Pathology Flashcards
Immunohistochemsitry Autopsy is
Done for unknown tumors, infectious dx and brain tissue in the case of dementria
Microbiology Autopsy
When COD is suspected to be infectious dx Includes - lung tissue culture - Viral nasal swab culture - Blood culture
What type of autopsies utilize a blood culture?
microbiology and toxicology
Toxicology Autopsy
Blood, urine, and vitreous humor in cases of overdose, motor vehicle accidents or sudden / unexplained death
Cytogenetic Autopsy
Take skin, pericardium and placenta in the case of miscarriage or still birth
Radiology Autopsy
Gunshot wound
Child abuse
Suspected pneumothorax / air embolism
Forensic Autopy
Sexual assault testing Bullets Pellets Nail clippings Trace evidence
What is a coroner autopsy
Performed by a coroner / medical examiner
- forensic pathologist prosects
- next of kin consent NOT needed
- death outside of hospital
- MAJORITY of natural deaths
Medical Autopsy
Pathologist + Resident prosect
Next of kin CONSENT NEEDED
Death often in hospital or nursing home
Majority of natural deaths
Cell Injury
When a cell is stimulated by severe stress and the cell’s adaptive capabilites are exceeded
What would result in an increase in protein degradation -to-synthesis ration?
Atrophy
When one adult cell type is replaced by another, less vulnerable one capable of withstanding more stress this is an example of?
Metaplasia
The replacement of columner EPI by squamous in the respiratory tract of a smoker is an example of…
Metaplasia
Metaplasia involves reprogramming of what?
Stem cells
When squamous cells are replaced by columnar cells in the the throat of someone with acid reflux, there is an example of?
Metaplasia
The glassy pink appearance seen in H&E staining as a result of intracellular or extracellular acccumulations of protein is called?
Hyaline change
What are Russell Bodies?
Immunoglobins in plasma cells
Whati s anthracosis?
Black discoloration of lung tissue and lymph nodes draining it.
This is due to carbon being phagocytosed by alveoli
What are CASPASES
A family of cysteine proteases that exist as pro-enzymes until cleaved
A pathological form of cell death associated with damage from an external source is?
Necrosis
What is congulative necrosis?
Dead tissue architecture is preserved for a few days b/c proteolytic enzymes are denatured
Saponification is an example of (is)
Fat necrosis: areas of fat destruction in which fat products combine with Calcium to produce chalky-white areas
Ischemia is caused by which type of necrosis?
Coagulative
When dead cells are completley digested and leave only viscous fluid this is known as?
Liquefactive necrosis
Hypoxic tissue damage in the CNS is an example of what type of necrosis?
Liquefactive
Pancreatitis and leakage of pancreatic lipase into adjacent tissue is an example of
Fat necrosis
TB is an example of what type of necrosis?
Caseous Necrosis: when dead tissue is transformed to ‘cheesy’ granular material
Small, dark chromatin due to chromatin condensation and cleavage into fragments during apoptosis is what?
Pyknosis
Karyorrhexis is
Chromatin fragmentation
Fading of chromatin is
Karyolysis
Molecules with an unpaired electron in their outer orbit are
Free Radicals
Deposition of calcium salts in dying tissues despite NORMAL Serum Ca levels is
Dystrophic Caclification
What initiates Ca concentration in cellular vesicles?
Membrane damage
Ca++ salts are deeply ________ and are seen in areas of _________
Basophilic (dark blue / purple)
Atherosclerosis (agining/damaged heart valves)
What does dystrophic calcification signify?
Prior cell damage but it can contribute to further organ dysfunction
How do dystrophic and metastatic calcification differ?
Metastatic is NOT initatied by cell damage or death; occurs when there is increased serum Ca++ in normal tissue
** This will have the same histology as dystrophic calcification
The widing of heart walls due to HT (Hypertension) is an example of what?
Pathological Hypertrophy (exercise and muscle growth would be an example of physiological)
When a normal, endogenous substance is produced at a normal or increased rate, but metabolism is inadequate to remove it, this is called?
Intracellular Accumulations (extracellular too?)
When you have intracellular accumulation of TGs you have
Steatosis
When you have extracellular accumulation of cholesterol you have?
Atherosclerosis
Intracellular Accumulations can be caused in 4 ways
1) Normal endogenous, produced at normal rate, but bad metabolism
2) Abnormal endogenous accumulates because cellular machinery cannot package, transport or secrete it
3) Normal endogenous substance accumulates because of defects in ENZYMES for its metabolism
4) Abnormal exogenous substance accumulates due to lack of cellular machinery to degrade or transport it
Necrosis is always what?
Pathological and also associated with cell membrane disruption and therefore INFLAMMATION
Apoptosis differs from necrosis how?
It is regulated and does not incur membrane distruption and therefore does not elicit an inflammatory response.
It may or may not be caused by cell injury
The intrinsic pathway of apoptosis is also known as the
Mitochondrial pathway
What happens in intrinsic apoptosis?
Proteins normally in the MITO (cytochrome C) are released into the cytoplasm
What controls the release of cytochrome C into the cytoplasm during intrinsic apoptosis?
Release is controlled by BCL proteins with BOTH pro and Anti apoptotic members
The balance between these two controls whether apoptosis occurs or not
When the PRO member of the BCL protein dominate what happens?
The from a channel into the MITO so proteins can leave and when this protein (cyto C) leaves it activates Caspases
Extrinsic Pathway for apoptosis
The plasma membrane death receptors receive signals from outside the cell
FAS R: binding of Fas Ligand expressed by T Lymphocytes brings together caspases that trigger the caspase cascade
What does Fas R Do?
This is part of the extrinsic pathway
When it binds (comes from T Lymphocytes) it brings together caspases that trigger the caspase cascade
What are some of the major causes of cell injury?
1) Hypoxia / Ichemia
2) Physical Agents: trauma, temp., pressure, radiation, electric shock
3) Chemical Agents / Drugs: some are fine at low concentrations (smoking, alcohol, etc)
4) Infection
5) Lesser: immunologic, genetic, nutritional
Which is more damaging: hypoxia/Ischemia?
Ischemia b/c there is no O2, glucose and other metabolic substances
What are 4 targets of cell damage? (Think: BCG P (Please))
B: Biochemical machinery of aerobic respiration
C: Cell Membrane
G: Genetic Apparatus
P: Protein Synthesis
One mechanism of cell damage is Depletion of ATP. Explain this
you lose the Na/K ATPase - the Na builds up and there is low K. The cell swells
Also inhibit glycolysis: build up of lactic acid and low glycogen stores
See a failure of Ca++ Pump so an influx of Ca
Damage to protein synthesis apparatus: reduction in synthesis
Abnormal protein folding
What type of cell damage results in the build up of lactic acid and low glycogen stores?
Depletion of ATP
How can MITO be damaged?
1) increased cytosolic Ca++
2) Increased ROSs
3) Ischemia
These will all from the MITO permeability transition pore and destroy MITO membrane potential for oxidative phosphorylation.
MITO protein leakage would also result in apoptosis
Loss of Ca++ homeostasis is a major mechanism of cell damage. What happens here?
1) You can activate enzymes like phospholipases, proteases, endonucleases and ATPases
2) Activation of caspases
Oxidative stress can result from:
1) Hydroxyl Radicals
2) Superoxide Anion
3) Hydrogen Peroxide
4) Peroxynitrite
When there is lipid peroxidation in the membrane from unsaturated FAs rxing what is yielded and what happens?
1) Yields Lipid Peroxides which disrupt the membrane
When there is oxidative modification of proteins what can happen?
This can cause damage to the proteins active site or conformation
What is the morphology of apoptosis (what will it look like?)
Cell Shrinkage
Increased Density of cytoplasm (dark Pink on H&E)
Nuclear Pynknosis: Small dark chromatin
Cytoplasmic Blebs: Apoptic bodies that are rapidly cleared by phagocytosis
When would you see dark pink on an H&E?
Apoptosis
Electron Microscope shows: Loss of microvilli, mito swelling, dilation of ER and Plasma Membrane Blebbing. What is doing on?
Reversible cell injury (necrosis)
Light microscope is showing cell swelling, clear cytoplasmic vacuoles, and fatty change. What is going on?
Reversible Cell injury
EM is showing membrane discontinuity, MITO swelling, myelin figure of whorled phospholipid masses. What is going on?
Irreversible injury (necrosis)
**Both reversible and irreversible have MITO swelling
LM is showing: dark pink cytoplasm (cytosplasmic eosinophilia), dystrophic calcification, Karyolysis (fading of chromatin) and pyknosis (small dark chromatiin) and loss of nucleus as well as chromatin fragmentation. What is going on?
Irreversible injury (necrosis)
What involves rubor, calor, dolor and tumor?
Inflammation
What is a non-specific rxn of the body to stimulus perceived to be injurious to the host?
Inflammation
What is categorized as innate immunity?
Skin barriers and inflammatory response
What is categorized as acquired immunity?
Antibodies produced for a specific antigetn
What can lead to inflammation?
1) Infections and microbial toxins
2) Trauma
3) Tissue necrosis (secondary to ischemia)
4) Foreign Bodies (Splinters, dirt, sutures, metal)
5) Immunie Rxns (hypersensitivity, autoimmune)
6) On-going inflammation (can lead to more inflammation – ha!)
What makes up 50-70% of WBC in the blood?
Neutrophils
Describe the characteristics of a neutrophil?
1) Segmented nucleus with 3-5 lobes
2) Cytoplasmic granules containing acid hydrolases
3) MOTILE phagocytes
What is the primary responder to acute inflammation?
Neutrophils
What makes up 25-35% of WBCs?
Lymphcoytes
What are the characteristics of Lymphocytes?
1) Very little cytoplasm
2) One nucleus
What is involved with chronic inflammation and acquired immunity?
Lymphocytes
What do lymphocytes produce?
1) Cytokines and immunoglobins to help eliminate foreign material
What makes up 4-6% of WBC?
Monocytes
What makes monocytes unique?
1) Produced in Bone marrow
2) Stay in blood for ~1 day (then go to tissue near blood vessels and are called macrophages
3) HORSESHOE shaped nucleus and granules
4) These are motile phagocytes with granules containing toxic substances
What is involved with acute and chronic inflammation and considered a bridge from innate to acquired immunity?
Monocytes
What do monocytes do?
They phagocytose foreign material and present it to lymphocytes
What become macrophages?
Monocytes (once they get to tissue near BVs)
What are involved in the inflammatory rxns to allergens and parasites?
Eosinophils
What make up 1-3% of WBCs and have bi or tri lobed nucleus
Eosinophils
What do eosinophilic granules contain?
1) HA
2) Proteolytic Enzymes
3) Major basic proteins
What are called mast cells when they are in tissue?
Basophils
What makes up .4-1% of WBCs and has a bilobed nucleus that is difficult to see due to the huge amount of granules
Basophils
What to basophilic granules contain?
1) HA
2) Proteoglycans
3) Proteolyic enzymes
4) Lipid mediators of inflammation
What area the slow reacting substances of anaphylaxis?
Lipid mediators of inflammation (from basophils which become mast cells)
Where are mast cells (formerly basophils) located?
Near
1) vessels
2) Mucosae
3) dermis
What are anuclear fragments of megakaryocytes with many granules but very litte in the way of organelles?
Plateletes
What contain platelet activating factors which affetec ALL features of inflammation?
Platelets
What are the two types of chemical mediators in inflammation?
1) Plasma Derived
2) Cell Derived
Where are the plasma derived chemical mediators of inflammation produces?
Liver
* Always present in plasma in pro-form and require activation
What are the plasma derived mediators of inflammation? (Think FKCC)
1) F: Factor XII (Hageman Factor)
2) Kinins
3) Complement Proteins
4) Clotting Proteins
When are cell derived chemical mediators made?
They exist in organelles or are made upon stimulation
What are the cell derived chemical mediators of inflammation? (Think: At the V-AA CC said NO to LYSO’s RSO)
V = Vasoactive Amines (HA and 5-HT) AA = Arachidonic Acid Metabolites CC = Cytokines and chemokines NO = Nitrous Oxide Lyso = Lysosomal Contents RSO = Reactive Oxygen Species??
Aspects of Acute Inflammation
1) Immediate Onset
2) Short duration (only as long as stimulus lasts)
3) BVs allows WBCs to leave and go into tissues
What is chronic inflammation?
1) prolonged onset and duration
2) Typically follows acute but it can be insidious
What are the principle cells of chronic inflammation?
Lymphocytes, plasma cells and macrophages
What are the vasoactive mediators in inflammation?
Bradykinin
Substance P
HA
Also Cytokines (IL-1, IFN-TFN)
During inflammation, how are endothelial gaps widened?
Via constriction of endothelial cells
Where is the the inflammation response most important?
In the efferent venule (dilation there) versus the afferent arteriole
