What circulations does lung have?
High-pressure lowflow circulation, and a low-pressure high flow circulation
What does high pressure low flow circulation supply?
It supplies systemic arterial blood to trachea, bronchial tree, supporting tissues of lung and outer coats (adventitia) of pulmonary arteries and veins
Low pressure high flow-circulation supplies what?
Venous blood from all parts of body to alveolar capillaries hwere oxygen is added and carbon dioxide is removed
What does the pulmonary artery receive its blood from?
From right ventricle (arterial branches carry blood to alveolar capillaries for gas exchange and pulmonary veins return blood to left atrium to be pumped by left ventricle through systemic circulation)
What does the pulmonary artery divide into?
Right and left main branches that supply blood to the two respective lungs
Tell more about the pulmonary vessels?
Pulmonary artery has a wall thickness one third that of aorta, pulmonary arterial branches are short and all pulmonary arteries have larger diameters than their counterpart systemic arteries
What does pulmonary arterial tree have?
A large compliance, averaging almost 7 ml/mm Hg, which is similar to that of entire systemic arterial tree
What does the large compliance of pulmonary arterial tree allow?
It allows the pulmonary arteries to accommodate the stroke volume output of right ventricle
What about the pulmonary veins?
They are like pulmonary arteries short, and empty their effluent blood into left atrium
How does blood also flow to the lungs?
Through small bronchial arteries that originate from systemic circulation (this bronchial arterial blood is oxygenaatd blood, in contract to partially deoxygenated blood in pulmonary arteries)
Bronchial arterial blood supplies what?
It supplies the supporting tissues of the lungs, including connective tissue, septa and large and small bronchi, and after it passes through supporting tissues, it empties into pulmonary veins and enter left atrium
Where are lymph vessels present?
In all supporitve tissues of the lung, beginning in the connective tissue spaces that surround the terminal bronchioles, coursing to the hilum of the lung, and then mainly into right thoracic lymph duct
What is the systolic pressure in right ventricle of normal human?
25 mm Hg
What is the diastolic pressure averaging in normal human in right ventricle?
About 0 to 1 mm Hg
Whaat happens during systole?
The pressure in the pulmonary artery is equal to pressure inr right ventricle (25 mm Hg)
What happens after the pulmonary valve closes at end of systole?
The ventricular pressure falls precipitously, whereas the pulmonary arterial pressure falls more slowly as blood flows through capillaries of lungs
What does systolic pulmonary arterial rpessure normally average?
About 25 mm Hg in human being, and idastolic pulmonary arteiral pressure is about 8 mm Hg, and mean pulmoonary arterial pressure is 15 mm Hg
What is the mean pulmonary capillary pressure?
It is about 7 mm Hg
What is the mean pressure in left atrium and major pulmonary veins?
About 2 mm Hgi n recumbent human being, varying from as low as 1 mm Hg to as high as 5 mm Hg
How can the left atrial pressure be sstimated?
By pulmonary wedge pressure (inserting a catheter through peripheral vein to right atrium, into one of small branches of pulmonar yartery, pushing catheter until it wedges tightly in the small branch)
What is the wedge pressure about?
5 mm Hg (this wedge pressure is usually only 2 to 3 mm Hg greater than elft atrial pressure) when left atrial pressure rises to higih values, the pulmonary wedge pressure also rises
In what ways can wedge pressure be used?
To study changes in pulmonary capillary pressure and left atrial pressure in patients with congestive heart failure
What is the blood volume of lungs about?
About 450 milliliters, about 9% of total blood volume of entire circulatory system, approximately 70 milliliters of this is in pulmonary capilaries and remainder is divided between pulmonary arteries and veins
Quantity of blood in lungs can vary, but what happens when blowing a trumpet?
As muchas 250 milliliters of blood can be expelled from pulmonary circulatory system into systemic circulation, (also loss of blood from systemic circulation by hemorrhage can be partly compensated for by the automatic shift of blood from lungs into systemic vessels)
What happens due to failure of left side of heart or increased resistance to blood flow through mitral valve due to mitral stenosis or mitral regurgitation?
It causes blood to dam up in the pulmonary circulation, sometimes increasing the pulmonary blood volume as much as 100 percent % and causing large increases in pulmonary vascular pressures
What is blood flow through the lungs?
It is equal to cardiac output (therefore factors that control cardiac output such as peripheral factors also control pulmonary blood flow)
What happens when concentration of O2 in air of alveoli decreases below normal?
Adjacent blood vessels constrict, with vascular resistance increasing more than fivefold at extremely low O2 levels
What about the standing position at rest?
There is little flow in the top of lung, but about five times as much flow in the bottom, the lung is divided into three zones, and in each zone the patterns of blood flow are quite different
What happens in zone 1 (no blood flow during all portions of cardiac cycle)?
Because local alveolar capillary pressure in that area of lung never rises higher than the alveolar air pressure during any part of cardiac cycle
What happens in zone 2 (intermittent blood flow)?
Only during peaks of pulmonar yarterial rpessure because systolic pressure is then greater than alveolar air pressure, but diastolic pressure is less than alveolar air pressure
What happens in zone 3 (continous blood flow)?
Because the alveeolar capillary pressure remains greater than alveolar air pressure during entire cardiac cycle
When does zone 1 blood flow occur?
Only under abnormal conditions (when either pulmonary systolci arterial pressure is too low or alveolar pressure is too high to allow flow) , severe blood loss can be one cause
What happens during exercise?
Blood flow through all parts of lungs increases (because pulmonary vascular pressures rise enough during exercise to convert lung apices from a zone 2 pattern into a zone 3 pattern of flow)
During heavy exercise, blood flow through lungs may increase fourfold to sevenfold, this extra flow is accommodated in lungs in what three ways?
1) increasing number of open capillaries 2) distending all capillaries and increasing rate of flow through each capillary more than twofold 3) increasing pulmonary arterial rpessure
Left atrial pressure in healthy person never rises what?
About +6 mm Hg
When can the left atrial rpessure rise from 1 to 5 mm Hg all the way up to 40 to 50 mm Hg?
When the left side of heart fails, blood begins to dam up in left atrium, the rise in atrial pressure up to 7 mm Hg has little effect on pulmonary circulatory function, but greater than 7 or 8 mm Hg can cause increased load on right heart
Any increase in left atrial pressure above 7 or 8 mm Hg increases what?
Increases capillary pressure almost equally as much and above 30 mm Hg causing increases in capillaruy pressure and pulmonary edema will develop
What are alveolar walls lined with?
With many capillaries, so that many capillaries almost touch one another side by side, therefore it is often said that the capillary blood flows in the alveolar walls as a sheet of flow, rather than in individual capillaries
What can measure pulmonary capillary pressure?
Isogravimetric measurement of pulmonary capillary pressure, giving a value of 7 mm Hg (this value is probably correct because mean left atrial pressure is about 2 mm Hg and mean pulmonary arteril pressure is only 15 mm Hg, so that is the mean value)
What happens when cardiac output is normal?
Blood passes through pulmonary capillaries in about 0,8 second, when cardiac output increases this time can shorten to as little as 0,3 second
What are the differences between lung capillary membranes and peripheral tissues quantitatively (because qualitatively they are the same)?
Pilmonary capillary pressure is low (7 mm Hg), capillary pressure in peripheral tissues is about (17 mm Hg)
What are the differences between lung capillary membranes and peripheral tissues quantitatively (because qualitatively they are the same)?2
Interstitial fluid rpessure in lung is slightly more negative than that in peripheral subcutaneous tissue
What are the differences between lung capillary membranes and peripheral tissues quantitatively (because qualitatively they are the same)?3
Colloid osmotic pressure of pulmonary interstitial flud is about 14 mm Hg, in comparison with less than half this value in peripheral tissues
What are the differences between lung capillary membranes and peripheral tissues quantitatively (because qualitatively they are the same)?
Alveolar walls are extremely thin, and alveolar epithelium covering alveolar surfaces is weak that it can be ruptured by positvie pressure in intertitial spaces grater than alveolar air pressure
What does the mean filtration rpessure +1 mm Hg tell us?
This filtration pressure causes a slight continual flow of fluid from pulmonary capillaries into interstitial spaces and, except for a small amount that evaporates in alveoli, this fluid is pumped back to circulation through pulmonary lymphatic system
What keeps the alveoli from filling with fluid under normal conditions?
Whenever extra fluid appears in alveoli, it will simply be sucked into the lung interstitum through small openings between alveolar epithelial cells, the excess fluid is then carried away through pulmonary lympahtics keeping the alveoli dry
What is causing pulmonary edema?
Left sided heart failure or mitral valve disease OR 2) damage to pulmonary blood capillary membranes by infectiosn such as pneumonia or noxious substances causing leakage of plasma proteins and fluid out of capillaries and into both lung interstitial spaces and alveoli
Pulmonary capillary pressure must do what in order to cause pulmonary edema?
Pulmonary capillary pressure must rise from normal level of 7 mm Hg to more than 28 mm Hg to cause pulmonary edema, giving an acute safety factor agianst pulmonary edema of 21 mm Hg
Total amount of fluid in each pleural cavity is what?
ONLY a few milliliters, and when the quantity becomes more than barely enough to begin flowing in the pleural cavity, the excess fluid is pumped away by lymphatiec vessels opening from pleural cavity to 1) mediastinum 2) superior surface of diaphragm 3) lateral surfaces of parietal pleura
What about the pleural space?
It is the space between parietal and visceral pleurae and is called a potential space because it normally is so narrow that it is not obviously a physical space
What is keeping the lungs expanded?
A negative force on outside of lungs
What is pleural effusion?
It is analogous to edema fluid in the tissues and can be called edema of pleural cavity
Which are the causes of pleural effusion?
They are the same as the causes of edema in other tissues including 1) blockage of lymphatic rainage from pleural cavity 2) cardiac failure 3) greatly reduced plasma colloid osmotic pressure 4) infection or any other cause of inflammation of the surfaces of pleural cavity, which increases permeability of capillary membranes and allows rapid dumping of both plasma proteins and fluid into the cavity
When is energy stored as fat?
When a person is overfed and energy intake exceeds expenditure
When does starvation occur?
When energy intake is insufficient to meet the body's metabolic needs
What is 4.1 Calories?
Energy liberated from each gram of carbohydrate as it is oxidized to CO2 and water
Describe the proportion of the carobhdyrates and so on in food?
Carbojhydrates are in vegetable and grain, proteins and arbohydrates are mixed in watery media
What is the average daily requirement for proteins?
30 to 50 grams
What are partial proteins?
Proteins that have inadequate quantities of certain essential amino acids and cannout be used to replace degraded proteins
What is kwashiorkor?
Individuals who consume cornemal as principal source of protein, which is a protein-deficiency syndrome
What does it mean protein spareres?
Carbohydrates and fats are protein sparers because all body's energy is derived fro mthese two components
What happens during state of starvation?
Body's protein stores are consumed instead
What is respiratory quotient?
Ratio of carbon dioxide production to oxygen utilization, which can be used to estimate fat and carbohydratae utilization
What is the respiratory quotient for metabolism of fat averaging?
0,70
What is the average respiratory quotient when proteins are oxidizied by cells?
0,80
What happens immediately after a mixed meal containing carbohydrates, proteins and fats?
Respiratory quotient approaches 1.0
What happens about 8 to 10 hours after a meal?
Respiratory quotient approaches that for fat metabolism which is about 0,70
What happens in untreated diabetes mellitus?
Little carbohydrate can be used, therefore respiratory quoteint remains near that for fat metabolism which is 0,70
What happens with nitrogen of protein during digestion?
During metabolism of protein, about 90% of nitrogen is excreted in urine in form of urea, uric acid, creatinine,
What does it mean that a person has a negative nitrogen balance?
His or her body stores of protein are decreasing daily
What is needed for stability of body's total amss and composition?
It requries that energy intake match energy expenditure
In athletes and laborers, energy expenditure for high level of muscle activity may be what?
6000 to 7000 Calories per day, compared with only bout 2000Calories per day for sedentary individuals(thus a largrge energy expenditure needs increase in caloric intake)
What does hypothalamus contain?
Hunger and satiety centers
Which neuronal centers of hypothalamus participate in contorl of food intake?
Lateral nuclei of hypothalamus (serving as a feeding center) and stimulation of this areas causes an animal to eat voraciously (hyperphagia)
What happens when there is a destruction of lateral hypothalamus?
It causes lack of desire for food and inanition, weight loss, muscle weakness and decreased metabolism
What does ventromedial nuclei of hypothalamus serve as?
As a major satiety center, sensing of nutritional satisfaction that inhibits feeding center (aphagia-animal refuses to eat)
What happens with destruction of ventromedial nuclei?
It causes voracious and continued eating (obesitey)
What also play a role in regulating food intake?
Paraventricular, dorsomedial and arcuate nuclei of hypothalamus
What does lesion of paraentricular nuclei cause?
Excessive eating
What does lesions of dorsomedial nuclei do?
It depress eating behavior
What does hypothalamus receive+
1) neural signals from GI tract providing sensory information about stomach filling 2)chemical signals from nutrients in blood (glucose, amino acids signify satiety) 3) signals from GI hormones, 4) signals from hormones released by adipose tissue and 5) signals from cerebral cortex (sight, smell and taste)
What are orexigenic substances?
They stimulate feeding
What are anorexigenic substances?
Inhibit feeding
Which are two distinct types of neurons in arcuate nuclei of hypothalamus that are important as controllers of both appetite and energy expenditure)
1) POMC neurons producing alpha-melanocyte-stimulaating hormone (alpha-MSH) together with cocaine- and ampheatmine-relate transcript (CART) and 2) neurons that produce orexigenic substances neuropeptide Y (NPY) and agouti-related protein (AGRP)
What happens with activation of POMC neurons?
It decreases food intake and increases energy expenditure
What happens with activation of NPY-AGRP neurons?
They have opposite effects, increasing food intake and reducing energy expenditure
What regulates appetite?
Leptin, insulin, CCK and ghrelin
What do POMC neurons release?
Releases alpha-MSH, which then acts on melanocortin receptors in neurons of paraventricular nuclei
Given examples of orexigenics?
Neuropeptide Y and Ghrelin)
What is regulation of quantity of food intake divided into+
Short-term regulation (concerned with preventing overeating at each meal) and long-term regulation (concerned with maintenance of normal quantities of energy stores in body)
What inhibits feeding?
When Gi tract becomes distended, stretch inhibitory signals are transmitted by vagi to suppress feeding centers, thereby reducing desire for food
What does CCK has as a role?
It activates receptors on local sensory enrves in duodenum, sending messages to brain via vagus nerve that contribute t o satiation and meal cessation
What is Peptdie YY (PYY)?
It is secreted from GI tract, especially from ileuum and colon, it has an unclear function
What is glucaogn-like peptide (GLP)?
Presence of food in intestines stimulates them to secrete GLP, which enhances insulin production from pancrea, and both GLP and insulin suppress appetite
GLP an insulin tend to do what?
To suppress appetite
What does ghrelin increase?
It increases feeding (blood elvels of ghrelin rise during fasting, peak just before eating and fall rapidly after a meal)
What happens if we give food to an animal which has been starving a lot?
It eats greater quantity than does an animal that has been on a regualt diet
What causes hunger?
A decrease in blood glcusoe concentration
What effect does temperature have on food intake?
When an animal is exposed to cold, it icnrease feeding, when it is exposed to heat, it tends to decresae its caloric intake (increased food intake in a cold animal increases its metabolic rate and provides increased fat for inulation, both of which tend to correct the cold state
From what is leptin released?
From adipocytes
Describe leptin?
When amount aof adipose tissue increases, adipocytes produce increased leptin, released into blood, circulating to breain, occupying leptin receptors in hypothalamus
What does stimulation of leptin receptors cause?
Decrease fat storage including 1) decreased production in hypthalamus of appetite stimulaors such as NPY and AGRP),2) activation of POMC neurons, causing release of alpha-MSH
What does stimulation of leptin receptors cause?
3)increased producton in hypothalamus of substances such as corticotropin-releasing hormone decreasing food intake 4)increased sympathetic nerve activity 5) decreased insulin secretion which decreases energy storage
What does leptin resistance mean?
Leptin receptors or postreceptor signaling pathways activated by leptin may be resistant to activation by leptin in obese people, who continue to eat despite having high levels of leptin
What drugs have been used for decreasing the degree of hunger?
Amphetamines, phentermine, topiramate (which can be dangerous aswell), and lorcaserin which activates serotonin receptors in brain and promotoes increased POMC expression
What is anorexia?
It is a reduction in food intake caused by diminished appetite
What is anorexia nervosa?
An abnormal psychic state in which a person lsoes all desire for food and even becomes nauseated by food, as a result ,svere inanition occurs
What is cachexia?
A metabolic disorder of increased energy expenditure elading to weight lsos greater than that caused by reduced food intake alone (anorexia and cachexia often occur together in cancer)
What can also cause anorexia and cachexia?
Several inflammatory cytokines, including tumor necrossi factor-alpha, interleukin-6, interleukin-1Beta and proteolysis-inducing factor
What effect does starvation have on the food stored of the body?
Quantity of carbohydrate stored in entire body is only a few hundred grams, so progressive depletion of tissue fat and protein occurs more, until most of fat stores in body are gone
What three phages does protein undergo during depletion during starvation?
Rapid depletion at first, followed by slowed depletion and finally rapid depletion shortly before death
What can the ketone bodies do+
They can cross blood-brain barrier like glucose, therefore about two thirds of brain-s energy is derived from ketone bodies principally from Beta-Hydroxybutyrate
What about vitamin deficincies in starvation?
Starvation of some vitamins, especially water-soluble vitmains, vitamin B group and vitamin C do not last long during starvation (can lead to death)
What is scurvy?
Absence of vitamin C in diet can cause symptoms within a few weeks and cause death from scurvy
In what form does vitamin A occur in animal tissues?
As retinol
What does vitamin A deficiency cause?
It causes night blindness and abnormal epithelial cell growth
What is one basic function of vitamin A?
It is its use in formation of retina pigments of eye, itamin A is needed for formation visual pigments and therefore to prevent night blindness
How does vitamin A deficiency manifest itself?
1)scaliness of skin and acne 2) failure fo growth of young animals 3) failure of reproduction 4) keratiniziation of corena
What more hapepns in vitamin A deficiency?
Damaged epithelial structures become infected (e.g. conjunctivate of eyes, linings of urinary tract and respiratory apssage)
What can thiamine defiiency cause?
Degeneration of myelin sheaths of nerve fibers, and also fiber tracts in cord can degenerate to such as extend that paralysis occasionally ersults
What happens with a severe thiamine deficiency?
Cardiac failure because of weakened cardiaca muscle, but also peripheral edema and ascites
What can thiamine deficiency lead to (GI tract)?
Indigestion, severe constipation, anorexia, gastric atony and hypochlorhydria
What happens with a deficiency of niacin?
Normal rate of dehydrogenation cannot be maintained, therefore oxidative delivery of energy from foodstuffs to functioning elements of all cells cannot occur at normal rates
What more happens with niacine deficiency?
Pellagra and black tongue (pellagra is exacerbated in people on a corn diet because orn is deficient in amino acid tryptophan, which can be converted in limitied quantities to niacin in body)
What does deficiency of ribovlavin cause?
Severe dermatitis, vomiting ,diarrhea, muscle spasticity
How does niacin occur?
It is also called nicotinic acid and is in the form of NAD and NAD phosphate
What is the other name for riboflavin?
Vitamin B2
Cobalt atom of vitamin B12 (related) has what role?
It combines reversibly with other substances
What does vitmain B12 deficiency cause?
Pernicious anemmia (a type of anemia caused by failure of red blood cell maturation when vitamin B12 is deficient)
What is the funtion of vitamin B12?
To act as a coenzyme for reducing ribonucleotides to deoxyribonucleotides, 1) promotoion of growth and 2) promotion of red blood cell formation and maturation
What can vitamin B12 defieincy cause?
Demyelination of large nerve fibers of spinal cord
What is the cause of vitamin B12 deficiency?
Deficeicny of formation of intrinsic factor, which is normally secreted by parietal cells of gastric glands and is essential for absorption of vitamin B12 by ileal mucosa
Describe folic acid (pteroylglutamic acid)?
It functions as a carrier of hydroxymethyl and formyl groups, and is part in the synthesis of purines and thymine, which are required for DNA formation
What is one of the significant effects of folic acid defiency?
Development of macrocytic anemia (almost identical to that which occurs in pernicious anemia)
Dietary lack of pyriodxine can casue what?
Dermatitis, decreased rate of growwth, development of atty liver, anemia and evidence of mental deterioration
Pantothenic acid is incorportated in the body into what?
coenzyme A (CoA), which has many metabolic roles in the cells such as 1) conversion of decarboxylated pyruvic acid into acetyl-CoA before its entry into citric acid cycle and 2) degradation of fatty acid molecules into acetyl-CoA
What can lack of pantothenic acid lead to?
It can lead to depressed metabolism of carbohyrates and fats
What can deficieincy of pantothenic acid lead to?
Retarted growth, failure of reproduction, graying of hair, dermatitis, fatty liver and hemorrhagic adrenocortical necrosis
What does ascorbic acid deficiency lead to?
Weakening of collagen fibers throughout body
What is ascorbic acid essential for activating?
The enzyme prolyl hydroxylase, which promotoes hydroxylation st ep in formation of hydroxyproline
What does scurvy lead to?
It leads to failure of wounds to heal, which is caused by failure of cells to deposit collagen fibrils and intercellular cement substances
What does lack of ascorbi acid also cause?
Cessation of bone growth
What happens with blood vessels in persons with scurvy?
Blood vessel walls become extremely fragile because of 1) failure of endothelial cells to be cemented together properly and 29 failure to form collagen fibrils normally presentin vessel walls, so capillaries are to rupture
What does vitamin D do?
It increases calcium absorption from gastrointestinal tract and helps control calcium deposition in bone
What can lack of vitamin E cause?
Degeneration of germinal epithelium in testis and therefore can cause male sterility, lack of vitamin E can also cause resopriton of a fetus after conception in female, so vitamin E is sometimes caleld antisterility vitmain
What is the protective role of vitamin E?
Prevention of oxidation of unsaturated fats
What is magnesium required for?
As a catalyst for many intracellular enzymatic reactions, particularly those related to cabrohydrate metabolism
What does increased extracellular concentration of magnesium do?
It depresses nervosu system activity, as well as skeletal muscle contraction
What can phosphates do?
They have the ability to combine reversibly with coenzyme systems and with multiple other compiunds that are necessary for operation of metabolic processes, for example phosphocreatine, adenosine triphosphate
In what form is iron in the body+
It is in the form of hemoglobin, iron is absolutely essential for both transport of oxygen to tissues and operation of oxidative systems within tissue cells, without which life would cease within a few seconds
What is a trace element?
Elements that are present in body in small quantities
What is iodine essential for?
For formation of thyroxine and triiodothyronine
What is zinc integral part of?
Carbonic anhydrase, lactic dehydrogenase, and peptidases
What effect does fluorine have?
For formation of teeth during period of life, suppressing cariogenic process
What is fluorosis?
Excessive intake of fluorine, which manifests in mild state by mottled teeth and in more severe state by enlarged bones
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