General Pathology Lecture *Finals

Local

INFARCT
Factors Influencing Dev’t of an Infarct
 Availability of alternate blood supply
 Rate of development
 Type of tissue
 Previous hypoxia

THROMBOGENESIS
- Associated with Tissue injury
- triggering inflammation (nagsasabay sila)

Tissue Injury
Thrombogenesis Infammation

Healing
Destruction Immune response
Thrombus Clot dissolution
(resolution)

Thrombogenesis Leads to:

a. blood clot --->thrombus or *macrophage
b. fibrinolysis --> clot dissolution -acts as their referee
*Endothelial cells
- acts as referee of a & b
- its presence indicates tissue injury

(Left)
Problem: Severe tissue injury needs endothelial cells but their damage so there no balancing
If imbalanced
 Thrombogenesis more than Clot dissolution ---> DIC ---> INFARCT
* INFARCT affects different parts and is specific
 Thrombogenesis less than Clot dissolution --> CONSUMPTIVE COAGULOPATHY --> HEMORRHAGE
* HEMORRHAGE is extensive and can decrease blood volume

Systemic

SHOCK
- Decrease in blood volume
- Final common pathway for potentially causing injuries
3 factors for Prognosis:
1. Cause
2. Duration
3. Patient characteristics
Types accdg to different Causative mechanism (how it is produced)
1) HYPOVOLEMIC shock
-decrease blood flow
-due to
 Trauma
 Severe dehydration (diarrhea & thirst)
 Constant vomiting
 Problem in pumping station
2) CARDIOGENIC shock
-due to
 Trauma
 Infarct
 Heart tumor
 3) NEUROGENIC shock
-peripheral vasodilation =peripheral blood vessels are enlarge causing blood to be diverted into the
central circ’n so blood is decreased leading to shock
-due to
 Abnormal release of neurotransmitters = vasa vasorum tells smooth muscles to stay contracted,
for some
o it happens to abnormal rxn to anesthesia
o Others with Trauma of the spinal cord like motor cycle accident
4) ANAPHYLACTIC shock
-hypersensitivity type I =eosinophils and mast cells releases histamine for vasodilation
-severe allergy
5) SEPTIC shock
-severe infection can lead to excessive inflammation w/c amplifies tissue injury
-due to peripheral dilation it release of histamines, vasoactive amines
-ischemia
-most associated with endothelial cell injury
-thus assoc w/ CONSUMPTIVE COAGULOPATHY and DIC

 Sepsis
-regardless the presence of bacteria in blood, present or absent
-focuses on infection and SIRS
*SIRS (Systemic Inflammatory Reaction Syndrome)
-due to chemical mediators during inflammation
-4 manifestations
1. Fever
2. Tachycardia
3. Tachypnea
4. Leukocytosis
-person can die due multi organ failure or specific organ failure
-or death assoc w/ hypovolemic shock of hemorrhage
 Septicemia
-presence of pathogenic bacteria in blood
 Bacteremia
-presence of bacteria whether viable or not, pathogenic or not
 Toxemia

Infection with Neisseria meningitidis

-damage of endothelial cells
-severe tissue injury: DIC
-Red infarct of adrenals(important bec it produces aldosterone for Na reabsorp. Effect: cant ctrl Na & water
loss
-hypotension
-hemorrhagic skin (petechiae)

 “WATERHOUSE-FRIDERICHSEN SYNDROME”
o Infection + consistent hypotension + petechiae + red infarct of Adrenals
o Dead adrenals -need replacement
o If too long recovery period with prolonged shock leads to Secondary Shock ,plasma cells ,B & T
cells , WBC accum can lead to death

UNIT 12: NEOPLASIA

 New growth of purposeless cells
 3A’s :
o Atypical – different appearance & fxn
o Aggressive – has potential destroying surrounding structures
o Autonomous – can grow continuously and independently, don’t respond to
contact inhibition( signals cells to stop dividing in a crowded area of cells)
 Neoplasms: assoc with persistent mutations
Neoplastic cells always with mutation
Cells with mutations comprises:
PARENCHYMA – neoplastic cells
STROMA – supporting structures
 Blood vessels – need nutrition for growth
 Macrophages – tortured to produce Growth factors for neoplasms but not always
present in the stroma
 fibroblasts – provide collagen fibers to support cells and protection from. Neoplastic
cells preventing spread
 DESMOPLASIA- excessive collagen deposition
- limits spread of tumor
- hardens neoplastic mass
- diagnosis for a tumor eg. In breast, prostate
 TUMOR
- An umbrella term: any swelling mass
a. Neoplastic
b. Non Neoplastic
 Hematoma (bLack eye)
 Placenta of a mother (growing tumor)
 Choristoma
 Hamartoma

Hamartoma Choristoma
Disorganized mature cell Disorganized mature cell
Found in an area where they are Found in an area where they’re
Located not usually located
Newly born with TI pneumocytes Eg. Gastric tisuue in appendix
TII pneumocytes
Macrophages
Fibers
BV
Grandular epith cells
Cartilage (bronchus)
Smooth mm.
 Chemicals:
INITIATOR PROMOTOR
 Causes damage to DNA  Amplify effect of mutation
 2 categories Eg. Nicotine- a neurotransmitter of
1. Carcinogens mammals for tobacco it’s a
-direct acting to DNA pesticide among smokers its
Eg. Polycyclic hydrocarbons addicting
2. Procarcinogens
-require metabolism prior to
damaging DNA

 EFFECTS:
1. Continuous proliferation
2. Decrease maturation/ cell death or apoptosis
3. Sustained angiogenesis
4. Immune evasion- lymphocytes cant see hidden tumors
5. Additional mutation

 Tumor staging
3 criteria for Prognosis
1. Tumor size
2. Nodal involvement
3. Distant metastatis – stage IV
  Neoplasia helps predict the behavior of tumor
GRADING
1. Grade 1 / Well differentiated : same appearance
2. Grade 2 / Poorly differentiated : different
3. Grade 3 / Moderately differentiated : in between
4. Grade 4 / Undifferentiated : can’t recognize

*Grade 1 & 2 / low grade

*Grade 3 & 4 / high grade

 ANAPLASIA – lack of differentiation

 DYSPLASIA – disorganized

Anaplasia Dysplasia Similarities

 Giant tumor cell
 Necrosis
 Seen in any type of
Tissue
 Irreversible
 Occurs in metaplastic  Cell division
epithelium  Atypical structure
(metaplasia first)  Atypical
 Reversible

MUTATIONS
A. Acquired
o Environmental
1. Chemicals
2. Radiation – direct damage to DNA causing mismatch base pair
3. Oncogenic microorganism
B. Inherited

VIRUSES
I. DNA VIRUSES
1. Hepatitis B virus – hepa B
2. Epstein Barr virus – kissing disease
Oral and mucosa
Head and neck cancer
a. Nasopharyngeal carcinoma – back of nose and throat
b. Burkitt lymphoma – neck and head ; children who cant be anesthesize ; can causes non
Hodgkin type
3. Kaposi sarcoma herpes virus/ HHV-8 – AIDS assoc KS
4. HIV I / II – AIDS :promotes neoplasia but not oncogenic
5. HPV – cervical cancer specific to women but can cause anal cancer for both sexes via Sexual T.
Also causes benign type of neoplasm: Wart/ Papilloma
6. Merkel cell polyoma virus – skin cancer/MCCL

II. RNA VIRUSES

- Needs to undergo reverse transcription to cause mutation (need to become DNA first)
1. HCV – hepatocellular carcinoma
2. HTLV-1 (human T- Lymphotrophic Virus) – adult TLC
B-cell lymphoma- affects Adults
T-cell lymphoma- children
NK-cells

Helicobacter pylori
 Only bacteria that injects toxin to epithelial cells damaging DNA
  Causative agent of Gastric carcinoma
TREMATODES
 Indirectly causing chronic inflammation- inducing prod’n of cytokines --> lymphokines promoting cell
division resulting to mutation causing MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA/
MALTOMA
1. Opistorchis viverrini & Clonorchis sinensis – bile duct cancer/ Cholangiocarcinoma
2. Schistosoma haematobium – squamous cell carcinoma of the urinary bladder
3. Schistosoma japonicum – hepatocellular carcinoma
4. Schistosoma mansoni – rectal carcinoma

DNA Repair mechanism

DNA
-dependent on genes
-if mutated end up with carcinoma
-genes must undergo mutation b4 leading to neoplasia
Groups of genes
a. Exposed
i. Oncogenes
ii. Tumor suppressor genes
iii. Pro-apoptotic genes
iv. MHC genes
v. DNA repair genes
b. Silent
-pro- oncogenes
-should be silent and not activated otherwise oncoproteins will make cell 3A’s
 General Pathology with Histo and Cytotech
PRINCIPLES
 FIXATION
Target:
o Protein = denaturation
o Lipids and Carbohydrate = oxidation
o Nucleic acids = precipitation
Case 2
*Ethanol- fixes proteins by coagulation. It dehydrates cell causing shrinkage.
*Acetic acid- fixes proteins by gelatination calling water making cell swell.

 POST CHROMATION
Case 1
2 effects:
a. Mordanting effect – fomalin/ formaldehyde for preservation of lipid and lipoproteins
(lipid is surrounded with cytoskeleton w/c is a protein fixed by formalin lipid is only preserved
or nakulong lng siya)
b. Fixation effect

 Lysochromy vs. dying

Case 1
LYSOCHROMY- involves dyes w/o ionic group , not true/complete dyes , dependent only to solubility
the only factor
*Lysochrome is an incomplete dye bec it has only chromogen except sudan black both
auxochrome and chromogen are present
DYING- true and comlete dye , associated with ionic bonds
*ionic bonding- metal loses electrons to become a positively charged ions, whereas the nonmetal
accepts electron to become a negatively charged. An electrostatic attraction b/n opposite charges.
*Dyes are colored, ionising, aromatic organic compounds
2 components of dying
1. Auxochrome
-ionizes the dye para kumapit ung dye
2. Chromogen
-the one with color. Important in resonance , absorbs all visible light if same wavelength.
Add chromophore azo group. Eg. Benzene
 ENZYME DIGESTION
Case 3
-The Diastase or a- amylase
-removal of glycogen from the tissue prior to PAS staining. A-amylase catalyzes hydrolysis of glycosidic
bonds breaking down the large glycogen to water sol disacch known as maltose.
Result is magenta in PAS and absent on PAS/D stained slide.
 MORDANT AND ACCENTUATOR
Case 4
*Bouins is an accentuator bec. It enhances stains
*Mordant acts a bridge b/n the tissue and the dye eg. Weigert hematox specifically iron, alum, copper
generally metals with ionic charge of +2

Case TARGET ORGAN FIXATIVE and STAINS/DYES and RESULT Important

# components REAGENTS remarks

LIPIDS 10% Formol Lysochrome Fats: RED Lysochromy vs.

-nonpolar calcium –preserve Nuclei: dying
1 intracell subs only lipid not fix blue/black
Surrounded by Mountant: Post
cytoskeleton Chromation
 -sol in org  2% ca acetate- Gycerin jelly (a
solvents more alkaline popular water
-insol to water than CaCl mounting medium)
-amphipathic  Rgt that fixes
lipids
- OsO4
- K2Cr2O7
- Cr2O3
(strongest
oxidizing
fixative of
lipids and
CHO)
MUCIN Carnoy’s –fastest Alcian Blue- Mucin: BLUE Principle of
-water sol fixative due to polyvalent basic dye Nuclei: reddish Differentiation
2 -polysacch chloroform , water sol, stain both pink
-attchd to  Chloroform carboxylated and
proteins  Ethanol sulfated
-detect gastro  Glacial HAc mucopolysacch
intestinal tract Fast red
carcinoma
GLYCOGEN BOUIN’s / Gendre’s PAS & PAS/D Red or Red BluingUses
-intracell  Picric acid- *PAS or Leukofuchsin magenta both regressive
3 nonionic alcohol sol 2 components: N: Blue and
polymeric  Acetic acid 1.rosanillin progressive
-surrounded by  Folmaldehyde 2.pararosanillin/basic hematoxylin
cotysk fuchsin for’mns while
differmtiation
Mountant: Clarite X- uses only
synthetic resin regressive
dissolved in toluene Hematox
form’n
COLLAGEN Bouin’s Masson’s Trichrome Collagen And Principle of
-extracell  Picric a- only  Weigert iron H- mucus- blue Displacement
4 polymeric one that make nuclear stain
fibrous joined by tissue soft  Beibrich scarlet N: blue-black Precipitation
peptide bonds acid fuchsin- vs. coagulation
-not surrounded cytoplasm and Mm, rbc,
by phospholipid mm stain keratin- red
-detect tumor
behavior and
extent of tissue
injury and
healing
RETICULIN 10% formalin Gomori’s silver Reticulin: BLACK Impregnation
FIBERS impregnation stain OR BROWN vs. dying
5 -v. Thin extracell
polymeric N: grey
fibrous joined by M: resinous
peptide bonds
-many hexose
grps
-liver dse

RNA Carnoy’s METHYL GREEN- R: RED Principle of

-large organic  Acetic acid- PYRONIN METHOD D: green blue differentiation
6 polymer bound nuclear  MG: Dna (Spatial
to proteins fixative bec  P: Rna allignmnet)
-seen in it can ppt.
cytoplasm Dna and Rna *feulgen tech-Dna
surrounded by
phospholipid
memb
 -use in ID of
protein synthesis

AMYLOID NEUTRAL CONGO RED A, eo,elastin: Dezenkerizing-

-fibrillar extracell BUFFERED BRICK RED use of iron to
7 linear polymer FORMALIN remove
joined by N: purple/blue mercury from
peptide bonds Polarized: apple Hg containing
-beta pleated green fixatives
birefringence
MAST CELL 10% formalin METACHROMATIC Mast cells:
GRANULES STAIN RED
8 -cytoplasmic  TOLUIDINE BLUE PURPLE/pink
polymer w/
varying chain
sizes
MYELIN FORMOL SALINE LUXOL FAST BLUE M: BLUE-GREEN FIX’n vs.
-phospholipid Osmium preservation
9 rich tetroxide:fixes all CRESYL VIOLET: nissl
-non living but preserves NA bodies Staining vs.
coloration
Formalin: fixes
proteins but Why not
preserves all formol calcium
*picric acid: only
fixative that stains Principle of
differentiation
PEPTIDOGLYCAN 10% FORMALIN SAFRANIN G+ : VIOLET/ Trapping agent
10 Aka. mucein dark purple vs. mordant
layer
- mesh like CRYSTAL VIOLET G- : PINK/red
polymer of
simple sugars
-as structural
strength
-insol in water
sol in alc and
acetone

Explanations of Doc Mostales :)

Case 2
Principle of Differentiation
-proteins are with residues can be acidic, basic or uncharged. Thus it has pKa
If increase pH. Protein gain more negative charge
If decrease pH. Protein gain more positive charge

Use HAc ( acetic acid) for more positive charges of proteins

Use NaHCO3 (Sodium bicarbonate) for more negative charges of protein
Why? Bec sometimes your carboxylated and sulfated moeities are not proteins but CHO and are negative
charges. Thus add acid acetic acid to more positive

*Differnce b/n carboxylated and sulfated mucins

- Differentiation is through their pH. Acetic acid as the accentuator
*action of chloroform: pinapaluwang niya ung phospholopid for easier entry of HAc and alcohol. Thus
preferred fixative. In CHO a lot of enzyme breakdown mucin in the cell but b4 breakdown they must be heated
to fix enzymes.

Case 3 glycogen PAS/D enzyme digestion

Case 8 Metachromasia
P: enhanced when intermolecular distances are reduced
Factors w/c enhances M
1) Increase con’c of the dye
2) Decrease temp
3) pH
4) Water a polar solvent contrib to the efficacy of van der waals forces