Pathophysiology ARF and CKD

ARF to CRF Overview

Predisposing Factors
Age
DM
Heredity/Genes
Primary
hypertension
- Cardio and
peripheral vascular
diseases
- SLE
- AIDS

Precipitating Factors

Prerenal causes (~55%)

Intrerenal causes (~40%)
Postrenal causes (~5%)

Legend:

Phenomen
on
Manifestation/
s
Direction of Pathogenesis (P)

Abrupt
deterioration of
renal structural
Renal
function
compromise
Major
manifestations
show:
Sustained
renal damages
or destruction
Total GFR
decreased

Possible Direction of P

- Fluid and Electrolyte imbalances

- Impaired wound healing
- Increased susceptibility to
infections
- Acidosis
- Gastrointestinal complications
- Anemia
- Increased incidence of
pericarditis
- Uremic encephalopathy
- Platelet dysfunction

End Stage
renal
Disease

Multisyste
m
involveme

Serious inability of
Renal
the kidneys to rid
damage
Pathophysiology:
ARF Concentration
body of all waste
advances

All Known
Predisposing
Factors

Stages

- Fluid and Electrolyte imbalances

- Metabolic changes
- Hematologic changes
- Gastrointestinal changes
- Immunologic changes
- Changes in medication
metabolism
- Cardiovascular changes
- Respiratory changes
- Musculoskeletal changes
- Integumentary changes
- Neurologic changes
- Reproductive chnges
- Endocrine changes
- Psychosocial changes

1st Precipitating Factors

Prerenal Causes:

-Volume depletion (from hemorrhage,

renal losses, GI losses)
-Impaired cardiac efficiency resulting
from MI, heart failure, dysrhythmias,
cardiogenic shock
-vasodilation from sepsis

Falling O2 levels,
High CO2 and H
ions
Excites
vasomotor
center

Hypovole
mia
Reduced arterial
(e.g. carotid sinus)
and cardiac
baroreceptors

(Allows) vasomotor
center to send
vasoconstriction
signals
1.Almost all arterioles to
constrict
2.Small and large veins
constrict
3. Heart stimulated to

Continues to
persist in the

Excites supraoptic
nuclei

Protein
molecules to
split causing

Causes posterior
pituitary to release
Vasopressin Arginine

Renin release
into kidney
and the
bloodstream
Reacts with
Angiotensinog
en in liver

Acts on the
basolateral
membrane of

Causes formation of cyclic

adenosine monophosphate
(cyclic AMP) in cytoplasm

Causes mild
vasoconstricti

Diffuses to the
laminal side

Inactivated by
Angiotensinase

General
constriction of
arterioles

Increased
tubular
reabsorption of
sodium

Activates the
enzyme adenyl
cyclase

Angiotensin 1
released

Becomes
Angiotensinogen
2

Decreased kidney
blood flow
Decreased
blood flow in
peritubular
capillaries

Excites osmoreceptors
located @ anterior
hypothalamus

Intrinsic kidney
secretions
causes:

Reacts with ACE

in the lungs

Causes adrenal
glands to
secrete
Aldonsterone

Increased osmolality of
exracecellular fluid

Development of elongated
vesicular structures

Fuses to the
laminal
membrane
Laminal membrane
becomes highly
permeable to H2O

Thirst
mechanism
activated
General thirst
sensation

H2O moves to the inside

of the cell
H2O proceeds to
basolateral membrane
H2O proceeds to
interstitial tissue

Drinking of H2O

Rapid osmotic
reabsorption of
fluid from
tubules

Decreased fluid
filters from
glomeruli to
tubules

H2O
conservation

Increase
arterial
pressure
Adequate
mechanism

Possibilities
Inadequate
mechanism

Isovolemia or
Homeostasis
restored
Decreased O2
delivery to
proximal tubules

Decreased renal
perfusion

Cycle
repeats

Decreased
GFR
Decreased
2nd
tubular flow

Precipitating Factors
Intrarenal Causes:

All Known
Predisposing
Factors

Decreased
cellular ATP

-Prolonged parenchymal ischemia from

pigment nephropathy, myoglubinuria,
hemoglobinuria
-nephrotoxic agents- aminoglycosides,
radiopaque contrast agents, heavy metals and
solvents, NSAIDs, ACE inhibitors, infectious
processes

1st stage
Damaged
tubules

Inability to
conserve sodium

2nd
oliguric
Less fluid
filtered
Large numbers of
excretory substances in
tubules of functional
nephrons

Some cell death

Some tubular
necrosis

Renin-angiotensinaldosterone
reactivation
More
vasoconstriction
Decreased
renal
perfusion

Throughout the
stages:
increased BUN
and creatinine

3rd diuretic
Acts as osmotic
diuretic pulling
water with it

Rapid fluid
flushing

4th
recovery
Too rapid
tubular fluid

Possibilities

Gradual improvement
in metabolic waste
removal

Disruption of
concentrating and
diluting mechanisms

3rd Precipitating Factors

Postrenal Causes:

All Known
Predisposing
Factors

-Urinary tract obstruction

-Calculi
-tumors
-BPH
-Strictures
-Blood clots

Obstruction @ lower
urinary tract
Backing up of urine
to the kidneys
Overloading of urinary
secretions

Increased
pressure in
collecting ducts
and tubules

Tubular
damage

More nephrons are

destroyed
progressively

Pathophysiology: CRF Concentration

Precipitating Factor

All Known
Predisposing
Factors

Untreated Acute Renal

Failure

More nephrons are

destroyed
progressively
Decreased GFR
Hypertrophy of remaining
nephrons

Inability to reabsorb
electrolytes

Inadequate urine
concentration

Sodium
wasting

H2O wasting

Thickening or an
increase in the
amount of collagen in
basement membrane
of small

Sluggish/impaired blood
flow
Glomerulosclerosis

Decreased GFR

Stage I DIMINISHED
RENAL RESERVE
GFR 50%
More than 75%
damage of nephrons
Stage IIRenal
Insufficiency
GFR 20-50%
BUN, creatinine levels
continue to rise

Sodium and water

balance disturbed

Increased vascular
volume

Edema and
hypertensi
on

Potassium balance
disturbed

Hyperkalmei
a
Accumulation of
nitrogenous wastes

Uremia

Skin disorders

Remaining nephrons undergo

changes to compensate for
those damaged nephrons

Gastrointestinal
Manifestations

Filtration of more concentrated

blood by the remaining nephrons

Neurologic
Manifestations

Hypertrophy of
nephrons
Intolerance and exhaustion
of the remaining nephrons
Further damage of
the nephrons
80-90% damage
Stage III RENAL FAILURE
GFR 10-20%
Impaired kidney
function and
Uremia

Pericarditis

Erythropoeitin
production impaired

Acid-base imbalances
Vitamin D activation
impaired
Vitamin D activation
impaired

Sexual
dysfunction

Anemi
a
Skeletal Buffering

Acidos
is

Osteodystrophies

Hyperparathyroidism

Stage IV End-Stage Renal

Disease
GFR 20% and below

Phosphate
accumulation