BS6051 SYSTEMS PATHOLOGY TUTORIAL 4 – RENAL DISORDERS

1. What are the functions of the renal system?

The main function of the kidneys is the production of urine, allowing the excretion of waste products, the maintenance of extracellular fluid volume, and the control of acid balance (excretion of H+ ions).

The kidneys also have an endocrine function, producing the hormones renin (regulation of blood pressure via the renin-angiotensin-aldosterone system), erythropoietin (red blood cell production) and calcitriol (active form of vitamin D--> calcium absorption across intestinal epithelium).

2. Complete the following table indicating the normal composition of filtrate (fluid within renal tubular system) and urine.

BS6051 SYSTEMS PATHOLOGY TUTORIAL 4 – RENAL DISORDERS

Substance Amount in filtrate (g) Amount in urine (g)Na+ 600 6K+ 35 2Ca2+ 5 0.2Glucose 200 0Urea 60 35Albumin 0 0 3. Glomerular function is used to assess renal function and in turn diagnose renal impairment/failure. a) Provide the names of two metabolites measured in plasma that can be used to measure glomerular function, and discuss how reliable an indicator of renal function they are.

Creatine is a substance derived from the turnover of creatine phosphate in muscle, a store of high energy phosphate. The amount of creatine produced is related to muscle mass and remains remarkably constant in an individual subject from day to day.

Creatine is a useful indicator of glomerular function beacuse it is freely filtered by the glomerulus but not reabsorbed by the tubules back into the blood. Thus a raised plasma creatine level is indicative of impaired renal function. However, the main drawback with creatine is that the glomerular filtration rate (GFR) needs to drop by at least 50% before the plasma creatine levels increase above normal levels. Thus, a normal creatine plasma level may not necessarily imply normal renal function.

Plasma urea concentration is also often measured along with creatine as an indicator of renal function. However urea does not give as accurate an indication of renal function as creatine. This is because urea, although filtered by the glomerulus, undergoes significant tubular reabsorption by passive diffusion back into the blood. This is more apparent in fluid depleted patient s whose GFR is low where the tubular reabsorption of urea increases. Thus, plasma urea concentration may be increased in patients with normal renal function, particularly if they are fluid-depleted.

b) What is the clinical significance of hyperkalaemia?

Hyperkalaemia (a plasma potassium ion concentration above 6mmol/l due to the inability of the kidney to excrete K+ ions) is a symptom of acute renal failure. Hyperkalaemia is a potentially life-threatening state as it reduces the threshold for initiation of action potentials and disturbs the normal electrical conducting system of the heart, potentially resulting in cardiac arrest due to severe arrhythmia.

c) What urinalysis results could indicate renal disease?

Proteinuria (albumin within urine, indicative of glomerulopathies caused by deposition of material within the glomerulus, such as immune complexes (Goodpasteur’s syndrome, SLE, IgA nephropathy) or glomerulosclerosis associated with diabetes and deposition of amyloid protein fibrils (amyloidosis).

Haematuria (presence of haemoglobin within urine, indicative of glomerulopathies as with proteinuria).

Presence of crystals (e.g. calcium oxolate) within urine, indicative of kidney stones

Presence of nitrites is indicative of bacterial infection.

Presence of white blood cells (pyuria) indicative of a urinary tract infection

4. Which autoimmune diseases can involve damage to the renal system?

BS6051 SYSTEMS PATHOLOGY TUTORIAL 4 – RENAL DISORDERSGoodpasture’s syndrome – auto-antibodies against glomerular basement membrane proteins, leading to deposition of IgG immune complexes within glomerulus and associated inflammation --> proteinuria and haematuria

IgA nephropathy is the most common glomerular disease and involves the deposition if IgA immune complexes within the mesangium (a structure within the glomerulus) and accompanied by proliferation of mesangial cells (mesangioproliferative glomerulopathy) and inflammation with resultant proteinuria and haematuria. Can occur following pharyngitis and normally resolves quickly, but can be progressive in some patients leading to chronic renal failure over many years.

Systemic autoimmune diseases involving circulating immune complexes (e.g. sytemic lupus srythematosus) result in glomerulopathy as a result of the deposition of such immune complexes within the glomerular membranes.

5. Acute renal failure

a) What is acute renal failure, and what are the most common causes?

Acute renal failure occurs when both kidneys stop working over a period of hours to days. It most often occurs in a patient who is already very unwell in hospital.

There are many causes of acute renal failure, and they are broken down into:

‘Pre-renal’ failure, Caused by hypo-perfusion of the kidneys, i.e. insufficient blood reaches the kidneys to produce enough urine to clear waste. A risk in any patient with shock,

‘Renal’ acute failure, Caused by massive damage to the kidney itself, e.g. acute tubular necrosis (caused by prolonged pre-renal failure), glomerular injury, interstitial nephritis, hypertensive emergency, infection

‘Post-renal’ failure, Obstruction within the renal tract needs to be ruled out early in diagnostic investigation, as can be easily treated with considerable impact on recovery.

b) What is the indicative clinical sign of acute renal failure, and how is its diagnosis confirmed?

The onset of acute renal failure is usually indicated by oliguria (the passing of small volumes of urine).

Diagnosis confirmed by metabolic tests on plasma:•High concentrations of urea and creatinine •Metabolic acidosis due to inability to excrete H+ions •Hyperkalaemia (>6mmol/l) due to inability to excret K+ions, can lead to cardiac arrest

6. Chronic renal failure

BS6051 SYSTEMS PATHOLOGY TUTORIAL 4 – RENAL DISORDERSa) What is chronic renal failure, and what are the most common causes?

Chronic renal failure is characterised by the progressive loss of kidney function over many years

Over time, nephrons are damaged and replaced by scar tissue•Compensatory hyperfiltration by healthy nephrons eventually leads to their scarring and destruction, resulting in progression of the disease•Rate of deterioration can be slowed, but not stopped or reversed – controlling hypertension most important factor in halting progression of chronic renal failure. Also, control of blood glucose.•Caused by chronic renal diseases (e.g. diabetic nephropathy, hypertensive nephropathy, autosomal dominant polycystic kidney disease.etc.) or unknown aetiology

b) Complete the table of how chronic renal failure graded, what the diagnostic indicators are and clinical manifestations of each stage?

Severity is graded according to GFR and creatinine concentration into mild, moderate, severe & end-stage renal failure (ESRF)

Severity (grading) GFR (ml/min) Creatine (umol/l) Clinical manifestationsHealthy 100-130 <110 -

Mild 30-50 170 Hypertension

Moderate 10-30 350 Anaemia (due to reduced EPO synthesis)

Severe <10 700 Anorexia

End stage <5 1500 Metabolic acidosis, hyperkalaemia, coma, death

Chronic renal failure is often asymptomatic during its development and is often diagnosed incidentally following a routine blood test or in a patient with hypertension. By the time symptoms of chronic renal failure occur, most of the renal mass has been destroyed.