PATH 3610 - Midterm 1

Number 1. Which of the following microscopic features is the best indicator of necrosis?

a. cytoplasmic swelling

b. blurring and/or loss of cellular outlines

c. nuclear pyknosis, karyorrhexis or karyolysis

c

Number 2. Which of the following is not a post-mortem change?

a. hemorrhage

b. rigor mortis

c. settling of blood in dependent parts, termed "lividity"

a

Number 3. Local death of a cell or cells due to injury is known as:

a. ischemia

b. necrosis

c. Infarction

b

Number 4. Which of the following is not true of jaundice?

a. yellow discolouration of connective tissues occurs

b. it is a disease of the liver

c. it can occur secondary to widespread hemolysis of red blood cells

b

Number 5. The switch of cells from aerobic to anaerobic metabolism can cause:

a. stabilization of organelle membranes

b. damage to lysosomal membranes, potentially worsening cell injury

c. acetic acid production

b

Number 6. Which of the following is not a cause of impaired cell energy production?

a. hyperglycemia

b. respiratory obstruction or disease

c. uncoupling of oxidative phosphorylation

a

Number 7. Apoptosis refers to:

a. shrunken nuclei seen in necrosis

b. programmed cell death to remove "old" cells

c. lysis of cells caused by membrane injury

b

Number 8. Swelling of mitochondria caused by impaired cell energy production can cause:

a. cloudy or vacuolar cytoplasmic changes

b. increased oxidative phosphorylation

c. acceleration of ATP synthesis

a

Number 9. Free radicals generated within cells are unstable and can lead to:

a. stabilization of lipid membranes

b. breaking down of protein cross-links

c. degradation of nucleic acids

c

Number 10. Alcohol comsumption can lead to fatty liver changes by:

a. decreasing hepatic oxidation of triglycerides

b. decreasing mobilization of adipose tissue due to increased caloric (alcohol) intake

c. induction of enzymes to increase fatty acid conversion into triglycerides

c

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

T

Bilirubin is:

a. lipid soluble when conjugated

b. water soluble when conjugated

c. conjugated in the kidney for excretion in the urine

b

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:

a. failed synthesis of structural proteins

b. failure of growth regulating proteins

c. interference with mitosis

Starvation can lead to a fatty liver. T/F

T

Free radicals can impair cell membrane function by causing:

lesions in DNA

lipid peroxidation

protein cross-linking

b

Apoptosis refers to:

the internalization of material by a cell

disintegration of tissues which occurs after death

programmed cell death

c

The colour changes in a bruise are related to:

necrosis of tissue

synthesis of hemoglobin

breakdown of hemoglobin

c

Elevated conjugated serum bilirubin levels are most likely caused by:

acute hypoxic hepatic injury

obstruction of the biliary tract

intravascular hemolysis

b

Dystrophic calcification refers to abnormal deposition of calcium salts:

in dead or dying tissues

in tissues due to high serum calcium levels

associated with inherited calcium metabolic disorders

a

Bilirubin is:

lipid soluble when conjugated

water soluble when conjugated

conjugated in the kidney for excretion in the urine

b

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

anemia

low blood glucose levels

inhibition of respiratory enzymes

a

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

coagulation necrosis

caseation necrosis

an abscess

a

What is an infarct?

A small area of dead tissue resulting from failure of blood supply

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

decreased oxidation of triglycerides

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

decreased mobilization of adipose tissue due to increased alcoholic caloric consumption

b

Cellular injury can result when bilirubin accumulates in:

parenchymal cells (such as the liver or brain)

connective tissue

skin

a

Cloudy swelling is the result of:

intracellular accumulation of fluid and electrolytes

decreased intracellular pH

triglyceride accumulation

a

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

insufficient oxygen

low glucose levels

enzyme inhibition

a

Death of cells in a living organism is termed:

gangrene

necrosis

ischemia

b

The primary change in hemolytic jaundice is:

inadequate bilirubin excretion

increased production of bilirubin

serum accumulation of conjugated bilirubin

b

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

true

false

T

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:

failed synthesis of structural proteins

failure of growth regulating proteins

interference with mitosis

c

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

cytoplasmic vacuolation

hyperglycemia

fatty degeneration

c

Epithelial tissue

covers surfaces, skin, and inner linings, houses secretory glands

Connective Tissue

also called stroma, supports structures of body, organs

Hermolymphatic Tissues

comprises the immune system, including blood and inflammatory response

When the ________________ of a cell is exceeded, cell injury and death occur

adaptive response

Why is the light microscope not the best method of detecting cell death?

Severe biochemical damage may be undetectable under light microscope

What is Etiology?

The actual cause of the disease

What is Pathogenesis?

The development of the disease

Is immunological abnormality etiology or pathogenesis?

etiology

Is genetic abnormality etiology or pathogenesis?

etiology

Is nutritional imbalance etiology or pathogenesis?

etiology

Is infection etiology or pathogenesis?

etiology

Is trauma etiology or pathogenesis?

etiology

Are toxins etiology or pathogenesis?

etiology

Is biochemical change etiology or pathogenesis?

pathogenesis

Is structural change etiology or pathogenesis?

pathogenesis

Reversible Cell Injury: explain cellular swelling

increased cell permeability

Reversible Cell Injury: explain fatty change

lipid vacuoles containing triglycerides in the cytoplasm

Reversible Cell Injury: explain compensation state

a state where an un-optimal function is sufficient enough for the cell to continue functional at a sub-efficient level

What are the 3 things that occur during Reversible Cell Injury

Cellular swelling, fatty change and compensation state

What are the 3 things that occur during the Transition point of "reversible" to "irreversible"

- inability to restore mitochondrial function

- loss of function of cell membranes

- loss of DNA and chromatin integrity

Somatic death

death of the whole body

What is eosinophilia

Higher than normal levels of white blood cells

In necrosis, what are the two types of cytoplasmic evidence?

cytoplasm become homogenous, and deeply staining : denaturing of cytoplasmic proteins and loss if ribosomes

cytoplasm becomes vacuolated/bubbly : impaired energy production. Leads to failure of cell membrane pumps, and can cause mitochondria to swell up

In necrosis, what are the 3 types of nuclear evidence?

Pyknosis means that the nucleus shrinks and increased basophilia.

Karyorrhexis: next, the nuclear fragmentation occurs.

Karyolysis: basophilia fades after the DNase (deoxyribonuclease) digests the DNA due to lysosomal enzymes.

Which is better evidence of necrosis - cytoplasmic or nuclear?

nuclear

Explain cause and brief description of following necrosis type:

coagulative

caused by ischemia (loss in blood supply)

underlying tissue architecture is preserved for days because of decreased blood flow and because the injury denatures proteins and enzymes

What is microscopic evidence of coagulative necrosis?

cell outline is present, but nuclei is lost

Injection sites and

infarcts are examples of ___________ necrosis

coagulative

Proteins are denatured in which type of necrosis?

coagulative

Explain cause and brief description of following necrosis type:

liquefactive

caused by bacterial infection

there are many inflammatory cells, and where enzymes of white blood cells liquefy the tissue. materials is sometimes yellow and creamy - pus

Fungal inflections & Focal bacteria are examples of ____________ necrosis

liquefactive

Explain cause and brief description of following necrosis type:

Gangrenous

loss of blood supply, often to entire limb - type of coagulative necrosis

death of multiple layers of tissue

Explain cause and brief description of following necrosis type:

caseous

seen in foci of tuberculous infection

collection of fragmented and lysed cells

What type of necrosis happens in foci of tuberculous infection?

caseous

What is a unique microscopic property of caseous necrosis

obliterated cell oulines

What necrosis looks cheese-like

& yellow-white color?

caseous

Explain cause and brief description of following necrosis type:

Fat necrosis

caused by pancreatic lipases that are released into peritoneal cavity and substance of pancreas

liquefies fat cell membranes

What type of necrosis produces chalky white areas?

fat necrosis

What type of necrosis happens during - release of pancreatic lipases into the pancreas and peritoneal cavity

- acute pancreatitis

fat necrosis

Explain cause and brief description of following necrosis type:

Fibrinoid necrosis

Caused by immune response where antigens and antibodies are deposited on the walls of blood vessels.

What type of necrosis causes wall of damaged blood vessels to produce pink, amorphous appearance on H&E preparation (Fibrinoid)

fibrinoid

What type of necrosis happens during - severe hypertension

- immunologically mediated diseases (polyarthritis nodosa)

fibrinoid

What are the 2 types of fat necrosis and explain each?

Enzymic fat necrosis: Occurs in pancreatic injuries and acute pancreatitis

Release of pancreatic enzymes (especially lipase) into adjacent tissue

There is considerable adipose tissue in abdominal mesentery and omentum.

Pancreatic lipase breaks down triglycerides in fat cells into glycerol and fatty acid

Creates Ca 2+ soaps which give white chalky appearance

Nonenzymic fat necrosis:

Occurs in breasts and or subcutaneous (under the skin) tissue following trauma

Induces inflammatory response - granulomatous

dystrophic calcification

- abnormal deposition in DEAD tissue

- Calcification of fatty plaques (atheroma) or atherosclerosis

Explain how loss of tissue occurs during tissue necrosis?

decreased vascular flow

typically in farthest reaches of body

Explain how secondary infection occurs during tissue necrosis?

- necrotic tissue minimizes blood flow, and reduces inflammatory response and delays repair

- great place for infection because it is outside the reaches of the immune system

Explain how systemic effect occurs during tissue necrosis?

- Fever and increased white cell blood count (due to inflammatory response)

- Occurs due to release of pyrogens (fever inducing agents) from necrotic cells

Explain how local effect occurs during tissue necrosis?

blood vessel rupture, pain, gastric ulcers and blood in stool

Explain how release of enzymes from necrotic cells occurs during tissue necrosis?

cytoplasmic enzymes of necrotic cells can be released by necrotic tissue, and can be examined for diagnosis via serum sample

Which type of cell death exhibits inflammation? apoptosis or necrotic

necrosis

What is physiological apoptosis?

unwanted cells are destroyed and replaced

What is apoptosis by pathological condition?

elimination of cells that are beyond repair

Apoptosis is regulated by biochemical pathways that cause the activation of ________.

caspases

What are caspases?

protease enzyme that plays a major role in cell death and inflammatory response - activates "executioner caspases" to degrade DNA and cell proteins

What are the names of the 2 pathways that apoptosis can occur?

Intrinsic and Extrinsic

Briefly explain the intrinsic pathway of apoptosis?

Mitochondria becomes permeable

cytochrome c leaks into cytoplasm

activates caspase-9

cell death

Briefly explain the extrinsic pathway?

FasL receptor on the T-lymphocyte binds to TNF receptor on the host

the receptor binds with receptor proteins in cytoplasmic side of membrane

activates caspase-8

cell death

In which pathway is caspase-8 activated?

extrinsic (involving T-lymphocyte)

In which pathway is caspase-9 activated?

intrinsic (involving mitochondrial death)

What is Necroptosis?

This is triggered when TNF receptors are activated, along with other triggers.

Pyroptosis

activation of cytosolic protein complex called inflammasome which activates caspases causing cell death.

Autophagy

self-eating

cell eats organelles through lysosomal enzymes & digestion

How does lysosomal enzyme release happen?

occurs due to lack of oxygen to utilize anaerobic metabolism - causes production of lactic acid

which lowers cell pH

causes damage to lysosomal membranes

enzymes are released

Rigid Mortis:

stiffening of body due to reduction of ATP in muscle

Post mortem lividity:

gravitational settling of blood in low parts - breakdown of hemoglobin causes green tone in the skin

Post mortem blood clotting:

large clots in chambers of the heart

Putrefaction:

fermentation caused by saprophytic (organism that lives off of dead material) bacteria, gas accumulation may rupture stomach and foamy liver

Autolysis:

disintegration of tissue due to action of own enzymes