Physiology Clinical Notes

Normal Ranges

According to The Core of Medical Physiology, 4th edition.

PCV (Packed Cell Volume):

 RBCs make up about 90% of PCV.

- Male = 40 – 50%
- Female = 37 – 47%

Red Bone Marrow Contents:

 Mature RBC count is 500 times more than that of WBCs, indicating longer life
span of RBCs.
- WBC Precursors = 75%
- RBC Precursors = 25%
Red Blood Cells:

RBC Count:

 A million can be represented as: 1 x 106

- Males = 4.8 – 5.8 million / mm3
- Females = 4.2 – 5.2 million / mm3 (differs in pregnant women)

RBC Life Span = 120 Days

RBC Characteristics:
- Diameter = 7.5 microns
- Thickness = 1 – 2 microns

Reticulocyte Percentage = about 1% of total RBCs

Erythropoietin: not mentioned, but there’s excess and deficiency.

Iron Metabolism
Iron Quantity in Body = 4 grams, divided into:

- Hemoglobin = 65%
- Myoglobin = 4%
- Cellular Enzymes = 1%
- Transferrin = 0.1%
- Ferritin (soluble) & hemosiderin (insoluble) = 25 – 30% stored in
reticuloendothelium

By Mohammed Eljack
Daily Iron Requirement:
- Adult Male = 1 mg/day
- Adult Female = 2 mg/day

Normal Iron Absorbed = 10 – 15% (didn’t mention what this percentage is of)

Plasma Iron Concentration = 100 – 130 microgram/dL

Total Daily Iron Loss:

 Remember that daily intake = daily loss

- Adult Male = 1 mg/day
- Adult Female = 2 mg/day

Vitamin B12 Metabolism

Daily Vitamin B12 Requirement = 1 – 2 microgram/day (very low!)

 Daily intake = daily loss

Vitamin B12 Storage Duration:

- Stored in liver for 3 years without more intake.

Folic Acid Metabolism

Daily Folic Acid Requirement = 100 microgram/day

Haemoglobin
Haemoglobin Concentration:

- Adult Male = 14 – 16 g/dL

- Adult Female = 13 – 15 g/dL
- Neonate = 18 – 20 g/dL

Haemoglobin Normal Types:

1. Hb A ( α2 β 2 ) (alpha 2 beta 2 chains)
- Adult Hb, constitutes about 98%
2. Hb A2 ( α2 δ2 ) (alpha 2 delta 2 chains)
- Adult Hb, constitutes about 2.5%
3. Hb A1c (Glycated Hb)
- Hb A subtype, constitutes about 5%
4. Hb F ( α2 γ2 ) (alpha 2 gamma 2 chains)
- Fetal Hb
- At birth = about 70%
- At age 6 months = <2%
By Mohammed Eljack
Haemoglobin S (Sickle Cell Disease / Trait):
- Heterozygote Patients = 50% of their Hb is Hb S
- Homozygote Patients = most of their Hb is Hb S

Normal Bilirubin Level = about 1 mg/dL

RBC Indices
MCV (Mean Cell Volume) = 80 – 95 femto Liter (fL)

MCH (Mean Cell Haemoglobin) = 25 – 32 pg

MCHC (Mean Cell Haemoglobin Concentration):

- Normal = 34% (34 g/dL)
- Range = 32 – 36 g/dL

White Blood Cells

Leukocyte Count = 4000 – 11000 / mm3

Granulocytes (Percentage of total WBCs):

 Neutrophils = 50 – 70%
 Eosinophils (Acidophils) = 1 – 4%
 Basophils = 0 – 0.4%

Agranulocytes:

 Monocytes = 2 – 8%
 Lymphocytes = 20 – 40%
- T – Lymphocytes = 80% of lymphocytes
- B – Lymphocytes = 20% of lymphocytes

Antibodies (Immuno-globulins)
IgG = >75% of total immunoglobulins in plasma
IgM, A, E, D = not mentioned

By Mohammed Eljack
 Blood Groups
Blood Group A = about 42% of population

Blood Group B = about 8% of population

Blood Group AB = about 3% of population

Blood Group O = about 47% of population

Rh +ve subjects = 85% of subjects

Rh –ve subjects = 15% of subjects

Platelet Count = 200,000 – 400,000 / mm3

Platelet Life Span = about 5 days (up to 10 days)

Warfarin Effects = start to appear 3 days after initiating therapy

Bleeding Time (BT) = normally 1 – 7 minutes

Clotting Time = normally <10 minutes

Prothrombin Time (PT) = normally 12 – 15 seconds

Activated partial thromboplastin time (aPTT) = normally 25 – 39 seconds

Plasma Volume = about 5% of total body weight in a 70 kg adult male ( = 3.5L)

 90% of plasma is water.

Plasma Proteins:
- Albumin = 3.5 – 5 g/dL
- Globulins = 2.3 g/dL
- Fibrinogen = 0.3 g/dL

 Total = 6 – 8 g/dL

By Mohammed Eljack
 Abnormalities and Conditions
Anemia:

 Types:
- Hemolytic Anemia
Caused by:
1. Vitamin E Deficiency
Indicators:
1. Jaundice
2. Reticulocytosis
- Hemorrhagic Anemia
Caused by:
1. Blood Loss
2. Acute Blood Loss (following trauma)
3. Chronic Blood Loss (GIT bleeding)
- Nutritional Anemia:
o Microcytic Hypochromic Anemia
Possible Causes:
1. Iron Deficiency
2. Thalassemia
Indicators:
1. Iron absorbed rate highly increases.
2. Low Hb
3. Low Ferritin
4. Low Iron Concentration
5. High Total Iron Binding Capacity (TIBC)
6. Small, pale RBCs (microcytic hypochromic)
o Macrocytic Normochromic Anemia (Megaloblastic Anemia)
Possible Causes:
1. Vitamin B12 Deficiency (associated with pernicious anemia)
2. Folic Acid Deficiency
- Normocytic Normochromic Anemia
Caused by:
1. Anemia of Chronic Illness
2. Chronic Renal Failure
 Indicators:
- Low PCV
- Low Hb Concentration
- Low RBC Count
- Erythropoietin Deficiency
 Signs & Symptoms:
- Weakness
- Fatigue

By Mohammed Eljack
 - Palpitation
- Pallor in skin & mucus membrane
- Neuromuscular Symptoms:
1. Headache
2. Dizziness
3. Drowsiness
Polycythemia:

 Indicators:
- High PCV
- Erythropoietin Excess

Extramedullary Hematopoiesis: condition after birth, a child suffering from chronic

anemia doesn’t resume hematopoietic activity in the bone marrow, but instead in
the liver and spleen.

 Normal Sites of Hematopoiesis:

1. Flat Bones: skull, sternum, ribs, scapula, vertebrae, iliac bone.
2. Epiphyses
3. Small Bones (hand and feet)
 Complementary Sites of Hematopoiesis:
1. Liver
2. Spleen

Reticulocytosis:

 Indicators: reticulocytes > 2% of total RBCs.

 Indicates: hyperactivity of bone marrow (rapid synthesis of RBCs to replace
lost ones)
 Occurs in:
- Hemolytic Anemia
- Recent treatment of anemia (following Vit B12 injection)

Normal erythropoiesis requires:

1. Normal Bone Marrow
2. Cytokines and Colony Stimulating Factors
3. Hormones:
- Erythropoietin
- Androgens (eg. Testosterone)
Q. How do androgens normalize erythropoiesis?

By Mohammed Eljack
 A. Androgens, like testosterone increase bulk of muscle in males, and
muscles need oxygen unlike fat which is present in females more than
males, so the body needs to produce more erythropoietin in males,
meaning RBC count is higher in males.
- Growth Hormones
- Cortisol
- Thyroid Hormones
4. Certain Nutrients:
Nutrient Function
Amino Acid Forms globin
Iron Forms heme
Vitamin B12 & DNA Synthesis (Cell Division)
Folic Acid
Vitamin C Iron absorption (keeps iron in ferrous state)
Other B Co-factors in metabolic reactions
Vitamins
Copper Iron absorption
Cobalt 1. Vit B12 Synthesis
2. May stimulate Erythropoietin

Q. Why do we need to know these factors?

A. If a patient shows up with deficiency or decrease in RBC production, these
factors could be one of the causes, so we can mend the deficiency by
replacing/treating the deficient factor.
Erythropoietin:

 I need to know, what is the level of erythropoietin in blood?

 Production:
- Adults (90% Kidney, 10% Liver)
- Fetus (Mostly in Liver)
 Stimulus: Hypoxia (Low Oxygen)
 Abnormalities:
- Erythropoietin Excess results in Polycythemia, caused by:
1. High Altitudes
* Considered physiological.
2. Renal Problems (renal tumors, polycystic kidney disease)
* Considered pathological
Q. Since this affects the renal system, why is it not deficiency
instead of excess?
A.
3. Chronic Respiratory Problems (lung fibrosis)
Q. Is this physiological or pathological?

By Mohammed Eljack
 - Erythropoietin Deficiency results in Anemia, caused by:
1. Chronic Renal Failure (normocytic normochromic anemia)
Note: erythropoietin is produced in the kidney and liver, so any problem affecting
them may cause deficiency, that’s why the main cause is Chronic Renal Failure.

Iron Metabolism:

 Normal Site of Absorption: duodenum (the closest part to the stomach)

 ↑ Metabolism Increasing Factors:
1. Pregnancy
2. Lactation
3. Infancy (1st year of life)
 ↑ Absorption Increasing Factors:
1. Iron in heme
- Must be in Ferrous State (Fe2+) by:
1. HCl
2. Vitamin C
3. Copper?
 ↓ Absorption Decreasing Factors:
1. Presence of … in diet:
1. Phosphates
2. Oxalates
3. Phylates
2. Achlorohydria (a: lack of, chlorohydr-: HCl, ia: condition)
3. Diarrhea
4. Clay (Paica?)
5. Tetracycline
 Iron Overload:
1. Hemochromatosis: hereditary condition characterized by excessive iron
absorption, resulting in accumulation of iron in many organs causing
damage.
Can Cause:
1. Liver Cirrhosis
2. Gonadal Atrophy
3. Cardiomyopathy
4. Skin Pigmentation
5. Diabetes Mellitus
2. Hemosiderosis: describes iron overload secondary to certain causes.
Caused by:

By Mohammed Eljack
 1. Repeated blood transfusion
2. Excessive iron therapy
Note: Iron Overload is the opposite of Iron Deficiency.

Vitamin B12 Metabolism:

 Site of Absorption: Terminal ileum

Note: absorption is assisted by the intrinsic factor which is produced by parietal cells
in the stomach.

Note: it’s found in food of animal origin, so vegetarians will have trouble with this.

 Function:
1. DNA Synthesis (RBC Replication by Cell Divison)
2. Nerve Myelination
 Abnormalities:
- Deficiency Causes:
1. Megaloblastic Anemia
2. Sub-acute combined degeneration of the cord (demyelination)
- Causes of Deficiency:
1. Low Intake (rare, except in strict vegetarians)
2. Resection of Terminal Ileum (decreases absorption)
3. Gastrectomy (removal of the stomach -> no intrinsic factor ->
decreases absorption)
4. Gastric Atrophy (caused by auto antibodies that attack the parietal
cells or intrinsic factor) known as pernicious anemia.

Folic Acid Metabolism:

 Site of Absorption: jejunum

 ↑ Metabolism Increasing Factors (daily requirement is increased):
1. Pregnancy
2. Lactation
3. Infancy
 Abnormalities:
- Deficiency Causes:
1. Megaloblastic Anemia
- Causes of Deficiency:
1. Decreased intake (malnutrition)
2. Decreased absorption (villous atrophy)
3. Increased requirements (pregnancy, drugs like methotrexate)

By Mohammed Eljack
By Mohammed Eljack