Introduction to Human Physiology - 1 Homeostasis and Endocrine System

Source: My personal notes from Introduction to Human Physiology | Coursera

Homeostasis

Looking at organ and organ systems. How do these organs and systems work and what are their advantages?

Physiology is an integrative science which considers the function of each organ and organ system and their interaction in the maintenance of life. Stability through homeostasis - balance of inputs and outputs to the body among organ systems.

Body components: cells > tissues > organ > organ systems (e.g. skin/barrier, respiratory, gastro-intestinal (GI), cardiovascular & diffusion, renal)

Flow of materials in body

Barrier = skin

Entry = respiratory, GI

Transport = CV & diffusion

Exit - renal, GI

Physiologist think about fluids in the body as 2 fluid compartments

IVF = blood plasma

ECF = extra cellular fluid

ICF = intracellular fluid

IS separated from IVF by blood vessels

ATPase = enzyme moving sodium and potassium between cells

Cell membranes are water resistant, hydrophobic

Example: You have a high salt intake over a couple days. To retain equal concentrations of salt in the body, the body must take in more ECF fluid volume which increase pressure in blood vessels since more ECF is present.

Regulation of Homeostasis

Local control

Paracrine - response message sent across cells

Autocrine - self regulation

Gap junction (nexus joined point between 2 cells)

Reflexes

Response made at a distance from target cell.

Communication systems: endocrine (messages via chemicals-blood to target cells) and neuron (via chemical in a small space close to effector/target cell, target recognizes chemical)

Example of a reflex loop (external change)

Cold air = stimulus > skin = sensors > hypothalamus = integration centre/brain > muscle shivering and vasoconstriction (blood moves away from skin) = effector > cold air = stimulus is eliminated… —> negative feedback loop because stimulus is removed

Whole example is similar to a thermostat in a home

Example of a reflex loop (internal change)

Fever (integration centre has raised the set point of the body temperature higher than 37 degrees C)

Positive feedback

Endrocrine cell secretes hormone to target cell —> target cell has more receptors on its surface

Tonic control

Decreased input (e.g. vaso dilation) <-> Basal state (medium open/close state) <-> increased input (e.g. vasoconstriction) vaso = blood vessel

Can be done with smooth muscle

Antagonistic Control

Parasympathic (slow heart rate, e.g. good athlete resting) - intrinsic heart rate - sympathetic (speed up heart rate, e.g. exercising athlete)

Feed-forward control

Body anticipates a stimulus and begins hormone secretion

Circadian Rhythms

Biological system changing on 24 hours basis, automatically without us thinking of it.

Set points are automatically determined in the rhythm. Set points are reset by sleeping and waking.

E.g. think jet lag when travelling, night owls/early birds = who have different rhythms

Pumps, Transporters, and Channels

Why study these things?

Basis of physiological process: growth, metabolic activities, sensory perception
Basis of disease
Basis of pharmacological therapies
- Effects of drugs influence these areas

Transmission

Flux = random movement of molecules across a surface per unit time.
Net flux is determined by gradient [high] -> [low]. From high to low concentration.
Gap junctions (nexus) permits diffusion of ions between coupled cells

Diffusion = movement until equilibrium

Fast for short distances, heat increases speed, surface area increases diffusion
Facilitated diffusion: transporter moves hydrophilic molecules (e.g. glucose) across lipid bilayer (the membrane). There are only so many transporters and they are only used for hydrophilic molecules
Simple diffusion is increased as solute concentration increases, BUT facilitated diffusion has a maximum rate.

Co-transporters = two solutes at ones (Na+ and glucose)

Symporter = two solutes moving in same direction
Antiporter = two solutes moving, but in opposite directions.

Channels

e.g. aquaporine = channel for water movement

Pores are open, allow diffusion from [high] to [low]. Opening and closing via gating:

Ligand - chemical - e.g. acetyl choline for skeletal muscles for sodium
Voltage - electrical charge gradient exists across the membrane. In part caused be negatively charges proteins inside cell —> so ECF is more positively charged compared to ICF. E.g. voltage gates Ca (Calcium) channels.
Mechanical - requires specific tension to open, occurs in smooth muscle e.g. muscle contraction can open gates.

Pumps

Pumps mediate active transport. Pumps cleave ATP (energy) within the cell. Pumps always use ATP

Note: active transport from [low] to [high], opposite of diffusion. e.g. move Ca to Ca++

Transcellular Transport

Movement of chemicals across cells

e.g. GI materials to blood.

Co-Transporters, pumps, and transports are used

Effective Solutes and Water Transport

Water is a hydrophilic, so it moves slowly across the plasma membrane without a transport.

Osmosis is how water is transported

Aquaporin channel is open at all times for water to go through rapidly - a facilitated diffusion

Highest concentration of water = pure water, lowest = water with solutes.

Occurs by diffusion only [high] to [low]

Osmosis can cause cells to have equal concentrations by increases water fluid in higher concentration cells

e.g. ICF to ECF osmosis to balance concentrations due to high NaCl intake.

Molarity vs. osmolarity

Osmolarity is concerned about number of molecules given a volume

e.g. 300 mOsM solution, it is a isosmotic to the body

200 mOsM is hypo osmotic

400 mOsM is hyper osmotic

Tonicity & Cell Volume

Tonicity is concerned with the number of non-penetrating molecules/volume. Water movement will be determined by osmolarity. Homeostasis will prefer tonicity to be equal between the ECF and ICF at all times.

e.g. someone is running a marathon and overhydrates causing their ECF osmolarity to increase rapidly. Water will naturally try to balance the osmolarity and water will move into the cells (ICF) to attempt to balance and cause the cells to expand. If cells expand too much, that can cause problems (e.g. brain cells)

Isotonic = same osmolarity

Health application

General Concepts

ICF and ECF are in osmotic balance
Water moves by facilitated diffusion through aquaporin channels
Non-permeable solutes are called effective solutes. Cellular volume is critically dependent on the steady state of effective solutes and water across the cell membrane
Cells shrink in hypertonic ECF conditions (water is moving out of the cell to dilute solutes). Cells swell in hypotonic ECF conditions (water moves into cells to balance solute concentrations and increase ECF solute concentrations)

Endocrine System - An Overview

Endocrine target cells must have high affinity receptors to hormones since blood is so large, while chemical is small concentration (dilute).

In nervous system, targets have low affinity due to high concentration of neurotransmitters near targets.

Endocrine glands = ductless glands whose secretions (hormones) are delivered by the blood to target tissues.

Endocrine homeostatic missions

Sodium and water balance
Calcium balance
Energy balance
Processes that cope with stress
Growth and development
Processes associated with reproduction

Hormone concentration matters

High concentration > too much stimulation and down regulation can be done
Low concentration > low response is insufficient
Concentration control:
- rate of production - most regulated, + and - feedback loops
- rate of delivery - dependent on perfusion and blood flow, follow mass action laws (carriers)
  - Mass action laws = hormone comes off carrier and becomes a free agent and binds to target cell which has high affinity to hormone
- rate of degradation and/or excretion (liver, kidney excretion)

Peptide/protein hormones

3 amino acids

Creation of hormones from preprohormone cleaved to hormone, when complete hormones can be secreted

They have a short 1/2 life once in blood

e.g. hormone is insulin

Steroid hormones

Secreted by adrenal, gonads, placenta (pregnant woman)

Insoluble in blood, transported via carrier proteins, must be synthesized and secreted on demand, conversion in target tissues

Amino Acid Derivatives (Hormones)

Tyrosine - thyroxine
Epinephrine

Transport Carriers

Extend half life of hormone E.g. thyroid hormones (several days), steroid (testosterone, estrogen, 60-90 minutes)
Keep hormone from target cell receptor
Total concentration in blood of hormone = free + bound, remember only free is active!

About Receptor

Types

Hormones can be received in different places (even inside cell in case of steroid/thyroid hormones).

There are many receptors on/in cells
Sensitivity

Depends on a couple factors:

Looking at examples of hormones

Stimulus = high [Na] in blood > Neuron > antidiuretic hormone to kidney from pituitary gland, neural control whose effect is for kidney to move from urine back into blood to dilute [Na] concentration

Stimulus = low [glucose] plasma > hypothalamus = sensor > growth hormone releasing hormone > pituitary gland to secrete growth hormone > liver/bone = target cells

Stimulus = low [Ca] plasma/blood > parathyroid gland secretes parathyroid > bone = target cell > release of Ca++

Stimulus = high [glucose] plasma > pancreas beta cells secretes insulin> muscle/fat= target cell > [glucose] absorption++

Inactivation of Hormone Signaling

Two options: receptor desensitization or negative feedback (remove stimulus)

e.g. type 2 diabetes has desensitized insulin receptors

General Concepts

Peptide hormones are soluble in plasma, bind cell surface receptors, are fast-acting, and are short lived
Thyroid hormones and steroid hormones are insoluble in plasma, act via intracellular receptors to change transcription, are slow-acting and long-lived
Binding proteins (carriers) regular hormone availability, physiologic function, and half lives
Hormone release is under neural, hormonal, and nutrient and ion regulation
Signaling is regulated by changing plasma hormone concentration and by change target cell receptor sensitivity

Assessment and Pathology

Assessment of Function

Too much: hyper secretion, hormone excess

Too little: hypo secretion, hormone insufficiency

Target cell resistance: unresponsive (e.g. desensitized receptors as in type 2 diabetes)

Just right: normal or eu-secretion

Assays

An assay is an investigative (analytic) procedure in laboratory medicine, pharmacology, environmental biology, continuous delivery, and molecular biology for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity (the analyte).

Competitive Binding Assay
- Checking concentrations of hormones.
- Using antibodies that binds with labelled and unknown hormones.
- Antibodies normally bind with labelled hormones. A mixture will along us to find out the amount of unlabelled (unknown) hormones are present.
- Can tell us the amount of hormones, but not their ability to function
Bioassay
- Checks whether hormones are functional
- e.g. cortisol secreted by adrenal gland, we want to check high cortisol
  - Cortisol is secreated (steroid is synthesized on demand) from CRH and ACTH hormone inputs
  - Give dexamethason to inhibit ACTH, to check if ACTH and CRH is the problem or other areas of the hypothalamus, pituitary, cortex axis is not functioning

Classification of Endocrine pathology

If adrenal cortex is problem = primary

If pituitary is problem = secondary

If hypothalamus is problem = tertiary

Classification can be done by measuring hormone levels compared to expected given stimulus.

General Concepts

Pathology in endocrinology occurs when there is either too little or too much hormone or resistance to the hormone due to receptor dysfunction
Interpretation of hormone levels requires consideration of either the trophic hormone(s) (i.e. downstream hormone stimulating hormones) or of the ion/nutrient controlled by the hormone.