Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline. Slide 2 Gross anatomy Ref: Goggle Images Slide 3 Microanatomy Robins Pathological Basis of Diseases, 6 th Ed. Figure 21.1 Slide 4 Glomeruli - Ultra filtration Slide 5 Glomeruli & Renal Capsule Slide 6 Blood Supply Slide 7 Juxtaglomerular Apparatus +low BP & Ischaemia +Low NaCl Slide 8 Renin-Angiotensin- Aldosterone System Ref: www.commons.wiki.org Slide 9 Slide 10 Chronic Renal Disease Definition: Chronic renal disease (CRD) is a pathophysiologic process with multiple etiologies, resulting in the inexorable attrition of nephron number and function, and frequently leading to end-stage renal disease (ESRD). Irreversible deterioration in renal function (C.R.W.Edwards et al, 1998, pg.631) Ref: Harrison 15 th Ed. Slide 11 Azotemia There is azotemia in chronic renal failure. Azotemia is the biochemical state in which there is an elevation of: 1. Blood urea nitrogen (BUN) and 2. Creatinine levels when there is a decreased glomerular filtration rate (GFR). Persistent azotemia gives rise to signs, symptoms and biochemical abnormalities, which is referred to as uremia. Slide 12 Types of azotemia TypeFeature Pre-renal azotemia Due to hypoperfusion of kidneys. For e.g. in congestive heart failure, shock, hemorrhage, and dehydration. Post-renal azotemia Due to any obstruction to the urinary flow below the level of kidneys. [Note azotemia is not specific for chronic renal failure.] Slide 13 Uremia Definition: Uremia is the clinical and laboratory syndrome, reflecting dysfunction of all organ systems as a result of untreated or under-treated acute or chronic renal failure. (CD-ROM 15th Harrison) Slide 14 Pathogenesis Due to disturbances in water, electrolytes & acid-base balance. Accumulation of substances such as phosphate, parathyroid hormone, urea, creatinine, guanidine, phenols,& idoles. Slide 15 Fig: Pathophysiologic pathway of chronic renal failure. 2003 American Medical Association. All rights reserved. on July 17, 2008 www.archinternmed.com Downloaded from Slide 16 Figure 1. Sympathetic over-activity and disease progression in chronic renal failure Slide 17 Pathophsiology of Chronic Renal Failure 1.Diminished renal reserve 3. Renal failure 2. Renal insufficiency 4. End-stage renal disease (Chronic Renal Failure) Slide 18 End Stage Renal Disease (ESRD) In ESRD there is a degree of irreversible damage to the kidney and its function. The patient usually becomes dependent on renal replacement therapy (dialysis or transplantation) in order to avoid life- threatening uremia. Slide 19 Gross Morphology Slide 20 Microscopic Morphology 1.Tubular atrophy 2.Interstitial fibrosis 3.Enlarged & hypertrophic tubules 4.Thickened basement membrane Slide 21 Clinical Features of Uraemia Anaemia Metabolic bone diseases(renal osteodystrophy) Neuropathy Myopathy Endocrine abnormalities Hypertension & atherosclerosis Acidosis Susceptibility to infection Slide 22 Signs & Symptoms of Uraemia Vague-ill health Generalized weakness & lack of energy Breathlessness on exertion Anorexia Nausea & vomiting particularly in mornings Disordered intestinal motility Headaches Visual disturbances Pruritis Pallor Pigmentations Loss of libido Slide 23 Laboratory Investigation Aim - Diagnosis and disease monitoring FBC - anaemia UEC electrolyte imbalances, urea and nitrogen abnormalities Renal biopsy Others Ca, phosphate, EPO, etc. Genetic & immunological studies - transplant Slide 24 Chronic Renal Diseases - Causes The causes of chronic renal failure can be due to any disease process affecting the following structures: Glomeruli (glomerulonephritis) Tubules (reflex nephropathy) Interstitium (pyelonephritis, reflux nephropathy) Blood vessels (Hypertension) Slide 25 Glomerular Diseases Types: Immune or Non-immune mediated injury Slide 26 Immune mediated Glomerular Diseases Immune mechanism can be of antibody-associated injury. Two forms are known: Immune response resulting in injury due to deposition of soluble circulating antigen-antibody complexes in the glomeruli. Referred to as Circulating Immune complex injury. Immune response resulting injury due to antibodies reacting in situ within the glomerulus. Referred to as Cell Mediated Injury. Others may be due to cytotoxic antibodies directed against the glomerular cells. Slide 27 Non-immune Mediated Glomerular Diseases 1. Metabolic glomerular injury. Diabetic nephropathy: the glomerular lesion is glomerulosclerosis whereby there is thickening of the glomeular basement membrane. 2. Hemodynamic glomerular injury. This is due to the high intra-glomerular pressure caused by systemic hypertension or local change in glomerular hemodynamics (glomerular hypertension). 3. Toxic glomerulopathies. The toxic verotoxic from the E.Coli is directly toxic to renal endothelium and induces hemolytic-uremic syndrome in patients with infective diarrhea caused by E.Coli.Verotoxic interacts with specific cell membrane receptor inducing thrombotic microangiopathy. Slide 28 Non-immune Mediated Glomerular Diseases 4. Deposition disease. There is deposition of abnormal proteins in the glomeruli inducing inflammatory reaction or glomerulosclerosis. For e.g. amyloidosis, cryoglobulins, light and heavy chain deposition disease. 5. Infectious glomerulopathies. Infectious microorganisms can cause injury by: Direct infection of renal cell Elaboration of nephrotoxic e.g. E.Coli Intraglomerular deposition of immune complexes e.g. post-infectious glomerulonephritis. Providing chronic stimulus for amyloidosis. 6. Inherited glomerular diseases. A common e.g. is: Alports disease: Transmitted, as X-linked dominant trait. There is mutation in COL4A5 gene that encodes -5 chain of type IV collagen located on X-chromosome. The glomerular basement membrane (GBM) is affected. Slide 29 The determinants of the severity of glomerular damage are 1. The nature of primary insult and secondary mediator system that evoke it. 2. The site of injury within the glomerulus. 3. The speed of onset, extend and intensity of disease. Slide 30 Common Chronic Renal Failure Causes Non-Immune Mediated - Diabetic Nephropathy Immune Mediated Glomerulonephritis Blood vessel - Hypertension Interstitial injury & Tubules - Reflux nephropathy in children Interstitial, tubules & Glomerular - Polycystic kidney disease Interstitial & tubules - Kidney infections & obstructions Source: Wendy DeMartino, MD, Teaching Slides. Downloaded via Goggle Search. Slide 31 Diabetic Nephropathy Ref: Robins Pathological Basis of Diseases, 6 th E. Table 20.1 Slide 32 Diabetic Nephropathy Capillary BM thickening. Diffuse glomerulosclerosis. Nodular glomerulosclerosis. Ref: www.unckidneycentre.org Slide 33 Basement membrane Thickening Ref: www.intechopen.com Thickened BM Slide 34 Amyloidosis Deposition of abnormal protein in the glomerulus & blood vessel wall Amyloid deposits Slide 35 Amyloidosis Congo red stain. Examined under polarization microscopy. Apple-green birefringence. Ref: www.pathology.vcu.edu Slide 36 Glomerulonephritis Ref: Robins Pathological Basis of Diseases, 6 th Ed. Table 21.3 Slide 37 Glomerulonephritis Ref. Robins Pathological Basis of Diseases, 6 th Ed. Figure 21.29 Slide 38 Histological Types of GN Post-streptococcal GN Rapidly Progressive Glomerulonephritis Membranous GN Focal glomerulosclerosis Membranoproliferative GN Slide 39 Post-streptococcal GN Normal glomerulusAcute proliferate GN Hypercellularity due to intercapillary leucocytes & proliferation of glomerular cells Ref: Robins Pathological Basis of Diseases, 6 th Ed. Fig 21.16 Slide 40 Rapidly Progressive (Crescentic) GN Ref: www.geekymedics.com Slide 41 Crescent GN Collapsed glomerular tufts Mass of crescent shaped proliferating cells & leucocytes Ref: Robins Pathological Basis of Diseases, 6 th Ed. Fig 21.17 Slide 42 Membranous GN Diffuse thickening of capillary wall without increase in number of cells Ref: Robins Pathological basis of Diseases, 6 th Ed. Fig. 21.19 Diagrammatic representation Slide 43 Minimal Change Disease (Lipoid Nephrosis) Visceral epithelial cells show uniform and diffuse effacement of foot process Thin BN. No proliferation Slide 44 Minimal Change Disease Normal glomerular tuft. No hypercellularity. Thin BM. Ref: www.kidneypathology.com Slide 45 Focal Glomerular Sclerosis Sclerotic segment shows deposition of hyaline masses Lipid in sclerotic area (small vacuoles) Ref:www.med.niigata-u.ac.jp Foam cells Slide 46 Membranoproliferative GN Ref: Robins Pathological Basis of Diseases, 6 th Ed. Fig 21.24 Differentiation based on electron microscopy Slide 47 Membranoproliferative GN Thickened in BM Proliferation of mesangial cells (glomerular cells) Leukocyte infiltration Ref: Robins Pathological Basis of Diseases, 6 th Ed. Fig 21.23 Slide 48 IgA Nephropathy (Berger Disease) IgA deposited within mesangium increasing its cellularity Immunofluorescence demonstrating positivity with antibody to IgA. Ref: www.pathologyoutlines.com Slide 49 Focal Proliferative & Necrotising GN (Focal GN) Main differential diagnosis for Focal glomerulosclerosis as histological features very similar. Main lesions are predominantly proliferative. Focal necrosis & fibrin deposition often occur within lesions. Occur as part of a systemic disease (e.g. SLE), component of known glomerular disease (e.g. IgA nephropathy) or primary (cause unknown). Slide 50 Blood Vessel Injury - Hypertension Atherosclerosis: Multifactorial The vascular injury is due to cholesterol- containing micro-emboli (atheroemboli) dislodged from atheromatous plaque in larger arteries. The micro-emboli occlude the small vessels in the kidney. Direct injury to blood vessel wall. It may result in renal artery stenosis and ischemic renal diseases. Slide 51 Pathogenesis Of Disease Involving Blood Vessels Hypertension: The persistent exposure of renal circulation to intraluminal hypertension results in hyaline arteriosclerosis of the afferent arterioles and finally loss of function (nephrosclerosis). That is, Benign arteriolar nephrosclerosis: found in patients who are hypertensive for sometime with BP > 150/90 mmHg. Hypertension has not progressed to malignant form. Malignant arteriolar nephrosclerosis: found in patients who have long-standing benign hypertension and not known hypertensive. There is sudden elevation in BP (diastolic 130mmHg). There is accompanied papilledema, cardiac decompensation, CNS involvement, and progressive renal deterioration. Slide 52 Hypertension Renal Changes Fibrinoid necrosis of afferent arteriole. Hyperplastic arteriolitis (onion-skin lesion) Robins Pathological Basis of Diseases, 6 th Ed. Figure 21.20 Slide 53 Others Reflux nephropathy renal scaring and loss of glomeruli. Polycystic kidney diseases multiple dilated cysts. Genetic. Kidney infections & obstructions acute to chronic inflammation. Renal scaring and loss of glomeruli. Focal GN/Focal proliferative & nectrotising GN. Main differential diagnosis of Focal sclerosis GN. Slide 54 Complications Anemia Bone disease Skin disease Gastrointestinal complications Metabolic abnormalities Endocrine abnormalities Muscle dysfunction Nervous complications Cardiovascular Slide 55 Prognosis Poor Treatment can only slow progression Renal transplant offers true cure (but has its own complications). Slide 56 END Main reference: Robins Pathological Basis of Diseases, 6 th Ed. Chapter on Kidney & Endocrine diseases.
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