FLG221 Exam Notes PDF

lOMoARcPSD|40661470 FLG221 Exam Notes Lung and renal physiology, acid-base balance and temperature (University of Pretoria) Scan to open on Studocu Studocu is not sponsored or endorsed by any college o...

lOMoARcPSD|40661470 FLG221 Exam Notes Lung and renal physiology, acid-base balance and temperature (University of Pretoria) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Filtration fraction Barriers of renal corpuscle % of total plasma volume that Þlters Cappilary endothelium into the tubules Basal lamina Glomerular Þltration rate BowmanÕs capsule endothelium Volume Þltered per minute (125mL/min) Auto regulation of GFR Pressures that inßuence GFR Why? Hydrostatic pressure (promotes) Protect Þltration barriers from high BP Colloid osmotic pressure (opposes) Occurs in afferent arteriole Fluid pressure (opposes) Myogenic response Intrinsic ability of vascular smooth muscle to respond to pressure changes Tubuloglomerular feedback Factors that inßuence EFP Paracrine signalling mechanism through COP of afferent arteriole which changes in ßuid ßow through loop of Decreases GFR Henle will inßuence GFR COP in bowmanÕs capsule Affect permeability, increase GFR Hydrostatic pressure increase with ureter Increased afferent resistance Filtration obstruction Decrease GFR Decrease hydrostatic BP Increases efferent resistance Nitric oxide- autoregulation Increase GFR Vasodilator, decrease BP as response Increase hydrostatic BP Bradykinin Increase GFR and RBF Dopamine Tubuloglomerular feedback loop Inhibits renin secretion GFR increases Increases RBF Flow in PT increases Sympathetic nerves & catecholamines Flow past macula densa increases Constricts aff arteriole Paracrine signaling from macula densa to aff arteriole Decrease GFR and RBF Aff arteriole constricts ANG II Resistance in aff arteriole increases Vasoconstriction Hydrostatic pressure decreases Eff arteriole more sensitive GFR decreases Low []= increase GFR , decrease RBF = eff constricts High []= decrease GFR and RBF = eff & aff constricts Glomerular hyperÞltration ( >140) Endothelin Pregnancy Vasoconstriction Diabetes type 1 Decrease GFR and RBF Diabetes type 2 Prostaglandins Autosomal dominant poly cystic Increase RBF, no GFR change kidney disease NSAIDÕs will inhibited synthesis Natriuretic peptides Causes sodium excretion Dilate aff, constrict eff Chronic kidney disease states Increase GFR, no change in RBF Stage 2: mildly reduced kidney function Stage 3A: moderately reduced kidney function Stage 4: severely reduced kidney function Stage 5: very severe, end stage failure, on dialysis Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Secretion Active process Mostly occurs in PT Via indirect active transport Direct active transport Ð (a.k.a primary active transport) uses uses chemical energy (such as from ATP in case of cell membrane) to transport all species of solutes across a membrane against their concentration gradient. ¥Secondary indirect active transport: ¥Secondary active transport is deÞned as the transport of a solute in the direction of its increasing electrochemical potential coupled to the facilitated diffusion of a second solute (usually an ion) in the direction of its decreasing electrochemical potential. ¥Indirect active transport uses the downhill ßow of an ion to pump some other molecule or ion against its gradient. The driving ion is usually sodium (Na+) with its gradient established by the Na+/K+ ATPase. ¥Tertiary active transport refers to the presence of three transporters functioning in series, where the Þrst transporter is directly coupled to energy utilization and establishes a favorable electrochemical gradient for molecular species X. Excretion i Excretion rate dependant on: Substance Þltration rate Clearance (mL/min) If substance was RA or SC Noninvasive way to measure GFR Rate at which solute disappears from body by excretion/metabolism GFR gives indication of kidney function Urine output very useful Concept= clearance Inulin- clearance indicator polysaccharide isolated from plant roots Filters through nephron Neither RA or SC by kidney tubules 100% clearance Clearance rate = GFR Why is inulin useful in research settings? If clearance is less than 100%, there is a problem in the kidney Þltration system. Restricted to research settings Alternatives to inulin for testing Creatinine (product of phosphocreatine breakdown Small amount secreted by PT Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Vasopressin action in water reabsorption Location 1. ADH secreted by posterior pituitary gland Water and Na separately regulated in distal nephron 2. Binds to collecting duct cell membrane receptor Required 3. Receptor activates cAMP 2nd messenger ADH in distal nephron system Reason 4. Cell inserts aquaporins into apical membrane Make distal nephron epithelium permeable to water 5. Water reabsorbed by osmosis into blood Combo Na reabsorption in PT, followed by water PT always water permeable. Major routes of water loss Diarrhoea Excessive sweating Water conservation Urine Create concentrated urine by specialised mechanisms in kidney like in loop of Henle Water loss impact on homeostasis I -ECF volume depleted then BP decreases Diagrams important -ßuid lost is hyposmotic, osmolarity will increase and disrupt cell function 1 Water balance Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Proximal tubule - osmolarity Urea 70% ßuid reabsorbed here Nitrogenous waste product Fluid isosmotic to plasma No active transporters in PT Moves via diffusion by urea gradient ' 1 What happens after the proximal tubule Filtrate enters loop of Henle Urea process More solutes reabsorbed than water Na & other solutes reabsorbed by PT Osmolarity decreases after loop This makes ECF more concentrated than lumen Uses countcurrent multiplication Creates osmotic gradient Response to gradient Water moves across epithelium by osmosis Countcurrent multiplication Then increased urea [] in lumen Process of using energy to generate an osmotic New gradient forms - urea gradient gradient that enables you to reabsorbed water Urea moves out lumen into ECF via from tubular ßuid and produce concentrated paracellular pathway or through cells urine Why should urea be reabsorbed ? IF in renal medulla has increased osmotic [] After the loop of Henle Permits excretion of urea with little H2O Filtrate passes to DT and CD Osmolarity -osmotic pressure of medullary ßuids RA & SC determines Þnal osmolarity -role in K excretion -40% urea Þltered, is found in urine Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Inßuenced by: NaCl reabsorption in 2nd half of prox tubule -vasoconstrictors and vasodilators -Cl in Þltrate is less than in plasma due to -natriuretic peptides negative charges that are repulsed by Þltration -renal sympathetic nerves membrane -Na reabsorption determines Cl reabsorption -water reabsorbed in Þrst half of prox tubule -Cl concentration increases along prox tubule Epithelial reabsorption -both then reabsorbed in 2nd half of prox T Substances cross apical & basolateral -makes use of NCC membranes of tubule epithelial cells to reach interstitial cells. Paracellular reabsorption Cl reabsorption in DT and collecting duct Transport via epithelium by passing Na reabsorption generates negative luminal through intercellular space bet ween cells voltage across late DT and CD Provides driving force Cl reabsorption across paracellular pathway Potassium handling : reabsorption If K depleted, K reabsorption increases a-intercalated cells Proteins In proximal tubule by pinocytosis Digested by tubular cells into AAÕs AAÕs then absorbed Potassium secretion dependant on: is Reabsorption - Na-K-ATPass activity -permeability of apical membrane to K -driving force for K movement Calcium reabsorption: Proximal tubule Via paracellular pathway, due to Na Aldosterone function in Na balance and water reabsorption Early response phase Loop of Henle apical Na & K channels increase open time Via paracellular pathway, due to Na Inßuence of unknown signal reabsorption Intracellular Na levels rise Distal tubule Na-K-ATPase pump speeds up Via active transcellular pathway Cytoplasmic Na transported into ECF ④ PTH & Vit D stimulate Ca-H-ATPase K from ECF to P-cell Result Rapid increase in N RA and K SC DoesnÕt require new pump & channels Aldosterone function Slower phase Increase Na reabsorption New pumps and channels inserted into Increase K secretion epithelial cell membranes Via activity of Na-K-ATPase Low [] = rapid response In DT & collecting duct High [] = slow response Targets P cells Enters by diffusion Combines with cytoplasmic receptor Fluid and electrolyte balance CVCC system ☆ Under neural control, rapid response Aldosterone action on P-cells Kidney 1. Combines with cytoplasmic receptor Homeostatic control,slower response 2. Hormone-receptor complex initiates TC in nucleus ④ Integrative system ④ 3. Translation and prot. synth. makes new pumps and channels 4. Aldosterone-induced proteins modulate existing pumps & ch 5. Increased Na reabsorption, increased Downloaded K by secretion Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Characteristics of mediated transport Saturation Saturation deÞnition SpeciÞcity Maximum rate of transport that occurs when all Competition available carriers are saturated with substrate Substrate concentration below SP Transport rate related to substrate concentration Substrate concentration above SP Glucose transport Transport rate at Tm -Secondary active transport -via glucose-Na cotransporter -energy provided by Na-K-ATPase Once carried over basolateral membrane Amino acid transport Glucose transporters via facilitated Secondary active transport diffusion AA-K-ATPase cotransporter Driven by Na-K-ATPass (creates gradient) Calcium handling Filterable if free or bound to citrate GIT and bone play important role Phosphate transport & handling *refer to reabsorption for more info -90% reabsorbed (majority in PT) -10% excreted Transport 7h -Only in urine if luminal cotransporter Micturition - urinating is saturated Filtrate called urine after leaving CD Transport Moves down uteter to bladder Secondary active in luminal membrane Opening closed by sphincters (muscle rings) Countertransport in basolateral Internal sphincter membrane (phosphate/anion) Continuation of bladder wall ④ PTH lowers Tm, more phosphate excreted Smooth muscle Normal tone keeps contracted External sphincter Skeletal muscle Controlled by somatic motor neurons Tonic stim from CNS maintains contraction Micturition process 1. Stretch receptors Þre 2. Parasympathetic neurons Þre Motor neurons stop Þring 3. -smooth muscle contracts - internal sphincter pulls open - external sphincter relaxes Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 Process summary Complex pathway Stimulate ANG II signals the release of Decreased BP Angiotensin II Aldosterone aldosterone usually Factors that modulate aldosterone release RAS pathway Increased ECF osmolarity Begins Inhibits secretion of aldosterone Juxtaglomerular granular cells in afferent Large decrease in plasma Na arteriolar of nephron secrete renin Stimulate aldosterone secretion What is renin? Convers angiotensinogen to ANG I Stimuli of RAS system (all low BP related) ANG I then converted to ANG II by an Granular cells angiotensin-converting enzyme Respond to low BP in renal arteriolar Next: Secrete renin ANG II reaches adrenal glands Sympathetic neurons Aldosterone then synth. and released Low BP activates them by CVCC Finally: Terminate on granular cells (renin secretion) Aldosterone initiates intracellular rxns Paracrine feedback In distal nephron Increased Na reabsorption Tissue action All aim to increase BP Effects of ANG II Increased vasopressin Conserve blood volume since water is reabsorbed in nephron Maintains BP Stimulates thirst Expand blood volume & BP Vasoconstriction Increases BP, no blood volume change CVCC receptors Sympathetic stim increase cardiac output & vasoconstriction Increase BP Na reabsorption increased in PT Na reabsorbed, water follows Reabsorption if isosmotic ßuid Conserves volume Renin-Angiotensin system : From macula dense in DT to granular cells High ßow= inhibit renin release Low ßow= secrete renin Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 pH HOMEOSTASIS DEFENCE MECHANISMS AGAINST PH FLUCTUATIONS Essential functions of body Range is 7.35 - 7.45 (slightly basic) pH of solution is measure of [H+] ICF & ECF buffers Usually expressed in logarithmic scale 0-14 Adjustment in pCO2 by altering ventilation rate of lungs pH 7 is neutral, below is acidic, above is basic Adjustments in renal net acid excretion ACIDOSIS Abnormal pH may affect nervous system activity ALKALOSIS pH too low - acidosis pH too high - alkalosis Neurons become less excitable Neurons become hyperexcitable CNS depression (dysfunction) Fires action potentials at slightest signal Patients become confused & disoriented Condition Þrst shows up as sensory changes: Can result in slipping into a coma Numbness, tingling, then muscle t witches If CNS depression progresses: Severe cases = muscle t witches turn into Respiratory centres wonÕt function = death sustained contractions (tetanus): Paralyse respiratory muscles HCO3- BUFFER SYSTEM Important ECF buffer Regulated by both lungs & kidneys Buffer = Henderson-hasselbach equation INTERCALATED CELL ROLE IN ACIDOSIS AND ALKALOSIS ↓ Carbonic acid Changes in bicarbonate and pCO2 leads to pH changes Kidneys primarily regulate bicarbonate Lungs regulate pCO2 Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 METABOLIC ACIDOSIS METABOLIC ALKALOSIS Characterised by decreased ECF [HCO3-] & decreased pH Characterised by increased ECF [HCO3-] & increased pH As a result of: As a result of: Addition of nonvolatile acids Addition of nonvolatile alkali (ingestion of antacids) Loss of nonvolatile alkali Volume contraction Kidney fails to excrete sufÞcient net acid Loss of nonvolatile acids (vomiting ) ↳ Thus not able to replenish HCO3- Compensation: Compensation: ICF & ECF buffers ICF & ECF buffers Hypoventilation Hyperventilation Decreased renal acid excretion Increased renal net acid excretion RESPIRATORY ALKALOSIS RESPIRATORY ACIDOSIS Characterised by decreased pCO2 & increased pH Characterised by increased pCO2 & decreased pH As a result of: As a result of: Increased gas exchange across alveoli Decreased gas exchange across alveoli Compensation: Compensation: ICF buffers ICF buffers (only ICF since ONLY in lungs) Decreased renal net acid excretion Increased renal net acid excretion Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 STRUCTURE FUNCTIONAL CLASSIFICATION NOSE AND NASAL CAVITY Structure Lined with mucous membrane Contains ciliated epithelium Contains mucus secreting goblet cells Rich blood supply If nasal blood vessels dilate, oedema of PHARYNX (THROAT) mucous membranes, which obstruct air ways Functions of mucous membrane Functions as common passage for: Warms air Transport of food from oral cavity to oesophagi Moistens incoming air Transport of air from nasal cavity to larynx Filters incoming air During swallowing: Nose hair guards nostrils Soft palate raised reßexely Cilia & mucous trap dust and microorganisms Prevents food from entering nasal cavity Larynx elevated, breathing inhibited reßexly Prevents food entering trachea, which causes chiking TRACHEA (WINDPIPE) Structure: Pulmonary system Larynx -> trachea -> primary bronchi Lecture 1 Contains mucous membrane Lined with ciliated columnar epithelium C-shaped cartilaginous rings Fibrous connective tissue type Gives Þrmness to wall Prevents collapsing of air ways Functions: Filtering incoming air BRONCHIAL TREE Trachea branches into R & L primary bronchi LARYNX (VOICE BOX) Bronchi: Structure: Lined with ciliated columnar epithelium Continuous in posterior of trachea Consists of smooth muscle Þbres Inner surface has mucous membrane Flow: Functions: Voice production Act as switching mechanism to route air & food into proper channels Important note: As branching increases, walls think out Alveoli are designed to allow for increased CELLS OF CONDUCTING AIRWAYS surface area Ciliated columnar epithelial cells Mucociliary movement, sweeps foreign substances upwards Mucus secreting goblet cells CONDUCTING AIRWAYS Produce mucins Upper air ways have to condition air before Mucins play added role in innate immunity of mucosa it enters the alveoli Serous cells Condition through: In air way epithelium Warming air (37 ÔC) Produce lysozymes, IgA Ensures core body temp doesnÕt change Clara cells Alveoli not damaged by cold air Found in bronchioles Adding water vapour Produce anti-inßammatory substances (phospholipase A2 inhibitor Filter foreign material out Other cells Ensures that it doesnÕt reach alveoli Neuroendocrine cells - regulate smooth muscle function & growth Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 LUNGS An exchange surface, with a large surface area Thin walled, moist Enclosed by pleural membranes Occupy most of the thoracic cavity Protected by ribs and skin Right lung 3 lobes & left lung 2 lobes PLEURA Double layered sac surrounding each lung Parietal pleura: Outer membrane attached to inner surface of thoracic wall Visceral pleura: Membrane covers surface of each lung ¥ PLEURAL FLUID Fills pleural cavity Forms plural seal (holds outer surface of lungs I against inner surface of thoracic wall) ALVEOLI Reduces friction bet ween pleural membranes Series of interconnected sacs 300 mil alveoli present PLEURAL SAC Rich supply of pulmonary arteries Forms double membrane Allows max gas exchange bet ween surrounding lung PULMONARY PHYSIOLOGY alveoli & blood Each alveolus has single epithelium layer RESPIRATORY ZONE LECTURE 1 Respiratory bronchiole MAIN TYPES OF EPITHELIAL CELLS Alveolar duct Type 1 alveolar cells: Alveoli Larger, occupy 95% of alveolar surface area SITE OF GAS EXCHANGE Barrier bet ween air & blood Very thin - ensures rapid diffusion Type 2 alveolar cells: Smaller but thicker Synthesize & secrete surfactant Aids to expand lungs during breathing Mixes with ßuid lining alveoli Alveolar macrophages: Removes dust particles & other debris from alveolar spaces ALVEOLI COMPONENTS SPECIAL CELL TYPES OF RESPIRATORY Thin walls donÕt contain muscle Þbres OR GAS EXCHANGE AIRWAYS No muscle (doesnÕt contract self) Capillary endothelial cells: Connective tissue bet ween alveolar epithelial cells Form walls of capillaries Contains elastin & collagen Þbres Blood exchange surface Creates elastic recoil when lung tissue stretches Alveolar epithelial cells Alveolar and capillary membranes Type 1 pneumocytes Respiratory membrane Low enzymatic activities Low oxygen expenditure RESPIRATORY MEMBRANE Low resistance to gas exchange Membrane separating air within alveoli from blood Large alveolar cells: within pulmonary capillaries Type 2 pneumocytes Consists of: Secrete phospholipid that secretes surfactant Alveolar and capillary walls, 0.1-1.5 micrometer thick Increase metabolic activity Contains lysosome, microvilli, ER & vesicles Phagocytes Aid recovery of alveolar membrane after injury Alveolar macrophages or dust cells: Phagocytise inhaled dust particles = cough out Cells enter lymphatics by lymph nodes in hilum or lung Lymphocytes T-cells, B-cells, Natural Killee cells Adaptive immune system Pulmonary dendritic cells Antigen presenting cells (APC) of lungs = immunity Neutrophils and mast cells: Innate immune system of respiratory apparatus Downloaded by Lesedi Magane ([email protected])  " ! lOMoARcPSD|40661470 FUNCTIONS OF RESPIRATORY SYSTEM NON-RESPIRATORY FUNCTIONS Respiratory Non-respiratory 1.PROTECTIVE FUNCTION MAIN FUNCTIONS OF RESPIRATORY SYSTEM To supply body with oxygen & dispose CO2 4 DISTINCT PROCESSES: Pulmonary ventilation: Exchange of air bet ween external environment & lungs (breathing) External respiration: Exchange of O2 & CO2 bet ween lungs & blood in pulmonary capillaries Transport of respiratory gases: Transport of O2 & CO2 bet ween lungs & tissues Internal respiration: Exchange of O2 & CO2 bet ween tissue cells & blood in systemic capillaries Mechanism of Þltering foreign material: Mucus secretion traps foreign particles Contains antibodies/immunoglobulins Which disable the pathogens Cilia continuously beats upwards MUCOCILIARY ESCALATOR towards pharynx/throat mucous swallowed stomach acid will digest particles Saline solution " * T Essential for mucociliary escalator function PULMONARY PHYSIOLOGY LECTURE 2 7 2. METABOLIC FUNCTIONS OF PULMONARY ENDOTHELIA Prostaglandins E1, E2 F2a Conversion of ANG | to ANG || - which increases BP PULMONARY SURFACTANT Norepinephrine - vasoconstriction of blood vessels Secreted by type 2 alveolar epithelial cells Composition: 3. PRODUCTION OF PULMONARY SURFACTANT Phospholipids, proteins and ions Lowers surface tension of alveolar surface FUNCTIONS: Prevents collapsing of lung Decrease surface tension on alveoli surface *more info on surfactant to the left of the page * Reduces attractive forces of H-bonding by becoming interspersed bet ween H2O molecules 4. pH REGULATION Helps lung expansion during inspiration Role in acid-base balance Prevents lung collapse during expiration Lungs expel CO2 from body Decreases work of breathing needed Rapid ventilation decreases CO2, reducing H+ ions How does [H+] affect pulmonary ventilation? i pH -> pCO2 -> pulmonary ventilation pH -> pCO2 -> pulmonary ventilation SURFACE TENSION The force exerted by ßuid in alveoli to resist distension Lungs secrete & absorb ßuid Leaves very thin Þlm of ßuid IMPORTANT FOR SURVIVAL OF PREMATURE INFANTS Causes surface tension Newborn Respiratory Distress Syndrome H2O molecules at surface are attracted to other H2O Inadequate surfactant concentrations molecules by attractive forces Type 2 alveolar cells not mature enough to Force directed inward produce adequate amounts of surfactant alveoli pressure Result: surface tension, compliance Common cause of death in premie infants Downloaded by Lesedi Magane ([email protected])  " !"! lOMoARcPSD|40661470 LUNG PRESSURES Air pressure relationships INTRAPLEURAL PRESSURE (PpI) Atmospheric pressure Pressure in pleural cavity Pressure exerted by air (760 mmHg at sea level) Negative due to lack of air in interpleural space Respiratory pressure always described relative to Patm INTRAPULMONARY PRESSURE (PA) negative respiratory P = less than Patm aka intra-alveolar pressure positive respiratory P = greater than Patm Pressure within alveoli Equalises itself with Patm INSPIRATION TRANSPULMONARY PRESSURE 1. Inspiratory muscles contract Pressure diff across wall of lung Diaphragm descends PA - PpI Rib cage rises Keeps lungs against chest wall 2. Thoracic cavity volume PULMONARY VENTILATION 3. Lungs stretched Physical movement of air into and out of lungs Intrapulmonary volume Inspiration - ßow of air into lung 4. Intrapulmonary pressure drops Expiration - air leaving lung (To - 1mmHg) *air ßows from high P to low P 5. Air (gases) ßow into lungs down P gradient Until intrapulmonary pressure is 0 (=Patm) BOYLESÕS LAW Volume changes lead to gas pressure changes volume -> pressure volume -> pressure PULMONARY FUNCTION TESTS PULMONARY Monitor respiratory function by measuring rates/volumes of air movement PHYSIOLOGY Factors that affect respiratory vol & capacity LECTURE 3 PersonÕs size, sex, age, physical condition EXPIRATION RESPIRATORY STATIC VOLUMES 1. Inspiratory muscles relax TIDAL VOLUME (VT)/(TV) Diaphragm rises Amount of air moved in/out lungs in single Rib cage descends due to recoil of respiratory cycle costal cartilages Normal quiet breathing 2. Thoracic cavity volume Average 500 mL 3. Elastic lungs recoil passively INSPIRATORY RESERVE VOLUME (IRV) Amount of air you can breathe in beyond TV Intrapulmonary volume Usually bet ween 2100 and 3200 mL 4. Intrapulmonary pressure rises EXPIRATORY RESERVE VOLUME (ERV) To about +1mmHg Amount of air you can exhale beyond TV 5. Air (gases) ßow out of lungs down P gradient Approx 1200 mL Until intrapulmonary pressure is 0 RESIDUAL VOLUME Amount of sir left in lungs after max exhalation About 1200 mL LUNG STATIC CAPACITIES FUNCTIONAL VOLUME VITAL CAPACITY Air that reaches respiratory zone Max vol of air that can be moved during single Usually 350 mL breath after max inspiration VC= TV + IRV + ERV TOTAL LUNG CAPACITY Max vol of air lungs can hold TLC = TV + IRV + ERV + RV Males = 6000 mL, female = 4200 mL INSPIRATORY CAPACITY Amount of air you can inhale after normal exhalation IC = TV + IRV FUNCTIONAL RESIDUAL CAPACITY Amount of air in lungs after complete quiet cycle FRC = ERV + RV Downloaded by Lesedi Magane ([email protected])  ! lOMoARcPSD|40661470 DYNAMIC LUNG VOLUMES ALVEOLAR VENTILATION (VA) Now you consider ßow rate & time factor Amount of air reaching alveoli per minute Some air never reaches alveoli RESPIRATORY MINUTE VOLUME (RMV) Remains in conducting portion of lungs Amount of air inhaled & exhaled per minute Anatomic dead space - at rest 150 mL RMV = ventilation rate x tidal volume Formula: Used to measure pulmonary ventilation Va = ventilation rate x (tidal volume - dead space volume RESPIRATORY ADAPTATION * tidal volume -> alveolar ventilation rate Respiratory system adapts to changing O2 demands * ventilation rate -> alveolar ventilation by varying: Number of breaths per minute (ventilation rate) Normal adult resting : 12-18 breaths/min WHY DO THE PRESSURES DIFFER BETWEEN Volume of air moved per breath (tidal volume) BRONCHIAL CIRCULATION Part of systemic circulation (which supplies oxygenated blood to all tissues in the body) Aorta -> bronchial arteries -> supply bronchi, bronchioles and connective lung tissue DOESNÕT supply alveoli PULMONARY CIRCULATION Low pressure system - vascular resistance Supply deoxygenated blood to lungs Pulmonary trunk -> L & R pulmonary arteries - -> alveoli capillary bed -> L & R pulmonary veins Receives 100% of cardiac output 280 bil capillaries, supplying 300 mil alveoli Surface are for gas exchange ! : PULMONARY PHYSIOLOGY LECTURE 3 & 4 PULMONARY & SYSTEMIC CIRCULATIONS Gravity and distance: Pressure required to move blood from heart to target tissue, is proportional to distance bet ween the heart and the tissue Consequences of P differences: LV work load greater than RV Difference in wall thickness indicates difference in work load FUNCTIONAL ANATOMY OF PULMONARY CIRCULATION Thin walled blood vessels Pulmonary arteries have less smooth muscle than systemic arteries As a result, vessels are: Distensible and compressible Reduced vascular resistance, capitance (blood reservoir) BLOOD SUPPLY TO LUNGS Blue = deoxygenated blood Red = oxygenated blood Downloaded by Lesedi Magane ([email protected])  " ! " lOMoARcPSD|40661470 HYPOXIC PULMONARY VASOCONSTRICTION Alveolar hypoxia -> active vasoconstriction at level of precapillary VENTILATION - PERFUSION arteriole Tidal volume not evenly distributed due to uneven Mechanism not completely understood: distribution of blood ßow through the lungs Response occurs locally Pulmonary ventilation: DoesnÕt require innervation Amount of gas reaching alveoli Mediators unidentiÞed Pulmonary perfusion: Function: Blood ßow reaching alveoli Reduce mismatching of ventilation & *ventilation & perfusion must be tightly perfusion regulated for efÞcient gas exchange *not a strong response, why ? Limited muscle in pulmonary vasculature it LYMPHATIC SYSTEM COMPONENTS: Lymph - ßuid Lymph vessels Lymph nodes FUNCTIONS: Return ßuid & proteins to bloodstream Transport fats from digestive tract to the bloodstream Immune surveillance & defence *LYMPH HAS ONE WAY MOVEMENT* PULMONARY Lymphatic capillaries: Small bind-ending vessels with single PHYSIOLOGY layer endothelial cells LECTURE 4 Freely permeable to plasma proteins Collection of excess interstitial ßuid LUNGS : LYMPHATIC SYSTEM Comprehensive system: Drains towards hilar lymph nodes Lymph transported to lymphatic duct Reaches blood *poor lymphatic drainage -> pulmonary oedema HOW IS THE DRY STATE OF THE ALVEOLI MAINTAINED? 1. Low capillary and high on optic pressures in pulmonary capillaries 2. Drainage by pulmonary lymphatics 3. Surfactant: lowers alveoli recoil which reduces potential force PULMONARY OEDEMA that can pull ßuid to alveoli Pathophysiological condition 4. Na+/CL- pump in alveolar epithelial cells pumps to interstitium Abnormal increase of ßuid in & around alveoli Interferes with gas exchange Increases work of breathing Types : Cardiogenic ( high pressure) Non-cardiogenic (high permeability) NON-CARDIOGENIC PULMONARY OEDEMA Not primarily due to LV failure Fluid leaks from pulmonary capillaries Into interstitial space & pulmonary alveoli Due to pulmonary capillaries more permeable or leaky due to: Direct/indirect pathologic injury Hydrostatic pressure unaffected CARDIOGENIC PULMONARY OEDEMA Due to secondary LV failure Abnormal in cardiac output from LV Result in BP build up in LV & LA Leads to abnormal high BP in pulmonary circulation Result: pressure in pulmonary capillary hydrostatic pressure (>28mmHg) Fluid exits capillary at rate Accumulation of ßuid in pulmonary intersititium distance bet ween alveoli & pulmonary capillaries Impairs gas diffusion across pulmonary respiratory membrane Downloaded by Lesedi Magane ([email protected])  !!" " " ! " ! " lOMoARcPSD|40661470 ! ! PULMONARY VENTILATION (PV) RESISTANCE AGAINST VENTILATION Inßow of air from atmosphere to alveoli Work load by respiratory muscles when lung volume changes Determined by: Work load depends on resistance forces Mechanism of air ßow Respiratory muscles must overcome this to ensure Resistance against air ßow adequate ventilation MECHANISMS OF PV TYPES OF RESISTANCE FORCES Rhythm: 12-16 respirations/min ELASTIC RESISTANCE Contraction & relaxation of respiratory Surface tension (67%) muscles - under intricate nervous control Elastic tissue (33%) Compliance determines in lung ßow NONELASTIC RESISTANCE Air way resistance Airßow into alveoli is down P gradient Friction resistance Inertial resistance ELASTIC RESISTANCE Resistance of elastic Þbres in lungs to stretch during inspiration Deeper the inspiration : ALVEOLAR SURFACE TENSION I elastic resistance for muscles to overcome Liquid coating alveolar surface is always acting to work of breathing reduce the alveoli to the smallest possible size Compliance : ability to stretch Surfactant reduces the surface tension High - stretch easily Low - required more force FRICTION RESISTANCE Restrictive lung diseases ( Þbrosis or surfactant) Develops when visceral & parietal pleural membranes Factors inßuencing compliance: slide over each other during respiration Alveolar surface tension & surfactant Pleural ßuid reduces friction PULMONARY INERTIAL RESISTANCE FACTORS THAT LUNG COMPLIANCE PHYSIOLOGY Tissue resistance Scar tissue or Þbrosis Reduces natural lung resilience LECTURE 5 Dimensions of thorax & lungs during inspiration Blockage of small respiratory passages Must be overcome when dimensions change during With mucus or ßuid respiration Reduced production of surfactant ßexibility of thoracic cage or ability of AIRWAY RESISTANCE thorax to expand Resistance of air ways to incoming/outgoing gas ABNORMALITIES: COMPLIANCE Magnitude determined by: FIBROSIS Gas ßow rate ( rate -> resistance) Accumulation of particles in alveoli Radius of individual air way passages Dust, immune response, collagen Þbre deposition Lung volume Features : Respiration phase compliance & lung volume Autonomic nervous stimulation Restrictive disease Elastic recoil integrity NEONATAL RESPIRATORY DISTRESS SYNDROME - Local release of histamine, prostaglandins and Features: leukotriene - which cause bronchoconstriction alveolar surface tension Lack of surfactant production ABNORMALITIES : AIRWAY RESISTANCE (OBSTRUCTIVE) compliance Large/upper air way obstruction: Restrictive condition air way resistance due to physical object ELASTANCE Tumours Ability to return to resting volume when stretching Small air way obstruction: force is released Factors inßuencing: Bronchitis - air way resistance due to mucus Elastin Þbres in alveoli Asthma - air way resistance due to bronchoconstriction Surface tension ABNORMALITIES: COMPLIANCE & ELASTANCE FACTORS AFFECTING AIRWAY RESISTANCE Emphysema - destruction of elastin Þbres Features : compliance elastance (ßoppy lungs) Exhalation is now an active process Causes : smoking or genetic Obstructive disease Flow rate negatively affected Downloaded by Lesedi Magane ([email protected])  " " #! ## # lOMoARcPSD|40661470 # # RESPIRATORY SYSTEM Main function : DALTONÕS LAW Convert O2 CO2 Total P exerted by mixture of gases is the sum of PÕs Exchange & transport depends on: exerted independently by each gas in mixture Partial pressure difference Partial P directly proportional to gas % in mixture Gas solubility Gas moves down concentration gradient partial pressure -> partial pressure PARTIAL PRESSURE Pressure of single type of gas in mixture of gases HENRYÕS LAW When a mixture of gases is in contact with a liquid Each gas dissolved in liquid proportional to itÕs partial P Amount of gas that will dissolve depends on its solubility CO2 most soluble (20x more than O2) GAS EXCHANGE ACROSS RESPIRATORY MEMBRANE Bet ween alveoli & pulmonary capillary blood GAS SOLUBILITY Occurs by diffusion Temperature: constant in warm blooded humans Diffusion of O2 & CO2 is passive Solubility is: According to P differences across Chemical property referring to ability of alveolar-capillary barrier given substance (solute) to dissolve in a solvent P differences maintained by: Ventilation of alveoli Perfusion of pulmonary capillaries Alveolar ventilation brings O2 into & CO2 out Mixed venous blood brings CO2 into & takes up alveolar O2 AIR-BLOOD BARRIER PARTIAL PRESSURES OF GASES ! Very thin, only 0.1-1.5 micrometer thick PULMONARY Partial pressure in alveolar air P O2 = 100mmHg, P CO2 = 40 mmHg PHYSIOLOGY Partial pressure in arterial blood LECTURE 6 P O2 = 100 mmHg, P CO2 = 40 mmHg Partial pressure in venous blood P O2 = 40 mmHg, P CO2 = 46 mmHg GAS EXCHANGE O2 As blood passes through it takes up O2 O2 diffuses from alveolar air to blood PO2 higher (100mmHg) than venous blood (40 mmHg) Diffusion continues until equilibrium reached PO2 in blood leaving also about 100mmHg PO2 in tissue ßuid & body cells is only about 40 mmHg ?: O2 continuously used by cells O2 diffuses from blood to tissues as it ßows through capillaries until PO2 in blood = PO2 in tissues * Steep partial pressure gradient * Rapid equilibrium GAS EXCHANGE CO2 As blood passes through , CO2 diffuses from blood to alveolar air PCO2 in venous blood (46mmHg) than in (40mmHg) Diffusion continues until equilibrium reached PO2 in arterial blood leaving also about 40mmHg PCO2 in tissue ßuid & body cells is about 46 mmHg CO2 continuously used by cells CO2 diffuses from tissues to blood as it ßows through capillaries, until PCO2 in tissue = PCI2 in venous blood * Lower partial pressure gradient * High solubility, diffuses in equal amounts with oxygen Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 !! " FACTORS AFFECTING GAS DIFFUSION PARTIAL PRESSURE GRADIENT MEMBRANE THICKNESS Partial pressure gradient (most important) gradient m membrane thickness Membrane thickness (diffusion distance) Fluid in interstitial space diffusion diffusion Membrane surface area Ex: asthma -> inßamed air ways Ex: Þbrotic lung disease Solubility of gases (CO2 > O2) -> narrowed. FICKÕS LAW Vgas = volume of gas transferred per unit time Delta P = partial pressure difference for a gas across respiratory membrane Delta PO2 = 60 mmHg Delta PCO2 = 6 mmHg A = surface area for tension D = diffusion coefÞcient FLUID IN INTERSTITIAL SPACE MEMBRANE SURFACE AREA High D for CO2 compensates for Gases travel further to reach small delta PCO2 surface area capillary T = thickness of respiratory membrane diffusion Increases with pulmonary oedema & Þbrosis interstitial space Since elastic Þbres decrease, Inversely proportional to Vgas diffusion diffusion is proportional to Ex: pulmonary Edelman membrane surface area TRANSPORT OF OXYGEN Due to heart attack Ex: emphysema Dissolved in plasma (98%) PULMONARY HAEMOGLOBIN (Hb) Formed of 4 subunits PHYSIOLOGY Each subunit contains heme group LECTURE 6 & 7 attached to polypeptide chain (a or B) O2 binds to ferrous Fe-atom in heme group in rapid oxygenation rxn (HbO2) Connection weak bet ween Fe & O2 1 Hb molecule carries up to 4 O2Õs PERCENT OF Hb SATURATION WITH O2 Called: % Hb saturation When all Hb molecules are carrying max O2 load Hb is 100% saturated PO2 of blood is primary factor used to: Determine % Hb saturation *CONTINUES ON NEXT PAGE* Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 UPPER PLATEAU OF CURVEÕS PHYSIOLOGIC SIGNIFICANCE arterial blood from 100 to 60 mmHg Little in Hb saturation to 90% SufÞcient to meet body needs Provide good safety margin against changes in blood PO2, changes in pathological conditions & abnormal situations STEEP LOWER PART OF THE CURVE In systemic capillaries- tissue (PO2 range 0-60 mmHg) At PO2 40 mmHg of venous blood More than 70% Hb saturation with O2 At PO2 20 mmHg (exercise) 30% Hb saturation with O2 PHYSIOLOGICAL SIGNIFICANCE: Small in tissue PO2 leads to : Rapid desaturation of Hb IMPORTANT POINTS FROM GRAPH Large amounts of O2 released to tissues In arterial blood (with high PO2) If arterial PO2 to below 60 mmHg: 97% Hb saturation PULMONARY Even more rapid desaturation of Hb In venous blood (with low PO2) PHYSIOLOGY O2 released to tissues 75% Hb saturation At the lung - high alveolar PO2 (100 mmHg) LECTURE 7 FACTORS THAT SHIFT O2-Hb curve Hb automatically binds to O2 Shift to RIGHT causes: At the tissues - low tissue PO2 (40 mmHg) Decreased Hb afÞnity to O2, O2 release to tissues Hb automatically releases O2 Shift to LEFT causes: TOTAL ARTERIAL O2 CONTENT Increased Hb afÞnity to O2, O2 release to tissues FACTORS: pH = will shift to left, will shift to right Temp = will shift to right, will shift to left PCO2 = will shift to right, will shift to the left CO2 will compete with O2, thatÕs why. 2,3DPG = will shift to right, will shift to left Metabolic compound released during hypoxia Downloaded by Lesedi Magane ([email protected])  " lOMoARcPSD|40661470 FETAL AND MATERNAL Hb ABNORMALITIES Fetal Hb (HbF) has higher O2 afÞnity than adult Hb (HbA) Hyperoxia HbF contains 2a, 2y polypeptide chains and no B chain Opposite of hypoxia B chain only found in HbA Excessive oxygen supply HbF can carry up to 30% more O2 Hypercapnia Materials blood O2 transferred to fetal blood Abnormally CO2 levels in blood May be caused by: Hypoventilation & lung disease OXYGEN PULMONARY Key factor for aerobic metabolism PHYSIOLOGY No storage system in tissues Continuous supply is needed LECTURE 8 CARBON DIOXIDE Volatile waste product of aerobic metabolism Production in resting adult = 200mL/min Can six times during exercise Produced almost entirely in mitochondria Importance of CO2 estimation: Lies in fact that ventilator control system is more responsive to PCO2 changes TRANSPORT OF CO2 Dissolved in plasma (less than 7%) Chemically bound to Hb (more than 23%) Carries in RBCÕs as carbaminohemoglobin 70% converted to bicarbonate Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 CONTROL OF VENTILATION RESPIRATORY CENTERS Controlled by respiratory centre of upper brain stem Dorsal respiratory group (medulla): Medulla oblongata and pons Mainly causes respiration Ventral respiratory group (medulla): OTHER BRAIN REGIONS AFFECTING VENTILATION Causes forced expiration & forced inspiration Cerebral cortex: Apneustic centre (lower pons): Voluntary control Promote inspiration Limbic system and hypothalamus: Controls intensity of breathing Emotional stress Pneumotaxic centre (upper pons): Inhibits apneustic center PROCESSING UNIT/ INTEGRATION CENTER Inhibits inspiration Helps control rate & pattern of breathing PULMONARY REGULATION OF VENTILATION LECTURE 9 Specialised cells/organs that respond to a change in chemical composition of the blood or other ßuid Central chemoreceptors: Located in medulla Respond to changes in PCO2 Peripheral chemoreceptors: Located in carotid and aortic arteries Sense changes in PO2, pH and PCO2 Specialised glomus cells I Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 LUNG RECEPTORS Pulmonary stretch receptors : (Slowly adapting pulmonary stretch receptors) Responsible for Hering-Breuer reßex Irritant receptors: (Rapidly-adapting pulmonary stretch receptors) J-receptors : (Juxta-capillary receptors) Bronchial C Þbers REGULATION OF VENTILATION 1. Respiratory neurons in medulla Control inspiratory muscles Controls expiratory muscles 2. Neurons in the pons Integrate sensory information Interact with medullary neurons To inßuence ventilation 3. Rhythmic pattern of breathing Arises from neural net work of spontaneously discharging neurons 4. Ventilation subject to continuous modulation by Chemoreceptor- and mechanireceptor linked reßexes And by higher brain centers PROTECTIVE REFLEXES Respond to physical injury or irritation (irritant receptors in air way) Bronchoconstriction Irritant receptors in air way mucosa send signals through sensory neurons Sneezing Coughing Hering-Breuer inßation reßex Limits tidal volume Prevents over stretching of lung (mechanoreceptors) Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 QUICK SKIN FACTS Largest organ (surface area: 1.6-1.9 m ) DERMIS Thickness of 1 to 2 mm Made of connective tissue Thinnest on eyelids (0.5 - 1 mm) Consists of different cells: Thickest on soles and palms (1.5mm) Fibroblasts, macrophages, mast Weighs 4kg cells & white blood cells 2 regions: Contains: Epidermis - outermost regions Blood vessels, lymph vessels and nerve endings Dermis - inner thicker region Collagen Þbres (provide Þrmness) Elastic Þbres (provide elasticity) EPIDERMIS Sebaceous, sweat glands & hair SuperÞcial layer Consists of 2 layers: Composed of : stratiÞed squamous epithelium Papillary layer - outer layer No blood vessels & no lymphatic ducts Reticular layer - inner layer Continuously rubbed off and replaced from deeper layers Cell division takes place in deepest basal layer DERMIS : SWEAT GLANDS New cells pushed upwards 1. ECCRINE GLANDS Consists of 4 distinct cell types In palms, soles of feet and forehead Secrete light secretion of water & salt (sweat) Ducts open onto skin surface CELLS OF EPIDERMIS 2. APROCRINE GLANDS 1. Keratinocytes SKIN Found in genitalia, anus and axillae (armpits) Most abundant (95%) Secrete waxy or viscous secretion Produces Þbrous protein - keratin Fear or sexual excitement Function: protection and waterproof Ducts open into hair follicle 2. Melanocytes MODIFIED APOCRINE GLANDS Produces brown pigment - melanin 1. Ceruminous glands Responsible for skim colour In external ear canal - produce ear ear Protects against UV radiation 2. Mammary glands 3. LangerhanÕs cells In breast - produces milk Epidermal macrophages for immunity system 3. Ciliary glands Clears area of debris and pathogens On margins of eyelid - produces lipids 4. Merkel cells Sensory cells for touch sensation Makes contact with nerve endings in dermis DERMIS : SEBACEOUS GLANDS Found all over body (except palms and soles) At side of hair follicle, opens into hair follicle EPIDERMIS Secretes oily substance 5 layers: ↳ sebum (mix of cholesterol and fats) 1. Stratum corneum FUNCTIONS: 2. Stratum lucidum - found in areas of thick skin Keeps skin smooth and prevents dehydration 3. Stratum granulosum Prevents infection and heat loss 4. Stratum spinosum - located above basal membrane ↳ (especially in cold climates) 5. Stratum germinativum - where keratinocytes and melanocytes are germinated from SKIN FUNCTIONS 1. Protection Protects underlying layer from injury, dehydration and pathogens PIGMENTATION OF SKIN 2. Regulation of body temperature 1. Freckles Constriction and dilation of blood vessels Accumulation of melanin Heat loss - sweat gland secretions 2. Vitiligo Prevent heat loss - sebum secretion & insulating layer Patches of depigmented skin 3. Cutaneous sensation Contains few/no melanocytes that canÕt produce melanin By sensory receptors of touch, pain, pressure, temp etc. Cause: not clearly known 4. Metabolic functions 3. Albinism Synthesis of Vit D in dermal blood vessels Depigmented skin, melanocytes ARE present 5. Storage of fat Melanin NOT produced due to a sense of tyrosinase enzyme 6. Excretion Thus not possible to convert tyrosine to melanin Nitrogenous waste eliminated through sweat Recessive disorder Downloaded by Lesedi Magane ([email protected])  lOMoARcPSD|40661470 DERMIS : HAIR & Strands of dead keratinized cells SUBCUTANEOUS LAYER (HYPODERMIS) ⑧ Produced by hair follicles O Located below dermis & Develop from group of epidermal cells ⑥ Contains fat cells O Consists of root & shaft G Rich supply of blood vessels ⑧ Expanded deep end - a hair bulb FUNCTIONS O Has papilla with blood vessels at root ↳ Store fat ↳ Act as insulator ⑧ Sensory nerve endings wrap around each hair O Smooth muscle (arrectores pilorium) ↳ Lies bet ween epidermis of each hair follicle CUTANEOUS CIRCULATION a Piloerection (goosebumps) * Blood supply of the skin ↳ Contraction of smooth muscle, pulls hair erect & No blood vessels in epidermis ↳ Prevent heat loss ↳ but there ARE blood vessels in dermis FUNCTIONS OF HAIR: O Arteries reach skin from subcutaneous layer & Prevent heat loss O Looped capillaries and veins = arteriovenous shunts ⑤ Detect presence of insects on skin ↳ In Þngers, toes, palms and earlobes & Protect scalp from physical trauma and sunlight ↳ Prevents heat loss G Constriction and dilation of blood vessels by SNS ↳ Determines amount of blood ßow in skin BODY TEMPERATURE g 3) Temperature regulation & Range is narrow within 1 degree (36 - 37.5 C ) As blood reaches surface of skin = heat is lost O Temperature inßuences metabolic processes ⑧ High temp = destroys proteins - & Low temp = inhibit enzyme reactions = prevent biochemical processes BODY TEMPERATURE EXTRA INFO ⑧ Changes corrected by homeostasis ⑧ Measured with thermometer Skin plays major role in thermoregulation Rectal temp is 0.5 C higher than oral temp g * O S Blood serves as major agent of heat transfer BODY TEMPERATURE MEASURING O Body can survive decrease in core temp ↳ In anus (rectal) ↳ Up to 14 C g ↳ In mouth (oral) THERMOREGULATION G Increase in temp more than 7 C is FATAL g ↳ Under arm (axillary) ↳ In the ear (tympanic) ↳ On forehead skin S ↳ Over temporal artery (temporal) MECHANISM OF HEAT EXCHANGE &