Cell Injury (Part 1) Flashcards
What is pathology?
study of disease which includes etiology, pathogenesis, morphologic (gross and histologic) changes in cells/tissues/organs
What is etiology?
cause of disease
What is pathogenesis?
how a particular disease develops to give the morphologic diagnosis
What is included in a pathology report?
description (objective)
morphologic diagnosis (interpretations)
etiologic diagnosis
What is a morphologic diagnosis?
descriptors of major features of lesions AND organ
i.e. necrosis and hepatitis
What is an etiologic diagnosis?
causative agent AND organ + process affecting organ
How does the objective description and interpretation of a pathology report differ?
description: remains valid
interpretations: subject to change
so, keep these separate
Describe a pathology report outline
history: signalment, etc
gross findings: describe all lesions, be as objective as possible
pathologic diagnoses (morphologic/etiology diagnoses)
case summary: most important part of the report to the clinician
What can the color red mean in pathology?
hyperemia
congestion
hemorrhage
What are petechiae?
1-2 mm red foci (essentially saying hemorrhage)
Describe how you can tell if an animal has abnormal fat characteristics
fat should be evenly distributed and the same general color in all locations
What does a diffuse lesion mean?
happens in more than one location
What is a focal lesion?
a lesion localized and limited to one area
What is a coalescing lesion?
fusing of originally separate parts; merging, becoming one
What does transmurally mean?
across the wall
What does mottled mean?
patchy, infers color - so you need to give range of colors
Give a morphologic diagnosis for parvovirus
fibrinonecrotizing and hemorrhagic enteritis
fibrinous peritonitis
Give an etiologic diagnosis for parvovirus
parvoviral enteritis
(causative agent AND organ + process affecting organ)
Give the etiologic agent for parvovirus
canine parvovirus-2
Describe the pathogenesis of parvovirus
oronasal exposure to contaminated feces —> viral uptake by epithelium over tonsils and peyer’s patches —> replication in nasopharyngeal lymphoid tissues —> lymphocytolysis realize virus, causes viremia and lymphopenia —> infection of gastrointestinal crypt epithelium and Peyer’s patches —> fibrinonecrotizing and hemorrhagic enteritis
What are other lesions you may see with parvo?
cerebellar hypoplasia (morphologic diagnosis)
myocarditis
What is the significance of this image with parvovirus?
parvovirus causes cerebellar hypoplasia - which can be from never developing to begin with or it shrinking
How does parvovirus cause myocarditis?
because of the viremic nature — goes straight to the heart
lymphocytes invade the myocardium —> SA node, in different places which will mess up condition
this is why a dog can suddenly drop dead
T/F: Parvovirus works its way from the duodenum down to the ileum
FALSE - starts in the ileum (location of Peyer’s patches) and works way UP
causes segmental lesions
What is the difference between a cytology and biopsy?
cytology: easy, low cost, visualize individual cells, can be less diagnostic
biopsy: time consuming, more invasive, formalin, better tissue detail
How do you tell the difference from hyperplastic or neoplastic cell?
hyperplastic: a lot of the same cells - look like complete clones, CONTROLLED
neoplastic: population proliferating UNREGULATED
T/F: Neoplasias are not always malignant
TRUE
What can hyperplastic lesions look like?
a benign neoplasia
What does hematoxylin stain?
stains nuclear material basophilic
nucleic acids, DNA, ribosomes, mitochondria
What does eosin stain?
red/pink
intracellular and extracellular proteins
What are the types of nuclei?
euchromatic nuclei
heterochromatic nuclei
Describe euchromatic nuclei
“open” - uncoiled chromatin
active in transcription (generation of mRNA)
nuclei are visible
Describe heterochromatic nuclei
dense nucleus - tightly coiled chromatin)
inactive in transcription
What do euchromatic nuclei tell us?
that the cell is actively producing something - ACTIVE
What do heterochromatic nuclei tell us?
cell is INACTIVE - but can change to active!
What is the importance of the rough endoplasmic reticulum?
synthesizes proteins, has ribosomes
responsible for the basophilia of a cell’s cytoplasm
What is the function of nucleoli?
synthesis of RNA
prominence of nucleoli measures the cell’s synthetic activity
What is a carcinoma?
malignant tumor of epithelial cells
How do you tell a benign vs malignant tumor?
benign: uncontrolled identical cells
malignant: not identical
Describe this epithelial sample
euchromatic nuclei - open, active
multiple nucleoli are observed
neoplastic
Regarding cellular components, ______ are often observed in neoplasia
multiple nucleoli
What is the function of the Golgi apparatus?
synthesizes and packaging center for proteins to be exported out of the cell
Describe the features of lysosomes
contain hydrolytic enzymes
enzymes are synthesized by rER, processed and packaged in Golgi, released in vesicles from the Golgi complex into the cytosol
aid in intracellular digestion
What cells contain large numbers of lysosomes?
macrophages
white blood cells
Describe how a macrophage aids in intracellular digestion
macrophages have lots of lysosomes —> created a phagosome around pathogen —> combines to form phagolysosome —> lysosome releases enzymes and degrades whatever is in the phagolysosome
What are lysosomal storage diseases?
primary: hereditary
secondary: acquired toxins
What happens when lysosomes don’t work?
bacteria like rhodococcus equi can evade lysosomes and hide in the phagosome
Explain the pathogenesis of rhodococcus equi and how it can avoid lysosomal mechanisms
some rhodococcus equi will evade lysosomes by hiding in the phagosome
causes the cell to continue to swell, macrophage eventually bursts —> bacteria leaks out
macrophages show antigens to lymphocytes in the lymph nodes
What is the etiologic diagnosis of rhodoccous equi?
rhodococcal lymphadenitis
What can happen with neoplasia?
starts in lymphatics then goes to thoracic duct and into blood
can form a neoplastic thromboembolism and now have a vascular problem
What are the causes of cellular injury?
DAMNNIT V scheme
What is the difference between hypoxia and ischemia?
hypoxia: decreased oxygen saturation of red blood cells
ischemia: decreased blood flow to tissues *
*could mean total loss of O2 and/or nutrients depending on how blood vessel is obstructed/not flowing
What are some causes of hypoxia?
iron deficiency
high altitudes
respiratory failure
anemia
cyanide poisoning
What are some causes of ischemia?
put on a tight bandage on an animal leg - distal part swells and results in edema
atherosclerosis
thrombosis
embolism
hypotension
Explain the pathway of hypoxic injury
mitochondria has no ATP because of no oxygen —> Na+ remains intracellular, thus water follows —> cell swells —> cells get bigger due to fluid influx —> accumulate waste products
also anaerobic glycolysis
also calcium goes in too
What is hydropic degeneration?
term used for swelling (& indicates the cell is hurt) - epithelial cell
balloon-like
DOES NOT mean it’s swelling with water
Explain how these cells are not normal
should have a centrally-placed nuclei
contains viral inclusions
swollen
What are some diseases that arise from parapox viruses?
bovine papular stomatitis
contagious echthyma (ORF)
seal pox
What does cell swelling look like grossly?
increased volume and weight
increased pallor
Is this normal or abnormal?
abnormal - increased pallor and is glistening
also has accentuated lobular pattern
Is this normal or abnormal?
normal
Describe the lesions on this sheep
dark spot: focal, irregular, raised brown-red lesion on the commissure of the right side of the mouth
pink outline: peripherally around the lesion is discoloration of the fur - yellowish/red/brown
Why is the lesion raised?
something is being added - viral intracellular replication causes cells to swell, also inflammation
Why does the sheep have the lesion on the mucocutaneous junction?
gets virus from the mom —> baby sucks from teats —> abrasions from teat affect lamb —> viremia
What are characteristics of pox lesions?
acanthosis (proliferation)
hydropic degeneration
+/- intracytoplasmic inclusions
secondary bacterial infections
Describe these lesions
multi-focal to coalescing lesions
green: cells are being taken away (depressed, necrotizing)
Explain how cells respond to injury (2 pathways)
reversible: injury, clumping of chromatin, recovery of cell
irreversible: injury, membrane blebs, swelling of ER and loss of ribosomes, irreversible cell injury —> fragmentation of cell membrane and nucleus —> cell death
What is dysplasia?
have immature cells with differentiated cells
cells that are in varying stages of maturity
- also lose their orientation
What is anaplasia?
loss of structural and functional dedifferentiation
anaplasia = to form backwards, associated with neoplasia
“they don’t look like their neighbor”
What is hypertrophy? Provide an example
increased cell size
- growth factors
- hormones
- increased workload
increase in size due to increased number of organelles within the cell
ex: working out
What is this an example of?
hydropic degeneration
acanthosis: proliferation
What is atrophy? Provide why (multiple reasons) and an example
decrease in cell size
loss of use
decreased innervation
decreased vascular supply
pressure atrophy
Why might someone have metaplasia? What can it turn into?
chronic injury - someone like a chronic smoker always injuring their lungs with smoke
can become neoplastic
With chronic injury, you can get [fibrin/fibrosis]
fibrOSIS - dense connective tissue
What was this an example of in the bovine kidney?
metaplasia - result of chronic injury
some mesenchymal cells (like fibroblasts) changed to bone
Why is the cortex and medulla so much thinner than usual?
have pressure atrophy due to hydronephrosis
What is wrong with this organ?
serous atrophy of fat - should be fat at base of the heart, also is glistening
What’s the difference between necrosis and apoptosis?
necrosis: cell death due to irreversible injury (hypoxia, ischemia, membrane damage)
- more than just one cell
- pushing cell over the edge — irreversible injury
apoptosis: programmed cell death - can also be pathologic
Explain how reperfusion can cause cellular injury
resupply of blood —> more influx of Ca2+ —> activates phospholipase (arachidonic cascade) —> precursors to cardinal signs of inflammation COX-1 and COX-2
What are free radicals arch enemy?
antioxidants like glutathione peroxidase, vitamin E, selenium, and vitamin C
If you look under a microscope, how do you know if the cell is dying from necrosis or apoptosis?
look for nuclear changes
What are the nuclear changes of necrosis?
pyknosis, karyorrhexis, karyolysis
What is pyknosis?
nuclei condense and become dark
What is karyorrhexis?
nuclei fragments
What is coagulative necrosis?
cell undergoing necrosis but cell itself (cell border) is retained - denaturation of cytoplasmic proteins
still retains the architecture of the tissue
preserved cell outlines
What is caseous necrosis?
older lesion compared to coagulative necrosis
loss of architecture
+/- calcification
What kind of necrosis is this?
caseous necrosis - lost architecture
What kind of necrosis is this? How do you know?
liquefactive necrosis - pinker with more space and fewer neurons
What kind of necrosis is this?
coagulative necrosis - still has an outline
What is gangrenous necrosis?
generally describes the damage that has occurred to the extremities (especially lower) where there is severe ischaemia
What is the pathophysiology of ergot toxicity? What gangrene type?
causes extreme vasoconstriction
tissue at very end of line die
gas gangrene
What are the types of fat necrosis?
enzymatic necrosis
traumatic necrosis
fat necrosis of abdominal fat
Describe the intrinsic pathway
Bcl “holding hands” with cytochrome C - anti-apoptotic, stimulated by growth factors
What are the pro-apoptotic factors?
Bak, Bim, Bax - replace Bcl
Loss of Bcl = increased ______
cell permeability
What are the caspase executioners?
Caspase 3,6
What stops the extrinsic pathway of apoptosis?
FLIP protein - inhibits caspase 8
Describe the extrinsic pathway steps
FasL on cytotoxic T cell + Fas/FADD on target cell initiates caspase 8 or 10 initiator
caspase 8 initiator + caspase 3,6 = executioner = cytoskeleton, nucleus breakdown
What do apoptotic bodies look like?
slivers
Contrast necrosis and apoptosis
necrosis: INFLAMMATION, cell swelling
apoptosis: NO inflammation, shrinkage
