 Define what physiology is and how this differs from anatomy, using examples

- Physiology = Mechanisms of living things

- Anatomy is the study of structure and relationship between body
- Physiology is the study of function of body parts and body as whole.

 List the different levels of organisation within the human body, describing how they
integrate
- Chemical level
- Molecular level
- Cellular level
- Tissue level
- Organ level
- Organ system level
- Organism level
 Describe the importance of homeostasis within the body and how the body responds
to changes in setpoints
- Homeostasis: stability of the internal environment body responds by
counteracting mechanisms if internal conditions are too far from the setpoint.

 Cell communication

Endocrine system: endocrine cell secretes hormones which act only on target cells containing
only receptors which leads to a response.

Nervous system: neurotransmitters are chemicals secreted by neurons that diffuse across
synaptic cleft to target cell to produce a response

Neurohormones: chemicals released by neurons into the blood for distant target cells.

 Autocrine, paracrine and endocrine signalling

Autocrine factors: expressed by a cell to act on itself or adjacent cells

Paracrine factors: expressed by a cell to act locally within a tissue

Endocrine factors: hormones produced in endocrine organ to effect distant organs, effect all
target tissues in body at once

Autocrine and paracrine factors establish spatial relationships between cells and build
structure within an organ, regulate differentiation of functional cells from stem cells, enable
coordinated and effective responses by mediating communication between cells.

Paracrine signalling is useful for clot formation, vessel repair, macrophage invasion, skin
repair.

 The endocrine system

Endocrine system controls activities that do not require immediate adjustment and exerts
effects for much longer periods of time

Hormones are transported by blood

Hormones control metabolism, internal environment regulation, reproduction, growth

Act on target cells by:

1. Controlling rate of enzymatic reaction

2. Controlling ion and molecular transport across membrane
3. Controlling gene expression and protein synthesis

 Structure, characteristics and synthesis of hormones

Tropic hormones regulate production of another hormone

Non-tropic hormones act directly on non-endocrine target tissues

Three types of hormones:

1. Peptide/protein hormones (hydrophilic)

2. Steroid hormones (lipophilic)
3. Amines (hydrophilic)

 Hormone secretion, transport and clearance

Synthesis:

1. mRNA on ribosome binds amino acids into preprohormone, chain is directed into ER
lumen by signal sequence of amino acids
2. Enzymes in ER chop off signal sequence, creating inactive prohormone
3. Prohormone passes from ER through Golgi Complex and secreted in vesicle
containing enzymes which chop prohormone into active peptide and other additional
peptide fragments
4. The active hormone is then passed into circulation via exocytosis.

Most amines are derived from tyrosine e.g. catecholamines, thyroid hormones

Steroid hormones are produced from parent compound cholesterol

 Mechanisms of action of hormones

Peptides and amines cannot enter their target cells (hydrophilic) combine with membrane
receptor (R) to initiate a response.

Steroid hormones act primarily on intracellular receptors, which usually are in cytoplasm or
nucleus, can also bind to membrane receptors that use second messenger systems to create
rapid responses.
 Hormone interactions

Hormone interactions are dictated by a reflex pathway, which involves an endocrine cell
sensing a stimulus and triggering the release of a hormone, which serves as a negative
feedback to switch off the response.

 Endocrine pathologies
1. Hypersecretion: excess levels of hormone caused by benign tumours,
cancerous tumours, exogenous application
2. Hyposecretion: Hormone deficiency caused by genetics, dietary deficiency,
removal of tissue/gland
3. Abnormal responsiveness of target tissues

Problems can arise when target cell can become unresponsive:

- downregulation: if hormone levels are abnormally high for extended time may down-
regulate receptor

- receptor and signal transduction may be impaired, by binding efficiency of hormone,

absence of receptors.

 Central Endocrine Glands

Hypothalamus

Pituitary gland

Hypothalamus and pituitary connected by a thin stalk – infundibulum

Anterior pituitary is a true endocrine gland of epithelial origin and posterior pituitary is an
extension of neural tissue.

Pineal gland

 Hypothalamus and hypothalamic hormones

Hypothalamus contains supraoptic nucleus and paraventricular nucleus

 Pituitary gland

 Posterior pituitary and posterior pituitary hormones

Releases vasopressin, oxytocin

 Anterior pituitary and anterior pituitary hormones

Hormones released from anterior pituitary are controlled by hypothalamic hormones, via
specialised portal system: hypothalamic-hypophyseal portal system which prevents dilution
of hormone

 Hypothalamic-hypophyseal portal system

Neurons synthesise tropic neurohormones, portal system carries them directly to anterior
pituitary, act on endocrine cells and release peptide hormones

 Prolactin (PRL)

Prolactin is the only anterior pituitary hormone that is not a tropic hormone acts on breast
tissue directly controlling milk production in breast tissue and enhances breast development.

 Adrenocorticotropic hormone (ACTH) and cortisol (HPA Pathway)

ACTH acts on adrenal cortex to release cortisol, which has a strong negative feedback effect
on anterior pituitary to inhibit ACTH secretion.

 Adrenal Gland and adrenal hormones

Adrenal medulla inside and secretes catecholamines as part of sympathetic nervous system.
Chromaffin cell is a modified post-ganglionic sympathetic neuron and release catecholamines

Adrenal cortex outside secretes steroids

Adrenal cortex composed of:

i) Capsule
ii) Zona glomerulosa  aldosterone, mineralocorticoids
iii) Zona fasciculata  glucocorticoids including cortisol promotes formation of
glucose
iv) Zona reticularis  sex hormones
 Actions of cortisol

Cortisol allows glucagon to respond to a hypoglycaemic event

1. Carbohydrate metabolism
i) Liver: gluconeogenesis & glycogen synthesis, increased protein synthesis
ii) Decreased rate of glucose utilisation by cells, decrease NADH oxidation, transport
of glucose into muscle and adipose tissue
iii) Hence Increased glucose in blood
2. Protein metabolism
i) Liver: increase protein enzyme synthesis, amino acid transport
ii) Decrease protein in cell, decreased amino acid transport, protein synthesis,
increased protein catabolism.
3. Fat metabolism:
i) Lipolysis
ii) Increased free fatty acids, glycerol
4. Vascular reactivity cortisol increases responsiveness of blood vessels to
catecholamines
5. Immunosuppressive and anti-inflammatory activity

 Gonadotropes (FSH and LH)

Controlled by GnRH from hypothalamus acts on gonads

FSH promotes gametogenesis

LH stimulates production of sex steroids

 Growth Hormone

Produced by anterior pituitary released throughout life, stimulated by nutrients, stress

GH influenced by GHRH and GHIH (somatostatin) triggered for release by stress, exercise,
diurnal pattern
Metabolically, binds with adipose tissue, skeletal tissue, liver increases fatty acid levels by
breaking down stored fat. Increases blood glucose by decreasing skeletal muscle glucose
uptake. Promotes glucose output from liver and stimulates protein synthesis.

  Recap - The HPA axis and adrenal gland anatomy: medulla & 3 cortical layers

HPA pathway for the control of cortisol secretion

 Adrenal stress response

Metabolic stress: maintain blood glucose, thru adrenaline, cortisol, glucagon, growth
hormone

Cardiovascular stress: maintain blood pressure, and flow thru angiotensin, ADH, adrenaline,
cortisol, thyroid hormone

Electrolyte stress: maintain blood Na, K levels: aldosterone, angiotensin, parathyroid

hormone, vitamin D.

 Pharmacological actions of glucocorticoids: immunosuppressive and anti-

immunosuppressive and anti-immunosuppressive and anti-immunosuppressive and anti-
immunosuppressive and anti-inflammatory

Clinical effects of glucocorticoids: immuno-suppression, anti-inflammatory, anti-allergic,

pain relief, decrease permeability of vessels.

 Glucocorticoid receptor mechanism and activity

GCs bind to cognate intracellular GC receptor (GR), and GC-GR complex translocated to
nucleus leads to increase in differentiation, apoptosis, IL-1, IL-6, TNFa down, Phospholipase
A2 down, COX 2 down.

 Corticosteroid pathophysiology

f syndrome due to cortisol excess  moon face, insulin resistance, abdominal fat,
osteoporosis

Addison’s disease due to cortisol and aldosterone deficiency symptoms of hypoglycaemia,

hypotension

Conn’s syndrome due to aldosterone excess produces symptoms of excess Na and water
retention and K loss

 Physiological actions of mineralocorticoids: salt and cardiovascular stress

Mechanism for aldosterone secretion

 Chronic and acute stress responses

Adrenal cortex is responsible for chronic stress

Adrenal medulla is responsible for acute stress regarding adrenaline and nor-adrenaline
Adrenaline & Glucagon:

- Both stimulate gluconeogenesis in liver

- Both stimulate glycogenolysis, glucagon mainly in liver
- Muscle glycogen not able to release glucose into blood as no phosphatase
- Both stimulate lipolysis
- Glucagon stimulates ketogenesis in liver

Cortisol and growth hormone:

- Both stimulate gluconeogenesis

- Both stimulate lipolysis
- Cortisol stimulates protein breakdown in muscle but enzyme synthesis in liver
- Cortisol stimulates glycogen synthesis in liver
- Growth hormone stimulates protein synthesis
- Both decrease glucose uptake in muscle and fat

 Diet vs endogenous stored substrates

Endogenous means internal, the internal stores of nutrients inside the body.

Glucagon increases and endogenous nutrient stores are used and enter blood stream

 Uptake & storage vs release

 Insulin anabolic

Insulin produced by beta cells of Islet of Langerhans

Produces glycogen, protein, fat synthesis

 Glucagon (cortisol, adrenalin) catabolic

Produced by alpha cells of Islet of Langerhans

Increased release of stored nutrients, glycogen breakdown, increase gluconeogenesis, protein

breakdown, lipolysis, ketogenesis.

Adrenaline, cortisol, and glucagon are catabolic hormones

 Growth hormone catabolic & anabolic

Growth hormone is anabolic

 Balance between insulin & counter regulatory hormones

Fasting releases counter regulatory hormones: glucagon, adrenaline, cortisol, growth

hormone (apart from that GH does not increase protein breakdown) which antagonise insulin
actions

 The thyroid axis and gland anatomy

Thyroid gland – butterfly shape below larynx

 Synthesis of thyroid hormones T3 and T4

2 tyrosine + 4I  Thryoxine (T4)

2 tyrosine + 3I  Triiodothyronine (T3)

1.Iodide trap concentrates I-

2.Iodide oxidation to iodine by peroxidase

3.Iodination of tyrosines on thyroglobulin

4.Coupling reaction:MIT + DIT → T3 DIT + DIT → T

5.Pinocytosis of TG with all these attached

6.Phagolysosome release of T3, T4, etc.

7.T3 and T4 secretion into blood when ↑TSH/thyrotropin

8.Plasma proteins transport variable

 Stimuli for hormone secretion
 Actions of thyroid hormones

T4>T3 amount secreted by thyroid gland, total and free plasma concentration, % bound to
plasma pre-albumin, half-life in circulation

T4<T3 volume of distribution, T3 additionally in cells, T4 is a prohormone for T3.

Thyroid hormones stimulate metabolism, increase calorigenesis/heat production, promote

growth, nervous system development, increased cardiac function, increased respiration and
red cell production, increased sympathetic/adrenaline actions
 Facilitation of catecholamine activity BMR (basal metabolic rates) and BMI (body
mass index).

BMR = Basal Metabolic Rate, when energy use is at its lowest level

BMR is increased by excess TH, expected to decrease BMI

BMR is decreased by lack of TH, expected to increase BMI

 Hypo- and hyper-thyroidism signs & symptoms
o myxedema vs Graves' disease

Hypothyroidism e.g. myxedema

- low oxygen consumption and slow metabolic rate  feeling cold

- decreased protein synthesis
- slowed reflexes, slow speech
- less feedback, increased TSH  goitre

Hyperthyroidism e.g. graves disease:

- increased oxygen consumption and metabolic heat production  feeling hot

- increased protein and fat catabolism and possible muscle weakness
- increased cardiac B1-adrenergic receptor and myosin expression 
tachycardia
- increased muscle B2- adrenergic receptors: vascular smooth muscle relaxation
 vasodilation  decreased total peripheral resistance  increased pulse
pressure
- goitre
 Immune modulation of thyroid gland & diseases

- Propylthiouracil (PTU) inhibits TH production by blocking iodination and

coupling reaction, interferes with conversion of T4 to T3
- Beta-blockers prevent adrenergic side-effects of excess TH
- Immunosuppressive drugs inhibit auto-immune antibodies targeting thyroid

 Synergism in growth

GH increases bone growth and muscle protein

Thyroid hormone develops neural tissue and that promotes GH actions

Androgens increases bone and muscle

 TH radioimmunoassay & Ab measurements

THs are measured by radioimmunoassay, measure TSH firstly: if raised most likely due to
low TH and less FB, if lowered, most likely due to high TH and more FB

 Calcitonin - synthesis and actions

Calcitonin is produced by the parafollicular cells of the thyroid gland.

Osteoclast = bone resorbing cells

Osteoblast = bone forming cells

Osteocytes = load sensing cells

Lining cells = line bone matrix

Bone matrix composition:

- Collagen: gives bone tensile strength

 Type 1
 Lamellar vs woven bone
- Non-collagenous proteins:
 Alkaline phosphatase
 Proteoglycans
 Growth factors in bone matrix
- Bone mineral:
 Calcium and phosphate as hydroxyapatite and compressive strength
RANK – L + RANK  stimulates osteoclast precursors to fuse together to form osteoclasts.

Osteoprotegerin (OPG)  blocks binding of RANKL to RANK stopping bone resorption

If not enough calcium in diet, parathyroid gland senses this and increases bone resorption 
decreased bone density

Chief cells produce PTH

Calcium-sensing receptor (CaSR): seven-pass transmembrane G protein-coupled receptor,

senses serum calcium levels.

Parathyroid hormone (PTH) binds to PTH-1-Receptor, G-protein coupled receptor, Gs 

increased cAMP, increased protein kinase C  increased IP3 and Ca2+
Estrogen, androgens help maintain normal balance between bone formation and resorption.
Estrogen is antiresorptive, promotes coupling

Estrogen deficiency = increased bone remodelling

Reduced osteoblast function with low estrogen, less growth factor release, less signal to
recruit and multiply new osteoblasts

Normal estrogen levels  reduced bone resorption, decreased osteoclast numbers via
increased osteoprotegerin, and better coupling  increases osteoblast activity

PTH: maintenance of blood Ca2+

Calcitriol (vit D): Ca2+& PO43-from diet bone

FGF23: phosphate regulation. Causes low phosphate when in excess.

Epithelial tissues regulate exchange of materials between internal and external environments

Skin Layers:

1. Epidermis: major cell is keratinocytes, prevents water loss and protein loss,
and enterance of pathogens
I. Stratum corneum
II. Stratum granulosum
III. Stratum spinosum
IV. Stratum basale
2. Dermis
3. Hypodermis

Thaysen’s two stage hypothesis:

1. Secretory coil secretes primary fluid plasma-like composition, primary fluid is then
modified in duct Na and Cl are absorbed to create final hypotonic sweat.
Direct DNA damage by sunlight  DNA lesions; cyclobutene pyrimidine dimer (CPD) most
abundant DNA lesion produced by UVB absorption

DNA damage: pyrimidine dimers: oxidative damage, faulty repair  mutations.

DNA damage  UV immunosuppression

UVR responses: melanogenesis, cornification of epithelium, DNA repair upregulation,

synthesis of vitamin D.

Melanin: absorbs in UV, melanosomes scatter and absorb UV, free radical quencher

Epidermal thickening important defence for pale people

Skin tumours:

- Basal cell carcinoma, keratinocytes most common, locally invasive, not

malignant usually
- Squamous cell carcinoma, keratinocytes, can metastasize
- Melanoma melanocytes, metastasizes, highly malignant

Acne occurs when the pores of your skin become blocked with oil, dead skin, or
bacteria. Each pore of your skin is the opening to a follicle. The follicle is made up of
a hair and a sebaceous (oil) gland. The oil gland releases sebum (oil), which travels
up the hair, out of the pore, and onto your skin. Inflammation

Neuron: Dendrite to Synapse

ECF: plasma + interstitial fluid

ICF

K+ = IC

Na+ = EC, more K+ leaves cell then Na+ enters the cell  inner surface of
membrane having negative charge relative to outside. If K+ permeability increases
potential more negative. Gated channels control ion permeability

1.Type A fibres –Myelinated, large diameter (4-20 μm), fast conduction (>100 m/s)
2.Type B fibres –Myelinated, smaller diameter (2-4 μm),moderate conduction (~18 m/s)

3.Type C fibres–Unmyelinated, small diameter (<2 μm), slow conduction (~1 m/s)

Action potential

Ligand-gated ion channels (ionotropic):fast response, ion channels open and ions
immediately flood into cell

G protein-coupled receptors (metabotropic):slow response, ion channel opening relies on an

intermediary ‘second messenger

Acetylcholine (Ach)  cholinergic, receptors include nicotinic and muscarinic

XX female

XY male

Testes two main functions: formation of spermatozoa: seminiferous tubules, hormone

synthesis: extra tubular stroma

3 stages to gametogenesis
Testosterone and FSH are required for spermatogenesis
Hypogonadotropic hypogonadism: little or no testosterone production  infertility

Epididymis assists in fluid absorption, sperm transfer, sperm storage, sperm maturation.

Sperm maturation:

1) forward progressive motility

2) attainment of fertilising ability

Prostate and seminal vesicles produce seminal fluid of ejaculate which assist in maintaining
viability and mobility of sperm

Uterus, ovary, vagina, anatomy

Female reproductive system:

i) sex steroids

ii) produce oocytes

iii) provide conduit for gamete transport

iv) site of fertilisation

v) maintain pregnanacy and birth

Ovarian steroids:
- Progestogen: activity of endometrium, implantation, maintain pregnancy
-Androgens: oestrogen synthesis

-Oestrogen: secondary sex characteristics, reproductive tract, breast ducts

Two cell – 2 gonadotrophin hypothesis: thecal cells produce C19 steroids in response to LH,
Granulosa cells are stimulated by FSH to aromatise androgens to oestrogens

The most accepted model of follicle development is the 2-cell 2-gonadotropin theory.
According to this theory, during the last 2 weeks of follicle development, the growth and
maturation of the follicle depends on follicle stimulating hormone (FSH) and luteinizing
hormone (LH)

Ovarian cycle: 2 phases: follicular phase and luteal phase punctuated by ovulation

Luteal phase is 14 days, follicular phase varies

Ovarian cycle starts by follicular recruitment

Luteal phase: Corpus luteum secretes increased estrogen, progesterone, inhibin, later corpus
luteum dies and estrogen and progesterone decreases.

Sperm release enzymes from acrosomes in order to penetrate the cells and zona pellucida and
fuse (sperm + oocyte) to form diploid zygote
Endocrinology of mid/late pregnancy

Placental estrogen and progesterone secreted continuously throughout pregnancy, begins

week 7. CL degenerates.

Progesterone maintains endometrium, blocks uterine contraction. Oestrogen stimulates

mammary gland development

Placenta secretes peptide hormones:

hCG (ceases after first trimester) hPL – human placental lactogen (aka hCS – human
chorionic sommatomamotropin): decreases insulin sensitivity, increases [blood glucose] -
gestational diabetes.
Parturition: Placental corticotropin releasing hormone CRH  induces foetal
dehydroepiandrosterone (DHEA)  cervical contractions  primes prostaglandin synthesis
to stimulate uterine contractions

Prolactin: oestrogen increases number of prolactin secreting cells during pregnancy

PIH (dopamine) suppresses prolactin release

PIH falls towards end of pregnancy, prolactin rises, suckling stimulates prolactin release and
milk secretion, and suppresses GnRH.

Pulmonary circulation: close loop of vessels carrying blood between heart and lungs

Systemic circulation: circuit of vessels carrying blood between heart and other body systems.

Two types of cardiac muscle cells: both excitatory: myocardial contractile cells, myocardial
autorhythmic cells.

Myocardial autorhythmic cells contain only a few contractile fibres and no organised
sarcomere. And provide the signal that causes heart to beat, pacemaker cells create rhythm
heart beats. Generate AP independently of nervous system, due to unstable membrane
potential  pacemaker potential

–Sinoatrial node (SA node)–Specialisedregion in right atrial wall near opening of superior
vena cava–Pacemaker of the heart

–Atrioventricular node (AV node)–Small bundle of specialised cardiac cells located at base
of right atrium near septum

–Bundle of His (atrioventricular (AV) bundle)–Cells originate at AV node and enters

interventricular septum–Divides to form right and left bundle branches that travel down
septum, curve around tip of ventricles, travel back toward atria along outer walls
–Purkinje fibers–Small, terminal fibers that extend from bundle of His and spread throughout
ventricular myocardium

Heart contraction begins with AP from autorhythmic cell: beginning in SA node  AV node
 AV bundle  purkinje fibres
Main difference with skeletal muscle contraction/depolarisation is that Ca2+ influx lengthens
the AP.

–Late diastole–ventricles fill with blood

–Atrial systole–atria contract

–Isovolumetric ventricular contraction–ventricles contract, all 4 valves are closed, pressure

rises

–Ventricular ejection–pressure forces blood past the semilunar valves

–Isovolumetric ventricular relaxation–ventricles relax causing semilunar valves to close

First heart sound: closure of AV valves–Second heart sound: closure of semilunar valves
Cardiac output (CO)–Volume of blood pumped (per ventricle), per given time–Indicator of
total blood pumped around the body CO = Heart Rate (HR) x SV–Can increase by altering
either or both by local or reflex mechanisms

Heart rate

Stroke volume directly related to force generated by cardiac muscle, affected by length of
muscle fibres, contractility of heart

The EDV is the filled volume of the ventricle prior to contraction and the ESV is the
residual volume of blood remaining in the ventricle after ejection.
Not included:

- Kidney, GIT