GERD - Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is an extremely common disease that is seen on the wards on Internal Medicine. Let's discuss how it presents and how its treated.

                                                              

Symptoms:

3 Most common symptoms:

• Heartburn
• Reflux
• Dysphagia

Other common symptoms:

• Bronchospasm
• Laryngitis
• Chronic cough

Less Common

• Chest pain - May mimic angina pectoris, and is typically described as squeezing or burning, located substernally and radiating to the back, neck, jaw, or arms, lasting anywhere from minutes to hours, and resolving either spontaneously or with antacids. It usually occurs after meals, awakens patients from sleep, and may be exacerbated by emotional stress
• Hypersalivation
• Globus sensation
• Odynophagia
• Nausea

Pearl: GERD is purely a clinical diagnosis, defined as having the above symptoms causing troublesome symptoms and/or complications.

                                                 

Approach to Therapy

Non-pharmacological

There are only two lifestyle modifications that improve symptoms:

• Weight loss
• Elevate head of bed
• Don’t ask patients to change their diet - except to avoid known dietary triggers specific to the patient.

Mild Disease:

• In patients with mild and intermittent (less than two episodes per week) symptoms:
• • Low dose histamine 2 receptor antagonists (H2RAs).
  • If continued symptoms, increase the dose of H2RAs to standard dose, twice daily for a minimum of two weeks.
• If symptoms persist, discontinue H2RAs and initiate low dose PPI once daily and then increase to standard doses as needed
• Reassess dosing Q2-4 weeks
• Minimum length of therapy is 8 weeks

Moderate to Severe Disease (symptoms >x2/week, including erosive esophagitis):

• Standard dose PPI once daily
• If failed, double dose and refer to GI. Definition of 'failure' is controversial. Note that the most common reason for failure is poor compliance - first address this issue before doubling the dose of the PPI.
• If symptoms resolve, try trial off of treatment except those with severe esophagitis or Barrett's
• If failed off of therapy in less than 3 months, need lifetime therapy
• If fail later on, can try repeated on/off courses

When should upper endoscopy be done?

1. Alarm features: Dysphagia, odynophagia, gastrointestinal bleeding, anemia, weight loss, and recurrent vomiting
2. GERD symptoms after adequate 4­-8 week trial of PPI
3. Any of the following features:

• > 50 year old man
• Chronic GERD x 5 years
• Nocturnal reflux symptoms
• Hiatal hernia
• Elevated BMI
• Smoker

Role of pH monitoring and manometry testing

Ambulatory pH monitoring: Confirm GERD in those with persistent symptoms who do not have evidence for mucosal damage on endoscopy, particularly if a trial of twice daily PPI has failed.

Esophageal manometry: Assess for motility issues like achalasia, the symptoms of which can mimic GERD. Suspect this with dysphagia and vomiting.

                                                         

Elevated Liver Enzymes in Pregnancy

Let's discuss the approach to this common problem in pregnancy.

Helpful Hints in determining the etiology of elevated liver enzymes:

• Use the gestational age to guide the diagnosis
• Need to rule out viral/gallstone/cancer/autoimmune/drugs as the cause of elevated liver enymes at any time of the pregnancy.
• Chronic hepatitis B or C poses a risk of transmission to the offspring
• All of the below diagnoses can recur in subsequent pregnancy.

Liver tests affected by pregnancy (decrease, except ALP):

• ALP (increased in the second and third trimester, due to the placenta)
• Albumin and total protein (decreased from the first trimester due to hemodilution)
• Bilirubin levels (slightly decreased from the first trimester)
• GGT (slightly decreased in late pregnancy)

Liver tests not affected by pregnancy:

• AST, ALT, PT, total bile acids, LDH

"Hi, can you please page GI to my cell phone?"

Differential Diagnosis

There are four main differential diagnoses to consider

• Hyperemesis gravidarum - 1st trimester. 
• Mild, often <200 alt="" often="">AST.
• Admit to hospital if hypovolemic
• Diclectin can be used for management for nausea
• If persistent, make sure to rule out molar pregnancy
• Cholestasis of pregnancy - 2nd Trimester. Common; 
• Affected pregnancies are at increased risk for prematurity and stillbirth, and early delivery should be considered when possible. 
• Pruritus starting in the hands and soles. NOT jaundiced but have high ALP
• Enzymes are often very high with normal GGT. 
• Measure bile acids  to help make the diagnosis (>10)
• Often have history of pruritus during current and previous pregnancies. Likely to recur
• Small risk to baby, none to the mom
• Treatment: 
• Deliver earlier
• Ursodeoxycholic acid
• Can also use hydroxizine, cholestyramine to help with symptoms
• Vitamin K if INR is up
• Acute fatty liver of pregnancy - Second half of pregnancy, usually 3rd trimester.
• True hepatic dysfunction. ACUTE LIVER FAILURE Baby's free fat damages mom
• Signs of pre-eclampsia and HELLP syndrome in 50% of patients.
• Nausea/vomiting, pain, jaundice
• Rare
• Enzymes vary from 200-500. 
• Uric acid, WBC, bilirubin, and INR elevated
• Glucose and platelets are low
• Must exclude HELLP (AFLP doesn't have hemolysis unless the patient also has DIC)
• Screen mom and baby for LCHAD.
• May recur in future pregnancies
• Treatment: 
• Deliver!
• Glucose infusion 
• Reversal of coagulopathy (FFP, cryoprecipitate, pRBC, platelets) PRN. 
• Watch for pulmonary edema due to loss of proteins 
• HELLP syndrome 
• Hemolysis, Elevated Liver Enzymes, and Low Platelets
• Present with neurological symptoms as well; abdominal pain, vision changes.
• Microangiopathy Hemolytic Anemia
• Elevated LDH, raised INR as well
• AST > 70
• Second half of pregnancy, usually 3rd trimester.
• Management:
• Prompt delivery!
• Magnesium sulphate for seizure prevention
• May recur in future pregnancies

Primary Hyperaldosteronism

An issue that commonly arises in both the outpatient and inpatient settings is the combination of hypertension and hypokalemia. When should these patients be worked up for primary hyperaldosteronism? How do you work these patients up? Let's discuss the diagnosis and management

• Primary aldosteronism commonly presents with hypertension and hypokalemia. However, normokalemia is present 50% of patients.
• The most common causes of primary aldosteronism are aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia.
• Abnormally high release of aldosterone leads to an increased risk of cardiovascular disease and morbidity, including left ventricular hypertrophy, myocardial infarction and stroke.
• 2008 Endocrine Society Guidelines, test for primary aldosteronism in patients with:
• Hypertension and hypokalemia (diuretic induced-hypokalemia less than 3 or spontaneous hypokalemia less than 3.5.
• Severe or resistant hypertension
• Hypertension and an adrenal incidentaloma
• Hypertension and a family history of early-onset hypertension or CVA age before the age of 40.
• Hypertension and first-degree relatives with documented primary aldosteronism

• The initial evaluation:
  • Measure plasma renin activity (PRA) or plasma renin concentration (PRC) and plasma aldosterone concentration.
  • In primary hyperaldosteronism, PRA and PRC are reduced and the plasma aldosterone concentration (PAC) is inappropriately high (approximately PAC/PRA greater than 20 (550 in SI units).
• This ratio is not sufficient for a diagnosis. You then need suppression testing.
• This can be performed with orally administered sodium chloride and measurement of urinary aldosterone excretion. Alternatively, it can be done with IV sodium chloride loading and measurement of the PAC. 

• Once Primary Hyperaldosteronism is confirmed, adrenal CT is done to distinguish between aldosterone-secreting adenoma and bilateral hyperplasia. Adrenal CT will also help to asses for adrenocortical carcinoma.
• When the CT scan is normal, shows bilateral abnormalities, or shows a unilateral abnormality but the patient is over age 35 years, adrenal venous sampling is recommended to confirm unilateral disease if the patient would like to pursue surgical management of their primary aldosteronism. 
• The reason 35 years is a significant cut-off is because patients above this age are more likely to have non-functioning adenomas, so you may not be certain that the detected mass accounts for the elevated hyperaldosteronism.

Hypertension

Since we often discuss inpatient issues during morning report and noon rounds, let's focus on an outpatient issue instead. Hypertension (HTN) is extremely common (20% of Canadians over the age of 18) and is a signifcant risk factor for end-organ dysfunction. The inpatient management of hypertension is very different from the outpatient management of hypertension. The information below is from the CHEP Guidelines, a Canadian hypertension guideline.

Diagnosis

High blood pressure is defined by a BP >140/90. The flow chart for the diagnosis of HTN can be complication, but basically the diagnosis is often made over the course of 3 ambulatory clinic visits. HTN is defined by a BP greater than 140/90.

The next step is to use either clinic BP monitoring (BPM), ambulatory monitoring (ABPM), or home monitoring. If using clinic BPM, a BP greater than 140/90 in three subsequent visits clinches the diagnosis, or a BP greater than 160/100 in any of those three diagnosis. For ABPM and Home BPM, a consistent BP of  greater than 135/85  makes the diagnosis.

Beware of two entities:

1. White Coat HTN: BP greater than 140 in the clinic but less than 135 via ABPM (should not treat as HTN).

2. Masked HTN: BP greater than 135 on APM but less than 140 in the clinic (should treat as HTN).

Investigations

Should be done for all patients with newly diagnosed HTN.

1. Urinalysis

2 .Blood chemistry (potassium, sodium and creatinine)

3. Fasting glucose and/or glycated hemoglobin (A1c)

4. Fasting total cholesterol and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides.

5. Standard 12-leads ECG

                                                   

Treatment

1) Non-Pharmacological

o    Physical Exercise – Should be recommended 30-60 minutes of moderate intensity exercise (walking, jogging, cycling, or swimming) x4-7/week

o    Weight loss - BMI should be 18.5 to 24.9 kg/m²

o    Alcohol Consumption -  less than 2 drinks per day, no more than 14 drinks/week for men and 9/week for women

o    Salt Intake – Restrict to 2,000 mg (5g of salt or 87mmol of sodium) per day

o    Stress - Keep it down! Don't make me come over there.

2) Pharmacological

The first step is to remove agents that can induce/aggravate HTN (NSAIDs, steroids, OCP, EPO, MAOIs, SSRIs). Next, decide on a target for BP, which are listed below:

Next, select an anti-HTN agent. Important considerations for choosing HTN treatment:

• Use caution when initiating therapy with 2 drugs in whom adverse events are more likely (e.g. frail elderly, those with postural hypotension or who are dehydrated).
• If a diuretic is not used as first or second line therapy, triple therapy should include a diuretic, when not contraindicated. 
• ACE inhibitors, renin inhibitors, and ARBs are contraindicated in pregnancy
• Don’t use an ACE inhibitor and an ARB together, except only in people with advanced heart failure or proteinuric nephropathy. This combination does not reduce cardiovascular events more than the ACEI alone and have more adverse effects.
• Two drug combinations of beta blockers, ACE inhibitors, and angiotensin receptor blockers have not been proven to have additive hypotensive effects. Therefore, use if together only if non-blood pressure lowering indication.
• ACE-inhibitors are not recommended (as monotherapy) for black patients without another compelling indication.

Here is the treatment algorithm for systolic/diasltolic HTN. Note that the algorithm is similar for Isolated Systolic HTN, except beta blockers and ACE inhibitors are not considered first line.

Phewf. That was a lot of stuff.

Why a picture of Wonder Woman at the top? Turns out, the same person who created Wonder Woman also invented the polygraph test. Hence the 'lasso of truth.' Doesn't have much to do with hypertension, except that liars have higher blood pressure....probably.

An excellent resource is  https://www.hypertension.ca/en/chep. There, you can find all the guidelines for HTN diagnosis and treatment.

Metabolic Acidosis and Alkalosis

A common problem faced by trainees in Internal Medicine is acid-base disorders. Here, we will discuss the causes of acid-base disorders rather than the diagnosis on the basis of arterial blood gases. Specifically, we will discuss metabolic disturbances.

1) How does potassium affect acid-base status?
Changes in potassium often affect the metabolic acid/base status and vice versa. This is explained by the movement of excess potassium into cells which is balanced in part by intracellular hydrogen ions moving out to the extracellular fluid, and vice versa. This is termed "Internal Potassium Balance:" 

Therefore:
Metabolic acidosis tends to be associated with hyperkalemia (exceptions below).
Metabolic alkalosis tends to be associated with hypokalemia (exceptions below).

2) How does volume status affect acid-base status?

Hypovolemia can predispose patients to contraction alkalosis in some cases. There are a few reasons for this:

1. Loss of large volumes of low-bicarbonate, sodium-containing fluid leads to bicarbonate concentration rises because of contraction of the ECF volume with a constant quantity of  bicarbonate. This often occurs with IV loop diuretics.

2. High aldosterone - In the cortical collecting duct, high aldosterone released due to volume contractions leads to potassium and hydrogen ion excretion to balance sodium reabsorption. Hydrogen ion loss causes alkalosis, as does hypokalemia itself for the reasons stated above.

3. Angiontensin II - Released as part of RAAS activation in hypovolemia, angiontensin II acts at the Na+/H+ exchanger in the proximal tubules to enhance sodium absorption and H+loss, leading to alkalosis.

Therefore, contraction alkalosis can be seen in some patients with volume depletion.

Metabolic Acidosis

A) Increased Anion Gap
In these cases, extra anions (paired with H+) are introduced to the blood. The H+ is consumed by HCO3- in the buffer system and the only component that remains is the anion, which creates the anion gap. One mnemonic that can be used to remember these causes is MUDPILES:


Methanol
Uremia (chronic kidney disease)
Diabetic Ketoacidosis
Propylene glycol/Paraldehyde
Iron overload/Isoniazid use
Lactic acidosis
Ethylene glycol
Salicylates 

B) Non-Anion Gap
In these cases, no new anions are being introduced to the blood. Instead, either HCO3-  is excessively lost or renal acid is not being excreted. 

Note that "hyperchloremic metabolic acidosis" is interchangeable with "non-anion gap metabolic acidosis." This is because chloride is proportionately increased when HCO3-  is lost or H+ accumulates (no extra anions are present).

Causes:
1. Diarrhea - Loss of bicarbonate rich fluid results in acidosis. It is  important to note that although diarrhea typically causes a metabolic acidosis, it can also cause a metabolic alkalosis in the following cases:
- Laxative abuse
- Villous adenoma
- Congenital chloroidorrhea (rare) 

2. Bowel conduits for urine - These conduits are created during ureteric or bladder operations. When urine is exposed to gut mucosa, it reabsorbs chloride in exchange for HCO3-, leading to acidosis.

3. Renal Tubular Acidosis
These diseases result from the kidney's inability to acidify the urine due to several reasons. Note that potassium and acid/base disturbance associations in these cases do not follow the usual pattern listed above.

Metabolic Alkalosis

Metabolic alkalosis results from additional creation of bicarbonate combined with a process which prevents renal excretion of the excess bicarbonate. Patients with metabolic alkalosis compensate by hypoventilating and should raise the PCO2 by about 0.7 mm Hg for every 1 meq/L elevation in the bicarbonate. This initially lowers the arterial pH toward normal and is most effective acutely, but then becomes less effective over time.

The differential diagnosis for metabolic alkalosis can be broken down into two groups, according to the urinary chloride levels:

Of these, the two most common causes are vomiting and diuretic therapy. One additional differential diagnosis for metabolic alkalosis of relevance is contraction alkalosis, mentioned earlier.

Grrrrrrrrrrrrrreat.
Here's a more physiological approach to acid-base disturbances from NEJM.