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Patomorfologia

Wykład 03

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created by: sobatolog

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Intracellular

Accumulations

• General principles

– Transient or permanent

– harmless or injurious

– Cytoplasm (lysosomes) or nucleus

– Synthesized by the affected cell or produced

elsewhere

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Intracellular Accumulations

• General Principles

– Endogenous

• normal substance produced at normal or increased

rate / rate of metabolism inadequate for removal

(fatty liver)

• normal or abnormal substance cannot be

metabolized (storage diseases)

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Intracellular Accumulations

• General Principles

– Exogenous

• cell cannot degrade substance (carbon)

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Intracellular Accumulations

• Fatty Change (Steatosis)

– Causes

• alcohol abuse, oyher toxins, anoxia, obesity, protein

malnutrion

– Pathogenesis

• various steps involved

• egress of hepatic triglycerides requires complexing

with apoproteins to form lipoproteins

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Intracellular Accumulations

• Fatty Change (Steatosis)

– Liver

• increased weight, yellow color

• fat vacuoles within cytoplasm of hapatocytes

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Intracellular Accumulations

• Fatty Change (Steatosis)

– Heart

• focal fat deposits in myocardium (anemia)

• diffuse fat deposits in myocardium (profund hypoxia,

diphtheric myocarditis)

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Intracellular Accumulations

• Cholesterol and Cholesterol Esters

– Atherosclerosis

• macrophages and smooth muscle cells filled with

vacuoles

– Xanthomas

• macrophage accumulation / hereditary and acquired

hyperlipidemias

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Intracellular Accumulations

• Proteins

– Renal tubular epithelium in proteinuria

– Plasma cells may accumulate

immunoglobulines (Russel bodiers)

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Intracellular Accumulations

• Glycogen

– Diabetes mellitus

• glycogen accumulation in renal tubular epithelium,

hepatocytes, cardiac myocytes, pancreatic beta cells

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Intracellular Accumulations

• Exogenous Pigments

– Tattoos

• dyes phagocytosed by macrophages

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Intracellular Accumulations

• Endogenous Pigments

– Lipofuscin („wear and tear pigment”)

• brownish yellow especially in heart, liver, and brain –

function of age or atrophy („brown atrophy”)

• represents complexes of lipid / protein

• derived from free radical peroxidation of subcellular

membranes

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Intracellular Accumulations

• Endogenous Pigments

– Melanin

• brown-black pigment derived from tyrosine

in melanocytes

• may also accumulate in basal keratinocytes

and dermal macrophages

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Intracellular Accumulations

• Endogenous Pigments

– Hemosiderin

• hemoglibin derived iron containing

golden-yellow pigment

• represents large aggregates of ferritin

micelles

• small amounts normal in phagocytic

cells of reticuloendothelial system

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Intracellular Accumulations

• Endogenous Pigments

– Hemosiderin

• local excesses in focal hemorrhage

• systemic iron oberload (hemosiderosis)

– in macrophages and parenchyma mainly

in liver, pancreas, heart and endocrime
organs

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Intracellular Accumulations

• Endogenous Pigments

– Hedmosiderin

• systemic iron overload (hemosiderosis)

– increases absorption or impaired

utilization of iron; hemolytic anemias;
transfusions

– ectensive accumulation –

hemochromatosis & organ fibrosis

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Forms and Morphology of

Cell Injury

PATHOLOGIC CALCIFICATION

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Pathologic Calcification

• Metastatic Calcification

– Occurs in normal tissue

– Occurs with hypercalcemia

٭hyperparathyroidism; bone catabolism with

tumors involving bone; vitamin D
intoxication, sacroidosis; renal failure

• Primary affects vessels, kineyes,

lungs ana gastric mucosa

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Pathologic Calcification

• Dystrophic Calcification

– Normal serum calcium

– Areas of necrosis or injury

– Intracelular or extracellular

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Amyloidosis

• Nature of Amyloid

– Abnormal proteinaceous substance

– Deposite between cells

– Not a single chemical entily

– Appears as a pink

translucentmaterial on H&E stain

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Amyloidosis

• Chemical nature of Amyloid

– AL (amyloid light chain)

• associatrd with B-cell dyscrasis

• produced by immunoglobulin – secreting

cells

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Amyloidosis

• Chemical nature of Amyloid

– AA (amyloid associated)

• non-immunoglobulin

• derived from SAA (serum amyloid –

associated precursor protein)

• associated with chronic inflammatory

diseases

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Immunocyte Ddyscrasias With

Amyloidosis

• Characteristics

– Complete immunoglobulin light

chains (AL.) produced by abberant
monoclonal B-cells, such as in
multiple myeloma

– Serum M (myeloma) spike

– Bence Jones protein (either lambda

or kappa light chains)

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Reactive Systemic Amyloidosis

• Characteristics

– AA protein deposits

– Occurs in setting of chronic

inflammation

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Other Types of Amyloidosis

• Heredofamiliar Amyloidosis

– Familiar Mediterranean fever

• AA protein – may be due to reccurent

bounts of anflammation of joints and
serosal surfaces

– Familiar amyloid polyneuropathies

• mutant transthyretins deposited

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Other Types of Amyloidosis

• Localized Amyloidosis

– Heterogenous chemical composition

and clinical presention

– Often associated with local infiltration

of plasma cells (AL type amyloid)

– Meduliary carcinoma of thyroid

(amyloid chemically related to
calcitonin – a hormone secreted by the
tumor cells

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Other Types of Amyloidosis

• Amyloid of Aging

– Senile cardiac amyloidosis

• transthyretin

– Senile cerebral amyloidosis (in

Alzheimer’s disease)

• beta-2 amyloid protein

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Morphology of Amyloidosis

• Histologic Apperance

– Pink staining intercellular substance

with H&E stain

– Red-orange staining with Congo red

• green birefringence under polarized light

– Often causes parenchymal cell

atrophy or drop out

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Amyloidosis of the Kidney

• Gross

– Unchanged or large and pale

• Microscopic

– Deposits mainly in glomeruli

• Also present in peritubular interstitium

and walls of blood vessels

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Amyloidosis of Other Organs

• Spleen

– „Sago spleen” – splenic follicles

– „Lardaceous spleen” – splenic sinuses

&pulp

• Liver, Heart, Endocrine glands

– Enlarged

– Interstitial deposits of amyloid

– Pressure atrophy

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Clinical Correlation

• Prognosis

– Poor

– Mean survival 1 to 3 years

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Lysosomal Storage

Diseases

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Sphingolipidoses

Tay-Sachs, Gaucher and Neimann-

Pick Diseases

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Neimann-Pick Disease

• Characteristics

– Sphingomyelinase deficiency

– Acculmulation of sphingomyelin

– Involves phagocytic cells and neurons

– Spleen, liver, bone marrow, lympph

nodes & lungs as well as CNS affected

– Enlarged vacuolatescells

– Visceromegaly & neurologic defects

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Gaucher Disease

• Characteristics

– Glucocerebrosidase dificiency

– Accumulation of glucocerebrosides

– Involves phagocytic cells

– Predominantly affects liver, spleen and

bone marrow; CNS in types 2 and 3

– Phagocytes enlarged with a fibrillar

:wrinkled tissue paper” cytoplasm

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Gaucher Disease

• Types

– Type 1 (99%) hepatosplenomegaly and

absence of CNS involvement-longevity
somewhat shortened

– Type 2 severe CNS involvement; secondary

involvement of spleen / liver –highly lethal

– Type 3 involves brain and viscera with a

course intermediate to types 1 and 2

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Mucopolysaccharidosis

• General Principles

– Progressive disorders

– Multiple organ invovlvment,

including liver, spleen, heart and
blood vessels

– Coarse facial features, clouding of

the cornea, joint stiffness, mental
retardation

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Glycogen Storage Disorders

von Gierke, McArdle and Pomp

Diseases

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von Gierke Disease

• Characterictics

– Glucose-6phosphatase deficiency

– Accumulation of glycogen in

cytoplasm

– Affects liver

– Hepatomegaly, hypoglycemia,

renomegaly, failure to thrive

– Mortality about 50%

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Hemodynamic Disorders

Learning Objectives

• Explain active hyperemia and

passive congestion and give
clinically important examples of
each process

• Describe the fate of thrombi, with

special emphasis to clinical effects,
organization, recanalization and
embolization

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Hemodynamic Disorders

Disorders of Perfusion (page 283)

„Hemodynamic disorders are

characterized by disturbed
perfusion that resultsin organ and
cellular injury.”

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Hemodynamic Disorders

Hyperemia and Congestion

• Active (arterial) – augmented supply of

blood to an organ, usually physiologic
(exercise)

• Passive (venous) – engorgement of an

organ by venous blood, usually the
result of left ventricular heart failure,
which leads, in turn, to right
ventricular failure

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Hemodynamic Disorders

Passive Congestion, Lung

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Hemodynamic Disorders

Pulmonary Edema, Gross

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Hemodynamic Disorders

Pulmonary Edema, Micro

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Hemodynamic Disorders

„Heart Failure Cells”, Lung, Micro

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Hemodynamic Disorders

Kitchen Patology - Nutmeg

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Hemodynamic Disorders

Nutmeg Liver (passive congestion)

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Hemodynamic Disorders

Nutmeg Liver (centri-lobular

congestion)

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Hemodynamic Disorders

Liver, Passive Congestion, Cell Dropout

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Hemodynamic Disorders

Hemorrhage

• Hemorrhage is a discharge of blood from the

vascular compartment to the exterior of the
body or into non-vascular body spaces,most
often caused by:

– Trauma (including surgeons)

– congenital defects (berry aneurysm)

– vessel wall defects (athreosclerosis, vasculitis)

– hypertension

– C

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Hemodynamic Disorders

Hemorrhage - Classifitation

• Hematoma – collection of blood

within a tissue (often muscle)

• Hemopericardium

• Hemothorax

• Hemarthrosis

• Hemoperitoneum

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Hemodynamic Disorders

Hemorrhage - Classification

• Petechia – pinpoint (capillary)

hemorrhage in the skin or elsewhere.
usually in conjunction with a
coagulophaty or vasculitis

• Purpura – diffuse superficial hemorrhage

in the skin, up to 1cm in diameter

• Ecchymosis (bruise) – A superficial skin

hemorrhage > 1cm size

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Hemodynamic Disorders

Hemorrhage – RMSF Petechial Rash

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Hemodynamic Disorders

Ecchymosis, Gross

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Hemodynamic Disorders

Hypertensive Hemorrhage, Gross

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Hemodynamic Disorders

Thrombosis - Definition

• Thrombosis refers to the formation

within a vascular lumen of a
thrombus, defined as an aggregate
of coagulated blood containing
platelets, fibrin and entrapped
cellular elements. For all practical
purposes, the term „clot” is
synonymous.

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Hemodynamic Disorders

Vascular Rheology – Laminar Flow

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Hemodynamic Disorders

Vascular Rheology – Stenosis

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Hemodynamic Disorders

Thrombosis – fate of thrombi

• Propagation

• Embolization

• Dissolution (lysis by the

thrombolytic system)

• Organization and re-canalization

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