Page 671 - Textbook of Pathology, 6th Edition

nephritis, membranoproliferative glomerulonephritis, lipoid CLINICAL FEATURES. Clinical manifestations of full- 655
nephrosis (minimal change disease) and anti-glomerular blown CRF culminating in uraemic syndrome are described
basement membrane nephritis. under 2 main headings: primary (renal) uraemic manifes-
ii) Systemic glomerular pathology: Certain conditions originate tations and secondary (systemic or extra-renal) uraemic
outside the renal system but induce changes in the nephrons manifestations.
secondarily. Major examples of this type are systemic lupus A. Primary uraemic (renal) manifestations. Primary
erythematosus, serum sickness nephritis and diabetic symptoms of uraemia develop when there is slow and
nephropathy. progressive deterioration of renal function. The resulting
2. Diseases causing tubulointerstitial pathology. Damage imbalances cause the following manifestations:
to tubulointerstitial tissues results in alterations in 1. Metabolic acidosis. As a result of renal dysfunction, acid-
reabsorption and secretion of important constituents leading base balance is progressively lost. Excess of hydrogen ions
to excretion of large volumes of dilute urine. Tubulointer- occurs, while bicarbonate level declines in the blood, resulting
stitial diseases can be categorised according to initiating in metabolic acidosis. The clinical symptoms of metabolic
etiology into 4 groups: vascular, infectious, toxic and acidosis include: compensatory Kussmaul breathing,
obstructive. hyperkalaemia and hypercalcaemia.
i) Vascular causes: Long-standing primary or essential 2. Hyperkalaemia. A decreased GFR results in excessive
hypertension produces characteristic changes in renal arteries accumulation of potassium in the blood since potassium is
and arterioles referred to as nephrosclerosis (page 687). normally excreted mainly in the urine. Hyperkalaemia is
Nephrosclerosis causes progressive renal vascular occlusion further worsened by metabolic acidosis. The clinical features
terminating in ischaemia and necrosis of renal tissue. of hyperkalaemia are: cardiac arrhythmias, weakness,
ii) Infectious causes: A good example of chronic renal infec- nausea, intestinal colic, diarrhoea, muscular irritability and
tion causing CRF is chronic pyelonephritis. The chronicity flaccid paralysis.
of process results in progressive damage to increasing 3. Sodium and water imbalance. As GFR declines, sodium
number of nephrons leading to CRF. and water cannot pass sufficiently into Bowman’s capsule
iii) Toxic causes: Some toxic substances induce slow tubular leading to their retention. Release of renin from
injury, eventually culminating in CRF. The most common juxtaglomerular apparatus further aggravates sodium and CHAPTER 22
example is intake of high doses of analgesics such as water retention. The main symptoms referable to sodium and
phenacetin, aspirin and acetaminophen (chronic analgesic water retention are: hypervolaemia and circulatory overload
nephritis). Other substances that can cause CRF after with congestive heart failure.
prolonged exposure are lead, cadmium and uranium. 4. Hyperuricaemia. Decreased GFR results in excessive
iv) Obstructive causes: Chronic obstruction in the urinary tract accumulation of uric acid in the blood. Uric acid crystals may
leads to progressive damage to the nephron due to fluid back- be deposited in joints and soft tissues resulting in gout.
pressure. The examples of this type of chronic injury are 5. Azotaemia. The waste-products of protein metabolism
stones, blood clots, tumours, strictures and enlarged prostate. fail to be excreted resulting in elevation in the blood levels
Regardless of the initiating cause, CRF evolves of urea, creatinine, phenols and guanidines causing
progressively through 4 stages: biochemical abnormality, azotaemia. The secondary
1. Decreased renal reserve. At this stage, damage to renal manifestations of uraemia are related to toxic effects of these
parenchyma is marginal and the kidneys remain functional. metabolic waste-products.
The GFR is about 50% of normal, BUN and creatinine values B. Secondary uraemic (extra-renal) manifestations. A The Kidney and Lower Urinary Tract
are normal and the patients are usually asymptomatic except number of extra-renal systemic manifestations develop
at times of stress. secondarily following fluid-electrolyte and acid-base
2. Renal insufficiency. At this stage, about 75% of imbalances. These include the following:
functional renal parenchyma has been destroyed. The GFR 1. Anaemia. Decreased production of erythropoietin by
is about 25% of normal accompanied by elevation in BUN diseased kidney results in decline in erythropoiesis and
and serum creatinine. Polyuria and nocturia occur due to anaemia. Besides, gastrointestinal bleeding may further
tubulointerstitial damage. Sudden stress may precipitate aggravate anaemia.
uraemic syndrome. 2. Integumentary system. Deposit of urinary pigment such
3. Renal failure. At this stage, about 90% of functional renal as urochrome in the skin causes sallow-yellow colour. The
tissue has been destroyed. The GFR is approximately 10% of urea content in the sweat as well as in the plasma rises. On
normal. Tubular cells are essentially nonfunctional. As a evaporation of the perspiration, urea remains on the facial
result, the regulation of sodium and water is lost resulting skin as powdery ‘uraemic frost’.
in oedema, metabolic acidosis, hypocalcaemia, and signs and 3. Cardiovascular system. Fluid retention secondarily
symptoms of uraemia. causes cardiovascular symptoms such as increased workload
4. End-stage kidney. The GFR at this stage is less than 5% on the heart due to the hypervolaemia and eventually
of normal and results in complex clinical picture of uraemic congestive heart failure.
syndrome with progressive primary (renal) and secondary 4. Respiratory system. Hypervolaemia and heart failure
systemic (extra-renal) symptoms. cause pulmonary congestion and pulmonary oedema due