The Renal System Pathology P2 (Phrm 252) PDF

The Renal system pathology Phrm 252 Ms G Butelezi  Objectives Explain the function of the renal system Integrate knowledge on homeostasis in renal conditions Explain the pathophysiology of common renal conditions Apply critical analysis of laboratory results in the diagnosis of renal condition...

The Renal system pathology Phrm 252 Ms G Butelezi  Objectives Explain the function of the renal system Integrate knowledge on homeostasis in renal conditions Explain the pathophysiology of common renal conditions Apply critical analysis of laboratory results in the diagnosis of renal conditions  Introduction The upper urinary tract consists of the kidneys, their vasculature and the renal parenchyma The lower urinary tract is composed of the peristaltic ureters from each kidney, the bladder and the urethra Disease can occur at any level of these functional structures Kidney maintains fluid and electrolyte homeostasis and removes metabolic waste products filtered by glomeruli https://www.youtube.com /watch?v=dFnLbgPjiUw  Signs Albuminuria: The pivotal clue to kidney diseases that begin primarily with glomerular dysfunction Electrolyte & dilution disorders and concentration of the urine diseases: Begin in the tubular structures  Presentation Either no symptoms or signs: renal mass picked up on ultrasound Non-specific findings: fatigue With signs highly specific for a syndrome of dysfunction referable to a structure, but not diagnostic of a particular disease: Proteinuria With a finding highly characteristic of a specific diagnosis: polycystic kidney disease  Routine testing Adrenal glands are located in the epigastrium at the top of the kidney. It is NB to perform renal testing in patients with systemic disease Routine screening: Albuminuria in diabetes mellitus (DM)  Nephritic syndromes Nephritis refers to an inflammatory condition affecting the kidneys It can arise due to infections, allergic reactions to medications, systemic autoimmune diseases, or exposure to toxins Inflammation often leads to kidney enlargement, commonly accompanied by tenderness in the flank area and, at times, significant tenderness, necessitating careful palpation for accurate diagnosis  Glomerulonephritis (GN) Associated with hypertension (HTN), fluid overload, and abnormalities in urinalysis Fluid overload manifests as edema and HTN Patients might experience orthopnea at night or dyspnoea during physical exertion, with or without evident peripheral oedema Acute glomerulonephritis (GN) typically presents with low urine output (oliguria or anuria), reduced urine sodium levels, and concentrated urine, leading to the retention of salt and water The are progressive destructive conditions, early diagnosis & treatment is critical  GN findings The nephritic urinalysis shows hematuria, proteinuria, cells or clumps of cells, and cellular casts in the spun urinary sediment (Urine sediment preparation is undertaken to identify cells, casts, crystals, and microorganisms) The cells in the urine are usually a mixture of red blood cells and inflammatory cells, including polymorphonuclear (PMN) leukocytes Microscopic hematuria is invisible to the naked eye, as opposed to macroscopic hematuria, identifiable as cola or “tea-colored” urine (haemoglobin entering an acid urine) The red cells enter the renal tubules through breaks in the basement membrane of glomeruli  Glomerulonephritis (GN) Syndrome Description Syndrome arises from various causes, associated with proliferation of glomerular parietal epithelial cells and inflammatory cells (cellular crescents). RAPIDLY PROGRESSIVE Over time, it leads to fibrosis, atrophy, and global loss of the GLOMERULONEPHRITIS glomerular tuft. (RPGN) Highly destructive process usually leads to glomerular sclerosis The syndrome can lead to complete and irreversible loss of kidney function Symptoms Sweating Anxiety Heightened alertness (part of fight-or-flight response) Glomerulonephritis (GN) Syndrome Description Acute GN is a complement-mediated POSTINFECTIOUS immune response to a bacterial antigen. GLOMERULONEPHRITIS Occurs 10 days to 3 weeks after a specific nephritogenic strain A streptococcal pharyngitis or after a skin infection (impetigo) Glomerulonephritis (GN) Syndrome Description Tubulointerstitial nephritis (TIN) comprises inflammatory disorders of the renal tubules and interstitium, which may be caused by infection, TUBULOINTERSTITIAL autoimmune disease, allergic immunologic responses NEPHRITIS (TIN) to certain drugs Drugs implicated: NDAIDS, Chemotherapeutics and lithium Allergic reactions: Antibiotics: (cephalosporins, rifampicin, quinolones) Immune: Systemic lupus erythematosus (SLE) Infections: TB ACUTE ALLERGIC AND IMMUNE INTERSTITIAL NEPHRITIS (AIN) Acute allergic or immune interstitial nephritis (AIN) usually occurs 1 day to 2 weeks following exposure to an offending drug May be associated with a rapid and potentially reversible loss of kidney function Associated glomerular proteinuria sometimes occurs with the use of NSAIDs or ampicillin Clinically, there may be fever, rash, and eosinophilia The urinalysis usually shows pyuria and at times eosinophiluria, but the most characteristic cell types are activated T lymphocytes and plasma cells ACUTE ALLERGIC AND IMMUNE INTERSTITIAL NEPHRITIS (AIN) The patient may experience symptoms of polyuria and tender kidneys, and signs of tubular dysfunction including nephrogenic diabetes insipidus, hypo- or hyperkalemia and hyperchloremic metabolic acidosis. Common drugs that cause AIN include proton pump inhibitors (PPIs) and sulfa drugs, especially sulfamethoxazole, but also extending to sulfa- containing diuretics such as acetazolamide, thiazides and furosemide Noninflammatory Interstitial Diseases Noninflammatory interstitial diseases are often caused by toxic exposures that damage the tubular interstitial structures a cancer patient on ifosfamide may develop Fanconi’s syndrome, indicating proximal tubule damage Perhaps the most common cause of chronic interstitial nephritis is prolonged analgesic use to treat chronic pain (not only NSAIDs but paracetamol) The clinician should ask about a prior history of pain and also gastrointestinal symptoms that may precede the kidney disease  Reference Seifter JL. Approach to the Patient with Renal Disease or Urinary Tract Disease. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. eds. Harrison's Principles of Internal Medicine, 21e. McGraw-Hill Education; 2022 The Renal system pathology P2 Phrm 252 Ms G Butelezi  Nephrotic syndromes This condition is defined by three primary characteristics: a. Oedema b. Hypoalbuminemia (below 3.5 g/dL) c. Proteinuria greater than 3.5 g/day This syndrome is often associated with lipid irregularities, such as raised LDL levels, decreased HDL levels and the occurrence of lipiduria Under polarised light, the urine may reveal large tubular epithelial cells that are engulfed with lipids, displaying a distinct shape  Nephrotic syndromes types Broken down into idiopathic and secondary causes  Presentation 1 Patients present with generalised oedema, orthopnea, facial, eyelid and periorbital swelling Penile and scrotal oedema can be severe enough to obstruct 2 urethral urine flow in men Oedema may form large bullae that may rupture, predisposing to 3 ulceration and cellulitis. The skin becomes smooth and may appear to “weep” 4 Patients may have hoarseness caused by vocal cord oedema  Presentation cont... 5 Immunodeficiency virus-associated nephropathy (HIVAN) Nephrotic range proteinuria not linked to oedema Rapid renal function loss due to glomerular capillary implosion from visceral epithelial cell proliferation Decreased capillary flow and filtering surface area due to crushed glomerular loops  Presentation NS is a hypercatabolic state Negative nitrogen balance (nitrogen loss) due to proximal tubule absorption and lysosomal catabolism that surpasses hepatic albumin synthesis Characteristic finding of rapid- onset hypoalbuminemia in NS is horizontal linear white lines in the nail bed, known as https://litfl.com/muehrcke-lines/ Muehrcke’s lines  Presentation cont... Age is important in the onset of NS NS in the adults: 1. Occurs abruptly 2. Severe elevation of cholesterol 3. Glomerular epithelial injury (podocytopathy) may be caused by idiopathic minimal change disease (MCD) NS in children: 1. Young children