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4 Virtual Patient - Elizabeth Harding

Describe the structure of the nephron

Each nephron is composed of an internal filtering component (renal corpuscle) and a tubule
specialised for the reabsorption and secretion (renal tubule).

Renal corpuscle

Beginning of the nephron composed of a glomerulus and the Bowman's capsule, it is the
nephron's initial filtering component.

 The glomerulus recieves its blood supply from an afferent arteriole of the renal
circulation
 Glomerulus blood pressure provides the driving force for water and solutes to be
filtered out of the blood and into the space made by the Bowman's capsule.
 The remainder of the blood passes into the efferent arteriole
 The diameter of efferent arterioles is smaller than that of afferent arterioles,
increasing the hydrostatic pressure in the glomerulus.
 The Bowman's capsule surrounds the glomerulus, it is composed of a visceral inner
layer formed by podocytes and a parietal outer layer composed of simple squamous
epithelium
 Fluids from blood in the glomerulus are filtered through the visceral layer of
podocytes, resulting in the glomerular filtrate
 The glomerular filtrate next moves to the renal tubule (now known as tubular fluid),
where it is further processed to form urine
Renal tubule

The renal tubule is the portion of the nephron containing the tubular fluid filtered through
the glomerulus. After passing through the renal tubule, the filtrate continues to the
collecting duct system.

The components of the renal tubule are:

 Proximal convoluted tubule - Lies in cortex and lined by simple cuboidal epithelium
with brush borders which help to increase the area of absorption
 Loop of Henle:
 Descending limb loop of Henle
 Ascending limb loop of Henle - Lower end is very thin and lined by simple
squamous epithelium, distal portion is thick and is lined by simple cuboidal
epithelium
 Distal convoluted tubule

Blood from the efferent arteriole, containing everything that was not filtered out in the
glomerulus, moves into the peritubular capillaries, tiny blood vessels that surround the loop
of Henle and the proximal and distal tubules, where the tubular fluid flows. Substances then
reabsorb from the latter back to the blood stream.

The peritubular capillaries then recombine to form an efferent venule, which combines with
efferent venules from other nephrons into the renal vein, and rejoins the main bloodstream.

Classes of nephrons

The two general classes of nephrons are:

 Cortical nephrons (majority) - Have their Loop of Henle in the renal medulla near its
junction with the renal cortex, shorter loop of Henle.
 Juxtamedullary nephrons - Have their Loop of Henle located deep in the renal
medulla, longer loop of Henle to create a hyperosmolar gradient that allows for the
creation of concentrated urine.

Describe the processes of filtration at the glomerulus and the methods of concentrating
glomerular filtrate

Glomerular filtration

 Blood enters the kidney via the renal artery

 The diameter of the afferent arteriole is greater than the diameter of the efferent
arteriole
 The pressure of the blood inside the glomerulus is increased due to the difference in
diameter of the incoming and out-going arterioles
  This increased pressure helps to force out the following components of the blood
out of the glomerular capillaries:
 Most of the water
 Most/all of the salts
 Most/all of the glucose
 Most/all of the urea
 Blood cells and plasma proteins are not filtered through the glomerular capillaries
because they are relatively larger
 The water and salts pass into the Bowman's capsule and are called glomerular
filtrate

Glomerular filtration rate

Glomerular filtration rate (GFR) is the volume of fluid filtered from the renal glomerular
capillaries into the Bowman's capsule per unit time.

Tubular reabsorption

 Only about 1% of the glomerular filtrate actually leaves the body because the rest is
reabsorbed into the blood while it passes through the renal tubules and ducts
 Tubular reabsorption occurs via three mechanisms:
 Osmosis
 Diffusion
 Active transport
 There are three stages:

In the PCT:

 Most of the volume of the filtrate solution is reabsorbed in the PCT

 This includes some water and most/all of the glucose
 Most of the energy is used in the reabsorption of sodium ions - sodium moves from
the tubular fluid into the cells of the PCT
 Following the movement of solutes, water is reabsorbed by osmosis

In the Loop of Henle:

 Descending - Permeable to water but much less permeable to salts and urea,
therefore water gradually moves from the descending limb and into the interstitium
 Thin ascending - Impermeable to water, highly permeable to salts, and somewhat
permeable to urea
  Thick ascending - Reabsorbs NaCl from the tubular fluid

In the DCT:

 The water, urea, and salts contained within the ascending limb of Henle eventually
pass into the distal convoluted tubule.
 The DCT reacts to the amount of ADH in the blood
 The more ADH is present in the blood, the more water is reabsorbed into it

Tubular secretion

 Tubular secretion involves the kidneys 'cleaning the blood' (regulating its
composition and volume) and involves substances being added to the tubular fluid.
 Removes excessive quantities of certain dissolved subsances from the body, and also
maintains the blood at a normal healthy pH.

Outline the hormonal control of urine osmolarity in response to changes in homeostasis

Renin-angiotensin-aldosterone system (RAAS)

 Blood pressure decreases and blood volume decreases

 Juxtaglomerular cells in the kidneys secrete renin into the blood stream
 Renin converts angiotensinogen to angiotensin I
 Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE)
in the lungs
 Angiotensin II increases blood pressure by:
 Constricting systemic arteries (vasoconstriction)
 Stimulates the adrenal cortex to secrete aldosterone, which increases
reabsorption of sodium and water by the kidneys (more concentrated urine)
 Increases sympathetic activity
 Stimulates the posterior pituitary gland to secrete ADH which will allow water
reabsorption in the collecting duct (more concentrated urine)
Outline the mode of action of major diuretic classes

A diuretic is any substance that promotes the increased production of urine.

High ceiling/loop diuretic

 Inhibit the body's ability to reabsorb sodium at the ascending loop in the nephron,
which leads to an excretion of water in the urine
 Water normally follows sodium back into the extracellular fluid

Thiazides

 Act on the distal convoluted tubule

 Inhibit the sodium-chloride symporter leading to a retention of water in the urine
 Also decreases blood pressure

Carbonic anhydrase inhibitors

 Inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted
tubule
 Bicarbonate accumulation in the urine
 Decreased sodium absorption

Potassium-sparing diuretics

 Prevent the secretion of potassium into the urine

 Aldosterone antagonists (e.g. spironolactone) - Prevents aldosterone from
entering the principal cells, prevents sodium absorption and potassium
excretion
  Epithelial sodium channel blockers

Osmotic diuretics

 Increase osmolality but have limited tubular epithelial cell permeability

 Expand extracellular fluid and plasma volume, therefore increasing blood flow to the
kidney, particularly the peritubular capillaries
 Reduces medullary osmolality and thus impairs the concentration of urine in the
loop of Henle

Outline the effect of ACE inhibitors on the kidney

ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II by inhibiting ACE.

 Induce vasodilation which will improve cardiac output (by reducing afterload) and
may decrease perfusion pressure on the glomeruli in the kidneys
 Reduction of aldosterone so enhances the renal excretion of salt and water
 Reduction of ADH so decreases water retention

Renal impairment

 Patients starting on ACE inhibitors usually have a modest reduction in glomerular

filtration rate (GFR) that stabilises after several days
 However the decrease may be significant in conditions of decreased renal perfusion
 In these patients, maintenance of GFR depends on angiotensin II

Outline the pathophysiology of kidney failure and distinguish between acute kidney injury
and chronic kidney injury

Kidney failure is a medical condition of impaired kidney function in which the kidneys fail to
adequately filter metabolic wastes from the blood. Kidney failure is mainly determined by a
decrease in GFR (the rate at which blood is filtered in the glomeruli in the kidney).

Kidney failure can be divided into two categories: acute kidney injury or chronic kidney
disease. The type of renal failure is differentiated by the trend in the serum creatinine.

Acute kidney injury

 Rapid progressive loss of renal function, generally characterised by oliguria

(decreased urine production) and fluid and electrolyte imbalance
 Usually occurs when the blood supply to the kidneys is suddenly interrupted or when
the kidneys become overloaded with toxins

Chronic kidney disease

 Can develop slowly and, initially, show few symptoms

 CKD can be the long term consequence of irreversible acute disease or part of a
disease progression
 Most common causes are diabetes mellitus, long-term uncontrolled hypertension
and polycystic kidney disease