cell injury

Question 1

Gold standard stain in pathology

Answer 1

Hematoxyline (nucleas- blue/purple) and Eosin (H & E) (cytoplasm. protein carb etc, but not fat)

Frozen section for Fat

Question 2

calcium ion takes up which stain in H & E staining

Answer 2

Hematoxyline (Basophilic)

Question 3

Multiple blood transfusion Brown pigment in macrophages of liver, spleen and Lymph nodes. Brown pigments in parenchymal cells of heart, liver and endocrinal cells. What is the composition of this brown pigments? what is a special stain that can be used?

Answer 3

Ferritin micelles form hemosiderin

special stain- Prussian blue (blue)

Question 4

Presenting complaint -fever, sweating, weight loss

X-ray- a cavity in the upper lobe of the lung

Staining procedure most appropriate from the sputum specimen?

Answer 4

Ziehl- Neelsen stain (Acid-fast)

Intracellular bacilli

Question 5

Kidney specimen shows pink agranular, hyalin like deposits in glomeruli (mesangium)

Polarized light shows apple green birefringence

what is this agranular pink substance?

Name the special stain used here?

Answer 5

Amyloid

Congo red

Question 6

man suffers a myocardial infarction

a decrease in the activity of the oxidative phosphorylation pathway

myocytes at this time reveal swelling of the smooth endoplasmic reticulum

what biochemical changes will be seen in the cell?

Answer 6

Na Influx

K Efflux

Calcium influx (intracellular)

H+ Influx

H20 influx

Question 7

A 90-year-old woman with Alzheimer disease dies

autopsy hepatocytes are noted to contain golden cytoplasmic granules that do not stain with Prussian blue

pathogenesis of pigment accumulation in hepatocytes?

Answer 7

Wear and tear pigment

Lipofuchin

lipid peroxidation ( damage by ROS)

Question 8

Reversible cell injury (hypoxic): Clinical causes, the morphology of the cell (all except liver and Heart), and biochemical alteration of the cells.

Answer 8

Clinical causes- CO poisoning, Anemia, Decreased perfusion of tissue ( cardiac failure, hypotension, and shock), Poor oxygenation of blood-pulmonary diseases, Ischemia.

Morphology- cell swelling, blebs, hydropic changes (water vacuoles), swelling of organelles, glycogen depletion, dissociation of ribosomes (decreased protein synthesis)

Liver and Heart- lipid vacuoles

Biochemical alteration : Refer card no 6

Question 9

Irreversible cell injury: Morphology of the cytoplasm and nucleus, biochemical alteration

Answer 9

Cytoplasm eosinophilic (glassy), Mitochondrial densities (EM feature)

nucleus changes - pyknosis, karyolysis, Karyorrhexis

Biochemical- ↑ free radical*, ↑ Ca in the cell**, lipid peroxidation →membrane damage***.

Question 10

Free radical injury: generation of oxygen-derived free radical and how they are removed. Example of free radical injury

Answer 10

Free radicals- superoxide, hydrogen peroxide, hydroxyl radical

Removal of free radical

1. enzymes- superoxide dismutase, catalase, Glutathione peroxidase
2. fe2+ and Cu2+ binding proteins (ferritin &ceruloplasmin)
3. Vitamin A, C & E

Examples of free radical injury- Inflammation, reperfusion injury, Radiation and chemical injury

Question 11

Morphological Evidence of membrane or cytoskeleton damage?

Answer 11

Cytoskeletal damage

1. Mallory body (intermediate cytokeratin) - alcoholic hepatitis
2. Neurofibrillary tangles- Tau proteins in microtubules- Alzheimer’s disease
3. Kartageners syndrome- microtubule dearrangement.

Membrane damage

Myelin figure

Question 12

How these cytoskeletal proteins can be used as a marker!

Answer 12

Intermediate filaments are used as markers of the cell in various tumor

1. CytoKeratin Filaments = Epithelial cells (adeno and squamous cell carcinoma)
2. Neurofilaments= Neurons
3. Desmin= Muscles
4. Vimentin = Connective tissues
5. Glial Filament = Astrocytes of Brain.

Question 13

Coagulative necrosis: cause

Micro and gross morphology description of coagulative necrosis

the fate of coagulative necrosis.

Answer 13

Cause -sudden loss of blood supply to an organ( Ischemia).

Micro- Maintenance of cell outline but the loss of nuclei

Gross- Wedge shapes well demarcated pale area (heart, kidney, spleen). If reperfusion Occur in a pale infarct it will be RED.

Fate- Fibrosis ( scar)

Question 14

mechanism of reperfusion injury

Answer 14

Reperfusion injury of Heart in a patient with Myocardial infarction following thrombolytic therapy.

Sudden Inflow of oxygenated blood to the infarcted area will generate Free radicles, by Neutrophils

Question 15

Liquefactive necrosis: cause, 2 types, morphology.

Examples of each type and fate of each type.

Answer 15

Causes or 2 types

1. Brain ( acute loss of blood supply)Autolysis 2. Abscess ( by lysozymes of neutrophils): localized accumulation of PUS (Heterolysis)

Morphology

Micro- Necrotic tissue with macrophage

Gross- Gelatinous

Fate-

Abscess: organization

Brain Infarct = Cavity formation

Question 16

Apoptosis: intrinsic mechanism pathway

Answer 16

Intrinsic ( Mitochondrial)- lack of growth signals, radiation or protein misfolding

Activation and dimerization of proapoptotic factors in the cytoplasm(bax, bim, bid)

they interfere and insert with anti-apoptotic factors (bcl 2 &bclx)on mitochondrial membrane

cytochrome c leaks out

Activation of caspase 9 (initiator)

Activation of executioner caspases 3,6

activation of the endonuclease and proteolytic enzymes

Question 17

Apotosis - extrinsic ( CD8 cells )

Answer 17

Fas receptor +Fasl (ligand on CD cells)

activation of a death domain

caspase activation (initiator) 8

activation of executioner caspase 3 and 6

activation of the endonuclease and proteolytic enzymes

apoptosis

Question 18

Apoptosis and electrophoresis band

Answer 18

step ladder

Question 19

Apoptosis Vs necrosis

Answer 19

Question 20

Gangrene: morphology (types of necrosis seen) and causes.

Answer 20

morphology (types of necrosis seen)

Dry gangrene- Coagulative necrosis

Examples- –Thromboembolism, Diabetes mellitus

Wet gangrene - liquefactive necrosis

Example- volvulus

Gross- Color change and distinct “line of demarcation” is visible between the necrotic tissue and normal tissue

Question 21

Fat necrosis: 2 causes and morphology. Clinical example for 2 types

Answer 21

2 causes

1. Traumatic fat necrosis- breast
2. enzymatic (lipase) fat necrosis- acute hemorrhagic pancreatitis

Morphology

Gross- Chalky white areas (due to the deposit of calcium).

Micr0- Dystrophic calcification(Saponification), and shadowy outline of necrotic fat, plasma cells.

Question 22

Fibrinoid necrosis: morphology and examples*

Answer 22

Necrosis in which the necrotic tissue around small blood vessels

Cause:

–Kidney in Malignant Hypertension

–In immunological Injury [transplant reaction]

–SLE

–PAN (polyarteritis nodosa)

Morphology- Fibrin like proteinaceous material in the arterial wall

Question 23

Hyperplasia: Physiologic Vs pathologic. Organ morphology

Answer 23

Physiological- Common in labile cells and stable cells

1. The proliferation of the glandular Hyperplasia (lobular hyperplasia) of female breast during puberty and pregnancy (effect of prolactin and estrogen).
2. Compensatory Hyperplasia in the liver following partial Hepatectomy
3. Uterus- myometrium; Hyperplasia/hypertrophy
4. Endometrial hyperplasia- estrogen

Pathological-

1. Endometrial hyperplasia: high chance of adenocarcinoma(Complications of Hyperplasia)
2. Prostatic hyperplasia
3. Viral infections – papillomavirus – skin warts

Question 24

Mechanism of hyperplasia - endometrium and prostate

Answer 24

• increased local production of growth factors
• increased number of growth factors on responding cells

Endometrium- estrogen

Prostate - DHT

Question 25

Hypertrophy: Causes- Muscle vs heart.

Answer 25

**Hypertrophy morphology**- Increased size of cell: increased cellular protein. ## Footnote Increased mitochondria. **SK muscle (**Molecular changes) Increased Protein (mRNA), increased mitochondria, myofilaments increases (normal) **Heart muscle (**Molecular changes)- Switch of contractile proteins(beta-myosin) from adult to fetal or neonatal forms. Increased gene expression of encoding transcription factors: c-fos, c-jun

Question 26

1. Atrophy: Molecular mechanism. Atrophy example of each: age, workload, hormone, nerve

Answer 26

SHRINKAGE OF THE SIZE OF THE CELL DUE TO LOSS OF CELL SUBSTANCE **Mechanism** 1. Autophagy 2. ubiquitin-proteasome pathway **Atrophy examples** * Sheehan's- adrenal cortex- ZF * Age- gonads, vaginal atrophy * Age- heart- brown atrophy * Age- thymus * Laxative use- intestine- melanosis coli (brown pigmentation of rectal mucosa) * Age- Brain Loss of innervation- group muscle atrophy

Question 27

Pigments in the atrophic cells ( melanosis coli, heart, liver)

Answer 27

Accumulation of Lipofuscin Oil O red positive

Question 28

Metaplasia: Definition and molecular mechanism. Examples of squamous, columnar, intestinal, mesenchymal tissue metaplasia;

Answer 28

Metaplasia: One adult cell type is replaced by another adult cell type ## Footnote **1.Epithelial metaplasia:** * Squamous metaplasia* 1. Respiratory Mucosa (smoking, pollution, vitamin A deficiency). * Columnar epithelial metaplasia* 1. The lower end of the esophagus ( reflux of acidic gastric juice: Barrett's Esophagus). 2. **Connective tissue metaplasia** 1. Myositis Ossificans: muscle is replaced by bone and fibrous tissue.

Question 29

Identify the metaplasia?

Answer 29

Non-ciliated Columnar metaplasia with goblet cells- Barett's esophagus