ADAPTIVE CHANGES OF KIDNEY IN KIDNEY DISEASES

2.  excretory function
 homeostatic function
 endocrine function
 metabolic function

3.  This include formation and excretion of urine.
 The main step involved are
 Glomerular filtration
 Tubular reabsorption
 Tubular secretion

4. 1. Regulate blood volume and blood pressure:
 by adjusting volume of water lost in urine
 releasing erythropoietin and renin
2. Regulate plasma ion concentrations:
– sodium, potassium, and chloride ions (by controlling quantities lost in urine)
– calcium ion levels
3. Help stabilize blood pH:
– by controlling loss of hydrogen ions and bicarbonate ions in urine
4. Conserve valuable nutrients:
– by preventing excretion while excreting organic waste products
5. Assist liver to detoxify poisons

5.  Kidneys have primary endocrine function since they produce
hormones
 In addition, the kidneys are site of degradation for hormones
such as insulin and aldosterone.
 In their primary endocrine function, the kidneys produce
erythropoietin, renin and prostaglandin.
 Erythropoietin is secreted in response to a lowered oxygen
content in the blood. It acts on bone marrow, stimulating the
production of red blood cells.

6.  Renin -the primary stimuli for renin release include reduction of renal
perfusion pressure and hyponatremia. Renin release is also influenced
by angiotension II and ADH.
 It is a key stimulus of aldosterone release. The effect of aldosterone
is predominantly on the distal tubular network, effecting an increase
in sodium reabsorption in exchange for potassium.
 The kidneys are primarily responsible for producing vitamin D3 from
dihydroxycholecalciferol
METABOLIC FUNCTION
 Kidney perform gluconiogenesis during periods of starvation.

7.  Humans have between 225,000 and 900,000 nephrons in each
kidney
 These nephrons determine how well the kidney will adapt to:
 The physiologic demands of blood pressure and body size
 Various environmental stresses,
 Unwanted inflammation leading to chronic renal failure.

8.  Residual nephrons hyperfunction to compensate for the loss of
those nephrons succumbing to primary disease.
 This compensation depends on adaptive changes produced by:
 Renal hypertrophy
 Adjustments in tubuloglomerular feedback
 Adjustments in glomerulotubular balance
 Some physiologic adaptations to nephron loss also produce
unintended clinical consequences and eventually some
adaptations accelerate the deterioration of residual nephrons
(hyperfiltration hypothesis)

9.  When the initial complement of nephrons is reduced by a sentinel
event, such as unilateral nephrectomy, the remaining kidney
adapts by enlarging and increasing its glomerular filtration rate.
 The remaining kidney grows by compensatory renal hypertrophy.
 This compensatory renal hypertrophy is only partially understood:
 Studies suggest roles for angiotensin II transactivation of heparin-binding
epithelial growth factor, PI3K, and p27kip1, a cell cycle protein that
prevents tubular cells exposed to angiotensin II from proliferating, and
the mammalian target of rapamycin (mTOR), which mediates new protein
synthesis.

10.  Hyperfiltration during pregnancy or in humans born with one
kidney or who lose one to trauma or transplantation generally
produces no ill consequences.
 By contrast, experimental animals that undergo resection of 80%
of their renal mass, or humans who have persistent injury that
destroys a comparable amount of renal tissue, progress to end-
stage disease.
 There is a critical amount of primary nephron loss that produces
maladaptive deterioration in remaining nephrons. This
maladaptive response is referred to clinically as renal progression,
and the pathologic correlate of renal progression is the relentless
advance of tubular atrophy and tissue fibrosis.

11.  There are six mechanisms that hypothetically unify this final common
pathway:
1. Persistent glomerular injury  local hypertension in capillary bed 
increases their single-nephron glomerular filtration rate  protein leak
into the tubular fluid
2. Significant glomerular proteinuria, accompanied by increases in the local
production of angiotensin II  induces the accumulation of interstitial
mononuclear cells
3. Cytokine bath: Cytokines and chemokines
4. The initial appearance of interstitial neutrophils is quickly replaced by
macrophages and T lymphocytes producing interstitial nephritis
5. Some tubular epithelia respond to this inflammation by disaggregating
from their basement membrane to undergo Epithelial-mesenchymal
transitions forming new interstitial fibroblasts
6. Surviving fibroblasts lay down a collagenous matrix that disrupts adjacent
capillaries and tubular nephrons, eventually leaving an acellular scar
(Fibrosis).

12. 6 stages that
include:
1.- Hyperfiltration
2.- Proteinuria
3.- Cytokine bath
4.- Mononuclear cell
infiltration
5.- Epithelial-
mesenchymal
transition,
6.- Fibrosis.

13.  The response to the loss of many functioning nephrons produces:
 Vasoconstriction in postglomerular efferent arterioles (and not in afferent
arterioles)  increasing the intraglomerular capillary pressure 
hyperfiltration
 Persistent intraglomerular hypertension is associated with progressive
nephron destruction.
 A number of vasoconstrictive and vasodilatory substances have been
implicated:
 Chief among them being Angiotensin II (incrementally vasoconstricts the
efferent arteriole)
 Rol of ARB-II

14.  Sodium:
 Remains near normal until limitations from advanced renal disease
inadequately excrete dietary Na+ intake.
 Eventually, with advancing nephron loss, the atrial natriuretic
peptides lose their effectiveness and Na+ retention results in
intravascular volume expansion, edema, and worsening
hypertension.

15.  Urinary dilution and concentration:
 Patients with progressive renal injury gradually lose the capacity
either to dilute or concentrate their urine
 Urine osmolality becomes relatively fixed about 350 mOsm/L
(specific gravity ~1.010).
 Tubulointerstitial damage also creates insensitivity to the
antidiuretic effects of vasopressin

16.  Potassium:
 Normally, the kidney excretes 90% of dietary K+, while 10% is
excreted in the stool with a trivial amount lost to sweat.
 Although the colon possesses some capacity to increase K+
excretion—up to 30% of ingested K+ may be excreted in the stool of
patients with worsening renal failure
 Aldosterone is released in direct response to elevated levels of
serum K+

17.  Acid-Base Regulation:
 The kidneys excrete 1 meq/kg/day of noncarbonic H+ ion on a
normal diet.
 To do this, all of the filtered HCO3
2– needs to be reabsorbed
proximally so that H+ pumps can secrete H+ ions
 Metabolic acidosis
 Type IV renal tubular acidosis.
 Once GFR falls below 25 mL/min, noncarbonic organic acids
accumulate
 The level of serum HCO3
2– falls severely

18.  Calcium and Phosphate:
 The expression of 1alpha-hydroxylase by the proximal tubule is
reduced  lowering levels of calcitriol  less Ca++ absorption by
the gut.
 Loss of nephron mass reduces the excretion of PO4  decreases
levels of Ca  secretion pf PTH  Ca movilization from bone 
Ca/PO4 precipitation in vascular tissues  abnormal bone
remodeling  bone demineralized from secondary
hyperparathyroidism.

19.  Compensatory renal growth occurs after any anomaly that
results in the loss of contralateral kidney mass and function.
This is an adaptive process which results in an increase of
size and the functional capacity of the remaining kidney.
Normal kidneys can compensate for the loss of contralateral
kidney function via increasing their clearances, which seems
to be dependent on the residual function. compensatory
differences in renal function seen between kidneys with
contralateral normofunctioning, hypofunctioning and
nonfunctioning .

20.  Pubmed.com
 Google.co.in
 Wikipedia
 Guyton and hall physiology book
 Slideshare.com