Physiology Flashcards
1
Q
α1 adrenoceptor
A
Smooth muscle contraction
Rise in intracellular calcium
2
Q
α2 adrenoceptor
A
Prefrontal cortex cognitive function increase
Smooth muscle mixed effects
Cardiac relaxation
Platelet activation
intracellular cAMP decrease
3
Q
β1 adrenoceptor
A
Heart
AGONIST: increase cAMP
increase HR
increase contraction (increase SV)
increased lipolysis in adipose tissue
4
Q
β2 adrenoceptor
A
Smooth muscle relaxation (bronchi & vascular dilator)
AGONIST: increase cAMP Smooth muscle relaxation bronchodilation vasodilation increase liver glycogenolysis
5
Q
Clearance
A
Clearance = [ (drug conc in – drug conc out) / drug conc in ] * blood flow
6
Q
Renal Clearance
A
CLrenal = GFR + TS - TR
7
Q
GFR
A
120mL/min
8
Q
Maximal CLrenal
A
800mL/min
9
Q
Coagulation
A
Initiation (TF exposed)
Amplification (prothrombin -> thrombiin = platelet activation)
Propagation (thrombin burst and fibrin clot formation)
Fibrinogen -(thrombin)-> fibrin = clot
10
Q
Type I Respiratory Failure
A
Gas Exchange Abnormality
Decrease Pa02 < 60
Ventilation Increases
Decrease in PaCO2
(Hypoxaemia without Hypercapnia)
11
Q
Type II Respiratory Failure
A
Inadequate ventilation (by any cause)
Ventilation Decrease
Decrease Pa02
Increase PaCO2
(Hypoxaemia with Hypercapnia)
12
Q
Normal body temperature
A
36 - 37.5 degrees
+0.6 degrees in the afternoon
+1 degree post-ovulation
Oral Temp < core body temp by 0.5deg
Axillary temp < core body temp by 1deg
fever = increase in set point induced by pyrogens
PGE2 synthesis in hypothalamus (inhibited by aspirin)
PUO - fever above 38.3 for 2-3 weeks with know known cause
Optimal temp for immune response is 39.5deg
Rigors - feeling intense cold, shivering, pallor (vasoconstriction), exhaustion
13
Q
Pulmonary Artery Pressure
A
20-30mmHg
14
Q
End Systolic Volume
A
75mL (reserve - can go up/down if needed)
15
Q
End Diastolic Pressure
A
15mmHg
16
Q
Early Diastolic Pressure
A
5mmHg
17
Q
Heart sounds
A
- AV valve closure (tricuspid/mitral)
- Semilunar valve closure (aorta/pulmonary)
- Occurs at begining of diastole - oscillation of blood back and forth between the walls of the ventricles initiated by the inflow of blood from the atria
- Blood being forced into stiff hypertrophic ventricle
18
Q
Veinous Pressure
A
1 to 5 mmHg inside great veins (IVC/SVC)
7mmHg mean circulatory filling pressure
19
Q
O2 / CO2 metabolic requirements
A
REST
use 250ml/min O2
produce 200ml/min CO2
EXERCISE
use > 4000ml/min 02
produce > 4000ml/min CO2
20
Q
Alveolar Volume & Surface Area
A
Volume
3-6 L
Surface Area
50 - 100 sqm
21
Q
Ficks Law (rate of diffusion of a gas)
A
V = A . D . (P1 - P2) / T
A = area P1-P2 = difference in partial pressure T = Thickness D = diffusion rate (CO2 is 20x O2)
22
Q
Partial Pressures of O2 and CO2
- inspired
- alveoli
- pulmonary artery
- pulmonary vein
A
Inspired
O2 = 150 (20% composition of air)
CO2 = 0
Alveoli
O2 = 100
CO2 = 40
Artery
O2 = 98
CO2 = 40
Vein
O2 = 40
CO2 = 46
23
Q
Lung Volumes TLC RV VC TV FRC FEV1
A
Total Lung Capacity - volume in lungs at full inspiration (5,700ml)
Residual Volume - volume in lungs at full expiration (1,200ml)
Vital Capacity - volume exhaled from TLC to RV (4,500ml)
Tidal Volume - volume of regular breath (500ml)
Functional Residual Capacity - volume remaining after regular breath (2200ml)
Forced Expiratory Volume 1 second (approx 70-80% of FVC)
24
Q
A-a Gradient for oxygen
A
Measure of overall efficiency of gas exchange across all A-C units
PAO2 = PiO2 - PACO2 / RQ A-a = PA02 - PaO2
(Normal < 15-30)
25
Suprachiasmatic Nucleus
```
SCN governs some circadian rhythms
Receives input from
- rods, cones (light)
- intergeniculate leaflet (activity)
SCN projects to the Paraventricular Nucleus which connects with the pineal gland (secrete melatonin)
```
26
Sleep Generation
Two ascending arousal systems
- ORX
- LC, TMN, Raphe
Inhibitions
VLPO (activated by ATP depletion of arousal systems)
27
Neural GI Control Reflex
Vago-vagal (moderates ENS)
- control swallowing
- regulate acid secretion in stomach
- coordinate stomach and duodenum contraction
Intestino-intestinal
- vagus / dorsal root ganglia
- GI -> sympathetic ganglia -> reflex inhibition proximally when distal regions are distended
CNS
- anticipation of cephalic digestive phase, mood, activity
28
Phases of digestion #1 - up to pylorus
Cephalic
- GI control systems activated prior to digestion
- salivation, gastric acid, pepsin, relaxation of corpus and fundus (storage)
- Vagal (stimulates ENS)
ACh M3 on parietal (H+) and ECL (histamine -> parietal), D-cell (somatostatin) inhibition of ECL histamine
G-Cell (gastrin) -> activate parietal via CCKR, activate distal D-Cell (somatostatin)[and H+] inhibition of G Cell
Distension (vagal afferent to hypothalamic appetite centre), stimulates pepsin & acid
(STRONG!) Pacemaker (ICC) propogation from corpus to antrum - mashing
Antrum
- reflex inhibition of acid secretion in corpus
- fat floats to top (fundus)
29
Phases of digestion #2 - duodenum onwards
Duodenum
- vago-vagal inhibition of gastric emptying (H+, distension, aa)
- D-cell (somatostatin) - via portal vein
- vago-vagal brunners gland secretion (bicarb)
- duodenal-pyloro-antral reflex close pylorus
- aa & fat trigger release of CCK from I-cells
- aa triger release of Secretin from S-cells
Retropulsion - towards pylorus
Segmentation (ICC)
Peristalsis
Fat empties stomach last giving surge of CCK (suppressing appetite substantially)
Colon
water absorption
fermentation produces acetate, butyrate, propionate, stimulating enteric reflexes
30
Cholecystokinin
released from I cells in duodenum
- excites vagal afferent neurons (vago-vagal reflex, reduce appetite)
- exicites ENS (activate mixing)
- causes gallbladder contraction -> bile secretion
- causes digestive enzyme production by pancreas
- promotes release of insulin
31
Secretin
released from S cells in duodenum
causes secretion of bicarbonate from pancreas
retroperistalsis brings bicarb up into duodenum (neutralizes H+, deactivates pepsin, allows gastric emptying)
32
GI sensing
```
Mechanic & Distension
- vagal afferents, spinal afferents, ENS
Taste
- EC cells release serotonin
- L Cells (sweet)
-- release glucagon like peptide 1&2 and pancreatic polypeptide Y (regulate appetite and insulin secretion)
Olfactory
- EC cells release serotonin
```
33
General Liver Activities
```
Energy storage (glycogen, fat, iron, Vit A etc.)
Production of cellular fuels
Lipid metabolism
Production of plasma proteins and clotting factors
Metabolism of toxins and drugs
Modification of hormones
Production of bile acids
Excretion of bilirubin
Storage of iron and vitamins
```
34
Protein Digestion
```
STOMACH:
pepsin (cheif cells)
pepsinogen I (acid regions)
pepsinogen II (pylorus)
hydrolysis of aromatic amino acid bonds (phe & tyr)
```
```
DUODENUM/JEJUNUM:
CCK stimulates release of pancreatic proteases
trypsinogen -(enterokinase)-> trypsin
chymotrypsin
elastase
carboxypeptidase A & B
```
BRUSH BORDER
aminopeptidases, carboxypeptidases break polypeptides to amino acids
di- tri- peptides transported directly into epithelial cells
free aminos carried by 7 different transporters (Na+, Cl-)
35
Carbohydrate Digestion
MOUTH:
α-amylase hydrolyses 1:4α linkages
DUODENUM/JEJUNUM:
pancreatic α-amylase & salivary activated at low pH
BRUSH BORDER:
isomaltase breaks 1:6α linkages
sucrase, maltase single large glycoprotein in membrane activated by pancreatic proteases
```
ABSORPTION:
Glucose/Galactose & Na+ SLGT1 of epithelium & GLUT2 into interstitium
Fructose GLUT5 (down conc. gradient) & GLUT2 into interstitium
```
36
Fat Digestion
| inc. fat soluble vitamins A, D, E, K
MOUTH:
lingual lipase
STOMACH:
gastric lipase
DUODENUM:
CCK causes pancreatic lipolytic enzyme release and gallbladder constriction
lipases
cholesterol esterase (break down cell membrane)
bile salts, lecithin, vigorous mixing - emulsify fat
micelles form
ABSORPTION
dissolve in membrane at tips of villi
Fatty acids reform triglycerides in SER
+ apolipoprotein glycosilation = chylomicrons
Short chain fatty acids produced in proximal colon by fermentation of dietary fibre
37
```
Development
Zygote
Morula
Blastomere
Blastocyst
Blastocoel
Trophoblast
Inner Cell Mass
```
ZYGOTE: single cell
BLASTOMERE: cell produced by cleaveage of the Zygote
MORULA: 16 cell stage (3days)
BLASTOCYST: 58 cell stage (4 days)
BLASTOCOEL: Cavity of Blastocyst
TROPHOBLAST: Outer membrane of blastocyst (forms placenta)
INNER CELL MASS: Cells in blastocyst beginning to specialise
38
Ectoderm Derivatives
```
Dorsal root ganglia
Sympathetic and Parasympathetic ganglia
Enteric ganglia
Schwann Cells
Melanocytes
Dentine
Muscle, Cartilage, and bone of skull, jaws, face, and pharynx.
```
(also neural crest derivatives - between ectoderm/neural tube)
39
Endoderm Derivatives
```
Epithelum of:
GI tract
Respiratory tract
Tonsils
Thyroid
Parathyroid
Thymus
Liver
Pancreas
```
40
Mesoderm Derivatives
PARAXIAL MESODERM
Derims of skin
Axial skeleton
Axial and limb muscles
INTERMEDIATE MESODERM
Urogenital System, kidney
```
LARTERAL MESODERM
Ventrolateral body wall
Limb skeleton
Visceral Pleura, Peritoneum, Pericardium
Blood Vessels and Blood forming tissue
Heart
Wall of Gut and Respiratory Tissues
```
41
Somitomeres
```
Swellings down length of paraxial mesoderm
Split into:
DERMOTOME: dermis of skin
MYOTOME: back muscles
SCLEROTOME: axial skeleton
```
Medial Myotome: intrinsic back muscles (extensors)
Lateral Myotome: limb muscles, muscles of ventrolateral body wall, intrinsic back muscles (flexors)
Medial Sclerotome: vertebral body, intervertebral disk, proximal rib
Lateral Sclerotome: vertebral arch, pedicle of vertebra, distal rib.
42
Allantois
Branch of hindgut
| Gives rise to bladder and urogenital tract
43
Proctodeum
| Stomadeum
PROCTODEUM: thin barrier where anus forms
STOMADEUM: thin barrier where mouth forms
44
Coelom
Forms body cavity around viscera
Somatic Mesoderm + Ectoderm = body wall
Splanchnic Mesoderm + Endoderm = visera
45
Kidney Development
Pronephros
Neprostomes (degenerates) & pronephrotic duct
Mesonephris duct (connects to testes) & tubules
Metanephros (kidney!)
46
NEAT
NonExercise Activity Thermogenesis
Fidgeting, Posture, etc.
Accounts for difference in fat storage (gain) correlated to overfeeding
47
Mediators of Weight / Eating (Neural)
```
Arcuate Nucleus (influences PHN + LN)
stimulatefood intake:
- neuropeptide Y
- AGRP
- CB1
inhibit food intake:
- Cocaine and Amphetamine Regulated Transcript (CART)
- POMC (Melanocyte Stimulating Hormone (MSH)
```
Paraventricular Hypothalamic Nucleus (inhibit food intake)
- oxytocin
- CRH
Lateral Hypothalamus (stimulate food intake)
- orexin
- MCH
48
Mediators of Weight / Eating (Peripheral)
Leptin (fat cells)
- Synthesised in adipocytes in proportion to cell size (inhibit eating)
- transported to brain by receptor in choroid plexus
- acts on Arcuate Nucleus of hypothalamus
Insulin (beta cells of islet)
- signals to brain about levels of bf
- action on liver = increase hunger
- action on brain = decrease hunger
- insulin insensitivity of liver may increase
Nutrients
- glucose -> Acetyl-CoA -(MCD)-> Malonyl-CoA --| CPT1
CPT1 breaks down LCFA-CoA (long chain fatty acid)
LCFA-CoA inhibits food intake
```
Stimulators:
- Ghrelin (stomach)
Inhibitors:
- CCK (intestine)
- PYY (intestine/colon)
- PP (phi cells of islet)
- GLP-1 (L cells)
- Amylin (β cells)
- Adrenaline
- Leptin
- Insulin
- Oxyntomodulin
```
49
Causes of weight Loss
```
ENDOCRINE
- untreated Type I Diabetes
- thyrotoxicosis
- Addison's (cortisol lack)
GI
- pancreatitis
- CF
- IBD
- parasitic
INFECTION
- TB
- endocarditis
- amoebic abcess
- HIV
MALIGNANCY
- GI
- Lymphoma
- Leukemia
```
50
Phase I Metabolism
Creates chemical functional group on drug
(e.g. -OH, -NH2, -SH, -COOH)
- typically due to Cytochrome P450
51
Phase II Metabolism
Conjugation of water soluble molecule to functional group on drug
- e.g. glucuronyl transferase (add glucuronyl acid)
- molecule typically becomes more water soluble
52
Rapid IV administration
```
dX/dT = -KX
X = Xo e^(-Kt)
logC = logCo - (K/2.303)t
t1/2 = 0.693/K
CL = KVd
```
```
X = amount of drug in body
K = elimination rate constant
C = plasma concentration
```
Cpeak ~ Xo / Vd
- drug distributes rapidly and reaches equilibrium
- behaves as if in single compartment
- first order kinetics
53
Short term I.V. infusion
dX/dT = ko -KX
- drug infused at constant rate ko
- rapid distribution
- peak not as high as for i.v. bolus
- first order kinetics
54
Long term I.V. infusion
```
Css = ko/(VdK)
Css = ko/CL
```
Css = steady state concentration
2x ko = 2x Css
Can be done through multiple dosing
- dose every half life
- gives two-fold variation in concentration (trough = peak/2)
- most drugs have greater than two-fold therapeutic window
55
Oral Administration
dX/dT =KaXa - KX
```
Ka = absorption rate constant
Xa = amount of drug at absorption site
```
- first order elimination
- peak not as high as with i.v. due to elimination
56
Drug Bioavailability
Proportion of active drug which enters systemic circulation
Area of C vs t curve
AUCoral / AUCiv %
Factors affecting bioavailability
- route of administration (I.V. = 100%)
- taken with food
- interactions
- drug properties (pKa, hydrophobicity, solubility)
- first pass metabolism
- disease states
- enzyme induction/inhibition for activation/deactivation
- age
57
Rapid IV administration of Slow Distributing Drugs
Problem if drug has small therapeutic window
Initial loading dose must be higher than if drug distrubuted rapidly (Cpeak high)
loading dose can be divided to avoid toxic Cpeak
58
Rapid IV administration of Zero Order Elimination
Elimination is saturated and occurs at constant rate
Multiple dosing never reaches steady state as elimination is not proportional to concentration
Increasing dose rate leads to disproportionate increase in concentration
59
Drug-drug interactions
- Pharmacodynamic
- Pharmacokinetic
(to be clinically important drug B must have narrow therapeutic index and have steep concentration response curve)
PHARMACODYNAMIC
Receptor antagonism (beta agonist/antagonists)
Physiological
Synergistic (co-trimoxazole)
```
PHARMACOKINETIC
Absorption
- gastric emptying rate (e.g. opioids)
- formation of poorly absorbed complexes
Distribution
- displacement from plasma protein
Metabolism
- induction/inhibition of cytochrome p450
Excretion
- protein binding and filtration
- inhibit tubular secretion (e.g. probenecid in sports)
- urine flow & pH (NaHCO3 in aspirin overdose)
```
60
Renal Plasma Flow
600ml/min
61
Kidney GFR maintenance mechanisms
Myogenic Reflex of afferent arteriole
Macula Densa detect NaCl and provide feedback via paracrine mediators (adenosine, prostaglandins)
Tubuloglomerula Feedback
Angiotensin II preferentially constricts efferent arteriole
Prostaglandins mediate afferent arteriole dilation
Renin release from JGA Granular Cells in afferent arteriole
- macula densa
- sympathetic
- contraction of afferent arteriole
62
Forces/Pressures that affect GFR
Hydrostatic Pressure in Glomerular Capillary - 50mmHg
Hydrostatic Pressure in Bowman's Capsule - 10mmHg
Oncotic Pressure in Glomerular Capillary - 25-40mmHg
Oncotic Pressure in Bowman's Capsule - 0mmHg
Oncotic pressure due to impermeable proteins (basal lamina highly negatively charged)
63
GFR Autoregulation Range
80mmHg - 180mmHg
64
RBF equation
Pressure equation
RBF = ΔP ÷ R
P = flow x R
65
Excretion vs Renal Clearance (equations)
Excretion = Urine Concentration * Urine Volume
Renal Clearance = Excretion / Plasma Concentration
clearance is defined as volume of plasma cleared of substance per time.
66
Filtration, Reabsoption, Secretion of
| Water & Na+
```
Water & Na+ almost entirely reabsorbed
Occurs throughout entire nephron
Only final bit in collecting duct is regulated
Water - ADH (vasopressin)
Na+ - Aldosterone
```
0.5-1% EXCRETION
67
Filtration, Reabsoption, Secretion of
| K+
K+ reabsorbed in proximal tubule and distal tubule (to an extent)
Undergoes net secretion in distal tubule and collecting duct
10% EXCRETION
68
Filtration, Reabsoption, Secretion of
| Ca2+
Ca2+ almost entirely reabsorbed (primarily in proximal and distal tubule).
Under control of PTH proximal and Vit D3 distal (favoring Ca2+ retention)
2% EXCRETION
69
Filtration, Reabsoption, Secretion of
| Phosphate
Phosphate mainly absorbed in proximal tubule (some distal)
Co-transport with Na+
20% EXCRETION
70
Filtration, Reabsoption, Secretion of
| Glucose
Glucose and amino acids are 100% reabsorbed (if plasma concentration < 15mmol)
Reabsorption in proximal tubule co-transport with Na+
0% EXCRETION
71
Plasma creatinine & GFR
If creatinine in the blood is rising it tells you that GFR is falling
15% of plasma creatinine is bound to plasma proteins (understimates GFR)
100% EXCRETION
72
Reabsorption & Ion channels in Early Proximal Convoluted Tubule
APICAL
- Glucose/AA,Na+ cotransport (in)
- Na+ (in) / H+ (out)
BASOLATERAL
- Glucose/AA channels (out)
- Na+ / K+ ATPase
- Na+ / HCO3- co-transport (out)
PARACELLULAR
Leak of Na+ into lumen (proximally), out (distally)
73
Reabsportion & Ion channels in Late Proximal Straight Tubule
APICAL
- HBase passive diffusion in
- Na+ (in) / H+ (out)
- Cl- (in) / Base- (out)
BASOLATERAL
- Cl- channels (out)
- Na+ / K+ ATPase
- Cl- / K+ co-transport (out)
PARACELLULAR
Leak of Na+ out of lumen (into interstitium)
74
Reabsportion & Ion channels in Thin Descending Limb
H20 passive diffusion (out)
| Epithelium is thin but has little mitochondria (can't pump effectively)
75
Reabsportion & Ion channels in Thin Ascending Limb
Na+ passive diffusion (out)
| Due to concentration gradient
76
Reabsportion & Ion channels in Thick Ascending Limb
APICAL
- Na+/K+/2Cl- co-transport (in) [Target for Frusemide]
- K+ channel (out)
- Na+ (in) /H+ (out)
BASOLATERAL
- K+ & Cl- channels (out)
- Na+ / K+ ATPase
- Cl- (in) / HCO3- (out)
PARACELLULAR
Leak of Na+ out of lumen (into interstitium)
77
Reabsportion & Ion channels in Distal Convoluted Tubule
APICAL
- Na+/Cl- co-transport (in) [Blocked by Thiazide Diuretics]
BASOLATERAL
- Cl- channels (out)
- Na+ / K+ ATPase
Thiazides not as effective as Frusemide because frusemide acts earlier (25% sodium absorbed in loop, <10% absorbed in DCT)
78
Reabsportion & Ion channels in Collecting Tubule
APICAL
- Na+ channel (in)
- K+ channel (out)
BASOLATERAL
- K+ channel (out)
- Na+ / K+ ATPase
[Aldosterone]
79
Plasma Buffer Systems
Carbon Dioxide
CO2 + H2O H+ + HCO3-
Plasma Proteins
PPR-- + H+ <> PPRH-
Phosphates
HPO4-- + H+ H2PO4- + H+ H3PO4
Haemoglobin
Hb + H+ HbH+
80
Normal anion Gap
12mmol/L
This is mostly due to anions contributed to by plasma proteins which are largely negatively charged (80% albumin)
Na+, K+ add up to 150mmol/L
HCO3-, Cl- add up to 138mmol/L
81
Kidney Acid-Base Balance Mechanism
HCO3- reabsorption (100%) in proxmial tubule
```
HCO3- and Na+ Filtered
Na+/H+ pumps H+ into lumen
CA forms H2O and CO2 which diffuse into cell
CA forms H+ (excreted again) and HCO3-
Na+/HCO3- co-transport into interstitum
```
Glutamine metabolised to NH4+ and HCO3- (in cell)
NH4+/Na+ pumps NH4+ into lumen
Na+/HCO3- co-transport into interstitum
Response to Acidosis:
(In cell) CA forms H+ and HCO3-
HCO3- reabsorbed to buffer acidosis
H+ excreted into lumen and binds with HPO4-- to form H2PO4-
```
Distal Tubule Intercalated Cell (type A)
HCO3- buffers H+ in interstitum to form CO2 and H2O
CO2 and H2O diffuse into cell
CA forms H+ (excreted again) and HCO3-
HCO3- and Cl- exchange basolateral
H+ exchanged with K+ apical
K+ absorbed basolateral
```
```
Distal Tubule Intercalated Cell (type B)
(In cell) CA forms H+ and HCO3-
HCO3- exchanged with Cl- apical
H+ exchanged with K+ basolateral
K+ diffuse out apical
```
82
Vesico-uretic Reflux
Failure to prevent urine flowing back up ureters
83
Neural Fold Closure Sequence
1. Back
2. Cranium - (Acromegaly - no structures above eyes)
3. Face
4. Occipital
5. Sacral - (Spina Bifida - open neural tube - folate protective)
84
Segmentation of Neural Tube
1. Prosencephalon (forebrain)
- Telencephalon (cortex, basal ganglia, hippocampus)
- Diencephalon (inc. optic vesicles)
2. Mesencephalon (midbrain)
3. Rhombencephalon (hindbrain)
- 7 segments
- Metencephalon (pons/cerebellum)
- Myelencephalon (medulla)
85
Sonic Hedgehog
Released by notochord -> induces floor plate in neural tube
Released by floor plate -> induces ventral horn motor neurons
(motor neurons then release Motor Neuron Factor which induces interneurons)
86
Dorsal Column Medial Lemniscus (mechanosensory)
Ascending pathway
Fine touch, Proprioceptoion, Vibration
Lower Mechanoreceptors travel in Gracile Tract (Medial) T7 and below
Upper Mechanoreceptors travel in Cuneate Tract (Lateral) T6 and above
Synapse with INTERNAL ARCUATE FIBRES in Caudal Medulla and cross over at MEDIAL LEMNISCUS (umr become medial)
Synapse in Ventral Posterior Lateral (VPL) nucleus of thalamus towards primary somatic sensory cortex
87
Corticospinal Tract
Descending pathway
Controls motor function
```
Cortex
Internal Capsule
Cerebral peduncle
Travels in ventral brainstem
Crosses at pyramids (medulla\)
Travels postero-lateral in spinal cord
```
88
Anterolateral System (Spinothalamic)
Ascending pathway
Pain, Temp, Crude Touch
Synapses then crosses in spinal cord (anterior white commissure)
Terminates at thalamus (VPN), midbrain, and reticular formation
89
Tracts & function:
1. Dorsal Column Medial Lemniscus System*
2. Spinocerebellar
3. Spinothalamic*
4. Spino-olivary
5. Extrapyramidal Tracts
6. Pyramidal Tracts*
ASCENDING
1a. Gracile - LL - fine touch, proprioception
1b. Cuneate - UL - fine touch, proprioception
2a. Posterior - proprioceptrion from muscle spindle and golgi
2b. Anterior - proprioception from golgi
3a. Lateral - pain/temp
3b. Anterior - crude touch / pressure
4. N/A - proprioceptive
DESCENDING
5a. Vestibulospinal - balance, posture (from vestibular nuclei)
5b. Olivospinal
5c. Reticulospinal - locomotion, posture (decerebrate posture) (from reticular formation)
5d. Rubrospinal - UL flexion (decorticate posture) (from red nucleus)
6a. Anterior Corticospinal - direct motor control (postural maintenance)(10-15% of fibres)
6b. Lateral Corticospinal - contralateral motor control (primary)
90
Short v Long Propriospinal Tracts
SHORT:
lateral, ipsilateral
complex/dextrous movement
over small region
LONG
medial, bilateral
large movements (e.g. pelvic girdle)
large area
91
UMNL vs LMNL
```
UMNL (loss of inhibition)
increased tone
decreased power
increased reflexes
positive Babinski
```
```
LMNL (no activation)
decreased tone
decreased power
decreased reflex
no Babinski
```
92
CSF & raised ICP
CPP = MAP - ICP
150mL each of blood and CSF
```
CAUSES:
Trauma
Tumour
Infection
Haemorrhage
Infarction
Oedema
- Vasogenic - BBB increased permeability (white matter affected) - steroids help
- Cytotoxic - increased intracellular fluid secondary to cell membrane injury (grey & white matter)
CSF disorders
```
93
Brain Herniations
Subfalcine (cingulate gyrus)
Transtentorial (medial temporal lobe)
Transforaminal (cereballar tonsils)
94
Pupillary Light Reflex
Sensory input from CNII
Melanopsin GC's project to the Optical Pretectal Nucleus (OPN) in midbrain
Synapse bilaterally on Edinger Westfal Nucleus
Motor output to Ciliary Ganglion then Sphincter Pupillae muscle in iris via CNIII (parasympathetic)
95
Corneal Blink Reflex
Sensory input to brainstem (ipsilateral pons) via CNV1
Bilateral motor output to eyelid (orbicularis oculi) by CNVII
(via IAM, facial canal, stylomastoid foramen, and parotid)
Used as test of Pontine function
96
Gag Reflex
Sensory input: IX from pharynx (ipsilateral) to trigeminal nucleus
Interneurons to nucleus ambiguus (bilateral)
Motor output: X to pharynx
Used as test of Medulla function
97
Types of Eye Movements
Saccadic - shift eye to new target
Smooth pursuits - following a moving object
Vergence - focusing on something coming closer
Vestibular-occular - hold image still during head movement
Optokinetic - e.g. sitting on a train looking out window
98
Horizontal Eye Movement (Saccade)
(L) Frontal Eye Fields (prefrontal cortex) ->
(R) Paramedian Pontine Reticular Formation (PPRF) ->
(R) Burst&Omnipause Neurons ->
(L) Abducens nucleus inhibition & (R) Abducens nucleus activation ->
(R) Abducens causes (R) eye abduction
(R) Abducens projects via Medial Longitudinal Fasiculus to (L) CNIII nucleus ->
(L) CNIII nucleus innervates Medial Rectus
= Look to the right
* Burst neuron: Fire at high frequency before movement
* Omnipause: Fire continuously during movement
99
Vestibular Occular Reflex
Turning Head Left
(L) CNVIII ->
(L) vestibular nuclei in medulla ->
inhibition of (L) CNVI nucleus, activation of (R) CNVI nucleus ->
(R) abducens actvivation
(R) CNVI nucleus projects via MLF to (L) CNIII and activates (L) Medial Rectus
Also a direct connection from (L) Vestibular Nucleus to (L) CNIII (Medial Rectus)
There is also inhibitory input from (R) CNVIII
100
Colour Vision Deficiencies
Protanope/Protanomal
Deutanope/Deutanomal
Tritanope/Tritanomal
Protanope - no red cone
Protanomal - abnormal red cone
Deutanope - no green cone
Deutanomal - abnormal green cone
Tritanope - no blue cone
Tritanomal - abnormal blue cone
101
Physiology of Breathing
INPUT:
Irritant receptors
stretch receptors
peripheral chemoreceptors (carotid & aortic bodies) - O2, pH, CO2
central chemoreceptors (ventral medulla) - pH
MEDULLA (nucleus solitarius)
OUTPUT:
phrenic nerve (diaphragm)
intercostal nerves (intercostals)
SCM (CNXI)
102
Metabolic Acidosis
decreased pH
Normal CO2
Decreased HCO3-
103
Metabolic Alkalosis
increased pH
Normal CO2
Increased HCO3-
104
Respiratory Acidosis
decreased pH
increased CO2
Normal HCO3-
105
Respiratory Alkalosis
increased pH
decreased CO2
Normal HCO3-
106
Monosynaptic Reflex
muscle spindles in intrafusal fibres -> Ia sensory afferent -> ventral horn -> α-motor neuron -> extrafusal fibres -> contraction
γ-motor neurons keep intrafusal fibres taut
107
Golgi tendon reflex
Prevent damage to contracted muscle by sensing increases in tension and causing relaxation
Golgi body senses tension -> inhibiting interneuron -> α-motor neuron inhibited -> relaxation
108
Cochlear Hair Mechanism
K+ channels partially open
Displacement towards kinocilia -> opening of K+ channel -> depolarisation -> opening of Ca2+ channels -> glutamate release
Hyperpolarization in opposite direction (not as strong as depolarization)
109
Auditory Pathway
Hair cells
CNVIII (spiral ganglion)
Cochlear Nucleus (medulla)
Superior Olive (work out where sound is coming from)
- Lateral (intensity), Medial(time), and Trapezoid body (contralateral inhibition)
Lateral Lemniscus
Inferior Colliculus
Medial Genticulate Nucleus (Thalamus)
Auditory Cortex (Temportal Lobe) - herschls gyrus
110
Vomiting Mechanism
```
Stimulants:
5-HT3
D2
H1&H2
Higher Centres
```
Chemoreceptor Trigger Zone (medulla oblongata - outside BBB) -> Solitary Nucleus / Vomiting Centre -> vomitting pattern generation
Retroperistalsis
Gastric Pyloric Contraction
Abdominal wall / thoracic contraction
epiglottis closure
111
Swallowing Mechanism
Afferents: IX
Efferents: V, X, XII
Salivation (VII, IX)
Mastication (V, VII, XII)
Bolus shaped by tongue (XII)
Soft palate decends, palatal arches grip and push bolus to oropharynx (X)
Soft palate elevates (V, X)
larynx/pharynx elevated (X)
epiglottis/laryngeal inlet closed (X)
bolus pushed down oropharynx over epiglottis (X)
bolus forced down laryngopharynx to oesophegus (X)
larynx return to normal (elastic recoil)
112
Pineal Gland
- Hormone(s)
- Target(s)
- Effect(s)
Melatonin [AA]
Brain/other
Circadian Rhythm, immune function, antioxidant
113
Hypothalamus
- Hormone(s)
- Target(s)
- Effect(s)
Trophic Hormones* [P]
Anterior Pituitary
Release/inhibit pituitary hormones
```
* PRH -> Prolactin
PIH (Dopamine) -> Prolactin
TRH -> TSH
CRH -> ACTH
GHRH-> GH
GHIH (somatostatin) -> GH (somatotropin)
GnRH -> LH & FSH
```
114
Posterior Pituitary (neurohypophysis)
- Hormone(s)
- Target(s)
- Effect(s)
Oxytocin [P]
Breast & Uterus
Milk ejection, labour, behaviour
Vasopressin (ADH) [P]
Kidney
Water reabsorption
115
Anterior Pituitary (adrenohypophysis)
- Hormone(s)
- Target(s)
- Effect(s)
Prolacin [P]
Breast
Milk production
Growth hormone (GH-somatotropin) [P]
Liver/other
Growth factor secretion (IGF-1), growth, metabolism
Hyperplasia, hypertrophy, increase protein synthesis, anti-insulin (increase blood glucose)
* more GH released in presence of Ghrelin!!
Corticoropin (ACTH) [P]
Adrenal Cortex
Cortisol, Aldosterone, & DHEA Release
Melanocortins & endorphins
Thyrotropin (TSH) [P]
Thyroid
Growth Hormone Synthesis
FSH/LH [P]
Gonads
Egg/Sperm production, sex hormone production
116
Thyroid
- Hormone(s)
- Target(s)
- Effect(s)
Triiodothyronine and thyroxine [AA]
Many Tissues
Increase BMR, O2 consumption, heat, growth, development, HR, CO
Cuboidal follicular cells surrounding GAG/TG mix
Calcitonin [P]
Bone
Plasma calcium levels (excrete & store calcium)
C-cells in interstitial spaces
117
Parathyroid
- Hormone(s)
- Target(s)
- Effect(s)
Parathyroid Hormone (PTH) [P]
Bone & Kidney
Increase Ca2+ plasma levels (and regulate Phosphate)
- increase [Ca2+] & [PO4] from bone
- increase [Ca2+] from kidney (proximal tubule) but decrease [PO4]
- indirectly (via Vit D) increase [Ca2+] & [PO4] from intestine
Essential for life
* minutes - kidney transport
* 1-2 hours - increased osteoclast activity (paracrine, not PTH directly)
* 2-3 hours - bone reabsorption
* 1-2 days - intestinal reabsorption
acutely PTH promotes osteoblast development and activity - favouring bone anabolism
118
Thymus
- Hormone(s)
- Target(s)
- Effect(s)
Thymosin, thymopoeitin [P]
Lymphocytes
Lymphocyte development
119
Heart
- Hormone(s)
- Target(s)
- Effect(s)
Atrial Natriuretic Peptide [P]
Kidneys
Increase Na+ excretion
120
Liver
- Hormone(s)
- Target(s)
- Effect(s)
Angiotensinogen [P]
Adrenal Cortex / Blood Vessels
Aldosterone secretion, increase BP
Insulin-like Growth Factors (IGF- somatomedins) [P]
Many tissues
Growth (bone, protein, antilipolytic)
121
Stomach/GI
- Hormone(s)
- Target(s)
- Effect(s)
Gastrin, Cholecystokinin, Secretin, others [P]
GI tract and pancreas
Assist Digestion and absorption of nutrients
122
Pancreas
- Hormone(s)
- Target(s)
- Effect(s)
Insulin, Glucagon, Somatostatin, Pancreatic Polypeptide [P]
Many Tissues
Metabolism of glucose and other nutrients
123
Adrenal Cortex
- Hormone(s)
- Target(s)
- Effect(s)
Aldosterone [S]
Kidney
Na+ and K+ homeostasis, BP
Cortisol [S]
Many Tissues
Stress Response (protein/carb/lipid metabolism, immune)
Androgens [S]
Many Tissues
Sex drive in females
124
Adrenal Medulla
- Hormone(s)
- Target(s)
- Effect(s)
Adrenaline, Noradrenaline [AA]
Many tissues
Fight or flight, increased glucagon, decreased insulin
125
Kidney
- Hormone(s)
- Target(s)
- Effect(s)
Erythropoeitin (EPO) [P]
Bone Marrow
RBC production
1,25 Dihyrdoxy-vitamin D3 (calciferol) [S]
Intestine
Increase calcium absorption
126
Skin
- Hormone(s)
- Target(s)
- Effect(s)
Vitamin D3 [S]
Intermediate form of hormone
Precursor to 1,25 Dihyrdoxy-vitamin D3 (calciferol)
127
Testes
- Hormone(s)
- Target(s)
- Effect(s)
Androgens [S]
Many tissues
Sperm production, secondary sex characteristics
Inhibin [P]
Anterior Pituitary
Inhibit FSH secretion
128
Ovaries
- Hormone(s)
- Target(s)
- Effect(s)
Estrogen, Progesterone [S]
Many Tissues
Egg production, secondary sex characteristics
Inhibin [P]
Anterior Pituitary
Inhibit FSH secretion
Relaxin (pregnancy) [P]
Uterine Muscles
Relaxtion of muscle
129
Adipose Tissue
- Hormone(s)
- Target(s)
- Effect(s)
Leptin, adiponectin, resisitin
Hypothalamus, other tissues
Food intake, metabolism, reproduction
130
Placenta
- Hormone(s)
- Target(s)
- Effect(s)
Estrogen, Progresterone [S]
Many Tissues
Fetal, maternal development
Chorionic somatomammotropin [P]
Many tissues
Metabolism
Chorionic gonadotropin [S]
Corpus Luteum
Hormone secretion
131
Growth Hormone (somatotropin)
- Stimulation
- Action
GHRH + Ghrelin stimulate Anterior Pituitary to release GH (somatotropin)
GHIH (somatostatin) inhibit Anterior Pituitary
GH act on peripheral tissues
GH act on liver to produce IGF-1 (somatomedins)
GH binds to monomer of GHR, binds another at second binding site (lower affinity) forming active dimer and receptor activation
Glycine at amino acid position 120 is necessary for GH activity -> mutate and pegylate
132
Cortisol
Released in response to ACTH on Adrenals (Zona Fasciculata)
* Binds to transcortin in the blood
* Stimulates protein breakdown to amino acids (Gluconeogenesis)
* Inhibits protein synthesis
* Increases blood glucose levels
* Inhibits utilization of glucose by adipose tissue
* Facilitates lipid breakdown to fatty acids (lipolysis)
* Promotes lipid storage in abodomen, head, chest
* Stimulates appetite and excessive eating (weight gain)
* decreases Ca2++ absorption, increases excretion & bone breakdown
* Suppresses immune responses by suppressing cytokine synthesis. I.e. elevates levels of IκBα which bind to NF-κB (induced by TNF-α)
* Peaks in morning, low at night
* inhibits childhood growth (but sick kids don't grow either)
Cortisone -11βHSD1-> Cortisol
Cortisol -11βHSD2-> Cortisone
* 11βHydroxysteroid dehydrogenase
133
Progesterone
- Signal
- Secretion From
- Function
LH
Corpus Luteum
Maintains (with estradiol) the uterine endometrium for iimplantation of fertilized oocyte
134
17β- Estradiol
- Signal
- Secretion From
- Function
FSH
Ovarian Follicle, Corpus Luteum, Sertoli Cell
(small amounts from adrenal cortex & testicles)
Females: regulates gonadotropin secretion in ovarian cycle, maintains uterine endometrium, growth of mammary gland.
Males: negative feedback inhibitor of Leydig cell synthesis of testosterone
135
Effects of CRH
Release of ACTH by pituitary
Inhibits appetite
Signals onset of Labor
136
POMC
Pro-opiomelanocortin
Large protein that yields several peptides by proteolysis
- ACTH = cortisol, aldosterone, sex hormone release
- β-endorphin = reduced pain sensation
- α & γ MSH = decreased appetite, increased melanin
137
GLP-1 (Glucagon-Like Peptide 1)
Secreted from L Cells of small intestine
Released in response to glucose and fatty acids
Binds to specific receptor on pancreatic β-cells
```
Inhibits glucagon secretion
Stimulates insulin synthesis
Promotes β-cell proliferation
Promotes β-cell differentiation
Stimulates β-cell maturation
Decreases β-cell apoptosis
Slows gastric emptying
Decreases appetite
```
Degraded by DPP-IV
Drug: Exenatide
Decreases BP and slightly increases HR
SITES: Nausea, diarrhoea, vomiting, abdo pain
138
Ghrelin
```
Secreted from stomach
Acts on hypothalamus
Increases appetite by increasing synthesis / secretion of NPY
Fluctuates preceding each meal
Opposes leptin
```
139
GIP
Released form K cells in duodenum and jejunum after digestion of food
Stimulates insulin release
Activates lipoprotein lipase (storage of fat)
140
PYY
Made in L cells of distal GI (same as GLP-1)
| Binds to Y2 receptor and reduces food intake
141
CCK
Made in I cells of small intestine.
Has short half life.
Stimulates Gallbladder and pancreas.
Acts on vagus to reduce appetite.
142
Oxyntomodulin
Product of glucagon gene.
Release from L-cells.
Reduces food intake, increases energy expenditure.
Acts on GLP-1 receptor and inactivated by DPP-IV. Slightly more potent than GLP-1.
Synergistic with PYY
143
Uroguanilin
Produced in distal gut and acts on hypothalamus to decrease food intake.
Acts on gut to increase intestinal fluid absorption
144
ILP-5
Predominantly expressed in colon and ileum.
Causes increase in food intake (not as powerful as ghrelin)
Modulated based on food intake (suppressed after eating)
145
Bone
- structure
- growth
Hydroxyapatite (Ca10 (PO4)6 (OH)2) - calcium phosphate
Outer compact / cortical bone (haversian systems)
Inner trabecular / cancellous bone (lamellae)
Marrow (red in scapula, skull, jaw, pelvis) w/ porous sinusoids
Outer Periosteum (fibroblasts, vessels, collagen, osteoprogenitor cells)
Inner Endosteum (osteoprogenitor cells)
Arteries supply discrete sections (diaphyseal, epiphyseal, metaphyseal, seperate periosteal), w/ abundant nerves
Sharpey's fibres - bone collagen continuous with tendon/ligament collagen
ENDOCHONDRAL GROWTH
- cartilage model produced first (Type II)
- bone collar forms around diaphysis
- cartilage beneath degenerates
- blood vessels invade w/ progenitors
- from diaphysis at epiphyseal growth plate
- chondrocyte columns continuously dividing and laying down collagen
- secondary ossification centre at epiphysis
- osteoblasts increase Ca2+ and PO-, causing precipitation
INTRAMEMBRANOUS GROWTH
- forms directly from mesenchyme
- skull, flatbones, mandible, clavicles
146
Osteoblasts
Bone forming cells (modified fibroblasts)
From osteoprogenitor cells of periosteum & endosteum
Flat when quiescent
Look like plasma cells when active (perinuclear hof)
Produce enzymes and OSTEOID
- osteocalcin/osteonectin - Ca2+ binding proteins
- collagen Type I
- adhesive proteins - sialoproteins, osteopontin
- proteoglycans
- growth factors and cytokines
- alkaline phosphatase
- osteocalcin/alkaline phophatase markers of blastic activity
```
express RANKL when stimulated by VitD & PTH
become osteoclasts (trapped in bone)
```
Increase Activity:
- PTH
- embedded cytokines (bone)
Decrease Activity:
- glucocorticoids (apoptosis)
147
Osteoclasts
Large multinucleate cells
Derived from haematopoietic stem cells
Secrete acid HCl and protease to destroy/remodel bone
Tartrate-resistant acid phosphatase is marker of osteoclast activity
Stimulated by RANKL and M-CSF from osteoblasts (increased PTH)
Increase Activity:
- PTH
- glucocoriticoids
Decrease Activity:
- Oestrogen
- Calcitonin
148
Osteocytes
Surrounded by bone (osteoblasts left behind)
Maintain bone in response to loading (mechanotransduction)
Osteocyte death -> bone resorption
Sustained by their canaliculae
149
ECF Ca2+ Homeostasis
Ca2+ Absorption from intestine
- Vitamin D3, Prolactin
Bone Resorption
- PTH, Vitamin D3, Cortisol
Bone Deposition
- Calcitonin
Kidney Resorption
- PTH (proximal tubule), Vitamin D3 (distal tubule)
Kidney Filtration
- Calcitonin
Vit D & PTH - increases ECF Ca2+
Calcitonin - decreases ECF Ca2+
150
Layers of Epiphyseal Growth Plate
Resting Zone - hyaline cartilage
Proliferation Zone - dividing chondrocytes
Maturation Zone - mature chondrocytes
Hypertrophic Zone - dying chondrocytes
Ossification - Degenerating cartilage replaced by bone
151
Myostatin
Negative regulator of muscle mass
Prevents muscle proliferation and differentiation
Knockout myostatin increases muscle mass in animals
152
Type I & Type II Muscle Fibres
Type I fibres (myosin heavy chain I)
- slow twitch
- increased ability to oxidise fat
- more mitochondria
- increased rate of disposal of glucose / kg of bodyweight
- stain dark after acidic preincubation
- 50% of whole muscle
Type II fibres (myosin heavy chain II)
- fast twitch
- 30-50% of whole muscle
- increased recruitment at high intensity
153
Development of Hip Joint
6-9 months
- femoral head appears (cartilaginous, not calcified)
- ilium, pubis, ischium not fused
10 years
- ischium and pubis fused (but not ilium)
- greater trochanter appears (cartilaginous, not calcified)
12 years
- femoral head fused to femur
14 years
- greater trochanter fused to femur
154
MET
Metabolic equivalent
resting oxygen consumption is 1 MET
1 MET = resting metabolic rate
250mL per minute
3.5mL per kilo per minute of oxygen consumption
Greater exercise capability = more METs = reduced risk of disease
155
Exercise Benefit
- lower incidence of CHD
- reduction in all cause mortality
- more years of life gained
- protective qualities on 'unknown' CVD risk factors (40%)
- more effective than drug/surgery for many conditions
- raised AMPK and PPARδ
```
AMPK = stress activated kinase in response to energy change in muscle
PPARδ = transcription factor that increases oxidative capacity
```
***daily sitting time is better predictor of mortality than active/inactive leisure time
156
mTOR vs Foxo
mTOR - promotes hypertrophy in response to IGF-1 pathway
Foxo - promotes atrophy (due to lack of IGF-1 or glucocorticoids)
157
Rate of ATP generation
PCr - fast but low capacity
Glycolosis - fast but low capacity
CHO oxidation - moderate w/ moderate capacity
Fat oxidation - low w/ infinite capacity
158
Mitochondrial adaptions to exercise training
- increased mitochondrial density
- increased oxidative enzymes
- reduced CHO use and lactate production
- increased fat oxidation
- enhanced endurance performance
- improved insulin action (skeletal muscle GLUT4 upregulation)
159
Fuels for sprinting
- primarily PCr, glycolosis, and free ATP
| - PCr & ATP fall over duration of sprint
160
Fuels for endurance
- muscle glycogen and glucose usage increase with intensity
- fat utilisation peaks at aprox 55% intenisty
- CHO high to begin but decreases over time
- Fat oxidation increases over time
- plasma glucose increases over time
161
Muscle response to high intensity resistance training
- neuromuscular changes precede increase in muscle mass
| - muscle wasting occurs quickly in response to deloading (esp. myofibril synth rate)
162
Factors influencing exercise metabolism
- exercise intensity and duration
- diet (high fat = fat oxidation, although limits intensity)
- training/conditioning (use less CHO and more fat @ same energy expenditure)
- environmental (high temp = more carb)
- age & gender (older = more carb due to lower VO2max and working at higher intensity)
- substrate availability
- hormone levels
- skeletal muscle biochemical characteristics
163
Fatigue
- inability to maintain required or expected force or power output
- due to metabolic feedback from skeletal muscle and lactate
- can occur at any point along the neuromuscular pathway (e.g. sarcoplasmic reticulum)
- IMP is indicator of fatigue (breakdown product of excess ADP)
- greater muscle glycogen (CHO diet) = longer time to fatigue
164
Cardiovascular response to exercise
- Increased O2 supply to skeletal and cardiac muscle
- microvascular adaptions (increased capillaries)
- Facilitate CO2 and heat removal
- Maintain MAP
- VO2 correlates directly to exercise intensity
VO2 = Q x (CaO2 - CvO2)
oxygen consumption = cardiac output x (oxygen extraction)
Athletes reach same oxygen extraction but higher cardiac output
Athletes have higher SV but lower HR
HR limits diastolic filling and causes plateau of SV
165
Distribution of cardiac flow in response to exercise
Muscle > Brain (maintained) > Skin > Gut
skin can constrict to maintain MAP at max intensity
gut can bechome ischaemic
166
Exercise hyperaemia
Metabolic vasodilators from muscle, endothelium, RBC
- endothelium (sheer stress causes release of NO)
- RBC (unloading of O2)
Muscle pump (venous return)
'conducted vasodilation'
- spread of vascular smooth muscle depolarisation through gap junctions
functional sympatholysis
- SNS less effective on contracted muscle (so less vasoconstriction)
167
Blood Pressure response to exercise
Aortic Systolic (CO) increase
Diastolic (TPR) slight decrease
Overall MAP increase
Baroreceptor reflex reset to allow HR and MAP to increase
HR increases over time
Blood volume decreases (sweating)
SV decreases (fluid loss and increase HR - reduced filling)
TPR increases (to offset SV)
168
Increased Cardiac Output following training
- Expanded Blood Volume (increases EDV and therefore SV)
- Increased heart size (increased LV mass and chamber size)
- Increased adrenergic sensitivity (SA node changes)
169
Respiratory response to exercise
- Maintain arterial O2 saturation
- CO2 removal
- Acid base balance (lactate)
- Fluid and temperature balance (animals)
170
Exercise Hyperpnea stimulants
- Motor cortical activation
- Muscle afferents (spindles, type III & IV)
- CO2 flux to the lungs (chemoreceptor?)
- Increased K+, H+, lactate
- Elevated catecholamines and temp
- NOT O2!
171
Exercise ventilation following training
- Reduced blood lactate/H+
- lower plasma K+
- lower plasma catecholamines
- reduced activation of muscle afferents?
- reduced central drive?
172
Heat loss and dehydration during exercise
- at cool temps - primarily convection+conduction
- at hot temps - primarily sweat+evaporation
- at hot temps - increased CO to skin w/ decrease SV
- hot temp correlates with shorter exercise time and lower power output
- precooling allows for longer performance time
- intracellular space loses most fluid, then interstitial
- dehydration reduces exercise time
173
Benefits of fluid ingestion for exercise
- Increased blood volume (therefore SV & CO)
- Decreased HR
- lower core temp
- lower plasma [Na+] and osmolarity
- reduced muscle glycogen use
- enhanced exercise performance
Higher sodium ingestion post-exercise increases water balance
174
Exercise for diagnosis
- can use step increments to get an idea of VO2 curves and extrapolate to VO2max
- high lactate responses at low VO2 correlate to Heart Disease
- can test PWC150 (i.e. what power output is obtained at HR of 150BPM)
175
Muscle oxidative capacity and endurance
Iron is an important component of the ETC -> greater oxidative capacity
increased muscle oxidative capacity is a better predictor of endurance than VO2max
Stronger correlation between lactate and oxidative capacity of muscle than VO2 and oxidative capacity
Higher VO2max at Lactate Threshold correlates to longer time to fatigue
Higher VO2max at Lactate Threshold correlates to lower glycogen used
176
Exercise Benefit vs Risks
BENEFITS:
- typical dose response curve
- small increase has greatest effect on mortality
- improved glycemic control in T2DM
- combined aerobic and resistance best
- reduction in diabetes risk
- greater exercise volume = greater VO2max change
- some may have adverse metabolic responses
- physical inactivity responsible for more global deaths than smoking
- increased insulin sensitivity (GLUT4 upregulation)
- improved fatty acid oxidation (rather than deposition especially in liver)
- higher levels of HDL
- reduced visceral obesity
- reduced blood pressure
- anti-inflammatory (IL-6)
RISKS:
- Increased risk of sudden death (but lower risk of non-sudden death)
177
Recommended Exercise Reigeme
5x30min moderate intensity per week
3x20min high intensity per week
2x strength training (3 sets 8-10reps) per week
178
Stand up intervention
- increase number of breaks in sitting time and reduce overall sitting time
- pre-assessement with accelerometer
- intervention session (barriers, benefits, goals etc)
- sedentary behaviour reduced by 30mins per day
179
In males FSH acts on
- sertoli cells
- leads to spermatogenesis and cell products
- androgen binding protein
- inhibin
- inhibin negative feedback to anterior pituitary only
180
In males LH influences
- testosterone production (acts on leydig cells)
| - testosterone negtive feedback to anterior pituitary and hypothalamus
181
In females FSH causes
- simulation of follicular development (maturation to secondary and tertiary follicle)
- granulosa cells to produce estrogen & inhibin
- estrogen has positive feedback on granulosa to produce more estrogen
- estrogen has negative feedback on anterior pituitary and hypothalamus
- inhibin has negative feedback on anterior pituitary (decrease FSH - inhibit new follicle)
- high estrogen stimulates GnRH
- increasing progesterone stimulates GnRH & LH suge
182
In females LH causes
- stimulation of thecal cells to produce androgens
- androgens converted to estrogens by aromatase in granulosa cells
- estrogens negatively feedback on anterior pituitary and hypothalamus
- inhibin has negative feedback on anterior pituitary (decrease FSH - inhibit new follicle)
- high estrogen stimulates GnRH
- increasing progesterone stimulates GnRH & LH suge
183
Human gametes contain how many chromosomes?
23
184
Duration of Pregnancy
```
38 weeks (266 days) from fertilisation
40 weeks (280 days) from last period
```
185
Periods of Pregnancy
- Early pregnancy (weeks 1 -2)
- formation of morula and blastocyst implantation
- not susceptible to teratogens
- susceptible to chromosomal abnormalities
- environmental disturbances interfere with implantation
- Embryonic period (weeks 3-8)
- most susceptible to teratogens
- all major organs present at end of week 8
- Foetal period (weeks 9-term)
- rapid growth
- physiological defects (i.e. not enough beta cells)
- minior morphological abnormalities
- functional disturbances
186
Hormones produced by the placenta
```
human chorionic gonadotropin (hCG)
- 'rescue' of corpus luteum (sustains production of hormones)
- high on pregnancy tests
human placental lactogen (hPL)
- breast development
- metabolic effects
estrogen and progesterone
- pregnancy maintenance
- breast development
additional hormones for adaptation to pregnancy
```
187
Lactation
before birth
- prolactin-inhibiting hormone (PIH) blocks prolactin
- high estrogen and progesterone levels suppress milk production
after birth
- high prolactin & low estrogen cause lactation
suckling
- inhibits PIH, allows prolactin to stimulate milk production
- oxytocin stimulates 'let-down reflex' - milk ejection (myoepithelial contraction squeezing TDLUs)
- inhibit GnRH and ovarian cycle
188
Determinants of foetal growth
- genetic factors (genotype and sex)
- IGF, thyroid, insulin promote fetal growth
- (excess) glucocoritcoids inhibit fetal growth
- hypoxia
- hyperthermia
- toxins (alcohol, drugs, etc)
- maternal disease / pre-eclampsia
- malnutrition
- placental insufficiency
- oligohydramnios
189
Spermatogenesis
```
Spermatogonium - (daughter cell on outer edge of seminiferous tubule)
Spermatogonia
Primary Spermatocyte
(first meiotic division)
Secondary spermatocyte
(secondary meiotic division)
Spermatids
```
190
Oogenesis
```
Oogonium
(mitotic proliferation)
Primary Oocytes
(arrested in meiosis 1)
Graafian follicle (releases oestrogen) enlargement & Release of oocyte
(completion of meiosis)
Secondary Oocyte & first polat body
(fertilisation &second meitotic division)
Mature Ovum
```
191
Menstrual Cycle
28 days
Two Phases
FOLLICULAR / PROLIFERATIVE PHASE (Oestrogen)
- new layer of endometrium in preparation of pregnancy (becomes a secretory structure)
- follicle growth in ovary (egg matures)
- granulosa cells produce Oestrogen w/ feedback
- days 0-13
OVULATION
- ripened follicles and release of oocytes
- clear non viscous mucous in cervix
- day 14
LUTEAL / SECRETORY PHASE (Progesterone and Oestrogen)
- corpus luteum produces high progesterone and moderate oestrogen
- no new follicle development
- cervical mucous becomes thick and sticky
- conversion of endometrium to secretory structure to promote implantation
- basal body temperature goes up
- ruptured follicle transforms into corpus lutem
- days 15-28
MENSES
- if no pregnancy - bleeding from uterus as endometrium is shed
192
Physiology of Erection
```
Parasympathetic
- relaxes cavernosal smooth muscle
- dilates arteries (acetylcholine & NO)
- swelling constricts venous outflow
Sympathetic (loss of erection)
- restricts inflow
- constricts cavernosal smooth muscle
```
193
Effects of HRT (oestrogen)
BENEFIT:
- imrpve bone density (decrease resorption)
- relief from flushes, fatigue, and vaginal dryness
- reverse atrophy of vulva, vagina, urethra
- imrprove sleep
- reduced incidence of colorectal cancers
- cardiovascular (reduced CHD?)
- reduced incidence of alzheimer's?
RISKS:
- fluid retention
- breast tenderness, nausea
- increased risk of breast / uterine cancer
- increased risk of thromboembolism / stroke
194
Oestrogen
crosses plasma membrane
acts on cytoplasmic receptors (forms dimer)
dimer binds to oestrogen response element (ERE) for gene expression
monomer + cofactor can lead to gene activation/repression
possible cell membrane receptors with rapid effects
EFFECTS;
- cell growth
- upregulation of progesterone receptor
negative feedback on anterior pituitary
(progesterone feedbacks on hypothalamus also)
195
Testosterone
```
crosses plasma membrane
acts on cytoplasmic receptors (forms dimer)
dimer binds to response element for gene expression
monomer + cofactor can lead to gene activation/repression
possible cell membrane receptors with rapid effects
EFFECTS;
- gonadotrophin release
- spermatogenesis
- sexual differentiation
- anabolic effects (skeletal growth)
DHT
- prostate development
- external virilisation
- sexual maturation
RISKS:
- increased LDL & decreased HDL
- acne, facial hair, baldness
- menstrual irregularity
- impotence
- gynecomastia
- closure of epiphyseal plates
```
196
Cell cycle
```
G0 - resting phase
G1 - cell growth
- awaiting stimulation to proliferate
- Ras -> Myc -> -> cyclinD -> initiation of replication
S - DNA replication
G2 - cell increases in size
M - mitosis & cytokinesis
```
197
Prostaglandin E2
- GPCR agonist at EP(1-4) receptors
- increase [cAMP] and PKA
- sensitizes pain mechanisms
- causes fever
- vasodilator
198
of
RBCs
WBCs
Platelets
RBCs
3-5 x 10^12 / litre
replaced every 120 days
WBCs
2-6 x 10^9 / litre
replaced every 3-5 days
Platelets
150-400 x10^9 / litre
replace every 10 days
199
Tissue Oxygen Delivery Equation
= CO x Hb x %Satn x 1.34
200
PCV
MCV
MCH
MCHC
PCV = Haematocrit - amount of RBCs
MCV - size of RBCs
MCH - haemoglobin per RBC
MCHC = haemoblobin per unit of RBC
201
What effects result in increased CO?
- Increased blood volume
- Increased venoconstriction
- decreased TPR
- increased contractility
202
ACT
APTT
PT/INR
ACT - activated clotting time
APTT - activated partial thromboplastin time
- used to monitor heparin
PT - prothrombin time
INR - (patientPT/normalPT))^ISI
- used to monitor warfarin
203
SA Node pacemaker
```
Phase 4
Spontaneous depolarisation (Na+in, Ca2+in)
```
Phase 0
Depolarisation (Ca2+ in)
Phase 3
Repolarisation (K+ out)
ACh/M2(GPCR) - decrease cAMP = opening of K+ channels = slowing of Ca2+ and Na+ influx = slowed phase 4
NA/β(GPCR) - increase cAMP = opening of Ca2+ channels = faster phase 4
204
Ventricular Action Potential
Phase 4
stable potential
Phase 0
Depolarisation (Na+ in)
```
Phase 1
Rapid repolarisation (K+ out)
```
Phase 2
Plateau (Ca2+ in, K+ out)
Phase 3
Repolarisation (K+ out)
205
Angiotensin II effects
```
Production of aldosterone (Na, H20 retention)
Vasoconstriction
Cell Growth (cardiac hypertrophy)
Sympathetic stimulation (& increased Renin)
```
