Lecture 2-5

What do postmortem changes result from?

Autolysis

Are postmortem changes considered lesions?

No

What are decompositions?

Dead organic substances that are broken down

What are the two mechanisms of decompostion?

1. Putrefaction

2. Autolysis

What is putrefaction?

State of decomposition where microorganisms cause dissolution of tissues into gases, liquids and simpler molecules

What is autolysis?

Destruction of cells/tissues by their own enzymes (self-digestion)

What tissues die faster than others? How long do they take?

Neurons: 3-4 minutes

What is the difference between autolysis and necrosis?

Autolysis occurs in dead tissue, involves the entire body and there is no inflammation

Necrosis occurs in live tissue in local/regional areas and inflammation is present

Autolysis begins in ______ of the last heartbeat and involves physical and chemical changes that are ______ and ______.

minutes, irreversible, unavoidable

What is the general process of autolysis beginning from the last hearbeat?

Last heartbeat → Hypoxia → CO2 accumulation → Drop in tissue pH → Rupture of cytosolic lysosomes → Lysosomal enzymes enter cytosol and cause autolysis

Postmortem autolysis can mask what?

Antemortem lesions

What does autolysis look histologically?

Lack of cellular architecture and detail. Saprophytic bacteria.

What is rigor mortis?

Muscle stiffening that occurs 2-36 hours postmortem

What position does rigor mortis leave muscles?

Hyperextension

How does rigor mortis occur?

Muscles are flaccid at death. Sarcoplasmic reticulum degrades and releases calcium, which floods the sarcomere and binds actin and myosin. No ATP to disengage, so body can’t relax.

What is livor mortis?

Purple tissue discoloration postmortem due to intravascular blood pooling due to gravitational pull

What is another word for intravascular pooling?

Hypostatic congestion

How does livor mortis occur?

Hypoxic capillaries dilate, causing blood to accumulate in skin and organs

How long after death does livor mortis develop?

30 minutes to 2 hours

How long after death does livor mortis become fixed?

8-12 hours

What is algor mortis?

Body cooling postmortem to match environment

Which is faster: external cooling or internal cooling?

External cooling

What characteristics allow a body to autolyze more rapidly?

Animals with thick fur or that are hyperthermic

What is hemoglobin imbibition?

Staining of tissues by free hemoglobin, causing a red discoloration to tissues

What is bile imbibition?

Staining of tissues near the gallbladder/ducts by bile, causing yellow/green discoloration

What is pseudomelanosis?

Putrefactive bacteria rapidly diffuse through tissues and react with iron in hemoglobin to create iron sulfide, causing black discoloration to tissues

Where does pseudomelanosis mostly occur?

GIT

What makes the black discoloration associated with pseudomelanosis?

Reaction of the iron in hemoglobin with putrefactive bacteria that grows on the organ post-mortem to create iron sulfide

Does pseudomelanosis an antemortem or postmortem reaction?

Postmortem

What is melanosis?

Normal melanin pigment that causes black discoloration to tissues in dark colored animals. Typically occurs in focal or multifocal spots.

How do postmortem clots appear?

Blood is stagnant and separates. RBCs stick towards the ground while plasma and platelets remain on top. AKA “chicken fat clot”

How long after dead do postmortem clots resolve?

2 hours

What causes postmortem clots to dissolve?

Fibrinolysin is released from endothelium and prevents clots from forming

What causes an antemortem clot?

Any element of Virchow’s trid (ex. hypercoagulability, endothelial damage, turbulent blood flow)

What are the characteristics of an antemortem clot?

• Rough

• Difficult to remove (friable, falls apart, loosely adhered to endothelial wall)

• Red and uniform in color

What are the characteristics of a postmortem clot?

• Smooth and shiny

• Simple to remove

• “Chicken Fat” appearance and feel

You’re doing a necropsy on an animal and notice pink coloration to the teeth. Is this a postmortem autolysis or pathology?

Postmortem autolysis → Hemoglobin imbibition

Is this considered an antemortem or postmortem clot? Why?

Antemortem → rough, uniform red color, no separation of RBCs and plasma

Pathology or non-lesion? Why?

Non-lesion. Pseudomelanosis, which occurs in GIT and is a postmortem condition (Putrefactive bacteria = putrefaction!)

Pathology or non-lesion? Why?

Non-lesion. Hemoglobin imbibition, results from free hemoglobin, but a pathological condition

Pathology or non-lesion? Why?

Non-lesion. Livor mortis, occurs post-mortem not due to pathology.

Pathology or non-lesion? Why?

Non-lesion. Bile imbibition due to GB/duct leakage, not pathological.

Livor mortis

Bile imbibition

Hemoglobin imbibition

Antemortem clot with heartworm

Postmortem clots

Pseudomelanosis

Pseudomelanosis

What is cell stress?

changes that are nonlethal and disrupts homeostasis

What is cellular injury?

alteration in cell structure or biochemical functioning that overwhelms the cell’s ability to compensate and adapt

When does injury occur?

Cell can’t adapt to the changes and cannot maintain normal, critical functions

How does the cell respond to stressors/injurious stimuli?

Adapts or dies

What does cell response vary based on?

cell type, nature and intensity of injury, metabolic state at injury

What’s the difference between reversible vs. irreversible cell injury?

Reversible the cell can reestablish function

Irreversible the cell cannot reestablish function

What can lead to irreversible cellular injury?

longer duration or higher intensity injuries

Which occurs faster in the cell: morphological/histological changes or functional changes?

Functional

Microscopic lesions develop ___ hours after an ischemic event

4-12

In what type of tissue/cell is acute cell swelling is worse?

Neurons

What is the most common reversible cellular injury?

Acute Cellular Swelling

What causes cell to swell?

Na/K pump failure causing influx of Na and H2O

How does hypoxia cause acute cell swelling?

Lack of ATP production → Na/K pump failure

What can cause cell membrane injury?

Free radicals, lytic pores, bacterial cytolysins, NK Cells

How does acute cellular swelling show macroscopically?

Rounded margins, bulges at the surface, pale, heavy, wet

What is being shown

hydropic degeneration

What is being shown? Parenchymal organ.

Hydropic degeneration

What characterizes irreversible cell injury?

Inability to repair cell damage

Inability to restore cell or mitochondria function

What cells are most susceptible to hypoxia causing irreversible cell injury?

Neurons, cardiomyocytes, renal tubular epithelium

What is the most crucial in the transition from reversible to irreversible damage?

membrane damage and calcium homeostasis

What things cause cytoplasmic changes in irreversible cell damage?

Mitochondrial swelling and increased membrane permeability

What are characteristics of mitochondrial swelling?

loss of dense granules, formation of amorphous densities, calcium deposits

What are signs of increased membrane permeability?

myelin figure formation, leakage of enzymes, inflammation

What are the irreversible nuclear changes?

pyknosis, karyorrhexis, karolysis

What is pyknosis?

chromatin condensation, nuclear shrinking

What is karyorrhexis?

nuclear fragmentation

What is karyolysis?

nuclear dissolution

What are the 4 mechanisms of cellular injury

1. Hypoxia

2. Free radicals

3. Chemical/traumatic

4. Infectious

What is hypoxia due to?

ischemia usually

Where do free radicals do most damage?

cell membrane

What are the 2 pathways of ATP production?

oxidative phosphorylation and glycolytic pathway

How is ATP made in oxidative phosphorylation?

Oxygen is reduced to transition ADP to ATP

Oxidative phosphorylation is a major pathway in what species?

mammals

How does oxidative phosphorylation cause reduction of oxygen?

by electron transport chain in mitochondria

How is ATP made in glycolytic pathway?

Hydrolysis of glucose in absence of oxygen

What is produced as a by product in glycolytic pathway?

lactate

ATP depletion as little as _____ has widespread effects and is the fundamental cause of ____.

5-10%, necrotic cell death

What does a loss of ATP do?

• Na/K and Ca pumps malfunction

• No oxidative phosphorylation

• Structure disrupted

• Accumulation of misfolded proteins

What are the major causes of ATP depletion?

• reduced supply of oxygen and nutrients

• mitochondrial damage

• toxins

How can the mitochondria be damaged?

increased cytosolic Ca, free radicals, oxygen deprivation

What are the consequences of mitochondrial damage?

Membrane proteins, cytochrome C and apoptosis-inducing enzymes (Capases) are released into the cytosol and causes apoptosis.

What does mitochondrial permeability transition pore cause?

loss of membrane potential, stopping oxidative phosphorylation, loss of ATP then necrosis

What does cytochrome C in cytosol do?

causes apoptosis

Cytosolic Ca is maintained at ___ concentrations

very low

Where is most intracellular Ca sequestered?

in mitochondria and ER

How does increased intracellular Ca cause cell injury?

• Opening of mitochondrial transmission pore

• Activation of phospholipases, proteases, endonucleases and ATPase

• Induction of apoptosis by caspases

What is a free radical?

any molecule with an unpaired electron

What do free radicals do?

react with substances to damage cells or create abnormal cells

What are reactive oxygen species (ROS)?

an oxygen free radical

What are the most important reactive oxygen species?

hydrogen peroxide, hydroxyl, nitric oxide

Where are hydrogen peroxide, hydroxyl, nitric oxide produced?

in mitochondrial respiration in cell