📌 causes of cell injury:
• Hypoxia
• Immune reaction
• Micro organisms
• Chemicals & drug
• Aging
• nutritional imbalance
• physical agent
• genetic agent

📌 Types of cell injury:
• ischemic & Hypoxic cell injury
•free radical mediated cell injury
• chemical mediated cell injury
• Cellular Aging

📌Increasing in cytosolic Ca :-
• activation of cellular enzymes➡️ membrane damage, nuclear damage, ⬇️ ATP

• ⬆️ mitochondrial permeability transition➡️ decrease in ATP

🧬 Injury to plasma membrane is the central factor in pathogenesis of irreversible cell injury

🧬Ca influx play an important role in membrane damge

📌 Effects of free radicals:-
• lipid peroxidation of membranes
• Nonperoxidative mitochondrial damage
• DNA damage
• protein oxidation

🧬 free radicals oxidation ➡️lipid, protein, DNA

Termination of free radicals
• spontaneous decay e.g(Superoxide)
• enzymatic degradation :-
🔸SOD decomposes Superoxide into (H2O2 and O2)
🔸 glutathione peroxidase converts (OH into H2O2)
🔸 catalase decomposes H2O2 into(O2 & H2O)
🔸 Antioxidant block initiation or activation of free radicals



📌necrosis(cell death):
🔸️death of "group" of cell in living organism
🔸️*induction of necrosis due to pathological injury .(irreversible)

🔸️causes of necrosis
1-digestion of cell by enzyme.
2-denaturation of protein.

🔬Morphology of necrosis
Under microscopic :-
1-changes in nucleus:
📌 pyknosis: condensation & shrinkage of DNA
📌 Karyorrhexis: fragmentation of pyknotic nuclear mass
📌 karyolysis: fading of basophila of chromatin.

2-changes in cytoplasm:-
⬆eosinophilia d/t loss of RNA
cytoplasm become vaculated & appear moth-eaten

💭Gross morphology(types of necrosis)
🔸-coagulative necrosis(most comm ) --->preservation of basic outline of coagulated cell for some days.
e.g:all hypoxic death cell except brain
(myocardial infarction -infarction in solid organ).
Wedge shaped infarct , yellow pale

🔸-liquefactive necrosis----> progressive catalysis of cell structure ;with loss of basic outline of cell.
e.g:- focal bacterial infection -brain infraction

🔸-caseous necrosis--->appeare white cheesy caseation & granuloma.
e.g:tuberculous infection

🔸-Fat necrosis----->2 type
•enzymatic :in acute pancrititis .
•traumatic: e.g trauma to subcutanous tissue of breast form breast lump(mistaken for malignancy)

🔸-fibrinoid necrosis ---->immunologic injuries to arteries & arterioles.
e.g (polyarteritis nedosa)

🔸-gangrenous necrosis----> massive necrosis and putrefaction

🖇📍1-Dry gangrene (coagulative necrosis predominant)
🔸️in limbs
🔹️2ry to chronic Deprivation
🔹️ Artery occlusion
🔸️black -foul smell (( formation of hydrogen sulphide-))
🔸️mummification & dryness .
🔸️line of demarcation & separation

🖇📍2-Wet gangrene
🔸️from sudden A &V occlusion
🔸️ strangulated hernia; intussusception; volvulus)-
🔸️no fluid evaboration-
🔸️presence of bacteria with rapid invasion of necrotic tissue 🔸️produce moist gangrene +toxaemia.(poor prognosis)
e.g:- bed sores, diabetic foot,

🔹diabetic gangrene start as dry then due to bacterial butrefaction & edema turn in wet gangrene


🖇📍3-Gas gangrene:
🔸️ M.O causing cell necrosis & gangrene - formation of gas giving bad smell & crackling noises after palpitation - mortality high due to toxin & toxemia.

🖇📍4-infective gangrene
🔹️bacteria causing both necrosis & putrefaction
•noma pudenda
•cancrum oris
•meleneys post operative synergistic gangrene.

📌Reversible cell injury
structure and function can be regained after removal patholohic stimuli, can be recognized under microscope:-
🔸Plasma membrane changes
🔸 Mitochondrial changes (swelling)
🔸 Nuclear changes Such have clumping of n chromatin
🔸 swelling ER , detachment of ribosomes, dissociation of polysomes

#pathology
cell injury

Mech of apoptosis:
1_initiation phase
🔸Intrinsic(mitochondrial) pathway: caspase( 9)
🔸extrinsic (death receptor): caspase (8,10)
2_Execution phase: caspases (3,6,7)

🔹 Apoptosis inhibited by (BCL-2 /BCL-x)
🔹 Apoptosis activated by (Bax, Bak , Bid)

📌Several mechanisms are known or suspected in cellular aging:-
• DNA damage
• decreased cellular replication
• aging of tumor suppressor gene
• accumulation of metabolic damage
• abnormal growth factors signaling

#pathology
cell injury

📌 fatty change (steatosis)➡️ most comm site (liver)
🖇 alcohol and diabetes associated with obesity are the most common causes of fatty change
🖇 fatty ch is reversible except in CCI4 poisoning

📍 Russell bodies :in multiple myloma (Ig accumulation in plasma Cs)
📍 Mallory bodies or alcoholic hyalin :inclusions composed of aggregated intermediate cytokeratin filaments
📍 Neurofibrillary tangle : in alzheimer ds is an aggregated protein inclusion contain microtubule associated proteins

📌 in poorly controlled DM glycogen accumulates in renal tubular epithelium , cardiac myocytes , β cells

📌 Carbon is the most comm exogenous pigment
📍 Anthracosis
📍 coal workers pneumoconiosis

📌Lipofuscin "wear & tear pigment" insoluble brownish yellow ➡️brown Atrophy
. seen in ( heart , liver , brain ) as a function of age or atrophy
⚠️it is not injurious to the cell but imp as a marker of past free radical injury


📌 Melanin act as screen against harmful UV radiation

📌 Hemosiderin : golden yellow brown. can be identified by prussian blue dye .
📍 Hemosiderosis: acc of hemosiderin without organ damage
📍 hemochromatosis : extensive acc with tissue damage
🔸hereditary hemochromatosis caused by mutation in Hfe gene


📌 Dystrophic calcification
📍 normal Ca deposit in dead tissue
📍 mostly in area of necrosis

📌 Metastasis calcification
📍 Deposit Ca in living tissue because hypercalemia

📍Causes :
1_ hyperparathyrodism
2_ hyperthyroidism
3_ Vit D toxicity
4_ Addison disease
5_ sarcoidosis
6_ bone marrow tumor
7_ immobilization
8_ milk alliance syndrome
#pathology
Accumulation

#pathology
Accumulation

⛔atrophy
⬇️
decrease in size of the cell(atrophic cell not' dead but if stimulation continues ↪die by apoptosis.
increase autophagic vaculoes -residual bodies-lipofuscin pigment. (Brown atrophy)

🔹️mechanism of atrophy:
decrease protein synthesis
increase protein degradation
(by ubiquitin-proteasome pathway)

🔹️causes of atrophy➡
1/reduced workload(in case of cast)
2/inadequate nutrition
3/ageing
4/loss of innervation
5/decreed B.supply-
6/ loss endocrine stimulation.

🔹️types of atrophy:
🖇physiological atrophy➡
atrophy of ductus arteriosus
-atrophy of thymus in adult-
atrophy of gonads in old age.
🖇pathological atrophy
💥generalized atrophy ↪atrophy due to starvation-senile atrophy.
💥localized atrophy⬇️
🔸️ischaemic atrophy 👉small atrophic kidney in atherosclerosis of renal .A.
🔸️disuse atrophy👉 wasting of ms of limb immobilised in cast.
🔸️neuropathic atrophy👉 poliomyelitis.
🔸️endocrine atrophy👉hypopituitarism lead to atrophy of thyroid ;adrenal & gonads.
🔸️pressure atrophy➡. erosion of spine
by tumour in nerve root

🚫hypoplasia
incomplete growth of organ
🚫agenesis
complete failure of development of organe in embryogenesis.

🏷 hypertrophy----> increase in size of cell

✔✔hypertrophy without hyperplasia affect mainly perminant cell(heart-skeletal ms-nerve cell)
🔹️ physiological hypertrophy:
❗enlargment of uterus during pregnancy due to estrogen stimulation-
❗ breast enlargment during pregnancy
❗-skeletal .ms hypertrophy d/t increase workload.
🔹️pathological hypertrophy
❗hypertrophy of uterine smooth ms (effect of estrogen secreted by ovarian tumor)
❗lt.v.hypertrophy-
❗Rt.v.hypertrophy.

🏷 hyperplasia:
increase in number of cells.
Du to 1-hormonal stimulation
2-tissue loss(labile cells & stable cells).

🖇physiological
🔹️hormonal.
proliferation of epith.of breast at puberty& during pregnancy d/t estrogen stimulation.
🔹️compensatory:
occure when portion of tissue removed or diseased. e.g➡compensatory hyperplasia of remaining liver after hepatectomy.
🖇pathological
🔸️.adenomatous hyperplasia of endometrium after normal M.C d/t increased esreogen /progesterone ratio.
🔸️hyperplasia of thyroid follicle in 1ry hyperthyroidism.
🔸️hyperplasia associated with viral infection(HPV)
🔸️benign prostatic hyperplasia.
🔸️ important in wound healing.

🚫Estrogen:
Hyperplasia and hypertrophy _▪︎ Normal : pregnancy (uterus and breast)
🏷Metaplasia:reversible changes ;ons cell type replaced by another cell type.
💭metaplasia fertile soil for malignant transformation
التغير ح نسميه حسب نوع الcell الي طلعلي '!

⛔ types of metaplasia:
1-epithelial(reversible)
🔸️Seq.metaplasia.
(replacement of columnar epith by st.seq.epith).
.
🔸️columnar metaplasia
barrett esophagus..(normal st.seq.epith.of lower esophagus replaced by gastric or intestinal type columnar epith
2-mesenchymal (irreversible)
🔸️fibroblast to chondroblast to produce cartilage.
🔸️fibroblast into osteoblast to produce bone.(myositis ossificans)
كل ال adaptation ح تكون reversible إلا النوع هذا.


🚩 barrett esophagus: metaplasia >>>
✔adaptation
✔dysplasia >>precancer >> cancer.
#pathology
Adaptation

#pathology
#endocrine