The Kidney and anatomy and pathophysiology

Kidney pathology

1. The Kidney and
Lower Urinary Tract -I
DrA. Rapsang

3. Concentration test •An artificial fluid deprivation is induced in the p atient
for more than 20 hours.
•If the nephron is normal, water is selectively
reabsorbed resulting in excretion of urine of high
solute concentration
•However, if the tubular cells are nonfunctional, th e
solute concentration of the urine will remain
constant regardless of stress of water deprivation.

4. Dilution test •An excess of fluid is given to the patient.
•Normally, renal compensation should result in
excretion of urine with high water content and lowe r
•If the renal tubules are diseased, the concentratio n
of solutes in the urine will remain constant
irrespective of the excess water intake.

5. Blood chemistry. •Impairment of renal function results in elevation o f
end-products of protein metabolism.
•Urea -
normal range 20-40 mg/dl
•Blood urea nitrogen (BUN)
-normal range 10-20
mg/dl
•Creatinine
-normal range 0.6-1.2 mg/dl
•An increase of these end-products in the blood is
called azotaemia.
•‘uraemia’ is defined as association of these
biochemical abnormalities with clinical signs and
symptoms.

6. Creatinine clearance test •The clearance of creatinine is determined by
collecting urine over 24-hour period
•A blood sample is withdrawn during the day.
•This test is routinely employed method of estimatin g
GFR.

7. Diseases of the kidneys are divided into 4 major gr oups •Glomerular diseases:
Often immunologically-
mediated
–Acute
–Chronic.
•Tubular diseases:
Often caused by toxic or infectious
agents and are often acute.
•Interstitial diseases:
Commonly due to toxic or
infectious agents
•Vascular diseases •Others
–Congenital anomalies
–Obstructive uropathy(including urolithiasis)
–Tumoursof the kidneys.

8. Acute Renal Failure (ARF)

9. •Acute renal failure (ARF) is a syndrome characteris ed
by
–Rapid onset of renal dysfunction
•Oliguria or anuria
–Sudden increase in metabolic waste-products in
the blood
•Urea
•Creatinine
–Development of uraemia.

10. Etiopathogenesis. •Pre-renal causes.
Pre-renal diseases are those which
cause sudden decrease in blood flow to the nephron.
–Inadequate cardiac output
–Hypovolaemia
–Vascular disease causing reduced perfusion of the kidneys.
•Intra-renal causes.
Disease of renal tissue itself.
•Post-renal causes.
Caused by obstruction to the flow
of urine anywhere along the renal tract distal to t he
opening of the collecting ducts.
–Mass within the lumen/wall of the tract
–External compression anywhere along the lower urinary
tract—ureter, bladder neck or urethra.

11. Clinical features.
Depend to a large extent on the underlying cause of
ARF and on the stage of the disease at which the
patient presents.
•Syndrome of acute nephritis. •Extensive proliferation of epithelial cells in the
glomeruli → decrease in GFR.
–Mild proteinuria
–Haematuria
–Edema
–Mild hypertension.
•E.g., Acute post-streptococcal glomerulonephritis

12. •Syndrome accompanying tubular pathology
.
•Destruction of the tubular cells of the nephron
•E.g., Acute tubular necrosis
•The disease typically progresses through 3 characte ristic
stages from oliguria → diuresis → recovery.
•Oliguricphase:
–First 7 to 10 days
–Urinary output < 400 ml/day.
–Accumulation of waste products
•Azotaemia
•Metabolic acidosis
•Hyperkalaemia
•Hypernatraemia
•Hypervolaemia
•Pulmonary oedema.

13. •Diuretic phase: •With the onset of healing of tubules, there is
improvement in urinary output.
•Urine is of low specific gravity.
•Phase of recovery:
•Full recovery with healing of tubular epithelial ce lls
•Death occurs in 50% cases

14. •Pre-renal syndrome. •ARF occurring secondary to disorders in which
neitherthe glomerulus nor the tubules are damaged
•E.g., Renal arterial obstruction
–Hypovolaemia
–Hypotension
–Cardiac insufficiency.
–Oliguria
–Azotaemia
–Fluid retention and oedema.

15. Chronic Renal Failure (CRF)

16. •Chronic renal failure is a syndrome characterisedby
progressive and irreversible deterioration of renal
function due to slow destruction of renal
parenchyma
Etiopathogenesis.
•Diseases causing glomerular pathology
.
–Primary glomerular pathology
•Chronic glomerulonephritis
–Systemic glomerular pathology
•SLE
•Diabetic nephropathy.

17. •Diseases causing tubulointerstitialpathology. •Vascular causes
–Long-standing hypertension
•Infectious causes
–Chronic pyelonephritis.
•Toxic causes:
–Intake of high doses of analgesics
–Other substances -lead, cadmium and uranium.
•Obstructive causes
–Stones, blood clots, tumours, strictures and enlarged
prostate.

18. CRF evolves progressively through 4 stages:
•Decreased renal reserve.
–Damage to renal parenchyma is marginal and the kidneys
remain functional.
–The GFR is about 50% of normal
–BUN and creatinine are normal
–Patients are usually asymptomatic
•Renal insufficiency.
–75% of functional renal parenchyma has been destroyed.
–The GFR is about 25% of normal
–Elevation in BUN and serum creatinine.
–Polyuria and nocturia

19. •Renal failure.
–90% of functional renal tissue has been destroyed.
–The GFR is approximately 10% of normal.
–Regulation of sodium and water is lost -oedema,
metabolic acidosis, hypocalcaemia, and signs and
symptoms of uraemia.
•End-stage kidney.
–The GFR at this stage is less than 5% of normal
–Uraemicsyndrome
–Progressive primary (renal) and secondary systemic (extra-
renal) symptoms.

20. Clinical features.
Uraemicsyndrome
•Primary uraemic(renal) manifestations.
–Metabolic acidosis -Kussmaulbreathing,
hyperkalaemiaand hypercalcaemia.
–Hyperkalaemia-cardiac arrhythmias, weakness,
nausea, intestinal colic, diarrhoea, muscular
irritability and flaccid paralysis.
–Sodium and water imbalance -hypervolaemiaand
circulatory overload with congestive heart failure.
–Hyperuricaemia-gout.
–Azotaemia.

21. •Secondary uraemic(extra-renal) manifestations.
–Anaemia–due to decreased production of
erythropoietin
–Integumentary system
•Deposit of urinary pigment such as urochromein the skin
causes sallow-yellow colour.
•The urea content in the sweat rises. On perspiration, urea
remains on the facial skin as powdery ‘uraemicfrost’.
–Cardiovascular system
•Fluid retention
–Congestive heart failure.
–Respiratory system
•Pulmonary congestion
•Pulmonary oedema

22. –Digestive system.
•Mucosal ulcerations
•Gastrointestinal irritation -nausea, vomiting and
diarrhoea.
–Skeletal system -renal osteodystrophy
•Osteomalacia-deficiency of vitamin D (which is
normally activated by the kidney)
•Osteitisfibrosa- due to elevated levels of
parathormone→ mobilisescalcium from bone →
hypercalcaemia→ deposits of excess calcium salts in
joints and soft tissues and weakening of bones (renal
osteodystrophy).

23. CONGENITAL MALFORMATIONS

24. Malformations of the kidneys are classified into 3 broad
groups:
•Abnormalities in amount of renal tissue.
–Renal hypoplasia
–Renomegaly
•Anomalies of position, form and orientation.
–Renal ectopia(pelvic kidney)
–Renal fusion (horseshoe kidney)
–Persistent foetallobation.
•Anomalies of differentiation.
–Cystic diseases of the kidney

25. CYSTIC DISEASES OF KIDNEY
•Cystic lesions of the kidney may be
–Congenital or acquired,
–Non-neoplastic or neoplastic.
•Majority of these lesions are congenital non-
neoplastic.
•Cystic lesions can occur at any age
•Their usual clinical presentation may include:
–Abdominal mass
–Infection
–Respiratory distress (due to accompanied pulmonary
hypoplasia)
–Haemorrhage
–Neoplastic transformation.

27. Polycystic Kidney Disease
•Major portion of the renal parenchyma is
converted into cysts of varying size.
•The disease occurs in two forms:
•An adult type - inherited as an autosomal
dominant disease
•An infantile type -inherited as an autosomal
recessive disorder.
•Adult polycystic kidney disease •Always bilateral and diffuse.
•Though the kidneys are abnormal at birth, renal
function is retained
•Symptoms appear in adult life, mostly between
the age of 30 and 50 years.

28. Grossly •Bilaterally enlarged, usually
symmetrical
•Heavy (weighing up to 4 kg)
•Lobulated appearance
Cut surface
•Cysts throughout the renal
parenchyma
•Varying sizes
•Cysts contents vary from
clear straw-yellow fluid to
reddish-brown material.
•Renal pelvis and calyces are
distorted by the cysts
•Cysts do not communicate
with the pelvis of the kidney

29. Histologically •Some cysts contain glomerular tufts
•Some cysts have epithelial lining
•The intervening tissue between the cysts shows
some normal renal parenchyma.
•There can be fibrosis and chronic inflammation

30. Clinical features.
•Commonly manifests in 3rd to 5th decades of life.
•Dull-ache in the lumbar region
•Haematuria
•Renal colic
•Hypertension
•Urinary tract infections
•Progressive CRF
–Polyuria
–Proteinuria.
•Other associated congenital anomalies seen less
frequently are cysts in the pancreas, spleen, lungs
and other organs.

31. Infantile polycystic kidney disease
•Less common
•Bilateral.
•The age at presentation may be perinatal, neonatal,
infantile or juvenile

32. Grossly •Kidneys are bilaterally
enlarged
•Smooth external surface
•Retain normal reniform
shape.
Cut surface
•Small, fusiform or
cylindrical cysts radiating
from the medulla and
extend radially to the
outer cortex.
•“sponge-like” appearance
•Pelvis, calyces and ureters
are normal.

33. Histologically •The total number of nephrons is normal.
•Since the cysts are formed from dilatation of
collecting tubules, all the collecting tubules show
cylindrical or saccular dilatations and are lined b y
cuboidal to low columnar epithelium.
•Many of the glomeruli are also cysticallydilated.

34. Clinical features.
•Depend on age of the child.
•In severe form, the gross bilateral cystic renal
enlargement -interfere with delivery.
•In infancy, renal failure may manifest early.
•Almost all cases of infantile polycystic kidney dis ease
have associated multiple epithelium -lined cysts in
the liver or proliferation of portal bile ductules.
•In older children -congenital hepatic fibrosis
–Portal hypertension
–Splenomegaly.

35. Assignment
•Short notes on
–Kidney function tests
–Dilution and concentration tests
–Creatinine clearance test
–Uraemicsyndrome
•Define
–Azotemia
–Uraemia
•Definition, etiopathogenesisand clinical features o f
–ARF
–CRF
•Pathological and clinical features of Polycystic ki dney
disease