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8/12/2019 4th Sc Phar 40060-Renal-2web
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4th Science:40060
ARP lecture - Renal Disease
Dr. Tara McMorrow
Tel: 01 716 6819
School of Biomolecular and Biomedical Science
Conway Institute
mailto:[email protected]:[email protected]8/12/2019 4th Sc Phar 40060-Renal-2web
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PHAR 40060ARP Lecture 2: Objectives
At the end of this lecture, students should
have an understanding of the kidney in
relation to renal disease
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Functional unit of the kidney - Nephron
Nephron
Tubular Vascular
component component
Approx. 1 million nephrons in each mammalian kidney
Can lose up to 75% of nephron function and renal
function will be maintained by reserve nephrons
difficult to detect damage early
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Renal Disease Backg round :
Renal disease is a major problem worldwide
Increasing incidence80,000 new cases / year inUSA
Major causes inc lude :1. Diabetes
2. Hypertension
3. Glomerulonephritis
Mechanisms of development are unknown
Thus limited therapies are available
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General Characteristics
Early Renal Disease: Abnormal urine volume
and/or composition
Advanced: Edema, electrolyte abnormalities,
anemia, etc. Rate of Progression: Disease-dependent
Disease Course: Transient-fatal: Disease-
dependent Pain: Variable, depending on nature of
disease
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Kidney Sites Susceptible to Renal Disease
General: Renal medulla:
Low oxygen environment: Ischemia
Glomeruli:
Structure predisposes it to immune complex depositionand complement fixation
Tubules
- generally involved in endstage or chronic kidney disease
Post-Renal Structures (ureters, bladder)
Malformations, Obstruction, Masses (i.e. cancer)
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Acute Kidney Disease
Prerenal:
Decreased cardiac output and urine volume depletion
Drug-induced or related
Intrarenal: Inflammatory disease
Acute tubular necrosis
Postrenal:
- Obstruction
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Slow decline in kidney function- eventually progresses to End Stage Renal
Disease (ESRD)
Generally develops as a result of another condition
- Diabetes (28%)- Hypertension (25%)
- Glomerulonephritis (21%)- Polycystic Kidney Disease (4%)
- Other (23%): Obstruction, infection, drugs.
Chronic Kidney Disease
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Renal diseases are varied and can result from a toxicinsult or may be immune mediated
They may be classified by their location of onset -
Glomerular disease- glomerulonephritis
Tubulointerstitial disease- tubulointerstitial nephritis
Most of the conditions result in a fibrotic or scleroticphenotype characterised by excess extracellular matrixdeposition
Regardless of the initial insult, development of renalfibrosis leads to end-stage renal disease and ultimatelykidney failure
Renal Disease Classification
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Renal ultra-structure of normal and fibrotic tissue
(a) Normal kidney architecture displaying a normal glomerulus ( ), bowmans
space ( ), mesangial cells ( ), basement membrane ( ) supporting the tubular
epithelial cells ( ) separated by the interstitial space ( ).
(b) In the glomerular nephritis section there is an enlarged glomerulus, reduced
bowmans space, proliferating mesangial cells, an expansive interstitium and
disruption of tubular function.
(a) (b)
Kidney Histology
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Glomerular Diseases
Glomerulonephritis (GN) is one of the most important causes of
renal disease world-wide.
Examples of GN include:
1. Membranous nephritis2. Post-infectious glomerulonephritis
3. Lupus glomerulonephritis
4. IgA Nephropathy
5. Goodpastures Syndrome
6. Diabetic Nephropathy
7. Glomerulosclerosis
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Glomerulonephritis
Glomerulonephritis is the third most commoncause of end-stage renal disease afterdiabetes and hypertension
Accounts for 10-15% of ESRD patients
Immunological events lead to
- complement activation
- fibrin deposition- platelet aggregation
- inflammation
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Acute Glomerulonephritis Chronic Glomerulonephritis
Glomerulonephritis:
scarring of the cortex
http://www.som.tulane.edu/classware/pathology/medical_pathology/McPath/GR_Renal/Renal5.jpghttp://erl.pathology.iupui.edu/C603/IMAGES/97152B.JPGhttp://erl.pathology.iupui.edu/C603/IMAGES/15KW.JPG8/12/2019 4th Sc Phar 40060-Renal-2web
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Tubular Diseases
The main tubular disease is tubulointerstitial
nephritis
Acute tubulointerstitial nephritis- due tohypersensitivity reactions to drugs
Chronic tubulointerstitial nephritis- due to
drugs, diabetes, chemicals
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Acute Tubulointerstitial Nephritis Chronic Tubulointerstitial Nephritis
Tubulointerstitial
Nephritis
http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=/websites/emedicine/med/images/Large/2490fig_7.jpg&template=izoom2http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=/websites/emedicine/med/images/Large/2484fig_1.jpg&template=izoom2http://www.humpath.com/IMG/jpg/chronic_interstitial_nephritis.jpghttp://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=/websites/emedicine/med/images/Large/2490fig_7.jpg&template=izoom28/12/2019 4th Sc Phar 40060-Renal-2web
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Progressive Renal Disease
Common histological end point: Scarr ing : 1. Glomerulosclerosis
2. Tubulointerstitial Fibrosis
Pathological process resulting from insult / injuryleading to tissue dysfunction and organ failure
Fibrosis - The Final Common Pathway for renal
diseases that progress to ESRF Level of fibrosis correlates closely with the degree of
renal dysfunction
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Glomerulosclerosis
Glomerulosclerosis is a key endpoint in
progressive renal disease
Leads to scarring of the glomeruli which
cannot be repaired
Eventually leads to end stage renal disease
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Tubulointerstitial fibrosis
Tubulointerstitial fibrosis is a hallmark ofprogressive renal disease
Progression of chronic renal insufficiency isclosely linked to the severity of tubulointerstitial
changes
Level of proximal tubular damage also correlatesclosely with the degree of renal dysfunction
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FIBROSIS :
1. Increased deposition of fibronectin,
collagens
2. Increased fibroblast proliferation
3. Increase in mononuclear cells
4. Accumulation of matrix proteins :- inadequate matrix degradation
The End-Stage K idney
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Kidney fibrosis (ESRD)
Tubulointerstitial Fibrosis is the final common pathway leading to
ESRF - correlates most closely with declining renal function
Caused by accumulation of excess extracellular matrix (ECM) in the
renal tubular interstitium
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ESRD
Patients with chronic renal impairment
tend to progress to ESRD
No treatment options except renalreplacement therapy i.e. dialysis
Transplantation-long waiting lists and
strict criteria
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Kidney Disease Summary
Prevalence of kidney disease
- 1 in 9 adults develop chronic kidney disease
Renal fibrosis is a common final pathway for
numerous kidney dysfunctions- e.g. Tubulointerstitial fibrosis, diabetic nephropathy
Renal fibrosis is characterised by:- loss of renal function
- decreased number of epithelial cells
- excess ECM accumulation
- infiltration of fibroblasts
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5 Stages of Kidney Disease
Many People With Kidney Disease Still in the Dark- March 2005 ReportAlmost 45 percent of people with stage 4 kidney diseaseonly one stage behind
kidney failurehad never been told there was anything wrong with their kidneys.
More than 20 million Americansone in nine adultshave chronic kidney
disease. More than 20 million more are at increased risk for developing
kidney disease, and most don't even know it.
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Relevant References
Detection and Evaluation of Chronic
Kidney Disease. Snyder S and Pendergraph
B. 2005AFP72(9): 1723-1732
Management of Acute Renal Failure.
Needham E.2005AFP72(9): 1739-1746
www.aafp.org/afp