Histopathology Flashcards by PATRICIA ONG

Cell that frequently divide to replace lost cells

Labile cells

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not typically dividing to replace injured cells

Do not frequently go cell division

Only undergo replication to replace injured cells

Stable cells

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Stable cells examples

Parenchymal cells of liver and kidneys

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Cell class that do not undergo replication following maturation

Permanent Cell

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Permanent cell example

neurons (nerve cell)

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incomplete or defective development of tissue/organ. Shows no resemblance to the normal mature structure. Usually happens in paired organs (kidneys, gonads)

Aplasia

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complete non-appearance of organ.

Agenesia

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failure of tissue/organ to reach normal mature adult size

Hypoplasia

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Failure of organ to form an opening

Example:
Imperforate anus (without opening)

Microtia - absence of ear canal

Atresia

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Cellular adaptation mechanisms

Atrohpy
Hypertrophy
Hyperplasia
Metaplasia
Dysplasia
Anaplasia

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acquired decrease in tissue or organ size

Atrophy

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Atrophy that occurs as consequence of maturation

example:

Atrophy of thymus at puberty

Decrease in uterus size after childbirth

Physiologic

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Pathologic atrophy:

occurs if blood supply becomes reduced or below the critical level (may develop as a result of pressure atrophy)

Vascular atrophy

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Pathologic atrophy:

persistent pressure on the organ or tissue may directly injure the cell or may secondarily promote diminution of blood supply

Pressure atrophy

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Pathology atrophy:

due to lack of hormones needed to maintain normal size and structure

Endocrine atrophy

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Pathologic atrophy:

due to lack of nutritional supply to sustain normal growth

Hunger/Starvation atrophy

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Pathologic atrophy:

too much workload can cause general wasting of tissues

Exhaustion atrophy

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Pathologic atrophy:

Inactivity/diminished activity/functions

Atrophy of disuse

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Increase in tissue/organ size due to an increase in size of cells making up the organ

Hypertrophy

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hypertrophy of skeletal muscles due to frequent exercise

Physiologic hypertrophy

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Hypertrophy of the myocardium (hypertension)

Aortic valve disease

Pathologic hypertrophy

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Type of hypertrophy that may develop as response to a deficiency (usually in paired organs– when one is removed)

Compensatory

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Example of compensatory hyperthrophy

Renal hypertrophy

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Increase in tissue or organ size due to an increase in the number of the cells making up the organ (new cells are formed)

Hyperplasia

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Hyperplasia: Happens in response to the need increase in uterus, breast during pregnancy. Increase in breast size during puberty (glandular stimulation)

Physiologic Hyperplasia

Type of hyperplasia: Erythroid bone marrow hyperplasia in people in high altitude

Physiologic hyperplasia

Type of hyperplasia: Grave’s disease - diffuse crowding of epithelial cells Hyperplasia of endometrium due to excessive estrogen TB of cervical lymph nodes - there is increase in the number of lymph nodules

Pathologic

Occur frequently together with hypertrophy and can be triggered by the same mechanism

Compensatory

Involves transformation of adult cell type into another adult type (reversible process)

Metaplasia

Mesenchymal metaplasia involves:

Connective tissues

Original tissue: Ciliated columnar epithelium of bronchi Stimulus: Cigarette smoking Metaplastic tissue:

Squamous epithelium

Original tissue: Transitional epithelium of bladder Stimulus: Trauma of bladder

Squamous epithelium

Original tissue: Columnar glandular epithelium Stimulus: Vitamin A deficiency Metaplastic tissue:

Squamous epithelial cells

Original tissue: Esophageal squamous Stimulus: Gastric acidity (too much drinking coffee) Metaplastic tissue:

Columnar epithelium

Dysplasia is also known as

atypical metaplasia

Pre-neoplastic lesion Change in cell size, shape, and orientation (reversible). May lead to cancer but not necessarily

Dysplasia (atypical metaplasia)

dedifferentiation (irreversible) transformation of adult cells into embryonic/fetal cells

anaplasia

Causes of cell injury

Anoxia - lack of oxygen supply Infectious agents Mechanical agents/Trauma Chemical Agents - carcinogens (chloroform, benzene)

No.1 cause of cell injury

Oxygen deprivation

Hypoxic cell injury for neuron is irreversible after (minutes)

3-5 minutes

Hypoxic cell injury in myocardial cells and hepatocytes is irreversible after (time)

1-2 hours

Skeletal muscle hypoxic injury is irreversible after (time)

many hours

Appearance of affected organs in gross change

Organ pallor (pale), Increased weight

Earliest change of tissue is seen

Microscopically

First manifestation of cellular change

cellular swelling

Irreversible changes

Enzymatic digestion of cells Protein denaturation Cytoplasmic changes Nuclear changes

Cytoplasmic changes includes

Increased eosinophilia (pink/orange) Large cells "cloudy swelling"

Irreversible nuclear changes

Pyknosis Karyolysis Karyorrhexis

condensation of nucleus

pyknosis

fragmentation/segmentation of nucleus

Karyorrhexis

Physiologic cell death Programmed cell death Death of single cell in a cluster of cells

Apoptosis

Cell shrinkage - integrity of membrane remains intact Cellular components do not leak out = no inflammation Chief morphologic features: Chromatin condensation Chromatin fragmentation Cell shrinkage Cytoplasmic bleb formation Phagocytosis of apoptotic cells

Apoptosis

Pathologic cell death Accidental cell death Cell swelling Leakage of cellular components = Inflammation Change in organ can be seen in gross

Necrosis

Type of Necrosis: due to to sudden cut off of blood supply

Coagulative

Type of Necrosis: Due to ischemia Appears ghostly (cell outline is maintained) Usually happens in solid organs (liver, kidneys, heart) Microscopically cell outlines are preserved On gross, affected organs somewhat firm, appearing like a boiled material Actions of hydrolytic enzyme is blocked (normal cell death releases lysozyme - hydrolytic enzyme for cell self destruction) I.e. Myocardial Infarct

Coagulative

Type of Necrosis: On gross, affected organ appears liquefied, creamy yellow (increased pus)

Liquefactive

Type of Necrosis: Softening of organs is due to actions of hydrolytic enzymes Complete digestion of cells i.e. brain infarct and supporative bacterial infections

Liquefactive

Type of Necrosis: On gross, tissue organ appears greasy resembling “cheese”

Caseous

Type of Necrosis: Combination of coagulative and liquefactive Usually seen in TB Microscopically it appears as amorphous granular debri surrounded by granulomatous inflammation

Caseous (cheeselike)

Type of Necrosis: Seen in immune reactions of the blood vessel Deposition of fibrin in vessel wall Cannot be seen in gross examination Can only be microscopically

Fibrinoid

Type of Necrosis: Destruction of fat cells due to release of pancreatic lipases

Fat

Type of Necrosis: Death of fat tissues due to loss of blood supply On gross, appears chalky white Microscope, infiltrates of foamy macrophage adjacent to adipose tissues Seen in pancreatitis Affected organ is usually breasts

Fat

Type of Necrosis: necrosis secondary to a ischemia Not a specific pattern of necrosis

Gangrenous

Type of Necrosis: Refers to a limb that loss its blood supply in the lower extremities Skin - dry, black, and is observed in various stages of decomposition

Gangrenous

due to venous occlusion, example of this is SUPPURATIVE BACTERIAL INFECTION

wet gangrene

due to arterial occlusion and example of this is FOOT EMBOLISM

Dry gangrene

Tissue reaction to injury

Inflammation

Goal of Inflammation:

1)To remove the initial cause of the injury 2)To remove the consequences of injury

Cardinal signs of inflammation

Dolor Rubor Calor Tumor Functio laesa

Cardinal sign of inflammation: pain

dolor

Cardinal sign of inflammation: redness due to increase blood flow

Rubor

Cardinal signs of inflammation: heat

Calor

Cardinal signs of inflammation: swelling

Tumor

Cardinal Signs of Inflammation: destruction of functioning units of the cell

Functio laesa

Type of inflammation: rapid response to an injurious agent

acute inflammation

Hallmark sign of acute inflammation

**Exudation**: escape of fluid proteins, blood cells from the vascular system) **Edema**: excess to fluid in interstitial tissues and cavities

escape of fluid proteins, blood cells from the vascular system)

Exudation

excess to fluid in interstitial tissues and cavities

Edema

Cellular infiltrate of acute inflammation

neutrophils

Prolonged duration of inflammation

Chronic inflammation

Cellular infiltrate of Chronic inflammation

Mononuclear cells (monocytes, macrophage, lymphocytes, plasma cells)

Resolution of inflammation

Healing

Healing stage: No destruction of normal tissues Offending agent is neutralized Vessels return to their normal permeability state Excess fluids is reabsorbed Clearance of mediators and inflammatory cells

Simple resolution

Healing stages:

Resolution Regeneration Replacement by connective tissue scar

Replacement of loss or necrotic or tissues with a new tissue that is similar to those that were destroyed

Regeneration

Death of the entire body

Somatic Death

Changes that can be observed immediately after somatic death

Primary changes

Primary changes in somatic death

1)CNS/Nervous failure 2)Respiratory failure 3)Cardiac failure

Changes that can be noted/observed few hours after death

Secondary changes

cooling of the body after death

Algor mortis

Algor mortis happens at a rate of

7 degF/hour

Helps establish time of death Faster in cooling in: cold weather, lean malnourished Delayed cooling in infectious disease followed by increase in temperature

Algor mortis

stiffening of the body

Rigor mortis

Rigor mortis starts ___ following death

2-3 hours

Rigor mortis completes in ___

6-8 hours

Rigor mortis remains _____ hours and persists for ____ days

12-36 hours 3-4 days

Rigor mortis hasten stiffness in:

warm environment and in infants

Delay of rigor mortis:

cold temperature and obese individuals

Postmortem hemolysis

Livor motis

Purplish discoloration of skin Sinking of fluid blood into capillaries of the dependent body parts

Livor mortis

Importance of livor mortis

determine if body position has changed at the scene of death

Occurs slowly or immediately after death

Post mortem clotting

due to the release of hydrolytic enzymes

autolysis

Rotting and decomposition by bacterial action

Putrefaction

Refers to the drying and wrinkling of cornea and anterior chamber

Dessication

Involves examination of a dead body

Autopsy/Necropsy

Main purpose of autopsy

determine cause of death

Important requirement to do autopsy

consent from the nearest kin

Types of autopsy as to purpose

1)Routine Hospital Autopsy 2)Medico Legal Autopsy - carried by govt. Agencies

Type of autopsy as to completeness of procedure:

1)Complete autopsy - from head to foot 2)Partial autopsy - examines the region of the body

Types as to manner of incision:

Y-shaped incision Straight incision

Type of incision: cadaver is opened from shoulders down from xiphoid area and incised down to pubis

Y-shaped incision

Incision done in adult cadaver

Y-shaped incision

Type of incision: opened from the midline of the body from the suprasternal notch down to the pubis (for babies)

Straight cut

Autopsy technique: organs are removed one by one

Rudolf Virchow

Autopsy technique: Involves in-situ dissection (original place)

Carl Rokitansky

Autopsy Technique: Involves en-bloc (by system) removal of organs

Anthon Ghon

Type of autopsy: Organs are removed “en masses” - all at the same time

M. Letulle

Advantage: Quick and Suitable for beginners Disadvantage: Causes loss of continuity

Virchow's method

Advantages: In infected bodies (HIV, Hepa B) Considered good in children Disadvantages: Difficult to perform

Rokitansky

Cervico-thoracic, abdominal, pelvic organs are removed in three blocks Neuronal system is removed as another block

Ghon's method

Advantage: Excellent preservation Handling organs easier Disadvantage: inter-relationships is difficult to study, if disease is extending to all blocks

Ghon's method

Advantage: inter-relationships are preserved body can be handed over quickly Disadvantage: Organs difficult to handle

Lettulle's method

Process of tumor formation Abnormal proliferation of cells New cells are produced which are functionless compared to a normal cell

Neoplasia

Removal of tumor cells

Biopsy

Types of tumor

Benign Malignant

Type of tumor Slowly growing mass Regular surface, capsulated, not attached to deep structures

Benign tumor

Type of tumor Rapidly growing mass Irregular surfaces, Non-capsulated attached to deep structures

Malignant tumor

Type of tumor Noninvasive to another organ or tissue No spread or metastasis

Benign tumor

Type of tumor Invasive to other organs Spread and metastasis

Malignant tumor

Type of tumor Well differentiated No recurrence after surgery

Benign tumor

Type of tumor Poorly differentiated, moderately, or well differentiated Recurrence after surgery

Malignant tumor

Type of tumor No bleeding in cut surfaces Named adding suffix -oma Slight pressure effect on the neighboring organ

Benign tumor

Type of tumor Bleeding from cut Named by adding suffix sarcoma or carcinoma Remarkable pressure effect on neighboring tissue

Malignant tumor

Gradings of tumor: Different cells

normal cells

Gradings of tumor abnormal cells

undifferentiated cells

Value of grading

Guide for treatment Prognostic guide

Broder's classification Grade I

Differentiated cells: 100-75% Undifferentiated cells: 0-25%

Broder's Classification Grade II

Differentiated cells: 75-50% Undifferentiated cells: 25%-50%

Broder's classification Grade III

Differentiated cells: 50-25% Undifferentiated cells: 50-75%

Broder's classification Grade IV

Differentiated cells: 25-0% Undifferentiated cells: 75-100%

Tumors that are amenable to surgery (good prognosis)

Lower grade tumor

Tumors that requires radical treatment (chemotherapy, radiation) (poor prognosis)

High grade tumor

Used to determine the spread of cancer in a patient Based on the size of primary lesions, extent of spread to regional lymph nodes and presence or absence of metastases

Staging of tumor

TMN Classification T N M

T- size of tumor N - No. of lymph nodes involved M- Presence or absence of metastasis

Tumor: Unable to assess primary tumor

Tumor: There is no evidence of primary lesions

Tumor: Carcinoma in situ

Tis

Tumor: Tuor penetrates submucosa and mucosa

Tumor: The tumor invades but fails to penetrate the muscle layer

Tumor: The tumor penetrates the subserosa

Tumor: Tumors penetrates deep into the peritoneum or other organs

N: Lymph node Unable to assess lymph node involvement

N Lymph node No lymph node involvement

N lymph node There is metastasis in perirectal nodes around one to three

N lymph nodes There is metastasis of four or more perirectal nodes

Metastasis Unable to assess distant metastasis

Metastasis There is no distant metastasis

Metastasis There is distant metastasis

Stage IA Tumor - Node - Metastasis - Grade

T1a, T1b N0 M0 G1,2

Stage IB Tumor - Node - Metastasis - Grade

T2a, N0, M0, G1,2

Stage IIA Tumor - Node - Metastasis - Grade

T2b, N0, M0, G1, 2

Stage IIB Tumor - Node - Metastasis - Grade

T1a, N0, M0, G3,4

Stage IIC Tumor - Node - Metastasis - Grade

T2a, N0, M0, G3, 4

Stage III Tumor - Node - Metastasis - Grade

T2b, N0, M0, G3,4

Stage IV Tumor - Node - Metastasis - Grade

Any T, N1 (any N), M0 (M1), Any G

Tumor size T-1

0-2 centimeters

Tumor Size T2

2-5 centimeters

Tumor size T3

>5 centimeters

Tumor size: T4

Tumor has broken through skin or attached to cell wall

Lymph node status N-0

Surgeon can't feel any nodes

Lymph nodes N-1

Surgeon can feel swollen nodes

Lymph nodes N-2

Nodes feel swollen and lumpy

Lymph node status N3

Swollen nodes located near collarbone

Metastasis: M-0

Tested nodes are cancer free

Metastasis M1

Tested nodes show cancer cells or micrometastasis

Identification of tissue or cellular antigens or phenotypic markers (found in tissues)

Immunohistochemistry

Make use of antigen antibody reactions by directly labelling of the antibody or by means of secondary labelling method

Immunohistochemistry

Most commonly used antibody used in IHC

IgG

Antibodies produced by different cells Can react with various epitopes (reacts with antibodies)

Polyclonal

Polyclonal antibody source

goats, pigs, sheep laboratory animals

More specific antibodies produced from individual clones of plasma cells

Monoclonal

Produces one type of antibody can react only with one specific type of epitope

Monoclonal

Animal source of monoclonal antibodies

mice

To detect antigens, antibodies must be

labeled

Most common enzyme for antigen retrieval

Horse Radish Peroxidase

Color developer for labeling antibodies

chromogen

Most common method for antigen retrieval

Enzyme

Diamino benzedene (DAB) color

brown

AEC - 3-amino-9ethylcarbazole color

brick red

Traditional counterstain for enzyme

hematoxylin

Alternative phosphatase for horse radish peroxidase

alkaline phosphatase

Optimum incubation time to link antibody with enzyme peroxidase

60 mins at Room temperature

Fluorochrome label dye used for fluorescence microscope

FITC - Fluorescein isothiocyanate

Plant or animal proteins which can bind to tissue carbohydrate Can also be used to detect antigens, can also be labelled like antibodies

Lectins

Cryostat frozen sections and fixed in a few seconds using

absolute methanol or acetone

Purpose of cryostat frozen sections

To prevent destruction of labile antigenic sites To preserve position of antigens

Processed specimens (antigen retrieval) specimens

Formalin fixed Paraffin embedded

Methods of antigen retrieval from processed tissues

1)Proteolytic enzyme retrieval (PIER) 2)Microwave antigen retrieval/ Heat Induced Epitope retrieval 3)Pressure cooking antigen retrieval 4)Autoclave heating 5)Waterbath heating 6)Steamer heating 7)Decloaker heating 8)Combination of microwave and enzyme digestion

Commonly used enzyme in proteolytic enzyme retrieval

trypsin and protease

Microwave antigen retrieval/ Heat Induced Epitope retrieval duration

20 minutes

Waterbath heating temperature

90 deg C or 95-98 deg C

control: tissue section with antigen being detected

positive

Control: omit primary antibody from the staining schedule

negative

Internal tissue control a.k.a

built in control

Internal tissue control contains

target antigen

dissolution of nucleus

karyolysis