CASE REVIEW

P.M., a 60 year old businessman, was admitted because of pallor.

He says that he has been experiencing easy fatigability and dyspnea for the past 2 months. He noticed that he has difficulty going up the stairs to his office on the third floor. Upon
reaching the 2nd floor, he would have to stop to catch his breath.

One day ago, his wife told him that he looks pale. He consulted at his company clinic, and was advised admission.

PERSONAL HISTORY
● smokes 1 pack a day, has been smoking for 40 years
● drinks alcoholic beverages only occasionally
● type A personality

PAST MEDICAL HISTORY

● HPN for 25 years, on Pritor 40 mg and Aspirin 80 mg
● admitted in 2012 for unstable angina

FAMILY HISTORY
● (+) HPN, DM

REVIEW OF SYSTEMS
● (+) intentional weight loss
● (+) lightheadedness when standing up
● no blurring of vision
● occasional chest heaviness on exertion, (+) palpitations
● occasional epigastric pain
● no dysuria, no frequency
● no heat/cold intolerance

PHYSICAL EXAMINATION
● Conscious, coherent, wheelchair borne
● BP 100/60, CR 100/min, RR 20/min, T 36, BMI 25
● Pale palpebral conjunctiva, no ictericia
● Supple neck, no palpable lymph nodes
● Symmetrical chest expansion, unimpaired fremiti, no adventitious breath sounds
● Dynamic precordium, apex beat 6th LICS AAL, S1 louder at apex, S2 louder at base
● Globular flabby abdomen, normoactive bowel sounds, tympanitic, tenderness on deep palpation epigastric area, liver dullness 10 cm along MCL, no splenomegaly
● Pale palms and soles

IMPORTANT
● CRITIQUE THE DATA GIVEN TO YOU
● SHOULD THERE BE A REVISION AS TO WHERE THEY SHOULD BE PLACED?
● IS THERE ANY DATA THAT IS MISSING?

FOCUS ON THE FOLLOWING:

● Normal red cell production
● Definition and etiology of anemia; the most common causes of anemia
● Correlation of clinical manifestations with anemia
● Evaluation of anemia in general—laboratory indices; evaluation of anemia in your patient
● Management of anemia; management of anemia in your patient
 MEDICINE
CRITIQUING LEGEND:
Missing information | Under wrong label | Should be part of HPI | Should not be part of ROS | Should be elaborated on |

I. SUBJECTIVE DATA

A. GENERAL DATA
Name P.M.
Age 60 years old
Sex Male
Occupation Businessman
Civil Status Married

B. PRIMARY HISTORY

i. HISTORY OF PRESENT ILLNESS

2 months PTA ● Easy fatigability
● Dyspnea
● Difficulty ascending stairs to 3rd floor
● Stops to catch breath at 2nd floor
1 day PTA ● Pallor
Admission day ● Pallor

OLDCAARTS a. PALLOR b. EASY FATIGABILITY c. DYSPNEA

Onset ● 1 day PTA ● 2 months PTA ● 2 months PTA
Location ● Is it localized or generalized?
○ If localized, it can be due to Raynaud’s
Phenomenon
Duration ● How long does the pallor take place? ● How long does this last? ● How long does this last?
● If transient, it can be due to Raynaud’s
Phenomenon
Character ● Is it like you are gasping for air or drowning?
Associated Factors ● 2 months PTA: ● Dyspnea ● Easy fatigability
○ Easy fatigability ● Any other symptoms such as weakness?
○ Dyspnea
● Any other symptoms that may accompany
pallor? (e.g. lightheadedness, weakness,
fainting)
Aggravating Factors ● Any activity done or medication taken that ● Physical exertion (ie. ascending stairs to 3rd ● Physical exertion (ie. ascending stairs to 3rd
precedes this? floor) floor)
● Any other activities that made dyspnea
worse? (e.g. doing occupational tasks)
Relieving Factors ● Anything done to relieve this? ● Pauses physical exertion (ie. at 2nd floor) to ● Pauses physical exertion (ie. at 2nd floor) to
● No medications taken? catch breath catch breath
● No physical activity done?
Temporal Factors ● Does the pallor occur intermittently or ● Does the easy fatigability occur at a specific ● Does the dyspnea occur at a specific time of
constantly? time of the day or constantly? the day or constantly?
● Does it occur at a specific time of the day or ● Does it worsen at any point of the day? ● Does it worsen at any point of the day?
constantly?
Severity ● Is it manageable or does it hinder the patient ● Is it manageable or does it hinder the patient ● Is it manageable or does it hinder the patient
from his activities of daily living? from his activities of daily living? from his activities of daily living?

NOTES FROM FACILITATORS:

● Fever is an inflammatory response to cases such as infections, and is a constitutional symptom of malignancy

C. SECONDARY HISTORY

i. REVIEW OF SYSTEMS
General ● (+) intentional weight loss
○ Intentionally losing weight may lead to less consumption of certain nutrients, vitamins, and minerals like iron
○ Could aggravate aspirin-induced PUD
● Presence of weakness?
○ Accompany easy fatigability
Integumentary ● Changes in the shape of the nail? (e.g. spoon-shaped, koilonychia, brittle)
● Feeling of coldness in hands or feet?
○ Poor blood circulation or poor oxygenation
HEENT ● No blurring of vision
● Condition of the gums? (e.g. bleeding)
● Condition of the tongue? (e.g. beefy red tongue)
Breast
Respiratory ● Note: Dyspnea already mentioned
● Orthopnea?
Cardiovascular ● Occasional chest heaviness on exertion
● (+) palpitations
Gastrointestinal ● Occasional epigastric pain
● Vomiting? Indigestion? Hematemesis? Stool color?
○ Vomiting may accompany dizziness
○ Indigestion may lead to less absorption of iron
○ Hematemesis may lead to decreased volume of blood
○ If the stool color is red, there may be hematochezia which can also decrease the volume of blood.
Genitourinary ● No dysuria
● No frequency
● Presence of blood in the urine or hematuria?
Hematologic ● Note: Pallor already mentioned
Endocrine ● No heat/cold intolerance
Musculoskeletal ● Note: Easy Fatigability already mentioned
Neurological ● (+) lightheadedness when standing up
● Presence of headache?
○ Poor oxygenation of the brain
● Paresthesia, numbness?
Psychiatric ● Presence of pica or the tendency to eat things not nutritious or things not considered as food (e.g. ice, soil, nails)?
○ Psychiatric condition that accompany anemia

NOTES FROM FACILITATORS:

● Lightheadedness, fatigability, and weakness should be included in the history of present illness

D. TERTIARY HISTORY
Personal History ● Smokes 1 pack a day, has been smoking for 40 years
○ Pack years: 1 pack/day x 40 years = 40 pack years
● Drinks alcoholic beverages only occasionally
○ Specific # of bottles and type of alcohol (e.g. beer, whiskey)
○ # of days per week
○ Duration in a year
● Type A personality
● Businessman
● Married
○ Children?
● Where does the patient currently live?
● Living environment and condition?
Current Health Status and Risk ● Nutrition/dietary habits? (e.g. low consumption of foods rich in iron)
Factors ● Exercise?
● Medication data (e.g. certain medications that can deplete iron)
Past Medical History ● HPN for 25 years (on Pritor 40 mg + Aspirin 80 mg) route? Frequency of use?
○ Should be under current health status and risk factors
● Admitted in 2012 for unstable angina
● Past hospitalizations, surgeries?
● Blood transfusions/reactions?
● Allergies?
Family History ● (+) HPN, DM
● Members of the family who had the disease
● History of hematologic diseases
● Deaths in the family with age of death and cause
 II. OBJECTIVE DATA

GENERAL SURVEY VITAL SIGNS

● Conscious ● Blood Pressure: 100/60 mmHg - should be high in patients with anemia, but may be
● Coherent lowered due to his maintenance drug
● (+) Pallor ● Respiratory Rate: 20 cpm - upper limit
● Wheelchair-borne (why? It is because of easy fatigability or dyspnea?) ● Cardiac Rate: 100 bpm - upper limit
● Obese (BMI 25) - Body frame? Endomorphic? ● Temperature: 36C
● Missing O2Sat - important since our patient has dyspnea and has pallor
● BP Information on recumbent, sitting, and standing positions? - since our patient suffers
from orthostatic hypotension

NOTES FROM FACILITATORS:

● During the presentation, reporters claimed that the patient’s blood pressure is considered hypotensive secondary to the patient’s maintenance medication
○ To confirm this finding: ask patient’s usual blood pressure and previous readings

HEAD, EYES, EARS, NOSE, & THROAT
● Pale palpebral conjunctiva - sensitive to
anemia
● No ictericia
● Supple neck
● No palpable lymph nodes
● Inspection of lips, tongue, gums? - there
might be bleeding and/or discoloration
● Presence of alopecia? - severe sign of
anemia
PHYSICAL EXAMINATION
EXTERNAL CHEST AND LUNGS
● Symmetrical chest expansion - no
respiratory mechanical dysfunction that
led to pt’s dyspnea
● Unimpaired fremiti - no underlying lung
conditions
● No adventitious breath sounds - no
underlying lung conditions
CARDIOVASCULAR SYSTEM
● Dynamic precordium, apex beat at 6th
LICS AAL, S1 louder at apex, S2 louder
at base
● Cardiac rhythm - presence of arrhythmia
may tell us the patient is suffering from
heart failure
● Presence of JVP? - Right-sided HF
● Presence of carotid pulsations? - Severe
hypertension
● Presence of heart murmur?
● S3/S4 Gallop?
ABDOMEN (GI)
● Globular flabby abdomen
● Normoactive bowel sounds
● Tympanitic
● Tenderness on deep palpation epigastric
area
● Liver dullness 10cm along MCL
● No splenomegaly
● Rectal examination? - for lower GI
bleeding
● Stool character observation? - for
presence of melena/hematochezia

NOTES FROM FACILITATORS:

● Splenomegaly during physical examination:
○ Percussion: (+) dullness
○ Normal:
■ Tympani to percussion
■ Non-tender
■ Traube’s space (left sternal border, costal margin, and lower border of 9th ribs) is not obliterated
● Importance of examining the stool: changes in color may indicated internal bleeding, specifically in the gastrointestinal tract

MUSCULOSKELETAL INTEGUMENTARY SYSTEM NEUROLOGICAL SYSTEM

● Weakness ● Pale palms and soles ● Presence of numbness or tingling? (iron deficiency can
● Muscle girth for atrophy ● Examine nails (e.g. koilonychia) cause numbness and/or tingling in hands or feet)
● Examine skin (e.g. bruises, rashes) ● Mini Mental State Exam? (to screen dementia in the
● Presence of edema? (e.g. right heart failure) elderly - adherence with medications)
● Cerebellar tests? (to assess patient’s dizziness and how
it can affect ADLs)
● DTR? (may be depressed in patients with hypothyroidism
or with vitamin deficiencies)

III. DISCUSSION OF MAIN SYMPTOM

A. PALLOR
I. Definition
● Paleness or absence of color in the skin
● The skin takes on a lighter tone (more white with decreased pink hue) than normal for the individual (a normally “fair” skin color should be ruled out)
○ For darker skin, pallor is apparent by loss of red tones
Reference: (O’sullivan, S. B., Schmitz, T. J., & Fulk, G. D. (2019). Physical rehabilitation (7th ed.). F.A. Davis Company.)

II. Sites of observation

● Face
● Palms and soles
○ The palms and the soles show changes more clearly than the skin.
● Mucous membranes
● Nail beds
Reference: O’sullivan, S. B., Schmitz, T. J., & Fulk, G. D. (2019). Physical rehabilitation (7th ed.). F.A. Davis Company.
Catherine Cavallaro Goodman, & Kelly, T. E. (2007). Differential diagnosis for physical therapists : screening for referral. Elsevier Saunders.

III. Etiology
● Associated with decrease in blood flow or low in hemoglobin
● Conditions that may cause pallor:
 ○ Anemia
○ Peripheral vascular diseases (e.g. Raynaud’s disease)
○ Shock
○ Internal bleeding/hemorrhage
○ Orthostatic hypotension
○ Emotional distress
Reference: O’sullivan, S. B., Schmitz, T. J., & Fulk, G. D. (2019). Physical rehabilitation (7th ed.). F.A. Davis Company.

V. Pathophysiology
● Pallor may develop either with decrease in blood supply to the body tissues or decrease in the oxygen-carrying capacity of the blood.
○ Conditions that may lead to decrease in blood supply to the body tissues include arterial occlusions, reflex peripheral vasoconstriction, and low cardiac output
secondary to an underlying heart failure or decrease in blood volume.
○ The most significant condition leading to a decrease in the oxygen-carrying capacity of the blood will be anemia, which will be the main case for today’s
discussion. To understand how pallor is related to anemia, let us discuss the normal physiology behind the red blood cells.

Erythropoiesis
● Erythropoiesis is a process by which the red blood cells are made and is primarily due to erythropoietin.
○ Erythropoietin is a hormone primarily produced in the peritubular interstitial cells of the kidney and partly by the liver. This is the principal stimulus for RBC
production in low oxygen states.
● Once the pluripotent hematopoietic stem cell has differentiated into a proerythroblast, it will eventually become an erythrocyte.

Regulation of Erythropoiesis
● Tissue oxygenation is the most important regulator of red blood cell production. If the oxygen level in the blood is too low, this will cause the kidney to release erythropoietin
to increase RBC production. Conditions that can lead to increased EPO production include blood loss (decreased RBC count), decreased availability of oxygen to the blood
(lung diseases, high altitudes, and anemia) and increased tissue demands for oxygen.
● When EPO is produced, it will stimulate the red bone marrow to increase RBC production. This will return the blood oxygen level to normal.

Hemoglobin synthesis
● Hemoglobin synthesis begins at the proerythroblast to the reticulocyte stage. Around 65% is formed in the nucleated stages and 35% during the reticulocyte stage.
● Hemoglobin is formed from precursors Succinyl-CoA and Glycine. The most common form of Hgb is 2 alpha and 2 beta chains.
● Each RBC has 4 heme and this is the location where the iron binds to form the protein hemoglobin. Having 4 iron atoms, this allows the hemoglobin to transport a total of 4
molecules of oxygen.
Iron Balance
● Iron is an essential mineral which is a component of the hemoglobin. It binds with heme to form the protein hemoglobin.
● This allows the hemoglobin to carry oxygen.
● The total quantity of iron in the body is about 4-5g.
○ 65% in the form of hemoglobin
○ 4% in the form of myoglobin
○ 1% in the form of other heme compounds
○ 0.1% in the form of transferrin
○ 15-30% stored in the liver in the form of ferritin

● Most of the iron needed for the new hemoglobin synthesis is just obtained from senescent red blood cells. After being phagocytized by macrophages, the iron is released
which will bind to transferrin in the plasma and interact with the cells that need iron.
● Iron may also be supplied in the diet and is mainly absorbed in the small intestines, specifically, the duodenum.

Reference:
Catherine Cavallaro Goodman, & Kelly, T. E. (2007). Differential diagnosis for physical therapists : screening for referral. Elsevier Saunders.
Hall, J. E., & Guyton, A. C. (2005). Guyton and Hall review of physiology. Elsevier Saunders. ‌
Boron, W. F., & Boulpaep, E. L. (2017). Medical physiology (3rd ed.). Philadelphia, Pa Elsevier. ‌

V. Clinical Grading of Pallor

● Mild: pallor of conjunctiva and/or mucous membrane
● Moderate: pallor of conjunctiva and/or mucous membrane + pallor of skin
● Severe: pallor of conjunctiva and/or mucous membrane + pallor of skin + pallor of palmar creases
 ■ Significance:
○ The clinical finding of pallor in a child is a reliable indicator of anemia.
○ The presence of clinical pallor in any of the body sites (conjunctival pallor, skin pallor, palmar pallor) is a reliable indicator of anemia.
○ The presence of palmar crease pallor is a good indicator of severe anemia in children.
Reference: Regina, D., C., S., & Rao, R. (2016). Correlation of pallor with hemoglobin levels and clinical profile of anemia in primary and middle school children of rural Telangana.
International Journal of Contemporary Pediatrics, 872–877. https://doi.org/10.18203/2349-3291.ijcp20162357 ‌

B. SALIENT FEATURES
Various Organ Systems Involved in Pallor
● Gastrointestinal system
○ Aspirin-induced peptic ulcer disease
● Cardiovascular system
○ Left and right heart failure
● Hematologic system
○ Anemia → Iron Deficiency Anemia

SUBJECTIVE DATA
PERTINENT (+) PERTINENT (-)
● 60 years old, male
● Businessman
● 40 pack years of smoking
● (-) unintentional weight loss
● Pritor 40 mg + Aspirin 80 mg for HPN of 25 years
● No blurring of vision
● Easy fatigability for 2 months
● No dysuria
● Dyspnea for 2 months
● No frequency
● Pallor
● No heat/cold intolerance
● (+) lightheadedness when standing up
● Occasional chest heaviness on exertion, (+) palpitations
● Occasional epigastric pain
OBJECTIVE DATA
PERTINENT (+) PERTINENT (-)
● Relatively low BP (100/60)
● Tachycardia (HR: 100 bpm) ● No ictericia
● Tachypnea (RR: 20 cpm) ● Supple neck, no palpable lymph nodes
● Low body temperature (36ºC) ● Symmetrical chest expansion
● Obese Class I (BMI: 25) (according to Asia-Pacific) ● Unimpaired fremiti
● Pale palpebral conjunctiva ● No adventitious breath sounds
● Dynamic precordium ● S1 louder at apex + S2 louder at base
● Apex beat at 6th LICS, AAL ● Normoactive bowel sounds
● Tenderness on deep palpation epigastric area ● Tympanitic
● Liver dullness 10 cm along MCL ● No splenomegaly
● Pale palms and soles

NOTES FROM FACILITATORS:

● The most common cause of anemia at this age and gender is occult gastrointestinal bleeding caused by gastric ulcers or malignancies

i. GASTROINTESTINAL SYSTEM (ASPIRIN-INDUCED PEPTIC ULCER DISEASE)

● Salient features
○ 60 years old
○ Aspirin 80 mg for HPN of 25
○ Occasional epigastric pain
○ Tenderness on deep palpation epigastric area
○ Normoactive bowel sounds; tympanitic
● Pathophysiology (why is this a possible diagnosis?)
○ Aspirin is an NSAID that irreversibly acetylates cyclooxygenase to block prostaglandin synthesis, ultimately inhibiting platelet aggregation.
○ However, prostaglandins play a critical role in maintaining gastrointestinal mucosal integrity and repair.
○ Hence, compromising prostaglandin synthesis, especially for 25 years, can impair mucosal defense and repair, thus facilitating mucosal injury beginning as gastric irritation to
erosion and ulceration.
○ Although not mentioned in the given history, the patient’s intentional weight loss may be a result of dieting, which could have aggravated mucosal irritation with aspirin intake.
○ Common manifestations of peptic ulcer disease are burning or gnawing epigastric pain and epigastric tenderness upon physical examination, both of which our patient is
experiencing.
○ Gastrointestinal bleeding is also a common complication of this disease, which could deplete iron stores and impair hemoglobin synthesis such that microcytic and hypochromic
RBCs are formed, manifesting in pallor in our patient.
■ Hypovolemia from this blood loss may directly cause pallor, hypotension, and low body temperature as well.
● BUT THERE HAVE BEEN NO REPORTED FINDINGS THAT CONFIRMS GI BLEEDING
○ If it is acute overt and originates from the upper GI, it manifests with hematemesis, coffee-ground emesis, or melena (black tarry stool)
○ If it originates from the lower GI, it manifests with hematochezia (passing of fresh red blood from rectum) instead
○ Meanwhile, chronic occult GI bleeding usually presents as positive fecal occult blood or iron deficiency anemia.
○ None of these were reported by or asked of the patient, so further examination and tests must be conducted to check for the presence of these important findings and consider
aspirin-induced peptic ulcer disease.
Sources:
● https://go.drugbank.com/drugs/DB00945
● https://pubmed.ncbi.nlm.nih.gov/9263351/
● https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/j.1532-5415.2009.02633.x

NOTES FROM FACILITATORS:

● Sign and symptoms regarding upper gastrointestinal bleeding involving epigastric pain and tenderness may be due to the patient’s chronic use of NSAIDS

ii. CARDIOVASCULAR SYSTEM (HEART FAILURE)

● Salient features
○ 60 years old
○ HPN of 25 years, on Pritor 40 mg + Aspirin 80 mg
○ Easy fatigability for 2 months
○ Dyspnea for 2 months
○ (+) lightheadedness when standing up
○ Occasional chest heaviness on exertion, (+) palpitations
○ No dysuria
○ No frequency
○ Relatively low BP (100/60)
○ Tachycardia (HR: 100 bpm)
○ Tachypnea (RR: 20 cpm)
○ Dynamic precordium
○ Apex beat at 6th LICS, AAL
○ Symmetrical chest expansion?
○ Unimpaired fremiti
○ No adventitious breath sounds
○ S1 louder at apex + S2 louder at base
● Pathophysiology (why is this a possible diagnosis?)
○ Left heart failure
■ Our patient has long-standing hypertension of 25 years, which could have caused the development of left ventricular hypertrophy as presented by the dynamic precordium
(visibly increased movement at the area of the chest over the heart) and the displaced apex beat from its normal location at the 5th left intercostal space along the
midclavicular to the 6th left intercostal space along the anterior axillary line.
● This is brought about by the myocardium undergoing structural and functional changes to accommodate the increased workload demanded by the heart
■ With time, there is resultant inability of the myocardium to generate enough force for the heart to contract strong enough to maintain adequate cardiac output, leading to
left heart failure.
■ Systolic dysfunction here then decreases blood flow during systole, leading to a relatively lower blood pressure as in our patient.
● Although this blood pressure could also be due to his anti-hypertensive medication, and could drop even more when he stands up and causes blood to pool in the veins
of the legs and trunk.
○ This orthostatic hypotension lowers the blood pressure and thus the amount of blood that gets pumped to the brain, causing transient lightheadedness when one
stands up from a sitting or recumbent position.
○ It is common in the elderly since with age, baroreceptors can slow down and the heart can struggle with quickly adapting to sudden changes in blood pressure.
■ Consequently, there may also be decreased tissue perfusion, causing weakness, fatigue, decreased urine output, and some degree of acidosis from tissue hypoxia,
stimulating respiratory centers to induce tachypnea and dyspnea
● Sympathetic stimulation, as in physical exertion, can also induce tachypnea, tachycardia, and palpitations to try and maintain cardiac output
■ Having experienced unstable angina already in the past, the patient’s chest heaviness on exertion may be angina once again
● This could be indicative of ischemia secondary to coronary artery disease from his hypertension as well.
○ Right heart failure
■ Left heart failure may eventually lead to right heart failure as well wherein blood backs up further into the systemic venous vasculature
● This can result in congestion of the liver, as presented by our patient with his liver dullness at 10 cm along the midclavicular line, but without splenomegaly
● The patient should also be checked for peripheral edema and distended jugular veins in relation to this
○ However, increased left end diastolic pressure forces blood back into the lungs, raising pulmonary vascular pressure which leads to transudative pulmonary edema
■ This usually produces pulmonary crackles and wheezing, and as per the gathered data, our patient appears to have no abnormal lung findings
● Adventitious breath sounds and even unimpaired fremiti with symmetrical chest expansion

Sources:
● https://www.msdmanuals.com/home/heart-and-blood-vessel-disorders/symptoms-of-heart-and-blood-vessel-disorders/dizziness-or-light-headedness-when-standing-up
● https://www.mayoclinic.org/diseases-conditions/orthostatic-hypotension/symptoms-causes/syc-20352548
iIi. HEMATOLOGIC SYSTEM (ANEMIA)
● Salient features
○ Easy fatigability for 2 months
○ Dyspnea for 2 months
○ Pallor
○ (+) lightheadedness when standing up
○ Occasional chest heaviness on exertion, (+) palpitations
○ Relatively low BP (100/60)
○ Tachycardia (HR: 100 bpm)
○ Tachypnea (RR: 20 cpm)
○ Low body temperature (36ºC)
○ Pale palpebral conjunctiva
○ Pale palms and soles
○ (-) paresthesia/numbness
○ No ictericia
 ○ Liver dullness 10 cm along MCL
○ No splenomegaly
● Pathophysiology (why is this a possible diagnosis?)
○ For the last organ system, anemia is most likely the direct cause of the patient’s main complaint of pallor, exemplified by pale palpebral conjunctiva, palms, and soles, as well as
easy fatigability, dyspnea, and reduced exercise capacity
○ We suspect that the patient may be experiencing blood loss, possibly of gastrointestinal origin, which depletes iron stores in the body such that RBCs have hemoglobin
irregularities and thus reduced oxygen-carrying capacity
○ The patient’s low body temperature and orthostatic hypotension may also point to the existence of blood loss
○ Hence, his manifestations of tachycardia, palpitations, and tachypnea indicate a compensatory attempt to maintain cardiac output for adequate perfusion and oxygenation of
tissues
○ Certain types of anemia could also lead to paresthesia, ictericia, and hepatosplenomegaly, although these manifestations except hepatomegaly were not reported in the patient’s
history

C. ANEMIA
Definition
● Anemia is defined as a reduction of the oxygen-carrying capacity of the blood resulting from decreased total circulating red cell mass below normal limits leading to tissue
hypoxia.
● Anemia is usually diagnosed based on a reduction in the hematocrit (ratio of packed red cells to total blood volume) and the hemoglobin concentration of the blood. These
two values correlate with the red cell mass except when the changes in plasma volume are caused by fluid retention/dehydration.

Classification
According to Onset
Onset Clinical Signs and Symptoms

Acute SOB/Dyspnea
Organ failure
Shock

Chronic Pallor
Easy fatigability
Dyspnea

According to Underlying Mechanism

● Blood loss
● Increased RBC destruction
● Decreased RBC production
Mechanism Examples

Blood loss Trauma, GI tract lesions

Increased RBC destruction (Hemolysis) G6PD Deficiency

Thalassemia
Sickle cell disease
Erythroblastosis fetalis
Disseminated intravascular coagulation

Decreased RBC production B12 and Folate deficiencies

Iron deficiency
Renal failure
Chronic inflammation

According to alterations in red cell morphology

● Often points to particular causes
Morphological Characteristic Examples

Microcytic hypochromic anemias Disorder of hemoglobin synthesis

(Low MCV and Low MCHC) ● Iron deficiency
● Thalasemia

Macrocytic normochromic anemias Abnormalities that impair the maturation of erythroid precursors in the bone marrow:
(High MCV and Normal MCHC) ● Vitamin B12 deficiency
● Folate deficiency

Normochromic normocytic anemias ● Hemolytic anemia

(Normal MCV and Normal MCHC) ● Anemia of acute hemorrhage
● Aplastic anemia

Discussion of Main Diagnosis: Iron Deficiency Anemia

Definition
● Iron deficiency is the most common nutritional disorder in the world and results in clinical signs and symptoms that are mostly related to inadequate hemoglobin synthesis
 ● Happens when iron stores are depleted and blood iron level begins to fall
● Results in low MCV and low MCHC → Microcytic and hypochromic RBCs

Etiology
● Iron deficiency can result from:
○ Dietary lack of iron (e.g. infants, the poor, and the elderly)
○ Impaired absorption (e.g. steatorrhea and other diseases of the duodenum))
○ Increased requirement (e.g. infants, children, pregnant women)
○ Chronic blood loss
■ Most common cause of iron deficiency in high income societies
■ Iron deficiency in adult men and postmenopausal women in high income countries must be attributed to gastrointestinal blood loss until proven
otherwise.
■ External hemorrhage or bleeding into the GI, urinary, or genital tracts depletes iron reserves.
■ An unexplained iron deficiency anemia which results from an occult bleeding source usually points to cancer.

Pathogenesis
● Iron deficiency leads to inadequate hemoglobin production.
● At the onset of chronic blood loss or other causes of negative iron balance, reserves in the form of ferritin and hemosiderin may be adequate to maintain normal Hgb and
Hct levels. Progressive depletion of these reserves first lowers serum iron without producing anemia.
○ In early stage: there is increased erythroid activity in the bone marrow
○ Anemia appears only when iron stores are completely depleted and is accompanied by lower serum iron, ferritin, and transferrin.

Clinical Manifestations:
● They are nonspecific and these include:
○ Pallor
○ Easy fatigability
○ Dyspnea/SOB
○ Reduced exercise capacity
● In severe long-standing iron deficiency:
○ Koilonychia (brittle nails)
○ Alopecia (balding)
○ Appearance of pica

Reference:
Kumar, J. C. (2020). Robbins & Cotran Pathologic Basis Of Disease. (10th ed.). Elsevier - Health Science. ‌

NOTES FROM FACILITATORS:

● Review previous history of gastrointestinal surgery on the patient which may affect the absorption of iron
○ Specifically areas such as the stomach, duodenum, and terminal ileum

D. OTHER ASSOCIATED MANIFESTATIONS

● Cardiovascular / Respiratory
○ IDA →dec Hgb → ↓Oxyhemoglobin → ↓ O2 delivery → ↓perfusion → ↓pO2 / ↑pCO2→ ↓pH → Compensatory activation of peripheral and central chemoreceptors →
Respiratory center → SNS → ↑ventilation (RR = 20) and ↑HR (palpitations, 100 bpm)
■ ↓perfusion→ inability to meet metabolic demands → Dyspnea
○ Dynamic precordium apex beat at 6th ICS, S1 louder at apex, S2 louder at base -
■ (probably due to long-standing hypertension, may or may not be related to anemia)
■ Isn’t this normal kasi dynamic naman
● In a normal heart S1 is louder than S2 in the apex, and S2 is louder than S1 in the base
● Apex beat normally palpable at 5th or 6th ICS
● GI
○ ↑ aspirin in elderly in high income population → epigastric pain
○ Easy fatigability of musculoskeletal system (muscle ache)→↑ consumption of aspirin (nsaids) among elderly→ ↑incidence of bleeding with aspirin intake → Occult GI
bleeding → epigastric pain / Tenderness on deep palpation epigastric area
■ “Overt GIB is manifested with hematemesis, vomitus of red blood or coffee-grounds material; melena black tarry stool; and/ or hematochezia (passage of red or
maroon blood from rectum)... In absence of overt bleeding, occult bleeding may present with symptoms of blood loss or anemia such as lightheadedness, syncope,
angine, or dyspnea, or with IDA or positive fecal occult blood test on routine testing (- Harrison’s chapter 44)
■ Low dose aspirin is associated with an increased risk of gastrointestinal bleeding with the risk highest among those who smoke and have high blood pressure or
kidney disease
■ ↑incidence of bleeding with aspirin intake → blood loss → IDA
○ Smoking → ↓vitamin C levels
● General
○ BMI 25 → Intentional weight loss → Improper diet → ↓ Nutrition Intake (Iron)* → ↓ Body Iron Stores (attributed by other factors) → ↓ Erythropoiesis in the BM → ↓ Hgb
Synthesis → ↑ Production of Microcytic, Hypochromic RBCs → ↓ O2 binding capacity to RBC → ↓ Delivery of Oxyhemoglobin to tissues → DIFF PATHWAY:
■ ↓ O2 supply to the brain → (+) Lightheadedness upon standing
■ ↓ O2 delivery to peripheral tissues → Lack of O2 supply to the muscles → Easy fatigability
E. CONCEPT MAP

**HEENT/ Musculoskeletal - pallor

- MSK: easy fatigability
 PATHOLOGY
KIM
Peripheral blood smear
● Peripheral blood smear reveals to us important information on red blood cell defects through their morphology. Visually, we’re able to compare the normal from the abnormal by their
differences in cell size (anisocytosis), color (hypochromia), and shape (poikilocytosis).
● Slide 1 - Normal vs IDA
○ Normal

■
■ Photo reference: https://histologyguide.com/slideview/MH-033hr-blood-smear/07-slide-1.html?x=7773&y=8874&z=24.4
■ Biconcave disc shape, measuring 7 to 8 um in diameter with a zone of central pallor ⅓ of its size
■ Its biconcave flexible membrane with a high surface-volume ratio allows it reversible deformability, readily squeezing through small capillaries as small as 3-4 µm
in diameter

○ IDA

■
■ Photo reference: Kumar, V., Abbas, A.K., & Aster, J.C. (2015) Robbins and Cotran pathologic basis of disease [9th Ed.]. Philadelphia, PA:Elsevier/Saunders
■ In comparing the diagnosis of IDA with the normal blood smear,
■ Microcytic
● The red cells in IDA are small, measuring less than 6 um in diameter with an MCV of less than 80 fL
■ Hypochromic
● Hemoglobin is composed of 4 globin chains (2 alpha, 2 beta-globin chains) that is bound to a porphyrin ring (heme) consisting of a ferrous iron in its
center
○ Hemoglobin is responsible for the red color in RBCs
● In iron deficiency anemia where there’s depleted iron stores
○ This decreases the synthesis of hemoglobin in RBCs → thus, newly synthesized RBCs appear pale due to less hemoglobin content
● Visible in how the zone of pallor is enlarged and hemoglobin is seen only in a narrow peripheral rim
■ Poikilocytes (abnormally shaped) in the form of small, elongated red cells (pencil cells) are also characteristically seen
● Slide 2 - Vitamin B12 Deficiency Anemia

○
○ Normochromic
○ Macrocytic
■ MCV greater than 100 fL with large RBCs greater than 8 um in diameter and oval in shape
○ Poikilocytosis is also seen with the presence of teardrop cells
○ Lack central pallor
○ Hypersegmentation of neutrophils with 5 or more lobes, pathognomonic for megaloblastic anemia
○ Howell-jolly bodies (small dark nuclear remnants composed of DNA)
 ● Slide 3 - Spherocytosis
○ Hemolytic anemia
○ Small hyperchromatic cells without the usual clear area in the center
○ X biconcave → sphere

VAN BONE MARROW ASPIRATION

SLIDE CONTENT INFO IMAGES
1 ● Bone marrow aspiration is a procedure that is performed to further examine an individual’s cellular morphology in
relation to hematologic disorders.
○ RECALL: Bone marrow is the site where hematopoiesis occurs and should there be anything wrong with our
blood cells, we have to examine the condition of our bone marrow in order to diagnose the disease
○ In normal conditions, we should be able to identify a normal looking red blood cell which means that it has a
hemoglobin that is not deficient of iron
■ (Characteristic: Normocytic, Normochromic)
● Iron is a critical component that is required for metabolic processes in the production of RBCs and therefore a
deficiency of iron would lead to a microcytic, hypochromic anemia wherein there will be an increase central pallor
observed on the smear (as discussed earlier by Dr. Advincula)

Source
2 ● In the Bone marrow aspirate, a prussian blue iron stain is commonly used to illustrate and indicate whether the iron
status of a patient is normal, absent, or increased in iron stores.
● Prussian Blue Stain, is a chemical compound that uses acidic potassium ferrocyanide as the reagent or stain and this
is considered as the gold standard for the assessment of body iron.
○ MOA: The ferric iron in the tissue would react with the reagent to form the dark blue dots that can be observed
microscopically and this is known as the prussian blue compound.
○ From sample slide A, we can appreciate the prussian blue dye on the marrow aspirate smear and this is how
normal iron stores would look like.
○ Comparing this with sample slide B, wherein there is no hint of blue compound observed, this would indicate
that iron stores are absent.
○ In sample slide C, we can evidently observe the increased intensity of the blue compound as compared to
sample slide A, meaning that there is an increase in the iron stores.

3 ● In the case of Anemia of Chronic Inflammation (ACI), it is known to be the most common anemia among
hospitalized patients and as the name would imply, it is associated with chronic infections.
● PBS would usually show a normocytic, normochromic appearance. However, in severe state, it may appear as
microcytic, hypochromic, similar to Iron Deficiency Anemia.
○ The difference between IDA and ACI is that the central feature of ACI is sideropenia, which means that it has a
low level of serum iron even though there are abundant iron stores present.
● In the normal RBC metabolism, Iron is usually recycled after an RBC expires.
○ This occurs when the senescent RBCs are being ingested by the macrophages in the spleen and as a result, the
hemoglobin is degraded wherein the iron would be released and be stored by the macrophages as ferritin. Normal
○ In ACI, inflammatory mediators of cytokines such as the IL-1 and IL-6 stimulates the production of Hepcidin
which is a master regulatory hormone for systemic iron metabolism.
■ It acts to inactive the ferroportin which is a protein that transports the iron from tissues to the blood.
■ Meaning to say, without the ferroportin, the macrophages from the tissue cannot release the iron stored into
the circulation and therefore this would account for the high level of iron stores but low levels of serum iron.
○ This is why in the slide we can observe the increased intensity of the blue compound compared to the normal
slide.
 Increased Iron Stored
STAGES OF IDA
4 TIBC (TOTAL IRON BINDING
STAGE 1 HEMOGLOBIN SERUM IRON FERRITIN
CAPACITY)
Storage Iron Depletion NORMAL NORMAL NORMAL DESCREASED
➔ AKA Latent / Subclinical iron deficiency
➔ Characterized by a progressive loss of storage iron
➔ RBC development is still normal due to the sufficient supply of the iron stores which maintains the usual transport and functional compartments
➔ Iron deficiency is not yet evident as new made RBCs takes 120 days to survive
◆ Therefore at this stage, the patient does not experience any symptoms of anemia yet
➔ Serum Ferritin levels are low as the stored iron is being used at this stage in compensation for the progressive loss of iron.
5 TIBC (TOTAL IRON BINDING
STAGE 2 HEMOGLOBIN SERUM IRON FERRITIN
CAPACITY)
Transport Iron Depletion NORMAL DESCREASED INCREASED DESCREASED
➔ After some time of depending on the stored iron (The ferritin), wherein RBC production continues normally, the hemoglobin content would decrease indicating the onset of iron
deficient erythropoiesis.
◆ However, the hemoglobin would still appear normal as majority of the circulating RBC were already produced during the latent period wherein there is still adequate iron
available.
◆ Hence at this stage, anemia is still not yet evident as the MCV would remain normal but a few microcytes may be observed on a Peripheral blood smear.
➔ As this stage is known as the exhaustion of the storage pool of iron, serum iron along with the ferritin is decreased while TIBC is increased.
◆ Because there is a depletion of iron, Free erythrocyte protoporphyrin (FEP), which is a porphyrin where iron is usually inserted to, begins to accumulate.
◆ As a compensation mechanism, transferrin receptors then increases on the surface of the iron starved cells as they would try to capture any available iron.
◆ If there is no iron captured, these transferrin receptors would be shed into the plasma as the Soluble transferrin receptor (sTfR) therefore increasing its levels in the
circulation.
◆ TIBC is referred to as the indirect measure of transferrin concentration.
● If there is an increase in sTfR, it would mean that no iron was captured as there weren't any available iron in the body and therefore indicating for IDA
6 TIBC (TOTAL IRON BINDING
STAGE 3 HEMOGLOBIN SERUM IRON FERRITIN
CAPACITY)
Functional Iron Depletion (Frank iron
DESCREASED DESCREASED INCREASED DESCREASED
Deficiency Anemia)
➔ AKA as the Frank anemia wherein Hgb concentration and Hct is evidently low.
➔ Since there is a total depletion of storage iron and diminished levels of transport iron, this would prevent normal development of RBC precursors.
◆ Microcytic, hypochromic can now be evidently detected.
➔ TIBC remains elevated as the Free Erythrocyte Protoporphyrin (FEP) and soluble transferrin receptor (sTfR) continues to increase in an attempt to capture any available iron in
the body.
➔ At this stage, clinical symptoms are now evident in the patient and this includes fatigue, weakness, shortness of breath especially with exertion and Pallor may also be
observed.

KIM Iron-deficiency maturation process

7 ● We begin from 2 progenitors derived from pluripotent hematopoietic stem cells,

○ Burst forming unit erythroid (BFU-E) capable of giving rise to multisubunit or burst colonies, and
○ Colony forming unit erythroid (CFU-E) capable of giving rise to smaller colonies
○ Both are committed to the erythroid line to give rise to the
● Pronormoblast
○ Earliest morphologically recognizable erythrocyte precursor
○ This divides into its daughter cells capable of maturing to the next stage of development
● Basophilic normoblast, whose daughter cells successively matures into Polychromatic normoblast → Orthochromic normoblast → Reticulocytes → mature
erythrocytes

8 ● There’s not much difference in the morphology between the normal erythropoiesis and the Iron-deficient erythropoiesis asides from the final mature erythrocyte stage where as
mentioned becomes microcytic and hypochromic
● Similar to the normal erythropoiesis,
○ During the initial immature stages, pronormoblasts and basophilic normoblasts have a larger nucleus to cytoplasm ratio (N:C)
○ Since the general trend of maturation proceeds with an overall decrease in cell diameter, with a more rapid decrease in nuclear diameter than the decrease in
cytoplasmic diameter
○ Thus, we can see that as we progress towards the more mature stages Polychromatic normoblast → Orthochromic normoblast
■ The N:C ratio gets smaller
■ The nuclear chromatin becomes coarser, clumped together, and condensed
○ The cytoplasm also changes from blue to gray to salmon pink
■ Where we began with an abundance of ribosomal RNA and active on protein production and thus appear blue
 ■ The ribosomes and organelles decline as we mature, and the blueness fade
■ And with the increase in eosinophilia with hemoglobin accumulation as the cell matures, the color transitions into salmon pink
○ Then for polychromatophilic erythrocytes (reticulocyte stage) the cytoplasm appears pink with a hint of blue due to the precipitated ribosome material that is usually
made evident through supravital stains such as NMB and BCB.
● Then finally, we have the mature erythrocyte that appears hypochromic with a central pallor greater than ⅓ of the cell, and overall decreased hemoglobin
VAN RETICULOCYTE COUNT (Added as per feedback from Patho Department)
9 ● Reticulocyte Count is done in order to effectively assess the RBC production by the bone marrow. It is also a measure of Effective
Erythropoiesis
● What is being counted: RETICULOCYTE
○ It is an immature, non-nucleated RBC which contains ≥ 2 blue stained, granular filamentous materials known as the Reticulum
○ This is only visualized after getting stained by supravital stains usually by the new methylene blue
○ Reticulocyte is the last immature RBC in the erythropoiesis stage.
■ It usually spends 2 days in the bone marrow and then only 1 day in the peripheral blood before it becomes a mature red blood cell.
○ In relation to the case, an increase in reticulocyte would be considered as the first sign or accelerated erythropoiesis and is observed in
individuals with acute and chronic blood loss. (With the increase in reticulocyte count, this can be an indication of a working bone
marrow)
■ However, if there is a decrease in the reticulocyte count, it would mean that the bone marrow is not functional as it is not producing any RBCs.
● Methods of Counting Reticulocytes (Manual Method)
○ Routine Light Microscope Method:
■ After the proper smear preparation, It is done by directly counting 1000 RBCs under the oil immersion objective lens wherein the
reticulocytes are included in the total RBC count.
𝑁𝑜. 𝑜𝑓 𝑅𝑒𝑡𝑖𝑐𝑠 𝑂𝑏𝑠𝑒𝑟𝑣𝑒𝑑
■ This is then calculated as: 𝑅𝑒𝑡𝑖𝑐 (%) = 1000 𝑅𝐵𝐶𝑠 𝑂𝑏𝑠𝑒𝑟𝑣𝑒𝑑 × 100
○ Calibrated Miller Disk Method:
■ The miller disk consist if two squares with the area of th smaller square measuring 1/9 the area of the larger square
■ The smaller square is where the RBC is counted
■ The bigger square is where the Reticulocyte is counted
■ A minimum of 112 cells should be counted in the small square as this is equivalent to 1008 red cells in the large squared
𝑁𝑜. 𝑜𝑓 𝑟𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒𝑠 𝑖𝑛 𝑆𝑞𝑢𝑎𝑟𝑒 𝐴 𝑥 100
■ This is then calculated as: 𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒𝑠 (%) = 𝑁𝑜. 𝑜𝑓 𝑅𝐵𝐶𝑠 𝑖𝑛 𝑆𝑞𝑢𝑎𝑟𝑒 𝐵 𝑥 9
10
METHOD OF REPORTING RETICULOCYTE COUNT
METHOD PRINCIPLE CALCULATIONS REFERENCE INTERVALS
Actual number of reticulocytes in 1 L or 12
𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒𝑠 (%) × 𝑅𝐵𝐶 𝐶𝑜𝑢𝑛𝑡 (× 10 /𝐿)
Absolute Reticulocyte Count 𝐴𝑅𝐶 = 20 to 115 x 1012/𝐿
1 microliter of blood. 100
Specimens with low hct may result in
falsely elevated retics. Therefore a 𝑃𝑎𝑡𝑖𝑒𝑛𝑡 𝐻𝐶𝑇 (%) The corrected reticulocyte count
Corrected Reticulocyte Count 𝐶𝑅𝐶 (%) = 𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 (%) ×
correction factor is used (45%) (Ave 45 depends on the degree of anemia
normal hct)
Reticulocyte Production Index RPI > 3 : Adequate bone marrow
AKA Shift correction. A general
response
indicator of the rate of erythrocyte 𝐶𝑜𝑟𝑟𝑒𝑐𝑡𝑒𝑑 𝑅𝑒𝑡𝑖𝑐𝑢𝑙𝑜𝑐𝑦𝑡𝑒 𝐶𝑜𝑢𝑛𝑡
𝑅𝑃𝐼 =
production (Increase above normal in 𝑀𝑎𝑡𝑢𝑟𝑎𝑡𝑖𝑜𝑛 𝑇𝑖𝑚𝑒 𝑖𝑛 𝑡ℎ𝑒 𝑝𝑒𝑟𝑖𝑝ℎ𝑒𝑟𝑎𝑙 𝑏𝑙𝑜𝑜𝑑
RPI < 2 : Inadequate bone marrow
anemias) - Refer to table on the left
response

NOTES FROM FACILITATORS:

● On aspirin causing the BP of 100/60
○ Does not DIRECTLY affect BP
○ Aspirin → gastric occult bleed → lowered BP
● Tachycardia
● Left ventricular hypertrophy
○ Secondary to chronic hypertension
● Displaced apex beat due to dynamic precordium, which itself is caused by increased HR
● RBC problems
○ Low RBC = anemia
○ Relate history of upper GI bleed
○ FINAL DIAGNOSIS = ANEMIA SECONDARY TO UPPER GI BLEED
● In CBC, see HCT, HGC, RBC indices, reticulocyte count
○ HGB to check severity
○ RBC indices: size and color of RBC
○ Used to classify anemia
○ MCV: mean corpuscular volume, size
○ MCH: mean corpuscular hemoglobin, color
○ MCHC: HGB concentration per unit
■ Microcytic, hypochromic: iron deficiency anemia, thalassemia, lead poisoning, sideroblastic anemia
■ Macrocytic, normochromic: megaloblastic anemia
○ Reticulocyte count: special request
■ Assess bone marrow production of RBC
■ If decreased, dysfunction in bone marrow
● Iron studies may be recommended to check iron levels
● FOBT: fecal occult blood test
○ Detect RBCs in feces that is not grossly observed as melena or hematochezia
 RADIOLOGY / DIAGNOSTIC OR ANCILLARY PROCEDURES

I. Laboratory Examinations For Anemia

A. Complete Blood Count
1. RBC Count
2. Hemoglobin
3. Hematocrit
4. Red Blood Cell indices
a) MCV, MCH, MCHC, RDW
5. Reticulocyte count
6. Leukocyte count
7. Platelet count
B. Peripheral Blood Smear
C. Iron Studies
1. Serum Iron
2. Serum Ferritin
3. Total Iron Binding Capacity (TIBC)
4. Transferrin Saturation
D. Fecalysis
E. FOBT
II. Laboratory Examination for LVH
A. ECG

III. Radiologic Examinations

A. Chest X-ray
B. Upper GI series
C. Esophagogastroduodenoscopy
D. Colonoscopy

RADIOLOGiC EXAMINATIONS

A. Chest X-ray
- Screening for lung cancer

B. Upper GI series
C. Esophagogastroduodenoscopy
D. Colonoscopy

Drew A. COMPLETE BLOOD COUNT

● A complete blood count is a necessary procedure done to able to make a proper diagnosis of anemia, but you will be able to see the quantity and the quality of the RBC’s
circulating in the patient's body. The factors that will be assessed are as followed.
● RBC Count
○ This is the total count of RBC that is circulating in the body
○ The normal values for male and female
■ Male: 4.20-6.00 x 10^12/L
■ Female: 3.80-5.20 x 10^12/L
■ Males will have a higher count due to the general larger muscle mass requiring a higher RBC count compared to that of females.
● Hemoglobin
○ The protein in the RBC’s that carry oxygen
○ Normal values for male and female
■ Male: 13.5 to 17.5 g/dL.
■ Females: 12.0 to 15.5 g/dL.
● Hematocrit
○ This is the percentage of RBC’s in your blood
○ Normal values for male and female
■ Male: 41% to 50%
■ Females: 36% to 48%
● Red Blood Cell Indices
○ MCV (Mean Corpuscular Volume)
■ This reflects the size of the RBC’s
○ MCH (Mean Corpuscular Hemoglobin)
■ This reflects the amount of hemoglobin present in a RBC
○ MCHC (Mean Corpuscular Hemoglobin Concentration)
■ This is average concentration of hemoglobin inside a group of red blood cells
 ○
● Reticulocyte Count
○ Reticulocytes are immature RBC’s released by the plasma
○ Normal range for adults is from 1-2%
■ An increased value would indicate the body needs more RBC’s to transport oxygen

○
● Leukocyte Count
○ Indicates amount of RBC’s in blood
○ Normal value: 4.5 to 11.0 × 109/L
■ High value would indicate infection
● Platelet count
○ Normal Value: 150,000 to 450,000 platelets per microliter of blood

Drew B. PERIPHERAL BLOOD SMEAR

● The peripheral blood smear provides important information about defects in red cell production. This reveals variations in cell size (anisocytosis) and shape (poikilocytosis).
 ○

Drew C. PERIPHERAL BLOOD SMEAR

● Measurements of marrow iron stores, serum ferritin, and total iron-binding capacity (TIBC) are sensitive to early iron-store depletion. Iron-deficient erythropoiesis is recognized
from additional abnormalities in the serum iron (SI), percent transferrin saturation, the pattern of marrow sideroblasts, and the red cell protoporphyrin level.

Drew D. Fecalysis

● A procedure done to examine feces of a patient

○ Melena
■ Melena refers to black stools that occur as a result of gastrointestinal bleeding
 ■
○ Hematochezia
■ Passage of fresh blood per anus, usually in or with stools

Drew E. FOBT

● Fecal occult blood test is a test done to check for blood which is not visible in the stool through ocular inspection

○
Drew F. FOBT

● Standard clinical tool used to measure the electrical activity of the heart
○ Essential in terms of measuring the electrical activities of the heart
○ Determines whether the heart is enlarged
○ If there are electrical irregularities that are present
○ It may detect individuals with Acute Myocardial Infarction (AMI)
● Recording of the smaller extracellular signals produced by the movement of the AP through cardiac myocytes

● When the myocardium is abnormally thickened, and electrical activity takes longer to traverse throughout the whole heart, the duration of the QRS complex may be widened.
This is referred to as “LVH with QRS widening.” Also, repolarization may be affected via similar mechanisms that can result in abnormal ST segments or T waves. This is
referred to as “LVH with strain” or “LVH with repolarization abnormality.”

●
 RADIOLOGiC EXAMINATIONS (DREI)
A. Upper GI series
● An Upper Gastrointestinal Series (UGIS) is a Radiographic (X-ray) examination of the upper gastrointestinal tract which is made visible on an X-ray film by the use of a liquid
suspension such as Barium or a water-soluble contrast
● The use of barium with standard X-rays contributes to the visibility of various characteristics of the esophagus, stomach, and duodenum.
● There are 2 types of UGIS:
● One is the Standard UGIS which only makes use of Barium
● The other one is the Double-Contrast UGIS which makes use of Air and Barium
● The purpose of using 2 contrast substances is to achieve an enhancement of the inside wall lining of the esophagus, stomach, and duodenum. This technique enhances
visualization by sharpening the outline of the inner surface layer of the esophagus, stomach, and/or duodenum, and is useful in diagnosing structural and tissue
abnormalities.
● Some indications in using UGIS would be for:
● Ulcers
● Gastritis
● Hernia
● Tumors
● Diverticula
● Some Contraindications for this procedure would be:
● Bowel or esophagus perforation
● Bowel obstruction or severe constipation
● Pregnancy
● Severe swallowing difficulty such that aspiration of any substances in the lungs (especially if barium) is likely

Source: Upper Gastrointestinal Series. (n.d.). Retrieved from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/upper-gastrointestinal-series

(A) Normal stomach (B) NSAID-induced gastritis

● Normal Stomach:
○ Double-contrast spot image of stomach with patient supine shows distal gastric body (B) and antrum (A). Greater curvature (white arrows) and lesser curvature
(black arrows) are coated by barium.
● NSAID-induced gastritis
○ Double-contrast spot image of distal gastric antrum that shows NSAID-induced erosive antral gastritis. Multiple varioliform erosions are seen as punctate (small
white arrow) and linear (large white arrow) collections of barium surrounded by radiolucent mounds of edema (black arrows). This patient was taking aspirin.

Source: Rubesin, S., Levine, M., & Laufer, I. (2008). Double-Contrast Upper Gastrointestinal Radiography: A Pattern Approach for Diseases of the Stomach.

B. Esophagogastroduodenoscopy
● Also referred to as upper endoscopy
● This is performed by passing a flexible endoscope through the mouth into the esophagus, stomach, and duodenum.
● The procedure is the gold standard for examining the upper gastrointestinal mucosa.
● It is superior for detection of gastric ulcers and flat mucosal lesions.
● Uses a specialized endoscope which is a flexible tube with a camera that provides a view of the upper GI tract lining
● Mainstay diagnostic procedure/Gold standard for gastric ulcer
○ Together with your Upper GI series
 ● Helpful in identifying lesions which are too small to be detected by radiographic examinations

Indications

● Upper gastrointestinal bleeding

● Abdominal pain
● Heartburn
● Persistent nausea or vomiting
● Swallowing difficulties
● Chest pain (without evidence of heart disease)
● Bloody stool

Source: Jameson, J. L., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Loscalzo, J., & Harrison, T. R. (2018). Harrison's principles of Internal Medicine. McGraw-Hill Education.

(L) Normal stomach (R) Stomach with gastric ulcer

● Normal stomach
○ Normal architecture of the gastric folds can be observed
● Stomach with gastric ulcer
○ Patient with GI bleeding

Source: Cohen, J., & Greenwald, D. (n.d.). Overview of Upper Gastrointestinal Endoscopy (Esophagogastroduodenoscopy).

C. Colonoscopy
● This is performed by passing a flexible colonoscope through the anal canal into the rectum and colon
● This is the gold standard for imaging the colonic mucosa
● Serves as a screening strategy for colorectal cancer
● Colorectal cancer incidence is generally higher with increasing age
● Initiating screening at age 50 years for average-risk adults is recommended by the American College of Physicians
● American Cancer Society and National Comprehensive Cancer Network suggest colonoscopy every 10 years at age 50 for asymptomatic patients with no
family history
● Cigarette smoking is linked to the development of colorectal adenomas, particularly after >35 years of tobacco use

Source: Doubeni, C. (2022). Screening for Colorectal Cancer: Strategies in Patients at Average Risk.
 (L) Normal Colon (R) Colon Cancer

● Normal colon:
○ Showing characteristic triangular folds of the transverse colon

Source: Lee, L., & Saltzman, J. (n.d.). Overview of Colonoscopy in Adults.

E. 2D Echocardiography
- Gold standard for measuring the cardiac chambers
- Uses high-frequency sound waves to penetrate the body, reflect from relevant structures, and generate an image
- This is used to see the various heart structures at work and evaluate them
- Portable, non-invasive, no radiation
- Best to have it to rule out significant heart failure in the patient mainly because of the presenting symptoms, such as easy fatigability and dyspnea
- Additionally, since the patient is hypertensive for 25 years already, this can definitely lead to structural and functional changes in the heart.
- Since the patient was admitted in 2012 because of unstable angina which is already part of acute coronary syndrome, this may lead to a future heart failure

Source: Jameson, J. L., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., Loscalzo, J., & Harrison, T. R. (2018). Harrison's principles of Internal Medicine. McGraw-Hill Education.

(L) Echocardiogram of a normal heart (R) Echocardiogram of a patient with Left Ventricular Hypertrophy

Source: Kroman, A., & Patton, K. (2020). Left Ventricular Hypertrophy.

NOTES FROM FACILITATORS:

● In upper GI series, the characteristics of the ulcer, if NSAID-induced, is small, shallow, multiple
● The upper GI series is not really being done a lot nowadays because they perform endoscopy instead
● What is the advantage of endoscopy for upper GI series? (applied to the patient/case)
○ It is diagnostic for gastric ulcer and at the same time it is therapeutic
● Complications of ulcer in upper GI series
○ Evidences of perforation (although shallow)
○ Obstruction
● In upper GI series, there is no bleeding
● What is the limit of an upper GI pathology?
○ Up to the Ligament of Treitz (duodenojejunal junction)
 PHARMACOLOGY

PHARMACOLOGIC INTERVENTION

PATHOLOGY INTERVENTION MECHANISM & NOTES PK & PD

Iron deficiency Iron salts Goodman and Gilman’s The Pharmacological Basis of Therapeutics (13E) Goodman and Gilman’s The Pharmacological Basis
of Therapeutics (13E)
IRON NEEDS
AVERAGE DOSES
● ADULT: 200 mg of iron per day (2-3 mg/kg)
given in three equal doses of 65 mg
● CHILD (15-30 kg): 100 mg (half adult dose)
● CHILDREN AND INFANTS: can take relatively
large doses of 5 mg/kg
● PREGNANT (prophylactic): 15-30 mg/day

AVERAGE RESPONSE

CONSIDERATIONS
● With increasing doses of oral iron, SI begins to limit iron absorption
● Natural ceiling of maximum iron absorption allows 40-60 mg of iron delivery
to the marrow
● Sufficient for production rates of 2-3x normal
● If no improvement in 3-4 weeks, reconsider diagnosis, missed conditions,
inflammatory diseases, or poor patient compliance
○ Reticulocyte count increases after 4-7 days post-start of treatment
○ Hemoglobin levels take longer than reticulocyte count to change
○ Effectiveness of treatment should be considered only after 3-4 weeks
○ POSITIVE RESPONSE: ≥20g/L increase of hemoglobin

ADVERSE EFFECTS
● Heartburn
● Nausea
● Upper gastric discomfort
● Diarrhea
● Constipation

💊 WORKAROUND: Begin administration at small dosages and increase

gradually to desired dosage

IRON POISONING
● Rare in adults
● Usually in children of 12-24 months
● As little as 1-2 g can cause death but often happens for 2-10 g intake

💊
●
TREATMENT:
Administer deferoxamine
● Deferiprone and deferasirox are also oral iron chelators

PARENTERAL IRON
● Indicated for iron malabsorption (e.g. sprue, short bowel syndrome), severe
oral iron intolerance, supplement to total parenteral nutrition, and in those
receiving EPO
● May be given if large doses of iron which will take longer if taken orally

ESSC
Efficacy, Safety, Suitability, Cost

IRON SALTS EFFICACY SAFETY SUITABILITY COST TOTAL

++++ +++ +++ ++++ 14

● Elemental iron COMMON ADVERSE ● Contraindicated in ● P2.00 (Watsons)

Ferrous sulfate content (65mg)[2] EVENTS active peptic ulcers
65-200 mg daily ● Nausea due to iron oxidation
in 2-3 divided doses ● Epigastric in the GI which can
discomfort damage the
● Abdominal cramps mucosal lining[1]
● Constipation ● Circumvent by
● Diarrhea advising use after
 ● Black stool meals but reduces
bioavailability by up
CHILDREN to 50%[3]
Acute toxicity ● Supplementation
● Necrotizing with Vitamin C (200
gastroenteritis with mg) to increase
vomiting absorption by 30%[4]
● Abdominal pain
● Bloody diarrhea
Followed by shock, ⚠️ TOXICITY
lethargy, and
dyspnea ● Taking >2 g of
vitamin C in a
ADULTS single dose may
Chronic toxicity result in
● Hemochromatosis abdominal pain,
due to excess iron diarrhea, and
deposited in the nausea
heart, liver, ● Chronic high
pancreas, and other doses of Vitamin
organs C can promote
● Can lead to organ iron overload
failure and death and iron toxicity

Harrison’s Principles
of Internal Medicine,
20E

++++ +++ +++ ++ 12

● Lowest elemental COMMON ADVERSE ● Contraindicated in ● P26.75 (Watsons)

iron content EVENTS active peptic ulcers
(36mg)[2] ● Nausea due to iron oxidation
● Epigastric in the GI which can
discomfort damage the
● Abdominal cramps mucosal lining[1]
● Constipation ● Circumvent by
● Diarrhea advising use after
● Black stool meals but reduces
bioavailability by up
CHILDREN to 50%[3]
Acute toxicity ● Supplementation
● Necrotizing with Vitamin C (200
gastroenteritis with mg) to increase
vomiting absorption by 30%[4]
● Abdominal pain
Ferrous gluconate
100-200 mg daily
● Bloody diarrhea
Followed by shock, ⚠️ TOXICITY
lethargy, and
in 2-3 divided doses ● Taking >2 g of
dyspnea
vitamin C in a
ADULTS single dose may
Chronic toxicity result in
● Hemochromatosis abdominal pain,
due to excess iron diarrhea, and
deposited in the nausea
heart, liver, ● Chronic high
pancreas, and other doses of Vitamin
organs C can promote
● Can lead to organ iron overload
failure and death and iron toxicity

Harrison’s Principles
of Internal Medicine,
20E

++++ +++ +++ +++ 13

Ferrous fumarate
65-200 mg daily
in up to 3 divided doses ● Highest elemental COMMON ADVERSE ● Contraindicated in ● P12.50 (Watsons)
iron content EVENTS[2] active peptic ulcers
 (106mg)[2] ● Nausea due to iron oxidation
● Epigastric in the GI which can
discomfort damage the
● Abdominal cramps mucosal lining[1]
● Constipation ● Circumvent by
● Diarrhea advising use after
● Black stool meals but reduces
bioavailability by up
CHILDREN[2] to 50%[3]
Acute toxicity ● Supplementation
● Necrotizing with Vitamin C (200
gastroenteritis with mg) to increase
vomiting absorption by 30%[4]
● Abdominal pain
● Bloody diarrhea
Followed by shock, ⚠️ TOXICITY
lethargy, and
dyspnea ● Taking >2 g of
vitamin C in a
ADULTS[2] single dose may
Chronic toxicity result in
● Hemochromatosis abdominal pain,
due to excess iron diarrhea, and
deposited in the nausea
heart, liver, ● Chronic high
pancreas, and other doses of Vitamin
organs C can promote
● Can lead to organ iron overload
failure and death and iron toxicity

Harrison’s Principles
of Internal Medicine,
20E

REFERENCES:
[1] Sunkara, T., Caughey, M. E., Nigar, S., Olivo, R., & Gaduputi, V. (2017). Iron Pill Gastritis: An Under Diagnosed Condition With Potentially Serious Outcomes.
Gastroenterology research, 10(2), 138–140. https://doi.org/10.14740/gr804w
[2] Katzung, B. (2018). Basic and Clinical Pharmacology 14E, 594-595
[3] Nanjundan P. Comparison of Various Treatment Modalities of Iron Deficiency Anemia in Pregnancy. World J Anemia 2017;1(1):23-26
[4] Jameson et al. (2018). Harrison’s Principle of Internal Medicine 18E

NOTES FROM FACILITATORS:

● In patients with iron-deficiency anemia, the first line of treatment is oral iron replacement
● Shift to intravenous form of iron replacement can be due to the intolerable gastrointestinal side effects, hence patients are not compliant with the treatment
● In the acute setting: the intravenous form is prioritized because patients are NPO (nothing per orem)
● Indications of Oral vs. Parenteral iron supplementation:
○ Oral - Rise in hemoglobin would take at least 7 to 10 days
○ Intravenous (IV) - Instant/direct delivery, but would still have to wait for the bone marrow to produce red blood cells
○ Hence treatment may be focused on providing ready-made RBCs through blood transfusion

NON-PHARMACOLOGIC INTERVENTION

● Iron is available in a wide variety of foods but especially abundant in meat

● Iron in meat can be efficiently absorbed because heme iron in meat hemoglobin and myoglobin can be absorbed intact without first having to be dissociated into elemental iron
● Iron in other foods (vegetables and grains) is often tightly bound to organic compounds and is much less available for absorption

FOODS RICH IN IRON INCLUDE

● Red meat, pork and poultry, Seafood, Beans, Dark green leafy vegetables, such as spinach, Dried fruit, such as raisins and apricots, Iron-fortified cereals, breads and pastas,
and peas.
● Organ meats are extremely nutritious. Popular types include liver, kidneys, brain, and heart — all of which are high in iron.
○ Liver is especially high in vitamin A

FOODS THAT MAY HINDER IRON ABSORPTION

● Foods containing phytate
○ Whole grains, cereals, soy, nuts and legumes
● Calcium-rich foods
○ Milk, cheese
● Foods containing polyphenols
○ Vegetables, fruits, some cereals and legumes, tea, coffee and wine

FOODS THAT MAY INCREASE IRON ABSORPTION

● Foods rich in Vitamin C
○ Citrus fruits, dark green leafy vegetables, bell peppers, melons and strawberries
● Foods with Vitamin A and Beta-Carotene
○ Carrots, sweet potatoes, spinach, kale, squash, red peppers
● Meat, Fish and Poultry

REFERENCE:
● Katzung, B. (2018). Basic and Clinical Pharmacology 14E,p 593
● https://www.healthline.com/nutrition/increase-iron-absorption#TOC_TITLE_HDR_4
● https://www.healthline.com/nutrition/healthy-iron-rich-foods#3.-Liver-and-other-organ-meats

PHARMACOLOGIC INTERVENTION

PATHOLOGY INTERVENTION MECHANISM & NOTES PK & PD

ESSC
Efficacy, Safety, Suitability, Cost

- EFFICACY SAFETY SUITABILITY COST TOTAL

++++ ++ +++ ++ 11

● 50 mg of ● Adverse effects ● Contraindicat ● $349 ~ P978

elemental iron include headache, ed in patients ● Brand: Infed (Not
per ml of lightheadedness, with known available in the
solution fever, arthralgias, hypersensitivi Philippines)
nausea, vomiting, ty and any
Iron Dextran back pain, flushing, form of
urticaria, and anemia which
bronchospasm is not the
● Monitor for result of iron
anaphylactic deficiency
reaction ● Not
● Rarely may cause commercially
death available for
humans

++++ +++ ++++ +++ 14

● 20mg of elemental ● Adverse effects ● Contraindicat ● P426.00 (MIMS)

iron per ml of include hypotension, ed in patients
solution muscle cramps, with known
headache and hypersensitivi
nausea ty and any
Iron sucrose form of
anemia which
is not the
result of iron
deficiency
● Indicated for
IDA
associated
with CKD
REFERENCES:

NON-PHARMACOLOGIC INTERVENTION

NOTES FROM FACILITATORS:

● Q: How did you arrive at the decision to give parenteral iron? What are the indications for oral versus IV?
○ A: Oral → more popular route; convenient and efficient; cost-effective
■ However, oral iron is contraindicated for those with problems or injury in the gastric mucosa
■ In a previous study, since oral iron is in its ferrous form and it is better absorbed through the divalent transporters, it is eventually transformed into
the ferric form → this oxidative process incurs damage to the gastric mucosa
● Which is why the three drugs (Ferrous sulfate, Ferrous gluconate, Ferrous fumarate) are contraindicated in those with on-going
gastric injury
■ Older people tend to have a higher risk of intolerance and reduced absorptive capacity
■ Administration of oral iron (which need to be given in multiple doses) may challenge the adherence of older patients
● Administration of parenteral iron may allow larger infusions to be given to the patient which can provide more iron
● If the patient is symptomatic, the parenteral iron can infuse larger amounts of iron as opposed to oral → helps to better relieve the
patient’s symptoms
■ Limit the pain that is being experienced by the patient through food consumption (of iron)
● Q: What is your third option in this patient?
○ A: Blood transfusion → only indicated in patients who are hemodynamically unstable and whose hemoglobin count is less than 7 g/dL
■ Temporary solution
■ Only indicated for moderate to severe IDAs
■ There is also a risk for infection
○ Q: Will you be able to replenish iron with blood transfusion? How much iron does one unit contain?
■ 1 bag of packed RBCs = 200 mg of iron
■ FACI: With the choice of what to give this patient, you have to consider:
● (1) The presence of cardiovascular instability
○ 1 unit pack of RBC to give to the patient because the patient is at high risk of CAD, presence of symptoms pertinent to
anemia, and the tachycardia of the patient which may push to further coronary artery compromise
○ Remember that if you give oral iron, the rise in hemoglobin will take 7-10 days
○ IV iron: direct, but need to wait for the blood marrow to make iron (still does not elicit needed effect immediately)
● (2) Acute setting: give IV iron because these patients are on NPO (non per orem)
 ○ NPO: nothing by mouth is a medical instruction meaning to withhold food and fluids; patients are still under observation
(e.g. if there is continuous bleeding)
○ Give IV iron if there is: inflammation (absorption is lower), intolerable GI side effects
● Still give oral iron to patients with upper GI bleeding and ulcers (first line)
○ Q: How long do we give iron?
■ FACI: You expect response after transfusion of 1 pack RBC → increase in hgb of 1 g/dL & hematocrit increase of 3%
● Length of treatment depends on the cause of anemia
○ Secondary to bleeding: continue until losses are addressed
● Corrected hgb to 12 → extend oral supplement around 3-6 months more for ferritin to improve
● IV iron - carboxymaltose - high dose iron 500 mg/ml; minimal hypersensitivity reaction
○ Give it once a week
○ Versus Iron sucrose which is given 2-3x a week