11- Physiology Explains Flashcards
What are the effects of parathyroid hormone (PTH) on calcium and phosphate levels?
Increases calcium levels and decreases phosphate levels
What is the immediate action of PTH on osteoblasts?
Increases calcium in extracellular fluid
What do osteoblasts produce that activate osteoclasts?
Protein signaling molecules
What does PTH stimulate the synthesis of in the kidney?
1,25-dihydroxycholecalciferol (active form of vitamin D)
What is the effect of 1,25-dihydroxycholecalciferol on plasma calcium and phosphate levels?
Increases both calcium and phosphate levels
What is the role of PTH in renal tubular reabsorption?
Increases calcium reabsorption
What does 1,25-dihydroxycholecalciferol increase in terms of calcium absorption?
Renal tubular reabsorption and gut absorption
What is the effect of calcitonin on renal tubular absorption of calcium?
Inhibits it
What is the effect of calcitonin on intestinal calcium absorption?
Inhibits it
What is the effect of calcitonin on osteoclast activity?
Inhibits it
What are the stimulators of glucagon release?
Decreased plasma glucose, increased catecholamines, increased plasma amino acids, sympathetic nervous system, acetylcholine, cholecystokinin
What are the main components of the stress response?
Substrate mobilization, muscle protein loss, sodium and water retention, suppression of anabolic hormone secretion, activation of the sympathetic nervous system, immunological and hematological changes
What are the inhibitors of glucagon release?
Somatostatin, insulin, increased free fatty acids, keto acids, increased urea
What are the effects of the sympathetic nervous system on the body during the stress response?
Stimulates catecholamine release, causes tachycardia and hypertension
Which hormones are stimulated by the hypothalamic releasing factors CRF and somatotrophin during the stress response?
ACTH and growth hormone (GH)
What happens to prolactin secretion during the stress response?
It increases due to release of inhibitory control
Which hormones remain unchanged significantly during the stress response?
Thyroid stimulating hormone (TSH), luteinizing hormone (LH), and follicle stimulating hormone (FSH)
What is the effect of ACTH on cortisol production during surgery?
ACTH stimulates cortisol production within a few minutes of the start of surgery
What are the metabolic effects of cortisol during the stress response?
Skeletal muscle protein breakdown, stimulation of lipolysis, anti-insulin effect, mineralocorticoid effects, anti-inflammatory effects
What is the role of growth hormone in the stress response?
It prevents muscle protein breakdown and promotes tissue repair
Which hormone is important for vasopressor activity and enhances hemostasis?
Antidiuretic hormone (ADH)
What is the effect of insulin during the stress response?
Release of insulin is inhibited, leading to functional insulin deficiency
What happens to circulating concentrations of thyroxine (T4) and tri-iodothyronine (T3) during the stress response?
They are reduced initially due to sympathetic activity, but normalize over a few days
What are the effects of the stress response on carbohydrate metabolism?
Hyperglycemia due to increased glucose production and reduced glucose utilization
What happens to protein metabolism during the stress response?
Initially, there is inhibition of protein anabolism, followed by enhanced catabolism if the stress response is severe
How does the stress response affect lipid metabolism?
It promotes lipolysis and ketone body production
Which hormone is increased during the stress response?
Growth hormone
Cortisol
Renin
Adrenocorticotrophic hormone
(ACTH)
Aldosterone
Prolactin
Antidiuretic hormone
Glucagon
What are cytokines and how are they involved in the stress response?
Cytokines are glycoproteins synthesized in response to tissue injury. They have various effects, including fever, granulocytosis, haemostasis, tissue damage limitation, and promotion of healing
What are the effects of the stress response on salt and water metabolism?
ADH causes water retention and concentrated urine, while renin causes sodium and water retention
What are some strategies to modify the stress response?
Opioids can suppress hormone secretion, spinal anesthesia can reduce certain hormone changes, less invasive surgery can reduce cytokine release, nutrition can prevent adverse effects, and normothermia can decrease the metabolic response
Which hormone is decreased during the stress response?
Insulin
Testosterone
Oestrogen
Which hormones do not change during the stress response?
Thyroid stimulating
hormone
Luteinizing hormone
Follicle stimulating
hormone
What factors are affected by heparin?
Factors 2, 9, 10, 11 (1129)
What factors are affected by warfarin?
Factors 2, 7, 9, 10(1927)
What factors are affected by DIC (Disseminated Intravascular Coagulation)?
Factors 1, 2, 5, 8, 11(1 2 5 118)
What factors are affected by liver disease?
Factors 1, 2, 5, 7, 9, 10, 11(1 2 5 1179)
interpretation blood clotting test results
Haemophilia:
APTT:Increased
PT: Normal
Bleeding time:Normal
interpretation blood clotting test results
von Willebrand’s disease:
APTT:Increased
PT: Normal
Bleeding time:Increased
interpretation blood clotting test results
Vitamin K deficiency:
APTT:Increased
PT: Increased
Bleeding time:Normal
How does the cranial vault accommodate rises in intracranial pressure (ICP)?
By shifting cerebrospinal fluid (CSF)
What happens once CSF shifting has reached its capacity in coning?
ICP will start to rise briskly
How does the brain autoregulate its blood supply during coning?
By causing changes in systemic circulation, usually leading to hypertension
What happens when ICP rises further in coning?
The brain will be compressed, cranial nerve palsies may occur, and essential brain stem centers may be compressed
What happens when the cardiac center is involved in coning?
Bradycardia often develops
What coordinates the control of ventilation?
Respiratory centres, chemoreceptors, lung receptors, and muscles
Where does the automatic, involuntary control of respiration occur?
In the medulla
What do the respiratory centres control?
The respiratory rate and the depth of respiration
Which part of the medulla controls forced voluntary expiration?
The ventral group
Which part of the medulla controls inspiration?
The dorsal group
What depresses the medullary respiratory centre?
Opiates
Which part of the lower pons stimulates and prolongs inhalation?
The apneustic centre
What overrides the apneustic centre to end inspiration?
Pneumotaxic control
Which part of the upper pons inhibits inspiration at a certain point?
The pneumotaxic centre
What is most important in ventilation control?
Levels of pCO (partial pressure of carbon dioxide)
What do peripheral chemoreceptors respond to in arterial blood?
Changes in reduced pO (partial pressure of oxygen), increased H (hydrogen ion concentration), and increased pCO (partial pressure of carbon dioxide)
Where are central chemoreceptors located and what do they respond to?
In the medulla and they respond to increased H in brain interstitial fluid to increase ventilation
What do stretch receptors in the lungs respond to?
Lung stretching, which causes a reduced respiratory rate
What do irritant receptors in the lungs respond to?
Smoke and other irritants, which can cause bronchospasm
What are J (juxtacapillary) receptors?
Lung receptors involved in regulating ventilation
What is the main function of vitamin B12 in the body?
Red blood cell development and maintenance of the nervous system
How is vitamin B12 absorbed in the body?
After binding to intrinsic factor and actively absorbed in the terminal ileum
What are the features of vitamin B12 deficiency?
Macrocytic anemia, sore tongue and mouth, neurological symptoms (e.g., ataxia), neuropsychiatric symptoms (e.g., mood disturbances)
What are some causes of vitamin B12 deficiency?
Pernicious anemia, post gastrectomy, poor diet, disorders of the terminal ileum (e.g., Crohn’s, blind-loop)
What is the management for vitamin B12 deficiency without neurological involvement?
1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months
What supplies each nephron with blood?
Afferent arteriole
What should be treated first if a patient is deficient in both folic acid and vitamin B12?
Vitamin B12 deficiency to avoid precipitating subacute combined degeneration of the cord
Where does blood flow after leaving the glomerular capillary bed?
Efferent arteriole, supplying the peritubular capillaries and medullary vasa recta
What percentage of resting cardiac output does the kidney receive?
Up to 25%
How does the kidney autoregulate its blood flow?
Through myogenic control of arteriolar tone, with input from sympathetic and hormonal signals
What determines the glomerular filtration rate (GFR)?
The concentration of a solute in the urine, the volume of urine produced per minute, and the plasma concentration of the solute
What substance is commonly used to measure GFR in clinical practice?
Creatinine
What features should a substance used to measure GFR have?
Inert, freely filtered from the plasma at the glomerulus, not absorbed or secreted at the tubules, and a constant plasma concentration during urine collection
Where does reabsorption and secretion of substances occur in the kidney?
In the tubules
What substances are co-transported with sodium in the proximal tubule?
Glucose, amino acids, and phosphate
How is urea concentration increased in the distal tubule?
Due to the reabsorption of water in the proximal tubules
How much of the filtered water is reabsorbed in the proximal tubules?
Up to two thirds
How are substances secreted into the tubules?
Tubular cells take them up from the peritubular blood
What is used to measure renal plasma flow?
Paraaminohippuric acid, which is cleared with a single passage through the kidneys
What influences the tubular reabsorption of calcium and phosphate ions?
Plasma PTH levels
Where is the osmolarity of fluid greatest in the loop of Henle?
At the tip of the papilla
What ions are co-exchanged with sodium in the kidney?
Potassium
What is the thick ascending limb of the loop of Henle impermeable to?
Water
What ions are reabsorbed in the thick ascending limb?
Sodium and chloride
What helps maintain the osmotic gradient in the kidney?
The energy-dependent reabsorption of sodium and chloride in the thick ascending limb
What is the equation for calculating the glomerular filtration rate (GFR)?
GFR = (concentration of solute in urine) x (volume of urine produced per minute) / (plasma concentration of solute)
Why is creatinine used in clinical practice to estimate GFR?
Because it is subjected to very little proximal tubular secretion
What does renal clearance measure?
The volume of plasma from which a substance is removed per minute by the kidneys
What is the typical GFR value?
125 ml per minute
What does helium dilution measure?
Functional residual capacity (FRC)
What does functional residual capacity (FRC) represent?
The volume of air remaining in the lungs at the end of a normal expiration
How can anatomical dead space be measured?
Using the Bohr equation or the Fowler method
What does the Fowler method involve for estimating anatomical dead space?
Using a nitrogen washout technique
What does the Bohr equation analyze to calculate anatomical dead space?
The concentration of carbon dioxide (CO2) in exhaled air and arterial blood
What is minute ventilation?
The total volume of gas ventilated per minute
How is minute ventilation calculated?
Tidal volume x Respiratory rate
What is dead space ventilation?
The volume of gas not involved in gas exchange in the blood
What is anatomical dead space?
The volume of gas in the respiratory tree not involved in gaseous exchange
What are some factors that can increase anatomical dead space?
Standing, increased size of person, increased lung volume, and drugs causing bronchodilation
What is physiological dead space?
The volume of gas in the alveoli and anatomical dead space not involved in gaseous exchange
What conditions can increase physiological dead space?
Ventilation/perfusion mismatch, such as pulmonary embolism (PE), chronic obstructive pulmonary disease (COPD), and hypotension
What is alveolar ventilation?
The volume of fresh air entering the alveoli per minute
How is alveolar ventilation calculated?
Minute ventilation minus dead space volume
What is tidal volume (TV)?
The volume of air inspired and expired during each ventilatory cycle at rest
What is the typical tidal volume for males?
500 ml
What is the typical tidal volume for females?
340 ml
What is inspiratory reserve volume (IRV)?
The maximum volume of air that can be forcibly inhaled following a normal inspiration
What is the typical inspiratory reserve volume?
3000 ml
What is expiratory reserve volume (ERV)?
The maximum volume of air that can be forcibly exhaled following a normal expiration
What is the typical expiratory reserve volume?
1000 ml
What is residual volume (RV)?
The volume of air remaining in the lungs after a maximal expiration
How is residual volume calculated?
RV = FRC - ERV
What is the typical residual volume?
1500 ml
What is functional residual capacity (FRC)?
The volume of air remaining in the lungs at the end of a normal expiration
How is functional residual capacity calculated?
FRC = RV + ERV
What is the typical functional residual capacity?
2500 ml
What is vital capacity (VC)?
The maximal volume of air that can be forcibly exhaled after a maximal inspiration
How is vital capacity calculated?
VC = TV + IRV + ERV
What is the typical vital capacity for females?
3500 ml
What is the typical vital capacity for males?
4500 ml
What is total lung capacity (TLC)?
The volume of air in the lungs at the end of a maximal inspiration
How is total lung capacity calculated?
TLC = FRC + TV + IRV = VC + RV
What is the typical total lung capacity?
5500-6000 ml
What is the prevalence of urinary incontinence in those aged greater than 65 years?
11%
What is forced vital capacity (FVC)?
The volume of air that can be maximally forcefully exhaled
Who are most commonly affected by urinary incontinence?
Females (80% of cases)
What are the three common variants of urinary incontinence?
Stress urinary incontinence (50%), urge incontinence (15%), mixed (35%)
Is urinary incontinence more common in males or females?
Females
What anatomical factors contribute to urinary incontinence in males?
Males have two powerful sphincters, one at the bladder neck and the other in the urethra
What can cause retrograde ejaculation following prostatectomy in males?
Damage to the bladder neck mechanism
What maintains continence following prostatectomy in males?
The short segment of urethra passing through the urogenital diaphragm, which consists of striated and smooth muscle
Why is the external sphincter complex functionally more important in females?
The sphincter complex at the level of the bladder neck is poorly developed in females
What nerve provides innervation to the bladder and external sphincter complex?
Pudendal nerve
What type of innervation controls bladder filling and emptying?
Somatic innervation via the pudendal, hypogastric, and pelvic nerves, as well as autonomic nerves
What happens during bladder filling in terms of detrusor and sphincter activity?
Bladder filling leads to detrusor relaxation (sympathetic) and sphincter contraction
What happens during bladder emptying in terms of detrusor and sphincter activity?
The parasympathetic system causes detrusor contraction and sphincter relaxation
Where is the overall control of micturition located in the brain?
In the centers in the Pons
What can cause sphincter dysfunction and result in stress urinary incontinence?
Neurological disorders, such as pudendal neuropathy or multiple sclerosis
What happens in terms of urethral mobility in stress urinary incontinence?
Pressure is not transmitted appropriately to the urethra, leading to involuntary urine passage during episodes of raised intra-abdominal pressure
What happens in terms of sphincter function in stress urinary incontinence?
The sphincter fails to adapt and compress the urethra, resulting in involuntary urine passage. Complete sphincter failure may lead to continuous urine passage
What may be the cause of urge incontinence?
Poor central and peripheral coordination of events surrounding bladder filling
What should be done to assess urinary incontinence over a period of time?
Keep a bladder diary for at least 3 days
What are the conservative measures for managing stress urinary incontinence or mixed symptoms?
Pelvic floor exercises for 3 months
What should be excluded before diagnosing urinary incontinence?
Other organic diseases, such as stones, UTI, or cancer
What should be considered if the diagnosis of urinary incontinence is unclear or if surgery is being considered?
Flow cystometry to further evaluate the symptoms
What is the recommended drug therapy for women with overactive bladder if conservative measures fail?
Oxybutynin (or solifenacin if elderly)
What is an alternative surgical option for women with detrusor instability?
Augmentation cystoplasty, which may require long-term intermittent self-catheterization
What can be considered for women with detrusor instability who fail non-operative therapy?
A trial of sacral neuromodulation, with conversion to permanent implant if there is a good response
What surgical procedure may be performed for women with stress urinary incontinence?
A urethral sling type procedure
According to NICE guidelines, how should urinary incontinence be initially classified?
As stress, urge, or mixed
What should be repaired if a cystocele is present in association with incontinence?
The cystocele, especially if it lies at the introitus
When should conservative treatment be started for urinary incontinence?
Before considering urodynamic studies, if the diagnosis is obvious from the history
How many days should a bladder diary be kept if the classification is unclear?
At least 3 to 7 days
When should urodynamic studies be considered for urinary incontinence?
If surgery is being planned
What is the recommended treatment for stress incontinence if pelvic floor exercises fail?
Consider surgery
What is the recommended treatment for urge incontinence if bladder training fails?
Oxybutynin (antimuscarinic drugs) or sacral nerve stimulation
What are the NICE guidelines for urinary incontinence assessment and management?
Initial classification, bladder diary, conservative treatment, urodynamic studies if surgery is planned
What is the first step in arterial blood gas interpretation?
Assessing the patient’s overall condition
What is the second step in arterial blood gas interpretation?
Determining if the patient is hypoxemic
What is the normal range for PaO2 (partial pressure of oxygen) on air?
10.0-13.0 kPa
What is the third step in arterial blood gas interpretation?
Evaluating if the patient is acidaemic (pH <7.35) or alkalaemic (pH >7.45)
What is the fourth step in arterial blood gas interpretation?
Analyzing the PaCO2 (partial pressure of carbon dioxide) levels
What does an elevated PaCO2 indicate if there is acidaemia?
It can account for the acidaemia
What is the fifth step in arterial blood gas interpretation?
Assessing the bicarbonate level or base excess
What does a low bicarbonate level and low base excess indicate?
A metabolic acidosis
What is the normal range for base excess?
Between -2 mmol and +2 mmol
What does a high bicarbonate level and high base excess indicate?
A metabolic alkalosis
What does heparin do?
Causes the formation of complexes between antithrombin and activated thrombin/factors 7,9,10,11 & 12
What are the advantages of low molecular weight heparin compared to unfractionated heparin?
Better bioavailability, lower risk of bleeding, longer half-life, little effect on APTT at prophylactic dosages, and less risk of HIT (heparin-induced thrombocytopenia)
What are the complications associated with heparin?
Bleeding, osteoporosis, heparin-induced thrombocytopenia (HIT), and anaphylaxis
When does heparin-induced thrombocytopenia (HIT) typically occur?
5-14 days after the first exposure to heparin
Why is unfractionated heparin preferred over low molecular weight heparin in surgical patients who may need a rapid return to the operating theatre?
Unfractionated heparin has a shorter duration of action and is easier to reverse compared to low molecular weight heparins
What are the pressure ranges generated by the heart pumps on the right and left sides?
0-25mmHg on the right side, 0-120mmHg on the left side
What proportion of the cardiac cycle does diastole make up at rest?
2/3
What is the intrinsic myogenic rhythm in cardiac myocytes responsible for?
Contraction of the heart, even in denervated hearts
What is the typical range for cardiac output per minute?
5-6 liters
What is the formula for cardiac output?
Heart rate x stroke volume
How does the SA node contribute to the resting heart rate?
It typically discharges around 100 times per minute
What is the resting membrane potential in the SA and AV nodes?
-70mV
What happens when the resting membrane potential in the SA and AV nodes reaches around -50mV?
An action potential is generated
What happens during the refractory period of cardiac cells?
They cannot be re-stimulated, allowing for adequate ventricular filling
What effect do parasympathetic fibers have on the heart?
They release acetylcholine, which slows down heart rate
What effect do sympathetic fibers and circulating adrenaline have on heart rate?
They increase heart rate by binding to β1 receptors in the SA node and enhancing pacemaker potential depolarization
What happens during mid-diastole in the cardiac cycle?
AV valves open, ventricles hold 80% of final volume, outflow valves shut, and aortic pressure is high
What happens during late diastole in the cardiac cycle?
Atria contract, ventricles receive 20% to complete filling, and typical end-diastolic volume is 130-160ml
What happens during early systole in the cardiac cycle?
AV valves shut, ventricular pressure rises, isovolumetric ventricular contraction occurs, AV valves bulge into atria (c-wave), and blood is ejected as aortic and pulmonary pressures are exceeded
What happens during late systole in the cardiac cycle?
Ventricular muscles relax, ventricular pressures drop, aortic pressure remains constant due to peripheral vascular resistance and aortic elasticity, and retrograde flow shuts the aortic valve
What happens during early diastole in the cardiac cycle?
All valves are closed, isovolumetric ventricular relaxation occurs, aortic pressure increases due to closure of the aortic valve, and atrial pressure exceeds ventricular pressure, causing AV valves to open
What are the mechanical properties related to cardiac physiology?
Preload (end-diastolic volume) and afterload (aortic pressure)
What does Laplace’s law state in relation to hollow organs?
The total circumferential wall tension depends on the circumference and thickness of the wall, as well as the wall tension
What does Laplace’s law explain in terms of cardiac physiology?
The rise in ventricular pressure during the ejection phase and the impaired systolic function of a dilated diseased heart
What happens when cardiac fibers are excessively stretched beyond a certain point?
Stroke volume will fall
What is the relationship between end-diastolic volume and stroke volume according to Starling’s law?
Increase in end-diastolic volume leads to a larger stroke volume
Why is Starling’s law important in cardiac transplant patients?
It helps regulate cardiac output and allows them to increase their cardiac output
Where are baroreceptors located in the body?
Aortic arch and carotid sinus
Which nerves transmit aortic baroreceptor impulses and carotid baroreceptor impulses?
Vagus nerve for aortic impulses, glossopharyngeal nerve for carotid impulses
What stimulates baroreceptors?
Arterial stretch
What are the effects of an increase in baroreceptor discharge?
Increased parasympathetic discharge to the SA node, decreased sympathetic discharge to ventricular muscle (causing decreased contractility and fall in stroke volume), decreased sympathetic discharge to venous system (causing increased compliance), and decreased peripheral arterial vascular resistance
Where are atrial stretch receptors located?
In the atria at the junction between pulmonary veins and vena cava
What stimulates atrial stretch receptors?
Atrial stretch
What happens when there is increased blood volume?
It causes increased parasympathetic activity
What is the Bainbridge reflex?
An increase in heart rate mediated via atrial receptors in response to a very rapid infusion of blood
What is released in response to increased atrial stretch?
Atrial natriuretic peptide
What are some causes of severe thrombocytopenia?
ITP, DIC, TTP, and hematological malignancy
What happens when there is a decrease in receptor stimulation?
It results in increased sympathetic activity, decreased renal blood flow, decreased glomerular filtration rate (GFR), decreased urinary sodium excretion, increased renin secretion by the juxtaglomerular apparatus, and an increase in angiotensin II
What are some causes of moderate thrombocytopenia?
Heparin-induced thrombocytopenia (HIT), drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides), alcohol, liver disease, hypersplenism, viral infection (EBV, HIV, hepatitis), pregnancy, SLE/antiphospholipid syndrome, and vitamin B12 deficiency
What is the mechanism of action of warfarin?
It inhibits the reduction of vitamin K, which is necessary for the formation of clotting factors II, VII, IX, and X, as well as protein C
What are the side effects of warfarin?
Haemorrhage, teratogenic effects, and skin necrosis
Why does skin necrosis occur when warfarin is first started?
When warfarin is first started, the biosynthesis of protein C is reduced, leading to a temporary procoagulant state. This can result in thrombosis in venules, leading to skin necrosis. Normally, this is avoided by concurrent heparin administration.
What are some factors that may potentiate the effects of warfarin?
Liver disease, P450 enzyme inhibitors (e.g., amiodarone, ciprofloxacin), cranberry juice, drugs that displace warfarin from plasma albumin (e.g., NSAIDs), and drugs that inhibit platelet function (NSAIDs)
What is a common cause of hyponatremia in surgery?
Over administration of 5% dextrose
What are the possible causes of hyponatremia?
Water excess or sodium depletion
What are some causes of pseudohyponatremia?
Hyperlipidemia (increase in serum volume) or drawing blood from a drip arm
What are the classification criteria based on urinary sodium levels?
Urinary sodium > 20 mmol/l suggests sodium depletion or renal loss, while urinary sodium < 20 mmol/l suggests sodium depletion or extra-renal loss
What are some possible causes of hyponatremia with urinary sodium > 20 mmol/l?
Diuretics (thiazides), Addison’s disease, diuretic stage of renal failure, or SIADH (syndrome of inappropriate antidiuretic hormone)
What is the mnemonic for remembering the causes of hyponatremia with urinary sodium > 20 mmol/l?
Syndrome of INAPPropriate Anti-Diuretic Hormone: Increased Na (sodium) PP (urine)
What are some possible causes of hyponatremia with urinary sodium < 20 mmol/l?
Sodium depletion due to diarrhea, vomiting, sweating, burns, or adenoma of the rectum (if villous lesion and large)
What is the management approach for symptomatic hyponatremia?
For acute hyponatremia with Na < 120, immediate therapy is required. Aim to correct the sodium level until it is > 125 at a rate of 1 mEq/h. Normal saline with frusemide is an alternative method. The sodium requirement can be calculated using the formula: (125 - serum sodium) x 0.6 x body weight = required mEq of sodium
What are some possible causes of hyponatremia with water excess?
Secondary hyperaldosteronism (e.g., congestive heart failure, cirrhosis), reduced glomerular filtration rate (renal failure), IV dextrose, or psychogenic polydipsia
What are the major hormones of the thyroid gland?
Triiodothyronine (T3), Thyroxine (T4), and Calcitonin
Which thyroid hormone is the most biologically active in target cells?
Triiodothyronine (T3)
Which thyroid hormone is the most prevalent form in plasma?
Thyroxine (T4)
What happens in Graves disease?
In Graves disease, patients develop IgG antibodies to the TSH receptors on the thyroid gland. This results in chronic and long-term stimulation of the gland, leading to the release of thyroid hormones. Typically, this leads to elevated thyroid hormones and low TSH levels. Thyroid receptor autoantibodies should be checked in individuals presenting with hyperthyroidism, as they are present in up to 85% of cases.
Describe the synthesis and secretion of thyroid hormones.
Iodide is actively concentrated by the thyroid gland. It is then oxidized to atomic iodine by peroxidase in the follicular cells. The atomic iodine iodinates tyrosine residues in thyroglobulin. The iodinated tyrosine residues undergo coupling to either T3 or T4. This process is stimulated by TSH, which also stimulates the secretion of thyroid hormones. The normal thyroid gland has approximately 3 months’ worth of thyroid hormone reserves.
What is the function of calcitonin?
It lowers plasma calcium levels
What is the approximate total volume of CSF in the brain?
150 ml
Where does cerebrospinal fluid (CSF) fill in the brain?
Between the arachnoid mater and pia mater (covering the surface of the brain)
How is CSF produced and by what percentage?
Approximately 500 ml is produced by the ependymal cells in the choroid plexus, with 70% from the choroid plexus and 30% from blood vessels
How is CSF reabsorbed?
CSF is reabsorbed via the arachnoid granulations, which project into the venous sinuses
What is the circulation pathway of CSF?
Lateral ventricles (via foramen of Munro) -> 3rd ventricle -> Cerebral aqueduct (aqueduct of Sylvius) -> 4th ventricle (via foramina of Magendie and Luschka) -> Subarachnoid space -> Reabsorbed into the venous system via arachnoid granulations into the superior sagittal sinus
What is the incisura?
The incisura, also known as the dicrotic notch, is a small dip or notch seen on the arterial waveform.
When does the incisura occur in the arterial pressure waveform?
The incisura occurs immediately after the peak of the arterial pressure waveform.
What causes the incisura?
The closure of the aortic valve causes a brief interruption in the arterial flow, resulting in the incisura.
What is the composition of hemoglobin?
Hemoglobin is a globular protein composed of 4 subunits. It consists of a protoporphyrin ring surrounding an iron atom in its ferrous state.
How does oxygen bind to hemoglobin?
The iron atom in hemoglobin can form a bond with oxygen, allowing it to bind to the hemoglobin molecule.
Describe the oxygen dissociation curve.
The oxygen dissociation curve shows the relationship between the percentage of saturated hemoglobin and the partial pressure of oxygen in the blood. It is not affected by hemoglobin concentration.
What is the role of the polypeptide chains in hemoglobin?
The polypeptide chains in hemoglobin, specifically the beta chains, can bind to carbon dioxide, hydrogen ions, and 2,3 diphosphoglycerate.
What causes a shift to the right in the oxygen dissociation curve?
Chronic anemia causes an increase in 2,3 DPG levels, resulting in a shift of the curve to the right.
What is the Haldane effect?
The Haldane effect describes the phenomenon where, for a given oxygen tension, there is increased saturation of hemoglobin with oxygen, leading to decreased oxygen delivery to tissues.
What is the Bohr effect?
The Bohr effect describes the phenomenon where, for a given oxygen tension, there is reduced saturation of hemoglobin with oxygen, leading to enhanced oxygen delivery to tissues.
What factors cause a shift to the left in the oxygen dissociation curve?
Factors such as HbF, methemoglobin, carboxyhemoglobin, low [H+] (alkali), low pCO2, low 2,3-DPG, and low temperature cause a shift to the left, resulting in lower oxygen delivery.
What factors cause a shift to the right in the oxygen dissociation curve?
Factors such as raised [H+] (acidic), raised pCO2, raised 2,3-DPG, and raised temperature cause a shift to the right, resulting in raised oxygen delivery.
What are the autonomic origins of the nerves involved in penile erection?
Sympathetic nerves originate from T11-L2, and parasympathetic nerves from S2-4 join to form the pelvic plexus.
What is the role of the parasympathetic discharge in penile erection?
Parasympathetic discharge causes erection.
What is the role of the sympathetic discharge in penile erection?
Sympathetic discharge causes ejaculation and detumescence (loss of erection).
Which nerves are involved in the somatic innervation of the penis?
The dorsal penile and pudendal nerves supply the somatic innervation of the penis.
What muscles are innervated by the efferent signals from Onufs nucleus?
Efferent signals from Onufs nucleus (S2-4) innervate the ischiocavernosus and bulbocavernosus muscles.
What happens during autonomic discharge to the penis?
Autonomic discharge triggers the veno-occlusive mechanism, leading to the flow of arterial blood into the penile sinusoidal spaces.
What is priapism?
Priapism is a prolonged, unwanted erection lasting more than 4 hours in the absence of sexual desire.
What are the two classifications of priapism?
The two classifications of priapism are low flow priapism and high flow priapism.
What causes low flow priapism?
Low flow priapism is caused by veno-occlusion, leading to high intracavernosal pressures.
What causes high flow priapism?
High flow priapism is caused by unregulated arterial blood flow.
What tests can be done to evaluate priapism?
Sickle cell and leukemia should be excluded. Blood sampling from the cavernosa can determine whether it is a high flow or low flow priapism.
What are some causes of priapism?
Some causes of priapism include intracavernosal drug therapies (e.g., for erectile dysfunction), blood disorders such as leukemia and sickle cell disease, neurogenic disorders such as spinal cord transection, and trauma to the penis resulting in arteriovenous malformations.
What is the main hormone secreted by carcinoid tumors?
Serotonin
What are some management options for priapism?
Management options include applying ice packs or taking cold showers. For low flow priapism, blood may be aspirated from the corpora or intracavernosal alpha adrenergic agonists can be tried. Delayed therapy of low flow priapism may result in erectile dysfunction.
Where else can carcinoid tumors occur?
Carcinoid tumors can also occur in the rectum and bronchi.
Where do carcinoid tumors mainly originate?
Neuroendocrine cells in the intestine, specifically the midgut (distal ileum/appendix)
When do hormonal symptoms of carcinoid syndrome mainly occur?
Hormonal symptoms mainly occur when the disease spreads outside the bowel.
How does carcinoid syndrome typically present?
Carcinoid syndrome has an insidious onset over many years and can present with symptoms such as flushing of the face, palpitations, pulmonary valve stenosis and tricuspid regurgitation causing dyspnea, asthma, and severe secretory diarrhea that persists despite fasting.
What are the recommended investigations for carcinoid syndrome?
Investigations for carcinoid syndrome include measuring 5-HIAA (a breakdown product of serotonin) in a 24-hour urine collection, somatostatin receptor scintigraphy, CT scan, and blood testing for chromogranin A.
What is the treatment for carcinoid syndrome?
The treatment for carcinoid syndrome includes the use of octreotide (a somatostatin analog) and surgical removal of the tumor when possible.
What are the two main causes of hyperuricaemia?
Increased cell turnover or reduced renal excretion of uric acid
Can hyperuricaemia be present in asymptomatic patients without a history of gout attacks?
Yes, hyperuricaemia can be found in asymptomatic patients without a history of gout attacks.
What other conditions are hyperuricaemia associated with?
Hyperuricaemia can be associated with hyperlipidaemia, hypertension, and the metabolic syndrome.
What is the length of the submandibular duct (Wharton’s duct)?
The submandibular duct (Wharton’s duct) is approximately 5 cm in length.
What are some causes of increased uric acid synthesis?
Causes of increased uric acid synthesis include Lesch-Nyhan disease, myeloproliferative disorders, a diet rich in purines, exercise, psoriasis, and the use of cytotoxic medications.
What are some causes of decreased uric acid excretion?
Causes of decreased uric acid excretion include the use of drugs such as low-dose aspirin, diuretics, and pyrazinamide, pre-eclampsia, alcohol consumption, renal failure, and lead exposure.
Where does the submandibular duct (Wharton’s duct) open?
The submandibular duct (Wharton’s duct) opens laterally to the lingual frenulum on the anterior floor of the mouth.
What are the superficial relations of the submandibular gland?
The superficial relations of the submandibular gland include the platysma muscle, deep fascia, mandible, submandibular lymph nodes, facial vein (near the mandible), marginal mandibular nerve, and cervical branch of the facial nerve.
What are the deep relations of the submandibular gland?
The deep relations of the submandibular gland include the facial artery (inferior to the mandible), mylohyoid muscle, submandibular duct (Wharton’s duct), hyoglossus muscle, lingual nerve, submandibular ganglion, and hypoglossal nerve.
What innervates the submandibular gland?
The submandibular gland is supplied by a branch of the facial artery. The facial artery passes through the gland to groove its deep surface and emerges onto the face by passing between the gland and the mandible.
What is the venous drainage of the submandibular gland?
The submandibular gland is drained by the anterior facial vein, which lies deep to the marginal mandibular nerve.
What is the lymphatic drainage of the submandibular gland?
The submandibular gland is drained by the deep cervical and jugular chains of lymph nodes.
What are the recommended crystalloids for resuscitation or fluid replacement?
Ringer’s lactate or Hartmann’s solution
When should 0.9% N. Saline be avoided as a crystalloid?
0.9% N. Saline should be avoided unless the patient is vomiting or has gastric drainage due to the risk of hyperchloraemic acidosis.
What are the recommended options for maintenance fluids?
4%/0.18% dextrose saline or 5% dextrose
What are the adult maintenance fluid requirements in terms of sodium (Na) and potassium (K) levels?
Na: 50-100 mmol/day, K: 40-80 mmol/day in 1.5-2.5L fluid per day.
How long should patients for elective surgery be nil by mouth?
Patients for elective surgery should not be nil by mouth for more than 2 hours, unless they have a disorder of gastric emptying.
What is the recommendation for carbohydrate-rich drinks before elective surgery?
Patients for elective surgery should be given carbohydrate-rich drinks 2-3 hours before, as part of a normal preoperative plan to facilitate recovery.
Should mechanical bowel preparation be avoided?
Yes, mechanical bowel preparation should be avoided.
How should excessive fluid losses from vomiting be treated?
Excessive fluid losses from vomiting should be treated with a crystalloid and potassium replacement. 0.9% N. Saline should be given if there is hypochloraemia, otherwise Hartmann’s or Ringer lactate should be given for diarrhoea, ileostomy, ileus, or obstruction.
What should be considered if bowel prep is used?
If bowel prep is used, simultaneous administration of Hartmann’s or Ringer’s lactate should be considered.
What should be given to high-risk patients?
High-risk patients should receive fluids and inotropes.
What should be used to detect pre or operative hypovolaemia?
Flow-based measurements should be used if available. Otherwise, clinical evaluation such as JVP (jugular venous pressure) and pulse volume should be performed.
What should be used to treat hypovolaemia caused by blood loss or infection?
A balanced crystalloid or colloid should be used, or blood if available in the case of blood loss. In critically ill patients, 5% dextrose should also be given to prevent interstitial edema.
What are the recommended crystalloids for IV fluid resuscitation?
Crystalloids containing sodium in the range of 130-154 mmol/l, with a bolus of 500 ml over less than 15 minutes. (NICE Guidance CG 174)
Which cells secrete parathyroid hormone (PTH)?
Chief cells of the parathyroid glands
What is the half-life of PTH in the plasma?
4 minutes
What are the effects of PTH on bone?
Binds to osteoblasts, signaling osteoclasts to resorb bone and release calcium
What is the role of PTH in increasing serum calcium concentration?
Stimulation of PTH receptors in the kidney and bone
What are the effects of PTH on the kidney?
Active reabsorption of calcium and magnesium from the distal convoluted tubule, and decreased reabsorption of phosphate
What happens during the haemostasis phase of wound healing?
Vasospasm in adjacent vessels, platelet plug formation, and generation of a fibrin-rich clot
How does PTH affect intestinal calcium absorption?
Increases intestinal calcium absorption by increasing activated vitamin D, which in turn increases calcium absorption
Which cells are involved in the haemostasis phase?
Erythrocytes and platelets
How long does the haemostasis phase typically last?
Seconds/Minutes
What occurs during the inflammation phase of wound healing?
Neutrophils migrate into the wound, growth factors are released (including basic fibroblast growth factor and vascular endothelial growth factor), fibroblasts replicate and migrate into the wound, and macrophages and fibroblasts couple matrix regeneration and clot substitution
Which cells are involved in the inflammation phase?
Neutrophils, fibroblasts, and macrophages
What happens during the regeneration phase of wound healing?
Platelet-derived growth factor and transformation growth factors stimulate fibroblasts and epithelial cells, fibroblasts produce a collagen network, angiogenesis occurs, and the wound resembles granulation tissue
How long does the inflammation phase typically last?
Days
Which cells are involved in the regeneration phase?
Fibroblasts, endothelial cells, and macrophages
Which cells are involved in the remodelling phase?
Myofibroblasts
How long does the regeneration phase typically last?
Weeks
How long does the remodelling phase typically last?
6 weeks to 1 year
What occurs during the remodelling phase of wound healing?
Fibroblasts become differentiated into myofibroblasts, which facilitate wound contraction, collagen fibers are remodeled, and microvessels regress, leaving a pale scar
Where is glucose stored in the liver and skeletal muscles in the presence of insulin?
As glycogen
Which cells in the body produce insulin?
Beta cells of the pancreas
Where is glucose stored in fat cells (adipocytes) in the presence of insulin?
As triglycerides
What is the structure of the human insulin protein?
A dimer of an A-chain and a B-chain, linked together by disulfide bonds; composed of 51 amino acids with a molecular weight of 5808 Da
How is insulin synthesized in pancreatic beta cells?
Pro-insulin is formed by the rough endoplasmic reticulum, then cleaved to form insulin and C-peptide
Where is insulin stored before being released?
In secretory granules
What stimulates the release of insulin?
Hyperglycemia
What are the functions of insulin?
Glucose utilization and glycogen synthesis, inhibition of lipolysis, and reduction of muscle protein loss
What is the primary effect of inotropes?
Increasing cardiac output
How do catecholamine type agents, such as adrenaline, work as inotropes?
By increasing cAMP levels through adenylate cyclase stimulation, leading to intracellular calcium ion mobilization and increased force of contraction
What are the receptor agonist properties of adrenaline at lower doses?
Beta adrenergic receptor agonist
What are the receptor agonist properties of adrenaline at higher doses?
Alpha receptor agonist
What effects does dopamine have on the body as an inotrope?
Dopamine receptor-mediated renal and mesenteric vascular dilation, and beta 1 receptor agonism at higher doses, resulting in increased cardiac output
What receptor agonist properties does dobutamine primarily have?
Beta 1 receptor agonist, with weak beta 2 and alpha receptor agonist properties
What is the primary receptor agonist action of noradrenaline as an inotrope?
Alpha receptor agonist and peripheral vasoconstrictor
Which specific enzyme do phosphodiesterase inhibitors, like milrinone, act on?
Cardiac phosphodiesterase
What is the overall effect of receptor binding to α-1 and α-2 receptors?
Vasoconstriction
What is the effect of receptor binding to β-1 receptors?
Increased cardiac contractility and heart rate
What is the effect of receptor binding to β-2 receptors?
Vasodilation
What is the effect of receptor binding to D-1 receptors?
Renal and spleen vasodilation
What is the effect of receptor binding to D-2 receptors?
Inhibition of the release of noradrenaline
What is the pH of gastric acid?
Around 2
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
What maintains the acidity of gastric acid?
The H/K ATPase pump
Which cells in the stomach produce gastric acid?
Parietal cells
What is the role of bicarbonate ions in the process of gastric acid secretion?
They are secreted into the surrounding vessels
Which ions are actively secreted from the parietal cell into the canaliculus?
Sodium and chloride ions
What sets up a negative potential across the membrane of the parietal cell?
The active secretion of sodium and chloride ions into the canaliculus
Which ions are left in the canaliculus after the hydrogen ions leave the parietal cell?
Hydrogen and chloride ions
How do hydrogen ions leave the parietal cell?
Via the H/K antiporter pump
What are the three phases of gastric acid secretion?
Cephalic phase, gastric phase, and intestinal phase
What stimulates gastric acid secretion in the gastric phase?
Stomach distension/low pH/peptides and gastrin release
What stimulates gastric acid secretion in the cephalic phase?
Smell/taste of food and vagal cholinergic stimulation
What inhibits gastric acid secretion in the intestinal phase?
High acidity/distension/hypertonic solutions in the duodenum, mediated by enterogastrones (CCK, secretin) and neural reflexes
What factors increase gastric acid production?
Vagal nerve stimulation, gastrin release, and histamine release from enterchromaffin-like cells
What factors decrease gastric acid production?
Somatostatin, cholecystokinin, and secretin
What stimulates the release of gastrin?
Distension of the stomach and extrinsic nerves
Which cells in the stomach produce gastrin?
G cells in the antrum of the stomach
What inhibits the release of gastrin?
Low antral pH and somatostatin
What are the effects of gastrin on food digestion?
It increases the secretion of HCL, pepsinogen, and intrinsic factor (IF), increases gastric motility, and has a trophic effect on the gastric mucosa
Which cells in the upper small intestine produce CCK?
I cells
What stimulates the release of CCK?
Partially digested proteins and triglycerides
What are the effects of CCK on food digestion?
It increases the secretion of enzyme-rich fluid from the pancreas, contraction of the gallbladder, relaxation of the sphincter of Oddi, decreases gastric emptying, has a trophic effect on pancreatic acinar cells, and induces satiety
What are the effects of secretin on food digestion?
It increases the secretion of bicarbonate-rich fluid from the pancreas and hepatic duct cells, decreases gastric acid secretion, and has a trophic effect on pancreatic acinar cells
Which cells in the upper small intestine produce secretin?
S cells
What stimulates the release of secretin?
Acidic chyme and fatty acids
Which organs does VIP affect in food digestion?
Pancreas and intestines
What are the effects of VIP on food digestion?
It stimulates secretion by the pancreas and intestines, and inhibits acid and pepsinogen secretion
Which cells in the pancreas and stomach produce somatostatin?
D cells
What stimulates the release of somatostatin?
Fat, bile salts, and glucose in the intestinal lumen
What factors affect cerebral blood flow?
Systemic carbon dioxide levels, CNS metabolism, CNS trauma, CNS pressure
What are the effects of somatostatin on food digestion?
It decreases acid and pepsin secretion, decreases gastrin secretion, decreases pancreatic enzyme secretion, decreases insulin and glucagon secretion, inhibits trophic effects of gastrin, and stimulates gastric mucous production
Which mediator is the most potent in regulating cerebral blood flow?
PaCO
How do acidosis and hypoxemia affect cerebral blood flow?
They increase cerebral blood flow, but to a lesser degree
What is the Monroe-Kelly Doctrine?
It is a concept that considers the brain as a closed box, where changes in pressure are offset by the loss of cerebrospinal fluid (CSF)
What is the mechanism of action of lidocaine as a local anesthetic?
It affects sodium channels in the axon, blocking their function
What happens when the offsetting of pressure changes by CSF loss is no longer possible?
Intra cerebral pressure (ICP) rises
How is lidocaine metabolized and excreted?
Hepatic metabolism, protein bound, renally excreted
What are the factors that contribute to lidocaine toxicity?
IV or excess administration, liver dysfunction or low protein states, and acidosis
What are the features of lidocaine toxicity?
Initial CNS overactivity followed by depression, cardiac arrhythmias
Which drugs can interact with lidocaine?
Beta blockers, ciprofloxacin, phenytoin
What is the advantage of combining adrenaline with lidocaine?
It limits systemic absorption
What is the form in which cocaine is supplied for local anesthetic purposes?
As a paste, usually cocaine hydrochloride
What are the systemic effects of cocaine?
Cardiac arrhythmias and tachycardia
How does bupivacaine work as a local anesthetic?
It binds to the intracellular portion of sodium channels, blocking sodium influx into nerve cells
What is the advantage of using bupivacaine for wound infiltration at the end of surgical procedures?
It has a longer duration of action, providing long-lasting analgesic effect
Why is levobupivacaine preferred over bupivacaine in some cases?
It is less cardiotoxic and causes less vasodilation
Why is prilocaine the agent of choice for intravenous regional anesthesia?
It is less cardiotoxic compared to other local anesthetic agents
What is the recommended dose of plain lignocaine?
3mg/Kg
What affects the efficacy of local anesthetic agents in tissues?
The dissociation constant, which shifts in acidic tissues and reduces their efficacy
What is the recommended dose of bupivacaine with adrenaline?
2mg/Kg
What is the recommended dose of plain bupivacaine?
2mg/Kg
What is the recommended dose of lignocaine with adrenaline?
7mg/Kg
What is the recommended dose of prilocaine with adrenaline?
9mg/Kg
What is the recommended dose of plain prilocaine?
6mg/Kg
What is the maximum total dose of lignocaine 1% plain?
3mg/Kg or 200mg (20ml)
What is the maximum total dose of lignocaine 1% with 1 in 200,000 adrenaline?
7mg/Kg or 500mg (50ml)
What is the maximum total dose of bupivacaine 0.5%?
2mg/Kg or 150mg (30ml)
What is the purpose of adding adrenaline to local anesthetic drugs?
It prolongs the duration of action and allows for higher doses
What are the contraindications for using adrenaline with local anesthetics?
Patients taking MAOIs or tricyclic antidepressants
How does the addition of adrenaline affect the total dose of bupivacaine compared to lignocaine?
The total dose of bupivacaine cannot be increased when adrenaline is added, unlike with lignocaine
What types of fibers innervate peripheral nociceptors in somatic pain?
Small myelinated fibers (A-delta) and unmyelinated fibers (C fibers)
What type of stimuli do A-gamma fibers register in somatic pain?
High intensity mechanical stimuli
What type of stimuli do C fibers usually register in somatic pain?
High intensity mechanothermal stimuli
Body fluid volumes
Compartment, Volume in litres, Percentage of total volume
Intracellular 28 L 60-65%
Extracellular 14 L 35-40%
Plasma 3 L 5%
Interstitial 10 L 24%
Transcellular 1 L 3%
Where is the parotid gland located?
Overlying the mandibular ramus; anterior and inferior to the ear
What structures pass through the parotid gland?
Facial nerve, external carotid artery, retromandibular vein, auriculotemporal nerve
Where does the salivary duct of the parotid gland drain?
Adjacent to the 2nd upper molar tooth (Stensen’s duct)
What are the anterior relations of the parotid gland?
Masseter, medial pterygoid, superficial temporal and maxillary artery, facial nerve, stylomandibular ligament
What are the posterior relations of the parotid gland?
Posterior belly of the digastric muscle, sternocleidomastoid, stylohyoid, internal carotid artery, mastoid process, styloid process
What is the arterial supply of the parotid gland?
Branches of the external carotid artery
What is the venous drainage of the parotid gland?
Retromandibular vein
Where does the parotid gland’s lymphatic drainage occur?
Deep cervical nodes
What is the parasympathetic innervation of the parotid gland?
Secretomotor
What is the sympathetic innervation of the parotid gland?
Superior cervical ganglion
What is the sensory innervation of the parotid gland?
Greater auricular nerve
What type of saliva does sympathetic stimulation produce?
Low volume, enzyme-rich saliva
What type of saliva does parasympathetic stimulation produce?
Water-rich, serous saliva
