Slajd 1

Patomorfologia

Wykład 03

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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

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)

Intracellular Accumulations

• General Principles

– Exogenous

• cell cannot degrade substance (carbon)

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

Intracellular Accumulations

• Fatty Change (Steatosis)

– Liver

• increased weight, yellow color

• fat vacuoles within cytoplasm of hapatocytes

Intracellular Accumulations

• Fatty Change (Steatosis)

– Heart

• focal fat deposits in myocardium (anemia)

• diffuse fat deposits in myocardium (profund hypoxia,

diphtheric myocarditis)

Intracellular Accumulations

• Cholesterol and Cholesterol Esters

– Atherosclerosis

• macrophages and smooth muscle cells filled with

vacuoles

– Xanthomas

• macrophage accumulation / hereditary and acquired

hyperlipidemias

Intracellular Accumulations

• Proteins

– Renal tubular epithelium in proteinuria

– Plasma cells may accumulate

immunoglobulines (Russel bodiers)

Intracellular Accumulations

• Glycogen

– Diabetes mellitus

• glycogen accumulation in renal tubular epithelium,

hepatocytes, cardiac myocytes, pancreatic beta cells

Intracellular Accumulations

• Exogenous Pigments

– Tattoos

• dyes phagocytosed by macrophages

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

Intracellular Accumulations

• Endogenous Pigments

– Melanin

• brown-black pigment derived from tyrosine

in melanocytes

• may also accumulate in basal keratinocytes

and dermal macrophages

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

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

Intracellular Accumulations

• Endogenous Pigments

– Hedmosiderin

• systemic iron overload (hemosiderosis)

– increases absorption or impaired

utilization of iron; hemolytic anemias;
transfusions

– ectensive accumulation –

hemochromatosis & organ fibrosis

Forms and Morphology of

Cell Injury

PATHOLOGIC CALCIFICATION

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

Pathologic Calcification

• Dystrophic Calcification

– Normal serum calcium

– Areas of necrosis or injury

– Intracelular or extracellular

Amyloidosis

• Nature of Amyloid

– Abnormal proteinaceous substance

– Deposite between cells

– Not a single chemical entily

– Appears as a pink

translucentmaterial on H&E stain

Amyloidosis

• Chemical nature of Amyloid

– AL (amyloid light chain)

• associatrd with B-cell dyscrasis

• produced by immunoglobulin – secreting

cells

Amyloidosis

• Chemical nature of Amyloid

– AA (amyloid associated)

• non-immunoglobulin

• derived from SAA (serum amyloid –

associated precursor protein)

• associated with chronic inflammatory

diseases

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)

Reactive Systemic Amyloidosis

• Characteristics

– AA protein deposits

– Occurs in setting of chronic

inflammation

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

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

Other Types of Amyloidosis

• Amyloid of Aging

– Senile cardiac amyloidosis

• transthyretin

– Senile cerebral amyloidosis (in

Alzheimer’s disease)

• beta-2 amyloid protein

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

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

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

Clinical Correlation

• Prognosis

– Poor

– Mean survival 1 to 3 years

Lysosomal Storage

Diseases

Sphingolipidoses

Tay-Sachs, Gaucher and Neimann-

Pick Diseases

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

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

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

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

Glycogen Storage Disorders

von Gierke, McArdle and Pomp

Diseases

von Gierke Disease

• Characterictics

– Glucose-6phosphatase deficiency

– Accumulation of glycogen in

cytoplasm

– Affects liver

– Hepatomegaly, hypoglycemia,

renomegaly, failure to thrive

– Mortality about 50%

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

Hemodynamic Disorders

Disorders of Perfusion (page 283)

„Hemodynamic disorders are

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

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

Hemodynamic Disorders

Passive Congestion, Lung

Hemodynamic Disorders

Pulmonary Edema, Gross

Hemodynamic Disorders

Pulmonary Edema, Micro

Hemodynamic Disorders

„Heart Failure Cells”, Lung, Micro

Hemodynamic Disorders

Kitchen Patology - Nutmeg

Hemodynamic Disorders

Nutmeg Liver (passive congestion)

Hemodynamic Disorders

Nutmeg Liver (centri-lobular

congestion)

Hemodynamic Disorders

Liver, Passive Congestion, Cell Dropout

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

Hemodynamic Disorders

Hemorrhage - Classifitation

• Hematoma – collection of blood

within a tissue (often muscle)

• Hemopericardium

• Hemothorax

• Hemarthrosis

• Hemoperitoneum

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

Hemodynamic Disorders

Hemorrhage – RMSF Petechial Rash

Hemodynamic Disorders

Ecchymosis, Gross

Hemodynamic Disorders

Hypertensive Hemorrhage, Gross

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.

Hemodynamic Disorders

Vascular Rheology – Laminar Flow

Hemodynamic Disorders

Vascular Rheology – Stenosis

Hemodynamic Disorders

Thrombosis – fate of thrombi

• Propagation

• Embolization

• Dissolution (lysis by the

thrombolytic system)

• Organization and re-canalization

Document Outline