Physiology new 3

A 56 year old lady reports incontinence mainly when walking the dog. A bladder diary is inconclusive. What is the most appropriate investigation?

Intravenous urography 1% Urodynamic studies 87% Flexible cystoscopy 3% Micturating cystourethrogram 8% Rigid cystoscopy 1% Urodynamic studies are indicated when there is diagnostic uncertainty or plans for surgery.

Which of the following is not linked to excess glucocorticoids?

Osteonecrosis 22% Osteoporosis 4% Hypokalaemia 20% Hyponatraemia 43% Growth retardation in children 10% There are many adverse effects associated with excess glucocorticoids. Thinning of the skin, osteonecrosis and osteoporosis are all common. Steroids are associated with retention of sodium and water. Potassium loss may occur and hypokalaemic alkalosis has been reported.

Renal Physiology

Overview Each nephron is supplied with blood from an afferent arteriole that opens onto the glomerular capillary bed. Blood then flows to an efferent arteriole, supplying the peritubular capillaries and medullary vasa recta. The kidney receives up to 25% of resting cardiac output. Control of blood flow The kidney is able to autoregulate its blood flow between systolic pressures of 80- 180mmHg so there is little variation in renal blood flow. This is achieved by myogenic control of arteriolar tone, both sympathetic input and hormonal signals (e.g. renin) are responsible. Glomerular structure and function Blood inside the glomerulus has considerable hydrostatic pressure. The basement membrane has pores that will allow free diffusion of smaller solutes, larger negatively charged molecules such as albumin are unable to cross. The glomerular filtration rate (GFR) is equal to the concentration of a solute in the urine, times the volume of urine produced per minute, divided by the plasma concentration (assuming that the solute is freely diffused e.g. inulin). In clinical practice creatinine is used because it is subjected to very little proximal tubular secretion. Although subject to variability, the typical GFR is 125ml per minute. Glomerular filtration rate = Total volume of plasma per unit time leaving the capillaries and entering the bowman's capsule Renal clearance = volume plasma from which a substance is removed per minute by the kidneys Substances used to measure GFR have the following features: 1. Inert 2. Free filtration from the plasma at the glomerulus (not protein bound) 3. Not absorbed or secreted at the tubules 4. Plasma concentration constant during urine collection Examples: inulin, creatinine GFR = urine concentration (mmol/l) x urine volume (ml/min) -----------------------------------------------------

Oxygen Transport

Oxygen transport Almost all oxygen is transported within erythrocytes. It has limited solubility and only 1% is carried as solution. Therefore the amount of oxygen transported will depend upon haemoglobin concentration and its degree of saturation. Haemoglobin Globular protein composed of 4 subunits. Haem consists of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds; one with oxygen and the other with a polypeptide chain. There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but is able to bind to carbon dioxide and hydrogen ions, the beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules. Oxygen dissociation curve The oxygen dissociation curve describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood. It is not affected by haemoglobin concentration. Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the right Haldane effect Shifts to left = for given oxygen tension there is increased saturation of Hb with oxygen i.e. Decreased oxygen delivery to tissues Bohr effect Shifts to right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e. Enhanced oxygen delivery to tissues Image sourced from Wikipedia Shifts to Left = Lower oxygen delivery HbF, methaemoglobin, carboxyhaemoglobin low [H+] (alkali) low pCO2 low 2,3-DPG low temperature Shifts to Right = Raised oxygen delivery raised [H+] (acidic) raised pCO2 raised 2,3-DPG* raised temperature *2,3-diphosphoglycerate

Which part of the ECG represents atrial depolarization?

P wave 88% Q wave 1% T wave 1% QRS complex 6% P-R interval 4% The P wave represents atrial depolarization. Note that atrial repolarization is obscured within the QRS complex

The normal ECG

P wave Represents the wave of depolarization that spreads from the SA node throughout the atria Lasts 0.08 to 0.1 seconds (80-100 ms) The isoelectric period after the P wave represents the time in which the impulse is traveling within the AV node P-R interval Time from the onset of the P wave to the beginning of the QRS complex Ranges from 0.12 to 0.20 seconds in duration Represents the time between the onset of atrial depolarization and the onset of ventricular depolarization QRS complex Represents ventricular depolarization Duration of the QRS complex is normally 0.06 to 0.1 seconds ST segment Isoelectric period following the QRS Represents period which the entire ventricle is depolarized and roughly corresponds to the plateau phase of the ventricular action potential T wave Represents ventricular repolarization and is longer in duration than depolarization A small positive U wave may follow the T wave which represents the last remnants of ventricular repolarization. Q-T interval Represents the time for both ventricular depolarization and repolarization to occur, and therefore roughly estimates the duration of an average ventricular action potential. Interval ranges from 0.2 to 0.4 seconds depending upon heart rate. At high heart rates, ventricular action potentials shorten in duration, which decreases the Q-T interval. Therefore the Q-T interval is expressed as a 'corrected Q-T (QTc)' by taking the Q-T interval and dividing it by the square root of the R-R interval (interval between ventricular depolarizations). This allows an assessment of the Q-T interval that is independent of heart rate. Normal corrected Q-Tc interval is less than 0.44 seconds.

Control of ventilation

- Control of ventilation is coordinated by the respiratory centres, chemoreceptors, lung receptors and muscles. Automatic, involuntary control of respiration occurs from the medulla. The respiratory centres control the respiratory rate and the depth of respiration. Respiratory centres Medullary respiratory centre Inspiratory and expiratory neurones. Has ventral group which controls forced voluntary expiration and the dorsal group controls inspiration. Depressed by opiates. Apneustic centre Lower pons Stimulates inspiration - activates and prolongs inhalation Overridden by pneumotaxic control to end inspiration Pneumotaxic centre Upper pons, inhibits inspiration at a certain point. Fine tunes the respiratory rate. Ventillatory variables Levels of pCO2 most important in ventilation control Levels of O2 are less important. Peripheral chemoreceptors: located in the bifurcation of carotid arteries and arch of the aorta. They respond to changes in reduced pO2, increased H+ and increased pCO2 in ARTERIAL BLOOD. Central chemoreceptors: located in the medulla. Respond to increased H+ in BRAIN INTERSTITIAL FLUID to increase ventilation. NB the central receptors are NOT influenced by O2 levels. Lung receptors include: Stretch receptors: respond to lung stretching causing a reduced respiratory rate Irritant receptors: respond to smoke etc causing bronchospasm J (juxtacapillary) receptors

Shock

- Shock occurs when there is insufficient tissue perfusion. The pathophysiology of shock is an important surgical topic and may be divided into the following aetiological groups: Septic Haemorrhagic Neurogenic Cardiogenic Anaphylactic Septic shock Septic shock is a major problem and those patients with severe sepsis have a mortality rate in excess of 40%. In those who are admitted to intensive care mortality ranges from 6% with no organ failure to 65% in those with 4 organ failure. Sepsis is defined as an infection that triggers a particular Systemic Inflammatory Response Syndrome (SIRS). In 2016, the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (SCCM) created a task force that proposed Sepsis-3, a new definition for sepsis. The new definition excluded the establishment of SIRS criteria to define sepsis and made it more nonspecific as any life-threatening organ dysfunction caused by the dysregulated host response to infection. The task force claimed that sequential organ failure assessment (SOFA) has a better predictive validity for sepsis than SIRS criteria. It has better prognostic accuracy and the ability to predict in-hospital mortality. To reduce the complexity of calculating the SOFA, they introduced q SOFA Q SOFA 3 component assessment system with: Systolic blood pressure below 100 mm Hg Highest respiratory rate exceeding 21 Lowest Glasgow coma score is under 15 Although the validity of q SOFA is limited in an ICU setting, it has consistently outperformed SIRS criteria in predicting organ dysfunction in a non-ICU and ER setting. The use of vasopressors, mechanical ventilation, and aggressive therapeutic interventions in ICU limit the efficacy of q SOFA. During the septic process there is marked activation of the immune system with extensive cytokine release. This

A 43 year old man has a nasogastric tube inserted. The nurse takes a small aspirate of the fluid from the stomach and tests the pH of the aspirate. What is the normal intragastric pH?

0.5 3% 2 68% 4 19% 5 6% 6 4% The intragastric pH is usually 2. Administration of proton pump inhibitors can result in almost complete abolition of acidity

A healthy man has a blood pressure of 120/80 mmHg and an intra cranial pressure of 17 mmHg. What is the approximate cerebral perfusion pressure?

103 mmHg 21% 63 mmHg 15% 83 mmHg 14% 91 mmHg 7% 76 mmHg 43% Cerebral perfusion pressure= Mean arterial pressure - intra cranial pressure The mean arterial pressure can be calculated as: MAP= Diastolic pressure+ 0.333(Systolic pressure- Diastolic pressure) In this situation the MAP = 93. The ICP is subtracted from this value; 93 - 17 = 76

A 32 year old man has a glomerular filtration rate of 110ml / minute at a systolic blood pressure of 120/80. If his blood pressure were to fall to 100/70 what would glomerular filtration rate be?

110ml / minute 75% 100ml/ minute 14% 55ml/ minute 3% 25ml/ minute 1% 75ml/ minute 7% The proposed drop in blood pressure falls within the range within which the kidney autoregulates its blood supply. GFR will therefore remain unchanged.

A man develops xerostomia. What proportion of salivary gland secretions is contributed by the parotid gland?

25%✅ 60% 50% 7% 75% 23% 80% 5% 5% 5% Parotid gland secretions account for around 25% of saliva. Most comes from the submandibular gland.

A 39 year old lady has recurrent attacks of biliary colic. What is the approximate volume of bile to enter the duodenum per 24 hours?

500 mL 59% 50 mL 5% 100 mL 6% 2000 mL 13% 150 mL 18% Between 500 mL and 1.5 L of bile enters the small bowel daily. Most bile salts are recycled by the enterohepatic circulation. When the gallbladder contracts the lumenal pressure is approximately 25cm water, which is why biliary colic may be so painful

Gastric secretions

A working knowledge of gastric secretions is important for surgery because peptic ulcers are common, surgeons frequently prescribe anti secretory drugs and because there are still patients around who will have undergone acid lowering procedures (Vagotomy) in the past. Gastric acid Is produced by the parietal cells in the stomach pH of gastric acid is around 2 with acidity being maintained by the H+/K+ ATP ase pump. As part of the process bicarbonate ions will be secreted into the surrounding vessels. Sodium and chloride ions are actively secreted from the parietal cell into the canaliculus. This sets up a negative potential across the membrane and as a result sodium and potassium ions diffuse across into the canaliculus. Carbonic anhydrase forms carbonic acid which dissociates and the hydrogen ions formed by dissociation leave the cell via the H+/K+ antiporter pump. At the same time sodium ions are actively absorbed. This leaves hydrogen and chloride ions in the canaliculus these mix and are secreted into the lumen of the oxyntic gland. This is illustrated diagrammatically below: Image sourced from Wikipedia Phases of gastric acid secretion There are 3 phases of gastric secretion: 1. Cephalic phase (smell / taste of food) 30% acid produced Vagal cholinergic stimulation causing secretion of HCL and gastrin release from G cells 2. Gastric phase (distension of stomach ) 60% acid produced Stomach distension/low H+/peptides causes Gastrin release 3. Intestinal phase (food in duodenum) 10% acid produced High acidity/distension/hypertonic solutions in the duodenum inhibits gastric acid secretion via enterogastrones (CCK, secretin) and neural reflexes. Regulation of gastric acid production Factors increasing production include: Vagal nerve stimulation Gastrin release Histamine release (indirectly following gastrin re

A 23 year old man is undergoing an inguinal hernia repair under local anaesthesia. The surgeon encounters a bleeding site which he manages with diathermy. About a minute or so later the patient complains that he is able to feel the burning pain of the heat at the operative site. Which of the following nerve fibres is responsible for the transmission of this signal?

A α fibres 11% A β fibres 12% B fibres 4% C fibres 70% None of the above 2% Slow transmission of mechanothermal stimuli is transmitted via C fibres. A γ fibres transmit information relating to motor proprioception, A β fibres transmit touch and pressure and B fibres are autonomic fibres.

Iron metabolism

Absorption Duodenum and upper jejunum About 10% of dietary iron absorbed Fe2+ (ferrous iron) much better absorbed than Fe3+ (ferric iron) Ferrous iron is oxidized to form ferric iron, which is combined with apoferritin to form ferritin Absorption is regulated according to body's need Increased by vitamin C, gastric acid Decreased by proton pump inhibitors, tetracycline, gastric achlorhydria, tannin (found in tea) Transport In plasma as Fe3+ bound to transferrin Storage Ferritin (or haemosiderin) in bone marrow Excretion Lost via intestinal tract following desquamation Distribution in body Total body iron 4g Haemoglobin 70% Ferritin and haemosiderin 25% Myoglobin 4% Plasma iron 0.1%

A 67 year old male is admitted to the surgical unit with acute abdominal pain. He is found to have a right sided pneumonia. The nursing staff put him onto 15L O2 via a non rebreathe mask. After 30 minutes the patient is found moribund, sweaty and agitated by the nursing staff. An arterial blood gas reveals: pH 7.15 pCO2 10.2 pO2 8 Bicarbonate 32 Base excess - 5.2 What is the most likely cause for this patients deterioration

Acute respiratory alkalosis secondary to hyperventilation 4% Over administration of oxygen in a COPD patient 48% Metabolic acidosis secondary to severe pancreatitis 6% Metabolic alkalosis secondary to hypokalaemia 1% Acute respiratory acidosis secondary to pneumonia 41% This patient has an acute respiratory acidosis, however this is on a background of chronic respiratory acidosis (due to COPD) with a compensatory metabolic alkalosis (the elevated bicarbonate is the main clue to the chronic nature of the respiratory acidosis). This blood gas picture is typical in a COPD patient who has received too much oxygen; these patients lose their hypoxic drive for respiration, therefore retain CO2 and subsequently hypoventilate leading to respiratory arrest. If the bicarbonate was normal, then the answer would be acute respiratory acidosis secondary to pneumonia

Renin-angiotensin-aldosterone system

Adrenal cortex (mnemonic GFR - ACD) Zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone Zona fasciculata (middle): glucocorticoids, mainly cortisol Zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA) Renin Released by JGA cells in kidney in response to reduced renal perfusion, low sodium Hydrolyses angiotensinogen to form angiotensin I Factors stimulating renin secretion Low BP Hyponatraemia Sympathetic nerve stimulation Catecholamines Erect posture Angiotensin ACE in lung converts angiotensin I → angiotensin II Vasoconstriction leads to raised BP Stimulates thirst Stimulates aldosterone and ADH release Aldosterone Released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels Causes retention of Na+ in exchange for K+/H+ in distal tubule Image sourced from Wikipedia

Adrenal physiology

Adrenal medulla The chromaffin cells of the adrenal medulla secrete the catecholamines noradrenaline and adrenaline. The medulla is innervated by the splanchnic nerves; the preganglionic sympathetic fibres secrete acetylcholine causing the chromaffin cells to secrete their contents by exocytosis. Phaeochromocytomas are derived from these cells and will secrete both adrenaline and nor adrenaline. Adrenal cortex Three histologically distinct zones are recognised: Image sourced from Wikipedia Zone Location Hormone Secreted Zona glomerulosa Outer zone Aldosterone Zona fasiculata Middle zone Glucocorticoids Zona reticularis Inner zone Androgens The glucocorticoids and aldosterone are mostly bound to plasma proteins in the circulation. Glucocorticoids are inactivated and excreted by the liver.

A 33 year old female is admitted for varicose vein surgery. She is fit and well. After the procedure she is persistently bleeding. She is known to have menorrhagia. Investigations show a prolonged bleeding time and increased APTT. She has a normal PT and platelet count. What is the most likely cause?

Anti phospholipid syndrome 13% Haemophilia 17% Factor V Leiden deficiency 11% von Willebrands disease 53% Protein C and S deficiency 6% Bleeding post operatively, epistaxis and menorrhagia may indicate a diagnosis of vWD. Haemoarthroses are rare. The bleeding time is usually normal in haemophilia (X-linked) and vitamin K deficiency.

A 47 year old lady is diagnosed as suffering from a phaeochromocytoma. From which of the following amino acids are catecholamines primarily derived?

Aspartime 3% Glutamine 11% Arginine 13% Tyrosine✅ 68% Alanine 6% Catecholamine hormones are derived from tyrosine, it is modified by a DOPA decarboxylase enzyme to become dopamine and thereafter via two further enzymic modifications to noradrenaline and finally adrenaline

Bile

Bile is produced at a rate of between 500ml and 1500mL per day. Bile is composed of bile salts, bicarbonate, cholesterol, steroids and water. There are three main factors regulating bile flow; hepatic secretion, gall bladder contraction and sphincter of oddi resistance. Bile salts are absorbed in the terminal ileum (and recycled to the liver). Over 90% of all bile salts are recycled in this way, such that the total pool of bile salts is recycled up to six times a day. Primary bile salts Cholate and chenodeoxycholate. Secondary bile salts Formed by bacterial action on primary bile salts. These are deoxycholate and lithocholate. Of these deoxycholate is reabsorbed, whilst lithocholate is insoluble and excreted. Pathophysiology of gallstones Bile salts have a detergent action. They aggregate to form micelles and these have a lipid centre in which fats may be transported. Excessive quantities of cholesterol cannot be transported in this way and will tend to precipitate, resulting in the formation of cholesterol rich gallstones.

Which of the following is not directly affected by warfarin?

Protein C 14% Factor II 4% Factor VII 3% Factor IX 2% Factor VIII 77% Warfarin affects synthesis of factors II, VII, IX, X and protein C.

What is measured to obtain renal plasma flow?

Creatinine 9% Para-amino hippuric acid (PAH) 59% Inulin 30% Glucose 0% Protein 2% Renal plasma flow = (amount of PAH in urine per unit time) / (difference in PAH concentration in the renal artery or vein) Normal value = 660ml/min

Calcium homeostasis

Calcium ions are linked to a wide range of physiological processes. The largest store of bodily calcium is contained within the skeleton. Calcium levels are primarily controlled by parathyroid hormone, vitamin D and calcitonin. Hormonal regulation of calcium Hormone Actions Parathyroid hormone (PTH) Increase calcium levels and decrease phosphate levels Increases bone resorption Immediate action on osteoblasts to increase ca2+ in extracellular fluid Osteoblasts produce a protein signaling molecule that activate osteoclasts which cause bone resorption Increases renal tubular reabsorption of calcium Increases synthesis of 1,25(OH)2D (active form of vitamin D) in the kidney which increases bowel absorption of Ca2+ Decreases renal phosphate reabsorption 1,25-dihydroxycholecalciferol (the active form of vitamin D) Increases plasma calcium and plasma phosphate Increases renal tubular reabsorption and gut absorption of calcium Increases osteoclastic activity at high levels and osteoblasts at low levels Increases renal phosphate reabsorption Calcitonin Secreted by C cells of thyroid Inhibits intestinal calcium absorption Inhibits osteoclast activity Inhibits renal tubular absorption of calcium Both growth hormone and thyroxine also play a small role in calcium metabolism.

A 23 year old man has taken an opiate overdose. Of the following structures, which will be most affected by opiates to produce a reduction in respiratory rate?

Carotid chemoreceptors 2% Central chemoreceptors 18% Medullary respiratory centre 68% Pneumotaxic centre 10% Juxtacapillary (J) receptors 1% Opiates typically affect the medullary respiratory centre to depress respiratory activity.

A 48 year old woman suffers blunt trauma to the head and develops respiratory compromise. As a result she develops hypercapnia. Which of the following effects is most likely to ensue?

Cerebral vasoconstriction 23% Cerebral vasodilation✅ 63% Cerebral blood flow will remain unchanged 6% Shunting of blood to peripheral tissues will occur in preference to CNS perfusion 6% None of the above 1% Hypercapnia will tend to produce cerebral vasodilation. This is of considerable importance in patients with cranial trauma as it may increase intracranial pressure.

Peristalsis

Circular smooth muscle contracts behind the food bolus and longitudinal smooth muscle propels the food through the oesophagus Primary peristalsis spontaneously moves the food from the oesophagus into the stomach (9 seconds) Secondary peristalsis occurs when food, which doesn't enter the stomach, stimulates stretch receptors to cause peristalsis In the small intestine each peristalsis waves slows to a few seconds and causes mixture of chyme In the colon three main types of peristaltic activity are recognised (see below) Colonic peristalsis Segmentation contractions Localised contractions in which the bolus is subjected to local forces to maximise mucosal absorption Antiperistaltic contractions towards ileum Localised reverse peristaltic waves to slow entry into colon and maximise absorption Mass movements Waves migratory peristaltic waves along the entire colon to empty the organ prior to the next ingestion of food bolus

Cellular metabolism

Circulating glucose enters the cell, subsequently a glycolytic process results in the generation of ATP and pyruvate In the presence of oxygen, the pyruvate from the glycolytic process then enters the Krebs cycle When oxygen is limited or absent, pyruvate enters an anaerobic pathway. In these reactions, pyruvate can be converted into lactic acid. In addition to generating an additional ATP, this pathway serves to keep the pyruvate concentration low so glycolysis continues, and it oxidizes NADH into the NAD+ needed by glycolysis. In this reaction, lactic acid replaces oxygen as the final electron acceptor. Anaerobic respiration occurs in most cells of the body when oxygen is limited or mitochondria are absent or nonfunctional. For example, because erythrocytes (red blood cells) lack mitochondria, they must produce their ATP from anaerobic respiration. This is an effective pathway of ATP production for short periods of time, ranging from seconds to a few minutes. The lactic acid produced diffuses into the plasma and is carried to the liver, where it is converted back into pyruvate or glucose via the Cori cycle In the presence of oxygen, pyruvate can enter the Krebs cycle where additional energy is extracted as electrons are transferred from the pyruvate to the receptors NAD+, GDP, and FAD, with carbon dioxide being a by product. The NADH and FADH2 pass electrons on to the electron transport chain, which uses the transferred energy to produce ATP. As the terminal step in the electron transport chain, oxygen is the terminal electron acceptor and creates water inside the mitochondria. The oxidative pathways eventually yield a total of 36 ATP molecules and are therefore far better at generating energy than anaerobic pathways.

Via which structure does cerebrospinal fluid enter the subarachnoid space?

Cisterna magna 5% Cerebral aqueduct 11% Foramen of Luschka 61% Cisterna chyli 4% Arachnoid granulations 19% CSF leaves the 4th ventricle via the laterally placed foramen of Luschka and also via the midline foramen of Magendie

Pancreas exocrine physiology

Composition of pancreatic secretions Pancreatic secretions are usually 1000-1500ml per 24 hours and have a pH of 8. Secretion Source Substances secreted Enzymic Acinar cells Trypsinogen Procarboxylase Amylase Elastase Aqueous Ductal and Centroacinar cells Sodium Bicarbonate Water Potassium Chloride NB: Sodium and potassium reflect their plasma levels; chloride and bicarbonate vary with flow rate Regulation The cephalic and gastric phases (neuronal and physical) are less important in regulating the pancreatic secretions. The effect of digested material in the small bowel stimulates CCK release and ACh which stimulate acinar and ductal cells. Of these CCK is the most potent stimulus. In the case of the ductal cells these are potently stimulated by secretin which is released by the S cells of the duodenum. This results in an increase in bicarbonate. Enzyme activation Trypsinogen is converted via enterokinase to active trypsin in the duodenum. Trypsin then activates the other inactive enzymes

With which of the following blood products is iatrogenic septicaemia with a gram positive organism most likely?

Cryoprecipitate 18% Platelets 43% Packed red cells 36% Factor VIII concentrate 3% Factor IX concentrate 1% Platelets are stored at room temperature and must be used soon after collection. This places them at increased risk of culturing gram positive organisms. Iatrogenic infection with gram negative organisms is more likely with packed red cells as these are stored at 4 degrees. Infections with blood products of this nature are both rare.

A 49 year old man undergoes a distal gastrectomy to treat peptic ulcer disease. Whilst he is recovering from surgery on the ward, which of the effects listed below is most likely to be encountered?

Decreased cardiac output 9% Bradycardia 11% Relaxation of the smooth muscle of the GI tract 60% Vasodilatation 10% Reduction in angiotensin II levels 10% The stress response to surgery is multimodal and encompasses a number of physiological responses. However, cardiac output is usually increased (sympathetic nervous system induces hypertension and tachycardia). Its also results in GI tract smooth muscle relaxation. The renin angiotensin system is activated resulting in vasoconstriction and increased angiotensin II levels.

A 23 year old is stabbed in the groin and develops hypovolaemic shock. What is the most likely finding on analysis of his urine?

Decreased specific gravity 13% Increased specific gravity 71% Increased urinary glucose 1% Increased urinary protein 3% Increased red blood cells in the urine 11% Hypovolaemic shock is likely to compromise renal blood flow especially if blood pressure falls below the range at which the kidney is able to autoregulate its blood flow. The result of this will be an increase of the specific gravity as water retention occurs in an attempt to maintain circulating volume

Disorders of acid - base balance

Disorders of acid- base balance are often covered in the MRCS part A. The acid-base normogram below shows how the various disorders may be categorised Image sourced from Wikipedia Metabolic acidosis This is the most common surgical acid - base disorder. Reduction in plasma bicarbonate levels. Two mechanisms: 1. Gain of strong acid (e.g. diabetic ketoacidosis) 2. Loss of base (e.g. from bowel in diarrhoea) - Classified according to the anion gap, this can be calculated by: (Na+ + K+) - (Cl- + HCO3-). - If a question supplies the chloride level then this is often a clue that the anion gap should be calculated. The normal range = 10-18 mmol/L Normal anion gap ( = hyperchloraemic metabolic acidosis) Gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula Renal tubular acidosis Drugs: e.g. acetazolamide Ammonium chloride injection Addison's disease Raised anion gap Lactate: shock, hypoxia Ketones: diabetic ketoacidosis, alcohol Urate: renal failure Acid poisoning: salicylates, methanol Metabolic acidosis secondary to high lactate levels may be subdivided into two types: Lactic acidosis type A: (Perfusion disorders e.g.shock, hypoxia, burns) Lactic acidosis type B: (Metabolic e.g. metformin toxicity) Metabolic alkalosis Usually caused by a rise in plasma bicarbonate levels. Rise of bicarbonate above 24 mmol/L will typically result in renal excretion of excess bicarbonate. Caused by a loss of hydrogen ions or a gain of bicarbonate. It is due mainly to problems of the kidney or gastrointestinal tract Causes Vomiting / aspiration (e.g. Peptic ulcer leading to pyloric stenosis, nasogastric suction) Diuretics Liquorice, carbenoxolone Hypokalaemia Primary hyperaldosteronism Cushing's syndrome Bartter's syndrome Congenital adrenal hyperplasia Mechanism of metabolic alkalosis Activation of renin-ang

Which of the following drugs is not positively inotropic?

Dopamine 5% Glucagon 33% Theophylline 16% Sodium thiopentone 41% Dobutamine 5% Inotropes are a class of drugs that increase the force or cardiac contractility. This may improve cardiac output. Increased blood pressure may have direct beneficial effects for the heart in that it improves myocardial perfusion pressure. Dopamine and dobutamine are both commonly used inotropes, they should be administered via a central line and in a monitored setting. Glucagon and theophylline are also positive inotropes (although not commonly used for this purpose). In contrast sodium thiopentone causes marked myocardial depression.

Which of the following is the equivalent of cardiac preload?

End diastolic volume 80% Stroke volume 9% Systemic vascular resistance 6% Mean arterial pressure 3% Peak systolic arterial pressure 2% Preload is the same as end diastolic volume. When it is increased slightly there is an associated increase in cardiac output (Frank Starling principle). When it is markedly increased e.g. over 250ml then cardiac output falls

von Willebrand factor is involved in the stabilization of which of the clotting factors listed below?

Factor VII 7% Factor VIII 78% Factor V 5% Anti thrombin III 3% Factor Xa 6% vWF stabilizes factor VIII If you answered this incorrectly check you did not select factor VII by mistake!

A 56 year old man has long standing chronic pancreatitis and develops pancreatic insufficiency. Which of the following will be absorbed normally?

Fat 8% Protein 8% Folic acid 30% Vitamin B12 49% None of the above 5% Pancreatic lipase is required for digestion of fat, Proteases facilitate protein and B12 absorption. Folate digestion is independent of the pancreas.

Management of hypercalcaemia

Free Ca is affected by pH (increased in acidosis) and plasma albumin concentration ECG changes include: Shortening of QTc interval Urgent management is indicated if: Calcium > 3.5 mmol/l Reduced consciousness Severe abdominal pain Pre renal failure Management: Airway Breathing Circulation Intravenous fluid resuscitation with 3-6L of 0.9% Normal saline in 24 hours Concurrent administration of calcitonin will also help lower calcium levels Medical therapy (usually if Corrected calcium >3.0mmol/l) Bisphosphonates Analogues of pryrophosphate Prevent osteoclast attachment to bone matrix and interfere with osteoclast activity Inhibit bone resorption. Agents Drug Side effects Notes IV Pamidronate pyrexia, leucopaenia Most potent agent IV Zoledronate response lasts 30 days Used for malignancy associated hypercalcaemia Calcitonin Quickest onset of action however short duration (tachyphylaxis) therefore only given with a second agent. Prednisolone May be given in hypercalcaemia related to sarcoidosis, myeloma or vitamin D intoxication

Management of hypercalcaemia

Free Ca is affected by pH (increased in acidosis) and plasma albumin concentration ECG changes include: Shortening of QTc interval Urgent management is indicated if: Calcium > 3.5 mmol/l Reduced consciousness Severe abdominal pain Pre renal failure Management: Airway Breathing Circulation Intravenous fluid resuscitation with 3-6L of 0.9% Normal saline in 24 hours Concurrent administration of calcitonin will also help lower calcium levels Medical therapy (usually if Corrected calcium >3.0mmol/l) Bisphosphonates Analogues of pryrophosphate Prevent osteoclast attachment to bone matrix and interfere with osteoclast activity Inhibit bone resorption. Agents Drug Side effects Notes IV Pamidronate pyrexia, leucopaenia Most potent agent IV Zoledronate response lasts 30 days Used for malignancy associated hypercalcaemia Calcitonin Quickest onset of action however short duration (tachyphylaxis) therefore only given with a second agent. Prednisolone May be given in hypercalcaemia related to sarcoidosis, myeloma or vitamin D intoxication.

A 25 year old man is undergoing respiratory spirometry. He takes a maximal inspiration and maximally exhales. Which of the following measurements will best illustrate this process?

Functional residual capacity 11% Vital capacity 68% Inspiratory capacity 3% Maximum voluntary ventilation 11% Tidal volume 7% The maximum voluntary ventilation is the maximal ventilation over the course of 1 minute.

A homeless 42 year old male had an emergency inguinal hernia repair 24 hours previously. He has a BMI of 15. His electrolytes are normal. What is the best initial feeding regime?

Give 10 kcal/kg/day initially, oral thiamine 200-300mg/day, vitamin B co strong1 tds and supplements.✅ 69% Give 35 kcal/kg/day initially, oral thiamine 200-300mg/day, vitamin B co strong 1 tds and supplements. 20% No change to diet needed 5% Oral thiamine 200-300mg/day, vitamin B co strong1 tds and supplements. 3% Give 35 kcal/kg/day initially 3% This patient is at high risk of refeeding syndrome

Cortisol

Glucocorticoid Released by zona fasiculata of the adrenal gland 90% protein bound; 10% active Circadian rhythm: High in the mornings Negative feedback via ACTH Actions Glycogenolysis Gluconeogenesis Protein catabolism Lipolysis Stress response Anti-inflammatory Decrease protein in bones Increase gastric acid Increases neutrophils/platelets/red blood cells Inhibits fibroblastic activity

The Cori cycle is important in lactate metabolism in the septic surgical patient. It is used to describe a pathway in which glucose is metabolised anaerobically to lactate in one tissue and the lactate is converted back to glucose in another. Which one of the following relies on this cycle to meet all of its energy needs?

Hepatocyte 31% Leucocyte 3% Erythrocyte✅ 59% Pneumocyte 2% Goblet cells 4% Erythrocytes lack a mitochondria and therefore they generate energy via glycolytic pathways only. All the other cell types have mitochondria and will therefore use the Krebs cycle unless true anaerobic conditions prevail.

A 70 year old lady with metastatic breast cancer is admitted to hospital confused and acutely unwell, with nausea and vomiting. Her vital signs are within normal limits. What abnormality is most likely to contribute to her clinical condition?

Hyponatraemia 26% Hypernatraemia 2% Hypocalcaemia 4% Hypercalcaemia 64% Hyperkalaemia 3% The commonest site of metastatic breast cancer is to a bony site (often the axial skeleton) and so hypercalcaemia is often present in those with metastatic disease who are acutely unwell.

The oxygen-haemoglobin dissociation curve is shifted to the right in which of the following scenarios?

Hypothermia 6% Respiratory alkalosis 13% Low altitude 16% Decreased 2,3-DPG in transfused red cells 24% Chronic iron deficiency anaemia 40% Mnemonic to remember causes of right shift of the oxygen dissociation curve: CADET face RIGHT C O2 A cidosis 2,3-DPG E xercise T emperature The curve is shifted to the right when there is an increased oxygen requirement by the tissue. This includes: Increased temperature Acidosis Increased DPG: DPG is found in erythrocytes and is increased during glycolysis. It binds to the Hb molecule, thereby releasing oxygen to tissues. DPG is increased in conditions associated with poor oxygen delivery to tissues, such as anaemia and high altitude.

A 56 year old male presents to the acute surgical take with severe abdominal pain. He is normally fit and well. He has no malignancy. The biochemistry laboratory contacts the ward urgently, his corrected calcium result is 3.6 mmol/l. What is the medication of choice to treat this abnormality?

IV Pamidronate✅ 76% Oral Alendronate 8% Dexamethasone 3% Vitamin D 4% Resonium salts 9% IV Pamidronate is the drug of choice as it most effective and has long lasting effects. Calcitonin would need to be given with another agent, to ensure that the hypercalcaemia is treated once its short term effects wear off. IV zoledronate is preferred in scenarios associated with malignancy

Arterial blood gas interpretation

In advanced life support training, a 5 step approach to arterial blood gas interpretation is advocated. 1. How is the patient? 2. Is the patient hypoxaemic? The Pa02 on air should be 10.0-13.0 kPa 3. Is the patient acidaemic (pH <7.35) or alkalaemic (pH >7.45) 4. What has happened to the PaCO2? If there is acidaemia, an elevated PaCO2 will account for this 5. What is the bicarbonate level or base excess? A metabolic acidosis will have a low bicarbonate level and a low base excess (< -2 mmol) A metabolic alkalosis will have a high bicarbonate and a high base excess (> +2 mmol)

Adult lung volumes. Which statement is false?

In restrictive lung disease the FEV1/FVC ratio is normal 19% Residual volume is increased in emphysema 4% Functional residual capacity is measured by helium dilution test 19% The tidal volume is approximately 340mls in females 6% The vital capacity is increased in Guillain Barre syndrome✅ 52% FEV1/FVC is normal or >80% in restrictive lung disease such as pulmonary fibrosis. The ratio is reduced in obstructive airways disease. The functional residual capacity, residual volume and the total lung capacity cannot be measured with spirometry. They can only be measured by helium dilution. The vital capacity is reduced in: 1. Pulmonary fibrosis/infiltration/oedema/effusions 2. Weak respiratory muscles e.g. MG, GBS, myopathies 3. Skeletal abnormalities e.g. chest wall abnormalities

Inotropes and cardiovascular receptors

Inotropes are a class of drugs which work primarily by increasing cardiac output. They should be distinguished from vasoconstrictor drugs which are used specifically when the primary problem is peripheral vasodilatation. Catecholamine type agents are commonly used and work by increasing cAMP levels by adenylate cyclase stimulation. This in turn increases intracellular calcium ion mobilisation and thus the force of contraction. Adrenaline works as a beta adrenergic receptor agonist at lower doses and an alpha receptor agonist at higher doses. Dopamine causes dopamine receptor mediated renal and mesenteric vascular dilatation and beta 1 receptor agonism at higher doses. This results in increased cardiac output. Since both heart rate and blood pressure are raised, there is less overall myocardial ischaemia. Dobutamine is a predominantly beta 1 receptor agonist with weak beta 2 and alpha receptor agonist properties. Noradrenaline is a catecholamine type agent and predominantly acts as an alpha receptor agonist and serves as a peripheral vasoconstrictor. Phosphodiesterase inhibitors such as milrinone act specifically on the cardiac phosphodiesterase and increase cardiac output. Inotrope Cardiovascular receptor action Adrenaline α-1, α-2, β-1, β-2 Noradrenaline α-1,( α-2), (β-1), (β-2) Dobutamine β-1, (β 2) Dopamine (α-1), (α-2), (β-1), D-1,D-2 Minor receptor effects in brackets Effects of receptor binding α-1, α-2 vasoconstriction β-1 increased cardiac contractility and HR β-2 vasodilatation D-1 renal and spleen vasodilatation D-2 inhibits release of noradrenaline

Insulin

Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides. Structure The human insulin protein is composed of 51 amino acids, and has a molecular weight of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Synthesis Pro-insulin is formed by the rough endoplasmic reticulum in pancreatic beta cells. Then pro-insulin is cleaved to form insulin and C-peptide. Insulin is stored in secretory granules and released in response to Ca2+. Function Secreted in response to hyperglycaemia Glucose utilisation and glycogen synthesis Inhibits lipolysis Reduces muscle protein lossHuman insulin is a 51-amino acid peptide hormone with a molecular weight of 5808 Da. It is composed of an A-chain (21 amino acids) and a B-chain (30 amino acids), which are linked by two disulfide bonds. Insulin is synthesized in pancreatic β-cells and secreted in response to elevated blood glucose levels.

A 38 year old lady presents with abdominal pain. On investigation, her serum calcium is found to be 3.5mmol/L. What is the most appropriate initial management?

Intravenous bisphosphonates 20% Oral bisphosphonates 4% Intravenous calcitonin 9% Intravenous 0.9% sodium chloride 63% Intravenous frusemide 3% The immediate treatment of hypercalcaemia involves intravenous fluid resuscitation. This may be complemented with the use of bisphosphonates and sometimes diuretics. However, fluids are administered first and because this question asks what the most appropriate initial treatment is, intravenous fluids are the most appropriate answer. Normal saline is usually preferred for this over dextrose containing solutions.

Urinary incontinence

Involuntary passage of urine. Most cases are female (80%). It has a prevalence of 11% in those aged greater than 65 years. The commonest variants include: Stress urinary incontinence (50%) Urge incontinence (15%) Mixed (35%) Males Males may also suffer from incontinence although it is a much rarer condition in men. A number of anatomical factors contribute to this. Males have 2 powerful sphincters; one at the bladder neck and the other in the urethra. Damage to the bladder neck mechanism is a factor in causing retrograde ejaculation following prostatectomy. The short segment of urethra passing through the urogenital diaphragm consists of striated muscle fibres (the external urethral sphincter) and smooth muscle capable of more sustained contraction. It is the latter mechanism that maintains continence following prostatectomy. Females The sphincter complex at the level of bladder neck is poorly developed in females. As a result the external sphincter complex is functionally more important, its composition being similar to that of males. Innervation is via the pudendal nerve and the neuropathy that may accompany obstetric events may compromise this and lead to stress urinary incontinence. Innervation Somatic innervation to the bladder is via the pudendal, hypogastric and pelvic nerves. Autonomic nerves travel in these nerve fibres too. Bladder filling leads to detrusor relaxation (sympathetic) coupled with sphincter contraction. The parasympathetic system causes detrusor contraction and sphincter relaxation. Overall control of micturition is centrally mediated via centres in the Pons. Stress urinary incontinence 50% of cases, especially in females. Damage (often obstetric) to the supporting structures surrounding the bladder may lead to urethral hypermobility. Other cases due to sphincter dysfunction, usually from ne

Which of the following is not a feature of normal cerebrospinal fluid?

It has a pressure of between 10 and 15 mmHg. 4% It usually contains a small amount of glucose. 9% It may normally contain up to 5 red blood cells per mm✅ 3 . 69% It may normally contain up to 3 white blood cells per mm 3 . 10% None of the above 9% It should not contain red blood cells

A 66 year old man is undergoing a difficult laparotomy and there is bleeding. His blood pressure is controlled by administration of blood products and fluids. An adrenaline infusion is started. What will be the effects of this on renin?

It will stimulate its release from the juxtaglomerular cells 73% It will inhibit its release from the juxtaglomerular cells 22% It will inhibit its interaction with angiotensinogen I 3% It renders it biologically inactive 1% It accelerates its cellular breakdown 0% The sympathetic nervous system stimulates renin release from juxtaglomerular cells via the beta adrenoreceptor cAMP pathway

What is the half life of insulin in the circulation of a normal healthy adult?

Less than 30 minutes 56% Between 1 and 2 hours 19% Between 2 and 3 hours 12% Between 4 and 5 hours 7% Over 6 hours 7% Insulin is degraded by enzymes in the circulation. It typically has a half life of less than 30 minutes. Abnormalities of the clearance of insulin may occur in type 2 diabetes

Hypercalcaemia

Main causes Malignancy (most common cause in hospital in-patients) Primary hyperparathyroidism (commonest cause in non hospitalised patients) Less common Sarcoidosis (extrarenal synthesis of calcitriol ) Thiazides, lithium Immobilisation Pagets disease Vitamin A/D toxicity Thyrotoxicosis MEN Milk alkali syndrome Clinical features Stones, bones, abdominal groans, and psychic moans High serum calcium levels result in decreased neuronal excitability. Therefore sluggish reflexes, muscle weakness and constipation may occur

Hypercalcaemia

Main causes Malignancy (most common cause in hospital in-patients) Primary hyperparathyroidism (commonest cause in non hospitalised patients) Less common Sarcoidosis (extrarenal synthesis of calcitriol ) Thiazides, lithium Immobilisation Pagets disease Vitamin A/D toxicity Thyrotoxicosis MEN Milk alkali syndrome Clinical features Stones, bones, abdominal groans, and psychic moans High serum calcium levels result in decreased neuronal excitability. Therefore sluggish reflexes, muscle weakness and constipation may occur.

Which of the following does not lead to relaxation of the lower oesophageal sphincter?

Metoclopramide✅ 51% Botulinum toxin type A 13% Nicotine 13% Alcohol 8% Theophylline 16% Metoclopramide acts directly on the smooth muscle of the LOS to cause it to contract. Theophylline is a phosphodiesterase inhibitor (mimics action of prostaglandin E1) which causes relaxation of the LOS.

von Willebrands disease

Most common inherited bleeding disorder All vWD is caused by mutations in the gene for von Willebrand factor. von Willebrand factor is an adhesive glycoprotein that is secreted by endothelium and megakaryocytes von Willebrand factor promotes platelet adhesion to damaged endothelium and other platelets. It is also involved in the transport and stabilization of factor VIII There are 7 subtypes of von Willebrand disease. The commonest is type I (autosomal dominant) which accounts for 80% of cases, type 2vWD (autosomal dominant or recessive) accounts for 15% of cases There is a significant spectrum of severity ranging from spontaneous bleeding and epistaxis through to troublesome excessive bleeding following minor procedures The test that is most commonly used are von willebrand factor assays Treatments include administration of tranexamic acid for minor cases undergoing minor procedures. More significant bleeding or more significant procedures respond well to DDAVP. This is most effective in type I, less effective in type 2 and contraindicated in type 2B. Patients with type 3 disease do not respond to DDAVP as they lack the ability to secrete vWF Individuals who cannot have DDAVP or in whom it is contra indicated usually receive factor VIII concentrates containing vWF

Which of the following is responsible for the release and synthesis of calcitonin?

Parathyroid glands 31% Anterior pituitary 3% Thyroid gland 64% Posterior pituitary 1% Adrenal glands 1% Calcitonin has the opposite effect of PTH and is released from the thyroid gland

Parotid gland secretions

Parotid gland secretions account for around 25% of salivary secretions Levels of sodium and chloride are lower than plasma, potassium and bicarbonate levels are higher Parotid secretions are watery and have high enzyme concentrations Parasympathetic stimulation produces a water rich, serous saliva. Sympathetic stimulation leads to the production of a low volume, enzyme-rich saliva. Fluid that is secreted within the acini is isotonic with plasma and undergoes modification within the ducts via process of ion exchange The ducts are affected by aldosterone and so will retain sodium and secrete potassium when aldosterone levels are elevated

Which of the following is the main site of dehydroepiandrosterone release?

Posterior pituitary 3% Zona reticularis of the adrenal gland 74% Zona glomerulosa of the adrenal gland 11% Juxtaglomerular apparatus of the kidney 3% Zona fasciculata of the adrenal gland 8% Adrenal cortex mnemonic: GFR - ACD DHEA possesses some androgenic activity and is almost exclusively released from the adrenal gland.

Applied neurophysiology

Pressure within the cranium is governed by the Monroe-Kelly doctrine. This considers the skull as a closed box. Increases in mass can be accommodated by loss of CSF. Once a critical point is reached (usually 100- 120ml of CSF lost) there can be no further compensation and ICP rises sharply. The next step is that pressure will begin to equate with MAP and neuronal death will occur. Herniation will also accompany this process. The CNS can autoregulate its own blood supply. Vaso constriction and dilatation of the cerebral blood vessels is the primary method by which this occurs. Extremes of blood pressure can exceed this capacity resulting in risk of stroke. Other metabolic factors such as hypercapnia will also cause vasodilation, which is of importance in ventilating head injured patients. The brain can only metabolise glucose, when glucose levels fall, consciousness will be impaired.

An over enthusiastic medical student decides to ask you questions about ECGs. Rather than admitting your dwindling knowledge on this topic, you bravely attempt to answer her questions! One question is what component of the ECG represents ventricular repolarization?

QRS complex 10% Q-T interval 6% P wave 1% T wave✅ 70% S-T segment 13% The T wave represents ventricular repolarization. The common sense approach to remembering this, is to acknowledge that ventricular repolarization is the last phase of cardiac contraction and should therefore correspond the the last part of the QRS complex.

Nutrition - Refeeding syndrome

Refeeding syndrome describes the metabolic abnormalities which occur on feeding a person following a period of starvation. The metabolic consequences include: Hypophosphataemia Hypokalaemia Hypomagnesaemia Abnormal fluid balance These abnormalities can lead to organ failure. Re-feeding problems If patient not eaten for > 5 days, aim to re-feed at < 50% energy and protein levels High risk for re-feeding problems If one or more of the following: BMI < 16 kg/m2 Unintentional weight loss >15% over 3-6 months Little nutritional intake > 10 days Hypokalaemia, Hypophosphataemia or hypomagnesaemia prior to feeding (unless high) If two or more of the following: BMI < 18.5 kg/m2 Unintentional weight loss > 10% over 3-6 months Little nutritional intake > 5 days History of: alcohol abuse, drug therapy including insulin, chemotherapy, diuretics and antacids Prescription Start at up to 10 kcal/kg/day increasing to full needs over 4-7 days Start immediately before and during feeding: oral thiamine 200-300mg/day, vitamin B co strong 1 tds and supplements Give K+ (2-4 mmol/kg/day), phosphate (0.3-0.6 mmol/kg/day), magnesium (0.2-0.4 mmol/kg/day)

A 43 year old lady undergoes a day case laparoscopic cholecystectomy. The operation is more difficult than anticipated and a drain is placed to the operative site. Whilst in recovery, the patient loses 1800ml of frank blood into the drain. Which of the following will not occur?

Release of aldosterone via the Bainbridge reflex 40% Reduced urinary sodium excretion 6% Increase in sympathetic discharge to ventricular muscle 6% Fall in parasympathetic discharge to the sino atrial node 12% Decreased stimulation from atrial pressure receptors 36% The Bainbridge reflex is the increase in heart rate mediated via atrial stretch receptors that occurs following a rapid infusion of blood. Note the question asks which will not occur and that is why it is A and not the other options.

A 28 year old man is shot in the abdomen and haemorrhages. Which of the following substances will produce vasoconstriction in response to this process?

Renin 16% Angiotensin I 5% Angiotensin II 63% Aldosterone 10% None of the above 6% Renin does not cause vasoconstriction. Angiotensin I is biologically inactive. Aldosterone will increase blood pressure but does not have direct vasospastic effects.

Renin

Renin is secreted by juxtaglomerular cells and hydrolyses angiotensinogen to produce angiotensin I Factors stimulating renin secretion Hypotension causing reduced renal perfusion Hyponatraemia Sympathetic nerve stimulation Catecholamines Erect posture Factors reducing renin secretion Drugs: beta-blockers, NSAIDs

Which of the conditions listed below is most likely to account for the following arterial blood gas result: pH 7.49 pO2 8.5 Bicarbonate 22 pCO2 2.4 Chloride 12meq

Respiratory alkalosis 80% Metabolic alkalosis 11% Metabolic acidosis 1% Type II respiratory failure 7% Metabolic acidosis with increased anion gap 1% The hyperventilation results in decreased carbon dioxide levels, causing a respiratory alkalosis (non compensated).

Pain - neuronal transmission

Somatic pain Peripheral nociceptors are innervated by either small myelinated fibres (A-delta) fibres or by unmyelinated C fibres. The A gamma fibres register high intensity mechanical stimuli. The C fibres usually register high intensity mechanothermal stimuli.

A 63 year old female is referred to the surgical clinic with an iron deficiency anaemia. Her past medical history includes a left hemi colectomy but no other co-morbidities. At what site is most dietary iron absorbed?

Stomach 4% Duodenum 52% Proximal ileum 17% Distal ileum 23% Colon 4% Iron is best absorbed from the proximal small bowel (duodenum and jejunum) in the Fe 2+ state. Iron is transported across the small bowel mucosa by a divalent membrane transporter protein (hence the improved absorption of Fe 2+). The intestinal cells typically store the bound iron as ferritin. Cells requiring iron will typically then absorb the complex as needed.

Stress response: Endocrine and metabolic changes

Surgery precipitates hormonal and metabolic changes causing the stress response. Stress response is associated with: substrate mobilization, muscle protein loss, sodium and water retention, suppression of anabolic hormone secretion, activation of the sympathetic nervous system, immunological and haematological changes. The hypothalamic-pituitary axis and the sympathetic nervous systems are activated and there is a failure of the normal feedback mechanisms of control of hormone secretion. A summary of the hormonal changes associated with the stress response: Increased Decreased No Change Growth hormone Insulin Thyroid stimulating hormone Cortisol Testosterone Luteinizing hormone Renin Oestrogen Follicle stimulating hormone Adrenocorticotrophic hormone (ACTH) Aldosterone Prolactin Antidiuretic hormone Glucagon Sympathetic nervous system Stimulates catecholamine release Causes tachycardia and hypertension Pituitary gland ACTH and growth hormone (GH) is stimulated by hypothalamic releasing factors, corticotrophin releasing factor (CRF) and somatotrophin (or growth hormone releasing factor) Perioperative increased prolactin secretion occurs by release of inhibitory control Secretion of thyroid stimulating hormone (TSH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) does not change significantly ACTH stimulates cortisol production within a few minutes of the start of surgery. More ACTH is produced than needed to produce a maximum adrenocortical response. Cortisol Significant increases within 4-6 hours of surgery (>1000 nmol litre-1). The usual negative feedback mechanism fails and concentrations of ACTH and cortisol remain persistently increased. The magnitude and duration of the increase correlate with the severity of stress and the response is not abolished by the administration of corti

A 22 year old man suffers a blunt head injury. He is drowsy and has a GCS of 7 on admission. Which of the following is the major determinant of cerebral blood flow in this situation?

Systemic blood pressure 3% Mean arterial pressure 27% Intra cranial pressure 62% Hypoxaemia 4% Acidosis 4% Hypoxaemia and acidosis may both affect cerebral blood flow. However, in the traumatic situation increases in intracranial pressure are far more likely to occur especially when GCS is low. This will adversely affect cerebral blood flow.

A 36 year old man develops cellulitis of the hand. This condition will involve the complement immunological system. Which of the cells types listed below provides the greatest contribution to complement protein and glycoprotein production?

T Cells 23% B Cells 25% Hepatocytes✅ 20% Endothelial cells 11% Polymorphonucleocytes 22% Whilst all the cell types listed can produce complement proteins, the greatest contribution is made from the hepatocytes. Indeed, most soluble proteins are synthesized by the liver.

Cerebrospinal fluid

The CSF fills the space between the arachnoid mater and pia mater (covering surface of the brain). The total volume of CSF in the brain is approximately 150ml. Approximately 500 ml is produced by the ependymal cells in the choroid plexus (70%), or blood vessels (30%). It is reabsorbed via the arachnoid granulations which project into the venous sinuses. Circulation 1. Lateral ventricles (via foramen of Munro) 2. 3rd ventricle 3. Cerebral aqueduct (aqueduct of Sylvius) 4. 4th ventricle 5. Subarachnoid space (via foramina of Magendie and Luschka) 6. Reabsorbed into the venous system via arachnoid granulations into superior sagittal sinus Composition Glucose: 50-80mg/dl Protein: 15-40 mg/dl Red blood cells: Nil White blood cells: 0-3 cells/ mm3

Cerebral perfusion pressure

The cerebral perfusion pressure (CPP) is defined as being the net pressure gradient causing blood flow to the brain. The CPP is tightly autoregulated to maximise cerebral perfusion. A sharp rise in CPP may result in a rising ICP, a fall in CPP may result in cerebral ischaemia. It may be calculated by the following equation: CPP= Mean arterial pressure - Intra cranial pressure Following trauma, the CPP has to be carefully controlled and the may require invasive monitoring of the ICP and MAP.

Complement system

The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. Proteolytic cascades include: potent proinflammatory mediators (anaphylatoxins), opsonization (coating) of the pathogenic surface through various complement opsonins (e.g., C3b), and targeted lysis of the pathogenic surface through the assembly of membrane-penetrating pores known as the membrane attack complex (MAC). Complement is activated via one of three major pathways; classical, lectin and alternative. The final output of the system is inflammation, lysis or opsonization.

Cardiac physiology

The heart has four chambers ejecting blood into both low pressure and high pressure systems. The pumps generate pressures of between 0-25mmHg on the right side and 0-120 mmHg on the left. At rest diastole comprises 2/3 of the cardiac cycle. The product of the frequency of heart rate and stroke volume combine to give the cardiac output which is typically 5-6L per minute. Detailed descriptions of the various waveforms are often not a feature of MRCS A (although they are on the syllabus). However, they are a very popular topic for surgical physiology in the MRCS B exam. Electrical properties Intrinsic myogenic rhythm within cardiac myocytes means that even the denervated heart is capable of contraction. In the normal situation the cardiac impulse is generated in the sino atrial node in the right atrium and conveyed to the ventricles via the atrioventricular node. The sino atrial node is also capable of spontaneous discharge and in the absence of background vagal tone will typically discharge around 100x per minute. Hence the higher resting heart rate found in cardiac transplant cases. In the SA and AV nodes the resting membrane potential is lower than in surrounding cardiac cells and will slowly depolarise from -70mV to around -50mV at which point an action potential is generated. Differences in the depolarisation slopes between SA and AV nodes help to explain why the SA node will depolarise first. The cells have a refractory period during which they cannot be re-stimulated and this period allows for adequate ventricular filling. In pathological tachycardic states this time period is overridden and inadequate ventricular filling may then occur, cardiac output falls and syncope may ensue. Parasympathetic fibres project to the heart via the vagus and will release acetylcholine. Sympathetic fibres release nor adrenaline a

Spleen- function

The spleen is a reticuloendothelial organ, it develops in the dorsal mesogastrium at around 5 weeks gestation. At this stage it has an irregular surface and migrates to the left upper quadrant over the following weeks. In most cases the irregular hillocks on the spleen surface unify, when they fail to do so, accessory spleens may develop and are found in around 20% of people. The spleen is composed of both red and white pulp. In the red pulp, blood filled venous sinuses are found. In the white pulp, reticuloendothelial cords and white lymphoid follicles are present. Blood flows into the spleen at a rate of 150ml per minute. As blood passes through the spleen, the erythrocytes have to pass through fine endothelial fenestrations, older and less deformable erythrocytes are trapped during this process and destroyed. Red cell inclusion bodies such as parasites or residual nuclear components are split off during this process which is termed pitting. Functions of spleen Maintenance of the quality of erythrocytes in the red pulp by removal of senescent and dysfunctional cells Antibody production in the white pulp Removal of antibody coated bacteria and blood cells from the circulation Because of these important functions, the spleen is seldom removed. Indications for splenectomy include major trauma and uncontrollable haemorrhage and the treatment of haemolytic anaemia. The absence of a spleen has minimal long term effects on the haematologic profile. In the immediate post operative period, both leucocytosis and thrombocytosis are seen. In the longer term, the main manifestations are visible on the blood film and include visible nuclear remnants (Howell Jolly bodies), denatured haemoglobin (Heinz bodies), basophilic stippling and occasional nucleated erythrocytes. The main risk following splenectomy is overwhelming sepsis w

What is the most common cause of hypercalcaemia in the UK in hospitalised patients?

Thiazide use 21% Metastatic malignancy 62% Primary hyperparathyroidism 15% Osteogenic sarcoma 0% Sarcoidosis 2% Metastatic cancer accounts for most cases of hypercalcaemia in hospitalised patients. In the community primary hyperparathyroidism is the commonest cause.

A patient has an arterial blood gas sample which provides the following result: pH 7.20 pO2 7.5 Bicarbonate 22 pCO2 8.1 Chloride 10meq What is the most likely cause?

Type II respiratory failure 71% Metabolic acidosis with increased anion gap 9% Metabolic alkalosis 1% Type I respiratory failure 17% Respiratory alkalosis 2% This is a sign of acute type 2 respiratory failure (non compensated). This is the result of carbon dioxide retention

Which of the following is not a characteristic of the proximal convoluted tubule in the kidney?

Up to 95% of filtered amino acids will be reabsorbed at this site 8% It is a risk of damage in a patient with compartment syndrome due to a tibial fracture 14% It is responsible for absorbing more than 50% of filtered water 19% Its secretory function is most effective at low systolic blood pressures (typically less than 100mmHg)✅ 51% Glucose is reabsorbed by combined active and passive (facilitated diffusion processes) 9% The proximal convoluted tubule may undergo necrosis in situations such as compartment syndrome. It is responsible for reabsorbing up to two thirds of filtered water. Low systolic blood pressures (below the renal autoregulatory range) are a risk factor for acute tubular necrosis. Within the autoregulatory range the absolute value of systolic BP has little effect. The process of facilitated diffusion of glucose refers to its co-transport with sodium

A 52-year-old woman with a history of gastrectomy reports lethargy and a sore tongue. Blood tests are reported as follows: Hb 10.7 g/dl MCV 121 fl Plt 177 * 10^9/l WBC 5.4 * 10^9/l What is the most likely cause?

Vitamin B12 deficiency 88% Vitamin C deficiency 3% Iron deficiency anaemia 6% Anaemia of chronic disease 2% Vitamin E deficiency 1% A history of gastrectomy and a macrocytic anaemia should indicate a diagnosis of B12 deficiency.

Vitamin B12 deficiency

Vitamin B12 is mainly used in the body for red blood cell development and also maintenance of the nervous system. It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach) and is actively absorbed in the terminal ileum. A small amount of vitamin B12 is passively absorbed without being bound to intrinsic factor. Causes of vitamin B12 deficiency pernicious anaemia post gastrectomy poor diet disorders of terminal ileum (site of absorption): Crohn's, blind-loop etc Features of vitamin B12 deficiency macrocytic anaemia sore tongue and mouth neurological symptoms: e.g. Ataxia neuropsychiatric symptoms: e.g. Mood disturbances Management if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

A 69 year old man has been living in sheltered accommodation for many months, with inadequate nutrition notices that his night vision is becoming impaired. Deficiency of which vitamin is responsible?

Vitamin B3 2% Vitamin A 94% Vitamin C 2% Vitamin B12 1% Vitamin E 1% Loss of vitamin A will result in impair rhodopsin synthesis and results in poor night vision.

Vitamin deficiency

Vitamin Effect of deficiency A Night blindness Epithelial atrophy Infections B1 Beriberi B2 Dermatitis and photosensitivity B3 Pellagra B12 Pernicious anaemia C Poor wound healing Impaired collagen synthesis D Rickets (Children) Osteomalacia (Adults) K Clotting disorders

Blood products

Whole blood fractions Fraction Key points Packed red cells Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise. Product obtained by centrifugation of whole blood. Platelet rich plasma Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery. It is obtained by low speed centrifugation. Platelet concentrate Prepared by high speed centrifugation and administered to patients with thrombocytopaenia. Fresh frozen plasma Prepared from single units of blood. Contains clotting factors, albumin and immunoglobulin. Unit is usually 200 to 250ml. Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery. Usual dose is 12-15ml/Kg-1. It should not be used as first line therapy for hypovolaemia. Cryoprecipitate Formed from supernatant of FFP. Rich source of Factor VIII and fibrinogen. Allows large concentration of factor VIII to be administered in small volume. SAG-Mannitol Blood Removal of all plasma from a blood unit and substitution with: Sodium chloride Adenine Anhydrous glucose Mannitol Up to 4 units of SAG M Blood may be administered. Thereafter whole blood is preferred. After 8 units, clotting factors and platelets should be considered. Cell saver devices These collect patients own blood lost during surgery and then re-infuse it. There are two main types: Those which wash the blood cells prior to re-infusion. These are more expensive to purchase and more complicated to operate. However, they reduce the risk of re-infusing contaminated blood back into the patient. Those which do not wash the blood prior to re-infusion. Their main advantage is that they avoid the use of infusion of blood from donors into patients and this may reduce risk of blood

Where are the reticulo-endothelial cells concentrated within the spleen?

Within the capsule 3% Within the red pulp 41% Within the trabeculae 10% Within the white pulp 42% Within the splenic cords 4% The reticuloendothelial cells are concerned with the immune functions of the spleen and these are therefore concentrated in the white pulp

Cortisol is predominantly produced by which of the following?

Zona fasciculata of the adrenal 66% Zona glomerulosa of the adrenal 22% Zona reticularis of the adrenal 6% Adrenal medulla 5% Posterior lobe of the pituitary 1% Relative Glucocorticoid activity: Hydrocortisone = 1 Prednisolone = 4 Dexamethasone = 25 Cortisol is produced by the zona fasciculata of the adrenal gland.

Which receptor does noradrenaline mainly bind to?

α 1 receptors 67% α 2 receptors 14% β 1 receptors 13% β 2 receptors 5% G receptors 1% Noradrenaline is the precursor of adrenaline. It is a powerful α 1 stimulant (although it will increase myocardial contractility). Infusions will produce vasoconstriction and an increase in total peripheral resistance. It is the inotrope of choice in septic shock.