This document discusses acute and chronic renal failure. It defines acute renal failure as a rapid onset of renal dysfunction characterized by oliguria or anuria and increased metabolic waste products in the blood. Causes include pre-renal issues reducing blood flow, intra-renal kidney tissue diseases, and post-renal urinary obstruction. Chronic renal failure is a progressive and irreversible deterioration of renal function due to kidney parenchyma damage, ultimately resulting in death. It discusses diseases causing glomerular or tubulointerstitial damage and the four stages of chronic renal failure. Clinical features of both include fluid, electrolyte, and acid-base imbalances leading to primary uraemic manifestations and secondary extra-renal symptoms

1. Renal Pathophysiology
Acute and Chronic Renal Failure
Dr. Vishal Balakrushna Jadhav
Assistant Professor (Pharmacology)
School of Pharmaceutical Sciences (SOPS), SUN
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2. Content
 Definition
a. Acute Renal Failure (ARF)
b. Chronic Renal Failure (CRF)
 Etiopathogenesis of COPD
 Pathological changes
 Clinical features
 Illustration- COPD and Microscopic changes
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3. Acute Renal Failure (ARF)
Definition
 A syndrome characterized by rapid onset of renal dysfunction,
chiefly oliguria or anuria, and sudden increase in metabolic
waste products (urea and creatinine) in the blood with
consequent development of uraemia.
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4. Etiopathogenesis of ARF
 Pre-renal, Intra-renal and Post-renal Causes.
a) Pre-renal Causes-
Pre-renal diseases are those which causes sudden decrease in the blood supply
to the nephron. Renal ischaemia results in the functional disorders or
depression of GFR or both. The causes includes an inadequate cardiac output
and hypovolaemia or vascular disease causing reduced renal perfusion.
b) Intra-renal causes-
Intra-renal disease is characterized by the disease of renal tissue itself. This
includes the vascular disease of the arteries and arterioles. Within the kidney,
diseases of the glomeruli, acute tubular necrosis due to ischaemia or the effect
of the nephrotoxin, acute tubulo-interstitial nephritis and pyelonephritis. 4

5. Etiopathogenesis of ARF
c) Post-renal causes-
Post-renal disease is characterized by urinary flow obstruction anywhere along
the renal tract distal to opening of the collecting ducts.
This may be caused by a mass within the lumen or from wall of tract or from
external compression anywhere along the lower urinary tract- ureter, bladder
neck or urethra.
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6. Clinical features of ARF
Depends on the underlying cause of ARF and on the stage of disease at which
the patient present-
A) Syndrome of acute nephritis-
 Associated with acute post-streptococcal glomerulonephritis and rapidly progressive
glomerulonephritis.
 The characteristic features of acute nephritis syndrome are-
 Proteinuria,
 Haematuria,
 Edema,
 Mild hypertension,
 Fluid retention due to diminished GFR and increased salt and water reabsorption in
the distal nephron
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7. Clinical features of ARF
B) Syndrome accompanying tubular pathology-
 When ARF is caused by the destruction of tubular cells of the nephron, the disease
typically progresses through 3 characteristic stages from oliguria to diuresis to
recovery.
 Oliguric phase-
 Lasting on an average from 7 to 10 days
 characterized by urinary output less than 400 ml per day.
 Oliguria leads to the accumulation of waste products of protein metabolism in the
blood and resultant azotaemia, metabolic acidosis, hyperkalaemia, hypernatraemia
and hypervolaemia due to secondary effect of circulatory overload and pulmonary
edema.
 The specific gravity of the urine is low, but the concentration of sodium in urine tends
to be elevated. 7

8. Clinical features of ARF
B) Syndrome accompanying tubular pathology-
 Diuretic phase-
 The urinary output is improved with the onset of healing of tubules due to drawing of
water and sodium by preceeding high levels of creatinine and urea. Since the tubular
cells have not regained normal functional capacity, the urine is of low or fixed specific
gravity.
c) Phase of recovery-
 In about 50% of the patients, full recovery with healing of tubular epithelial cells is
observed while rest terminates in death.
 The process of healing may take up to one year with restoration of normal tubular
function.
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9. Clinical features of ARF
C) Pre-renal syndrome-
 It results due to ARF occurs secondary to disorders in which neither the glomeruli
nor the tubules are damaged.
 Typically this pattern is seen in marginal ischaemia caused by renal arteriolar
obstruction, hypovolaemia, hypotension or cardiac insufficiency.
 Due to decreased renal blood flow, GFR is also reduced and causing azotaemia
(elevation of BUN and creatinine), oliguria and possible fluid retention and edema.
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10. B) Chronic Renal Failure (CRF)
Definition
 A syndrome characterized by progressive and irreversible deterioration of renal
function due to slow destruction of renal parenchyma, eventually terminating in
death when sufficient numbers of nephron have been damaged.
 Acidosis is the major problem in CRF with development of biochemical
azotaemia and clinical uraemia syndrome.
Etiopathogenesis- All chronic nephropathies can leads to CRF. The diseases
leading to the development of CRF are classified into two major groups-
1) Those causing glomerular pathology, and
2) Those causing tubulo-interstitial pathology.
In the final stage of CRF, all the parts of nephron are involved.

11. 1) Diseases causing glomerular pathology-
Glomerular destruction results in the changes in filtration process and leads
to the development of nephrotic syndrome characterized by proteinuria,
hypoalbuminaemia and edema.
The important chronic glomerular diseases are-
a) Chronic glomerulonephritis,
b) Certain conditions originates outside the renal system but induces the
changes in nephron secondarily such as systemic lupus erythematosus
(SLE), serum sickness nephritis and diabetic nephropathy.

12. 2) Diseases causing tubulo-interstitial pathology-
Damage to the tubulo-interstitial tissue results in alterations in
reabsorption and secretion of important constituents leading to
excretion of large volume of dilute urine. Tubulo-interstitial diseases
categorized according to initiating etiology into the following groups-
a) Vascular causes-
Long lasting primary or essential hypertension produces characteristic
changes in the renal arteries and arterioles referred as nephrosclerosis.
Nephrosclerosis causes progressive renal vascular occlusion terminating in
ischaemia and renal tissue necrosis.

13. b) Infectious causes- Chronic pyelonephritis is an example of chronic
renal infection causing CRF. The progress of chronic renal infection
causes increase in the damage of nephrons leads to CRF.
c) Toxic causes- Some toxic substances induce slow tubular injury,
eventually causes CRF. The most common examples are-
1) intake of high doses of analgesics such as phenacetin, aspirin and
acetaminophen (paracetamol)- causes chronic analgesic nephritis.
2) prolonged exposure of lead, cadmium and uranium also causes CRF.
d) Obstructive causes- Chronic obstruction in the urinary tract leads to
progressive damage to the nephron due to back fluid pressure. The
examples of this type of chronic injury are stones, blood clots,
tumours, strictures and enlarged prostate.

14. Regardless of the initiating cause, CRF evolves progressively through the
four stages-
i) Decreased renal reserve- At this stage, damage to renal parenchyma is
marginal and the kidneys remains functional. The GFR is about 50%
of normal, BUN and creatinine values are normal and the patients
are usually asymptomatic except at times of stress.
ii) Renal insufficiency- At this stage about 75% of functional renal
parenchyma has been destroyed. The GFR is about 25% of the
normal, accompanied by the elevation of BUN and serum creatinine.
Polyuria and nocturia occurs due to tubulo-interstitial damage.
Sudden stress may precipitates uraemic syndrome.

15. iii) Renal failure- At this stage, about 90% of functional renal tissue
has been destroyed. The GFR is approximately 10% of normal.
Tubular cells are essentially non-functional. As a result, sodium
and water regulation is lost resulting in edema, metabolic
acidosis, hypokalaemia, and signs and symptoms of uraemia.
iv) End-stage kidney- The GFR at this stage is less than 5% of
normal and results in complex clinical pictures of uraemic
syndrome with progressive primary (renal) and secondary
systemic (extra-renal) symptoms.

16. Clinical features-
Clinical manifestations of CRF resulting in uraemic syndrome are
described under two main headings-
1) Primary uraemic (renal) manifestations-
Primary symptoms of uraemia develops when there is slow and
progressive deterioration of renal function. The resulting imbalance
causes the following manifestations-
 Metabolic acidosis,
 Hyperkalaemia,
 Sodium and water imbalance,
 Hyperuricaemia,
 Azotaemia

17. 2) Secondary uraemic (extra-renal) manifestations-
Number of secondary extra-renal systemic manifestations develops
secondarily following the fluid-electrolyte and acid-base imbalances.
These includes the followings-
 Anaemia,
 Integumentary system related symptoms,
 CVS related symptoms,
 Respiratory system related symptoms,
 Digestive system related symptoms,
 Skeletal system related symptoms.

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