HEMATOPOIETIC FUNCTION AND DISORDERS EOSINOPHILS

• Similar in size to Neutrophils

COMPOSITION OF BLOOD AND FORMATION OF BLOOD CELLS •increase in number during _______
BLOOD
• specialized connective tissue BASOPHILS
• consists of blood cells (red blood cells, white blood cells, and platelets) •The basophils, also of similar size to neutrophils,
•suspended in plasma • are the least numerous
• 7% to 8% of total body weight. •Related to, but not identical with, the connective tissue mast cell that
• The total volume of blood in the average adult is about 5 to 6 L, contains similar granules.
•ideal vehicle for transport
LYMPHOCYTES
PLASMA • Lymphocytes are the most common agranulocytes
• carries nutrients & oxygen • defend against microorganisms through the immune response.
• transports hormones • The B lymphocytes (B cells) differentiate to form antibody-producing
• participates in electrolyte and acid–base balance plasma cells and are involved in humoral-mediated immunity.
• contribute to the osmotic regulation of body fluids • The T lymphocytes (T cells) activate other cells of the immune system
• can absorb and distribute heat that is generated in the body. (helper T cells) and are involved in cell-mediated immunity (cytotoxic T
cells).
• Natural killer (NK) cells participate in innate or natural immunity and
their function is to destroy foreign cells.

MONOCYTES
• LARGEST
• Called macrophages when they enter the tissues.
• chronic inflammation
•Immune response by activating lymphocytes and by presenting antigen to
T cells.

THROMBOCYTES
•Aka ______
• cell fragments of large megakaryocytes that are derived from the myeloid
stem cell.
•Thrombocytes have a membrane but no nucleus, cannot replicate

HEMATOPOIESIS

BLOOD CELLS
• originate in the bone marrow
• not all true cells
• Erythrocytes have no nuclei or organelles
• Platelets are just cell fragments

ERYTHROCYTES
• Most numerous of the formed elements
• average diameter of 7.8 μm
• thickness of approximately 2.5 μm.
• RBCs have a large surface area
• Can easily deform into just about any shape to move through the small BLOOD COUNT
capillaries
• Contain the oxygen-carrying protein
• For transport of oxygen

LEUKOCYTES
• 10 to 12 μm in diameter, thus much larger than RBCs.
• Constitute only 1% of the total blood volume
• responsible for the immune response
• identify and destroy cancer cells.
• participate in the inflammatory response and wound healing.
• Granulocytes/agranulocytes

NEUTROPHILS
• constitute 55% to 65% of the total white blood cells
• nuclei that are divided into three to five lobes, they are called ____
DISORDERS OF HEMOSTASIS HEMOSTASIS
Hemostasis
• Hemostasis is divided into three stages:
• 1. Vascular constriction
• 2. Formation of the platelet plug
• 3. Blood coagulation

VASCULAR CONSTRICTION

FORMATION OF PLATELET PLUG

HYPERCOAGULABILITY STATES
•Increased Platelet Function
•Increased Clotting Activity
BLOOD COAGULATION
HYPERCOAGULABILITY ASSOCIATED WITH
INCREASED PLATELET FUNCTION
•Thrombocytosis : platelet count above 1,000,000/μL.
• platelet adhesion
•formation of platelet clots
• disruption of blood flow

HYPERCOAGULABILITY ASSOCIATED WITH

INCREASED CLOTTING ACTIVITY
•Thrombus formation due to activation of the coagulation system
•Inherited : mutations in factor V gene and prothrombin gene
•Acquired: venous stasis, slow and disturbed flow

BLEEDING DISORDERS
• Platelet disorders
• Coagulation factor deficiencies

PLATELET DISORDERS
• decreased production
• increased destruction,
• impaired function of platelets
• Thrombocytopenia HEMOGLOBIN
• decrease in platelet production
• increased sequestration of platelets in the spleen
• decreased platelet survival

PLATELET DISORDERS: THROMBOCYTOPENIA DISEASE FEATURES

RED CELL DESTRUCTION

COAGULATION FACTOR DEFICIENCIES
• Metabolic activity in the cell decreases
• Enzyme activity declines
• ATP decreases
• Membrane lipids become reduced
• Cell membrane becomes more fragile
• Self-destruction

LABORATORY TESTS

ABO BLOOD GROUPS

RED BLOOD CELLS

DISORDERS OF RED BLOOD CELLS

ANEMIA
HEMOLYTIC ANEMIAS WHITE BLOOD CELLS
• RBCs shortened life span LEUKOCYTE DEVELOPMENTAL STAGES
• bone marrow usually is hyperactive, resulting in an increased number of
reticulocytes in the circulating blood.
• CM: pallor, jaundice, splenomegaly, easy fatigability, dyspnea, and other
signs and symptoms of impaired oxygen transport.

HEMOLYTIC ANEMIAS

HYPOPROLIFERATIVE ANEMIAS

AUTOIMMUNE NEUTROPENIA
• Primary: Mild to moderate infections for children.
• Self-limiting
•Treatment: use of antimicrobial agents
• Secondary immune-associated neutropenia: rheumatoid arthritis (RA)
and systemic lupus erythematosus (SLE)
MEGALOBLASTIC ANEMIA • Felty syndrome: a triad of splenomegaly, recurrent pulmonary infections,
and neutropenia.

THE THALASSEMIAS

INFECTION-RELATED NEUTROPENIA
• viral, bacterial, and parasitic, may cause neutropenia
•the most common : viral
• decreased neutrophil production
•loss of neutrophils by toxins
• problems resulting in neutrophil sequestration in the spleen.

DRUG-RELATED NEUTROPENIA
• antipsychotic drug : clozapine, have been shown to cause accelerated
apoptosis of neutrophils — agranulocytosis
• Other drugs, such as the β-lactam antibiotics (e.g., cephalosporins)
• anticonvulsant drugs (e.g., carbamazepine) may inhibit the
colony-forming units of granulocytes
• reversible on discontinuation of the drug.
CARDIOVASCULAR FUNCTION HEART SOUNDS

IMPORTANT PRINCIPLES
BLOOD PRESSURE (BP)
BP = CO x TPR
= (HR x SV) X TPR
*Cardiac output: volume of blood being pumped by the heart per minute
*Stroke volume: volume of blood pumped with each heart beat (N:
55-100mL)
At rest: 5L/min
Max CO (Non-Athlete): 20L/min
Max CO (Athlete): 30L/min

Pulse Pressure
PP = SBP - DBP

Mean Arterial Pressure

MAP = SBP + (2 x DBP)
3
Normal: > 60 mmHg
AUSCULTATORY AREAS

Pulmonary and Systemic Circulations

DISORDERS OF THE CIRCULATORY SYSTEM

HYPERTENSIVE VASCULAR DISEASE

Primary or Essential
- No identifiable cause
- Seen in 90-95% of cases
Key points
- Genetic factors
CAPILLARIES: Largest total cross-sectional area; has endothelial cells
- Insufficient renal sodium excretion
only; slowest blood flow velocity;
- Vasoconstrictive influences
VEINS: a.k.a. Capacitance Vessels—MORE DISTENSIBLE; 64% of blood
- Environmental factors (stress, obesity, smoking, physical
found here, with one-way valves
inactivity, heavy salt consumption)
Secondary
THE HEART
- Renal, endocrine, neurologic causes
Located between the lungs
Its tip (i.e., apex) pointing downward, forward, and to the left.
ATHEROSCLEROSIS
Positioned obliquely--the right side of the heart is almost anterior
Diagnostic lesion: Atheroma/atheromatous plaque
Point of maximum impulse (PMI): __________

THE HEART
Pericardium
Myocardium
Endocardium
Fibrous skeleton
Interatrial & Interventricular septa
Atrium
Ventricle
Pericardial cavity
Myocardium Venous Thrombosis
Endocardium Virchow’s Triad: (risk factors)
Fibrous skeleton Stasis of blood
Interatrial & Interventricular septa Hypercoagulability
Atrium Vessel wall injury
Ventricle
*note: inflammation if a sign and not a risk factor

ANEURYSM AND DISSECTION

ANEURYSM: Localized, abnormal dilatation of the blood vessel or the
heart
DISSECTION: Blood tunnels in between layers of the wall; most common ● Can cause pressure and/or volume overload on upstream
cause: intimal tear chambers → CHF

CAUSES: MNEMONIC FOR MURMURS (TIMING)

Advanced age SYSTOLIC MURMURS:
Smoking - STENOSIS OF SL VALVES
Trauma - REGURGITATION OF AV VALVES
Vasculitis DIASTOLIC MURMURS:
Congenital defects (aneurysms) - REGURGITATION OF SL VALVES
- STENOSIS OF AV VALVES
CLINICAL MANIFESTATIONS
● General (for aneurysms and dissections) RHEUMATIC FEVER
● PRESENCE OF A MASS AND MASS EFFECT - Acute, immunologically mediated, classically occurring a few
- Palpable, pulsating abdominal mass (abdominal aneurysm) weeks after an episode of Group A Streptococcal pharyngitis or
- Specific clinical manifestations depend on the site of aneurysm pyoderma
and structures compressed - Antibodies and CD4+ T-cells directed against Streptococcal M
● EROSION OF BONE proteins also recognize cardiac self-antigens “molecular
- Secondary to contact with aneurysm; presents as excruciating mimicry”
pain - Sequelae: Rheumatic heart disease
● RUPTURE
- Presents as hemorrhage and cardiovascular collapse RHEUMATIC HEART DISEASE
- Most commonly involved valve: Mitral > Aortic > Tricuspid >
HEART FAILURE Pulmonic
- Inability of the heart to pump blood at a rate sufficient to meet - Cardinal changes: Leaflet thickening, commissural fusion and
the metabolic demands of the tissues, or can do so only at an shortening, and thickening and fusion of the tendinous cords
elevated filling pressure. - In ARF, the characteristic manifestation of carditis is Mitral
regurgitation (MR). In RHD, the characteristic finding is Mitral
Left-sided HF stenosis (MS).
Etiology: Ischemic heart disease, Hypertension, Aortic and mitral valvular - In the exam, pay close attention to the timing of the murmur if
diseases it’s systolic (MR) or diastolic (MS).
Left ventricle is usually HYPERTROPHIED AND DILATED
Lungs: Pulmonary congestion and edema INFECTIVE ENDOCARDITIS (IE)
- Microbial infection of heart valves and mural endocardium
Right-sided HF - Common in IV drug users who are previously healthy (S.aureus)
Etiology: Most common cause is Left sided heart failure
Pulmonary disease (cor pulmonale) PERICARDIAL EFFUSIONS
Hypertrophy and dilation of right chambers - Normal pericardial cavity: 50 mL serous fluid
- In Pericardial Effusion: Accumulation of serous fluid, blood, or
pus
ISCHEMIC HEART DISEASE (IHD) - Acute: symptomatic even at low-volume accumulations (no time
● Resulting from myocardial ischemia (imbalance between to adjust)
myocardial supply and demand) - Chronic: asymptomatic even at large-volume accumulations
● Most common cause: atherosclerosis of epicardial coronary (pericardium dilates)
arteries (coronary artery disease) - Radiographically: water-bottle appearance
Syndromes:
Angina pectoris (literally “chest pain”) Pericarditis
Myocardial infarction (MI) - Inflammation of the Pericardium
Acute: most common: exudative/purulent (infection)
ANGINA PECTORIS Chronic: FIBROSIS
- STABLE ANGINA or Typical (most common form) : Occurs due *note: Pain is abrupt, sharp, radiates to the neck, back, and abdomen;
to exertion (demand problem); RELIEVED BY REST typically worse with deep breathing, coughing, swallowing, positional
changes
UNSTABLE ANGINA (NSTE-ACS*/NSTEMI)
- Prolonged, severe; may happen even at rest
- Usually caused by plaque disruption and superimposed
thrombosis, and/or vasospasm (supply problem)
*ACS: ACUTE CORONARY SYNDROME

MYOCARDIAL INFARCTION (STEMI)

- Death of cardiac muscle due to prolonged ischemia
- Earliest detectable feature of myocyte necrosis: membrane
disruption → myocardial proteins in blood
- INCREASED CARDIAC BIOMARKERS (TROPONINS)

VALVULAR HEART DISEASE

Stenosis and insufficiency
● Stenosis: incomplete opening → impedes forward flow
● Insufficiency (regurgitation): incomplete closing → permits
reverse flow
RESPIRATORY FUNCTION AND DISEASES
FUNCTIONAL ANATOMY OF THE RESPIRATORY SYSTEM
RESPIRATORY SYSTEM
• UPPER AIRWAYS: Nose, Sinuses, Larynx
• LOWER AIRWAYS: Trachea, Airways, Alveol
NOSE FUNCTIONS: Warms, humidifies, & filters air, smell, defense
NOTE:
“The nostrils cause conditioning of air during inspiration (unlike breathing
through the mouth) – it will warm the air (cold air can damage respiratory
lining), humidify the air (dry air can damage the respiratory lining, the
water vapor can act as lubricant) via the capillaries of the nose, filter the
air (preventing large particles from obstructing/damaging the respiratory
lining), and is involve in the special sense of smell (which also has an
impact in terms of taste)
SINUSES
• Frontal sinuses, Maxillary sinus, Sphenoid sinus, Ethmoid sinus
• FUNCTIONS: Lighten the skull & offer resonance to voice
LARYNX
• Vocal Cords: Protects the airway form choking, Produces sounds used
for speech
• Epiglottis, Arytenoids: Covers vocal cords during swallowing
• 24TH WEEK AOG: Start of Surfactant production
• 35TH WEEK AOG: Maturation of Surfactant
• NEONATAL RESPIRATORY DISTRESS SYNDROME (RDS): Deficiency
in surfactant
• STEROIDS, SURFACTANT: Treatment for newborn RDS
DEAD SPACE
• ANATOMIC DEAD SPACE: Air from the Nose to Terminal Bronchioles
(conducting zone) that does NOT undergo gas exchange (Normal Value:
150 mL)
• ALVEOLAR DEAD SPACE: Air in the respiratory unit of the lung
(respiratory zone) that does NOT undergo gas exchange due to V/Q
mismatch (Normal Value: 0 mL)
• PHYSIOLOGIC DEAD SPACE: Anatomic + Alveolar Dead Space.
Normally EQUAL to Anatomic Dead Space Value
NOTE: “When you see the term “dead space” in physio, it means an
area with no gas exchange. Normal Anatomic dead space is 150mL –
physiologically, there is no gas exchange from the nose to the trachea
to the terminal bronchioles. Normal Alveolar Dead Space meanwhile is
0mL – physiologically, all alveoli should be capable of gas exchange,
therefore alveolar dead space should ideally be zero. Physiologic dead
space is just the sum of anatomic dead space and alveolar dead space.”
• RESPIRATORY UNIT OF THE LUNG: Respiratory bronchiole, alveolar
ducts, alveolar sacs

TRACHEA
• In the trachea, C-shaped cartilages are found anteriorly LUNG VOLUMES AND CAPACITIES
• Right bronchi is wider, shorter and more vertical (hence it is more prone NOTE: “These are the only 3 areas in the respiratory system capable of gas
to aspiration of material) exchange. Be careful with terminal bronchiole vs. respiratory bronchiole –
respiratory bronchiole is the first part of the respiratory unit of the lung
• Trachea → Main Stem Bronchi → Lobar Bronchi → Segmental Bronchi capable of gas exchange. Not terminal bronchiole.”
→→→ Terminal bronchioles → Respiratory bronchiole → Alveoli
COMMON COLD
BRONCHIOLE • Most common causative agent: Rhinoviruses
• Respiratory Bronchiole is capable of Gas Exchange • Others: Parainfluenza viruses, Respiratory syncytial virus RSV,
• (+) presence of Respiratory Epithelium Coronaviruses
• GOBLET CELLS: Produces Mucus; Hyperplasia, Hypertrophy seen in • Most commonly affected are SCHOOL CHILDREN
chronic smokers • Most common source of spread: FINGERS (poor hand hygiene)
• CLARA CELLS (CLUB CELLS): Metabolize air-borne toxins • Most common portals of entry: Nasal mucosa, Conjunctiva
• DUST CELLS (ALVEOLAR MACROPHAGES): Blood element that • Highly contagious on the first 3 days after onset of symptoms
removes particles trapped in the alveoli • Incubation Period: 5 days
• Self-limiting: 5-6 days
LUNGS • Complication: Acute Otitis Media (40-75% of cases in children)
• Weighs 1kg • Antibiotics are ineffective in common cold
• 60% lung tissue
• 40% blood
• RIGHT LUNG RHINOSINUSITIS
• 3 Lobes (Upper, Middle, Lower) • Inflammation of nasal passages and paranasal sinuses
• Oblique Fissure, Horizontal Fissure • Mucosal swelling from either allergic rhinitis/acute upper respiratory
• LEFT LUNG tract infection causing obstruction to the ostia that impairs mucociliary
• 2 Lobes (Upper, Lower) clearance mechanism—no drainage system
• Oblique Fissure • (+) facial pain/tenderness
• PLEURAL FLUID • Resolves 5-7 days without treatment NLE-relevant fact: “Handwashing is
• Found in potential space between the two pleura the single, most effective method to prevent the spread of communicable
• Keeps the 2 pleura together (allows them to slide) diseases.”

ALVEOLI INFLUENZA
• TYPE I PNEUMOCYTE • Rapid onset of profound malaise
• 96-98% of surface area • Complication: Viral pneumonia > Hypoxemia > Survivor with diffused
• thin, flat, does NOT secrete surfactant pulmonary fibrosis or Death
• For Gas Exchange • Spread via inhalation of droplet nuclei
• TYPE II PNEUMOCYTE
• 2-4% of surface area COMMUNITY-ACQUIRED PNEUMONIA
• Small, cuboidal, found at corners of alveoli • Most common causative agent: Streptococcus pneumoniae
• For Surfactant production • 2 types:
• Decreases surface tension (preventing alveolar collapse) • Bacterial: Neutrophilic infiltrates; intraalveolar inflammation
• Viral: Mononuclear infiltrates (lymphocytes, macrophages); interstitial
KEY POINTS: LUNG SURFACTANT inflammation
• LUNG SURFACTANT: Helps prevent alveolar collapse; Decreased in the
lungs of chronic smokers
Pulmonary Tuberculosis
• *insert book NTP 2020*
• Caused by Mycobacterium tuberculosis infection
• Droplet nuclei—aerosolized by coughing, sneezing, speaking
• Caseation necrosis & cavitation (Typical TB lesion)
• Clinical manifestation: Fever, chills, cough for more than 2 weeks, night
sweats, hemoptysis
• Bacteriologically confirmed: Smear/culture/Xpert MTB/RIF (+)
• Clinically diagnosed: AFB (-) but radiologic evidence is consistent with
PTB
Acute Respiratory Distress Syndrome
• Failure in gas exchange due to either heart/lung failure or both
• *not a specific disease—occurs due to numbers of conditions that impair
ventilation
• Mismatching of ventilation-perfusion: occurs when areas of lung are
ventilated but not perfused/perfused but not ventilated
• Ventilation (V): movement of air in and out of airways (aka Breathing)
• Perfusion (Q): exchange of O2 or CO2

Pulmonary Tuberculosis
• Mantoux test – PPD
• >/= 5 : positive for HIV patients
• >/=10 : positive for healthy individuals
• *treatment*

Pleural Effusion
• (Normal) Pleural fluid: 15 mL – serous, acellular, clear fluid
• PE: excess fluid in pleural cavity
• Congestive heart failure: increased capillary hydrostatic pressure
• Pneumonia: Increased capillary permeability
• Nephrotic syndrome: decreased capillary oncotic pressure

Pneumothorax
• Presence of air in the pleural caivity
• Assocated in Emphysema, asthma, PTB (airspaces may rupture)

OBSTRUCTIVE VS. RESTRICTIVE PULMONARY DISEASE

Bronchial Asthma
• *GINA guidelines*
• Chronic change: Airway remodeling
• X-ray: Hyperaerated lungs (due to air trapping)
• Strongest risk factor: Genetic predisposition—development of
IgEmediated response to common allergens
• Environmental triggers: Tobacco smoke/pollution, dust mites, GERD,
AURI, exercise
• Exaggerated hyperresponsiveness to a variety of stimuli
• Clinical manifestations: Wheezing, breathlessness, chest tightness, cough
worse at night and early in the morning
• Reversible clinical manifestations, (compared to COPD that is
IRREVERSIBLE)
• Use of Inhaled corticosteroids: risk for oral candidiasis/oral thrush;
encourage proper oral hygiene after use of ICS

Emphysema
• Increased (Antero-posterior) AP chest diameter “Barrel chest”
• Patho: Airway destruction and loss of elastic recoil (air trapping)
• Morphology: Large alveoli
• Types:
• Panacinar – a1 antitrypsin protein deficiency
• Centriacinar – Cigarette smoking

Chronic bronchitis
• Increased secretions
• Chronic productive cough
• Patho: Airway inflammation “-itis”
• Chronic inflammation + mucus gland hypertrophy leads to fibrosis