Transcript MBBS IV chronic renal diseases seminar 2013

Chronic Renal Diseases:
Pathological aspects
Dr Rodney Itaki
Division of Pathology,
SMHS, UPNG
Anatomical 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-AngiotensinAldosterone 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 chronic
renal failure
Pathophsiology of Chronic Renal
Failure
1. Diminished renal reserve
2. Renal insufficiency
3. Renal failure
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 lifethreatening 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

Headaches

Generalized weakness & lack
of energy

Visual disturbances

Breathlessness on exertion

Pruritis

Anorexia

Pallor

Nausea & vomiting
particularly in mornings

Pigmentations

Loss of libido

Disordered intestinal motility
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.


2. Hemodynamic glomerular injury.


Diabetic nephropathy: the glomerular lesion is
glomerulosclerosis whereby there is thickening of the
glomeular basement membrane.
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.


5. Infectious glomerulopathies.






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.
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
Thickened
BM
Ref: www.intechopen.com
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 GN
Collapsed
glomerular
tufts
Mass of
crescent
shaped
proliferating
cells &
leucocytes
Ref: Robins Pathological Basis of Diseases, 6th Ed.
Fig 21.17
Membranous GN
Diagrammatic representation
Diffuse thickening of capillary
wall without increase in number
of cells
Ref: Robins Pathological basis of Diseases, 6th Ed. Fig. 21.19
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
Ref:www.med.niigata-u.ac.jp
Foam
cells
•Lipid in
sclerotic
area (small
vacuoles)
Membranoproliferative GN
Differentiation
based on
electron
microscopy
Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig
21.24
Membranoproliferative GN
•Thickened in
BM
•Proliferation
of mesangial
cells
(glomerular
cells)
Ref: Robins Pathological Basis of Diseases, 6th Ed. Fig
21.23
•Leukocyte
infiltration
Blood Vessel Injury Hypertension





Atherosclerosis:
Multifactorial
The vascular injury is due to cholesterolcontaining 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
Changes
Fibrinoid 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.