 Maintain homeostasis
By maintaining water,
electrolyte balance, acid-base
regulation and endocrine
Component of urinary system:
1. Kidney: formation of urine
2. Ureter: convey urine from kidney
3. Urinary bladder: Reservoir
4. Urethra: excrete urine from
bladder to exterior
Functions of kidney:
1. Formation of urine: regulate water, electrolyte and acid-base balance
2. Endocrine function:
a. Formation of erythropoietin
b. Conversion of 25 hydroxycholecalciferol to 1, 25
Dihydroxycholecalciferol (active vit D)
c. Secretion of renin
d. Produce prostaglandin
Excretes waste products, e.g., urea, uric acid, creatinine, drugs and
toxic substances from body
4. Degradation of several polypeptide hormones,
Insulin, glucagons, PTH
 Structural and functional unit of kidney.
 About 1 million nephrons in each kidney
1. Glomerulus: Through which large quantity of fluid are
filtered from blood
2. Renal tubules: Filtered fluid is converted into urine. It
a. Bowman’s’ capsule
b. Proximal convoluted tube
c. Descending limb
d. Loop of Henle
e. Ascending limb
f. Distal convoluted tubule
g. Collecting tubule
The filtration that occurs through glomerular capillary - glomerular filtration
How filtration occurs?
It occurs due to effective filtration pressure
1. The force that forces the fluid outward
Glomerular capillary pressure = 60 mmHg
2. The force that opposes movement of fluid outward
Capsular pressure = 18 mmHg
Colloidal osmotic pressure in glomerulus: 32 mmHg
Total +18+32 = 50 mmHg
Effective filtration pressure = Force that forces fluid outward – force that opposes
= (60-50) = 10 mmHg
This 10 mmHg of effective filtration pressure that causes filtration
Amount 180 lit/day
Urine formed is less than 1% of glomerular filtrate
99% of glomerular filtrate is reabsorbed
Composition of glomerular filtrate:
a. It is isotonic to plasma
b. It contains no cellular element
c. It contains about 0.03% protein, about 1/240 the protein in plasma
d. The electrolyte and other solute composition is similar to that of
The quantity of glomerular filtrate formed each minute by all the nephrons of both
kidney is called GFR.
It is about 125 ml/min.
Factors that effect GFR:
A) Major factors:
1. Glomerular capillary pressure: It promotes filtration.
2. Plasma colloidal osmotic pressure: It opposes filtration.
3. Bowman’s capsular pressure: It opposes filtration.
4. Colloidal osmotic pressure of protein in Bowman’s capsule, insignificant.
5. Surface area of filtration.
Glomerular filtration rate:
B) Other factors:
a. Renal blood flow:
b. Constriction of afferent arteriole –
c. Constriction of efferent arteriole:
d. Sympathetic stimulation:
Vasoconstriction of afferent arteriole-- -– decrease GFR
e. Arterial blood pressure:
Increase arterial blood pressure- decrease GFR due to autoregulation
Kidney effectively maintains renal blood flow and GFR relatively
constant over an arterial pressure range between 80-170 mmHg.
This is called auto regulation.
Mechanism of autoregulation of GFR:
•GFR is autoregulated by tubuloglomerular feedback mechanism
•This mechanism has two components that can act together to control GFR.
1. Afferent arteriolar feedback mechanism
2. Efferent arteriolar feedback mechanism
The feedback mechanism depends on “JG complex” especially macula densa.
Autoregulation of GFR:
Formation of urine:
 Mechanism of formation of urine:
Urine formation takes place by the
following three mechanisms:
 1. Formation of glomerular filtrate.
 2. Reabsorption of glomerular filtrate from tubule
 3. Tubular secretion.
Volume: 1000-1500 ml/24 hrs in adult man
Specific gravity: 1.010-1.035
Reaction: Usually slight acidic
PH 4.5-8 (varies on diet)
Color: Yellow due to urochrome
Odor: Aromatic (when fresh)
Ammonical (bacterial decomposition of urea to ammonia)
Obligatory urine volume:
The minimal volume of urine that must be excreted to rid the body waste
products is obligatory volume.
Human kidney can produce a maximal urine concentration of 1200-1400 mosm/l
A normal 70 kg human must excrete about 600 mosmole of solute each day to rid the
body of waste products of metabolism and ion that are ingested.
The minimal volume of urine that must be excreted to rid the body waste products is
If maximal urine concentrating ability is 1200 mosm/l
Obligatory volume = 600 MOSM/day = 0.5 L/day
When there is a water deficit in the body, the kidney forms concentrated urine by
continuing to excrete solute while increasing water reabsorption and decreasing
volume of urine formed.
 Renal failure is a pathological process in which the
functions of the both kidneys is severely
compromised, leading to the accumulation of
metabolic products and disorder of water, electrolyte
and acid base balance and endocrine dysfunction.
 Broadly the causes of renal failure are divided in
to two categories.
1. Renal diseases-
 Glomerulonephritis , pyelonephritis, renal TB,
acute tubular necrosis, polycystic kidney disease.
2. Non-renal diseases
 shock, heart failure, diabetes, hypertension,
atherosclerosis, SLE, drugs and chemicals, calculus,
Basic pathology of renal failure
1. Dysfunction of glomerular filtration
2. Renal tubular dysfunction
3. Renal endocrine dysfunction.
A) Dysfunction of glomerular filtration
The function of glomerulus is to filtration, the first step in the formation
of urine. Its capacity is measured by GFR (glomerular filtration rate). The
following mechanisms may be responsible for decreased GFR.
1. Decreased renal blood flow
In the condition like shock and HF, the CO and BP decreased leading to
decreased blood flow to kidney and decreased GFR.
2. Decreased effective glomerular pressure
Effective glomerular filtration is the driving force to form the GFR, if it is
decreased due to any cause GFR decreases.
Decreased blood pressure renal tubular obstruction, renal interestial
edema causes increased tubular hydrostatic pressure resulting in
3. Decreased glomerular capillary surface area-
inflammation, destruction or removal of kidney
substances causes the surface area to decrease, GN,
basement membrane diseases, nephrectomy all lead to
4. Alteration of permeability: the glomerular
membrane has size barrier and charge barrier.
GN damage the membrane and cause hematuria
B) Renal tubular dysfunction :
Impaired renal Reabsorption, secretion and excretion.
- Ischemia, infection and nephrotoxic drugs damage
the renal epithelial cells.
The function of cells is modified by Aldosterone,
antidiuretic hormone, natriuretic peptide, so presence
or absence of these substance and responsiveness of
renal tubules to these hormones determines the
formation of urine.
1. Dysfunction of PCT
Reabsorption of most of the filtered glucose, AA,
bicarbonate, phosphate, Na occurs in this segment,
so its dysfunction causes, glycosuria, aminoaciduria,
renal tubular acidosis.
2. Dysfunction of Loop of Henle
Ascending loop permeable to Na, Cl but not
permeable to water, main contributor of medullary
hypertonicity and urinary concentration, so
dysfunction causes polyuria, hypotonic urine.
3. Dysfunction of DCT
Aldosterone – may secret H, K, NH3
in exchange of Na, so its dysfunction
cause Na, K and acid base imbalance.
C) Renal endocrine dysfunction
1. RAAS –
 Renin, regulation of circulatory volume, blood
pressure, metabolism of water and sodium.
 Inappropriately activated RAAS causes renal
hypertension, Na and water retention.
2. Erythropoetin – 90% of EPO source.
3. 1, 25 dihydroxycholecalciferol
7- dehydrocholesterol (skin)– hepatic 25
hydroxylation, renal 1 alpha hydroxylation (1, 25
dihydroxy cholecalciferol), it is an active vit-D.
 Calcium imbalance.
4. Kallikrein– Kinin and prostaglandin
 Kallikrein produced by kidney converted in to
bradykinin, synthesize prostaglandin E2, A2.
 It dilates the renal vessels and promote
excretion of Na and water.
5. Parathyroid hormone and gastrin
 kidney deactivates PTH and Gastrin.
 PTH mobilizes calcium and phosphorus
from bone and promotes phosphate
excretion from PCT and DCT.
 In CRF these hormones are not deactivated
causing renal osteodystrophy and peptic ulcer.
Acute renal failure
 Acute kidney injury (AKI) is defined as an
abrupt or rapid decline in renal filtration
 Renal function deteriorates over hours to
 Results in fluid and electrolyte derangement
and retention of normally excreted
substances in the blood
In relation to the nature of onset RF is divided
into Acute and Chronic RF
The pathophysiology, causes, prognosis
and the strategy for management of
acute and chronic RF is different.
Effects of ARF
 Failure of the kidney to excrete
nitrogenous waste products.
 Unable to maintain water and electrolyte
balance and homeostasis.
 Acid base disorder.
- Renal artery occlusion/stenosis
2. Intrinsic renal disease
 Acute tubular necrosis
 Prolonged renal ischemia :
Thrombosis, emboli, vasculitis
 Exposure to nephrotoxic drugs, heavy
metals, and organic solvents
 Intratubular obstruction resulting
 Hemoglobinuria, Myoglobinuria,
or uric acid casts
 Acute renal disease (acute
 3. Post-renal
• Postrenal AKI is a consequence
of urinary tract obstruction.
• This may be related to
• Benign prostatic hyperplasia,
• Kidney stones,
• Bladder stone,
• Bladder, ureteral or renal
Pathogenesis of ARF
The basic changes occurring in ARF are
 Renal hemodynamic alteration
 Renal glomerular injury
 Renal tubular injury
A. Renal hemodynamic alteration
1. Decrease renal perfusion pressure-- renal blood flow loses auto
regulation if systemic BP is less than 80 mmHg.
2. Renal vasoconstriction: during the initial phase of ARF, the symp.
nervous system, RAAS, activated, decrease prostaglandin, kinin,
decrease NO secretion -- causes vasoconstriction mainly of afferent
3. Renal vascular endothelial swelling– renal-ischemia induced
4. Intrarenal DIC
B. Renal glomerular injury
 In intrinsic diseases of renal glomerulus like Acute
glomerulonephritis, glomerular membrane damage
occurs leading to increase pore size, loss of electrical
polarity, and ultimately fibrosis and loss of glomerulus.
 It causes loss of filtration area and ARF.
Renal tubular injury
 Tubuloglomerular feedback
 Regulation of GFR in response to the solute
concentration in distal renal tubule is called
 When PCT and loop of Henle are damaged by
ischemia during the course of ARF, the Na load is
increased and sensed by the macula densa, and
Alteration of metabolism and functions
 The course of ARF is divided into 3
 The oliguric stage
 Diuretic stage
 The recovery phase
The oliguric stage
 Persists days to weeks, significant homeostatic
 it is marked by
1. Urinary alteration
- Oliguria or anuria
- Dilute urine sp. Gr. 1.01-1.02
- Increase urinary Na
- Hematuria, albuminuria, casts
are found in urine.
2. Water intoxication: Oliguria, less removal of water
from the body causes dilutional hyponatraemia,
pulmonary edema and neurological dysfunction
3. Hyperkalaemia – Decreased excretion, leading to VF
and cardiac arrest.
4. Metabolic acidosis: Due to decreased GFR and
decreased secretion of H+, and decreased HCO3
generation causes acidosis.
5. Azotemia- normal BUN is 10-15 mg
 The marked increase of non protein nitrogen (NPN),
eg urea, creatinine and uric acid is called azotemia.
 More protein degradation, less excretion causes it
 This phase can last for 1~3 weeks.
 In Diuretic phase, the urine output in 24 hours can exceed
400 ml and even 2500 ml.
 When diuretic phase starts, as the glomerular filtration rate
does not recover and the concentration ability of renal
tubule is very poor so the urine output is usually very high.
 The levels of urea nitrogen, creatinine and potassium in
blood will increase further.
 Moreover, water and electrolyte disturbance, infections are
also very common in this phase.
The recovery phase
 In recovery phase, the renal tubule grows
again and the glomerular filtration rate
recovers normal as well as the urea
nitrogen level and creatinine level decline
to the normal range.
 Only few go into CRF due to significant
injury to renal epithelium, basement
membrane; leading fibrosis.
 In some of the forms of ARF, the renal
pathological changes are less and oliguric
phase is less marked and urine output is
400- 1000/ day, it is called non-oliguric
 The specific Gravity of urine is low and
fixed and urine sodium is low.
 Have beter prognosis.
How to diagnose
 The clinical history
 The symptoms
 The lab: increased creatinine, BUN,
acidosis, decreased HCO3, urine vol and
casts, sp gr, low sodium content.
1. Polyuria, Oliguria or Anuria, hematuria
5. Flank pain
6. Facial edema
a. Symptomatic azotemia
b. Acidosis (± tachypnea)
c. Mental Status changes
d. Hypervolemia / Hypertension
Most of the patients are asymptomic
Treatment of ARF
 Eliminate the toxic insult
 Hemodynamic support
 Respiratory support
 Fluid management
 Electrolyte management
 Medication dose adjustment
Dialysis or continuous renal replacement therapy
(CRRT) may be indicated when nitrogenous wastes
and the water and electrolyte balance cannot be kept
under control by other means.
Chronic renal failure
 It is the permanent reduction in glomerular
filtration rate (GFR) sufficient to cause sign and
symptoms of organ dysfunctions.
 This is obvious when GFR is below 15 ml/min.
Azotemia - Elevated
 blood urea nitrogen (BUN >28mg/dL) and
 Creatinine (Cr>1.5mg/dL)
• Uremia - azotemia with symptoms or signs of
• Silent phase of CRF; until GFR upto 50 ml/min
• Renal insufficiency; GFR 25-50, polyuric, nocturia,
mild azetomia, anemia.
• Renal failure; GFR 5-25 ml/ min, clinical
evidence of uremia established
• End Stage Renal Disease (ESRD) - GFR < 5
ml/min. uremia requiring transplantation or
• Creatinine Clearance (CCr) - the rate of filtration
of creatinine by the kidney (GFR marker)
 Common Underlying Causes of CRF
a. Diabetes: most common cause ESRD (risk 13x )
b. HTN causes at 23% ESRD cases
c. Glomerulonephritis accounts for ~10% cases
d. Polycystic Kidney Disease - about 5% of cases
e. Rapidly progressive glomerulonephritis (vasculitis) - about 2% of
f. Renal (glomerular) deposition diseases
g. Renal Vascular Disease - renal artery stenosis, atherosclerotic lesion
 Chronic renal results from irreversible
 The pathogenesis is not fully understood.
 There is evidence of progression of renal
failure even if the primary inciting cause
 However it is best tried to explained as
1. Intact nephrone hypothesis
 There is progressive loss of nephrones with remaining
nephrones fully functional.
 As disease advances the amount of solutes to be
excreted does not change, but number of nephrones
 The level of Na and K does not changes until GFR is <5
ml/min and phosphate and urate level remain normal
until GFR is below 20 ml/min.
 According to this hypothesis in the process of adaptation for one
component second component becomes disordered. i.e.
acquires a new lesion.
 The retention of phosphates in CRF reduces the concentration of
Ca++ in blood, there by stimulating the release of PTH.
 The PTH stimulates renal phosphate excretion but at the same
time release Ca from bone and increases Ca reabsorption from
 This can maintain the Ca and phosphate level but develops
parathyroid gland hypertrophy and renal osteodystrophy.
 Thus in correcting one abnormality it acquired other disease.
3. Glomerular hyperfiltration hypothesis
 When the number of nephrones sufficiently reduced, the
functioning single nephrone GFR increases which causes
intraglomerular hypertension and hyperfiltration, this in turn
causes damage to the glomerulus endothelial cells,
activation of platelets, increased protein flux, and decreased
permeability of glomerulus.
 Ultimately it causes sclerosis of glomeruli, atrophy of
tubules and interstitial fibrosis.
 Thus giving continuity to nephrone loss and aggravating
Metabolic and functional alterations
Early polyuria, nocturia, proteinuria, RBC, WBC and
casts. But later oligouria develops.
it is due to compensatory hyperperfusion and
filtration from the intact nephrone, accelerated
motion of fluids -- less chance of reabsorption,
osmotic diuresis, decreased concentration of solute
in the renal interstitium.
- BUN increase
3. Water electrolyte and acid base imbalance
- Volume and salt over load-if used deliberately,
- Causes dehydration and hyponatraemia if restricted.
- If overloaded pulmonary edema, brain edema and heart failure
4. Hyperkalaemia when GFR < 15 ml/min
Results in cardiac arrythemia.
5. Disorders of Mg, Ca and phosphorus
hypermagnesemia, hyperphosphatemia, hypocalcaemia.
6. Metabolic acidosis
7. Renal HTN
8. Renal osteodystrophy
- osteoporosis, osteosclerosis.
9. Haemorrhage , bruising, GI hemorrhage, IC
hemorrhage due to inhibitory effect of
uremic toxin on platelets and deficit of
some coagulation factors.
10. Anemia – normochromic normocytic.
 It is a symptom complex due to accumulation of
uremic toxins in acute and chronic renal failure.
 Different retained products of metabolism, under and
overproduction of different hormones results in
 It is manifested by
1. nervous system- neuropathy, intellectual slow down, or
overt encephalopathy with confusion, stupor and coma.
2.Water electrolyte, acid base, accumulated poisons,,
vascular spasm, hypoxia all contribute for the symptom.
2 Digestive system
Early symptoms: nausea, vomotting,
diarrhea, mucosal ulcerations and
HTN, arrythmia, Cardiac failure.
- Uremic pericarditis and pericardial effusion, it is a leading
cause of death in CRF