Unit 1: Cellular Adaptation, Injury, and Death Flashcards
1
Q
Atrophy
A
decrease in cell size
2
Q
Cellular adaptation can be physiologic (______ and ______ _____) or pathologic (due to a ________)
A
Cellular adaptation can be physiologic (normal and expected) or pathologic (due to a disease process)
3
Q
Physiologic example of atrophy
A
ovaries atrophy with age, which coincides with menopause and the inability to reproduce
4
Q
Pathological example of atrophy:
________________________________________________________
This is why you must always ____ _____ _____ to ________ ____ ___
A
long term use of exogenous steroids causes atrophy of the adrenal cortex
Why you must always slowly taper corticosteroids to re-stimulate adrenal cortex
5
Q
Hypertrophy
A
Increase in cell size
6
Q
Hypertrophy can be triggered by ______ (______) or tropic (______ _____ or ______ _____ signals
A
Can be triggered by mechanical (stretch) or tropic (growth factor or vasoactive agents) signals
7
Q
Example of hypertrophy:
A
HF causes backup of blood in heart chambers 🡪 cardiac tissue is stretched 🡪 LV must pump harder to eject blood and maintain CO 🡪 increased functional demand 🡪 increase in cell size
8
Q
Physiological example of hypertrophy, plus 2 points
A
exercising will increase functional demand 🡪 increases muscle mass
-Can become pathologic if excessive as muscle will break down (rhabdomyolysis – protein accumulation in kidneys)
-Reversible 🡪 when functional demand decreases (you stop working out so much), cell size returns to normal
9
Q
Physiological example of hypertrophy, plus one point
A
uterus stimulated by pregnancy hormones to increase in size to support fetus
Reversible 🡪 when baby is delivered, uterus will return to normal size
10
Q
Pathologic example of hypertrophy
A
Left Ventricular Hypertrophy (LVH)
-Anything that impairs the forward flow of blood and causes a decrease in cardiac output (hypertension, aortic stenosis, polycythemia, ect) causes the left ventricle to work harder to adequately pump blood to the body
Harder worker LV = increased functional demand of LV 🡪 LVH
11
Q
Hyperplasia
A
Increase in number of normal cells
12
Q
Physiologic example of hyperplasia
A
mammary glands increase in number in response to estrogen during pregnancy
13
Q
Physiologic example of hyperplasia (2)
A
Liver regeneration
14
Q
Pathologic example of hyperplasia
A
Endometrial cells increase in number
15
Q
Pathologic example of hyperplasia (2)
A
long term irritation of one area can cause bone spurs
-Bone cells increase in number
16
Q
Metaplasia is
A
Different cell maturation pathway signaled by cytokines & growth factors
17
Q
Metaplasia is basically the _____ of ___ cells with ____ ____ cells
A
Replacement of normal cells with lower level cells
18
Q
Metaplasia includes _________ of stem cells (epitheilia) or undifferentiated mesenchymal cells (connective tissue)
A
Reprogramming of stem cells (epitheilia) or undifferentiated mesenchymal cells (connective tissue)
19
Q
Pathologic example of metaplasia
A
long term smoking causes constant irritation/inflammation and will change bronchial tissue
20
Q
Metaplasia: what happens with long term smoking?
________ cells stop dividing into ______ ______ cells and begin dividing into _______ ________ cells (lower level and LESS FUNCTIONAL cells)
_______,______🡪 _______ _____
No ____ so _____ can’t escape = problems _____, ___________, etc
A
Bronchial cells stop dividing into columnar ciliated cells and begin dividing into squamous non-ciliated cells (lower level and LESS FUNCTIONAL cells)
Ciliated, columnar 🡪 stratified squamous
No cilia so mucus can’t escape = problems breathing, increased risk for infection, etc.
21
Q
Second pathologic example of metaplasia
A
kidney stones cause constant irritation/inflammation and will change bladder tissue
transitional 🡪 stratified squamous
22
Q
Dysplasia:
_______ cells that are ____ from the original cells from which they derived
______, _____, ______, and ______ are ______
Increased risk for progressing to ______( _____ cells)
A
Disorganized cells that are distant from the original cells from which they derived
Size, shape, organization, and function are different
Increased risk for progressing to neoplasia (cancer cells)
23
Q
Pathologic example of dysplasia: most notably occurs in _____ ___
2 points
A
most notably occurs in cervical tissue
Cervical cells can become disorganized and increase the risk for development of cervical cancer
Why women get frequent pap smears
24
Q
Hypertrophy + Hyperplasia 🡪 an increase in cell size and number can occur together
What’s a physiologic example of this?
_____ cells increase in size and number when ______ in response to _____to support the _____ _____
A
Uterine cells increase in size and number when pregnant in response to hormones to support the growing fetus
Once the baby is delivered, the uterus reverts back to its original size (reversible adaptation)
25
Hypertrophy + Hyperplasia 🡪 an increase in cell size and number can occur together
What's a pathologic example of this?
_______ _____
-_______ cells are stimulated by ______ to grow in both size and number 🡪 forms _____ ____in the ______
- Causes ______, ______, and decreases _______
**Uterine fibroids**
**Uterine** cells are stimulated by **hormones** to grow in both size and number 🡪 forms **fibrous masses** in the **uterine lining**
Causes discomfort, bleeding, and decreases fertility
26
4 common biochemical ways cells die or become injured –
Lack of ATP
Reactive Oxygen Species (ROS)
Ca+ in cell (AKA point of no return)
Membrane Permeability Defects
27
NaK ATPase pump transports...
Na+ out and K+ in
28
Common biochemical ways cells die or become injured –
Lack of ATP 🡪 no ______ metabolism and _____ ____ ___ fails 🡪 ___ can’t get out and ____ can’t get in 🡪 ______ follows Na+ into cell 🡪 cell _____ 🡪 organelles cannot function 🡪 ribosomal _______from ER 🡪 protein synthesis _____ 🡪 _______ in ____ ______ as there are no carrier proteins to transport _____ out of the cell
Common biochemical ways cells die or become injured –
Lack of ATP 🡪 no **aerobic** metabolism and **NaK ATPase pump** fails 🡪 **Na** can’t get out and **K+** can’t get in 🡪 **water follows Na+ into cell** 🡪 cell **swell** 🡪 organelles cannot function 🡪 ribosomal **detachment** from ER 🡪 protein synthesis **ceases** 🡪 **increase** in **lipid deposition** as there are no carrier proteins to transport **lipids out of the cell**
29
NOTE:
the NaK ATPase pump maintains intracellular and extracellular ____ ______ and is crucial to keeping a cell functional and healthy
NOTE:
the NaK ATPase pump maintains intracellular and extracellular **ionic concentrations** and is crucial to keeping a cell functional and healthy
30
NaK ATPase pump transports Na+ out and K+ in
When it does not work, Na+ is ___ ______ _____🡪 cell ____ and loss of function of organelles; K+ is not pumped ___🡪 accumulation of __ _______ of the cell + _____ ____build up from anaerobic metabolism (because there is no ATP) 🡪 _________ _______ and __________
NaK ATPase pump transports Na+ out and K+ in
When it does not work, Na+ is **not pumped out** 🡪 cell **swell** and loss of function of organelles; K+ is not pumped **in** 🡪 accumulation of **K+ outside** of the cell + **lactic acid** build up from anaerobic metabolism (because there is no ATP) 🡪 **metabolic acidosis and hyperkalemia**
31
Reactive Oxygen Species (ROS) 🡪 in ______ (_______ stress), ROS will ______ the _____ _______ by ____ _______ (ROS steal electrons from lipids and disrupt CM structure) 🡪 organelles can come out of cell and substances can go into cell (like Ca+ or water) 🡪 _______ and _______ of cell
Common biochemical ways cells die or become injured –
Reactive Oxygen Species (ROS) 🡪 in **excess**(**oxidative** stress), ROS will **destroy the cell membrane by lipid peroxidation** (ROS steal electrons from lipids and disrupt CM structure) 🡪 organelles can come out of cell and substances can go into cell (like Ca+ or water) 🡪 **apoptosis and necrosis** of cell
32
ROS = atoms with _______ electron that are a normal byproduct cellular metabolism or can come from _______ sources (poor diet, stress)
ROS = atoms with **unpaired electron** that are a normal byproduct cellular metabolism or can come from **exogenous** sources (poor diet, stress)
33
Common biochemical ways cells die or become injured –
ROS will attempt to steal e- from other cells/structures in the body 🡪 chain reaction of molecules needing another e-
In excess, they overwhelm and outnumber their natural opponent, antioxidants (Vit A, E, C) 🡪 ______ ______
oxidative stress
34
Common biochemical ways cells die or become injured –
Ca+ in cell (AKA point of no return) 🡪 excess Ca+ will _____ ________ (no ATP) and other ______ function 🡪 activate enzymes that breakdown many substances 🡪 intracellular damage from enzymes and promote of apoptosis
Ca+ in cell (AKA point of no return) 🡪 excess Ca+ will **decrease mitochondrial** (no ATP) and **other organelle function** 🡪 activate enzymes that breakdown many substances 🡪 intracellular damage from enzymes and promote of apoptosis
35
Normally, there is a Ca+ pump that only allows for a small amount Ca+ inside of the cell
When disrupted, Ca+ floods the cell and there is ________ damage
Ca+ acts as an activator for many enzymes such as protease (breaks down proteins of CM and cytoskeleton), endonuclease (breaks down DNA), and ATPase
**irreversible**
36
Common biochemical ways cells die or become injured –
Membrane Permeability Defects 🡪 damage to the CM increases permeability and ____ for substances to come in and out of the cell _____ 🡪 decrease in proteins, co-enzymes, RNA, and ATP substrates
Can be caused by ROS from lipid peroxidation 🡪 Ca+ into cell and organelle dysfunction
Membrane Permeability Defects 🡪 damage to the CM increases permeability and **allows for substances to come in and out of the cell freely** 🡪 decrease in proteins, co-enzymes, RNA, and ATP substrates
Can be caused by ROS from lipid peroxidation 🡪 Ca+ into cell and organelle dysfunction
37
Free Radicals 🡪 _______ molecules with an _______ electron
Disrupt chemical bonds of CM 🡪 destroy CM and structure 🡪 cell death
Free Radicals 🡪 **unstable** molecules with an **unpaired electron**
Disrupt chemical bonds of CM 🡪 destroy CM and structure 🡪 cell death
38
Free radicals can damage the cell with 3 mechanisms:
Lipid peroxidation 🡪 destroys CM and allows for substances to go in/out
Protein modification 🡪 protein dysfunction (need proteins for so many cell functions)
DNA damage 🡪 genetic mutations 🡪 increases risk for cancer development
39
Free radicals inactivated by _________ and some enzymes, but if there is an imbalance of ROS and free radical inactivators 🡪 oxidative stress
Free radicals inactivated by **antioxidants** and some enzymes, but if there is an imbalance of ROS and free radical inactivators 🡪 oxidative stress
40
Ischemia
reduction/cessation of blood flow
41
Hypoxia
inadequate amount of oxygen in tissues
42
sign of irreversible cell damage when there is a lack of O2 🡪 mitochondrial dysfunction and loss of mitochondrial membrane integrity
Mitochondrial vacuolization
43
3 things to remember about a reduction in ATP
- cellular swelling
- decrease in protein synthesis
- decrease in membrane transport
44
Which common biochemical derangements destroy the cell membranes and structure?
Reactive Oxygen Species (ROS)
45
An increase in Ca in the cell leads to
intracellular damage from enzyme activation
46
Membrane permeability defects lead to release of ________ _____, which leads to _______ _____
Membrane permeability defects lead to release of **lysosomal enzymes**, which leads to **cellular digestion**
47
When calcium enters the mitochondria,
the cell dies
48
A decrease in ATP does not effect
the movement of water pressure (passive)
49
Reactive Oxygen Species are a part of our physiology, they're a byproduct of
cellular metabolism (but it does so in a manageable manner)
50
If ROS rises, but ______ do not rise, there's an _____. This is not good (antioxidants don't change- we get it exogenously)
This is imbalance is called _____ _____, which can lead to ____ _____
If ROS rises, but **antioxidants** do not rise, there's an **imbalance**. This is not good (antioxidants don't change- we get it exogenously)
This is imbalance is called **oxidative stress** which can lead to **cell injury**
51
Hypoxemia
Too little oxygen in the blood
52
Can ischemia lead to hypoxia
yes !
53
______ will produce ____, but you can have ______ without ______
**Ischemia** will produce **hypoxia**, but you can have **hypoxia** without **ischemia**
54
What is vacuolization?
A way to compensate for flooding of the cell (acute cellular swelling). It's only temporary- it buys a little time before the cell dies
55
Cellular Injury Mechanisms: Hypoxia (1st part):
Obstruction or cessation of blood flow --> _______ --> _______ in mitochondrial oxygenation. This can lead to either ____ ________ of ______ (end) or _____ in ATP.
Cellular Injury Mechanisms: Hypoxia (1st pathway):
Obstruction or cessation of blood flow -->**ischemia** --> **decrease** in mitochondrial oxygenation. This can lead to either **severe vacuolization of mitochondria** (end) or **decrease** in ATP.
56
Cellular Injury Mechanisms: Hypoxia (1st pathway):
Obstruction or cessation of blood flow -->**ischemia** --> **decrease** in mitochondrial oxygenation. This can lead to either **severe vacuolization of mitochondria** (end) or **decrease** in ATP.
(1) From this decrease in ATP, this can lead to a decrease in ___ _____ --> _______ Na ______, ________ K ______, _______ Ca _______ --> _____ increases --> ____ ____ ______ increases
(1) From this decrease in ATP, this can lead to a decrease in **Na pump** --> **Intracellular Na increases** , **Extracellular K increases, Intracellular Ca increases** --> **H2O** increases --> **acute cellular swelling** increases
57
Cellular Injury Mechanisms: Hypoxia (1st pathway):
Obstruction or cessation of blood flow -->**ischemia** --> **decrease** in mitochondrial oxygenation. This can lead to either **severe vacuolization of mitochondria** (end) or **decrease** in ATP.
(1) From this decrease in ATP, this can lead to a decrease in **Na pump** --> **Intracellular Na increases** , **Extracellular K increases, Intracellular Ca increases** --> **H2O** increases --> **acute cellular swelling** increases
This causes 4 things: A _____ of the ____ ____, a _____ of ribosomes, a _____ in ____ ______, and ___ ____
**A dilation of endoplasmic reticulum, a detachment of ribosomes, a decrease in protein synthesis, and lipid deposition**
58
Cellular Injury Mechanisms: Hypoxia (**2nd** pathway):
Obstruction or cessation of blood flow -->**ischemia** --> **decrease** in mitochondrial oxygenation. This can lead to either **severe vacuolization of mitochondria** (end) or **decrease** in ATP.
(2) From this decrease in ATP, this can lead to an ____ in _____ ______, a ____ in ____, an _____ of ______, and a _____ in ____. Lastly, this pathway ends with ____ ___ ______
From this decrease in ATP, this can lead to an **increase** in **anaerobic glycolysis**, a **decrease in glycogen**, an **increase of lactate**, and a **decrease in pH**. Lastly, this pathway ends with **nuclear chromatin clumping**
59
Cellular Injury Mechanisms: Hypoxia (**1st** pathway):
Why do you think the decrease in ATP -> decrease in Na pump eventually leads to lipid deposition?
We need proteins to transport fat out of the cell. So when we have a reduction of protein synthesis, there's no protein carrier that can transport the fat out of the cell.
60
What is chromatin
It's part of the packaging of DNA, to form it into a chromosome. It binds DNA so that it's not so prone to breaking
61
At a high altitude, oxygen is ____ due to _____
At a high altitude, oxygen is **reduced** due to **pressure**
62
Cellular Injury Mechanisms: Hypoxia
Increase in altitude -> decrease in effective FiO2 -> hypoxia -> reduction in ____ -> anaerobic metabolism -> increase in ____ ___ ->______ _____ -> increase in ___
Increase in altitude -> decrease in effective FiO2 -> hypoxia -> reduction in **ATP** -> anaerobic metabolism -> increase in **lactic acid** -> **metabolic acidosis -> increase in K**
63
Too much circulating potassium is called..
hyperkalemia
64
Hyperkalemia can lead to
abnormal heart rhythms or cessation heart beat (cardiac arrest)
65
Cellular Injury Mechanisms: Hypoxia
Increase in altitude -> decrease in effective FiO2 -> hypoxia -> reduction in **ATP** -> anaerobic metabolism -> increase in **lactic acid** -> **metabolic acidosis -> increase in K**
NaK ATPase pump failure -> increase in ___ and ___ -> decrease of ____ in the cell -> cell swell -> decrease in level of ______ (LOC) -> increase of circulating _____ (dysrhythmia, cardiac arrest)
NaK ATPase pump failure -> increase in **Na and Ca** -> decrease of **K** in the cell -> cell swell -> decrease in level of **consciousness** (LOC) -> increase of circulating *potassium** (dysrhythmia, cardiac arrest)
66
Cellular Injury Mechanisms: Hypoxia
Increase in altitude -> decrease in effective FiO2 -> hypoxia -> reduction in **ATP** -> anaerobic metabolism -> increase in **lactic acid** -> **metabolic acidosis -> increase in K**
NaK ATPase pump failure -> increase in **Na and Ca** -> decrease of **K** in the cell -> cell swell -> decrease in level of **consciousness** (LOC) -> increase of circulating *potassium** (dysrhythmia, cardiac arrest)
This change effects the whole body, but this is what happened in the lungs in particular:
______________ membrane damage --> ______ in ______ _______--> interstitial fluid --> ______ ______ --> _____ -->_____ -> dysrhythmia --> cardiac arrest
**Capillary-alveolar** membrane damage --> **increase in capillary permeability --> interstitial fluid** --> **pulmonary edema** --> **hypoxia** --> **hypoxemia** dysrhythmia --> cardiac arrest
67
Lipid peroxidation
destruction of unsaturated fatty acids (constitutes our cell membrane)
68
Radiation/toxins --> production of ROS --> Superoxide, Hydrogen peroxide, Hydroxyl radical
This can lead to three pathological effects:
Lipid peroxidation -> membrane damage
Protein modifications -> breakdown misfolding
DNA damage -> mutations
69
IRI
Ischemia-Reperfusion Injury
70
Ischemia-Reperfusion Injury (IRI) is a complication of
ischemia
71
Original problem= ischemia is commonly related to a stroke as there is a blood clot occluding a vessel and ceasing blood flow (ischemia).
During this ischemic episode, there is an increase in O2 consumption as the body attempts to metabolize the clot _______ are produced in the process. When the clot is freed (_______), blood flow and ___ is restored and the enzyme xanthine oxidase uses the catabolites and O2, which produces ____
During this ischemic episode, there is an increase in O2 consumption as the body attempts to metabolize the clot-**catabolites** are produced in the process. When the clot is freed (**reperfusion**), blood flow and **O2** is restored and the enzyme xanthine oxidase uses the catabolites and O2, which produces **ROS**
72
Original injury of ischemia leads to cell ___ which is _______ (as long as there's no accumulation of calcium. But when we get reinjured with the reperfusion injury, it leads to cell ___ (_____)
Original injury of ischemia leads to cell **swell** which is **reversible** (as long as there's no accumulation of calcium. But when we get reinjured with the reperfusion injury, it leads to cell **death** (**necrosis**)
73
Between reperfusion and ischemic injuries, which is usually worse?
Reperfusion
74
IRI:
Enzyme conversion (______ _____) with o2 exposure
Increase of _____ consumption during ischemia --> ______ -> increase of _____ with ______ -> results in cell membrane _____, ATP ___, ______, and _____
Enzyme conversion (**xanthine oxidase**) with O2 exposure
Increase of **ATP** consumption during ischemia --> **catabolites**-> increase of **ROS** with **reperfusion** -> results in cell membrane **damage**, **ATP loss, apoptosis, and necrosis**
75
IRI:
______ ______ due to excess ROS from reperfusion and the cell’s inability to produce antioxidants during the ischemic episode 🡪 CM damaged 🡪 ____ influx into cells (overload in _______)🡪 mitochondrial dysfunction 🡪 ATP loss 🡪 apoptosis and necrosis
**Oxidative stress** due to excess ROS from reperfusion and the cell’s inability to produce antioxidants during the ischemic episode 🡪 CM damaged 🡪 **Ca+** influx into cells (overload in **mitochondria**)🡪 mitochondrial dysfunction 🡪 ATP loss 🡪 apoptosis and necrosis
76
IRI:
ROS excess is perceived as a threat by the immune system and stimulate an _____ ____ 🡪 neutrophils respond and adhere to the vessel epithelium to reach injury site 🡪 neutrophils accelerate injury by increasing capillary permeability (brings more blood and O2 = more ROS!!!)
ROS excess is perceived as a threat by the immune system and stimulate an **inflammatory response** 🡪 neutrophils respond and adhere to the vessel epithelium to reach injury site 🡪 neutrophils accelerate injury by increasing capillary permeability (brings more blood and O2 = more ROS!!!)
77
IRI:
_________ _____🡪 cell lysis from MAC 🡪 more tissue injury
Complement activated
78
Treatment for IRI
antioxidants (reverse neutrophil adhesion) and anti-inflammatories
79
What is considered a major burn injury
Covers 20% or more of body area
80
Cellular injury mechanism: burns
(major burn)
Nerves are _____, so the patient does not feel pain from the burn 🡪 patient feels pain from _____
Skin loses _____ & vapor functions
Nerves are **destroyed**, so the patient does not feel pain from the burn 🡪 patient feels pain from **EDEMA**
Skin loses **barrier & vapor function**
81
Cellular injury mechanism: burns
_______ _____ ________ from the direct tissue damage from the burn and the MASSIVE inflammatory response from the extensive tissue damage for the first ___ hours prior to capillary seal (AKA burn shock)
**Increased capillary** permeability from the direct tissue damage from the burn and the MASSIVE inflammatory response from the extensive tissue damage for the first **24** hours prior to capillary seal (AKA burn shock)
82
Hypoalbuminemia
Too little of the protein albumin level in the blood
83
Hypovolemia
Too little circulating blood volume
84
Burns:
↑ capillary permeability allows for fluid to escape the blood vessels and enter tissues/interstitial space (3rd spacing effect) 🡪 ____ and _________as albumin that normally resides in blood plasma is now able to pass through the damaged vessel and get into the ISS 🡪 ______ _____ ____ pressure (lower PULLING pressure) 🡪 no force to pull fluid back into blood vessel 🡪 MORE EDEMA 🡪 ______ and ________ 🡪 tissue ________ as there is less blood in the vasculature that is able to reach tissues
↑ capillary permeability allows for fluid to escape the blood vessels and enter tissues/interstitial space (3rd spacing effect) 🡪 **edema and hypoalbuminemia** as albumin that normally resides in blood plasma is now able to pass through the damaged vessel and get into the ISS 🡪 **decreased capillary oncotic pressure** (lower PULLING pressure) 🡪 no force to pull fluid back into blood vessel 🡪 MORE EDEMA 🡪 **hypovolemia and hypotension** 🡪 tissue **ISCHEMIA** as there is less blood in the vasculature that is able to reach tissues
85
INFLAMMATORY RESPONSE further increases capillary permeability as ______ ______through vessel walls and create ______ that albumin and fluid can pass through 🡪 MORE EDEMA AND HYPOTENSION + formation of exudates from wound (dead neutrophils that have phagocytized debris)
INFLAMMATORY RESPONSE further increases capillary permeability as **neutrophils diapedeses** through vessel walls and create **holes/rents** that albumin and fluid can pass through 🡪 MORE EDEMA AND HYPOTENSION + formation of exudates from wound (dead neutrophils that have phagocytized debris)
86
Ischemia with burns is no different that the ischemia you learned previously - lack of O2 reaching tissues 🡪 decreased ATP production 🡪 NaK ATPase pump fails 🡪 cell swell and hyperkalemia 🡪 _______ ________
Ischemia with burns is no different that the ischemia you learned previously - lack of O2 reaching tissues 🡪 decreased ATP production 🡪 NaK ATPase pump fails 🡪 cell swell and hyperkalemia 🡪 **METABOLIC ACIDOSIS**
87
3rd spacing means
fluid moves to a third space- it's usually in the vasculature or the cells- not the interstitial space
(same as **edema**)
88
Burns:
Because the patient is severely hypotensive, there is a lack of blood reaching all organs 🡪 ____ of _____reaching organs 🡪 tissue ischemia🡪 MOF (______ ______ ____)and MODS, ROS from tissue damage, _______ ____ ______ (low blood volume and ischemia to heart) causing ischemia, and ____ with compensatory mechanisms when blood flow/O2 supply is temporarily restored
Because the patient is severely hypotensive, there is a lack of blood reaching all organs 🡪 **lack of O2** reaching organs 🡪 tissue **ischemia**🡪 MOF (**Multiple organ failure**) and MODS, ROS from tissue damage, **decreased cardiac output** (low blood volume and ischemia to heart) causing ischemia, and **IRI** with compensatory mechanisms when blood flow/O2 supply is temporarily restored
89
Burn-
Remember: increased capillary permeability happens in the first 24 hours after suffering a burn prior to capillary seal.
So, what are the markers of the first 24 hours of a burn?
the severe edema, hypotension, and MODS are markers of the first 24 hours of a burn
90
Burns-
_______ response as the body is attempting to catch up with the metabolism created by the burn (mass tissue destruction = mass tissue repair/immune response/ect that require mass amounts of energy/nutrients!!!)
**Hypermetabolic** response as the body is attempting to catch up with the metabolism created by the burn (mass tissue destruction = mass tissue repair/immune response/ect that require mass amounts of energy/nutrients!!!)
91
Hypermetabolic response is characterized by...
↑ HR, hyperpnea (fast breathing), ↑ core body temperature, ↑ blood glucose, cachexia (muscle wasting)
92
Cachexia
break down/destruction of muscle and tissue
93
The hypermetabolic response lasts ____ ____ ____injury - wound closure/repair (can last week’s/months/years
The hypermetabolic response lasts **24 hours after injury** - wound closure/repair (can last week’s/months/years
94
Immunosuppression following burn shock from massive stress response 🡪 patient is very susceptible to infection 🡪 ______ and _____ ______ are the main concerns
Immunosuppression following burn shock from massive stress response 🡪 patient is very susceptible to infection 🡪 **wound and systemic sepsis** are the main concerns
95
Treatment –
First 24 hours (burn shock/↑ capillary permeability) 🡪
fluid/electrolyte replacement with colloidal IV fluids
Remember at this point, the patient is suffering from severe edema and hypotension, so we are trying to prevent tissue ischemia
96
Treatment- following burn shock ->
nutrition, wound management, excisions/grafting, scar reduction, comfort measures, infection control, thermoregulation
97
5 clinical manifestations of cellular injury
- Fever
- Increase HR (increase metabolism)
- Increase in WBC - infection
- Pain (release in bradykinins, pressure)
_ Increase in serum enzymes (LDH, ALT, AST, CK)
98
Another clinical manifestation of cellular injury is _____, malaise, and _____- but these are referred to as sickness behaviors- doesn't matter what's wrong with you
fatigue, malaise, anorexia
99
Sequence of Cell Death:
1. ↓ ATP production
2. NaK ATPase pump failure (active transport – needs ATP)
3. Cellular swelling (NaCl influx into cells – water follows)
4. Ribosome _______ from endoplasmic reticulum
5. ↓ protein synthesis
6. Intracellular ____ → _________ _____
7. Cytoplasmic ________ (ER breaks off and tries to wall off/enclose the water)
8. _______ leakage of ______ ________
9. ________ of intracellular structures (nucleus, nucleolus, halting DNA/RNA synthesis)
10. ________ ____ ______
1. ↓ ATP production
2. NaK ATPase pump failure (active transport – needs ATP)
3. Cellular swelling (NaCl influx into cells – water follows)
4. Ribosome **detachment** from endoplasmic reticulum
5. ↓ protein synthesis
6. **Intracellular Ca++ → mitochondrial swelling**
7. Cytoplasmic **vacuolation** (ER breaks off and tries to wall off/enclose the water)
8. **Lysosome leakage of digestive enzymes**
9. **Autodigestion** of intracellular structures (nucleus, nucleolus, halting DNA/RNA synthesis)
10. **Plasma membrane lysis**
100
Apoptosis = **programmed** and orderly cell death (physiologic or pathologic)
The cell shrinks, nucleus fragments, chromatin condenses
Apoptotic bodies form and are phagocytized
Plasma membrane stays INTACT
There is **NO inflammatory response**
Apoptosis = _________ and orderly cell death (physiologic or pathologic)
The cell shrinks, nucleus fragments, chromatin condenses
Apoptotic bodies form and are phagocytized
Plasma membrane stays INTACT
There is ___ _______ ______
101
Apoptosis EX
RBC has a programmed lifespan of 120 days
102
Necrosis = cell death due to ________ irreversible cell injury or programmed cell death 🡪 messy and may harm other cells
Sum of pathologic cellular changes after local cell death & cellular autodigestion (autolysis)
Characterized by cell swelling, membrane blebs, breakdown of plasma membrane, rupture of organelles, and stimulation of an
_________response
Necrotic cells seen as an intruder
Necrosis = cell death due to **unplanned** irreversible cell injury or programmed cell death 🡪 messy and may harm other cells
Sum of pathologic cellular changes after local cell death & cellular autodigestion (autolysis)
Characterized by cell swelling, membrane blebs, breakdown of plasma membrane, rupture of organelles, and stimulation of an **inflammatory response**
Necrotic cells seen as an intruder
103
4 types of necrosis
Coagulative
Liquefactive
Caseous
Fat
104
Necrosis:
Coagulative
________ ________ due to ________
Protein denaturation due to hypoxia
105
Necrosis:
Liquefactive
**Hydrolysis** causes cells to become soft/liquid
**Cysts** form to wall off liquid
necrosis with autophagy and cysts
106
Necrosis: Caseous (and example)
Mass apoptosis of cells
Granulomas walls off dead cells
Ex: TB tubercles
**necrosis enclosed by granuloma**
107
Necrosis: Fat
Lipase breaks down free fatty acids 🡪 ___________
Fat
Lipase breaks down free fatty acids 🡪 **saponification**
108
Gangrenous necrosis is not a type of necrosis, it's when you have a _____ ____ of tissue. It must include _____ and _______ invasion in order to develop gangrene.
Gangrenous necrosis is not a type of necrosis, it's when you have a **large area** of coagulative necrosis. It must include **hypoxia
and bacterial invasion** in order to develop gangrene.
109
Dry gangrene
Arterial insufficiency + bacteria
Usually occurs in **distal extremities** (feet/toes)
Skin becomes dry and turns black
110
Wet gangrene
Impaired venous return + bacteria
Large area of **liquefactive** necrosis
Usually occurs in **internal organs**(sigmoid colon)
Neutrophils invade an infected area and softened it 🡪 cyst forms
Tissue area is cold, black, swollen, and very stinky
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Gas Gangrene =
**Clostridium**
Pockets of gas in tissue
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Which gangrene is coagulative?
Dry
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Which gangrene is liquefactuve?
Wet
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Necrosis with large area of tissue
Gangrenous
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Necrosis with protein denaturation
Coagulative
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Necrosis with autophagy and cysts
Liquefactive
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Necrosis enclosed by granuloma
Caseous
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Condition of internal organs with cold, swollen, black, and foul smelling tissue
Wet gangrene
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Osmosis
passive movement of water (no ATP) from a lower water concentration to a higher concentration
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Osmolality
Ratio of solute (ions) to solvent (water)
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Tonicity
Term used within the body to describe relative osmolality
122
A high osmolality means
the solute is greater than the solvent
123
A low osmolality means the
solute is less than the solvent
124
Osmolality refers to specific _____/____ while tonicity describes relativity (inside of cell is more concentrated than outside of cell)
values/numbers
125
A normal osmotic equilibrium is when
the solute (ions) is equal to the solvent (water)
126
Hypertonic/Hyperosmotic solution:
________ solute to solvent ratio outside of the cell in the ECF (extracellular fluid)
The fluid ______ of the cell is ____ _______than the fluid _____ of the cell (fluid inside of the cell is less conc.)
**HIGHER** solute to solvent ratio outside of the cell in the ECF (extracellular fluid)
The fluid **outside** of the cell is **MORE CONCENTRATED** than the fluid **inside** of the cell (fluid inside of the cell is less conc.)
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Hypertonic/Hyperosmotic solution:
The fluid will move from _____ of the cell to _____ of the cell to attempt to dilute the ECF 🡪 ____ _____
move from **inside** of the cell to **outside** of the cell to attempt to dilute the ECF 🡪 **CELL SHRINK**
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Shrinkage of the cell is also known as
crenation
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What does a Hypertonic/Hyperosmotic solution do to the osmolality
Increases osmolality inside of the cell and decreases osmolality outside of the cell
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Hypotonic/Hyposmotic solution =
LOWER solute to solvent ratio outside of the cell in the ECF
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Hypotonic/Hyposmotic solution =
Fluid ______ of the cell is ____ _____ than the fluid _____ of the cell (fluid inside of the cell is more conc.)
Fluid **outside** of the cell is **LESS CONCETRATED** than the fluid **inside** of the cell (fluid inside of the cell is more conc.)
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Hypotonic/Hyposmotic solution
Fluid will move from the ECF into the cell to attempt to ______ the ______ of the cell 🡪 ____ ______
Fluid will move from the ECF into the cell to attempt to **dilute** the **inside** of the cell 🡪 **CELL SWELL**
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In an isotonic solution,
the solute to solvent ratio outside of the cell in the ECF is equal to the ratio inside of the cell
134
Is there movement of water in an isotonic solution?
No
What the cell is trying to maintain with its environment (equal concentration)
135
Capillary Hydrostatic Pressure = ____ ______ pressure from aorta to _____ capillaries
Capillary Hydrostatic Pressure = **driving filtration** pressure from aorta to **arterial** capillaries
136
Capillary Hydrostatic Pressure is
PUSHING pressure
It PUSHES fluid from the vessel into the interstitial fluid (ISF)
137
Capillary Oncotic Pressure = force _______ end that ______ filtration
Capillary Oncotic Pressure = force **venous** end that **opposes** filtration
138
Capillary Oncotic Pressure =
- _________ _________
- ______fluid from the ISF into the vessel 🡪 brings fluid back _____ the vessel
- Mainly due to the plasma protein ____
- **PULLING PRESSURE**
- **PULLS**fluid from the ISF into the vessel 🡪 brings fluid back **into** the vessel
- Mainly due to the plasma protein **albumin**
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When the pushing forces push water into the interstitial pace, or the interstitial oncotic pressure is pulling water into the interstitial space, it leads to..
edema
140
Capillary membrane damage = movement of _____ into the interstitial space, which changes the ______ and causes ______
Capillary membrane damage = movement of **proteins** into the interstitial space, which changes the **pressures and causes edema**
141
Capillary membrane damage:
_______ in the capillary membrane (ex: due to neutrophil diapedesis with inflammation) allows for albumin to leave the vessel and enter the ISS (interstitial space)
Albumin in the ISS = _____ ______ _____ PRESSURE
The force pulling fluid back into the vessel is gone 🡪 fluid stays in the ISS 🡪 edema
Fluid is now unavailable for circulation causing ________ and ______
Fluid is now unavailable for metabolism causing cell ________
Capillary membrane damage:
**Holes** in the capillary membrane (ex: due to neutrophil diapedesis with inflammation) allows for albumin to leave the vessel and enter the ISS (interstitial space)
Albumin in the ISS = **DECREASED CAPILLARY ONCOTIC** PRESSURE
The force pulling fluid back into the vessel is gone 🡪 fluid stays in the ISS 🡪 edema
Fluid is now unavailable for circulation causing **hypotension and ischemia**
Fluid is now unavailable for metabolism causing cell **dysfunction**
142
Edema = **accumulation** of fluid in the **interstitial space** (locally or systemically)
Edema = ________ of fluid in the _____ ______ (locally or systemically)
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Types of edema:
**lymphedema** (backup of lymph fluid), **pitting** edema (leaves an indentation), **cerebral** edema, **pulmonary** edema, **ascites**(fluid in the peritoneal cavity; associated with liver failure)
S/S = weight gain, swelling, puffiness, impaired wound healing (poor circ 🡪 decreased nutrient delivery)
________ (backup of lymph fluid), _______ edema (leaves an indentation), ________ edema, _________ edema, _______ (fluid in the peritoneal cavity; associated with liver failure)
S/S = weight gain, swelling, puffiness, impaired wound healing (poor circ 🡪 decreased nutrient delivery)
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Edema mechanisms:
_____ _______ _____ _____ due to venous obstruction, Na+/H2O retention, HF
Backup of fluid/more fluid from retention increases pushing pressure on arterial end
___ ______ _____ due to liver disease (can’t synthesize proteins) and protein malnutrition
Lower pulling pressure 🡪 fluid stays in ISS
__ _____ _____ due to inflammation (neutrophil diapedesis), burns, immune cell injury
_______ ________
due to infection, tumor, surgical removal 🡪 lymphedema
**↑ capillary hydrostatic pressure** due to venous obstruction, Na+/H2O retention, HF
Backup of fluid/more fluid from retention increases pushing pressure on arterial end
**↓ plasma albumin** due to liver disease (can’t synthesize proteins) and protein malnutrition
Lower pulling pressure 🡪 fluid stays in ISS
**↑ capillary permeability** due to inflammation (neutrophil diapedesis), burns, immune cell injury
**Lymph obstruction**
due to infection, tumor, surgical removal 🡪 lymphedema
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Renin-angiotensin-aldosterone system (RAAS) 🡪 maintains Na+ levels and BP (↑Na+/BP)
RAAS system is activated when ___ BP/BV, ___ serum ____, ___ _____ ____, ___
**↓BP/BV, ↓serum Na+, ↑urine Na+, ↑K+**
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JGA (Juxtaglomerular apparatus) of ______ release ______ into blood stream 🡪 Renin converts ______________ that is constantly circulating, into ___________ _🡪 _________ __ passes by pulmonary vessels 🡪 _________ _________ release _________ ________ _________ ______ 🡪 ______ converts ___________ ___ to ______ ____ 🡪 ______ ____ __________ _______ ______ 🡪 ↑peripheral resistance/.afterload to_____ 🡪 ______ ___ signals the _____ _____ to release __________ 🡪 aldosterone stimulates kidneys to _______ ___ and _____ and excrete ____ (as Na moves into blood, water follows) 🡪 Na+ and H2O retention results in _____🡪 ____ 🡪 ↑renal perfusion, causes RAAS system to end by ceasing renin release
JGA (Juxtaglomerular apparatus) of **kidneys** release **renin** into blood stream 🡪 Renin converts **angiotensinogen** that is constantly circulating into **angiotensin 1** 🡪 **angiotensin 1** passes by pulmonary vessels 🡪 pulmonary vessels release **angiotensin converting enzyme (ACE)** 🡪 **ACE** converts **angiotensin 1 to angiotensin 2** 🡪 **angiotensin 2 vasoconstricts blood vessels** 🡪 ↑peripheral resistance/.afterload to **↑BP** 🡪 **angiotensin 2** signals the **adrenal cortex** to release **aldosterone** 🡪 aldosterone stimulates kidneys to **reabsorb Na+ and H2O + excrete K+** (as Na moves into blood, water follows) 🡪 Na+ and H2O retention results in **↑BV 🡪 ↑BP 🡪 ↑renal perfusion** causes RAAS system to end by ceasing renin release
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Water Balance Regulation:
Thirst perception 🡪
Osmolality receptors sense ________ (solute > solvent) 🡪 _________ stimulates _____ to get you to drink
Osmolality receptors can be triggered due to low ________ ______ or ____________ (high concentration of solute, like Na+)
Water Balance Regulation:
Thirst perception 🡪
Osmolality receptors sense **hyperosmolality**(solute > solvent) 🡪 **hypothalamus** stimulates **thirst** to get you to drink
Osmolality receptors can be triggered due to low **plasma volume or hyperosmolality** (high concentration of solute, like Na+)
148
Water Balance Regulation:
ADH secretion from the ______ ______
ADH = ___ ____ hormone 🡪 stimulates _________of H2O from renal tubules
ADH secretion from the **posterior pituitary**
ADH = **NO PEE** hormone 🡪 stimulates **reabsorption** of H2O from renal tubules
149
ADH controls
plasma osmolality
150
ADH chart (1) Increase in ______ _____ will cause a detection by brain _________. OR a detection by __ _______ will cause a detection by _____ _____.-----> _________ ---> increases _____ and fluid intake ----> decreases _____ _______
Increase in **plasma osmolality** will cause a detection by brain **osmoreceptors** OR a detection by **volume receptor** ----> hypothalamus ---> increases **thirst** and fluid intake ---> causes **decrease in plasma osmolality**
151
ADH chart (2)
Increase in **plasma osmolality** will cause a detection by brain **osmoreceptors** OR a detection by **volume receptor** ----> hypothalamus ---> pars nervosa of _____ ______ -> ____ -> renal _____ ______> end result: __________________________________
Increase in **plasma osmolality** will cause a detection by brain **osmoreceptors** OR a detection by **volume receptor** ----> hypothalamus ---> pars nervosa of **posterior pituitary** -> **ADH** -> **renal water retention**-> end result: **decrease in plasma osmolality and increase in plasma volume**
152
Baroreceptors and volume receptors increase ADH secretion when
(osmolality, BV, BP)
High osmolality, low BV, low BP
153
What does ADH cause
ADH causes increased renal absorption of H2O 🡪 BP/BV increases, and osmolality decreases 🡪 posterior pituitary stops secreting ADH (negative feedback mechanism)
154
Hypotonic fluid alteration = too **little solute** to solvent outside of the cell (inside of the cell is **MORE conc** and outside of the cell is more **diluted**)
Hypotonic fluid alteration = too _____ _____ to solvent outside of the cell (inside of the cell is ____ ____ and outside of the cell is more ______)
155
What happens to the osmolality of the ECF in hypotonic fluid alteration
It decreases (outside of cell has a lower concentration)
156
Hypotonic fluid alteration
Fluid moves _____ cell to decrease the osmolality of the intracellular fluid 🡪_____ _____
Fluid moves **INTO** cell to decrease the osmolality of the intracellular fluid 🡪 **CELL SWELL**
157
Hyponatremia 🡪
too little Na+ in blood
158
Hypotonic fluid alteration causes
renal failure = kidneys can’t reabsorb Na+
SIADH = excess ADH causing excessive H2O retention 🡪 large amount of fluid dilutes plasma 🡪 hyponatremia
159
Hypotonic fluid alteration signs and symptoms
confusion, irritability, **cerebral edema** (remember cell swell even with neurons!!!), HA, lethargy, nausea, **seizures, coma**, hyper/hypovolemia
160
ALWAYS think ____ when there is a Na+ imbalance!
neuro
161
Hypertonic fluid alteration = too ____ solute to solvent ______ of the cell (inside of the cell is relatively ____ conc)
Hypertonic fluid alteration = too **much** solute to solvent **outside** of the cell (inside of the cell is relatively **LESS** conc)
162
Hypertonic: Fluid moves from inside of cell to outside of the cell to decrease the osmolality of the ECF/plasma (depending on what cells this is occurring in) 🡪 _____ ______
cell shrinks
163
Hypovolemia is associated with hypotonic alteration. It means there's ____ _____ ____ ____ Whereas hypervolemia has _____ _____ ____ _____and is associated with hypertonic alteration
Hypovolemia is associated with hypotonic alteration. It means there's **too little blood volume**. Whereas hypervolemia has **too much blood volume** and is associated with hypertonic alteration
164
Membrane excitability: abnormal levels of potassium- there's a problem with the
resting membrane potential
165
With low potassium, (hypokalemia) it takes a ____ distance to reach the threshold potential which means it needs a ____ stimulus.
So, what type of manifestations can you expect to see in a patient with hypokalemia?
With low potassium, (hypokalemia) it takes a **longer** distance to reach the threshold potential which means it needs a **stronger** stimulus.
May see lethargy, muscle weakness, decreased muscle tone, decreased tendon reflexes
166
With hyperkalemia, the resting membrane potential is ______. The distance is more ________ to reach the threshold potential, so it takes_____of a stimulus to initiate something (cells are easily excitable)
With hyperkalemia, the resting membrane potential is **increased**. The distance is more **compressed**, so it takes **less** of a stimulus to initiate something (cells are easily excitable)
167
What manifestations can you expect to see from a patient who has hyperkalemia?
cardiac dysrhythmia, especially v-fib, muscle spasms, twitching/tremors
168
The biggest sign of hyperkalemia is
ST segment depression
169
Another sign of hyperkalemia is a
peaked T wave
170
When there is a K imbalance, think
heart- K+ is essential for transmission/conduction of nerve impulses, normal cardiac rhythms, and skeletal/smooth muscle contraction
171
Abnormal levels of calcium- the problem is with the
threshold potential
172
Low __ and High __ will decrease excitability. High __ and Low __ will increase excitability
**Low K and High Ca will decrease** excitability. **High K and Low Ca will increase** excitability
173
Hypercalcemia- increased _____ ____ and decreased ______. What manifestations can you see from this?
Increased threshold potential, decreased excitability
lethargy, muscle weakness, decreased muscle tone, decreased tendon reflexes
174
Hypocalcemia- lower than normal threshold potential, decreased distance, more excitability.
What manifestations?
cardiac dysrhythmia, especially v-fib, muscle spasms, twitching/tremors
175
ST depression and shallow T wave
hypokalemia
176
ST depression and tall peaked T wave
hyperkalemia
177
K and H relation:
_____: hydrogen is pushed into the cell and kicks out potassium and Mg
_____: Mg and K is pushed into the cell and kick out hydrogen to the blood
1. Acidosis
2. Alkalosis
178
What always comes with hyperkalemia?
acidosis
179
normal blood pH
7.35-7.45, **7.4 is ideal**
180
systemic increase in hydrogen (ion) concentration
acidosis
181
systemic decrease in hydrogen (ion) concentration
alkalosis
182
higher pH than 7.4 is
lower pH than 7.4 is
higher pH than 7.4 is alkalotic
lower pH than 7.4 is acidic
183
________________ = partial pressure of CO2 (how much CO2 is in the arterial blood)
CO2 is acidic 🡪 high amounts of CO2 = acidosis (lower pH)
Respiratory component 🡪 PaCO2
184
Metabolic component 🡪
HCO3-/bicarbonate
185
More HCO3 means
it's more basic/alkaline
186
Metabolic component 🡪 HCO3-/bicarbonate
Bicarb levels are mediated by the _______ via reabsorption
Bicarb neutralizes H+ and increases pH
Think bicarb = BASIC
kidneys
187
Normal levels of PaCO2
above ___ is ____
below ___ is ____
Normal: 35-45 **40 is ideal**
above 45 is acidic
below 35 is alkalotic
188
Normal levels of HCO3
above ___ is ____
below ___ is ____
Normal: 22-26 **24 is ideal**
above 26 is alkalotic
below 22 is acidic
189
Respiratory acidosis -
↑ PaCO2 (> 45) (ventilatory depression)
190
Respiratory alkalosis
↓ PaCO2 (< 35) (alveolar hyperventilation)
191
Metabolic acidosis
↓ HCO3 (< 22) (↑ acid or ↓ base)
192
Metabolic alkalosis
↑ HCO3 (> 26) (↓ acid or ↑ base)
193
body’s attempt to correct the acid base imbalance
compensation
194
Natriuretic peptides 🡪 maintain BP and Na+ levels by inhibiting RAAS to ↓BP/Na+
RAAS antagonist 🡪 NPs _____________________________________
↓BP and ↑excretion of Na+/H2O (salt LOSS)
195
Natriuretic peptides:
↑serum ____ (hypertonic) 🡪 hypothalamus signals ______ and causes you to drink to _ _______🡪 fluid shifts out of _______________________ ↓osmolality 🡪 __ ____/___ 🡪 ____ ______sensed by stretch receptors 🡪 ____/___ ______ 🡪 signals glomerulus to ____(make more urine to ↓BV) 🡪inhibits ____ and _____ _____ ___ from _____ Na+🡪 **↑excretion of Na+/H2O 🡪 ↑urination 🡪 ↓BV 🡪 ↓BP**
Natriuretic peptides:
↑serum **Na+** (hypertonic) 🡪 hypothalamus signals **thirst** and causes you to drink to **↓osmolality** 🡪 fluid shifts **out of cells and into plasma** to ↓osmolality 🡪 **↑BV/BP** 🡪 **atrial stretching** sensed by stretch receptors 🡪 **ANP/BNP released** 🡪 signals glomerulus to **↑GFR**(make more urine to ↓BV) 🡪inhibits **RAAS and proximal convoluted tubule from reabsorbing Na+** 🡪 **↑excretion of Na+/H2O 🡪 ↑urination 🡪 ↓BV 🡪 ↓BP**
196
Natriuretic peptides:
↑serum **Na+** (hypertonic) 🡪 hypothalamus signals **thirst** and causes you to drink to **↓osmolality** 🡪 fluid shifts **out of cells and into plasma** to ↓osmolality 🡪 **↑BV/BP** 🡪 **atrial stretching** sensed by stretch receptors 🡪 **ANP/BNP released** 🡪 signals glomerulus to **↑GFR**(make more urine to ↓BV) 🡪inhibits **RAAS and proximal convoluted tubule from reabsorbing Na+** 🡪
result: ________________________________________________________________
**↑excretion of Na+/H2O 🡪 ↑urination 🡪 ↓BV 🡪 ↓BP**
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