open ended questions gen path

define necrosis, steps

types of necrosis

1. Coagulative ➡ inhibits lytic enzymes in organs with high protein content and low water

• Heart, Liver, spleen and Kidneys

• organ becomes pale, firm and then becomes yellow

• It occurs when blood flow stops

• ischemic —> hypoxia —> enzyme and protein denaturation

• denatured enzymes —>

• The cell has an outline but no nucleus

2. Liquefactive ➡ dissolution of tissue using lytic enzymes

• commonly in the brain and forms a pseudocyst

• also occurs in purulent inflammation

• liquified tissue is soft and made from disintegrated cells and tissue

3. Caseous ➡ coagulative and liquefactive necrosis

• occurs in the centre of a tuberculous granuloma

• white, cheesy centre

Definition of Amyloid - Describe sago spleen and lardaceous spleen:

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3. Definition of Amyloid - Describe sago spleen and lardaceous spleen:

• Amyloid refers to an abnormal extracellular deposition of insoluble protein material in tissues.

  • 95% - Fibrillar part = B-pleated sheet

  • 5% - Non fibrillar = P-component

• Macroscopically = large, firm, waxy

• Microscopically = structureless

• Staining = congo red + = orange

Sago's spleen

• Translucent, pale, waxy nodules

• no splenomegaly

• microscopically = Amyloid in walls of arterioles in white pulp

  • overtime replaces follicles

Lardaceous spleen

• Splenomegaly

• cut surface shows streaks of Amyloid

• microscopically = deposits in CT of red pulp

Kidney

1. Gross Changes

• Enlarged, pale, firm, waxy kidneys (early stage).

• Shrunken, fibrotic kidneys (late stage).

2. Microscopic Changes

• Glomerular deposits → Thickened capillary walls, glomerulosclerosis, proteinuria.

• Tubular deposits → Tubular atrophy, protein casts.

• Vascular deposits → Thickened vessels, ischemia.

• Interstitial fibrosis → Chronic damage and renal dysfunction.

Clinical Consequences

• Nephrotic Syndrome (proteinuria, oedema).

• Chronic Kidney Disease (CKD) → requiring dialysis.

• Hypertension

what are the pathological methods of examination?

types of chronic inflammation?

Types:

• (1) Non-specific:

  = irritant produces non-specific chronic inflammatory response, formation of granulated tissue and healing by fibrosis (e.g. chronic ulcer/lung abscess)

• (2) Specific:

  = injury causes a characteristic histological tissue response (e.g. TB, leprosy, syphilis)

Hypertrophy- definition

Hypertrophy

• Definition - increase in size of parenchymal cells

• Enlargement of organ or tissue without changing the number of cells

Hypertrophy- types and examples

- Types: physiological or pathological

Physiological Hypertrophy

1. Neurohormonal Stimuli:

   • Female breast: Enlargement during puberty and lactation.

   • Uterus: Growth during pregnancy.

   • Prostatic hyperplasia: In elderly men due to hormonal changes.

2. Working Hypertrophy:

   • Skeletal muscle in athletes: Increased functional demand leads to the production of more myofilaments, enlarging the muscle fibers.

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Pathological Hypertrophy

1. Neurohormonal Stimuli:

   • Atrophy of testes: Due to hormonal imbalances or dysfunction.

   • Hyperfunction of anterior pituitary: Excessive growth hormone production.

   • Hypertension: Increased workload causes hypertrophy of cardiomyocytes due to the production of more myofilaments.

2. Working Hypertrophy:

   • Cardiac muscle hypertrophy: Occurs in hypertension or aortic valve disease.

   • Smooth muscle hypertrophy: Seen in pyloric stenosis.

   • Bladder hypertrophy: Due to obstruction caused by an adenoma of the prostate gland.

3. Compensatory Hypertrophy:

   • Liver regeneration: Following partial hepatectomy, remaining liver cells grow to compensate for the lost tissue.

   • Epidermis: Increased thickness following abrasion or injury.

   • Myocardium: Enlargement after a myocardial infarction as a compensatory mechanism.

4. Substitutional Hypertrophy:

   • After nephrectomy: In young patients, the remaining kidney may be replaced by connective tissue as an adaptive response.

5. Hypertrophic Vegetations:

   • Chronic inflammation of mucous membranes: Leads to tissue thickening.

   • Granulation tissue formation: During wound healing.

which organs are most affected by fat degeneration?

Fat degeneration refers to the abnormal accumulation of lipids in cells

1. Liver Causes:

• Alcoholic steatosis (chronic alcoholism):

  • Increased fatty acid (FA) synthesis and reduced FA oxidation due to alcohol.

• Diabetes mellitus:

  • Decreased insulin leads to increased lipid accumulation.

• Malnutrition:

  • Reduced lipoprotein production prevents lipid transport from the liver, causing fat buildup.

Morphological Features:

• Macroscopically:

  • Enlarged, round, pale, greasy, and waxy liver.

• Microscopically:

  • Lipid vacuoles appear in the cytoplasm of hepatocytes.

  • Vacuoles push the nucleus to the periphery of the cell.

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2. Heart (Tiger Heart) Causes:

• Fatty degeneration of cardiac muscles occurs due to hypoxia or systemic metabolic disorders.

Morphological Features:

• Macroscopically:

  • Enlarged heart with flabby, stretched chambers.

  • Striped or “tiger-like” appearance due to fatty streaks in the myocardium.

• Microscopically:

  • Fatty vacuoles are seen in the papillary muscles and trabeculae, giving the myocardium a striped look.

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3. Kidney Causes:

• Commonly seen in nephrotic syndrome, associated with lipid metabolism abnormalities.

Morphological Features:

• Macroscopically:

  • Enlarged and flabby kidneys.

  • The cortical substance appears grey with yellow lipid droplets.

• Microscopically:

  • Lipids accumulate in the cytoplasm of epithelial cells in the convoluted tubules.

Microscopic Proof of Fat Degeneration

Light Microscopy (Normal Staining) 🔬

• Unfixed or Formalin-fixed tissue: Best observed without alcohol-based fixation since alcohol dissolves lipids.

• Cryosectioning (Freezing Microtome): Used to preserve lipids.

• Stains Used:

  • Sudan III → Lipids appear orange-red.

  • Oil Red O → Lipids appear red.

  • Hematoxylin and Eosin (H&E) → Shows clear vacuoles (ring-like appearance) since fat dissolves during processing.

Polarized Light Microscopy

• Purpose: Detects neutral lipids & cholesterol esters using birefringence (double refraction of light).

• Key Finding:

  • Cholesterol crystals → Show bright birefringence under polarized light.

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Electron Microscopy (Ultrastructural Level)

• Fixation: Uses osmic acid, which binds lipids and hardens them for detailed observation.

• Processing: Tissue is cut into ultrathin sections using an ultramicrotome.

• Key Findings:

  • Lipid droplets → Seen as dark-staining structures.

  • Membrane-bound liposomes → Abnormal lipid accumulation in organelles.

Morphological Proof of AMYLOIDOSIS

• Amyloidosis Overview

  • Definition: Extracellular accumulation of insoluble amyloid proteins.

Morphological Proof:

1. Macroscopic Features:

   • Affected organs are enlarged, firm, and waxy.

   • Staining Test:

     • Paint the surface with iodine (I₂), then add sulfuric acid (H₂SO₄):

       • Positive test: Color changes to yellow, then blue.

2. Microscopic Features:

   • Hematoxylin and Eosin (H&E) staining shows a structureless homogenous appearance.

   • Congo red staining:

     • Turns amyloid deposits orange-red.

     • Under polarized light: Exhibits apple-green birefringence.

Distinction Between AA and AL Amyloidosis:

• Treat with potassium permanganate, then Congo red:

  • AA amyloidosis: Congo red becomes negative.

  • AL amyloidosis: Congo red remains positive.

How many types of hemoglobinogenic pigments do you know? Describe a histochemical reaction which is used to prove them

• 2 groups of hemoglobinic pigments:

  • ① Non-iron containing : bilirubin

  • ② Iron containing :

    • ➡ Ferritin = blood protein that stores iron, located in the spleen, liver, BM and LN

    • ➡ Hemosiderin = iron storage molecule which contains ferritin in mononuclear phagocytes, looks like golden brown pigment

• Stain = prussian blue / Pearls ➡ stained blue

Describe morphologically coagulative, fat and fibrinoid necrosis

• Coagulative ➡ inhibits lytic enzymes in organs with high protein content and low water

  • Heart, Liver, spleen and Kidneys

  • organ becomes pale, firm and then becomes yellow

  • It occurs when blood flow stops

  • The cell has an outline but no nucleus

• Fat ➡ occurs in adipose tissue of the pancreas after leakage of the lipase enzyme due to injury or obstruction of the pancreatic ducts

  • looks like yellow-white deposits in the adipose tissue

  • microscopically = pale outlines and soap filled cytoplasm

• Fibrinoid ➡ in hypertension, the walls of small arteries get damaged which causes deposition of fibrin

  • Identification = bright eosinophilic hyaline-like deposits in vessel walls

Definition of hemorrhagic infarction. Explain its mechanism and give examples of organs it is seen in:

• Hemorrhagic infarction Type I: Occlusion of arteries of organs with double blood flow (lungs, collateral arteries in intestines), necrosis occurs first then hemorrhage

• Hemorrhagic infarction Type II: Venous infarction, veins dilate then rupture (intestines), hemorrhage first then necrosis

Describe the structure of granulomas in TB and sarcoidosis

• TB has caseous granuloma but sarcoidosis has non-caseous granuloma.

• Sarcoidosis has a small amount of lymphocytes and giant cells with no necrosis.

What does the term 'nutmeg liver' mean? What is its morphological appearance:

• cyanosis of the liver that turns into nutmeg liver

• mottled appearance of liver due to hepatic venous congestion

- 2 types:

• ① Straight = hypoxia causes cell injury and fatty degeneration of liver around the central vein and middle of sinusoid

• ② Reverse = peripheral cells are also damaged and have fatty degeneration, causes fibrosis and cardiac cirrhosis because all the hepatocytes die

• macroscopically = red and yellow dots on the surface

• microscopically = centrilobar hemorrhagic necrosis and fibrosis

How do we form the names of benign and malignant mesenchymal tumors? Give 3 examples:

• Benign have suffix 'oma'

• Malignant are given 'sarcoma' or 'carcinoma'

• Glandular tissue:

  • Benign = Adenoma

  • malignant = Adenocarcinoma

• Squamous epithelium:

  • Benign = papilloma

  • malignant = squamous cell carcinoma

• Other:

  • Benign = fibroma, lipoma, leiomyoma, osteoma

  • malignant = fibrosarcoma, liposarcoma, leiomyosarcoma

what are exceptions of the tumour naming rule?

Exceptions:

• Hepatocellular carcinoma: This is a malignant tumor of the liver, but it ends in "-carcinoma" even though it arises from hepatocytes (liver cells), which are epithelial in origin.

• Lymphoma: This is a malignant tumor of the lymphoid tissue, but it doesn't follow the "-sarcoma" rule.

• Melanoma: This is a malignant tumor of melanocytes, but it doesn't end in "-sarcoma."

Describe the types of hemorrhages depending on their mechanism of development and give examples

• Hemorrhage = bleeding of vessels

• According to origin: cardiac, arterial, venous, capillary

• According to mechanism of development:

  • ① External

    • Epistaxis = nose bleed

    • Hematemesis = vomiting blood

    • Hematuria = blood in urine

    • Melena = dark faeces from upper GI bleed

    • Hemoptysis = coughing blood

    • Menorrhagia = severe / long menstruation

  • ② Internal

    • Petechiae = mini puncture hemorrhages, usually on skin or conjunctiva

    • Purpura = blood accumulation in tissue between cells

    • Bruise = blood accumulation in skin or mucous membrane (purple -> green -> yellow as bilirubin is oxidised)

    • Hematoma = blood in soft tissue

    • Hemothorax = blood in pleural cavity

    • Hemoperitoneum = blood in peritoneal cavity

    • Hemopericardium = blood in pericardium

Describe the morphological changes in nutmeg liver. What are the reasons for its development?

• Liver is enlarged, tender and tense capsule

• The cut surface of the liver shows red and yellow mottled appearance

• More severe hypoxia in the centrilobular zone instead of the peripheral zone so more pronounced changes

• Shows nutmeg appearance because of dilated central veins and unaffected surrounding tissue

Describe the mechanism of the third type of hypersensitivity reaction?

• involves tissue injury mediated by immune complexes ➡ example of immune complex-mediated injury where antigen-antibody complexes

• Not normally organ specific and formed in circulation.

• IgM / IgG antibodies form complexes with antigens which causes inflammation which attracts more immune cells

• ➡ by activating complement system

  • ⬇

  • activates neutrophils and macrophages

  • ⬇

  • releases inflammatory mediators responsible for injury

18. List at least three types of granulomas containing different types of giant multinucleated cells. Describe

Tuberculosis

• granuloma = tubercle

• central caseous necrosis surrounded by epithelioid cells, Langhans cells, lymphoid cells + plasma cells

Syphilis

• area of gummous (clay-like) necrosis

• surrounded by mononuclear inflammatory cells

• granulation tissue also forms around the gumma

Sarcoidosis

• tissue contains few granulomas made of epithelioid macrophages, a few lymphocytes and giant cells

• NO central necrosis

Giant cells

• fusion of macrophages or epithelioid cells

• 20+ nuclei with different arrangements:

  • ➡ at periphery like a horse shoe ring

  • ➡ clustered at 2 poles = Langhans cells

  • ➡ centrally = foreign giant body cells

Which are the reasons for the brown induration of the lungs? Briefly describe the pathological changes

① Right heart Failure

• Brown coloured lung and congested

• due to enlargement of right ventricle

• ↑ BP in the lungs caused by chronic lung disease

② Left heart Failure

• Aortic Stenosis / weakened left ventricular wall

• causes pulmonary oedema due to dilated and congested capillaries

• capillaries rupture resulting in small hemorrhages

• Hemoglobin is phagocytosed by alveolar macrophages

  • ➡ lysis of heme = bilirubin and iron

  • ➡ stored as hemosiderin

• cells uptake hemosiderin pigments in macrophages

• converted into 'heart failure cells'

• Phagocytes with brown pigment = brown induration

20. List types of exogenous pigments - which pigment is proven by Pearl’s reaction?

Inhaled:

• Coal/carbon in alveolar macrophages, looks like black pigment around bronchi = anthracosis

Ingested

• Lead in mineralized tissue, looks like blue lines on teeth

• Silver in skin/liver/kidneys; causes hemorrhages, ⬇ Erythrocytes and immune dysfunction

• Copper in eyes/brain/liver; causes Cu poisoning

• Carotenoids in skin, makes skin look orange

Injected

• Tattoo ink ➡ in skin macrophages which stay in the CT

  • can cause LN infection

• # Hemosiderin stained in Pearls reaction

. What are the most common source of pulmonary thromboembolism:

• Pulmonary thromboembolism ➡ fatal as occludes pulmonary arterial tree, more common in bedridden patients, most fatal from deep veins of lower extremities

• causes:

  • detachment of thrombi which flows through venous drainage and enters right heart side

  • a large thrombus could lodge at the bifurcation of the pulmonary arteries of the right ventricle

  • OR could be multiple emboli or a fragmented large one

Define an abscess. What form of pathological process is it? Describe an acute and chronic abscess.

• Abscess = localized inflammation caused by acute bacterial infection and neutrophils infiltrating the inflamed tissue ➡ causes necrosis

• The cavity formed = abscess

  • ➡ contains pus

Benign and malignant tumors of smooth muscle tissue - names, morphology and organ localization:

• Tumors are characterised by:

  • macroscopic features

  • microscopic features

  • growth rate

  • local invasion ➡ lymph nodes

  • metastasis

• Benign tumours:

  • spherical or ovoid

  • encapsulated

  • freely movable

  • firm structure

• malignant tumors:

  • irregular shape

  • extend into adjacent tissue

  • metastasize

  • sarcomas = flesh like consistency

  • carcinomas = firm

• Names:

  • CT ➡ fibroma / fibrosarcoma

  • Fat tissue ➡ lipoma / liposarcoma

  • Smooth muscle ➡ leiomyoma / leiomyosarcoma

  • Cartilage tissue ➡ chondroma / chondrosarcoma

  • Bone ➡ osteoma / osteosarcoma

  • Blood vessels ➡ hemangioma / hemangiosarcoma

Describe the type of hemorrhages depending on their mechanism of development and give examples

• Mechanism of hemorrhage:

  • Destruction of blood vessel wall

  • Diapedesis of erythrocytes because of increased permeability of vascular wall

  • Ulceration of vessel wall

• Type depending on location:

  • Hemothorax = in pleural cavity

  • Hemoptysis = from lungs

  • Metrorrhagia = from uterus

  • Hemoarthrosis = in joint cavity

  • Hemopericardium = in pericardial cavity

  • Hemoperitoneum = inside abdominal cavity

• Depending on site of origin:

  • Cardiac = after heart wound

  • Arterial = due to trauma and rupture of dissecting aneurysm

  • Capillary = due to vessel wall weakness / trauma

  • Venous = trauma / surgical procedures

What are benign pigment tumors:

Benign:

• Nevi ➡ brown spots of different size, can be flat or elevated or wart like

• Junctional nevi ➡ nests of nevus cells on the borders of epidermis and dermis, round or oval, homogenous slightly granular cytoplasm

• Compound nevus ➡ Nevus cells are present in both the epidermis and dermis.

• Intradermal nevus ➡ Nevus cells located only in the dermis, forming compact nests.

• Epitheloid cells ➡ often on the face, flat node

• Blue nevus ➡ bluish - Brown/grey spot, round or oval and is not elevated

What are malignant pigment tumors:

Malignant:

• Melanoma ➡ one of the most malignant, spreads through lymphatic and blood, 70% on the skin, 4 types:

  • ① Lentigo maligna melanoma: develops from lentigo

  • ② Invasive melanoma: slightly elevated lesion with different colours and ulcerated surface, may not contain pigments, contains haemorrhages and necrosis, localised on: skin, the pigment of the eye, meninges and a medullar layer of the adrenal gland

  • ③ Acral lentigenous melanoma: more common on soles and palms with ulceration

  • ④ Nodular melanoma: elevated and deeply pigmented nodule with rapid growth and ulceration ➡ worst prognosis