Pathophysiology

of
Disorders of Renal system

Dr P Mayurathan
Consultant Physician (Acting)
Anatomy

• The kidneys are bean-shaped organs .

• About 11 cm x 7 cm x 3 cm.

• Vertically they extend between the

T12 to L3 vertebrae.

• Left kidney typically somewhat more

superior in position than the right.

• The upper poles are normally

oriented more medially and posterior
than the lower poles.

• Adrenal gland is located in the upper

pole of each kidney.
 Function

Excretory
Excretion of waste products and drugs
Regulatory
Control of body fluid volume and composition
regulation of electrolytes and acid-base balance
Metabolic
Activation and metabolism of vitamin-D and small molecular proteins
Endocrine
Erythropoietin
Renin
Prostaglandins
 Symptoms and signs of renal disorders
• Anuria/Oliguria/Polyuria • Oedema
• Dysuria • Anaemia
• Haematuria
•
• Scratch marks
Stranguria
• Proteinuria • High blood pressure
• Urgency/hesistancy • Fine lung crepitations
• Nausea • Renal angle tenderness
• Vomiting
• Ballotable kidneys
• Loss of appetite
• Fatigue and weakness
• Sleep problems
• Decreased mental sharpness
• Muscle twitches and cramps
• Periorbital swelling
• Swelling of feet and ankles
• Itching
• Chest pain - Pericarditis
• Shortness of breath
 Congenital anomalies of kidneys
• Normal renal development is dependent upon the interaction between the
ureteric bud and metanephric mesenchyme, which induces organogenesis.

• Nephrogenesis, which starts at 10 weeks of gestation, can be disturbed by

mutations in genes or by environmental factors, such as nutrition during
pregnancy or by some drugs/toxins.

• About 10% of all people are born with potentially significant malformations of the
urinary system.

• Congenital renal disease can be heriditary, but is most often due to an acquired
developmental defect that arises during gestation.
 Congenital anomalies of kidneys

• Renal agenesis

• Hypoplasia of kidney

• Ectopic kidneys

• Horse-shoe kidneys

• Polycystic kidney disease

Renal agenesis
 Renal agenesis
• One (Unilateral Renal Agenesis - URA) or both (Bilateral renal Agenesis -
BRA) fetal kidneys fail to develop.

• Occur in less than one percent of births annually.

• Between one in 450 and one in 1,000 newborns has URA.

• BRA occurs in about one in 3,000 births.

• Both URA and BRA occur when the ureteric bud fails to develop at an early
stage of fetal growth.

• In URA, compensatory hypertrophy occurs in opposite kidney and it causes

progressive glomerular sclerosis in some patients.
 Risk factors for Renal agenesis
• Babies born with a single umbilical artery and caudal regression syndrome have a
higher risk of URA.

• Those who have a parent or sibling with either URA or BRA also have an
increased chance of developing URA.

• Prenatal Risk factors:

– diabetes mellitus
– black race
– younger maternal age
– consumption of alcohol during pregnancy.

• Some drugs:
– Retinoids
– Thalidomide
– Arsenates
– cocaine
 Clinical features of Renal agenesis
• Both types of renal agenesis are associated with organ abnormalities.

• The most commonly affected area is the respiratory system and it causes
ologohydramniosis.

• Defects also occur in the digestive, genital, cardiac and musculoskeletal

systems.

• Newborns affected with BRA typically have distinct features that include:
– widely separated eyes with skin folds over the upper eyelids
– Low set ears
– a nose that is pressed flat and broad
– a receding chin
– limb defects
 Clinical features of Renal agenesis
• Babies born with URA may not have any symptoms at birth.

• Symptoms of URA may not be present until later in life.

• They include:
– Haematuria
– Proteinuria
– High blood pressure
– Reduced glomerular filtration rate (GFR)
– Swelling in the face, hands or legs
– Developmental defects in the inner ear, genital tract, head and
vertebrae
 Renal agenesis - Investigation
• Renal agenesis is typically found during routine prenatal ultrasounds.

• When URA/BRA is identified, prenatal MRI can be used to confirm the

complete absence of kidneys.

• Once diagnosed, patients of any age with URA need to have their blood
pressure, urine and other renal functions tested annually to ensure the
health of the remaining kidney.
 Renal agenesis – Treatment
• BRA is not compatible with life outside the uterus.

• The condition is typically fatal within the first few days of life.

• Newborns usually die from underdeveloped lungs shortly after birth.

• Some newborns with BRA survive. They need long term dialysis to replace
renal function.

• Factors such as lung development, overall health, and family support

determine the success of this treatment.

• The goal is to sustain these infants with dialysis until they grow strong
enough to have a kidney transplant.
Hypoplasia of kidney
 Hypoplasia of kidney
• Characterized by a reduction in the number of nephrons leading to a small
overall kidney size.

• It can affect one kidney (unilateral renal hypoplasia) or both kidneys

(bilateral renal hypoplasia).

• Renal hypoplasia is relatively common – it is estimated that one baby in a

few hundred is born with a small kidney.

• But, true renal hypoplasia is extremely rare and most cases probably
represent acquired scarring due to vascular, infectious or other
parenchymal diseases.
 Risk factors for Renal hypoplasia

• There is no specific causes or risk factors.

• It is unlikely that a future pregnancy will result in renal hypoplasia or other

problems with the kidneys.

• Sometimes, renal hypoplasia is thought to be another type of problem

with the kidney(s).
– Renal dysplasia – one or both kidneys are smaller than usual, but have
also not developed properly and may have cysts.
– Multicystic dysplastic kidney (MCDK) – a more severe form of renal
dysplasia. The whole of the affected kidney is a bundle of many cysts
and does not work.
– Reflux nephropathy – scars on the kidney.
 Clinical features of Renal hypoplasia
• Unilateral renal hypoplasia does not have any long-term problems and
does not need special treatment. However, they may be at risk of urinary
tract infections and/or hypertension later in life.

• Bilateral renal hypoplasia is more serious. Some babies have no immediate

complications. All children with bilateral renal hypoplasia need monitoring,
as some may go on to develop renal failure.

• All need regular blood pressure, urine and other renal functions tests and
follow up.
 Renal hypoplasia - Investigation
• Renal hypoplasia may be diagnosed at the 20 week antenatal ultrasound
scan or soon after birth.

• It may also be picked up in an older child who has some symptoms.

Ectopic kidneys
 Ectopic kidneys
• ectopic kidney is a birth defect in which a kidney is located below, above, or
on the opposite side of its usual position.

• About one in 900 to 1000 people has an ectopic kidney.

• During fetal development, a baby’s kidneys first appear as buds inside the
pelvis, near the bladder. As the fetal kidneys develop, they climb gradually
toward their normal position near the rib cage in the back.

• Sometimes, one of the kidneys remains in the pelvis or stops moving before
it reaches its usual position.

• In other cases, the kidney moves higher than the usual position.

• one may cross over so that both kidneys are on the same side of the body.
When a crossover occurs, the two kidneys often grow together and become
fused.
May remain in the pelvis, near Cross over and become fused
the bladder with the other kidney
 Ectopic kidneys

• Factors that may lead to an ectopic kidney include:

– poor development of a kidney bud

– a defect in the kidney tissue responsible for prompting the

kidney to move to its usual position

– genetic abnormalities

– the mother being sick or being exposed to an agent, such as a

drug or chemical, that causes birth defects
 Clinical features of Ectopic kidneys
• An ectopic kidney may not cause any symptoms usually and may function
normally.

• Incidental finding in many people - tests done for other reasons.

• Sometimes, a health care provider may discover an ectopic kidney after

feeling a lump in the abdomen during an examination.

• In other cases, an ectopic kidney may cause abdominal pain or urinary

problems.
 Complications of Ectopic kidney
• Possible complications are due to problems with urine drainage
from that kidney.

• Sometimes, urine can even flow backwards from the bladder to the
kidney, a problem called vesicoureteral reflux (VUR).

• Abnormal urine flow and the placement of the ectopic kidney can
lead to various problems:
– Infections
– Stones - such as calcium and oxalate
– Urinary tract obstruction and kidney damage
– Trauma - may be susceptible to injury from blunt trauma
 Ectopic kidneys - Investigations
• Ultrasound scan

• Intravenous pyelogram (IVP)

• Micturating cystourethrogram (MCUG)

• Radionuclide scan

• Magnetic resonance imaging (MRI)

 Ectopic kidneys – Treatment
• No treatment for an ectopic kidney is needed if urinary function is normal
and no blockage of the urinary tract is present.

• If tests show an obstruction, surgery may be needed to correct the position

of the kidney to allow for better drainage of urine.

• Reflux can be corrected by surgery to alter the ureter.

• If extensive kidney damage has occurred, surgery may be needed to

remove the kidney.
Horse-shoe kidneys
 Horse-shoe kidneys
• Most common type of renal fusion anomaly.

• It consists of two distinct functioning kidneys on each side of the midline,

connected at the lower poles by an isthmus of functioning renal
parenchyma or fibrous tissue that crosses the midline of the body.

• occur in 1 per 400-800 live births.

• Twice as common in males as in females.

• 90% - fused at the lower pole.

• 10% - fused at the upper pole.

 Etiology of Horse-shoe kidneys
• Mechanical fusion is formed during organogenesis, when the inferior
poles of these early kidneys touch, fusing in the lower midline. The theory
of mechanical fusion is valid for horseshoe kidneys with a fibrous isthmus.

• Abnormal fusion of tissue associated with the parenchymatous isthmus of

some horseshoe kidneys is the result of a teratogenic event involving the
abnormal migration of posterior nephrogenic cells, which then coalesce
to form the isthmus.

• This teratogenic event may also be responsible for the increased

incidence of related congenital anomalies and of certain neoplasias, such
as Wilm’s tumor and carcinoid tumor associated with the isthmus of the
horseshoe kidney.
 Horse-shoe kidneys

• By itself, the horseshoe kidney does not produce symptoms.

• However, by its embryogenesis and anatomy, it is predisposed to a higher

incidence of disease than the normal kidney.

• The variable blood supply, presence of the isthmus, high insertion point,
and abnormal course of the ureters all contribute to these problems.
 Complications of Horse-shoe kidneys
• Ureteropelvic junction (UPJ) obstruction - Obstruction is due to the high
insertion of the ureter into the renal pelvis. Most common association. It
can cause hydronephrosis.

• Stone formation - Due to the associated hydronephrosis or UPJ

obstruction.

• Infection - Urinary stasis and stone disease. Ascending infection from

vesicoureteral reflux is another cause of infection.

• Cancers - Due to teratogenic factors present at birth. Renal cell carcinoma

(45%) is the most common. Others are transitional cell cancer (20%) and
sarcoma (7%). Wilms tumor accounts for 28% of malignant lesions. The
relative risk of Wilms tumor is increased 2-fold and half from the isthmus.
The relative risk of a carcinoid tumor in a patient with a horseshoe kidney
is 62 times of the normal population.
Clinical features of Horse-shoe kidneys
• Nearly one third of patients with a horseshoe kidney remain
asymptomatic, and the horseshoe kidney is an incidental finding during
radiological examination.

• Physical examination may reveal a midline lower-abdominal mass.

• Symptoms are usually due to obstruction, stones or infection.

 Horse-shoe kidneys - Investigations
• CT scan

• Abdominal and pelvic CT scanning or renal ultrasonography is helpful to

screen for the presence of stones, masses, or hydronephrosis.
 Horse-shoe kidneys - Treatment
• Surgery – may be needed for Ureteropelvic junction (UPJ) obstruction,
stones or tumours.

• Infections may need treatment.

• Horseshoe kidneys can be used for transplantation. They can be

transplanted into a single recipient or can be divided and transplanted into
two individuals.