Kidney Disorders

Alemwosen T(MD,Pathologist)
 Function
Regulation of water & electrolyte balance
Regulation of acid-base balance
Excretion of metabolic waste products & foreign
chemicals
Regulation of arterial pressure
Regulation of erythrocyte production
Production of 1,25-dihydroxy vit D3
 Kidney is made of
Cortex
Medulla
 The basicunit of the kidney is the nephron
Each comprises a glomerulus connected to
a tubule
Blood vessels
Glomeruli consisting of anastomosing network of capillaries
lined by fenestrated endothelium invested by two layers of
epithelium
The glomeruli capillary wall consists of the following
structures
Thin layer of fenestrated endothelium
Glomerular basement membrane
consisting of collagen type IV, laminin, proteoglycans , fibronectin, entacin
& other glycoprotein
Visceral epithelial cells (podocytes)
the adjacent foot processes are separated by filtration diaphragm
Mesangial cells
lie b/n capillaries & have contractile, phagocytic & supportive function
are also capable of proliferating & secreting biologically active mediators
 Major characterstics of glomerular filtration
Highly permeable to water & small solutes
Impermeability to proteins discriminating among
various protein molecules depending on their
charge & size
 Juxtaglomerular apparatus
The juxtaglomerular cells
modified smooth muscle cells in the media of afferent
arterioles & secret renin
Macula densa
special region of distal tubules & it is sensor that controls
the release of renin in response to sodium concentration of
the tubular fluid of each individual nephron
Tubules
Proximal convulated tubule
Descending & ascending limb of loop of
Henle
Distal convulated tubule
The collecting ducts
 Interstitium
consists of fenestrated peritubular capillaries
& small number of fibroblast like cells
 Pathology
In general diseases of the kidney are classified into
those that affect the four basic morphologic
components
Glomeruli
Tubules
Interstitium
Blood vessels
Clinical manifestations of renal diseases
Azotemia
Biochemical abnormality that refer to an elevation of the
BUN & creatinine levels
Related to decreased GFR
Q.Why is creatinine level used as a reliable marker of GFR?
Causes
Prerenal
hypoperfusion of the kidneys (eg. shock)
Renal
Postrenal
occurs when urine flow is obstructed below the level of the kidney
Uremia
When azotemia is associated with clinical symptoms &
signs
Uremia is also characterized by a host of
metabolic and endocrine alterations incident to
renal damage
Secondary gastrointestinal (e.g., uremic
gastroenteritis), neuromuscular (e.g., peripheral
neuropathy), and cardiovascular (e.g., uremic
fibrinous pericarditis) involvement may be seen
Syndromes
Acute nephritic syndrome
A glomerular syndrome dominated by
The acute onset usually of grossly visible hematuria (red
blood cells in urine)
Mild to moderate proteinuria
Hypertension
Diffuse edema specially in periorbital area
It is a classic presentation of poststreptococcal
glomerulonephritis
The nephrotic syndrome
It is characterized by
o Heavy proteinuria (more than 3.5gm/day)
o Hypoalbuminemia
o Severe edema
o Hyperlipedemia
o Lipiduria
 NB:Asymptomatic hematuria or proteinuria
or combination of these two, is usually a
manifestation of subtle or mild glomerular
abnormalities
 Acute renal failure
Implies a rapid & frequently reversible deterioration
of renal function
Acute renal failure is dominated by oliguria or anuria
with recent onset of azotemia
Can result from glomerular, interstitial or vascular
injury or acute tubular necrosis
 Chronic renal failure
It characterized by prolonged symptoms &
signs of uremia
End result of all chronic parenchymal diseases
The most important causes include
diabetes mellitus
hypertension &
glomerulonephritis
 Chronic renal failure progresses through four
stages that merge into one other
1. Diminished renal reserve
GFR is about 50% of normal
Serum BUN & creatinine values are normal, &
the patients are asymptomatic
2. Renal insufficiency
GFR is 20% to 50% of normal
Azotemia appears
usually associated with anemia & hypertension
3. Renal failure
GFR is less than 20% to 25% of normal
the kidneys can not regulate volume & solute
composition & patients develop edema, metabolic
acidosis & hypocalcemia. Overt uremia may ensue.
4. End-stage renal disease
GFR is less than 5% of normal
this is the terminal stage of uremia
Renal tubular defects
dominated by polyuria (excessive urine formation),
nocturia, & electrolyte disorders (eg metabolic
acidosis)
are the result of either diseases that directly affect
tubular structure or defects in specific tubular
functions
 Urinary tract infection
characterized by bacteriuria & pyuria (bacteria &
leukocytes in the urine)
the infection may be asymptomatic or
symptomatic
it may affect the kidney (pyelonephritis) or the
bladder (cystitis).
Nephrolithiasis (renal stone)
Manifest by renal colic, hematuria, & recurrent
stone formation.
 Congenital anomalies
About 10% of all people are born with
potentially significant malformations of the
urinary system
Agenesis of the kidney
Total bilateral agenesis is incompatible with life
Unilateral agenesis is uncommon anomaly but is
compatible with normal life
The opposite kidney is usually enlarged as a
result of compensatory hypertrophy later
leading to chronic renal failure
Hypoplasia
Refers to failure of the kidneys to develop into a
normal size
May occur bilaterally but is more commonly
unilateral
A truly hypoplastic kidney shows no scars & has a
reduced number of renal lobes & pyramids
Ectopic kidneys
May be found at abnormally low levels
They are usually normal
B/c of their abnormal position, kinking or tortuosity of the
ureters may cause some obstruction to urinary flow which
predisposes to bacterial infections
Horseshoe Kidneys
Fusion of the upper or lower poles of the kidneys produces
a horseshoe - shaped structure that is continuous across
the midline anterior to the great vessels
found in about 1 in 500 to 1000 autopsies
90% of such kidneys are fused at the lower pole, & 10% are
fused at the upper pole
Cystic Diseases of the Kidney
heterogenous group comprising hereditary,
developmental & acquired disorders
Cystic renal dysplasia
sporadic disorder is due to an abnormality in
metanephric differentiation
characterized histologicaly by the persistence in the kidney
of abnormal structures cartilage, undifferentiated
mesenchyma, & immature collecting ductules & by abnormal
lobar organization
Dysplasia can be unilateral or bilateral & is almost always
cystic
In gross appearance, the kidney is usually enlarged &
multicystic
Autosomal-Dominant (adult) Polycystic Kidney
Disease
Inherited autosomal dominant trait
Commonest form of congenital cystic disease
The kidneys contain bilateral large number of cysts
which enlarge throughout life & destroy the renal
parenchyma & cause renal failure
50% of patients develop HTN or uremia in fourth
or fifth decade of life
 Adult Polycystic Kidney Disease .ctd
In 90% of families, PKD1, the defective gene, is on the
short arm of chromosome 16
This gene encodes a large and complex cell membrane-
associated protein, called polycystin-1, that is mainly
extracellular
The polycystin molecule has regions of homology to
proteins known to be involved in cell-cell or cell-matrix
adhesion
It is thought that the resultant defects in cell-matrix
interactions may lead to alterations in growth,
differentiation, and matrix production by tubular
epithelial cells and to cyst formation
The PKD2 gene, implicated in 10% of all cases
 Morphology of Adult PKD
The kidneys may achieve enormous size, and weights of
up to 4 kg for each
On gross examination the kidney seems to be composed
solely of a mass of cysts of varying sizes up to 3 or 4 cm
in diameter with no intervening parenchyma
Microscopic examination reveals some normal
parenchyma dispersed among the cysts
Cysts may arise at any level of the nephron, from tubules
to collecting ducts.
 Clinical Course OF PKD
In adults usually does not produce symptoms until the fourth
decade, by which time the kidneys are quite large
The most common complaint of the patient is flank
pain or at least a heavy, dragging sensation.
Sometimes attention is first drawn to the lesion by
palpation of an abdominal mass
Clinical Course OF PKDctd
The most important complications are hypertension and
urinary infection
Hypertension of varying severity develops in about 75% of
patients
End-stage renal failure occurs at about age 50, but there is
wide variation in the course of this disorder
Those who develop renal failure are treated by renal
transplantation. Death usually results from uremia or
hypertensive complications
Pateints with PKD tend to have extrarenal anomalies such as
Polycytic liver disease
Asymptomatic liver cysts occur in one third of patients
Intracranial berry aneurysm
Saccular aneurysms of the circle of Willis are present in 10% to
30% of patients, and these individuals have a high incidence of
subarachnoid hemorrhage
Mitral valve prolapse
Autosomal-Recessive (Childhood) Polycystic
Kidney Disease
Inherited in an autosomal recessive pattern, giving a 25%
recurrence risk for parents having subsequent children
The kidneys are affected bilaterally, so that in utero, there is
typically oligohydraminos because of poor renal function and
failure to form significant amounts of fetal urine
The most significant result from oligohydramnios is
pulmonary hypoplasia, so that newborns do not have
sufficient lung capacity to survive, irrespective of any attempt
to treat renal failure
 Childhood Polycystic Kidney Disease..ctd
Grossly, the kidneys are markedly enlarged and tend
to fill the retroperitoneum and displace abdominal
contents
The kidneys tend to be symmetrically enlarged
The cysts are quite small and uniform, perhaps 1 to 2
mm on average
 Childhood Polycystic Kidney Disease..ctd
Microscopically, the characteristic finding in the
later third trimester is cystic change of collecting
tubules with the cysts elongated and radially
arranged
The few remaining glomeruli are not involved by
the cysts
 A helpful finding at autopsy is the presence of
congenital hepatic fibrosis, which accompanies
RPKD
Simple cysts
occur as multiple or single
usually cortical cystic spaces that vary widely in
diameter
commonly 1 to 5cm in diameter
usually postmortem finding without clinical
significance