PATH 3610 UNIT ONE

Cell Degeneration and Death

Gangrene

Regional tissue necrosis due to ischemia, followed by secondary bacterial infection defines:

Fatty Degeneration

Triglyceride accumulation in the cytoplasm of parenchymal cells (such as the liver) is termed:

Lipid Peroxidation

Free radicals can impair cell membrane function by causing:

Obstruction of the biliary tract

Elevated conjugated serum bilirubin levels are most likely caused by:

Insufficient Oxygen

Anemia will lead to impaired energy production by the cell because there is:

Necrosis

Death of cells in a living organism is termed:

Increased production of bilirubin

The primary change in hemolytic jaundice is:

Bilirubin is:

Water soluble when conjugated

Breakdown of hemoglobin

The colour changes in a bruise are related to:

coagulation necrosis

A myocardial infarct is seen as a dry, well demarcated area of pale tissue. This would be described as:

interference with mitosis

Agents such as radiation, mutagenic drugs and viruses can lead to acquired DNA abnormalities. Damage to cells such as blood cell precursors in the bone marrow is the result of:

dead or dying tissues

Dystrophic calcification refers to abnormal deposition of calcium salts in:

increased activity of hepatic enzyme systems, leading to increased conversion of fatty acids to triglycerides

Chronic over-consumption of alcohol can lead to fatty liver due to:

Nuclear pyknosis, karyorrhexis or karyolysis

Which of the following microscopic features is the best indicator of necrosis?

Hemorrhage

Which of the following is not a post-mortem change?

Necrosis

Local death of a cell or cells due to injury is known as:

A disease of the liver

Which of the following is NOT true of jaundice?

damage to lysosomal membranes, potentially worsening cell injury

The switch of cells from aerobic to anaerobic metabolism can cause:

Which of the following is NOT a cause of impaired energy production?

Hyperglycemia

Apoptosis

Programmed cell death to remove old cells

Cloudy or vacuolar cytoplasmic changes

Swelling of mitochondria caused by impaired cell energy production can cause

Degradation of nucleic acids

Free radicals generated within cells are unstable and can lead to:

Induction of enzymes to increase fatty acid conversion into triglycerides

Alcohol consumption can lead to fatty liver changes by:

True

Starvation can lead to the development of fatty liver.

True

The release of cytoplasmic enzymes from necrotic cells may be useful diagnostically.

Intracellular accumulation of fluid and electrolytes

Cloudy swelling is the result of:

Nuclear pyknosis and karrhyorhexis

The most definitive microscopic evidence of cell necrosis is:

Anemia

Hypoxia, leading to impaired energy production by the cell, may be caused by:

Breakdown of hemoglobin

The colour changes in a bruise are related to:

False

The nucleus contains large amounts of RNA

Parenchymal cells

Cellular injury can result when bilirubin accumulates in:

True

Following tissue injury, there is an early and transient vasoconstriction

If basic requirements for normal cell function aren't met, 3 things can happens:

Cell function altered, degeneration, and cell death

Cells not functioning normally

All diseases are a result of:

Cell signalling

Some cell phospholipid constituents are integral to:

Cytoskeletal elements, ECM components

Membrane proteins provide anchors for internal _______ and external _________.

Intracellular change

Membrane bound protein receptors trigger:

Receptor signals

Some proteins bound to inner leaf of membrane are enzyme system components that propagate _________ into cell.

Nutrients, constant removal of metabolic waste, and a normal cell environment

Normal cellular function depends on continuous supply of:

Injured cells

Underlying malfunctioning organs are:

injury type, duration and severity

Cellular response to injury stimuli depends on:

type, status, adaptability and genetic makeup of injured cell

Consequences of injurious stimuli depend on:

differences in response to injurious stimulation

Genetic diversity in metabolic pathways contributes to:

pharmacogenomics

_________ study of genetic polymorphisms in response to drugs and toxins

mitochondria and their ability to generate ATP + ROS under pathological conditions, disturbance in calcium homeostasis, damage to cellular membranes, and damage to DNA and misfiling proteins

Principal targets and biochemical mechanisms of cell injury: (4)

reversible damage, irreversible injury

Cells may rapidly become nonfunctional after onset of injury, but they're still viable, with potentially _______. With longer injury duration ________ or cell death may occur

cell death

________ typically precedes ultrastructural changes, light microscopic changes and gross morphological changes

cell degeneration

_________ is characterized by the abnormality of cell biochemical function, a recognizable structural change or a combination of both

compensated state

Cells, tissues and organs may degenerate for a time, then reach static condition in which they continue to function at a sub-maximal level, referred to as:

lethal cell injury

________ can result from a progression from a state of degeneration or immediate if cell injury is large enough

living organisms, local cell death

Necrosis can only occur in ________. It refers to _________, not death of whole body (somatic death).

hypoxia, hypoglycaemia, enzyme inhibition, uncoupling of oxidative phosphorylation

Factors that impair energy production leading to the depletion of ATP: (4)

cytochrome oxidase (functional enzyme in the respiratory chain)

cyanide interferes with _______, causing all cells in body to experience acute ATP shortage, leading to death

Intracellular accumulation of water and electrolytes, swelling of organelles, switch to anaerobic metabolism

Effects of impaired energy production in cells: (3)

sodium and water to move into the cell

Lack of ATP leads to dysfunction of cell membrane energy dependant sodium pump, causing:

enzyme inhibition and changes in electrical activity in cell

Disruption of intracellular concentrations of potassium, calcium and magnesium, leads to:

cloudy swelling

Influx of sodium and water leads to ___________, which imparts granular/vacuolated appearance to cytoplasm.

physical uncoupling of oxidative phosphorylation

Mitochondrial swelling causes:

Switching to anaerobic metabolism leads to _______ production, _______ intracellular pH, which disrupts organelle membranes. Damage to lysosomal membranes leads to the _________, causing cell death.

lactic acid, decreased, release of lysosomal enzymes into the cytoplasm

highest BMR (with highest oxygen demand)

Effect of defective energy production affects cells with _________ first.

attack nucleic acids, cellular proteins and lipids; initiate reactions with molecules and turn them into free radicals, evoke direct lysis of cell membrane

How do free radicals cause cell injury? (3)

Effects of cell membrane damage: (3)

Loss of structural integrity, loss of function, deposition of lipofuscin pigment

injury to cell membrane, leading to some membrane loss, causing change in shape of affected cell

The change from normal red blood cells to spherocytes occurs due to:

lack of cellular antioxidants, which normally prevent lipid peroxidation injury

The deposition of lipofuscin pigment into myocardial cells, liver cells and neurons results from organelle membrane damage caused by:

fatty degeneration (fatty change)

_________ occurs when triglyceride accumulate in the cytoplasm of parenchymal cells in organs, such as the liver.

fatty liver

______ occurs when free fatty acids, normally carried in portal blood, travel from intestine to liver, where they're processed into triglycerides, phospholipids and cholesteryl esters, which complex with apoproteins and are secreted into plasma as lipoproteins

fatty liver

Caused by things like alcohol abuse

friable

Liver tissue that's abnormally fragile, softer and easier to break, would be described as:

hemoglobin breaks down at site of hemorrhage

local accumulation of iron occurs when:

bruises/contusions are areas of ______ within tissue caused by blunt trauma that damages _________ and tissues.

hemorrhage, blood vessels

________ is a hemoglobin derived granular pigment deposited in ______ throughout the body, particularly in _______, ______ and _______, when iron's in excess.

hemosiderin, macrophages, bone marrow, spleen, liver

hemochromatosis

________ is a rare inherited defect in iron metabolism in which intracellular storage mechanisms are overwhelmed, causing free ferric ion to accumulate, which is then reduced to produce toxic free radicals, which harm cells in heart, liver and pancreas

porphyrin, bilirubin

When old RBCs are broken down and recycled, hemoglobin is broken down into components including ________, which is catabolized into ________.

bilirubin

_______ binds to albumin and is carried in plasma in unconjugated (lipid-soluble) form to liver

bilirubin is conjugated (attached to glucuronide) in the liver making it ______, allowing it to be excreted by liver cells into _____.

water soluble, bile

an increase in serum bilirubin

Jaundice is a sign of disease, caused by:

3 types of jaundice:

hemolytic, hepatocellular, and obstructive

excreted in urine

conjugated plasma bilirubin is carried to kidney, where it's:

bilirubin bound to albumin (unconjugated) is ________ and therefore _________.

lipid soluble, not excreted in bile

hemolytic jaundice

_________ occurs when RBCs are broken down in excessive numbers, which increases bilirubin production. Liver can't conjugate it fast enough so unconjugated bilirubin accumulates in serum

hepatocellular jaundice, increased, conjugated, unconjugated

________ occurs if liver's injured, which changes uptake, conjugation and excretion of bilirubin, leading to _____ levels of ______ and _______ bilirubin.

obstructive jaundice

If biliary tract is obstructed, bilirubin's not excreted adequately and conjugated bilirubin will reflux into plasma, causing:

increased serum bilirubin, leading to bilirubin deposition in tissue

Jaundice is characterized yellowish discolouration of the skin, connective tissue, sclera and internal organs, which is caused by:

cell injury/death

bilirubin deposited in parenchymal cells causes:

Interferences with mitosis, failure of synthesis of structural proteins, failure of growth regulating proteins, and filature of enzyme synthesis

At cellular level, DNA abnormalities are manifested as: (4)

enzymatic cell digestion and protein denaturation

The morphological appearance of necrosis results from concurrent:

gross, cytoplasmic and nuclear

3 types of morphological evidence of cell death:

coagulation necrosis

_________ is cell death due to ischemia

fat necrosis

________ results from the release of activated pancreatic lipase

pancreatic lipase, calcium, soaps

The chalky white appearance of fat necrosis is due to _______ action, which breaks down triglycerides in fat cells, which complex with plasma _____ to form ______.

denaturation of cytoplasmic proteins and loss of ribosomes

after necrosis, cytoplasm becomes more homogenous and deeply staining because of the:

undergone autolysis through the release of lysosomal enzymes

When the cytoplasm appears fuzzy, it suggests that the cell has:

enzyme release is a result of, not cause of, cell death

The suicide bag hypothesis suggest that the release of destructive enzymes was the event pushing the cell past the point of no return, setting it on the irreversible path to cell death, but it's now known that:

______ evidence is a more definitive indicator of necrosis than ________

nuclear, gross or cytoplasmic

pyknosis

In dead cells, nuclear chromatin clumps and becomes smaller and more densely staining, through the process of:

karrhyorhexis, karrhyolysis

______ breaks pyknotic nucleus into fragments, while _______ causes complete lysis using lysosomal enzymes.

dystrophic calcification

_______ is abnormal calcium deposition in dead/dying tissues

Altered function, tissue loss, secondary infection, systemic effects, local effects, release of enzymes

Problems associated with tissue necrosis: (6)

myocardial infarction

_______ occurs because blood supply to area of heart is occluded, causing necrosis of infected area

gangrene

______ results from a loss of arterial blood supply to an area