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Pathology block 1 > Adaptation, injury, death (lecture) > Flashcards

Adaptation, injury, death (lecture) Flashcards

1
Q

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

A

necrosis

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2
Q

What is ISCHEMIA?

A

REVERSIBLE INJURY
due to inadequate blood supply

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3
Q

What is an infarction?

A

IRREVERSIBLE
NECROSIS
due to ischemia not relieved in time

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4
Q

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

A

Liquefactive: Drainage

Caseous: Anti-fungal and –TB

Gangrenous: Amputation

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5
Q

Pathologic apoptosis is important in what?

A
  • certain cancers
  • chemotherapy
  • radiation
  • transplant rejection
  • Hypoxia
  • Certain viral infections
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6
Q

What is etiology?

A

cause

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7
Q

What is morphology?

A

visible manifestation

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8
Q

What does the term gross mean?

A

visible w/o a microscope

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9
Q

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

A

adaptation

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10
Q

What is the general princicple of adaptation?

A

most vital organs have a large reserve capacity

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11
Q

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

A

adaptation

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12
Q

What is a general principle of adaptation wrt disease?

A

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

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13
Q

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

A

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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14
Q

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

A

pulmonary emphysema

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15
Q

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

A

injury

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

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16
Q

Describe cells of Injured tubules:

A

Some cells shrunken and hypereosinophilic,
a few swollen

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17
Q

Describe cells of Partially necrotic tubules:

A

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

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18
Q

The injurious reactive oxygen species (ROS) include what?

A

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

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19
Q

What happens when there is mitochondrial damage?

A

decrease ATP => downstream effects

increase ROS => damage to lipids, proteins, DNA

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20
Q

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

A

increase Mt permeabilityactivation of multiple cellular enzymes

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21
Q

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

A

plasma membrane => loss of cellular components

lysosomal membrane => enzymatic digestion of cellular components

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22
Q

What is the result of protein misfolding, DNA damage?

A

activation of pro-apoptotic proteins

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23
Q

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

A
  1. decrease in Na pump => influx of Ca, H20, Na and efflux of K = > resulting in ER and cellular swelling and loss of microvilli, Blebs
  2. increase in anaerobic glycolysis => decrease of glycogen and pH (clump of nuclear chromatin), increase of lactic acid which will further decrease pH
  3. detachment of ribosomes => decrease in protein synthesis
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24
Q

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

A

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

Increase Mt permeability transition => decrease in ATP

25
Q

What is the restoration of blood supply to ischemic cells?

A

reperfusion

26
Q

Why can reperfusion be injurioius as well as restorative?

A

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

27
Q

What are the results of the production of ROS?

A

removal of free radicals

pathologic effects (membrane damage, misfolding, mutations)

28
Q

What 3 items can cause membrane damage?

A
  • phospholipid loss
  • lipid breakdown products
  • cytoskeletal damage
29
Q

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

A

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

30
Q

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

A

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).
31
Q

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

A 
CREATINE PHOSPHOKINASE (CPK):
 creatine kinase (CK)

MB fraction released into blood
with myocardial injury.

32
Q

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

A

troponins

released into blood with myocardial injury

33
Q

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

A

ALT

more released by liver injury than AST

34
Q

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

A

AST

released by
muscle, liver and other organ injury

35
Q

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

A

ALP

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

36
Q

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

A

GGT

released by liver injury (especially toxic injury)

37
Q

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

A

LDH

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

38
Q

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

A

COAGULATIVE NECROSIS

39
Q

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

A
  • 3 minutes in brain,
  • 20 minutes in heart,
  • 2 hours in liver
40
Q

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

A

Preservation of ghost cell outline

** Cytoplasm**: increased pink eosinophilia

Nucleus: pyknosis (increased blue basophilia and shrinkage)
karyorrhexis (fragmentation)
karyolysis (fading away)

** Acute inflammatory response**

41
Q

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

A

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

42
Q

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

A

LIQUEFACTIVE NECROSIS

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

43
Q

What is localized area of liquefactive necrosis?

A

ABSCESS

44
Q

What is localized area of liquefactive necrosis visible only microscopically?

A

Micro-abscess

45
Q

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

A

blackening and shrinkage

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

46
Q

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

A

fat necrosis

47
Q

Apoptosis can be initiated how?

A

internal over time => Mt pathway

external via trauma => death receptor pathway (Fas, TNF)

48
Q

What are features of apoptosis?

A
  1. Cell shrinkage
  2. Cytoplasmic hypereosinophilia
  3. Chromatin condensation and karyorrhexis (nuclear DNA clumping and fragmentation)
  4. Phagocytosis by macrophages
49
Q

How can you identify apoptosis in skin?

A

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

50
Q

Describe the pathway of apoptosis

A
  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
51
Q

What is the difference in apoptosis and necrosis?

A

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
52
Q

Physiologic apoptosis is important in what?

A
  • Embryogenesis
  • Involution
  • Ending inflammation
  • Eliminating self-reactive lymphocytes
  • Eliminating virally infected cells*
  • Eliminating tumor cells*

* when due to host response

53
Q

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

A
  • conversion of H2O2 by SOD
  • decomposition to H2O by glutathione peroxidase, catalase
54
Q

What can cause an excess of misfolded proteins?

A
  • metabolic alterations decreases energy stress
  • genetic mutations in proteins, chaperones
  • viral infections
  • chemical insults
55
Q

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

A

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

Failure of adaptation causes apoptosis

56
Q

What is the differential diagnosis of fatige?

Toxic, autoimmune, metabolic

A

Toxic causes

  1. Drugs, downers
  2. Anti-allergy and Anti- anxiety
  3. Alcoholic liver disease

Autoimmune causes

  1. Lupus

Metabolic Causes

Hypothyroidism

Hypoadrenalism

57
Q

What are the idiopathic causes of fatigue?

What are the neoplastic causes of diseases?

A

Depression, Sarcoidism

Anemia due to leukemia,

58
Q

What are the caues of hypoglycemia

A

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.

59
Q
A

Pathology block 1 (24 decks)

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