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Pathology

Herpes Simplex Viruso Vesiculo-pustular eruption

Macule (flat spot), papule (bump), vesicle (fluid-filled papule, less than1cm), pustule (vesicle with pustular fluid), erythema (red), bulla (fluid-

filled papule, greater than 1cm)o Multinucleated giant cells

Stained w/ H&E very dark purple/blue

Nuclei undergo ground glass (frosted, etched look) change in latelesion

HSV I, HSV II, Varicella-Zoster

Synctia (clumping of giant cells)o Intranuclear Inclusion Bodies

Cowdry Type A (eosinophillic)

Versus ground glass different stages of infection

Present in single cellso Vesicle formation

Although normally dont biopsy Well above basal layer of skin (basement membrane)

No scar in uncomplicated infection due to distance frombasement membrane very superficial

Exfoliated cells and cellular debris

Some contain CPEs

o Herpetic Whitlow

Finger

Enter through small breaks in the skin

Very painful/debilitating

Similar regression/latency/reactivation patterno Genital Herpes

Same CPEs Type II

o Immunocompromised host

Deeper lesion, more extensive

Scar formationo Herpes Esophagitis

Multiple mucosal ulcerations

More common in immunologically compromised host

Painful

Difficult to eradicate

Vocabularyo Gross: Macroscopic

o Metaplasia: Substitution of one mature cell type for another Transformation zone of uterine cervix: squamous metaplasia in

reproductive years

Squamous meet columnaro Atrophy: Loss of cell volume / tissue volume

Reduced in size, cell still intact and alive yet have lost substance

Tissue size reduced

Same number of cells

PDH case: atrophic brain

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Radiologist playing fast and loose with terminology

In reality some brain tissue probably failed to develop or waslost overall brain would look smaller

o Ventricles dilate

o Hypertrophy: Increase in size of tissue due to increase of individual cell size

Frequent in heart (cardiac muscle cells cant multiply)

Hypertension Individual cardiac muscle cells have gotten bigger to compensate

o Hyperplasia: Increase in size of tissue due to increase in cell number

Endometrium estrogen stimulation; lining increased in size frequently seen at extremes of reproductive life

More cells produced

Thyroid hormone stimulation causes cellular outpouching due toincreased number

o Apoptosis: Programmed cell death

o Necrosis: Pathological cell death

o Caseation: Necrosis, granular

Death mors gaudet succurere vita death rejoices in teaching life

o Apoptosis Peripheral localization of chromatin

Chromatin disruption

Organelle clustering

Nucleus systematically degraded into pyknotic (densly stainingblue/black blob) then fragment (karyo)

Flipping to change distribution of phospholipids in inner/outermembranes

Phosphatidylserine: eat me label to macs

Degredation is systematic (particularly of nuclear DNA)

Apoptotic ladders

Part of normal development, response to injury (wound healing),

attempt to rid body of cells that have undergone viral/neoplasticchanges

Lack of apoptosis keloid, appendage formation, etc

Two major pathways:

Intrinsic: Involves mitochondria, release of cytochrome c,interaction with caspases to nuclear/cytoskeletal breakdown

Extrinsic: Death Receptor / Death Domain, receptor-ligandinteractions; FAS, TNF

Cytotoxic T cells Granzyme B

Final common pathway involving caspases*

o Cleave cysteine and aspartic acid

Cell remains packaged, blebs come off membrane remains intact

No big inflammatory response although targeted to be eaten

Diabetes: endocrine pancreas islets; lymphocytes engaging -cells to induce apoptosis [ascinar cells feed into intercalating ducts]

Lipemia retinalis (vessels filled with triacylglycerides)

Very tidy death!o Necrosis

Messy death, leakage of cellular contents into surrounding tissue

Point of no return: irreversible injury difficult to determine in vivo

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Nuclear changes are pathologic indicator

Injurious Stimuli:

Decreased ATPo Lose electrochemical gradient (Na/K/ATPase)

o Loss of energy-dependent cellular function

Membrane Damage

o Mitochondria Cell death: apoptosis

o Lysosome

Enzymatic digestion of cello Plasma membrane

Loss of cellular contents

Rapid or gradual

Increased Intracellular Calcium

o Protein breakdown, nuclear breakdown, etc

Reactive Oxygen Species

Irreversible

Nuclear changes: decreased basophilia, etc

Membrane completely disrupted Mitochondrial crystals, disrupted cristae , electron densities

Ischemia: insufficient blood flow, oxygen flow decreases: hypoxia; nomore oxygen for ETC (OxPhos stops, ATP decreases, TCA stops runoff of anaerobic glycolysis)

pH decreases, glycogen depleted, protein synthesis decreases

Influx of Ca, water, Na; efflux Ko Sodium pulls in more water

Abnormal cellular swelling

Calcium Responsibilities

Influx into cell or efflux from mito/ERo Decreased ATP

o

Decreased phospholipidso Decreased pumps/gradient maintenance

o Ultimately nuclear damage

Infarction: ischemic (coagulative) necrotic tissue death as a result ofischemia

Classical example: myocardial

Thrombus: blood clot can cut off blood flow

Causes increased eosinophilia (loss of cytoplasmic basophilia &glommed denatured proteins)

o Influx of calcium/enzymes nucleases activated and

degraded ribosomes/mRNA/etc in cytoplasm

Cells more condensed on themselves

Most have lost nucleio Further in process: NO NUCLEI, DENSE eosinophilia

Overall structure still maintained

With time: healing/inflammation occurso Types of Necrosis

Coagulative: Architecture maintained, ghostlike changes

Liquefactive: Architecture not maintained, obliterated, frequentlybacterial/fungal infections

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Brain tissue: liquefactive necrosis normal when injured by ischemia

Tissue abnormal, yet not completely obliterated secondaryliquefactive changes large fluid, filled hole

Gangrene: clinical, not pathological term

Results from longstanding ischemia leading to coagulativenecrosis absence of adequate blood flow also prevents healing mummified tissue (dry gangrene)

o Few nuclei in underlying dermal tissue

o Arthrosclerosis, arteriolesclerosis limits blood flow

*Diabetes

Wet gangrene: coagulative necrosis due to ischemia withsuperimposed liquefactive necrosis by bacteria (frequentlynormal flora)

o Tissue dies first, then bacteria eat it

o Frequently diabetic neuropathy limits pain

o Gas Gangrene: Clostridial myonecrosis bacterial infection elaborating toxin

attacking previously healthy tissue (form of liquefactive necrosis) BETTERterm: myonecrosis

Excruciating pain rapid progression Muscle has cooked meat appearance and does not bleed/contract

Microscopically: necrotic muscle cells and many bacteria; littleinflammation

Toxin is leuckocidal, interferes with trafficking signals, BVdamaged and out of service toxin causes ischemia, hypoxia

Causes:

S/P trauma

S/P surgery especially GI

S/P septic abortion

Co-existing colorectal cancer (presenting phenomenan)

Primarily hydrogen gas (carbon dioxide lesser), methane

Toxins destroy PREVIOUSLY HEALTHY TISSUE Directly responsible for the death of the tissue like a predator

o Wet gangrene like a scavenger bacteria didnt kill

tissue, but fed after ischemic hypoxia

Progression:

Intense pain @ site

Rapid spread

Gas may be evident on X-ray; crepitance is a late finding

Overlying skin first pale then magenta/bronze

Patient:

o Fever may be mild/absent

o Diaphoretic

o Surprisingly alert/anxious

o Tachycardic out of proportion to temperature

For each degree C, heart rate increases by 10bpm

Death caused by:

o Circulating red cell mass may decrease by half in a few

hours (hypoxia of tissues in general)

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o Hypotension, renal failure, metabolic acidosis, lack of

perfusion to cardiac muscle (arrhythmia)

Clostridium probably wouldnt grow in blood, but would eat othertissues via blood and spread toxins

Gas pockets are radioluscent on Xray

o Tuberculosis (Captain of all these men of death Sir William Ossler)

Caseous necrosis (cheese analogy gross / blue cheese in lung)

Form of coagulative necrosiso Transient local ischemia

Characteristic of infectious diseases that lead to granulomaresponse

Granuloma formation host inflammatory cells (activated macs) form acircumscribed aggregate

Cant see organisms on H&E (waxy cell wall), only activatedmacs/lymphocytes seen

Cant kill organism macs can only wall off

With time, some multinucleated giant cells formed by fusion ofmacrophages

Center of granuloma undergoes caseous necrosis (low pO2 andlow pH)

o Central region will die

o Outside intact/viable to protect host

* Caseation first occurs with TB test +o May enlarge pink amorphous material

Can eat away the organ consumption

Acid fast for mycobacterium

o Fat Necrosis: Lipase released from the pancreas attacked lipid in tissues (itself

and surrounding) fatty acids then combine with calcium to form chalky areas(soaps)

Pancreatic insult (acute pancreatitis alcoholics trauma)

Microscopically: complete digestion in areas Dystrophic vs. Metastatic calcification

o Dystrophic: occurs at site of injury if dead tissue not removed (fat necrosis) or

a consequence of wear & tear

Serum calcium WNL

Initiated intracellularly by ppts in mitochondria and interaction ofcalcium with phosphate groups due to phospholipids damage

o Metastatic (later-site): occurs in otherwise normal tissues as a consequence of

hypercalcemia

Serum calcium above normalo Calcium very dark purple/blue on H&E

Intracellular accumulations

o Abnormal metabolism Fatty liver * can be reversible phenomenon

Frequent in alcohol abuse, diabetics, toxins

Macrovesicular steatosis

VLDLs cant be formed as normal (normally triacylglycerolspackaged with cholesterol, proteins into VLDL and sent toadipocytes)

Oil Red O highlights

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Microvesicular steatosis less frequent, life threateningconditions

o Fat in much smaller droplets

o Reye Syndrome ASA, viral infections association

o Protein folding transport

o Lack of an enzyme

Glycogen storage diseases Clear, white spaces in H&E, magenta in PAS

Diastase degrades glycogeno Two sections compared one treated, one not; stained

with PAS

o PAS + Mucus, polysaccharides, glycan in fungi, glycogen

Lysosomal storage diseaseo Ingestion of indigestible material

Iron

Hemosiderin a breakdown product of hemoglobino Brownish/yellow granules

Melanin also brown

Lipofuchsin also brown Wear and tear pigment

Typical with agingo Prussian blue stains hemosiderin blue

Lipofuchsin caused by autophagy as part of house keeping

Brown/gold/yellow colored granules

Prussian blue negative

No great consequence to cell

Electron dense granules on EM

Both iron/Lipofuchsin in liver Prussian blue to distinguishing

Lipid

Ischemia vs. Hypoxia

Ischemia cause hypoxia

Not all hypoxia due to ischemia

Hypoxia causes: anemia, CO poisoning, etc

* -lymphocytes stain small & dark blue in H&E *