Module 2 - Macrocytic - Pernicious Anemia Flashcards
What is the most common type of macrocytic anemia?
PA - Pernicious anemia
This is caused by B12 deficiency
PA - Pernicious anemia
What is PA often associated with?
End stage type A chronic atrophic gastritis
Which population does PA commonly affect?
Individuals older than 30
Norther European descent
It has now been recognized in all populations and ethnic groups
What is the underlying problem in PA
Absence of intrinsic factor
What is intrinsic factor (IF)
a transporter required for gastric absorption of dietary vitamin B12
What is B12 needed for ?
a vitamin needed for nuclear maturation and DNA synthesis in red blood cells.
What can be some of the causes of IF deficiency?
-congenital or autoimmune process directed against gastric parietal cells
Congenital IF deficiency is a _________
Genetic disorder with autosomal recessive inheritance pattern.
Does the autoimmune form of IF deficiency have a genetic component?
Yes
What percentage of individuals related to person with PA also have PA?
20-30%
Relatives , especially first degree female relatives will show higher frequency of __________
the presence of gastric autoantibodies
PA also if often a component of what?
autoimmune polyendocrinopathy
What is autoimmune polyendocrinopathy
This disorder includes a cluster of autoimmune diseases of endocrine organs (e.g., chronic autoimmune thyroiditis, type 1 diabetes mellitus, Addison’s disease, primary hypoparathyroidism, Graves’ disease, and myasthenia gravis) that frequently present as comorbidities.
What is typically associated with PA?
Type 1 DM and autoimmune thyroiditis
Most cases of PA result from what?
autoimmune gastritis (Type A chronic gastritis)
Gastric atrophy in autoimmune gastritis results from ?
Destruction of parietal and zymogenic cells
What type of autoantibodies does an individual with PA have?
Individuals with PA commonly have autoantibodies against the gastric H+–K+ ATPase, which is the major protein constituent of parietal cell membranes.
What’s the results of destruction of gastric parietal cell?
- Causes gastric mucosal atrophy and results in a deficiency of all secretions of the stomach.
-This includes hydrochloric acid, pepsin, and IF.
Initiation of the autoimmune process may be secondary to what type of infection?
H.Pylori
What are some of the environmental factors that may contribute to chronic gastritis?
- excessive alcohol or hot tea ingestion and smoking
-Complete or partial removal of the stomach (gastrectomy) causes IF deficiency. - ## Medications known as proton pump inhibitors (PPIs) are used to decrease gastric acidity and may decrease vitamin B12 absorption, but it is not thought that they actually cause PA.
People with type A chronic gastritis are at risk for ?
developing gastric adenocarcinoma and gastric carcinoid type 1
What is the rate of carcinoma in individuals with PA?
2-3%
How long does it take for PA to develop?
It develops slowly: 20-30 years. By the time a person seeks treatment, it is usually severe.
Why are early symptoms of often ignored?
They are non-specific and vague
What are some of the early symptoms of PA?
- infections
- mood swings
- and GI
- cardiac
- kidney diseases
When does classic symptoms of PA usually manifests?
When Hgb level has decreased to 70-80 g/L
What are the classic symptoms of PA
- Weakness
- fatigue
- paresthesia of feet and finger
- difficulty walking
- loss of appetite
- abdominal pain
- weight loss
- sore, smooth, beefy tongue
- skin may become lemon yellow (sallow) – this is caused by a combination of pallor and jaundice
- Hepatomegaly - a sign of right sided HF ( may be present in the older person along with nonpalpable splenomegaly )
Neurological manifestation of PA results from ?
Nerve demyelination that may produce neuronal death.
What parts of the spinal cord may be affected
Posterior and lateral columns
Damage to the nerves can cause?
- Loss of position and vibration sense
- ataxia
- spasticity
Low levels of B12 have been associated with what other disorders?
Neurocognitive disorders
An increased prevalence of serum vitamin B12 deficiency has been reported among individuals with
what type of disease?
Alzheimers
What type of manisfestations can indicate that the cerebrum is involved?
Manifestations of affective disorders , most commonly depressive types.
Diagnosis of PA are based on what?
Clinical Manifestations and several test resutls
What are some of the tests ?
- Blood test, bone marrow aspiration, serological studies, and gastric biopsy (reveals total achlorhydria - absence of hcl) - diagnostic for PA.
- Presence of circulating antibody against parietal cells and IF is also useful in diagnosis
What are some of the treatments?
- Oral B12 (cobalamin) - treatment of choice. Dosing for PA or food bound cobalamin malabsorption is 1000 ug/day
- If not corrected by the oral administration then monthly Vb12 injections.
What determines the effectiveness of cobalamin replacement therapy?
rising reticulocyte count
When does bloodcount return to normal?
Within 5-6 weeks
Can PA be cured?
No, maintenance therapy is lifelong
Is untreated PA fatal ?
Yes, usually because of HF
What are causes of relapses?
results of nonadherence therapy
