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Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.
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Page 1: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Chronic Renal Diseases: Pathological aspects

Dr Rodney ItakiDivision of Pathology, SMHS, UPNGAnatomical Pathology Discipline.

Page 2: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Gross anatomy

Ref: Goggle Images

Page 3: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Microanatomy

Robins Pathological Basis of Diseases, 6th Ed. Figure 21.1

Page 4: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Glomeruli - Ultra filtration

Page 5: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Glomeruli & Renal Capsule

Page 6: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Blood Supply

Page 7: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Juxtaglomerular Apparatus

+low BP & Ischaemia

+Low NaCl

Page 8: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Renin-Angiotensin-Aldosterone System

Ref: www.commons.wiki.org

Page 9: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.
Page 10: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 11: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 12: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.]

Page 13: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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)

Page 14: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Pathogenesis Due to disturbances in water,

electrolytes & acid-base balance.

Accumulation of substances such as phosphate, parathyroid hormone, urea, creatinine, guanidine, phenols,& idoles.

Page 15: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Fig: Pathophysiologic pathway of chronic

renal failure.

©2003 American Medical Association. All rights reserved.on July 17, 2008 www.archinternmed.com Downloaded from

Page 16: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Figure 1. Sympathetic over-activity and disease progression in chronicrenal failure

Page 17: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Pathophsiology of Chronic Renal Failure

1. Diminished renal reserve

3. Renal failure

2. Renal insufficiency

4. End-stage renal disease (Chronic Renal Failure)

Page 18: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 19: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Gross Morphology

Page 20: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Microscopic Morphology

1. Tubular atrophy

2. Interstitial fibrosis

3. Enlarged & hypertrophic tubules

4. Thickened basement membrane

Page 21: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Clinical Features of Uraemia Anaemia

Metabolic bone diseases(renal osteodystrophy)

Neuropathy

Myopathy

Endocrine abnormalities

Hypertension & atherosclerosis

Acidosis

Susceptibility to infection

Page 22: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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

Page 23: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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

Page 24: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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)

Page 25: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Glomerular Diseases Types:

Immune or

Non-immune mediated injury

Page 26: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 27: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 28: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 29: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 30: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 31: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Diabetic Nephropathy

Ref: Robins Pathological Basis of Diseases, 6th E. Table 20.1

Page 32: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Diabetic Nephropathy Capillary BM

thickening. Diffuse

glomerulosclerosis. Nodular

glomerulosclerosis.

Ref: www.unckidneycentre.org

Page 33: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Basement membrane Thickening

Ref: www.intechopen.com

Thickened BM

Page 34: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Amyloidosis Deposition of abnormal protein in the glomerulus & blood vessel wall

Amyloid deposits

Page 35: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Amyloidosis

Congo red stain. Examined under polarization microscopy. “Apple-green” birefringence.

Ref: www.pathology.vcu.edu

Page 36: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Glomerulonephritis

Ref: Robins Pathological Basis of Diseases, 6th Ed. Table 21.3

Page 37: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Glomerulonephritis

Ref. Robins Pathological Basis of Diseases, 6th Ed. Figure 21.29

Page 38: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Histological Types of GN Post-streptococcal GN Rapidly Progressive

Glomerulonephritis Membranous GN Focal glomerulosclerosis Membranoproliferative GN

Page 39: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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

Page 40: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Rapidly Progressive (Crescentic) GN

Ref: www.geekymedics.com

Page 41: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Crescent GNCollapsed glomerular tufts

Mass of crescent shaped proliferating cells & leucocytes

Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.17

Page 42: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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

Page 43: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Minimal Change Disease (Lipoid Nephrosis)

Visceral epithelial cells show uniform and diffuse effacement of foot process

Thin BN. No proliferation

Page 44: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Minimal Change Disease

Normal glomerular tuft. No hypercellularity. Thin BM.

Ref: www.kidneypathology.com

Page 45: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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

Page 46: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Membranoproliferative GN

Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.24

Differentiation based on electron microscopy

Page 47: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Membranoproliferative GN

•Thickened in BM

•Proliferation of mesangial cells (glomerular cells)

•Leukocyte infiltration

Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig 21.23

Page 48: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 49: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 50: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Hypertension – Renal ChangesFibrinoid necrosis of afferent arteriole.

Hyperplastic arteriolitis (onion-skin lesion)

Robins Pathological Basis of Diseases, 6th Ed. Figure 21.20

Page 51: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

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.

Page 52: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Complications Anemia

Bone disease

Skin disease

Gastrointestinal complications

Metabolic abnormalities

Endocrine abnormalities

Muscle dysfunction

Nervous complications

Cardiovascular

Page 53: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

Prognosis Poor Treatment can only slow progression Renal transplant offers true cure

(but has its own complications).

Page 54: Chronic Renal Diseases: Pathological aspects Dr Rodney Itaki Division of Pathology, SMHS, UPNG Anatomical Pathology Discipline.

END Main reference: Robins Pathological

Basis of Diseases, 6th Ed. Chapter on Kidney & Endocrine diseases.


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