PATHOLOGY

NOTES FROM
DR.
PREETHISHARMA MAAM
ROBBINS & COTRAN,
SE-IOMEd
By-R. Sai Shivani
and year,
2023
(Apul)
Osmania Medical
College,Hyderabad
 CELL INJURY
April
Friday, 7th 2023.

Du PreethiSharma 2:17pm.
prepladder
· -

INTRODUCTION Reversible Cell

Injury

"I
hypoxia
cause;
common cause of cell
injury HUPOXIA
common cause
of Hypoxia Ischemia
ist
change of
Brain/Neurons (3-5mins) mitochondrial
cell mostsensitive to hypoxia CNS -

dysfunction A cell
injury
cell most Resistant to Hypoxia Fibroblast
Proteins
numerousene
A

·
CELL INJURY

Reversible
INJURY
↓
I amleadat + pin.

.
ADAPTATION
Iuveversible
I
·

3 Nat ↑

REVERSIBLE SELLINJURY Out

&

->
2kt
2kt
↓ Injury continues
In
IRREVERSIBLE
CELL INJURY H2
S E · WATER BALLOON THEORY
↓ ⑧
i
CELL DEATH/NECROSS. Results us

⑱
cellular
swelling
i
Hydropic change
* This is the 1st
MORPHOLOGICAL CHANGE
↓
rig

or
/Cloudy
Normal: swelling of
pink/blue
& Abnormal
Hydropic

Chancethe
cytosol

(ii) Cell swelling

is essence
a
(iv) Flattered Cell
V (v) cytoplasmic blebs
(vi) Myelin figures
 Reversible cell injury
Decreased ATP leads to

1) Failure of Nat_ K+ATPase Pump

(i) Myelin Figure made

up of concentric lamellae

composition phospholipids (cell membrane] >>> Calcium (Ca2+)

Seen in & Irreversible

Reversible Cell
Injury.
↓d POINTS:
-. HIGH YIELD

myelin Figure formation Numerous myelin Figures.

Injury.
castis seen in
Every
justbegins. Rev & Iver
i.e.

Reversite:
2) Anaerobic Glycolysis. Low oxygen levels
-> In

myelin figures, have both phospholipids

↓ & Cart.
Butphospholipids
Cal.
Anaerobic Glycolysis In Irreversible:
->

Castf rom
Due do membrane Rupture,
I ECF Enters ICF.

Increased by
"[Cat,(a*]yen
LacticAcid
production -> ·

cury

Nuclear chromatin
dumping
RER
3) Low oxygen, NO ATP

↓
Ribosomes get detached

↓
Decreased protein Synthesis

↓
Increased Synthesis.
fatty
Irreversible two movements to mark Reversible Irreversible
cell
injury defining ->

1)Severe membrane damage

Amorphous document
getthe
amenitesaremiquates into cytosol
among
AMORPHOUS
in name

FLOCCULENT DENSITIES

composition Calcium-Cat
-> Nares**K ->

mun
mitochondria
·

organelle
Injury Irreversible

- 8-
③
2

I
Ca** Functions inside the ① Activates Enzymes.
Cytosol: Karyhovexis Kavyolysis
·
phospholipase -Nuclear chromatic
-
Nuclear -
Nuclear

Breakdown dissolution.
·
condensation.
·
Protease
NECROSIS Pathological Cell death.

Associated with Inflammation.

microscopin examination ·
Pink -

Eosonophilic
·
Amorphous -
No
morphology
·

Inflammatory Appearance

Types of Necrosis:

① Coagulative most common

mechanism of Action Denaturation of proteins.

**A
·

site
of Hearts, liver, kidney. (Solid Organs
Eden.
· occurence

↓I
Coagulative Pilomatuixoma
CGrave Yard
Necrosis
Too
many

Stone
Ghosts.

I I

Coagulative Row of Tombstones

necrosis
↓
* Tissue Architecture Remains Intact in Pemphiqus Vulgar's
Coagulative Necrosis.

i.e. Solid Remains solid

② Liquefactive Necrosis/
Colliquative necrosis: forms Abscess.

common
organs: Brain, Pancreas

causes for lig. Necrosis Rich in Hydrolytic Enzymes

3) Cseous
cheese like.
Necrosis liquefactive coagulative
common India.
very in

Eq: Tuberculosis -> High lipid content in cell wall.

Fungal Infections
Syphilis
4) Fat Necrosis

Site of occurence Breast, omentum

·Trauma I
I
Acute pancreatitis
tease, Amylase
rat breakdown is released

↓
#Ca*
Ads
fatty

white.
Chalky

FatNosi's

Pancrealitis:
*

within Pancreas:Liquefactive necrosis

CNO fat inside pancreas

Around Fat Necrosis.

paneers:
Peripancreatic Fatis presentaround pancreas

5) Fibrinoid necrosis
Ag-Ab reaction

Formation of Immune complex

Eq:Rheumatic heart disease (Aschoff bodies

poly arteritis nodosa Hepatitis B
-

SLE

malignantHypertension
6)Ganquene Blackish discoloration & foul smelling of organ.

Blood vessel occlusion

2 types: DRY GANGRENE WET GANGRENE

a) Evy Ganquene
(similar to coagulative necrosis)
·
Blood vessel occluded · Blood vessel occluded

b) Wet Ganquene infection of the organ persists

(similar to liquefactive
line of demarcation line of demarcation.
necrosis ·
is · No

present
·
Similar to Coagulative · Similar to liquefactive necrosis.
necrosis
7) Zenker's degeneration. Similar to coagulative necrosis

Skeletal muscles. (i.e. Rectus Abdominis;

seen in:Necrosis
of
Diaphram

causes: Typhoid
Enteric Fever
 APOPTOSIS 7thApril, 2023
Dr. Preeti Sharma man -

prepladder Friday
5: POPM

Apoptosis Caspases dependent -

Programmed cell death

physiological & pathological

Both

Apoptosis ATP
usage
-

Active process.

* No Inflammation.

Physiological Apoptosis ·
Organogenesis -

Embryonic stage
·
Neurons
·

webbing of digits.

of
leads
to syndectyly.

·
After Inflammation

↓
Neutrophil clearance occurs via physiological Apoptosis

· Endometrial shedding during menstration.

Pathological Apoptosis. Viral hepatitis 2 -

Councilman bodies

·
Lichen planus -

civatte/colloid/cytoid bodies

caspases: residues.
Has
cysteine

Paminpartner
rea.

of
an alt
Chemotherapy of cancer cells

CHEMOTHERAPY
↓ leads to

Apoptosis + Necrosis
of Cancer cells

(88(0) (20%)
↓
cell death/Necrosis of Cancer cells
mechanism of Apoptosis: Apoptosis
A -

7
Initiation (Caspases 8,9,10) -
Execution A

3,6,7

I
caspases
-

Extrinsic (8, 10]

->
Intrinsic (9)

-
INITATION
Are ⑧ T-cell
extrinsic
(D-95 liqand/FAS liq and
·
pathway:
(Death Receptor pathways
As
re

Apoptotic cell

↓
FADD =
Fas Associated death domain
- - - > caspases (8, 10]
Procaspases (8,10]
(Anti-Apoptotic
FLIP & molecule -
For Extrinsic pathways

I
Intrinsic
pathway light ↑ puotpoptotic factors
UV
(mitochondrial pathway Me *
↑ ↓ Anti-apoptotic Factors

↑
Stress sensors
BIM
BAD
BIP
NOXA
PUMA
 pro-Apoptotic Anti-Apoptotic
-
p53 -BC 2

-
BAK -MCC 1

·
BAX -BC1-XL

·BCL-XS

stress sensors increase pro-Apoptotic bodies.

b
Goes to mitochondria

protpoptotic proteins

·mar'
&
mitochondria.
->
combines with Apoptosis Activating Factor-1
& Forms Apoptosome.

bohmane

Apoptosome
Procaspase- 9 - > Caspase- 9
(Cyt -c Apaf D
+
-
 EXECUTION 8,9,10 caspases (Initiation)
Activate
1
3, 6, 7 caspases (Executions

↓
Activates Enzymes
·
phopholipase
·
Protease

I
* Endonuclease -
Internudeosomal deavage
step ladder
Breaks at regular Intervals (180-200bp after
↓ patter.
-
CPTO- written on

Page 14]

-200bp200b

it
.
.

⑧...imbospondin
Apoptotic bodies.
I eatmee
Phosphatidylserines
Phagocytosis.

macrophages.

· ceumembrane bound bodies with

or withoutorganelles phosphor bilayer

EFFEROMTOSS
GHiratamsenna
⑧ Parto f phospho-
lipid
outer
to
membrane

part

2D.recetort
⑱-
SLE
Defectin Efferosome:
signals -> to manoparties
Bromchiectasis Enime
COPB

cystic fibrosis. po-Apoptotic bodies -> BH1-3 optic

Glw
Defect in PS Flipping:SCOTT SYNDROME
Apoptotic
A bodies -> BH1-I sexsteroids

toptosisdeflect Bloodcat I nee

Anti-Apoptotic
-

tomation is
stress sensors -

BME
 Paanch(V]
exin
Identification of Apoptosis APOPTOSIS
marker

molecular marker
ANNEXIM

CD-95/
5
=
CA marker thatd etects

FAS (Extrinsic pathways

PS-Flipping) I
[ANNEXINAD-HAIRY
Al-> Annexin
I
CELL LEUKEMIA

microscopic examination.

↓
-
Apoptotic tion

cel

Tiny Groups in nuclear

Hallmark:Nuclear chromatin condensation.

factors)
Hallmark of neuronal Apoptosis:All (Apoptosis Induring
Neurons do not have Caspases.

stai Tunnel stain.

⑦
in Apoptosis

⑦ in Necrosis

Step ladder pattern.

 Newer cell deaths
-
cell
injury April
Friday, 7th 2023

SUARMA MAM 6:56 pm.

DU. PREETHI
-

prepladder

cell deaths -
Newer.

① NECROPTOSIS caspase independent programmed cell death.

Necrosis +

Apoptosis Necrosis + Apoptosis

↓ ↓
COD
morphology programmed cell death

Programmed Necrosis inflammation ·

physiological -
plate Formation
Growth

·Pathological -

steatohepatitis
Injuries (M1. Heartattack patients]
Repurfusion
pancreatitis
A (caspase Inhibitors present
* A cytomegalovives
are

↓
Plan A: Apoptosis does noto ccur

↓
Plan B.: Necroptosis occurs.

in
mechanism of mprosis

the Step Binding of to

1: TNF Receptors INF

Step 2: Formation of a trio:

neter Gets Activated.

Reeperinevangelinateen
·

MLKL -

Phosphorylation.
Step
I
3:MLKL -

phosphorylation

ceumembranerupture
 cell death

②PYROPTOSIS Associated with

micro-organisms

Eq:Shigella, Salmonella

Receptors Involved in pyroptosis:NOD Receptor

Entry of micro-organisms

↓
Recognised by NOD Receptors

↓
Forms Inflammosome

↓
Activates Caspases -

Q11
↓ -
causes CELL DEATH
Activates Interleukin-1

↓
causes FEVER

3 Natural Environment.
ANOIKIS
lack
seen in
of

Type of Apoptosis
 Cellular Adaptations. April
Fri, 7th 2023

Dr. PreethiSharma man-prepladder 7:51pm.

A
Cellular
Adaptations ① HYPER TROPHY &
HYPERPLASIA

① Increase in size. Increase number

Hypertrophy in cell
·

② Hyperplasia · Increased Transcription Factors. Increased mitosis.

GATA4, NFAT, MEF2.

③ Atrophy

⑫ metaplasia

⑤
Dysplasia A
Eg: -
Pregnancy/Gravid Utems -> HT+HP

development -
Puberty &
Pregnancy -> HT
H
+

~Breast

builders skeletal muscle HT.

Body ->
-

staff
~ proximal to obstruction:

camerais
Bladder I
urinary distal
Intestive

Endometrial hyperplasia Cestrogen): (orman,

Granulosa
- cell tumor

·
Post menopausal women
Too much of estrogen is produced
↓ ↓
If untreated, leads to Endometrial
Cancer
Endometrial Hyperplasia.
1.
Type -

- Nodular Prostatic hyperplasia:NPH

leads
52-redutase
Dihydrotestosterone NPH.
*Testosterone -->
->

TypeI to

YO *A
Cara FINASTERIDE A
③
ATROPHY size
↓
& d no.
of cell.

mechanism: ubiquitin proteosome pathway

are- muscleAtrophy.
Eg:· Disuse cast
Atrophy - ->

x 6 weeks

·
Denervation Atrophy -

size of organ t

Eq:Polio.

· Ischemic Atrophy:1 Blood

Supply.
Eq:Semile/Elderly people

Alzheimer's disease
·
Malnutrition.

Endometrial
·
Atrophy:
Estrogen
↓o
-

leads to Endometrial cancer type-I0

worse
prognosis

- All celular adaptations are REVERSIBLE

-
Toughest to Revert -

ATROPHY.
④ METAPLASIA 100. Reversible.

one tissue to -
Another tissue

Spithelial - Epithelial

mesenchymal - mesenchymal
Stem

mechanism programmismoking
ng
of cells.

spithelial basic
Eg:
.

lungs w iA
excess/deficient
squamous Epithelium.

Pseudostratified ciliated columnar Epithelium

Precancerous condition (Adenocarcinoma of Esophagus)

·
Barrett's esophagus -

esophageal
Refluxdisease
intestinal columnar Epithelium
in

[Goblet (els]

oesophagus.
-

squamous Epithelium
-
Sc
releases

blue.
Special stain: Alcian
mesenchymal metaplasia occurs in mesodermal parts.

myositis
Eq: ossificans.
trauma
muscle-> calcium/stones.

,
*A

Hypertrophy Hyperplasia Atrophy metaplasia

/ -
I -
senile
puberty Chronic
smoking.
·

Pregnancy ·
Results in SMOLD

squamous metaplasia of lactiferous ducts

 Intracellular Accumulations.
Fri, IMApril.
DV. Preethi Sharma Ma'am-Prepladder 20:40.

-Endogenous
Intracellular Accumulation ·

Pigments (Exogenous
-

Lipids
-

Proteins
Glycogen
-

Parkinson's disease:
· calcium
decreased DOPA &

Endogenous pigments:A Melanin. -

Brownish black pigment. melanin

↓
skilhair Eyes
seen in
Pale Substantia Niqua.
in Brieen

stains ③ Enzyme Histochemical Stain z

Dopa oxidase

④ Immuno histochemistry
-
always hasblast
discoloration

* Hemosiderin/Iron: * Lipofuscin/lipochrome
Wear & tear pigment
Hemowhage/Hematoma.
yellowbrown/Refractile. Telltale sign of Free Radical Injury (Liexidating
Stain:Prussian blue/ Perl" stainfest Brown in color

Lillie's stain (Fe2t] senile

Atrophy.
Stain:Oil Red O
In stain.

EIM.
Exogenous pigments

Copper ↑Cu:Wilson's disease

stain:Rhodanine, Rubeanic acid

ceruloplasmin
Protein copper:
with

orein stain.

~cenuloplasmin.
RCEElastin
organism for
Hepatitis B
Ag.

trematin/Hemozoin malavia

Anthracotic
pigmentCarbon

Homogentistic id Alkaptonusia

Lipids m/c:Fatty liver./Steatosis

Tabby Cat/Tiggered
Lipids in heart - Effect

cardio myopathy
Arrythmogenic Right ventricular
cell
injury

Riphthelial myocarditis.
Atherosclerosis
stains for lipids

⑪
Proteins: mallocy hyaline/denk bodies
[

Cytokeratin (K8/18

Seen in Alcoholic
-

diseases.
L
composition

⑦ multiple
myeloma.
 ③ crooke
hyaline change

Glycogen Accumulates in

Glycogen storage disorders

·Diabetic
Nephropathy
PCT= Armaniebstein lesion.
·
Glyrogen in

stain:PAS:Periodic Acid Schiff

special
PAS+ diastase sensitive.

Glycogen +
PAS -> Pink color. se, Rink color disappears.
Calcification. Types

Dystrophic calcification metastatic calcification.

dead/ tissue Tissue Normal.

degenerative
-

cast Blood:Normal Blood Cast

of -

(9-11 mg/dL)
- Affects lungs
Eq:. TB
Eq:. Hyperparathyroidism
Atheroma
↑ PTH, & Cart
dead parasite
- cancers -

Renaleuca
ninoma
at the

monckeberg sclerosis
vit-D Intoxication. ↑Cact
calcific medial
degeneration. ~

-Milk Alkali-Cast

cat
multiple myeloma -

Bonelysis -

-
SARCOIDOSS

non-castating Granuloma

·Psammoma bodies
Producing Vitamin Dy
d
↑ Cat

↑Castlevel:AFFECTS lungs,
 ⑰in
Stains
④
Ca2+:
of
I Aban stain
① von Kossa ② Alizank
Red's To differentiate
↓
Black ↓ mineralised & osteoid.
Red Color
minute Amountof Cacty

Firstplace of cat mitochondria.

deposition
Exception:Kidneys.
Basement membrane.
They getdeposited in

CongoRed stain:Amyloid
masson trichome:Collagen.
 Autophagy/Cell Cannabilism
Ar; It April, 2003.
Dr. PreethiSharma Ma'an
11:09pm

Recognised & Explained by YoshinoviOhsumi ITOR increases staration

Autophagy. in

seen in : senile ↓MACROPHAGY.

malnutrition
cancers
Autophagy fderives
stimulates
nutrients.
Neurodegenerative diseases (A3, Park)

& Types of Autophagy ①Macroautophagy & microautophagy

&
Chaperon mediated Autophagy & mitoAutophagy

① MACROAUTOPHAGY
A
-

SHOME

mechanism of macrophagy

-
markerof
⑪ ② ③
Autophagy.
lysis.
&
microautophagy. (HOSTEL) direct uptake by Endocytosis,by lygosome

③ ChAPERON MEDIATED misfolded protein

(contactebd y EATsousDRO --
AUTOPHAGY

itit dose ~

188888 /
misfolded hsp
-

:-
_ysosomes. degraded
misfolded
Protein via
Protein.
cysosomes.
⑧ MITOPHAGY Type of macroautophagy.
↓ ↓
eating of mitochondria. Autophagosome formation.

Pink& Parkin it surface

old mitochondria:recognised
by on
by macrophages.
eaten 1st.
old & damaged mitochondria are

Autophagy
-

· Marker L-3 (light chain 3)

· MostImp Gene ATG-1

ATG161 mutation in
Inflammatory bowel disease.
-

~
ATG5mutation *B
 Cellular
Aging:

Cellular causes:
Aging:

Why do we
Age? - Free Radical
miny
·Telomere
shortening
· Insulin Resistance

~DNA
Repair defects
Telomere Shortening:Telomeres:Terminal ends of chromosome.

DefaultSequence TTAGGG

Gets shortened with Each cell division, Reduces with Age.

Telomerase:RNAdependent DNApolymerase

prevents telomere shortening.

IMMORTALITY GENE

HAYFLICK LIMIT: 40-60 or 60-70 = 60 cell divisions of cell occur

before cell gets old & telomeres shorter.

How to life?SIRT- Genes (SIRT1-6).
prolong
↓
(Histoden deacetylases
SIRTUN
↑ Proteins (Activated)

Anti-Aging
Role of SIRTUINS: A -

Anti-Aging
B -

benefits.

2 -
Cancer Treatment (Promote Cell Repair)

D -
Diabetes treatment(Increases Insulin sensitivity

How to SIRTUINS?Calorie deficit i

Red wine consumption:(minimum]

Premature
Aging

Hutchinson Gilford Syndrome

-> LONAFARNIB:drg.

↓ corrects shape of Nucleus

famesyl transferase Inhibitors

Free Radical
Injury 02
Formation.
↓ Toxins, Reperfusion Injury, Poisons, toxins.

0: exide> 18- OH
dismutase

(SOD)
Felt
Fest
-
Fenton" Reaction.

Lipid peroxidation.

or Reactive
oxygen Cross,
species.

ane

Lipofuscin pigment

DIET:Anti-oxidants.

TransferredareBurgerspat
TRANSPORT PROTENS:

ENZYMES
* SOD

Ok -> Moz-> On

10
Jase/al
oz utathione
peroxidase

H20 02+