PHYSIOLOGY –

METABOLISM
CASE
LACTOSE INTOLERANCE

A person feels discomfort and experiences abdominal cramps and

diarrhoea after meals rich in diary
TESTING FOR INTOLERE NCE

• Test must be done to determine if person is lactose intolerant

o A lactose rich fluid give
o Persons glucose is measured every 15 mins for 2 hrs
o

POSITIVE TEST
If no rise in glucose lactose intolerant
• Adjust diet BUT must ensure they get sufficient calcium
•
CAUSES
Can take products containing lactase
• Primary lactase deficiency is genetic, only affects adults and is
caused by the absence of a
lactase persistence allele.
• Secondary, acquired, or transient lactase
deficiency is caused by an injury to the small
intestine, usually during infancy, from acute
gastroenteritis, diarrhoea, chemotherapy, intestinal
 parasites or other environmental causes.
•
WHY DO YOU GET CRAMP S AND DIARRHOEA?
Congenital lactase deficiency is a very rare,
autosomal recessive genetic disorder that
prevents lactase expression from birth
• The lactose passes through the small intestine into the colon
where it starts
Anabolic
pathways
to ferment
uses energy and reducing
Catabolic
pathways
breaks down complex
• This results intoosmotic substances
power which
molecules to makes water stay in
construct complex molecules yield energy and reducing
the GIT as well as gas to form power
• Gas cramps
• Water diarrhoea
​
METABOLISM
DEFINITION

• thousands of complex chemical reactions rapidly taking place

in living cells, at a constant
body temperature and pH under the influence of enzymes
CHEMICAL REACTIONS M AKE UP PATHWAYS TO:

• Extract energy from foodstuffs

• Use energy for work
o Mechanical work and cell movements
o Active transport of molecules and ions
o Synthesis of macromolecules

• Store excess energy

NORMAL BALANCED DIET
 MACROMOLECULES

• Carbohydrates provides 55% of total energy or 4 kcal/g

• Fats provides 30% of total energy or 9 kcal/g
• Proteins provides 15% of total energy or 4 kcal/g
***(1 kilocalorie = 4.18 kilojoules)***
MICROMOLECULES (PROVIDES NO ENERGY)

• Vitamins (A, B complex, C, D, E, K)

o Required in very small quantities
o Vitamins not synthesised in the body
o Converted to co-factors required by enzymes
o Two classes:
▪ Water-soluble B&C
▪ Fat-soluble K, A, D, E
• Minerals
o Two groups, those that are required in large
quantities and those that are required in small
quantities

Mineral Function
Calcium and phosphorus Structural components of bone
Calcium hormone action and blood clotting
Phosphorus ATP
Magnesium Activates many enzymes and forms complex with ATP

​
Sulphur Found in connective tissue, particularly cartilage and skin
Sodium, potassium & chloride Establish ion gradients across membranes, maintain water balance
Iron Trace mineral, component of haemoglobin and is part of many enzymes

• Water
STAGES IN THE EXTRAC TION OF ENERGY FROM
FOODSTUFFS

​
 ATP

• ATP is a nucleotide: adenine – ribose – triphosphate

• Active form of ATP usually a complex with Mg2+ or Mn2+
• ATP is an energy rich molecule because it contains 2
phosphoanhydride bonds – high energy bonds and
1 ester bond
• ATP, ADP, AMP are interconvertible
• Reactions
o ATP + H 0
2 ADP + Pi ∆G= -7.3kca/mol
o ADP + H 02 AMP + Pi ∆G=-6.6kcal/mol
o AMP + H 0 2A + Pi ∆G=-3.4kcal/mol
• ATP + AMP ↔ ADP + ADP (enzyme: myokinase or adenylate
kinase)
TURNOVER RATE OF ATP

• Very high
• ATP serves as IMMEDIATE donor of free energy –
rather than long-term storage form of free energy
• CONSUMED WITHIN ONE MINUTE following its formation
• ATP – ADP cycle is the fundamental mode of energy exchange
in biological systems
BASIC STRATEGY OF ME TABOLISM

• Production of ATP
• Reducing power – in most biosynthesis both ATP and
reductive power is necessary (NADPH is the major
electron donor in reductive power)
• Building blocks for biosynthesis

CARBOHYDRATES
FUNCTIONS OF CARBOHYDRATES
 • Source of energy
• Storage of energy – glycogen in liver and skeletal muscle
• Structural components:
o Cell membranes
o glycoproteins
o glycolipids

CLASSIFICATION OF CA RBOHYDRATES

MONOSACCHARIDES
• Simple sugars
• Crystalline, sweet, water soluble
​

OLIGOSACCHARIDES
• Contain 2-6 monosaccharides
• Most common: disaccharides, e.g., maltose, sucrose, lactose
• Crystalline, sweet, water soluble

POLYSACCHARIDES
• contain very long chains of monosaccharides linear or branched
• Starch, glycogen
• Tasteless, insoluble
ALDOSES AND KETOSES

ALDOSE
• D-glyceraldehyde
• D-ribose
• D-deoxyribose
• D-glucose
 KETOSE
• D-fructose
• Dihydroxyacetone

AND GLUCOSE

Starch Cellulose Glycogen

2 forms of starch occur unbranched branched
in
plants
amylose – unbranched
amylopectin – branched

​
amylose – 1,4 1,4 1,4 glycosidic
linkages amylopectin – glycosidic linkages with an
1,4 linkages with an linkages 1,6 branch point
1,6 branch point every ten glucosyl
every 30 glucosyl units units
starch digestible in cellulose NOT storage form of
humans
-amylase, maltase and digestible in humans glucose in human
-
dextrinase digest starch specific enzyme liver and muscle
in
the GIT lacking to hydrolyze
1,4 bond
​

GLUCOSE TRANSPORT PROTEINS (GLUT

PROTEINS)
• 5 isoforms of glucose transporters are found in membranes of
cells (GLUT 1-GLUT 5)
• Isoforms: multiple molecular forms of a given protein
• Isoforms have different tissue distributions and
properties, some cell types have more than one
isoform

GLUT Where
GLUT 1 erythrocytes, blood brain barrier, kidney, colon
GLUT 2 liver, b-cells of islets of Langerhans
GLUT 3 neurons, placenta, testis
GLUT 4 is insulin-dependent adipocytes, skeletal muscle, a-cells of
islets of Langerhans, satiety centre
GLUT 5 transports fructose
Sodium-dependent GLUT proteins absorption of glucose in GIT and kidneys

GLUCOSE REQUIREMENT OF 70 KG ADULT

• 160 g of glucose needed per day

• 120 g hereof (70%) used by brain of 1400 g in mass
glucose provided by diet, body stores,
gluconeogenesis
• Diet and body stores only sufficient for one day
• Body stores:
o body fluids: 10-20 g
o glycogen stores: 70 g in liver and 250 g in muscle
o NOTE: stores in liver available for general mobilisation
o NOTE: stores in muscle not available for
general mobilisation since muscle lacks
glucose-6-phosphatase
 o Liver and kidney can increase blood glucose directly
• Gluconeogenesis are the synthesis of glucose from non-
carbohydrate precursors
• Gluconeogenesis supplies glucose during longer periods of
starvation and long-term exercise
​

LIPIDS
FUNCTIONS OF LIPIDS

• Reserve store of energy

• Heat insulation – subcutaneous adipose tissue
conducts heat only 1/3 as readily as other tissues
• Electrical insulation of nerves – myelin sheath
• Supply of fat-soluble vitamins (A, D, E, K) fat-
soluble vitamins can be stored for longer periods
in fatty tissue and in liver
• Supply of essential fatty acids (polyunsaturated:
linoleic, linolenic) – precursors of prostaglandins,
prostacyclins, leukotrienes and thromboxanes
• Production of hormones, e.g., estradiol (steroids)
• Components of membranes
CLASSIFICATION OF LIPIDS

ENERGY RESERVES OF A 70 KG MAN

• 100 000 kcal in triacylglycerols (± 11 kg)

• 25 000 kcal in proteins (mostly muscle)
• 600 kcal in glycogen
 • 40 kcal in glucose
**1 cal = 4.18 J**
TRIACYLGLYCEROL

• Accumulate in cytoplasm of adipose cells

• Highly concentrated stores of metabolic energy
• ANHYDROUS: non-polar
• Complete oxidation of fatty acids yield 9 kcal/g
incontrast to 4 kcal/g for carbohydrates and protein –
as fatty acids are more highly reduced
• 1 gram of glycogen binds 2 grams of water (water – not energy
providing)
BIOLOGICAL MEMBRANES

• Lipophilic: penetration is
proportional to solubility
in lipids
• Fluid mosaic model
replaces the rigid “lipid
bilayer” model
• Membrane proteins and
lipids can rapidly diffuse
laterally or rotate within the
bilayer
• Mosaic
o fluid and dynamic
state (selective
transport)
o Peripheral and integral proteins

FUNCTIONAL PROTEINS OF BIOLOGICAL

MEMBRANES
• Transport proteins (GLUT 4)
 • drug and hormone receptor sites
• antigens (blood groups)
• membrane-bound enzymes (e.g., Na+/K+ ATPase)
AMPHIPATHIC MOLECULES

• biological membranes: amphipathic because they contain both

polar and non-polar regions
• non-polar ends towards each other within the membrane
• polar ends towards the aqueous phase
ASYMMETRICAL PROTEINS

• hydrophilic portions of the proteins are located on

both surfaces of the membrane, hydrophobic
portions of the proteins are within the membrane
​

MEMBRANE
10 | P a g eLIPIDS: 3 M AJOR CLASSES
Metabolism –
•physiology
Glycerophospholipids
• Sphingolipids
• Sterols
MEMBRANE PHOSPHOLIPASES

• phospholipases are responsible for turnover of membrane lipids

resynthesis enter metabolic
pathways
• phospholipase A1 (PLA1) removes fatty acyl group from C1 of
glycerol
• phopholipase A2 (PLA2) removes fatty acid group from C2
(usually arachidonic acid)
•
ESSENTIAL FATTY ACID TERMINOLOGY
 phospholipase C (PLC) cleaves bond between C3 of glycerol
and P diacylglycerol
• linoleic acid
o n-6 fatty acid (omega-6 fatty acid)

o double bond is six

carbon atoms away
from the “omega”
carbon
o omega 6 derived
eicosanoids (20C)
synthesised from
arachidonic acid
▪ prostaglandins
(PGs), PGE2:
vasodilation
▪ thromboxanes
(TXs), TXA2:
platelet
aggregation and
vasoconstriction
▪ leukotrienes (LTs),
mediators of
inflammation and
10 | P a g ebronchoconstriction
o PGs and TXs are collectively identified as prostanoids
Metabolism –
physiology
• alpha-linolenic acid
o n-3 fatty acid (omega-3 fatty acid)
o double bond is three carbon atoms away from the “omega”
carbon
 LIPOPROTEINS
STRUCTURE AND FUNCTION

• Globular, micelle-like particles consisting of:

o Hydrophobic core of
triglycerides and
cholesterol esters
(cholesterol + fatty
acid)
o Surrounded by an
amphipathic coat of:
protein, phospholipid
and cholesterol
• Apoproteins on the surface help to
o Solubilize lipids
o Target lipoproteins to correct tissue via interaction with
receptors
• Major function of lipoproteins transport of triglycerides,
cholesterol and phospholipids
FIVE CLASSES OF LIPOPROTEINS IN PLASMA

• chylomicrons (CM)
• very low density lipoproteins (VLDL)
• intermediate density lipoproteins (IDL)
• low density lipoproteins (LDL)
• high density lipoproteins (HDL)
**increase in density
from 1-5**
TRANSPORT MECHANISM
10 | P a g e
Metabolism –
​ physiology
 FAMILIAL HYPERCHOLESTEROLEMIA

• Mutations affecting the LDL receptor

• Cells lacking functional LDL receptors cannot take
up LDL circulating LDL, leading to enhanced risk
of developing atherosclerosis

PROTEIN
OVERVIEW

LEVELS OF ORGANIZATI ON IN PROTEIN

MOLECULES
 10
2 ||PPaaggee
Metabolism
etabolism ––
physiology
physiology
​

PLASMA PROTEINS
FUNCTIONS OF PROTEINS

• Alpha, beta globulins: transport lipids and fat-soluble vitamins

• Haptoglobulin: binds free Hb (from worn-out RBC, transport to
liver for degradation)
o Too much Hb can lead to oxidative damage, as
free iron released from Hb promotes oxygen free
radicals, to membrane
 • Transferrin: iron transport
o Iron absorbed by enterocytes then transported to
bone marrow to produce blood cells
MATRIX PROTEINS

• proteoglycans (mainly carbohydrate substances bound to small

protein cores), glycoproteins
• part of extra-cellular matrix
• mediate cell-cell adhesions
MEMBRANE PROTEINS:
1
13 | P a g e
•M
Metabolism
transmembrane– glycoproteins
physiology
• absorbed glycoproteins
• transmembrane proteoglycans enzymes (e.g., Na+/K+
ATPase, etc.)
o carrier proteins (uniporters/antiporters for large
H2Osoluble molecules (e.g., GLUT proteins)
o ion channels (ligand gated / voltage gated)
o receptors (involved in activation / deactivation of proteins
through phosphorylation)

INTRACELLULAR PROTEI NS:

• enzymes (biological catalysts)

• proteins of cytoskeleton (actin, tubulin)
• contractile proteins (muscle) actin + myosin
• proteins which activate gene expression transcription factors
DYNAMIC EQUILIBRIUM BETWEEN DIETARY
PROTEINS, CELLULAR PROTEINS AND THEIR
CONSTITUENT AMINO ACIDS AMINO ACIDS IN
BLOOD :
​
dietary protein (± 100 g/day) (hydrolysed to amino acids and absorbed from GIT)
breakdown of tissue
protein (200-300 mg/day) synthesis of amino acids

synthesis of body proteins (200-300 mg/day) structural proteins, enzymes,

plasma proteins
synthesis of non-protein, nitrogen containing compounds: hormones
Energy production
​

14 | P a g e
Metabolism
In
–
physiology
PROTEIN
cr TURNOVER RAT E IN 70 KG MAN
e
• as
body
protein ± 10 kg
es D
• half in muscle
ec
• turnover rate varies from tissue to tissue re
• blood and liver protein ½-life: 2-10 days as
• muscle protein ½-life: 180 days es
• collagen ½-life: 1000 days
• lens: life-time
ESSENTIAL AND NON-ESSENTIAL AMINO ACID S

• all required for protein synthesis in body

• Essential amino acids cannot be synthesised in body
o 10 amino acids
 o Must come from diet
o Best source – animal protein
o threonine, histidine, arginine, tryptophan*,
valine, methionine*, phenylalanine, isoleucine,
leucine, lysine*

* often deficient in plant protein

• non-essential amino acids can be synthesised in the body (10)
NITROGEN BALANCE
POSITIVE NITROGEN BA LANCE

• when dietary N intake > N excretion

• thus body protein increases
• anabolism of N compounds (also proteins) greater than
theircatabolism
• growing children, pregnant women, bodybuilders
NEGATIVE NITROGEN BALANCE

• when dietary N intake < N excretion

• thus body protein is lost
• catabolism of N compounds greater than their
14synthesis
| P a g e(caused by release of stress hormones)
•Metabolism –
cancer patients, severe infections, burn patients
physiology
ROLE OF LIVER IN AMINO ACID METABOLISM

• dietary protein digested to peptides and amino acids (in GIT)

• absorbed into portal circulation by four different active transport
mechanisms
• transported to liver
o some amino acids used for protein synthesis in liver
 o some exported to peripheral tissue for use there
o some converted to other amino acids by transamination
▪ transaminase (aminotransferase)
• catalyze the reversible transfer of an amino group

to
• ketogenic or glucogenic acid to form a different

amino acid
• glucogenic acid:

o amino acid which carbon

skeleton can be used for
gluconeogenesis to form
glucose
• ketogenic acid:

o amino acid broken down to acetyl CoA

o amino acids cannot be stored or excreted but amino group

is
o removed by deamination

17 | P a g e

14 | P a g e
TRANSPORT
Metabolism –
physiology
 transpor
t

passiv activ
e e

simple facilitate primary secondary

diffusion d active active
MEMBRANE TRANSPORT P ROTEINS
(no
diffusion
(transpor
transport
(transpor
transport
(transpor
transport
protein) t protein) t protein) t protein)
​

18 | P
Metabolism
age –
physiology

PASSIVE FACILITATED DIFFUSION

FACILITATED DIFFUSIO N BY MEANS OF A CARRIER

PROTEIN

SECONDARY ACTIVE TRANSPORT

​ Metabolism –
physiology
MEMBRANE RECEPTORS

Cell surface receptors – integral membrane proteins

bind hormone (ligand) conformational change in
receptor information transmitted into cell (SIGNAL
TRANSDUCTION) cell response
FOUR CATEGORIES OF M EMBRANE RECEPTORS

CELL SIGNALLING
• cells communicate with one another though extracellular
19signalling
| P a g emolecules (hormones)
• Metabolism –
endocrine signalling – hormone acts at a distant site from where
physiology
produced
• paracrine signalling – hormone acts on nearby cells

• autocrine signalling – hormone acts on the same cell from which

it was secreted
• lipophylic hormones (steroids, thyroxine, Vitamin D, retinoic acid)

o ​intracellular receptors – thus in cytosol or

nucleus (nuclear proteins bind steroids and act
as transcription factors)

• hydrophylic hormones (insulin, glucagon,

epinephrine, histamine) – receptors in plasma
membrane
SECOND MESSENGERS – INTRACELLULAR
SIGNALLING MOLECULES
• Produced in response to activation of G-

proteins by cell surface receptors G PROTEIN-

COUPLED ADENYLYL CYCLASE-CAMP
SYSTEM

19 | P a g e
Metabolism –
physiology
 THE PHOSPHOLIPASE C SYSTEM

STRUCTURE OF ENZYMES
ENZYMES

• proteins, synthesized in cells, protein structure affected by

temperature and pH

TEMPERATURE:
• < 45°C – • rate of enzyme reaction

• >45°C – denaturation of enzyme (protein)

​
PH:

pH changes affect ionic state of -NH2 and –COOH groups of enzyme

can affect19
conformation
| P a g e of protein and thus catalytic sitevery low / very
high pH Metabolism –
physiology of enzyme
possible denaturation
 FUNCTION OF ENZYMES

•act as biological catalysts

• increase reaction rate by lowering the activation energy

• increase reaction rate without being consumed

• chemically unchanged

• small amount needed and re-used

SPECIFICITY OF ENZYMES

ensures organization of metabolism, due to its

•

protein nature the substrate binds to a specific

region of the enzyme called the CATALYTIC or
ACTIVE SITE
• RELATIVE specificity catalyses one type of

reaction involving many compounds e.g.

hexokinases
• ABSOLUTE group specificity acts only on one

compound (substrate) e.g. intestinal trypsin only

cleaves peptide bond where R1 = lysine/arginine and
R2 = any group thrombin in blood only cleaves peptide
bonds where R1 = arginine and R2 = glycine
CONTROL OF ENZYME CATALYTIC ACTIVITY

INACTIVE ENZYME (ZYMOGEN OR PROENZYME) ACTIVE

ENZYME
• stomach: pepsinogen pepsin
• pancreas: chymotrypsinogen chymotrypsin
• pancreas: trypsinogen trypsin
 COVALENT MODIFICATIO N, ENZYME CAN BE
ACTIVATED OR INACTIVATE D BY
PHOSPHORYLATION
• specific serine residues of enzyme molecule
19 | P a g e
phosphorylated
Metabolism – by phosphorylases or phosphate
group removed by phosphatases
physiology

• glycogen phosphorylase (active)

• glycogen synthase (inactive)

NEURO – BLOCK 1
ALLOSTERIC CONTROL, IN ADDITION TO CATAL YTIC
SITE, THERE IS ALSO A REGULATORY SITE ON
• some enzyme molecules (then called allosteric
enzymes) at a different position, molecules bind to
this regulatory site resulting in conformation change in
enzyme and thus of catalytic site altered ability of
enzyme to bind
substrate or release product
• co-operative effector,

when substrate also

binds to regulatory
site and enhances
enzyme activity
• negative feedback

control or positive
feedback control
FREE FORMAT QUESTIONS
EXPLAIN THE LACTOSE INTOLERANCE TEST
AND THE REASON FOR PRESCRIBING THIS
TEST. (5 MARKS)
 The lactose intolerance test is a test done in order to
determine whether or not a person is intolerant and thus
lacks lactase an enzyme that converts lactose into glucose
and galactose to be absorbed. In the test the person is
given a lactose rich product to drink and then every
15minutes for the next 2 hours the person’s blood glucose
level is taken. If there is not significant rise in the level it
indicates that the person lacks the lactase enzyme and
thus cannot metabolize the lactose into a form that can be
absorbed.
19 | P a g e
Physiology
Metabolism behind
– it: Lactase metabolizes lactose into
glucose
physiology
and galactose as lactose cannot be absorbed
only the simple subunits. The unmetabolised lactase then
passes into the colon where it ferments and produces
gases, responsible for the cramps, and osmotic fluid,
which attracts water and is responsible for the diarrhoea.
EXPLAIN GLYCOGENOLYSIS AND
GLYCOGENESIS. INCLUDE ENZYMES AND WHEN
THEY MOSTLY TO OCCUR. (5 MARKS)
Glycogenolysis occurs when the blood sugar levels in the
blood begin to drop. This is during periods of exercise or
between meals. Glycogen is turned to glucose-6-phosphate
and then the glucose-6- phosphate is converted into
glucose by an enzyme called glucose-6-phosphatase which
is only present in the liver. The glucose can then exit the
cell and maintain the blood glucose levels.

Glycogenesis is a process that entails the formation of

glycogen. It normally occurs after a meal so that the body
has excess stores of energy for periods when blood sugar
levels drop. The glucose enters the cell via GLUT 4 and
then is immediately phosphorylated by hexokinase to form
 glucose-6- phosphate which is then turned into glycogen by
the process of glycogenesis.
​

ANATOMICAL TERMS
THE ANATOMICAL POSIT ION IS AS FOLLOWS:

Person is standing
Head, gaze and toes are directly
pointed anteriorly Arms are
adjacent to sides with palms
facing anteriorly Lower limbs are
1 | P a g ewith feet parallel
together
Neuro-
POSITIONS
Anatomy

aqueduct of
Mesencephalo
n • Superficial
mesencephal
on near themidbrai
n ssurface
pon 4th
mesencephal
ventricle
on
• Intermediate between the superficial and deep structures
metencehalo
n Cerebral
telencephalo
cerebellu 4th 2 lateral
• Deep furthers from n m the surface ventricle
hemispher
Rhombencephal ventricles
es
on Prosencephal
• Proximal
on near to the trunk or point thalamus +
of origin
myelencephalo diencephalo
medulla 4th 3rd
• Distal n Farther from trunk or point s of origin
hypothalamu
n
oblongata ventricle ventricle

• Superior (cranial) towards the head

• Inferior (caudal) toward the feet
• Posterior (dorsal) more to the back
• Anterior (ventral) more to the front
• Medial nearer to the median plane
• Lateral further from the media plane
• Palmar Palm (anterior hand)
• Dorsal Dorsum (Posterior hand)
• Planter Sole (inferior foot surface)
•

Dorsal Dorsum (superior foot surface)

PLANES

• Median plane vertical plane passing through the body

Middle finger as well as second toe
• Sagittal plane any vertical line passing through body, parallel to
median plane
• Corronal
1 | P a g e plane vertical line passing through the body as right
Neuro-
angles
Anatomy to median plane
• Transverse
POLES: plane horizontal plane passing through
the body at right angles to the corronal and median
plane
• Transpyloric plane Horizontal plane at the level between L1 and
L2.
• Umbilical plane Horizontal plane at the level between L2 and L3/
through the umbilicus
 • Intertubercular plane Horizontal plane at the level of L5.
• Midclavicular line (MCL) Line extends downward from the
midpoint of the clavicle.
• Midaxillary line (MAL) Line extends downward from the midpoint
of the axilla

SECTIONS

• Transverse section Slices of body parts at right

angle to longitudinal axis of body or any part
• Oblique section Slices of body or part not cut along longitudinal
axis or at right angles to it
• Longitudinal section Runs lengthwise or parallel to long axis of
the body or any part

1|Page
CEREBRAL HEMISPHERES
Neuro-
Anatomy

LIMBIC LOBE:
DEVELOPMENT

LOBES

• Frontal lobe
o anterior to central sulcus
• Parietal lobe

o posterior to central sulcus

• Occipital lobe

o posterior to imaginary line between upper end of

parieto-occipital sulcus and pre- occipital notch
• Temporal lobe

o Inferior to lateral fissure and anterior to occipital lobe

• Insula (Island of Reil)

o Hidden beneath frontal, parietal and temporal opercula

o
 1|Page
Neuro-
Anatomy

Has a circular sulcus

• Frontal pole
• Temporal pole
•

MEDIAN LONGITUDINAL FISSURE

Occipital pole
• Divides left and right cerebral hemispheres

SURFACES OF THE CERE BRAL HEMISPHERE:

• Superiolateral
• Medial
•

LANDMARK STRUCTURES
SUPEROLATERAL SURFACE:
Inferior/basal

• Central Sulcus NB!!!!!!

• Lateral Fissure (of Sylvius)

o Divided into 3 rami

▪ Anterior ascending ramus
▪ Anterior horizontal ramus
 ▪ Posterior ramus
• Cerebellum
• Pons

• Medulla Oblongata

MEDIAL SURFACE:

• Corpus Callosum
• Cingulate Gyrus

• Thalamus
5|Page
Hypothalamus
• Neuro-
• Uncus
Anatomy

PRIMARY FUNCTIONAL CORTICAL AREAS

• Fornix (see later heading)

• Pineal body

• Dentate gyrus

•Also called limbic

system or visceral
brain
• Controls emotions,

behaviour and
memory
• Elements:
o Cingulate gyrus
o Parahippocampal
gyrus with its
medially directed
hook- like part, the
uncus
o Septal area in
the frontal lobe
o Fornix
o Medullary stria of the thalamus

o Stria terminalis in the interval between the caudate

nucleus and the thalamus (when the septum
pellucidum is removed)
o Habenular commissure
o Pineal gland
• The following components can
6|Page
be identified on the inferior
Neuro-
surface:
Anatomy

o Olfactory bulb and tract

o Medial and lateral olfactory stria
o Anterior perforated substance
• The hypothalamus is the

principal executive centre

of the system.
 FORNIX

LOBULES:
• Precuneus
o anterior to the cuneus
o between the
marginal sulcus
and the parieto-
occipital sulcus
• Cuneus
o Between the
parieto- occipital
sulcus and the
calcarine sulcus
• Paracentral
o Between paracental
6
8|Page
|and
Pag
Neuro-
marginal
e sulcus
• Superior parietal
Neuro-
Anatomy
• InferiorAnatomy
parietal

SKETCHS
CORPUS CALLOSUM
• Parts: (Anterior to
​ posterior)
o Rostrum
o Genu
Brocca’s Motor Speech
o •Corpus
 Primary auditory
o •Splenium
Function
o •Tapetum
Auditory association (planum temporale)
Mainly connects
• oo •Sublentiform
Wernicke’s lobes
auditory association
with each
o •optic
other Relations:
radiation
Primary visual
o Superior structures covered by
o •Postlentiform
Visual association
grey matter
o •forceps
Induseum
Primaryminor
somatomotor (in precentral gyrus)
griseum
(frontalis) is
• Primary somatosensory (in postcentral gyrus)
o Inferior structures in relation to
smaller
Sensory association (Behind postcentral gyrus)
cco •forceps major
• Frontal eye field
(occipitalis) is
• Premotor
larger
• Prefrontal cortex
•
9|PFunctional
ag Area Location Function
e Primary Somatomotor Precentral gyrus, between Voluntary motor activity of the
Neuro-
An
Area central and precentral sulci opposite side of the body
Divided into thirds:
-Lower 1/3 = face
-Middle 1/3= upper limbs
-Upper 1/3= trunk

Sensory Association Behind postcentral gyrus Associationa nd preception of sense

Area
Premotor Area - Medial surface - anterior to Gross coordination and voluntary
paracentral lobule motor activity

- Superolateral surface - posterior

ends of the sup, mid, inf frontal gyri
atom
Frontal Eye Field y Posterior end of middle frontal gyrus Conjugate eye movement
especially in the horizontal plane
Broca’s Motor Speech Pars Opercularis and Pars
Area Triangularis of the inferior frontal
gyrus
HABENULAR
COMMISSURE
Prefrontal Cortex Entire frontal lobe except motor areas
Primary Postcentral gyrus, between
Somatosensory central and postcentral sulci
Area
Somatosensory Ass. Superior parietal lobule
Area
Primary Auditory Area Anterior transverse temporal gyri,
within the lateral fissure, and for a
short distance onto the superior
temporal gyrus
Auditory Association Long posterior transverse,
Area immediately caudal to 10 hearing
area
Wernickes Auditory - Posterior part of superior temporal
Ass. Area gyrus
- Inferior parietal lobule
(angular and supramarginal
gyri)
Taste (gustatory) Area Parietal operculum, ventral to
primary somatosensory area
Primary and Ass Anterior pole of temporal lobe
Areas for Olfactation
Primary Visual Area Medial surface of occipital lobe
adjacent to calcarine sulcus,
extending onto suplat surface
- One is responsible for
formulation of meaningful
speech
- The non-dominant one is
rsponsible for emotional inflection
and tone
- Judgement, foresight and
perception
- Works with limbic system
Perception of major senses (pain,
temperature, pressure, crude
touch, fine
touch, proprioception and vibration)
- Integration of sensory input
for goal directed voluntary
movement and manipulation of
objects
- Synchronization of eyes and hands
Receives auditory radiations from
medial geniculate bodies of
thalamus
Has contact with frontal eye fields
Comprehension of sound
- Comprehension of spoken
language (hearing ass area)
- Written language (wernicke’s)
Taste sensation
Smelling
Visual input from lat geniculate
bodies
 Visual Ass Area Adjacent to prim visual area of - Depth perception and movement
temporal and occipital lobes on
suplat surface - Analysis of colour
Limbic Association Located rostrally along the medial Emotion and memory storage
Area edge of
the temporal lobe
Primary Vestibular area Information of the location

ASSOCIATION FIBRES
▪ “Head”
▪ Cricobulbular &
corticoreticular
fibres
o Posterior leg
▪ “Body”
▪ Corticospinal fibers
o Retrolentiform
o Sublentiform

MEDULLARY CENTRES

• Essentially the white matter of the cerebral hemispheres

• Made up of 3 different types of fibres

o Commissural fibres
▪ connect identical areas between hemispheres
o Association fibres
▪ connects parts within the same hemisphere
o Projection fibres
▪

COMMISSURAL FIBERS
 Most of the projection fibres pass through the internal
capsule
• Connect the same functional areas of different cerebral

hemispheres with one another

• Examples

o Anterior commissure
o Corpus callosum
o Posterior commissure
o Habenular commissure
o Fornices commissure
11 | P a g e
Neuro-
Anatomy
 ANTERIOR COMMISSURE
• Connects the temporal lobes

• Between the pre- and

postcommissural
columns of the fornix
• Associated with smell (olfactory) sense

POSTERIOR COMMISSURE
• Connects the pretectal areas of midbrain

• Between pineal gland (above) and superior colliculi

11 | P a g e (below)
Neuro-
Anatomy • Associated with the consensual light reflex

VENTRICLES
Cerebral aqueduct (of Sylvius)

Fourth ventricle

Median foramen (of Magendie) Lateral foramina (of Luschka)

Subarachnoid space and circulates down

spinal cord & around brain

Lateral
ventricles
Interventricular foramen (of Monro)
 Third ventricle
​

• Connects different areas in the same hemisphere

• Do not cross mid-line

• There are two types:

o Short association fibres

▪ Short pass from part of one gyrus to another
or from gyrus to gyrus around a sulcus,
shape is sharply curved – arcuate fibres
o Long association fibres
▪ Long run longer distances. Following are important:

• A few examples:

o Superior longitudinal fasciculi

▪ Frontal parietal
o inferior longitudinal fasciculi
▪ Temporal occipital
o Short association fibres (arcuate)
▪ gyri
o Cingulum
Arachnoid granulations
▪ cingulate gyrus
o Uncinate fasciculus
13 | P a g Superior sagittal sinus
Neuro-
e ▪ Frontal temporal
Anatomy
o External capsule
LATERAL VENTRICLES
between lentiform
nucleus and
Cerebral aqueduct
claustrum
o Extreme capsule between
Lateral foramen (Lushchka)
claustrum and insular cortex PROJECTION
FIBRES
• Course from superior to inferior and vice versa
 • A few examples:
o Corona radiate
o Internal capsule

o Spinal tracts

INTERNAL CAPSULE
• Situated between
caudate nucleus &
thalamus on medial
side & lentiform
nucleus on lateral
side.
• 5 parts:

o Anterior leg
▪ Associated
with head
of caudate
o Genu (knee)

Neuro-
Anatomy

THALAMUS
BASAL NUCLEI

structures most adjacent to the nuclei as seen on a horizontal

•

section of the brain

CAUDATE NUCLEUS

• Rostral portion unites with putamen

• Dorsolaterally to thalamus &

curls posteriorly around

thalamus
• Separated from lentiform

nucleus by internal capsule

•

LENTIFORM NUCLEUS
Has a head, body and tail
 •Lateral to internal capsule
• Consists of the:

o Putamen (darker in colour)

14 | Poa Globus
ge palliduss I and II
Neuro-
(lighter
Anatomyin colour) AMYGDALOID
BODY
•

CLAUSTRUM
Situated in temporal lobe, deep to uncus
• Thin plate of gray matter

• Lateral to lentiform nucleus

• Separated from lentiform nucleus by external capsule

• Role in visual attention

12 | P a g e
​

• Consists of a series of cavities that are filled with CSF

o 2 lateral ventricle
o Third ventricle
o Fourth ventricle
o Cerebral aqueduct
o Central canal
• Choroid plexus produces CSF
 14 | P a g e
Neuro-
Anatomy

CRANIAL NERVES

• One in each hemisphere

• Only central & inferior horns of lateral ventricles contain a
choroid plexus
• Parts:
o Anterior horn
o Body
o Trigone (antrum)
o Posterior horn
o
THIRD VENTRICLE
 Inferior horn
• In diencephalon
• Connections to lateral ventricles via interventricular foramina
•
FOURTH VENTRICLE

Connects to the 4th ventricle via cerebral aqueduct

• Superior border of the pons middle of medulla oblongata
• Dorsal to these structures stated above
• Diamond in shape (with the points of the diamond being the
openings)
o Superior narrows where the cerebral aqueduct enters
o Inferior narrows where the foramen of magendie/ median
Foramen
o Widest at the pontomedullary junction

o Laterally lateral foramen/ foramen of lushchka

14 | P a g e
Neuro-
Anatomy

FOR GENERAL FUNCTION S

Some Say Marry Money But My Brother Says Big Boobs Matter More

CN 3,7,9,10 are
parasympathetic

Median
foramen
(magendie)

DIENCEPHALON
 • Consists of:
o Epithalamus
o Pineal gland
o Thalamus
o Pulvinar
o Intermediate mass
o Metathalamus
o Hypothalamus
o Stalk of hypophysis (pituitary gland)
HISTO
RY
P arm
• Charles Darwin stated that something are carried are one
generation

1859 ​ to the next res

• 2 grey masses in lateral wall of 3rd ventricle.

• Pangenesis was coined
• All sensory tracts, except the olfactory nerves,Qhave
1868 arm
direct
projections to the thalamus.
• 1990
-
2003
1884
• Human Genome
• Project
Mendial explained inheritance via pea plants
EPITHALAMUS
TYPES OF GENETIC DIS
The thalamus has vital motor connections
EASES

• The pineal gland

1953
• Watson and Crick created the DNA model

METATHALAMUS

• down syndrome, turner & klinefelter identified

• This is composed of the medial and lateral geniculate nuclei.

1959

• Medial geniculate nuclei

14 | Po aauditory
ge
reflexes
Neuro-
o connected to the inferior colliculus via the brachium of the
Anatomy

inferiorPARTS
colliculus
• Lateral geniculate nuclei
o optic tract and the optic radiations
(geniculocalcarine fibres) for visual input to the
occipital lobe.
o
Median sagittal Vestibulocerebellum

HYPOTHALAMUS section of
cerebellum and
brain stem
Spinocerebellum
Cerebrocerebelum
Figure 5.22 (3)
Page 167

connected to the superior colliculus via the brachium of the Slide 31

 superior colliculus
• Nuclei of the hypothalamus are divided into four areas from
rostral to caudal:
o Preoptic area
o Supraoptic area – dorsal to the optic chiasm.
o Tuberal area – dorsal to the tuber cinereum.
o
SUBTHALAMUS

Mamillary area – dorsal to and including the mamillary

1 | P a g ebodies.
•GIte nise tcontinuous
ic with the tegmentum of the midbrain.
s
BRAIN STEM: OVERVIEW STAINING TECHNIQUES USED IN
CYTOGENETICS

• Consists of:
o Midbrain
o Pons
o Medulla Oblongata
• 4 main components throughout brain stem:
o Tegmentum (anterior)
▪ Contains all cranial nerves (except olfactory
and optic), reticular nuclei and fibre tracts
directed toward cortex.
o Tectum (posterior)
o Lumen
o
MIDBRAIN

Huge collection of descending fibre tracts

(afferent) on ventral aspect that travels from
cortex to spinal cord.
TECTUM OF THE MIDBRAI N
14 |Page
• contains 2 pairs of colliculi:
Neuro-
Anatomy
o Superior colliculus Acts as reflex centre for visual
impulses
 o Inferior colliculus Involved in auditory tract as reflex
centre

TEGMENTUM

•
PONS

Made up of the Cerebral Crus

• The Tegmentum of the Pons receives descending efferent fibers
from the crura of the
midbrain above, which split into the three longitudinal fasciculi
of the pons:
o Corticopontine fibres
1|Page
G e n eot iCorticospinal
c fibres
o Corticonuclear (corticobulbar) fibres
s

• The dorsal part of the pons is continuous with the

dorsal tegmentum of the midbrain above and the
medulla oblongata below.
• This contains:
o Nuclei of trigeminal (V), abducent (VI), facial (VII) and
vestibulocochlear (VIII) nerves
o Ascending afferent fibres
o
MEDULLA OBLONGATA

Reticular formation
• Lowest part of the brain stem
• Separated from pons by
pontomedullary junction

CONSISTS OF:

THE PYRAMIDS.
• These are two elongated elevations on either side of the
 fissure.
• Each is continuous with the anterior white column of the spinal
cord below.
•14
It contains
|Page descending corticospinal fibres for
voluntary
Neuro-
Anatomy
muscle action in the trunk and limbs, and
corticonuclear fibres to cranial nerve nuclei in the
medulla oblongata that are involved in voluntary
muscle activity in the head and neck.
THE PYRAMIDAL (MOTOR) DECUSSATION
• It is superficially located immediately below the
pyramids and consists of crossing fibres that will form
the lateral corticospinal tract.
• The ventral corticospinal tract forms the smaller part
of the tract, but stays ipsilateral and continues down
in the ventral white column.
THE VENTROLATERAL (PRE-OLIVARY) SULCI

• These are located lateral to the pyramids.

1|Page
Genetic
s
THE OLIVES
• These are smaller, ovoid elevations found lateral to
each ventrolateral sulcus and each contain an
olivary nucleus.
• Below, the olives continue down as the lateral white column of
the spinal cord
THE POSTEROLATERAL (POSTOLIVARY) SULCI

• Located lateral to the olives.

• The glossopharyngeal, vagal and accessory nerves exit
the medulla oblongata, from superior to inferior, in the
posterolateral sulci.
​
 STRUCTURES ON THE DORSAL SURFACE OF THE
MEDULLA OBLONGATA

• Dorsal tracts & nuclei

• Cuneate & gracile Nuclei
• Cuneate tubercle
• Gracile tubercle
• Cuneate fasciculus
• Gracile fasciculus

Cranial Nerve ORIGIN (NB! In Gen. function Function

second
year)
I Olfactory Glomeruli of olfactory Special sensory • Smell
bulb
II Optic At optic chiasma Special sensory • Vision from retina
III Oculomotor Interpeduncular fossa Motor • Somatic motor:
o Innervates palpebrae superioris,
superior, medial and inferior rectus,
inferior oblique muscles
• Visceral motor:
o Innervates sphincter pupille for
pupil constriction, cilliary muscles
4|Page for
Genetic accommodation of the lens for near vision
s
IV Trochlear Inferior of inferior Motor • Somatic motor:
colliculus o Innervates superior oblique muscle
V Trigeminal nerve branches
V1 Ophthalmic Both • Somatic sensory from cornea, skin of
forehead, scalp, eyelids, nose, mucosa of
nasal cavity and
aA paranasal sinuses
AaAAA
Middle cerebral
peduncle
V2 Maxillary • Somatic sensation from skin of face over
maxilla and upper lip, maxillary teeth, nose
mucosa, maxillary sinuses and palate
V3 Mandibular • Somatic sensation from skin of face
 overlying mandible including lower lip,
mandibular teeth, temporomandibular joint,
mouth mucosa and anterior 2/3 of tongue
• Somatic motor to muscles of
mastication, mylohyoid, anterior belly
of digastric
VI Abducent Medullopontine groove Motor • Somatic motor: abducts eyeball via lateral
opposite peduncle rectus muscle
VII Facial Posterior to olive Both • Somatic motor:
& lateral end of o Motor to muscles of facial expression
pontomedullary and scalp
juncition o Motor to stapedius of middle ear,
stylohyoid and posterior belly of digastric
• Special sensory
o ​Taste from lateral 2/3 of tongue and
palate
• Visceral motor
o ​Parasympathetic innervation of
submandibular and sublingual salivary
glands,
lacrimal glands and glands of nose and
palate

VIII Vestibulocochlear At pontomedullary Special sensory • Vestibular division – balance (proprioception)

junction, lateral and • Cochlear division – hearing
posterior to facial
nerve
IX Glossopharyngea Lateral to brainstem, Both • Somatic motor
l posterior to olivary o Motor to stlopharyngeus that
nucleus, upper part of helps in swallowing
medulla oblongata, • Visceral motor
between VIII and X o Parasympathetic innervation of parotid
gland
• Visceral sensory
o Taste from posterior 1/3 of tongue
• Special sensory
o Visceral sensation from parotid gland,
carotid body and sinus, pharynx and
middle ear
• Somatic sensory
o Cutaneous sensation from external ear
X Vagus 10 | P a gLateral to medulla Both • Somatic motor:
e oblongata, Posterior to o To muscles of pharynx, intrinsic
G e n e t i colivary nucleus, muscles of larynx, palate muscles,
s between IX and XI striated muscle in superior 2/3 of
esophagus
• Visceral motor:
father
Grandp
a age
son o ​Parasympathetic innervation to
smooth muscle and glands of trachea,
age 70 60 age bronchi, GIT,Prader-williAngel
coronary arteries and
syndrome
nodes of conduction system of heart
50
 Normal
• VisceralMaternal off
sensation: Maternal on Paternal
o ​ Paternal ​Fromon base ofoff
tongue,
pharynx,
Prader-willi larynx,
Maternal off trachea, bronchi,
Maternal heart,
on Paternal
esophagus, stomach and intestine off to left
Paternal
colic flexure
deleted
• Special sensory
Angel
o Maternal
​Taste fromoff epiglottis
Maternal deleted
and palate
Paternal on Paternal off
• Somatic sensory
o ​Sensation from auricle, external
acoustic meatus and dura mater of
posterior cranial fossa
XI Accessory Cell column in lateral Motor • Motor to sternocleidomastoid and trapezius
aspect of ventral grey
horn of spinal cord:
C1-
C5
XII Hypoglossal Exits ventrally from Motor • Motor to intrinsic and extrinsic muscles
medulla oblongata of tongue (Except palatoglossus)
through several roots
between olives and
pyramids

RHYMES

FOR NAMING
Oh Oh Oh To Touch And Feel Very Good Virgins After Hours

CEREBELLUM
PEDUNCLES

• 3 peduncles attach
10cerebellum
|Pag to brain stem
e
G e n eot iSuperior
c cerebellar
s
 peduncle –
midbrain
INDIRECT DNA

o Middle
DIRECT DNA cerebellar peduncle - pons.
TECHNOLOGY
o

VERMIS (REFER TO RED

NEURO BOOK PAGE 75
Inferior
HAS GOOD cerebellar
IMAGES NB!)
peduncle - medulla
oblongata
• Situated deep in groove (like a worm)
• Separates it into two hemisphere

Cut

VESTIBUBOLCEREBELLUM
• Arachcerebellum
• Floccilonodular lobe
• Controls eye movement

​
SPINOCEREBELLUM
• Paleocerebellum
• anterior lobe
 • muscle tone
10 | P a g
PONTOCEREBELLUM
e

•GsNeocerebellum
enetic
DISCONTINUOUS OR QUALITATIVE

• Posterior lobe
HEREDITABILITY
• Skills learnt
SYMPTOMS

Unfolded

Regulation of muscle tone, coordination of skilled voluntary movement

Planning and initiation of voluntary activity

Maintenance of balance, control of eye movements

 10 | P a g
e
Genetic
s

RESULTS OF CONGENITA L RUBELLA

CONGENITAL RUBELLA
SYNDROME

Vestibulocerebellum
Spinocerebellum
Cerebrocerebelum
Figure 5.22 (2)
Page 167
Slide 30

GENETICS SUMMARY
DOWN SYNDROME
• Was discovered by Dr. Langdon Down
 • Is a chromosomal abnormality
• Incidence rate 1 in 650/700
• Associated with advancing maternal age
• Trisomy 21

o ​XX, 47, +21

o ​XY, 47, +21

• Types of down/causes:
o Non-disjunction
10o |Translocation
Pag
e o Mosaicism
Genetic
s
APPEARANCE/SYMPTOMS

NEW BORN
• Large head
• Protruding tongue
• Hypotonic

GENERAL
• Large gap between big toe and second toe
• A single palmer crease
• Anal atresia
• Duodenum atresia
• Epicantic folds
• Flat nasal bridge
• Small, low set ears
• Small eyes
• Cardiac defects
•
Single crease on fifth finger
 MENTAL DEVELOPMENT
• IQ between 25 and 75
• At 40 – 45 development of Alzheimers

ROLE OF GENETICS
10
• It is important| in
P medicine
ag
• Most diseases
e are genetically based
• Helps with
G eunderstanding
netic and explaining the mechanisms
• Helps with
s diagnosis
• It is important in medical research

VAGIN OVARY
ADEFINITIONS
FEMALE GENETALIA
• Genetics study of biological factors and inheritance
• Human Genetics study of biological factors and inheritance in humans
• Medical Genetics Study of genetics in terms of medicine
• Clinical genetics genetics used to diagnose and treat disease and illness
• Genomics study of the genome

Incidences new cases

Prevalence all cases
Congenital present at birth

CYTOGENETICS
Telomeres
 Centrome

• Chromosomal
o Having an extra or less than normal number of chromosome
• Single gene
o One gene has an abnormality
• Multifactorial
o Many genes and factors (e.g. environmental) play a role in leading to the abnormality
• Mitochondrial
o The DNA in the mitochondria cause the abnormality
• Acquired somatic disease
o Genetic makeup is correct at birth but due to cell division errors and defects occur

10 |Pag
e
IMPACT OF GENETIC DI SEASES
Genetic
• Causes
s spontaneous miscarriages -40-50%
• Causes adult abnormality e.g. breast cancers

MEDICINE AND GE NOMICS

BENEFITS
• Improved diagnosis
• Early detection
• Rational drug design
• Gene therapy
• Pharmacogenomics
•
Is the study of chromosomes
• The cells have to be actively dividing e.g. bone marrow, chornic villi
• Person has 46 chromosomes:
o 22 pairs of autosome chromosome
o 1 pair of sex chromosomes
• Chromosomes are:
o Super coil of DNA
 o With proteins associated with it (histones)
o Nucleosome (beads on a string)
o Coils and connects to a scaffolding protein
o A dark band on a chromosome = densely packed DNA
o A little band on a chromosome = less densely packed DNA

KARYOTYPE

​
o ​
Is a set of a person’s chromosomes
• Types of chromosomes
o Metacentric chromosome

10 | P a
ge
Embryolog
y
GAMETOGENESIS

o Submetacentric chromosome
 o Acrocentric chromosome

CHROMOSOME NUMBERS
• Diploid = 2n (Somatic cells)
• Haploid = n (Gamete cells)
• 22 homologous pairs = autosomes
• 1 pair of sex chromosomes

MITOSIS AND MEIOSIS

Mitosis ​Meiosis
46 Chromosomes ​23 Chromosomes
Somatic cells ​Gamete cells
1 step process ​2 steps:
-Meiosis I
-Meiosis II

TISSUES USED FOR CYT OGENETICS

• Peripheral blood – lymphocytes
• Amniotic fluid
• Bone marrow
• Skin
**the cells must be actively dividing

SCREENING BEFORE BIR TH

• Amniocentesis
• Chorionic villus sampling

• G banding: Geimsa Staining

• Q banding: Quiacrine mustard for fluorescent microscopy
• R banding: Reverse of G
10
• C banding: Staining
| P a constitutive heterochromatin
ge
Embryolog
FISH – FLUORESCENCE IN SITU
y
HYBRIDIZATION

Summary of
• It is a technique used which label probes are hybridized to: Primordia
o Prophase l
Male o Metaphase Germ
 o Interphase
gametogenesis
• Advantages: don’t need rapidly dividing cells
cells
Type A
• Disadvantages: only get what you test (very specific) Type B
At spermatogoni
Primary
a (Stem
puberty Cells)
Spermatocyte
PROCESS s
• Use DNA and a probe to label a specific part
• Heat up denatures 2
Mieosis
• Cool don re-natures secondary
I
• Look under microscope spermatocte
• A whole chromosome or just a part of a chromosome can be labeled s

4 spermatids -
Mieosis
CGH – COMPARATIVE GENOMIC
->
large and
II
HYBRIDATION immoble

Spermiogenesis
mature
takes
CYTOGENETICS – ABNORMAL CHROMOSOMES spermatozo
days and is a

TYPES OFtemp ABNORMALITIES

dependent
• Numerical
• Structural
• Different cell lines

NUMERICAL

​
• Polyploidy
o An complete extra set of chromosomes
o For Example: Triploidy (3n)

o Tetraploidy (4n)

10 | P a
 ge
Embryolog
y

• Aneuploidy
o Is a single missing or extra chromosome
o For example:
▪ Trisomy – 1 extra Trisomy 21 – Down (47, XX, +21)

Trisomy 13 – Patau (47, XX, +13)

Trisomy 18 – Edward (47, XX, +18)

Klinefelter Syndrome (47, XXY)

▪ Tetrasomy – 2 extra
 ▪ Monosomy – 1 less Turner Syndrome (46, X)

10 | P a
ge
Embryolog
y

Summary of
Primordial Germ
Female cells
gametogenesis
oogonia ->
Pre-
CAUSES OF NUMERICAL ABNORMALITIES
die
Primary
• Polyploidy oocytes
natal
o Dispermy
off
Pre-
o Diploid sperm primodial
o Diploid egg follicle
• Aneuploidy
antral
zona pellucida secreted +
o Non-disjunction formation
off stratum granulosum
​ antr Primary foillicle
al
antrum forms + Cumulus
​ oophorus + two layers of
Theca
Pre-
STRUCTURAL Mature Graafian
ovulation follicle

​ meiosis I -> secondary

oocyte +
polar body
• Translocation
o Reciprocal translocation
meiosis II
▪ Balanced halts
Ovulatio
▪ Unbalanced
o Robertsonian
n Translocation
▪ Translocation of two long arms of an acrocentric chromosome namely: 13, 14, 15, 21 & 22
• Deletion
o Part of the chromosome is deleted
o Cri-du-chat syndrome 46, del 5 p13
• Duplication
o A piece of DNA is duplicated
o Charcot Marie tooth syndrome 46, dup17, p21
• Inversion
o pericentric – around the centromere causes heteromorphisms
o paracentric
• Ringed chromosome

DIFFERENT CELL LINES

• Constitutional – all cells
• Mosiacism – most cells, one cell line
 • Chimeric – 2 cell lines

FAMILIAR HYPERCHOLESTEROLEMIA
• Is an inheritable disorder involving a single gene
• Clinical characteristics
o ↑ LDL in plasma
o Cholesterol deposits in tendons and skin (xantomatas)
o High risk of atherosclerosis

before 25 10 | P55
​after a
ge
• Risk factors
oEmbryolog
Family history
y
o Smoking
o Diet
If fertilized and successful
o Stress
implantation has taken
• Treatment place then trophoblast
o Diet changes secrets hCG, which tells
o Stress ↓ The theca layers form the the hypothalamus to
o Medication corpus luteum, max size secrete LH to maintain
th
at 25 day
o Lipid modifying treatment pregnancy
• Causes
o Reduced/ defective biosynthesis of LDL-receptors
o Reduced/ defective transport of the receptors from the ER to the Golgi If unfertilized corpus
o Abnormal binding to the LDL receptor luteum is broken down
o Abnormal internalization of LDL receptors and forms a scar on the
Cell enlarges to about 25mm
ovaries surface called the
corpus albicans as no
hCG released no LH
oestrogen + progesterone
stops cycle starts again
SINGLE GENE INTRODUCTION
• Gene – a region of inheritability
• Allele – a form of a gene
• Locus – a place where the allele is found
• Genotype – the genetic composition
• Phenotype – outward characteristics
• Homozygous – 2 of the same alleles
• Heterozygous – 2 different alleles

PEDIGREE
• Is a family tree
• Main person = proband
• 3 generations

​
Homozygous Heterozygous
 Mutation in both mother Mutation in only one parent
and father
Autosomal dominant Autosomal dominant
LDL-C = 12 mmol/L + LDL-C = 5-12 mmol/L
Coronary artery disease Coronary artery disease

A aA AA

10 | P a
ge
Embryolog
y

TYPES OF DISORDERS

• Autosomal
• Sex linked

DOMINANTS AND RECESS IVE

• Is determined by the phenotype
• Dominant = heterozygous will express the phenotype, if homozygous more severe phenotype
• Recessive = homozygous in order to express phenotype, if heterozygous person is a carrier
• X linked recessive = mostly in males (as only 1 X chromosome) females normally carriers
• X linked dominant = heterozygous females express and males with mutated X will express
• Y linked = Only in males

SINGLE GENE INHERITANCE

AUTOSOMAL DOMINANT
• Male and females equally affected
• Vertical transmission
• Grandfather father daughter
• Heterozygous for disorder will express phenotype
 •
Homozygous for disorder will express a severe phenotype
• Affected person normally has affected parents
• Exceptions to this rule due to:
o New mutation (de nova)
o Non-penetrance or reduced penetrance
▪ Phenotype is reduced or not shown at all
▪ “skipping a generation”
▪ Due to mutations in other genes
• Variable expressivity
o The severity differs from person to person
o E.g. Down syndrome
• Pleiotropy
o The disorder affects more than 1 organ
o E.g. Tubercular Sclerosis

AUTOSOMAL RECESSIVE
• Horizontal transmission
• Normally due to consanguity
• Have to be homozygous to express disorder

a A
a aa Aa
A aA AA
10 | P a
ge
Embryolog
y
• Heterozygous for disorder = person is a carrier
• Pseudodominance
o Appears dominant but is actually recessive
• Locus heterogeneity
o More than one gene is mutated and can cause the disorder
• Mutational heterogeneity
o The gene is mutated in different ways but still causes disorder
o Compound heterozygous

X LINKED RECESSIVE

• Mostly affects males

• Affected males can’t give to sons
• Females normally carriers
• Duchene muscular dystrophy, colour blindness and heamophilia
• Affected females can be due to:
o Skewed inactivation
o Translocation
o Homozygously effected
 o Numerical disorder (e.g. turner)

X LINKED RECESSIVE
• Males and females can be effected
• Affected males can’t give to sons females are normally carriers
• Exceptions to the rule: Females affected when:
o Homozygous for disorder
o Numerical X-chromosome disorders
o Heterozygous for females to express but normally less severe due to skewed inactivation

Y LINKED (HOLANDRIC)
• Only in males
• Fathers give to all sons

NON – MENDELIAN INHERITANCE

4 TYPES:
• Anticipation
• Mitochondrial
• Uniparental disomy
• Genomic imprinting

ANTICIPATION
• Due to unstable tandem triplet repeats
• On set is more progressive in each generation

10 | P a
ge
Embryolog
y

Prechordal plate:
Circular thickened region in endoderm
• E.g. Fragile X syndrome
near cranial end of embryo.
• Pre mutation full mutation
Buccopharyngeal membrane will
temporarily develop from it. Cloacal
MITOCHONDRIAL membrane:
• Mothers give to all children Circular area near caudal end of
• Sons don’t pass EMBRYONIC
it on to their children embryo (ectoderm and
INTRA MESODER M
• MtDNA in normal person is only of one type endoderm), widening of hindgut.
• 2 populations of mtDNA causes effects Septum transversum:
• Has a variable expression nature Thick transverse band of intra-embryonic
mesoderm, lies before cephalocaudal
folding and cranial to prechordal
UNIPARENTAL DISOMY
plate.
• Uniparental isodisomy
 o 2 of the same copies of a homologues chromosome from one parent
Allantois:
• Uniparental heterodisomy Diverticle of caudal wall of yolk sac,
o 2 of the different copies of a homologues chromosome from one parent
projects into connecting stalk.
• Example Hemophilia father with an effected son Associated with development of
urinary bladder
GENOMIC IMPRINTING Intra-embryonic mesenchyme:
Multipotential embryonic connective
• Some genes are switched on or off
tissue, arises from any germ layer.
• If switched off on the paternal chromosome
= paternal imprinting
Can form nearly all types of tissue.
• If switched off on the maternal chromosome = maternal imprinting

DNA DIAGNOSIS
• Restriction enzymes
• Southern blotting – proteins (electrophoresis, agarous gel)
• Northern blotting – RNA
• Western blotting – Protein
• Polymerase chain reaction
• Cloning

• Detection of known or common mutation

• Look for a specific mutation
• Purpose:
o Risk of current pregnancy being affected
o Carrier risk
o Predictive testing for adult onset condition
•
Unaware of where the gene is but know which chromosome and arm it is associated with
• Use markers (polymorphism)
o Restriction length fragment polymorphism
o Hyper variable DNA length polymorphism
10 |P a
▪ Tandem repeats
ge ▪ Microsatellite (di, tri, tetra)
Embryolog
▪ Minisatellite (10-15)
y
• Uses southern blotting NB! to have accurate pedigree
• Linkage is formed when LOD score >3 and a marker is found that is always inherited with the disease

Mutation detection Genetic linkage

Pedigree not needed Gene does NOT need to be
identified
Identified by confirming Few markers needed
mutation
Expensive Accurate pedigree is NB!
​
• Causes
o Chemical
o Spontaneous
o Replication error
• Point mutation
o Transition (purine to purine or Pyrimidine to pyrimidine)
o Transversion (purine to pyrimidine)
NOTE: Purine = A & G NOTE: pyrimidine = T & C
• Point mutation
o Silent – no effect
o Missense – depends
o Nonsense – serious
o RNA processing
o Regulatory
• Insertion or deletions
o Triplet repeat expansion
o Large deletion/ insertion due to recombination

MULTIFACTORIAL INHERITANCE
• More than 1 factor at play
• Environmental and genetic
• No one gene is more important than another
• Examples

Congenital
​
Acquired

Cleft lip and palate ​Asthma

Congenital dislocation
of ​Depression the
hip ​Hypertension
Talipes ​Epilepsy
Neural tube defects ​Diabetes
Pyloric stenosis

CONTINUOUS OR QUANTITATIVE
• Normal phenotype
10
• E.g. eye colour
|Pa
ge
​ Embryolog
y
 • Congenital defect and adult disorder
• Environmental + genetic factors = liability
• Draw graph

• There is a threshold of liability to determine whether or not you have the disorder or not
= threshold liability model
• Reoccurrence rate (RR) = √population incidence
• Factors affecting RR:
o Severity
o Number of people affected
o Closeness
o Sex

• Multi-factors
• The higher the hereditability the more genetic the disorder
• 1.0 for genetic only
• 0.0 for environment only
• Between 0.0 and 1.0 combo
• Twin studies NB!
o Monozygotic twins = Same DNA, diff environment
o Diazygotic twins = Deff DNA,
Same environment
o Concordance = both twins got it
o Disconcordance = 1 twin got it

CHRONIC MYELOID LEUKEMIA

• Tired
• Abdominal discomfort
•
Weight loss

CLINICAL SIGNS
• Enlarged spleen
 • <<< Platelets
10
• >>> WBC | P a
g e of part of chromosome 9 onto chromosome 22 forming Philadelphia chromosome
• Translocation
Embryolog
y
TREATMENT
• Conventional treatment
o Kinase inhibitors
o Low dose of chemo
• Myeloablative Therapy

o ​Bone marrow transplant

• Other

o ​Interferon – X

POPULATION GENETICS
• NB! in understanding how genetics occurs in a population
• Allele and genotype frequency
• Determine how it impacts the population

HARDY – WEINBERG LAW

• Large population
• No mutation
• No selection
• Random mating
• No migration
• Equilibrium = p2 q2 and 2pq stays constant
• p2 + 2pq + q2 = 1
•p+q=1
• Disturbing:
o Selection
▪ T – normal
▪ C – over
o Non-random mating
▪ Positive or negative
​
▪ Consanguniy
▪ Assortive mating
o Mutation
o Gene flow
▪ Intermarriages
o Small population
▪ Genetic drift
▪ Founders effect
 RUBELLA
10
• Rubella virus
|Pa is a togavirus
BRAIN DISORDERS
• Causes
g eviraemia
• RashEmbryolog
after 5-7 days
HYDROCEPHALUS
y

• If a pregnant woman develops rubella before 17 weeks

• Placenta becomes infected
• Maternal viraemia leads to fetal viraemia
• Disseminated fetal infection
• Before 11 weeks – 90% affected
•
Microcephaly

OTHER DEFECTS
• Sensorineural deafness
• Growth retardation
• Radiolucent bone disease
• Hepatosplenomegaly
• Hematological abnormalities: thrombocytopaenia, purpura
• Pneumonitis
• Endocrine dysfunction: Insulin dependent diabetes mellitis, thyroiditis
• Subclinical infection also present

DIAGNOSIS
• Confirmation of maternal infection: Rubella specific IFM antibodies

NON-SPECIFIC IN INFANT:
• Thrombocytopenia, anaemia, hepatitis, radiographic changes, cells and raised protein in CSF

​
• Between 11 and 16 weeks – 35% affected ​ ​
SPECIFIC IN INFANT:
• Isolation of virus from pharyngeal swab, CSF, lens,
urine or any other tissue

​
EYE DEFECTS
• Cataracts
• Micropthalmia
• Glaucoma
• Retinitis
 HEART DEFECTS
• Patent ductus arteriosus
• Atrial septal defect
• Ventricular septal defect
• Peripheral pulmonic artery stenosis

CENTRAL NERVOUS SYSTEM DEFECTS

• Mental retardation
• Meningoencephalitis
• Progressive rubella panencephalitis

PREVENTION
10
• Immunization of
| Pchildren
a – MMR
• Immunization
g e of young girls – Rubella
Embryolog
• Limit contact with infected persons
y
• Immunoglobulin not of value
• Termination of pregnancy

MANAGEMENT
• Neonate-self limiting
• Multidisciplinary approach-manage cardiac lesion, cataract, glaucoma, mental retardation and deafness
• Prognosis depends on the timing of the infection

Apert syndrome
SIGNS

• Premature fusion of the cranial sutures

• Abnormalities of the hands and the feet
syndactyly

CAUSE

• Caused by a mutation in the gene that codes for

fibroblast growth receptor gene specific FGFR2

OTHER CONDITIONS WITH SIMILAR

PRESENTATION

• Crouzon syndrome
 • Pfeiffer syndrome

MANAGEMENT

• Supportive
• Counselling – autosomal dominant
• Surgery
o open cranial sutures
o divide the fingers and toes

10 | P a
ge
Embryolog
y Function of amniotic fluid
Shock absorption

EMBRYOLOGY Prevents dehydration

Organ development

DEFINITIONS

EMBRYOLOGY:

• The study of embryos (3rd to 8th week).

•
EMBRYO:

Human embryology, focuses on human development from

fertilization to birth.
• This is an organism in the period between the 3 to the 8 week of
rd th

development
FOETUS:

• This is the unborn baby of a viviparous organism between the

beginning of the 9 week of
th

CONCEPTUS:

development up till full term

• The products of conception namely embryo and its membranes.
ZYGOTE:

•
TERATOLOGY

A diploid cell formed by the union of the male and female gametes
• The section of embryology concerned with the formation,
development, anatomy and

classification of congenital (birth) defects

10 | P a
ge
Embryolog
• y

UTERUS

Smooth muscle
• Thick walled, hollow muscular structure
• Pear shaped
• 8 cm
• Vagina + uterus = birthing canal
• 3 parts:
o Fundus
o Corpus
o Cervix
• Uterus wall has 3 layers:
o Myometrium
o Perimetrium
 o Endometrium
▪ Undergoes changes during menstruation
▪ If unfertilized the mucosa layer is broken down
***Pouch of Douglas (Recto-uterine pouch) NB! In
absorptions***

•
• 2 of them
• ½ size of testis
• NB! in oogenesis
•
UTERINE TUBES

Progestone and
estrogen secreted
here
• 2 of them
• Connects ovary to uterus
• 5 parts:
o Isthmus
o Ampulla
o Intramural part
10o |Infundibulum
Pa
ge
o Frimbria “Little fingers that catch the eggs”
Embryolog
y
• Abdominal ostium opening of the infundibulum into the
peritoneal cavity (ectopic pregnancy)

MALE GENETALIA
TESTIS

• 2 of them
• Divided into lobules In the lobules there is seminiferous tubules
 • This is where spermatogenesis occurs
•
EPIDIDYMIS

Secrete testosterone (leydig cells)

• Head, body, tail
• Storage of spermatozoa
•
DUCTUS DEFERENS

Provides nutrients and fluid for movement

• Smooth muscles contracts to propel spermatozoa
SEMINAL VESSE LS

into ejaculatory ducts

• Secretions released for nutrients and mobility of
sperm
•
EJACULATORY DUCT

Joined to ejaculation duct

• Passes through prostate
PROSTATE

• Watery substance that adds to seminal fluid

​

•
SEMINAL FLUID
10 |Pa
The prostatic urethra passes
ge
Embryolog
through it and the ejaculatory
y

duct opens into the urethra

• 10% spermatozoa
• 90% secretions from epididymis,
seminal vesicles, prostate,
bulbo-urethral glands
 • 3,5ml = 350million sperms

ROUTE OF SPERM

• Testis – seminiferous tubules

• Epididymis
o Head
o Body
o Tail
• Ducts deferens
• Ejaculatory duct
• Urethra
o Membranous
o Prostatic
o Penile
• Vagina
• Uterus
o Cervix
o Corpus
10 | P a
• Uterine
ge tube
o Isthmus
Embryolog
y
o Ampulla
 *****FERTILIZATION
*****

• Is a process of maturation of the germ cells in preparation for

fertilization
• Males = spermatogenesis
• Females = oogenesis
• Two main functions:
o ½ number of chromosomes (haploid number)
o Reduce the amount of cytoplasm
▪ In ovum keep all cytoplasm
▪
SPERMATOGENESIS

In sperm loss most of the cytoplasm

• Occurs in males
• Is a process of maturation spermatogonia undergo to mature into
spermatozoa
• At the beginning of the 3 weeks, the primordial germ
rd

cells migrate and differentiate to the gonad area. They

reach the gonad area by the 4th week
AT BIRTH
• Testis chord is solid
• 2 types of cells that are undifferentiable
• Dormant till puberty
AT PUBERTY
• Primordial cells differentiate into speramatogonia
• FSH released
• Cells differentiate into spermatogonia
• Testosterone completes the process
 SPERMATOGONIA GIVES RISES TO TWO T YPES OF CELLS:
10 | PA:
• Type a spermatogonia (stem cells)
ge
• Type B: primary spermatocytes
Embryolog
y
o 1st meiosis
o 2 secondary spermatocytes
o 2nd meiosis
o 4 spermatids
SPERMATOGENESIS
• Series of changes that spermatids undergo to form mature
spermatozoa
• Spermatids are large and immobile thus the following is lost
o Cytoplasm reduced
o Head, tail, body formed
o Acrosome enzyme is acquired (NB! Reaction for penetration
into the oocyte)
• 4 mature spermatozoa
• Then stored in the epididymis
​
 OOGENESIS

10
PRE NATAL
|Pa
ge
• At 3 weeks the progenital cells differentiate and move to gonad
rd
Embryolog
y
area
• They reach the gonad area by the 4 week
th

• The cells differentiate into primary oocytes and oogonia

• The oogonia proliferate and form egg nests
• Primary oocytes replicate and halt in the 1 meiosis cycle
st

• 5 months max number of primary oocytes approx. 7 million,

hereafter degeneration begins
• At birth primary oocytes have a flat follicular layer covering =
primitive follicle
• NO OOGONIA SURVIVE and approximately 2 – 7 million primary
oocytes survive
POST NATAL
• Only 40000 oocytes are present at puberty and only 400-500 will
mature
AT PUBERTY
• 15 – 20 released and begin to mature
• Only 1 fully matures
• 3 stages of maturation:
​

o Primary/ pre-antral
o Secondary/ antral
o Pre-ovulatory
• Primitive follicle under goes the following in the Pre-antral stage:
 o Zona pellucida secreted
o Stratum granulosum forms
• The Primary follicle now formed and then undergoes the following
changes in the Antral stage:
o Liquor follicles unit and form an atrium
o Cumulus oophorus surrounds the oocytes
o Acquires two layers, Theca interna (oestrogen) and theca
externa (connective tissue)
• The Mature Graafian follicle is now formed and enters the Pre
ovulation
10 | P a stage:
ge
o 1 meiosis completed
st
Embryolog
y o 2 daughter cells form

▪ Secondary oocyte all the cytoplasm

▪ Polar body no cytoplasm
o Enters secondary meiosis and halts at metaphase until
fertilized
o Ovulation occurs
o Ovum sheds theca layers and these layers become known as
the corpus luteum
​

o Meiosis II is completed on fertilization

 REPRODUCTION CYCLES

• Only in females
• Phases of 2 cycles correlate with each other
• 2 cycles occur simultaneously
• Influenced by hormones:
10 o |Follicle
Pa
stimulating hormone (FSH)
g eo Oestrogen
Embryolog
y o Luteinising hormone (LH)
o Chorionic Gonadotropin (hCG)
o Progesterone
​
 Sperm ​Ovum
Size Small Large
Motility Yes No
Cytoplasm 10
Little
|Pa Lots
Chromosomes
g e22 + X/Y 22 + X
Duration Embryolog
Puberty to death Puberty to menopause
y
​

1 TWO WEEKS OF HUMAN D EVELOPMENT

ST

FERTILIZATION

• Has to occur within 24 hours of ovulation

• Sperm meets ovum – acrosome reaction
• The male and female gametes form a zygote (it is diploid with
determined sex)
• Ovum performs zona reaction so that no other sperms will
 penetrate it
• Meiosis 2 is completed
• Two pronuclei come close Envelope lost DNA replicated 1 st

mitosis
CLEAVAGE

• Mitotic divisions begin 2 4 8

• 12 cells + = a morula
• Liquid penetrates zona pellucida forming a blastocele
• This then results in 2 layers to form
o The trophoblast (outer)
o The embryoblast (inner)
• This is now known as the blastocyte
• 5 – 6 day the zona pellucida is removed and thus ready for
th th

implantation
IMPLANTATION

• Day 7 to day 12
• Implants in superior, posterior part of uterus
• Endometrium in secretory phase
• Trophoblast attaches and digs into the endometrium
o The endometrium has three layers:
10 | P a ▪ Stratum compactum
ge
Embryolog▪ Stratum spongiosum
y
▪ Stratum basalis
• Decidua reaction and the three layers become known as:
▪ decidua parietalis (opposite side of the uterus)
▪ decidua capsularis (separates blastocyte from uterus
cavity)
▪ decidua basalis (base of the blastocyte)
• NOTE: trophoblast secrets hCG which acts on the
hypothalamus which tells pituitary glands to secrete
FSH and LH this tells the corpus luteum to continue to
 secrete the progesterone and oestrogen the corpus
luteum will release the hormones till the 4 month
th

thereafter the placenta will take over

• Trophoblast forms two layers
o Cytotrophoblast (inner)
o Syncitotrophoblast (outer)
​

• Syncitotrophoblast has proteolytic enzymes to dig further into

endometrium
NUTRIENTS

• The zygote depends on diffusion

• First few days uses the glycogen in the cytoplasm of the ovum
• Diffusion distance of <5mm is possible
• Decidua reaction
PRIMITIVE URETHRA -PLACENTAL CIRCULATIO N

• Maternal blood starts to circulate the lacunae in the

syncitotrophoblast on 17 day th

• Diffusion greater
• Some bleeding my occur and this may cause some
confusion as it is in time with menstruation cycle
BILAMINAR DISC

• 2 week implantation has occurred and the bilaminar disc starts to

nd

10 | P a
develop
ge
• Embryoblast
Embryolog
y
differentiates into:
o Epiblast
Hypoblast layer secretes the – columnar
primitive yolk sac,othen
Hypoblast – cuboidal
heuser’s layer forming the
secretes

sace
• Hypoblast secretes a hearsum layer and the primitive yolk sac
a secondary layer definite yolk

forms
 • Hypoblast then secretes a second layer the extra
embryonic endoderm and the definite yolk sac is formed
• Embryo is between the yolk and the aminon sac
• Trophoblast secrets an extra embryonic mesoderm layer between
itself and yolk sac
• Liquid vacuoles come together in the extra embryonic
mesoderm layer and forms a cavity called the extra
embryonic coelom
• This separated the extra embryonic mesoderm into two layers:
o Somatoplueric (inner)
o Splanicoplueric (outer)
• The coelom does not completely surround the embryo and as a
result a chord is formed
• The prechordal plate is formed at the end of the 2 week nd

3 WEEK
RD

GASTROLATION

• 3 week 3 layers are formed

rd

Fluid penetrates
• Starts with the
zona pellucida, fluid primitive streak due to
the epiblast
unites, forms
blastocele.
proliferating in all directions
and forming the intra embryonic
Inner mass of
cells = embryoblast
mesoderm
Outer mass of cellsbetween
= the two layers of
theImplantati
bilaminar disc (i.e. between the
Epiblast onand the hypoblast)
​ Blastocyte
attaches to the
endometrium,
• NOTE: doesn’t form where notochord, cloccal membrane and
trophoblast
secretes hCG
prechordal plate is
acts on
hypothalamus
• The Epiblast and hypoblast changes names:
LH
+ FSH released
27
o Epiblast = ectoderm
|P a
corpus luteum
ge
o Hypoblast = endoderm
sustains
Embryolog
pregnancy
y
NEURALISATION
• Formation of the neural tube
• The ectoderm divides into the
surface ectoderm and neuro-
ectoderm (view segmentation)
• Process NB!
o Slipper shaped hardening
between the caudal end
of the prechondal plate
and primitive node
forming the neural plate
o More folding the neural groove forms
o Neural crest cells form and
proliferate in all directions
o Further folding occurs and
the two folds join at the
middle to form the neural
tube
o Caudal and cranial ends
are open and elongate
only close on 27 day
th

o The neural tube contains the spinal chord

o CNS forms from this tube
▪ Brain
▪ Spinal chord

•
 • The following develops form the mesoderm:
27 o |Bone
Pa
g eo Cartilage (no for the face!!)
Embryolog
y o Connective tissue
o Blood vessels
o Lymph vessels
o Smooth and striated muscles
o Kidneys
​

o Sex glands
o Spleen
o Diaphragm
• Mesoderm divides into 3 bands:
o Paraxial mesoderm
o Intermediate mesoderm
o Lateral plate mesoderm
• Paraxial mesoderm
o Divides into somites
(42 to 44 somites
develop)
o Each somite divides into a:
▪ Sclerotome one vertebra
▪ Dermatome specific of dermis
▪ Myotome skeletal muscle
• Intermediate mesoderm
o Urogenital system
• Lateral plate mesoderm
o Intra-embryonic coelom (view below)
o Somatic lateral + ventral walls of the trunk
o Splanchnic endoderm + splanchnic = wall of the gut
INTRA EMBRYONIC COEL OM
 • Formation of a cavity
• Horseshoe cavity
• In the lateral plate part splitting it into two layers:
o Somatic
o Splanic
• All cavities form here:
27o |1P aPericardial
ge
o 2 Pleura
Embryolog
y
o 1 Peritoneum
SEGMENTATION

ECTODERM
• Neural
o Brain
o Spinal chord
• Neural crest cells
o C cells of the thyroid
o Odontoblasts
​

o Glial cells
o Schwann cells
o Adrenal medullary
o Meninges (forebrain only)
o Melanocytes
o Smooth muscle cells to blood vessels of the face
o Cranial nerve ganglia
o Connective tissue of face and skull
• Surface
o Epidermis
o Eyes
o Hair
 o Nails

ENDODERM (ENDO = IN, OR GANS INSIDE)

• Foregut
o Esophagus
o Stomach
o Liver
o Gallbladder
o Pancreas
o 1 and 2 duodenum
st nd

• Midgut
o 3 and 4 duodenum
rd th

o Ileum
o Jejunum
o Ascending colon
o 2/3 of transverse colon
• Hindgut
o 1/3 of transverse colon
o Descending colon
o Sigmoid colon
o Anus
PERIOD 3 8 WEEK TH

FOLDING

• Flat disc becomes a cylindrical body

• This is the beginning of the general body formation
• Cephalocaudal folding along the length
• Lateral folding along the width
​

• Is due to the growth of the brain and the somites as well as the
enlargement of the organs
 LATERAL FOLDING

• Due to the development of the somites

• Ectoderm folds fusing whole embryo covered by
ectoderm but does not form where umbilical ring is
• This process pulls yolk sac in

CEPHALOCAUDAL FOLDIN G

• Head
o Folding due to brain growth (especial forebrain)
o Helps form the heart bulb (helps move the heart
primordium to the ventral position) and the
pharyngeal arches
​
• Tail

o Moves the connecting stalk from a distal to a ventral position

o Allantois project into connecting stalk
​

VITILLINE DUCT

• During lateral folding yolk sac under goes some changes

• Yolk sac pulled inwards
• The narrowing part is the vitilline duct
• It will later form part of the umbilical chord
UMBILICAL CHORD

• Consists of:
o Umbilical vessels
o Allantois
o Vitilline duct
o Connecting stalk
 o Original connecting stalk
• Approx. 60cm
• Chord like
​

A medical condition in which there is an

abnormal accumulation of cerebrospinal fluid
(CSF) in the ventricles, or cavities, of the brain.
This may cause increased intracranial pressure
inside the skull and progressive enlargement of
the head, convulsion, tunnel vision, and mental
disability. Hydrocephalus can also cause death.
MENINGOCELE

Hernial protrusion of the meninges

through a defect in the cranium (cranial
m.) or vertebral column (spinal m.)
MICROCEPHALI

Microcephaly is a neurodevelopmental disorder

in which the circumference of the head is more
than two standard deviations smaller than
average for the person's age and sex.
ANENCEPHALUS

Congenital absence of most of the brain and spinal cord.

 PLACENTA FORMATION

• As the embryo develops the need for oxygen and

nutrients increases and thus the placenta has to form
• Has a maternal part (from decidua basalis) and fetal part
(trophoblast)
• At 4month fully developed
FETAL PART

• During implantation trophoblast differentiates into two

layers which become the Syncitium – lacunae
• Syncitium erode deeper and the maternal blood fills the lacunae
(17 day) th

• Trabeculae between the lacunae is where villi will form

• The chorionic cavity replaces the extra embryonic coelom
• The chorion consists of:
o Somatopleuric (chorion plate)
o Cytotrophoblast
o Syncytiotrophoblast
• Primary villi
​

Core of cytotrophoblast
o

o Layer of syncitum
• Secondary
o Chorion plate grows in

• Tertiary
o Blood vessels form
 o Mature villi
▪ Tree like
▪ SA up
o Cytotrophoblastic shell
o Chorion fondosum
contains many villi
o Chorion laeve no villi
MATERNAL PART

• Deciduas basalis
• Lacunae coalesce and then known as intervillus spaces
• 15 – 20 cotyledons
GENERAL STRUCTURE OF PLACENTA

• 15 – 20cm in diameter
• 3cm thick
• Discoid
• Maternal and fetal part
• Expelled at birth
BARRIER OF THE PLACENTA

• Not a true barrier anything smaller then 1000Da can cross it

• It separates the maternal blood from the vital blood
• Initially consists of:
o Syncytiotrophoblast
o Cytotrophoblast
o Mesoderm
o Endothelium
• As development carriers on:
o Endothelium
o Syncitium

NB! TABLE OF BREAK DOWN

FUNCTION
 • Gas exchange Characteristics
​ Simple squamous Single layer
Irregular
Nuclei centrally placed (looks like an
egg)
• Immunity – IgG Examples
• Hormones Alveoli
• Excretion – 5 months drinks amnion NB! for development of
kidneys
• Nutrients
FOETAL MEMBRANES

• Amnion cavity enlarges

• Embryo is suspended in the fluid
• Chorionic cavity is replaced by the amnion cavity
• Amnion comes in contact with chorion and forms the
amniochorionic membrane
PRENATAL SCREENING TECHNIQUES:

• Ultrasonography – placenta and foetal growth

• Amniocentesis – Congenital malformations
•
CLINICAL CORRELATES:
Chorionic villus sampling – Chromosomal abnormalities e.g. Down
• Hydramnios/Polyhydramnios – excess amniotic fluid
• Oligohydramnios – Decrease in
amount of amniotic fluid, may result
in clubfoot due to compression
• Amniotic bands – Tears in amnion,
encircle body parts, limb may be
amputated
•
VASCULAR SYSTEMS
 ANGIOGENESIS

Umbilical cord – may wind around

foetus,
10 | P a lessening blood supply,
ge
amputating limbs. May tear placenta
Histolog
away
y from uterus too early and
result in hypoxia.

• Mesenchymal cells differentiate into angioblastic islands

• They elongate and form the endothelium
• Due to the:
o Increase need of 0xygen and nutrients
o Genetic factors
o Haemodynamic factors
• 3 week need increases
rd

• Heart tube forms in floor of intra embryonic coelom

• Arteriole pole – aortic arch
• Venous pole – umbilical vein
• 4 week heart beats
th

• Mother and baby blood never mix!!!

• Umbilical veins transports oxygenated blood from placenta to the
embryo
​

CIRCULATION

• Adult and embryo circulation similar just some shunts are used in
the embryo
• Shunts some organs out of circulation as the mothers
organs/placenta perform task
• Circulation as follows:
o Placenta
o Umbilical vein
o Ductus venosus – shunts liver
 oIVC
oRA
o Oval Foramen – shunts lungs
o LA
o LV
o Aortic arch
o Descending arch
o Umbilical artery
o SVC also brings blood back
10 |Pa
g eo RA
o RV
Histolog
y o Pulmonary trunk

o Ductus anteriosus – shunts lungs

• Some blood does go to organs to maintain them
• Blood is less oxygenated form
o IVC
o SVC
o Pulmonary vein
o Portal vein
o All goes to aorta
• Changes at birth
o LA up, RA down oval foramen closes
o Ductus anteriosus spasms and closes
o Structures form remnants

Foetal structure Adult remnant Position in Foetus

Umbilical vein Ligament teres hepatis Placenta, through umbilicus
(round ligament of liver) to
porta hepatis
Ductus venosus Ligamentum venosum Porta hepatis to inferior
vena
cava
Ductus arteriosus Ligamentum arteriosum Pulmonary trunk to aortic
arch
Oval foramen Fossa ovalis Interatrial septum
Umbilical arteries Medial umbilical ligaments Aorta to umbilicus
 EMBRYOPATHY

• Morbid condition effecting the normal process of development

• Being able to explain abnormalities:
o Removes quilt
o Prevent similar situations
o Identifies teratogens
o Helps avoid teratogens
o Questions about childs future
• NB! For counselling of parents of teratology
ABORTION

• Refers to the early birth of a foetus before it is able to sustain life

10its
on |Pa
own
ge
• Spontaneous
Histolog
= natural
• Induced
y = before 20 weeks
• 50% of all conceptions end in spontaneous abortion
• 50-60% of these are due to chromosomes abnormalities
CONGENITAL ABNORMALI TIES

• Birth defects, congenital anomaly, congenital malformation

congenital abnormalities
• Abnormalities may include:
o Structural
o Behavioral
o Functional
o Metabolic
JUNCTIONS
• Very few are usually identified at birth
o 2% at birth
o 50% at 1 year
 o 26% at 5 years
o Some never picked up or only at an autopsy
STRUCTURAL:

MALFORMATION

• During organogenesis (17 to 56 day) th th

• Structure may be partially absent or completely absent

• When a genetic factor is the cause known as an intrinsic
malformation

DYSPLASIA
• Abnormal formation of tissue
​

• Also referred to as dishistogenesis

DEFORMATION

• Mechanical forces over a prolonged period of time can impact the moulding of the foetus
• E.g. Clubfoot
DISRUPTION

• Structural changes due to destructive processes interfering with

organ formation
10 | P a
• E.g.
g e amniotic bands and teratogen
ABNORMALITY EXAMPLES
Histolog GENETICS
y

MINOR ABNORMALITIES:

• Microtia = small ears

• Postaxial polydactyly
• Pigment spots
• Short palpebral fissures
MAJOR ABNORMALITIES
 • Atrium septum defect
• Microencephaly
• Anencephaly
• Ventricle septum defect
• Ductus arteriosus remaining open after birth
• Cleft lip
• Spina bifida
•
TERATOLOGY
Renal agenesis

• Study of environmentally induced abnormalities (embryo’s

environment is the mother)
•
PRINCIPLE OF TERATOL OGY

Teratogens may be a drug, chemical, infectious or

physical agent, maternal disease, altered maternal
metabolic state that by acting on the embryo causes
an abnormality
STAGE SENSITIVITY

• The stage of development when the teratogen is developed

determines susceptibility
• Most critical period is when cell differentiation and morphogenesis
takes place (Day 17 to 56)
• Pre-implantation period (from conception to day 17).
o All or none
o Teratogenic exposure doesn’t cause congenital abnormalities
• Embryological period (day 17 to 56)
​ 10 | P a
ge
Histolog
y o When organs form
o Damage results in major abnormalities Blast Builds
 • Teratogens have greater access to embryo as a result of the
Cyte mature
functional foeto-placental unit
• Foetal period
o Less susceptible to teratogens
o NOTE: Cells and tissues may still
be affected by alcohol Brain
always susceptible to teratogens

Pre-embryo Embryo Early foetus Late foetus

None Anencephaly Microcephaly Damage by foetal pathology
Hydrocephaly infections causing cell break
Mental retardation down
Scar formation
Calcification

ORGAN SUSCEPTIBILITY

• Each organ has a

critical period during
which development
may be affected by a
teratogen.
• This period is linked
to cell
differentiation,
proliferation,
migration and
growth.
• Organs grow at different
rates Organs with a
slower rate of
development are more
susceptible than
organs that develop
 quickly
• A teratogen may affect
10 | P athan 1 organ or a
more
ge
system
Histolog
y
Chondroblas
Differentiate They undergo Then
Mesenchym ts Chondroblast
into a mature
al secrete the s
chondroblas few mitotic into
cells cartilage in become
ts divisions chondrocyt
all directions isolated
WINDOWS OF ACTION es

• Each teratogen has a period in which it causes damage

• Correlates with the sum of differentiation periods
• Examples
o Alcohol : day 17 to birth
o Thalidomide: day 21 to 36
o Rubella: 6 week to 9th week
th

o Toxoplasma gondii: from embryonic period to birth

DOSE -RESPONSE RELATIONSHI P

• ↑Damage as ↑dose
• All doses have a threshold above which damage occurs
• Period of exposure ↑ risk ↑
​

GENETIC DIFFERENCES IN SUSCEPTIBILITY

• Teratogens act by interfering with normal embryonic and

foetal cellular growth, proliferation, differentiation and
migration.
• Not all foetus’s or embryos exposed to a specific teratogen will be
affected
CLASSIFICATION OF HU MAN TERATOGENS:

MATERNAL DISORDERS

• Maternal diabetes
 o If untreated high risk
o Abnormalities include:
▪ Spinal
▪ Heart
▪ Kidneys
▪ External genitalia
o ‘sirenomelus’ (mermaid) babies associated with IDDM
• Maternal phenylketonuria
o Cannot metabolise phenylalanine
10 | P a
g eo Untreated, high levels of phenylalanine are teratogenic
o Can cause:
Histolog
y
▪ spontaneous abortion
▪ Mental retardation
▪ Microcephaly
▪ Congenital heart disease
• Maternal epilepsy
o Child has a greater risk of congenital abnormality
o Risk factor:
▪ Inheritance
▪ Drugs
▪ Hypoxia
• Maternal hyperthermia
o Temp. +38.5 due to infection, saunas, marathon
o Leads to:
▪ CNS defects
▪ Mid facial hypoplasia
▪ Micrognathia
• Maternal hypothyroidism
o Caused by anti-thyroid drugs or iodine deficiency
o Can lead to goitres
 MATERNAL INFECTIONS = TORCHES

• TO=toxoplasmosis
o Eating uncooked meat and contact with faeces
o Protozoan infection from cats
o Leads to:
▪ Mental retardation
▪ Hydrocephaly
▪ Microphthalmia
▪ Hepatosplenomegally
• R=rubella
o Time of infection impacts on abnormality
Eye (cataracts) 6th week
Deafness 9th week
Cardiac abnormalities 5th to 10th week
Teeth abnormalities 6th to 9th week
CNS 2nd trimester
CNS deafness After 12th week
10 | P a
ge
Histolog
y
Eyes Cataracts, microphthalmia,
glaucoma retinopathy
Ears Sensory-neural deafness,
due to destruction of organ
of Corti.
Only detected when speech
does
not develop
Heart Open ductus arteriosus,
Pulmonary valve stenosis,
ventricular and atrial septal
defects. Results in heart
noises and oxygen
deficiency characteristic of
congenital heart
disease
Teeth Absence of enamel layer
Abdomen Hepatosplenomegaly
Skin Blue berry muffin spots,
purpura
 Brain Microcephaly, mental
retardation
General Growth retardation, anaemia,
jaundice thrombocytopenia

• C=cytomegalovirus
o No symptoms in mother BUT foetus can be effected
o Leads to:
▪ Microcephally
▪ Growth retardation
▪ Mental retardation
▪ Deafness

▪ Hepatosplenomegally
• HE=herpes simplex (type 1)
o If genital caesarean operation NB!
• S=syphilis
o May result in spontaneous abortions or still born
o Leads to:
▪ Microcephally
▪ Hydrocephaly
▪ Hepatosplenomegally
10 | P a ▪ Rhitinis
ge
Histolog
• HIV
y

o Cross placenta
o Leads to
▪ Microcephally

• Human Pavovirus B19

o Causes severe non-immune hydrops
• Varicella Zoster (chicken pox)
 o Low risk
o Rare
o Leads to:
▪ Growth deficiency
▪ Mental retardation

ENVIRONMENTAL CHEMICALS

• Methyl mercury dumped in dam Mother ate fish child born with
mental retardation
RADIATION

• Nuclear explosion
• Associated with mental retardation

• Any type of defect may result

DRUGS
• Difficult to link the specific drugs to defects as:
o Drug may be administered to treat disease and disease
caused defect
o May prevent spontaneous abortions
o Two drugs together may cause defect

ALCOHOL
• Maternal use of alcohol is most common cause of mental
retardation
• Can be prevented

• Foetal Alcohol Syndrome

• Clinical features:

o Growth deficiencies
o Developmental delay
10 |Pa
ge
Histolog
y
o Behaviour problems
o Mental retardation
 o Poor hand and eye coordination
o Poor concentration
o Craniofacial dysmorphology
o Congenital heart disease

ANTI-COAGULANTS

• Warfarin is teratogenic while Heparin is not

• Features:

o Prenatal growth deficiency

o Chondrodysplasia punctata
o Mental retardation

ANTI-CONVULSANTS

• Carbamazepine and phenytoin

ANTINEOPLASTIC DRUGS Positive inside

High [Na+]
• E.g. Aminopherin
• Features: Negative inside
o Skeletal and CNS defects
High [K ] +

ANTIBIOTICS
Resting Potential
• E.g. Tetracycline acts on teeth development
11 | P a g e
• Causes enamel hypoplasia and staining
2
+
K

HORMONES
• Androgenic hormones cause masculinisation of female foetus
• Anti-androgenic hormones cause feminisation of male foetus

PSYCHIATRIC DRUGS

• Lithium containing drugs cause:

o Congenital heart abnormalities
o Blood vessel abnormalities
• Thalidomide (banned in 1962) causes:

o Amelia
 o Micromelia
o Phocomelia
10 | P a
ge
ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS
Histolog
• Exposure
y
of foetus to this antihypertensive drug causes:
o Oligohydramnios
o Foetal death
o Growth retardation
o Renal dysfunction

VITAMIN A (RETINOIC ACID)

• Roaccutane can cause:

o Craniofacial dysmorphism
o Cleft palate
o Neural tube defects
o Heart anomalies
• Any dose of Vitamin A that exceeds the threshold may result in

abnormalities
THYROID DRUGS

• Overdose of anti-thyroid drugs may cause congenital goitre

NICOTINE

•Can result in:

o Growth retardation
o Low weight at birth
o Hypoxia
Craniosynostosis
2. Reachesofiring/threshold level and then there is rapid in flow of sodium. The
membrane is depolarized but then it over shoots and the voltage goes to
+35mV and this is
STREET DRUGS
unstable/unsuitable for Sodium channels so they close and the potassium channels
open.
• Cocaine associated with number of congenital abnormalities
o intracranial haemorrhage
 o gastro-intestinal
o urogenital abnormalities
o

FREE FORMAT QUESTIONS

DISCUSS THE ORIGIN, STRUCTURE , AND SIGNIFICANCE O F THE SOMITE S

limb reduction
12 | P a g e
The somites
Excitable cellsoriginate
physiology
- from the paraxial intraembryonic
mesoderm. They appear as little beads on the side of the
10 | P a
nueralg etube, where the spinal canal will form. The somites are
formed around the spinal canal and thus create part of the
Histolog
y
vertebral column. The somites appear in pairs on either side of
the neural tube/spinal canal. There are 42 - 44 somites and
thus 21 - 22 pairs of somites. Each somite will form a
sclerotome, myotome and dermatotome.

These three parts ultimate fate is the following:

• A sclerotome - forms one vertebra.

• A myotome - forms part of a skeletal muscle.

• A dermatotome - forms part of the dermis.

The somites are of high significants and if they do not form

correctly around the spinal chord possible meningocele can
occur.

Primordial germ cell

Primary oocyte ​Oogonia

Primordial germ cell
​
 Primordial follicle

13 | P aAtgpuberty
e and onwards 15 – 20
Excitable released
cells - per month BUT 1
physiology matures

Oocyte secretes zona pellucida

Follicular cells proliferate to form

the stratum granulosum

Primary follicle
Liquor folliculi unit and form the
follicular antrum and the cumulus
oophorus covers the oocyte

​
Mature Graafian follicle

2 more layers develop: Theca interna Theca externa

Levels resting state complete meiosis 1 and enters meiosis 2 and halts only to be completed on fertilization

10 | P a
ge
Histolog
y

ejaculatory duct vas ductus epididymis Seminiferous tubules Urethra

​
Vagina

Uterus

Uterine tube

FERTILIZATION ​Acrosome Reaction

 Sperm enters Zona
Reaction
Meiosis II completed
Pronucluei come close
together
Envelope disappears
1st mitosis morula

10 | P a
ge
Histolog
y

Eison
phils
Granulo Baso
R
​ cytes phils
B
Neutro
Bl Cell W
C
phils
oo ular B
Mono
 d
Dura reaction Plate
C Agranul cytes
lets ocytes Lymph
Embryoblast ocytes
differentiates

​ Epiblast

​
Trophoblast forms two layers: Cytotrophoblast (inner) Syncytiotrophoblast (outer)

columnar Hypoblast cubiodal

Between the trophoblast and the yolk sac extra-embryonic

mesoderm Small vacuoles form in the mesoderm and forms
the extra-embryonic coelom. The mesoderm now has 2 layers:
Somatopleuric (closer to yolk) and Splanchnopleuric

10 | P a Pre chordal plate develops

ge Epiblast proliferates and between the 2
Histolog layered disc, a third layer formed called
y the intra-embryonic mesoderm
 WBC – LEUKOCYTES (GRANULOC YTES)

NEUTROPHILS

• 2 – 5 nucleus with thread of DNA

• Granulated cytoplasm
• Most common
• Cytoplasm stains very light pink

o Primary: lysosome
o Secondary: inflammation
o Tertiary: cell adhesion
• Function

Folding
Lateral and cephalocaudal

Epiblast ectoderm Hypoblast endoderm Neural tube is

formed

The intra-embryonic mesoderm differentiates into 3:

Paraxial, intermediate, lateral plate
​
 10 | P a
HISTOLOGY
ge
Histolog
y

HISTOLOGY SUMMARY
HISTOLOGY IN MEDICIN E
PURPOSE

• Abnormal vs. normal

• Function
• Regrowth
USES:

• Microsurgery
• Organ transplants
• Re-growth of tissue
FIXATION

1. Specimen
2. Freeze
3. Paraffin wax
4. Cut
5. Remove wax
6. Stain
7. Cover slip
STAINING

• Heamotoxylin
o Basophilic
o Mostly Al3+
o DNA and RNA purple
• Eosinophilic
 o Acidophilic
o Mostly negative
o Binds to cytoplasm
• Silver and gold
o Neurons
• Immunocytochemistry
o Fluorescence
o Colourmetric
• Van
10 Geisan
|Pa
g e o Elastic fibers

​ Histolog
y

MICROSCOPES

LIGHT MICROSCOPE

ELECTRON MICROSCOPE
• Scanning
• Transmission
MAJOR FUNCTIONS

• Fertility
• Tissue re-growth
• Diagnosis
• Treatment
EPITHELIAL CELLS

• Lining or secretory
• Barrier function
• Absorption function
• Secretion function
• Classified according to type and arrangement
 SHAPE CLASSIFICATION :

• Squamous (flat, plate like)

• Cubiodal (height + width similar)
• Columnar (height 2-5times larger then width)
ARRANGEMENT CLASSIFICATION :

• Simple
• Stratified multiple layers, top layer not in contact with ECM
• Pseudo-stratified

10 | P a
ge
Histolog
y

Mesothelium – cavities
Endothelium – blood
vessels

Simple Characteristics
cuboidal Single layer
Centrally placed nuclei
Example
Kidney

Simple ciliated columnar Characteristics

 Single layer
Ciliated
Longer then wide
Example
Uterus

Simple non-ciliated columnar Characteristics

Single layer
Longer then wide
Example
GIT

Pseudo-stratified ciliated Characteristics

columnar Single layer
Nuclei at different
levels Ciliated
Example

10 | P a
ge
Histolog
​ y

Trachea, nasal cavity,TERMINOLOGY

bronchi
Pseudo-stratified non-ciliated Characteristics
columnar Single layer • Cells – Fibres
Nuclei at different levels • Plasma membrane – Sarcolemma
Example • Cytoplasm – Sarcoplasm
Male reproductive system
• ER – Sarcoplasmic reticulum
• Units of Contraction – Sarcomeres
• Elements of Contraction –
 Stratified squamous Keratinized
-Skin
-5 layers:
1. stratum basale
2. stratum spinosum
3. stratum granulosum
4. stratum lucidum
5. stratum
cornea Unkeratinized
-thin (cornea)
-thick (esophagus)
-3 layers:
1. Stratum basale
2. Stratum spinosum
3. Stratum planum

Stratified cuboidal Sweat glands and mammary glands

Stratified columnar Pharynx and male urethra
Transitional Characteristics
Umbrella cells
Appear cuboidal
Can open up and flatten out
Example
NB! in bladder
Male Urethra

10 | P a
ge
Histolog
y
 • Tight/occluding
o Proteins
o Main function
▪ Barrier
▪ Prevents leakages
▪ Prevent lateral diffusion
▪ Prevent diffusion into cells
o NB! in GIT
• Gap/communication
o Allow flow of molecules
o NB! in cardiac and smooth muscles
• Anchoring
o Desmosomes
o Hemi-desmosomes
o Connect cells together
EPITHELIAL CELL SURFA CE SPECIALISATION

• Function of the specialisations

o Increase SA Microvilli (finger like), Basolateral folds
o Move substrates over surfaces cilia (hair like)
​

SECRETION CELLS ​
• Merocrine exocytosis
 • Halocrine shed whole layer
• Apocrine pinch off
10 | P a endocytosis
• Capillary
ge

SUPPORT CELLS AND ECM

Histolog
y

• Support cells + ECM = connective tissue

• Characteristics
o Mechanical support is provided
o Embryonic tissue derivation from mesenchyme
o Production of a variety of extracellular matrix material
o Defines the physical characteristics of the tissue
o Provides scaffolding of the tissue
• ECM = gives specific characteristics to cells
• 5 classes of support cells
Name ​Secretes
Osteoblast Bone
Chondrocyte Cartilage
Adipocyte Fat
Myofibroblast Collagen and contractile function
Fibroblast
2 TYPESCollagen
OF FIBERand elastin
= TYPE 1 + 2A, 2B & 2C

ECM • Type 1, dark, posture

• Type 2, lighter, burst of
2 major materials
energy
Type Type
1
• GAG (glycoaminoglycons) 2
o Karetin sulphate
o Haperin
o Hyaluronic acid
o Chondroitin sulphate
o Dermaton sulphate
• Fibrillar
o Collagen
o Elastin
 oColour
Fibronectin Stain dark, high level of activity Stain paler, low level of activity
Mitochondr
oia Fibrillin
Fiber
Name diameter
​Characteristics
Collagen Contractio
• 20 types
n fibtillor, facit, short
• Divided into:
chain, basement membrane Many Few
​ Small Large
Slow action, long duration, Fast action, short duration,
• Produced by fibroblasts weaker stronger
• Pink in colour
10 | P a
• Reticular fibres
ge
• Type 3 collagen
Histolog
• Thin
y
Elastin • More purple in colour
• Produced by fibroblasts
• Main component of elastic fibres
• Can recoil
Fibrillin • Produces fibrin
Fibrobectin
• Glycoprotein NB! for cell adhesion

• 5 families
o Osteoblast/cytes
▪ Bone
▪ Osteoid
o Chondrocytes/blasts
▪ Cartilage
o Adipocytes/blasts
▪ Unilocular white fat
▪ Multilocular brown fat, more in new born
o Myofibroblasts
▪ Few
o Fibroblasts
▪ Spindle like
▪ Fibrocollagenous
• Loose
• Dense
• Irregular
• Regular

BASEMENT MEMBRANE
 • Consists of:
o Type 5 collagen
o Haperin
o lamine
o Fibronectin
o Entactin
• Supports the epithelia cells
• Brown in colour
• Helps regulate diffusion
​

MUSCULOSKELETAL SYST EM

CARTILAGE
10 | P a
ge
Histolog
y
CARTILAGE DEVELOPMEN T • Axodendritic = Axon + dendrite
• Axosomatic = axon +cell body
•
Serial axoaxonic = many
connections

CELLS AND LAYERS

• Perichondrium
o A layer around the cartilage
o 2 layers
▪ Inner: chondrogenic
▪ Outer: fibrous
• Chondroblasts
o Darkly stained, large nuclei
 o Found in a lacuna
• Chondrocytes
o Pale nuclei
o Lightly stained
o Less active

TYPES OF CARTILAGE
Cartilage Details
Hyaline -Type 2 collagen
-Glassy
-Most common
Chondrocytes found in lacunae and lacunae are in
egg nests
-found in the trachea

Fibrocartilage -type 1 and 2 collagen

-Wazy
-dense
Chondrocytes in lacunae

10 | P a
ge
Elastic -Type 2 collagen and elastic fibers
Histolog -In ear
y
-fibrous
 TYPES OF GROWTH

• Appositional – thickness
• Interstitial – height
BONE

FUNCTION
• Locomotion (long bone)
• Protection (skull)
• Mechanical support (ribs)
• Reserve of mineral salts

CONSISTS OF:

• Osteoid
• Support cells (osteoblast/ osteocytes)
• Inorganic minerals
• Remodeling cells (osteoclasts)
​

OSTEOID:

• Type 1 collagen embedded in GAG

• Glycoprotein
• It gets mineralized to form the bone we know
• To be mineralized needs to be above the threshold
• Ca and PO4+ mineralize

10
2 TYPES OF BONE:
|Pa
•Woven
ge

o Weak
Histolog
y
• Lamellae
o Strong
 CELLS

• Osteoblast
o Secretes osteoid
o Stains dark
• Osteoprogenital
o Differentiates into osteoblasts
• Osteoclasts
o Multi nuclei
o Resorption
o In howship’s lacunae
o Remodel the bone
• Osteocytes
o Isolated
​

o In lacunae
o Lightly stained
o Less/inactive
STRUCTURE
 10 | P a
ge
Histolog
y
• Inner trabecular bone – spongy bone
o Sinus
o Bone marrow filled
• Outer compact bone – cortical bone
o 4 systems:
▪ The haversian/osteon (Seen in a transverse section, vertical)
– concentric lamellae
▪ The inner circumferential lamellae
▪ The outer circumferential lamellae
▪ Interstitial lamellae
2 o Volkmann’s (horizontal) and haversian systems carry blood vessels
• Periostium
o Covers the bone
o Has two layers:
▪ Inner: osteoprogenitor cells
▪ Outer: fibrous
• Endostium
o surrounds inner trabecular bone
o Has two layers a:
▪ Oestoblastic
▪ CNS
​

GROWTH

INTAMEMBRANOUS – FLAT (E.G. SKULL)

• Membrane is formed
• In membrane there are islands of mesenchymal cells
• They differentiate into osteoprogenital cells
• Which differentiate into osteoblasts
 • They secrete osteoid
• The osteoblasts mature into osteocytes
• The osteoid is mineralized
• The remodeling cells come and transform bone in to the normal
structure

ENDOCHONDRIAL – LONG
• The mesenchymal cells differentiate into chondroblasts
• They secrete hyaline cartilage
8|Pag
• They
e forms a template for where the bone will form
Histolog
• Cartilage
y is calcified and chondrocytes die off
• Blood vessels invade this calcified matrix
• Perichondrium known as periostium
• The blood brings osteoprogenital cells
• They differentiate into osteoblasts
• Osteoblasts secrete osteoid
• Mature into osteocytes
• Osteoid is mineralized and osteoclast remodel bone
• This process occurs first on the shaft
• Just before birth the epipysial plate is ossified
​
 THE EPIPYSIAL GROWTH PLATE IS WHERE POST
NATAL GROWTH WILL OCCUR FROM.
Layers include:
• Resting
• Proliferation – stacks of coins
• Hypertrophic – enlarging not
dividing
• Calcification – mineralized and
further enlargement
• Ossification

Histolog
y
NAME AND DESCRIBE THE MAIN CHARACTERIS TICS OF THE THREE TY PES OF MUSCLE
PRESEN T IN THE HUMAN BODY.

JOINTS

• Free movement – elbow

o Synovial fluid sacs
• Limited movement – skull
FRACTURES

• Open
• Closed
• Compression
 • Avulsion
• Impact
• Repair similar to the ossification process
HISTOLOGICAL CONDITI ONS
MARFANS SYNDROME

• Heritable disorder of the connective tissue

• Autosomal dominant
• Features
o Extremely tall
o Long limbs
o Thin fingers
o Ocular
▪ Myopia
▪ Lens displacement
o Skeletal
▪ Overgrown bones
▪ Joint laxity
▪ Overgrown ribs
▪ Scoliosis
o Cardiovascular
▪ Dilation of the aorta
29 | P a ▪ Predisposed to aortic tears
ge ▪ Tricuspid valve prolapse
Histolog
• Treatment
y
o Treat systematically
o Drug treatment
​

ACHONDROPLASIA

• Genetic disorder autosomal dominant disorder

• Phenotype
 o Short stature
o Enlarged head
o Short hands
o Disproportionate size
• FGFR3 – mutation in the type 3 receptor for fibroblast growth factor
• Short limbs
• Treatment
o Growth hormones
o Limb extensions
OSTEOSARCOMA

• Malignant tumour of the osteoblast

• Tumour resembles an osteoblast but the produced osteoid is irregular,
abnormal in mineralizing
• Symptoms
o Swelling
o Pain at site
• Diagnosis
o Imaging techniques
o Biopsy
• Treatment
o Chemo
o Surgery
o Amputation
RICKETS

• Vit D and Ca deficiency

• Bow legs due to ossification not occurring at the right time
29EAR
CAULIFLOWER |Pa
ge
Histolog
• Trauma
y to ear
• Development process
​
 Trauma bleeding in the cartilage Hematoma forms rich in growth
factors stimulates chondroblasts mass of collagen forms
• Type 1 and 2 collagen fibres covers hematoma
• Common in rugby players
OSTEOPOROSIS

• Osteoclasts working faster than osteoblasts

• Due to hormone changes
RHEUMATOID ARTHRITIS

• Disease of the joints

• Auto-immune disease
• Not age limited
OSTEOARTHRITIS

• Diseases of the joints

• Wear and tear
• Aged (normally older people)
• Painful
•
BLOOD
Degeneration of the articular cartilage
 29 | P a
ge
​ Histolog
y

• Haemopoeitic tissue Final step in the

RBC – ERYTHROCYTES Adherenc process is the
• Antibodies and e • The intracellular
C3b bind to macrophage killing
antigen • The engulfs the
macrophage antigen and is
• Biconcave binds to the Fc
arm of the
known as the
phagosome
• No nucleiOpsonizatio
n
antibody
Ingestio
n
• Many of them
• No organelles
• Hb
• Carries oxygen
• 100 – 120 days life span

• 3 types of granules

o Phagocytosis
o Neutrophilia
o Defensive role
• Pus = dead
 EOSINOPHILS

• Bilobule
• Granulated cytoplasm: RER, mito
• Dark pink cytoplasm
• Function:
o Phagocytosis
o Allergic reactions
​
1|Page
Immunolog
y
BASOPHILS

• U/S shaped nuclei

• Stains very dark blue/purple
• Cytoplasm has histamine and heparin
• Least common
• Function:
o Phagocytosis
o Allegoric and inflammation reaction
o Mast cells
AGRANULOCYTES

MONOCYTES
• Large bean shaped
• Little bit of cytoplasm
• In blood
• Leaves blood to form macrophage

LYMPHOCYTE

• B and T
 • Similar size to RBC
• Large nuclei
• Hardly any cytoplasm
• Function: immune response

B CELLS – PLASMA CELLS

• Eccentric nuclei
• Cartwheel
• Antibodies produced from this cell

PLATELETS
​
1|Page
• Tiny
Immunolog
• Biconcave
y

• Produced from megakaryocytes

• Clotting factor
• Lays down a mesh work
HAEMOPOEITIC TISSUE

ANTIGENS USED
• Erythropoeisis
1. Progenital cells
2. Pro-erythroblast – large nucleus
3. Polychromatic erythroblast – smaller N, Hb in cytoplasm
4. Orthochromatic erythroblast – nucleus expelled
5. Reticulocyte – no nucleus
6. RBC
 • Granulopoeisis
1. Progenital
2. Myeloblast
3. Pro-myelocyte
4. Myelocyte
5. Metamyelocyte
6. Band/ stab forms
7. BEN
• Agranulopoeisis
1. Monoblast
2. Pro-monocyte
3. Monocyte
4. Lymphoblast
5. Pro-lymphocyte
6. Lymphocytes
• Thrombopoeisis
1. Megakaryoblast
2. Polyoid megakaryocyte
3. Astomonic membranes
​

4. Platelet ribbons
5.

1|Page
Immunolog
y

Platelets form
​

STEM CELL TRANSPORT

• Leukemia
 • Lymphoma
• Bone marrow stem cells
o 1 hrs
o Pain and discomfort
• Peripheral blood stem cells
o 4-5hrs
o Growth hormones
• Umbilical cord stem cells
o At birth form placenta
• Risks for patient
o Rejection
o Infection
o Bleeding
CONTRACTILE CELLS

FOUR GROUPS OF CONTRACTILE CELLS

MYOFIBROBLAST

• Contractile ability
• Lays scaffolding
PERICYTES

• Around the blood vessels

MYOEPITHELIAL CELLS
• Secretory epithelial
• Push secretion out of the gland

MUSCLE CELLS
1
Skeletal
|Page Cardiac Smooth
Cell Immunolog
Elongated Branching Spindle-shaped
y
Nucleus Multiple peripheral Single central Single central
Striations Cross-striated Cross-striated None
Motor Control Voluntary Isolate theInvoluntary Involuntary
virus
​ Grow virus on
medium

Polet
virus

• Skeletal muscles
Clinical trials
o Endomysium
1,2,3 around a single fibre
o Perimysium
Publi around a fascicle (group of
fibres) c

o Epimysium around the whole

o Voluntary
o Fibers
▪ Striations
o Cellular morphology
▪ Many nuclei below surface
▪ Long cylindrical structure (can be up to 10cm)
▪ Many mitochondria, glycogen, energy
​
1|Page
Immunolog
INNER yWORKING OF THE MUSCLES
• Myelin (thick) and actin (thin)
• A band (dark Actin and myosin)
o H band (Only myosin)
o M line (thickenings of myosin)
• I band (light Actin)
o Z line (Alpha-actinin)
•

Fibers connected to dytrophin which is connected to cell membrane and

thus cell surface
​

• Cardiac Muscles
o Involuntary
 o Intercalated discs
o Striations
o Branched at nuclei
o Cantraction same as skeletal
muscles
• Smooth muscle
o No striations
o Involuntary
o Has a crises cross network and
1 | P a gthese
e
fibers constrict making the
Immunolog
y spindle shaped fined contact and
the nuclei coil

NEURAL CELLS

• CNS and PNS

NEURON

• Dendrites
• Axon
• Cell body
3 TYPES (LOOK AT CELL BODY)

• Motor – multipolar
• Sensory – unipolar
• Interneurons – bipolar

1|Page
Immunolog
y

SYNAPSES

• Direct communication
• Transmitter substance secreted by one cell,
received by other
• Triggered by membrane depolarization
• Different pathway types:
o axons and dendrites,
o axons and cell bodies,
o axons and axons
​

MYELIN

• Oligodendrocytes in CNS
• Schwann Cells in PNS
• Axon covered
• Increase speed of conduction
• Then the cell twists around and the layers fuse to
form a myelin sheath

MYELINATION
1. Invagination (indentation) of
single axon into support cell
2. Both outer cell membranes in
close apposition
3. Seals together to form sheet of
internal membrane – mesaxon
4. Line of fusion mediated by
proteins in outer surfaces
5. Support cell wraps numerous
layers myelin around an axon
6. Cytoplasm of support cell is excluded (pushed out)

7. Tight spiral double thickness membrane fuse together

1|Page
Immunolog
8. yInner surfaces also fuse and forms major dense line

9. Thickness depends of number of layers wrap around axon, Small bare

Sent to left hemi
areas between myelin sheaths – Nodes ofcorpus
Sent to Ranvier
callosum

​ BUT! With a
commissurotomy brain split
Can say what Processed
Left hemi Right hemi and things seen in
the stimuli is the LVF can’t be explained
CNS as the link is broken

• Astrocytes Stimuli in LVF Stimuli in RVF

o Large, multiprocessed with oval, irregular

nuclei
 o Stellate “star shaped” morphology
o Fine processes radiating in all directions
o 2 types:
▪ Fibrous in white matter, long cell
processes
▪ Protoplasmic in gray matter, thin
processes
• Microglial
o Specialized immune cells in CNS
o Specialized macrophages
o Not easily seen with H&E
o Extensive fine processes can be seen with
IHC
o Form widespread network of cells
throughout brain
o Activate, increase in size and number in
disease
• Oligodendrocytes
o Several cell processes
o Myelinates several nearby axons
o Round nucleus, dense staining chromatin
o Cytoplasm, halo around nucleus
• Ependyma
o Like epithelial cells
o No Basement membrane
o Sheet of cuboidal cells, lining cavities
in brain, and central canal in spinal
cord
o Small, oval basal nucleus
o Many are ciliated
o Processes merge with processes of
1 | P a gunderlying
e astrocytic cells
Excitable cells -
physiology

• Multipolar neuron many dendrites only 1 axon

• Bipolar cell 2 extensions
 • Unipolar cell=spinal ganglion cells in PNS Sensory

27 | P a g e

MENINGS

• Dura
o Outer coat, blends with periosteum of
skull, attached by dentate ligaments
o Covered on inside by incomplete layer of
epithelial cells
o Forms sheets of tissue
• Aranchoid
o Beneath dura (not anchored to)
o Fibrocollagenous tissue
o Covered by flat epithelial cells
o Web-like strands of friborcollagenous
tissue extend into subarachnoid space
o Contains cerebrospinal fluid
o Main arteries and veins run in subarachnoid space
o
​
• Pia

o Delicate layer of epithelial cells, loose fibrocollagenous tissue

o Cells lie external to basement membrane, formed by special astrocytes
o Limiting glia
​

CHORIOD PLEXUS

• Responsible for production of spinal fluid

BLOOD BRAIN BARRIER

 • 33 layers
1 |Page
| Poa Endothelium
Excitableg cells
e - of capillaries,
Excitable
physiologycells -
o Basal lamina and
physiology
o Foot processes of
WORKING OF A NEURON:
astrocytes
Afferent fibres take impulses to the CNS
Efferent fibres take impulses away from
CNS

4|Pa
Excita
bl
​

PNS

• Ganglion
• Nerves
• Schwann cells
o Schwann cells support both m
yelinated & unmyelinated fibers
o Produce myelin for only one axon
o Support non-myelinated axons – bury themselves in Schwann cell
cytoplasm
• Satellite cells
Layers of the Nerves (similar to the muscles)

• Perinuerium
• Endonuerium
• Epinuerium
LOOK AT GLANDS LECTURE NOTES

FREE FORMAT QUESTION EXAMPLES

CLASSIFY THE DIFFERE NT TYPES OF EPITHELI UM FOUND IN THE HUMA N BODY AND
PROVIDE AN EXAMPLE
g e OF EACH (10MARKS)
e cells -
physiology

ASTROCYTES
Simple squamous epithelium – alveoli, endothelium (blood
vessels) and mesothelium (abdominal cavity lining)
Simple cubiodal epithelium – kidney
Simple ciliated columnar epithelium – uterus
Simple non-ciliated columnar epithelium –
alimentary canal and gall bladder Stratified
unkeratinized squamous epithelium – Thin –
cornea, Thick – GIT Stratified kerantinized
squamous epithelium – Skin
Stratified columnar epithelium – pharynx and male urethra
Stratified cubiodal epithelium – sweat glands and
conjunctiva of the eye Pseudostratefied ciliated
columnar epithelium – trachea, nasal cavity and
bronchi Pseudostratefied non-ciliated columnar
epithelium – male reproductive system
Transitional epithelium – bladder

• Skeletal muscles
 Are striated
o
Have multi nuclei
o
o Are responsible for voluntary movement (for example the
tongue)
• Smooth Muscles
o Has no striations
o Are responsible for involuntary movement
o Has single centrally place nuclei
• Cardiac muscles
o Has striations and has intercalated discs
o Is branched
o Has single centrally placed nuclei
o Involuntary movement
DESCRIBE THE PROCESS OF ENDOCHONDRIAL OSS IFICATION THAT OCCUR S IN
LONG BONES SUCH AS THE HUMERUS AND FEMUR. (MAX 5 MA RKS, ½ MARK PER FACT
)

• Endochondrial ossification is a one of the ways in which bone

formation occurs.
• The prenatal process occurs as follows:
• The mesenchymal cells differentiate into chondroblasts where
they secrete hyaline cartilage.
• The chondroblasts become isolated and mature into
chondrocytes.
• The cartilage matrix starts being calcified and the chondrocytes
die off.
• Blood vessels then invade this calcified matrix and the
blood brings with osteoprogential cells which
differentiate into osteoblasts.
• The osteoblasts secrete osteoid.
• The osteoblasts become isolated and mature into osteocytes.
• The osteoid is then mineralized and the mineralization
starts at the primary ossification centre which is in the
centre of the bone shaft. Ossification also occurs at the
 secondary epiphysis centre this normally happens just
before birth, this is in the two knobs of the bone.
• The osteoclasts, remodeling cells, start remodeling
the bone so that it has the inner trabecular spongy
bone and the outer compact bone.
• For the postnatal endochondrial ossification the process
is relatively the same however the growth occurs at the
epiphysis growth plate.
MULTIPLE CHOICE TYPE QUESTIONS
WHAT TYPE OF TISSUE LINES THE BLADDER?

a. Simple squamous epithelium

b. Simple cuboidal epithelium
c. Simple columnar epithelium
d. Stratified squamous epithelium e.
Transitional epithelium

WHAT TYPE OF TISSUE MAKES UP THE DERMIS OF THE SKIN?

a. Mucous connective tissue

b. Mesenchyme
c. Loose irregular connective tissue d.
Dense irregular connective tissue
WHAT TYPE OF EPITHEL IUM FOR MS THE EPIDERMIS?

e. Dense regular connective tissue

a. Simple squamous epithelium
b. Simple cuboidal epithelium
c. Simple columnar epithelium
d. Stratified squamous epithelium
e.
WHAT TYPE OF EPITHEL IAL CELLS ARE AS TALL AS THEY ARE WID E?
Pseudostratified epithelium
a. Simple
b. Columnar
c. Squamous
d. Stratified
e.
WHAT TYPE OF EPITHEL IUM IS COMPOSED OF FLAT CEL LS?

Cuboidal
a. Simple
 b. Stratified c.
Squamous
d. Cuboidal
e. Columnar
​

IMMUNOLOGY
​ ​

IMMUNOLOGY SUMMARY
HISTORY

Primitive immunization was performed by the Greek and Chinese.

•

• The Golden era (1910)

o Lots of discoveries were made.
o Edward Jenner – cowpox vaccine
o Louis Pasteur – attenuated virus
• The Dark era (1910 – 1960)

• The Ressaniance (1960)

o Large gain of knowledge and understanding.

o This includes immunization, immunopathology and immune
transplants.
IMMUNE SYSTEM

• Main Function is to protect the host against infectious diseases/

pathogens.
• Different types of pathogens:
o Marco worms
o Micro Virus, protozoan, bacteria, fungi
RECEPTOR/GENERATOR P OTENTIAL

Intracellular ​Extracellular
Antigen
 presenting ​Phagocytes
cells
During action potential slight gain
T lymphocytes ​B lymphocytes of Na+ intracellular and loss of
Antibodies K+. This speeds Na+/K+ pump
Complements and [ ] are restored.

INTERNAL DEFENSE SYS TEM

Innate Immunity ​Acquired Immunity
Rapid ​Slow in primary response
Non-specific ​Secondary response rapid
No memory ​Specific
Don’t change in intensity ​Memory
Present from birth ​↑in intensity with exposure
Phagocytes and complements NB! ​Acquired by exposure to Ag’s
Lymphocytes (T and B) and antibodies
NB!

Lymphatic organ
An organ where the immune cells are produces
Primary lymphoid organs thymus and bone
marrow
Secondary lymphoid organs Spleen and payers patches

​
ANTIGEN
• It is a substance that is identified as foreign by the

immune system and leads to a specific immune

response.
• Includes:

o Microbes
o Parts of microbes
o Secretions of microbes
• To be immunogenic:
o Molecular weight of >1000
o Has to have epiptopes (antigen determinants).
Note: the number of epiptopes is determined by
the size of the antigen
 Classes of antigens:
•

o Microbial and viral

o Auto-antigen result in auto immune diseases as
theLarge
Slow
glycoprotein’s
diameter nerve
on your own cells are seen as
Fast Narrow diameter nerve
foreign and the Phase
fibres: fibres
immune system
fibres:
closed.attacks
fibres
4: Na+ channels Stable them
resting membrane potential.
o Allergen Phase 0: At threshold Na+ channels
open and rapid influx Na+ and
HAPTENS depolarisation.(Ca2+ influx in slow fibres)
Phase 1: Na+influx decrease, K+
efflux increase.
Not true antigens as weight less than 1000
• Phase 2: Inflow of Ca2+ in fast
fibres preventing repolarisation.
• Have to bind to something in order to be immunogenic
Phase 3: Efflux K+ increases

IMMUNE COMPONENTS IN BLOOD INCLUDE:

Leukocytes – phagocytes
•

• Lymphocytes – T and B

• Plasma – antibodies, complements and cytokines

PHAGOCYTES

• Neutrophils
o 2 to 5 nucleus connected by a thread of DNA
o Most common
o Chemotaxin is a directed action to a specific area to
perform phagocytosis
o Short life span
o Dead neutrophils found in pus
o Function:
▪ NB! Defensive role
▪ Phagocytosis
▪ Neutrophilia abnormally high levels of
neutrophils can indicate an inflammation or
a bacterial infection
• Macrophages

o Bean shaped nucleus

 o Precursor is the monocyte which is found in the blood
o Macrophages are found in the tissue
o Have a long life span

o Contains lysosomes
o Function:
▪ Phagocytosis
ag Phagocytosis consists of three steps:
e

SPONTANEOUS ACTION P OTENTIALS:

LYMPHOCYTES (PRECURSOR IN THE BONE NARRO

W)
• T-lymphocyte – mature in the thyroid gland

o CD4+ T helper cells

▪ Th efficiency of APC, macrophages
1

▪ Th activation of B-lymphocytes
2

▪ Th attraction of neutrophils
17

o CD8+ T cytotoxins
▪ Involved in specific killing of virus and bacterial infections
• B-lymphocytes – mature in the bone marrow

o NB! in antibody production

o The B-lymphocytes that produce the antibodies are known
as plasma cells
• Natural Killer cells (Nk)

ANTIGEN PRESENTING CELLS

 3 types
•

o Dendrites
o Macrophages
o B-lymphocytes

PROTEIN COMPONENTS OF THE IMMUNE SYSTEM

COMPLEMENTS

• NB! in the creation of inflammation and the lysis of bacteria

• Consists of:
o Cb3 – opsonises antigens
o C3e – increases production of neutrophils
o C5b,6,7,8,9 – MAC (lysis)
9 | P o C3a & C5a – increases vascular permeability and attracts
Excitable cells -
phagocytes
physiology

CYTOKINES

•NB! in cell communication

• Consists of:

o Interferons
o Interleukins
o Coleny stimulating factors

ANTIBODIES/ IG

• Y shaped – Fab and Fc

• Consists of:

o IgG – placenta, opsonises, memory

o IgM – first to respond, localizes infection
o IgA – breast milk, siliva,
 bronchial fluid. Prevents
infection (microbial)
o IgD – no known immune function
o IgE – prevents parasitic infection,
harmful in allergic reactions

*** Antibody Deficiency syndrome: ***

Abnormally low B-lymphocytes

o
o Thus low Ig
o Thus susceptible to infection
o Treated with gammaglobulin (high in IgG)

IMMUNISATION

• Is a process of creating protection for a non-immune or not yet

exposed individual

Active – T & B lymphocytes, Passive – no immune response

creating an immune
response
Natural Artificial Natural Artificial
Natural encounter Vaccines – safe IgG and IgA Removing antibodies from
with the 10 | P a g eencounter with the immune individuals or animals
Excitable cells
microorganism -
virus
physiology
(pathogen)
For example: “Giving antibodies”
person next to
you
coughs
​

ARTIFICIAL ACTIVE IMMUNISATION

Live attenuated Virus:
-measles
-mumps
-rubella
-chicken pox
-hepatitis A
Bacteria:
-tuberculosis

Killed Whole Virus:

-polio
-rabies
Bacteria
:
-peritussis
-cholera
-typhoid

Sub-cellular fragments
Inactivated toxins (toxiod) Bacteria:
-tetanus
-Diphtheria

Capsular polysaccharides Bacteria:

-Haemophilia influenza type B
Recombinant subunit Virus
vaccine -Hepatitis B

NOTE: Live vaccines are more effective and long lasting but
more unstable at room temperature in comparison to killed
whole viruses

Birth
BCG Intradermal
Polio Drops by Mouth
6 weeks
Polio Drops by Mouth
Rota virus Drops by Mouth
DTP + Hib Left thigh
Heb B Right thigh
PC Right thigh
10 weeks
Polio Mouth
DTP + Hib Left thigh
Hep B Right thigh
14 weeks
Polio Mouth
Rota virus Mouth
DTP + Hib Left thigh
Heb B Right thigh
PC Right thigh
9 months
Measles Left thigh
PC Right thigh
18 months
Measles Right arm
DTP + Hib Left arm
Polio Mouth
6 years and 12 years
DT Left arm
• Other vaccines:
o Health professionals – hep A and B
o Travelers – cholera and yellow fewer
o MMR – 18 months and 6years
o Elderly – haemophilia influenza type B and streptoloccocal
pneumonia
• Live attenuated vaccines can’t not be given to:

o Pregnant
o Immune compromised
o Until Maternal IgG is out of infants system approx. 6 moths
• Requirements of a vaccine:

o Safe
o Protection
o Sustained
o Cost effective
 o Easy to administer

• Development

Impulse arrives at presynaptic nerve terminal

Transmitter substance is released

Substances reacts with a postsynaptic membrane

receptors

chemical dependent ion channels (receptor or ligand)

HUMAN IMMUNODEFICIENCY
effected VIRUS

membrane potential of the postsynaptic cell changes.

• HIV – 1
Major cause of deaths
o initiate a specific metabolic response
OR It can also
via
10 subgroups (A-J)
o a second messenger
o A in sub-Saharan Africa
o B in Europe
• HIV – 2

o Less progressive
o Mostly in West Africa
• Contraction:

o Needles
o Blood
o Semen
o Vaginal fluid
o Baby to mother
• Prevention:

o Condoms
o Circumcision
 o Caesarian section (bloodless)
• Structure
o Gp120 that binds to CCR5
o MCH proteins hid it from immune system
o 8 times smaller than a red blood cell
• CD4+T-lymphocytes

o It targets the CD4+

o Kills 5 % per day
o No immune system (compromised)
o Normal levels: 500 – 1500 cell/mm
3

o ARV’s:
EPSP <200 cell/mm
EXCITATORY POSTSYNAPTIC POTENTIAL:
3

o Pregnant: <350 cell/mm

3

o Co-infection <250 cell/mm

3

o Phases:
▪ Chronic
▪ Accelerated
▪ Acute
▪ AIDS
• Replication
o 10 -10 virons per day
8 9

• AIDS-defining infections

o Bacterial: pulmonary Tuberculosis

o Virus: Oral candadiasis
• Influencing progression factors

o Age
o Malnutrition
o Concurrent chronic infection
o ARV’s
o Replication ability of virus
• Treatment

o Nucleoside reverse transcriptase inhibitor

 Non-nucleoside reverse transcriptase inhibitor
o
CCR5 and CRX4
o
o Intergrase inhibitor
o Protease inhibitor
• Combination treatment is most NB!

o 2 nucleosides and 1 non-nucleoside

o Prevents resistance
o Advantages : quality up, CD4+ up
o Disadvantages: cost, adherence

VACCINATION IN CASE OF SPLENECTOMY

•Spleen = NB in immune system

• It is a soft spongy organ on left side in the left hypochondrium

• Most common organ to be injured

STRUCTURE
14 | P a g e
Excitable cells -
physiology
•Red pulp red blood cells that are aged or abnormal are
removed
• White pulp Where the immune system components are found
FUNCTION

• Filtration
o Cleans blood
o Removes abnormal blood cells
• Immunological function
o Cleaves blood borne pathogens

o Antibodies synthesised
▪ Polysaccharide antigen B cells Ag

*** Removal of spleen sepsis as can’t remove encapsulated

 bacteria ***
PREVENTION

• Vaccination NB!
o Pneumococcal polysaccharide vaccine (23 valent) [2years
and older]
o Younger than 2 years pneumococcal conjugate vaccine
o Conjugated heamophilus influenza type B
o Meningococcal vaccine

EXCITABLE CELLS -
PHYSIOLOGY
THE SPLIT-BRAIN
LOBES OF THE BRAIN

• Frontal
• Occipital
14 | P a g e
• Parietal
Excitable cells -
physiology
• Temporal

• Limbic

RIGHT VS. LEFT HEMISPHERE

Right hemisphere ​Left hemisphere
Art/creative ​Analytical
Music ​Logic
Holistic thoughts ​Languages
Math and science

VISION
 Right side of your brain controls your Left body functions
•

Left side of your brain controls your Right body functions

•

• Each eyeball is divided into 2 parts

o Right Visual Field

o Left Visual Field
• Right Hemisphere receives visual info from LVF only

• Left Hemisphere receives visual info from RVF only

SEIZURES
WHAT IS A SEIZURE?

• Abnormal discharge of electrical impulses within the brain

• Rather than smooth constant production of Action

Potentials, neurons fire without any regulation,

causing disruption to brain function at the
biochemical level
SEIZURES GENERALLY H AVE 3 PARTS:

• Aura - period of warning, usually olfactory or visual

• Ictus - actual seizure period

• Postictal state - time where body “resets” itself

3 BASIC TYPES

• Grand Mal Involves total body convulsions, aka “tonic-clonic”

• Petit Mal Involves isolated body part convulsion, aka “focal”
• Absence Patient becomes unresponsive, and has no
memory of occurrence. Appears to be day-dreaming
14
but| Pcannot
age
awake. Very rare
Excitable cells -
physiology

CAUSES OF SEIZURES
 Alcohol Poisoning
•

• Drug Overdose/Reaction

• Head Injury
• Fever (especially in children)

• Neurological Defect (usually genetic)

• Sepsis (in brain)

EPILEPSY
WHAT IS IT?

• A seizure disorder in which reoccurring seizures are

the main symptom caused by an abnormal
discharge of electrical activity from the neurons in
the cerebral cortex.
• Risk of epilepsy is greatest in early childhood and late adulthood.
TREATMENTS FOR EPILE PSY

DRUGS

• Generally first line of attack because it is effective, relatively

inexpensive, and safe

DIET
• Ketogenic diet - lots of fat and almost no carbohydrates
• This diet drastically alters the way our bodies get

energy from food - instead of making glucose, it

makes ketones
SURGERY
• Commissurotomy
o Surgically splitting the corpus callosum
 EXCITABLE
14 CELLS
|Page
Excitable cells -
physiology
INTRODUCTION: OVERVIEW
SMOOTH MUSCLE:
Somatic
• Central nervous system
Autonomic
nervous
o CNS
nervous
system:
o Brain and spine
system:
Peripheral nervous system
•

o PNS
o Afferent (to the CNS) and efferent (away from CNS) neurons

NEURONS

• A neuron is a nerve cell.

o These are functional neural elements

Axon Hillock = No ER

• Ganglia =groups of nerve cells in PNS

• PNS: Nerves consist of ganglia and nerve fibres.

• 31 pairs spinal nerves

connecting spinal cord to
peripheral sensory endings
and muscles/glands (effectors)
 • 12 pairs cranial nerves
connecting brain with
structures in the head
TYPES OF NEURONS

18 | P a g e
Excitable cells -
physiology

• Three parts:
o Cell body/soma
o Dendrites
o Axon

CELL BODY/SOMA
• Referred to as a nerve cell
• Has a nucleus and organelles (NOTE: Nissl body RER)
• Metabolic processes take place here

DENDRITES

• Elongated cytoplasmic processes; information receptors

• Function increase surface area and reception for neuron.
AXON

• Single cytoplasmic process; conduct nerve impulses to nerve,

muscle or glands.
• Axon transport is:
o Retrograde up to cell body
o Anterograde down to axon terminal
• Axons end in end bulbs/synaptic knob/terminal

• divergence
•
SYNAPSE

convergence
• Contact point between presynaptic neuron or postsynaptic cell
• Axon terminals transmit impulses to muscle fibres has specialised

endings=motor endplate.
19 | P a g e
• Trasmission takes place via neurotransmitter in synaptic vesicles
Excitable cells -
• Abundant
physiology mitochondria due to high metabolism
•
SEQUENCE OF EVENTS THAT OCCURS IN A NEUR ON

Nerve impulse arrives presynaptic end

Exocytosis=release neurotransmitter into cleft
Combine with chemical receptors membrane
postsynaptic cell Impulse generation first part of axon
Active transport used to take neurotransmitter
substance up again for reuse.
• Receive info transform into coded electrical impulse conduct
it transmit it to other
GLIAL CELLS
cells
​

• Send processes to brain blood vessels blood brain barrier.

•

EPENDYMAL CELLS
Produce neurotropic substances, assist in
maintaining K+ conc. of ECF and take up
neurotransmitter
• Line ventricles and canals in CNS
•

MICROGLIAL CELLS
Ciliated=circulation CSF
• Phagocytes
19 | P a g e function
• Protective
• Excitable cells -
physiology
SATELLITE CELLS
Not true glial cells, part of Macrophages.
• Support neurons in peripheral ganglia

SCHWANN AND OLIGODENDROCYTES

MYELINATION OF FIBRE S

• Formed by Oligodendrocytes in
 CNS
• Formed by Schwann cells in PNS
• Surrounds large

diameter nerve fibres

• Myelin is a lipoprotein material

• Myelin sheaths are extra

lipid cell membrane

wrappings around
fibres.
• Schwann cells wrap

themselves many
times around fibre in
PNS.
• Unmyelinated fibres in

PNS also encased by

Schwann cells but in a
different way.
• One Schwann cell may

enclose several fibres

• In CNS processes of oligodendrocytes wrap around the fibres.

• Myelin sheaths interrupted at nodes of Ranvier

• Functioning of fibres depend upon myelination
•
PROCESS OF MYELINATI ON

Starts in fetus, completed by age 7 or 8.

Schwann cell surrounds axon wraps multiple times
pushes cytoplasm out cell membranes fuse myelin
sheath forms
19 | P a physiology
ge
CLASSES OF
Excitable cells - NERVE FIBRES
physiology
CSF
• Myelinated Group A
o Alpha Vibration and touch
 o Beta Touch and pressure
o gamma
​

o delta Pain and temperature

• Myelinated Group B
• Unmyelinated Group C Pain and afferent autonomic info
***Thick to thin: A, B, C***
DEGENERATION AND REGENERATION
PNS

***Greater diameter, lower threshold for activation,

shorter refractory period and greater speed of
impulse***

• Peripheral nerve severed and cut ends sewn together:

regeneration can take place.
o Small sprouts grow from proximal cut ends Can
enter sheaths of degenerated fibres with the
help of neurotropins=growth factors aids neuronal
growth
• Full or partial recovery can occur
• If healing un able to take place:

o Fibres distal to injury deprived of substances

provided by cell bodies = Wallerian
degeneration/Anterograde
o
CNS

Retrograde degeneration takes place along intact axon

(proximal to the injury)
• Regeneration not possible/limited in the central nervous system
i.e. brain and spinal cord.
• Depends on plasticity
•
 PLASTICITY
Decreases
22 | P a g e with age.
• Is lifelong possibility of the occurrence of long term structural,
Excitable
cells -
physiological and biochemical
changes in synaptic function
MEMBRANE POTENTIALS
• Functioning nervous and muscular system depends upon
excitability of neurons.
• Receptor endings respond to stimulus

• Electrical, mechanical, chemical or thermal Impulse is

generated
• Sent to CNS via afferent nerves processed
Impulses from CNS sent along efferent nerves to
effectors=contraction or secretion.
•

TYPES OF MEMBRANE PO TENTIALS:

In living cells an electric potential difference exists
between outside and inside of cell membrane.
• Resting potential
• Receptor potential

• Action potential
•
RESTING POTENTIAL

Spontaneous action potential.

• In the resting state
o Outside of membrane is positive relative to the
inside of the membrane which is negative.
• The potential difference exists as a result of charge

difference between the outside surface and the inside

surface of the cell
• It is a result of difference in ion concentrations e.g. Na+ and K+
inside and outside cell.
 • -70mV in nerve
• -90mV in muscle

MAGNITUDE OF CHARGE ACROSS M EMBRANE DEPENDS ON:

• Difference in concentration of ions

• Electrical charges of ions
23 | P a g e
• Permeability of membrane for ions
Excitable cells -
physiology
PARASYMPATHETIC
IONS, [] AND PERMIABILITYDIVI SION

• [K ]inside > [K ] outside

+ +

• [Na ]inside < [Na ] outside

+ +

• Cl is also permeable but since inside

-

the cell is negative as soon as it is

transported in it is repelled out
therefore [Cl]inside < [Cl]outside
• On stimulation the permeability increases

• The distribution of ions is adjusted.

• This results in change in the potential of membrane

• The cell is activated.

• The change in the resting potential is called depolarisation

INFLUX AND EFFLUX MA INTAINING THE RESTIN G POTENTIAL

•K+ ions efflux

• Na+ ions influx
**Down their [] gradient**
• A consistent resting membrane
potential can therefore not be
maintained by diffusion alone. (K+
efflux>K+ influx at resting
membrane potentials. When one
K+ flows out: excessive + outside
 and excessive – inside)

FLUX OF IONS DEPENDS UPON:

• Permeability of membrane
• Concentration of ion
• Electrical gradients.

K/NA PUMP

• This diffuse would continue until equilibrium and there

would be not voltage HOWEVER there is an K/Na
pump which pumps 2K+ into the cell for every 3Na+
out thus maintaining the resting potential
• Maintains constant intra and extracellular [ions]

***Resting potential is thus the equilibrium potential. ***

NB
23
EXCITABILITY OF A MEMBRANE DEPENDS ON ITS RESTING MEMBRANE POTENTIAL AND
|Page
THIS DEPENDS UPON:
Excitable cells -
Any condition affecting Na+/K+ pump
• physiology

• Any condition affecting the ion concentration/diffusion

(Gated channels, specific channels, concentration
gradient, electrical gradient)
• Any condition affecting the permeability of the membrane.​

• At rest: sensory receptor membranes=polarised

• Afferent nerve fibres: membranes of receptor endings are very

excitable.
• Adequate stimulus: Form of energy to which a receptor responds.
• Stimulation sensory receptors: Increases membrane permeability
for Na+ ↑Na+ influx.
• Na+ is positively charged thus decline in membrane potential.

(Inside cell less negative)

• Membrane hypopolarised and this hypopolarisation is known as a

receptor potential
 • Thus stimulus intensity influences number of Na+
channels open which influences extent of
hypopolarisation.
• NB! receptor response is NOT an all or nothing response
•
ACTION POTENTIAL/IMP ULSE

Receptor potential lasts for duration of stimulus

There is a stimulus that disturbs resting
membrane

Permeability for Na+ increased

Na+influx

Decrease membrane potential

Decline by 15mV=reaches firing/threshold

level

Voltage gated Na+ channels open with rapid

23 |Page
Excitable cells -
physiology
Na+ influx

Membrane potential=zero=depolarised

BUT cells overshoots and reaches potential

of +35mV

This overshoot is unfavorable for Na+ influx

and voltage dependent K+ channels open
 Efflux of K+ increases and membrane begins to
repolarise

Spike potential = rapid rise and rapid fall

exceeds resting value

K+ voltage channels close and the

normal leak channels and Na+/K+
​pump begin to work and restore the
​resting potential​

DURATION ACTION POTE NTIAL

• Nerve is <1ms
• Skeletal muscle 5 ms

• Cardiac muscle 150-300ms

• Depolarisation in all of them=rapid

• Repolarisation differs (depend on voltage dependant K+ channels)

• Heart has a prolonged repolarization and plateau due

to prolonged influx of Ca2+ and continued influx of

Na+.

THRESHOLD INTENSITY:

• It is the weakest stimulus required to elicit an action potential.

• No action potential if sub-threshold.

• If above threshold, regardless of strength, the magnitude

23
of |action
Page
Excitable cells - potential is the same (the frequency of action
potential “waves” changes with the strength)
physiology

• Action potential is thus an all or none response

REFRACTORY PERIOD
 • For a short while after depolarisation membrane cannot be re-
excited
• Refractory period: two phases

ABSOLUTE REFRACTORY PHASE:

• Following onset of action potential
• Totally inexcitable

RELATIVE REFRACTORY PHASE:

• Just after overshoot until normal excitability returns.

***NOTE: Heart muscle is refractory until after end of
plateau***

LARGE FIBRES VS. NAR ROW FIBRES

​
- Shorter refractory period
- Stimulation possible at higher frequencies
- Greater speed of conduction.

- longer refactory period

- slower speed
​

ACTION POTENTIAL IN MYOCARDIUM

​
- SA and AV node
- Resting membrane potential -50mV to -60mV
- Unstable resting membrane potential

-
Normal muscle fibres and conducting tissue

- Resting membrane potential -80mV to -90mV

- Stable resting membrane potential
​
1|Page
Muscles-
physiology

• Pacemaker potentials
• Develop rhythmically in certain nerve cells
o e.g. the respiratory centre,
specialised heart cells and
some smooth muscle fibres
• There is a specific pace at
which these tissues activated
• Characterized by unstable membrane potential.
• Impulses not followed by steady resting potential.

PRE -POTENTIAL:
• The slow spontaneous decline
of potential. Also called
pacemaker potential.
• Steeper slope of pre-potential,
higher frequency of impulses.
• The pre-potential primarily
due to reduced permeability
for K+
• Increased permeability for Na+ may also contribute
 •
PROPAGATION OF ACTIO N POTENTIALS:
Action potential in pacemaker cells of heart is largely due
to rapid influx of Ca2+ with some contribution of Na+
influx.
• Along nerve and muscle fibres
• Action potential is not affected
• Due to local electric current flow between depolarised site and
1|Page
adjacent sites
Muscles-
• Depolarisation cannot occur behind area as in the refractory
physiology
period
NEUROMUSCULAR JUNCTION AND SLDING
3. •The
Speed of conduction
Ca2+ results in the <1mS-120mS
FILAMENT THEORY
neurotransmitters to bind
• Myelin acts as insulator
and exocytose acetylcholine
o Depolarisation
1. Action Potential travels down jumps from one node of Ranvier
axon towards terminal knob
(high density Na+ and K+ ion channels) to the
next thus speeding conduction in myelinated
fibres.
o This is called saltatory conduction
• Axon/muscle fibre can conduct in either direction when
artificial stimulation takes place in the middle
• In body axons normally pass from receptors/synaptic junctions to
their termination only
orthodromic conduction
• In opposite direction = antidromic
​

2. Voltage gated Ca channels

open and Ca2+ flows into
knob as [Ca2+] outside >
[Ca2+] inside
 S
t
i
1|Page m
Muscles- u
physiology l
i
t
h
**The Ca2+ is pumped out of the
knob when the stimuli
a
completed and acetylcholine
t
esterase degrades the
acetylcholine ithus closing the
Na+ ligand channels
s
a
t
t
h
7. The Ca2+ binds to the troponin C and results
e in a
conformational change exposing the myosin binding site to
AD
P
t can
which the cocked myosin (the actin binding site)
bind h
P
r
e
s
 h
o
l
d
l
i
m
i
t

3
N
a
+

Channels leak some of the ions

BUT due to the sodium Potassium
Pump that pumps 3Na+ out and
2K+ in this 1 |Page
resting potential is
maintained.Muscles-
Resting potentials:
• In muscles = -90mV
physiology
• In nerves = -70mV

Excitable cells - physiology

AD
10. ATP binds to the myosin ATPase site. The
​ P myosin then releases the actin
AT
P
P

11. ATP is hydrolyzed and the myosin becomes

AD
P
cocked again and ready for next contraction
 12. The Ca2+ falls off the troponin C and thus the
troponin I hides the myosin binding site. The Ca2+ is
AD
pumped back into the sacroplasmic reticulum
P

Myosin – think fibres

2 heads 1. Voltage gated sodium ch
Each head has two binding andsites sodium ions
- Actin binding site
- ATPase site
The tail is light
The head is heavy
​ Connected by a hinge
2 types of configurations
- High energy (ADP + Pi)
- Low Energy (ATP)

1|Page
Muscles-
physiology
Actin – thin fibres
Is a helix of globular protein
It sites on a nubelin “string”
 Tropomyosium is coiled around it to hold the helix together
Troponin
- T – binds to tropomyosium
- I – heads the Myosin binding site
- C – Is the Ca2+ binding site
Dystrophin – connects the actin to the cell membrane I Band – actin only
A Band – actin
Titin – is important for correct alignment. It is elastic and runs between
andthe
actin and myosin myosin
Z line – alpha actinin
M line – Shortens during contraction as the Actin
thickening is pulled into the A band
myosin
Sacromere – does not
shorten during a
contraction

3. The potassium rushes out and repolarisation occurs. However the potassium pumps
also overshoot as they take long to close and the membrane becomes
hyperpolarized.
​
4. The Sodium potassium pumps works and then brings the
membrane back to resting potential.
H Band – myosin only

SYNAPTIC TRANSMISSION
 6|Page
Muscles-
physiology

IMPULSE TRANSMISSION

• Transmission of impulses in humans are mainly chemical.

• Gap junctions with electrically mediated transfer does occur.
•
 10 | P a g e
Muscles-
physiology Synaptic transmission: takes
place in one direction: presynaptic to postsynaptic neurons.

• This potential develops when transmitter alters the

permeability in such a way that membrane is
hypopolarised
• Hypopolarisation or EPSP reaches threshold impulse generated
• Impulse then propagated all along axon.
• EPSP is not an all or nothing response.
•
SUMMATION

EPSP due to discharge from one synaptic knob not

usually enough to exceed threshold for impulse
generation but Usually there are many synapses on
each neuron (the same neuron summate)
• Spatial: Impulses arrive at several knobs at the same time.
• Temporal: Impulses arrive repeatedly at the same
synaptic knob before the previous EPSP’s have
subsided.

10 | P a g e
Muscles-
physiology

•
EXCITATORY TRANSMITTER SUBSTANCES

Facilitation: Discharge by one synaptic knob is said to facilitate th

effect of another.
• Acetylcholine Ach

• Noradrenaline NA

• Enzymes present at synapses inactivate the

transmitters after release to stop effect at
postsynaptic membrane.
• Ach inactivated by acetylcholine esterase

• NA inactivated by monoamine-oxidase (MAO)

• NA also inactivated by catechol-Omethyltransferase (COMT).
TRANSMITTER SUBSTANC ES DISPOSED BY

• Re-uptake by presynaptic terminals

• Uptake by glial cells
• Removal by circulation-broken down by liver.

NORADRENALINE

• Formed from amino acid phenylalanine or tyrosine

ACETYLCHOLINE

• Synthesis in nerve endings from choline and acetyl-CoA.

o Choline+Acetyl-CoA CAT Ach
• CAT (cholineactyltransferase) is enzyme catalyzing reaction.
10 | P a g e
• After release Ach is rapidly hydrolysed by enzyme
Muscles-
acetylcholinesterase (ACE) and the products are
physiology
taken up by presynaptic nerve endings.
o Ach ACE choline and acetate
•

IPSP INHIBITORY POSTSYNAPTIC POTENTIAL:

Works on muscarinic and nicotinic receptors
• When transmitter alters permeability of postsynaptic membrane in
such a way that the
membrane becomes hyperpolarised.
• May for instance increase permeability for K+. K+ efflux
 increases, and membrane more positive outside than
at rest.
• Membrane now less excitable than at rest.

• This is postsynaptic or direct inhibition

• Indirect inhibition also takes place: due to any

condition that prevents discharge of any neuron in the

chain. (e.g. if the neuron is refractory)
•
INHIBITORY NEUROTRAN SITTERS:

Presynaptic inhibition is also indirect inhibition:

Neurotransmitter release by presynaptic ending is
reduced/prevented.
GAMMA-AMINOBUTYRIC ACID GA BA

• Formed by decarboxylation of Glutamate

• Glutamate decarboxylase catalyses reaction
• Glutamate GABA

• B6 is a cofactor for GAD

• GABA-transaminase catalyzes metabolism of GABA

• Most common inhibitory neurotransmitter in CNS.
• Benzodiazepines facilitate GABA effects.

GLYCINE

• Brain stem and spinal cord

• Inhibitory neurotransmitter

• Increases membrane permeability for Cl-

•
10 | P a g e
NOTE!!
Muscles-
Binds to NMDA receptors.
physiology
• Action potentials do not develop, only excitatory/inhibitory

potentials-conducted
 electronically towards soma/cell body.
• Large part lost before it reaches soma
• Influences:

o Very dependent continuous O2 supply.

o Sensitive to pH:
▪ Acidosis depresses neural activity
▪

VOLUME TRANSMISSION:
Alkalosis increases neural excitability
• Extrasynaptic mechanism of transmission

• Neurotransmitters released by neurons into extracellular fluid.

• Diffuse through fluid and react with extrasynaptic receptors on

distant neurons.
• Mechanism for sustained mass activation of large numbers of

neurons.
•

IMPULSE TRANSMISSION TO MUSCLE FIBRES:

Responsible for “brain tone” and helps with sleep, vigilance,
attention, emotion, mood.
• Nervous stimulation needed for
o Excitation skeletal muscle
o Multi-unit type smooth muscle fibres.
•

SKELETAL MUSCLE:
Pacemaker cells have nerves that modulate their activity.
• Each muscle fibre supplied by only one nerve terminal and has a

single motor endplate.

• Axons of motor neurons branch extensively.

• Each branch supply one fibre.

• Thus when a single motor neuron activated all

the muscle fibres are activated simultaneously.
• Single motor neuron with all the muscle fibres innervated by
is=motor unit.
10 | P a g e
Muscles-
physiology Impulse arrives at motor endplate

Ach released (only transmitter

releases by motor endplate).

Binds to Ach receptors

Channels open

hypopolarised - Called Enplate

Potential

EPP reaches threshold action pot

 generated in adjacent membrane and
conducted all along muscle fibre

Depolarisation

Muscles-
physiology

contraction

known as excitation-contraction
Coupling.
​

• Supplied by autonomic nervous system

• Nerve terminals not specialized structures.
•

THE HEART:
Fibres receive two types of nerve fibres which release Ach and NA
respectively.
• Supplied by autonomic nervous system

• Modifies cardiac activity

• Substances Ach and NA

FUNCTIONAL ORGANISATION
OVERVIEW
 • Nervous system anatomical division:
o CNS and PNS
• Nervous system functional division:

o Somatic and autonomic system

​
-Controls voluntary action
-Sensory perception
-Higher functions of nervous system.

-Regulates organ activity e.g. heart, secretory glands and

involuntary muscles of viscera e.g. blood vessels, digestive
tract etc.
Muscles-
-No voluntary control: we are unaware of functions:
physiology
vegetative
NEURAL functions.
CONTROL
-Both systems have peripheral and central parts.

action potential
propogates
CNS down T-tubules
VGC
• Consists of brain and spinal
Ca2+cord
open column
• Protected by skull and vertebral

• Brain includes: Ca2+

o Cerebrum enters
o Cerebellum cell
Opens
o Brain stem
• Ryanodine
CEREBRUM: receptors
Brain stem connectschannels
Ca2+ isinand
cerebrum SR cerebellum with spinal cord.
 •Left and right hemispheres
released
•Corpus callosum = thickCa2+ band
nerve fibres connecting sparks
hemispheres across midline.
Summed sparks
• Cerebral cortex: outer gray layer each

hemisphere=mainly cause
cell Ca2+
bodiesto
diffuse to the
• Inner white matter = nerve fibres
contractile
Ca2+ binds protein
to
FIBRES CONNECT: troponn and
sliding
• Different parts same hemisphere=association fibres
Ca2+ back
filament to
• Hemispheres in two directions with lower regions
SRoccurs
and ECF fibres
(efferent + afferent fibres)=projection
via
• Hemispheres with each other=commissural fibres=corpus

callosum. Na+/Ca2+
exchanger

5 LOBES:

• Frontal
• Parietal
• Occipital
14 | P a g e
• Temporal
Muscles-
• Limbic
physiology
• Smaller grooves
subdivide these into
convolutions.
***6th lobe=insula***

FUNCTIONS:
• Frontal lobes: Mainly
motor functions
• Prefrontal areas associated with personality and association.
 • Parietal lobes: General sensations and associative functions.
• Temporal and occipital lobes: Receptive areas: hearing and vision
• Limbic lobes=involved behavior and emotion

NEOCORTEX:
• Consist of Frontal, parietal, occipital and temporal
lobes=phylogenetically the more recent additions to the
neocortex.
LIMBIC LOBE

• on medial and inferior surface each

hemisphere=phylogenetically older part
cortex=paleocortex
BASE EACH HEMISPHERE

• Thalamus and basal nuclei=grey matter.

• Thalamus has connections to lower parts and cortex esp. sensory
areas.
o Integrates sensory impulses from eyes, ears, skin,
muscles and joints and sends it to cortex
•
CEREBELLUM:

Basal nuclei and part of thalamus is NB in motor system

• Posterior to pons and medulla oblongata
• Vermis connects these.
• Neocerebellum, paleocerebellum, archicerebellum
• Each hemisphere connected to brain stem via three bundles
nerve fibres.
• 14 | P a g e
BRAIN STEM:
Muscles-
Cerebellum is involved in muscle control
physiology
• Consists of:
o Midbrain connected to cerebral hemispheres
o Pons
 o Medulla Oblongata continuous with spinal cord
• Afferent and efferent fibres connecting cerebrum to spinal cord.
• Nuclei include sensory and motor nuclei of cranial nerves
• Also nuclei of hypothalamus.
• Also contains reticular formation RF.
​

•
SPINAL CORD

RF=multisynaptic network of nerve cells with a number

of nerve cells e.g. motor nuclei involved in breathing,
heart rate, circulation, swallowing and vomiting=vital
centres.
• From medulla down vertebral canal.
• Particular segment corresponds to particular vertebra.
• 40-45cm long in adult.
• Stretches to L2 in an adult
• Full length of canal at birth.

STRUCTURE

• Grey matter=central
• Central canal
throughout whole
length.
• Anterior part “butterfly”=ant horn
• Posterior part=post horn
• Intermediate part=pars intermedia
•
PNS
Surrounding white matter
divided into dorsal, lateral
and anterior columns (or
anterolateral column) It
 contains ascending
14
afferent
|Page
sensory fibres and
Muscles-
descending efferent motor
physiology
fib
• Consists of ganglia and nerve fibres
• Include 31 pairs spinal nerves
• 12 pairs cranial nerves
• Spinal nerves connect spinal cord and sensory endings/effectors
•
SPINAL NERVES:

Cranial nerves connect brain stem with sensory and motor

structures of the head
• One pair, one L one R emerge from cord between each of the
vertebrae
• Comes through intervertebral foraminae
• C1 emerge between skull and 1 Vertebrae Thus 8 pairs
st

cervical spinal nerves C1-C8 and 7 cervical vertebrae.

BREAKDOWN

• 12 Thoracic T1-T12
• 5 Lumbar L1-L5
• 5 Sacral S1-S5
• 1 Coccygeal nerve
• 31 nerves on each side.

STRUCTURE
• Each spinal nerve: Afferent and efferent fibres that
originate form anterior and posterior root from the
spinal cord.
• Anterior root: Efferent fibres
• Axons of:
o Supplying voluntary muscles of body with motor cells in
anterior horn.
 o Autonomic nerves: motor cells located in
intermediolateral nucleus supplying glands and
involuntary muscles.
• Posterior root: Afferent
fibres enter cord through
post
14 | P a root
ge
• These
Muscles- fibres are axons of
unipolar sensory cells in spinal
physiology
ganglia
• These are situated outside
the CNS on post roots
before they enter spinal
cord.
• SUMMARY
o Anterior roots thus purely efferent/motor
o Posterior roots purely afferent/sensory.
o This arrangement =Bell-Magendie law.

CRANIAL NERVES:

• 12 Pairs originating from brain stem

• No post and ant roots
• Some purely sensory, some purely motor
• Motor: III,IV,VI XI and XII
• Sensory: I, II and VIII
• Autonomic fibres as well: III, VII, IX and X
CSF, MENINGES AND VE NTRICLES:
MENINGS

****GO TO NEURO NOTES AND STUDY THE CRANIAL

NERVE TABLE!!****

• CNS surrounded by three

 membranes known as meninges.
• Meningitis=inflammation thereof
• From within pia mater,
arachnoid mater, dura
mater.
• Pia mater=vascular
covering all
convolutions of surface
brain and cord.
• Space btw pia and
spidery arachnoid is
subarachnoid space
filled with CSF.
• Dura is thick and fibrous double membrane.
o Outer layer lines skull, inner layer seperates in
certain parts from the outer layer to form venous
sinussses between the two layers-venous blood
from brain drain into these.
o
VENTRICLES

Thus dura has periosteal and meningeal layer.

• One each hemisphere=lateral ventricles
• One in midline between two thalami=3 ventricle
rd

• 4 ventricle on medial dorsal aspect of pons and medulla

th

• From 4 ventricle continuous with central canal spinal cord.

th

• Ventricles connected to subarachnoid space through 3 openings

roof 4th ventricle
​

• Formed by
o Blood capillaries of brain tissue (extracellular fluid of tissue)
o Capillaries of pia mater
 o
BLOOD BRAIN BARRIER

Complex network blood capillaries in choroid plexuses in bra

ventricles
• Stable special internal environment necessary for brain cells in
provided by special qualities
of blood capillares.
• Transport and diffusion mechanisms allowing selective
passage of certain molecules and excluding others.
• Protects brain cells
• This mechanisms is the blood brain barrier.
• Composition of brain ECF and CSF differs from blood
plasma and these fluids are formed by filtration,
diffusion, osmosis and active transport.

EXCHANGE OF SUBSTANC ES THROUGH CAPILLARY WALLS RESTRICTED BY

• Tight junctions
• Electrical charge of basal lamina of endothelial cells

GENERAL FA CTS
• Barrier less effective in infections or injuries.
• BBB not exist at median eminence and chemoreceptor zone e.g
vomit centre.
• With kernicterus in newborn free bilirubin crosses BBB and
damages brain.
• CSF volume 140ml
• Daily production=600ml
• Brain has no lymphatic system
o Excessive production or failure of absorption
leads to accumulation of fluid in ventricles.
o
MAIN FUNCTIONS CSF:

Increased intracranial pressure as skull encases brain

• Protect brain tissue from mechanical trauma-shock absorber
 • System for removal excessive fluid from extracellular
space of brain-serves as lymphatic system
• Provides optimal fluid environment for brain functioning.
•
REFLEX ACTIVITY:
Distribution chemicals to brain centres involved in
adjusting vital functions e.g. H+ in resp centre
stimulates breathing.
• Reflex arc
o Basic unit of integrated neural activity,

i.e. a complete neural

circuit extending from
peripheral receptor to a
centre in CNS to perform
constantly recurring
stereotyped responses of
the body to environmental
stimuli.
• Reflex arc consist of sensory nerve ending, afferent
neuron, centre in CNS, efferent neuron and effector.
​

• Afferent nerve fibres enter via posterior nerve roots or

afferent cranial nerves (structures in the head)
• Cell bodies are in posterior root ganglia in the spine
or homologous ganglia on cranial nerves.
• Efferent fibres leave via ant roots or cranial motor nerves.
• Reflex=response to stimulus involving a reflex arc.
• Monosynaptic reflex arc=simplest.
•
AUTONOMIC VS. SOMATI C REFLEX ARC

Some reflexes inborn and other result of learning

 • Simplest somatic reflex arc is monosynaptic
• Autonomic reflex arc at least three neurons (disynaptic)
• Autonomic arc always contains a synaptic junction btw
axon of central neuron leaving CNS and effector organ
and this is present in peripheral autonomic ganglion.
• Somatic nervous system the axon of the central
neuron which leaves the CNS is not interrupted on
the way to effector.
• Afferent autonomic fibres=unmyelinated.
• Receptors in visceral organs (blood vessels, heart, lungs,
digestive tract, bladder etc.)
• Re specifically sensitive to:
o pressure/extension of the walls of organs like the
intestines, blood vessels and urine bladder (Stretch,
Baro, volume, chemoand osmoreceptors) and
o

OTHER NB STRUCTURES
MEDULLA:

Changes in O2, CO2, pH and electrolyte [ ] of the

body fluids e.g. blood, gastric juice etc. (chemo and
osmoreceptors.)

• Cardiomotor and resp centre

HYPOTHALAMUS:

• temp regulation, thirst and hunger centres.

• Hypothalamus formed below thalamus.
• Connections to pituitary gland.
• Neuroendocrine organ (autonomic nervous system and
hypophysis function)
•
ANS
Controls all autonomic processes in body.
 • Divided into two divisions:
o Sympathetic division=thoracolumbar outflow
o Parasympathetic division=Cranial +sacral outflow.
• Preganglionic mainly myelinated group B fibres
•
SYMPATHETIC DIVISION

Postganglionic mainly unmyelinated group C fibres

• Preganglionic efferent fibres enter paravertebral ganglia=about 22
ganglia each side
vertebral column
• Fibres of digestive tract do not relay in chain but
synapse incollateral ganglia on arteries supplying
intestines.
• Postganglionic fibres supply most organs
• Adrenal medulla receives only preganglionic fibres.
​

• Preganglionic fibres of III, VII, IX form synapse in ganglia in head

• Some of nerve X/vagus also synapse in some ganglia,
but most of its fibres terminate in terminal ganglia
close to structures supplied by it.
• Vagus supplies most organs in abdomen and thorax.
•
TRANSDUCTION
The efferent fibres of S2-4 supply pelvic organs.
• All the processes involved in converting a stimulus into an action
potential.
ADAPTATION

• When a stimulus is applied for a prolonged period of time, most

sensations eventually
 CLASSIFICATION OF RECEPTORS:
PROPRIORECEPTORS:

subside of become reduced-the receptors are desensitised

• Info concerning movement and position of body parts in space:

inner ear and muscles,
EXTERORECEPTORS:

tendons.
• Info on changes in external environment: skin-touch, light
pressure, cold, heat, pain
INTERORECEPTORS:

•
TELERECEPTORS:

Impulses from visceral organs-autonomic nervous system.

• Stimuli from remote source: sight, hearing, olfaction.
CHEMORECEPTORS, MECH ANORECEPTORS, NOCIRECEPTORS (PAIN) .

AFFERENT PATHWAYS: NB! NB! NB! NB! NB!

• Receptors-afferent nerves-posterior roots group together to form

ascending tracts.
BODY AND LIMBS:

SPINOCORTICAL SYSTEM

• Low threshold, fast conducting, A

alpha fibres mediating fine touch, light
pressure and proprioception ascend
in posterior columns on the
ipsilateral side to medulla to form the
posterior column system=
 spinocortical system/Goll and
Burdach tracts.
• In medulla synapse with cells in Goll and Burdach nuclei
Axons cross the midline and
continue on contralateral side in
brain stem as the medial lemniscus
to thalamus.
• In thalamus they synapse with cells
in specific sensory projection
nuclei.
• From here to primary somatic
sensory areas SI and SII of cortex.
​

SPINOTHALAMIC TRACTS.

• Other fibres mediating touch, pressure and

proprioception and also fibres for temp and
pain synapse in posterior horn of spinal cord.
• These cross the midline (immediately) and ascend in
anterolateral system
= spinothalamic tracts.
• Fibres for pain and temperature ascend in lateral spinothalamic
tract.
• The rest in the anterior spinothalamic tract.
• Both proceed through the brain stem as
spinal lemniscal system to specific
sensory projection nuclei in thalamus.
• From thalamus fibres project to cortical somatic sensory areas.
• Anterolateral system contains different types
group A fibres and high threshold slow
unmyelinated group C fibres.
HEAD AND FACE:

• Sensory division of trigeminal nerve V Enters pons

• Primary afferent fibres synapse with superior
sensory nucleus (touch, presssure and
proprioception)
• And spinal sensory nucleus (temperature and pain.)
•
THE THALAMUS:
Axons cross midline and proceed as trigeminal lemniscus-to
thalamus.
• Two thalami at base cerebrum interlinked with brainstem and
each hemisphere.
• Nuclei:
o Sensory projection nuclei: gateway for sensory impulses.
o Nonspecific projection nuclei: Receive fibres
from RAS and project diffusely to neocortex.
o Nuclei for motor control: work with basal ganglia
o

PAIN:
Nuclei for integrated functions e.g. speech.
• Protective value.
• Pain receptors: All tissues of body except neural tissue of
brain.(present in meninges, venous sinuses and blood
vessels of brain)
• Thin myelinated A delta and unmyelinated C fibres. (Fast pain
and slow dull pain)
•
FREE FORMAT QUESTIONS
NAME THE 5 LOBES AND THEIR FUNC TIONS. (10X½ = 5MARKS)

To posterior horn in spinal cord.

 • Frontal lobe – motor
• Occipital lobe – vision
• Parietal lobe – general sensation
• Temporal lobe – hearing
•
LIST THE MAJOR SENSO RY P ATHWAY S, AND NAM E TWO SENSATIONS TRA NSMITTED BY EACH P AT
HWAY .
Limbic lobe – behaviour and emotion
• The major sensory pathways/ tracts are the spinocortical tract and
spinothalamic tract.
• Spinocortical tract – transmits fine touch and light pressure
• Spinothalamic tract – transmits hard touch and hard pressure as
well as pain.​

MUSCLES -
PHYSIOLOGY
SKELETAL MUSCLES
GENERAL
VOLUNTARY

• Can move by conscious effects

• Requires direct nerve stimulation
STRUCTURAL
ORGANISATION
• Skeletal muscle
↓subdivided into
• Fascicles
↓each fascicles is made up of
• Muscle fibres/cell
 ↓each muscle fibre is made up of
• Myofibril
↓each myofibril is made up of
• Myofilaments
***Myoblast mature
cannot repair damage***

CONNECTIVE TISSUE CO MPONENT

• Entire muscle is surrounded by dense connective tissue sheath =

EPIMYSIUM
• Each fascicle is surrounded by connective tissue = PERIMYSIUM
o Blood vessels
o Nerves
o Lymphatic vessels
• Each muscle fibre is surrounded by connective tissue =
ENDOMYSIUM
o Reticular fibres
o Collagen
o Connective tissue cells
o Blood vessels

MUSCLE FIBRES:

• Long cylindrical cell

• Many peripheral nuclei (located below sarcolemma)
• Each fibre has organised bundles (myofibrils) that
consist of many contractile and elastic fibres/proteins
that carry out contraction = MYOFILAMENTS
​

MYOFILAMENTS
 MYOSIN

• Thick filament
• Tail and head region (golf club with 2 heads)
• Tail = light meromyosin, Head= heavy meromyosin
• tail and head are linked by elastic hinge region
• Head has 2 binding sites, one for actin, one for ATP
• Can exist in a high energy conformation (bound to ADP
and Pi) or low energy conformation (bound to ATP)
ACTIN

• Thin filament
• Each actin molecule is a globular protein (ball) that join up to form
a long chain
• 2 long chains of actin twist around each other to form a double
helix type structure
• On each actin sub-unit you will find myosin binding sites
• A tropomyosin protein also entwines around with the
actin chain hiding the specialised myosin binding
sites
• Topinin (another protein) will be spaced periodically
on the tropomyosin, covering the myosin binding
sites

• Myofilaments are arranged parallel to one another and

overlap each other forming cross striations – dark and
light bands
BAND STRIATION MYOFILAMENT COMPOSITION
A band dark Overlapping myosin and actin
I band light actin
Z line Dark line in centre of I band Alpha actin
H band Lighter zone on A band myosin
 M line Dark line in centre of H band Connecting strands and thickening of
myosin
• Functional unit = sarcomere which extends from one Z
line to the next •During contraction sarcomere shortens

SARCOLEMMA:

• Sarcolemma invaginates at A-I band junction of each

sarcomere to form T tubules which are continuous with
the sarcolemma
• T tubules encircle myofibrils
• On either side of the t tubule, you will have terminal
cisterna which are essentially little sac’s of sarcoplasmic
reticulum
• T tubule + terminal cisterna on either side = TRIAD
• Ca2+ is store in the terminal cisterna
​

REGULATORY ROLE OF T ROPONIN AND

TROPOMYOSIN
• Ca2+ increases in cytosol
• Binds to troponin
• Troponin ca2+ complex pulls tropomyosin away from binding site
• Powerstroke
• Myosin detached
• Ca2+ pumped out and tropomyosin covers binding site
ROLE OF ATP

• Power stroke of myosin cross bridge

• Disconnecting of myosin cross bridge
• Energizing the Ca2+ pump
WHAT AFFECTS ACH?
 • Curare – interferes with receptor sites, paralyses skeletal muscle.
• Organo-phosphates – destroy receptors.
NEURAL CONTROL OF THE MUSCLE

• Each skeletal muscle supplied by the SOMATIC nervous system

• Nerve fibres DO NOT converge on a muscle fibre
• They diverge Each motor neuron branches with 1 branch
supplying 1 muscle fibre
• Consequently when a single motor neuron is
activated all muscle fibres supplied by its branches
are activated – muscle moves as a whole unit
• Motor neuron and all the muscle fibres it stimulates = MOTOR
UNIT
• Number of muscle fibres per motor unit varies:
o Fine precise movements (eye) = few fibres per unit
o Gross large movements (legs) = many fibres per unit
• Each motor neuron terminates on a muscle fibre via a motor end
plate
NERVES

• Large
• Myelinated A alpha
• Speed 60 – 120 m/s
• Axons travels via spinal nerve to muscle ends in terminal
branches

***NOTE! During a long muscle contraction the myosin heads

release at different times to get more energy and this
always the muscle to stay contracted***
 4. The acetylcholine is now in the synaptic cleft and binds to nicotinic
receptors that are Na+ ligand receptors and thus these open and Na+ diffuses
down its concentration gradient. An action potential develops
following the normal process (depolarization, repolarization)

5. Action potential propagates

along the sarcolemma and down
the T-Tubule
 6. This action potential then activates the dihydropyridine channel, linked to the terminal
cisterna and Ca2+ flows into the cytosol

​
8. Myosin bind to actin
9. ADP and Pi are released and a power stroke
occurs. Actin pulled in and muscle contracts.

Key for colour details

Ca
2+
​ ​ ​ SR

Na
+
​ ​ ​ Nicotinic receptors

Ach ​ ​ ​ VGC Ca 2+

Actin ​ ​ ​ Myosin
Dihydropyrid
​
​

ASPECTS OF MUSCLE CONTRACTION

ATP SUPPLY

• ATP supply is NB! In muscles

MUSCLES GET ATP IN M ANY WAYS:

• Phosphocreatine found in muscle cells has high

energy bonds and ATP is release via the enzyme
creatine kinase
• Carbohydrates give rise to glucose which enter
glycolysis and the citric acid cycle to form ATP
• When O2 levels are low, glucose enters anaerobic glycolysis and
forms lactic acid
• Fatty acids are also a source of ATP but is very slow
(converted to acetyl CoA via beta- oxidation)
MUSCLE FIBRES

WHITE MUSCLE FIBRES RED MUSCLE FIBRES

Small amounts of myoglobin – light in Large amounts of myoglobin – darker in colour
colour
Few mitochondria Many mitochondria
Large diameter Small diameter
Few capillaries Many capillaries
High glycogen content Low glycogen content
“fast twitch glycolytic fibres”
Glycolysis used for ATP production
Activities requiring power or speed for
short duration
Rapid cross bridging = fast
contraction
Large number of myofilaments
Build up of lactic acid and depletion of
glycogen = FATIGUE
Eg, Body builder, sprint runner
“slow twitch oxidative fibres”
Krebs cycle used for ATP production
Activities requiring endurance and continuous
contraction
Slow cross bridging = slow contraction
Small number of myofilaments
Fatigue resistant
Eg, marathon runner

OXYGEN DEBT

• After exercise is complete, muscle restores the depleted

energy stores used. This process is know as repaying
the oxygen debt.
o Lactic acid converted back to pyruvic acid which enter the
Kreb cycle
o ATP is used to rephosphorylate creatine into
creatinephosphate
o Glycogen is synthesized from glucose molecules
o Additional O2 re-binds to myoglobin

WHAT DETERMINES CO NTRACTILITY

AVAILABILITY OF

• ATP
• Actin sites
• Myosin head binding
• ATPase activity
AVAILABILITY OF FREE CA2+
 • Mobilization from the sarcoplasmic reticulum
• Depolarization of muscle membrane
• The pattern of nerve stimulation to the muscle fibre
MUSCLE TWITCH

• Muscle contraction to a single stimulus of adequate

strength – a single contraction relaxation cycle

1. LATENT PERIOD •Sarcolemma and T tubules depolarize

•Ca2++ released into the cytosol
• Cross bridge begins to cycle but no visible shortening of muscle
•5ms long

2. CONTRACTION •Sarcomeres shorten

PERIOD •Tension developed
•40ms long

3. RELAXATION •Ca2+ transported back into terminal cisterna

PERIOD •Cross bridge cycling decreases and ends
•Muscle returns to original length
•50ms long

SUMMATION

• If interval time between action

potentials is shortened, muscle
fibres do not have adequate
time to relax between 2 stimuli
• This will result in a more powerful contraction
TETANUS

• Action potentials that stimulate

the muscle fibre repeatedly at
short intervals
• Relaxation between contractions
 diminishes and muscle reaches
a state of maximal contraction
​

• Incomplete tetanus – stimulation rate is not at a

maximum and muscle has time to relax slightly
between stimulations
• Complete tetanus – stimulation rate is fast enough
so no relaxation occurs between stimulations
TYPES OF CONTRACTION
ISOMETRIC

• Contractions that create force without moving a load

• E.g. Pushing against a wall
ISOTONIC

• Any contraction that creates force and moves a load

• Concentric: muscles shorten during force production (eg, bicep
curl)
• Eccentric: muscle lengthens during force production (eg,
resisting tendency of weights to put them down)
PRELOAD

• Is the load on a muscle in a relaxed state, prior to contraction

• Affect the relationship between myosin heads and available actin
‘active’ sites
AFTERLOAD

• Is the load the muscle is working against or trying to move during

stimulation
STARLING'S LAW
 • A muscle responds to increased stretching at rest by an
increased force of contraction when stimulated
• You can increase force of contraction if you increase the preload
within certain range

INTRA VS. EXTRA

INTRAFUSAL MUSCLE FIBRES EXTRAFUSAL MUSCLE FIBRES
Skeletal muscle fibers that comprise of standard muscle that fibers comprise of myofibrils
specialiazed sensory receptors
• the muscle spindle (in connenctive tissue capsule)
• golgi tendon organ
Innervated by gamma motor neurons Innervated by alpha neurons
Proprioceptors in the muscle – monitor degree of Movement in muscle via contraction
stretch

• When extrafusal muscle fibres contract so do the

intrafusal muscle fibres due to the fact that they also
contain actin and myosin
​

MUSCLE TONE

• Muscles are never flaccid unless something is wrong.

 MUSCLE HYPERTROPHY

• Anaerobic exercises – resistance training.

• Proteins increase – myofibril number increase and cell expands,
(no increase in cell number)
MUSCLE ATROPHY:

• Use it or lose it!

• Muscle immobile – proteins degenerate.
DEGENERATION OF SKEL ETAL MUSCLE:

• Damage to muscle
o trauma, disease (genetic or metabolic)
• Damage to motor neurons
o Upper motor neurons (brain cannot signal to
contract) – spastic paralysis with muscle atrophy.
Direct corticospinal nerves – excitatory. Others –
inhibitory. Inhibitory nerves not functioning – leads
to contraction. Muscles will have high tone (cannot
move voluntarily) but still paralyzed.
o Lower motor neurons (no stimulation to muscle-
cannot contract or relax) – flaccid paralysis with
muscle atrophy. Lose reflexes. Final common
pathway not functioning
– cannot send commands to muscle.
MUSCLE REGENERATION

• Mature muscle cells do not have the ability to divide

• Satellite cells (myoblasts which did not mature) divide
and attach to myocytes and aid muscle regenerated
​
 SMOOTH MUSCLE
OVERVIEW

• Non-striated
• Involuntary
• Single centrally located nuclei
DIFFERENCES FROM SKELETAL MUSCLE

• Neural innervation is autonomic

• Neurotransmitter is released from varicosities
surrounding the muscle cell – there is no motor end
plate
• No TROPONIN
• Poor sarcoplasmic reticulum – no t tubule system
ARRANGEMENT
SINGLE UNIT

• Individual muscle cells contract as a joint unit

• Forms walls of internal organs (blood vessels and GIT)
• Nerve supply via varicosities
• The cells are connected to each other via
o Gap junctions
o Tight/occluding junctions
MULTI UNIT

• Made up of cells that are not electrically linked and need to be

stimulated independently
• Each cell is associated with an axon terminal or
varicosity ( a number of these cells are supplied by 1
postganglionic autonomic fibre)
 • In iris, uterus, male reproductive system
MYOFILAMENTS

• Thick – Myosin
• Thin – Actin
• Intermediate:
o Desmin in non vascular smooth muscle

o Vimentin in vascular smooth muscle

ARRANGEMENT

• Not arranged in sarcomeres no striations

• Arranged as diagonal bunches of fibres across the cell
• Actin attaches to dense bodies and terminate at attachment
plaques

12 | P a g e
​

Myosins entire surface is covered by myosin heads

•

o This enables smooth muscle to stretch and contract more

• Intermediate filaments stretch between actin and myosin filament

bundles
CONTRACTION

• innervated by autonomic nerves

• neurotransmitter is released from varicosities to
influence cells (no direct innervation by nerves)
• Relies on [Ca2+] to initiate contraction (not Ach)

• Ca2+ is obtained from the extracellular environment

• Channels open:

o Autonomically
o Mechanical stretch – channels open via stretch
o Chemical molecules
▪ Neurotransmitter (acetylcholine, norepinephrine)
▪ pH
▪ Hormones

o
MECHANISM
Temperature

Ion channel gates open

Ca enters cell

Ca binds to calmuldin

Activates myosin light chain kinase

Phosphorylates myosin heads with ATP

Bind to actin
 Contraction

Ca2+ is removed via

Ca2+ ATPase,
dephosphorylation of the
myosin by
myosinphosphatase

​Muscle relaxes ​
13 | P a g e

AUTONOMIC INNERVATION

• PARASYMPATHETIC NERV OUS SYSTEM

• Sleep and weep / rest and digest

• ↑ Smooth muscle contraction (GIT movement)

• ↑ Glandular secretion
• Bronchocontriction

• Visceral vasoconstriction
SYMPATHETIC NERVOUS S YSTEM

Fight and flight

•

• ↓ smooth muscle contraction

• ↓ glandular secretion
• Bronchodilation

• Parietal vasoconstriction

CHEMICAL SIGNALS
ADRENALINE AND NORAD RENALINE

• This depends on the receptor present

• Relaxes smooth muscle

• Eg, given in asthma attacks to dilate bronchiole

OXYTOCIN

• Acts on mammary myoepithelial cells that surround the ducts

• Causes contraction and generation of milk
• Also acts on uterus

• Causes uterine contraction for birth

• This depends on the number of receptors present

ESTROGEN AND PROGEST ERONE

• Progestrone relaxes uterus

• Estrogen cause it to contract

CARDIAC MUSCLE
OVERVIEW

Striated
•

• Branched

• Oval centrally placed nuclei

• Control involuntary

CELL TYPES

• Nodal cells AV and SA = slow

• Normal muscle fibres
• Working muscle fibres = fast
 Heart is able to contract without nerve stimulation
•

• Generates spontaneous action potential

• Auto-rhythmic cells is where is starts (SA node)

• Have unstable membrane potential = pacemaker potential -

60mV
• If channels allow the current to flow then Ca2+ leaks in

• Pacemaker then reaches threshold frequency intensity,

cells fire, action potential generated, muscle contracts
CONTRACTION MECHANISM
​

ECG

• Diastolic relaxation
• Systolic contraction

• P = depolarization of atria
• QRS = ventricles depolarise

• T = repolarization

PRE- AND POST-NATAL GROWTH

STAGES IN THE DEVELO PMENT OF THE CONCEPT
US:
• Zygote

• Blastocyst
 Embryo
•

Foetus
•

ALL STAGES OF DEVELO PMENT

New born
•

Infancy
•
• Childhood

• Adolescence

• Adulthood

• Old age

TERMS

Hypertrophy
•

• Hyperplasia

• Differentiation – cells become established functionally in

particular way e.g. differentiate into muscle cells

• Specialisation – much better at particular function than other cells

in body
• Resolution

• Substitution

• Growth is defined as increase in number or size of

cells, or combination of the two. Hyperplasia
(number) or hypertrophy (size).
POST-NATAL GROWTH PROCESSES:
THE NEWBORN:

• Maturation and increase in efficiency of systems:

o Cardio-respiratory systems
o Liver
o Nervous system
 Reflexes of the newborn
▪
Limited ability to communicate
▪
o Gastro-intestinal tract
• Loss of fetal tissue and adaptation

o Fetal haemoglobin
o Fetal vascular shunts
o Thymus and fetal adrenal cortex (quite prominent in fetus
during development)
• Temporary cessation/reduced rate of growth

o Reproductive organs and glands

• Maturation and increase in efficiency of systems

o Cardio-respiratory system (as fetus develops heart

becomes more mature, size of heart muscles
increases, increased ability to pump blood. Lungs
– start producing substance that prevents lungs
from collapsing)
o Liver (bilirubin is produced when red blood cells are
broken down and needs to be removed from
circulation by the liver, or jaundice can develop)
​

o Gastrointestinal tract (when baby is born, no more

transfer of nutrients and removal of metabolic waste
through mom)
o Nervous system: 1. Reflexes of newborn –
involuntary response die to specific stimulus
indicates that nervous system is functioning
properly. 2. Limited ability to communicate – crying
and later smile reflex.
INFANCY

• Myelination increase
 • Synapse formation increase in pattern and complexity
o Determined by stimulation
o Learning and memory – affected by information input

THE CHILD

• Circadian rhythm of hormone secretion

o Growth hormone at night
• Increase in maturation of hypothalamo-hypophyseal-gonadal

function
•
THE ADOLESCENT:

Hypothalamo-hypophyseal-gonadal axis – role in growth and

development
• Girls early developers menarche

• Boys overtake and outgrow

YOUNG ADULT

• Maturation and peak in efficiency of systems (about 25 years):

o Cardio-respiratory systems
o Liver
o Nervous system
o Gastrointestinal tract
AGING

• Free radicals damage body.

• Waning in efficiency of systems