ILA

Question 1

Key facts about DNA transcription

Answer 1

Transcription – 1st stage protein synthesis
First step of gene expression, where the DNA sequence is copied to make an RNA molecule.
Performed by RNA polymerases.
Occurs in the nucleus.

Question 2

Describe the process of preparing the DNA for transcription

Answer 2

*DNA helicase breaks the hydrogen bonds in the DNA double helix, unwinding it
* RNA polymerase binds to the TATA promoter region of the gene

Question 3

Describe the actual process of DNA transcription

Answer 3

Single stranded binding proteins stop DNA strands reannealing
The RNA polymerase then adds complementary mRNA nucleotides to this template strand, building an RNA chain. (C-G, but A-U (not T as in DNA)). Moves in a 3’to 5’ direction. This transcript now contains the same information as the non-template (coding) strand of DNA.

Question 4

Describe the process of ending transcription

Answer 4

Sequences called terminators or stop codons signal the transcript to be released from the RNA polymerase. → mRNA strand produced with a poly-A tail (end – stops DNA degrading) & a 5’ cap (beginning)

Question 5

Describe the modification of pre-mRNA

Answer 5

The molecule formed is called pre-mRNA, as it forms exons and introns. Introns are removed in a post-transcriptional modification phase = Splicing → carried out in nucleus by slicosomes & mRNA leaves nucleus via nuclear pore

Question 6

Key facts about translation

Answer 6

Second step of gene expression, where proteins are synthesised.
Occurs in the cytoplasm – mRNA binds to ribosome

Question 7

Key facts about tRNA and ribosomes

Answer 7

• tRNAs connect mRNAs to the amino acids they code for
• At the end of each tRNA there’s an anticodon, which can bind to specific mRNA codons.
• Each ribosome has a small and a large part. These join together over the mRNA. The ribosome provides sites for the tRNA to bind. Ribosomes also act as enzymes and catalyse the reaction

Question 8

Describe the process of translation

Answer 8

A ribosome binds to the start codon on the mRNA. mRNA moves in a 3’ to 5’ direction. tRNA molecules bind to the ribosome via codon-anticodon interactions. A peptide bond forms between the two amino acids attached to the tRNA.
* The ribosome moves along the mRNA one codon at a time, until it reaches a stop codon. This is the end of the process. Post-translational modification may then occur.

Question 9

What is the role of mRNA?

Answer 9

synthesized in the nucleus using nucleotide triphosphates and RNA polymerase II - Attaches to ribosomes during translation to allow correct tRNA to bind to form polypeptide chain.

Question 10

What is the role of tRNA?

Answer 10

Binds to specific amino acids at complementary mRNA codon to hold the amino acids in place to form the polypeptide chain.

Question 11

What is a transcriptome?

Answer 11

The sum total of all the mRNA molecules

Question 12

What is single nucleotide polymorphism (SNP)?

Answer 12

• DNA sequence variation when a single nucleotide (ATCG) differs/is substituted * Most common type of genetic change & occur normally → SNPs can occur once in every 1000 nucleotides → 4-5 million in persons genome

Question 13

What are some of the consequences of SNP?

Answer 13

Can result in a different codon which generates a different protein and thus disease – but most don’t (often introns) E.g. sickle cell anaemia or cystic fibrosis
* If present in recognition sequence of restriction enzyme or affect recognition / promoter/termination sequences they can change the length of proteins or produce different length DNA fragments
* Can act as biological markers to locate genes associated with disease

Question 14

What causes sickle cell anaemia?

Answer 14

Haemoglobin S (Hb S) = sickle cell haemoglobin. It’s caused by a SNP of adenine to thymine ((GAG codon changes to GTG) on 17th nucleotide.
In sickle cell anaemia, both genes that code for haemoglobin are abnormal (Hb SS). In sickle cell trait, only one chromosome carries the abnormal allele (Hb AS).
Mutation occurs in the HBB gene (codes for beta subunit) & in sickle cell disease only one of the beta-globin subunits is replaced by Hb S.

Question 15

What changes are made to haemoglobin with sickle cell disease?

Answer 15

Haemoglobin has two subunits ( 2 alpha & 2 beta subunits) . The alpha subunit is normal in people with sickle cell disease. The beta subunit has the amino acid valine at position 6 instead of the normal glutamic acid = different primary structure

Question 16

Why does the haemoglobin form differently in people with sickle cell disease?

Answer 16

The substitution of glutamate for valine is a nonconservative replacement → different biochemical properties, in this case glutamate is a negatively charged amino acid whereas valine is a hydrophobic branched chain aliphatic amino acid.
When hemoglobin is in its deoxygenated, the additional valine residues bind to a hydrophobic area on other S-hemoglobin molecules, forming a chain of hemoglobin that in turn pulls the red blood cell into its signature sickle shape, therefore it now has a different quaternary structure.

Question 17

Why does the altered haemoglobin cause the RBC to be a sickle cell?

Answer 17

Abnormal haemoglobin molecules clump together into linear chains (polymerisation) which reduces the haemoglobin’s affinity for oxygen
NB this is Temperature dependent

Question 18

What are the functional changes to the RBC in sickle cell ?

Answer 18

• Cells don’t live as long
• Lower affinity for oxygen
• Gets stuck in blood vessels
• Overall, leads to reduced delivery of O2 to muscles

Question 19

Describe the different levels of protein structure

Answer 19

Primary= chain if amino acids – covalent bonds
Secondary = alpha helix, beta pleated sheets – H+ bonds
Tertiary= 3D structure of a single chain of amino acids
- Van der Waals bonds
- H+ bonds
- Electrostatic
- Ionic
- Disulphide bridges
Quartenary = overall 3D structure of a polypeptide

Question 20

Can sickled cells return to their original shape?

Answer 20

Deoxygenated Hb S molecules are insoluble and polymerise. The flexibility of cells is decreased, and cells become rigid and take up the characteristic sickle appearance.
This process is initially reversible, but with repeated sickling, cells will eventually lose their membrane flexibility. They then become irreversibly sickled

Question 21

What are some of the complications of sickle cell disease?

Answer 21

Complications can include infections, delayed growth, and these episodes of pain which are sometimes called pain crises.
Pain crises typically occur in the bone.
Sickle cell patients are at increased risk of stroke but this is far less common than in the bone.

Question 22

What is a positive of sickle cell disease?

Answer 22

Because people with one copy of the “faulty” gene are resistant to malaria, it is beneficial in areas with a high risk of malaria - Africa, the Mediterranean, the Middle East, India, South America or the Caribbean - so people who are from or have ancestors from these areas are more likely to carry the “faulty” gene. This means they are also more likely to have two copies of it, and so suffer from sickle cell disease

Question 23

What are the symptoms of sickle cell anaemia?

Answer 23

In cold weather, our blood vessels narrow to retain heat (vasoconstriction). Sickle-shaped red blood cells can become stuck in small blood vessels due to their abnormal shape. This can lead to the blood vessel becoming blocked, and can also mean that oxygen may not reach certain tissues, and can lead to tissue death. This can cause a pain episode or crisis to start suddenly, usually in the lower back, arms, legs, chest and belly. When blood returns to the affected area, it can also cause inflammation and pain. If lots of these crises occur, it could cause long term damage to the tissues.

Question 24

What are some of the treatments of sickle cell anaemia?

Answer 24

• Hydroxyurea used as treatment because it stimulates the bone marrow to make foetal haemoglobin (foetal Hb) → foetal Hb has a better ability for carrying the oxygen around the blood
• This is why newborn babies don’t present with sickle cell → HbF prevents sickle cell but stops being produced after a year
• Embolising drugs
• Can give a plasma exchange to reduce the number of sickle cells

Question 25

Describe the distribution of water and sodium

Answer 25

2/3 body’s water (60%) in intracellular fluid compartment (all fluid in cells, enclosed by plasma membrane) * 1/3 body’s water in extracellular fluid compartment → further divided into plasma (fluid part of blood) & interstitial (fluid surrounding cells) * 70% body’s sodium is ‘exchangeable * 30% in bone crystal * ECF – 50% total body sodium * ICF – 5% total body sodium NB 60% of body weight = water

Question 26

Define osmolality

Answer 26

Concentration of solution expressed as solute particles per kg

Question 27

Define osmolarity

Answer 27

Concentration of solution expressed as solute particles per L

Question 28

Define oncotic pressure/colloid osmotic pressure

Answer 28

Pressure exerted by plasma protein on capillary wall (e.g. albumin displacing water molecules in plasma) - opposing effect = hydrostatic blood pressure & interstitial colloidal oncotic pressure & determine balance of total extracellular water

Question 29

Define osmosis

Answer 29

Process by which molecules within a solvent pass through a semi permeable membrane (high conc. To low conc.)

Question 30

Define hydrostatic pressure

Answer 30

force exerted by a fluid against a wall, causes movement of fluid between compartments

Question 31

Describe the response to low blood volume

Answer 31

Blood volume drops (dehydration or blood loss) --> hydrostatic pressure becomes less than oncotic pressure → fluid from IF moves into blood to restore volume via osmosis --> gradient change between IF and ICF --> fluid from ICF moves into IF to restore the balance → cells shrink

Question 32

What is albumin?

Answer 32

Protein made by your liver found in the blood Low albumin (Hypoalbuminaemic) Decreased oncotic pressure Less water moves from interstitial space into plasma Causes excess accumulation of fluid in interstitial space

Question 33

What causes hypoalbuminaemia?

Answer 33

- Liver failure- makes albumin so less made - Heart failure- they don't know - Kidney damage- more into urine - Protein losing enteropathy- GI conditions - Malnutrition- Not eating enough protein Inflammation throughout the body- e.g by surgery, sepsis and mechanical ventilation

Question 34

Key routes of water loss in the body

Answer 34

* Urine * Faeces – lack of water = constipation, water loss = diarrhoea * Sweat * Breath – via evaporation from respiratory tract * Vomiting

Question 35

What are the two types of water loss?

Answer 35

Two types of water loss – sensible (can be perceived and measured e.g. urine) and insensible (not perceived and can’t be measured e.g. sweat, lungs. Faeces, through breathing + evaporation during surgery → estimated 40-60 cc)

Question 36

What do osmoreceptors in the hypothalamus do?

Answer 36

* Osmoreceptors in hypothalamus detect when water potential in blood is low (detect changes in osmotic pressure) * Water diffusion into osmoreceptor cells changes when osmolarity of blood changes (cells expand when plasma is more dilute) * Loss of water (high plasma osmolarity) reduces their volume, triggering stimulation of nerve cells in hypothalamus * Triggers ADH to release from posterior pituitary * NB also signals biological sensation of thirst

Question 37

Describe the role of the posterior pituitary and arginine vasopressin

Answer 37

* Posterior pituitary stimulated by hypothalamus * Action potentials travel down & cause ADH release into bloodstream (acts to reduce plasma osmolarity back to normal) * This acts on kidneys causing insertion of aquaporin channels into membrane, increasing fluid retention

Question 38

Describe the process of water conservation by reabsorption in the nephron

Answer 38

* Urine is diluted as it moves through the loop of Henle * It is concentrated again in the distal tubules and collecting ducts * The descending loop is impermeable to sodium chloride and permeable to water * The ascending loop is permeable to sodium chloride and impermeable to water * Once dilute urine enters the distal tubules, water is reabsorbed without sodium chloride → concentrated urine * Water reabsorption driven by concentration gradient created as sodium is pumped into interstitial space, creating osmotic gradient * ADH acts upon collecting duct & DCT, increasing number of aquaporins

Question 39

How does vasopressin work?

Answer 39

ADH binds to receptors on the collecting duct membrane, causing intracellular production of cAMP which activates protein kinase, which phosphorylates proteins that increase the rate of fusion of vesicles containing aquaporins with the membrane.

Question 40

Describe the mechanism of thirst

Answer 40

- Thirst is stimulated by an increase in plasma osmolarity & a decrease in extracellular fluid volume - Also induced via angiotensin II (RAAS system)

Question 41

Describe sodium homeostasis- RAAS

Answer 41

* When renal blood flow is reduced, juxtaglomerular cells convert prorenin to renin (in kidneys) * Plasma renin then converts angiotensinogen to angiotensin I * This is converted to angiotensin II by ACE

Question 42

What does angiotensin II do?

Answer 42

Angiotensin II increases blood pressure via vasoconstriction and simulates secretion of aldosterone from the adrenal cortex

Question 43

What does aldosterone do?

Answer 43

Aldosterone causes renal tubules to increase the reabsorption of sodium and water into the blood (and excretion of potassium) + increased expression of ATPase pumps in nephron, increasing water resorption through sodium co transport * This increases the volume of ECF and increases blood pressure

Question 44

How does ADH work?

Answer 44

NB ADH increases water reabsorption by increasing the nephron’s permeability to water, while aldosterone works by increasing the reabsorption of both sodium and water

Question 45

What is the link between Na+ balance and BP?

Answer 45

- Na+ balance determines ECF volume, blood volume and blood pressure - Increase in Na+ in ECF → increase in ECF volume, increase in blood plasma volume → increased BP - Decrease in Na+ in ECF → ECF decrease → blood volume decrease --> blood pressure decreases

Question 46

What is the mechanism of sodium loss in the body?

Answer 46

Extra sodium is lost from the body by reducing the activity of the renin angiotensin system that leads to increased sodium loss from the body → Sodium is lost through kidneys, sweat and faeces

Question 47

Normal homeostatic fluid

Answer 47

Excess fluid causes a decrease in the ECF osmolality (lower concentration of particles in the fluid). This is detected by osmoreceptors and causes 3 things to occur: * It causes water to move into the ICF * It stops the stimulation of the thirst centre in the hypothalamus * It inhibits ADH in the posterior pituitary. This will result in an increased urine volume.

Question 48

What are the potential dangers of excess water consumption?

Answer 48

Too much water in the bloodstream can cause hyponatremia. Hyponatremia Is where the large amount of water = low concentration of sodium in the blood plasma = cells in the body to swell up. I f these cells are in the brain it can cause an increase in intracranial pressure which can interrupt the brain's blood flow and cause seizures, unconsciousness or coma. Excess fluid accumulation in the brain = cerebral oedema (can affect the brain stem and CNS dysfunction.)

Question 49

What are the symptoms of excess water consumption?

Answer 49

Symptoms can include: Headache, Nausea, Vomiting. Severe cases can produce more serious symptoms, such as: o Increased blood pressure. o Confusion. o Double vision. o Drowsiness. o Difficulty breathing. o Muscle weakness and cramping. o Inability to identify sensory information

Question 50

Normal response to dehydration

Answer 50

During dehydration, a loss of water from ECF will increase the ECF osmolality.

Question 51

Describe the 3 ways that the hypothalamus acts in response to increased ECF osmolality

Answer 51

* Move water from the ICF to ECF * Stimulate thirst centre of hypothalamus to increase water intake * The hypothalamus of a dehydrated person sends signals via the sympathetic nervous system to the salivary glands in the mouth. The signals result in a decrease in watery output (and an increase in stickier, thicker mucus output). These changes in secretions result in a “dry mouth” and trigger thirst.. * Release ADH (Antidiuretic hormone) from the posterior pituitary gland which causes

Question 52

Water distribution in the body?

Answer 52

Total body water for a healthy 70kg man = 42L, made up of: * Intracellular 28 L * Interstitial 11 L * intravascular 3 L

Question 53

Equation for estimated osmolality

Answer 53

Estimated plasma osmolality = 2[Na] + 2[K] + urea + glucose mmol/L (this was in the lecture Water and sodium concentration)

Question 54

What happens if plasma osmolality increases?

Answer 54

If plasma osmolality increases → sensed by hypothalamus → more ADH released → concentration of ADH increases → fluid retention intravascularly.

Question 55

Where are all of the hormones involved in water regulation produced?

Answer 55

* ADH made in hypothalamus, stored in the posterior pituitary, then acts on the kidneys * Aldosterone is produced and secreted from the adrenal cortex * Renin is produced and secreted in the juxtaglomerular cells of the kidney

Question 56

Equation for cardiac output

Answer 56

Cardiac output = stroke volume x heart rate

Question 57

What is cardiac output?

Answer 57

Cardiac output = volume of blood heart pumps around the circulatory system in one minute

Question 58

What is stroke volume?

Answer 58

Stroke volume is a measure of the blood that is pumped out of the ventricles with every contraction

Question 59

What is the equation for stroke volume?

Answer 59

SV = EDV – EDS

Question 60

What is the average CO?

Answer 60

Average CO is 5L/min

Question 61

What are the factors affecting heart rate?

Answer 61

Autonomic innervation (autonomic control of HR via parasympathetic NS - involves the vagus nerve) , hormones, fitness levels & age

Question 62

What are the factors affecting stroke volume?

Answer 62

contractility (force of heart contraction, performed by myocytes), preload (myocardial distension prior to shortening Preload is, in simplest terms, the stretching of ventricles), afterload (force against which ventricle must act in order to eject blood Afterload is a fancy word for the pressure required for the left ventricle to force blood out of the body to exert during systole), heart size, fitness, gender & contraction duration

Question 63

Factors affecting blood pressure

Answer 63

(smaller ones) vasopressin, aldosterone, ANP, haemorrhage, sweating, stressors, hydration, weight, muscular activity, posture - Blood viscosity - Volume of circulating blood - Elasticity of blood vessels - Peripheral vascular resistance - Cardiac output

Question 64

How does blood viscosity affect blood pressure?

Answer 64

Thicker the blood = reduced fluidity = travels slower = increased force

Question 65

How does the volume of circulating blood affect blood pressure?

Answer 65

Increased volume in the circulatory system = larger volume in a specific capacity = causes partial expansion (via elasticity of the vessels)

Question 66

How does the elasticity of blood vessels impact blood pressure?

Answer 66

Capacity of the heart vessels to resume normal shape after stretching, stiffening of any vessels or the heart due to reduced elasticity, as heart has to pump blood all the way around the body, increased resistance (no assistance by elastic vessels) = increased blood pressure

Question 67

What is the impact of peripheral vascular resistance on blood pressure?

Answer 67

Greater compliance leads to regulated ability to deal with more blood (surges via ventricular contraction) , stiffening of vessels leads to reduced compliance, hence more turbulence reduced blood flow = increased BP

Question 68

What is the impact of cardiac output on blood pressure?

Answer 68

Any factor affecting SV or HR with have stimulating affect to blood pressure, increased SV/HR = increased BP

Question 69

Why do patients with heart failure feel exhausted?

Answer 69

Heart overworking so exhaustion caused by further work of the heart or lack of function of the heart to supply enough blood to tissues of the body.

Question 70

Why do patients with heart failure feel short of breath?

Answer 70

Cardiac failure increases BP and put increased strain on the heart, usually requiring more contraction in order to pump required volume of blood around the heart, requiring more aerobic and anaerobic respiration. More ventilation required to supply more oxygen to blood and remove more waste products from blood.

Question 71

Why do patients with heart failure have swollen ankles?

Answer 71

Oedema caused by cardiac failure and increased blood pressure prevents the correct circulation of blood back to the heart = the blood plasma filtered out of the blood enters the tissue fluid and is unable to re-enter due to reduced blood flow = accumulation of tissue fluid (oedema in the legs/ ankles)

Question 72

Describe the frank-starling law

Answer 72

Frank-starling law → greater the stretch on the myocardium before systole (pre-load), the stronger the ventricular contraction - stroke volume of heart increases in response to increased volume of blood in ventricles before contractions (end diastolic volume) Increased force because actin & myosin filaments are brought to more optimal degree of overlap for force generation

Question 73

What is end diastolic volume?

Answer 73

End diastolic volume = normal ventricle filling leads to ventricle volume 110-120ml

Question 74

What are the signs and symptoms of heart failure?

Answer 74

- potentially affect Ca2+ uptake, so less Ca released during heartbeat so contraction is not as strong – reduced contraction effectiveness - shortness of breath + increased exhaustion: lack of oxygen to respiring tissues - ankle swelling: increased venous capillary pressure, decreased plasma oncotic pressure – build up of fluid in lower limbs - low mood: reduced quality of life, hospitalisation & mortality risk

Question 75

Why does the heart contract harder when there is a higher volume of blood?

Answer 75

In skeletal muscle, the normal point for contraction is the optimal length, but in cardiac muscle, the optimal length is reached only when the fibres are stretched, so the heart will contract harder when the fibres are stretched by increased volume of blood.

Question 76

What is diastolic heart failure?

Answer 76

In diastolic heart failure - ventricle has reduced compliance, so it can’t fill properly and there’s a lower end-diastolic volume.

Question 77

What happens in diastolic heart failure?

Answer 77

This results in a reduced stroke volume by the Frank-Starling mechanism, so a lower blood pressure. This pressure is detected, leading to increased HR (increased sympathetic and reduced parasympathetic) and fluid retention (renin-angiotensin-aldosterone system). This increased fluid leads to the consequences of heart failure: larger volume means greater resistance, so the heart has to work harder in order to continue to pump the blood.

Question 78

What is the first step in the cardiac cycle?

Answer 78

Cycle initiates when SAN node fires —> causes the atria to depolarize. This is represented by the P wave on the ECG. (DIASTOLE)

Question 79

What is the second step of the cardiac cycle?

Answer 79

Atrial contraction happens shortly after the P wave starts —> causing an increase in atrial pressure —> this forces blood into the ventricles causing an increase in ventricular volume (Note: Ventricular volume does not start at zero as there is passive movement of blood from the atria to the ventricles as the AV valves are open due to the pressure gradient) —> thus increases ventricular pressure (DIASTOLE)

Answer 80

Atrial pressure then drops --> forces the AV valves shut —> produces first heart sound S1 (SYSTOLE)

Answer 81

During the closing of the AV valves, ventricular depolarization is half way through, this is represented by the QRS complex on the ECG —> causes ventricles to contract — > causing a rapid increase in ventricular pressure (Note: the ventricular volume does not change for a while, this is due to the semilunar valves being shut, this is known as isovolumetric contraction) (SYSTOLE)

Answer 82

Ventricular ejection occurs when the ventricular pressure exceeds that of the aorta and pulmonary artery —> causes the semilunar valves to open —> blood is ejected out of the ventricles (known as the rapid ejection phase) (SYSTOLE)

Answer 83

When ventricular repolarization occurs, represented by the T wave on the ECG—> ventricular pressure starts to fall along with ventricular volume (SYSTOLE)

Answer 84

Once ventricular pressure falls below aortic pressure —> the semilunar valves shut — > producing the second heart sound S2 (DIASTOLE)

Answer 85

Ventricles start to relax with all valves closed (known as isovolumetric relaxation) — >ventricular pressure decreases rapidly (Note: the ventricular volume is unchanged as the valves are closed) (DIASTOLE)

Answer 86

At the same time, atria are being filled again —> slowly increases the atrial pressure —> when atrial pressure becomes greater than ventricular pressure —> AV valves open —> allows passive filling of the ventricles which slowly increases ventricular volume (DIASTOLE)

Question 87

What happens to the subendocardial vessels during ventricular systole?

Answer 87

During contraction of the ventricular myocardium (systole), the subendocardial coronary vessels (the vessels that enter the myocardium) are compressed due to the high ventricular pressures. This compression results in momentary retrograde blood flow (i.e., blood flows backward toward the aorta) which further inhibits perfusion of myocardium during systole.

Question 88

Do the epicardial coronary vessels close during ventricular systole?

Answer 88

No, the epicardial coronary vessels (the vessels that run along the outer surface of the heart) remain open

Question 89

When does most of the myocardial perfusion occur?

Answer 89

Most myocardial perfusion occurs during heart relaxation (diastole) when the subendocardial coronary vessels are open and under lower pressure.

Question 90

Describe the coronary circulation of the heart

Answer 90

Coronary arteries supply oxygenated blood to the heart muscles - Cardiac veins draining deoxygenated blood → drain into the coronary sinus → then drain into the right atrium.

Question 91

Describe the left main coronary artery

Answer 91

supplies blood to the left side of the heart (left ventricles and atrium). Left anterior descending artery branches off the left coronary artery and supplies blood to L. side of the heart. Left marginal descending (MAD). Circumflex artery branches off left coronary artery and encircles heart muscle. Artery supplies blood to outer side and back of heart.

Question 92

Describe the right coronary artery

Answer 92

Supplies blood to right ventricle, right atrium, SA and AV nodes regulating the heart rhythm. Will branch out into right posterior descending artery and acute marginal artery. Also supplies blood to middle/septum of the heart.

Question 93

Describe the left anterior descending artery (LAD)

Answer 93

Largest coronary artery, running in the anterior ventricular groove & giving rise to the septal branch & diagonal branch

Question 94

Describe the septal branch of the LAD

Answer 94

Septal branch supplies the anterior two thirds of the septum, including interventricular septum, bundle branches & Purkinje fibres.

Question 95

Describe the diagonal branch of the LAD

Answer 95

Diagonal branch runs over the anterior section of the left ventricle, terminating at the apex of the heart

Question 96

Describe occlusion of the LAD

Answer 96

Most common occlusion = plaque from cholesterol (atherosclerosis)

Question 97

Describe the territory of an LAD occlusion

Answer 97

Anterior 2/3 of interventricular septum, lateral wall of left ventricles and anterolateral papillary muscle

Question 98

Describe the effects of an LAD occlusion

Answer 98

lock impulse conduction between atria and ventricles * Left/right heart block

Question 99

What are the symptoms of an LAD occlusion?

Answer 99

Infarction of conducting system, atheroma production, ST elevation (indicates blockage in coronary artery - ST elevation on ECG), heart block and arrhythmia (impulses can’t 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

Question 100

Why is an LAD occlusion known as the widow maker?

Answer 100

Due to high mortality rate

Question 101

Territory of an occlusion of the RCA

Answer 101

RCA supplies SAN and AVN (branches to form RMA & PDA)

Question 102

Describe the effects of a RCA occlusion

Answer 102

Conduction of nodes affected, contractions become out of rhythm or slower → inefficient blood flow (ischaemia) and potential backflow

Question 103

What are the symptoms of an RAC occlusion?

Answer 103

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

Question 104

How to reduce risk of future heart problems?

Answer 104

- Cut down alcohol intake - Stop smoking - More active - Vaccinations (won't help directly but are at risk for other diseases so helps with that)

Question 105

What does sympathetic innervation do to the peripheral blood vessels?

Answer 105

Sympathetic stimulation of peripheral blood vessels causes vasoconstriction → increases blood pressure. Peripheral blood vessels aren’t innervated by parasympathetic.

Question 106

What is EDV and how does it give us ESV?

Answer 106

Total amount of blood in ventricle just before systole. This is given as 120 in the question. In contraction, blood leaves (stroke volume). Average stroke volume is around 70. So 50ml left, this gives us the ESV.

Question 107

Describe the impact of mitral valve stenosis

Answer 107

Mitral valve stenosis → stiffer and requires more pressure to overcome this → left atrium therefore has to contract with more force to generate more pressure to overcome the valve stenosis → atrium contracts with more force so we see an increase in left atrium pressure.

Question 108

What us the ductus arteriosus?

Answer 108

Ductus arteriosus → ligamentum arteriosum (between pulmonary artery to the aorta)

Question 109

What is included in the upper airways?

Answer 109

Nose, nasal cavity, pharynx, larynx

Question 110

What is included in the lower airways?

Answer 110

Trachea, bronchi, bronchioles, alveoli

Question 111

Where in the respiratory system is there greatest resistance?

Answer 111

resistance increases as airway diameter is reduced BUT greatest resistance is in trachea and larger bronchi → branching of airways means there are many more of the smaller bronchioles airways in parallel, reducing the resistance

Question 112

Differences between the main bronchi

Answer 112

Right main bronchus has a larger diameter and is aligned more vertically then the left.

Question 113

Describe the lobar bronchi

Answer 113

two on left and 3 on right, supply each of the main lobes of the lungs.

Question 114

Describe the segmental bronchi

Answer 114

Supply individual bronchopulmonary segments of the lungs.

Question 115

What is the pathway of air from the conducting bronchioles to the alveolar sacs?

Answer 115

Conducting bronchioles → Terminal bronchioles → Respiratory bronchioles → Alveolar ducts → Alveolar sacs

Question 116

Spaces conducting dead space

Answer 116

Anatomical = 150ml Alveolar = 25ml SO physiological = 175ml

Question 117

Describe flow resistance in the lungs

Answer 117

Greatest flow resistance = segmental bronchi (These are medium sized ) * If diameter is doubled, resistance decreases by 1/16 * If diameter is halved, resistance increases 16-fold

Question 118

What is the equation for Poiseuille's law?

Answer 118

R = 8µl / πr*4

Question 119

How is ventilation?

Answer 119

Nerves fire to the pontine respiratory group * Apneustic centre has a positive firing - respiratory intensity * Pneumotaxic centre has a negative firing - time dependent inhibition * Signal to dorsal respiratory group, then stimulate the external intercostals and diaphragm * The dorsal respiratory group signals to the ventral respiratory group, stimulates internal intercostals and accessory respiratory muscles * Homeostatic control – inputs to nucleus accumbens, nucleus tractus solitaius * Inputs from CN IX and X

Question 120

What are central chemoreceptors?

Answer 120

Located on the ventral lateral surface of medulla oblongata & detect changes in pH of spinal fluid. They can be desensitized over time from chronic hypoxia. They detect H+ from CO2 diffusing across the blood-brain barrier.

Question 121

What are peripheral chemoreceptors?

Answer 121

Include aortic body (detects changes in blood oxygen & CO2 but NOT pH) and carotid body (detects all three). They don’t desensitize & have less impact on ventilation compared to central chemoreceptors.

Question 122

What is the main drive to breathe?

Answer 122

CO2 is main driver to breathe as chemoreceptors respond to small changes in CO2 levels but only large O2 changes

Question 123

Describe how CO2 levels cause us to breathe

Answer 123

* Increase in CO2 levels → decrease in blood pH due to production of H+ ions from carbonic acid when CO2 combines with H2O. * In response, the respiratory centre (in medulla) sends nervous impulses to the external intercostal muscles & diaphragm to increase breathing rate & lung volume during inhalation.

Question 124

What is the impact of O2 conc. levels on breathing?

Answer 124

* Monitored by peripheral chemoreceptors → low arterial O2 level stimulates chemoreceptors, increasing number of action potentials sent to centre in medulla * Leads to an increase in ventilation, meaning more oxygen reaches the alveoli, minimising decrease in alveolar and arterial O2 levels

Question 125

Which chemoreceptors detect CO2 change?

Answer 125

CO2 change is detected in both types of chemoreceptors, with the stimulus being t increased H+ concentration in extracellular fluid & arterial blood →increased stimulation of centre in the medulla oblongata & increase in ventilation.

Question 126

What are the two stimulation centres in the medulla and what do they stimulate?

Answer 126

* Ventral respiratory group (VRG) → stimulates both inspiratory and expiratory movements * Dorsal respiratory group (DRG) → primarily stimulates inspiration

Question 127

Describe the pleura of the lungs

Answer 127

2 membranes – visceral and parietal pleura Space in between is the intrapleural cavity

Question 128

Describe inspiration

Answer 128

* The respiratory muscles expand the cavity which creates a negative pressure in the pleural cavity * Pulls the visceral pleura which pulls on the lungs and decreases the pressure * Air rushes in to the lungs to equalise the pressure = inspiration (increase in transpulmonary pressure greater than elastic recoil of lungs – lungs expand, alveolar pressure reduced below zero) * diaphragm contracts - dome moves downward into abdomen, enlarging the thorax. * external intercostal muscles simultaneously contract, leading to an upward and outward movement of the ribs

Question 129

Why does airflow cease at the end of inspiration?

Answer 129

End of inspiration - pressure in alveoli = atmospheric pressure again because of the additional air within them, so air flow ceases.

Question 130

Describe expiration

Answer 130

* diaphragm and external intercostal muscles relax. The diaphragm and chest wall are no longer actively pulled out by their muscles, so begin to recoil inwards, due to their elastic properties. * intrathoracic pressure increases (decreasing transpulmonary pressure, less than elastic recoil of lungs, so they passively recoil) and this forces the air out * As they become smaller, the alveoli are temporarily compressed, so their volume decreases and their pressure becomes greater than atmospheric pressure, causing flow of air out of the lungs.

Question 131

What is the definition of and equation for flow?

Answer 131

Flow = (Palv – Patm)/R, where Palv is alveolar pressure, Patm is atmospheric pressure and R is a constant. When Palv is less than Patm, the driving force for air flow is negative, indicating that air flow is inward: inspiration. During expiration, the opposite is true.

Question 132

What is the definition of and equation for Boyle's law?

Answer 132

Boyle’s law: P1V1 = P2V2: at a constant temperature, an increase in the volume of a gas will cause a decrease in pressure

Question 133

What is the definition of and equation for transpulmonary pressure?

Answer 133

The difference in pressure between the inside and outside of the lungs. Ptp = Palv - Pip. Because the lungs must always have some air in them, this is always positive relative to atmospheric pressure.

Question 134

What is the definition of Pip

Answer 134

Pressure of the intrapleural fluid surrounding the lungs. This is negative, because the elasticity of the lungs and the chest wall mean they tend towards collapsing and enlarging respectively, so they more apart from each other. This reduces the pressure of the intrapleural fluid.

Question 135

What is active expiration?

Answer 135

This can occur under certain circumstances, e.g. exercise. The internal intercostal muscles contract, depressing ribs 1-11, causing a decrease in thoracic volume. Additionally, contraction of the rectus abdominis increases intra-abdominal pressure, forcing the relaxed diaphragm up into the thorax

Question 136

Describe respiratory failure

Answer 136

A syndrome in which the respiratory system fails in one or both of its gas exchange functions: oxygenation and carbon dioxide elimination

Question 137

What is hypoxemia?

Answer 137

A drop in the oxygen carried in blood

Question 138

What is hypercapnia?

Answer 138

A rise in arterial carbon dioxide levels

Question 139

What are the thresholds for hypercapnia and hypoxemia?

Answer 139

Hypercapnia (PaCO2 >6.0kPa) and Hypoxemia (PaO2 <8kPa)

Question 140

What is type 1 respiratory failure?

Answer 140

Gas exchange failure (e.g. v/q mismatch, hypoxaemia, high altitude, pneumonia)

Question 141

What is type 2 respiratory failure?

Answer 141

pump failure (COPD, ventilation failure due to hypercapnia/hypoxaemia)

Question 142

Define type 1 respiratory failure

Answer 142

low level of oxygen in the blood (hypoxemia) with either a normal or low level of carbon dioxide (PaCO2).

Question 143

Causes of type 1 respiratory failure

Answer 143

This type of respiratory failure is caused by conditions that affect oxygenation such as: * Low ambient oxygen (e.g. at high altitude) * Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it, e.g. pulmonary embolism) * Alveolar hypoventilation (decreased minute volume due to reduced respiratory muscle activity, e.g. in acute neuromuscular disease); this form can also cause type 2 respiratory failure if severe * Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia or ARDS) * Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt)

Question 144

Define type 2 respiratory failure

Answer 144

Because of inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the buildup of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated and low oxygen levels.

Question 145

What are the causes of type 2 respiratory failure?

Answer 145

* Increased airways resistance (COPD, asthma, suffocation) * Reduced breathing effort (drug effects, brain stem lesion, extreme obesity) * A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis) * Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease) * Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest

Question 146

What are the three types of pulmonary stretch receptors?

Answer 146

Slow adapting Rapidly adapting Juxtapulmonary receptors

Question 147

What do slowly adapting stretch receptors do?

Answer 147

Inhibit inspiration; smooth muscle response to stretch

Question 148

What do rapidly adapting stretch receptors do?

Answer 148

Epithelial cells; response to volume change and irritates. Leads to bronchoconstriction

Question 149

What do juxtapulmonary receptors do?

Answer 149

Respond to irritants/noxious agents/interstitial fluid volume. Leads to bronchoconstriction

Question 150

What are the roles of the parts of the upper GI tract?

Answer 150

* Early digestion – mouth * Taste – tongue * Saliva – enzymes, antibacterial, pH control, taste, lubrication * Palate – press against to aid digestion * Tonsils – immunity, lymph * Teeth – digestion * Oesophagus = passage

Question 151

Describe the pathway of food from the mouth to the duodenum

Answer 151

Mouth → pharynx → oesophagus → stomach → duodenum

Question 152

What does the pharynx do?

Answer 152

Pathway for food movement

Question 153

What does the oesophagus do?

Answer 153

Continuation of the pharynx at C6, emerges through the diaphragm at T10, passes to the cardiac orifice of the stomach. Food movement & peristalsis Arterial supply includes: oesophageal branches from the left gastric artery and oesophageal branches from the left inferior phrenic artery

Question 154

Outline the stomach

Answer 154

Most dilated part of the GI tract, lies in the umbilical, epigastric and left hypochondrium regions of the abdomen

Question 155

What are the 4 regions of the stomach?

Answer 155

Cardia, fundus, body and pylorus

Question 156

What is the function of the stomach?

Answer 156

Temporary food storage, mixing and breakdown of food & digestion (gastric juices + digestive enzymes from mucosa)

Question 157

Outline the duodenum

Answer 157

First part of the small intestine, around 20 – 25cm long, retroperitoneal - means behind peritoneum - organ (except for beginning which is connected to the liver by the hepatoduodenal ligament)

Question 158

What is the function of the duodenum?

Answer 158

Receives partially digested food (known as chyme) from stomach & secretions from the pancreas, liver and gallbladder mix with chyme in duodenum to facilitate chemical digestion.

Question 159

How is the oesophagus innervated?

Answer 159

Upper 1/3 is skeletal muscle supplied by the superior laryngeal and recurrent laryngeal nerve. The lower 2/3 is smooth muscle and supplied by the enteric nervous system

Question 160

Outline upper gastro-oesophageal motility

Answer 160

* Peristaltic waves (coordinated waves of contraction) move food after swallowing * Cardiac sphincter = entrance into stomach * Enters into the cardia * Poor oesophageal motility is a common cause of GORD * Oesophageal (cardiac) sphincter weakened, takes less pressure for fluid to move back up * Can be dependent on body position

Question 161

What controls peristalsis in the gastro-oesophageal pathway?

Answer 161

Peristalsis controlled by medulla oblongata + aided by gravity

Question 162

Describe the peristaltic waves

Answer 162

Circular muscles contracts, reducing diameter and increasing pressure, forcing food down oesophagus Longitudinal muscles contract & pull oesophagus over the food

Question 163

What is a primary peristaltic wave?

Answer 163

Occurs when food enter oesophagus during swallowing & forces food down to stomach

Question 164

What is a secondary peristaltic wave?

Answer 164

If bolus gets stuck, stretch receptors in oesophageal lining are stimulated & a second wave happens

Question 165

What is GORD?

Answer 165

Gastro-oesophageal reflux (GORD) = acid reflux → stomach acid rises up into oesophagus

Question 166

What causes GORD?

Answer 166

caused by failure of the lower oesophageal sphincter - In healthy patients, the angle of His (angle at which oesophagus enters stomach) creates a valve that prevents bile, enzyme & stomach acid travelling back into oesophagus - in those with GORD, the valve is weakened or doesn’t close properly - this exposes the mucosa of the oesophagus to stomach acid, bile & pepsin & causes damage to the lining

Question 167

Describe the physiology of acid production in the stomach

Answer 167

* HCl made by parietal cells. * H2O and CO2 combine with the parietal cell cytoplasm to produce carbonic acid (H2CO3) - catalysed by the enzyme carbonic anhydrase * Carbonic acid dissociates into a hydrogen ion (H+) and a bicarbonate ion (HCO3-). * Hydrogen ion enters the lumen of the stomach 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 cell. * Bicarbonate ion is transported out of the cell into the blood in exchange for a chloride ion (Cl-), using an anion exchanger located on the basolateral membrane. * Chloride ion transported into the stomach lumen through a chloride channel * Both H+ ions and Cl- ions in the lumen of the stomach – they have opposite charges, so associate with each other to form hydrochloric acid (HCl)

Question 168

Describe control of acid production

Answer 168

If an increased amount of acid is needed, stimulation can be increase the insertion of more H+ K+ ATPases into the membrane, causing an increased movement of hydrogen ions into the stomach

Question 169

What is the first way of increasing acid production?

Answer 169

ACh (released from the vagus nerve). Released firstly during the cephalic phase of digestion, activates upon seeing/digesting food, this directly stimulates the parietal cells. It is also produced during the gastric phase of digestion when intrinsic nerves detect distention of the stomach stimulating Ach production.

Question 170

What is the second way of increasing acid production?

Answer 170

Main regulation pathway involves gastrin, secreted from G cells in stomach. G cells activated by the vagus nerve & then released into the blood until it reaches the parietal cells. Gastrin binds to CCK receptors on the parietal cells which also elevates calcium levels causing increased vesicular fusion, results in increased insertion.

Question 171

What is the third way of increasing acid production?

Answer 171

Enterochromaffin like cells in the stomach secrete histamine which binds to H2 receptors on the parietal cells. These cells release histamine in response to the presence of gastrin and ACh. This leads to increased fusion however it is via the secondary messenger cAMP as opposed to calcium in the other methods.

Question 172

What is the first way of decreasing acid production?

Answer 172

Accumulation of acid in the empty stomach between meals leads to a lower pH within the stomach, which inhibits the secretion of gastrin, via the production of somatostatin from D cells.

Question 173

What is the second way of decreasing acid production?

Answer 173

When food has been broken down into chyme, it passes into the duodenum, triggering the enterogastric reflex → Inhibitory signals sent to the stomach via the enteric nervous system, + signals to medulla – reducing vagal stimulation of the stomach.

Question 174

What is the third way of decreasing acid production?

Answer 174

Presence of chyme within duodenum stimulates entero-endocrine cells to release cholecystokinin and secretin – both play roles in completing digestion + inhibit gastric acid secretion.

Question 175

How is stomach acid controlled by pharmaceuticals?

Answer 175

* Can inhibit H+ production with proton pump inhibitor (PPI) * Or can use antacid to buffer the acid * Or ranitidine

Question 176

Describe the defences of the gastric and duodenal mucosa against acid damage

Answer 176

* Produce HCO3- (alkaline – neutralising stomach acid on top of epithelial surface) and mucous which act as a protective lining and buffer against the HCl * Thick lining means stomach wall isn’t in direct contact with acid * Irritation causes surface mucous cells to produce more mucous * A loss of this lining means acid can damage the wall and cause ulcers * Exacerbated by H. bacter pylori Brunner’s glands in wall of first few cm of duodenum secretes alkaline mucus

Question 177

What is dyspepsia?

Answer 177

Group of symptoms that alert doctors to consider disease of the upper GI tract, and states that dyspepsia itself is not a diagnosis. Symptoms: typically are present for 4 weeks or more, include (but are not limited to) upper abdominal pain or discomfort, heartburn, gastric reflux, nausea or vomiting

Question 178

Symptoms of reflux disease

Answer 178

Can include bloating, blood in vomit or faeces, dysphagia, hiccups, burping, nausea and unexplained weight loss. Patients may also report a burning pain or discomfort that can move up from the stomach to the middle of the abdomen and chest.

Question 179

Risk factors for GORD

Answer 179

Family history of heartburn or GORD, older age, hiatus hernia or obesity.

Question 180

Key diagnostic factors for GORD

Answer 180

Presence risk factors along with heartburn and acid regurgitation (can include dysphagia, bloating and laryngitis)

Question 181

Risk factors for reflux

Answer 181

Overweight (extra pressure on stomach/diaphragm), smoking (loosen sphincter), alcohol (damage stomach lining/glands) & large meals (stomach stretches, increasing pressure on lower oesophageal sphincter so food not forced into stomach) may aggravate reflux

Question 182

Why does food get stuck in the oesophagus when someone has GORD?

Answer 182

Damage to the lower oesophagus from stomach acid can lead to formation of scar tissue. This narrows the oesophagus, leading to problems swallowing.

Question 183

How does GORD cause bloating?

Answer 183

Bloating is a symptom of GORD (though I couldn’t find anything explaining why), with bloating particularly bad after eating, especially raw salad, due to the roughage. The two are linked the other way though: burping in order to release air can lead to acid entering the oesophagus

Question 184

How does GORD cause abdominal pain?

Answer 184

Reflux is leading to acid irritating the lower oesophagus.

Question 185

How does GORD cause sore throat and cough?

Answer 185

If the acid reflux gets past the upper oesophageal sphincter, it can enter the pharynx, causing a sore throat.

Question 186

Why does acid reflux get worse in pregnancy?

Answer 186

* More pressure on the oesophageal sphincter due to baby. * Generalised smooth muscle relaxation due to progesterone → more relaxation in gut → stomach stays full for longer, gastric motility decreases. * Prone to constipation → more water absorbed is in small bowel due to slower movement * Normal changes, not pathological

Question 187

Describe the lobes of the liver

Answer 187

Liver divided into anatomical right and a left lobe by the falciform ligament. (functional left and right divided by drawing a line vertically halfway through the IVC and gallbladder). There are 2 “accessory lobes that arise from the right lobe on the visceral (posterior inferior) side of the liver

Question 188

Where are the two accessory lobes?

Answer 188

* Caudate lobe: lies superiorly. * Quadrate lobe: lies inferiorly, roughly square shaped.

Question 189

How are the accessory lobes of the liver separated?

Answer 189

These lobes separated by a deep transverse fissure - the porta hepatis, the bundle of blood vessels, nerves and ducts entering or leaving the liver (excluding the hepatic vein which drains into IVC).

Question 190

What is the functional structure of the liver?

Answer 190

Hepatocytes arranged in lobules - hexagonal shaped units with a portal triad at each corner, surrounding a central vein.

Question 191

What is the portal triad?

Answer 191

Venule of a portal vein, an arteriole hepatic artery and a bile duct, along with lymphatic vessels and vagus nerve (parasympathetic) fibres.

Question 192

Describe how hepatocytes are arranged

Answer 192

Hepatocytes arranged in cords (converge on central vein) with sinusoids between them

Question 193

What are sinusoids?

Answer 193

Low pressure vascular channels that receive blood from the terminal branches of the hepatic artery & portal vein at the periphery of the lobule. They deliver blood to the central vein.

Question 194

Describe the mechanism of gas exchange in the liver

Answer 194

Hepatocytes are in contact with a sinusoidal & canalicular membrane. Sinusoidal membrane → allows materials to be exchanged with blood & the space between the sinusoid endothelium & hepatocytes = space of Disse & this contains blood plasma

Question 195

What allows better nutrient exchange in the liver?

Answer 195

Fenestrated endothelium of the sinusoids means the hepatocytes are bathed in plasma for nutrient exchange.

Question 196

What happens when the liver is damaged?

Answer 196

Hepatic stellate cells (ito cells) are found in the space of Disse. When the liver is damaged, hepatocytes & immune cells release factors that stimulate the stellate cells to secrete proteins such as collagen - useful until liver injury becomes chronic & continued collagen secretion causes the liver to become fibrosed

Question 197

What does the canalicular membrane do?

Answer 197

Canalicular membrane lies between hepatocyte & bile canaliculi and permits bile excretion

Question 198

What do kupffer cells do?

Answer 198

Kupffer cells present in the walls of the sinusoids – they phagocytose blood borne pathogens (portal blood has more blood borne pathogens than systemic blood) & have a role in bilirubin production (taken up & excreted by hepatocytes)

Question 199

Outline hepatic ducts

Answer 199

Drain bile from the canaliculi among the cells of the liver lobules right and left hepatic ducts: merge at the porta hepatis to form the common hepatic duct.

Question 200

Describe the process of moving from the hepatic ducts to the main pancreatic duct

Answer 200

Descends between the layers of the lesser omentum → merges with the cystic duct to form the bile duct → descends behind the first part of the duodenum, deep to or through the head of the pancreas → joins with the main pancreatic duct.

Question 201

What happens in the liver when RBCs come to the end of their lives?

Answer 201

RBC is ingested --> macrophage (phagocyte, Kupffer cell, etc), Hb --> heme and globin (initiates heme catabolism)

Question 202

What is the globin from haemoglobin broken down into?

Answer 202

Amino acids, used in bone marrow to form new RBC

Question 203

What is the haem from haemoglobin broken down into?

Answer 203

Biliverdin, catalysed by heme oxygenase, also liberating Fe2+and CO2

Question 204

What happens to the iron in haemoglobin when it is released?

Answer 204

Fe2+ is shuttled --> bone marrow using plasma transferrin to be again incorporated → new RBC

Question 205

What is biliverdin and what it is it converted into?

Answer 205

unconjugated bilirubin, catalysed by biliverdin reductase, undergoes biotransformation (glucuronidation) to form bilirubin (occurs in the liver, detoxification)

Question 206

What is the pathway of bilirubin out of the body?

Answer 206

Bilirubin can then dissolve in bile (more water soluble), and thus during digestive processes will end up in the small intestine, where the glucuronic acid is removed by bacteria to form urobilinogen

Question 207

What happens to urobilinogen?

Answer 207

Urobilinogen is either recycled via the ETC or oxidised by a different type of intestinal bacteria to form stercobilin

Question 208

Why is faeces brown?

Answer 208

Stercobilin is excreted in faeces and is what gives the characteristic brown colour

Question 209

Describe haemopoesis

Answer 209

- Haemopoieses of erythrocytes begins in haemopoietic bone marrow - Reticulocytes are released into blood, they mature and circulate for 120 days - Old/damaged erythrocytes are phagocytosed by macrophages in the bone marrow, liver and spleen - The globin (protein) portion of Hb is metabolised into amino acids and reused for protein synthesis . The cell components (organelles) are recycled - The haem portion is broken down into biliverdin for transport in blood. The iron ions bind to the blood protein transferrin for transport. - Unused haem groups can be used for haemopoiesis or converted into bilirubin and used to make bile in the liver. Iron ions can be transferred into ferritin for storage in the liver

Question 210

Describe the subcostal plane

Answer 210

- corresponds to a line drawn joining the lower most bony point of the rib cage, usually 10th costal cartilage - body of the L3 vertebra; the origin of the inferior mesenteric artery and 3rd part of the duodenum lie on this plane

Question 211

Describe the transtubercular plane

Answer 211

- corresponds to a line uniting the two tubercles of the iliac crests - upper border of the L5 vertebra and the confluence of the common iliac veins(i.e. IVC origin) lie on this plane

Question 212

What is haemolytic/ pre-hepatic jaundice?

Answer 212

increased unconjugated bilirubin due to excess erythrocyte breakdown, exceeding the capacity of the liver to transport it. This is the jaundice present in newborns, as foetal haemoglobin is being broken down. NB physiological jaundice of the newborn. Different causes, e.g. if the baby is not feeding well, can’t get the glucuronic acid to conjugate bilirubin. + gut flora not well-established. Can be treated w/ UV light.

Question 213

What are the causes of haemolytic/pre-hepatic jaundice?

Answer 213

Infection, trauma to erythrocytes, sickle cell anaemia, drugs and toxins and antibodies.

Question 214

What are some distinguishing features of haemolytic/pre-hepatic jaundice?

Answer 214

Absence of bile pigments in urine and normal stool colour, because unconjugated bilirubin is insoluble so not filtered by the kidneys and bile can circulate to enter the intestine as normal

Question 215

What is hepatocellular/hepatic jaundice?

Answer 215

Hepatocytes are damaged so unable to transport bilirubin into the biliary system, so it enters the bloodstream instead. The bilirubin may be conjugated.

Question 216

What are the causes of hepatocellular/hepatic jaundice?

Answer 216

Hepatitis, cirrhosis and congestive liver disease

Question 217

What are the distinguishing features of hepatocellular/hepatic jaundice?

Answer 217

Dark amber urine, as much of the bilirubin has been :conjugated so is water soluble and so can be filtered by the kidneys. Stools are usually normal because some bile pigment manages to be excreted into the biliary tract and intestine.

Question 218

What is cholestatic/obstructive/post-hepatic jaundice?

Answer 218

Inability of hepatocytes to transport bilirubin either through the capillary membrane due to damage in the area, or through the biliary tract due to anatomical obstructions, e.g. gallstones, cancers e.g. carcinomas of the pancreas or ampulla of Vater.

Question 219

What are the causes of Cholestatic/obstructive/post-hepatic jaundice?

Answer 219

Many types of hepatitis, especially those caused by drugs, diseases which damage small bile passages (intrahepatic cholestasis), as well as obstructive disorders of the biliary tract (extrahepatic cholestasis).

Question 220

What are some of the key features of Cholestatic/obstructive/post-hepatic jaundice?

Answer 220

Amber coloured urine, as the bilirubin has been conjugated so can be filtered by the kidneys. Pale stools, as bile can’t enter the intestine. Itching of the skin(pruritis), due to build-up of bile salts below the skin, which triggers the inflammatory response.

Question 221

What happens with cholestasis?

Answer 221

With cholestasis → bile flow impaired at some point between the liver cells (which produce bile) and the duodenum (the first segment of the small intestine).

Question 222

What happens when bile flow is stopped?

Answer 222

When bile flow is stopped, the pigment bilirubin (a waste product formed when old or damaged red blood cells are broken down) escapes into the bloodstream and accumulates. Urine may become dark because of high levels of bilirubin being excreted from the kidneys. Stools may become light-colored because the passage of bilirubin into the intestine is blocked, preventing it from being eliminated from the body in stool. Stools may contain too much fat (steatorrhoea) because bile cannot enter the intestine to help digest fat in foods.

Question 223

How is bilirubin usually excreted?

Answer 223

Normally, bilirubin joins with bile in the liver, moves through the bile ducts into the digestive tract, and is eliminated from the body. Most bilirubin is eliminated in stool, but a small amount is eliminated in urine.

Question 224

Why might urine become dark and stools become light?

Answer 224

Urine may become dark because of high levels of bilirubin being excreted from the kidneys. Stools may become light-colored because the passage of bilirubin into the intestine is blocked, preventing it from being eliminated from the body in stool. Stools may contain too much fat (steatorrhoea) because bile cannot enter the intestine to help digest fat in foods.

Question 225

Describe the major anatomy of the brain

Answer 225

- Brain is separated → 2 hemispheres by the deep longitudinal fissure, the corpus callosum is the large bundle of white matter connecting the two - Brain surface is formed of gyri (ridges) and the grooves between the gyri and sulci

Question 226

What does the frontal lobe contain and what does it do?

Answer 226

* motor cortices and association areas (primary motor cortex (pre-central gyrus), supplementary motor area; association area for organising behaviour and working memory) * controls movement in contralateral part of body * regions controlling behaviour, decision making and personality (prefrontal association area) * Broca’s area is found in the left frontal lobe, responsible for fluent speech, writing (expressive aphasia without – no motor control of speech) → if R handed, L hemisphere is dominant

Question 227

What can damage to the frontal lobe result in?

Answer 227

Damage can result in a worse ability to assess risk and hence to react to danger, as well as reduced facial expressions and changes in personality.

Question 228

What separates the frontal and parietal lobes?

Answer 228

Central sulcus separates the frontal and parietal lobes.

Question 229

What do the parietal lobes contain and do?

Answer 229

PARIETAL LOBES contain the primary somatosensory cortex (post-central gyrus). Function is to receive and interpret sensations (e.g. pain, touch, pressure, etc.). Damage can result in attention deficits.

Question 230

What do the temporal lobes contain and do?

Answer 230

* auditory cortices (primary = Herschel’s gyrus, association cortex and belt/ parabelt areas; assoc. for sensory stimuli recognition and storage of semantic memory) * separated by lateral sulcus * medial temporal lobe for long term memory and emotion (hippocampus, amygdala, entorhinal and perirhinal cortex. LIMBIC SYSTEM) * Wernicke’s area for understanding speech and written language (damage = Wernicke’s receptive / fluent aphasia)

Question 231

What happens if there is damage to Wernicke's area but not Broca's?

Answer 231

The person is able to produce grammatically correct and normal sounding speech, but the content will be non-sensual

Question 232

What do the occipital lobes contain and do?

Answer 232

* located posteriorly – contain the primary visual cortex. * Damage can result in complete or partial blindness or visual agnosia (unable to comprehend visual stimuli, despite still being able to view them).

Question 233

What is the anatomy of the cerebellum?

Answer 233

(‘mini-brain’ – 2 hemispheres. 10% weight total brain weight – around ½ brains total neurons) * 3 cerebellar peduncles that connect it the other parts of CNS (superior to cerebral cortex, middle to pons and inferior to spinal cord, tegmentum and vestibular nuclei) * Made up of folded cortex, white matter + deep nuclei * responsible for converting voluntary motor actions to automatic, which are stored in the deep nuclei (dentate, interposed, emboliform, globose and fastigial).

Question 234

Describe the brainstem

Answer 234

(midbrain, pons, medulla - location of cranial nerves) * Midbrain consists of tectum, tegmentum (red nuclei, periaqueductal grey, substantia nigra) * Pons – nuclei for breathing, sleeping, swallowing, bladder control; middle cerebellar peduncle * Medulla oblongata – autonomic regulation, corticospinal pyramids, inferior cerebell. Peduncle, somato, tubercles

Question 235

Which part of the brain is often badly damaged by a stroke and why?

Answer 235

Medulla can be badly damaged by a stroke - proximity of the vertebral artery and posterior inferior cerebral artery.

Question 236

Which cranial nerves originate from the cerebrum?

Answer 236

Olfactory and optic (I and II) cranial nerves originate from the cerebrum, whereas the remaining ten originate from the brainstem

Question 237

Describe tracts

Answer 237

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 Divided into 2 major groups - Pyramidal tracts and extrapyramidal tracts

Question 238

Describe the pyramidal tracts

Answer 238

(name derived from medullary pyramids of the medulla oblongata,which they pass through) * originate in cerebral cortex + carry motor fibres to spinal cord and brainstem responsible for the voluntary control of body & face musculature * Divided into: Corticospinal and corticobulbar tracts

Question 239

Outline corticospinal tracts

Answer 239

(supply musculature of body) * Begins in the cerebral cortex and receives input from * Primary motor cortex * Premotor cortex * Supplementary motor cortex * Somatosensory cortex

Question 240

Outline corticobulbar tracts

Answer 240

(Facial and neck muscles) ▪ Begins in lateral aspect of primary motor cortex ▪ Cortex → descends through internal capsule → crus cerebri → brainstem (pons+medulla)→ terminate on motor nuclei of cranial nerve

Question 241

Outline extrapyramidal tracts

Answer 241

originates in brain stem + carries motor fibres to spinal cord o Involuntary and autonomic control of musculature Types- Vestibulospinal, reticulospinal, rubrospinal, tectospinal

Question 242

What do vestibulospinal extrapyramidal tracts do?

Answer 242

Ipsilateral information (balance and posture). Medial and lateral.

Question 243

What do reticulospinal extrapyramidal tracts do?

Answer 243

Facilitates (medial) and inhibits (lateral) voluntary movements increase (medial) and decrease (lateral) muscle tone

Question 244

What do rubrospinal extrapyramidal tracts do?

Answer 244

Fine control of hand movement

Question 245

What do tectospinal extrapyramidal tracts do?

Answer 245

Coordinates movement of head in relation to visual stimuli

Question 246

Outline upper motor neurones

Answer 246

Brain and brainstem to the ventral horn of the spinal cord. Typically, those in descending tract will be these.

Question 247

Outline the lower motor neurones

Answer 247

Ventral horn of the spinal cord to the peripheral muscles.

Question 248

Outline the cortical homunculus

Answer 248

Contains the motor and sensory homunculus. Region of the brain dedicated to processing motor and sensory functions for different parts of the body. Nerve fibres will conduct somatosensory information from all over the brain.

Question 249

What does the motor homunculus do?

Answer 249

Motor processing for different bodily anatomical positions. Handles signals coming from premotor area of frontal lobes

Question 250

What does the sensory homunculus do?

Answer 250

Sensory processing for different anatomical positions. Handles signals coming from the thalamus

Question 251

What is the corona radiata?

Answer 251

* 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 (supply vital proteins to cells). * Sheets of both ascending and descending axons will carry most of the neural traffic to (afferent) and from (efferent) the cerebral cortex. * Fibres will include auditory radiation, optic radiation, thalamic radiations.

Question 252

Outline the internal capsule

Answer 252

* White matter structure situated in the inferomedial part of the cerebral hemisphere of the brain carrying information past the basal ganglia. * Contains both ascending and descending axons going to and from the cerebral cortex. * Fibres will connect the thalamus with the cerebral cortex.

Question 253

Where does the anterior cerebral artery supply?

Answer 253

Supplies the corpus callosum and the medial region of brain, including lower limb area of M1

Question 254

Where does the middle cerebral artery supply?

Answer 254

Lateral parts of each hemisphere and anterior deep structures

Question 255

Where does the posterior cerebral artery supply?

Answer 255

Posterior region and the posterior inferior structures (caudate nucleus, occipital lobe, etc.)

Question 256

What would an occlusion of the middle cerebral artery (MCA) show up as?

Answer 256

is largest of the terminal branches of the Internal Carotid Arteries * Broca’s area (frontal lobe) supplied by the (left) middle cerebral artery. Inability to form speech (expressive aphasia) could be due to stroke in the middle cerebral artery / the anterior circulation. (Note: in right handed people, Broca’s area is almost always on the left side of the brain. In left-handed people, Broca’s area is on the right side in about 60% of people.) * Wernicke’s area (parietal lobe) supplied by the middle cerebral. Stroke here can cause difficulty understanding written or spoken language (receptive dysphasia).

Question 257

Would be the symptoms of an occlusion of the posterior cerebral artery?

Answer 257

Occlusion of posterior cerebral artery could lead to a hemianopia (blindness over half the field of vision) → this type of stroke affects the visual pathways from the optic chiasm onwards towards the occipital lobe.

Question 258

What type of stroke causes motor weakness?

Answer 258

From any area affecting the motor cortex. The primary motor cortex is supplied by the anterior and middle cerebral arteries → anterior circulation stroke will produce motor weakness.

Question 259

Why might a PCA stroke cause muscle weakness?

Answer 259

This is because the corticospinal tracts have to travel through the brainstem and spinal cord. So a stroke affecting the brainstem (e.g. posterior circulation stroke affecting basilar arteries) could also result in motor weakness.)

Question 260

What is the Upper motor neurone's role and how does it do it?

Answer 260

Not responsible for muscle stimulation of the muscle as they don’t carry information down to the final common pathway. - work through the neurotransmitter glutamate which transmits the nerve impulses from UMN to LMN where it is detected by glutamatergic receptors.

Question 262

How to tell if it is an upper or lower motor neurone disorder?

Answer 262

Upper motor disorders usually cause spasticity; lower motor disorders usually cause flaccidity.

Question 263

What is the lower motor neurone's role and how does it do it?

Answer 263

receive impulses from the upper motor neurons and connect the spinal cord and brainstem to the muscle fibers. - They are the cranial and spinal nerves + work using glutamate released from UMN, triggering depolarization in the lower motor neurons signalling the muscle to contract.

Question 264

UMN weakness symptoms

Answer 264

Slight/absent muscle wasting, muscle weakness in the extensors (in the flexors for the legs), hyperlexia and muscle spasticity · Weakness is majority found on the contralateral side of the lesion due to 85% of the fibres crossing over (decussation) NB UMN lesion causes weakness sparing the forehead.

Question 265

Outline LMN lesions

Answer 265

Caused by severing of the LMN (e.g a car crash), certain viruses that target the ventral horn and autoimmune conditions such as MS which target the nerves Symptoms: Severe atrophy, hypotonia, hypoflexia, flaccid muscle weakness NB LMN weakness affects the whole side of the body, including the forehead.

Question 266

Describe the effect of Myasthenia Gravis

Answer 266

autoimmune destruction of nicotinic ACh receptors - Ach release is normal but there’s decreased number of receptors - treatment: acetylcholinesterase inhibitors can compensate for lack of Ach by increasing amount of time Ach is available for OR immunosuppressants OR removal of antibodiesby plasmapheresis OR thymus removed NB MG is a collection of neuromuscular disorders characterised by fatigue + weakness, worsening as muscle is used

Question 267

Outline muscular dystrophy

Answer 267

X-linked genetic disorders resulting in malformed dystrophin – loss of cell membrane cytoskeletal connections, unregulated influxes of calcium to sarcolemma - progressive degeneration of skeletal + cardiac muscle fibres → death from respiratory/cardiac failure

Question 268

What causes Duchenne muscular dystrophy

Answer 268

caused by a non-functional or absent form of the gene for the protein dystrophin, which is on the X chromosome (so Duchenne’s is sex-linked). Dystrophin links cytoskeletal proteins to membrane glycoproteins, maintaining the structure of the plasma membrane or elements within it, such as ion channels. Therefore, without it, fibres which are subjected to repeated structural deformation during muscle contraction are susceptible to membrane rupture and cell death.

Question 269

Describe dysphasia

Answer 269

delayed swallowing (form of dysphagia). Dysphagia affects the vast majority of acute stroke patients. This is because normal control of swallowing requires appropriate function of the brain stem, the basal ganglia, the thalamus, the limbic system, the cerebellum, and the motor and sensory cortices. The latter two of these structures would have definitely been impacted by a stroke somewhere in the middle cerebral artery,

Question 270

Outline carpal tunnel syndrome

Answer 270

Carpal tunnel syndrome (CTS) is pressure on a nerve in your wrist. It causes tingling, numbness and pain in your hand and fingers. You can often treat it yourself, but it can take months to get better. Check if you have carpal tunnel syndrome (CTS) The symptoms of carpal tunnel syndrome include: * an ache or pain in your fingers, hand or arm * numb hands * tingling or pins and needles * a weak thumb or difficulty gripping These symptoms often start slowly and come and go. They're usually worse at night

Question 271

What is included in the CNS?

Answer 271

Brain and spinal cord - can be divided into Lower Centres (including spinal cord and brainstem) and Higher Centres communicating with brain via effectors. - info sent to CNS via afferent sensory neurons

Question 272

What is included in the PNS?

Answer 272

the rest of the nervous system ( i.e. everything excluding the brain and spinal cord). Contains sensory receptors which help process changes in the internal and external environment. - PNS is subdivided into somatic and autonomic nervous systems.

Question 273

Outline the somatic nervous system

Answer 273

Part of peripheral nervous system → always stimulatory o Voluntary movement (conscious movement of skeletal muscle) o Reflex arc (involving muscles)

Question 274

Outline the autonomic nervous system

Answer 274

o Heart rate, digestion, salivation, urination and digestion o Parasympathetic - rest and digest responses. Acetylcholine is neurotransmitter. o Sympathetic - fight or flight. Neurotransmitter = noradrenaline. o But they both use nicotinic receptor at the first synapse.

Question 275

What is resting portential?

Answer 275

Resting potential is when there is a higher concentration of sodium ions on the outside → - 70mV (maintained by N+/K2+ active transport – 3 Na out, 2 K in)

Question 276

Describe the physiology of an action potential

Answer 276

* Action potential begins with a depolarising stimulus e.g. neurotransmitter binding to ion channel → cell then depolarises (becomes less negative), stimulating voltage gated Na+ channels to open so more depolarisation * The threshold is -55mV for an action potential to be fired * The increase in sodium ions continues until the cell membrane potential reaches +30mV (via positive feedback loop) * At this point, membrane potential reaches its peak value & sodium channels are blocked by inactivation gates. Potassium voltage-gated channels open (K+ moves out) and K ion leave rapidly, repolarising the cell + membrane potential becomes negative + voltage gated sodium channels close * The membrane potential begins to move back to its resting state * Potassium channels experience a delay in closing resulting in hyperpolarisation → where the potential is lower than -70mV (where K+ permeability is raised above resting levels * Once voltage gated potassium channels close, resting potential is restored

Question 277

What is the absolute refractory period?

Answer 277

No stimulus can produce a second action potential - sodium channels are already open or have been inactivated by inactivation gates. The inactivation gate must be removed before channels can open + this only occurs by repolarising the membrane.

Question 278

What is the relative refractory period?

Answer 278

2nd action potential can happen, but needs stronger stimulus. - some of the voltage-gated sodium channels have returned to their resting state + some potassium channels are still open.

Question 279

Why can an action potential only travel down a neuron if each point is depolarised to the threshold potential?

Answer 279

Because areas that haven’t been depolarised are -ve relative to the areas which have been, +ve ions will flow from the depolarised region, causing slight depolarisation of the adjacent region. This causes voltage-gated sodium channels to open, causing depolarisation.

Question 280

What effect does K+ levels have on the axon?

Answer 280

Raised K+ increases membrane potential - closer to threshold value High K+ levels can impact the threshold value Less K+ influx and less stimulation is required for depolarization - membrane can be more readily depolarized.

Question 281

What are the factors affecting conduction speed?

Answer 281

Diameter Myelin

Question 282

How does diameter affect conduction speed?

Answer 282

Larger fibre will have a faster action potential → more ions can flow in a given time

Question 283

How does myelin affect conduction speed?

Answer 283

Prevents leakage of charge from inside to outside the cell, so the local current can spread further. It also means sodium channels are only found in the nodes of Ranvier, so action potentials jump from one node to the next (saltatory conduction), which is faster. (+ more energy efficient → only get depolarisation in small areas.)

Question 284

What are the four aspects of a stimulus?

Answer 284

Modality, intensity, location and duration.

Question 285

Outline sensory receptors

Answer 285

Are specialised to respond to stimuli E.g. chemical - chemoreception, mechanical - mechanoreception, thermal - thermoreception or nociceptive – noiciception stimuli, proprioception

Question 286

Outline sub-modalities

Answer 286

Are different variations within a stimulus – specific receptors sensitive to specific modalities E.g. pitch, volume and timbre in audible stimuli

Question 287

What happens to sensory receptors when they are triggered by a stimulus?

Answer 287

Sensory receptor activity is triggered by a stimulus, resulting in ion channels opening (if the stimulus is large enough) → receptors either endings of afferent neurons or separate cells that signal neuron by releasing neurotransmitter - results in graded potential, this must be sufficient to flow to an area with voltage gated channels to trigger action potential

Question 288

What are the 2 processes of the afferent neurons?

Answer 288

- Once to site of reception - Once to spinal cord to synapse with interneurons

Question 289

What role do interneurons play in the sensory pathway?

Answer 289

Interneurons synapse with ascending neurons in the corresponding pathway to stimulus - decussation occurs at interneuron or at brainstem (usually medulla) e.g. DCML + ventral spinothalamic pathways

Question 290

What happens after decussation in the interneuron/ brainstem?

Answer 290

Information gets passed to brainstem and thalamus before reaching the somatosensory cortex (posterior to central sulcus) for processing

Question 291

What are the 2 types of sensory receptors?

Answer 291

o Tonic → slow adapting receptors o Phasic → rapid adapting receptors

Question 292

Outline the knee jerk reflex

Answer 292

patellar reflex - tests the nervous tissue between & including L2 - L4 segments of the spinal cord 1.Patella tendon (just below the patella) is tapped, thus pushing the tendon back and the muscle spindle in the quadriceps muscle is stretched – activating the stretch receptors 2.Stimulates a burst of AP in the afferent nerve fibres from the stretch receptors of the muscle spindle which travels to the spinal cord at the level of L3/4. These fibres then synapse with 1 interneuron & alpha-motor neurone 3. The extensor muscle contracts whilst the flexor muscle relaxes, causing the knee to jerk

Question 293

Outline the inhibitory path of the sensory neuron

Answer 293

Sensory neuron synapses with an interneuron. Interneuron then synapses with alpha motor neuron in the spinal cord. AP then travels via this neuron to the flexor muscle (hamstring) → poly synaptic pathway

Question 294

What is the excitatory path of the sensory neuron?

Answer 294

Sensory neuron synapse in spinal cord with alpha motor neuron & AP goes to the extensor (quadricep), conducting efferent impulse back to muscle→ monosynaptic pathway

Question 295

What is Westphal's sign?

Answer 295

Absence/ decrease of the reflex

Question 296

What is Brown sequard syndrome?

Answer 296

lesion in one half of the spinal cord due to hemisection. Usually cervical. Rarely seen clinically. - characterised by weakness on one side (hemi paraplegia) + loss of sensation on opposite side (hemianesthesia) CONSTRAS to DCML lesions, where sensory loss is ipsilateral (spinal thalamic tracts decussate in spinal cord)

Question 297

Possible causes of Brown sequard syndrome

Answer 297

* Traumatic injury e.g. bullet / stab wound / kick / car accident * Non-traumatic e.g. tumour / disc hernia / multiple sclerosis

Question 298

Clinical presentation of Brown sequard syndrome (ipsilateral)

Answer 298

Loss of touch, vibration, proprioception, (all caused by injury to DCML system, ascending tracts) and loss motor function (caused by injury to descending tracts)

Question 299

Clinical presentation of Brown sequard syndrome (Contralateral)

Answer 299

loss of pain and temperature sensation (caused by injury to anterolateral system)

Question 300

How does where the lesion occurs in relation to the point of decussation affect the presentation?

Answer 300

* If the lesion is below / after the point of decussation, the ipsilateral (same side) is affected * If the lesion is above / before the point of decussation, the contralateral (opposite side) is affected

Question 301

What are the kidneys?

Answer 301

* Paired retroperitoneal organs that filter the plasma and produce urine

Question 302

Where are the kidneys?

Answer 302

They are located bilaterally high in the posterior abdominal wall just anterior to the muscles of the posterior wall Typically extend for T12 to L3— right kidney usually slightly lower due to presence of liver

Question 303

Describe the layers of the kidney

Answer 303

Each kidney is enclosed within a capsule and internally, has a distinct cortex (outer layer) and medulla (inner layer)

Question 304

Describe the renal pyramids

Answer 304

Renal medulla is characterised by the presence of 8-15 pyramids (collection of tubules), which taper down at their apex to form the papilla, where the urine drips into a minor calyx.

Question 305

Outline the pathway from the minor calyx to the proximal ureter

Answer 305

Several minor calyx form a major calyx, and several major calyx empty into a single renal pelvis and the proximal ureter

Question 306

Outline the ureter

Answer 306

* Pair of tubes that carry urine from the kidney to the urinary bladder. * They are about 10-12 inches long and run parallel to the vertebral column. Situated bilaterally. * Uretic walls comprised of smooth muscle which is needed for peristaltic waves

Question 307

Where does the ureter narrow?

Answer 307

- Where pelvis of kidney becomes ureter - At the pelvic brim - Where the ureter passes through the bladder

Question 308

What is the urinary bladder?

Answer 308

A sac-like hollow organ used for the storage or urine at the inferior end of the pelvis.

Question 309

What stops urine passing back up from the bladder to ureter?

Answer 309

- 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

Question 310

Outline the urethra

Answer 310

* tube though which urine passes from the bladder to the exterior. * female urethra: about 2 inches long and ends inferior to the clitoris and superior to the vaginal opening. * Males: 8-10 inches long and ends at the tip of the penis

Question 311

Outline the nephron

Answer 311

function unit of the kidney - Between 0.8-1.5 million nephrons in each kidney

Question 312

What are the two types of nephron?

Answer 312

Cortical nephrons: tubules extend only a short distance into medulla then back into cortex Juxtamedullary nephrons: tubules extend deep within the medulla—have vasa recta around them

Question 313

What are the nephron sections?

Answer 313

Renal corpuscle Glomerulus Bowman's capsule Renal tubules: PCT Loop of Henle DCT Collecting duct

Question 314

Outline the renal corpuscle

Answer 314

Part of nephron in which blood plasma is filtered

Question 315

Outline the glomerulus

Answer 315

Capillary tuft formed by the afferent and efferent arterioles and encased in Bowman’s capsule

Question 316

Outline the bowman's capsule

Answer 316

First step in filtration of blood to produce urine

Question 317

Outline the PCT

Answer 317

Bulk of reabsorption happens here → receives plasma ultrafiltrate and brings it down to the loop of Henle in the cortex. Lined with cuboidal epithelium

Question 318

Outline the loop of henle

Answer 318

Tubule lined with thin squamous epithelial Descending loop = H20 permeable Ascending loop = H20 Impermeable ; solute reabsorption occurs here

Question 319

Outline the DCT

Answer 319

Fine regulation of Ca2+, Na+, K+ and HCO3 reabsorption is Cl dependent

Question 320

Outline collecting duct

Answer 320

Terminal end of nephron; final concentration of urine is “fine-tuned” before it goes to minor calices

Question 321

Outline glomerular filtration and urine production

Answer 321

- occurs due to pressure gradient in glomerulus - occurs when blood hydrostatic pressure exceeds hydrostatic pressure of glomerular capsule & blood colloid pressure - passive process

Question 322

Outline the 3 layers of the filtration barrier

Answer 322

From glomerulus into nephron → small molecules and ions up to 10 kDa get through but larger and negatively charged molecules can’t - Podocytes with negatively charged foot processes which are negatively charged prevent albumin getting through → Form glomerular filtrate

Question 323

What is the filtration of the glomerulus determined by?

Answer 323

1) Size of molecule 2) Pressure 3) Size of molecule 4) Charge of molecule 5) Rate of blood flow 6) Renal blood flow is approximately 20% of the CO at rest

Question 324

Key facts about the glomerular filtration

Answer 324

* The volume of fluid filtered by the renal glomeruli per unit of time is the GFR * On average, 180L of fluid is filtered per day (125ml/min)…since plasma accounts for about 3L of our total blood volume, our kidneys therefore filter the blood plasma about 60 times/day

Question 325

Outline renal clearance

Answer 325

* The virtual plasma volume per minute, from which a substance is completely eliminated. If a substance is chosen, which is not secreted or reabsorbed in the renal tubules, the measured clearance corresponds to the glomerular filtration rate (GFR) * Substances with exclusive glomerular filtration (without tubular secretion or reabsorption) like creatinine have serum concentrations in direct dependence with GRF

Question 326

Outline tubular reabsorption and urine production

Answer 326

* 99% of the glomerular filtrate volume, filtrated Na+ and Cl- are reabsorbed in the renal tubules of the nephron. * The reabsorption is an energy consuming process. * The most common drive for reabsorption is the basolateral located sodium potassium pump which transports 3 Na+ out and 2 K+ into the cells, energy from the hydrolysis of 1 ATP molecule.

Question 327

What happens in the PCT and the descending part of the loop of Henle

Answer 327

* 2/3 of primary urine volume are reabsorbed * PCT has villi to increase SA * Reabsorption of Na, Cl, glucose, amino acids, HCO3 * Drive of Na transport via the basolateral Na-K pump * HCO3− reabsorption is dependent on sodium reabsorption and proton secretion

Question 328

What happens in the ascending part of the Henle loop?

Answer 328

* Impermeable to water, transports electrolytes to interstitium * Produces high osmotic pressure * 30% of the filtered Na is reabsorbed using a lumen Na-K-2Cl co-transport mechanism

Question 329

What happens in the DCT?

Answer 329

* Active Na transport via thiazide-sensitive Na-Cl co-transporter * 10% of filtered sodium is reabsorbed here * Thiazides inhibit the sodium reabsorption is the distal tubule

Question 330

What happens in the collecting duct?

Answer 330

* The permeability of the CTs for water lead to a concentration of the urine into the fivefold osmolarity of the plasma * High osmotic pressure of the renal medulla is responsible for the force for the urine concentration

Question 331

How is reabsorption of water regulated by the collecting duct?

Answer 331

* Permeability regulated by ADH (causes incorporation of additional aqua-porins into the luminal membrane * A deficiency of ADH secretion leads to diabetes insipidus, a disorder with massive diuresis and excessive thirst

Question 332

Outline renin

Answer 332

Rate determining step of RAAS system Released from granular cells of renal juxtaglomerular apparatus (JGA)

Question 333

What is renin released in response to?

Answer 333

- reduced NaCl delivery to distal tubule detected by macular densa cells - reduced perfusion pressure in kidney detected by baroreceptors in afferent arteriole - sympathetic stimulation of JGA JGA cells innervated by beta 1 adrenergic sympathetic nerve fibres Angiotensin II

Question 334

Outline the RAAS system

Answer 334

* Angiotensinogen is a precursor protein produced in liver, cleaved by renin to form angiotensin 1 * Then converted to angiotensin II by angiotensin converting enzyme (ACE – found in renal endothelium, lungs & capillary endothelium) * Bonds to various receptors Stimulates the release of vasopressin (ADH) from the posterior pituitary

Question 335

Outline aldosterone

Answer 335

principal mineralocorticoid - Acts on principal cells of collecting ducts * Increases Na+ reabsorption in exchange for K+ * It affects BP by regulating the amount of Na+ that is reabsorbed in the Distal convoluted tubule through altering expression of ENac channels

Question 336

Oultine ADH/vasopressin

Answer 336

* affects BP by causing release of aquaporin (Aq2) channels into the membrane of principle cells (in collecting duct) * Causes increased water retention

Question 337

Common causes of chronic renal failure

Answer 337

- high blood pressure (strain on small blood vessels) - diabetes (too much glucose can damage small filters) - high cholesterol (build up fatty deposits in vessels of kidneys) - infection - glomerulonephritis (kidney inflammation) - polycystic kidney disease (growths in kidneys) - blockages in urine flow (e.g. kidney stones, enlarged prostate)

Question 338

Major complications of chronic renal failure (CRF)

Answer 338

- Fluid retention - Hyperkalaemia - Cardiovascular disease - Weak bones and increased risk of bone fractures

Question 339

Outline fluid retention as a complication of CRF

Answer 339

Can lead to swelling in arms and legs, high blood pressure, or fluid in your lungs (= pulmonary oedema) This is because kidneys remove excess fluid from the body, so with chronic renal failure there can be too much fluid in the blood which can then build up in the tissues!

Question 340

Outline hyperkalaemia as a response to complications of CRF

Answer 340

Extra, unused potassium is usually removed from the blood by the kidneys. * Chronic renal failure can lead to too little or too much potassium in the blood. Too little potassium can make you weak, experience palpitations. Too much potassium can also make you feel weak, give you problems breathing, pain in your chest, nausea, heart problems

Question 341

Outline cardiovascular disease as a complication of CRF

Answer 341

* kidney helps regulate blood pressure with the renin-angiotensin system * With chronic renal failure there is high blood pressure which can lead to heart attacks or strokes.

Question 342

Outline weak bones and increased risk of bone fractures as a complication of CRF

Answer 342

* kidneys maintain bone health by regulating the amounts of calcium and phosphorous. If you have chronic renal failure, you may have too much phosphorous in your blood (hyperphosphatemia) which would pull calcium from your bones making them weak. * kidneys activate vitamin D so that it can be used in the bone. BUT with chronic renal failure less/no vitamin D will be activated.

Question 343

Outline the indifferent stage

Answer 343

first stage of gonadal development - gonads begin as genital ridges (pair of longitudinal ridges derived from intermediate mesoderm & overlying epithelium)

Question 344

Genital development in the 4th week

Answer 344

Germ cells migrate from endoderm lining of yolk sac via dorsal mesentery of hindgut

Question 345

Genitalia development in 6th week

Answer 345

Germ cells reach genital ridges Simultaneously, epithelium of genital ridges proliferate & penetrates intermediate mesoderm to form primitive sex cords → combination of germ cells & primitive sex cords form indifferent gonad

Question 346

Development of ovaries

Answer 346

- no Y chromosome is present so no SRY gene to influence development & without it, primitive sex cords degenerate and don’t form testis cords - epithelium of gonad continues to proliferate, producing cortical cords 3rd month → these break up into clusters, surrounding each oogonium (germ cell) with layer of epithelial follicular cells – forms primordial follicle

Question 347

Embryological genital ducts -> internal genitalia

Answer 347

- all embryos have 2 pairs of ducts, ending at cloaca → mesonephric (Wolffian) ducts & Paramesonephric (Mullerian) ducts No Leydig cells to produce testosterone & in its absence, mesonephric ducts degenerate - absence of anti mullerian hormone allows for paranephric duct development (has 3 parts) The 2 Mullerian ducts fuse to form the broad ligament - This divides the pelvic cavity into the utero-rectal pouch and the utero-vesicle pouch

Question 348

What do the 3 parts of the paramesonephric duct become?

Answer 348

cranial: becomes fallopian tubes horizontal: becomes fallopian tubes caudal: fuses to form uterus, cervix & upper 1/3 of vagina

Question 349

What forms the lower 2/3 of the vagina?

Answer 349

Sinovaginal bulbs

Question 350

Internal genitalia development by the 5th month

Answer 350

By 5th month the vaginal outgrowth is entirely canalised The lumen on the vagina remains separated from the urogenital sinus by a thin tissue plate → hymen

Question 351

Outline development of external genitalia

Answer 351

Oestrogens responsible for this - genital tubercle elongates slightly to form clitoris - urethral folds form labia minora - genital swellings form labia majora - urogenital groove remains open, forming vestibule into which vagina & urethra open to

Question 352

Adult female internal reproductive organs

Answer 352

Vagina, uterus, fallopian tubes, cervix, and ovary.

Question 353

Adult female external structures of the reproductive tract

Answer 353

Mons pubis, pudendal cleft, labia majora and minora, vulva, Bartholin’s gland, and the clitoris

Question 354

Main parts of the reproductive system

Answer 354

- uterus: hosts the developing fetus, produces vaginal and uterine secretions, and passes the anatomically male sperm through to the fallopian tubes - ovaries: produce the anatomically female egg cells.

Question 355

Corpus luteum

Answer 355

A corpus luteum is a mass of cells that forms in an ovary and is responsible for the production of the hormone progesterone during early pregnancy. The role of the corpus luteum depends on whether or not fertilization occurs.