chronic renal diseases: pathological aspects dr rodney itaki division of pathology, smhs, upng...
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Chronic Renal Diseases: Pathological aspects
Dr Rodney ItakiDivision of Pathology, SMHS, UPNGAnatomical Pathology Discipline.
Gross anatomy
Ref: Goggle Images
Microanatomy
Robins Pathological Basis of Diseases, 6th Ed. Figure 21.1
Glomeruli - Ultra filtration
Glomeruli & Renal Capsule
Blood Supply
Juxtaglomerular Apparatus
+low BP & Ischaemia
+Low NaCl
Renin-Angiotensin-Aldosterone System
Ref: www.commons.wiki.org
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 15th Ed.
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.
Types of azotemia
Type Feature
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.]
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)
Pathogenesis Due to disturbances in water,
electrolytes & acid-base balance.
Accumulation of substances such as phosphate, parathyroid hormone, urea, creatinine, guanidine, phenols,& idoles.
Fig: Pathophysiologic pathway of chronic
renal failure.
©2003 American Medical Association. All rights reserved.on July 17, 2008 www.archinternmed.com Downloaded from
Figure 1. Sympathetic over-activity and disease progression in chronicrenal failure
Pathophsiology of Chronic Renal Failure
1. Diminished renal reserve
3. Renal failure
2. Renal insufficiency
4. End-stage renal disease (Chronic Renal Failure)
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.
Gross Morphology
Microscopic Morphology
1. Tubular atrophy
2. Interstitial fibrosis
3. Enlarged & hypertrophic tubules
4. Thickened basement membrane
Clinical Features of Uraemia Anaemia
Metabolic bone diseases(renal osteodystrophy)
Neuropathy
Myopathy
Endocrine abnormalities
Hypertension & atherosclerosis
Acidosis
Susceptibility to infection
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
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
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)
Glomerular Diseases Types:
Immune or
Non-immune mediated injury
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.
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.
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: Alport’s 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.
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.
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.
Diabetic Nephropathy
Ref: Robins Pathological Basis of Diseases, 6th E. Table 20.1
Diabetic Nephropathy Capillary BM
thickening. Diffuse
glomerulosclerosis. Nodular
glomerulosclerosis.
Ref: www.unckidneycentre.org
Basement membrane Thickening
Ref: www.intechopen.com
Thickened BM
Amyloidosis Deposition of abnormal protein in the glomerulus & blood vessel wall
Amyloid deposits
Amyloidosis
Congo red stain. Examined under polarization microscopy. “Apple-green” birefringence.
Ref: www.pathology.vcu.edu
Glomerulonephritis
Ref: Robins Pathological Basis of Diseases, 6th Ed. Table 21.3
Glomerulonephritis
Ref. Robins Pathological Basis of Diseases, 6th Ed. Figure 21.29
Histological Types of GN Post-streptococcal GN Rapidly Progressive
Glomerulonephritis Membranous GN Focal glomerulosclerosis Membranoproliferative GN
Post-streptococcal GN
Normal glomerulus Acute proliferate GN
Hypercellularity due to intercapillary leucocytes & proliferation of glomerular cells
Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.16
Rapidly Progressive (Crescentic) GN
Ref: www.geekymedics.com
Crescent GNCollapsed glomerular tufts
Mass of crescent shaped proliferating cells & leucocytes
Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.17
Membranous GN
Diffuse thickening of capillary wall without increase in number of cells
Ref: Robins Pathological basis of Diseases, 6th Ed. Fig. 21.19
Diagrammatic representation
Minimal Change Disease (Lipoid Nephrosis)
Visceral epithelial cells show uniform and diffuse effacement of foot process
Thin BN. No proliferation
Minimal Change Disease
Normal glomerular tuft. No hypercellularity. Thin BM.
Ref: www.kidneypathology.com
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
Membranoproliferative GN
Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.24
Differentiation based on electron microscopy
Membranoproliferative GN
•Thickened in BM
•Proliferation of mesangial cells (glomerular cells)
•Leukocyte infiltration
Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.23
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.
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.
Hypertension – Renal ChangesFibrinoid necrosis of afferent arteriole.
Hyperplastic arteriolitis (onion-skin lesion)
Robins Pathological Basis of Diseases, 6th Ed. Figure 21.20
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.
Complications Anemia
Bone disease
Skin disease
Gastrointestinal complications
Metabolic abnormalities
Endocrine abnormalities
Muscle dysfunction
Nervous complications
Cardiovascular
Prognosis Poor Treatment can only slow progression Renal transplant offers true cure
(but has its own complications).
END Main reference: Robins Pathological
Basis of Diseases, 6th Ed. Chapter on Kidney & Endocrine diseases.