Human phys y2 s1 Flashcards

Question

Why does 90% of the oxygenated blood a foetus recieves from the placenta bypass the lungs?

Answer 1

Hard work to get blood into lungs as alveoli contain low o2 amniotic fluid that makes them constrict (hypoxic pulmonary vasoconstriction)

Answer 2

Links foetus and placenta, has two umbilical arteries: one for oxygenated blood, other for deoxygenated blood and waste

Answer 3

Oxygenated blood from placenta --> umbilical vein --> inferior vena cava --> right atrium --> left atrium (via foramen ovale) --> left ventricle (via mitral valve) --> aorta --> blood to body

Answer 4

Blood enters foetal heart via superior vena cava --> partially mixes with oxygenated blood from placenta --> right ventricle (tricuspid valve) --> mostly bypasses lungs --> ductus arteriosus --> descending placenta aorta

Answer 5

One-way valve that links right and left foetal atria and opens when the pressure is greater in the right atrium as the lungs are not functional (pressure in pulmonary > systematic circulation)

Answer 6

Links pulmonary artery with aorta, allows deoxygenated blood to enter descending aorta and leave via umblilical arteries

Answer 7

The formamen ovale closes and the baby takes its first breath, clearing the alveoli fluid, reducing pulmonary pressure and increasing systemic blood pressure AND the foramen ovale fuses closed to form the septum

Answer 8

- There is an initial constriction due to increase in arterial pO2, a drop in circulating prostaglandins and a drop in ductus blood pressure which causes smooth muscle cell death due to hypoxia (scar forms) - Functional closure is 18-24 hours after birth - Full anatomical occlusion is over days or weeks

Answer 9

Cyanosis (blue tinge of skin due to low O2) Ultrasound

Answer 10

Genetic conditions, maternal type I diabetes, foetal alcohol syndrom, rubella, flu, some medications, organic solvent exposure

Answer 11

A hole between atria or ventricles that causes blood mixing which increases the pressure of the blood entering the lungs = pulmonary hypertension Symptoms = breathlessness, tiredness when feeding, poor weight gain, heart murmur, chest infections and high blood pressure Treated via keyhole surgery

Answer 12

Ductus arteriosus remains open after birth which keeps aorta and pulmonary artery connected (abnormal blood flow) which causes pulmonary hypertension and strain on the heart and increases risk of lung and heart infection/damage Symptoms = breathlessness, heart murmur, sweating, rapid heart rate, poor feeding/weight gain Treated with prostaglandin inhibitors to stimulate closure OR surgical closure

Answer 13

Part of aorta not forming correctly normally near the ductus arteriosus where the arteries branch to take blood to head and arms (further narrowing can occur at birth when ductus arteriosus closes Symptoms are dizziness, fainting, breathlessness, sweating, pounding headache, chest pain and nosebleeds due to high blood pressure in upper body Treatments = removing narrowed section and reconnecting OR inserting catheter into aorta to widen with a balloon OR high blood pressure can be controlled through lifestyle

Answer 14

- Narrower than normal so less blood reaches lungs from right ventricle so ventricle works harder = right ventricular hypertrophy (wall thickening) Heart murmur, tiredness, breathlessness, fainting, chest pains, cyanosis Balloon valvuloplasty = thin tube with balloon inserted in groin which is threaded to narrowed heart valve and balloon inflates to stretch valve open OR surgery

Answer 15

- Mitral valve (between left ventricle and atrium) is narrowed which reduces blood flow and blood collects in left atrium and back flow into lungs occurs = heart weakening Tiredness, breathlessness, fatigue, irregular heartbeats, heart murmur, dizziness, chest pain, coughing up blood Balloon valvuloplasty OR open-heart surgery to replace/repair

Answer 16

Pulmonary and aortic valves and their respective arteries have swapped positions so the pulmonary artery is on the right and the aorta on the left which means oxygenated blood goes to the lungs and low oxygen blood is in circulation Cyanosis, pounding heart, weak pulse, breathlessness, poor feeding Surgical switching of vessels in first month of birth OR prostaglandin injection so the ductus arteriosus doesn't close and blood mixes

Answer 17

Four problems: 1. Ventricular septal defect 2. Pulmonary stenosis 3. Right ventricular hypertrophy 4. Overriding aorta (enlarged aortic valve, blood received from both ventricles) Cyanosis (can occur in tet spells when baby cries or feeds), endocarditis (increased risk of heart infection), irregular heart rhythm, dizziness, fainting, seizures, delayed growth Treatment must be surgery soon after birth whereby pulmonary valve is widened/replaced, passage to pulmonary artery widened, VSD patched and repaired

Answer 18

Atherosclerosis and aneurysms

Answer 19

Thickening of artery walls with fat and cellular matter that restricts blood flow and eventually causes rupture and even occlusion that prevents blood flow = hypoxia

Answer 20

1. Intima = lines blood vessel lumen, made of endothelial cells and connective tissue 2. Media = smooth muscle, matrix proteins, provides strength and elasticity and allows expansion 3. Adventitial layer = outer layer, fibrous connective tissue

Answer 21

1. Normal artery has a large open lumen 2. Fatty streak develops during childhood (reversible) but does not protrude lumen 3. This can develop into stable plaque that protrudes and restricts blood flow, fibrous cap of smooth muscle and extracellular matrix forms to increase tensile strength 4. Stable plaques can become unstable (larger lipid pool, thinner fibrous cap) 5. This can rupture, exposes underlying collagen and lipid core that is highly thrombogenic, thrombus occurs, blood vessel occluded = hypoxia 6. The plaque can also heal and leave a larger plaque = further narrowing

Answer 22

Smooth muscle cells in intima proliferate and produce extracellular matrix molecules

Answer 23

1. T cell mediators weakening smooth muscle cells' ability to synthesise collagen 2. Activated macrophages produce matrix metalloproteinases to break down collagen 3. Smooth muscle cell apoptosis and macrophage death causes debris = lipid rich necrotic core that creates unstable plaque

Answer 24

Blockage of coronary arteries that causes angina (chest pain) and sometimes myocaridal infarction if heart muscle becomes ischaemic

Answer 25

Angina (low blood flow to heart), myocardial infarction (if blood flow is occluded), aching, tightness, pain in upper body, sweating

Answer 26

1. Angiography - catheter inserted in groin, threaded to coronary artery, dye injected, x-ray shows narrowing 2. Blood tests - heart muscle damage during heart attack releases substances like troponin 3. ECG changes - during a heart attack it can differentiate between complete occlusion and a milder form called non-STEMI (not occluded)

Answer 27

- Blood thinning meds like aspirin - Surgery - Coronary angioplasty and stent replacement (balloon opens artery, stent remains to hold it open, drug eluting stents can increase patency) - Coronary artery bypass graft (blood vessel taken from elsewhere in the body and attached above and below artery where it is narrowed or blocked)

Answer 28

When carotid or cerebral arteries are occluded

Answer 29

Face drooping on one side, weakness in one arm, slurred speech, unable to speak, severe headache, difficulty swallowing, blurred vision, dizziness, confusion

Answer 30

1. Brain scan - dark areas = low O2 (must be done within the hour) 2. Swallow test = observed swallowing as they may inhale food or drink which can cause pneumonia 3. Carotid ultrasound = shows narrowing or blockages of carotid arteries (must occur within 48 hrs)

Answer 31

Short term = thrombolytic drugs to break down blood clots, throbectomy to remove thrombus, carotid endartectomy (neck incision to remove fatty deposits) Long term = medication combination (anti-platelets, anti-coagulants, anti-hypertensive meds and cholesterol reduction in diet)

Answer 32

Atherosclerosis in peripheral arteries that causes ischaemia in limbs

Answer 33

Hardening and obstruction of blood vessels causing lack of blood flow to legs and feet

Answer 34

Critical limb ischaemia (hypoxic = ulcers, unhealing wounds and gangrene), intermittent leg cramp during exercise (claudication)

Answer 35

Stethoscope identifies weak/absent pulse below narrowed artery, whooshing sounds suggest poor wound healing, ankle-brachial index compares blood pressure in ankle and arm, ultrasound or angiography shows blood flow and diagnoses affected arteries

Answer 36

Lifestyle changes - exercise, smoking cessation, weight loss, better diet Surgery e.g. angioplasty, bypass grafting, amputation (for limb ischaemia)

Answer 37

Localised, blood-filled dilation of a blood vessel caused by disease or weakening of the vessel wall that occur in specific locations in the vasculature (most are abdominal aorta or brain) Vessel wall weakening eventually causes rupture that causes major internal bleeding

Answer 38

1. Inflammation -- many inflammatory cells are in aneurysmal tissue, cytokine production by immune cells and cells native to the vessel wall cause inflammatory responses 2. Proteolysis = excessive reactive oxygen species from things like smoking activate matrix metalloproteinases (MMPs) that break down the extracellular matrix and elastin and collagen to weaken vessel wall 3. Smooth muscle cell apoptosis = loss of structural integrity in vessels, thinning and weakening too

Answer 39

Sudden, severe abdominal pain, dizziness, sweaty, pale, clammy skin, fast heartbeat, shortness of breath, fainting (all at the point of rupture)

Answer 40

Abdominal ultrasound

Answer 41

1. Small (<5.5cm) dilation = 3-6 monthly scans to see if it is growing, lifestyle changes 2. Large (>5.5cm) dilation = surgical intervention, graft inserted by endovascular surgery (in groin, guided to aneruysm to strengthen vessel and prevent rupture) OR open surgery (graft placed directly)

Answer 42

45% of the blood, composed of RBCs

Answer 43

1% of blood, made up of platelets and WBCs

Answer 44

Prevent use of oxygen so more O2 is delivered to tissues

Answer 45

A polypeptide with 2 alpha and beta chains, and a haem group attached to globins, it is red when it is carrying O2 and blue when it is not, combines with O2 to form oxyhaemaglobin reversibly

Answer 46

- Transport to lungs - Buffers ionised carbonic acid in blood - Causes carbon monoxide poisoning (occupies O2 binding sites) - Acts as a vasodilator - binds to sulfur in haemaglobin to form SNO which is then released into tissues where it dilates arterioles to allow O2 rich blood to pass round and it stabilises blood pressure

Answer 47

Erythrocytes express agglutinogens which determine it, all the blood types express the H gene: A = A antigen expressed B = B antigen expressed AB = Both antigens O = Neither antigens so H antigen persists

Answer 48

It encodes fucose transferase and adds a terminal fucose which forms the H antigen if the transferases in A and B are not present

Answer 49

They differ in their terminal sugar added by the transferase enzymes - A express second transferase that adds acetylgalactosamine - B express transferase that add galactose

Answer 50

No. There are smaller groups such as the Rhesus factor

Answer 51

+ means you have the antigen and are Rhesus protein positive, - means you only have the antigen

Answer 52

Yes and they are bi- or multi- in most cases

Answer 53

1. Polymorphogranulocytes/ myeloid cells (multi-nucleated, nuclei segmented into lobes, have many granules in cytoplasm) 2. Mononuclear agranulocytes (one large and non-segmented nucleus, no granules)

Answer 54

Secretory vesicles that contain cytotoxic molecules (enzymes and antimicrobial peptides) that destroy foreign cells

Answer 55

Basophils, neutrophils, Eosinophils

Answer 56

- Basic dyes such as methylene blue dye - Granules - Bi or tri-lobed

Answer 57

- No preference, neutral, remain pale-pink - Multi-lobed

Answer 58

- Granules take up eosin stain to be bright red/pink - Bi

Answer 59

- Acidic dyes like eosin stain basic components like cytoplasm - Basic dyes like methylene blue stain acid components like nucleus

Answer 60

1. Monocytes - large, oval/crescent shaped nucleus, circulate briefly then reside in tissue, mature into macrophages 2. Lymphocytes - small, large spherical nucleus, are either T or B cells

Answer 61

1. Histamine for hypersensitivity responses, causes vasodilation, increases blood flow to injured tissue and blood vessel permeability, allows neutrophils and clotting proteins to get to connective tissue 2. Heparin = anticoagulant, removes fat particles in blood, inhibits blood clotting, attracts WBCs to area

Answer 62

- The first line of defence against bacterial infections - Attracted towards bacteria by chemotactic factors released by damaged tissue/antibodies attached to antigens on surface of microorganism and then they engulf bacteria by endocytosis or phagocytosis and destroy them by releasing granule contents - Have limited protein synthesis machinery so cannot replenish active enzymes

Answer 63

- Defend against parasitic infection, role in allergic responses, inflammation by amplifying it through activating synthesis of chemical mediators - The cytotoxic molecules can destroy healthy cells

Answer 64

Spend 3 days in circulation and then mature in tissues into macrophages which do phagocytosis of bacteria and then act as antigen presenting cells that present components of bacteria to lymphocytes to amplify immune response

Answer 65

- Recognise self vs non-self antigens presented by APCs 1. B-lymphocytes 2. T-lymphocytes

Answer 66

Produce many antibodies to neutralise a pathogen or they tag it for destruction by cells like macrophages

Answer 67

Can respond as Helper T-cells to produce cytokines to direct immune system OR Cytotoxic T-cells that release cytotoxic proteins that destroy pathogen or pathogen-infected cells They also produce memory cells

Answer 68

Coagulation and haemostasis

Answer 69

Fragments of megakaryocytes found in bone-marrow bound cells, they are detached anucleate vesicles with cytosolic enzyme systems that enables them to have a secretory function

Answer 70

They have a high conc of actin and myosin so they can contract and be motile

Answer 71

1. Vessel injury exposes collagen and thromboplastin that activates platelets and recruits them for plug formation (primary haemostasis) 2. Vasoconstrictors released by platelets = smooth muscle contracts 3. Collagen and thromboplastin activate clotting cascade = thrombin activation 4. Thrombin catalyses conversion of circulating soluble fibrinogen to insoluble fibrin monomers 5. Fibrin monomers polymerise, cross-link and accumulate with platelets into a dense and tight aggregate (clot) (secondary haemostasis)

Answer 72

Acellular fluid component of blood containing ions, inorganic and organic molecules (5% of body weight)

Answer 73

1. Albumin = contributes to osmotic pressure and it exerts osmotic force across capillary wall as they are impermeable to plasma proteins so water is pulled across blood -- transports bilirubin, bile salts and penicillin 2. Globulins - there are many types = 1. Gamma globulins (immunoglobulins) are antibodies 2. Alpha and beta globulins are transport proteins and have a role in blood clotting 3. Some inactive precursor proteins 3. Fibrinogens 4. Others that are less abundant

Answer 74

From bone marrow where haematopoiesis occurs (haematopoietic stem cell --> committed stem cell or progenitor cell)

Answer 75

Erythropoietin from the kidney

Answer 76

Multiple cytokines depending on the action of granulocyte and macrophage colony stimulating factor (GM-CSF) and thrombopoietin

Answer 77

Cytokines in different development stages -- most important = interleukin-3, granulocyte colony stimulating factor and GM-CSF

Answer 78

GM-CSF then macrophage colony stimulating factor (G-CSF)

Answer 79

GM-CSF and interleukin-5

Answer 80

Interleukin-3 and 4

Answer 81

B complete most of it in bone marrow T are generated in thymus from precursor cells that migrate from bone marrow

Answer 82

Anaemia (no. of erythrocytes and o2-carrying capacity is not sufficient for body's physiological needs)

Answer 83

Iron deficiency, nutritional deficiencies, acute and chronic inflammation, parasitic infection, inherited/acquired disorders affecting haemoglobin synthesis/RBC production and survival

Answer 84

Affects number, size and colour

Answer 85

Enlarges erythrocytes (defective maturation) to become reticulocytes --- causes vitamin deficiencies

Answer 86

Shrinks erythrocytes due to abnormal haemoglobin production

Answer 87

Thalassemia

Answer 88

Reduced erythrocytes due to normal factors like cancer, viruses, chronic kidney disease, RBC destruction

Answer 89

Sickle cell anaemia, autoimmune haemolytic anaemia

Answer 90

When the body produces auto-antibodies against erythrocyte antigens so immune system targets them --- these antibody-opsonised erythrocytes are phagocytosed by macrophages in the spleen which damages the membrane and cases haemolysis = spherical erythrocytes and then the complement system is activated and lysis occurs

Answer 91

The auto-antibodies are directed against high incidence antigens on all erythrocytes

Answer 92

Fatigue, dizziness, dysponea on exertion (due to low O2), jaundice, tea-coloured urine (increased bilirubin in plasma = increased urobilin in urine)

Answer 93

Direct Coombs test - Uses anti-human antibodies that bind to human antibodies - If disease is present there will be an agglutination in the bottom of the tube as the auto-antibodies on the erythrocytes' surface are tagged

Answer 94

1. Immunosuppressive therapy using corticosteroids that suppress immune system (prevents RBC destruction) 2. Plasmapheresis -- filters blood, removes harmful antibodies

Answer 95

RBCs become sickle shaped and do not flow well due to sticky and inflexible nature and they get stuck at branch points and in small blood vessels which can block blood flow, stopping oxygen-rich blood movement = sickle cell crisis and organ damage

Answer 96

Point mutation in gene encoding beta haemoglobin -- changes glutamic acid to valine = haemoglobin changes shape and clumps and causes rigid, non-liquid protein strands to form in RBCs in hypoxic conditions = sickle shape

Answer 97

The cells block the spleen filter (also causes spleen damage)

Answer 98

Blood test for haemoglobin S (defective)

Answer 99

Anaemia, fatigue, frequent infection, sickle cell crisis

Answer 100

Blood transfusion, bone marrow transplant

Answer 101

Cells rupture prematurely and cannot host parasite

Answer 102

Mutations cause unpaired globin polypeptide chains = aggregates and precipitate = RBC damage and lysis

Answer 103

Mutations or deletions in haemoglobin gene (either alpha or beta) = insufficient haemoglobin production = anaemia

Answer 104

Anaemia, fatigue, palpitations, shortness of breath, bone distortion, hepatosplenomegaly (enlarged liver and spleen)

Answer 105

Extramedullary heamatopoiesis to produce more erythrocytes

Answer 106

Blood or genetic testing

Answer 107

Blood transfusion, folic acid supplements (promotes erythropoiesis), bone marrow in severe child cases

Answer 108

Iron chelation to remove excess iron build up

Answer 109

A leukocytic disease that is an autosomal blood disorder caused by mutations in the ELANE gene (encodes neutrophil elastase) which causes neutrophil maturation failure

Answer 110

Normally neutrophil elastase inhibits neutrophil differentiation but when mutated it is excessively inhibitory so there are longer trough periods of decrease to 0 every 3 weeks and then for up to 5 days it rebounds

Answer 111

Frequent infections, fever, ulcers of mucous membranes in mouth

Answer 112

Blood cell count, bone marrow biopsy

Answer 113

Stimulation of neutrophil production e.g. granulocyte colony-stimulating factor treatment or haematopoietic stem cell transplant

Answer 114

Increased number of leukocytes

Answer 115

1. Neutrophilia = infections and inflammation 2. Lymphocytosis = viral infections and leukaemia 3. Monocytosis = certain infections and cancer 4. Eosinophilia = allaergies and parasites 5. Basophilia = leukaemia

Answer 116

Blood cell counting

Answer 117

1. Antibiotics for infection 2. Anti-inflammatories for inflammation 3. Antihistamine/inhaler for allergic reaction 4. Chemotherapy/radiation/stem cell transplant for leukaemia 5. Medication changes if a drug is causing it 6. Treatment for causes of stress and anxiety

Answer 118

Cancer of WBCs due to DNA damage/mutation during haematopoiesis - starts in blood-forming tissue to over-produce abnormal, immature WBCs

Answer 119

1. Acute myeloid leukaemia 2. Chronic myeloid leukaemia

Answer 120

Abnormal differentiation of myeloid cells, accumulation of immature myeloid precursor cells in bone marrow and peripheral blood which causes differentiated RBCs, platelets and WBC shortage

Answer 121

Splenomegaly due to more differentiated myeloid cells in blood

Answer 122

Anaemia, weakness, tiredness, shortness of breath, light-headed, palpitations, frequent infection, fever, malaise, sweating, bleeding and bruising, heavy periods, nosebleeds, bleeding gums

Answer 123

Full blood count, genetic testing, X-rays, scans, lumbar puncture, bone marrow biopsy

Answer 124

1. Glycoprotein spikes on HIV virions recognise and bind CD4 reeptors and CCR5 coreceptor on surface 2. HIV endocytosed 3. HIV injects viral enzymes (including transcriptase and integrase) and RNA 4. Reverse transcriptase transcribes single stranded RNA genome of HIV into cDNA 5. Reverse transcriptase uses host cell's DNA polymerase to create double stranded viral DNA 6. Viral integrase integrates viral DNA into host cell genome so it produces viral mRNA and protein 7. Protein forms viral particles that bud off of T cell and infect other CD4+ T cells

Answer 125

Infects and destroys CD4+ helper T cells that normally produce cytokines to activate immune cells

Answer 126

Chronic inflammation that inhibits haematopoiesis which slows CD4+ cell production Thymus can become infected which inhibits T-cell maturation

Answer 127

Acquired immune deficiency syndrome (AIDS) as cell mediated immunity can be fully lost eventually

Answer 128

Short flu-like symptoms in early weeks, then asymptomatic for years but immune damage is occurring

Answer 129

Blood, saliva or blood spot tests

Answer 130

Post-exposure prophylaxis if patient was at risk, antiretroviral meds to prevent viral replication

Answer 131

An X-linked recessive platelet disorder caused by mutation and deficiency in clotting factors = clotting is defective

Answer 132

Convert prothrombin to thrombin and fibrinogen to fibrin

Answer 133

A is factor VIII deficiency, B is factor IX deficiency

Answer 134

Internal/external bleeding after injury, spontaneous bleeding into joints (chronic pain and disability)

Answer 135

Blood test, amniocentesis prenatally if family history

Answer 136

No long term cure but replacement therapy for clotting factors or gene therapy works

Answer 137

Functional copy of clotting factor is packaged in a recombinant adeno-associated viral vector that is then taken up into liver cells and expressed

Answer 138

1. Serosa outer (mesothelium, single squamous epithelium) 2. Fibrous inner (fibroplasts like collagen)

Answer 139

1. 25% of cardiac output from hepatic artery 2. Portal vein -- from intestine, left gastric vein (stomach and oesophagus) and superior mesenteric (rectum)

Answer 140

1. Parenchymal (hepatocytes) 2. Non-parenchymal

Answer 141

Periportal, intermediate and perivenous

Answer 142

Endothelial, kupffer, lipocytes, biliary epithelial (cholangiocytes)

Answer 143

Liver lobules that have a portal triad on each point of the hexagon shaped lobule

Answer 144

Branch of hepatic artery, branch of portal vein and a bile duct

Answer 145

Drains at sinusoid Has lower O2 but more waste products

Answer 146

Mixing of blood from hepatic artery and portal vein

Answer 147

Porto-venous axix

Answer 148

Periportal --> intermediate --> perivenous

Answer 149

Periportal Perivenous

Answer 150

More o2 in periportal means there are more enzymes for oxidative reactions

Answer 151

Different reactions occur in each hepatocyte type

Answer 152

Apical (upper) and basolateral (bottom near endothelial cells of sinusoid)

Answer 153

Via apical membrane

Answer 154

Bile produced by liver --> enters gall bladder via bile duct --> when gall bladder is full the bile empties into small intestine and emulsifies fats --> reabsorbed into portal vein into liver

Answer 155

1. Metabolic (glucose production, gluconeogenesis, store glucose in form of glycogen, makes cholesterol) 2. Protein synthesis (plasma proteins, clotting factors) 3. Solubilsation and transport (bile synthesis, transferrin) 4. Protection (detoxification phases i and iii, urea cycle, clearance of bacteria by kupffer cells)

Answer 156

Partial glycolysis reversal with non-equilibrium reactions that must be separate and distinct

Answer 157

1. Glucose --> G6P (f = glucokinase, r = glucose-6-phosphatase) 2. Fructose-6-phosphate --> fructose-1,6-diphosphate (f = PFK, r = phosphatase) 3. PEP --> pyruvate (forward), pyruvate --> oxaloacetate --> PEP (reverse) Enzymes = pyruvate carboxylase, PEPCK

Answer 158

Binding/carrier for hormones and fatty acids AND osmoregulation

Answer 159

- Ceruloplasmin (up to 6) - Transferrin (2 at a time) - Transthyretin

Answer 160

Fe binds to form TFN-Fe which changes conformation which makes it a higher affinity for TFN receptors on cells so TFN-Fe enters internalised endocytic pathway which makes cell more acidic so complex disassociates and Fe is in the cell and TFN via blood and TFN receptor goes back to cell surface

Answer 161

Naturally produced substances that require metabolism to regulate their levels or facilitate their excretion (such as bilirubin)

Answer 162

Phase I = oxidative and reductive reactions by addin o2 to functional groups Phase II = covalent attachment of endobiotic drugs that are water soluble

Answer 163

Bilirubin gluconuride (catalysed by UDP-glucuronosyltransferase) by adding water soluble glucuronic acid

Answer 164

It can cause hepatic encephalopathy

Answer 165

Urea cycle: 1. Converted to carbonyl phosphate (by carbonyl phosphate synthetase) 2. Then into citrulline with ornithine (by ornithine transcarboxylase) 3. Then aginosuccinate with aspartate (by arginosuccinate syntase) 4. Then arginine with fumarate (by arginosuccinate lyase) 5. Then ornithine (by arginine) RELEASING UREA

Answer 166

Reducing agent preventing oxidative damage

Answer 167

1. Reversible or irreversible 2. Acute or chronic

Answer 168

Mild (viral hepatitis) or severe fulminant hepatic failure that can require a transplant

Answer 169

It is progressive and can be caused by alcoholism that can result in cirrhosis that reduces liver function

Answer 170

Quiescent and can proliferate (not in severe damage)

Answer 171

Bio artificial liver that pumps blood through that is then detoxified

Answer 172

Loss of hepatocyte function that results in difficulty regulating blood glucose

Answer 173

Increases liver blood pressure which causes back pressure, increased hepatocyte pressure

Answer 174

Store vitamin A and can produce ECM (containing fibrin, collagen and proteoglycans) in response to injury

Answer 175

ECM deposition narrows the sinusoid and causes higher blood pressure which results in backflow into the portal vein which increases venal pressure --- veins have thin walls so they bulge and form varices (can rupture)

Answer 176

Q = pi x p x r^4 / 8 x n x l (Q is flow, p is pressure, r is radius, n is a constant, l is length) !/r^4 is proportional to pressure

Answer 177

1. Metabolic = lowered glucose (hypoglycaemia), lipid accumulation in liver (hyperlipidaemia), protein metabolism changed so more NH3 releases and less urea produced 2. Solubilisation = bile acids not produced effectively = poor fat emulsification = lipids not absorbed = fatty faeces (steatorrhoea) 3. Detoxification = THIS PROCESS BEING DYSREGULATED CAUSES JAUNDICE phase ii involves glucuronidation involves bilirubin (from haemoglobin) being combined with water soluble UDP-glucuronic acid to form bilirubin glucuronide (catalysed by bilirubin UDP-glucuronosyl transferase)

Answer 178

Deficiency of UDP-glucuronosyl transferase meaning bilirubin cannot be broken down

Answer 179

Bile duct obstruction by gallstones or cancer

Answer 180

Ethanol can cause liver to produce more drug-metabolising enzymes which break down drugs such as warfarin quicker which reduces their effectiveness

Answer 181

Reduced albumin causes oncotic pressure dysregulation and water cannot enter vessels so fluid build up (ascites) occurs due to increased hydrostatic pressure Causes reduced coagulation too

Answer 182

Lactulose (causes osmotic diarrhoea to release it)

Answer 183

Altered hormone clearance causes lower androgen clearance (increases blood conc) which increases oestrogen via aromatisation (conversion) in periphery (increased breast tissue and testicular atrophy)

Answer 184

Terminal liver failure --- ammonia has crossed blood brain barrier (irreversible)

Answer 185

Portal hypertension

Answer 186

Hormonal disorders

Answer 187

Catecholamine hormones like epinephrine and norepinephrine

Answer 188

Steroid hormones

Answer 189

1. Glucocorticoids (cortisol and cortisone) that regulate carbs, fat and protein metabolism 2. Mineralocorticoids (aldosterone) that regulate Na and K balance 3. Sex steroids (androgens)

Answer 190

Hypercortisolaemia (raised cortisol)

Answer 191

Syndrome is the symptoms resulting from high cortisol Disease is a subtype of syndrome caused by an ACTH-producing pituitary tumour and chronic exposure to excessive levels of circulating glucocorticoids

Answer 192

Fibrous capsule

Answer 193

1. Zona Glomerulosa 2. Zona Fascilulata 3. Zona Reticularis

Answer 194

Mineralocorticoids like aldosterone

Answer 195

Glucocorticoids like cortisol and corticosterone, sex hormones like androgens/dehydroepiandrosterone

Answer 196

Cholesterol

Answer 197

Unbound but in the cytoplasm they are bound to corticosteroid binding globulin (CBG, also known as transcortin)

Answer 198

Basophilic cells secrete follicle stimulating hormone (FSH), leutinising hormone (LH), adenocorticotropic hormone (ACTH) and thyroid growth hormone (TSH) Acidophilic cells secrete growth hormone and prolactin

Answer 199

Oxytocin and vasopressin

Answer 200

Corticotropin releasing hormone (CRH) is produced in the hypothalamus and transported to the anterior pituitary and released to stimulate ACTH release which stimulates cortisol secretion from adrenal cortex -- cortisol feedsback and inhibits CRH and ACTH secretion (negative feedback) ACTH is said to be diurnal

Answer 201

Translocates into the nucleus where the complex acts as a transcription factor that regulates target gene expression via glucocorticoid response element (GRE) in promoter region

Answer 202

Catabolic effect that decreases glucose uptake, metabolism and protein synthesis but increases amino acid release

Answer 203

Lipolytic effect that stimulates lipolysis and increases free fatty acids and glycerol release

Answer 204

Synthetic effect that increases glycogen synthesis, gluconeogenesis and blood glucose

Answer 205

1. Suppression effect whereby circulating monocytes, lymphocytes, basophils and eosinophils are decreased 2. Anti-inflammatory effect whereby migration of neutrophils to site of injury is decreased

Answer 206

Iatrogenic = due to external factor like intake of oral corticosteroids Non-iatrogenic = disease

Answer 207

1. ACTH-dependent Cushing's 2. Ectopic ACTH syndrome 3. ACTH-independent Cushing's

Answer 208

ACTH-secreting pituitary adenoma (benign tumour of epithelial origin) that causes increased ACTH 68% of Cushing's cases and is common 20-40 year olds and more in women

Answer 209

ACTH secreting tumour in the lung (small cell carcinoma) or bronchial carcinoid tumour 15% if Cushing's, 40-60 year olds, more in men

Answer 210

Adrenocortical tumour that secretes excess cortisol (either adenoma or carcinoma) 17% of cases, 35-40 year olds, more in women

Answer 211

There is a loss of feedback inhibition due to increased ACTH secretion and a loss of cortisol sensitivity

Answer 212

Moon face, buffalo hump, thin extremeties, striae, diabetes mellitus, muscle wasting, fat trunk or abdomen, psychiatric effects

Answer 213

Headaches caused by pituitary tumour stretching dura Decreased peripheral vision as pituitary gland sits below optic chiasma (any swelling of adenoma will press on this and reduce vision)

Answer 214

Cortisol increases glucose synthesis (increased expression of G6P) in liver, decreases glucose uptake into fat and muscle, increased lipolysis (more fatty acids to be used instead of glucose for energy)

Answer 215

Decreased protein synthesis and increased protein catabolism

Answer 216

Central adiposity --- redistribution of body fat

Answer 217

It inhibits insulin-stimulated GLUT4 translocation

Answer 218

Striae (stretch marks), skin thinning (due to glucocorticoids inhibiting fibroplast proliferation and decreasing collagen synthesis), easy bruising as subcutaneous fat depots increase which thins the skin and ruptures subdermal tissues

Answer 219

Pituitary = transsphenoidal hypophysectomy and replacement therapy for hormones Adrenal = bilateral adrenalectomy and steroid replacement therapy

Answer 220

In via renal arteries and out via renal veins that carry it to the inferior vena cava

Answer 221

Maintains homeostasis of water, electrolytes and pH via filtration and reabsorption (excess removed in urine) and removes toxic waste products

Answer 222

Filter blood and transport filtrate to medullary pyramids and eventually bladder

Answer 223

1. Blood from renal artery enters aterioles then glomeruli capillaries and it is filtered to remove small molecules, ions and water 2. Filtrate enters renal tubules (weaves in and out of cortex and medulla) into proximal convoluted tubule (ions + small molecules reabsorbed) then narrow descending loop of Henle and then wide ascending 3. Into distal convoluted tubule and then collecting duct 4. Renal tubules link glomerulus to renal pelvis which links kidney to ureter and bladder

Answer 224

Contains renal corpuscles (glomerulus and bowmans capsule) -- causes intense stain, dense and containing round structures --- tubules fill most of the space (rings) and most are proximal

Answer 225

Many ring-like structures (cross sections of loop of henle and collecting ducts --- henle has a thinner and thicker loop, collecting ducts widest)

Answer 226

1. Filtration of blood plasma 2. Regulation of blood pressure 3. Regulation of erythropoiesis

Answer 227

1. Glomerular filtration 2. Tubular reabsorption 3. Tubular secretion

Answer 228

Blood enters glomerulus through afferent arteriole and water and small hydrophobic molecules leave the capillary through fenestrated endothelial cells that line the capillaries, the blood then leaves through efferent arteriole

Answer 229

Single layer of flattened cells surrounding the glomerulus

Answer 230

They are specialised endothelial cells that have extensions that wrap around capillaries to increase SA and increase filtration efficiency Also creates filtration barrier with fenestrated endothelium

Answer 231

1. Paracellularly = between tubular cells 2. Transcellularly = through tubular cells

Answer 232

Active transport, passive diffusion or osmosis

Answer 233

Bulk flow and is mediated by hydrostatic and osmotic force

Answer 234

They are lined with tall cuboidal cells with microvilli which create brush border for facilitated diffusion of glucose and amino acids

Answer 235

Increases SA for Na+ pumps

Answer 236

Descending = simple squamous with no microvilli or infolding and few mitochondria (no active transport) Ascending = simple cuboidal, no microvilli, extensive infolding of basal membrane

Answer 237

Lined with simple cuboidal epithelium and extensive infolding with many mitochondria

Answer 238

Lined with 2 types of simple columnar epithelial cells: 1. Principle cells (continue reabsorption and express aquaporins) 2. Intercalated cells (have microvilli, role in regulating acid-base balance of glomerular filtrate

Answer 239

Absorption into tubules from blood can occur as a secretory process if there is high concentrations of solutes and wastes in the blood in peritubular capillaries

Answer 240

Osmosis - high salt intake increases [Na+] = draws water out of blood vessels into surrounding tissues = increased intravascular fluid volume = increased cardiac output = increased peripheral resistance = increased blood pressure

Answer 241

Distal convoluted cells in macula dense detect blood [Na+] and fluid flow and regulate via renin-angiotensin system

Answer 242

1. Low fluid flow/[Na+] detected = juxtaglomerular cells secrete renin 2. Renin cleaves angiotensinogen to remove 10 amino acids = angiotensin i 3. Angiotensin i concerted to angiotensin ii by angiotensin converting enzyme 4. Angiotensin increases bp 5. Increase in bp detected by juxtaglomerular cells = renin release ceases

Answer 243

1. Vasoconstriction = increased peripheral resistance --> cardiac output and then bp 2. Alsodesterone release so Na uptake/reabsorption by nephrons increases to increase blood Na+ 3. Direct promoting of Na+/water reabsorption in distal convoluted tubules to increase blood volume (and bp) 4. ADH release from pituitary = aquaporin mobilisation = increased blood volume (and bp)

Answer 244

Kidney secretes erythropoietin in hypoxic conditions: -- hypoxia-inducible transcription factor 1 binds to enhancer region of erythropoietin gene = increased expression = release into blood where it binds to erythropoietin receptors on erythrocyte prgenitor cells = increased RBC production

Answer 245

Build-up of waste products and water in the blood and a lack of homeostasis of ions and small molecules

Answer 246

1. Drugs/medication being combined (nephron damage) 2. Inflammatory diseases like vasculitis or glomerulonephritin (nephron damage) 3. Tubular necrosis (due to factors like nephrotoxic drugs and ischaemia) = tubular epithelial cell death which slough off = blocked lumen of tubules 4. Urinary tract obstruction = increased pressure and slowed urine production = increased pressure and swelling = nephron damage

Answer 247

Damaged nephrons can be regenerated

Answer 248

Diabetes (glucose damages filtration units), hypertension (high bp causes damage), medication, repeated acute renal failure

Answer 249

Irreversible nephron loss = fewer nephrons = increased glomerular filtration pressure and hyperfiltration = fibrosis and scarring = further nephron damage

Answer 250

1. Uremia (nitrogen-containing waste product build up) 2. Increased hormone build-up (decreased metabolic clearance, changed feedback and secretion patterns) 3. Loss of normal kidney products 4. Reduced body temperature 5. Increased Na+, K+ and water in blood 6. Haematological abnormalities

Answer 251

1. Congestive heart failure (osmotic balance disrupted, increased blood volume and bp) 2. Oedema/ascites (water accumulated in peripheral tissues and abdominal cavity) 3. Hyponatemia (excessive water consumption lowers [Na+] = fatigue, muscle spasms and vomiting) 4. Hyperkalemia (increased K+ = fatal abnormal heart arythmias as K+ changes cardiomyocyte cell membrane polarisation so resting potential is closer to threshold which can cause ventricular fibrillation (uncoordinated contraction) and asystole

Answer 252

Anaemia, increased susceptibility to infections due to leukocyte suppression by uremic toxins, altered clotting parameters = increased bruising, blood loss in surgery, and risk of spontaneous haemorrhage

Answer 253

Blood tests: 1. Serum creatine test = creatinine levels show glomerular function and filtration rate as it is a waste product from muscle metabolism/protein digestion/metabolism (could also use albumin to creatine ratio) 2. Blood urea nitrogen test

Answer 254

Chest wall, respiratory muscles to alter thoracic cavity size, brain regions controlling muscles, and the pathways and nerves linking that

Answer 255

1. Upper airway (nasal passages and pharynx) 2. Conducting airway (trachea, bronchi, bronchioles, terminal bronchioles --- conduct inhaled air into lungs) 3. Alveolar/respiratory airway (respiratory bronchioles, alveolar ducts, alveolar sacs --- where gas exchange occurs)

Answer 256

Slightly smaller to make room for the heart

Answer 257

Pleura (tissue layer consisting of outer/parietal membrane and inner/visceral membrane -- difference is pleural cavity)

Answer 258

Thin layer of fluid that acts as a lubricant to allow lungs to slip smoothly as they expand and contract

Answer 259

Layer of mesothelium and a layer of underlying elastic fibrous connective tissue

Answer 260

1. Airway mucosa = layer of mucous/surfactant, an epithelial layer and a basement membrane 2. Lamina propria = loose connective tissue containing capillaries 3. Layer of smooth muscle cells (in trachea/bronchus/bronchioles) 4. Fibrocartilaginous layer (in trachea/some bronchioles)

Answer 261

Pseudostratified epithelium (looks stratified/layer but its just dense cells)

Answer 262

Innate immunity in airway

Answer 263

Progenitor cells in injury

Answer 264

Mucous secretion for lubrication and removal of particulate matter/pathogens via coughing

Answer 265

Removal of inhaled particles

Answer 266

Secrete surfactant proteins, defensins, peptides, proteases, reactive oxygen species, reactive nitrogen species = anti-microbials

Answer 267

Secrete chemokines and cytokines in infections

Answer 268

Layer of cartilage

Answer 269

1. Non-ciliated epithelial cells like club/clara cells 2. Ciliated cells

Answer 270

Secrete defence markers and act as progenitor cells post-injury

Answer 271

Gas exchange

Answer 272

Type 1 = thin, squamous, large cytoplasmic extensions, make up thin-walled layer of lining Type 2 = thicker, cuboidal, contain granules, produce and store surfactant (stored in lamella inclusion bodies)

Answer 273

Loose,open with many air pockets, close contact with pulmonary capillaries (only separated by their respective endothelium), connected by alveolar walls (contain network of connective tissue fibres called interstitium)

Answer 274

1. Inhalation and exhalation (pulmonary ventilation) 2. External respiration (gas exchange lungs and air) 3. Internal respiration (gas exchange blood and cells) 4. Phonation (air vibrating around vocal cords to create sound) 5. Olfaction (chemical sensation for smelling)

Answer 275

Inhalation = diaphragm moves down, intercostal muscles pull up, volume of chest increases, air in Exhalation = diaphragm relaxes and moves up, intercostal muscles relax and move down, reduced chest cavity, air forced out

Answer 276

Spirometry = graphic record of different volumes being combined to give total lung capacity

Answer 277

O2 poor blood enters lungs via pulmonary artery and divides into capillary network to alveoli --- CO2 enters alveolar space through type 1 epithelial cells and o2 leaves into blood and this goes to heart for circulation via pulmonary vein

Answer 278

Pathogen defence and reducing surface tension (allows alveolus expansion = increased SA)

Answer 279

1. Surfactant proteins 2. Phospholipids like DPPC to reduce surface tension

Answer 280

1. SP-A = activates macrophages, can induce uterine contractions 2. SP-B = organised into tubular network to reduce surface tension 3. SP-C = enhances phospholipid function to reduce surface tension 4. SP-D = role in pathogen defence

Answer 281

Surface tension allows liquids to acquire a small SA as the molecules of water at the surface are solely attracted sideways and downwards ---- inner alveoli surface contains alveolar fluid (water) and the molecules are attracted to one another so reducing it = increased SA

Answer 282

1. Reduces collapse of under-inflated alveoli (atelcatasis) 2. Provides more even distribution of ventilation amongst alveoli 3. Improves lung compliance 4. Infection protection

Answer 283

Lack surfactant so gas exchange is less efficient and blood o2 is lower Mechanical ventilation and antenatal corticosteroid administration to induce surfactant production by type 2 cells

Answer 284

Chronic bronchitis, emphysema, asthma (all cause progressive lung damage)

Answer 285

Reduced conducting airway diameter (fixed airway obstruction) that leads to increased resistance during ventilation and reduced air flow to the lungs

Answer 286

Increased secretions and inflammation, bronchial smooth muscle contraction, loss of supporting structures and airway collapse

Answer 287

Chronic cough, wheezing, frequent chest infection, breathlessness, fatigue, muscle wasting

Answer 288

Airway obstruction caused by mucous thickening and hypersecretion of mucous -- also causes crackling and wheezing

Answer 289

Hyperventilation to remove it (not in chronic bronchitis patients as they have a resistance to co2)

Answer 290

1. Inhalation of noxious particles = mucousal infllamation = increased wall thickness = narrow lumen 2. Blockage/narrowing of bronchioles = prevented efficient gas exchange = hypoxia and hypercapnia (co2 build-up) 3. Hypercapnia = respiratory acidosis (excess co2 reacts with water = carbonic acid\0 4. Alveolar hypoxia 5. Right sided heart failure 6. Fluid retention

Answer 291

Polycythaemia (increased RBC production), cyanosis, hypoxic pulmonary vasoconstriction (due to lack of o2), pulmonary hypertension, right-sided heart failure, fluid retention

Answer 292

O2 poor, co2 rich blood return to right atrium and exits via left and right pulmonary arteries Constriction of pulmonary blood vessels = hypertension = back flow to right side of heart = sustained backflow = increased workload = hypertrophy

Answer 293

Pulmonary hypertension reduced blood flow to left side of heart = lower left ventricular output = reduced cardiac output and blood volume = aldosterone release = water retention = peripheral oedema

Answer 294

Chronic bronchitis = visible cyanosis and peripheral oedema Emphysema = pink-tinged skin and barrel chest

Answer 295

Dyspnoea (difficulty breathing) and tachypnoea (rapid breathing)

Answer 296

Air trapping = diaphragm and intercostal muscles cannot support breathing alone

Answer 297

In response to increased alveolar co2 levels

Answer 298

Oxidants inhibit protease inhibitors which activates protease and elastase Loss of elastin fibres prevents alveolar recoil and causes airway collapse, hypercapnia and hyperventilation

Answer 299

Connective tissue between alveoli degrades = larger air sacs = lower SA

Answer 300

Air trapping = chronically inflated lungs = reduced expiratory reserve volume and vital capacity (but residual volume is higher)

Answer 301

Physiological dead space

Answer 302

Connects CNS to limbs and organs

Answer 303

1. Somatic nervous system 2. Visceral motor system

Answer 304

Delivers voluntary control of body movements via skeletal muscles

Answer 305

Controlled by autonomic nervous system (involuntary control of smooth muscle and glands)

Answer 306

Muscles that contract in response to nerve innervation Visceral = smooth muscle Somatic = striated skeletal muscle

Answer 307

1. Brainstem and spinal cord have local circuit neurons that synapse at the axon with upper motor neurons 2. Upper motor neurons make synaptic connections with the relevant lower motor neurons 3. Lower motor neurons transmit information to skeletal muscles (alpha motor neurons directly innervate striated skeletal muscle fibres and can innervate many at once (multiple synapses formed = end plates)

Answer 308

A neuron and all the muscle fibres it innervates

Answer 309

Synthesised at nerve terminals of alpha motor neurons (have many mitochondria for this) from acetyl CoA and choline (catalysed by choline acetyl transferase) and then transported and stored in synaptic vesicles

Answer 310

Folds and indentations to increase the SA

Answer 311

Nicotinic acetylcholine receptors that are activated by Na+ influx into muscle fibre which causes depolarisation (end plate potential) = muscle action potential reached = contraction

Answer 312

Hydrolysed to acetyl choline esterase and choline is recycled

Answer 313

Ligand gated ion channels with 5 subunits that form a cylinder and 2 ACh binding sites (at alpha-gamma and alpha-delta interfaces)

Answer 314

Conformational change via twisting mechanism = ion channel opening = Na+ entry into muscle cell = end-plate potential = nAChR closure = ACh unbinds and is degraded

Answer 315

Once end-plate potential reaches -50mV the Na+ channels on muscle cell membrane open = action potential propagated along muscle membrane down the t tubule causing contraction

Answer 316

An autoimmune disease that causes transient or persistent weakness/abnormal fatigue of skeletal muscles or be limited to ocular muscles (droopy eyelids)

Answer 317

Postsynaptic membrane (loss of folds/indentations = fewer nAChRs) and there are autoantibodies against nAChR or MuSK

Answer 318

Action potential stimulation -- will show decreasing amplitude as they cannot sustain a muscle contraction

Answer 319

1. Inhibition of nAChR 2. Antigenic modulation 3. Complement mechanisms

Answer 320

Blocks ACh binding site or ion channel will prevent end-plate potential, action potential and muscle contraction generation --- antibodies bind to loop called main immunogenic region (MIR) in alpha subunit (not on ACh binding site)

Answer 321

Antibodies can cross-link 2 antigen molecules = cellular signals for accelerated endocytosis and degradation Autobodies can cross-link 2 nAChRs = internalisation and degradation

Answer 322

Autoimmune response caused membrane attack complex (MAC) to destroy post-synaptic membrane which causes loss of junctional folds = a loss of action potential ----- occurs as antigen-antibody complex is bound by C1q that recruits C1 complex which cleaves C2 and C4 = C4bC2a (C3 convertase) ---- a cascade occurs = MAC production = pores in cell membrane = lysis and destruction

Answer 323

Autoantibodies against other neuromuscular junction proteins associated with nAChRs like MuSK (muscle specific kinase) and low density of lipoprotein receptor related protein 4 (Lrp4) and agrin

Answer 324

1. Agrin is secreted by motor nerve terminal and binds to Lrp4 2. MuSK dimerises and autophosphorylates itself 3. Associated proteins of MuSK pathway (e.g. nAChR beta subunit) are also phosphorylated 4. Rapsyn is recruited to phosphorylate nAChRs to stabilise postsynaptic clusters of nAChRs

Answer 325

Block assembly of agrin-Lrp4-MuSK complex = MuSK autophosphorylation prevented = nAChR phosphorylation = rapsyn recruited = cytoskeleton tethering

Answer 326

Disassembly of postsynaptic AChR clusters = inefficient muscle stimulation

Answer 327

1. Routine maintenance = acetylcholinesterase inhibitors to boost ACh levels and low dose corticosteroids to inhibit immune cells 2. Acute crises = plasmapheresis to remove lgG or intravenous immunoglobulin to stop complement cascade by binding to C1q 3. Thymectomy (removal of thymus to stop T cell production) in severe cases 4. B cell proliferation inhibitor = monoclonal antibody blocks it and reduces autoantibody production 5. Complement cascade inhibitor = monoclonal antibody that binds C5 and reduces MAC 6. Neonatal Fc receptor inhibitor = reduces circulating autoantibodies by reducing circulating lgG

Answer 328

Under sarcolemma (multinucleate)

Answer 329

Where 2 actin strands connect

Answer 330

Thick myosin ii filaments

Answer 331

Thin actin filaments and titin connectors attached to z disc

Answer 332

Actin filaments are pulled towards the centre as the end of the bipolar myosin filament moves towards the positive ends of actin

Answer 333

Synchronised shortening of multiple sarcomeres

Answer 334

1. CNS innervates alpha motor neurones 2. Alpha motor neurones innervate skeletal muscles 3. Exocytosis of ACh into synaptic cleft 4. ACh binds nAChRs = conformation change = pore opens = influx of Na+ = local depolarisation (end-plate potential) 5. Depolarisation reaches -50mV = voltage-dependent Na+ channels on muscle membrane open = action potential propagates along muscle membrane and down the T tubules 6. Action potential triggers Ca2+ release from the sarcoplasmic reticulum (surrounds all myofibrils) 7. Calcium release synchronously causes muscle contraction

Answer 335

Diseases causing early onset progressive muscle weakness that all have a genetic cause (like a gene coding for muscle proteins or transcription factors) that determines type

Answer 336

X-linked recessive, abscence or reduction of dystrophin, causes muscle weakness and wasting with onset of 2-5 years old and life expectancy of 30 --- results in delayed motor developmental milestones, learning difficulties

Answer 337

X-linked recessive, shorter dystrophin, milder than dmd but similar, onset >7, cardiomyopathy usually causes death and cardiac disease common in males and females, females also get cardiac arrythmias, cardiomyopathy and heart failure

Answer 338

Stiffening and thickening of the heart muscle

Answer 339

A gene on the X chromosome that codes for a rod-like cytoskeletal protein on the inner muscle membrane that connects muscle fibre's cytoskeleton to the extracellular matrix via laminin Males only have one X chromosome (no inactivation occurs like in females)

Answer 340

Anchors F-actin via actin binding domains to connect to intermediate filaments

Answer 341

3 binding partners: 1. Beta-dystroglycans = transmembrane protein linking extracellular alpha-dystroglycan to further link laminin and extracellular matrix 2. Sarcoglycans (transmembrane) 3. Dystrobrevin,syntrphin and nNOS (intracellular)

Answer 342

- The complex protects muscle from physical forces by transmitting contraction/relaxation force to tendons and connective tissue - nNOS produces nitric oxide to cause vasodilation so muscles get o2 - Contains spectrin-like repeats = rigidity - Proline-rich regions for bends - Acts as a linker to connect muscle fibre to the cytoskeleton, extracellular matrix, tendons and ligaments

Answer 343

65% deletion, 25% point mutation, 10% partial duplications

Answer 344

Premature stop codons = unstable truncated transcripts with low expression

Answer 345

1. Exons 45 to 55 to remove central portion of rod domain 2. Exons 3 to 19 to remove some or all of actin binding domain 1 and a portion of the rod

Answer 346

Loss of associated proteins = muscle membrane fragility Also causes nNOS mislocation = ineffective vasodilation = ischaemic damage to muscle

Answer 347

Dystrophin is partially functional as the reading frame, csytein-rich domain and C-terminal are all preserved as dystrophin undergoes small, internal truncations If actin binding domain 2 is missing then dystrophin is less stable and effective

Answer 348

Normal satellite cells respond to damage by proliferating and differentiating but in DMD they cannot keep up and progressive telomere shortening occurs which causes muscle wasting --- these damaged muscle cells disintegrate and are proteolysed and replaced by connective tissue and fibroblasts

Answer 349

1. Corticosteroids (standard treatment) 2. Gene replacement therapy of defective gene 3. Exon skipping therapy using anti-sense oligonucleotides to restore open reading frame with frame shifting deletions (makes it BMD) 4. Gene editing with CRISPR/Cas9 to repair/excise mutations via target modification 5. Stem cell therapy to introduce functional dystrophin gene for muscle repair

Answer 350

- Replacement of defective dystrophin - Most viral vectors do not infect skeletal muscle (adeno-associated viruses do though), gene is huge and these viruses cannot fit it, low effect in trials

Answer 351

Antisense oligonucleotide binds to defective region so translation machinery skips it and this can excise and exon to join other exons together (BMD symptoms) Personalised, costly, time-consuming

Answer 352

Induces exon skipping to restore dystrophin expression and is delivered via adeno-associated viruses

Answer 353

Use of satellite cells, bone-marrow derived cells, mesenchymal stem cells, induced pluripotent stem cells Limited capacity to expand numbers in vitro/iPSCs risk uncontrolled growth, delivery is a challenge, many muscles to restore

Answer 354

There are thousands of dystrophin mutations so every person needs a completely individual strategy Restoring the reading frame would not compensate for functional loss of deletions of critical dystrophin domains

Answer 355

AON-induced skipping for most common frameshift mutation sites

Answer 356

Relays information from internal and external environment back to CNS via sensory nerves

Answer 357

1. Spinal cord motor neurons (can be somatic or autonomic) and efferent neurons send signals from CNS to muscles 2. Dorsal root ganglion sensory neurons --- afferent neurons carry sensory information from receptors to skin and other organs to CNS

Answer 358

Axon damage (slows down axonal signalling)

Answer 359

1. Myelinating = envelops axon and wraps around membranes many times 2. Non-myelinating = envelops axon in a single layer of membrane to give nutrients and support

Answer 360

A bundle of peripheral axons

Answer 361

Packs fascicles and blood vessels together and blood vessels provide oxygen and nutrients and remove waste products

Answer 362

Connective tissue wrapped around each nerve fibre

Answer 363

Loose, arealar connective tissue surrounding fasicles

Answer 364

Tough, fibrous connective tissue sheath around nerve and its blood vessels

Answer 365

Damage to peripheral nerves (extremities first), diabetes, alcoholism, uremia, drug related, infection Result is damage to myelin sheath (repairable) or axon (limited repair)

Answer 366

Sensory loss, altered pain sensation, muscle weakness, poor balance, autonomic dysfunction

Answer 367

Nerve conduction studies and electromyography taken at distal and proximal site --- loss of myelin shows slower speed of conduction (time for distal stimulation to produce action potential increases)

Answer 368

Prolonged distal motor latency and slowed nerve conduction

Answer 369

Decreased amplitude in distal and proximal action potential, distal motor latency and conduction velocity are unaffected

Answer 370

Hyperglycaemia compromises Schwann cell and axonal function and damages supporting blood vessels --- sensory nerve damage reduces quality of life

Answer 371

Excess glucose increases glycolysis which perturbs normal homeostasis and causes high energy demands for sustaining action potentials Osmotic and redox stress damages nerves --- hyperglycaemia causes hexokinsase to become saturated and G6P is converted to sorbitol via the polyol pathway (this cannot pass through cell membrane = accumulation = osmotic stress), sorbitol is also converted to fructose = protein glycation = use of NAD+ = redox stress

Answer 372

Small = myelin ruffling, loosens (due to loss of adhesion molecules) Moderate = large spaces between myelin layers = axon exposure = damage

Answer 373

Group of heterogenous conditions due to mutations affecting schwann cell function, axonal proteins, neuronal function (mutations in any of these groups causes peripheral neuropathy) Normally due to gene dosage effect - duplication unbalances myelin formation

Answer 374

Balance issues, clumsiness, muscle weakness, foot abnormalities, more ankle injury, lower leg weakness

Answer 375

Autoimmune peripheral neuropathy (acute) that follows respiratory infection or gastroenteritis that causes axonal degradation and/or demyelination of peripheral nerves due to macrophage

Answer 376

Plasma exchange to remove circulating antibodies, intravenous lgG (binds C1q = reduced complement activation)

Answer 377

1. Infection by Campylobacter jejuni which expresses lipoloigosaccharide on its surface which is similar to ganglioside (GM1) on nerve cell membrane 2. Antibodies are produced against C jejuni which also target GM1 3. Complement cascade is activated and MAC causes membrane damage

Answer 378

Leprosy (mycobacterium leprae), HIV, herpes zoster (cold sores), lyme disease, diptheria

Answer 379

Initially demyelinates and then causes axonal damage to sensory, motor and autonomic parts of PNS 1. Sensory loss = anaesthesis, anaglesia, inability to distinguish hot/cold 2. Motor deficit = muscle weakness, paralysis and atrophy 3. Autonomic nerve fibre damage = impaired sweating, dry skin

Answer 380

Damage to peripheral nerves in eyes, face, hands and feet (majorly) causing ulcers, bone destruction, finger and toe shortening

Answer 381

Enters nerves via epineurium blood vessels and binds to specific schwann cell sites and becomes ingested = axonal atrophy and segmental demyelination = impaired conduction It also binds to alpha-dystroglycan complex = activation of PI3K signalling = actin cytoskeleton reorganisation = phagocytosis and internalisation of M.Leprae = cell damage

Answer 382

Endocrine and exocrine

Answer 383

1. Acinar (produces pancreatic enzymes) 2. Ductal (transports pancreatic juice to duodenum)

Answer 384

1. Alpha (glucagon) 2. Beta (insulin) 3. Delta (somatostatin) 4. PP (pancreatic polypeptide) 5. Epsilon (ghrelin)

Answer 385

Ductal cell secretion composed of water, bicarbonate, chloride, sodoim, and potassium to neutralise acid contents of stomach when they enter the intestine

Answer 386

Proteins like digestive enzymes, proenzymes and trypsin inhibitor

Answer 387

Protein --> peptide (trypsin and chymotrypsin) --> smaller peptide ("") --> amino acids (carboxypeptidase)

Answer 388

Produced in inactive form (proenzymes or zymogens), packed into granules and trypsin inhibitor is present

Answer 389

1. Acinar cells produce trypsinogen and release it into duodenum 2. Enterocytes of intestine secrete enterokinase 3. Enterokinase converts trypsinogen to trypsin 4. Trypsin activates all other pancreatic enzymes

Answer 390

1. Secretin (alkaline aqueous component) 2. Cholecystokinin (CCK) (enzyme component) Both are released by enteroendocrine cells in intestinal mucosa

Answer 391

1. Acidic chyme stimulates secretin release from enteroendocrine cells 2. Chyme is rich in lipids, fatty acids and proteins = CCK release 3. CCK and secretin travel to pancreas 4. CCK stimulates release of enzymes from zymogen granules, secretin causes bicarbonate and water release

Answer 392

1. Indirect = vagal nerve activation = pancreas signalled and acinar cells stimulated to release enzymes 2. Direct = CCK acts on acinar cells via calcium mediated mechanism to allow exocytosis of zymogen granules

Answer 393

Gallstone blocks pancreatic duct and pancreas becomes inflames

Answer 394

Bile deposits that have precipitated

Answer 395

Can make mucous plug that blocks ducts Patients should ingest enzymes that cannot leave pancreas

Answer 396

Biliary disease, alcohol, poisons, blunt abdominal trauma, drugs, infection

Answer 397

Epigastric pain, nausea, vomiting, ileus (hypomobility of small intestine = constipation), feverdue to leukocyte infiltration into pancreas causing interleukin-1 release

Answer 398

Causes lysomal enzymes and digestive enzymes from zymogen granules to become localised which suggests intra-acinar activation of zymogens by lysomal hydrolases = trypsin activation

Answer 399

Duct obstruction, acinar cell injury, defective intracellular transport (all can be caused by alcohol) = acinar cell injury which activates enzymes causing acute pancreatitis

Answer 400

Can be mild swelling, infiltration of neutrophils and oedema and supparation may cause necrosis and abcesses Can be severe with major necrosis and liquefaction of the pancreas with brown serous fluid in abdomen (fat globules, blood and enzymes)

Answer 401

Hypoglycaemia as islets of langerhans are damaged

Answer 402

Recurrent acute pancreatitis (mostly due to alcoholism) Pseudocysts, fibrosis and intraductal calculi (calcium carbonate stones)

Answer 403

1. Acinar protein hypersecretion 2. Necrosis-fibrosis sequence

Answer 404

1. Increase in acinar cell size 2. Increased area of endoplasmic reticulum 3. Decreased number of zymogen granules and colocalisation with lysosomes (causing trypsinogen activation)

Answer 405

Peptide secreted into pancreatic juice that normally inhibits protein plug and calcium carbonate crystal formation Secretion is inhibited by alcohol

Answer 406

Hypersecretion causes cathepsin b to be released from lysosomes and trypsin is released which cause lithostathine to be converted to lithostathine h2 which is an insoluble peptide that forms fibrils which form the matrix of protein plugs = combined with calcium carbonate in protein rich pancreatic juice = calculi

Answer 407

Blocking of pancreatic juice leaving = autodigestion of acini, calculi formation, acinar cell atrophy and ectasia (dilation)

Answer 408

Lithogenic pancreatitis due to recurrent acute pancreatitis causing scarring and fibrosis: Acute pancreatitis causes necrosis and inflammation = periductular fibrosis = partial duct obstruction = stasis in ductules = protein plug and calculi = obstruction of ducts by calculi = necrosis of acini and fibrosis

Answer 409

Connects pharynx to stomach and is a conduit for food and liquids, has 2 sphincters and does peristalsis

Answer 410

1. Striated (voluntary) -- innervated by nucleus ambiguous 2. Smooth (involuntary) --- innervated by dorsal motor nucleus

Answer 411

1. Lower oesophageal sphincter (top end) 2. Pyloric sphincter (bottom)

Answer 412

1. Mucin by surface mucous cell and mucous neck cells 2. Hydrochloric acid and intrinsic factor by parietal cells 3. Pepsinogen and lipase by chief cells 4. Gastrin by G cell

Answer 413

1. Cephalic phase 2. Gastric phase 3. Intestinal phase

Answer 414

Taste or smell of food triggers vagus nerves to trigger HCl, pepsinogen and gastrin production

Answer 415

Stomach stretches to prepare for food (distension) and gastrin enters blood stream, pepsinogen converted to pepsin and stomach muscles start to churn

Answer 416

Small intestine regulates the release of chyme from the stomach --- CCK and secretin slow emptying and reduce acid production and digestive enzymes production is triggered

Answer 417

CO2 and H2o combine to form h2co3 which form hco3- and h+ ---> h+ enters blood and combines with cl- PROTON PUMP

Answer 418

Duodenum, jejunum, ileum

Answer 419

1. Paneth cell = pathogen defence 2. Tuft cell = "" 3. Absorptive enterocytes = nutrient absorption 4. Enteroendocrine cell = secrete digestive hormones and enzymes 5. Goblet cells = mucin

Answer 420

Amylase converts it to its respective monosaccharides --> enter absorptive enterocyte by sodium-glucose transporter protein (glucose, galactose) or GLUT-5 (fructose) --> enter circulation by GLUT 2

Answer 421

Convert them to amino acids using pepsin in the stomach or pancreatic peptidases in duodenum --> amino acids enter absorptive enterocyte or tri-/di-peptides enter by PepT-1 transporter --> enter circulation by amino acid transporters

Answer 422

Lipids emulsify to be droplets --> become micelles in presence of bile salts --> diffuse into absorptive enterocytes --> packaged into chylomicrons in ER which enter vesicles --> exocytosis into circulation

Answer 423

Cecum --> colon --> rectum --> anus

Answer 424

Finish absorption of nutrients and h2o, synthesise some vitamins, form faeces and dispose

Answer 425

1. Absorptive enterocytes = complete absorption 2. Microvacuolated columnar cell = complete absorption 3. Enteroendocrine cell = hormones 4. Goblet cell = mucin

Answer 426

1. Abdominal or chest pain 2. Altered food ingestion due to: nausea, vomiting, dysphagia (difficulty swallowing), odynophagia (painful swallowing), anorexia 3. ALtered bowel movements 4. GI tract bleeding

Answer 427

Motor disorder that leads to functional obstruction -- LOS fails to relax with swallowing = dysphagia, regurgitation

Answer 428

Using manometry (pressure along oesophagus) -- peristaltic wave of pressure after swallow --> drop in pressure once it reaches LOS --> sphincter relaxes --> food enters stomach

Answer 429

Loss of inhibitory neurons so they get the peristaltic wave but sphincter cannot relax as it is not inhibited If both types of neuron are lost there is not peristaltic wave

Answer 430

Condition where lining of stomach becomes inflamed after it has been damaged by excess acid or pepsin

Answer 431

H.pylori bacterial infection, excessive cocaine or alcohol, aspirin, ibruprofen, stressful event, autoimmune reaction

Answer 432

Open sores on the stomach lining

Answer 433

H.pylori bacterial infection, lifestyle, aspirin, ibruprofen, stessful event

Answer 434

Inflammatory bowel disease

Answer 435

Genetic, infection, smoking, diet, defective immune response

Answer 436

Diarrhoea, pain, impaired growth, malabsorption, weight loss, inflammation without infection

Answer 437

Acquired deformity whereby mucosa and submucosa herniate through underlying muscularis in large intestine

Answer 438

Age, highly refined diet, low fibre

Answer 439

Stomach pain, fever and chills, swelling, gas, loose bowels, constipation, low appetite, sickness

Answer 440

Diverticula to clog with faeces = inflammation = infection