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Human Physiology Lecture Notes

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Principles of Physiology

What is Physiology?
- How organisms work
→ Bacterial (unicellular) physiology
- Not limited by taxa
→ Plant physiology
- Not limited by complexity
→ Animal physiology
- Contemporary physiology: concept of structure-function
→ Human (biomedical) physiology
relationships
- Not just how a structure executes its particular function, but also
why

→ Cell physiology Physiological Systems
→ Tissue physiology  Circulatory system
→ Organ physiology  Digestive system
→ Systemic physiology  Endocrine system
→ Organismal/ integrative  Immune system
physiology  Integumentary system
 Muscular system
 Nervous system
 Reproductive system
 Skeletal system
 Urinary system



Homeostasis
= Essentially the fluid that bathes all cells- extracellular fluid. Contains blood and interstitial
fluid.
= Homeostasis is the maintenance of a constant internal environment through the action of
active regulatory processes.




Antagonistic Controls
 Internal environment
commonly modulated by
antagonistic controls: pair of
regulators which modulate
controlled variables in opposite
directions.
 Body Temperature: increased
by shivering and thermogenesis.
Decreased by heat dissipation (panting/sweating).
 Plasma (glucose): increased by glucagon (a-cells of pancreatic islets).
Decreased by insulin (𝛽-cells of pancreatic islets).

Fine Control
- Antagonistic controls + feedforward control.
- Physiological control system “anticipates” the change that will be required (rather
than waiting for that signal)

,- Event that alters the controlled variable also has a direct feedforward effect on the
effector.


Thermal Physiology
o Let temperature of the body= TB
o Let ambient temperature be= TA
o Only 4 combinatorial possibilities;
- TB could be constant or variable
- TB could be same as TA or different


 Homeotherm: humans. TB is constant and different from TA.
 Poikilotherm: cold blooded animals. Mimics TA. Body temperature is variable. Could be same as T A. If TA
is constant TB is constant to (same as TA).
 Heterotherm: TB is variable but not necessarily same as TA.
 Endotherm: organisms who increase of decrease TB internally. Humans.
 Ectotherm: organisms who increase or decrease TB externally. Fish, reptiles.


Heat Transfer
→ Sequential energy transfer between molecules:
o From core (CNS) to periphery (e.g. skin).
o From periphery to boundary layer of external environment.
o From boundary layer to bulk external environment.
→ Speed of heat transfer depends on physical state of external environment:
o Heat dissipation (Wm-1K-1) fastest to a solid and slowest to a gas.
o Reflects molecular density.


Preventing Heat Loss
▪ Keep blood away from the periphery/skin- vasoconstriction of capillaries.
▪ Insulation
▪ Can be layer of air or water trapped between skin and boundary layer; by feathers, by body hair
(piloerection increases insulation).
▪ Can be under the skin (e.g. subcutaneous adipose tissue/ “blubber”-conducts thermal energy slower than
muscle).



Dissipating Excess Heat
= Can increase blood flow to periphery/skin (dilate capillaries).
= Can increase fluid on skin to accelerate heat dissipation (i.e. perspiration).
= Can evaporate saliva from tongue (i.e. panting).
= Can increase fluids in the boundary layer:
- E.g. get into water
- E.g. take fluid into digestive tract (technically outside the body, so can serve as a heat
sink).


Generating Heat-Thermogenesis
• Can break chemical bonds-i.e. metabolism of respiratory substrates (may involve futile cycling:
phosphofructokinase and fructose-1, 6-bisphosphatase.
• Can have isometric/antagonistic muscle contractions- generates heat (by driving hydrolysis of ATP) without
resulting movement.

, Thermogenesis in Mammals
• Can break chemical bonds (e.g. curry and postprandial thermogenesis).
• Can dissipate ion gradients-drives ATP hydrolysis to pump ions back across
the membrane.
• Can uncouple metabolism-electron leakage from mitochondria can generate
heat.
• Can have isometric/antagonistic muscle contractions- generates heat by
hydrolysis of ATP, resulting in limited, jerky movements-shivering.



Cell Signalling
*Cell to cell communication via chemical messengers (signalling molecules) can be direct (between adjacent
cells): gap junction, juxtracrine signalling. Can be indirect: autocrine, paracrine, endocrine and neuronal
signalling.


How do cells signal? Receptor Types
-Hormones → Ion channels (nicotinic acetylcholine
-Growth factors receptor)
-Inflammatory molecules → G-protein-coupled receptors (adrenoceptors)
-Neurotransmitters → Enzymatic receptors (insulin receptors)
→ Nuclear receptors (vitamin D or hormone
receptors)



1) Gap Junction Signalling
▪ Ions and small molecules exchanged between cells via gap
junctions.
▪ Each adjacent cell has hemichannels (molecular hexamer) in
plasma membrane.
▪ Hemichannels (connexon) formed of hexametric connexin proteins.
▪ Each connexin monomer has 4 transmembrane α-helixes.



2) Juxtracrine Signalling
▪ Ligand in plasma membrane of signalling cell A.
▪ Receptor in plasma membrane of adjacent target B.
▪ Important for cell migration.

3) Indirect Signalling
▪ Signalling cell produces a chemical messenger/ signalling molecule.
▪ In most cases, signalling molecule secreted into ECF/lymph/blood.
▪ Signalling molecule transported over distance (short, medium or long) to target cell.
▪ Signalling molecule acts as ligand for receptor on/in target cell.

4) Autocrine Signalling
▪ Cell produces a local ligand that acts back on the receptor in the same cell.
▪ Signalling molecule leaves cell but acts back on the same cell- minimal
diffusion.

5) Paracrine Signalling
▪ Cell produces a local ligand that acts on neighbouring cells.
▪ Moves over short distances by diffusion (e.g. local recruitment of
inflammatory cells via histamine).

, 6) Endocrine Signalling
▪ Cell to cell communication over long distances.
▪ Signalling cell termed on endocrine cell.
▪ Signalling molecules (hormones) transported in circulatory system-
blood or lymph.



7) Neural Signalling
▪ Messages (nerve impulses) travel along distance but chemical
messengers only travel short distances.
▪ Long distances- action potentials.
▪ Synaptic transmission- signalling molecules.


Speed of Communication
 Autocrine: short distance, msec to sec.
 Paracrine: short distance, msec to sec.
 Endocrine: long distance, sec to mins, hours to days.
 Neural: long distance, msec only.

Hydrophilic→ soluble in aqueous solutions (ECF/blood/lymph).
Activate plasma membrane receptors.
Hydrophobic→ insoluble in aqueous solutions (soluble in
lipids/lipophilic). Require globular transport proteins to solubilize in
ECF/blood. Active intracellular (nuclear) receptors.

Classes of Signalling Molecules
 Peptides (hydrophilic)
 Amines
 Steroids (hydrophobic)
 Lipids (hydrophobic)
 Purines (hydrophobic)
 Gases (hydrophilic)

Peptides
= Single amino acids act as neurotransmitters (e.g. Asp, Cys, Glu-latter decarboxylated to form GABA)- can
be excitatory amino acids (EAA) or inhibitory amino acids (IAA).
= Peptides (2-200aa) act as neurotransmitters or hydrophilic hormones.
= Translated from mRNA in rough endoplasmic reticulum.
= Subject to post-translation modifications (e.g. glycosylation) in rough ER and Golgi apparatus.
= Packaged into secretory vesicles and released by exocytosis
(membrane depolarisation).
= Immediate (paracrine peptides-cytokines).
= Storage (most peptide hormones and neurotransmission).
= Act via cell surface/transmembrane receptors: conformational
change-affects ion flux (ionotropic receptor) and enzymes
(metabotropic receptors).\degraded by action of
proteases/peptidases-dictates peptide ‘half-life’; generally
short secs for simple peptides, hours for glycoproteins.
= Consequence continued action dependent on continued
synthesis.


Biogenic Amines→ organic molecules containing amine (NH2)-usually derived from an amino acid.



Catecholamines
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