SCOFYL - First Semester

-SOMITES 2020

HISTOLOGY
Bacteria was transmitted through air droplets (air-borne)
Alveolar macrophage try to contain the bacteria (via macrophage system of the innate immunity)
Mycobacterium tuberculosis inhibit phagolysosome formation (phagolysosome - fusion of the lysosome within the
phagocyte, the macrophage)
Lymphocytes are activated: recruit more lymphocytes and activate macrophages = epithelioid histiocytes--hallmark of
granuloma (lymphocytes - function: activate and help the macrophage)
Mycobacteria - difficult to eliminate, refuse ingestion and digestion
Epithelioid histiocytes conglomerate to form a granuloma
GRANULOMA: aggregation of epithelioid histiocytes that are rimmed by lymphocytes and plasma cells
Casseous necrosis: type of tissue destruction specific for TB; Chronic caseating granulomatous inflammation
White nodules or patches found usually in apices of the lung = Ghon focus or complex: signifies lymphatic involvement
Ghon focus + affected lymph nodes = Ghon complex
Granuloma formation causes destruction of the alveoli which affects the respiration of the patient causing the signs and
symptoms
Ranke: calcification of caseous lesion
Granuloma can errode blood-air barrier, system of tubes, and site for gaseous exchange
Inflammation of blood vessels: blood seeps to the respiratory channels = blood streaked sputum (hemoptysis)
Type IV - cell mediated hypersensitivity
Pleural effusion: dullness on percussion, dyspnea
Effect of chronic inflammation
Blockage of lymphatic system which should have absorbed the excess fluid
BIOCHEM
1.Discuss the chemistry of respiration
Oxygen Transport
In the lungs, oxygen diffuses from alveolar air into the blood because the venous blood has a lower partial pressure. The
oxygen dissolves in the blood. Only a small amount is carried as a physical solution (0.31 ml per 100 ml). The remainder of the
oxygen is carried in chemical combination with the hemoglobin in red blood cells.
Carbon Dioxide Transport
More soluble in blood than is oxygen
About 5 to 7 percent of all carbon dioxide is dissolved in the plasma
Can bind to plasma proteins or can enter red blood cells and bind to hemoglobin (10%)
Carbaminohemoglobin - carbon dioxide bound to hemoglobin i
Reversible
Majority (85 percent) are carried as part of the bicarbonate buffer system
Bicarbonate Buffer System:
Carbon dioxide diffuses into the red blood cells
Carbonic anhydrase within the red blood cells converts the carbon dioxide into carbonic acid
Carbonic acid is an unstable, immediately dissociates into bicarbonate ions and hydrogen ions
Reaction allows for the continued uptake of carbon dioxide into the blood, down its concentration gradient
Results in the production of H+ ions (H+ can alter blood pH in excess)
Hemoglobin binds to the free H+ ions, limiting shifts in pH
Newly-synthesized bicarbonate ion is transported out of the red blood cell into the liquid component of the blood in
exchange for a chloride ion; this is called the chloride shift
Bicarbonate ion is transported back into the red blood cell in exchange for the chloride ion
H+ ion dissociates from the hemoglobin and binds to the bicarbonate ion producing carbonic acid that is converted
back into carbon dioxide through the enzymatic action of CA
Carbon dioxide produced is expelled through the lungs during exhalation.
Chloride Shift
aka the Hamburger shift or Hamburger phenomenon,
named after Hartog Jakob Hamburger
occurs in a cardiovascular system
refers to the exchange of bicarbonate (HCO3) and chloride (Cl) across the membrane of red blood cells (RBCs)
use the anion exchanger protein Band 3

results from the rise in intracellular bicarbonate

SCOFYL - First Semester

-SOMITES 2020

Bohr Effect
Discoverer: Christian Bohr
Effect of CO2 and pH
Oxygen-carrying capacity of blood hemoglobin varies with pH
At high pH values, hgb has a high affinity for oxygen, but more acid conditions cause hemoglobin to release its oxygen, as
in tissues with a high concentration of dissolved carbon dioxide
Haldane effect
Binding of oxygen to hemoglobin promotes the release of carbon dioxide. In many ways, the Haldane Effect is the mirror
image of the Bohr Effect, making clear that oxygen and carbon dioxide compete for hemoglobin occupancy. This
competition is a helpful biochemical feature which facilitates exchange of carbon dioxide for oxygen in the pulmonary and
peripheral circulations.
2. Discuss the oxygen dissociation curve and the effect of the following factors as presented in the case.
Hemoglobin versus Myoglobin
Hemoglobin
tetramer (2 alpha, 2 beta subunits , each surrounding heme that contains iron and bind O2 thus Hgb can bind 4
O atoms)
better at transport because it exhibits cooperativity (binding of one molecule facilitate faster binding of another
due to change in shape)
T state of Hemoglobin: more salt bridges and more covalent bonds
R state: breaks bonds = oxygenated
O2 dissociation curve: sigmoidal (Increased PO2 will increase O2 saturation exhibiting cooperativity)
P50 Hemoglobin (26 mmgHg)

Myoglobin
Monomer
O2 dissociation curve: hyperbolic = high affinity at low concentration
P50 of myoglobin (1 mmHg)

Oxygen saturation curve

X-axis: PO2 in mmHg
Y-axis: O2 saturation
Allosteric factors:
1. Temperature
2. Hydrogen ion
3. Carbon dioxide
4. Exercise
5. Altitude
6. 2,3 BPG
Left shift = increased affinity (less P50)
Right shift = decreased affinity (higher P50)
Patient: shift to the right because
1. Febrile - high temp
2. Dyspnea which is like in exercise
3. High carbon dioxide = carbonic acid production = increased hydrogen ion
3. Discuss the role of isoniazid and Vitamin B6 in TB treatment
Mycobacterium tuberculosis = Mycolic acid (waxy substance)
Acid fast = withstand decolorization; appear as reddish pink

Isoniazid and Vitamin B6

INH: cause polyneuropathy body becomes deficient of Vit B6
INH MOA: inhibits mycolic acid synthesis (Mycolic acid - essential part of mycobacterial cell wall;
result to cell death)
aka isonicotinylhydrazide (INH)
first-line agent for the prevention and treatment of both latent and active tuberculosis
effective against mycobacteria, specifically mycobacterium tuberculosis
Metabolism: acetylation, formation of acetlyhydrazone
INH and Vit B6 are structural analogs

SCOFYL
- First Semester

-SOMITES 2020

Isoniazid interferes competitively with pyridoxine metabolism by inhibiting the formation of the active
form of the vitamin, Pyridoxal-5-Phosphate (coenzyme for amino acid synthesis)
INH + Pyridoxal Pyridoxal hydrazone
Enzyme involved: Pyridoxine phosphokinase
To reverse competition: give more substrate

Pulse oximetry
Measures oxygen saturation
Red light: 600-750 nm
Infrared light: 850-1000 nm
Oxygenated hemoglobin absorbs more infrared light and allows more red light to pass through
Deoxygenated hemoglobin absorbs more red light and allows more infrared light to pass through
Regular healthy person: normal SpO2 = 94-99%
Patients with mild respiratory diseases: SpO2 = 90% and above

ANATOMY
How TB got into the lungs
Transmitted through droplets
Enters through the tracheobronchial tree first
Right lung: shorter, wider and more angulated = preferred
Upper lobe: more ventilated = TB loves air
Effusion @ the recess: Costodiaphragmatic and Costomediastinal
Possible spaces
Patient: T7 below = effusion covers entire lower lobe, found at the right costodiaphragmatic recess
Lower lobe
From 5th to 6th rib, T8 to T10
Oblique fissure
Dullness in percussion
Air is hyperresonant
Decreased breath sounds
If something is found between the pleural space, there is decreased breath sounds
Decreased tactile fremitus
Chest pain
Parietal layer is innervated by the phrenic and intercostal nerves which can detect pain
Visceral layer: autonomics only and no somatic
Compression causes the pain which is aggravated by respiration
Pain is transmitted epigastric (?)
Thoracentesis
Aspiration of fluid @ T7 below
Insert needle 1-2 cm below the level of T8 or T9
Beyond T9 is not preferred = may hit the diaphragm
Preferred site is below the tip of the scapula @ T7 midscapular
Structures that can be hit
Skin
Subcutaneous tissue
Latissimus dorsi
Serratus posterior
Intercostal muscles (internal and external)
Parietal pleura
PHYSIOLOGY
Pathophysio of Signs and Symptoms
Tachypnea: due to increased work of breathing and infection
Fever: infection, inflammation response
Non-productive cough: secondary to possible respiratory infection; irritative effect of pleural disease
Hemoptysis: cavitary lesions, not specific for TB
Chest pain exacerbated by inspiration: detected by intercostal nerves of parietal pleura
Dyspnea: increased work of breathing = increased compliance
Weight loss: non-specific; due to chronic infection = think other causes like cancer
Night sweats: presence of systemic infection

SCOFYL - First Semester

-SOMITES 2020

TB infection of younger brother: exposure

Smoking history: cause of coughing = COPD or lung cancer
Anemia with leukocytosis in CBC: infection
(+) AFB smear: PTB infection
Work of breathing graph [ insert figure 21-7 ]
Restrictive = decreased chest wall compliance
Compliance curve is shifted to the RIGHT = decreased compliance due to pleural disease
If COPD = increased compliance
Algorithm
Restrictive
FEV1/FVC is normal
FVC is low = only suggestive
Confirm by measuring total lung capacity (not done by spirometry)
FEV is low
VQ relationship
Low VQ
Compensation: other respiratory units will increase ventilation
Dont decrease perfusion!!
Increase ventilation through bronchodilators (in general) or increasing compliance remove fluid
and/or give oxygen
Arterial Blood Gas
Decreased PCO2 stimulate CPG receptors to increase ventilation (????)
Increased pH
PO2 of 90%
UNCOMPENSATED RESPIRATORY ALKALOSIS