NURS1005 Final Lectures PDF

Biomolecules Metabolic reactions Energy production NURS1005 Michael Morris [email protected] The University of Sydney Page 1  Water – Inorganic and vital to life solvable in water...

Biomolecules Metabolic reactions Energy production NURS1005 Michael Morris [email protected] The University of Sydney Page 1  Water – Inorganic and vital to life solvable in water linetewater ~ Polar solvent properties – dissolves other polar and charged molecules but also (O2, CO2Iwaste product a attaching to haemoglobin Very t Reactivity – participates in many biological reactions cellular respiration (glucose -1 energy) High heat capacity – prevents rapid temperature changes (compare to metals) High heat of vaporisation – useful in sweating to remove heat for blood flow * to pump Low viscosity – flows readily, good diffusion rates for small dissolved molecules -easy Cushioning – protects from physical trauma (e.g., cerebrospinal fluid) The University of Sydney Page 2  Organic vs Inorganic Inorganic – Water -easily split up – Simple salts (NaCl, CaCl2, MgF2) – Simple acids and bases (HCl, NaOH) Organic – Contains at least 1 carbon molecule – Covalently bonded – Very small [CH4 (methane), CH3CH2OH (ethanol)] – Very large (DNA, proteins, starch) The University of Sydney Page 3  Fatty acid Carbon – Electro-neutral – Up to 4 covalent bonds (versatile) 19:34 · I Aldosterone – Can form Sucrose – glucose + fructose (steroid) – Chainlike molecules (e.g. fats) disacchaiche – Ring structures (carbohydrates, steroids) – Polymers (chainlike molecules made of monomers…DNA/RNA, proteins, polysaccharides) molecules chains of Carbohydrate ↳ long DNA Protein keep adding monosaccharides to (when you The University of Sydney the disaccharide) Page 4  What is a biomolecule? Any molecule involved in the maintenance or metabolic processes in an organism Carbon containing organic biomolecules Small Large bloodSugara Carbohydrates Sugars (glucose, lactose) Polysaccharides (starch, glycogen) Lipids Fatty Acids (FAs) Waxes (bee wax) Nucleotides Adenine, guanine, thymine, cytosine, uracil Polynucleotides (DNA, mRNA, tRNA) Amino acids 20 proteinogenic AAs (Asp, Ser, Phe) Proteins (enzymes, growth factors, structural) Locatalyse reactions Combinations Ganglioside Polysaccharide + FAs Low density lipoprotein FAs, cholesterol + (Apo B-100I-protein Glycoprotein Polysaccharides + protein Ribosomes AAs + rRNA + mRNA + tRNA + proteins ↳ make new proteins The University of Sydney Page 6  What’s in the key biomolecules that make food? S = sulpher S The University of Sydney Page 7  Small carbohydrates Glyceraldehyde ↳ triose monosaconside Sucrose i provides method of Glucose – Glucose – Disaccharide to extracting ATP energy open form ring form make Monosaccharide The University of Sydney Page 9  Carbohydrates Glycogen Polysaccharide of glucose (storage) form Note protein core The University of Sydney Page 10  Fatty acids modifications ↓ protein + inflammation regulation j * most common fatty acids Palmitic acid (Long-chain FA - saturated) Butyric acid (Short-chain FA) Up produced in the gut by the Triglyceride bacteria dietry fiber (Storage form FA) that breaks down ↳ balancing got microbiota, maintaining up backbone the muscosal barrier (which keeps bactrial + 3 fatty acids attached products from crossing into the blood + Circulates in the brain up bloodstream to be used causing inflamation) as energy by response regulating modulating host immune , G Li Fuels the cells , energy expedite the body between meals fat tissue Arachidonic acid - growth development , ↳ in (Long-chain FA precursor of numerous lipid mediators The University of Sydney - unsaturated) Page 12 un double bonds  Triglycerides – a storage form of lipid in adipose tissue (small carbohydrates The University of Sydney backbone structure Page 13  More complex fatty acid-containing molecules Phosphatidylinositol-3,4,5-trisphosphate Carbohydrate + glycerol + Fas) Signaling molecule to its ↳) allows cells to respond environment and make appropriate decisions On how to behave Organising Segreganone base molecules Phosphatidylserine (AA + FAs) Lipid bilayers The University of Sydney Istructural Page 14 integrity of cellula membranes)  Phospholipids – key molecules in cell membranes -because it undergoes hydrolysis /lose one fatty acid) – Modified triglycerides: 1 fatty acid chain replaced by a phosphorus-containing polar group. ! – 1 polar head group and 2 non-polar fatty acid tails. – Two layers of phospholipids form lipid bilayers such as plasma membrane. the (metabolic flow) Enzyme (LPAT) binds to the triglyceride molecule at a specific to the site -> LPAT cleaves a fatty acid from the triglyceride backbone - enzyme attaches a phosphorous containing polar group vacat spot Phospholipid on the glycerol molecule # Triglyceride - (Storage form of FA) The University of Sydney Page 15  A simple lipid bilayer * With a small modification , by taking off one chain and replacing with pola head it results in group , a molecule that is similar but is different enough to bethe central lipid membranes for cells component of forming * Modifications made by adding a polar head oily - - attracts water The University of Sydney Page 16  Cholesterol – cell membranes, and steroid precursor – Most important steroid molecule – present in food, can be made in the body – Four interconnected carbon rings. base moveable and combining nation * by being present in membranes and can FUNCTIONS be modified – Present in all cell membranes. – Used to synthesise steroid hormones such as sex hormones, vitamin D, bile and hormones from the adrenal cortex. The University of Sydney Page 17 Components of nucleotides: monosaccharides, bases and phosphate ↳4 different base - combination which makes the poly nucleotides In RNA, uridine replaces thymine The University of Sydney Uridine Page 19  Polynucleotides – the cell’s information storage systems 23 chromosomes 20, 000 genes Gene mRNA transcription translation Protein m The University of Sydney Page 20  Amino acids – the building blocks of proteins (20) The University of Sydney Page 22  Strings of amino acids make peptides and proteins (short proteins) The University of Sydney Page 23  Protein size and function vary enormously the transfer of catalyses between 2 ↑ a phosphate group ADP molecules forming ATP + Amp , IgG Haemoglobin Insulin Adenylate kinase Glutamine synthase Antibody O2 carrier Hormone Enzyme I Enzyme important for nitrogen metabolism , the efficient ulisation+ The University of Sydney ensuring Page 24 detox of ammonia  …So does protein structure Haemoglobin Aquaporin The University of Sydney Page 25 Mega-structures: Lipid bilayer membranes and membrane proteins Extracellular Fluid (ECF) luytoSkeletal proteirs) - joins the lipid bylaye and stabilises it allows strength for the membrane The University of Sydney Intracellular Fluid (ICF) Page 26 Cytoskeleton proteins: Cell strength, shape, and stability Em The University of Sydney Page 27  Red cells take a pounding in the circulation but survive e - distine - hypersonic The University of Sydney isa Page 28  The membrane as a selective barrier - protein channels Extracellular Phospholipid bilayer Aquaporin Intracellular will bonce off unless * polar + changed molecules there are specific carries in the membrane The University of Sydney Page 30  Enzymes: Catalytic proteins, cellular workhorses were onwards from examined not The University of Sydney Page 31  Metabolism Catabolism = Degradation Anabolism = Biosynthesis The University of Sydney Page 33 Catabolism of Food – Degradation of Dietary Components The University of Sydney Page 34 Catabolism = Degradation Anabolism = Biosynthesis DIET Complex Fats Carbohydrates Proteins Fatty Acids/ Glucose Amino Acids Monoglycerides Uptake and distribution in body Fatty acids/ Glucose Amino Acids Monoglycerides Triglycerides Cholesterol/ Lactate/ Glycogen Proteins Adipose Tissue Steroids Pyruvate (Storage) (Storage) The University of Sydney Page 35  Production and roles of ATP ATP is produced by Glycolysis – smaller amount of ATP rapidly Mitochondria – produce larger amounts but more slowly Cells have a balance of production from both ATP Powers >95% cellular activity Short-term form of energy storage – most cells run out of ATP in ~10 s if production inhibited Very high consumption: Heart turns over 6 kg/day, body turns over 30 kg/day ATP used for Muscle contraction (myosin protein powerstroke) Cilia movement, sperm motility (dynein protein motor) Ion pumping (e.g., Na+/K+-ATPase maintains high Na+ outside and high K+ inside cells) Facilitating many enzymatic reactions Cell signaling – cells receive information signals from the outside and ATP helps amplify that signal inside the cell. The University of Sydney Page 37  ATP–ADP cycle The University of Sydney Page 38  Ion pumping The University of Sydney Page 40 Gastrointestinal Physiology redux NURS1005 Michael Morris School of Medical Sciences [email protected] Last updated 30 July, 2024  Purpose of food and its digestion and absorption Nutrient intake for maintenance of homeostasis Body can generate and store energy (triglycerides, glycogen, ATP, etc.) Build and maintain things So, absorption of: Life’s building blocks (e.g., sugars, amino acids, fats, cholesterol) OR Generation of building blocks via GIT metabolism Things we can’t make: (e.g., vitamins, essential amino acids) enzymes) ~ ( for Water and maintain water balance (we sweat, pee, poo, digest) Ions to maintain ion gradients (e.g., Na+, K+, Cl-, Ca2+, Mg2+) Ions as cofactors for protein/enzyme function (e.g., Ca2+, Fe+) Ions for structural elements (e.g., Ca2+, PO43- for bone) Remove waste (e.g., roughage, bilirubin)-from naemoglobin) Heat generation to help maintain body T emp composition dief of food Immune defence and (maintain healthy gut flora) - foodcontents from · The ultimately Tastes and smells good (hopefully often) gets exposed to the outside environment Catabolism of food: Degradation of dietary components Catabolism = Degradation Anabolism = Biosynthesis ↳) chemical process that creates DIET complex molecules from simpler ones. (macromolecules) Complex Fats Carbohydrates Proteins Fatty Acids Glucose etc. Amino Acids Monoglycerides Cholesterol Uptake and distribution in body ATP prod. Fatty acids Glucose etc. Amino Acids ATP prod. Monoglycerides Cholesterol Triglycerides Lactate Glycogen Proteins Adipose Tissue Cholesterol Pyruvate (Storage) (Storage) Steroids Phospholipids ATP prod. Fatty acids, amino acids, monosaccharides → → → → → →  produce hormones + enzymes) detox) filter metabolism , - blood, immue response Ibile , , - storage recycling , store - bile 4 processes of the digestive system ↳ release of substances from cells or glands to did digestion A closer look at the 4 processes in different parts of the GIT Camalyse) - pepsin -lipids Fig 21.6 - pH levels to protect cells up in stomach regulation ↳ heps return to normal pf  Enteric and central nervous system control the food - anticipate sensest thoughts through or -long reflexes The NS works together to begin t elaborate a on the normal digestive tract function gasticPhasecontl - Short reflexes Preparation for and breakdown of food in stomach Cephalic phase receives stimulation from food which - controlled by CNS - activates the nervous Long reflexes system Feedforward (anticipatory) circuit Stimulates Increased motility (stomach grumbling) Some HCl secretion (gastric) Enteric phase Short reflexes Activated by distension, peptides, amino acids Stimulates Pepsinogen release HCl secretion Pepsinogen to active pepsin by HCl Final result HCl, pepsin, motility break down food Generate chime Released into small intestine Acid and enzyme secretion and negative feedback control by somatostatin = - ensures that the body responds appropriately to the influx of nutrients after eating preventing , imbalances + protect organs indirect basically reducing tre of release direct mis  A cellular view of acid secretion: Interplay of transporters and enzymes Variety of transporter types required Carbonic anhydrase (CA) – lots of it, not efficient, but does H2O splits to H+ and OH- the job. ATP required to pump H+ into stomach Some evolutionary problems are difficult to solve. OH- and CO2 make HCO3- CO2 is not always a waste product! Cl- goes with H+ - hence HCl Histology of the stomach ruga - increase SA of Stomach to take in more nutients mucosa - bloodstream that submucosa absopts nutrients muscularis externa muscles that help the movement of food serosa 3 layers of muscle tissue to churn food  Histology of the small intenstine Duodenum Jejunum Ileum mucosa submucosa muscularis serosa externa Muscularis externa: - the breaks food Inner layer – circular muscle for segmentation Outer layer – longitudinal muscle for peristalsis pusk - the food along GIT  Huge surface area of the small intestine Villus Plicae circularis Microvilli Goblet cell Microvilli Mucous droplets Mitochondria Microvilli -increase SA GIT Pathophysiology + meeting energy needs NURS1005 Michael Morris School of Medical Sciences [email protected] Last updated 4 August, 2024  Energy production, storage, and use of stores A refestothe euposotefficienta through cellular respiration Producing ‘at-call’it'senergy molecules for – largely ATP # period there a short of time Storing ‘excess energy’ for later use Glycogen stores, fat stores, protein stores I store of lexcess glucose) energy Using ‘at-call’ energy molecules – e.g., short or mild exercise Largely ATP Using stores to make ATP – e.g., prolonged exercise (marathon) or fasting Glycogen stores, then fat stores Using stores to make ATP – e.g., starvation Glycogen stores, then fat stores, then protein stores (muscle protein)  ATP production from glucose: anaerobic vs aerobic metabolism Anaerobic Aerobic Glycolysis – Metabolism Metabolism Mitochondria smaller 1 Glucose G NADH FADH2 ATP CO2 1 Glucose G NADH FADH2 ATP CO2 – larger amount of L Y L Y amounts of C C +4 ATP rapidly ATP more 4 O 2 O 2* L L -2 Y S I -2 Y S I slowly S S 2 Pyruvate 2 Pyruvate -2 2 2 2 Lactate 2 Acetyl CoA 0 2 TOTALS NADH ATP Citric acid 6 2 2 4 cycle - OnlyResona Mitochond High-energy electrons 6 O2 and H+ in ELECTRON TRANSPORT 26-28 Cells have a balance of Sanaerobic&and SYSTEM aerobic ATP production TOTALS 6 H2 O 30-32 ATP 6 CO2 * Cytoplasmic NADH sometimes yields only 1.5 ATP/NADH instead of 2.5 ATP/NADH.  Adenosine triphosphate (ATP) and important analogs ATP ADP _ → _ ← _ _ _ _ _ dAMP _ ↓ Main fuel cycle of the body _ ↓↑ AMP _ _ Signalling – Used in DNA/RNA controls energy balance -E  ATP – critical fuel and roles Powers >95% cellular activity Short-term form of energy storage – most cells run out of ATP in ~10 s if production inhibited Very high consumption: Heart turns over 6 kg/day, body turns over 60 kg/day Examples of use: Muscle contraction (myosin protein powerstroke) Cilia movement, sperm motility (dynein protein motor) Ion pumping (e.g., Na+/K+-ATPase maintains high Na+ outside and high K+ inside cells) Facilitating many enzymatic reactions Cell signaling ATP–ADP cycle O Ion pumping  Problems in the mouth and face Teeth Mechanical break-up Painful mouth Saliva Soften and moisten food for swallowing Cavity Amylase Enzymatic breakdown of starch Abscess Lingual lipase Enzymatic breakdown of triglycerides Bruxism Ulcers Inflammed/damaged facial nerves Slipped disc Unable to chew No teeth Lost dentures Loss of salivation/taste Radiotherapy for throat or parotid cancer How do you care for patients with problems and their food intake if… Confused after surgery by general anaesthetic (can last many days) Mental health problems Depression Autism Bipolar disorder Schizophrenia Can talk but have dementia Can’t talk Advanced dementia Severe autism Neurological disorders – e.g., NMD Can’t talk and limited or no movement Advanced dementia Quadraplegia Advanced NMD  Heliobacter pylori – bacterial stomach infection Takes are a twater which converts into ammonic raises which neutralises HC) > - pH levels Gastric HCl G Mucus ↳> secreted goblet cells by thathelpsmaintais on walls ⑳ Phospholipase A Breaks down mucus viscous which the layer penetrates CagA 00 VacA HTR-A End result: Bacterial infection Interstitial fluid Apoptosis Inflammation (cell death) Dead/dying gut cells Protease CagA G Inflammation Exposure of gut lining to HCl (cell detachment) by breaking down protein (white cells) Exacerbated by NSAIDS that combines the well together Blood supply Heliobacter pylori pathogenesis – Hussein Biology  (A) Gastric glands abundantly colonized with Helicobacter pylori, shown as dark, curved bacilli closely aligning with the Clin Microbiol Rev. 2006 Jul; 19(3): 449–490 mucosal surface. (B) Endoscopic view of a gastric ulcer, with a clean base at the angulus.  Surface area is important Increased surface area of food by: Mastication Expansion with food bolus Enough cells for: Acid-based breakdown Enough cells for: Absorption, mucous secretion Enzyme breakdown HCl, pepsinogen, mucous secretion Cell replacement Churn in stomach and small intestine Cell replacement Fat emulsification  Huge surface area of the small intestine Microvilli Plicae circularis Villus Goblet cell Microvilli Mucous droplets Mitochondria Microvilli  Absorption: Surface area problems Diverticulitis Coeliac disease Crohn’s disease Diverticula (multiple pouches) trying to meet the Endoscopic showing deep ulceration Biopsy of small * stem all throughneeds building new bowel showing coeliac of Villi disease manifested by blunting of villi, crypt hypertrophy, and lymphocyte infiltration of crypts undeamidated wells that are presented to Thells trigge immune response which read to the release of inflammatory cytilizes , Resected ileum hence Diverticula abscesses damages villi (by flattening)  Cholera Cholera toxin  Cholera toxin chronically activates the CFTR Cl- channel Thus dragging out ↑ var due to increased receptors voside C) ion concentratin gang open + release chlorideiors inesural Immer phosphorykles - - of toxin is released A, subunit adding ADP ribose " modifies by group CFTR ~ Al catalyses into ATR cycliz AMP * locks activationof activates G protein leading + protein kinase A Adenylyl cyclase loss of fluid rapid Starvation and plasma protein – kwashiorkor and marasmus Middle East Africa India Buchenwald 1945 1st world Respiratory Pathophysiology 1 NURS1005 Presented by Jaimie Polson, PhD School of Medical Sciences [email protected] The University of Sydney Page 2 Learning Outcomes On completion of this topic you will be able to: Explain the factors that determine diffusion of gases across the respiratory membrane. Explain what diffusing capacity of the lung measures in terms of its unit of measurement, and why carbon monoxide us usually used for this test. State factors that cause the lung’s diffusing capacity to be reduced. Describe the process of ventilation-perfusion matching, including defining hypoxic pulmonary vasoconstriction Explain the circumstances when VQ mismatch can cause hypoxaemia. The University of Sydney Page 3  What are the functions of the respiratory system? The primary function of the respiratory system is gas exchange (movement of oxygen into body and carbon dioxide from body) for metabolic activity produce - ATP - Transport O2 & CO2 across the gas exchange site (respiratory membrane). - diffusion - Move air to and from the gas exchange site from/to the external environment. - ventilation - Move O2 & CO2 to/from the tissues. via bloodstream Secondary functions to produce carbonic acid Acid-base balance 5)( O2 bloodstream He0 ↑ acidity of blood) in + : Production of sound. Lexpiration) Provide the anatomical substrate for the sense of smell. Chemoreceptors) airways -in maintain homeostasis Protect respiratory surfaces from dehydration, temperature changes and invading - pathogens. if 1) more blood is cooled down it become solvable to , a gases - cause measurehowwelllugsaccapade air embolism Diffusion can be examined by the diffusing capacity of lungs for carbon monoxide (DLCO) test. Ventilation can be examined by lung function tests, such as spirometry. The University of Sydney Page 4  Steps of external respiration blood to delivers deoxygenated ↑ alveoli so blood becomes pulmonary Oxygenated+ capillaries r trns to rect + ~ diffusion other organs CO2 O2 systemic capillaries ↳) diffuses oxyger to out of blood and go tissues to provide oxygen for cellula metabolism Fig. 13-1 Sherwood L (2016) Human Physiology: From Cells to Systems, 11th edition Cengage Learning, Ca. The University of Sydney 4) metabolic process of oxidation Page 5 for the production of ATP  The respiratory membrane – where gas exchange occurs – The respiratory membrane is made up of the wall of the alveolus and the wall of the pulmonary capillary. – Gas exchange occurs by diffusion. Respiratory – There are 4 main factors that determine the effectiveness of diffusion of a gas. Membrane – 1. A high driving force for diffusion (which for a gas is provided by produces pulmonary surfactant ↑ that helps to increase the partial pressure gradient). compliance I ligs of (inflation) – 2. A short diffusion distance, whicheventually is provided by the very thin would have type II respiratory membrane. "goes into that bloodstream Coxygen) the alveolar cell The alveolar wall is made up of a single layer of flattened Type I alveolar cells, diffusion & the capillary wall is made up of a single layer of endothelium. alveolis O2 Total thickness ~ 0.5 µm – 3. A large surface area across which the gas diffuses. This is type I alveolar cell provided by capillaries encircling the alveoli. crespiratory membrane There are ~500 million alveoli in the 2 human lungs, and the total surface area available for exchange is ~ 75 m2 (35-100 m2 depending on ventilatory state). – 4. Solubility of the gas. capillaries The gas must first dissolve in the alveolar fluid lining the inner surface of the alveolus before it can diffuse. CO2 is ~20x more soluble than O2. The University of Sydney Page 6 (taben out of blood plasma) in the blood as O2 diffuses it binds onto the haemoglobin. Amount - naemoglobin , 5 of , partial is maintained higher to keep driving force of diffusion so pressure gradient partial ↳> no longe contributes to pressure of oxygen in blood  The concept of partial pressure (the driving force for gas diffusion) - up Overall concept: what proportions of the atmospheric pressure is that gas contributing to In lungs, PO2 is Partial pressure of N2 79% N2 L) drives the diffusion usually ~ 100 mmHg - mixed with old gas+ in atmospheric air: Partial pressure of used in blood stream PN2 = 79% x 760 mm Hg N2 = 600 mm Hg - Lungs = 600 mm Hg net diffusion of O2 /until partial pressure is the Sama (0) Alveolar gas O2 concentration Total O2 5.20 ↓ atmospheric When in PO2 = 100 mmol/litre pressure equilibrium…. = 760 mm Hg PO2 = 100 O2 100 0.15 until this reaches mmol/litre Partial pressure of O2 Capillary blood ↳) now much O2 is dissolved in blood plasma + contributes in atmospheric air: to 21% O2 partial pressure determined by solubility PO2 = 21% x 760 mm Hg Partial pressure of depending on partial pressure gradient , you'll get = 160 mm Hg O2 = 160 mm Hg net movement in one direction From Sherwood L (2017) of oxygen Human Physiology: From Cells to Systems, 6th ed. Brooks/Cole The University of Sydney Page 7  Gas Exchange produces equilibration of PO2 & PCO2 air The driving force for diffusion is the partial pressure gradient alveolar gas – PO2 in alveolar gas = ~100 mmHg. ↑ patial presserts numbe to – PO2 in blood arriving in pulmonary capillaries = ~40 mmHg drop but pluver Initially, ∆PO2 = 60 mmHg à O2 diffuses from alveolus to blood. (driving force) blood through pulmonary - as the travels 1) Ibasalleval) Capillaries Average ∆PO2 at rest is ~11 mmHg (Guyton & Hall, 2011). I according to how much – PCO2 in alveolar gas = ~40 mmHg – PCO2 blood arriving in pulmonary capillaries = ~46 mmHg Or is dissoled in plasma ∆PCO2 = -6 mmHg à CO2 diffuses from blood to alveolus 10 (PO200 PO2 40) ~ patial pressure gradient reaches to , = – Note that equilibration occurs very rapidly, normally within ~0.3s, much less than the capillary transit time of 0.75s. – By the time the capillary blood passes the alveoli there should be nearly total equilibration. – If not, it indicates: reduced diffusing capacity of the lungs. ventilation-perfusion mismatch Fig. 14.12 in Mulroney SE & Myers AK. Netter’s – In reality, there is not total equilibration. Essential Physiology, 2nd ed. Elsevier, 2016 – Arterial PO2 is usually ~ 5 mmHg lower than alveolar PO2 The University of Sydney (Alveolar-arterial gradient). Page 8 -Deffect of gravity on lings which impacts ventilation perfusion mismatch  What is the diffusing capacity of the respiratory membrane? – The diffusing capacity of the lung (DL) measures how effectively the lungs exchange gases between the alveoli and pulmonary blood. It quantifies the volume of gas (in mL) that diffuses across the respiratory membrane per minute for each mmHg of partial pressure difference of the gas. the role of neutralises – As mentioned previously, the 4 factors that influence diffusion are: (i) partial pressure gradient, (ii) surface area, (iii) membrane thickness & (iv) solubility of gas.- fixed factor a that varies depending on gas the – The DL technique focuses on how well (ii) and (iii) are functioning. – To measure the DL “all” we need to know: (i) the volume of gas that diffuses across the membrane per minute and (ii) the average partial pressure gradient of the gas (∆Pgas). – However, measuring PO2 or PCO2 in the pulmonary capillary is technically difficult. Therefore, clinics normally use carbon monoxide (CO) to measure DL and make a conversion for O2 & CO2. – Can assume the PCO pulmonary blood = 0 – In a healthy adult, DLCO is reported ≅17 ml/min/mmHg (Guyton & Hall, Medical Physiology 12th Ed, 2011). DLO2 = 1.23x DLCO = ~21 ml/min/mmHg. DLCO2 = ~400 ml/min/mmHg, because of the higher solubility of CO2. Variations: other sources suggest DLCO may be 10-35% higher (eg. Howarth et al., 2021 PLoS ONE 16(4): e0248900 reports DLCO at ~ 23.05 for Australian Caucasians). The University of Sydney Page 9  Diseases that reduce oxygen diffusion Oxygen diffusion across the respiratory membrane will be reduced if: 1. Driving force (∆PO2) is reduced (usually a problem of ventilation). 2. The distance the gas has to travel increases. This will happen with an increased thickness of the respiratory membrane. – eg. pulmonary oedema, interstitial (fibrotic) lung disease, Alveolus pulmonary hypertension (thickening of capillary wall). pulmonary capillary 3. The respiratory membrane surface area decreases. This occurs with a decrease in the number of alveoli (loss of lung tissue) or a O2 decrease in the number of open capillaries. – eg. emphysema Endothelial cell Normal lung Pulmonary oedema Fibrotic lung disease Adapted from Fig. 13.4a Sherwood L. Thickened alveolar membrane (2017) Human Physiology: From Cells Fluid in interstitial space increases Respiratory Membrane to Systems, 6th ed. Brooks/Cole diffusion distance. Arterial PCO slows gas exchange. Also 2 may be normal due to higher loss of lung compliance may CO2 solubility in water. decrease ventilation. All these diseases can reduce Exchange PO oxygen levels in the blood & PO PO surface 2 normal 2 normal normal 2 normal therefore increase Alveolar- or low arterial PO2 gradient because Increased diffusion of reduced O2 diffusion. PO normal distance PO low 2 The 2 University of Sydney Page 10 PO low 2  Question failure : low arterial ROn t normal-low steid ~ Type I respiratory PCOz If a patient has a diffusion problem in their lungs (as measured by a low DLCO), which of the following 2 : low arterial POz PC O2 + high Caterial caused Type by conditions would you expect to see in their arterial ventilation problems blood? a. normal PO2 O into capacity pulmonary blood b. low PO2 > - reduced diffusion 1 less capacity of oxygen c. high PO2 to diffuse from gas in alrea O d. normal PCO2 > - diffusing capacity is much high than 10 so the effect is minimal # it could deares - due to ⑧ e. low PCO2 hyperventilation (blowing out more (On from logs) ep increase partial pressure gradient for driving 10- f. high PCO2 The University of Sydney Page 11  flow flow air blood ~ X The importance of ventilation-perfusion (V-Q) matching not be the case - may impact – everytime as it can Effective gas exchange requires (good ventilation of the alveoli with oxygen& and good part of longs perfusion of the pulmonary capillaries with blood. – When this is compromised it can cause hypoxaemia. necessarily every time - not the case normal situation, good ventilation bronchoconstriction, poor ventilation arteriole bronchiole ventilation low oxygen ~Poorprovide passingOr sufficient the alrea blood Alveoli Alveoli PO2 = 100 airflow poor PO2 = 100 PO2 = 100 - C PO2 = 40 PO2 = 40 PO2 = 100 PO2 = 100 PO2 = 100 high mixed blood oxygen (mid-oxygen blood level) The University of Sydney PO2 = 100 mmHg PO2 = 70 mmHg Page 12  Ventilation-perfusion matching - able to highe maintain level of oxygen in blood to – There are local controls on the smooth muscle of the pulmonary become redirected lood vessels it so pulmonary arteries. vasoconstriction other can flow past alreais that it means there has been a ~ are working well decrease in ventilation (say reduced a decreased oxygen concentration in the alveoli causes to 10% vasoconstriction of pulmonary arterioles, whereas an blood flow) increased oxygen concentration causes dilation of pulmonary arterioles. PCO 2 PO2 = 100 this is called hypoxic pulmonary vasoconstriction (HPV). PO 2 PO2 = 40 – There are local controls on the smooth muscle of the PO2 = 40 bronchioles. reduced blood Trees flow a PO2 = 100 - meas to long region a decrease in CO2 concentration in a lung region causes constriction of bronchioles in that region, whereas an increased CO2 concentration causes dilation of the bronchioles. PO2 = 94 mmHg assuming 10% of flow through constricted blood vessels The University of Sydney Page 13  Ventilation perfusion matching Lung region in which blood flow Lung region in which air flow (ventilation) (perfusion) is greater than airflow is greater than blood flow (perfusion) (ventilation) Helps Helps Helps Helps balance Large blood flow balance balance Large airflow balance Small airflow Small blood flow CO2 in lung region O2 in lung region CO2 in lung region O2 in lung region Relaxation of local airway Contraction of local pulmonary Contraction of local airway Relaxation of local pulmonary smooth muscle artery smooth muscle smooth muscle artery smooth muscle Dilation of local airways Constriction of local blood vessels Constriction of local airways Dilation of local blood vessels Airway resistance Vascular resistance Airway resistance Vascular resistance Airflow Blood flow Airflow Blood flow The University of Sydney Fig. 13.23 Sherwood L (2007) Human Physiology, 4th ed., Page 14 Brooks/Cole, Pacific Grove, Ca.  V/Q ratio and V/Q mismatching – If ventilation (V) and perfusion (Q) are perfectly matched, then V/Q =1. – There are several patterns V/Q matching/mismatch that can be described: both ventilation and perfusion to lung region = – V/Q = 1.0 - A lung region with perfectly matched gas and blood flows. 1.5 L/min. in well-matched lungs, V/Q will be close to 1.0 ∴ V/Q = 1 i.e. for every unit of gas flow it will receive a unit of blood flow. – V/