ILA Flashcards
what is the first stage of protein synthesis?
transcription
what is the second stage of protein synthesis?
translation
where does transcription occur?
nucleus
which enzyme carries out transcription?
RNA polymerase
NOT DNA polymerase
what is transcription?
DNA sequence is copied to make an RNA molecule
function of DNA helicase
unzips
breaks hydrogen bonds in the DNA double helix to unzip the DNA double helix and expose nucleotides
function of topoisomerase
unwinds
relieves the supercoils
function of single stranded binding proteins
SSBPs
stop DNA strands reannealing
where does RNA polymerase bind?
at the TATA promoter region
what is the promoter region?
TATA
in what direction does RNA polymerase move?
3’ to 5’
in what direction does RNA polymerase read?
3’ to 5’
in what direction does RNA polymerase code?
5’ to 3’
what are the stop codons?
UAA
UAG
UGA
for transcription, are one or both strands copied?
one
how does RNA polymerase work?
adds complementary mRNA nucleotides to the template strand to build an RNA chain
does the RNA transcript contain the same information as the template or non-template strand?
non template strand
this is called the coding strand
which nucleotides does RNA contain?
AUCG
what is the start and end of an mRNA strand?
poly-A tail (end) and 5’ cap (start)
product of transcription
pre mRNA
what part of pre-mRNA is removed?
introns
splicing
process of removing introns to form a fully coding strand
what part of mRNA remains after splicing?
exons
where does splicing occur?
in the nucleus
which enzymes carry out splicing?
spliceosomes
how does mRNA leave the nucleus?
nuclear pore
what is translation?
protein is synthesised from mRNA
where does translation occur?
ribosome in cytoplasm
3 bases on tRNA
anticodon
what does the tRNA anticodon bind to?
mRNA codon
3 DNA bases
triplet
describe translation
tRNA anticodons bind to mRNA codons
tRNA carries the correct amino acid
peptide bonds form between the amino acids
stop codon is reached
product of translation
polypeptide
where is mRNA broken down after translation?
cytosol
in which direction does mRNA move?
3’ to 5’ direction
transcriptome
the sum total of all the mRNA molecules
what is an SNP?
single nucleotide polymorphism
DNA sequence variation when a single nucleotide is substituted
consequences of an SNP
can result in a different codon which generates a different protein and thus disease
can affect recognition/ promoter/ termination sequences to change the length of proteins
most don’t (e.g if in an intron)
name two diseases caused by an SNP
cystic fibrosis
sickle cell anaemia
what is sickle cell haemoglobin?
HbS
genetic cause of HbS
SNP of adenine to thymine
GAG becomes GTG on 17th nucleotide
glutamic acid to valine
different primary structure
difference between sickle cell anaemia and sickle cell trait
sickle cell anaemia - both genes that code for haemoglobin are abnormal (HbSS)
sickle cell trait - only one chromosome carries the abnormal allele
how many of the beta subunits are replaced by HbS in sickle cell disease
just one
which subunits does haemoglobin have?
2 alpha
2 beta
what is normal adult haemoglobin?
HbA
is sickle cell anaemia autosomal dominant or recessive?
recessive
functional changes in HbS
red blood cells become sickle shaped
cells don’t live as long
lower affinity for oxygen
gets stuck in blood vessels
reduced oxygen delivery to muscles
primary structure of a protein
sequence of amino acids
covalently bonded
secondary structure of a protein
alpha helices and beta pleated sheets
hydrogen bonds
tertiary structure of a protein
3D structure of a single chain of amino acids
- London forces
- hydrogen bonds
- ionic bonds
- disulphide bonds
quaternary structure of a protein
the presence of more than one polypeptide chain
what fraction of water is in the intracellular fluid compartment?
2/3
what fraction of water is in the extracellular fluid compartment?
1/3
what volume of water is in the intracellular fluid compartment?
28L
what volume of water is in the extracellular fluid compartment?
14L
what volume of water is in the plasma fluid compartment?
3L
what volume of water is in the interstitial fluid compartment?
11L
what percentage of body sodium is exchangeable?
70%
what percentage of body sodium is bone crystal?
30%
what percentage of the total body sodium is in the ECF?
50%
what percentage of body sodium is in the ICF?
5%
what percentage of the body weight is water?
60%
define osmolality
concentration of a solution expressed as solute particles per kg
define osmolarity
concentration of solution expressed as solute particles per L
define oncotic pressure
pressure exerted by plasma proteins on capillary wall
force keeping water in a capillary
define osmosis
process by which molecules within a solvent pass through a semi-permeable membrane from a high to low concentration
what is hydrostatic pressure?
force pushing water out of the capillary
what part of the brain detects a low water potential?
osmoreceptors in the hypothalamus
what does the hypothalamus trigger?
release of ADH from the posterior pituitary
where is ADH released from?
posterior pituitary gland
what stimulates the posterior pituitary?
hypothalamus
what does ADH act on?
kidney
effect of ADH
increased fluid retention
is urine diluted or concentrated in the loop of Henle?
diluted
where is urine concentrated?
distal tubules and collecting ducts
is the descending limb of the loop of Henle permeable to sodium chloride and water?
impermeable to sodium chloride
permeable to water
is the ascending limb of the loop of Henle permeable to sodium chloride and water?
permeable to sodium chloride
impermeable to water
where is renin released from?
granular cells (juxtaglomerular cells) of the renal juxtaglomerular apparatus
what triggers renin release?
- reduced sodium delivery to DCT detected by macula densa
- reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole
- Sympathetic stimulation of the JGA via β1 adrenoreceptors
what inhibits renin release?
ANP
atrial natriuretic peptide
when is ANP released?
released by stretched atria in response to increases in blood pressure
where is angiotensinogen made?
liver
what converts angiotensinogen to angiotensin I?
renin
what converts angiotensin I to angiotensin II?
ACE
angiotensin converting enzyme
effects of angiotensin II
arteriolar vasoconstriction
Na+ reabsorption in the kidneys
triggers the sympathetic nervous system to release noradrenaline
aldosterone release from the adrenal cortex
hypothalamus - increases thirst sensation and stimulates anti-diuretic hormone (ADH) release
increases the volume of ECF and increases blood pressure
where is aldosterone released from?
zona glomerulosa of the adrenal cortex of adrenal gland
effect of aldosterone
acts on principal cells of the collecting ducts of the nephron
increases absorption of sodium and water into the blood
increases the excretion of potassium
where is albumin produced?
liver
what is the main plasma protein contributing to oncotic pressure?
albumin
what does low albumin cause?
oedema
what is low albumin levels called?
hypoalbuminemia
why does hypoalbuminemia cause oedema?
fluid moves from capillaries into interstitium
key routes of water loss from the body
urine
faeces
sweat
breath
vomiting
what are sensible water losses?
can be measured
what are insensible water losses?
cannot be measured
examples of insensible water losses
breath, sweat, faeces
give examples of sensible water loss
urine
what is vasopressin also called?
ADH
how does ADH/ vasopressin work?
binds to receptors on the collecting duct membrane
causes intracellular production of cAMP which activates protein kinase, which phosphorylates proteins that increase the rate of fusion of vesicles containing aquaporins with the membrane
what stimulates thirst?
an increase in plasma osmolarity
decrease in extracellular fluid volume
angiotensin II
what happens when renal blood flow is reduced?
juxtaglomerular cells convert prorenin to renin in the kidneys
what are the components of the juxtaglomerular apparatus?
- macula densa - part of DCT
- juxtaglomerular cells (granular cells) - afferent arterioles
- extraglomerular mesangial cells
where is the macula densa?
DCT
function of the macula densa?
sensitive to changes in NaCl
where are the juxtaglomerular (granular) cells?
afferent arteriole
function of the juxtaglomerular cells
release renin
where are mesangial cells?
central stalk of the glomerulus
what is the difference between the action of ADH and aldosterone?
ADH increases the nephron’s permeability to water whereas aldosterone increases the reabsorption of both sodium and water
effect of sodium on ECF volume, blood volume and blood pressure
an increase in Na+ in ECF =
- increased ECF volume
- increase in blood plasma volume
- increased blood pressure
a decrease in Na+ in ECF
- ECF decrease
- blood volume decreases
- blood pressure decreases
where is the thirst centre?
hypothalamus
normal homeostatic response to excess fluid
decrease in ECF osmolality detected by osmoreceptors
- water moves into ICF from ECF
- stops the stimulation of the thirst centre in the hypothalamus
- inhibits ADH in the posterior pituitary, leading to an increased urine volume
where are osmoreceptors found?
hypothalamus
consequence of excess water consumption
hyponatremia
normal homeostatic response to dehydration
increase in ECF osmolality detected by osmoreceptors
- water moves from ICF to ECF
- stimulates thirst centre of hypothalamus
- ADH released from posterior pituitary to decrease urine volume
state how much water a 70kg man has, and how much of this is intracellular, interstitial and intravascular
42L in total
28L is intracellular
11L is interstitial
3L is intravascular
estimated plasma osmolality
2[Na] + 2[K] + urea + glucose mol/L
normal range for plasma osmolality
270-310
where is ADH made?
hypothalamus
where is ADH stored?
posterior pituitary
where does ADH act?
kidney
where is aldosterone produced?
adrenal cortex of adrenal gland
where is aldosterone secreted from?
adrenal cortex
where is renin produced and secreted from?
juxtaglomerular cells of the kidney
equation for cardiac output
stroke volume x heart rate
what is cardiac output?
volume of blood pumped by the heart per minute
unit of cardiac output
L/ minute
what factors affect heart rate?
autonomic innervation, hormones, fitness levels, age
equation for stroke volume
SV = EDV - ESV
stroke volume = end diastolic volume - end systolic volume
what factors affect stroke volume?
contractility, preload, after load, heart size, fitness level, gender, duration of contraction
what is contractility?
how hard/ fast muscles flex
what is preload?
degree of myocardial distension prior to shortening
what is afterload?
force against which ventricle must act in order to eject blood
what does the LAD supply?
anterior 2/3 of interventricular septum, lateral wall of left ventricles and anterolateral papillary muscle
what does the right coronary artery supply?
SAN and AVN
right ventricle, right atrium
equation for blood pressure
blood pressure = cardiac output x total peripheral resistance
BP = CO x TPR
equation for pulse pressure
PP = SP - DP
pulse pressure = systolic pressure - diastolic pressure
equation for mean arterial pressure
MAP = DP + 1/3PP
mean arterial pressure = diastolic pressure + 1/3pulse pressure
what is pulse pressure?
difference between systolic and diastolic pressure
what is mean arterial pressure?
average arterial pressure throughout one cardiac cycle, systole, and diastole
what is stroke volume?
volume of blood pumped out of the left ventricle of the heart during each systolic cardiac contraction
which factors affect blood pressure?
vasopressin (ADH), aldosterone, ANP, haemorrhage, sweating, stressors, hydration, weight, muscular activity, posture
average cardiac output
5L/min
what is Frank Starling’s Law?
the greater the stretch of myocardium before systole, the stronger the ventricular contraction
stroke volume of the heart increases in response to increased volume of blood in ventricles before contraction
stroke volume increases with EDV
what is the physiology behind the Frank-Starling Law?
increased force because actin and myosin filaments are brought to more optimal degree of overlap for force generation
normal range of EDV
110-120ml
when is the cardiac cycle initiated?
SAN fires
what does firing of the SAN cause?
atrial depolarisation
how is atrial depolarisation represented on an ECG?
p wave
when does atrial contraction start?
shortly after the p wave
consequence of atrial contraction
blood enters ventricles
why doesn’t ventricular volume start at zero?
there is a passive movement of blood from the atria to the ventricles as the AV valves are open due to the pressure gradient
why do the AV valves shut?
ventricular pressure rises above atrial pressure
what causes the first heart sound?
closing of AV valve
how is ventricular depolarisation represented on an ECG?
QRS complex
why does the ventricular volume initially not change?
semilunar valves are shut
what is isovolumetric contraction?
ventricles contract when the semilunar valves are shut, so the volume does not change
what is the rapid ejection phase?
ventricular pressure exceeds pressure in the aorta and pulmonary artery
semilunar valves open and blood is ejected out of the ventricles
how is ventricular repolarisation represented on an ECG?
T wave
what is the second heart sound?
ventricular pressure falls below aortic pressure
semilunar valves shut
what is isovolumic relaxation?
ventricles start to relax with all valves closed
what increases ventricular pressure on the graph?
contraction
filling with blood
when is most myocardium perfused and why?
diastole
subendocardial coronary vessels are compressed during ventricular systole which results in momentary retrograde blood flow
however, the epicardial coronary vessels remain open
blood supply to the heart muscles
coronary arteries
where does venous blood from the heart muscle go?
cardiac veins drain into coronary sinus, which drains into right atrium
what does the right coronary artery supply?
right ventricle, right atrium, SAN, AVN
septum
which is the largest coronary artery?
LAD
where does the LAD run?
anterior ventricular groove
what is the most common coronary artery occlusion?
LAD
how is the LAD occluded?
plaque from cholesterol
atherosclerosis
territory supplied by the LAD
anterior 2/3 interventricular septum
lateral wall of left ventricle
anterolateral papillary muscle
consequence of occlusion of LAD
block impulse conduction between atria and ventricles
left/ right heart block
symptoms of occlusion of LAD
infarction of conducting system, atheroma production, ST elevation, heart block and arrhythmia, (impulses cannot travel down left and right ventricle branches simultaneously), or heart failure, prolonged PR (type 1 heart block), nausea, shortness of breath, pain in head, jaws, arms
which type of coronary occlusion is called a widowmaker, and why?
LAD
high mortality rate
consequence of occlusion of right coronary artery
conduction of nodes affected, contractions become out of rhythm or slower, inefficient blood flow (ischaemia) and potential backflow
symptoms of occlusion of right coronary artery
chest pain, if complete block then heart muscle dies and MI results, pain radiating in arms, shoulders, jaw, neck or back, shortness of breath, weakness and fatigue
ways to reduce risk of heart problems
cut down alcohol intake
stop smoking
be more physically active
vaccination
how many units of alcohol per week?
14 units
effect of sympathetic stimulation on peripheral blood vessels
vasoconstriction to increase blood pressure
are peripheral blood vessels innervated by parasympathetic fibres?
no
the occlusion of which coronary artery is most likely to result in a fatal heart attack?
left main coronary artery
the occlusion of which coronary artery is most likely to result in a fatal heart attack and why?
left main coronary artery
supplies the largest area of heart muscle
which nerve supplies the pericardium?
phrenic
phrenic supplies the 3 p’s
pericardium, pleura, peritoneum
what is end diastolic volume?
total amount of blood in the ventricle just before systole
average stroke volume?
70ml
mitral valve stenosis
narrowing of the mitral valve
left atrium has to contract with more force to generate more pressure to overcome the valve stenosis
increase in left atrium pressure
what is the embryological ductus arteriosus?
connects the pulmonary artery to the aorta
what does the embryological ductus arteriosus become?
ligamentum arteriosum
what is the foramen ovale?
hole between the right and left atrium
what type of heart failure causes pulmonary oedema and why?
left heart failure
blood backs up in the pulmonary system
what type of heart failure causes peripheral oedema?
right heart failure
failure of both sides of the heart
biventricular failure
movement of oxygen and carbon dioxide in and out of the respiratory system
oxygen rich air from environment - nasal cavities - pharynx - trachea - bronchi - bronchioles - alveoli - oxygen and carbon dioxide exchange at alveoli - bronchioles - bronchi - trachea - pharynx - nasal cavities - carbon dioxide rich air to the environment
how is physiological dead space calculated?
anatomical (conducting) dead space + alveolar dead space
what is conducting/ anatomical dead space?
volume of the conducting airways
from the nose, mouth and trachea to the terminal bronchioles
what is the alveolar dead space?
comprises alveoli which are ventilated, but not supplied by the pulmonary arterial circulation
where is greatest resistance to air flow?
segmental bronchi
if diameter is doubled, how does resistance change?
decreases by 1/16
if diameter is halved, how does resistance change?
increases 16-fold
what is Poiseuille’s Law?
R = 8ul/pi x r^4
two types of pulmonary stretch receptors
slow and rapidly adapting
what is the Hering-Breuer reflex?
inhibits inspiration
smooth muscle response to stretch
what are juxtacapillary receptors?
in the alveolar walls, close to capillaries
also called J receptors
respond to
- irritants
- noxious agents
- interstitial fluid volume
leads to bronchoconstriction
space between pleural membranes
intrapleural cavity
what is type 1 respiratory failure?
hypoxemia
inadequate oxygen
definition of type 1 respiratory failure
low level of oxygen with a normal or low level of carbon dioxide
definition of type 2 respiratory failure
high carbon dioxide and low oxygen levels
causes of type 1 respiratory failure
caused by conditions that affect oxygenation such as
- hypoventilation
- ventilation/ perfusion mismatch e.g pulmonary embolism
- low ambient oxygen at altitude
pneumonia
- shunt - oxygen blood mixes with non-oxygenated blood
what is type 2 respiratory failure?
pump failure
ventilation failure due to hypercapnia/ hypoxaemia
causes of type 2 respiratory failure
increased airway resistance
- COPD, asthma, suffocation
reduced breathing effort
- drugs
- brain stem lesion
reduction in the area of the lung available for gas exchange e.g chronic bronchitis
what is the main driver for respiration?
carbon dioxide
upper airways
nose, nasal cavity, pharynx, larynx
lower airways
trachea, bronchi, bronchioles, alveoli
compare the right and left main bronchus
right is shorter and more vertically aligned
how many lobar bronchi does the left lung have?
two
how many lobar bronchi does the right lung have?
three
what do segmental bronchi supply?
each supplies a bronchopulmonary segment of the lung
what are the two pontine respiratory centres?
pneumotaxic and apneuistic
what are the two medullary respiratory groups?
dorsal respiratory group
ventral respiratory group
DRG and VRG
which respiratory group is predominantly active during inspiration?
DRG
which respiratory group is active during inspiration and expiration?
VRG
are the DRG and VRG bilateral or unilateral?
bilateral
function of the apneustic centre
positive firing
stimulates inspiration
function of the pneumotaxic centre?
negative firing
antagonist to the apneustic centre
signals to the dorsal respiratory group
stimulates the external intercostals and diaphragm
function of the dorsal respiratory group
signals to the ventral respiratory group
stimulates internal intercostals and accessory respiratory muscles
where are central chemoreceptors?
ventral lateral surface of medulla
function of central chemoreceptors
detect changes in pH of spinal fluid
so carbon dioxide levels
where are peripheral chemoreceptors?
be specific
aortic body - aortic arch
carotid body - bifurcation of the common carotid
what do peripheral chemoreceptors in the aortic body detect? and what do they not detect?
changes in blood oxygen and carbon dioxide but not pH
what do peripheral chemoreceptors in the carotid body detect?
changes in blood oxygen, carbon dioxide and pH
do central chemoreceptors desensitise?
yes
do peripheral chemoreceptors desensitise?
no
which chemoreceptors have the greater impact on ventilation?
peripheral
why is carbon dioxide the main driver to breathe?
chemoreceptors respond to small changes in carbon dioxide but only large oxygen changes
what happens when there is an increase in carbon dioxide levels?
decrease in blood pH due to production of H+ ions from carbonic acid when carbon dioxide combines with water
respiratory centre in medulla sends nervous impulses to the external intercostal muscles and diaphragm to increase breathing rate and lung volume during inhalation
what happens when a decrease in oxygen is detected?
by peripheral chemoreceptors
low arterial oxygen stimulates chemoreceptors, increasing number of action potentials sent to ceentre in medulla
leads to an increase in ventilation, meaning more oxygen reaches the alveoli
how are changes in carbon dioxide detected?
increased H+ concentration in extracellular fluid and arterial blood
increased stimulation of centre in the medulla and an increase in ventilation
what does the ventral respiratory group stimulate?
both inspiratory and expiratory movements
what does the dorsal respiratory group stimulate?
primarily inspiration
equation for flow of air in/ out of lungs
flow = (p(alv) -p(atm))/R
p(alv) is alveolar pressure
p(atm) is atmospheric pressure
R is a constant
when flow is negative, in which direction does air flow?
into lungs
is alveolar pressure is less than atmospheric pressure, where does air flow?
into lungs
what is Boyle’s Law, and what does it mean?
P1V1 = P2V2
at a constant temperature, an increase in the volume of a gas will cause a decrease in pressure
equation for transpulmonary pressure
P(tp) = P(alv) - P(ip)
the difference between the alveolar pressure and intrapleural pressure
with intrapleural pressure being the pressure in the pleural space
what is transpulmonary pressure?
difference in pressure between the inside and outside of the lungs
is transpulmonary pressure always negative or positive relative to atmospheric pressure and why?
positive
because the lungs must always have some air in them
what is P(ip)?
pressure of the intrapleural fluid surrounding the lungs
is P(ip) negative or positive and why?
negative
the elasticity of the lungs and the chest wall mean they tend towards collapsing and enlarging respectively, so they move apart from each other
this reduces the pressure of the intrapleural fluid
what is respiratory failure?
a syndrome in which the respiratory system fails in one or both of its gas exchange functions: oxygen and carbon dioxide elimination
what is a drop in arterial oxygen?
hypoxemia
what is a rise in arterial carbon dioxide levels?
hypercapnia
define hypercapnia
PaCO2 > 6kPa
define hypoxemia
PaO2 < 8kPa
definition of type 2 respiratory failure
high carbon dioxide and low oxygen levels
role of saliva
enzymes, antibacterial, pH control, taste, lubrication
muscular composition of the oesophagus
upper 1/3 skeletal muscle
lower 2/3 smooth muscle
innervation of the different parts of the oesophagus?
upper 1/3 skeletal muscle supplied by superior laryngeal and recurrent laryngeal nerve
lower 2/3 smooth muscle supplied by enteric nervous system
two names for the sphincter at the entrance of the stomach
lower oesophageal sphincter
cardiac sphincter
what is GORD?
stomach acid refluxes into oesophagus
oesophageal mucosa is exposed to stomach acid, bile and pepsin which damages the lining
what can cause GORD?
cardiac sphincter weakened (also called the LES)
takes less pressure for fluid to move back up
poor oesophageal motility
passage of food from the mouth to the duodenum
mouth, pharynx, oesophagus, stomach, duodenum
at which spinal level is the oesophagus continuous with the pharynx?
C6
at which spinal level does the oesophagus emerge through the diaphragm?
T10
arterial supply of the oesophagus
left gastric artery
oesophageal branches from the left inferior phrenic artery
which regions of the abdomen does the stomach lie in?
umbilical, epigastric and left hypochondriac
regions of the stomach
cardia, fundus, body, pylorus
function of the stomach
temporary food storage
mixing and breakdown of food
digestion (gastric juices and digestive enzymes from mucosa)
function of the duodenum
receives partially digested food (chyme) from stomach and secretions from the pancreas, liver and gallbladder mix with chyme in duodenum to facilitate chemical digestion
in the oesophagus, what is the orientation of the circular and longitudinal muscle layers?
inner circular
outer longitudinal
what is a primary peristaltic wave?
occurs when food enters the oesophagus during swallowing and forces food down to stomach
what is a secondary peristaltic wave?
if a bolus gets stuck, stretch receptors in oesophageal lining are stimulated and a second wave happens
what does GORD stand for?
gastro-oesophageal reflux disease
which cells make HCl?
parietal cells
physiology of acid production in the stomach
water and carbon dioxide combine in the parietal cell to form carbonic acid (H2CO3)
this is catalysed by carbonic anhydrase
carbonic acid dissociates into a proton (H+) and a bicarbonate (HCO3-)
H+ enters the stomach lumen via an H+ - K+ ATPase on the apical membrane
this channel uses ATP to exchange k+ ions in the stomach with H+ ions in the parietal cells
bicarbonate ion is transported out of the cell into the blood in exchange for a chloride ion (Cl-) using an ion exchanger located on the basolateral membrane
chloride ion is transported into the stomach lumen through a chloride channel
the H+ and Cl- associate in the stomach lumen to form HCl
3 ways of increasing acid production
ACh from vagus nerve
- released firstly during the cephalic phase of digestion
- activated upon seeing food
- directly stimulates parietal cells
- also produced during the gastric phase of digestion when intrinsic nerves detect distension of the stomach, stimulating ACh production
gastrin
- hormone secreted from stomach G cells
- G cells activated by vagus nerve
- gastrin released into blood until it reaches the parietal cells
- gastrin binds to CCK receptors on the parietal cells
enterochromaffin like cells in the stomach secrete histamine which binds to H2 receptors on the parietal cells
these cells secrete histamine in response to the presence of gastrin and ACh
decreasing stomach acid production
low pH
- accumulation of acid in the stomach between meals leads to a lower pH
- inhibits gastrin secretion via the production of somatostatin from D cells
when food passes into duodenum, enterogastric reflex
- inhibitory signals sent to stomach via enteric nervous system
- signals to medulla to reduce vagal stimulation of the stomach
presence of chyme in the duodenum stimulates entero-endocrine cells to release cholecystokinin and secretin
- both complete digestion and inhibit gastric acid secretion
defences of gastric and duodenal mucosa against acid damage
produce HCO3-
- alkaline neutralises stomach acid on top of epithelial surface
mucous production
which glands in the duodenal mucosa secrete alkaline mucus?
Brunner’s glands
what is dyspepsia?
group of symptoms altering doctors to consider disease of the upper GI tract
- nausea
- vomiting
- heartburn
risk factors for GORD
family history
older age
obesity
hiatus hernia
risk factors for reflux
overweight
- extra pressure on stomach/ diaphragm
smoking
- loosen sphincter
alcohol
- damage stomach lining/ glands
large meals
- stomach stretches increasing pressure on lower oesophageal sphincter
pregnancy
- more pressure on sphincter
- generalised smooth muscle relaxation due to progesterone
why can acid reflux cause a sore throat?
acid enters pharynx
what divides the liver into anatomical left and right lobes?
falciform ligament
how is the liver divided into a functional left and right?
line vertically halfway through the IVC and gallbladder
which lobes are present on the visceral surface of the liver?
caudate and quadrate
which accessory lobe of the liver is superior?
caudate
what separates the caudate and quadrate?
porta hepatis
what is the porta hepatis?
bundle of blood vessels, nerves and ducts entering or leaving the liver
excludes the hepatic vein which drains into the IVC
arrangement of hepatocytes
hexagonal lobules
portal triad at each corder
surround a central vein
what is the portal triad?
venule of a portal vein
arteriole of hepatic artery
bile duct
along with lymphatics and vagus nerve fibres
function of sinusoids
deliver blood to central vein
what is the space of Disse?
between the sinusoid endothelium and hepatocytes
what does the space of Disse contain?
blood plasma
where are Ito cells found?
space of Disse
another name for Ito cells
hepatic stellate cells
function of Ito cells
store fat
produce proteins such as collagen when liver is damaged
action of Kupffer cells in the walls of the sinusoids
phagocytose blood borne pathogens
what happens to old erythrocytes in the liver, bone marrow and spleen?
phagocytosed by macrophages
globin portion of Hb is metabolised into amino acids and reused for protein synthesis
organelles are recycled
haem portion is broken down into biliverdin for transport in the blood
the iron ions bind to the blood protein transferrin for transport
unused haem groups can be used for haematopoesis or converted into bilirubin and used to make bile in the liver
iron ions can be transferred into ferritin for storage in the liver
where are old red blood cells broken down?
spleen, liver, bone marrow
how are old red blood cells broken down?
macrophages
when red blood cells are broken down, what happens to the globin portion?
it is protein
metabolised into amino acids and reused for protein synthesis
when red blood cells are broken down, what happens to the cell organelles?
recycled
when red blood cells are broken down, what happens to the haem groups?
separated into iron ions and haem group
haem group broken down into biliverdin for transport in the blood
biliverdin is used in haemopoesis or converted into bilirubin for bile
iron ions bind to the blood protein transferrin for transport
iron ions stored as ferritin in liver or used for haemopoiesis
describe the formation and recycling of bile
formed from haem group
haem portion is converted to biliverdin by haem oxygenase (Fe2+ is liberated)
biliverdin is converted into unconjugated bilirubin by biliverdin reductase 6
unconjugated bilirubin undergoes biotransformation to form bilirubin in the liver
bilirubin dissolves in bile, and through digestive processes end up in the small intestine
bacteria remove glucuronic acid to form urobilinogen
urobilinogen is recycled by enterohepatic circulation or oxidised by different bacteria to form stercobilin
stercobilin is excreted in faeces to give it a brown colour
subcostal plane
10th costal cartilage
lower most bony point of the rib cage
body of L3 vertebra
which spinal level does the inferior mesenteric artery arise from?
L3
which part of the duodenum is at L3?
third
transtubecular plane
unites the tubercles of the iliac crests
upper border of L5
confluence of the common iliac veins (i.e IVC origin) lie on this plane
where and how does the IVC originate?
confluence of the common iliac veins
L5
what is haemolytic/ pre-hepatic jaundice?
increased unconjugated bilirubin due to excess erythrocyte breakdown, exceeding the capacity of the liver to transport it
which jaundice is present in newborns and why?
haemolytic/ pre-hepatic
foetal haemoglobin is broken down
causes of pre-hepatic jaundice
infection, trauma to erythrocytes, sickle cell anaemia, drugs and toxins and antibodies
signs of haemolytic/ pre-hepatic jaundice
absence of bile pigments in urine and normal stool colour
this is because unconjugated bilirubin is insoluble so not filtered by kidney and bile can circulate to enter the intestine as normal
what is hepatocellular/ hepatic jaundice?
hepatocytes are damaged so unable to transport bilirubin into the biliary system, so it enters the bloodstream instead
the bilirubin may be conjugated
which type of bilirubin is elevated in haemolytic/ pre-hepatic jaundice?
unconjugated
which type of bilirubin is elevated in hepatocellular/ hepatic jaundice?
conjugated and unconjugated
what causes heptocellular/ hepatic jaundice?
hepatitis, cirrhosis and congestive liver disease
signs of hepatocellular/ hepatic jaundice
dark amber urine due to water soluble conjugated bilirubin that has been filtered by the kidneys
normal stools because some bile pigment manages to be excreted into the biliary tract and intestine
what is cholestatic/ obstructive/ post-hepatic jaundice?
obstruction in the biliary system due to anatomical obstructions e.g gallstones, cancers of the pancreas of ampulla of Vater
what causes post hepatic jaundice?
hepatitis
intrahepatic cholestasis
extra hepatic cholestasis
signs of post-hepatic jaundice
amber urine - bilirubin is conjugated so can be filtered by kidneys
pale stools as the bile cannot enter the intestine
itching of the skin as bile salts build up below skin, triggering an inflammatory response
function of the frontal lobe
motor cortices and association areas
regions controlling behaviour, decision making and personality (prefrontal association area)
Broca’s area in the left frontal lobe - responsible for fluent speech
role of Broca’s area
motor control of speech
consequence of damage to Broca’s area
expressive aphasia
no motor control of speech
when you know what you want to say, but you have trouble saying or writing your thoughts
blood supply to Broca’s area
middle cerebral artery
blood supply to Wernicke’s area
middle cerebral artery
role of temporal lobe
auditory cortices
medial temporal lobe for long term memory and emotion
- hippocampus
- entorhinal and perirhinal cortex
limbic system
Wernicke’s area for understanding speech and written language
role of Wernicke’s area
understanding speech and written language
consequence of damage to Wernicke’s area
receptive/ fluent aphasia
when someone is able to speak well and use long sentences, but what they say may not make sense
function of the parietal lobe
somatosensory cortices
where is the primary somatosensory cortex?
postcentral gyrus
parietal lobe
function of the occipital lobe
vision
where exactly is the primary visual cortex?
calcarine fissure of occipital lobe
function of the cerebellum
balance, posture, receiving information from vestibulocochlear organs
symptoms of cerebellar damage
DANISH
dysdiadokokinesia, ataxia, nystagmus of eyes, intention tremor, slurring of speech, heel-shin test positive
parts of midbrain
tectum and tegmentum
parts of the brainstem
midbrain, pons, medulla
grey matter surrounding the cerebral acqueduct
periaqueductal grey
function of the pons
breathing, sleeping, swallowing, bladder control
function of the medulla
autonomic regulation, corticospinal pyramids
what does the anterior cerebral artery supply?
corpus callosum and medial region of the brain
what does the middle cerebral artery supply?
lateral parts of the hemisphere and anterior deep structures
what does the posterior cerebral artery supply?
posterior region and the posterior inferior structures
e.g caudate nucleus, occipital lobe
draw and label the circle of willis
.
what is myasthenia gravis?
autoimmune destruction of nicotinic ACh receptors
role of upper motor neurons
cell body originates in the cerebral cortex or brainstem and terminates within the brainstem or spinal cord
role of lower motor neurons
alpha motor neurons exiting the spinal cord to innervate muscles
cause of upper motor neuron weakness
brain injury and trauma
capsular stroke
spinal cord lesion
cerebral palsy
symptoms of upper motor neuron lesion
effects will be mainly contralateral if damaged above the medulla, or ipsilateral if below
develop spasticity and stiffness over time
abnormal increased reflexes, such as babinski’s sign
clonus
cause of lower motor neuron weakness
peripheral trauma
Guillain-Barre syndrome
botulism
nonclassical polio
cauda equina syndrome
amyotrophic lateral sclerosis
symptoms of lower motor neuron lesion
weakness and atrophy of muscle
spontaneous neuronal discharge causing fasciculations
loss of reflexes - areflexia
does the frontal lobe control movement in the ipsilateral or contralateral part of the body?
contralateral
which hemisphere is dominant in a right handed person?
left
which sulcus separates the frontal and parietal lobes?
central sulcus
function of the primary somatosensory cortex
receive and interpret sensations e.g pain, touch, pressure
which cranial nerves originate from the cerebrum?
olfactory and optic
two major groups of descending tracts
pyramidal and extrapyramidal
why do the pyramidal tracts have that name?
they pass through the medullary pyramids of the medulla oblongata
where do pyramidal tracts originate?
cerebral cortex
what are descending tracts?
pathways by which motor signals are sent from the brain to lower motor neurons in efferent neurons
the lower motor neurons then directly innervate muscles to produce movement
function of the pyramidal tracts
voluntary control of body and face musculature
which pyramidal tract supplies the musculature of the body?
corticospinal
which pyramidal tract supplies the facial and neck muscles?
corticobulbar
where do the corticobulbar tracts begin?
lateral aspect of primary motor cortex
path of corticobulbar tracts
cortex, descends through internal capsule, crus cerebri, brainstem (pons and medulla), terminate on motor nuclei of cranial nerve
where do extrapyramidal tracts originate?
brainstem
what aspect of the primary motor cortex supplies the facial and neck muscles?
corticobulbar tract - lateral
function of extrapyramidal tracts
involuntary and autonomic control of musculature
carry motor fibres to spinal cord from brain stem
name the extrapyramidal tracts
vestibulospinal, reticulospinal, rubrospinal, tectospinal
function of the vestibulospinal tract
balance and posture
has medial and lateral pathways
function of the medial reticulospinal tract
facilitates voluntary movement by increasing muscle tone
function of the lateral reticulospinal tract
inhibits voluntary movements by decreasing muscle tone
function of the rubrospinal tract
fine control of hand movement
function of the tectospinal tract
coordinates movement of head in relation to visual stimuli
where do upper motor neurons travel between?
brain and brainstem to ventral horn of the spinal cord
where do lower motor neurons travel between?
ventral horn of the spinal cord to the peripheral muscles
what is the cortical homunculus?
contains the motor and sensory homunculus
region of the brain dedicated to processing motor and sensory functions for different parts of the body
motor homunculus
motor processing for different bodily anatomical positions
where does the motor homunculus handle signals coming from?
premotor area of frontal lobes
sensory homunculus
sensory processing for different anatomical positions
where does the sensory homunculus handle signals coming from?
thalamus
what is the corona radiata?
white matter sheet that continues ventrally as the internal capsule and dorsally as the centrum semi ovale
group of nerves key for sending messages between regions of the brain
internal capsule
white matter structure situated in the inferomedial part of the cerebral hemisphere of the brain, carrying information past the basal ganglia
connects the midbrain and cerebral cortex
which blood vessels are part of the anterior circulation?
anterior and middle cerebral arteries
which blood vessels are part of the posterior circulation?
posterior cerebral, vertebral, basilar and their branches
what links the posterior and anterior circulations?
circle of Willis
largest terminal branch of the internal carotid arteries
middle cerebral artery
occlusion of which artery causes hemianopia?
posterior cerebral artery
this stroke affects the visual pathways from the optic chiasm onwards towards the occipital lobe
can a stroke of the posterior circulation also cause muscle weakness? why?
corticospinal tracts have to travel through the brainstem and spinal cord
which neurotransmitter do upper motor neurons use?
glutamate
which receptors detect the neurotransmitter glutamate?
glutamatergic receptors
function of lower motor neurons
receive impulses from the upper motor neurons and connect the spinal cord and brainstem to the muscle fibres
do upper or lower motor neuron disorders cause spacicity?
upper
do upper or lower motor neuron disorders cause flaccidity?
lower
symptoms of an upper motor neuron lesion
muscle weakness in the extensors (in the flexors for the legs)
hypermedia and muscle spacicity
weakness on the contralateral side of the lesion due to 85% of the fibres crossing over (decussation)
upper or lower motor neurons cause forehead sparing?
upper
symptoms of lower motor neuron lesions
severe atrophy, hypotonia, hypoflexia, flaccid muscle weakness
affects the whole side of the body, including the forehead
what is muscular dystrophy?
X-linked genetic disorders resulting in malformed dystrophin
loss of cell membrane cytoskeletal connections, unregulated influxes of calcium to sarcolemma
e.g Duchenne’s
what is the CNS?
brain and spinal cord
is the somatic nervous system always stimulatory?
yes
function of the somatic nervous system
voluntary movement - skeletal muscles
reflex arcs involving muscles
functions of the ANS
heart rate, digestion, salivation, urination, digestion
main parasympathetic neurotransmitter
ACh
main sympathetic neurotransmitter
noradrenaline
what is the resting potential?
-70mV
which pump maintains the resting potential and how?
Na+/ K+ pump
3 Na out, 2 K in
describe the physiology of an action potential
action potential begins with a depolarising stimulus e.g neurotransmitter binding to ion channel
cell is depolarised (becomes less negative)
voltage gated Na+ channels open
influx of sodium ions
threshold potential reached at -55mV
action potential occurs if threshold potential reached
influx of sodium ions continues until +30mV via a positive feedback loop
the sodium channels close
potassium voltage gated channels open and potassium ions leave the cell to repolarise the membrane
membrane potential approaches resting potential
potassium channels experience a delay in closing resulting in hyperpolarisation
once voltage gated potassium channels close, resting potential is restored
what is hyperpolarisation
potassium voltage gated channels experience a delay in closing
potential falls below -70mV
what is the absolute refractory period?
no stimulus can produce a second action potential
what is the relative refractory period?
second action potential can happen, but needs stronger stimulus
is there a higher or lower concentration of sodium ions on the inside or outside during the resting potential of the cell?
outside
what do sensory receptors respond to?
stimuli
what are sub-modalities?
different variations within a stimulus e.g pitch and volume in audible stimuli
how are sensory receptors triggered?
ion channels if the stimulus is large enough
types of sensory receptors
tonic - slow adapting receptors
phasic - rapid adapting receptors
which receptors detect pain?
nociceptors
are nociceptors phasic or tonic?
phasic
what are Pacinian corpuscles?
phasic receptors
respond to pressure changes and vibration
which spinal segments control the knee jerk reflex?
L3 L4
describe the knee jerk reflex
patellar ligament is struck
afferent signal travels to spinal cord
synapses with 1 interneurons and 2 alpha-motor neurons
inhibitor - via interneuron, goes to flexor (hamstrings). polysynaptic
excitatory, via alpha motor neurons, to extensor (quadriceps)
monosynaptic
extensor contracts and flexor relaxes
knee jerks
brown sequard syndrome
an incomplete spinal cord lesion, typically in cervical region
lesion in one half of the spinal cord due to hemisection
usually cervical
weakness on one side (hemiparaplegia) and loss of sensation on the opposite side (hemianaesthesia)
ipsilateral loss of
- motor function
- vibration
- proprioception
- deep touch
to lesion
contralateral loss of
- pain
- temperature
how does diameter affect conduction speed?
larger fibre has a faster action potential as more ions can flow in a given time
are sodium channels found in the nodes of ranvier or myelinated regions?
nodes of ranvier
what is saltatory conduction?
action potentials jump from node to node
what are the four aspects of a stimulus?
modality, intensity, location, duration
MILD
absence of the patellar reflex
Westphal’s sign
causes of brown sequard - traumatic and non traumatic
traumatic
- bullet, stab wound, kick, car accident
non-traumatic
- tumour
- disc hernia
- MS
what happens if the lesion is below the point of decussation?
ipsilateral side is affected
what happens if the lesion is above the point of decussation?
contralateral side is affected
what is the spnothalamic tract?
ascending tract which carries pain sensation
does the spinothalamic tract decussate, and where?
yes
spinal cord
which spinal segments are responsible for
a. achilles
b. patellar
c. biceps
d. triceps
reflexes
S1, S2 - achilles
L3, L4 - patellar
C5, C6 - biceps
C7, C8 - triceps
1,2 buckle my shoes
3,4 kick down the door
5,6 pick up the sticks
7,8 lay them straight
layers of the kidney
outer cortex
inner medulla
kidney anatomy
pyramids taper to form the papilla
from the papilla, the urine drips into a minor calyx
several minor caylx form a major calyx
major calyx empty into the renal pelvis
pelvis empties into ureter
where does the ureter narrow?
where the pelvis of the kidney becomes ureter (ureteropelvic junction)
pelvic brim
where the ureter passes through the bladder (uretovesical junction)
what stops urine passing back up from the bladder into the ureter?
ureter enters bladder at oblique angle
as pressure in bladder rises, it presses on part of ureter which is in the bladder wall so stops urine from passing back up to the kidney
what is the tube through which urine passes from the bladder to the exterior?
urethra
length of female urethra
2 inches
length of male urethra
8-10 inches long
where does the female urethra end?
inferior to clitoris and superior to vaginal opening
where does the male urethra end?
tip of the penis
functional unit of the kidney
nephron
cortical nephron
tubules extend only a short distance into medulla then back into cortex
juxtamedullary nephrons
tubules extend deep within the medulla - have a vasa recta around them
what is the part of the nephron in which blood plasma is filtered?
renal corpuscle
glomerulus
capillary tuft formed by the afferent and efferent arterioles and encased in Bowman’s capsule
where does bulk of reabsorption happen?
PCT
what type of epithelium is the PCT?
cuboidal epithelium
what type of epithelium is the loop of henle?
squamous epithelium
is the descending limb permeable or impermable to water?
permeable
where does solute reabsorption take place in the LOH?
ascending limb
is the ascending limb permeable or impermeable to water?
impermeable
function of the DCT
fine regulation of Ca2+, Na+, K+ and HCO3
what size molecule can get through tthe filtration barrier?
10kDa
what prevents albumin getting through the filtration barrier?
podocytes with negatively charged foot processes
what does the Bowman’s capsule contain?
glomerular filtrate
whaich factors affect the filtration of the glomerulus?
size of molecule
pressure
charge of molecule
rate of blood flow
what percentage of cardiac output is renal blood flow?
20%
normal cardiac output
5L min
normal renal blood flow (RBF)?
1L/ min
volume of liquid filtered by the kidneys per day/ GFR per day
180L
GFR per minute
125ml/ min
how many times is the blood plasma filtered per day?
60
how many capillary beds does the nephron have?
two
when does glomerular filtration occur?
blood hydrostatic pressure exceeds hydrostatic pressure of glomerular capsule and blood colloid pressure
blood filtration barrier layers
fenestrated capillary endothelium
glomerular basement membrane
podocytes
GFR means
glomerular filtration rate
volume of fluid filtered by the renal glomeruli per unit time
renal clearance
virtual plasma volume per minute, from which a substance is completely eliminated
which types of substances have serum concentrations in direct dependence with GFR?
substances with exclusive glomerular filtration (without tubular secretion or reabsorption)
what percentage of glomerular filtrate is reabsorbed?
99%
what does the PCT have to increase surface area?
villi
function of the PCT
reabsorption of Na, Cl, glucose, amino acids, bicarbonate
what is diabetes insipidus?
deficiency of ADH
massive diuresis and excessive thirst
which protein is produced in the nephron?
Tamm Horsfall/ uromoduliin
urine flow rate
1ml/kg/hr
what is the rate determining step of RAAS?
renin
which cells release renin?
granular cells of juxtaglomerular apparatus
what 3 things trigger renin release?
reduced NaCl delivery to distal tubule detected by macula densa
reduced perfusion pressure in kidney detected by baroreceptors in afferent arteriole
sympathetic stimulation of JGA cells
which nerve fibres innervate JGA cells?
beta 1 adrenergic sympathetic nerve fibres
where is angiogensinogen produced?
liver
action of renin
cleaves angiotensinogen to angiotensin 1
action of ACE (angiotensin converting enzyme)
converts angiotensin I to angiotensin II
where is ACE found?
renal endothelium , lungs, capillary endothelium
action of angiotensin II
ADH release
aldosterone release
sympathetic stimulation
another name for ADH
vasopressin
what are mineralocorticoids?
class of steroid hormones that regulate salt and water balances
which is the principal mineralocorticoid?
aldosterone
which cells does aldosterone act on?
principal cells of the collecting duct
action of aldosterone
regulates blood pressure by altering the amount of Na that is reabsorbed
increases the retention of sodium and excretion of potassium
action of ADH
affects blood pressure by causing release of aquaporin channels into the membrane of principal cells of the collecting duct
causes increased water retention
causes of chronic renal failure
high blood pressure
diabetes
high cholesterol
complications of chronic renal failure
fluid retention - oedema
hyperkalaemia - usually excess potassium is removed from the blood by the kidneys
cardiovascular disease - chronic renal failure causes high blood pressure
weak bones
how is GFR regulated?
myogenic reflex
tubuloglomerular feedback
RAAS system
describe the kidney myogenic reflex
not dependent on nerve supply or blood-bornee substances
intrinsic property of the smooth muscle in the capillaries of glomerulus
what happens to the GFR when the macula densa detect a fall in sodium chloride levels?
increases
which mechanism regulates GFR?
tubuloglomerular feedback
if a substance is not secreted or reabsorbed in the renal tubules, how do we measure renal clearance?
GFR
what is the most common drive for reabsorbtion?
sodium potassium pump
what is prerenal kidney failure?
sudden reduction of blood flow to the kidneys
causes of pre-renal kidney failure?
hypotension
volume depletion e.g vomiting
oedema
what is renal kidney failure?
direct damage to kidney
causes of renal kidney failure
glomerular disease
acute interstitial nephritis
eclampsia
allergic reactions to medications
what is post-renal kidney failure?
obstruction in the urinary tract
causes of post renal kidney failure
kidney stones
urethral stricture
bladder tumour
