Workshop 4 - Cellular injury 2 Flashcards by Olyvia Chatzigianni

chronic reversible cell lesion
intracellular accumulation
3 types of substances

accumulation in excess of normal cellular components
( lipids, protein, carbohydrates )
accumulation of exogenous pigments
( carbon, Si )
and endogenous pigments
( bilirubin )
accumulation of abnormal substances
exogenous ( mineral substances )
-endogenous ( by abnormal metabolism )

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Fat intracellular accumulations
( disturbances in fat metabolism )

what are lipids and whats their role?
categories of lipids

Lipids are nutritive substances
with energy role in cell metabolism

categories :

triglycerides / neutral fats
( steatosis, obesity )
cholesterol and **cholesterol esters **
( ATPs )
phospholipids-PL
( storage diseases )

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
normal mechanism

Fatty change is accumulation od triglyceride in the cytoplasm of parenchymal cells

Normal -> triglycerides metabolised in the liver
free fatty acids are carried in the blood to the liver where they convert in :

triglycerids
phospholipids
cholesterol esters

these lipids then form complexes with proteins ( apoproteins - also synthetised in liver )
and secreted into plasma as ‘‘lipoproteins’’

when the triglycerides are metabolized normally ,
there is just a small amount of them in the liver cells
that cannot be seen

IN LIVER STEATOSIS:
Hepatic steatosis is excessive accumulation of triglycerides in parenchymal cells.
common in liver.
rare in kidney, myocardium

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
definition
organs

IN LIVER STEATOSIS:
Hepatic steatosis is excessive accumulation of triglycerides in parenchymal cells.
common in liver.
rare in kidney, myocardium

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
causes

diabetes mellitus
malnutrition
toxic substances ( alcochol, CHCL3 )
chronic hypoxia
over-feeding

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
pathology mild , chronic

Fatty liver is rare but serious condition

mild fatty liver
triglyceride accumulation as
small membrane-bound droplets
in cytoplasm
( microvacuolar fatty change )
chronic fatty liver
more common
fat droplets in the cytoplasm fuse to form progressively larger globules
( macrovacuolar fatty change )

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
Mild fatty liver

triglyceride accumulation as
small membrane-bound droplets
in cytoplasm
( microvacuolar fatty change )

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
Chronic fatty liver

more common
fat droplets in the cytoplasm fuse to form progressively larger globules
( macrovacuolar fatty change )

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
appearance

Liver is :

enlarged
yellow
greasy ( when cut )

Mild steatosis : do not affect macroscopic
in severe cases : liver can reach 3-6 kilos

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
Microscopic

in ealry stages of fatty liver:

pale , foamy cytoplasm

as fat accumulation increases:

empty cytoplasm vacuoles appear

in the begging cytoplasm contains
small empty vacuoles with distinct limits
aroundthenucleus
( microvacuoles )

if process progresses :
the vacuoles fuse , resulting in large clear spaces
( macrovacuoles )
occupying the entire cell

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Fat intracellular accumulations
( disturbances in fat metabolism )

Steatosis ( fatty change )
special stains

to determine the fat :
use frozen section made by fresh tissue

fat remains in the cytoplasm in frozen sections
can be demonstrated by fat stains :

oil red
sudan black B

resulting stained black lipids

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intracellular accumulation of pigments

what are the pigments?

pigments are colored substances

endogenous
exogenous

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intracellular accumulation of pigments

endogenous pigments

hemosiderin
billirubin

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intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)

definition, whats hemosiderin?

Hemosiderosis is an excessive accumulation of hemosiderin in tissue and organs

hemosiderin is an endogenous pigment
containing iron

results from degradation of hemogobin ( Hb )

hemosiderin :
form of iron storage in tissue macrophages

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intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)

microscopically

hemosiderin appears as a
yellow brown granular pigment

special stain :
Prussian blue - Perls reaction

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intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)

Macroscopically

Organs accumulating hemosiderin have
brown tint

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intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)

Forms

3 forms :

Localized hemosiderosis
Generalized hemosiderosis
Hemocromatosis

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intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)
LOCALIZED

location , causes

Common in any tissue that is a site of hemorrhage

hemoglobin is broken down and its iron is deposited locally in :

macrophages
connective tissue
in the form of hemosiderin ( like a bruise )

Cause:
organs is conditions of chronic stasis
(lungs, liver)
or at periphery of bleeding
( ecchymosis )

intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)
LOCALIZED

appearance in lungs

in passive congestion of the lung :

brown granular material
in alveolar macrophages

intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)
LOCALIZED

appearance in liver

In passive congestion of the liver
hepatocytes contain

hemosiderin granules
coloured in blue
( because of Perls reaction staining )

intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)
GENERALIZED

Less common

minor excess iron due to :

multiple tranfusions
excessive dietary iron
excess absorption ( hemolytic anemias )

the excess iron is deposited as hemosiderin in **macrophages **

in :
bone marrow
spleen
liver

intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)
HEMOCHROMATOSIS

It is uncommon

Can be :

inherited disease
following major iron overload

organs :
liver
heart
pancreas

intracellular accumulation of pigments
endogenous pigments

Hemosiderin pigments accumulation
(hemosiderosis)
HEMOCHROMATOSIS

differences with hemosiderosis

major difference is the

degree of iron overload
presence of parenchymal cell
*damage** / necrosis

( In hemochromatosis )

intracellular accumulation of pigments
endogenous pigments

Bilirubin pigment accumulation
( jaundice, icterus )

What is it?

Jaundice ( increase in serum bilirubin ) represents the excessive accumulation of
bile pigment ( bilirubin )
in cells and tissues

clinicaly manifested by yellow color of
sclerae and skin

Bilirubin:
endogenous pigment without iron
result from degradation of hemoglobin ( Hb)

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Bilirubin metabolism

Bilirubin is the *end product* of *hemoglobin* molecule it doesnt contain iron or protein. * Is formed in the **reticuloendothelial** system. * Is tranformed via plasma ( bound to **albumin** ) to **liver** ( **_unconjugated_** form) lipid - soluble form * In the liver : conjugated **enzymatically** with **glucuronide** ( **_conjugated_** form ) water- soluble form * excreted by **liver cells** into **bile** and then **intestine** * in the intestine with bacterial activity: **bilirubin** -\> **urobilirogen ** urobilirogen is disposed in one of 3 ways : 1. stercobilin - directly excreted into **feces** 2. in **urine** in small amounts 3. absorbed in the **portal vein** and reexcreted into **bile** by the liver in the enterohepatic circulation

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) causes

1. increased production 2. decreased excretion by liver 3. bile duct obstruction

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Hemolytic Jaundice

Jaundice due to **increased production** too much capacity of the liver to conjugate bilirubin -\> accumulation of **uncojugated bilirubin** in serum ( because it is lipid- soluble bound to albumin in the blood is **NOT** excreted in **urine** )

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Hemolytic Jaundice why is the bilirubin not excreted in urine?

because its the **unconjugated** form which is **lipid-soluble ** ( bound to albumin in the blood )

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Hepatocellular Jaundice

Failure of the liver to * **take up** * **conjugate** * **excrete** bilirubin , increases level of **serum** bilirubin Usually both **CONJUGATED** , **UNCONJUGATED** levels are elevated the conjugated one ( water soluble ) is excreted in urin **urobilinogen** levels : *elevated*

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Obstructive Jaundice

due to **decreased** excretion accumulation of conjugated bilirubin proximal to the **obstruction** in biliary tract and live ( **cholestasis** ) **bilirubin** _elevated_ : conjugated in **plasma** because the bilirubin doesnt reach the intestine : levels of **urobilirogen** in **feces** and **urine** are **Decreased** ( colour of feces )

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Morphology of jaundice

skin, sclera, organs : ## Footnote **greenish-yellow**

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) why yellow turns into green?

Yellow colour in jaundice turns into green because of **bilirubin oxidation** to **biliverdin**

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Macroscopically liver

the liver is * **pale** * **green-ish yellow** *

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) Microscopically liver

we have two forms of bilirubin accumulation * **billiary cylinder** ( small biliary channels are distended through greenish - yellow pigment ) ( characteristic in cholestatic jaundice ) * **intrahepatocyte granular pigment** ( hepatocyte cytoplasm contains billirubin as small greenish-brown granules )

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) whats billiary cylinder?

In microscopic examination in icteric liver : **small biliary channels** are distended through greenish - yellow pigment characteristic in **cholestatic** jaundice

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) What's intrahepatocyte granular pigments?

In microscopic examination in icteric liver : hepatocyte **cytoplasm** contains billirubin as small **greenish**-**brown** granules

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) In hemolitic jaundice, what is elevated?

Unconjugated bilirubin in serum

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) In hepatocellular jaundice, what is elevated?

both conjugated and uncojugated bilirubin levels are elevated also bilirubin in urine

intracellular accumulation of pigments endogenous pigments Bilirubin pigment accumulation ( jaundice, icterus ) In obstructive jaundice, what is elevated and what decreased?

Conjugated bilirubin in plasma is elevated fecal and urinary urobilirogen levels are decreased

Extracellular accumulations which are the extracellular lesions?

* **Hyalinosis** * **amyloidosis**

Extracellular accumulations what is hyalinosis? examples?

**Hyalinosis** represents an abnormal **accumulation** of **hyaline ** examples * _benign nephroangiosclerosis_ * hyalinosis of _splenic capsule_ surface * hyaline _arteriolosclerosis_ of _renal afferent arteriole_

Extracellular accumulations Whats hyaline and how does it look like?

Hyaline is a descriptive term that refers to damaged intracellular and extracellular protein appearance : * homogenous * eosinophilic