Case study:

Tyrotoxicosis

Patient's history:

37 yr-old woman

P/C : unintentional weight loss

HoPC :

• over past 3 months - lost appx 15 lb w/o changing her diet / activity level
• feels great
• excellent appetite
• no GI complaints - except occasional loose stool
• good energy level
• no fatigue
• no heat / cold intolerance

O/E :

• HR 108 bpm
• BP 142/82 mmHg
• afebrile
• stare-looking, protuberant eye
• large, smooth, non-tender thyroid gland
• 2/6 systolic ejection murmur
• skin warm and dry
• no tremor

1)most likely diagnosis:

• Thyrotoxicosis / Graves Disease

2) how to confirm?

• TSH - serum low
• free T4 - increased
• clinical presentation
• OTHER TESTS : thyroid-stimulating immunoglobulin / diffusely elevated uptake of radioactive iodine on thyroid scan

3)tx options

• anti-thyroid drugs
• radioactive iodine ablation
• surgical ablation of thyroid

Clinical approach

Cardiac : long standing thyrotoxicosis can cause cardiomegaly

GI : hyperdefecation - increased GI motility

Eyes : retraction of upper eyelid - increased of sympathetic tone

Skin : warm, moist, velvety. sweating - vasodilation and heat dissipation

reproduction : oligomenorrhea (infrequent menstruation), impotence, gynaecomastia

metabolism: weight loss, preference for cold temperature

Etiology: Graves disease

• most common cause of hyperthyroidism
• women
• 30-50 yr old
• autoimmune disease
• autoantibodies that activate TSH receptor of thyroid follicular cells
• autoantibodies - cross placenta and can cause neonatal thyrotoxicosis

other causes of thyrotoxicosis:

• toxic multinodular goiter
• autonomous hyperfunctioning adenoma (hot nodule)
• increased uptake (hot)
• thyroiditis
• medications : exogenous thyroid hormones
  

clinical:

• goiter (enlarged thyroid gland)
• thyroid bruit
• hyperthyroidism
• ophthalmopathy
• inflammation of extraocular muscle, orbital fat, and connective tissue - proptosis. periorbital edema
  
• dermopathy
• raised hyperpigmented orange peel texture papules
• common site : shin - pretibial myxedema

Tx:

• meds
• beta-blockers (for symptoms relief)
• antithyroid drugs (methimazole , propylthiouracil)
• decreasing production of thyroid hormone
• short term, prior to radioactive treatment
• long term treatment
• SE : rash, allergic reactions, arthritis, hepatitis, agranulocytosis
• radioactive iodine (treatment of choice)
• C/I pregnancy, women of child-bearing age
• graves ophthalmopathy exacerbated by radioactive, may use glucocorticoid
• Surgery
• reserved for large goiter (if obstructive symptoms)
  

Strategy?
- to return lung function to as near normal as possible.
- primary classes of drugs used to treat asthma : bronchodilator and anti-inflammatory agents
- alternative therapies : leukotrines modulators, cromolyn sodium nedocromil sodium
1) bronchodilator
- for maintenance therapy
- reliever : rapid symptomatic relief
Epinephrine

• both a and b
• subcutaneous route : acute and status asthmaticus
• therapeutic effects: increased HR, CO, SV, elevated systolic and decrease diastolic, decreased systemic vascular resistance.
• adverse effects: anxiety, tremor, palpitations, extreme HTN, Pulmonary oedema, angina, ventricular arrhythmias
  

B2-agonists

• Albuterol (Proventil/Ventolin) ,Terbutaline (Brethine) ,Salmeterol (Serevent)
• MoA : enhance production of cAMP
  

• Terbutaline and albuterol - either oral / inhalation ( rapid onset thus for acute symptoms)
  
• Salmeterol - inhalation only
• B2-agonist - tachycardia at large dose
• Salmeterol - longer half-life (prophylactic use) and short duration of action (not to be used to treat acute symptoms)
• Terbutaline - control premature labour (by abolished contraction of uterine smooth muscle)
• Adverse Effects: Orally --> muscle tremor, tachycardia, palpitations. IV for premature labour-->tachy cardia, pulmonary oedema (mother), hypoglycaemia (baby)
• inhalation - minor SE

Theophylline

• MoA : inhibits phosphodiesterase enzyme (enzyme that inactivates cAMP and cGMP)
• narrow therapeutic index
• slow metabolism in disease state (i.e heart failure, liver disease, respiratory obstruction)
• SE : nausea and vomiting (common in first time user), restlessness, diuresis, fever
• CI : used cautiously in MI, liver disease, myocardial disease
• half-life prolonged in CCF
• interaction with : cimetidine, zileuton

Anti-cholinergic

• Ipratropium bromide (Atrovent)
• slow onset
• suitable for prophylactic
• ipratropium + albuterol (Combivent) used in COPD
• devoid of CNS SE
• peripheral SE : dry mouth, headache, nervousness

2) Anti-inflammatory Agents
- inhaled corticosteroid, along with b2-agonist -> firstline therapy of CHRONIC ASTHMA.

Corticosteroid

• Oral : Prednisolone
  
• Parenteral : Hydrocortisone
  
• Inhalation : Beclometasone dipropionate

• Effects take hours to develop (can't be used for quick relief of acute)
• inhaled steroid not effective for relief of acute episodes of severe bronchospasm
• systemic corticosteroid (eg. Prednisolone) used for short-term treatment that does not respond to B2-agonist
• not to be used as maintenance unless other options failed (due to SE)
• SE of systemic admin > SE of inhalant admin
• SE : adrenal suppression, cushingoid changes, growth retardation, cataracts, osteoporosis, infection vulnerability

3) Alternative therapy
- not to be used as monotherapy
- for prophylactic

Leukotrine modulator

• Zafirlukast (accolate), montelukast(singulair), Zileuton (Zyflo)
  

What is it?

· Chronic inflammatory disorder of airways

Clinical

· Recurrent wheezing

· Cough

· Dyspnea

· Chest tightness

Causes?

· Repeated hypersensitivity

· Late-phase reaction

Results?

· Triad

o Intermittent / reversible airway obstruction

o Chronic bronchial inflammation

o Bronchial smooth muscle cell hypertrophy and hyperactivity

Epidemiology?

· 70% - extrinsic / atopic – due to IgE and Th2-mediated immune response to environmental antigens

· 30% - intrinsic/non-atopic – triggered by non-immune stimuli (eg. Aspirin, pulmonary infections

Pathogenesis?

· Genetic predisposition to type 1 hypersensitivity (atopy) and Bronchial hyper-responsiveness to variety of stimuli

· Role of Th2 helper – excessive response against environmental stimuli

o Cytokines – IL4 (IgE production), IL-5 (activation of eosinophils), IL-13(mucus production)

· Role of epithelial cells

o Produces chemokines -> attracts more Th2 and eosinophils + leukocytes à amplying inflammatory reaction.

· Structural changes in bronchial wall (airways remodeling) (ie bronchial smooth muscle hypertrophy)

o Thickening of basement membrane of bronchial epithelium

o Edema and inflammatory infiltrate in bronchial wall

o Increased size of mucosal glands

o Hypertrophy of bronchial muscle wall

· Mast cells – produce growth factors à stimulates SM proliferation

Types?

1) Atopic

· Most common

· Childhood onset

· Family hx – common

· Other atopic diseases (i.e rhinitis, eczema)

· Triggered by environmental antigens

· Skin test -> immediate wheal-flare reaction

· Process? Initial sensitization to inhaled antigens à thus stimulate Th2 cells à cytokines

· IgE production

· IgE binds to mucosal mast cells

· Results : immediate response + late phase reaction

· Subsequent exposure of IgE-coated mast cell to same antigen

· Crosslink and releasing of chemical mediators

· Results : opening of mucosal intercellular junctions à thus allowing penetration of antigen to more mucosal mast cells

· In additions : direct stimulation of subepithelial vagal (parasympathetic) receptors à provokes reflex bronchoconstriction

· Occurs within minutes after stimulation

· Called acute/immediate response (minutes)

o Bronchoconstriction

o Oedema (increased vascular permeability)

o Mucus secretion

· Late phase reaction (hours)

o Mast cells – cytokine release

o Thus, influx of other leukocytes + eosinophils

o Activation of eosinophils -> rich source of leukotrines C4

2) Nonatopic

· Family hx is uncommon

· Serum IgE normal

· No associated allergen

3) Drug-induced asthma

· Eg. Aspirin

· Presentation : recurrent rhinitis + nasal polyps, urticaria, bronchospasm

Status asthmaticus (prolonged severe asthma attack)

Asthma

Definition
• Characterized by : recurrent dyspnea, cough, wheeze
• Caused by : reversible airway narrowing
• Factors :
o Bronchial muscle contraction (triggered by stimuli)
o Mucosal swelling/inflammation (mast cells)
o Excess mucus production (inflammatory mediators)

Pathogenesis:?

Microbiology??

Symptoms
• Intermittent dyspnea
• Cough
• Wheeze
• Sputum

Signs
• Tachypnoea
• Audible wheeze
• Hyperventilation
• Diminished air entry
• Polyphonic wheeze
• RR >25/min
• Cyanosis
• Pulse >110bpm

Hx
• Precipitants
• Diurnal variation
• Exercise
• Disturbed sleep
• Acid reflux
• Other atopic disease
• Occupation
• Days off?

Test
1) Acute asthma
• PEF
• Sputum culture
• FBC
• U&E
• CRP
• Blood culture
• ABG analysis
• CXR (to exclude infection/pneumothorax)

2) Chronic asthma
• PEF
• Diurnal variation
• Spirometry
• Skin-prick test
• Serology (aspergillosis)

Tx:
1) Chronic asthma
• Behavior – smoking, avoidance of precipitants, education
• BTSG:
Step 1: Ocassional short-acting inhaled B2-agonist (eg. Salbutamol) – next step if used >1 daily.
Step 2: standard-dose inhaled steroid (eg. Beclometasone 200ug/12h)
Step 3: long-acting B2-agonist (eg. Salmeterol) – if inadequate, increase dose of beclometasone 400ug/12h. if no effect of long-acting  stop
Step 4: trials of beclometasone 1000ug/12h,
modified-release of theophylline,
modified-release B2-agonist / oral leukotrine receptors
Step 5: prednisolone


DDx:
• Pulmonary oedema
• COPD
• Large airway obstruction
• SVC obstruction
• Pneumothorax
• PE
• Bronchiectasis
• Obliterative bronchiolitis

Case study 1: (taken from medscape student)

47 yr-old gentleman

A/E admission

P/C : waking up with severe abdominal pain

HoPC :

- Over past week

- Intermittent

- Gas-like epigastric pain

- Sensation ‘like I need to burp’.

As of this morning

- Pain acutely worsened

- Radiating in a bandlike pattern throughout the patient’s upper abdomen and to his back

- Intense when lying flat on his back

- Slightly better when sitting upright

Associated symptoms

- Mild nausea but no vomiting

- No fever / chills

- No diarrhoea

RFs:

- No NSAIDs

PMHx:

- No chronic medical conditions

Meds: Nil

Allergy: NKDA

SHx:

- Drinker - ~6-8 beers daily

System review:

- No chest pain

- No SOB

- No palpitation

O/E:

General appearance :

- Thin

- Slightly emanciated man

- Uncomfortable

- Distressed

- Diaphoretic and writhing around

Vital signs:

- Temp: 35.4

- Pulse: 87bpm

- Resp. Rate : 28 breaths/min

- BP : 111/62 mm Hg

- O2 sat : 98% (room air)

HEENT

- Sclera is anicteric (normal)

- Oropharynx clear with slight dry mucus membrane

CVS:

- Regular rhythm

- No murmurs

- Lungs clear

Abdo:

- Tenderness in epigastric and bilateral upper quadrant regions with focal rebound tenderness and guarding

- No tenderess or palpable masses in lower abdomen

- Rectal exam : heme-negative, brown stool

Mx:

- Cardiac monitor

o ECG:

§ normal sinus rhythm at ventricular rate of 88bpm

§ non specific ST flattening

- IV line – normal saline

- 2 doses of IV hydromorphone (pain killer) – but no significant improvement in his pain / abdo tenderness

- CXR – Normal, no air visualized under the diaphragm

- Abdo USS – no evidence of gallstones or biliary wall thickening, kidney and liver appear normal

- CBC (complete blood count/ FBC), metabolic panel, hepatic panel with lipase, tropnonin --> within normal limits

- CT abdomen + pelvis

Comments of CT abdo:

- Free air under diaphragm à consistent with a perforated viscus

- Also fluid in region of distal antrum/pylorus with small pocket of air in this fluid

- Pt’s hx of alcohol à pointed to perforated gastric ulcer

DDx:

- Cardiovascular etiology (eg. ACS, aortic dissection)

- GI (eg. Mild esophagitis and gastritis

- Gallbladder diseases (eg. Mild biliary colic to acute cholecystitis)

- Liver (eg. Acute hepatitis, masses, gonococcal or chlamydial perihepatitis, acute cholangitis)

- Acute pancreatitis

- Acute appendicitis (may first present with upper abdo/mid abdo pain before localizing to right lower quadrant)

- Pulmonary processes (eg. Pneumonia) – must be considered even in absence of cough/SOB

The workup:

- Based on age and risk factors

- Characteristics and assoc. symptoms of each potential diseases

- Hx and physical examination

*CXR upright à no evidence of perforation

Uncomplicated PUD

- 90% DU, 75% PUD caused by H.pylori infection

- Second cause : NSAIDs

o Risk / complications are proportional to daily dose taken

- Others: anticoagulant, steroids, alcohol, smoking, infection

- DUD : majority occurs at anterior wall of duodenal bulb

Perforated ulcers:

- 3 classical stages:

o 1^st stageà caused by rapid release of gastric juice into peritoneal cavity à thus abrupt onset of intense abdominal pain

o 2^nd stage à spontaneous improvement in symptoms à as result of fluid pouring out of injured intraperitoneal tissues à causes buffering of acidic gastric juice

o Final stage à frank peritonitis à characterized by increased pain and signs of systemic inflammatory response.

- CT scan : higher sensitivity of visualizing free air and may show evidence suggesting location of perforation

- C/I : endoscopy à because of air insufflations

- Thus, alternative : water-soluble contrast agent