Anatomy Function Block III

Calcium Homeostasis

Essential for ▪︎ Bones and teeth ▪︎ all cells ▪︎ nerve and muscle function ▪︎ blood clotting

Effects on insulin on protein metabolism

Overall: ↓ blood amino acids and ↑ protein synthesis ▪︎ ↑ transport of blood aminoacids into muscle and other cells. ▪︎ ↑ Protein synthesis ▪︎ Inhibits protein degradation

If a patient is given 30% of O2. What will be PAO2?

PAO2 = (760-47)0.31 - 40/0.8

V/Q ratio = 0.8

PaO2= 100 PCO2= 40. PaO2↓ PCO2↑ than normal

In upper zone, what will be PO2 and PCO2

PaO2↑ PCO2↓ ■ Because of more ventilation, PO2 in alveoli is increased and thus PaO2 also increased to equilibrium. Because Ventilation is more, CO2 moves into alveoli, and arterial PCO2 decreases. ■ V↑ Q↓

V/Q ratio=0.5 (Lower zone)

PaO2↓ PCO2↑ than normal

Ans: PO2= 98 Hb% = 70

Patient admitted to Hospital with CN- poisoning. His Blood result in the picture. What is PO2 and Hb% in venous end *IF NOT MENTIONED, ITS ALWAYS VENOUS BLOOD IN QUESTIONS

Determination of Anatomical DSV ( Fowler's method -single breathe pure O2- Nitrogen measurement)

Patient breath in pure O2 and get mixed with alveolar gas. Alveolar have mostly N2. When Patient breaths out, initial air wont have any N2 and only O2 comes our. later N2 comes out.

Normal hematocrit: 38-50% ▪︎ Ans: PO2 = 38, Hb = 60% Patient is suffering from anemia. RBC is low in anemic hypoxia.

Patient was admitted to Hospital lethargic, breathlessness. His hematocrit= 35%. What is PO2 and Hb saturation in this patient?

Regulation of aldosterone secretion

Renin is secreted by JG cells when: • increased sympathetic stimulation • decreased renal blood pressure • decreased sodium chloride in renal tubular fluid ▪︎ These occur when blood pressure drops or when ECF volume or sodium concentration is low.

Bone is continuously being remodeled

▪︎ Osteoblasts create new bone by secreting organic-osteoid- and then mineralizing it with calcium phosphate crystals ▪︎ Osteoclasts dissolved bone (bone resorption) by solubilizing the crystals ▪︎ Osteoblasts create bone

hypoxia

▪︎ Oxygen deficiency at tissue level

Student A has better ventilation than B - Increasing Depth of breathing is more important than rate.

Student A has double Tidal Volume and Student B has double Respiratory Rate Who has higher ventilation of alveolar rate? Student A = TV X 2 = 1000-150= 850 => 850 x15= 12750 Student B = RR X 2= 500-150=350 => 350 x 30 =10500

This pressure can be calculated Laplace's law

Surface forces in a bubble tend to reduce the area of the surface and generate a pressure within the Bubble

How does velocity of air change moving through the respiratory tree?

decreases as you go down the tree due to greater cross sectional area

Alveoli Capillary membrane

gas exchange between alveoli and blood capillaries. < 0.5 mic. met From alveoli to B. capillaries layers - Endothelium → Basement membrane → cells → surfactant

Thebesian Veins

numerous small valveless venous channels that open directly into the chambers of the heart from the capillary bed in the cardiac wall, enabling a form of collateral circulation unique to the heart.

2 factors local alveolar ventilation depends on?

resistance and compliance

What happens to the alveolar ventilation time constant in restriction (decreased compliance) and obstruction (increased resistance)?

restriction - decreased T due to less compliant alveoli obstruction - increased T due to increased airway resistance

Daltons Law

total pressure exerted by a mixture of gases is equal to the sum of the partial pressures of all the gases present in it.

Which is better ventilation at the base or the apex?

ventilation is better in the base

Henrys Law

when temperature kept constant, amount of gas dissolved in any solution is directly proportional to the partial pressure of the gas

1,25-(OH)2-Vitamin D3 activates

• Bone • Breast • Fat • Intestine • Immune cells • Kidneys • Liver • Neurons • Pancreas • Parathyroid gland • Prostate • Skin keratinocytes

Lung Volume and Resistance

↑ Lung volume ↓ Resistance Each bronchiole is attached to an airway. whenever alveoli expand, it pulls airway and increases diameter of airway (airway size increases) * Patient with emphysema- lateral traction is less, bronchus size will be small

Factors shifting O2 dissociation curve to right ( Less affinity of O2 to Hb)

■ In the blood level increase in - 1. Temperature 2. H+ ion concentration ( pH) 3. PCO2 4. 2,3-DPG (2,3-BPG) level

Bohr's Effect

■ Loading of CO2 and unloading of O2 ■ Takes place at tissue level ■ Helps in unloading & O2 delivery to tissue Hence, increase in blood pCO2 shifts the O2 dissociation curve to right is called Bohr's effect.

Regulation of thyroid hormone synthesis and secretion

▪︎ Every step controlled by TSH (thyroid hormone) form anterior pituitary ▪︎ TSH controlled by hypothalamic TRH (thyrotropin releasing hormone).

Hyper-secreting tumor of the anterior pituitary

▪︎ Excessive amount of hormone 2 is produced which causes Hormone 3 production to increase which causes negative feedback to hypothalamus increase and causes hormone 1 to decrease. * Negative feedback will be increased.

Exogenous corticosteriods vs. Endogenous corticosteroids

▪︎ Exogenous corticosteriods inhibit CRH, ACTH, and endogenous cortisol secretion.

▪︎ PEF 25 and PEF 50 effort independent -

▪︎ In this part you cannot expire out forcefully, it takes its own time and thus called Effort Independent part. This is because of recoiling of alveolus and lung * If there was a coving, it could indicate narrowing of small bronchioles in initial stages of obstructive lung disease.

Mechanism of action aldosterone

▪︎ Increases renal reabsorption of sodium and excretion of potassium ▪︎ Increases synthesis and activity of: • Epithelial Na channels (ENaCs) • Na/k-ATPase

Endocrine function is finely controlled by feedback mechanisms:

▪︎ Negative feedback- most functions ▪︎ Positive feedback - two examples ▪︎ Feed forward

Normal Variation in VA/Q ratio

▪︎ Normal individual, in upright posture ▪︎ VA/Q ratio variation from Top to Bottom of lungs is -from 3 at top to 0.6 at bottom ▪︎ Reasons - • Effect of gravity • Variation in intra-pleural pressure

Total compliance

▪︎ Normal value - 0.11L / Cm H2O ▪︎ Measurement -- ∆V / ∆P (Airway pressure -Intra pulmonary Pressure) * Total compliance is both lung and chest wall together. Because both are opposite and equal to each other individually they have 0.22 as compliance.

Bioactivity if catecholamines

▪︎ Not essential for life, but important in stress response ▪︎ Sympathetic response ▪︎ Most cells have receptors for catecholamines • Beta 2 receptors have a high affinity for epinephrine but not norepinerphrine ▪︎ Epinephrine especially important for function of these cells.

Causes of Vit D deficiency

▪︎ Obesity ▪︎ Using too much sun block ▪︎ Wearing too much clothing ▪︎ Being old

HISTOTOXIC HYPOXIA

▪︎ Occurs due to cyanide or sulfide poisoning ▪︎ Poisonous substances destroy the cellular oxidative enzymes ▪︎ Leads to complete paralysis of cytochrome oxidase system ▪︎ Even if the oxygen is supplied the tissues are not in the position to utilize it

HYPOXIC HYPOXIA

▪︎ Occurs due to decreased oxygen tension (pO2) of arterial blood(Hypoxemia) ▪︎ A-a gradient:

Action of insulin on liver cells

* Glucokinase not hexokinase

Surface tensionAir and saline P-V curve

* Infant Respiratory distress syndrome does opposite to surfactant does ⇒Patients are given steroids to increase production of surfactant ➭ No expansion initially ( on the graph) because water molecules are holding it eventually pressure causes expansion and when relaxed recoils fast. * Administrating normal saline acts as surfactant in breathless patients (Nebulizer).

Avogadro's law

Equal volume of different gas at the same temperature and pressure has the same number of molecules

Restrictive Disorders

-Only suggestive ▪︎ Difficulty in inspiration. ➤ Reduced FEV1 and FVC ➤ The ration of FEV1/FVC is normal ▪︎ Issue with rib cage, e.g: Pscoliosis, scarsosis. ▪︎ Lung cannot expand so cannot inspire more air (↓Vital capacity) ▪︎ In restrictive FVC is decreased because they cannot breath in. They have no problem in expiration so FEV1 remain normal.

Transport in blood of thyroid hormones

-Thyroid hormones bind reversibly with proteins ▪︎ Mostly TBG (thyroxine-binding globulin) ▪︎ Bound form in equilibrium with free, which is the bioactive form ▪︎ More than 99% is bound, acting as a reservoir for T3 and T4

Pulmonary Resistance (Total non elastic tissue resistance)

1. Air-way resistance 2. Viscous resistance (non-elastic tissue resistance) ➤ Resistance are measured during dynamic condition R = ∆P/ V (flow) in liter/sec * Patients with pulmonary diseases, the max resistance will be at terminal bronchioles.

Biological effects of cortisol

1. Carb, protein and fat intermediary metabolism 2. Protective during acute stress 3. Anti-inflammatory and immunosuppressive 4. Permissive actions for other hormones

Measurement of RV

1. Closed circuit method ( Helium method) 2. By Body Plethysmograph method

Pathological causes of Hypoxia

1. Congestive heart failure 2. Uremia 3. Elevating intracranial pressure

Factors determining Lung Compliance

1. Elastic nature of pulmonary tissue (contribute 1/3rd) 2. Surface tension (contribute 2/3rd)

Characteristics of Hormones

1. Feedback control 2. Cell specificity 3. Relatively low plasma concentration 4. Interaction with nervous system

Synthesis of thyroid hormones I

1. Follicular cell synthesizes enzymes and thyroglobulin for colloid

Three families of anterior pituitary hormones

1. Glycoprotein family 2. POMC (Pro-opiomelanocortin) family 3. GH/ prolactin family

Diseases caused by Calcium Homeostasis

1. Hypoparathyroidism 2. Hyperparathyroidism 3. Vitamin D deficiency 4. Osteoporosis

Reasons for Hypoxia

1. Hypoxic Hypoxia High altitude => less O2 so less O2 reaching alveoli 2. Anemic Hypoxia Any lung disease will cause decrease in Po2 in alveoli eg: Anemia Hypoxia Any lung disease will cause decrease in PO2 in alveoli 3. Histologic Hypoxia Cyanide poisoning= tissue cannot utilise oxygen 4. Stagnant Hypoxia Blood flow is less for example cardiac arrest.

Classification of hypoxia

1. Hypoxic hypoxia or Arterial hypoxia 2. Anemic hypoxia 3. Stagnant hypoxia or Ischemic hypoxia 4. Histotoxic hypoxia

Dead space and Shunt

1. If something blocks Alveoli, Blood flow will get wasted and ventilation becomes 0. so its Shunt. 2. If a embolism (Pulmonary blood vessels gets blocked then blood flow is completely stopped and ventilation is normal. Air flow is getting wasted so its a dead space.

Effects of activated vitamin D

1. Increases total body calcium by increasing GI absorption of calcium ▪︎ Dose-dependent response ▪︎ Slow, long lasting response ( gene activation) ▪︎ Adjustment of Ca intake from diet to match needs occurs via changes in ratio of active/ in active Vit D 2. Increases ECF ionized calcium by enhancing response of bone to PTH (Resorption)

Pulmonary Functions

1. Inspiratory capacity (IC) =IRV + TV =3600ml 2. Functional residual capacity (FRC) =RV + ERV = 2400ml 3. Vital capacity (VC) or Forced Vital capacity (FVC) =IRV + TV (=IC) + ERV = 4800ml 4. Total lung capacity (TLC) = IRV + TV (=IC) + ERV + RV = 6000ml (6 liters)

Actions of insulin on its target cells

1. Insulin binds to tyrosine kinase receptor 2. Receptor phosphorylates insuline receptor substrates (IRS) 3. 2nd messenger pathways alter protein synthesis and existing proteins 4. Membrane transport is modified 5. Cell metabolism

Hyperventilation

During Hyperventilation, rate of removal of PCO2 is increased. This causes decreases acidity and increase alkalinity causing constriction of Blood vessel in brain. This will make the patient unconscious.

Non Respiratory Functions of the Lungs

1. Lung Defense Mechanism: Respiratory passage a. Humidify & cool or warm the inspired air b. Immunoglobulins (IgA): Bronchial secretion help to resist infection c. Prevent foreign particle to reach alveoli (PAM) 2. Metabolic & Endocrine Function: a. Surfactant b. Substances synthesised & released : Histamine, Kallikrein c. Substances removed from blood: Adenine derivatives, PG, Sertonin, Ach d. Substance activated---- Angiotensin I e. Storage of some hormones --- VIP, CCK-Pz f. Fibrinolytic system ---- lysis the clot in pulmonary vessel

Bioactivity of thyroid hormones

1. Metabolism 2. Growth and development 3. Nervous system development and function

Why is Lung Elastic?

1. Parenchyma cells (Like nylon socks) due to Elastin 2. Alveoli is coated with thin layer of water. (water particles attract each other) ↑ surface tension making lungs collapse. But alveoli doesn't know recoil completely due to surfactant, it reduces surface tension

Types of Volumes in lung functions

1. Tidal Volume: Ait breathing in and out. 2. Inspiratory Reserve volume: Amount of Air forcefully breath in. 3. Expiratory Reserve Volume: Amount of air forcefully breath out. 4. Residual Volume: Air presents in lungs all the time.

Factos influencing oxygen diffusion/saturation

1. Velocity of Blood Flow 2. Alveolar oxygen partial pressure (High altitude).

Respiration

1. Ventilation 2. Gas Transport 3. Gas Exchange

▪︎ Graph C, expiration takes longer time to reach the Peak expiration point compared to normal. ▪︎ At graph B, Residual volume is greatest, it also have lowest vital capacity and lowest PEFK (Peak expiratory flow rate)

1. Which graph have expiration taking the longest? 2. Which graph have the greatest Residual Volume?

What are the factors affecting airway resistance?

1.Airway structure As the airways branches they become narrower and the resistance tend to increase. however at the same time with increase number of branches and cross section area, the airways resistance will reduced as the airway penetrate in the periphery of the lung. The following diagram shows the highest resistance is at 4th airway generations 2. Lung volume As the lung volume increases, the airway radius increases by radial traction and transmural pressure which in turn reduces resistance to air flow. 3. Control of airway smooth muscle by autonomic nervous system. a. Stimulation of Adrenergic receptors couses bronchodilatation. B- Adrenergic receptors are of two types: B1 located mainly in the heart and B2 receptors relax smooth muscles in the bronchi, blood vessels, and uterus. Selective B2-adrenergic agonist are used to treat patients with asthma. b. Parasympathetic activity (ach) causes brochoconstriction

Physiological Hypoxia

1.High altitude 2. After hyperventilation 3. In deep sleep 4. In anesthetic condition 5.Quite common in healthy infants

Oxygen transport

2 forms: ■ Physical form: Dissolved form in plasma as simple solution ■ Combination with Hemoglobin =>HbO2.

Synthesis of thyroid II hormones

2. Iodide is co-transported into the cell with Na+ and transported into colloid. ▪︎ Sodium-Iodide symporter (NIS) transports against its gradient-"Iodide trap" ▪︎ Na/k-ATPase creates the Na gradient

Synthesis of thyroid hormone III

3. Enzymes add iodine to thyroglobulin to make T3 and T4.

Mucociliary transport

A 35 year old coal worker exposed to industrial dust for past 20yrs. Which of the following is the primary defense mechanism that clears the respiratory tract of deposited particles about 2 micro meter in size? a. Cough and sneezing b. Upper airway trapping c. Mucociliary transport d. Phagocytosis e. Immunologic memory

FEV1 cannot be found because there is no time in the axis.

A 45-year-old man inhaled as much air as possible and then expired with a maximum effort until no more air could be expired. This produced the maximum expiratory flow-volume curve shown in the following diagram. What is the forced vital capacity of this man (in liters)?

Ciliated cells

A 5 year old boy in a dusty field in windy weather inhales many small particles that become lodged in his terminal bronchioles. Which of the following are most important in clearing the particles? a. Ciliated cells b. Clara cells c. Type I pneumocytes d. Type II pneumocytes e. Submucosal glands

Coving

A frequently recognized abnormality in the flow-volume loop is the concave upward or "scooped-out," or "coved" pattern encountered in asthma or chronic obstructive pulmonary disease

Section at various level of brain stem

A — Above pons (both respiratory centers are intact)- normal respiration -with vagus; normal respiration with decrease rate & increase depth without vagus B - Mid pons (Pneumotaxic center of pons is removed)- Normal respiration with decrease rate & increase depth -with intact vagus; Apneustic type of breathing without vagus that is prolonged inspiration and sudden expiration C - Between pons & medulla (only medullary center is present)- gasping (shallow rapid breathing) D - Below medulla (medullary center also removed) - Respiration ceases

Lung Compliance (∆V/∆P)

A. Regional differences ▪︎ In an up right position, the compliance of the top is less than the bottom as the top alveoli are expanded. ▪︎ The inspired air will enter the alveoli with more compliance ▪︎ The distribution of inspired air is uneven from to bottom. * So reduce pressure lung volume keep on increasing. Expiration is not taken into consideration here because its a passive process. * Inspiration and expiration are not following the same path in the graph due to surface tension and also expiration is a passive process. * Between -5 to -10 is the amount of air entering the lung.

ADH mechanism of action

ADH increases permeability of renal collecting tubule cells to water - More water will be reabsorbed in kidneys and less, more concentrated urine will be produce i.e., antidiuresis occurs

Gigantism

Abnormal height caused by excessive GH secretion before the epiphyses close

At TLC where is ventilation best at: Apex or base? Why?

About the same, both are large/noncompliant

ACTH

Actions: ▪︎ Target cells in adrenal gland cortex ▪︎ ACTH controls or modulates secretion of adrenal cortical hormones (all steroids) - Aldosterone - Cortisol - Androgens

Types of Capacities in lung functions

Adding volumes gives capacities 1. Total Lung Capacity: Amount of air remaining in lungs after forceful inspiration 2. Vital Capacity: Amount of air that is forcefully breathed out after forceful inspiration 3. Inspiratory Capacity: Tidal Volume + IRV 4. Functional Residual Capacity: ERV + RV

ANS: B (-4, 0) * After norma expiration outer atmospheric pressure and alveoli is same=0. After expiration, intrapleural pressure will become normal = -4.

After expiration, intrapleural pressure and intra-alveolar pressure? A. -4, -1 B. -4, 0 C. 0, -1 D. -8, -1 E. +6, -1

Compliance changes in disease

Emphysema Fibrosis Pulmonary vascular congestion Pneumonia Pleural effusion Obesity Chest wall deformity

At RV where is ventilation best at: Apex or base? Why?

Apex - regional difference diminished due to equally large/less compliant at apex and base

Describe relative pressures/effects on ventilation in the apex vs the base: intrapleural pressure, transmural pressure, alveoli size, and ventilation.

Apex: more negative intrapleural, greater transmural, larger/less compliant alveoli, less ventilation Base: intrapleural less negative, smaller transmural, alveoli smaller/more compliant, more ventilation

Anemic Hypoxia

Arterial End: - PO2 is Normal - Hb% is Normal - O2 content ↓ => because bound O2 is less because number of Hb is less ▪︎ When dissolved O2 is taken in, more bound O2 is released. Saturation occurs between dissolved O2 and PO2 in tissue when O2 content is less, Both dissolved and bound are taken

CO2

Arterial blood - ■ CO2 content (concentration) - 48 ml/dL ■ CO2 tension -- PCO2 of 40 mm Hg Venous blood- ■ CO2 content (concentration) - 52 ml/dL ■ CO2 tension -- PCO2 of 46 mm Hg ■ A-V CO2 difference = 4 ml/dL

Oxygen content

Arterial: 20ml/dl Venous: 15ml/dl ■ 5ml is utilized by tissues of oxygen.

Purpose of Pulmonary function tests

As a diagnostic tool, PFTs help classify diffuse lung disease into one of the three broad categories √ Obstructive Lung Disease: ▪︎ COPD ▪︎ Asthma ▪︎ Bronchiectasis ▪︎ Cystic Fibrosis √ Restrictive Lung Disease ▪︎Interstitial lung disease (e.g. Pulmonary fibrosis, sarcoidosis) ▪︎ Chest wall pathology (Kyphosis, scoidosis) ▪︎ Obesity ▪︎ ALS, neuromuscular disease √ Pulmonary Vascular Disease ▪︎ Pulmonary Hyper tension ▪︎ Chronic thromboembolic disease

Physiological Shunt

At Zone 3, perfusion is getting wasted. Blood flow is high compared to ventilation. PO2 is not completely saturated so PO2 will be ↓ in Zone 3.

Boyles Law

At constant Temperature P1V1=P2V2

At FRC where is ventilation best at: Apex or base? Why?

Base - regional difference exaggerated due to larger/less complaint at apex

Haldane's effect

Binding of O2 with Hb reduces CO2 affinity for Hb is called Haldane's effect Takes place at lung level O2 tension at alveoli causes oxygenation of Hb and thereby decreases CO2 affinity for Hb & releases CO2 from blood into alveoli Haldane's effect accounts for 50% of CO2 release from the blood into alveoli Out of 4 ml/dL expelled - 2 ml due to PCO2 difference between blood & alveoli Another 2 ml is due to Haldane's effect

Factors determining Pulmonary diffusion capacity

Blood-gas exchange depends upon - 1. Surface area of the Respiratory membrane 2. Thickness of the respiratory membrane 3. Diffusion capacity of the gas 4. Partial pressure of the gas 5. Solubility of the gas 6. Affinity of the gas with Hemoglobin *Diffusion depends on affinity to Hb (Hb-O2 dissociative curve). CO2 diffuses more faster than O2. Co has more affinity than O2 for Hb do it does not affect dissolved O2 and binds to Hb. So PP of O2 remains same for CO poisoning. ➢ Treatment ↑ Saturation of O2 at ↑ pressure. So instead of 100 , 200 or 300 is given at ↑atm. Emphysema patients will have less surface area and more Residual Volume. and so less diffusion of gas in blood. During exercise Surface Area of alveoli increases more alveoli opens up to compensate demand for O2.

Calcium regulation

Both plasma concentration of ionized calcium and total body calcium are regulated ▪︎ Free ionized Ca in ECF by: - Primarily by exchange between bone and ECF - Renal excretion ▪︎ Total boy Ca by: - GI absorption of CA ▪︎ Renal excretion (over long term)

Compliance example question

C= ∆V/∆P 250-350/-1 = 150/-1 = 1.5L/-1

Alveolar ventilation= 9000ml

Calculate alveolar ventilation of a subject with tidal volume of 600 ml, anatomical dead space of 150 ml and Resp rate of 20. Alveolar ventilation= VD-VE VD= Total ventilation - Tidal volume= 600-15-= 450 AV=450 X 20= 9000ML

Spirometer

Cannot measure FRC and TLC. Values measures by spirometery can identify Obstructive vs. Restrictive (suggestive) or mixed

Structural component of Respiratory system

Cartilage in trachea is important for dynamic airway compression and will help it not to collapse • Terminal and Respiratory have large smooth muscle to contract (vasoconstriction)

Hypothyroidism

Causes ▪︎ Primary= failure of thyroid gland, often due to autoimmune inflammation (thyroiditis and subsequent fibrosis. ▪︎ Secondary = failure of pituitary to secrete TSH ▪︎ Tertiary= Failure of hypothalamus secrete TRH ▪︎ Lack of iodine in diet Signs & symptoms ➤ Depressed nervous system activity ▪︎ Slow, weak pulse ▪︎ Slow reflexes, mentation and speech ▪︎ Lack of alertness ▪︎ Poor memory ➤ Low metabolic rate ▪︎ Intolerance of cold ▪︎ Elevated blood cholesterol ▪︎ Weight gain ▪︎ fatigue ▪︎ Puffy, doughy appearance (myxedema)

Hyperthyroidism

Causes: ▪︎ Autoimmune disease (Grave disease of thyrotoxicosis), in which TSI (thyroid stimulating immunoglobulin) stimulates TSH receptors ▪︎ Primary: thyroid tumour that hypersecretes thyroid hormones ▪︎ Hypersecretion of TRH or TSH by hypothalamus or pituitary. * Marlene's exophthalmos due to hyperthyroidism of Graves disease

Role of Pancreatic secretions

Central role in: ▪︎ Digestion ▪︎ metabolism, utilization and storage of energy substrates ▪︎ Controlling glucose homeostasis - provides a constant supply of glucose to CNS

Control of Respiratory system

Chemo receptors are present in arch of aorta and bifibrication of trachea.

Calcitonin

Effects on bone remodelling opposite to PTH: ▪︎ Calcitonin decreases movement of ionized calcium from bone fluid to ECF ▪︎ Inhibits activty of osteoclasts- decreases bone resorption ▪︎ No significant clinical findings associated with calcitonin excess or deficiency

Oxygen-dissociation curve

Curve shifts to the right: ■ Increased Temperature ■ Increased 2, 3, BPG ■ Decreased pH Curves shifts to the left: ■ Decreased Temperature ■ Decreased 2, 3 BPG ■ Increased pH.

Pulmonary Diffusion of Gas Ficks Law of Diffusion

D = (A/T) (Dc x ∆P x S) A—surface area of the membrane; T-thickness of the membrane; * Alveolar membrane (↑Thickness ↓ Diffusion) Dc -Diffusion coefficient of the gas ∆P— Partial Pressure difference of gas * Gas moves from High to low Concentration S- solubility coefficient of the gas * ↑solubility ↑diffusion. Diffusion depends on affinity to Hb (Hb-O2 dissociative curve). In the case of Blood, the Partial pressure also depend upon the affinity of the gas with Hb.

Fractional Inspiration of FiO2

FiO2=21% ▪︎ 21% of gas will be oxygen, if you take 100 molecules of air. ▪︎ Fraction of oxygen present in atmospheric air and this will never change above sea level or below sea level 21 FiO2 remains same.

Comparative relationships between lung volume and airway

Fibroitic lung resistance is more compliance is less (inspiration is hard). Resistance depends on radius.

Significance of chemical regulation

Helps in Homeostasis of ■ PO2 ■ PCO2 & ■ H+ ions Achieved through Chemoreceptors

Primary Hyperparathyroidism

High PTH level with Ca Causes: ▪︎ Depressed muscle and nerve excitability - Depolarization threshold raised due to high [Ca2+] ▪︎ Increased risk fractures - due to demineralization of bone. ▪︎ Increased risk of kidney stones - due to high concentration of calcium in renal filtrate.

▪︎ FVC = volume of air that forcefully exhaled have FEV1 in it. e.g Volume total for both lungs together will be 6L. After removing one lung, Volume becomes cut in Half which will be 3L. so overall all the volumes decreases. ▪︎ FEV1/FVC ratio will be normal. FEV1 is related to vital capacity. So even with one lung, it expires out 80% of air inspired in first second. So its normal even with less air coming in.

IF you remove one Lung, What will be FEV1/FVC ? and Volume?

ACTH level is controlled by the CRH/ACTH cortisol feedback loop

In all 3 Zones, ACTH also: ▪︎ Stimulates and maintains cellular growth ( ACTH is a trophic hormone) • Too much ACTH → hypertrophy • Too little ACTH→ atrophy ▪︎ Up-regulates LDL receptors

Fick's law of Diffusion

In the steady state, Flux is directly proportional to concentration gradient.

▪︎ Lower lobe because of smaller alveoli and can expand more

In which lobe compliance is highest at erect posture?

Lower Lobe

In which upper lobe elastance is higher?

Factors that influence secretion of GH (GH regulated by GHRH & GHIH)

Inhibited by : Obesity, insulin resistance, chronic hyperglycemia. ▪︎ Stimulated by: - Stress - Exercise - Hypoglycemia, fasting - Some amino acids, esp. arginine and leucine - first 2 hours of deep sleep

Reciprocal Inhibition

Inspiration centers sends signals to inhibit expiration. And Expiration centers send signals to inhibit inspiration. * Apneustic center is inhibited by pneumotaxic center and lungs. *Hering Breuer Reflex: Pulmonary stretch receptors present in the smooth muscle of the airways respond to excessive stretching of the lung during large inspirations.

Mechanism of Respiration

Involves 3 processes: ▪︎ Creation of Force (for operation of respiratory pump) -by respiratory muscles ▪︎ Pressure changes (in the thoracic cavities) ▪︎ Resistance to over come (for air movements)

Major effects of insulin on carbohydrate metabolism

Overall: decreases blood glucose and increase carbohydrate storage ▪︎ ↑ Glycogenesis in skeletal muscle and liver ▪︎ ↓ Hepatic gluconerogenesis ▪︎↑Glu uptake by fat cells and resting skeletal muscle

Embolism blocking Pulmonary vessels. What will be PO2, PCO2?

Lower Zone= PO2↓ PaCO2↑ ■ Because of the↑ blood flow and ↑ air moving into Blood, PO2 decrease at alveolar. A PO2 also changes to 98. Because of less ventilation less CO2 moves into alveoli so PCO2 increases in arterial end. ■ ↓V and Q↑

Physiological Dead Space Volume

Measurement by using Bohr's formula (Bohr's Equation)

Embryology of the adrenal glands

Medulla and cortex have different origins: ▪︎ Medulla arises from neural ectoderm ▪︎ Modified sympathetic ganglion ▪︎ Cortex from mesoderm

Alveolar ventilation (VA)

Minute Ventilation - Dead Space Ventilation

Metabolic effects of cortisol

Mobillizes fuels by: ▪︎ Raising blood glucose - stimulates liver gluconeogenesis - Inhibits glucose uptake ▪︎ Raising blood amino acid level by increasing muscle catabolism ▪︎ Raising blood fatty acid level by stimulating lipid breakdown in fat cells

Metabolism of thyroid hormones

Most of circulating T4 is converted to T3 by deiodination in liver and kidneys ▪︎ 80% of circulating T3 has been converted from T4. ▪︎ T3 is 4 times more bioactive than T4 ▪︎ Therefore T3 is the principal thyroid hormones.

Human Respiratory system

Nasal Cavity : Filters, warms, and moistens air

All anterior pituitary hormones are controlled by Hypothalamic hormones

Nemonics: FLAT PiG FSH-LH-ACTH-TSH-Prolactin-i-GH ▪︎ 4 hypothalamic releasing hormones - A 5th (PRH) does not exist - But TRH has a mild stimulatory effect on prolactin release ▪︎ 2 inhibiting hormones -Dopamine and GHIH

Inspiratory center

Nerves at the dorsal aspect of medulla when stimulated causes inspiration. These centers are called Inspiratory center ■DRG ( Dorsal root ganglion) * On the ventral side is VRG, when stimulated causes expiration

Gaseous Transport

O2 Consumption = 250ml/mim CO2 excretion by body= 200ml/min

Effects of insulin on fat metabolism

Overall: decreases blood fatty acids and increases triglyceride storage ▪︎ ↑ transport of fatty acids into fat cells ▪︎ ↑ Triyglceride synthesis by increasing glucose transport into fat cells. ▪︎ Activates enzymes that catalyze synthesis of fatty acids from glucose ▪︎ Inhibits lipolysis

Smaller Alveoli vs. Larger alveoli

Pressure is directly proportional to radius. ▪︎ Smaller alveoli collapse into larger alveoli but because smaller alveoli is covered by surfactant, it wont collapse. ▪︎ Surfactant prevents over-expansion of alveoli.

poiseuille's law

Pressure is directly proportional to radius. Alveoli is smaller in size means radius is decreased causing pressure ↑ and lung collapse

Why is there more ventilation at the base of the lungs vs the apex?

Pressure is less at the apex, compared to the base, due to gravity, so the alveoli in the apex are larger and less compliant

Significance of RV

Prevent collapse of alveoli Ensuring continuous Blood-Gas exchange Buffering of alveoli gas - Keep the composition of alveolar gases constant

Dead Space

Purifies air + defense mechanism Functions: 1. Purification of air- Removal of solid particles of various size from air • >6 micrometer -trapped by hair of nose • 1 to 5 micrometer- trapped by mucus with escalator action of cilia removed; • < 1micrometer- enter alveoli & removed by PAM ( Pulmonary alveoli Macrophage) ➤ Loss of ciliary motility cause chronic sinusistis, lung infections & bronchiectasis ➤ Causative factors: air pollutants & congenital form 2. Air-conditioning function- air temperature of 370C. 3. Humidifying function: air water vapor pressure (aqueous tension) of 47mmHg

If a thrombus blocks Pulmonary artery. What will be V/Q ratio?

Q=0 (No Perfusion) V/Q= N/0= infinity

Roles of pancreatic hormones

Respond to "feasting and fasting": ▪︎ The fed state- during eating and first hours after eating ▪︎ The fasted state- between meals ➤ Insulin dominant in fed state: ▪︎ Cellular uptake of nutrients ▪︎ Carbohydrate and fat storage ▪︎ Protein anabolism ➤ Glucagon dominant in fasted state: ▪︎ Catabolism-- breakdown of carbohydrate, fat, and protein stores ✓ Most significant regulate variable: blood glucose concentration ✓ Insulin & glucagon secretion controlled primarily by blood glucose concentration ✓ Insulin and glucagon have mostly opposite effects

Role of ADH and aldosterone during stress

Retention of Sodium and water • Protects ECFV and blood volume • Important during heavy sweating and in case of blood loss

ADH secretion

Secretion stimuli: ▪︎ High osmolarity of extracellular fluids ▪︎ Low blood volume ▪︎ Low arterial blood pressure - Factors affecting thirst ▪︎ Increase plasma osmolarity ▪︎ Decrease in blood volume ▪︎ Dryness of mouth and throat ▪︎ Monitoring of water intake by GI tract

chyme- stroke breathing

Seen in children Periodic breathing with periodic hyperventilation. • is an abnormal pattern of breathing characterized by progressively deeper and sometimes faster breathing, followed by a gradual decrease that results in a temporary stop in breathing called an apnea.

Glycoprotein family

Small glycoproteins: Water soluble stored in endocrine cell in secretory vesicles, secreted by exocytosis, receptors on outside of target cells -FSH -LH -TSH ▪︎ FSH & LH act on gonadal target cells: ⇒Stimulate secretion of estrogen and progesterone by ovaries ⇒ Stimulate spermatogenesis and secretion of androgens in testes ▪︎ TSH acts on thyroid gland target cells to stimulate secretion of thyroid hormones.

Feedback control of GH & IGF-1 secretion

Somatostatin =GHIH Somatotropin = GH Somatomedin =IGF-1

Apnea

Stoppage of breathing.

GH/ Prolactin/ hPL( human placental (hCS)* family

Structure: ▪︎ Proteins, with multiple forms of GH in the blood ▪︎ GH, prolactin & hPL are structurally related - so they have some cross-activity when concentrations are elevated * hPL produced by placental Lactogen

Synergism of Hormones

Synergism of hormones raises blood glucose to a higher level than if the effects of each were added together

The diagram shows a forced expiration for a healthy person (curve X) and a person with a pulmonary disease (curve Z). What is the FEV1/FVC ratio (as a percent) in these individuals?

The Graph A is OBSTRUCTIVE ▪︎ y Axis Vital Capacity for X=5L ▪︎ FEV1= 4L ▪︎ Ratio =4/5= 80% √ For Z graph ▪︎ Vital capacity= 4L ▪︎ FEV1= 2L ▪︎ Ratio= 4/2= 50% The Graph B is obstructive √ For X graph ▪︎ Vital Capacity= 5L ▪︎ FEV1= 4 ▪︎ Ratio =4/5= 80% √ For Z graph ▪︎ Vital Capacity = 3.5 L ▪︎ FEV1= 3 L Expiring out 3L of 3.5 VC in first second is less Expiring out the almost 90% so its restrictive. * Start expiration from Point 1, So FEV1 is calculated from 1s.

Henry's law

The concentration of a gas dissolve in a liquid is proportional to its partial pressure

Perfusion limited gas Exchange

The gas equilibrates between the capillary and the alveolar air. for low affinity gases-Example -N2O, He ( Gas equilibrate with blood within <0.1s ▪︎ O2 transport is both diffusion and perfusion limited gas exchange; equilibrate with blood in 0.3sec *Perfusion means blood coming in so the gas getting across membrane is limited by whether new blood comes in. *N2 is also highly diffusing gas and gets saturated fast so to stop diffusion, ↑perfusion.

Vital Capacity =4.5L Residual Volume= 0 ▪︎ Initially you can forcefully expire air. But the last part, you cannot expire out forcefully , it takes its own time. This is called effort Independent part. ( at point D is effort independent). ▪︎ This is because of recoiling of alveoli and lung.

The maximum expiratory flow-volume curve shown in the following diagram is used as a diagnostic tool for identifying obstructive and restrictive lung diseases. At which of the following points on the curve expiration is effort independent?

Severe Obstructive ▪︎ ↓Vital Capacity ▪︎ ↑Residual Volume Presence of Coving compared to normal

The maximum expiratory flow-volume curves shown in the next diagram were obtained from a healthy individual (red curve) and a 57-year-old man who complains of shortness of breath (green curve). Which of the following disorders is most likely present in the man?

Dalton's law

The partial pressure of a gas in a gas mixture that this gas would exert if it occupied the total volume Ptotal= P1+P2+P3....Pn

Why is there a dip in curve?

Thebesian venous mixture of blood

Minute Ventilation (VE)

Tidal Volume X Breaths per minute (Respiratory Rate) =500 X 5= 7500 ml of Air

Lung Volumes

Tidal volume (TV) -500ml Inspiratory reserve volume (IRV) -3100ml Expiratory reserve volume (ERV) -1200ml Residual volume (RV) -1200ml

Spirogram

Tidal volume: 500 ml ERV= 1.2L RV= 1.2 L IRV= 3L

Compliance * Resistance = ?

Time to ventilate

Bronchi, Bronchioles & Alveoli

Trachea divides into Primary Bronchii divide into Secondary Bronchi into Bronchioles divide into terminal bronchioles divide into Respiratory bronchioles divide into Alveolar ducts end in alveoli

Tracheo-Bronchial tree

Tracheo Bronchi (Bronchus) Bronchiole(s) Respiratory Bronchioles (s) Alveolar ducts-Atria-Alveolar Sacs-(Pulmonary) Alveoli (functional respiratory units) • In each generations as the generations advances the number of divisions increases • Has got -23 generations of airways • Up to 16 generation ( up to terminal bronchioles- Conductive Zone (no gas exchange) • Rest 7- Respiratory Zone or Transitional (3) & Respiratory zone (last 4)

Actions of peptide hormones

Two main mechanisms: ▪︎ G-protein couples second messenger ▪︎ Tyrosine kinase

Alveoli (alveolus)

Two types of cells:- • Type I cells ( Type I pneumocytes)- flat squamous cells form lining cells- 90% • Type II cells ( Type II pneumocytes or granular pneumocytes)- 10% of cells; secrete surfactant • Other cells -PAMs; Lymphocytes, Plasma cells • Inner surface lined by (alveolar) fluid with thin surface film of surfactant.

Dead Space ventilation (VD)

VD= Total ventilation - Alveolar ventilation

Activation of Vitamin D

Vit D activated by addition of hydroxyl groups: • 1st OH added in liver → 25‐OH Vit D • 2nd OH added in kidneys → 1,25(OH)2 Vitamin D3

ANS: -4 (intrapleural pressure) 0 (alveolar pressure). ➯ This happens only during normal inspiration (open mouth), You are not holding your breath and outside atmosphere connects to your lungs ( Both pressure is same and both lung and thoracic wall are relaxed.

What happens to intra-alveolar and intrapleural pressure if you open your moth and relax ( no inspiration or expiration)

Dynamic Airway compression

When forcefully expiring, intrapleural pressure becomes positive. The lung recoiling give +10. alveoli will have a pressure of + 30, when air starts moving out, it loses pressure +29...+28...+20....until it reaches 0 (expiration). At pressure 15, Bronchus collapse, because there are higher pressure in pleural space. So normally outside 20 and inside 20 ( Equal pressure point) falls in trachea to prevent collapse of bronchus and trachea is protected by cartilage

24, 25 (OH)2 vIT d3

When plasma ionized calcium is high, renal hydroxylation produces inactive form of this

■ Point A: PO2 in artery (100) at PaO2 of 100 almost and Hb saturation⟹ 97% of Hb is saturated ( Arterial Point) ■ At point D PO2 of 40. Saturation of Hb is 75% ( Venous point) ■ At Point B, P50 Hb saturation at P26 (Hb will be saturated 50% at PO2of 26).

Which Graph Has highest Hb releasing O2 -Graph A Which Graph has the highest Hb holding O2? - Graph C

Oxygen -Hemoglobin Dissociation: Exercise

Which Graph corresponds to CO poisoning ? ■ Ans: C (Will not get 100% saturation of O2) Cyanide prevents downloading of O2 from Hb whereas CO prevents uploading of O2 to Hb

▪︎ Graph A has higher compliance and graph B has higher elastance. ▪︎ For Graph A, change in volume is much higher ▪︎ For the same pressure one, graph A has volume of 2.5 L and Graph B has 0.5L.

Which graph has highest compliance and highest elastance

Graph B is more Obstructive

Which graph is more obstructive?

ANS: E + 20

Which of the following is intrapleural pressure when the patient is sneezing or coughing A. -4 B. -8 C. -0 D. -20 E. +20

Pressure-Volume relationships of respiratory system

Which part of the graph corresponds to relaxed respiratory muscle ANS: at FRC (B) after normal respiratory muscle are relaxed. * FRC: The recoil force of Lung and chest wall is equal and opposite ▪︎ At RV (recoil force of chest wall is at Maximum) ▪︎ The equilibrium position at FRC on the chest wall is exactly equal to collapsing force on lungs. ▪︎ You cannot measure chest wall compliance alone. Recoil force of lung is very less compared to Recoil force of chest wall at Residual volume ▪︎ When you are forcefully expiring out, lung is collapsed to its maximum. Chest wall comes away from original position and it tends to recoil more.

Ans: A • Distensibility is more but more recoiling back. • Damage to parenchyma • Oldage (A) compliance increases and loses elasticity • Normal Saline into lungs ( graph moves to left). The graph follows same pathway for inspiration and expiration. When you add water, there is no Surface tension.

Which patient graph suffer from chronic Obstructive lung Disease?

________ __________ - the volume of air that gets into and our of the alveoli per given unit of time.

alveolar ventilation

Residual volume

cannot measured in spirometery

Edema

• Change in Sterling Forces ➤ Fluid accumulation in interstitial place, the alveolar-capillary membrane becomes more, less diffusion of gas ➤ Cause of Edema: ↑ Hydrostatic pressure ➤ Causes of Edema: 1. Damaged Endothelium eg: due to toxins , drug induced 2. Decreased Capillary Oncotic pressure 3. Increased Capillary Hydrostatic pressure 4. Lymphatics Net Filtration = Filtration process - reabsorption process=(Pc -Pif)-(Пp-Пif) • Pc- Hydrostatic pressure of capillary • Pif- Interstitial hydrostatic pressure • Пp- Oncotic for plasma in capillaries. Пif- Oncotic pressure in Interstitial fluid.

Types of Ventilation

• Dead Space Ventilation • Minute ventilation • Alveolar ventilation

2 Processes of Respiration

• External Respiration: Atmospheric air→ Lungs→ Blood→ cells→ back to lungs • Internal Respiration: Utilization of O2 in cells

Conducting Zone

• From Trachea up to terminal bronchiole (16th generation) forms conducting zone. • Mere conducting the air in &out •Including Larynx (up to terminal bronchiole) Lower Respiratory Tract • Also forms Dead Space

Regulation of GH secretion

• GHRH receptor: Gsa • GHIH receptor:Gia GHIH=SS (Somatostatin)

Respiratory System Function

• Gas Exchange: Oxygen enters blood and carbon dioxide leaves. • Regulation of blood pH: Altered by changing blood carbon dioxide levels • Voice production: Movement of air past vocal folds makes sound and speech • Olfaction: Smell occurs when airborne molecules drawn into nasal cavity • Protection: Against microorganisms by preventing entry and removing them

Perfusion

• HOW blood moves in Blood vessel. • Process of body delivering blood to capillary bed.

Physiological Dead Space

• In certain pathological conditions some alveoli may be ventilated but not perfused. This section of the lung function similar to anatomical dead space • The combination of this section and anatomical dead space is known as physiological dead space. * One of Alveoli is ventilated but not proper blood supply. The air present in that alveoli is not participating in gas exchange. This is called Pathological Dead Space (PDS). That alveoli will be diseased so Dead Space = PDS + ADS. In Normal individual without any pathological dead space, ADS= PDS • If PDS is more than one of Alveoli is ventilating but not getting enough blood (Gas Exchange). Physiological dead space is when some of the alveoli are not ventilating or blood flow to them. ADS=PDS

Role of cortisol in stress

• Increases metabolic fuels ( glucose, fatty acids, amino acids) • Permissive for catecholamine- stimulated vasoconstriction • Induces enzymes for production of epinephrine- proportion of epinephrine increased.

Alveolar Ventilation

• Increasing Tidal volume increases Alveolar ventilation. Tidal volume = 500 ml Dead Space Air= 150 ml Amount of Air entering alveoli= 500- 150= 350 (Amount of gas exchange) = 350. • Alveolar Ventilation (AV) = 350 X 15= 5000

Helium Method ( Closed circuit method)

• Keep the known concentration of Helium Gas mixture ( of known volume) Chamber & during experiment period, the subject rebreath in & out with in the chamber ( for 10 minutes) Calculation - RV = {(Ci He/Cf He) -1} V1 Ci He = Initial conc. Of He in the chamber (e.g. 6%) Cf He = Final conc. Of He in the chamber (e.g. 5%) V1 = Volume of gases in the chamber (e.g. 6 liters) C1= known concentration of Helium V1= Known gas volume * FRC= V1 (He1-He2)/He2 Expiring Forcefully Only RV remains in lungs Breathing in and out into spirometer. C2 will be low. C2 will be less than C1

Acromegaly

• Large facial features, hands, and feet • Elevated blood glucose (type 2 disease) • Limited lateral peripheral vision (Enlarged pituitary presses against optic chiasm where optic nerves from lateral fields cross) • Elevated blood GH level • Enlarged pituitary gland ▪︎ Gigantism caused by oversecretion in children.

Ondine's curse ( primary alveolar hypoventilation syndrome)

• Loss of automatic control without loss of voluntary control Occurs in disease due to bulbar polio, disease process that compress medulla,

Role of glucagon during stress

• Opposite effects of insulin- so increases blood glucose concentration • Glucagon, cortisol, and epinephrine exhibit the phenomenon of synergism: their combined effects on raising glucose levels are greater than additive.

Synthesis and secretion of posterior pituitary hormones

• Oxytocin & ADH - antidiuretic hormone (or Vasopressin or AVP- arginine vasopressin) • 9aa peptides differ by 2 • Overlap in bioactivity • Secretion independently controlled ▪︎ Each cell produces only one hormone from its large precursor, either preproxyphysin or preprophressophsin

Mechanics of Breathing

• Patients with emphysema loses lateral traction. Bronchiole size will be small. • Patients with pulmonary fibrosis have not resistance because fibrous tissue will be pulling airway * As you increase lung volume, resistance decrease. This is because of lateral traction.

Regulation of Insulin secretion

• Primary control: negative feedback between beta cells and glucose concentration in the blood • ↑blood glucose→ ↑insulin secretion, etc.

Pulmonary Circulation

• Receive entire cardiac output • Low resistance circulation & B. vessels are highly distensible (hold 20% of Total B.V). • Low BP • Operate in series with systemic circulation

Important Normal Values

• Respiratory Rate: 12to 18 /min • O2 uptake per minute -250ml • CO2 expulsion per minute -200ml Respiratory Exchange ration: Vco2/Vo2 = 200/250= 0.8

Bronchopulmonary Segments

• Things goes first into right lung, lower lobe • Less angle in the right side between Primary Bronchii and trachea compared to Left side of the lungs. • Because of multiple divisions of the airways- • Diameter decreases from 2.5cm of trachea to 1.5cm of bronchus -to—<1mm of bronchiole -to -0.5mm of respiratory bronchiole to 200µm of alveoli • Total cross-sectional area (A) increases from • Trachea 2.5 cm2; --Terminal bronchioles 180cm2 & alveoli—11800cm2 • Velocity of air flow falls in small air way as (V=1/A) • Number of branches from 1trachea to 65000 terminal bronchioles to 3 million alveoli.

Flight or Fight response

→indicates responses enhanced by epinephrine • Increased oxygen delivery to skeletal muscles and heart • Increased heart rate and contractility • Dilation of coronary & skeletal muscle blood vessels, constriction of others • → Relaxation of smooth muscle in airways • Increased metabolic fuels - fatty acids and → glucose • Reduced digestion and excretion • → Relaxation of bladder and GI tract • Constriction of bladder and intestinal sphincters. • Increased secretion of cortisol, ADH, aldosterone, pancreatic hormone glucagon, growth hormone • All coordinated by hypothalamus through posterior & anterior pituitary, or through SNS

Causes of Hypoxia

↓ Oxygen tension in the arterial blood ↓ Oxygen carrying capacity ↓ Blood flow rate to the tissues ↓ Oxygen utilization by the tissues

Lung diffusion capacity

√ DLCO decreased: ▪︎ Alveolar destruction - Emphysema ▪︎ Decreased Perfusion- Pulmonary embolism ▪︎ Increased thickness of resp. membrane- Pulmonary edema/fibrosis ▪︎ Low Hb - Anemia √ DLCO increased: ▪︎ Exercise - Increased CO ▪︎ Polycythemia- Increased Hb.

Differences in Volume-loop of Obstructive vs Restrictive

√ Normal ▪︎ Expiration is above the X axis and Inspiration is below the X-axis √ Mid Obstruction ▪︎ FVC PRESERVED, Late plateau ▪︎ PEFR mildly reduced and there is a notable Coving. √ Severe Obstruction ▪︎ No Plateau, FVC reduced ▪︎ PEFR severely reduced with bigger coving

Physical form or Dissolved form in plasm

■ Account for about 1% to 2% of O2 transport ■ Solubility coefficient of O2= 0.003ml/dL/mmHg ■ O2 content in arterial blood (PO2 100mmHg)= 0.3ml/dl ■ O2 content in venous blood (PO2 40mmHg) = 0.12 ml/dl

Simple solution (Dissolved form in plasma)

■ Accounts for about 7% of CO2 transport ■ Solubility of CO2 is 24 times to that of O2 ■ CO2 in arterial blood -- with PCO2 of 40 mm Hg -2.4 ml/dl ■ CO2 in venous blood -- with PCO2 of 45 mm Hg

Anemia

■ Anemia => Decreased O2 carrying capacity ■ ↓ Hb ■ ↑ RBC ■ Hb saturation: Normal ( number of Oxygen molecules are good and number of Hb molecules are less but all 4 sides are bound ■ O2 Content: ↓ bound form ■ PO2: Dissolved O2 (Normal)

3 points in O2 dissociation curve are:-

■ Arterial point -- PO2 of 100 mm Hg & Hb saturation of 97.5% ■ Venous point --PO2 of 40 mm Hg & Hb saturation of 75% ■ P50 -- PO2 of 28 mm Hg & Hb saturation of 50% ■ P50 - is the partial pressure at which Hb saturation is 50%.

CO2 transport

■ As CO2 to gets into the RBC, it combines with h20 to form Carbonic acid ■ Carbonic acid is broken down to form HCO3- and and H+ by Carbonic anhydrase. ■ HCO3- moves out of the RBC makes it less negative inside RBC, so Cl- ion moves in to RBC) ■ More carbonic anhydrase is present in RBC than plasma.

Perfusion vs. Ventilation

■ At the Apex, ventilation is more compared to persuion is less than V/Q>1 ■ At the base, Ventilation is low compared to perfusion thus V/Q<1

CO2 is transported in the blood in 3 forms

■ CO2 is transported in the blood in 3 forms 1.Simple solution -- 7% (dissolved) 2. Bicarbonate form (HCO3) - 70% 3. Carbamino-compound -- 23% ( combined with Hb) (Carbamino-Hemoglobin)

Voluntary control system

■ Center -Neocortex through motor cortex - Efferent through collateral fibers from Corticospinal tract - to respiratory motor neurons of the spinal cord * We can control respiration because cerebral cortex is in our control and it will control centers for short duration * Deep hyperventilation for 30s=> unconscious due to chemical regulation

Morphine Poisoning

■ Central chemoreceptors are suppressed. ■ PO2↓( when it gets <70, then peripheral chemoreceptors are activated; ■ Person starts breathing in and out, then if you administer O2, then Peripheral chemoreceptors will be suppressed (PO2 goes above 70%) causing peripheral chemoreceptors to suppress, causing death of the patient.

Patient shifted to a room with 24% CO2 AND 21% fiO2

■ Central receptors will be stimulated. ■ Ventilation will be ↑ ■ Less PO2

Pontine Respiratory Centers

■ Control the medullary respiratory centers activity ■ Two types ■ (Upper) Pneumotaxic center ■ (Lower) Apneustic center

Main parts of the Brain

■ Cortex ■ Mid Brain ■ Pons ■ Medulla ■ Spinal Cord * Respiration has 4 centers • 2 centers are in medulla • 2 centers in Pons

Dorsal Group Neurones (DRG) or Inspiratory neurons

■ DRG -produce inspiratory 'Ramp signal' -The impulses (depolarization) generated here are weak to begin with & increase steadily in a ramp fashion for about 2 seconds. Abruptly ceases for 3 seconds & then the cycle repeats again & again ■ Significance -there is a steady increase in lung volume (rather than inspiratory gasps).

Factors shift O2 dissociation curve to left (increase affinity)

■ Decrease in temperature ■ Decrease in H+ ion concentration ( pH) ■ Decrease in pCO2 level ■ Fetal Hb

Significance of dissolved form of Oxygen

■ Dissolved form determine PO2 in the blood; which in turn determine O2 combining capacity of Hb and oxygen. ■ When O2 carrying capacity of Hb is affected; as int eh case of CO poisoning, Hyperbaric O2 treatment is essential because this increases the dissolved form of O2 and provide necessary O2 for tissue * ↑ 0.3 when CO poison is treated (more O2 is supplied at higher pressure). CO poisoning cherry red color alveoli.

(P.C.V) Hematocrit

■ Fat cell volume ■ size of RBC ↑ in venous blood and if you centrifuge arterial and venous blood separately, there will be ↑ PCV in venous blood due to water going inside RBC to Cl- shift. ■ Arterial RBC is smaller in size than venous RBC

Central chemoreceptors

■ H+ Ions cannot cross Blood Brain Barrier. But CO2 crosses Blood Brain Barrier and mixes with water to become H+ ions and HCO3-. It is the H+ ions that act on the chemoreceptors ■ H+ Ions in bloos is not going to affect the central chemoreceptors * In the case of Meningitis, H+ increases and stimulate chemoreceptors.

Cl- shift

■ Happens in venous blood ■ Movement of Cl- to maintain electrical neutrality because HCO3- is moving out of RBC and this causes decreases in negativity

Pneumotaxic center

■ Located in the upper pontine region They inhibit Apneustic center (when sufficiently stimulated). ■ Significance - • control of normal rhythmic respiration by sending impulses to apneustic center -- • Its signals alter the respiratory rate • Damage of this area -respiration becomes slower & deeper (tidal volume increased)

Hemoglobin

■ Molecular weight= 68,000 ■ Consists of 4 Heme moieties conjugated with 4 polypeptide chains. ■ Each Hb molecule carry 4 molecules of O2 ( Hb4O8) ■ This oxygenation and deoxygenation are rapid reactions that require < 0.01 sec. * If all 4 SPAC

Combined form (Oxy-hemoglobin)

■ Normal Hb level= 15gm/dl ■ With full saturation (100%) O2 carrying capacity of Hb= 1.34ml/gm of Hb ■ O2 carrying capacity of 100 ml blood = 1.34 x 15= 20.1ml/dl (with 100% Hb saturation) ■ Arterial blood (PO2 of 97 mmHg) with 97.5% Hb saturation (due to physiologic shunt)= 19.8 ml/dl * 4 Oxygen per Hb molecule. As one O2 molecule binds to Hb affinity keeps ↑

Central chemoreceptors vs. Peripheral chemoreceptors

■ Normal breathing is controlled by PCO2. There are central chemoreceptors in the brain that senses H+ changes duet o change in PCO2 ■ Central chemo receptors stimulate accessory muscles to breath more to wash out CO2 ■ If PO2 goes ↓ 70, then it will act on peripheral chemoreceptors and regulate breathing. Another way O2 regulates is when FiO2 falls below 17.

2 types of ChemoReceptors

■ Peripheral - Aortic Body - Carotid Body * <70= Po2 FiO2 < 17 % ■ Central - Brain (H+) PO2, PCO2 and H+ regulates breathing. ➤ But its the PCO2 that controls breathing, changes in PCO2 are sensed by brain by way of H+ ions to ↓↑ breathing. ➤Whereas O2 controls breathing in only 2 conditions • < P70 or FiO2 <17% for O2 It acts on Aortic and Carotid body. • CO2 cannot directly stimulate chemoreceptors but will do by converting to H+.

Apneustic center

■ Present in lower pons Send stimulatory impulses to - ■ DRG thereby prevent "switch off" the ramp signal [cause prolong depth of respiration (Apneusis)] Receive impulses from - ■ Pneumotaxic center - (inhibitory) ■ Periphery (lungs) through vagus - (inhibitory)

Patient has been shifted to room with PO2= 100% Central? Peripheral? ventilation?

■ Since everything is normal, central chemoreceptors are acting on the respiration ■ Ventilation is normal because there is no changes or stimulation that can cause ↓ or ↑ in ventilation ; Hb saturation is 100%

Ventral group neurons (VRG) or Expiratory neurons

■ They are stimulated by impulses from DRG ■ They in turn inhibit DRG ■ In normal quiet respiration, their peripheral output are almost inactive ■ When sufficiently stimulated by higher respiratory drive (ventilation greater than normal), they stimulate expiratory muscles.

Regulation of Respiration

■ Three basic elements:- 1. Sensors • Chemoreceptors - central - peripheral • Pulmonary receptors • Other receptors 2. Central controller • Brain stem (Pons, medulla) • Cortex • Other parts of the brain 3. Effectors • Resp Muscles - Diaphragm - ABD muscles - Accessory muscles

Medullary Respiratory centers

■ Two groups of respiratory neurons: ✓Dorsal respiratory group neurons (DRG neurons) or I (Inspiratory) neurons. ✓Ventral respiratory group neurons (VRG neurons) or E (expiratory) neurons * DRG has pulsatile cells. They fire for 2 seconds and stops abruptly for 3sec. These innervate diaphragm. So Diaphragm contracts for 2 seconds and relaxes fro 3 sec. This firing is in a ramp fashion (Ramp signal), stepwise. Second stimulus higher than first

Chemoreceptors

■ Two types - Peripheral chemoreceptors - Central chemoreceptors - Hypoxia stimulate respiration through peripheral chemoreceptor - Through central chemoreceptors PCO2 aids in determination of normal respiratory rhythm; as it is more sensitive to central than peripheral chemoreceptors - H+ ions has got stimulatory effect on both central & peripheral chemoreceptors

Respiratory centers

■ Two types ✓ Medullary respiratory centers -contains the main components of the 'respiratory control generator' of autonomic respiration. ✓Pontine respiratory centers - control the autonomic respiration by influencing the medullary centers activity.

Control of Respiration

■ Whenever Inspiratory center is activated, Expiratory is inhibited (So when you are breathing in, you cannot expire out) and vice versa and whenever expiratory Center is stimulated, inspiratory Center is inhibited. This process is called Reciprocal innervation. ■ Apneotic center airways stimulate inspiratory center ( Breathing stops in inspiration) deep inspiration, then breathing stops ■ Pneumotaxic center inhibits apneotic center. Higher center control depth and rate of respiration through lower center (medullary) ■ Whenever Medullary (I.C) is stimulated, it stimulates Pneumotaxic center, so the RAMP signals stimulate neurotaxic center. Pneumotaxic centers in turn inhibits apneotic center so there is no stimulus from apneotic center to I.C so animal breaths in ■ EC is stimulated when animal wants to forcefully expire out and will inhibits I.C If animal wants to breath in forcefully for the longest time, inhibition from Pneumotaxic center to apneotic center will be less. This causes apneotic center to stimulate I.C longer and breathing becomes more until sufficient amount. ■ Whenever Tidal volume becomes more than 1L, lung parenchyma have stretch receptors that will sense the stretch and inhibit apneotic center

Polycethemia

■ ↑ RBC Hb Saturation: Normal (Analogy: cant fit 5 people in 4 seated car). ■ PO2: ↑ ■ Oxygen content ↑

Thyroid Hormones

▪︎ "Thyroid hormone" is 2 hormones: • T3 (triiodothyronine) & T4 (tetraiodothyronine or thyroxine) • Members of class of tyrosine hormones • Tyrosine synthesised in body, but iodine (essential trace element) must be obtained from the diet. • Iodine is deficient in the environment in some parts of the world

Circadian rhythm of secretion

▪︎ 1 major peak each 24hrs ▪︎ Related to sleep/wake cycle ▪︎ Each anterior pituitary hormone peaks at a different time.

Functional anatomy of pancreas

▪︎ 98% Exocrine - Digestive enzymes and bicarbonate - Secreted through pancreatic duct ▪︎ 2% endocrine - Peptide hormones regulating glucose and other intermediary metabolism - Secreted by exocytosis- drains into hepatic portal vein

Hypoparathyroidism

▪︎ A rare condition usually caused by autoimmune disease or inadvertant damage to parathyroids during thyroid surgery ▪︎ Deficiency of PTH secretion results in low plasma ionized calcium level ▪︎ Low ECF (Ca2+) due to hypoparathyrodisim causes increased neuromuscular excitability ( threshold for depolarization is lowered) ▪︎ Paresthesia (e.g., "Pins and needles" sensation) ▪︎ Tetany

negative and positive feedback

▪︎ A signal is continuously stimulating hormone secretion by the endocrine cell The signal could be external or constitutive - Negative feedback reduces the effect of the stimulus - Positive feedback increases the effect of the stimulus.

Actions of growth hormone

▪︎ Acute metabolic effect- "diabetogenic" actions ▪︎Long term growth effects- via IGF-1 (Somatomedin)

Beta 2 receptors

▪︎ Affinity for E> NE, so epinephrine is especially important for these responses to acute stress: ▪︎ Intestinal relaxation ( decreased motility) ▪︎ Bladder wall relaxation ▪︎ Dilation of airways ▪︎ Glycogenolysis

Function of Calcitonin

▪︎ After complete thyroidectomy with removal of all calcitonin-secreting tissue, plasma [Ca2+] remains normal provided the parathyroids are not injured. Conversely patient with a rare calcitonin-secreting tumour of the C-cells frequently have plasma calcitonin levels that are 50 to 100 times normal, yet they maintain normal plasma levels of Ca2+, Vitamin D, and PTH

Dieuresis and thirst after alcohol intake

▪︎ Alcohol inhibits ADH secretion ▪︎ Causes physiologically-inappropriate dieuresis ▪︎ Results in dehydration ( low blood volume and high ECF osmolarity) ▪︎ Dehydration stimulates ADH secretion as alcohol is cleared ▪︎ Morning thirst is stimulated through hypothalamic thirst center neurones connected to osmoreceptors.

Synthesis of adrenal cortex hormones

▪︎ All derived from cholestrol, transported in bloods as LDL ▪︎ LDL surface receptors: endocytosed and cholestertol liberated ▪︎ Modified by enzyme action, different set in each zone. ▪︎ ACTH from the anterior pituitary regulates the rate-limiting scc ENZYME ▪︎ ACTH regulates the amount of cortisol and androgens produced in the middle and inner zones ▪︎ Angiotensin II ( or elevated plasma K) regulates the amount of aldosterone produced in the outer zone.

Feedback control of anterior pituitary hormones

▪︎ All except prolactin exhibit complex feedback loops

Surfactant

▪︎ Alveolar type II cells synthesized and release a surface active material called surfactant ▪︎ Surfactant is a phospholipid and dipalmitoyl phosphatidylcholine ( DPPC) ▪︎ These molecules can reduce surface tension by reducing attractive force between water molecules

Normal arterial venous perfusion

▪︎ Alveoli - PO2= 100 ▪︎ Arterial end - PO2= 95-100 - Hb Saturation = 100% - O2 content = 20ml in 100 ml of blood oxygen is bound to all Hb in arterial blood. ▪︎ Tissues - 5ml is utilized of 100 ml of blood - PO2= 40 ▪︎ Venous - PO2= 40 - Hb Saturation= 70% - O2 content= 15ml/dl * Venous end O2 is bound to only 3 places, making it 70-75% saturation.

Significance of intra pleural pressure

▪︎ Always negative (sub-atmospheric) in normal respiration 1. Prevents collapse of alveoli 2. Prevents collapse of small air ways 3. Aids in venous return (Respiratory pump) ▪︎ In Pneumothorax when it becomes equal to atmospheric pressure -alveoli collapse

Reverse triiodothyronine (rT3)

▪︎ An isomer of triiodothyronine.

Feed Forward Mechanism

▪︎ Anticipatory responses that start a feedback loop in anticipation of a change that is about to occur ▪︎ Usually involves both endocrine and neural reflexes ▪︎ Examples: ▪︎ HEART RATE INCREASES BEFORE ACTUALLY STARTING A RACE ▪︎ INSULIN STARTS TO BE RELEASED BEFORE BLOOD GLUCOSE RISES DURING MEAL

Histologic Anemia

▪︎ Arterial End - PO2 is Normal - Hb% is Normal - O2 content is Normal ▪︎ Venous End - PO2 is ↑↑ - Hb% is ↑↑ - O2 content is Normal (20) PO2 should be 40 but here it is 100. Hb % = 100%, instead of 75%. ▪︎ Cells are not using O2. oxygen partial pressure ↑. Hb saturation is ↑ in venous end because no O2 is been utilized by cells so instead of CO2 in 3 places of Hb, it will be all O2 ( fully saturated)

Stagnant Hypoxia

▪︎ Arterial End - PO2 is Normal - Hb% is Normal (Hb bound) - O2 content is Normal (Dissolved and bound are normal) ▪︎ Tissues - 5ml utilized by tissues - 10ml utilized by stagnant ▪︎ Venous End - PO2 is ↓↓ - Hb% ↓ ↓ - O2 content ↓ ↓ ▪︎ Since blood is flowing slow, cells are utilising more blood, instead of 5ml, 10 ml of O2 is utilized. Problem is flow rate Cyanosis is present because more CO2 is bound to Hb. Hb saturation ↓ CO2 is bound more than 5mg/dl

Hypoxic Hypoxia

▪︎ Arterial End - PO2 is ↓↓eg: 80 - Hb% ↓ => eg: 80% - O2 content ↓ => 18ml ▪︎ Venous End - PO2 is ↓↓ - Hb% ↓ ↓ - O2 content ↓ ↓ * CO2 is bound to Hb more than 5% causing cyanosis ( Blueish) 2 types of Cyanosis ▪︎ Peripheral= due to cold climate ▪︎ Central = due to disease

At Point A, the air is maximum

▪︎ At Which point the air is maximum?

Blood Flow Distribution in the Lung

▪︎ At apex -Zone 1 -Minimum blood flow Capillaries pressures are close to intra alveolar pressure (flow only during systole) ▪︎ Middle -Zone 2 - Intermittent blood flow Pul. Arterial capillary pressure is > alveolar pressure both during inspiration & expiration; Pul.venules pressure is < alveolar pressure ▪︎ Bottom -Zone 3 - continuous blood flow Both arterial & venous pressure is well above alveolar pressure through out respiratory cycle

Importance of adrenal blood circulation

▪︎ Cortisol is secreted into blood in the middle and inner zones of cortex, then flows to medulla ▪︎ Elevated secretion of cortisol stimulates conversion of norepinephrine to epinephrine ▪︎ Epinephrine rises to > 80% of total catecholamines ▪︎ Its effects are stronger

Effects on nervous system development and function

▪︎ Essential for normal CNS development and function ▪︎ Replacement therapy (thyroxine) or iodine required for congenital deficiencies (cretinism) ▪︎ Fortification of table salt with iodine ▪︎ Enhances sympathetic effect - upregulates catecholamine receptors -Increases speed of nervous reflexes

Dynamic airway compression

▪︎ At low lung volume, expiratory flow is limited. ▪︎ This limitation is effort independent. ▪︎ Small airway narrowing and even closer may occur during expiration ( dynamic compression) ▪︎ Equal pressure point may develop that limits air flow. * Equal pressure point always falls at trachea ( trachea cannot collapse due to rings). + 20 pleural pressure is applying everywhere in lungs. And as alveoli losses pressure till 0 ( → pressure). There is a point where pressure inside bronchus will be same as pleura pressure (+20 in lungs and +20 in bronchus, EQUAL PRESSURE). * In Low volume, when you try to expire our forcefully intrapleural pressure goes up +20 and in lungs, elastic recoil force= +10 and both elastic and pleural force goes toward alveoli. And total alveolar pressure will be +30 and as air gets expired, the pressure decreases to 25→20→15→10 until 0.

Pressure changes during a normal respiratory cycle

▪︎ At the onset of inspiration, diaphragm and intercostals muscle being activated ▪︎ Chest wall dimensions will increased ▪︎ Pleural space pressure will decreases ▪︎ Negative intra-pleural pressure will pull the lung open ▪︎ Lung expansion create a transient negative intra alveolar pressure. ▪︎ Driving force will be created to move the air from atmosphere in to the alveoli As the air moves in the lungs and fill the expanded volume the pressure difference between the mouth and alveoli will reduce ▪︎ At the end of inspiration the differences between the alveoli and mouth pressure will be zero hence no air flow will be seen ▪︎ At the onset of expiration Inspiratory muscle will relax and lungs and chest wall will recoil back to per-inspiration position ( recoil inwards) ▪︎ A transient positive pressure will be created in the alveolar space which force the air out of the lungs ▪︎ At the end of expiration, intra alveolar pressure will be the same as atmospheric pressure hence no flow of air will be seen * Venous drainage is more during inspiration because of the negative pressure, pull the blood from periphery mainly from limbs

Insulin abuse by athletes

▪︎ Attempt to increase glycogen storage ▪︎ Inject insulin and then eat high sugar foods ▪︎ Risk of hypoglycemia and coma

Cell communication

▪︎ Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. ▪︎ Paracrine signals on neighbouring cells

Corticosteriods are used to treat

▪︎ Autoimmune diseases ▪︎ Allergic reactions * Undesirable side effects of treatment include: ▪︎ Lowered resistance to infection ▪︎ Atrophy of adrenal cortex

Relationship between arterial blood pressure and ADH release

▪︎ Baroreceptor reflex mechanism signals ADH neurons in hypothalamus ▪︎ Decrease in BP signals for ADH release.

Vitamin D

▪︎ Bioactive form is 1, 24 (OH)2 Vitamin D3 ▪︎ AKA calcitriol ▪︎ Derived from Vit D produced in skin by action of sunlight, and in some food ▪︎ from biologically inactive precursor in skin, 7-dehydrocholesterol

Signs and symptoms of hypercalcemia

▪︎ Bones - Bone pain and fractures ▪︎ Stones -Kidney stones ▪︎ Moans -Abdominal pain (peptic ulcer constipation) ▪︎ Groans -General malaise and weakness ▪︎ Psychiatric overtones - Depression, delirium, coma

Adrenal functional anatomy

▪︎ Both cortisol and androgens are secreted by fasciculata and reticularis zones ▪︎ Blood flows from glomerulosa zone to medulla

Pseudohypoparathyroidism

▪︎ Caused by a defect in the G-protein receptor for PTH ▪︎ Result is low [Ca2+], which stimulated increased secretion of PTH ▪︎ Clinical picture of low [Ca2+] resembles that of hypoparathyroidsim, even though PTH is elevated a type of secondary hyperparathyroidism

Lesion of anterior pituitary

▪︎ Causes Hyposecretion of hormone 2 which causes Hormone 3 to be low and this causes negative feedback to decrease causing Hormone 3 to decrease.

Peptide Hormones

▪︎ Chains of amino acids as short as 3 amino acids, up to very large proteins, that are relatively water soluble (hydrophilic) ▪︎Storage: - in vesicles as large prohormones ▪︎ Release: - by exocytosis ▪︎ Transport: - Soluble in blood ▪︎ Receptors: - On target cell surface membrane

Inspiration vs. Expiration Pressure difference Blood Flow

▪︎ Change during inspiration and expansion causes changes in alveoli pressure, causing changes in blood flow ▪︎ During inspiration pressure in lungs in negative, Alveolar pressure is less, so not much effect on Blood vessel. ➤ Apex ( Zone 1) ▪︎ During Expiration pressure inside Lungs ↑and alveolar pressure ↑ and blocks blood vessel flow is not continuos. During Expiration alveolar pressure is more than arterial pressure and thus less blood flow. ➤ Middle (Zone 2): ▪︎ Flow will become continuous. Alveolar pressure. Arterial pressure is greater than alveolar pressure. ➤ Base (Zone 3) Arterial pressures is higher than Alveolar pressure and venous pressure.

Biot's breathing

▪︎ Characterized by period of apnea and hyperpnea ▪︎ After apneic period , hyperpnea occurs ▪︎ Occurs only in pathological conditions affect CNS -such as meningitis

Elastic properties of chest wall

▪︎ Chest compliance can not be measured directly. However in real life chest and lung elastic forces interact with each other. ▪︎ We can measure and plot P-V curve of total system ( chest wall and lung together) by having the subject inhale to variable lung volume and then relax his muscle while the mouth pressure and volume will be recorded ▪︎ Lung P-V curve will be recorded on the same graph ▪︎The difference between the 2 gives chest P-V

Osteoporosis- 'Brittle bones'

▪︎ Condition in which bone resorption is greater than bone formation - Reduced osteoblast activity, increased osteoclast activity - Plasma calcium, phosphate, PTH, and Vitamin D levels are usually normal ▪︎ Results in reduction of bones mass ▪︎ Osteoporotic bone - L-normal; R-osteoporotic ▪︎ Estrogen inhibits bone resorption by decreasing osteoclast activity and increasing osteoblast activity - Therefore increased incidence of osteoporosis as estrogen levels fall in post-menopausal women

Negative feedback

▪︎ Control Limits responses, keeping them within normal ranges. ▪︎

Steroid Hormones

▪︎ Derived from cholestrol ▪︎ Relatively lipid soluble (lipoholic) ▪︎ Storace: -Synthesized upon signal, not stored ▪︎ Release - Diffuses out of endocrine cell down concentration gradient ▪︎ Transport - Bound to protein carrier in equilibrium with free hormone ▪︎ Receptors: - intracellular, but also surface ➤ Steroid hormones are transported in plasma bound to protein carriers, but bound and free forms are in equilibrium ➤ Only the free form is biologically active ➤ Bound form prolongs half life and buffers acute changes in secretion ( a kind of "storage")

Tyrosine (amine) hormones

▪︎ Derived from tyrosine amino acid ▪︎ Two groups: - Catecholamines - Thyroid hormones

Trans-pulmonary pressure

▪︎ Difference between intra thoracic (pleural) pressure & intra pulmonary (alveolar) pressure ▪︎ Pressure operating inner & outer wall of the alveoli ▪︎ Measure the elastic forces in the lungs

obstructive Disease

▪︎ Difficulty in expiration ▪︎ Reduced FEV1 ▪︎ Reduced FEV1/FVC ratio ▪︎ FVC variable Eg: Asthma ▪︎ Inflammation in tracheo-Bronchial tree. ↑secretion, cells becomes swollen. Inspiration is fine, But expiration is different because inflammation block expiration e.g: Emphysema. ▪︎ FEV1 is decreased in obstructive because you cannot expire out everything (Obstruction to expiration). normally 80% in first second, with obstructive patients <80% of air is expelled that they inspired. ▪︎ FVC is normal because no issue in inspiration (active process) (forceful breathing). Initially FVC is normal in chronic Obstructive patients (COPD) then gradually FVC↓

Diffusion capacity of Lung (DLCO)

▪︎ Diffusion Limited gas Exchange - The gas does not equilibrates between the capillary and the alveolar air. ▪︎ CO can never equilibrate between the alveolar air and the capillary blood, so it is used to measure the diffusion capacity of the lung (CO uptake in ml/min/mm Hg) * Only way to stop CO, if it cant diffuse across membrane anymore. * Diffusion capacity of lung is measured using CO because of its easily diffuses and its affinity Hb. *CO keeps on diffusing till end because it does not get saturated and its affinity for Hb. * Heart beats 72beats/minute and blood stays near alveoli for 0.75s.

Pulmonary Diffusion of Gas

▪︎ Diffusion depends on partial pressure of O2 in blood and does not depend on Hb bound O2 or gas. ▪︎ If Alveoli has 100 partial pressure for Oxygen and Blood then diffusion stops ▪︎ As Oxygen comes into alveoli , the PP is 100 and as it starts dissolving in blood PP of gas in Blood starts Increasing from 0 to 100 until both alveoli and blood dissolved gas reach equilibrium. Then O2 starts binding to HB in RBC, this causes decreases in dissolved O2 in blood which causes more O2 to get through alveoli to blood * In arteries, O2 decreases because thebesian vein drains into arteries (mixture of deoxygenated blood). In tissues, they are utilizing O2, so PP of O2 ↓ and releases CO2, so PP of CO2↑.

Measurement of intra pleural pressure

▪︎ Direct-- ▪︎ Indirect- Principle --pressure at lower 3rd of esophagus beneath the lungs is same as intra thoracic pressure -as esophagus also present in the thoracic cavity. ➤ Procedure - Catheter tipped with a balloon is swallowed & kept at lower 3rd of esophagus and inflate & connect the catheter with manometer.

ANEMIC HYPOXIA

▪︎ Due to decreased O2 carrying capacity of blood ➤ Causes ▪︎ Decreased number of RBC ▪︎ Decreased hemoglobin content in the blood ▪︎ Formation of altered hemoglobin

Airway Resistance

▪︎ Due to friction between molecules of flowing gas & also with walls of the tube ▪︎ Raw = (Pmouth - Palv) / V in L/sec ▪︎ Raw --Increases in obstructive type respiratory diseases ▪︎ Main site of air way resistance in normal condition is larger bronchi near trachea ▪︎ In disease condition air way resistance is increased mainly by smaller bronchioles

Variation in pulmonary blood flow due to effect of gravity

▪︎ Due to gravitation effect; from the heart level - to above BP decreases & below BP increases -- 0.7mm Hg/ cm ▪︎ Vertical dimension of lungs is 30 cm amount variation of 21mm Hg ▪︎ From heart level above to apex BP by 14 mm Hg & below to base by up to 7mm Hg ▪︎ Accordingly, blood flow to lungs can be divided into 3 zones. * Gravity causes to have different blood pressure in different lobes of lungs. If you go above heart level Blood pressure decreases and below Heart level blood increases. From Apex to Base of lung, there is nearly 21 mmHg of pressure difference. So because of gravity, lots of changes in blood flow in different parts of lungs.

Clinical problems of growth

▪︎ Dwarfism: Extreme shortness in humans with proportional body parts usually has a hormonal cause, such as growth-hormone deficiency, once called pituitary dwarfism ▪︎ Gigantism: is a condition characterized by excessive growth and height significantly above average. In humans, this condition is caused by over-production of growth hormone ▪︎ Acromegaly: is an extremely rare syndrome that results when the anterior pituitary gland produces excess growth hormone (GH) after epiphyseal plate closure at puberty.

Airway resistance

▪︎ Elastic resistance:-Resistance due to elastic nature of lungs & thoracic cage ▪︎ Non-elastic resistances are; 1. Air-way resistance 2. Non-elastic tissue resistance (Viscous resistance) * Compliance: ability to distend, increase volume Elastance: measure of tendency of a hollow organ to recoil COMPLIANCE IS INVERSELY PROPORTIONAL TO ELASTANCE • Less expansion = Less compliant * Stretching a rubber band is hard but it goes back to normal once the tension is relieved=> Elastance is higher * Stretching is easy but going back is hard => Compliance is High. Elastic resistance is due to Lung and thorax - Non-elastic=resistance when air is moving through tracheal bronchial tree and diaphragm has to push the intraabdominal wall downward ⇚ (creates resistance)

Vit D deficiency raises health risks

▪︎ Elevated risk of cancer, cardiovascular disease, autoimmune disease, multiple sclerosis, osteroporosis

Isovolume Pressure-Flow curves

▪︎ Emphysema patients do purse lip breathing when they close the lip pressure increases and tracheobronchial tree wont collapse and maintain pressure in tracheobronachial tree (Severe emphysema patients use CPAP). ▪︎ In Emphysema patients lateral traction is lost, Bronchus are slightly collapsed, alveoli broken down compared to normal. And the equal pressure points falls inside lungs. That's why emphysema patients have difficulty breathing out (pressure falls fast and equal pressure falls inside).

Principle of relaxation pressure volume curve

▪︎ First picture: Only lung wants to expand chest wall in normal position. * at 70% of TVC is normal. Equilibrium position of chest wall (its recoil equals zero). ▪︎ At total lung capacity - Elastic recoil of both lung and chest wall indirected inward, favouring decrease in lung volume

Thyroid hormones are synthesized by and stored in follicles

▪︎ Follicular cells secret thyroid hormone.

Total vital capacity in Normal vs. Restrictive vs. Obstructive

▪︎ For Total Vital Capacity, the first second is 80%. ▪︎ Restrictive: FEV1 IS NORMAL with reduced Vital capacity. ▪︎ For obstructive, breathing is normal but is taking longer time to breath out. First second, less air. Vital Capacity is normal 4.8, same as normal but FEV1 is reduced more than restrictive and Normal.

Flow-Volume Loop vs Line graph

▪︎ For Volume-flow loop, the Expiration = Flow gradually ↑ and reaches Peak Expiratory flow rate and then decreases .

Thyroid Physiology

▪︎ Functional anatomy of the thyroid ▪︎ Hormones of the thyroid: T3, T4, and calcitonin ▪︎ Diseases of the thyroid gland ▪︎ Biological effects of the hypo- and hyperthyroidism. ▪︎ Causes of goiter

Actions of GH and IGF-1

▪︎ GH causes acute metabolic effects- "diabetogenic" actions; provides "fuel" and raw materials for growth, an indirect effect on growth. -IGF-1 causes growth, a direct effect on bone and soft tissue $

4 causes of dwarfism

▪︎ Gene defect for cartilage FGF (fibroblast growth factor) receptor (achondroplasia) ▪︎ GHRH, GH, IGF-I deficiency (pituitary dwarfism) ▪︎ Unresponsive GH receptors ( Laron dwarfism) ▪︎ Hypothyroidism (cretinism) • Thyroid hormones are " permissive for action of GH)

Mechanism of beta cell insulin secretion

▪︎ Glucose transporter GLUT 2 allows rapid diffusion into beta cells ▪︎ Glucose level determines rate of glucose metabolism in beta cell • glucokinase initiates 1st step in glycolysis → generates ATP • ATP closes K+ channels → cell depolarizes → Ca2+ channels open, Ca2+ rises and insulin granules exocytosed

TS stimulates every step in thyroid hormone synthesis

▪︎ Growth ▪︎Synthesis

Hyperthyroidism

▪︎ High metabolic rate - Intolerance of heat, excessive sweating - Weight loss - Muscle wasting and weakness ▪︎ Increased nervous system activity - High heart rate, palpitations - Irritability, anxiety, inappropriate emotionality ▪︎ Bulging eyes ( exopthalmos)

Diabetes insipidus vs. D. mellitus

▪︎ High urine production is characteristic of both diseases, when untreated ➢ D. insipidus: tasteless urine ( like water) ➢ D. mellitus: sweet urine ( contains glucose)

Non-pathlogical situation

▪︎ Hormones 2& 3 will also will be low ▪︎ Negative feedback will be reduced ▪︎ So hormone 1 level goes up, then hormones 2 & 3 go up. * In non-pathological situations, negative feedback only reduces an endocrine cell's response to whatever is stimulating. In pathological situations of primary and secondary hormone hypersecretion, negative feedback can completely turn off hormone production.

Hyper and hypo-secretion of pancreatic hormones

▪︎ Hypersecretion of glucagon ➞ hyperglycemia • alpha cell tumour - glucagonoma ▪︎ Hypersecretion of insulin → hypoglycemia • beta cell tumour →insulinoma ▪︎ Overdosage of insulin in diabetics CNS effects of hypoglycemia: sweating, Pallor ↑ heart rate, anxiety , confusion, convulsions, coma

High negative feedback in Graves disease

▪︎ Hyperthyroidism due to Graves disease

Osmolarity sensors that control ADH secretion

▪︎ Hypothalamic osmoreceptor neurons detect changes in extracellular fluid osmolarity ▪︎ When ECF osmolarity rises , water shifts out of the intracellular compartment and all cells shrink due to osmotic forces ▪︎ When osmoreceptors shrink, they signal SON and PVN cells to increase ADH secretion.

Rhythmic secretion of anterior pituitary hormones (except Prolactin)

▪︎ Hypothalamic releasing hormones , their anterior pituitary hormones, and their target cell hormones exhibit circadian (diurnal) rhythms . ▪︎ These rhythms arise from intrinsic neural oscillators

Stagnant and Hypoxic cyanosis

▪︎ Hypoxias that have cyanosis ▪︎ more than 5 gm of Hb is bound to CO2 Normally 14gm/dl = Hb. For cyanosis its 10g, as its flowing to venous end there is less chance of getting 5gm/ml of out of 10 Hb getting attached with CO2. Cyanosis happens only if more than 10gm/dl gets attached.

Pulmonary Perfusion

▪︎ If pressure in alveoli is greater than arteries, it will compress the arteries and stop blood flow. ▪︎ If pressure is less in alveoli than artery then blood flows through artery, artery is open ▪︎ In erect position , alveoli are bigger in size in upper part than lower part. ▪︎ Highest Blood flow will be in the lower part due to gravity. Base have higher blood flow than Apex ▪︎ Upper part of Lung has lowest ventilation and lower part of the lung has higher ventilation. ▪︎ Alveoli is smaller in size at the base and can ventilate more. Most of the Tidal volume reach at the Base. ▪︎ Pulmonary circuit is low pressure

Vitamin D deficiency

▪︎ Impairs GI absorption of calcium ▪︎ Resulting high PTH causes bone demineralization, bones become deformable - In children, results in rickets - In adults, result is called osteomalacia

Causes of Goiter

▪︎ In hypothyroidism- due to lack of iodine in diet ▪︎ In hyperthyroidism- • Due to excess secretion of TRH and/ or TSH • In Graves disease due to autoimmune antibodies that stimulate TSH receptors ( TSI-thyroid-stimulaitng immunoglobulins)

Cortisol's permissive actions

▪︎ In the absence of cortisol, many other hormones are less effective e.g: Cortisol is necessary for epinephrine and norepinephrine to adequately constrict blood vessels. ▪︎ Without cortisol, hemorrhage and severe dehydration are more likely to result in shock.

PTH stimulates

▪︎ Movement of ionized Ca & phosphate from bone to fluid to ECF ▪︎ Bone dissolving activity of osteoclasts- an indirect action via cytokines released from osteoblasts

Biological effects of aldosterone

▪︎ Increases retention of Na+ and excretion of K+ • Kidneys, sweat glands, salivary glands, and intestine ▪︎ Aldosterone plays a role in feedback loops that control body fluid volume and osmolarity • Total body Na+ is the primary determinant of extracellular fluid volume (ECFV)- and therefore blood volume ▪︎ Thus, aldosterone has an indirect role in regulating blood pressure.

Androgens

▪︎ Insignificant amount compared to production in male testes ▪︎ Significant source of testosterone in women- important for libido and hair growth

Respiratory muscles -Inspiratory & Expiratory muscles

▪︎ Inspiratory muscles - ▪︎ Chief inspiratory muscles (operate during quite respiration) -Diaphragm & External inter-costal muscles ▪︎ Expiratory muscles -(operate only during forceful expiration) -Internal inter-costal muscles; Abdominal muscles ▪︎ Accessory respiratory muscles (operate only in forceful respiration) -Scaleni, Sternocledo-mastoid, Anterior Serati, Extensor muscles of vertebral columns * Chronic Asthma patients uses accessory muscles

Glucose uptake mechanism during exercise

▪︎ Insulin is not needed for glucose uptake in exercising muscle : muscle work causes insertion of GLUT-4 into cell membranes. -Increased cellular metabolism increases adenosine monophosphate kinase, which increases GLUT4 insertion. - During exercise sympathetic stimulation of beta cells inhibits insulin secretion and so prevents hypoglycemia.

Insulin abuse by young women

▪︎ Insulin omission is a growing problem among young women ▪︎ Young women most common diabetics admitted to hospital for diabetic keto-acidosis ▪︎ A high proportion of type 1 diabetic women ages 15-30 skip insulin injections to lose weight. ▪︎ This practice called Diabulimia ▪︎ Causes potential renal and vision damage

Roles of Pancreatic hormones

▪︎ Insuline- stimulates uptake and storage of energy ▪︎ Amylin- slows gastric emptying, inhibits digestive enzyme secretion, promotes satiety, inhibits glucagon secretion; helps to prevent post-prandial glucose spikes ▪︎ Glucagon- stimulates production of glucose by liver ▪︎ Somatostatin- general inhibition of exocrine & endocrine pancreatic secretion; acts in paracrine fashion

Elastic nature of pulmonary tissue

▪︎ Inter woven of elastin & collagen fibers like nylon stocking arrangement ▪︎ In emphysema -degradation of elastin & collagen frame work -leads to increase distensiblity ▪︎ In old age -change in physico-chemical properties of elastin & collagen -increase distensibility ▪︎ In pul.fibrosis -increase in interstitial tissue -stiffness -↓↓distensibility

Thyroid hormone synthesis V

▪︎ Intracellular enzymes separate T3 and T4 from the protein -10% is T3 - 90% is T4 ▪︎ T3 and T4 probably exit via transporters

Thoracic compliance

▪︎ Is due to Sterno-costal joints ▪︎ Normal value - 0.22L / cm H2O ■ Cannot measure directly ▪︎ If lung lost elasticity; then chest wall expand ▪︎Chest wall compliance decreases in Kyphoscoliosis; Ankylosis spondylitis; Extreme obesity * Chest wall cannot expand easily for these disease so compliance ↓.

STAGNANT HYPOXIA

▪︎ Ischemic hypoxia or circulatory hypoxia ▪︎ Congestive heart failure ▪︎ Hemorrhage ▪︎ Surgical shock ▪︎ Thrombosis

Structural & functional units of endocrine pancreas

▪︎ Islets of Langerhans - Alpha cells- secrete glucagon - D cells- secrete somatostatin - Beta cells- secrete insulin, amylin

Anti-inflammatory and immunosuppressive effects

▪︎ Limits immune responses ▪︎ Suppresses all steps in inflammation ▪︎ Destroys lymphocytes and reduces antibody production ▪︎ Effects evident at high pharmacological levels.

Blood volume sensors that control ADH secretion

▪︎ Located in low pressure, compliant ( relatively stretchable) vessels - large veins and heart atria- that accommodate blood volume changes and therefore buffer arterial pressure changes ▪︎ Sensory nerve endings detect changes in stretch of vessel and atrial walls and signal SON and PVN neurons. ▪︎ Decreased stretch causes increases ADH secretion. - A negative feedback system

HYPOXIC HYPOXIA (Hypoxemia) Causes

▪︎ Low oxygen tension in the atmospheric air: High altitude ▪︎ Respiratory disorders associated with decreased pulmonary ventilation: Hypoventilation, diffusion defects, V/Q defects

Diseases of thyroid

▪︎ Low secretion of thyroid hormones = hypothyroidism ▪︎ Excessive secretion of thyroid hormones = hyperthyroidism ▪︎ Normal secretion =euthyroidism

Opposite force ( Expansion of ribs and collapsed lungs)

▪︎ Lungs always wants to collapse, thoracic walls wants to expand both are acting opposite creating negative pressure. Another reason is lymphatic drainage that creates suction. * Intrapleural pressure

Respiratory muscle force is needed to over come the following resistances

▪︎ Lungs and chest elastic force ▪︎ Alveolar surface tension ▪︎ Airway resistance

Growth Hormone (GH)

▪︎ Modulates metabolism and body composition ▪︎ Stimulates linear growth and development via IGF-1 - GH also known as somatotorpin - IGF-1 also known as somatomedin * GH acts both directly to modulate metabolism and body composition and indirectly via IGF-1 to stimulate linear growth and development.

Hormones

▪︎ Molecules, secreted by endocrine cells into circulating blood, that act on cells that express their specific receptors. ▪︎ Hormones affect reproduction, growth, development, homeostasis, and metabolism.

Mechanism of action of peptide hormones

▪︎ Most target cells: cytoplasmic or nuclear receptors - Gene activation - Protein synthesis ▪︎ Some cells: cell surface receptors activate second messenger systems.

Ventilation

▪︎ Movement of air is less in the apex or upper part of the lungs, because alveoli is bigger in size and is limited in expansion. (cannot expand as much). ▪︎ Movement of air is higher at the base of the lungs (ventilation is more) because the alveoli's are smaller in size and can expand more.

Alveolar gas equation:

▪︎ PAO2= (Patm-47)FiO2 - PACO2/R. ▪︎ PAO2: Partial pressure of alveolar oxygen ▪︎ Patm: Atmospheric pressure at sea level 760 ▪︎ FiO2: fractional concentration, room air 0.21 ▪︎ PACO2: alveolar pressure of CO2, 40mmHg ▪︎ R: respiratory exchange ratio: CO2 produced/o2 produced per mi =0.8 ▪︎ PAO2= (760-47)0.21- 40/0.8 =100mmHg *PA= partial pressure in Alveoli Pa= arterial partial pressure PAo2= alveolar O2 PaO2= arterial O2 Water partial pressure: 47

POMC (pro-opipmelanocortin) family of anterior pituitary hormones

▪︎ POMC synthesized by anterior pituitary cells and by the liver (POMC circulates in blood) ▪︎ CRH stimulates POMC synthesis and cleaving of POMC in anterior pituitary cells to produce : - ACTH - Beta-endorphin - Gamma-lipotropin

Kidney hydroxylation enzyme is stimulated by

▪︎ PTH ▪︎ Low plasma inoized calcium ▪︎ Low plasma inoized phosphate ▪︎ Prolactin ( during pregnancy & lactation)

PTH effects on kidneys

▪︎ PTH increases renal reabsorption of calcium - and increases excretion of phosphate - prevents precipitation of Ca phosphate- "metastatic calcification". - Allows separation of control of calcium & phosphate - The control of plasma Ca is dominant over control of plasma phosphate ▪︎ PTH induces activation of Vitamin D in renal cells.

Parathyroid hormone (PTH)

▪︎ PTH synthesis & secretion stimulated by low plasma ionized Ca ▪︎ PTH raises free ionized Ca in ECF (negative feedback loop) ▪︎ Parathyroid cells sense ionized Ca and synthesize and secrete PTH

3 hormones responsible for calcium homeostasis

▪︎ Parathyroid hormone (PTH) ▪︎ Calcitonin ▪︎ 1, 25 (OH)2 Vitamin D3

ADH-Vasopressin-VPN

▪︎ Part of feedback loops that control body fluid volume and concentration ▪︎ Contributes to maintenance of arterial blood pressure in some situations ▪︎ Target cells: -Kidney- reduces urine production ▪︎ Vascular smooth muscle - causes vasoconstriction.

Partial Pressure of the Gas

▪︎ Partial pressure of a gas in fluid determined by dissolved gas molecules not by the bound molecules. ▪︎ Partial pressure of a gas in blood depend upon its solubility and Hb affinity also ▪︎ Depending on Diffusion coefficient and Solubility coefficient diffusion capacity of CO2 is about 20 times more than O2.

Circadian (diurnal) and pulsatile secretion of CRH, ACTH and cortisol

▪︎ Peak rate of secretion in early morning.

Classification by chemical nature

▪︎ Peptide hormones ▪︎ Steriord hormones ▪︎ Tyrosine (amine ) hormones

Partial Pressure

▪︎ Pressure exerted by one gas in a mixture of gases ▪︎ Partial pressure of water in the boys is 47 and never change even if you have cold or dry air ▪︎ Atm pressure at sea level =760mmHg and gradually decreases as going above sea level (e.g if you have a container at sea level with a certain amount of gas, as we go above, number of gas molecules decreases to atmospheric pressure decreases. ▪︎ Individual with partial pressure of Oxygen of 100 is dissolving more oxygen than an individual with Partial pressure of O2 at 50. ▪︎ Partial pressure of O2 and CO2 differs in inspired air vs. Alveoli because of dead space and residual volume.

Causes of Hyperparathyroidsim

▪︎ Primary hyperparathyroidsim due to hypersecreting parathyroid tumour -Hypercalcemia results from high PTH ▪︎ Secondary hyperprathyroidism due to chronic renal disease, Vit.D deficiency or PTH receptor defect causing hypocalcemia. -hypocalcemia causes high PTH production

Pressure within and around Pulmonary blood vessels

▪︎ Pulmonary capillaries are surrounded by alveolar gas ▪︎ They are therefore liable to collapse or distend depends on the transmural pressure ( pressure difference between inside and outside) ▪︎ i.e. during forced expiration alveolar pressure may rise above capillary pressure leading to collapse of the capillaries and interruption of blood flow through the lungs.

Number and affinity of insulin receptors moderate target cell responses

▪︎ Receptors are down -regulated by chronically high insulin ( resulting from chronic hyperglycemia of obesity or acromegaly) ▪︎ Affinity of receptors is decreased by excess glucocorticoids ▪︎ Result is insulin resistance. ▪︎ Receptors are up-regulated by starvation ▪︎ Affinity of receptors is increased by chronically low insulin level or adrenal insufficiency

Effect of surface tension on lung compliance

▪︎ Reduce compliance ▪︎ Increase inflation force by reducing end expiration volume ( FRC) ▪︎ Tendency to collapse the lung ▪︎ Small alveoli force the air in to the big one ▪︎ Collapse of some alveoli and over expansion of others ▪︎ Development of lung edema

Characteristic features of anemic hypoxia

▪︎ Reduced oxygen carrying capacity of the blood.- due to anemia or altered Hb ▪︎ Normal oxygen tension in the arterial blood. ▪︎ Normal rate of blood flow ▪︎ Normal utilization of oxygen by the cells.

Characteristic features of hypoxic hypoxia

▪︎ Reduced oxygen tension in the arterial blood. ▪︎ Normal oxygen carrying capacity of blood. ▪︎ Normal rate of blood flow ▪︎ Normal utilization of oxygen by the cells.

Characteristic features of stagnant hypoxia

▪︎ Reduced rate of blood flow ▪︎ Normal oxygen tension in the arterial blood. ▪︎ Normal oxygen carrying capacity of the blood ▪︎ Normal utilization of oxygen by the cells.

Characteristic features of histotoxic hypoxia

▪︎ Reduced utilization of oxygen by the cells. ▪︎ Normal oxygen tension in the arterial blood. ▪︎ Normal oxygen carrying capacity of the blood ▪︎ Normal rate of blood flow

A 62-year-old man complains to his physician that he has difficulty breathing. The following diagram shows a maximum expiratory flow-volume (MEFV) curve from the patient (green line) and from a typical healthy individual (red curve). Which of the following best explains the MEFV curve of the patient?

▪︎ Restrictive ▪︎ No Coving ▪︎ Vital Capacity is decreased ▪︎ Residual volume decreased

Elastic Resistance Properties of the LungLu

▪︎ Static pressure volume of the lung ▪︎ Hooke's law applies to a spring, elastic band and the lungs. ▪︎ For any elastic structure, the increase in length (or volume) changes directly with the increase in force. ▪︎ This linear relationship applies to normal lungs, over physiological range.

Cortisol is protective during acute stress

▪︎ Stimulates CRH/ACTH cortisol secretion ▪︎ Metabolic actions increase "raw materials" needed to response to stress.

Prolactin

▪︎ Stimulates milk production in lactating women ▪︎ Probable roles in fertility in men and women and in maintenance of immune system

Actions of Oxytocin during breast feeding

▪︎ Stimuli- sensory signals form nipples as infants suckles ▪︎ Target cells- mammary gland smooth muscle ▪︎ Stimulates ejection of milk from mammary glands during breastfeeding

Actions of OXytocin during childbirth

▪︎ Stimulus: sensory afferent signals from cervix when infant's head presses on it with each contraction ▪︎ Target cells: uterine smooth muscle ▪︎ Stimulates Labor contractions ▪︎ Each contraction causes further release of oxytocin and stronger contractions ▪︎ An example of positive feedback

Pulsatile rhythm of secretion

▪︎ Superimposed over circadian rhythm, with many short bursts of secretion in 24hours ▪︎ Pulse amplitude and frequency - rather than just amount of hormone determines repsonse ▪︎ Treatment with releasing hormones must be given in pulses

Myxedema

▪︎ Swelling of the skin and underlying tissues giving a waxy consistency, typical of patients with underactive thyroid glands. ▪︎ The more general condition associated with hypothyroidism, including weight gain, mental dullness, and sensitivity to cold.

Synthesis, secretion and action of steroid hormones

▪︎ Synthesized from cholestrol ▪︎ Diffuse down their concentration gradient out of endocrine cells into blood

Goiter

▪︎ TSH (a trophic hormone) maintains structural integrity of thyroid gland - Deficiency of causes atrophy of gland - Excess TSH produces hypertrophy and hyperplasia of follicular cells • Enlarged thyroid called goiter

Thyroid Gland

▪︎ The thyroid Gland is butterfly shaped gland, located just below the larynx

Thyroid hormone synthesis IV

▪︎ Thyroglobulin is taken back into the cell

Effects on growth and development

▪︎ Thyroid hormones are permissive for GH ( growth hormone) activity i.e., normal levels of thyroid hormones are necessary to permit GH to act on cells ▪︎ Thyroid hormone-deficient children show growth retardation (dwarfism)

Thyroid peroxidase

▪︎ Thyroid peroxidase oxidizes iodide ions so they are incorporated into tyrosine moieties of thyroglobulin; then MITs and DITs couple to make T3 and T4.

Surface area of Respiratory membrane

▪︎ Total surface of the alveoli decrease in various respiratory diseases such as emphysema, atelectasis. ▪︎ Normally some of the alveoli and capillaries are in collapsed condition and during exercise as they open increase surface area.

Thickness of Pulmonary membrane

▪︎ Total thickness of the respiratory membrane (Blood-gas barrier) is 0.5 micrometer ▪︎ Increase in pulmonary edema, pulmonary fibrosis

Ventilation-Perfusion ratio

▪︎ Two factors that determine the alveolar PO2 & PCO2 are - ▪︎ Rate of alveolar ventilation (VA) -4 liters ▪︎ Rate of alveolar perfusion (Q) -CO=5liters ▪︎ The ventilation-perfusion ratio = VA/Q = 4/5 = 0.8

Conversion & Mechanism of action of thyroid hormones

▪︎ Type 1 - 5' deiodinase (in most tissues) converts T4 to T3

T4 is converted to inactive reverse T3

▪︎ Type 3 deioidinase converts T4 to rT3 ▪︎ Ratio of rT3/T3 regulated ▪︎ rT3 increases and T3 decreases during fasting or carbohydrate restriction because type 3 deiodinase is upregulated and Type I deiodinase is downregulated ▪︎ This response to starvation conserves energy since T3 stimulates metabolism but rT3 does not.

Diabetes mellitus

▪︎ Under-secretion of or resistance to insulin results in diabetes mellitus and hyperglycemia ▪︎ Chronically high glucose damages blood vessels • Neuropathy, nephropathy, cardiovascular disease including blindness ▪︎ 2-5% od diabetic are type I (IDDM-insulin-dependent) ▪︎ 95-98% (17+ million Americans) are type 2 (NIDDM- Non-insulin dependent) * Diagnosis if repeated fasting glucose > 126mg/dl and glucose> 200 mg/dl 2hrs after oral glucose

Type 1 diabetes

▪︎ Usually develops in children , or at least before age of 40 ▪︎ Etiology: autoimmune destruction of beta cells and interference with secreting and storing insulin. ▪︎ Tx- Insulin injections, dietary control, exercise

Type 2 diabetes mellitus

▪︎ Usually in older patients - but now also being seen in overweight children ▪︎ Characterized by impaired insulin secretion and resistance of target cells to its effects. * 90% of people who develop type 2 diabetes are overweight ▪︎ Chronic over-eating → ↑blood glucose➞ ↑ insulin ▪︎ Chronic hyperinsulinemia down-regulates insulin receptors ▪︎ Result : ↓ sensitivity of target cells to insulin ("insulin resistance") ▪︎ Often associated with hypertension and hyperlipidemia - " metabolic disease" ▪︎ Treatment: dietary restriction, weight loss, exercise, medications - e.g., sulfanylureas that stimulate beta cells or metformin (Glucophage) that inhibits hepatic glucogenesis. ▪︎ Chronic insulin secretion can cause beta cell " exhaustion" then insulin injections are needed.

Control of glucagon secretion

➤ Primary control: negative feedback between alpha cells and blood glucose concentration ↓ Blood glucose → ↑ glucagon secretion ➤ Other factors ↑ secretion: ▪︎ ↑ sympathetic activity and epinephrine ▪︎ ↑ amino acids ➯ Counteracts insulin effect and prevents hypoglycaemia after high-protein, low carb meal

Mechanics of Respiration

▪︎ Ventilation -Breathing in & out of air from lungs ▪︎ Inspiration -Taking in of air -Active process ▪︎ Expiration -Given out of air -Passive process (normally) -Active process in forced expiration ▪︎ Normal respiration by ▪︎ Negative pressure breathing - [Not by --Positive pressure breathing] ▪︎ Advantage -increase venous return * 1. Force 2. Pressure changes due to muscle movement 3. Resistance as the air enter lungs • During Forceful expiration, pressure is more inside. Normal inspiration/expiration pressure is equal. • Inspiration is an active process and needs energy whereas Expiration is not because its done by recoiling of Lungs and Thoracic wall. • Contraction of Diaphragm pulls the lungs down, vertical length of thoracic increase. • External intercostal muscle pulls the ribs and sternum outward and increases antroposterior diameter. Movement of Rib causes increase in lateral diameter. These muscle movements aids in increase in Lung Volume. • • During inspiration, Muscles of inspiration acts on Thoracic cage and makes it expands antroposteriorily, laterally and also vertically, Parietal Pleura, along with visceral pleura gets pulled and lungs expand. The pressure inside becomes negative compared to atmosphere -> This causes air to come inside and both atmospheric and intrapleural pressure becomes same. Then recoil of lungs happens, collapses of lungs, ↑ pressure in lungs, then air comes out

Alveoli and surfactant

▪︎ Water molecule (alveolar fluid) attract to each other and makes alveoli collapse. Surfactant prevent collapse. • Alveoli have both hydrophobic on one end and hydrophilic on other end. * The middle part is always dry (air space) to prevent pulmonary edema). * Prevents Surface tension by making hydrophobic end of surfactant goes to center and hydrophilic end

Ventilation/Perfusion Distribution in the Lung

▪︎ When VA is normal & Q is also normal =VA/Q is normal ▪︎ When VA/Q is below normal Physiological shunt is increased ▪︎ When VA/Q is above normal Physiological dead space is increased * Tuberculosis is seen in Upper zone of Lung because there is less ventilation. Large alveoli in upper zone dont move much and air will stay there for long time.

Periodic breathing

▪︎ When breathing is non-rhythmic & irregular, it is said to be periodic breathing ▪︎ Two types ➯ Cheyne-Stoke breathing -Regularly irregular type of periodic breathing. ➯ Biot's breathing -Irregularly irregular type of periodic breathing

Positive Feedback

▪︎ control continues until stopped by an "explosive event"

Major effects of glucagon on fat and carbohydrate metabolism are opposite those of insulin

▪︎ ↑ blood glucose by ↑ liver gluconeogenesis and glycogenolysis ▪︎ ↑ blood fatty acids and ketone bodies by ↑ production in liver and adipocytes: • ↑ Lipolysis and metabolism of fatty acids to ketones

The posterior pituitary

▪︎Hypothalamic nuclei are clusters of neuronal cell bodies ▪︎ Posterior pituitary hormones are synthesized in neurones of the SON and PVN.

Normal Respiration

➤ During inspiration - ▪︎ By operation of respiratory pump (Muscle Force)—Thorax expand -along with Lungs also expand- ▪︎ Decrease pressures in thoracic cavity ▪︎ By over-coming resistance ▪︎ Rushing of air from atmosphere through the respiratory tract into lungs ▪︎ Till intra-pulmonary & atmospheric pressure equal ➤ During expiration - (cessation of inspiratory activity) ▪︎ By elastic recoiling - Thorax assumes its original position -Lungs get compressed - ▪︎ Thoracic cavity pressure rises ▪︎ Air goes out (through the same routes) -till the air pressure between intra-pulmonary & atmospheric are equal ▪︎ Hence normal expiration is passive process

Forced Vital Capacity in unit time (FVC) or Forced Expirarory volumes.

➤ FEV1- 80 to 85% (Ist second) ➤ FEV2- 90 to 95% (2nd second) ➤ FEV3- >97% (3RD second) ▪︎ These are used to differentiate Restrictive vs. Obstructive. ✓ FEV1=Forced Expiratory Volume Amount of air breath out forcefully after deep inspiration in 1st second * Deep inspiration- FVC ✓ FEV2= 2nd Second

Factors affecting surfactant

➤ Factors ↓ surfactant - 1. Occlusion of main bronchus 2. Occlusion of pulmonary artery 3. Long-term inhalation of 100% O2 4. Cutting of both vagi 5. Cigarette smoking ➤ Factors ↑ surfactant - 1.Thyroid hormone - ↑ production 2. Glucocorticoids - accelerate maturation (IRDS)

Pleura

➤ Have visceral & parietal pleural layer ➤ Space in between- Pleural space ➤ Filled with fluid -Pleural fluid (2ml) ➤ Intra pleural pressure- negative pressure of minus 2mm Hg (-5 cm H2O)- due to opposite recoil effect of lungs & chest • By introducing Fluid or air, you can separate Visceral layer from Parietal layer • Parietal Layer is attached to chest wall • During inspiration, parietal pleura is pulled by muscles of chest wall, creating negative pressure in pleural cavity. This expands lungs

In which zone ventilation is wasted?

➤ In Zone 1, ventilation is higher compared to perfusion, air here is not participating in gas diffusion. air gets wasted (dead space) ➤ If Dead Space is present pathologically, this dead space and anatomical dead space is called PDS ( Physiological dead space).

Pleural Effusion

➤ Increase of pleural fluid volume ➤ Due to - Blockage of Lymphatic channels - Cardiac failure - Decrease plasma colloidal osmotic pressure - Infection & inflammation leads to breakage of Pulmonary capillaries

Factors influencing secretion of insulin

➤ Insulin secretion increased by: • ↑blood amino acid level (arg, leuc, lys) • ↑blood FFA level (minor effect) • Entry of glucose into small intestine stimulates secretion of GI hormones called incretins: • GIP (glucose-‐dependent insulinotropic peptide) • GLP‐1 (glucagon‐like peptide‐1) •↑parasympati activity ➤ Insulin secretion of inhibited by: -Somatostatin (paracrine, from delta cells) ▪︎ ↑ sympathetic activity & epinephrine ( alpha 2 receptors) • Appropriate response during exercise or acute stress • Ensures glucose supply to brain and active muscle.

Nerve supply- Autonomic Nervous system

➤ Parasympathetic nerve (Vagus)- Broncho-constriction • Stimulus--- Irritant chemicals (SO2, NO2, CO, Lead, Hydrocarbon), cool air, Exercise, leukotrines. • Normal Bronchiole tone by parasympathetic nerve - exhibits circadian rhythm-- Max constriction at 6am & dilation at 6pm ➤ Sympathetic • 𝛃2 adrenergic receptor- broncho-dilation & secretion • Alpha adrenergic receptor -decrease secretion • Vasoactive Intestinal peptide, VIP (receptor are also present)- Broncho-dilation • Histamine-Broncho-constiction.

Pressure of Thoracic Cage

➤ Two types of pressures 1. Intra-Pleural pressure (Or) Intra-Thoracic pressure (Pressure between two pleura) 2. Intra-Alveolar pressure (Or) Intra-Pulmonary pressure (Pressure in the lungs -alveoli) * Intrapleural pressure is always negative (-4) because the lungs has tendency to collapse and thoracic wall have tendency to expand (because of its attachments). Lung and thoracic wall are held together by parietal and visceral pleura and it will not allow lungs to collapse or thoracic wall to expand; they balance each other. This balancing causes negative pressure.