PRIN 8 Homeostasis Flashcards
1
Q
What is normal core body temp?
A
36.8 C
normal rectal is 0.6 C higher
2
Q
What happens when we have the disturbance of loss of water as sweat?
A
Drop in blood sodium concentrations are sensed by Osmoregulators in Ant. Hypothalamus
Triggers Hypothalamic supraoptic & preoptic nuclei including thirst center
Effector:
Post Pit increases ADH = increased H20 absorption
Brain cortex increases thirst sensation
3
Q
Negative Feedback Loop Template
A
Regulated Variable
Sensor
Controller
Effector
4
Q
Bad Example of Positive Feedback Loop
A
Significant loss of blood volume triggers drop in arterial pressure
Weakening of the heart causes a further decrease in heart’s ability to pump
…DEATH
5
Q
Blood clotting is what type of feedback loop
A
Postive Feedback Loop
Clotting factors within it act on enzymes that further the clotting process
6
Q
Childbirth is what type of feedback loop?
A
Positive Feedback Loop
Uterine Contractions cause pressure against cervix and releases oxytocin
RESULT: Oxytocin stimulates more uterine contractions
7
Q
What are the 3 components of the ANS?
A
(1) Afferent
(2) CNS
(3) Efferent`
8
Q
Where are most ANS centres found?
A
in Nuclei in the brain stem and hypothalamus
(eg) NTS
Nucleus Tractus Solitarii
9
Q
Uniqueness of Epinephrine
A
acts as BOTH a neurotransmitter AND a hormone
10
Q
Origins of Sympathetic & Parasympathetic NS
A
Sympathetic:
CN III, VII, IX, X,
S2-S4
Parasympathetic:
T1-L2
11
Q
Which neurotransmitters do pre-ganglionic fibres use in the Parasympathetic NS?
A
Ach
12
Q
Which neurotransmitters do pre-ganglionic fibres use in the Sympathetic NS?
A
Ach
13
Q
Which neurotransmitters do post-ganglionic fibres use in the Parasympathetic NS?
A
Ach
14
Q
Which neurotransmitters do post-ganglionic fibres use in the Sympathetic NS?
A
NE to Adrenal Medulla
(via Sym Chain Ganglia)
Ach to sweat glands
NE / E to blood vessels
(from liver)
NE to other targets
15
Q
What is the Paravertebral Ganglion?
A
Same as Sympathetic Chain Ganglia
16
Q
What is an Ionotrophic Receptor?
A
Ion Channel Receptor
Nicotinic
Na+/K+
17
Q
What is a Metabotropic Receptor?
A
G Protein / 2nd Messenger Receptor
Muscarinic
18
Q
What are the 2 types of Cholinergic receptors?
A
via Ach
(1) Nicotinic
Na+/K+
(2) Muscarinic
G-Protein
19
Q
What are the 5 types of Adrenergic receptors?
A
ALL coupled via G-proteins
a1 vasoconstriction a2 GI sphincter constriction B1 increase cardiac output B2 dilate skeletal muscle arterioles & dilate bronchioles B3 lipolysis in adipose tisse
20
Q
a1
A
vasoconstriction
21
Q
a2
A
GI sphincter constriction
22
Q
B1
A
increase cardiac output
23
Q
B2
A
dilate skeletal muscle arterioles
dilate bronchioles
24
Q
B3
A
lipolysis in adipose tisse
25
Examples of non-peptide NANC
NANC = non-adrenergic / non-cholingeric
GABA, Serotonin, Histamine, Dopamine, ATP, NO
26
Examples of peptide NANC
NANC = non-adrenergic / non-cholingeric
Substance P, Somatostatin, Enkephalin
Vasoactive Intestinal Peptide (VIP)
Cholecystokinin (CCK)
Galnanin
27
Where does E / NE release from?
| What does it stimulate?
released from adrenal medulla
| stimulates skeletal muscle glycogenolysis
28
What is meant by Paradoxical co-inactivation?
May occur during intense conflict behaviors
| -uncertainty between active or passive response
29
What is meant by Vaso-vagal Reflex?
some stressors like sight of blood or public speaking cause parasympathetic predominance
Fall in blood pressure and syncope
30
Describe autonomic control of ventilation
```
TYPE 1 (GLOMUS) CELLS
"Carotid Body" located in Carotid Sinus
```
Sense drop in O2, drop in pH, or rise in CO2 and trigger a reflex an action potential sending a message to increase ventilation
31
What is Dysautonomia?
Rare neurological condition with partial or complete autonomic failure
Autoimmune destruction of ANS neurons
Most patients recover
32
Orthostatic Hypotension
"head rush"
| common in the elderly
33
Autonomic Failure in the Elderly
demyelination of preganglionic ANS neurons
40% of patients over 65 have orthostatic hypotension
4% have body temp <35C
10% show urinary incontinence
34
What is Diabetic Neuropathy?
Hyperglycemia reduces GF secretion, suppresses brain blood flow, causes ischemia, and increases production of reactive oxygen species
These factors result in damage and destruction of autonomic neurons
35
What is Alcoholic Neuropathy?
Alcohol causes de-myelination and destruction of axons in spinal nerves.
36
Primary Endocrine Glands
HEAD:
Pineal Gland
Hypothalamus
Pituitary Gland
MEDIASTINUM:
Parathyroid Gland
Thymus
ABDOMEN:
Adrenal Gland
Pancreases
Ovaries/Testes
37
Secondary Endocrine Glands
**Not immediately associated with endocrine, BUT do have individual cells that secrete hormones
```
Heart
Stomach
Liver
Kidney
Small Intestines
Skin
```
38
FOUR Chemical Classes of Hormones
(1) Peptides & Proteins
(2) Steroids
(3) Amines
(4) Eiocosanoids
39
In what cells are testosterone produced?
Leydig Cells
| produce testosterone in testis
40
Examples of Steroid Hormones
(1) Gonads (testis & ovaries) produce Testosterone & Estrogen
(2) Adrenal Cortex produces Aldosterone & Cortisol
(3) Placenta producing Estrogen & Progesterone
41
Examples of Amines Hormones
MODIFIED AMINO-ACIDS
(1) Der. of TYROSINE: E, NE, Dopmaine, T3, T4 (Catecholamines)
(2) Der. of TRYPTOPHAN: Serotonin, Melatonin
(3) Der. of HISTIDINE: Histamine
42
Examples of Eicosanoids Hormones
(1) Prostaglandins: Allergic & Inflammatory Responses
(2) Prostacyclins: blood clotting
(3) Thromboxanes: Vasoconstriction
(4) Leukotrines: Gastric Acid secretion
43
How is most Hormone Secretion Regulated?
Negative Feedback Loops
(eg) Ant. Pituitary releases TSH
Thyroid releases Thyroid Hormones which then act on the Ant. Pit and inhibit release of TSH
44
What is the most common delivery method of hormones in the body?
Endocrine:
| secreted INTO blood and act on a different tissue
45
What is the Neuroendocrine delivery mode?
Specialized neurons release hormones into blood
46
What is the Paracrine delivery mode?
Endocrine Cells secrete hormones into the ECM to be picked up by LOCAL cells
47
What is the Autocrine delivery mode?
Endocrine Cells secrete hormones into the ECM to be picked up by the SAME cell
48
What is the Intracrine delivery mode?
Horomones act WTIHIN the cell of origin
| do not leave cell
49
What type of receptor does E/NE act on?
7 Transmembrane G-Protein coupled Receptors
small molecules (E/NE) bind within the transmembrane domains, whereas larger one bind the N-Terminus
50
Describe:
| Single Transmembrane Spanning Receptors
*Span membrane only once
GROUP 1:
Possess intrinsic TK activity:
(Insulin, IGF-1, EGF receptors)
GROUP 2:
Interact with intracellular proteins that possess kinase activity
(GH receptor)
51
What are the 4 most common second messenger systems?
(1) Cyclic Nucelotides
(2) Inositol phosphates & DIacylgylcerol
(3) Ca2+ and Calmodulin
(4) TK
52
Describe 2nd Messenger System:
| (1) Cyclic Nucleotides
Involves:
7 transmembrane receptor
G-Protein (a,B,y)
Adenylyl cylcase (AC)
End result: production of cAMP
53
When is the G-Protein activated?
when bound to GTP
54
What are examples hormones produced via Cyclic Nucleotides?
```
ACTH
LH, FSH
Glucoagon
PTH
Catecholamines:
E, NE, Dopmaine, T3, T4
```
55
What are catecholamines?
Derivatives of Tyrosine:
| E, NE, Dopmaine, T3, T4
56
Describe 2nd Messenger System:
| (2) Inositol phosphates & Diaglycerol
PIP2 ... IP3 / DAG
also utilizes A G protein(q) which activates PLC
2nd messengers:
IP3 releases Ca2+ from intracellular stores
DAG activates PKC ... ser/thr
57
What are examples hormones produced via Inositol phosphates & Diaglycerol?
GnRH
GRH
Oxytocin
TRH
58
Describe 2nd Messenger System:
| Ca2+ & Calmodulin
Within the cell, Ca2+ can bind to calmodulin
Complex then acts on enzymes
59
What are HREs?
Hormone Response Elements
| Specific DNA regions that acted on by Intracellular Receptor * Respective Hormone
60
What are the modes of heat transfer from the body?
| MOST common to LEAST common
(1) Radiation (60%)
(2) Evaporation (22%)
(3) Convection (15%)
(4) Conduction (3%)
61
What is the most accurate temperature?
Rectal Temperature
| (0.3 to 0.5C higher than oral
62
What temperatures defines Hypothermia & Hyperthermia?
Hypo 40C
63
What is the Hypothalamic Set Point?
CORE BODY TEMP
(head & trunk)
equilibrium state to which temperature is regulated
64
How do we produce heat?
```
Shivering
Non-shivering (BAT)
Peripheral Vasoconstriction
Piloerection
Increased HR, metabolism
Behavioral adpations`
```
65
How do we lose heat?
Sweating
Vasodilation
Skin Relaxation (hairs lie flat)
Behavioural adaptations
66
What senses temperature changes?
Peripheral Thermoreceptors (free nerve endings in skin, oral cavity)
Mostly A delta and C fibres
Transient receptor potential (TRP) channels open, depolarize nerve endings
67
Where do the Peripheral Thermoreceptors send their message?
crosses midline at level of spinal cord
Targets: Hypothalamus & Cerebral Cortex
68
Important Nuclei of Hypothalamus & Role in Temperature Regulation
PREOPTIC AREA
senses heat or cold, can initiate effectors for heat loss or heat production
ANT. HYPOTHALAMUS
senses heat & initiates heat loss effectors
POST. HYPOTHALMAUS
initiates heat production/retention
69
A lesions in which part of the Hypothalmus could cause hypothermia ?
Posterior Hypothalamus
lesion causes hypothermia
(PH induces heat production)
70
How do we achieve vasodilation in the periphary?
due to inhibiting sympathetic pathways that act on a-adrenergic receptors on smooth muscle of arteries and arterioles
71
How does Non-shivering thermogenesis work?
Brown Adipose Tissue (BAT)
*present in newborns and adults
UCP permits H+ into mitochondrial matrix = ruins H+ gradient
*acts as an uncoupler
72
"I'm too cold"
| What happens
Pre-optic Area senses and does 2 things:
(1) stimulates release of TRH to increase basal metabolism (fat, heart, skeletal muscle)
(2) communicates with Post H. which instructs Spinal cord to initiate
(i) Shivering
(ii) Sympathetic Activity
73
I'm too hot!
| What happens?
Ant H/PreOptic Area:
(1) initiates sweating
(2) inhibits sympathetic response normally responding to cold
74
What defines fever?
An a.m. oral temperature of > 37.2 °C
OR a p.m. oral temperature of > 37.7 °C
(circadian rhythm is retained during fever)
Fever associated with signs of infection/inflammation (increased C-reactive protein, neutrophils)
75
What is a Pyrogene?
Fever inducing substance (endogenous or exogenous)
Examples:
(1) Tumors: lymphoma
(2) Autoimmune disorders: rheumatoid arthritis, lupus
(3) Tissue damage: surgery, infarction
(4) Infectious disease: AIDS, malaria, influenza, gastroenteritis o Lipopolysaccharide (LPS: bacterial cell wall)
(5) Used for experimental study of fever
(6) Drugs (antibiotics)
(7) Fever of unknown causes (persist for several days-weeks)
76
Describe temporal pattern of Simple Fever
Set point suddenly set to high value (eg) 39C
BRAIN IS TELLING BODY TO BE HOT
Therefore, heat conservation via sympathetic kicks in: Vasoconstriction, Piloerection, Shivering
"Crisis" is the fever breakpoint (usually after 36 hrs)
77
How do Pyogenes cause fever?
Neutrophils, Macrophages/monocytes migrate to site of damage/infection and release cytokines
TNF, IL-1 & IL-6, Interferons
78
How do blood cytokines tell the brain to start a fever?
Cytokines are biggish can only cross the BBB where it is leaky. Occurs at OVLT, right next to the pre-optic/AH
OVLT: organum vasculosum of the lamina terminals
79
What is the final step in generating fever?
Cytokines (IL-1,6, TNF-a) stimulate the production of prostaglandin E2 (PGE2) in endothelial cells of brain vessels
PGE2 diffuses into preoptic/anterior hypothalamus and reduces firing rate of warm-sensitive neurons, thereby inhibiting heat loss mechanisms.
PGE2 increases firing rate of cold-sensitive neurons, thereby increasing heat gain mechanisms.
Net effect is a resetting of the hypothalamic set point to a new higher value
80
How can we treat fever?
NSAIDs (ibuprofen or aspirin) inhibit PGE2 synthesis via cyclo-oxygenase
Corticosteroids blocks inflammation by inhibiting PLA2 & COX
(note: PLA2 is used to make arachidonic acid & COX converts arachidonic acid to prostaglandins)
81
When might Intermittent fever occur?
Malaria
| causes multiple temperature spikes
82
In an OGTT, what glucose values are diagnostic for Diabetes Mellitus?
Fasting > 6.1 mmol/L
End of OGTT > 10.0 mmol
83
What is Pre-Diabetes?
Revealed by glucose levels:
Impaired Glucose Tolerance (IGT)
Impaired Fasting Glycaemia (IFG)
84
What are normal glucose levels?
3.3 - 8.0 mM
| normal physiological range with variable nutritional availability
85
What are the 3 sources of blood glucose?
(1) Intestinal absorption (diet)
(2) Glycogenolysis
breakdown of glycogen (muscle and liver)
(3) Gluconeogenesis
production of glucose from precursors
(liver/cortex of kidney)
86
Postprandial
VS
Post-absorptive
**Postprandial:
Immediately after a meal.
Insulin UP
Counter-regulators LOW
**Post-absorptive
Once blood glucose levels drop below ideal
Insulin DOWN
Counter-regulators UO
87
What happens to consumed glucose?
(1) Used for immediate energy
(2) Stored as glycogen in skeletal muscle and liver till saturated
(3) Excess glucose is shunted to FA synthesis
88
During fasting, when do glycogen stores become depleted?
24 hours
89
What defines hypglycemia?
below 3.3 mM/L
90
Where is Insulin produced?
β-cells of Liver (comprise
| 60-80% of the islet)
91
What is C-Peptide?
Pro-Insulin becomes processed within secretory vesicles to produce Insulin & C-Peptide.
C-peptide is a surrogate marker for insulin. It is produced in a 1 to 1 ratio to insulin. Therefore, C-peptide conc reveals endogenous insulin
92
HOW is insulin released?
(1) Glucose is imported into cell and undergoes glycoylsis & cellular respiration
(2) Excess ATP closes K+ channel blocking it from entering the cell
(3) Lack of K+ in cell causes depolarization
(4) Depolarization activates voltage-gated calcium channel
(5) Rise in intracellular Ca+ causes exocytosis of insulin granules
93
What are the Incretin Hormones?
GIP & GLP-1
Released from intestinal endocrine cells during a meal to act on the pancreas and augment insulin production
GIP: Glucose-dependent Insulinotropic
GLP-1: Polypeptide Glucagon-Like Peptide-1
94
How is the rate of glucose absorption different between IV and digestive?
IV glucose does not trigger Incretin and therefore there is a lower Insulin release.
Ingested glucose triggers a more powerful insulin response.
95
Once released in the blood and encountering the tissues, what does Insulin bind to and what does it do?
Insulin binds to its own TK receptor and causes an intracellular cascade that promotes GLUT 4 translocation to membrane
96
Where is GH produced?
produced in somatotrophs of the anterior pituitary
Released during a prolonged fast
97
Hierarchy of Counter regulation
| Order in which regulators are released
```
Insulin – 4.6 mM
Glucagon – 3.8 mM
Epinephrine – 3.8 mM
GH - 3.7 mM
Cortisol – 3.2 mM
```
Hypoglycemia ~3.0 mM
Hypoglycemia is rare
98
Type 1 DM
5-10% of diabetes
| Autoimmune destruction of β-cells = no insulin
99
Type II DM
Defective insulin secretion and insulin resistance
B Cells become exhausted and eventually fail
Genetic and environmental
Risk factor: obesity
100
What causes hands and feet to get cold?
NE released from the sympathetic nerve endings to alpha receptors on blood vessel walls
a1 = vasoconstriction
101
In our hypothermic case, why was old Mary not shivering?
Two Possibilities:
(1) Her glycogen stores were used up and she was was past the shivering stage
(2) Some elderly people do not shiver
102
What is Therapeutic hypothermia?
Intentionally induced hypothermia during surgery.
| Cerebral metabolism is reduced by 7% per 1 degree C
103
What is the danger of warming a hypothermic patient too quickly?
Hypovolemic Shock
104
What is Hashimoto's thyroiditis?
Hypothyroidism
Due to Iodine def (issue mostly in developing countries)
Presentation of goiters
105
What is the role of Peripheral Thermoreceptors?
To sense temperature changes in the peripheral and to induce vasoconstriction even before the core temp has dropped.
They anticipate changes ahead of time.
106
Is Alchohol warming?
Provides short-term warming sensation
But, as a vasodilator it inhibits the body's own peripheral vaso-constriction mechanisms. Thus, heat is lost and the core temp drops.
Alcohol speeds hypothermia.
107
The G-protein coupled receptors consist of a single polypeptide chain which crosses the membrane seven times.
Where does peptide hormone binding occur?
(1) N-terminal extracellular domain.
OR
(2) first extracellular loop
108
The release of this neurotransmitter results in vasoconstriction
Which Hormone?
NE
109
Where is glucocorticoid released from?
cortex of the adrenal gland.
110
cAMP production involves what components?
(1) 7 transmembrane receptor
(2) G-protein
(3) Adenylyl cyclase
111
During cAMP production, when the horomone binds to the receptor, what happens?
GDP is exchanged for GTP causing change in G protein subunits
Result: GTP-alpha subunit is released from G protein
112
What does GTP-alpha subunit do?
Binds to adenylyl cyclase (AC)
AC converts ATP to cAMP
113
What does cAMP do?
activates PKA
114
What are the major means of heat loss in water?
conduction
| convection
115
Peptide / Protein Hormones
Examples:
Insulin
| Vasopressin (ADH)
116
Steroid Hormones
Examples:
```
Testosterone
Estrogen
Progesterone
Aldosterone
Cortisol
```
117
Amine Hormones
Examples:
(1) Tyrosine - E, NE, Dopamine, Thyroid H.
(2) Tryptophan - Seretonin, Melatonin
(3) Histidine - Histamine
118
Eicosanoid Hormones
Examples:
Prostaglandins (allergy / inflamm response)
Prostacyclins (blood clotting)
Thromboxanes (vasoconstriction)
Leukotrines (gastric acid secretion)
