PBL Review Flashcards
What can be given as a treament for microcytic anaemia? [1]
What alternative can be given if first line treatment causes bad side effects? [1]
Oral iron: Ferrous sulphate.
Can give ferrous gluconate if side effects are bad
Name a disease that commonly causes Anaemia of chronic inflammatory disease [1]
rheumatoid arthritis
State two drugs that can cause B12 deficiency [2]
Name two autoimmune conditions that can cause B12 deficiency [2]
Drugs:
* Nitrous oxide
* Metformin
Autoimmune conditions:
* Crohns diease
* Pernicious anaemia
Describe the process of normal metabolism of B12 [7]
i. B12 broken down from protein
ii. Binds to haptocorrin in stomach
iii. Dissociates from haptocorrin
iv. Binds to stomach intrinsic factor
v. Absorbed in terminal ileum into blood
vi. In blood, binds with transcobalamin
vii. Stored in liver
Explain why assessing serum B12 levels may be deceptive [1]
B12 is either active or inactive in blood. Therefore may say have normal levels even though patient is deficient as they only have inactive B12
How do you calculate MCV? [1]
What is the unit [1]
MCV = Haematocrit / (Hb X RBC). It is expressed in femtolitres (fl) (1015 fl = litre)
Following haemorrhage there will be a what type of anaema in the short term? [1]
Explain your answer [1]
Following haemorrhage there will be a normocytic anaemia due to haemodilution, in the short term.
What serum markers would indicate someone is suffering from pernicious anaemia? [2]
- Antibodies to intrinsic factor
- Antibodies to gastric parietal cells occur in serum.
Which cell in the bone marrow differentiates into a common myeloid progenitor? (1 mark)
Haematopoietic stem cells
Which cells secrete intrinsic factor and where are they located? (1 mark)
Parietal cells [0.5] gastric mucosa [0.5]
How can reticulocytes be differentiated from erythrocytes on a blood film (1 mark).
Each point is worth half a mark
Reticulocytes are stained blue [0.5]
Reticulocytes bigger [0.5]
Ribosomes present [0.5]
How will the blood count of someone suffering from acute blood loss differ from someone suffering from chronic blood loss? (2 marks)
Acute: normocytic anaemia [1]
Chronic: IDA -> hypochromic microcytic anaemia [1]
Calculate a patient’s mean corpuscular volume, if their haematocrit = 0.45, Hb = 120 g/l, red cell count = 5 x 1012 /l (2 marks)
MCV = 0.45 / 5 x1012
= 90 fL
Heart Failure
Explain why the patient is breathless [1]
This is because the pulmonary venous pressure exceeds the oncotic pressures maintaining fluid within the pulmonary capillaries (cf Starling Principle). Breathlessness may then be due to inadequate transfer of oxygen from the alveoli to the blood.
Heart failure
Explain why the patient’s breathlessness is raised at night [3]
- This becomes exaggerated at night as the pulmonary venous pressure increases when someone is lying down and also because the respiratory drive is reduced during sleep.
- there is less sympathetic bronchodilation during sleep and this decreases oxygen diffusion into the alveoli.
- nerve endings in the lungs are activated and trigger an alarm reaction that wakes him up.
Heart failure
Explain the different lung sounds heard in the during heart failure [2
Crackles: bubbling or popping sounds that represent the presence of fluid or secretions, or the sudden opening of closed airways.
* Crackles that result from fluid (pulmonary edema) or secretions (pneumonia) are described as “wet” or “coarse,”
* Crackles that occur from the sudden opening of closed airways (atelectasis) are referred to as “dry” or “fine.”
Explain 5 symptoms of aortic stenosis [5]
i. Dyspnoea - increase in diastolic pressure in stiff non-compliant LV. LV is thicker because has to use more energy to expel blood (hypertrophy)
ii. Angina - increase O2 demand of hypertrophied LV
iii. Syncope - either paroxysmal ventricular arrhythmias or exertional cerebral hypoperfusion (less blood is leaving)
iv. LVF - contractile failure as ventricle dilates – causes heart failure
v. Sudden death - ventricular arrhythmias
What is the preferred imaging for aortic stenosis? [1]
Echocardiogram
What are the treatments for systolic heart failure? [9]
- ACE-Is (all grades of heart failure). Can cause dry cough.
- ARBs (if ACE-Is cannot be tolerated)
- beta-blockers (all grades of heart failure)
- spironolactone (NYHA grade III and IV only)
- Devices:
* cardiac resynchronization therapy (CRT) (pacemaker: causes two sides of heart to pump together – increases EF)
* ± ICD implanted cardiac defib: monitors heart rhythm – if goes into VF or VT, will give a shock into normal rhythm) - ARB/neprilysin inhibitor (neprilysin inhibits breakdown of BNP) (It includes the neprilysin inhibitor sacubitril (AHU377) and the ARB valsartan)
- SGLT-2 inhibitors (ESC guidelines 2021).
- Heart transplant
How does dilated cardiomyopathy lead to HF?
i. Causes nonsynchronous myocytes: impaired ventricular filling
ii. Decreases stroke volume
iii. Decreases cardiac output
iv. Increases preload
Acute LVF causes what type of lung failure? [1]
Type 1 resp. failure
Testing for BNP is sensitive but not specific. This means that when negative it is useful in ruling out heart failure, but when positive result
can have other causes. Other causes of a raised BNP include:? [5]
- Tachycardia
- Sepsis
- Pulmonary embolism
- Renal impairment
- COPD
Acute managment for LVF? [4]
Chronic HF management? [4]
ABAL
- ACE inhibitor (e.g. ramipril titrated as tolerated up to 10mg once daily)
- Beta Blocker (e.g. bisoprolol titrated as tolerated up to 10mg once daily)
- Aldosterone antagonist when symptoms not controlled with A and B (spironolactone or eplerenone)(spiro causes man boobs)
- Loop diuretics improves symptoms (e.g. furosemide 40mg once daily)
- What is the minimum number of days a patient with pneumonia may receive antibiotics? (1 mark)
Minimum duration of 5 days (1 mark)
Describe the pathophsyiology of asthma [4]
i. Allergen picked up by dendritic cells and presented by MHC Class II molecules
ii. CD4 cells activate the TH-2 lymphocytes through the release of IL4, IL5, IL13.
iII. IL 4 leads to the production of IgE antibodies: coat mast cells and stimulate degranulation and the release histamines, leukotrienes and prostaglandins
iv. IL-5 activates eosinophils: causes more cytokine & leukotrienes release
v IL-9 = mast cell proliferation
Describe the difference in IL-5 and IL-9 in asthma pathophysiology [2]
- IL-5 = Eosinophil activation
- IL-9 = mast cell proliferation
Describe the symptoms of asthma [5]
Episodic symptoms:
ii. Diurnal variability. Typically worse at night.
iii. Dry cough with wheeze and shortness of breath
iv. A history of other atopic conditions such as eczema, hayfever and food allergies
vi. Bilateral widespread “polyphonic” wheeze heard by a healthcare professional. BUT: neither sensitive nor specific for asthma
vii. Prolonged expiratory phase (respiratory and expiratory phases should be equal)
Describe asthma treatment pathway
Reliever medication: Short acting beta 2 agonists (SABAs)
1. Adrenalin acts on the smooth muscles of the airways to cause relaxation.
2. This results in dilatation of the bronchioles and improves the bronchoconstriction present in asthma
First line therapy:
* Low dose inhaled ICS (if need, may required higher doses)
Add on therapy:
* ICS + inhaled long acting beta 2 agonists (LABA) or long acting anti muscarinic (LAMA)
Add on therapy:
ICS + LAMA / LABA + specialist therapies
What is MART / SMART therapies? [1]
is a form of combined ICS and LABA treatment in which a single inhaler, containing both ICS and a fast-acting LABA, is used for both daily maintenance therapy and the relief of symptoms as required.
ICS causes a reduction in why three pro-inflammatory mediators in asthma? [3]
IL-6, TNF-a & CXCL8
Describe the management for mild, moderate and severe pneumonia [3]
i. Mild CAP: 5 day course of oral antibiotics: amoxicillin or a macrolide (azithromycin)
ii. Moderate to severe CAP: 7-10 day course of dual antibiotics (amoxicillin AND macrolide (azithromycin)
iII Severe Benzylpenicillin if blood culture tells you something different
What is ‘silent chest’ in life threatening asthma? [1]
- No wheeze. This occurs when the airways are so tight that there is no air entry at all. This is ominously described as a “silent chest”.
What are the PEFRs for:
Moderate
Severe
Life-threatening asthma
Moderate: 50-75% predicted
Severe: 33-50% predicted
Life-threatening asthma: < 33%
Acute asthma management? [5]
O! SHIT!
Oxygen
Salbutamol - (? in cardiac patients with presenting tachy, monitor potassium!)
Hydrocortisone - (or any steroid)
Ipratropium Bromide - (acetylcholine antagonist via blockade of muscarinic cholinergic receptors)
Tube (intubation) - (only if VVV severe)
Magnesium (calcium channel blockade)
First line investigations for asthma diagnosis? [2]
Second line? [2]
First line
* Fractional exhaled nitric oxide
* Spirometry with bronchodilator reversibility
Second line
* Peak flow variability measured by keeping a diary of peak flow measurements several times per day for 2 to 4 weeks
* Direct bronchial challenge test with histamine or methacholine
Characteristic chest signs of pneumonia? [3]
Bronchial breath sounds. These are harsh breath sounds equally loud on inspiration and expiration. These are caused by
consolidation of the lung tissue around the airway.
Focal coarse crackles. These are air passing through sputum in the airways similar to using a straw to blow in to a drink.
Dullness to percussion due to lung tissue collapse and/or consolidation.
Describe the MoA of amoxicillin [1]
Amoxicillin competitively inhibit penicillin binding proteins, leading to up-regulation of autolytic enzymes and inhibition of cell wall synthesis.
Describe the MoA of Macrolides [2]
Macrolides inhibit bacterial protein synthesis.
The mechanism of action of macrolides revolves around their ability to bind the bacterial 50S ribosomal subunit causing the cessation of bacterial protein synthesis.
Name an ICS used to treat asthma [1]
Beclomethasone
What is pabrinex and explain which pathology it may prevent by providing it [2]
Pabrinex: provides additional vitamins B and C to correct deficiencies that may have occurred. Incudes Thiamine. Thiamine deficiency can lead to Wernicke Encephalopathy
Desribe the action (and site of action) of terlipressin
- Terlipressin: is a synthetic analogue of vasopressin, which is an endogenous neurohormone that acts as a vasoconstrictor – maintains pressure for the kidneys
How do you treat Hepatic Encephalopathy? [1]
Lactulose: clears toxins from your blood by leading to frequent bowel movements, with less time for ammonia absorption and increased fecal nitrogen excretion.
Describe the pathophysiology of cirrhosis [3]
State 4 disease it can lead to [4]
Hepatic fibrosis leads to cirrhosis with nodule formation. Prevents regeneration
* Activation of hepatic stellate cells: cause accumulation of collagen type I and III in the hepatic parenchyma and space of Disse
* Stellate cells also become more contractile
* Accumulation of collagen causes altered exchange between hepatocytes and plasma
* Disrupts blood flow and causes increased pressure in the portal venous system: portal hypertension, causing:
i. Ascites
ii. Gastro-oesophageal varices
iii. Rectal varices
iv. Promotes the diversion of nutrient carrying blood away from the liver and cause hepatic encephalopathy
Explain the results
Low Hb, Low plts and High INR: liver disease causes coagulation disorder leading to bleeding and subsequent anaemia.
Low albumin: the liver makes less albumin leading to deviations of the equilibrium between osmotic pressure and hydrostatic pressure in the blood vessels. Low albumin along with portal hypertension, results in the patient suffering from ascites and oedema. Albumin is also a marker of nutritional status.
High bilirubin: bilirubin (waste product from the breakdown of RBC). The liver has reduced ability to conjugate bilirubin, so it can’t be excreted, leading to high levels being present in blood. This causes jaundice
.
High ALP, AST, ALT and GGT: these liver enzymes are present at higher levels in the blood when leaking out of dying hepatocytes. Not extremely as liver was previously damaged by HCV.
High urea: main nitrogenous breakdown product of protein metabolism. High urea due GI bleeding being digested as a “protein rich meal”.
Low end of normal glucose: liver is unable to maintain blood glucose level due to damage.
Explain the consequences of liver failure on the metabolic state [2]
Which energy store is the patient with decompensated liver most likely using as main energy supply? [1]
(There are similarities to the starved state here)
- Blood glucose is on the low side and this is symptomatic of the liver not being able to store glycogen/do glycogenolysis and gluconeogenesis thus blood glucose homeostasis will be impaired.
- Similarly, ketones are unlikely to be as high as they would if the liver was fully functioning. In this case, the patient is likely to be using fats as their main energy supply.
Explain why gallstones made lead to a prolonged INR? [1]
Lack of bile salts gives malabsorption of fats and slows absorption of fat-soluble vitamin K, which is required for synthesis of some clotting factors including prothrombin.
A portal pressure above [] mmHg causes portal hypertension? [1]
Pressure rise above 14 mmHg (usual: 5-10 mmHg)
Explain why hepatic encephalopathy is a complication of liver cirrhosis [3]
Ammonia: the liver clears almost all of the portal vein ammonia, converting it into glutamine and urea, preventing entry into the systemic circulation. Ammonia is a by-product of the metabolism of nitrogen-containing compounds, and is neurotoxic at elevated concentrations.
GI bleeding: the presence of blood in the upper GI tract results in increased ammonia and nitrogen absorption from the gut.
Aromatic amino acids (AAA): the increase in plasma AAA, resulting from a change in the** ability of the liver to process them** has been suggested to contribute to an increased influx in the brain leading to imbalances in neurotransmitter synthesis.
Explain why spontaneous bacterial peritonitis is a complication of liver cirrhosis [2]
Weakened immune system
- The liver contains 90% of the reticuloendothelial (RE) cells, such as Kupffer and sinusoidal endothelial cells, which are central to clearing bacteria.
- Most of the proteins of the “complement system” (part of the immune system that enhances the ability to clear microbes) are made by the liver. This increases the risk of bacterial peritonitis and thus the need for antibiotics
3) (i) What role does the liver plays in immunity? (ii) Why is the patient at risk of infection? [2 marks]
Weakened immune system due to reduction in energy metabolism, reduced formation of complement system protein, compromised reticuloendothelial function (Kupffer cells etc…) [1 mark].
Build-up of fluid increases risk of infection (providing a perfect 37C niche for bacterial growth) [1 mark]
5) Pabrinex, Lactulose and terlipressin are all part of the treatments for decompensated liver cirrhosis: describe their mode of action. [3 marks]
Pabrinex
* (via intravenous injection) provides these: mix of B vitamin (essential for a range of bodily processes and form part of the co-enzyme involved in carbohydrate, protein and lipid metabolism). (i) Thiamine is an important co-factor for the conversion of Pyruvate to AcetylCoA (which feeds into the Krebs cycle). If Thiamine is lacking, then Pyruvate forms lactic acid instead (which is neurotoxic).
Pabrinex also contain glucose, as the liver has impaired gluconeogenesis. [1 mark]
Lactulose - By acidifying the contents of the gut, lactulose reduces the absorption of ammonia from the gut, thereby helping to prevent encephalopathy. [1 mark]
Terlipressin - (analogue of vasopressin). It is important to reinstall correct blood circulation and support kidney function. (Main factors in the pathophysiology of hepatorenal syndrome are splanchnic vasodilation and increased cardiac output).
[1mark]
Describe mode of transmission for Hep A [1] and Hep B viruses? [1]
Hep A: faecal-oral route (contanimated water)
Hep B: Blood bourne / vertical transmission
What are normal kPa fibroscan scores? [1]
2-7kPa is normal, highest is 75
The four most common causes of liver cirrhosis are? [4].
- Alcoholic liver disease
- Non Alcoholic Fatty Liver Disease
- Hepatitis B
- Hepatitis C
What is a tumour marker for hepatocellular carnicoma? [1]
Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma and can be checked every 6 months as a screening test in patients with
cirrhosis along with ultrasound.
Which drug reduces the number of intestinal bacteria producing ammonia? [1]
rifaximin
Which HLA do most type 1 diabetic patients have? [2]
HLA-DR3-DQ2 or HLA-DR4-DQ8
What are the 3Ps of symptoms of type 1 diabetes? [3]
Polyuria (lots of urine)
o Glucose draws water into the urine by osmosis - not enough glucose can be reabsorbed as kidneys have reached the renal maximum reabsorptive capacity
o Can cause bed wetting
Polydipsia (extreme thirst)
o Due to high water loss due to XS glucose and water loss
Polyphagia (extreme appetite)
o Weight loss due to lipolysis in adipose tissues and break down of muscle protein because glucose is lost
What are the random [1] and fasting [1] plasma glucose levels that would indicate type 1 diabetes?
Random plasma glucose:
* > 11.1 mmol/L
Fasting plasma glucose:
* ≥7.0 mmol/L
Explain the consequence of insulin deficiency on glucose levels [3]
Explain the consequence of insulin deficiency on ketone body levels [2]
TN
Glucose
* Glycogen breakdown stimulated
* Gluconeogenesis stimulated
* Decreased removal of glucose by peripheral tissues
Ketone bodies
* Increased activity of acetyl CoA undergoing B-oxidation of fatty acids in liver
* Causes an increase (in acetoacetate; which leads to more) acetone
Describe the mechansim of diabetic ketoacidosis [5]
- Uncontrolled breakdown of glycogen & increased GNG due to lack of insulin; causes hyperglycaemia and therefore glycosuria
- Glycosuria causes osmotic diuresis; loss of electolytes and water
- Lipolysis; causing ketone bodies acetoacetate and 3-hydroxybutyrate ionised; results in an accumulation of ketone bodies; increased pH
- Some unionised acetoacetic and 3-hydroxybutyric acids are excrete in urine
- Increased pH can cause enzyme degradation, CNS depression, cerebral oedema and coma
What is the name for the characteristic breathing in DKA? [1]
What speficially causes this symptom? [1]
Kussmauls respiration: rapid deep breathing
Stimulation of H+ on the medullary resp. centre
Why is HCO3- low in DKA? [1]
Excess hydrogen ions bind the bicarbonate, resulting in decreased serum bicarbonate levels
Acidosis in DKA is due to the overproduction of which two molecules? [2]
Acidosis in DKA is due to the overproduction of β-hydroxybutyric acid and acetoacetic acid
( At physiological pH, these 2 ketoacids dissociate completely)
What mmol/L of blood ketones would indicate DKA? [1]
> 3.0mmol/L
What levels of HCO3- would indicate DKA? [1]
< 7.3 mmol/L
What is a possible consequence of not monitoring K+ levels in DKA management? [1]
How can you avoid this? [1]
o Hypokalaemia is important because when give insulin drives glucose and K into the cell; Large scale: cause cardiac arrythmias
Manage: Supply K at the same time as insulin
To diagnose DKA you require [3]
Hyperglycaemia (i.e. blood glucose > 11 mmol/l)
* Ketosis (i.e. blood ketones > 3 mmol/l)
* Acidosis (i.e. pH < 7
Causes of a normal anion gap or hyperchloraemic metabolic acidosis? [5]
Causes of a raised anion gap metabolic acidosis? [5]
Management for C. trachomatis [2]
- Doxycycline everyday for a week
- Azithromycin once a day for three days
Describe the test used to diagnose C. trachomatis [1]
ii. Positive nucleic acid amplification test (NAAT; checks directly for RNA or DNA of organism)
1. Vulvovaginal swab
2. Endocervical swab
3. First catch urine sample
4. Urethral swab in men
5. Anal swab
6. Pharyngeal swab
What is the most common cause of PID? [1]
i. Chlamydia trachomatis
How do you diagnose PID? [3]
i. Elevated white blood cell count
ii. Presence of polymorphonuclear cells on vaginal smear
iii. Genetic probe / culture of vaginal secretions for chlamydia or gonorrhoea
Know this
Management of PID [3]?
i. Parenteral cephalosporin & oral doxycycline & oral metronidazole
Describe the MoA for:
- Parenteral cephalosporin
- oral doxycyclin
- oral metronidazole
Cephalosporin:
* The beta-lactam rings bind to the penicillin-binding protein and inhibit its normal activity. Unable to synthesize a cell wall, the bacteria die
Doxycycline:
* allosterically binding to the 30S prokaryotic ribosomal unit during protein synthesis
metronidazole
* binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis
Signs and symptoms of ectopic pregnancy? [6]
- Missed period
-
pain in the tip of your shoulder
a. Sign that this pain is caused by blood leaking into the abdomen and is a sign that the condition is getting worse - Constant lower abdomen pain in right or left iliac fossa
- Vaginal bleeding
- Lower abdomen tenderness
- Cervical motion tenderness (pain when moving cervix in bimnaul exam)
- Palour
Describe the treatment plan for ectopic pregnancy if requires:
Expectant management
Medical managment
Surgical management
-
Expectant management
a. Await natural termination
b. Needs to not ruptured
c. No significant pain
d. No visible heartbeart -
Medical management
a. IM Methotrexate (in buttock)
i. Need to have oral contraceptives 3 months after treatment because is tetragenic) -
Surgical management (if tube has ruptured)
a. Laparoscopic salpingectomy
b. Laparoscopic salpingotomy
Name the two of the three complications of pelvic inflammatory disease and the reason that this arises. (3 marks)
Any 2 from
Chronic pelvic pain (0.5 marks) : This pain is thought to be related to cyclic menstrual changes, but it also may be the result of adhesions or hydrosalpinx. (1 mark)
Infertility (0.5 marks): Infection and inflammation can lead to scarring and adhesions within tubal lumens. The rate of infertility increases with the number of episodes of infection. (1 mark)
Ectopic pregnancy (0.5 marks): Ectopic pregnancy is a direct result of damage to the fallopian tube. (1 mark)
Explain why transvaginal ultrasound is the preferred imaging modality for early pregnancy monitoring. (2 marks)
By inserting the ultrasound wand into the vagina it provides a better view of the reproductive organs and the contents of the uterus as it is closer to the structures (1 mark)
and the ultrasound waves do not have to travel through the abdomen (1 mark)
What is the mode of action of methotrexate in this case? (2 marks)
Its mechanism of action, competitive inhibition of folate-dependent steps in nucleic acid synthesis, (1 mark) effectively kills the rapidly dividing ectopic trophoblast. (1 mark)
( if the student puts Methotrexate works by blocking the enzymes in the body that maintain the pregnancy. It stops the tissue from growing bigger and prevents it from rupturing (bursting). The pregnancy tissue is then gradually reabsorbed by the body. (1 mark) only)
Which organism causes more severe PID? [1]
- Neisseria gonorrhoeae tends to produce more severe PID
- A 27 year old woman who is 12 weeks pregnant attends the antenatal clinic for the results of her nuchal translucency scan and serum screening tests. The results reveal she has an increased nuchal translucency and decreased pregnancy-associated plasma protein A (PAPP-A) levels. What is the single most appropriate intervention at this point and why? (3 marks)
Chorionic villus sampling (1 mark)
Her results indicate a risk of her baby having Down syndrome (1 mark)
CVS would give a definitive diagnosis via karyotyping (1 mark)
What is normal newborn resp rate? [1]
- Newborn respiratory rate: 30-60 breaths/min
State 4 acyanotic heart lesions
- Atrial septal defects
- Ventricular septal defects
- Patent ductus arteriosus
- Patent ductus arteriosus:
Describe 5 consequencies of meconium aspiration [5]
o Airway obstruction -> increased lung resistance / hypoxia
o Infection
o Pulmonary inflammation
o Surfactant inactivation
o Persistent pulmonary hypertension
State 5 causes of non-reassuring fetal status [5]
Hypoxia
Maternal anaemia
Gestational hypertension
Intrauterine growth retardation
Meconium stained amniotic fluid
Presentation of non-reassuring fetal status [3]
Irregular heart beat
* Drop after maternal contraction can be sign of uteroplacental insufficiency
Problems with muscle tone / movements
Oligohydramnios
Complications [4] and management [3] of shoulder dystocia?
Complications:
Erb’s palsy (brachial plexus)
Fetal fracture
Hypoxemic-ischaemic brain injury
Maternal tearing / bleeding
Management:
Change mother’s position
Turn baby’s shoulders (McRoberts maneuver)
Episiotomy
State what tachy- and bradycardia in fetus [2]
Tachycardia > 160bpm
Bradycardia < 100 bpm
Describe why a fetus HR decelerates during stress [1]
Hypoxic stress fetus reduces its heart rate to preserve myocardial oxygenation and perfusion
Unlike an adult, a fetus cannot increase its respiration depth and rate. This reduction in heart rate to reduce myocardial demand is referred to as a deceleration.
State three causes of late deceleration [3]
- Maternal hypotension
- Pre-eclampsia
- Uterine hyperstimulation
What do late fetal HR deceleration indicate? [1]
Show insufficient uteroplacental flow -> hypoxia / acidosis to the fetus
Describe why variable decelerations occur [4]
Umbilical cord compressed often in oligohydramnios
Vein gets compressed -> acceleration
Artery gets compressed -> rapid deceleration
Pressure reduced -> baseline
Describe how established cervical cancer presents? [3]
- Symptoms of established cervical cancer:
a. Vaginal discharge
i. Intermittent or continuous
b. Bleeding
i. Spontaneous
ii. After sex
iii. After micturition
iv. After defecation
c. Vaginal discomfort
Late symptoms
1. Painless haematuria.
2. Chronic urinary frequency.
3. Painless fresh rectal bleeding.
Describe the different types of surgery for cervical cancer [5]
a. Conisation or simple hysterectomy
b. Radical trachelectomy: remove the cervix, nearby tissue and upper part of vagina
c. Laparoscopic hysterectomy and lymphadenectomy
i. Doesn’t preserve fertility
d. Radical hysterectomy
e. Anterior, posterior or total pelvic exenteration: remove reproductive organs & bladder
Describe endocrine management of breast cancer [2]
a. Tamoxifen:
i. Pre-menopausal women with ER+ (oestrogen receptor) cancer
ii. Blocks oestrogen receptors
b. Aromatase inhibitors
i. Only for postmenopausal women with ER+ cancer (oestrogen receptor)
Describe three forms of surgical management of breast cancer [3]
-
Wide local excision
a. Removes breast cancer with a margin of healthy tissue around the cancer
b. Useful if cancer is small -
Mastectomy
a. Entire breast removal -
Sentinel node sampling
a. Axillary node sampling:
i. Inject radioactive technetium into nipple
ii. Travels to first draining lymph
iii. Targeted removal of effect lymph
Describe the pathophysiology of colon cancer [1]
Majority arise from dysplastic adenomatous polyps
State 5 reasons why PSA may be raised [5]
- BPH
- UTI
- Ejaculation
- Vigorous exercise
- Urinary retention
c. Investigations used for prostate cancer [3]
- PSA
- Prebiopsy MRI
- Prostate biopsy
Describe the differences between D1 and D2 receptor inputs to the direct and indirect pathways
Describe the pathophysiology of Parkinson’s disease [4]
Selegiline should not be treated alongside which drug class? [1]
SSRIs
Describe the symptoms of L-dopa induced dyskinesia [6]
a. Dystonia:
i. This is where excessive muscle contraction leads to abnormal postures or exaggerated movements.
b. Chorea:
i. These are abnormal involuntary movements that can be jerking and random.
c. Athetosis:
i. These are involuntary twisting or writhing movements usually in the fingers, hands or feet.
d. Depression
e. Psychosis
f. Insomnia
Describe the MoA of citalopram [3]
- Increases amount of serotonin by reducing the reuptake of serotonin from synaptic cleft into the presynaptic neuron
- Antagonise serotonin transporter (SERT) on presynaptic membrane
- Allows more serotonin to bind to 5HT receptors on post synaptic membrane
What drug class is Mirtazapine? [1]
i. Tricyclic antidepressant
Describe the MoA of Mirtazapine [1]
inhibits the central presynaptic alpha-2-adrenergic receptors, which causes an increased release of serotonin and norepinephrine.
- Explain why physiotherapy improves the initial condition [3]
A physiotherapist will identify the muscles involved and then design a program of stretching and strengthening exercises, to be done within the limits of pain.
Physiotherapy is suggested because the damaged muscles may have shortened and atrophied, and in severe cases scar tissue may be present.
The muscles need to be loosened and stretched, and this will lessen the pain through increasing blood flow and healing as well as decreasing inflammation
Exercises will help break down the scar tissue in the muscle allowing it to regain its normal flexibility and lessening the chance of further injury.
- How are the electric shock-like and burning pains thought to occur? [3]
Nerve root and/or sensory ganglion compression or irritation occurring:
- This can lead to ectopic neural activity originating from the site of the compression
- Compression can also lead to severing of axons within the nerve roots or spinal nerves, causing inflammatory responses within the nerve which sensitise other cells
- Changes may also take place in the spinal cord at the first synapse and produce spontaneous activity in these central neurons
Describe how / why burning pain may occur with Jerry [1]
Burning sensations are often associated with alterations in nociceptor function as a result of injury.
These can result from both peripheral sensitisation (affecting threshold of activation of the sensory neurons themselves) and central sensitisation after injury. The burning sensations that evolve after Jerry’s nerve injury are characteristic of this chronic, neuropathic pain.
Explain the MoA of Paracetamol (acetaminophen) [3]
Paracetamol appears to act via at least 2 pathways: it reduces the active oxidized form of the COX-2 enzyme (this form of cyclooxygenase is induced by inflammatory stimuli), preventing it from forming pro-inflammatory substances such as prostaglandins and thromboxanes
Effects on prostaglandin synthesis in the central nervous system are thought primarily responsible for its antipyretic and much of its analgesic actions. One way this occurs is
decreasing prostaglandin E2-induced reduction of glycine inhibition of spinal cord cells
may act through the inhibition of reuptake of endogenous cannabinoids.
Why may paracetemol not anti-inflam.? [1]
In the presence of peroxides which are abundant at sites of inflammation, the COX-2 inihibition is inefficient, which appears to explain why it is a poor anti-inflammatory agent.
Explain the difference between diclofenac and ibuprofen [2]
Diclofenac is longer acting than ibuprofen
The additional activity may partly be explained by binding and inhibition of phospholipase A2 and reductions in the substrate arachidonic acid necessary for prostaglandin synthesis (as well as leukotriene) synthesis.
Diclofenac has a low but significant COX-2 selectivity
Describe MoA of pregabalin [3]
Its mechanism of action is via binding to the α2δ1 subunit of the N-type voltage gated calcium channels.
These subunits are increased in some neuropathic conditions on nociceptor and other terminals in the spinal cord. Binding of the drug to the subunit leads to a reduction in calcium entry into neuronal terminals
Therefore, pregabalin decreases the release of neurotransmitters such as glutamate, substance P and noradrenaline.
Briefly describe how acupuncture is thought to relieve pain [2]
Acupuncture is a form of diffuse noxious inhibitory control (DNIC): hereby pain in one part of the body may reduce pain in all other parts of the body.
Nociceptive input then activates the descending inhibitory neurons in the brainstem reticular formation (periaqueductal gray, raphe nuclei and locus coeruleus)
Describe the three types of symptoms of SCH [3]
Positive symptoms include delusions, hallucinations, thought disorder and catatonia (altered movement and muscle tone).
Negative symptoms include apathy, affective blunting, incongruity of emotions (e.g. laughing at a funeral) and a lack of initiative and drive.
Cognitive symptoms - schizophrenic patients suffer from a major information-processing deficit. Their impaired cognitive ability is reflected in poor learning, memory, attention and decision-making.
Describe environmental factors that influence SCH developement [5]
There is a higher risk for people born in winter months, and also after viral epidemics
excessive cannabis use in adolescence and older paternal age at birth.
stress or tiredness
Name two SCH drugs that can be given as slow release preperation? [2]
haloperidol, flupenthixol (IM)
Name three atypical antipsychotics [3]
clozapine, olanzapine, risperidone
- Chlorpromazine is a typical neuroleptic drug. Define the class of receptors blocked by this type of drug that is responsible for the patient experiencing dry mouth and constipation. (1 mark)
Muscarinic cholinergic receptors (1 mark).
- Name two atypical antipsychotic drugs used in the treatment of schizophrenia. What 5-HT receptors do atypical neuroleptics bind to? (2 marks)
Olanzapine, risperidone, sulpiride, amisulpride, quetiapine, aripiprazole.
5-HT2 receptor (1 mark).
Which anti-psychotics causes reduced seizure threshold? [1]
clozapine
Which anti-pyschotic is generally good side-effect profile, particularly for prolactin elevation? [1]
aripiprazole
atypical anti-pyschotic
Adverse effects of atypical antipsychotics? [2]
Adverse effects of typical antipsychotics? [2]
typical:
* Extrapyramidal side-effects (EPSEs)
* increased risk of stroke
* increased risk of venous thromboembolism
* impaired glucose tolerance
atypical:
* weight gain
* hyperprolactinaemia
Which typical anti-psychotic causes an increased QT interval? [1]
Haloperidol
- What is alpha-synuclein, where is it found in the brain and what is its genetic link with Parkinson’s disease? (2 marks)
Alpha-synuclein is a protein found in Lewy bodies in neurons (½ mark).
Lewy bodies are a major histopathological feature of Parkinson’s disease (½ mark).
The gene for alpha-synuclein is the SNCA gene; mutations associated with this gene (e.g. PARK1/4) have been identified as a genetic risk factor for Parkinson’s disease (1 mark).
- List and briefly describe three long-term complications of levodopa (L-DOPA) therapy. (3 marks)
- Motor fluctuations: include the ‘on-off’ phenomenon in which sudden and dramatic fluctuations of motor performance occur; periods of normal mobility (on) followed by sudden ‘freezing’ (off). End of dose deterioration and delayed (or ‘no on’ - freezing) responses also occur.
- Dyskinesias: include choreiform movements (purposeless involuntary dance-like movements) and dystonias (sustained intense muscle contractions).
- Non-motor complications: tingling, pain, akathisia, and autonomic dysfunction.
- Neuro-psychiatric problems: hallucinations, delirium, mood changes, sleep disturbance and nightmares.
- What is rotigotine and what is its route of administration? (2 marks)
Rotigotine is a dopamine receptor agonist (non-selective agonist), with affinity for both the D1 family and D2 family receptors (1 mark). It is applied transdermally as a patch (1 mark).
Which drugs are best used to treat milder PD symptoms? [5]
TN
selegiline (an MAOB inhibitor) or the newer drug rasagiline
amantadine: causes release of dopamine
anticholinergic drugs (e.g. orphenadrine, procyclidine, trihexyphenidyl)
These drugs are less efficacious than L-DOPA, and are mainly used as adjunctive therapy
Which vitamin may be useful for treating PD? [1]
Why? [1]
TN
Vitamin E is an anti-oxidant, and there is convincing evidence that Parkinson’s disease is associated with increased oxidative stress in the nervous system
Which hypothesis explains many pro-dromal non-motor symptoms of PD? [1]
Braak hypothesis:
* Parkinson’s disease start many years before the clinical diagnosis is made, and involve a particular propagation of neurodegeneration
What is the Hz of PD tremor? [1]
Tremor
* most marked at rest, 3-5 Hz
more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural
hypotension are also seen in some patients
This applies to which drug class? [1]
Dopamine agonists
Which drug is useful post myocardial infarction as there is more evidence for its safe use in this situation than other antidepressants? [1]
sertraline
citalopram and escitalopram are associated with what important AE? [1]
associated with dose-dependent QT interval prolongation
SSRIs should not be combined with which drug classes to increase the risk of seratonin syndrome? [2]
triptans - increased risk of serotonin syndrome
* monoamine oxidase inhibitors (MAOIs) - increased risk of serotonin syndrome
When stopping a SSRI the dose should be gradually reduced over a [] week period (this is not necessary with fluoxetine).
Which SSRI has a higher risk of discontinuation syndrome? [1]
When stopping a SSRI the dose should be gradually reduced over a 4 week period (this is not necessary with fluoxetine).
Paroxetine has a higher incidence of discontinuation symptoms.
Name some symptoms of SSRI discontinuation syndrome
increased mood change
* restlessness
* difficulty sleeping
* unsteadiness
* sweating
gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
* paraesthesia
What type of bone is most susceptible to developing osteoporosis and explain why?
2 marks
Trabeculae bone 1 mark
Because it turns over quicker and more often than cortical bone.
What biochemical changes are observed in the osteoarthritic articular cartilage?
(2 marks)
Reduced proteoglycan content
Change from collagen type 2 to type 1
Describe the MoA of Denosumab [1]
o is a monoclonal antibody that works by blocking the activity of osteoclasts.
Describe the MoA of Raloxifene [1]
It is a selective oestrogen receptor modulator that stimulates oestrogen receptors on bone but blocks them in the breasts and uterus.
Which foods should be targeted for OP patients
- Salmon and mackerel
- Maintain a healthy weight
- Adequate calcium intake
- Adequate vitamin D
o Ergocalciferol (Vit D) - Stop smoking
- Reduce alcohol consumption
Explain the results table
Explain results table: ALP raised osteoblasts are making more of enzyme. Low 25 (OHD) suggests that not absorbing much calcium from gut, so increased extraction from bones. Ca is normal so PTH is also normal
Name three genes linked to RA [3]
HLA DR4
PTPN22 gene
TRAF5 gene
Name 3 infective agents linked to triggering RA [3]
EBV
Rubella
Mycoplasma organisms
o For classification purposes, patients are said to have RA if they satisfy at least 4 of which 7 criteria? [7]
Morning stiffness: lasting ≥1 hour before maximal improvement.
Arthritis of three or more joint areas: simultaneously have had soft tissue swelling or fluid, observed by a physician
Arthritis of hands:
at least one swollen area in a wrist, MCP, or PIP.
Serum RF
Symmetrical arthritis
Radiographic changes
Rheumatoid nodules
What is the name for PIP deformity? [1]
o Boutonniere’s deformity
Name 3 TNF-alpha inhibitors used to treat RA [3]
Etanercept
* Binds to TNF-a
Infliximab
* Monoclonal antibody
* Binds to transmembrane and soluble forms of TNF-a
Adalimubab
RA treatment
o T cell co-stimulation blocker? [1]
Abatacept
Name 3 Janus kinase-1 selective inhibitors
All end in ibib
- Tofactibib
- Baricitinib
- Upadacitinib
2 What class of drug does Naproxen belong to and what is its mode of action and explain why it is given as a gastro-intestinal preparation?
Nonsteroidal anti-inflammatory drug (1/2 mark) It inhibits competitively cyclooxygenase 1 and 2 converting **arachidonic acid to prostaglandins **(COX1 and 2) (1 mark)
Prostaglandins are essential for production of bicarbonate and mucus that protects the stomach from the acid secretion. (1 mark) So the inhibition of Cox1 in the stomach will mean there is less mucous and less bicarbonate so more damage (1/2 mark)
3 What is the name of the overgrowth of the synovium in RA and explain how this affects the joint.
(3 marks)
Pannus (1/2 mark)
It grows over and into the articular cartilage (1/2 mark), it produces cytokines that attack the cartilage and break it down, (1 mark) plus the cytokines also induce synovial fibroblasts to differentiate as osteoclasts that break down the peri-articular bone. (1 mark)
4 Bella is seropositive for ACPAs? Briefly explain how NETosis is thought to be linked to the formation of these ACPAs
Neutrophils release extracellular traps and as part of this process release protein arginine deiminase 4 (1 mark) which will citrullinate peptides (1 mark). These are taken up by antigen presenting cells to T cells that activate plasma cells to produce the anti-citrullinated peptide antibodies (1 mark)
Explain why ulnar drift and subluxations occur in RA [2]
The ulnar drift and subluxations are due to the flexor muscles being larger and stronger than the
extensors so there is more likely to be flexor contractions
Osteomyelitis pathogenesis? [6]
Osteomyelitis may be caused by the haematogenous spread (more common) or non-haematogenous spread of pathogens to bone
Bacteria produce a polysaccharide extracellular matrix, forming a biofilm
Haematogenous osteomyelitis usually involves the metaphysis of long bones in children or the vertebral bodies in adults
In acute haematogenous osteomyelitis, infection spreads through bone via Haversian
and Volkmann canal systems.
The joint is usually spared, unless pus breaks through the metaphyseal cortex forming a subperiosteal abscess in an intracapsular metaphysis, as is found at the proximal radius, humerus, or femur and ankle
capillary anatomy in the metaphyseal area contains venous sinusoids which allow the bacteria to stagnate, while the lower pH and oxygen tension near the growth plate facilitate bacterial growth.
X-rays often do not show any changes, particularly in early disease.
They cannot be used to exclude osteomyelitis. The potential signs of osteomyelitis on an x-ray are: [3]
Periosteal reaction (changes to the surface of the bone)
Localised osteopenia (thinning of the bone)
Destruction of areas of the bone
State what the following mean with regards to imaging of osteomyelitis:
Sequestrum [1]
Involucrum [1]
Cloaca [1]
Sequestrum: Refers to a dead piece of devitalised bone that has been separated (i.e. sequestered) due to necrosis from the surrounding bone.
Involucrum: New growth of periosteal bone around a sequestrum.
Cloaca: An opening in an involuvcrum that allows the internal necrotic bone and pus to discharge out.
Symptoms and prensentation of spinal tuberculosis?
The onset is gradual.
Back pain is localised.
Fever, night sweats, anorexia and weight loss.
Signs may include kyphosis (common) and/or a paravertebral swelling.
Affected patients tend to assume a protective, upright, stiff position.
A psoas abscess may present as a lump in the groin and resemble a hernia
Investigations for spinal TB? [6]
- MRI is best to assess risk to the spinal cord
- Elevated ESR
- Strongly positive Mantoux skin test
- Spinal X-ray may be normal in early disease, as 50% of the bone mass must be lost for changes to be visible on X-ray: Plain X-ray can show vertebral destruction and narrowed disc space
- Biopsy of bone or synovial tissue is usual: if it shows tubercle bacilli this is diagnostic but usually culture is required
- chest X-ray and, if possible, culture of a spontaneously-produced respiratory sample to exclude or confirm co-existing pulmonary tuberculosis
Osteomyelitis commonly affects which vertebrae? [1]
T10 /11
Name and explain this sign of Pott’s disease? [1]
Pott’s Disease Cold Abscess: abscesses typically lack all the inflammatory signs obvious in abscesses
What is the difference between complicated and uncomplicated spinal TB?
Uncomplicated spinal TB is essentially a medical disease
Complicated spinal TB patients need surgical intervention in addition to chemotherapy
What is the first sign of cauda equina? [1]
Urinary retention is first sign of cauda equina
1 Name the two joints that connect the pelvic girdle together, and state what type of joint they are structurally.
(2 marks)
Sarcoiliac joint synovial (planar)
Pubic symphysis cartilaginous symphysis
3 Once the osteomyelitis is managed explain why he may still require orthopedic intervention for his vertebral column and suggest one possible intervention. [2]
The infection has weakend and damaged the bone and cause compression fractures already (1 mark)
Any from (1 mark)
Vertebroplasty
Spinal fusion with bone graft or similar
1 Explain why it is important to confirm the patient has no loss of bladder and bowel control?
(4 marks)
If the compression fracture or back problem had caused cauda equine syndrome (1 mark) then more spinal nerve roots would have been compromise including the sacral nerve roots (1 mark) that innervate the sphincter muscles that control urination and defecation. (1 mark) which is far more serious and needs urgent surgical intervention (1 mark)
- Describe the pathway, starting with the nociceptive afferents, with terminals in the lower back, through the spinal cord and ultimately to the cerebral cortex, for the transmission of pain sensation, specifically responsible for localization of the noxious stimulus. Ensure that you give the name of a) the sites where the neuronal cell bodies are located and b) the projection taken by their axons. (3 marks)
Nociceptive afferents with cell bodies in the dorsal root ganglia (½ mark), project axons which synapse in laminae I, II and V of the spinal cord (½ mark).
Axons from projection neurons in lamina I and V cross over at this segment (or 1-2 segments above) (½ mark) and ascend in the spinal cord contralaterally in the spinothalamic tract (½ mark).
The axons synapse in the ventroposterolateral (VPL) nucleus of the thalamus (½ mark), which projects to the primary somatosensory cortex (½ mark) where the localization of the stimulus is perceived.
- Explain the likely cause, the location of the injury and mechanism that generates the pain radiating down the side of Jerry’s leg to his toes. (4 marks)
It is likely due to herniation of the L4/L5 vertebral disc or vertebral degeneration (1 mark).
Compression or irritation of the nerve root/ dorsal root ganglion (1 mark) causes sensitisation and spontaneous activity in the affected fibres and thus the radiating pain (1 mark).
The nerve root affected is L5 as suggested from the distribution of the shock-like pains, which correspond to its peripheral distribution (1 mark).
Which subunit on primary afferents is upregulated in neuropathic pain conditions? 1[]
The α2δ1 subunit on primary afferents and other central terminals is upregulated in neuropathic pain conditions (½ mark).
- What class of drug is pregabalin? Explain its proposed mechanism of action in neuropathic pain. (2 marks)
Pregabalin is an anticonvulsant drug used in the treatment of neuropathic pain (½ mark).
It works on the α2δ1 subunit of N-type voltage gated calcium channel (½ mark).
The α2δ1 subunit on primary afferents and other central terminals is upregulated in neuropathic pain conditions (½ mark).
Pregabalin causes decreased release of neurotransmitters linked to hyperexcitability (e.g. glutamate, substance P, noradrenaline) (½ mark).
State 5 reasons when case control is worse than cohort [5]
May suffer from recall bias.
Different sorts of people (& their health) may be more likely to take part, depending on whether they are a case or a control, not true of a cohort where patients are usually all well at the start
Can only study one outcome (cohort studies can look at several outcomes)
May suffer from bias in selecting patients for cases and controls.
Cannot calculate absolute risks.
(If controls are not representative of the population from which the cases have arisen this can lead to bias in the results and the [] could be wrong.)
(If controls are not representative of the population from which the cases have arisen this can lead to bias in the results and the odds ratios could be wrong.)
Odds Marijuana use in cases = 113/26 = 4.35
Odds Marijuana use in controls = 222/70 = 3.17
Calculate the odds ratio [1]
Odds ratio Marijuana use in cases compared with controls = 4.35/3.17 = 1.37
Adjusted OR = 1.94 for smoking weed and testicular cancer. What does this mean? [1]
meaning that men that used Marijuana in this study had a 94% increased risk of developing testicular germ cell tumours after taking into account their other risk factors.
How what 95% confidence interval of 1.02 to 3.68 mean? [1]
The 95% confidence interval of 1.02 to 3.68 can be interpreted as meaning that we are 95% confident that the true increased risk of developing testicular germ cell tumours after taking into account their other risk factors lies between a 2% risk and a greater than 3 fold risk
What do crude (univariate or unadjusted) results mean? [1]
Crude (also called univariate or unadjusted) results, tell us the relationship between one risk factor and the outcome for everyone in the study.
What do adjusted (multivariate) results show us? [1]
Adjusted (also called multivariate) results tell us the effect we would get if we changed that factor if all the adjusting factors remain the same
Name the Bradford Hill Criteria
Strength of the association
Dose response
Reversibility
Temporality
Consistency
Biological Plausibility
Coherence of Evidence
Specificity
Acanthosis nigricans is a common sign of? [3]
diabetes and insulin resistance; PCOS;
State 4 roles of cortisol in glucose homeostasis
a. Liver GNG
b. Immobolises extrahepatic substances for GNG
c. Inhibits GNG in peripheral tissue
d. Stimulates lipid breakdown in adipose tissue
How does T3 work? [1]
- Act on nuclear receptors to regulate gene transcription
c. TSH release stimulated by? [4]
i. Cold
ii. Acute psychosis
iii. Circadian rhythm
iv. Negative feedback: T3 inhibits TSH levels
State effect of T3 at mitochondria [1]
b. More ATP synthesis is mito & overall more Causes mitochondriogenesis
Describe the role of T3 at the liver [2] and at peripheral tissues [2]
-
Opposes insulin at liver: Long term changes because they effect gene expression
a. Increased glucose intestinal absorption
b. Increases hepatic GNG - **Mimics insulin at peripheral tissues / muscle **
a. Upregulates GLUT4
b. Increased glycolysis
c. Propylthiouracil moa? [1]
stops conversion of T4 to T3
How do you diagnose Addisions?
Synacthen is another name for tetracosactide, the chemical used in the test.
ACTH is the chemical (hormone) released by your pituitary gland, which stimulates the adrenal glands to produce cortisol. If the adrenal glands are working properly they should respond to the tetracosactide by producing cortisol. Levels of cortisol are checked by taking a blood sample.
If levels of cortisol remain low, despite the tetracosactide injection, this suggests there is a problem with the function of the adrenal glands
3) What tissue is the source of (i) Leptin and (ii) GLP-1? For each hormone, state what will cause an increase? [2 marks]
(i) Leptin: Source: Adipocytes (OR fat cells OR white adipose tissue, NOT fat) [0.5 mark] Level is increased by an increase in adipose tissue (OR body fat mass) [0.5 mark]
(ii) GLP-1: Source: Intestinal L cells in mucosa of distal ileum & in colon [0.5 mark] Level is increased by a glucose or fat rich meal [0.5 mark]
4) Define what is acanthosis nigricans and where it is usually visible on the body. What metabolic change does it indicate and what does it suggest regarding Mr Phastaphuda’s pancreatic function? [2 marks]
Dry, dark patches of skin that usually appear in the armpits, neck or groin. [1 mark] Hyperinsulinemia –pancreas is hypersecreting to compensate for insulin resistance- may lead to pancreatic exhaustion in long term [1 mark]
5) Metabolic syndrome is defined according to several diagnostic criteria. List two criteria determining that a patient has metabolic syndrome [2 marks]
Any 2 among:
Increased waist circumference (there are sex and ethnicity-specific cut offs – the patient in the scenario has a waist circumference in excess of 90cm, the cut off for South Asian males)
Triglyceride levels high > 1.7 mmol/l or on treatment for high TGs
HDL cholesterol low < 1.03 in men, < 1.29 in women, or on treatment for low LDL
Systolic BP high > 130, diastolic BP > 85, or on treatment for hypertension
Fasting glucose high >5.6 mmol/l, or previously diagnosed T2DM
6) What AST:ALT ratio is consistent with NAFLD? [ 1 mark]
< 0.8
Why does skin colouration occur in hypothyroidism? [1]
(iii) Increased skin pigmentation is due to elevated levels of ACTH, released from the negative feedback usually induced by low levels of cortisol. ACTH binds to melanocortin-1 receptors in the skin, leading to increased melanin production [1 mark]
4) (i) Stating the precise region doing so, which organ releases cortisol? (ii) In the results table, why is it important that the cortisol sample was taken at 9AM? [2 marks]
(i) The zona fasciculata of the adrenal gland.
(ii) Cortisol levels are high in the morning and fall throughout the day.
5) (i) Which treatments was Adie prescribed, in addition to her anti-thyroid treatment, and (ii) which hormones were these drugs replacing? [2 marks]
(i) Hydrocortisone to replace cortisol [1 mark]
(ii) Fludrocortisone to replace aldosterone [1 mark]
What type of drug is Liraglutide? [1]
What is it prescribed for? [1]
GLP-1 agonist
How do you calculate BMI? [1]
kg/ m2
What waist sizes in men and women would suggest likely to get obesity related problems?
- Male waist size > 94cm or woman waist size >80cm = more likely to develop obesity-related health problems.
What is a clinical marker for hyperinsulinaemia? [1]
Acanthosis Nigicans is a clinical marker for hyperinsulinemia
What type of drug is o Sitagliptin? [1] Describe MOA
(DPP)-4 inhibitor
Inhibits breakdown of GLP-1: causes decreased serum glucose
* GLP-1 inhibits food intake
o inhibiting gastric emptying
o Direct action on CNS at satiety
State action of metformin [3]
- Main action: acutely decreases hepatic glucose production (inhibits liver GNG)
- Increases glucose uptake via GLUT4
- Increases GLP-1
Where in the hypothalamus are the sateity and hunger centres? [2]
Satiety centre = paraventricular nucleus
Hunger centre = lateral hypothalamic area
State a malabsorb. procedure for obesity treatment? [1]
bilo-pancreatic diversion
State a restrictive procedure for treating obesity
Banding
Which nucleus in the hypothalamus secretes alpha MSH?
POMC
Name three activators of POMC? [3]
o CCK
o Insulin
o Leptin
Describe the role of obesity causing DMT2
Metformin increases the formation of which molecule?
- Metformin also increases GLP-1
