Cellular accumulations

3 pathways 1.normal substance-normal/increased rate ,metabolic rate inadequate to remove.fat,mucin

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Pathway 2
Normal/abnormal
endogenous./aquired/genetic.Storage disorders. Fat,lipochrome,bilirubin,hemosiderin, Melanin,Cu,alpha 1 antitrypsin,glycogen Gangliosides Calcium amyloid
2

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Pathway 3
Exogenous-silica Carbon etc

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FATTY CHANGE-STEATOSIS
Triglycerides-parenchymal cells. Liver-major organ involved in fat
metabolism Heart Skeletal muscle kidney

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causes

Toxins Protein malnutrition Diabetes mellitus Obesity. Anoxia ALCOHOL ABUSE-most common cause

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significance
Mild-reversible Severe-irreversible

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morphology

Clear vacuoles Water(hydropic),glycogen,mucin Process without organic solvents Frozen Sudan 4,oil red o(orange red) PAS glycogen red violet Mucicarmine-mucin Both negative-water.
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Fatty liver

Enlarged yellow 3-6 kgms(1.5 to 3 times normal) Soft greasy Early-small vacuoles in cyto around nucleus Later coalesce .dislplace nucleus. Rupture-fatty cysts

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Fatty change with micronodular cirrhosis

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Micronodular cirrhosis with moderate fatty change

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Mallorys hyaline

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heart
Small droplets in one or two patterns Prolonged moderate hypoxia(anaemia)focal intracellular fat deposits,grossly apparent bands of yellow myocardium alternate with bands of dark brown /red uninvolved heart(tigered effect) More profound hypoxia(diphtheritic myocarditis)uniformly affected myocytes
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hemachromatosis

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Lipochrome(wear and tear)

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Copper in lysosome-wilsons

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Alpha 1 antitrypsin

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calcification
1.Dystrophic-previously damaged
tissue.normal calcium levels.local precipitation of insoluble calcium salts.

2.Metastatic-due to hypercalcemia in
normal tissues(metastatic-literally means widespread)
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Examples of dystrophic calcification

Atheromatous plaques Congenitally bicuspid aortic valve Mitral valve ring Old tuberculous focus Fat necrosis Breast lesions Calcinosis cutis
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Clinical importance
Hard,X-ray opacity. Calcified bicuspid mitral-thick,rigid,cause
stenosis,incompetence and cardiac failure. Biochemical basis of calcification in fat necrosis(trauma,pancreatitis)-liberated fatty acids bind calcium to form insoluble calcium soaps.cause hypocalcemia and tetany.
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Dystrophic calcification in cancer

Mammograms.screening for breast cancer Psammomma (greek-sand)bodies multiple
concwentric lamellated calcified bodies in Meningioma,papillary carcinoma thyroid,papillary carcinoma ovary.

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Causes of metastatic calcification

Hyperparathyroidism(adenoma,hyperplasiaparathormone liberate ca from bonehypercalcemia,

Hypercalcemia of malignacy.parathormonelike
substance or extensive bone erosion due to metastasis.ca is precipitated on to connective tissue fibres(collagen,elastin)

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Metastatic calcification

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Dystrophic calcification

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AMYLOID(starchlike-greekAmylon)
Extracellular betapleated molecular

configuration,fibrillary ultrastructure Affinity for congored,sirius red dyes Composed of immunoglobulin light chains,serum amyloid protein A,eptide hormones ,prealbumin SYSTEMIC-due to plasmacell neoplasm or chronic inflammatory disorder LOCALISED-in peptideproducing tumours Impaired function of organComplications-cardiac failure,nephrotic syndrome
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Classification of amyloid
ACCORDING TO 1.chemical composition(clinical and
etiological) 2.tissue distribution 3.aetiology Clinically(systemic,local)

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classification
Myelomaassociated(prima
ry) Reactive(secondary)

AL(Ig light chain or

fragment) AA(serum amyloid protein A) A beta Abeta2M(beta2 microglobulin) ATTR(transtheritin in neuropathic) ,AA (fami.medite.fever) AF(calcitonin.precursor or subunits)
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Alzheimers Hemodialysis Hereditary/familial

Medullary ca thyroid
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Primary(AL) &secondary(AA)
Primary(myeloma associated)if without clinically
obvious myeloma(occult plasma cell tumour),presence of monoclonal immunoglobulin band on serum electrophoresis.(benign monoclonal gammopathy) Reactive(secondary)with a predisposing causerhematoid disease,bronchiectasis,osteomyelitis.tuberculosis,l eprosy etc-predilection to liver ,spleen ,kidney.
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Organ involvementin systemic

All organs-no organ excempt-connective

tissue within the organ. Hepatomegaly Splenomegaly Macroglossia renal Evidence of organ dysfunction(heart failure,proteinuria)
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morphology
Hard,waxy organ Small amounts in spleen,brain,heart,joints of
elderly. Remain permanently in tissues,resistant to removal by natural processes Extracellular location usually basement membrane Presence of glycoprotein of pentraxin family(amyloid P protein)
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Amyloid spleen
enlarged spleen has
the appearance and feel of wax. This amyloid proved to be of the AL type and the patient had multiple myeloma.

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amyloid kidney
chronic renal disease
that may actually increase the size of the kidney.. Pale deposits of amyloid are present in the cortex, most prominently at the upper center.

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infiltrative(restrictive) cardiomyopathy-amyloid

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Restrictive cardiomyopathy(hemosiderin)

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Amyloid kidney
The amorphous pink
depositis of amyloid may be found in and around arteries, in interstitium, or in glomeruli. A Congo red stain will demonstrate the pink material to be amyloid. Such collections of amyloid add to renal bulk, but diminish renal function.
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Adrenal-congo red-amyloid
Congo red stained
deposits of amyloid in the adrenal cortex. Amyloid may collect in adrenal as well as other organs.

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Medullary carcinoma-amyloid
At the center and to the
right is a medullary carcinoma of thyroid. At the far right is pink hyaline material with the appearance of amyloid. These neoplasms are derived from the thyroid "C" cells and, therefore, have neuroendocrine features such as secretion of calcitonin
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Congo red
amyloid stroma of the
medullary thyroid carcinoma has been stained with Congo red. Medullary carcinomas can be sporadic or familial. The familial kind are associated with multiple endocrine neoplasia syndrome.

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Amyloid-islets of langerhans
islet of Langerhans
demonstrates pink hyalinization (with deposition of amyloid) in many of the islet cells. This change is common in the islets of patients with type II diabetes mellitus.
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Alzheimers plaques
Plaques of Alzheimer's
disease have an amyloid core as seen here. There appears to be a problem with beta amyloid precursor protein, but the exact pathogenesis is unknown. It is interesting that the gene coding for cerebral amyloid is on chromosome 21--and persons with trisomy 21 living to age 40 invariably develop Alzheimer's 6/29/2012 disease.

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Cerebral amyloid angiopathy

small cerebral artery
branch in the cortex shows extensive orange-red Congo red staining indicative of amyloid deposition. This otherwise healthy elderly woman had extensive subarachnoid hemorrhage as a consequence of bleeding from cerebral amyloid angiopathy
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Amyloid fibrils-electron microscopy

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Amyloid immunofluorescence with antibody to lambda light chain.

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Hemodialysis associated
Clinical manifestations-arthropathy,carpel
tunnel syndrome Beta 2 microglobulin

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solitary
Clinical significance-mimics a tumour on
plain xray Or because it compress a vital structure (eg ureter) Localised amyloid in a tumour helpful to pathologist in correctly identifying the tumour /primary or secondary(eg-medullary carcinoma thyroid0
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Clinical manifestations of amyloidosis

Nephrotic syndrome-renal failure Hepatosplenomegaly Cardiac failure Macroglossia Purpura Carpel tunnel syndrome Coagulation factor X def in AL amyloid
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diagnosis
Nephrotic-proteinuria Sysemic-best by biopsy og rectal mucosasafe,painless Congo red (examine using one fixed and one rotating polarising filter in lightpath on either side of the section-(red to apple green-dichroism)
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Apple green birefringence-congo red

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