Pathophysiology of orthostatic hypotension

Q: In a normal individual, orthostatic hypotension results in diastolic blood pressure to? - select one

A) fall

B) rise

Answer: B

The objective of this question is to understand the complex pathophysiology behind orthostatic hypotension. In a normal individual, a sudden change in posture to an upright position may pull up to a litre of blood in the lower extremities. Also, underestimated the pooling of blood in the splanchnic circulation during such instances. In such an event, venous return rapidly decreases, reducing ventricular filling and cardiac output. This provokes a compensatory neurological reflex, the baroreflex, which increases sympathetic and reduces parasympathetic outflow.

Overall effect is a rise in peripheral vascular resistance, venous return, and cardiac output, and so stabilizing the blood pressure via a slight fall in systolic blood pressure of about 5-10 mmHg, but an increase in diastolic blood pressure of almost similar value. Overall, heart rate increases by 10-25 beats per minute.

Failure at any stage of this compensatory mechanism causes exaggerated clinical signs of orthostatic hypotension.

#hemodynamic

#cardiology

References:

1. Magkas N, Tsioufis C, Thomopoulos C, Dilaveris P, Georgiopoulos G, Sanidas E, Papademetriou V, Tousoulis D. Orthostatic hypotension: From pathophysiology to clinical applications and therapeutic considerations. J Clin Hypertens (Greenwich). 2019 May;21(5):546-554. doi: 10.1111/jch.13521. Epub 2019 Mar 22. PMID: 30900378; PMCID: PMC8030387.

2. Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic Hypotension: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Sep 11;72(11):1294-1309. doi: 10.1016/j.jacc.2018.05.079. PMID: 30190008.

PESI

Q: In the Full Pulmonary Embolism (PE) Severity Index (PESI), which gender is included? (select one) 

 A) Male 
B) Female 


 Answer: Male

Contrary to popular belief that females are more prone to getting more severe pulmonary embolism, males are found to have a higher risk of more severe PE. 

The full PESI comprises 11 identified points, which were subsequently reduced to 6.

1. Age
2. Male
3. History of cancer
4. Heart failure
5. Chronic lung disease
6. Pulse ≥110/min
7. Systolic blood pressure 
8. Respiratory rate
9. Temperature 
10. Altered mental status
11. Arterial oxygen saturation 

Simplified pulmonary embolism severity index (sPESI)

1. Clinical feature
2. Age >80 years
3. History of cancer
4. Chronic cardiopulmonary disease
5. Pulse ≥110/min
6. Systolic blood pressure <100 mmHg
7. Arterial oxygen saturation 

Many online calculators are available to score PESI

#pulmonary

#hemodynamic

#vascular

 
References: 

1. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172:1041. 

2. Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170:1383.

3. Hassine M, Kallala MY, Mahjoub M, Boussaada M, Bouchahda N, Gamra H. Embolie pulmonaire: indice de sévérité de l’embolie pulmonaire (ISEP) score et facteurs prédictifs de mortalité [Pulmonary embolism: the Pulmonary Embolism Severity Index (PESI) score and mortality predictors]. Pan Afr Med J. 2023 May 19;45:48. French. doi: 10.11604/pamj.2023.45.48.39031. PMID: 37575526; PMCID: PMC10422038.

MALA and metformin level

Q: A serum metformin level usually correlates with the severity of the poisoning, known as MALA (Metformin Associated Lactic Acidosis).

A) True

B) False

Answer: B

Serum metformin level is usually not ordered during suspected MALA for two reasons. First, it takes several days to report the level. Second, serum metformin concentrations typically do not correlate with the severity of toxicity or patient outcomes; however, a caveat of 'treatment bias' may be present, as by the time the level is reported, patients may be treated differently across institutions based solely on clinical signs and suspicion. Additionally, associated factors, such as renal insufficiency, may have played a role.

That said, some experts still advocate obtaining a serum metformin level, as it has a good negative predictive value. An undetectable metformin concentration basically rules out MALA.

#toxicity

#pharmacology

#acid-base

References:

1. Vecchio S, Giampreti A, Petrolini VM, et al. Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy. Clin Toxicol (Phila) 2014; 52:129.

2. Dell'Aglio DM, Perino LJ, Kazzi Z, et al. Acute metformin overdose: examining serum pH, lactate level, and metformin concentrations in survivors versus nonsurvivors: a systematic review of the literature. Ann Emerg Med 2009; 54:818.

3. Kajbaf F, De Broe ME, Lalau JD. Therapeutic Concentrations of Metformin: A Systematic Review. Clin Pharmacokinet 2016; 55:439.

Anti-GBM - Rx

Q: A 52-year-old male presented to the Emergency Department (ED) with hemoptysis and a creatinine level of 6.2 mg/dL. There is a high degree of suspicion for the Anti-glomerular basement membrane (anti-GBM) disease, also known as Goodpasture syndrome. What is the first line of treatment?

A) Immunosuppressive therapy

B) Plasmapheresis

C) Plasmapheresis plus immunosuppressive therapy

Answer: C

The initial management of anti-GBM disease plays an essential role in immediate and long-term survival. The treatment is two-pronged:

• Plasmapheresis removes circulating anti-GBM antibodies and other inflammatory mediators, and 
• Immunosuppressive agents minimize new antibody formation

#rheumatology

#pulmonary

#nephrology

References:

1. McAdoo SP, Pusey CD. Anti-glomerular basement membrane disease-treatment standard. Nephrol Dial Transplant. 2025 Dec 23;41(1):42-54. doi: 10.1093/ndt/gfaf190. PMID: 40973182; PMCID: PMC12722177.

2. Bharati J, Jhaveri KD, Salama AD, Oni L. Anti-Glomerular Basement Membrane Disease: Recent Updates. Adv Kidney Dis Health. 2024 May;31(3):206-215. doi: 10.1053/j.akdh.2024.04.007. PMID: 39004460.

3. Taylor DM, Yehia M, Simpson IJ, et al. Anti-glomerular basement membrane disease in Auckland. Intern Med J 2012; 42:672.

4. Canney M, O'Hara PV, McEvoy CM, et al. Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease. Clin J Am Soc Nephrol 2016; 11:1392.

Azoles and pseudohyperaldosteronism

Q: Which of the following azoles may cause pseudohyperaldosteronism? - select one

A) Fluconazole

B) Voriconazole

C) Isavuconazole

D) Itraconazole 

Answer: D

Itraconazole and posaconazole are two azoles known to cause pseudohyperaldosteronism with its triad of

• severe hypokalemia
• hypertension, and
• metabolic alkalosis

Itraconazole is also known to cause congestive heart failure, and all azoles are known to cause hepatotoxicity.

#pharmacology

#endocrinology

References:

1. Kuriakose K, Nesbitt WJ, Greene M, Harris B. Posaconazole-Induced Pseudohyperaldosteronism. Antimicrob Agents Chemother 2018; 62.

2. Brandi SL, Feltoft CL, Serup J, Eldrup E. Pseudohyperaldosteroism during itraconazole treatment: a hitherto neglected clinically significant side effect. BMJ Case Rep. 2021 Jun 18;14(6):e243191. doi: 10.1136/bcr-2021-243191. PMID: 34144953; PMCID: PMC8215247.

3. Katharina R. Beck, Lucija Telisman, Chris J. van Koppen, George R. Thompson III, Alex Odermatt - Molecular mechanisms of posaconazole- and itraconazole-induced pseudohyperaldosteronism and assessment of other systemically used azole antifungals - The Journal of Steroid Biochemistry and Molecular Biology, Volume 199, May 2020, 105605. Link: https://www.sciencedirect.com/science/article/abs/pii/S0960076019306958

Patient height and PES

Q: Which of the following is a risk factor for post-extubation stridor (PES)? - select one

A) High ratio of patient height (in mm) to ETT diameter (in mm)

B) Small ratio of patient height (in mm) to ETT diameter (in mm)

Answer: B

Post-extubation stridor is a common occurrence in the ICU. Various risk factors have been identified. One of the less discussed risk factors is:

A small ratio of patient height (in mm) to ETT diameter (in mm)

Some other well-known factors are:

• Prolonged intubation
• Old age
• Large ETT 
• Elevated APACHE score
• Low GCS score 
• Traumatic intubation
• Female gender
• Previous pulmonary history
• Excessive tube mobility due to insufficient fixation

#ventilators

#pulmonary

#procedures

References:

1. Maury E, Guglielminotti J, Alzieu M, et al. How to identify patients with no risk for postextubation stridor? J Crit Care 2004; 19:23.

2. Wittekamp BH, van Mook WN, Tjan DH, et al. Clinical review: post-extubation laryngeal edema and extubation failure in critically ill adult patients. Crit Care 2009; 13:233.

3. Shinohara M, Iwashita M, Abe T, Takeuchi I. Association between post-extubation upper airway obstruction symptoms and airway size measured by computed tomography: a single-center observational study. BMC Emerg Med. 2022 Mar 31;22(1):55. doi: 10.1186/s12873-022-00615-7. PMID: 35361111; PMCID: PMC8974026.

4. Sunil Rathore, Adam Bates, Lawrence Nolan, Trevena Anton, Mckay Jarman, and Gwendolyn Lynch - Neurology - Neurocritical Care: Procedures - Identifying Post-extubation Stridor (PES) Risk Factors in a Neurocritical Care Population (P2-2.002) - April 9, 2024 issue 102 (7_supplement_1) 5689 https://doi.org/10.1212/WNL.0000000000205984

Vision in HELPP

Q: A 28-year-old female is admitted to the ICU with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). Delivery was planned. The patient began reporting bilateral blurring of vision. What could be your concern?

Answer: Retinal detachment

Retinal detachment is an unusual but very well-documented complication of severe preeclampsia and patients with HELLP syndrome. An emergent ophthalmic consultation should be obtained in conjunction with the planned delivery.

#ob-gyn

# ophthalmology

#hepatology

Reference:

1. Teodoru CA, Tudor C, Cerghedean-Florea ME, Dura H, Tănăsescu C, Roman MD, Hașegan A, Munteanu M, Popa C, Vică ML, Matei HV, Stanca H. Bilateral Serous Retinal Detachment as a Complication of HELLP Syndrome. Diagnostics (Basel). 2023 Apr 26;13(9):1548. doi: 10.3390/diagnostics13091548. PMID: 37174940; PMCID: PMC10178147.

2. Vigil-De Gracia P, Ortega-Paz L. Retinal detachment in association with pre-eclampsia, eclampsia, and HELLP syndrome. Int J Gynaecol Obstet. 2011 Sep;114(3):223-5. doi: 10.1016/j.ijgo.2011.04.003. Epub 2011 Jun 29. PMID: 21719013.

3. Li M, Qu J. Exudative retinal detachment and hypertensive choroidopathy in a patient with suspected HELLP syndrome: a case report. BMC Ophthalmol. 2025 Jul 1;25(1):353. doi: 10.1186/s12886-025-04176-8. PMID: 40597840; PMCID: PMC12210448.