[08.09] Diseases of the Tubules, Interstitium and Blood Vessels (TG09-CG05) (V2).pdf

Diseases of the Tubules, Interstitium and Blood Vessels Module 08: Renal, GU and Gynecologic Pathologies Alan T. Koa, MD | February 07, 2024 TABLE OF CONTENTS PATTERNS OF ACUTE TUBULAR INJURY I. DISEASES AFFECTING THE TUBULES AND INTERSTITIUM................... 1 A. ACUTE TUBULAR INJURY (ATI)..........

Diseases of the Tubules, Interstitium and Blood Vessels Module 08: Renal, GU and Gynecologic Pathologies Alan T. Koa, MD | February 07, 2024 TABLE OF CONTENTS PATTERNS OF ACUTE TUBULAR INJURY I. DISEASES AFFECTING THE TUBULES AND INTERSTITIUM................... 1 A. ACUTE TUBULAR INJURY (ATI)......................................................1 B. TUBULOINTERSTITIAL NEPHRITIS................................................ 2 C. PYELONEPHRITIS......................................................................... 3 D. TUBULOINTERSTITIAL NEPHRITIS INDUCED BY DRUGS AND TOXINS............................................................................................. 5 II. DISEASES OF THE BLOOD VESSELS: NEPHROSCLEROSIS.................... 6 A. PATHOGENESIS.............................................................................6 B. BENIGN NEPHROSCLEROSIS......................................................... 6 C. MALIGNANT NEPHROSCLEROSIS................................................. 6 QUESTIONS......................................................................................... 7 ANSWER KEY.......................................................................................8 RATIONALE..........................................................................................8 Ischemic ATI LEARNING OBJECTIVES 1. Discuss the pathogenesis, morphology, and clinical findings of diseases affecting the tubules and interstitium 2. Discuss the pathogenesis and morphology of nephrosclerosis I. DISEASES AFFECTING THE TUBULES AND INTERSTITIUM A. ACUTE TUBULAR INJURY (ATI) Formerly called as acute tubular necrosis A reversible condition A clinicopathologic entity characterized by the following: ○ Morphologically: destruction of tubular epithelial cells ○ Clinically: acute diminution or loss of renal function Most common cause of acute kidney injury (AKI) ○ Accounts for 50% of AKI in hospitalized patients CAUSES Ischemic ATI Due to decreased or interrupted blood flow ○ E.g. diffuse involvement of the intrarenal blood vessels such as in: ▸ Microscopic polyangiitis ▸ Malignant hypertension ▸ Microangiopathies ▸ Systemic conditions associated with thrombosis, such as: – Hemolytic uremic syndrome (HUS) – Thrombotic thrombocytopenic purpura (TTP) – Disseminated intravascular coagulation (DIC) Direct Toxic Injury to the Tubules May be caused by endogenous agents: ○ Myoglobin ○ Hemoglobin ○ Monoclonal light chains ○ Bile or bilirubin May also be due to exogenous agents: ○ Drugs (e.g., gentamicin) ○ Radiocontrast dyes or contrast agents ○ Poisons: heavy metals (e.g,. mercury) ○ Organic solvents (e.g., carbon tetrachloride) YL6:08.09 Inadequate blood flow accompanied by shock and hypotension Nephrotoxic ATI Caused by: ○ Drugs (e.g., gentamicin) ○ Radiographic contrast agents ○ Poisons, including: ▸ Heavy metals (e.g., mercury) ▸ Organic solvents (e.g., carbon tetrachloride) Combination of Ischemic and Nephrotoxic ATI Can also occur Exemplified by the following: ○ Mismatched blood transfusions and other hemolytic crises causing hemoglobinuria ○ Skeletal muscle injuries causing myoglobinuria Injuries result in characteristic intratubular hemoglobin or myoglobin casts The toxic iron content of these globin molecules contributes to the ATI PATHOGENESIS The critical events in both ischemic and nephrotoxic ATI are: ○ Tubular injury ○ Persistent and severe disturbances in blood flow The patchiness of tubular necrosis and maintenance of the integrity of the basement membrane along many segments allow: ○ Repair of the injured foci and recovery of function if the precipitating cause is removed ○ Hence, ATI is a reversible condition Tubular Cell Injury Tubular epithelial cells, especially those of the proximal tubules, are sensitive to ischemia and vulnerable to toxins Several factors that predispose tubules to toxic injury: ○ An increased surface area for tubular reabsorption ○ Active transport systems for ions and organic acids ○ A high rate of metabolism and oxygen consumption required to perform transport and reabsorption functions ○ Capability for resorption and concentration of toxins Ischemia causes numerous structural and functional alterations in epithelial cells Disturbances in Blood Flow Intrarenal vasoconstriction results in reduced glomerular blood flow and reduced oxygen delivery to the functionally important tubules in the outer medulla MORPHOLOGY Focal tubular epithelial injury Tubulorrhexis: rupture of the basement membrane (BM) Because of epithelial injury, there might be occlusion of tubular lumens by casts formed by denudation of the injured tubular epithelial cells Interstitium shows edema and accumulation of leukocytes within the vasa recta TG09: Choudhry, Cu, Jamisola, Sanota, Simbulan, So, Tagulob, Umil, Urrutia, Velasco, Yu CG05: Artillaga, Avila, Cheng, Escalante, Lim, Marcos, Palencia, Quimson, Remitio, Salvador, Sandoval 1 Figure 3 Tubules with: ○ Low epithelial lining ○ Single cell drop-out and necrosis ○ Cellular debris in the lumen ○ Regenerative changes such as mitotic figures and nucleomegaly (yellow arrows) Figure 1. Acute tubular injury Figure 1 Note that the tubules have simplified lining epithelium (flattened) and some epithelial cells are detached from the tubular epithelial basement membrane Also note the degenerated epithelial cells in the lumen of several tubules (yellow arrows) Figure 4. Acute tubular injury Figure 4 Tubular vacuolization and dilation secondary to ethylene glycol poisoning (violet arrows) Take Note! ATI resulting from toxins usually has diffuse tubular involvement ATI resulting from ischemia (i.e., profound hypotension from cardiac failure) has patchy tubular involvement B. TUBULOINTERSTITIAL NEPHRITIS Figure 2. Acute tubular injury Figure 2 Note the dilated tubules with flattening of lining epithelium Some of the tubular epithelial cells are detached and degenerated, which are now seen in the lumen of several tubules (encircled) Evidence of epithelial regeneration in the form of flattened epithelial cells with hyperchromatic nuclei and mitotic figures is present This group of renal diseases involves inflammatory injuries of the tubules and interstitium that are often insidious in onset Principally manifested by azotemia Tubulointerstitial nephritis (TN) may be acute or chronic ACUTE TUBULOINTERSTITIAL NEPHRITIS Rapid clinical onset Histologically characterized by: ○ Interstitial edema ○ Leukocytic infiltration of interstitium and tubules ○ Tubular injury CHRONIC TUBULOINTERSTITIAL NEPHRITIS Characterized by: ○ Infiltration with mononuclear leukocytes ○ Prominent interstitial fibrosis ○ Widespread tubular atrophy Take Note! In chronic tubulointerstitial nephritis, there is: ○ Interstitial fibrosis ○ Tubular atrophy Unlike in acute tubulointerstitial nephritis where there is: ○ Interstitial edema SECONDARY TUBULOINTERSTITIAL NEPHRITIS Figure 3. Acute tubular injury YL6:08.09 Diseases of the Tubules, Interstitium and Blood Vessels Present in a variety, which may also contribute to progressive damage: ○ Vascular ○ Cystic (polycystic kidney disease) ○ Metabolic (diabetes) renal disorders 2 Table 1. Causes of tubulointerstitial nephritis Infections Acute bacterial pyelonephritis Chronic pyelonephritis (including reflux nephropathy) Other infections (e.g., viruses, parasites) Toxins Drugs Acute-hypersensitivity interstitial nephritis Analgesics Heavy metals Lead, cadmium ○ Through the bloodstream (hematogenous infection) ▸ Results from bacteremic spread ○ From the lower urinary tract (ascending infection) ▸ Most common cause of clinical pyelonephritis ▸ Results from a combination of: – Urinary bladder infection – Vesicoureteral reflux – Intrarenal reflux Metabolic Diseases Urate nephropathy Nephrocalcinosis (hypercalcemic nephropathy) Oxalate nephropathy Immunologic Reactions Transplant rejection Sjögren syndrome Sarcoidosis Vascular Diseases Miscellaneous Nephronopthisis “Idiopathic” interstitial nephritis Take Note! The table above was reorganized and is based on Table 20.8 found in Robbins Dr. Koa emphasized the causes of tubulointerstitial nephritis (the headers) and discussed “chronic pyelonephritis” and “acute hypersensitivity interstitial nephritis” in detail Take Note! Tubulointerstitial disorders are distinguished clinically from glomerular diseases by the following hallmarks: ○ Absence of nephritic or nephrotic syndrome ○ Presence of defects in tubular function ▸ May be subtle ▸ May include: – Impaired ability to concentrate urine ▪ Polyuria or nocturia – Salt wasting – Diminished ability to excrete acids ▪ Manifested as metabolic acidosis – Isolated defects in tubular reabsorption or secretion C. PYELONEPHRITIS One of the causes of tubulointerstitial nephritis Inflammation affecting the tubules, interstitium, and renal pelvis ○ Acute pyelonephritis ▸ Caused by bacterial infection ▸ The renal lesion associated with urinary tract infection (UTI) ○ Chronic pyelonephritis ▸ Bacterial infection also plays a dominant role ▸ Other factors (e.g. vesicoureteral reflux, obstruction) predispose to repeat episodes of acute pyelonephritis PATHOGENESIS More than 85% of UTIs are caused by gram negative bacilli that are normal inhabitants of the intestinal tract Most common: Escherichia coli ○ Followed by Proteus, Klebsiella, and Enterobacter Streptococcus faecalis, also of enteric origin, staphylococci, and virtually every other bacterial and fungal agent can also cause lower UTI and renal infection Two routes by which the bacteria reach the kidneys: YL6:08.09 Diseases of the Tubules, Interstitium and Blood Vessels Figure 5. Renal infection pathways Figure 5 Normal human bladder and bladder urine are sterile ○ Thus, a number of steps must occur for renal infection to exist Steps include: ○ Colonization of distal urethra and introitus (in women) by coliform bacteria ○ From the urethra to the bladder, organisms gain entrance during urethral catheterization Predisposing Conditions for Microbe Movement to Kidneys Urinary tract obstruction and stasis of urine ○ Outflow obstruction or bladder dysfunction results in incomplete emptying and residual urine ○ In the presence of stasis, bacteria introduced into the bladder can multiply unhindered Vesicoureteral reflux ○ Incompetence of vesicoureteral valve allows bacteria to ascend the ureter into the renal pelvis Intrarenal reflux ○ Vesicoureteral reflux can propel infected bladder urine up to the renal pelvis and deep into the renal parenchyma through open ducts at the tips of the renal papillae ACUTE PYELONEPHRITIS Morphology Acute suppurative inflammation of the kidney Histological hallmarks: ○ Patchy interstitial suppurative inflammation ○ Intratubular aggregates of neutrophils ○ Neutrophilic tubulitis ○ Tubular injury 3 ○ Urine contains many leukocytes derived from the inflammatory infiltrate Diagnosis Quantitative urine culture CHRONIC PYELONEPHRITIS A disorder in which chronic tubulointerstitial inflammation and scarring involve the calyces and pelvis An important cause of kidney destruction in children with severe lower urinary tract abnormalities Morphology Figure 6. Gross acute pyelonephritis Figure 6 The kidneys are irregularly scarred If bilateral, the involvement is asymmetric ○ In contrast, both kidneys in chronic glomerulonephritis are diffusely and symmetrically scarred Coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces, and flattening of the papillae Yellow circle: cortical surface shows grayish-white areas of inflammation and abscess formation Figure 8. Gross chronic pyelonephritis Figure 7. Histology of acute pyelonephritis Figure 7 Acute neutrophilic exudate within the tubules Interstitial inflammation Complications Papillary necrosis ○ Seen in diabetics, sickle cell disease, and in those with urinary tract obstruction Pyonephrosis ○ Seen with total or almost complete obstruction ○ Suppurative exudate is unable to drain and fills the renal pelvis, calyces, and ureter with pus Perinephric abscess ○ Extension of inflammation through renal capsule into perinephric tissue or tissue surrounding the kidney Figure 8 The cortical surface contains many irregular depressed scars (reddish areas) On cut section (right picture): caliectasia (stars) ○ Marked dilatation of the calyces ○ Caused by inflammatory destruction of papillae Atrophy and scarring of the overlying cortex Histology Tubules: Atrophy, hypertrophy, or dilation Dilated tubules with flattened epithelium may be filled with casts resembling thyroid colloid ○ Called thyroidization of the kidney Varying degrees of chronic interstitial inflammation and fibrosis in cortex and medulla Clinical Features Often associated with the following: ○ Urinary tract obstruction ○ Instrumentation (e.g. catheterization) ○ Vesicoureteral reflux ○ Pregnancy ○ Gender and age ○ Pre-existing renal lesions ○ Diabetes mellitus ○ Immunosuppression and immunodeficiency Presents with a sudden onset of pain at the costovertebral angle Fever and malaise ○ Systemic evidence of infection Dysuria, frequency, and urgency ○ Indications of bladder and urethral irritation Pyuria YL6:08.09 Diseases of the Tubules, Interstitium and Blood Vessels 4 ○ Diuretics (e.g. thiazides) ○ NSAIDs ○ Miscellaneous other drugs (e.g. allopurinol, cimetidine, checkpoint inhibitors) Begins 2-40 days after drug exposure Clinical Features Fever Eosinophilia (which may be transient) Rash in about 25% of patients Renal abnormalities (hematuria, mild proteinuria, and leukocyturia) In 50% of cases: a rising serum creatinine or acute kidney injury with oliguria develops Pathogenesis Suggests an immune mechanism ○ Late-phase reaction of an IgE-mediated (Type I) hypersensitivity ▸ Due to the presence of eosinophilia, rash, increased IgE serum levels ○ T cell-mediated (Type IV) delayed-hypersensitivity reaction ▸ Manifested with mononuclear or granulomatous reaction ▸ Positive results of skin tests to drugs Morphology Figure 9. Chronic pyelonephritis Figure 9 Top image ○ Chronic interstitial inflammation Bottom image ○ Thyroidization of the kidney ○ Dilated tubules: with colloid cast material (encircled portions) XANTHOGRANULOMATOUS PYELONEPHRITIS Interstitial edema and infiltration by mononuclear cells (principally lymphocytes and macrophages) Eosinophils and neutrophils may be present Interstitial non-necrotizing granulomas may be seen when tubules rupture Tubulitis is common Normal glomeruli ○ Except in some cases caused by NSAIDs, when minimal change disease and nephrotic syndrome develop concurrently ▸ Recall: minimal change disease may be associated with NSAIDs Inflammation may be more prominent in the medulla ○ Where the inciting agent is more concentrated Rare form of chronic pyelonephritis Characterized by accumulation of: ○ Foamy macrophages ○ Plasma cells ○ Lymphocytes ○ Polymorphonuclear cells (PMNs) ○ Leukocytes ○ Occasional giant cells Associated with Proteus infection and obstruction May produce large and yellowish-orange nodules that can be grossly confused with renal cell carcinoma Clinical Features Silent onset or may present with manifestations of acute recurrent pyelonephritis (i.e. fever, back pain, pyuria, and bacteriuria) D. TUBULOINTERSTITIAL NEPHRITIS INDUCED BY DRUGS AND TOXINS Drug and toxin-induced tubulointerstitial nephritis is the second most common cause of acute kidney injury ○ After pyelonephritis Toxins and drugs can injure kidneys in three ways: ○ Trigger an interstitial immunologic reaction ▸ Exemplified by the acute hypersensitivity nephritis induced by drugs (e.g. methicillin) ○ Cause ATI ○ Cause subclinical but cumulative injury to tubules that takes years to result in chronic kidney disease ▸ Especially worrisome because it may be unrecognized until the renal damage is irreversible ACUTE DRUG-INDUCED INTERSTITIAL NEPHRITIS Most frequently occurs with: ○ Synthetic penicillins (e.g. methicillin, ampicillin) ○ Synthetic antibiotics (e.g. rifampin) YL6:08.09 Diseases of the Tubules, Interstitium and Blood Vessels Figure 10. Morphologic findings of drug-induced acute interstitial nephritis Figure 10 Upper left picture (a): eosinophilic infiltrates in the interstitium Upper right picture (b): tubulitis ○ Marked by the presence of lymphocytes between the tubular epithelial cells (encircled, and pointed by the arrowhead) Lower left picture (c): interstitial fibrosis (pointed by the arrowhead) Lower right picture (d): granuloma (star) ○ May be seen especially when the tubules rupture NEPHROPATHY ASSOCIATED WITH NSAIDS NSAID-associated renal syndromes include the following: ○ Acute kidney injury ▸ Due to the decreased synthesis of vasodilatory prostaglandins and the resultant ischemia 5 ○ Acute hypersensitivity interstitial nephritis ▸ Resulting in renal failure ○ Acute interstitial nephritis and minimal change disease ▸ This association, one leading into renal failure and the other to nephrotic syndrome, suggests a hypersensitivity reaction – Affecting the interstitium and possibly the glomeruli ▸ It is also consistent with injury to podocytes – Mediated by cytokines released as part of the inflammatory process ○ Membranous nephropathy (discussed under the nephrotic syndrome) Active Recall Box 1. T/F: Acute tubular injury is an irreversible condition. 2. Which of the following morphologic changes can be seen in acute tubulointerstitial nephritis? A. Interstitial edema B. Prominent interstitial fibrosis C. Widespread tubular atrophy 3. What is the most common cause of UTI? A. Proteus B. Klebsiella C. Escherichia coli D. Enterobacter 4. In which of the following diseases can thyroidization of the kidneys be seen? A. Acute kidney injury B. Acute pyelonephritis C. Chronic pyelonephritis D. Tubulointerstitial nephritis caused by drugs and toxins 5. What diseases can be grossly confused with renal cell carcinoma? Luminal narrowing of arterioles and small arteries caused by thickening and hyalinization of the walls ○ Termed as hyaline arteriolosclerosis ○ Recall: This has been discussed under blood vessel pathology Fibroelastic hyperplasia ○ Interlobular and arcuate arteries exhibit the following: ▸ Medial hypertrophy ▸ Re-duplication of internal elastic lamina ▸ Increased myofibroblast tissue in the intima ○ These all result in narrowing of the lumen Tubular atrophy and interstitial fibrosis Glomerular alterations which include: ○ Glomerular basal membrane (GBM) collapse ○ Deposition of collagen within the Bowman’s space ○ Periglomerular fibrosis ○ Glomerulosclerosis Figure 11. Gross appearance of benign nephrosclerosis (left) and hyaline arteriosclerosis (right) Figure 11 Answers: 1F, 2A, 3C, 4C, 5 Xanthogranulomatous pyelonephritis Rationale: 1F: ATI is a reversible condition since the patchiness of tubular necrosis and maintenance of the integrity of the basement membrane allows the repair of the injured foci and recovery function if the precipitation cause is removed. II. DISEASES OF THE BLOOD VESSELS: NEPHROSCLEROSIS Term used for the renal pathology associated with sclerosis of renal arterioles and small arteries ○ Parenchymal effects include glomerulosclerosis and chronic tubulointerstitial injury producing a reduction in functional renal mass Strongly associated with hypertension ○ Can be both a cause and consequence of nephrosclerosis A. PATHOGENESIS 2 processes that participate in the arterial lesions observed in nephrosclerosis: ○ Medial and intimal thickening ▸ Response to hemodynamic changes, aging, genetic defects, or some combination of these ○ Hyalinization of arteriolar walls ▸ Caused by extravasation of plasma proteins through injured endothelium ▸ Also due to increased deposition of basement membrane matrix Due to thickened walls, affected vessels will have a narrowed lumen → decreased blood flow ○ Results to focal parenchymal ischemia Ischemia leads to glomerulosclerosis and chronic tubulointerstitial injury ○ Produces a reduction in functional renal mass The picture on the left show the gross appearance of the cortical surface in benign nephrosclerosis ○ Illustrating the fine, leathery granularity of the surface The picture on the right shows the arteriole with hyaline deposition (pointed by the arrow) C. MALIGNANT NEPHROSCLEROSIS Renal lesions associated with malignant hypertension have been referred to as malignant nephrosclerosis Characterized by: ○ Severe pressure elevations ▸ Systolic pressure of more than 200 mmHg ▸ Diastolic pressure of more than 120 mmHg ○ Renal failure ○ Retinal hemorrhages and exudates ▸ With or without papilledema – Swelling of the optic nerve that reflects increase in intracranial pressure MORPHOLOGY Kidney may be normal in size or slightly shrunken Accelerated or malignant hypertension causes pinpoint petechial hemorrhages on cortical surface ○ Due to the rupture of arterioles and glomerular capillaries ○ Imparts a flea-bitten appearance B. BENIGN NEPHROSCLEROSIS MORPHOLOGY Cortical surfaces of the kidney show a fine, even granularity resembling grain leather YL6:08.09 Diseases of the Tubules, Interstitium and Blood Vessels 6 Active Recall Box 1. Which of the following diseases will result in a fine, even granularity resembling grain leather? A. Benign nephrosclerosis B. Malignant nephrosclerosis C. AOTA D. NOTA 2. What is characteristic of malignant hypertension? A. Focal parenchymal ischemia B. Periglomerular fibrosis C. Deposition of collagen within the Bowman’s space D. Vessels that are thickened by concentric cellular layers Figure 12. Flea-bitten appearance of malignant nephrosclerosis QUICK REVIEW Take Note! Malignant nephrosclerosis: flea-bitten appearance on cortical surface Benign nephrosclerosis: fine, leathery, granular appearance HISTOLOGY Fibrinoid necrosis of arterioles Onion-skin appearance of arteries and larger arterioles ○ Due to the proliferation of intimal cells ○ Termed as hyperplastic arteriosclerosis Microthrombi in the glomeruli Figure 13. Afferent arteriole with fibrinoid necrosis Figure 14. Hyperplastic arteriosclerosis Figure 14 Vessels in the center have a wall that is thickened by concentric cellular layers ○ Characteristic of malignant hypertension YL6:08.09 Answers: 1A, 2D Diseases of the Tubules, Interstitium and Blood Vessels QUESTIONS 1. Which of the following is a possible route by which bacteria can reach the kidneys and cause pyelonephritis? A. Hematogenous infection B. Direct seeding C. From the lower urinary tract D. Both A and C 2. Which of the following presents with an interstitium showing edema and accumulation of leukocytes within the vasa recta? A. Acute tubular injury B. Tubulointerstitial nephritis C. Pyelonephritis D. Benign nephrosclerosis 3. What disorder is characterized by foamy macrophages, plasma cells, lymphocytes, and occasional giant cells, and can produce large and yellowish-orange nodules that can be grossly confused with renal cell carcinoma? A. Acute tubular injury B. Benign nephrosclerosis C. Xanthogranulomatous pyelonephritis D. Tubulointerstitial nephritis 4. What complications may arise in acute pyelonephritis, particularly in those with diabetes, sickle cell disease, and those with urinary tract obstruction? A. Papillary necrosis B. Pyonephrosis C. Perinephric abscess D. NOTA 5. In nephrosclerosis, medial and intimal thickening of arterioles and small arteries is caused by the extravasation of plasma proteins through injured endothelium. Hyalinization of arteriolar walls refers to the response to hemodynamic changes, aging, genetic defects, or some combination of these. A. First statement is true B. Second statement is true C. Both statements are true D. Both statements are false 6. A 55-year old male presents to the emergency department with acute kidney injury. Further investigation reveals ischemic acute tubular injury as the underlying cause. Which of the following is true of ischemic ATI? A. It may be caused by endogenous agents B. It may be caused by exogenous agents C. It is an irreversible condition D. It has diffuse involvement of the intrarenal blood vessels 7. A patient presents with a sudden onset of pain at the costovertebral angle with fever and malaise. Upon checking for a urine culture, it was positive for E. coli. What is a possible predisposing condition for this disease? A. Hyperactive vesicoureteral valve B. Extrarenal reflux C. Urinary tract obstruction 7 D. NOTA 8. A patient comes in with a fever and a rash after ingesting rifampin. The results of their blood test show eosinophilia and a rising serum creatinine level. What is a possible immune mechanism of this disease? A. Type I: IgE mediated B. Type II: cytotoxic reaction C. Type III: immune complex mediated D. NOTA 9. Due to thickened walls, affected vessels will have a narrowed lumen which can lead to decreased blood flow. What kind of ischemia will be seen in nephrosclerosis? A. Diffuse parenchymal ischemia B. Focal parenchymal ischemia C. AOTA D. NOTA 10. A patient comes in after having a systolic pressure of 220 mmHg and a diastolic pressure of 150 mmHg. What may be seen on a gross specimen? A. Normal kidney B. Cortical surfaces show a fine granularity resembling grain leather C. Flea-bitten appearance on cortical surface D. Grayish white areas of inflammation and abscess formation ANSWER KEY REFERENCES 📄 ASMPH2027. 08.09: Diseases of the Tubules, Interstitium and Blood Vessels by Koa, A.T., MD REQUIRED Concerns and Feedback form: http://bit.ly/YL6CFF2027 How’s My Transing? form: https://bit.ly/2027YL6HMT Mid-Semester Evaluation form: https://bit.ly/2027YL6MidSem End-of-Semester Evaluation form: https://bit.ly/2027YL6EndofSem Errata Points Trackers: https://bit.ly/YL62027EPT YL6 TransMap: https://bit.ly/2027YL6TransMap FREEDOM SPACE 1D, 2A, 3C, 4A, 5D, 6D, 7C, 8A, 9B, 10C RATIONALE 1. D. Both A and C. There are 2 routes by which bacteria can reach the kidneys. The first is through the bloodstream (hematogenous infection) which results from bacteremic spread. The second is from the lower urinary tract (ascending infection) which results from a combination of urinary bladder infection, vesicoureteral reflux, and intrarenal reflux. 2. A. Acute tubular injury. Acute tubular injury shows an interstitium with edema and accumulation of leukocytes within the vasa recta. 3. C. Xanthogranulomatous pyelonephritis. It is a rare form of chronic pyelonephritis and is characterized by foamy macrophages, plasma cells, lymphocytes, polymorphonuclear cells, leukocytes, and occasional giant cells. It may produce large and yellow-ish nodules that can be grossly confused with renal cell carcinoma. 4. A. Papillary necrosis. Pyonephrosis is seen with total or almost complete obstruction which results in the inability to drain. Perinephric abscess is an extension of the inflammation through the renal capsule into perinephric tissue. 5. D. Both statements are false. In nephrosclerosis, medial and intimal thickening of arterioles and small arteries refers to the response to hemodynamic changes, aging, genetic defects, or some combination of these. Hyalinization of arteriolar walls is caused by extravasation of plasma proteins through injured endothelium. 6. D. It has diffuse involvement of the intrarenal blood vessels. Ischemic ATI is due to decreased or interrupted blood flow as in diseases with diffuse involvement of the intrarenal blood vessels such as in microscopic polyangiitis, malignant hypertension, microangiopathies, and systemic conditions associated with thrombosis. 7. C. Urinary tract obstruction. The symptoms are indicative of pyelonephritis. A predisposing condition for microbe movement to kidneys includes urinary obstruction. 8. A. Type I: IgE mediated. The described symptoms are clinical features of tubulointerstitial nephritis induced by drugs and toxins. The pathogenesis suggests an immune mechanism, either a late-phase reaction of an IgE-mediated (Type I) hypersensitivity or T-cell mediated (Type IV) delayed-hypersensitivity reaction. 9. B. Focal parenchymal ischemia. The thickened walls in nephrosclerosis results in focal parenchymal ischemia. 10. C. Flea-bitten appearance on cortical surface. Severe pressure elevation (systolic pressure of >200mmHg and diastolic pressure >150mmHg) is indicative of malignant nephrosclerosis. Its morphology has a flea-bitten appearance on the cortical surface of the kidney. YL6:08.09 Diseases of the Tubules, Interstitium and Blood Vessels 8