Adaptation, injury, death (lecture) Flashcards Preview

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Flashcards in Adaptation, injury, death (lecture) Deck (59)
1

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

necrosis

2

What is ISCHEMIA?

REVERSIBLE INJURY
  due to inadequate blood supply

3

What is an infarction?

IRREVERSIBLE
NECROSIS
  due to ischemia not relieved in time

4

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

Liquefactive:   Drainage

Caseous:   Anti-fungal and –TB

Gangrenous:   Amputation

5

Pathologic apoptosis is important in what?

  • certain cancers 
  • chemotherapy 
  • radiation
  • transplant rejection
  • Hypoxia
  • Certain viral infections

6

What is etiology?

cause

7

What is morphology?

visible manifestation

8

What does the term gross mean?

visible w/o a microscope

9

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

adaptation

10

What is the general princicple of adaptation?

most vital organs have a large reserve capacity

11

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

adaptation

12

What is a general principle of adaptation wrt disease?

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

13

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].

14

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

pulmonary emphysema

15

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

16

Describe cells of Injured tubules:

 

Some cells shrunken and hypereosinophilic,
a few swollen

17

Describe cells of Partially necrotic tubules: 

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

18

The injurious reactive oxygen species (ROS) include what?

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

19

What happens when there is mitochondrial damage?

decrease ATP => downstream effects 

increase ROS => damage to lipids, proteins, DNA

20

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

increase Mt permeabilityactivation of multiple cellular enzymes

21

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

plasma membrane => loss of cellular components

lysosomal membrane => enzymatic digestion of cellular components

22

What is the result of protein misfolding, DNA damage?

activation of pro-apoptotic proteins

23

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

  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

24

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

25

What is the restoration of blood supply to ischemic cells?

reperfusion

26

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

27

What are the results of the production of ROS?

removal of free radicals

pathologic effects (membrane damage, misfolding, mutations)

28

What 3 items can cause membrane damage?

  • phospholipid loss
  • lipid breakdown products
  • cytoskeletal damage

29

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

30

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). 

31

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.

32

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

troponins

released into blood with myocardial injury

33

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

34

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

35

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. 

36

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)

37

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

38

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

COAGULATIVE NECROSIS

39

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

40

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

41

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

42

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

43

What is localized area of liquefactive necrosis?

ABSCESS

44

What is localized area of liquefactive necrosis visible only microscopically?

Micro-abscess

45

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

46

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

fat necrosis

47

Apoptosis can be initiated how?

internal over time => Mt pathway

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

48

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

49

How can you identify apoptosis in skin?

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

50

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

51

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

52

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

53

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

54

What can cause an excess of misfolded proteins?

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

55

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

56

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 

57

What are the idiopathic causes of fatigue?

 

What are the neoplastic causes of diseases?

Depression, Sarcoidism

 

Anemia due to leukemia, 

 

58

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. 

 

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