelial cells: Epithelial cells are cells that form the covering on all internal and external surfaces of your body and line body cavities and hollow organs. Urinary tract is lined with epithelial cells. It’s normal to have some epithelial cells in your urine, but elevated numbers of epithelial cells may indicate infection, inflammation and/or cancer in urinary tract Bacteria, yeast and parasites: Sometimes, bacteria can enter the urethra and urinary tract, causing an urinary tract infection. The urine sample can also become contaminated with bacteria, yeast and parasites, especially for people with a vagina. Yeast can contaminate the sample for people who have a vaginal yeast infection. Trichomonas vaginalis is a parasite that may also be found in the urine of people who have a vagina. It’s the cause of a STD called trichomoniasis. Urinary casts: Casts are tiny tube-like particles that can sometimes be in urine. They’re formed form protein released by your kidney cells. Certain types of casts may indicate kidney issues, while others are completely normal. 8 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II ACUTE KIDNEY INJURY 1.Definition The definition of ARF (Acute Renal Failure=Acute kidney injury) is: “clinical syndrome denoted by decline in GFR” (glomerular filtration rate) -with reduced excretion of nitrogenous waste (urea and creatinine). -other uremic toxins. 2.Renal function measurement For the measure of renal function, GFR, an important indicator is the level of creatinine serum, but this level has some problems. Problems are: 1. SCr does not accurately reflect the GFR in non steady state 2. Creatinine is removed by dialysis 3. studies and clinical trials have used different cut-off values 3. Attempt of definition In the context of acute kidney injury, the challenge lies in defining specific criteria to address the issue. In 2004, an international team initiated this effort, forming the Acute Dialysis Quality Initiative (ADQI). They introduced the Rifle Criteria as the initial framework to characterize and understand the condition. 9 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II 4.Rifle criteria On the left side, there's a scale indicating escalating kidney damage: Risk, Injury, Failure, Loss, ESRD. On the right, we assess the presence of urine in patients with both high sensitivity and specificity. These factors not only characterize kidney damage but also signify the progression toward more severe impairment. 10 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II 5.Limitations of Rifle Criteria The Rifle Criteria for acute renal failure have limitations, because they need baseline creatinine serum (SCr), involve a complex determination of urine output (UOP), and are often not used in clinical situations. 6. Akin group’s work Some years ago, the next step involved defining a new method for describing acute kidney injuries. The group introduced an alternative approach, outlining parameters such as Acute Renal Failure (ARF) and a rapid decline in Glomerular Filtration Rate (GFR). 11 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II Diagnostic criteria of this group, called AKIN, was “an abrupt within 48 h reduction in kidney function currently defined by any of the following”: 1. Absolute increase in serum creatinine of either 0.3 mg/dl; 2. A percentage increase in SCr of 50% or more; 3. A reduction in UOP. The classification of AKI: Non oliguria, in which urine output >400 ml/24 hr Oliguria, in which urine output 1A, treatment involves vasoconstrictors and albumin. Terlipressin can be administered by IV boluses or by continuous IV infusion. In case of nonresponse after 2 days, the dose of terlipressin should be increased in a stepwise fashion to a maximum of 12 mg/day. Other therapy is albumin solution that should be used at 20-40 g/day. A serial assessment of central blood volume aids in titrating the dose. Noradrenaline can be an alternative to terlipressin. Other drugs are midodrine+octreotide that can be an option when terlipressin or noradrenaline are unavailable. 16 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II Non pharmacological treatment—>Liver Transplantation Definition of AKI in Hepatorenal Syndrome present Major Criteria: 1. Low glomerular filtration; 2. Absence of shock; 3. No sustained improvement in renal function; 4. Proteinuria lower than 500 mg/day. Additional criteria are: 1. Urine volume lower than 500 ml/day 2. Urine sodium lower than 10 mEq/liter 3. Urine osmolality greater than plasma osmolality 4. Urine red blood cells less than 50 per high power field 5. Serum sodium concentration lower than 130 mEq/ liter Additional criteria are also perfectly listed, but remember that only major criteria are necessary for diagnosis of hepatorenal syndrome. 17 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II In the presence of cirrhosis, sinusoidal portal hypertension occurs. This is linked to splanchnic vasodilation, arterial underfilling, and subsequent activation of systemic vasoconstrictor factors through baroreceptor mediation. This process leads to increased intrarenal vasoconstrictor factors and reduced renal vasodilator factors, ultimately causing renal vasoconstriction and, consequently, hepatorenal syndrome. 1. Liver transplantation in HRS The indications for liver transplantation vary for both candidates and non-candidates. For non-candidate patients, the recommended approach involves the use of vasoconstrictors along with albumin. If there is no response, renal replacement therapy may be considered in selected cases. In the case of candidate patients, high priority for liver transplantation is indicated. However, when vasoconstrictors and albumin are employed, two scenarios should be considered: ○ If there is no response, renal replacement therapy may be contemplated; ○ If there is a response, the treatment should be stopped either after achieving a complete response or within a maximum period of 14 days. 18 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II This is last slide was not explained PLANNING OF THE COURSE 19 Roberto Rutigliano - Revisione: Valentina Conforto Prof. De Paolis- 5/03/2024 (10:50-11:40) Systematic pathology II 20