Describe the pathological changes occurring in acute tubular necrosis and recovery

I.
Acute tubular necrosis is defined pathologically as damage to tubular epithelial cells seen
through microscopy
a. Also clinically defined as an acute suppression of renal function
b. It is the most common cause of acute renal failure, but the damage caused is
usually reversible
c. Common causes include: Trauma, acute pancreatitis, septicaemia, inadequate
perfusion of peripheral organs
II.
Ischaemic ATN
a. Damage
to
the
nephrons due to
lack of perfusion of
the kidneys
b. Often seen in shock.
Loss
of
blood
volume results in
decreased perfusion
of
the
kidneys
through
ANS
activation in order
to retain fluid
c. Also
caused
by
blood
transfusion
mismatch
and
myoglobulinuria
III.
A second form of ATN
caused
by
drugs,
chemicals, and poisons is
known as nephrotoxic ATN
IV.
Pathogenesis
a. Both ischaemic and nephrotoxic ATN affect the kidneys by decreasing perfusion.
Nephrotoxic pathways may also be directly cytotoxic to nephron epithelial cells
b. Initial damage of the tubular epithelial cells due to hypoxia and cytotoxic
chemicals results in loss of cell polarity (initially reversible)
i. To maintain efficient transport of ions and nutrients, the epithelial cells need
to distinguish between an apical side (facing the tube lumen) and a
basolateral side (facing the interstitial and the peritubular capillaries
ii. The reason for this distinction is that expression of transporters and
channels differs depending on the area of the cell, this is disrupted when
the cell loses polarity
iii. This damage is initially seen as decreased reabsorption of Na + in the
proximal convoluted tubule (where most Na is reabsorbed)
iv. The resulting increased sodium in the distal convoluted tubule promotes
vasoconstriction of the afferent arterioles by tubuleglomerular feedback,
further decreasing blood flow to the kidney
c. The second major result of the loss of polarity is the rearrangement of integrins,
destabilizing cellular interactions with the extracellular matrix and detaching
epithelial cells into the tubule lumen
i. The build-up of debris in the lumen may eventually block the tube,
increasing backpressure and directly decreasing GFR
ii. Fluid may also leak into the interstitia, increasing external pressure and
causing the tubules to collapse
d. Ischaemic tubular epithelial cells release chemokines, cytokines, and P-selectins,
which recruit leukocytes and induce an immune response
1. Ischaemic cell injury of endothelial cells in the arterioles and
glomeruli further constricts the afferent arterioles due to the release
of endothelin, and reducing the secretion of NO and prostaglandins
(vasodilators)
V.
Current studies show that upward of 90% of acute tubular necrosis is reversible with
current treatment and sufficient time lapse

Interpret simple tests of renal function, including plasma creatinine urea and eGFR,
explaining the limitations of each
I.
Urea and Creatinine in the blood
a. The levels of urea and creatinine in blood represent an equilibrium between
production and elimination
b. For most healthy patients, there is a large reserve of renal function available if
urea or creatinine levels rise, therefore the levels remain normal until glomerular
filtration drops by 50-60%
c. Urea levels can be affected by a multitude of factors, mainly related to diet, while
creatinine levels vary with age, sex and muscle mass
d. Generally creatinine is used as an indirect measure of GFR, but neither normal
urea or normal creatinine is definitive for a normal GFR
II.
Measuring GFR
a. Serum creatinine is used as an indirect measure because it is assumed that daily
production of creatinine in muscle cells is constant for a single person and not
affected by protein intake
b. A major problem with using creatinine is that it is excreted both by glomerular
filtration and secretion by the tubular epithelial cells, however the latter is
normally quite low
c. With increasing renal failure, creatinine levels may overestimate GFR (usually
clinically insignificiant)
d. Requires a 24 hr collection of urine for sampling
i. Creatinine Clearance= [Creatinine]urine x [Creatinine]plasma x Rate of urine flow
ii. Creatinine clearance is
used as the equivalent of
GFR
e. Due to the time-consuming
nature of measuring GFR,
equations were developed to
estimate the values
i. Multiple exist such as the
Cockcroft-Gault equation
(probably dont needed to
know them)