Adaptation, injury, death (lecture) Flashcards by Hunter Garrett

What is Death of cells, tissues or organs in a living person?

necrosis

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What is ISCHEMIA?

REVERSIBLE INJURY
due to inadequate blood supply

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What is an infarction?

IRREVERSIBLE
NECROSIS
due to ischemia not relieved in time

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The type of necrosis determines the Tx. Name the types and associated Tx

Liquefactive: Drainage

Caseous: Anti-fungal and –TB

Gangrenous: Amputation

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Pathologic apoptosis is important in what?

certain cancers
chemotherapy
radiation
transplant rejection
Hypoxia
Certain viral infections

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What is etiology?

cause

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What is morphology?

visible manifestation

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What does the term gross mean?

visible w/o a microscope

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What are physiologic and morphologic changes, modulating function, bringing it to a new altered steady state of homeostasis?

adaptation

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What is the general princicple of adaptation?

most vital organs have a large reserve capacity

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surgical removal of 60% of the liver
in a normal person causes minimal (or transient)
hepatic impairment. What is this an example of?

adaptation

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What is a general principle of adaptation wrt disease?

Disease commonly uses up
an organ’s reserve capacity
silently until it is too late.

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What is an example of a disease adaptation that slowly uses up vital organs reserve capacity?

atherosclerosis gradually narrows
the lumen of critical blood vessels in the heart
until suddenly something (like severe exertion)
demands more blood flow than can be delivered
or something (like a blood clot) reduces blood
flow below the minimum needed at rest, and
then the person dies, [suddenly].

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What is the irreversible enlargement of airspaces due to the destruction of the walls constituting them?

pulmonary emphysema

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What is a reversible pathophysiologic and morphologic response to stress or noxious stimulus? Describe it

injury

exceeding capacity of cell, tissue, organ or person to adapt, but not enough to be lethal

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Describe cells of Injured tubules:

Some cells shrunken and hypereosinophilic,
a few swollen

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Describe cells of Partially necrotic tubules:

more cells swollen, some with lost nuclei, some
sloughed into lumen

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The injurious reactive oxygen species (ROS) include what?

superoxide, hydrogen peroxide, hydroxyl radical and
peroxynitrite (apt chemical name ONOO-)

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What happens when there is mitochondrial damage?

decrease ATP => downstream effects

increase ROS => damage to lipids, proteins, DNA

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What are the results if calcium entry to a cell is affected?

increase Mt permeabilityactivation of multiple cellular enzymes

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What happens if there is plasma membrane damage? lysosomal membrane damage?

plasma membrane => loss of cellular components

lysosomal membrane => enzymatic digestion of cellular components

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What is the result of protein misfolding, DNA damage?

activation of pro-apoptotic proteins

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If the Mt damage occurs and ATP is decreased due to decrease in oxidative phosphorylation. What are the downstream effects? (3)

decrease in Na pump => influx of Ca, H20, Na and efflux of K = > resulting in ER and cellular swelling and loss of microvilli, Blebs
increase in anaerobic glycolysis => decrease of glycogen and pH (clump of nuclear chromatin), increase of lactic acid which will further decrease pH
detachment of ribosomes => decrease in protein synthesis

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What 2 actions are disrupted due to increased cytosolic Ca+? What are the 3 results?

Activation of cellular enzymes => membrane damage, nuclear damage and decrease in ATP

Increase Mt permeability transition => decrease in ATP

What is the restoration of blood supply to ischemic cells?

reperfusion

Why can reperfusion be injurioius as well as restorative?

it brings oxygen that can be converted to ROS and calcium that can increase mitochondrial permeability and activate enzymes inappropriately in cells already damaged

What are the results of the production of ROS?

removal of free radicals pathologic effects (membrane damage, misfolding, mutations)

What 3 items can cause membrane damage?

* phospholipid loss * lipid breakdown products * cytoskeletal damage

Injured and dead cells and tissues leak their contents into the bloodstream. How is this helpful to know?

Blood tests for these contents can be used to diagnose tissue injury or necrosis

In doing the blood tests to diagnose tissue injury or necrosis, Name 2 enzymes that would be present. Describe them

AMYLASE = an enzyme that digests carbohydrates, secreted by both the pancreas (into the duodenum) and by the salivary glands (into the saliva). ``` LIPASE = an enzyme that digests fats, secreted by the pancreas (into the duodenum, good) and released into the retroperitoneal peri-pancreatic fat with pancreatitis (bad). ```

What is an enzyme concentrated in muscle and brain composed of M and B dimers? How will you know if there is an injury?

``` CREATINE PHOSPHOKINASE (CPK): creatine kinase (CK) ``` MB fraction released into blood with myocardial injury.

What are proteins that regulate calcium-mediated contraction of cardiac and skeletal muscle? When are they released?

troponins released into blood with myocardial injury

What is a transaminase that catalyzes the interconversion of glutamate and alanine? When does it signify injury?

ALT more released by liver injury than AST

What is a transaminase that catalyzes the interconversion of glutamate and aspartate? What does it signify when it is released?

AST released by muscle, liver and other organ injury

What is a phosphatases who transfer phosphate from donor to receptor molecules at alkaline pH? When is it released?

ALP released by liver or bone injury, especially with biliary obstruction or hepatic space-occupying disease.

What is an outer cell membrane enzyme that functions to transport amino acids into cells? When is it released?

GGT released by liver injury (especially toxic injury)

What enzyme that catalyzes the conversion of lactate to pyruvate by removing two hydrogens? When is it released?

LDH released by injury to red blood cells, liver, muscle or other organs

What is morphological manifestation of irreversible injury to cell, tissue or organ due to ischemia (except in brain)?

COAGULATIVE NECROSIS

ischemia is reversible for certain periods for different organs. Give in relation to brain, heart, liver

* 3 minutes in brain, * 20 minutes in heart, * 2 hours in liver

What are features of coagulative necrosis? What does it cause?

Preservation of ghost cell outline ** Cytoplasm**: increased pink eosinophilia **Nucleus:** pyknosis (increased blue basophilia and shrinkage) karyorrhexis (fragmentation) karyolysis (fading away) ** Acute inflammatory response**

The renal tubules are much more susceptible to ischemic injury and necrosis than the glomeruli. Why?

the glomeruli get first dibs on the blood supply to the kidney

What is necrosis with conversion of solid tissue to liquid? What is it due to?

LIQUEFACTIVE NECROSIS due to severe acute infection, toxicity or (brain only) ischemia

What is localized area of liquefactive necrosis?

ABSCESS

What is localized area of liquefactive necrosis visible only microscopically?

Micro-abscess

What distinguishes gangrene from coagulative necrosis? Where is it found?

blackening and shrinkage typically of distal extremity, but sometimes of internal organs such as gallbladder

What occurs when adipose tissue digested by pancreatic lipase, creating chalky white saponification?

fat necrosis

Apoptosis can be initiated how?

internal over time =\> Mt pathway external via trauma =\> death receptor pathway (Fas, TNF)

What are features of apoptosis?

1. Cell shrinkage 2. Cytoplasmic hypereosinophilia 3. Chromatin condensation and karyorrhexis (nuclear DNA clumping and fragmentation) 4. Phagocytosis by macrophages

How can you identify apoptosis in skin?

shrunken cell with a halo around it, condensed pink-red cytoplasm, irregularly clumped DNA

Describe the pathway of apoptosis

1. normal nucleus recieves signal or damage 2. nucleus condenses (pyknosis), cell shrink, blebs form 3. nucleus fragmenting (karyorrhexis), apoptotic body forms 4. professional or non-professional phagocyte engulfs apoptotic bodies

What is the difference in apoptosis and necrosis?

**Apoptosis:** * single cells or small clusters * cell membrane intact * no inflammatory response **Necrosis:** * large groups of cells * cell membrane disrupted * does have an inflammatory response

Physiologic apoptosis is important in what?

* Embryogenesis * Involution * Ending inflammation * Eliminating self-reactive lymphocytes * Eliminating virally infected cells\* * Eliminating tumor cells\* \* when due to host response

Name 2 ways which the production of ROS is involved removal of free radicals

* conversion of H2O2 by SOD * decomposition to H2O by glutathione peroxidase, catalase

What can cause an excess of misfolded proteins?

* metabolic alterations decreases energy stress * genetic mutations in proteins, chaperones * viral infections * chemical insults

In protein misfolding, if the cell adapts, then what happens? if cell is unable to adapt?

adaptation =\> decreases protein synthesis and increase production of chaperones to guide to a mature folded protein Failure of adaptation causes apoptosis

What is the differential diagnosis of fatige? Toxic, autoimmune, metabolic

**Toxic causes** 1. Drugs, downers 2. Anti-allergy and Anti- anxiety 3. Alcoholic liver disease **Autoimmune causes** 1. Lupus **Metabolic Causes** Hypothyroidism Hypoadrenalism

What are the idiopathic causes of fatigue? What are the neoplastic causes of diseases?

Depression, Sarcoidism Anemia due to leukemia,

What are the caues of hypoglycemia

Sepsis- systemic inflammatory response syndrome due to infection. Insulin- Given for diabetes or secreted by a tumor. Alcohol- several day binge of drinking without eating. Hormone defficency- epinephrine, cortisol, glucagon, or combination.