EPHE 160 midterm 2 - cardiovascular and endocrine

primary function of the cardiovascular system

to transport molecules and heat over long distances between:
- the internal cells and the surface
- the various specialized tissue and organs

what is the flow like in cardio systems?

flows primarily in parallell to ensure that everywhere gets fully oxygenated blood and it can easily regulate flow to each organ
- only series is the GI tract to the liver because the liver packages all of the nutrients from the GI tract

types of blood vessels

- arterioles(muscular, well innervated)/
- arteries (muscular, highly elastic): carry blood away from the heart
- Venules (thin walled,some smooth muscle)/
- veins(thin walled: carry blood to the heart
-capillaries: used for gas exchange, made of endothelial tissue, super thin, one cell thick

what regulates the status of bi and tri cuspid valves?

pressure gradient
BLOOD ALWAYS FLOWS FROM AN AREA OF HIGH TO LOW PRESSURE!

cardiac muscle

-Has intercalated discs which are physical connections between our cardiac muscle cells which help to transport APs smoothly between cells
-Calcium comes from extracellular fluid and SR

special features of cardiac muscle

- myoenic (it can contract without outside stimulus) found within the SA node of the heart.
→ Autorhythmicity
- Pacemaker cells
- Conduction fibers
• Larger diameter → conduct action potentials faster (4 m/sec as opposed to 0.3-0.5 m/sec in contractile cells)
→ Contractile cells

conduction system of the heart

- AP in SA node→AV node via internodal pathways
Also travels through interatrial pathways
- AV nodal delay
- Bundle of His→ right and left bundle branches
- Purkinje fibers → into ventricles which starts the wave of depolarization of the ventricles (starts at the BASE of the ventricles b/c it needs to generate pressure to push the blood up towards the valves)

blood

most dynamic tissue we have in the body.
landscape changes constantly
contains 45% erythrocytes, 55% plasma and leukocytes are the Buffy coat

the hematocrit

the percent of blood volume that is occupied by erythrocytes

physics of blood flow

flow\=pressure gradient/resistance

FLOW IS PROPORTIONAL TO THE PRESSURE GRADIENT

the effect of resistance on flow in a tube

-when resistance to flow increases, flow decreases
- when resistance to flow decreases, flow increases

INVERSLEY PROPORTIONAL RELATIONSHIP

factors which affect resistance

- viscosity of the fluid (resistance is proportional)
- length of the vessel (resistance is proportional)
- radius of the vessel (major determining factor of resistance)

pulmonary vs systemic

pulmonary:
- systolic pressure: 24 mm Hg
- diastolic pressure: 8 mm Hg
- low pressure system
systemic:
- systolic pressure: 120 mm hg
- diastolic pressure: 70 mmhg
-high pressure system

what affects the movement of blood in the cardiac cycle?

arterioles capacity to stretch and recoil. During diastole, recoil pushes blood, through increase in pressure to keep it moving

Pacemaker cells

No steady membrane resting potential
After an AP, it immediately begins to depolarize again• Na+, K+ and Ca + + all play an important role

types of channels and depolarization of pacemaker cells

- THE "FUNNY" [UNUSUAL] Na+ CHANNELS [F- type] [orange]
Allows sodium to enter the pacemaker cells. Under control of ANS, Leak channels.
- T-type AND L-type Ca++ CHANNELS [voltage regulated]
T stands for transient (they are only open for a short period of time)
L channel is open for a little longer than T changes. Open at threshold.

APs in Cardiac Contractile Cells

- Different in time course, level of depolarization & speed of propagation (compared to pacemaker cells)
-Vary in \# & type of ion channels
- Physical dimensions
Ventricular Muscle Cell Saveastable Resting potential & longer lasting APs.
- Do have a stable resting membrane potential, get rapid depolarization then a really slow repolarization. This is due to the fact that we want to excite these cells and get them to contract but we also need time to let them relax and fill with blood.

typical ecg with the ventricular ap included

p wave: blood from atria goes into ventricles
qrs: matches ventricular depolarization
t wave: matches the repolarization

cardiac output

CO\=HR x SV (ml/min or L/min)

SV \= EDV- ESV

control of the heart by the ANS

-Parasympathetic innervation is to the pacemaker cells which has an effect on heart rate
- Sympathetic innervation goes right into the contractile tissue of the myocardium as well as the pacemaker cells

what would happen to heart rate if there was no neural innervation

the SA node would fire at about 110-110 bts/mins

THE EFFECT OF THE AUTONOMIC NERVOUS SYSTEM ON THE PACEMAKER POTENTIALS IN NODAL CELLS

- Sympathetic: decrease the time to get to threshold which allows for heart rate to increase
- Parasympathetic: hyperpolarizes and takes us longer to get to threshold

differences in pacemaker potentials with and without different autonomic influences

pacemaker potentials are affected not the action potentials

endocrine and ANS control of the heart

Increase sympathetic stimulation of adrenal medulla → increase plasma epinephrine → increase heart rate (increase the activity of sympathetic nerves to heart and decrease activity of parasympathetic nerves to the heart) \= INCREASED AUTORHYTHMICITY OF NODAL CELLS

changes in nerve activity, symp vs para

→ Sympathetic - Epi and Norepi
- ↑ funny channel (Na+) permeability
- ↑ Ca++ inward current
→ Parasympathetic -ACH
- ↑ K+ outflow
- ↓ Na+ and Ca++ inward currents
- Hyperpolarizes cell

Heart Rate Variability (HRV)

HRV refers to variations in time (measured in milliseconds) between an individual's heartbeats.
- time between beats is very consistent \=low variability
- High variation or inconsistency in time between heart beats \= high variability.

what is low HRV associated with?

-asthma
-diabetic neuropathy
-congestive heart failure
-concussion
-sudden cardiac death
-predictive of death after a heart attack

what do we use HRV for?

- Is a TOOL to look at autonomic balance in the body (like an xray or an MRI)
- It doesn't CAUSE the associated conditions
• indicates that the conditions are causing autonomic imbalance in the body
• an indicator of stress

the cardiac cycle

1)Ventricular filling
2)Isovolumetric ventricular contraction
3)Ventricular ejection
4) Isovolumetric ventricular relaxation

how can you increase the force of contraction in the ventricle to increase stroke volume by decrease ESV?

frank starling effect and by contractility

frank starling effect

due to length- tension relationship
- In the sarcomeres of cardiac muscle, at rest, you don't have optimal overlap, we have MORE than optimal, which means they can't generate as much force. By increasing the filling of the ventricles, we get closer to optimal length. Increase venous return to the heart → stretch out ventricles → increased cardiac volume → more optimal overlap.

contractility effect

due to increase the force generate by the contractile proteins through ca
-Increase in sympathetic activity increases force of contraction→ more blood is pumped out and stroke volume increase.

how can we alter the length of ventricular muscle and invoke the frank starling effect?

by altering venous return

factors that affect venous return

Increase activity of sympathetic nerves to veins → increase skeletal muscle pump, increase inspiration movements → increase blood volume : all increase venous pressure which increase venous return which increase atrial pressure which increases end-diastolic ventricular volume which increases stroke volume.

the effect of sympathetic activity and or epi on the ventricular myocardium

1. OPENS L-Type Ca++ CHANNELS IN THE MEMBRANE. THIS 2. INCREASES INTRACELLULAR CONCENTRATION OF Ca+
INCREASES Ca++ RELEASE FROM THE SR.
3. INCREASES RATE OF MYOFIBRILLAR ATPase
4. INCREASES THE RATE OF Ca++ RE-UPTAKE INTO SR


NOTE: THE CONTROL IS VIA ACTIVATION OF Beta RECEPTORS [METABORECEPTORS]

what happens when epinephrine binds in the cardiac cycle?

- increase entry of CA both from the SR and extracellular fluid\= stronger contraction
- Protein kinase increases myosin ATPase activity \= contract cardiac muscle faster
- Increase Ca ATPase activity as well \= faster relaxation of the muscle

what works to increase stroke volume?

-Increase end diastolic volume,
-Increase activity of sympathetic nerves to heart, --Increase plasma epinephrine

cardiac cycle

→ Phase 1: ventricular pressure is lower than atrial pressure: blood is "pumped" (mostly passive filling) into the ventricles. "P wave" AV valves are OPEN, SL valves: CLOSED
→ Phase 2 ISOVOLUMETRIC CONTRACTION: ventricles are contracting yet they have not yet generated enough pressure to exceed the pressure within the aorta but pressure is too high to recieve any more blood from the atria. NO BLOOD IN, NO BLOOD OUT. AV valves and SL valves are CLOSED
→ Phase 3: ventricles have exceed pressure within the aorta which opens semilunar valves and allows blood to go into the aorta. Ventricular volume decreases rapidly. AV valves are CLOSED. SL valves are OPEN.
→ Phase 4: T wave: repolarization, ventricles pressure falls, semilunar valves CLOSE, no change in volume at this point because ventricular pressure is still higher than atrial pressure. ISOVOLUMETRIC RELAXATION. AV valves and SL valves are CLOSED
→ Start of Phase 1: Ventricular pressure falls below atrial pressure; have pressure gradient again and ventricles can begin to refill.

what determines pressure inside a vessel?

- the volume of blood in the vessel
- how easily the walls can be stretched (compliance)

vasoconstriction and vasodilation of arterioles

- arteriolar smooth muscle is single unit which means it has pacemakers and gap junction that ensure partial contraction at rest (arteriolar tone)
- arterioles have intrinsic (local fine tuning) and extrinsic control (ANS)

Arterioles

-Responsible for determining blood flow to particular organs
- Are the major site of resistance to blood flow in the vascular tree
- Can either vasoconstrict or vasodilate
- Can be regulated locally or extrinsically

active hyperemia

Increase metabolic rate → increase o2 consumption and co2 production → decrease tissue [o2], increase tissue [co2] → arteriolar smooth muscle → increase vasodilation → decrease resistance → increase blood flow → increase o2 delivery and co2 removal → increase tissue [o2] and decrease tissue [co2]

reactive hyperemia

Decrease in blood flow → decreased tissue [o2] and increase tissue [co2] → arteriolar smooth muscle → increase vasodilation → decrease resistance → increase blood flow → increase o2 delivery and co2 removal → increase tissue [o2] and decrease tissue [co2]

Reynaud's Disease

A form of reactive hyperemia
Arteries in fingers and toes go into vasospasm when exposed to cold or stress, temporarily limiting blood supply
When intrinsic factors cause vasodilation, blood flow is greatly increased, causing pain and discomfort.

intrinsic control hyperemia

steady state: o2 delivered \= co2 removed.
- decrease [o2] and increase [ o2] stimulate local vasodilation
increased metabolic rate:
o2 consumed \> o2 delivered
co2 produced . co2 removed
vasodilation results in increase blood flow; increase o2 delivery and increase co2 removal

Capillaries

Estimated 25,000 miles of capillaries in the adult human
Are a thin-walled tube of endothelial cells one layer thick attached to basement membrane
Cells are separated by intercellular clefts

what is MAP responsible for?

driving the force for blood flow through all our organs except the lungs

what is high pressure implicated in and where does it come from?

- implicated in poor circulation stroke, cardiovascular disease, kidney disease
- causes: age, genes, drinking, drugs, not exercising, high insulin levels

blood pressure classifications

normal: S:

the sensory link to the cardiovascular control

Venous and cardiac baroreceptors, arterial chemoreceptors, proprioceptors in muscles and joints and receptors in internal organs send info into the spinal cord. That info then goes into sympathetic activity.

how should BP respond to exercise?

→ Systolic
Trained→ up to 180 mmHg
Untrained→ifé's above 150, work should stop
A fall near the end of exercise indicates heart failure: pressure should go up and ventricles should be contracting more forcefully.
→ Diastolic
No change or even a slight decrease

The major factors affecting the arteriolar radius

•Neural and Hormonal regulation control whole body status
•Local regulation controls regional status

two special cases where CV control is challenged

-during exercise
- with hemorrhage

the change in blood flow distribution from rest to strenuous exercise

-increase co by about 3x (from 5 L/ min to 17,500 L/ min)
- majority of CO goes to the skeletal muscles
- increase in blood flow to the skin (vasodilation of arteries to the skin) because we need to release heat and sweat.

NOTE: there are changes in both total flow and % of cardiac output

Changes in exercise

-muscle blood flow increase (asking for vasodilation)
- co and hr increase and heart rate
- map slightly go up
- end diastolic volume (through venous return and frank starling effect)
-decrease in TPR b/c of vasodilation

control of the CV system during exercise cause

- Exercising skeletal muscle: contractions → stimulate mechanoreceptors which have input into the CV control centre. Theres also local chemical changes which stimulate chemoreceptors in the muscle and dilate arterioles in the muscle \= increase muscle blood flow. Mechano and chemo receptors provide afferent feedback into the medullary CV centre
- Brain "exercise centers": exercise directly impacts the ANS (increase symp, decrease para). Also resets arterial baroreceptors so that they adapt to the higher blood pressure that we need during exercise. Usually when BP goes up, the body wants to bring it back down but during exercise, we want BP to increase. Does not DIRECTLY affect ANS. : both work to increase CO and vasoconstriction in abdominal organs and kidneys and vasodilation in cardiac and skeletal muscle

what gets priority when you are dehydrated?

skeletal muscle

VO2- Ability to Deliver and Use Oxygen:

-Measure of the amount of oxygen you can take in, transport and utilize in the working tissue.
Physiological factors influencing VO2 max:
→ Delivery of oxygen to working muscles
Cardiorespiratory system
→ utilization of oxygen by working muscles
Metabolic system (aerobic)

Oxygen delivery during exercise:

→ Oxygen demand by muscles during exercise is 15-25x greater than at rest
→ Increase O2 delivery accomplished by:
- Redistribution of blood flow from inactive organs to working skeletal muscle (not global)
- Increase cardiac output

central factors influencing O2 consumption

Cardiac output (Q)
-HR, SV

Training increases max SV, does not influence max HR (if anything we might see a slight drop in heart rate)

peripheral factors influencing O2 consumption

Extraction by tissues (a-VO2)
- Oxygen carrying capacity and ability for cells to take O2
-Training increases capillary density, mitochondria number, Hb, Mb

Active skeletal muscle during intense aerobic exercise:

VO2 \= Q x (a-v)O2difference
Avo2 difference is the amount of blood that goes into the capillary and what comes out (goes up in trained individuals)

Changes in CV Variables During Exercise:

- HR increases linearly until it hits max
- CO increases quite steeply until about 40-50% of VO2 max and continues to increase but not at the same rate until it hits max
- SV increases until about 40% VO2 max then plateaus b/c its basically at max

→linear relationship between HR and VO2 (work rate) provides opportunity to monitor physiological process simply, HR monitors

how does epinephrine function to control smooth muscle surrounding arterioles during exercise?

When epi binds to smooth muscle initially when starting to exercise, it causes vasoconstriction but as symp activity increases and epi concentration increases, it binds to different receptors on that same smooth muscle and tells them to relax

comparing endocrine vs nervous systems

- Both are the body's major regulatory systems
- Nervous system → rapid precise responses
- Endocrine system→ control of activities requiring duration rather than speed

things that are under hormonal control

-Growth & development (smooth & sequential)
-Metabolism
-Red blood cell production
-Core temp
-Water & electrolyte balance
-Reproduction

Endocrine System Overview/Organization

→ Consists of host organ, minute quantities of chemical messengers, and target organ
→ Endocrine glands are ductless
secrete substances directly into extracellular spaces
→ Hormones secreted from endocrine glands travel in blood to exert influence on different tissues

types of hormones

4 main categories:
peptide hormones, steroid hormones, catecholamines, thyroid hormones.
- Some we can manufacture and store ahead of time. Other ones such as steroid hormones (lipid based) need to be produced and released on demand.
- Most of our hormones, the receptors are on the plasma membrane that causes a cellular response on the inside. Steroid hormones have receptors in the cell because they can diffuse through the plasma membrane.

Hormone-Target Cell Specificity

→ Hormones alter cellular reactions of specific target cells by:
-Modifying rate of intracellular protein synthesis by stimulating nuclear DNA
- Changing rate of enzyme activity
-Altering plasma membrane transport via a second-messenger system
- Inducing secretory activity
→ A target cell's response to a hormone depends on specific protein receptors that bind the hormone

Hormone-Receptor Binding

→ Represents first step in initiating hormone action
→ Extent of target cell's activation by hormone depends on:
- Hormone concentration in the blood
- Number of target cell receptors for the hormone
- Sensitivity or strength of the union between the hormone and its receptor

Factors that determine plasma concentration of a hormone:

-Quantity synthesized in host gland
-Rate of either catabolism or secretion into blood
-Quantity of transport proteins present
-Changes in plasma volume

Factors that Stimulate Endocrine Gland Activity

Three factors--(hormonal, humoral, and neural)\-- stimulate endocrine gland activity

Patterns of Hormone Release

→ Hormones respond to peripheral stimuli as needed
- Some release at regular intervals during a 24-h cycle in a diurnal pattern or cycle of secretion
- Some secretory cycles span several weeks, while others follow daily cycles
→ Patterns of release and/or amplitude and frequency of discharge provide more information on hormone dynamics than average concentration at any single time

Complexity of the Endocrine System

- a single endocrine gland may produce multiple hormones
- a hormone may be secreted by more than one endocrine gland
- the hormone may have more than one target cell
- a single target cell may be influenced by more than 1 hormone

where is somatostatin produced?

→ Digestive system
1. Pyloric antrum, duodenum, pancreas
→ Nervous system
1. Hypothalamus
2. Hippocampus
3. Brainstem

what does oxytocin affect?

- breasts and uterus
- brain
- testosterone production
- sperm movement

primary endocrine organs

known for the production of that hormone, its predominant function is to produce that hormone.
-Hypothalamus and pituitary gland
-Pineal gland
-Thyroid gland and parathyroid glands
-Thymus
-Adrenal glands
-Pancreas
-Gonads

master hormone control

hypothalamus and pituitary:
The hypothalamus and the posterior pituitary gland are derived from embryonic brain tissues, whereas the anterior pituitary gland arises from tissue in the roof of the mouth.
Hypothalamo-pituitary portal vessels (connect the capillaries in the anterior pituitary to the capillary beds in the hypothalamus) : These portal vessels, which deliver hypothalamic hormones to the pituitary, are unusual in that they connect two capillary beds.

hormones of posterior pituitary

→ Antidiuretic Hormone (ADH or vasopressin)
-Paraventricular nucleus secretes ADH
-Helps to retain water, keep fluid levels in your body up to maintain a normal BP
-Water balance and osmolarity
→ Oxytocin
-Supraoptic nucleus secretes oxytocin
-Also known as the 'cuddle hormone', females have a higher level, men only come close to the levels that women have after orgasm.
-Milk letdown, bonding, sperm movement

HYPOTHALAMUS & ANTERIOR PITUITARY

A "tripartite" (three part) endocrine axis is prominent in the control of the reproductive, adrenocortical, and growth hormone systems:
Hypothalamus (increase hormone 1 secretion) → increased plasma hormone 1 (in hypothalamo-pituitary portal vessels) → increase hormone 2 secretion in the anterior pituitary → increased plasma hormone 2 → third endocrine gland (target organ) increase hormone 3 secretion → increase plasma hormone 3 → target cells of hormone 3 response to hormone 3

Tropic (Nourishing) Hormones:

Affect release of another hormone or inhibit that cell of releasing another hormone.
→ Releasing hormones
→ Inhibiting hormones

Pituitary Gland Secretions and Targets

-Lactogen → breast
-Gonadotropic hormones FSH,LH → ovaries/testes → estrogen, progesterone and testosterone
-ACTH → adrenal cortex → cortisol, aldosterone
-Thyrotropin → thyroid → thyroxine, T3
-Growth hormone → many organs
-Endorphins → diverse organs and tissues

Control of Hypothalamic Tropic Hormone Release

→Neural input
→ Hormonal - negative feedback
→ Circadian rhythm
• Suprachiasmatic Nucleus of Hypothalamus
• 'clock of the brain'
• Gets signal from optic nerve (sunlight) to reset each morning

Feedback Loops

-Negative
-Positive
-Long (hormone 3 secretion to the anterior pituitary and/or the hypothalamus *third is always LONG**)
-Short (tropic hormone 2 to the hypothalamus)

Growth Hormone (GH)

→ GH promotes cell division and cellular proliferation throughout the body
→ GH facilitates protein synthesis by:
- Increasing amino acid transport through plasma membrane
- Stimulating RNA formation
- Activating cellular ribosomes that increase protein synthesis
- GH levels peak at night during REM sleep and deep sleep
→ GH also slows carbohydrate breakdown and initiates mobilization and use of fat for energy

Growth Hormone, Physical Activity, and Tissue Synthesis

→ Physical activity augments GH's action on target tissues
- Benefits muscle, bone, and connective tissue growth and remodeling
- Optimizes fuel mixture during physical activity
- Net metabolic effect preserves plasma glucose concentration for CNS and muscle functions
→ Trained and sedentary individuals similarly increase GH concentration with exhaustive exercise, but the sedentary maintain higher GH levels for several hours into recovery

Pineal Gland

→ Glandular tissue in brain
→ Secretes melatonin
- May be involved in circadian rhythms
- Inhibited during the day by suprachiasmatic nuclei
→ In many animals part of seasonal biology (coat growth, reproduction, behaviour)

Hormones of the Thyroid Gland

→ Two thyroid hormones
T4, tetraiodothyronine
T3, triiodothyronine
both Regulate metabolism, temperature
and Play a permissive role in skeletal muscle growth (effect of growth hormone
→ Calcitonin - Regulates calcium & phosphate levels in blood

Graves Disease:

- Autoimmune disease that is most common cause of hyperthyroidism
→ Body produces long-acting thyroid stimulator (LATS)→ secretion & growth of thyroid (10-15X normal rate)
Bind to receptors for TSH
→ No negative feedback of LATS

how do the thyroid gland and parathyroid gland compare each other?

they work antagonistically. parathormone inhibits thyroid gland and thyrocalctinon inhibits parathyroid

thymus

→Secretes thymosin
Regulates T cell function
→ Largest during neonatal and pre- adolescent periods
By early teens starts to atrophy & replaced by adipose tissue
Still have some lymphopoiesis continue

Adrenal Medulla

→ Secretory cells \= Chromaffin cells
80% epinephrine
20% norepinephrine

Hormones of the Adrenal Gland: Adrenocorticoids

→ Mineralocorticoids (aldosterone)
secreted from zonae glomerulosa
regulates sodium and potassium levels
→ Glucocorticoids (cortisol)
secreted from zona fasciculata and reticularis
regulates body's response to stress
regulates metabolism
→ Sex hormones (androgens)
secreted from zonae fasciculata and reticularis
regulate reproductive function

Glucocorticoids (Cortisol)

→ increase blood glucose at expense of fat & protein stores
→ Permissiveness for other hormones
Eg. Helps catecholamines induce vasoconstriction
→ Helps with coping with stress (makes glucose available to the brain)

Anti-inflammatory & immunosuppressive

→ Higher-than-physiological doses → new actions
→ Inhibits inflammatory response
Eg. Rheumatoid arthritis
→ Knock B-cells out of commission
Managing allergic disorders & organ transplant rejection

Exocrine Pancreas vs Endocrine Pancreas

- Exocrine Pancreas
Acinar and duct cells secrete fluid and enzymes into digestive tract
- Endocrine Pancreas
Islets of Langerhans
→ Alpha cells - glucagon
→ Beta cells - insulin
→ Delta cells - somatostatin (inhibits GH)
→ F cells - pancreatic polypeptide

Gonads

→ Male - testes
- Testosterone
- Androstenedione
→ Female - ovaries
- Estradiol
- Progesterone
- Placenta of pregnant female becomes an endocrine organ (estrogens and progesterone)

Secondary Endocrine Organs

→ Heart-atrial natriuretic peptide
→ Kidneys- erythropoietin
→ GI tract- several
Cholecystokinin
Secretin
Gastrin
→ Liver: insulin like growth factors
→ Skin and kidneys: calcitriol

what's the largest endocrine organ

skeletal muscle

Hormone Actions at the Target Cell

→ Control of Hormone Levels in Blood
→ Transport of Hormones
→ Hormone Interactions