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Flashcards in Genitourinary I Deck (57)
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1

Fluid and electroyte function

1) Approximately one-fifth of the cardiac output
passes through the kidneys each minute, resulting in a renal blood flow of up to 400 mL per 100 g of kidney per min (650 mL/min per kidney). The renal blood pressure remains extremely constant despite profound changes in systemic blood pressure, and the survival advantage of this mechanism is apparent on reflection.

2) This phenomenon is described as autoregulation
and is principally mediated via effects on preglomerular vascular resistance. Whilst the underlying mechanism is the subject of intensive study, it is thought to be related to intrinsic myogenic tone within blood vessels, independent of neural factors.

2

Glomerular filtration

A total of 170–180 L of plasma per day are filtered
through the glomeruli at an approximate rate of
125 mL/min. The glomerular membrane acts as a main fi ltration mechanism and is impermeable to molecules larger than 4 nm diameter, which relates to an average molecular weight of 70 000 Da. The ultrafi ltrate of plasma then passes down to the tubules.

3

Proximal tubule

1) The proximal tubule This decreases the volume
of glomerular fi ltrate by 75–80%, with active resorbtion of glucose, phosphate, bicarbonate, potassium and chloride.

2) It is important to realise that glucose is resorbed entirely from the proximal tubules, unless the glucose load exceeds the capacity for absorption. The majority of fi ltered sodium and bicarbonate are reabsorbed from the proximal tubules, and sodium is actually pumped via hydrogen/potassium-linked pump mechanisms.

3) The proximal tubular fi ltrate is iso-osmotic as a consequence of passive absorption of both water and urea. Sulphates, amino acids and low molecular weight proteins are reabsorbed, as is
potassium.

4

Loop of Henle

1) Sodium chloride and water are resorbed passively. Water is resorbed from the moreproximal part (descending limb) in combination with sodium, whilst the distal part (ascending limb) is impermeable to water, with active sodium resorbtion.

2) This produces a concentration gradient in the renal medulla which is important in maintaining water balance. Loop diuretics, e.g. furosemide, inhibit chloride and sodium resorbtion from the descending limb.

5

Distal tubule and collecting duct I

1) The filtrate is hypotonic as it leaves the loop of Henle, entering the distal tubules where water resorbtion is under the control of anti-diuretic hormone (ADH).

2) Sodium is actively pumped out of the distal tubules, and resorbtion is modified by aldosterone secretion. The collecting tubules pass through the renal medulla, and water absorption is independent of sodium resorbtion and is regulated by ADH secretion.

6

Distal tubule and collecting duct II

1) Sodium is actively pumped out of the collecting tubules against a concentration gradient to maintain the hypertonicity of the renal medulla, with associated passive resorbtion to a small degree.

2) Large amounts of urea also are resorbed passively from the collecting tubules. A number of substances are secreted in the distal tubule,
including potassium and hydrogen and drugs. At this level 75% of the potassium content of urine results are due to tubular secretion.

3) Potassium secretion is linked with sodium and hydrogen concentrations and is modifi ed by aldosterone secretion. Hydrogen secretion occurs in the distal tubules against a concentration gradient.

7

Water balance: Loop of Henle I

1) Sodium and chloride are transported out
of the ascending limb of the loop of Henle, and the
sodium concentration falls progressively as the distal tubule is reached. The remainder of the loop of Henle is in osmotic equilibrium with the substance of the kidney.

2) As the iso-osmolar filtrate reaches the bottom of
the loop of Henle the contents of the descending limb become more concentrated as a result of being pushed towards the ascending limb.

8

Water balance: Loop of Henle II

1) Further concentration occurs due to active sodium resorbtion in the ascending limb, resulting in an osmolar gradient in the renal medulla.

2) Any increase in medullary blood flow results in dissipation of medullary osmolality, decreased water
resorbtion and the production of large quantities of
dilute urine.

3) Dehydration results in release of ADH, increasing permeability in the distal nephron and results
in increased water resorbtion. ADH is released from
the posterior lobe of the pituitary gland.

4) The endogenous control of ADH release is under the regulation of osmoreceptors adjacent to the supraoptic nucleus, which is under the infl uence of sodium and chloride concentration in the plasma. There are also volume receptors in the atria and great veins which seem to be under the control of the vagus nerve.

9

Acid base balance

The kidney cannot excrete urine of pH < 4.5. Maintenance of acid-base balance relies upon a complex series of buffer mechanisms.

1) In the proximal tubules the predominant buffer system is dependent on bicarbonate HCO3
-/H2CO3, whilst in the distal tubules the
predominant buffer is HPO4 2"/H2PO4- and the weakest is the ammonium NH4+ system.

2) The phosphate buffer system is the most important during normal renal function, but the NH4+ system has a particular advantage in that it allows excretion of acid without loss of metallic cations such as Na+.

10

Hormone production by the kidney

1) A number of important hormones are produced within the kidney. The renin-angiotensin system is important, with renin being released from juxtaglomerular cells in response to sympathetic nerve stimulation via a decrease in afferent arteriolar pressure and hyponatraemia.

2) Renin acts on circulating angiotensinogen
to produce angiotensin I, which is converted by a
circulating enzyme to angiotensin II.

3) Angiotensin II stimulates the zona glomerulosa of the adrenal gland to produce aldosterone, which increases the sodium resorbtion by the kidneys and also produces vasoconstriction.

4) These effects feed back in a negative fashion
and switch off renin secretion and, therefore, maintain homeostasis. This is a gross oversimplifi cation of an extremely complex system, but nevertheless it is evident that this homeostatic mechanism is essential to maintain a smooth blood pressure and compensate for changes in extracellular fl uid volume and sodium excretion.

11

Kallikrein

Other important hormones which are the subject
of contemporary study include kallikrein (produced
in the distal nephron) and other related agents. These substances are important vasodilators and also have been shown to have motor effects within the lower urinary tract and may be involved in sensorimotor mechanisms within the bladder.

12

Calcium and Kidney

The kidney is also involved in calcium metabolism
and produces 1 alpha-hydroxylase in response to low circulating levels of calcium, which acts to convert 25-hydroxycholecalciferol into the active metabolite 1,25-dihydroxycholecalciferol, which then promotes calcium reabsorbtion and decreases urine excretion to maintain homeostasis.

13

EPO

Erythropoietin is produced by the kidney in
response to hypoxia (either due to anaemia or respiratory causes), high circulating levels of the products of red cell destruction, and vasoconstriction. It is also produced in smaller amounts by the liver and spleen.

Erythropoietin stimulates an increase in the number of nucleated red cells in the haemopoietic tissue, thereby raising red cell and reticulocyte counts in peripheral blood. Indeed synthesised erythropoietin is used in contemporary haematological practice, for these very purposes, especially in intractable anaemia associated with chronic renal failure.

14

Nephrotoxic drugs

Nephrotoxic drugs include heavy metals, organic solvents, radiological contrast media (the combination of radiological contrast
plus metformin has recently been recognised as
being toxic), antibiotics such as aminoglycosides and some cephalosporins, chelating agents, paraquat and penicillamine.

Ureteric obstruction can occur either as a direct result of drug action (predominantly of historical interest now), e.g. retroperineal fibrosis due
to methysergide and practolol or as a consequence of blockage of the ureters due to renal papillary necrosis consequent upon analgesic abuse.

15

Uric acid stones

Uric acid stones can result from the use of high dose aspirin, thiazide diuretics and furosemide. Increased symptoms can result from the effect of agents increasing urine production, e.g. diuretics, or acting directly on the bladder; and relative underactivity of the bladder possibly leading
to retention can result from anticholinergics, particularly if there is an additional factor such as obstruction to the bladder outlet.

16

Acute renal failure

This is an abrupt decline in renal function with a loss of normal activity. A daily urine output of less than 500 mL is termed oliguria; the absence of urine formation is anuria. The underlying cause of acute renal failure is a persistent fall in renal blood fl ow to levels 30–40% of normal with a consequent reduction in glomerular fi ltration to less than 5 mL/min. The causes of acute renal failure can be divided broadly into prerenal, renal and postrenal.

17

Prerenal ARF

Prerenal acute renal failure usually results from dehydration or circulatory collapse producing hypovolaemia associated with conditions
such as blood loss, septicaemia, or trauma.

18

Renal ARF

Renal causes can be broadly considered to be interstitial (drugs or infection), glomerular (autoimmune conditions, diabetes), tubular damage (antibiotics, drugs, toxic chemicals), or renal (vasculitis or thrombosis).

19

Investigating ARF

The diagnosis of acute renal failure is usually
apparent from the history. An ultrasound scan is a particularly useful diagnostic investigation and is usually combined with a plain abdominal x-ray.

20

Treating ARF

1) Fluid intake is restricted to 500 mL/24 h (equivalent to insensible loss). Fluids are usually given orally.

2) Sodium intake is restricted to 20–30 mmol per day, and careful monitoring of metabolic and nutritional status is important.

3) H2 receptor antagonists and antacids are often used because of the associated incidence of upper gastrointestinal haemorrhage.

4) Dialysis is indicated if conservative measures fail to control the situation, and usually in the acute situation it is instituted via haemodialysis.

21

Indications for haemodialysis

Indications for haemodialysis include:
• hyperkalaemia;
• metabolic acidosis
• fluid overload with pulmonary oedema.

22

Clinical course of ARF

The clinical course of acute renal failure is highly
variable depending upon the aetiology and can be considered to comprise oliguric, diuretic and postdiuretic phases.

1) The oliguric phase usually starts early on but may be prolonged for up to three months or more.

2) A diuresis can occur at any time and is often a sign that recovery is occurring. It is important to maintain vigilance particularly during this time because of the potential for loss of fluid and electrolytes.

3) Renal function may continue to improve for up to a year, but distal tubular function is often permanently impaired, although this may be difficult to determine clinically.

23

Chronic renal failure

1) The commonest causes of chronic renal failure include diabetes mellitus, glomerulonephritis, chronic pyelonephritis, hypertension, connective tissue diseases, and polycystic kidneys.

2) Other causes include renal calculi, vesicoureteric
refl ux, bladder outlet obstruction and myeloma and
hypercalcaemia.

Patients with chronic renal failure usually have
polyuria with loss of normal concentrating ability.

Nocturia is often said to be an early sign and the
urine contains protein with granular casts and white
blood cells.

24

Pathology in CRF

1) Sodium is gradually retained in chronic renal failure, albeit the serum sodium level is a poor
reflection of this.

2) In end stage chronic renal failure potassium levels may rise and acidosis is inevitable due to decreased ammonium ion excretion and decreased excretion of buffer phosphate, the urine pH usually being less than 5.

3) Since calcium levels may fall, secondary hyperparathyroidism is not uncommon and osteomalacia may occur which is sometimes vitamin D resistant.

4) Magnesium levels may rise because of the inability to excrete a magnesium load. Characteristically the urea, uric acid and creatinine levels rise. Serum creatinine levels are a useful way of monitoring chronic renal failure. Anaemia occurs as a consequence of chronic renal failure, which is usually normochromic and normocytic and is likely to be due to marrow suppression with reduced red cell survival.

25

Investigation of CRF

1) Appropriate investigation of patients with chronic
renal failure in addition to biochemical investigations includes ultrasound scan of the upper tracts and a check on postvoiding residual urine.

2) It must be remembered that up to a third of patients with chronic retention of urine present with chronic renal failure.

3) The aim of conservative treatment is to delay the progressive deterioration of renal function and its consequences.

26

Treatment of CRF

1) Fluid intake should be controlled to produce
a urine output of approximately 1 L/24 h, blood pressure is controlled by the use of antihypertensive drugs, and cardiac failure is treated using standard measures.

2) The anaemia of chronic renal failure responds
well to the use of exogenous erythropoietin and may be treated by transfusion, although this is not usually used unless the patients are severely symptomatic.

3) In some patients protein intake is restricted to 40 g/24 h in order to reduce the production of nitrogenous waste products.

27

Dialysis in CRF

When conservative measures fail, dialysis is instituted, and this is usually in patients in whom the serum creatinine has risen above 1000 mmol/L or if the creatinine clearance is less than 1 mL/min. The options for dialysis lie between haemodialysis and peritoneal dialysis.

28

Haemodialysis

In brief, the principle of haemodialysis is to allow selective diffusion of molecules below a certain size from the peripheral blood into the dialysis fluid.

Haemodialysis uses an artificial semipermeable membrane which is disposable.

29

Peritoneal dialysis

In contrast, peritoneal dialysis is less efficient and uses the peritoneum as a membrane, and is more commonly complicated by infective sequelae. However, it is particularly useful in the home situation and is cheaper than haemodialysis.

Wherever possible, renal transplantation should be carried out.

30

Lower UTI assessment

Urodynamic assessment of the urinary tract relates to the study of pressure and fl ow relationships within the urinary tract.

Urodynamic tests should be considered to represent a hierarchy of investigations:

• Fluid volume chart
• Flow rate
• Ultrasound post-void residual volume estimation
• Urodynamic assessment; and
• Video urodynamic assessment.