Amyloidosis of kidney. Morphological characteristics, outcomes, complications

1. Theme:
"Amyloidosis of kidney.
Morphological
characteristics, outcomes,
complications"
Done By: Myrzakhanov Yerik
3course GMF 348 group
Checked By: Abishev Zhasulan
Zhumataevich
Semey 2014

2. Plan
 Introduction
 Characteristics of amyloidosis. classification
 Amyloid: morphological characteristics
 Development stage renal amyloidosis
 Complication of renal amyloidosis
 Macroscopic characterization
 Microscopic characterization
 Conclusion
 List of References

3. Introduction
 In medicine, amyloidosis refers to a variety of conditions
wherein normally soluble proteins become insoluble and are
deposited in the extracellular space of various organs or tissues,
disrupting normal function. The insoluble fibrous protein
aggregates that develop in amyloidosis are known as amyloids.
They result from a change in the protein's secondary structure,
which causes the protein to take on a particular aggregated
insoluble form, similar to the beta-pleated sheet. Symptoms
vary widely depending upon where in the body amyloid
deposits accumulate. Amyloidosis may be inherited or
acquired. Senile systemic amyloidosis was determined to be the
primary cause of death for 70% of supercentenarians who have
been autopsied.

4.  Amyloidosis - a kind of protein dystrophies, which
is a complication of many diseases: infectious,
inflammatory, neoplastic nature. In this case we
are talking about acquired (secondary)
amyloidosis. Amyloidosis may be due to unknown
reasons - is primary amyloidosis. Term amyloidosis
was proposed in 1853 by R. Virchow. He showed
that this disease appears in organs substance that
is painted with iodine like starch. Before Virchow,
disease was described by K. Rakitanskim called
"greasy disease" for the microscopic features of
amyloidosis - the body gets greasy shine.

5. Composition of amyloids
 Amyloid is a complex substance - glycoprotein in
which globular and fibrillar proteins is always closely
associated with mucopolysaccharides. If proteins
have about the same composition, the
polysaccharides are always different composition.
Thus, amyloid has never constant chemical
composition. Stake proteins have 96-98% of the mass
of amyloid. Carbohydrates are presented with 2
fractions - acidic and neutral polysaccharides. The
physical properties of amyloid: anisotropy - that is
ability to birefringence that is detected in polarized
light microscope amyloid forms yellow glow, unlike
collagen, elastin from. Anisotropy associated with the
ordering of the molecular structure.

6. Micropicture of amyloids

7. Clinical classification of
amyloidosis
1. Primary amyloidosis appearing for no apparent reason
Associated with Multiple Myeloma
2. Secondary amyloidosis in chronic infections
rheumatoid arthritis and other connective tissue diseases
for cancer
3. Family (hereditary) amyloidosis with periodic disease
Portuguese version of the family and other forms of
amyloidosis
4. Senile amyloidosis
5. Local amyloidosis

8. The types of amyloid and
corresponding amyloidosis forms (1)
Official
abb.
Amyloid
type/Gene
Description
AA SAA
Serum amyloid A protein (SAA) is an acute-phase reactant that is
deposited in the tissues in AA amyloidosis.
AANF
atrial
natriuretic
factor
Senile amyloid of atria of heart
APro prolactin Prolactinoma
? OSMR Primary cutaneous amyloidosis
Aβ2M
β2microglobuli
n
Not to be confused with Aβ, β2m is a normal serum protein, part
of major histocompatibility complex (MHC) Class 1
molecules. Haemodialysis-associated amyloidosis
ACal calcitonin Medullary carcinoma of the thyroid
APrP prion protein
In prion diseases, misfolded prion proteins deposit in tissues and
resemble amyloid proteins. Some examples are Creutzfeldt–Jakob
disease (humans), BSE or "mad cow disease" (cattle),
and scrapie (sheep and goats).
AIAPP amylin Found in the pancreas of patients with type 2 diabetes.
Aβ β amyloid/APP Found in Alzheimer disease brain lesions.

9. The types of amyloid and
corresponding amyloidosis forms (2)
Official
abb.
Amyloid
type/Gene
Description
AGel GSN Finnish type amyloidosis
AApoA1 APOA1 Familial visceral amyloidosis
AFib FGA Familial visceral amyloidosis
ALys LYZ Familial visceral amyloidosis
AKer
keratoepitheli
n
Familial corneal amyloidosis
ACys CST3 Cerebral amyloid angiopathy, Icelandic-type
ABri
Cerebral amyloid angiopathy, British-type
ITM2B
ADan
Danish-type
AL
amyloid light
chain
AL amyloidosis / multiple myeloma. Contains immunoglobulin
light-chains (λ,κ) derived from plasma cells.
ATTR transthyretin
A mutant form of a normal serum protein that is deposited in the
genetically determined familial amyloid polyneuropathies. TTR is
also deposited in the heart insenile systemic amyloidosis.[9] Also
found in Leptomeningeal amyloidosis.

10. Primary amyloidosis
 Primary or idiopathic
generalized amyloidosis, first
described by Wilde in 1886,
is a generalized process with
a predominant lesion of an
organ or system. Allocate
following its clinical variants:
the system, kardiopatichesky,
neuropathic, neuropathic and
other dominant pathology can
change throughout the
disease.

11.  Microscopic picture

12. Secondary amyloidosis
 occurs with chronic
inflammatory diseases of the
current long-term (such as
rheumatoid arthritis,
tuberculosis, osteomyelitis,
ulcerative colitis,
limfogranulematose, some
tumors, etc.). In most cases,
the clinical picture associated
with renal impairment and
patients die from chronic
renal failure (CRF). In
addition, affects the adrenal
glands, liver, spleen and
gastrointestinal tract.

13.  Microscopic picture

14. Hereditary amyloidosis
 1. Neuropathic
with lesions of the lower extremities : Portuguese, Japanese , Swedish, and other
types of
affecting the upper extremities : the types of Switzerland - Indiana, Maryland ,
Germany
 2 . Neuropathic
periodic disease
fever and abdominal pain Swedes and Sicilians
combination of rash , deafness and renal disease
kidney disease and arterial hypertension
 3 . Kardiomiopatichesky
Danish - progressive heart failure
Mexican- American - sick sinus syndrome , cardiac fibrillation
 4 . Mixed
Finnish - corneal dystrophy and the defeat of the cranial nerves of stroke

16.  Senile amyloidosis detected in the elderly
 Local composition amyloid amyloidosis is a
heterogeneous group. In nodules as it may appear in the
lungs, throat, skin, bladder, language, etc.
 Dialysis amyloidosis (associated with dialysis
amyloidosis) has now become a complication of chronic
renal failure patients, long on hemo-or peritoneal
dialysis

18. Development stage renal amyloidosis
(1)
 1. Preclinical (latent, asymptomatic) stage, in which amyloid is
present in the zone of intermediate and downstream direct
vascular pyramids edema and foci of sclerosis. Stage lasts 3-5
years or more. During this period, when the reactive amyloidosis
predominate main clinical manifestations of disease (e.g.,
suppurative lung process, tuberculosis, rheumatoid arthritis, etc.).
 2 . Proteinuric ( albuminurieatic ) stage - amyloid appears
primarily in the mesangium, in the loops of capillaries, in the
pyramids and cortex glomeruli in the blood vessels. Developing
multiple sclerosis and atrophy of nephrons , hyperemia and
lymphostasis . The kidneys are enlarged and dense , dull gray-pink
color . Proteinuria at the beginning is moderate , some may
even be a transitory period , to decrease and increase, but then
becomes resistant (step Intermittent proteinuria). Some
researchers have identified two stages in this period : selective
and non-selective proteinuria. Duration of stage 10 to 13 years.

19. Development stage renal amyloidosis
(2)
 3 . Nephrotic ( swollen , edematous hypotonic ) stage - amyloid -
lipoid nephrosis - amyloid in all parts of the nephron. There
sclerosis and amyloidosis medulla, cortex but without marked
sclerotic changes . Duration stage to 6 years. In proteinuric and in
nephrotic stage kidney enlarged, dense (large kidney tallow) .
Clinically, this stage manifests classical nephrotic syndrome with
all its features: the development of massive proteinuria ( protein-losing
in the urine more than 3-5 grams per day),
hypoproteinemia with hypoalbuminemia, hypercholesterolemia,
lipidourea with edema to the extent of hydrops. In the urinary
sediment are hyaline, and with progression of proteinuria -
granular casts . Possible micro-and gross hematuria, leukocyturia
without signs of pyelonephritis.

20. Latent stage

21. Nephrotic stage

22. Development stage renal amyloidosis
(3)
 4. Uremic (terminal,
nitrogenшс) stage -
amyloid contracted kidney
- reduced in size, thick,
scarred kidney. Chronic
renal failure is not very
different from that in other
kidney diseases.

23. Complication of renal amyloidosis
 Complication of renal amyloidosis is usually any infection
(pneumonia, erysipelas, mumps), which is due to a sharp
decline in the body's resistance on the basis of immune
deficiency and metabolic disorders. Possible complications of
developing amyloidosis renal arterial hypertension (heart
attacks, bleeding, heart failure).
 Relatively rare bilateral of renal venous system thrombosis.
Amyloidosis patient at any stage of acute renal failure
threatens. To this complication can lead to excessive
accumulation of blood protein decomposition products, the
reduction in renal blood flow in shock-like lowering blood
pressure, vascular disorders due to renal vein thrombosis,
intercurrent diseases, etc.

24. Macroscopic characteristics
 In the kidney, amyloid appears under the membrane of glomerular
capillaries, vessels under the membrane cortex and medulla,
membranes under direct and convoluted tubules and in the stroma
of the kidney during the reticular fibers. This is an ongoing
process: the first stage - a hidden, latent. Amyloid appears in the
pyramids in glomerular blood vessels, the second stage -
proteinuria. Characterized by a greater amount of protein in the
urine. At this stage approximately 50% of the glomeruli comprise
amyloid in the form of small focal deposits. In the stroma of the
phenomena of multiple sclerosis , due to growing ischemia. In
epithelium are signs of fat and hyaline droplet degeneration. The
third stage - nephrotic. Macroscopic picture corresponds to a large
sebaceous kidney : kidney enlarged, pale thick cortical layer with
a greasy luster and swollen purple-bluish pyramid.
Microscopically evident that all glomeruli contain amyloid
diffusely located. Last , the final stage - uremic . At this stage, the
shrinkage of the kidney. Renal failure results in death.

26. Microscopic characteristics
 Amyloid in micropreparations looks like amorphous
eosinophilic mass, which can be differentiated from hyaline
special color and character of accumulation in tissues. When
using the dye Congo red amyloid selectively dye red, but to
exclude false-positive results using study in polarized light.

28. Conclusion
 Problems of amyloidosis studied for over 100 years. Riddle of
the disease, which may result in any organs and tissues, and
hence, the emergence of a variety of clinical symptoms, is not
fully unraveled to this day. Disease received its name because
of a pathological substance formed in the bodies resembles
starch (due to its ability to be stained with iodine). It is now
known that in amyloidosis in bodies play a special substance -
amyloid - abnormal eosinophilic proteinaceous material which
is deposited between the cells of various tissues of the body.

29. List of References
 1. Маколкин В.И., Овчаренко С.И.
«Внутренние болезни». М. «Медицина»,
1987.
 2. Тареев Е.М. «Клиническая нефрология»,
М. «Медицина», 1983.
 3. Панкратов В.В., Савичкин А.И. «Терапия в
нефрологии», 2000.
 wikipedia.org/wiki/Amyloidosis
 vip-doctors.ru/nephros/amiloidoz
pochek_patologicheskaia_anatomia.php