DENT2052 Course Summary (Part B)

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1 DENT2052 Course Summary (Part B) MODULE IVA RESPIRATORY PHYSIOLOGY (Dr H Ernst) 2 MODULE IVB RESPIRATORY PHARMACOLOGY (Dr M Cheesman) 24 MODULE V RENAL PHYSIOLOGY (A/Prof C Sernia) 32 Produced by cyrion TM All rights reserved. 1

Module IVA Respiratory Physiology RESPIRATORY MECHANICS The lungs occupy most of the thoracic cavity (or chest cavity).

The diaphragm forms the floor of the thoracic cavity, separating it completely from the abdominal cavity.

The layer of the pleural sac that closely adheres to the surface of the lung is called the visceral pleura.

2 Module IVA Respiratory Physiology RESPIRATORY MECHANICS The lungs occupy most of the thoracic cavity (or chest cavity). The outer thoracic wall (outer chest wall) is formed by 12 pairs of ribs, providing protection for the lungs and heart. The diaphragm forms the floor of the thoracic cavity, separating it completely from the abdominal cavity. o A double-walled, closed sac called the pleural sac (or intrapleural space) separates each lung from the thoracic wall. The layer of the pleural sac that closely adheres to the surface of the lung is called the visceral pleura. This visceral pleura reflects back on itself to form another layer lining the interior of the thoracic wall, called the parietal pleura. The interior of the pleural sac is called the pleural cavity this cavity has been greatly exaggerated in the adjacent diagram (in reality the visceral and pleural pleura are in close contact with one another). The surfaces of the pleura secrete a thin intrapleural fluid, lubricating the pleural surfaces as they slide past each other during respiration. o A common analogy for the pleural sac is pushing a lollipop into a water-filled balloon this produces a relationship similar to that of the double-walled, closed pleural sac surrounding the lung, separating it from the thoracic wall. Air tends to move from a region of higher pressure to a region of lower pressure (i.e. down a pressure gradient). Three different pressure considerations are of particular importance: o Atmospheric pressure is the pressure exerted by the weight of air in the atmosphere on objects on the Earth s surface. At sea level, this value is 760 mmhg. This value can fluctuate with different altitudes and weather conditions. o Intra-alveolar pressure is the pressure within the alveoli. As the alveoli are connected to the atmosphere via the conducting airways, air can move between the two environments at will, and thus the intra-alveolar pressure equilibrates with atmospheric pressure (760 mmhg). 2

LUNG VOLUMES Lung volumes are determined by four factors: o Size Tall people have larger lungs than short people o Age Older people have stiffer lungs and cannot inflate them as well o Gender Males

For the average male: o During maximal inspiration, the lungs can inflate to a maximum volume of 5700 ml this is the total lung capacity.

Thus, the maximum volume of air that can be moved out during a maximal expiration is 5700 1200 = 4500 ml this is the vital capacity.

During a normal, quiet inspiration, the lungs inflate to a capacity of 2700 ml. Thus, each typical breath inspires about 500 ml of air this is the tidal volume.

3 LUNG VOLUMES Lung volumes are determined by four factors: o Size Tall people have larger lungs than short people o Age Older people have stiffer lungs and cannot inflate them as well o Gender Males have larger lungs than females o Anatomical build This determines the volume of the thoracic cavity and diaphragm Lung volumes vary depending on the force of respiration. For the average male: o During maximal inspiration, the lungs can inflate to a maximum volume of 5700 ml this is the total lung capacity. At the end of a maximal expiration, the lungs deflate to a minimum volume of 1200 ml this is the residual volume (the lungs can never be fully emptied due to small dynamic airway collapse). Thus, the maximum volume of air that can be moved out during a maximal expiration is = 4500 ml this is the vital capacity. o At the end of a normal, quiet expiration, the lungs deflate to a capacity of 2200 ml this is the functional residual capacity (a good clinical indicator for the elastic recoil). During a normal, quiet inspiration, the lungs inflate to a capacity of 2700 ml. Thus, each typical breath inspires about 500 ml of air this is the tidal volume. o The inspiratory reserve volume (IRV) is the extra volume of air that can be maximally inspired over and above the resting tidal volume. The expiratory reserve volume (ERV) thereby refers to the extra volume of air maximally expired. Together, the IRV, ERV and tidal volume make up the vital capacity, and the vital capacity together with the residual volume make up the total lung capacity. These changes in lung volumes can be visually represented with a spirogram, shown above. 3

CONTROL OF RESPIRATION Control of respiration involves three distinct components: o Factors responsible for generating the alternating inspiration/expiration rhythm o Factors that regulate the

o The medullary respiratory centre is the primary control centre, providing output to the respiratory muscles.

4 CONTROL OF RESPIRATION Control of respiration involves three distinct components: o Factors responsible for generating the alternating inspiration/expiration rhythm o Factors that regulate the magnitude of ventilation to match body needs o Factors that modify respiratory activity to serve other purposes (e.g. speech, coughing, holding breath) The respiratory control centres in the brainstem establish the rhythmic pattern of breathing. o The medullary respiratory centre is the primary control centre, providing output to the respiratory muscles. It consists of two neuronal clusters: The dorsal respiratory group consists mostly of inspiratory neurons which provide motor innervation to the diaphragm and external intercostal muscles during passive, quiet expiration only. Firing of these neurons cause inspiration to take place, and when they cease firing, expiration occurs. The ventral respiratory group consists of both inspiratory and expiratory neurons, which not only innervate the diaphragm and external intercostal muscles, but also innervate the abdominal and internal intercostal muscles. This group functions only during active, forced expiration (the dorsal group ceases all activity). Both these groups adjust the ventilation by detecting changes in the brain ECF via central chemoreceptors (see later). o The pons respiratory centres include the pneumotaxic centre and apneustic centre these influence output from the medullary respiratory centre. The pneumotaxic centre sends impulses to the dorsal respiratory group that help switch off the inspiratory neurons, limiting the duration of inspiration. The apneustic centre prevents the inspiratory neurons from switching off, boosting inspiratory activity. However, it is dominated by the pneumotaxic centre. The oxygen-haemoglobin dissociation curve expresses the relationship between the partial pressure of oxygen (P O2 ) in the blood and the percent haemoglobin (% Hb) saturation (the extent to which Hb is bound with O 2 ). o At the upper end between a P O2 of mmhg, o the curve plateaus this means a significant rise in P O2 will only produce a small increase in % Hb saturation. At the lower end between a P O2 of 0 60 mmhg, the curve is steep this means a small rise in P O2 will produce a significant increase in % Hb saturation. 4

5 ARTERIAL BLOOD GAS REPORTS An arterial blood gas (ABG) report is a blood test performed using blood from an artery. A thin needle and syringe is used to draw out a small volume of blood, usually from the radial artery at the wrist. The sample is then analysed to determine a variety of values: Analyte Abbreviation Explanation Predicted range Temperature Temp This is simply the internal temperature of the body. 37 C This is the fraction or percentage of oxygen in the Fraction of FiO inspired oxygen 2 space being measured. Natural air includes 20.9% oxygen, equivalent to an FiO 2 of Barometric This is simply the standard atmospheric pressure at bar. press. pressure sea level. 760 mmhg ph ph The ph indicates the level of H +, which shows whether the patient has acidosis or alkalosis Partial pressure of carbon dioxide Partial pressure of oxygen Bicarbonate levels Alveolararterial gradient p CO2 p O2 Bicarb p A-a O 2 The p CO2 indicates the level of CO 2 production and elimination, which shows whether the patient is experiencing hypo- or hyperventilation. The p O2 indicates the level of O 2 in the body, again showing whether the patient is experiencing hypo- or hyperventilation. The level of bicarbonate indicates whether renal compensation has started or not, and thus whether the condition is acute or chronic. The p A-a O 2 is a measure of the difference between the alveolar (A) and arterial (a) concentration of oxygen. It shows whether or not a physiological shunt is present, and whether there is a V/Q mismatch. EXAMPLE: Observe the adjacent ABG report and diagnose the patient. o The first point of reference should be the p CO2, as o o this is always inversely proportional to ventilation. On the ABG, the patient s p CO2 is below the normal range, suggesting that the patient is breathing too much and hyperventilating mmhg mmhg mm/l < 10 mmhg Pred. range Observed Temp 37 FiO bar. press. 760 ph p CO mmhg p O mmhg Bicarb mm/l p A-a O 2 < 10 4 mmhg Hyperventilation would result in more oxygen being taken in, increasing the p O2. On the ABG, the patient s p O2 is indeed above the normal range, concurring with the explanation. The decreased p CO2 would also decrease the concentration of CO 2 -induced H + ions, increasing the ph. On the ABG, the patient ph is indeed above the normal range, fitting with the explanation. Thus the patient is experiencing respiratory alkalosis. o Renal compensation for ph changes will cause the kidneys to secrete more bicarbonate. However, this compensation takes a few days to initiate. On the ABG, the patient s bicarbonate levels are within the normal range, suggesting that renal compensation has not started yet. Thus the condition is still in an acute state (less than few hours old). o Lastly, on the ABG, the p A-a O 2 is also within the normal range, suggesting that there is no physiological shunting occurring. The overall diagnosis is acute respiratory alkalosis due to hyperventilation. 5

Module IVB Respiratory Pharmacology ASTHMA Recall the basic physiology of the respiratory system: o On the external surface of the bronchioles, smooth muscle bands wrap around the entire diameter.

o On the internal surface of the bronchioles, a ciliated lining is present to increase the gas exchange (also optimised by a 1 2 membrane thickness proximity of the alveolar lumen to the blood

6 Module IVB Respiratory Pharmacology ASTHMA Recall the basic physiology of the respiratory system: o On the external surface of the bronchioles, smooth muscle bands wrap around the entire diameter. These bands of muscle can expand and contract. o On the internal surface of the bronchioles, a ciliated lining is present to increase the gas exchange (also optimised by a 1 2 membrane thickness proximity of the alveolar lumen to the blood vessel). There are also gland ducts which secrete mucus to trap foreign particles, preventing their interference with gas exchange this mucus is swept upwards towards the pharynx by the epithelial motion of the cilia. o The residual volume is the amount of air that remains in the lungs after a maximal exhalation. In an asthma attack, all three of the above physiological factors are affected: o Asthma triggers (e.g. smoke) irritate the bronchioles, causing the smooth muscle bands on the external surface to tighten and contract abnormally, resulting in increased bronchoconstriction. o This results in inflammation, causing the inner lining of the bronchioles to become red and swollen, further narrowing the airways and trapping air in the alveoli. o Mucus secretion is also increased in an attempt to trap the foreign particles, but this simply worsens the problem the excess mucus blocks the airways and prevents air movement in and out of the alveoli. o These factors all lead to an increase in residual volume and a reduction in forced expiratory volume (FEV1) this means that breathing is still possible, but breathing out is inhibited, so the volume of air breathed in decreases. o The classical symptoms of bronchial asthma will be present this includes intermittent attacks of wheezing, shortness of breath, and regular coughing events. 6

Module V Renal Physiology GENERAL FEATURES The renal system (or urinary system) consists of the kidneys and the structures that carry urine from the kidneys to the outside.

o Each kidney is supplied by a renal artery and a renal vein. The kidney acts on the plasma flowing through it to produce urine.

The bladder is periodically emptied via the urethra. o Each kidney is composed of about 1 million nephrons these are the basic functional units of the kidney.

7 Module V Renal Physiology GENERAL FEATURES The renal system (or urinary system) consists of the kidneys and the structures that carry urine from the kidneys to the outside. The kidneys are a pair of bean-shaped organs found at the back of the abdominal cavity, slightly above the waistline (at the level of the 12 th rib). o Each kidney is supplied by a renal artery and a renal vein. The kidney acts on the plasma flowing through it to produce urine. o After urine is formed, it drains into a central collecting cavity called the renal pelvis. From there, urine is channelled into the ureter, to be carried to the urinary bladder where it is stored. The bladder is periodically emptied via the urethra. o Each kidney is composed of about 1 million nephrons these are the basic functional units of the kidney. The arrangement of nephrons gives rise to two distinct regions an outer renal cortex and an inner renal medulla. Each nephron consists of a vascular component and a tubular component. o The vascular component begins at the renal artery, which gives off an afferent arteriole. This arteriole enters Bowman s capsule to deliver blood to the glomerulus this is a ball-like tuft of capillaries where water/solutes is filtered from the blood. The blood then leaves via the efferent arteriole, which quickly subdivides into the peritubular capillaries. These capillaries are interwoven around the tubular system, supplying the renal tissue with blood. The capillaries eventually rejoin the renal vein, allowing blood to leave the kidney. o The tubular component is a continuous, fluid-filled tube formed by a single layer of epithelial cells. It begins at Bowman s capsule an 7

EXCRETION The ECF osmolarity (solute concentration) in the kidneys depends on the H 2 O : solute ratio (relative amount of H 2 O compared to solute). This ratio is generally constant in the ECF.

o If too much H 2 O is present relative to solute, the body fluids will be hypotonic (or hyposmotic) at < 300 mosm/l (too dilute).

8 EXCRETION The ECF osmolarity (solute concentration) in the kidneys depends on the H 2 O : solute ratio (relative amount of H 2 O compared to solute). This ratio is generally constant in the ECF. o At a normal fluid balance and solute concentration, the body fluids are isotonic at 300 mosm/l. o If too much H 2 O is present relative to solute, the body fluids will be hypotonic (or hyposmotic) at < 300 mosm/l (too dilute). o If too little H 2 O is present relative to solute, the body fluids will be hypertonic (or hyperosmotic) at > 300 mosm/l (too concentrated). As H 2 O reabsorption is caused by an osmotic gradient between the tubular lumen and the surrounding interstitial fluid, it would be logically to assume that the kidneys could not excrete urine more or less concentrated than the body fluids. However, there is a large vertical osmotic gradient maintained in the interstitial fluid of the medulla this refers to the progressively increasing osmolarity with deeper areas of the kidneys. This gradient enables the kidney to produce urine that ranges in concentration from 100 (hypotonic) to 1200 mosm (hypertonic), depending on the body s state of hydration: o If the body has too much water in the ECF, then urine will be hypotonic. o If the body has too little water in the ECF, then urine will be hypertonic. The vertical osmotic gradient is established by a mechanism known as countercurrent multiplication in the loop of Henle. Recall that in juxtamedullary nephrons, the loop of Henle is very long and dips down into the medulla, with the vasa recta closely parallelling its passage. The loop of Henle establishes the gradient, their vasa recta preserve this gradient, and the collecting ducts of the nephrons use this gradient to produce urine of varying concentrations. The two limbs of the loop of Henle must be functionally distinguished: o The descending limb of the loop of Henle is highly permeable to H 2 O as it has many open aquaporins to allow the passage of water. It also does not actively extrude Na +, but may be passively permeable to Na + o The ascending limb of the loop of Henle is always impermeable to H 2 O, but also actively transports NaCl out of the tubular lumen into the interstitial fluid. Thus, salt leaves the tubular fluid without H 2 O following along. As the flow in these adjacent limbs of the loop moves in opposite directions, the flow is referred to as countercurrent. The close proximity and countercurrent flow of the two limbs allow important interactions between them: 0. Initially, before the vertical osmotic gradient is established, the medullary interstitial fluid and tubular fluid concentration is uniformly 300 mosm. 8

By getting rid of Na + and H 2 O, diuretics reduce the ECF volume, which in turn reduces venous return, cardiac output, and thus blood pressure.

9 DIURETICS Diuretics are medicinal compounds that help the body to get rid of sodium and water. They are mainly used in cardiovascular pathology such as hypertension and congestive heart failure, where blood pressure builds up. By getting rid of Na + and H 2 O, diuretics reduce the ECF volume, which in turn reduces venous return, cardiac output, and thus blood pressure. There are four types of diuretics: o OSMOTIC DIURETICS Osmotic diuretics (e.g. mannitol, urea, glycerine, isorbide) are pharmacologically inert substances with a low molecular weight that are freely filtered in the glomerulus, but only undergo limited reabsorption by the renal tubule. SITE They act on the PCT and the loop of Henle (permeable to water). MECHANISM Their main effect is to inhibit reabsorption of H 2 O they do this by increasing the osmolarity of the plasma and tubular fluid, and also by reducing its medullary tonicity (the ability of the plasma/fluid to exert an osmotic pressure upon a membrane). As osmotic diuretics cannot be reabsorbed from the urine, a larger volume of fluid remains within the PCT, preventing equilibrium from being established across the tubule membrane. RESPONSE As a result, excretion of water, and all electrolytes disolved in the fluid (including Na +, K +, Ca 2+, etc.), is increased. ABSORPTION AND ELIMINATION They can either be injected intravenously (IV) into the plasma (mannitol, urea) or administered orally (glycerin, isorbide). They have a short duration of action (0.5 2 hrs). o LOOP (HIGH CEILING) DIURETICS Loop diuretics (e.g. furosemide, bumetanide) are the most powerful diuretics, capable of causing excretion of 15 25% Na. SITE They act on the thick ascending limb of the loop of Henle. MECHANISM Their main effect is to inhibit reabsorption of Na +, K + and Cl they do this by interacting with the Cl binding site of the Na + /K + /2Cl symporter, inhibiting its action (H 2 O also does not get reabsorbed as a result). They also inhibit the transport of Ca 2+ and Mg 2+. RESPONSE As a result, excretion of Na +, K +, Cl, Ca 2+ and Mg 2+ is increased. As water is trapped in the collecting duct, urine flow is also greatly increased (described as torrential urine flow ). The resultant volume depletion tends to induce the release of renin and reflexly activate the sympathetic nervous system. ABSORPTION AND ELIMINATION When given orally, around 60 90% of the drug is absorbed. Elimination is via secretion in the PCT (organic acids secretory pathway). 9

Physiology of Respiration

Physiology of Respiration External Respiration = pulmonary ventilation breathing involves 2 processes: inspiration expiration Inspiration an active process involves contraction of diaphragm innervated