Pbl Exam 1 Case 1

Front 1

1. Metabolic disorders

Back 1

1. Reactions are catalyzed by enzymes
2. Enzymes are proteins
3. Proteins are coded for by genes
4. Genes can be mutated
5. Most enzymes are produced in mild excess
6. One good gene is usually sufficient
7. Defective genes can persist in populations

Front 2

2. Classes of Metabolic disorders

Back 2

1. Carbohydrate disorders
2. Amino acid disorders
3. Lipid disorders
4. Organic acid disorders
5. Urea cycle defects
6. Energy production defects
7. Transport defects

Front 3

3. Prevalence of metabolic disease

Back 3

1. Over 350 different inborn errors of metabolism have been described
2. 1 / 2,500 births or 10% of all monogenic conditions in children
3. Although individual metabolic disorders are rare, their overall direct and indirect contribution to morbidity and mortality is substantial

Front 4

4. Inheritance of metabolic defects

Back 4

Most disorders are inherited in an autosomal recessive pattern.

The carrier state is usually not associated with morbidity.

Carrier and diagnostic testing are becoming widely available for many disorders.

Front 5

5. Types of metabolic processes that cause disorders

Back 5

1. The pathological effects of the pathway blocked (e.g. absence of the end product)
2. Different functional classes of proteins (receptors, hormones)
3. Associated cofactors
4. Pathways affected (glycolysis, citric acid cycle)

Front 6

6. Carbohydrate metabolism

Back 6

Metabolized into three principal monosaccharides:
1. Glucose
2. Galactose
3. Fructose

Galactose and fructose are converted to glucose before glycolysis. The failure to effectively utilize these sugars accounts for the majority of inborn errors of carbohydrate metabolism

Front 7

7. Classical galatosemia

Back 7

1. Most common carb defect (1/55,000)
2. Galactose 1-phosphate(GAL-1-P) uridyl transferase
3. 11 exons, 4 kb, most same missense mutation in exon 6
4. Cannot convert galactose to glucose efficiently
5. Alternative pathways to galactitol and glactonate
6. Pathophysiology not well understood

Front 8

8. Galactosemia symptoms

Back 8

1. Failure to thrive
2. Hepatic insufficiency
3. Cataracts
4. Developmental delay
5. In long term, poor growth and mental retardation
6. Screening by checking blood for enzyme activity, dietary restriction of galactose

Front 9

9. Fructose metabolism defects

Back 9

1. Deficiency of hepatic fructose-1-phosphate
2. Hereditary fructose intolerance (HFI)
3. Deficiency of hepatic fructose 1,6-bisphosphatase (FBPase)

Front 10

10. Deficiency of hepatic fructose-1-phosphate

Back 10

Caused by mutations in the gene encoding hepatic fructokinase.

This enzyme catalyzes the first step in the metabolism of dietary fructose, the conversion to fructose-1-phosphate.

Inactivation of hepatic fructokinase results in asymptomatic fructosuria

Front 11

11. Hereditary fructose intolerance (HFI)

Back 11

Caused by a deficiency of fructose 1,6-bisphosphate aldolase in the liver, kidney cortex and small intestine.

Those affected are asymptomatic unless they ingest fructose or sucrose (a sugar composed of fructose and glucose)

Results in poor feeding, failure to thrive, hepatic and renal insufficiency and death.

Front 12

12. Deficiency of hepatic fructose 1,6-bisphosphatase (FBPase)

Back 12

Causes impaired gluconeogenesis, hypoglycemia, and sever metabolic acidemia (serum pH less than 7.4).

Front 13

13. Glucose disorders

Back 13

Abnormalities of glucose metabolism are the most common errors of carbohydrate metabolism

Disorders with elevated levels of plasma glucose have been classified into 3 categories:
1) Diabetes mellitus Type 1
2) Diabetes mellitus Type 2
3) Maturity onset diabetes of youth (subtype of Type 2)

Front 14

14. Diabetes mellitus Type 1

Back 14

Associated w/reduced or absent levels of plasma insulin and usually presents in childhood

Front 15

15. Diabetes mellitus Type 2

Back 15

Characterized by insulin resistance and typically, adult onset

Front 16

16. Lactose disorders

Back 16

The ability to metabolize lactose is dependent in part on the activity of an intestinal brush border enzyme called lactase-phlorizin hydrolase (LPH)

On or more regulatory elements contribtute to lactase nonpersistance or lactose intolerance

Front 17

17. Von Gierke's disease

(Glycogen metabolism)

Back 17

1. Glycogen storage disorder
2. Defect in glucose-6-phosphatase
3. Glucose from glycogen not release from liver, G-6-P otherwise metabolized
4. Liver, skeletal muscle, kidney affected
5. Hepatomegaly and hypoglycemia
6. Uncommon, but many other diseases in class
7. Requires early intervention

Front 18

18. Phenylketonuria (PKU)

Amino acid metabolism

Back 18

Hyperphenylalanemias are most widely studied metabolic disorders

High phenylalanine disrupts brain myelination, protein synthesis, and eventually produces retardation

Classical PKU is most common defect

Caused by mutations to phenylalanine hydroxylase (PAH) gene

Front 19

19. PKU prevalence

Back 19

1. From 1 in 10,000 Caucasians to 1 in 90,000 Africans
2. All newborns in US are tested
3. Requires dietary restriction to limit symptoms
4. Difficult as phenylalanine is an essential AA, but possible
5. High maternal blood levels will affect fetus
6. Pregnant women w/PKU must be especially careful

Front 20

20. Tyrosinemia Type 1

Back 20

Deficiency of fumarylacetoacetate hydrolase (FAH) causes hereditary tyosinemia type 1 (HT1).

Accumulation of the substrates of FAH leads to neurological, kidney, and liver dysfunction.

Front 21

21. Tyrosinemia type 2 (oculocutaneous tyrosinemia)

Back 21

Caused by a deficiency of tyrosine aminotransferase.

Characterized by corneal erosions, thickening of the skin on the palms and the soles, and variable mental retardation.

Front 22

22. Tyrosinemia type 3

Back 22

Associated w/reduced activity of 4-hydroxyphenylpyruvate dioxygenase and neurological dysfunction, although only a few affected individuals have been reported.

Front 23

23. Maple syrup urine disease (MSUD)

(Type of branched chain amino acid disorders)

Back 23

Maple syrup urine disease (MSUD) is caused by defects in the branched-chain α-ketoacid dehydrogenase.

Accumulation of branched-chain amino acids (BCAAs) causes progressive neurodegradation and death.

Treatment of MSUD consists of restricting dietary intake of BCAAs to a minimal level.

Front 24

24. MCAD Deficiency

(Lipid metabolism)

Back 24

Medium chain acyl-coenzyme A dehydrogenase (MCAD)

1. Most common fatty acid metabolism defect
2. Episodic hypoglycemia after fasting
3. Present with vomiting and lethargy after minor illness (upper respiratory, gastroenteritis)
4. Fatty acid intermediates accumulate, insufficient ketone bodies, glycogen exhausted

Front 25

25. MCAD treatment

Back 25

1. Provide supportive care during episode
2. Provide usable calories promptly (glucose)
3. AVOID FASTING!
4. Cerebral edema and exhaustion of glucose supplies can be fatal
5. Most of northwest European descent
6. 90% of mutation a single missense A-to-G lysine to glutamate

Front 26

26. LCHAD Deficiency

Back 26

Long-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency

Most severe fatty acid oxidation disorders.

Presents w/severe liver disease ranging from fulminant neonatal liver failure to chronic, progressive destruction of the liver.

Also causes cardiomyopathy, skeletal myopathy, retinal disease, peripheral neuropathy, and sudden death.

Front 27

27. Smith-Lemli-Opitz (SLO) syndrome

(Defects in cholesterol biosynthesis)

Back 27

Characterized by various congenital anomalies of the brain, heart, genitalia, and hands.

Individuals have reduced levels of cholesterol and increased levels of 7-dehydrocholesterol (a precursor to Δ7-sterol reductase, DHCR7)

Caused by mutations in the DHCR7 gene.

Supplementing the diet of SLO children w/cholesterol may ameliorate their growth and feeding problems, although the effect on cognitive development is less clear.

Front 28

28. Dysmorphology

Back 28

the study of abnormal physical development

Front 29

29. Difference btwn medical genetics and clinical genetics

Back 29

Whereas medical genetics is the study of the genetics of human disease, clinical genetics deals with the direct clinical care of persons with genetic diseases.

The diagnostic, counseling, and management issues surrounding genetic disease are the principal foci of clinical genetics.

Front 30

30. Accurate diagnosis

Back 30

In clinical genetics, accurate diagnosis is the most important first step in patient care.

Accurate diagnoses require the clinician to identify a condition of known etiology.

If a specific diagnosis is made, then the rest of the genetic counseling process starts.

Front 31

31. Process of diagnosing a genetic disorder

Back 31

Depends upon:

1) Diagnostic decision making
2) Biochemistry
3) Dysmorphology
4) Laboratory diagnosis
5) Basic prinicples of medical genetics
6) Practitioner guidelines (e.g. NIH)

Front 32

32. Beckwith-Wiedemann syndrome

Back 32

Characterized by:
1. Large for gestational age
2. Omphalocele
3. Large tongue
4. Facial hemangioma
5. Flank mass
6. Asymmetrical limb length

Children w/this syndrome have a 5-10% chance of developing Wilms tumor and hepatoblastoma.

Front 33

33. Genetic counseling

Back 33

Genetic counseling is a communication process which deals w/the human problems associated with the occurrence or risk of occurrence of a genetic disorder in a family. This process involves an attempt by one or more appropriately trained persons to help the individual or family to: continued...

Front 34

34. Goals of genetic counseling:

Back 34

1. Comprehend the medical facts including the diagnosis, probable course of the disorder, and the available management
2. Appreciate the way heredity contributes to the disorder and the risk of recurrence in specified relatives
3. Understand the alternatives for dealing with the risk of recurrence
4. Choose a course of action which seems to them appropriate in their view of their risk
5. Make the best possible adjustment to the disorder in an affected family member and or to the risk of recurrence of that disorder.

Front 35

35. Nondirectiveness

Back 35

Respect for the family's autonomy and their perceptions of risk and the disorder itself.

The counselor leaves all decisions about future reproduction up to the family.

Front 36

36. Negative vs. positive family history

Back 36

The majority of individuals who have a genetic disease do not have a "positive" family history.

Review of mendelian, chromosomal, and multifactoral disease inheritance shows that a lack of other affected persons in the family is common and does not by any means rule out the presence of a genetic disease.

Front 37

37. Bayes theorem

Back 37

Relates the conditional and marginal probabilities of two random events.

It is often used to compute posterior probabilities given observations.

For example, a patient may be observed to have certain symptoms. Bayes' theorem can be used to compute the probability that a proposed diagnosis is correct, given that observation.

Front 38

38. Five themes of genetic counseling

Back 38

1. Medical management
2. Risk determination
3. Risk options
4. Reproductive decision making
5. Support services

Front 39

39. Clinical genetic evals

Back 39

Include:
1. Physical examination
2. Detailed family history
3. Ancillary tests as needed
4. Communication of info to the family

Front 40

40. Family history

Back 40

1. Gender of each individual and their relationship to other family members
2. 3-generation family history
3. Age of each individual
4. All known miscarriages and stillbirths
5. The ethnic origin of family
6. Information about consanguinity
7. Changes in family histories

Front 41

41. Teratology and morphogenesis

Back 41

Teratology is the study of the environmental causes of congenital anomalies

Morphogenesis is the study of abnormal physical development

Front 42

42. Malformation

Back 42

Primary morphological defect of an organ or body part resulting from an intrinsically abnormal developmental process (e.g. cleft lip)

Front 43

43. Dysplasia

Back 43

A primary defect involving abnormal organization of cells into tissue

Front 44

44. Sequence

Back 44

A primary defect w/its secondary structural changes (e.g. Pierre Robin sequence)

Front 45

45. Syndrome

Back 45

A pattern of multiple primary malformations with a single etiology (e.g. trisomy 13)

Front 46

46. Deformation

Back 46

Alteration of the form, shape, or position of a normally formed body part by mechanical forces

Front 47

47. Disruption

Back 47

A morphological defect of an organ, part of an organ, or a larger region of the body resulting from the extrinsic breakdown of, or interference with, an originally normal developmental process

Front 48

48. Main causes of malformations among infants

Back 48

43.2% Unknown
23.0% Multifactorial
14.5% Familial
10.1% Chormosomal
3.2% Teratogens

Most happen during weeks 3-8 of gestation

Front 49

49. van der Woude syndrome

Back 49

The deformities present in van der Woude syndrome, which form the basis for diagnosis, typically consist of:

A split (cleft) in the roof of the mouth (palate) and/or in the upper lip. This may occur on one or both sides of the mouth.

Small pits in the center of the red part of the lower lip. They may appear as bumps on an infant’s lip, changing to depressions as the child grows older.

Front 50

50. Trisomy 13

Back 50

Patau Syndrome
Oral/facial clefts, microopthalmia (small eyes) malformations of the CNS
Survival not much after the first week if at all
(so a 1 year old child is not a likely clinical presentation)
Most are spontaneously aborted
Heart defects and renal abnormalities, rocker bottom feet

Front 51

51. Potter phenotype or oligohydraminos sequence

Back 51

Infants with Potter sequence have characteristic facial and limb deformities and pulmonary hypoplasia.

Severe renal malformations are usually the cause of oligohydramnios. It is the latter that gives rise to the facial and limb deformities and impairs normal development of the lungs, hence a sequence.

Front 52

52. Sequence vs. syndrome

Back 52

A sequence is a primary defect w/secondary structural changes

A syndrome is a collection of malformations whose relationship to one another tends to be less well understood.

Front 53

53. Bendectin or doxyclamine

Back 53

Is a mixture of pyridoxine (Vitamin B-6), and doxylamine, is a drug prescribed to treat nausea and vomiting associated with morning sickness. It was voluntarily removed from the market in 1983 by its manufacturer, Merrell Dow Pharmaceuticals, following numerous lawsuits alleging that it caused birth defects, although an FDA panel concluded that no association between Bendectin and birth defects had been demonstrated.

Proves the point that its very difficult to prove epidemiologically that any exposure is "safe"

Front 54

54. Fetal alcohol syndrome

Back 54

Condition consists of prenatal and postnatal growth deficiency, microcephaly, a wide range of developmental disabilities, and a constellation of facial alterations.

Front 55

55. Leading cause of infant deaths

Back 55

Birth defects (approx 21% of infant deaths)

Front 56

56. Principles of teratology

Back 56

1. Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this genetic composition interacts w/the environment.
2. Susceptibility to teratogens varies w/the developmental stage at the time of exposure
3. Manifestation of abnormal development depend on dose and duration of exposure to teratogen
4. Teratogens act in specific ways
5. Manifestation of abnormal development are death, malformation, growth retardation, and functional disorders.

Front 57

57. Infectious agents

Back 57

1. Rubella
2. Cytomegalovirus
3. Herpes simplex virus
4. Varicella virus
5. HIV
6. Toxoplasmosis
7. Syphilis

Front 58

58. Cytomegalovirus

Back 58

Often, the mother has no symptoms, but the effects on the fetus can be devastating. The infection is often fatal, and if it is not, meningoencephalitis caused by the virus produces mental retardation

Front 59

59. Herpes simplex virus, varicella virus, and HIV

Back 59

Can all cause birth defects. Herpes induced abnormalities are rare, and usually infection is transmitted as a veneral disease to the child during delivery.

HIV appears to have a low teratogenic potential.

Infection w/varicella causes a 20% incidence of birth defects

Front 60

60. Hyperthermia

Back 60

Defects produced by exposure to elevated body temps include anencephaly, spina bifida, mental retardation, micropthalmia, cleft lip and palate, limb deficiencies, omphalocele and cardiac abnormalities.

Front 61

61. Toxoplasmosis

Back 61

Causes cerebral calcifications

Often caused contamination of soil by the protozoan parasite Toxoplasmosis gondii via cats.

Front 62

62. Ionizing radiation

Back 62

Kills rapidly proliferating cells, so it is a potent teratogen producing virtually any type of birth defect depending upon the dose and stage of development at teh time of exposure.

Front 63

63. Thalidomide

Back 63

Causes amelia and meromelia

Front 64

64. Anticonvulsants

(Phenytoin, valproic acid, trimethadione)

Back 64

Used by epileptic women, produces a broad spectrum of abnormalities that constitute distinct patterns of dysmorphogenesis known as the trimethadione and fetal hydantoin syndromes.

Facial clefts are particularly common to these syndromes and valproic acid causes craniofacial abnormalities but has a particular propensity for producing neural tube defects.

Front 65

65. Isotretinoin

Back 65

An analogue of vitamin A, has been shown to cause a charactgeristic pattern of malformations known as isotretinoin embryopathy or vitamin A embryopathy.

Can produce virtually any type of malformation, i.e. crainiofacial, cardiac and neural tube defects.

Front 66

66. Diethylstilbestrol

Back 66

Used to prevent abortion, but raised the incidence of carcinomas of the vagina and cervix in women exposed to the drug in utero and a high percentages of these women had reproductive dysfunction due to congenital malformations of the uterus, uterine tubes, and upper vagina.

Front 67

67. Heavy metals

Mercury and lead

Back 67

Organic mercury can cause neurological symptoms resembling cerebral palsy.

Lead has been associated w/increased abortions, growth retardation, and neurological disorders.

Front 68

68. Fetal age and growth are assessed by?

Back 68

Via ultrasound, the crown-rump length during the 5th to 10th weeks of gestation.

After that, the diameter of the skull, femur length, and abdominal circumference are used to determine the extent of fetal growth.

Front 69

69. Ultrasonography

Back 69

Non-invasive method of fetal imaging
No X-ray exposure
Used to guide needles in amniocentesis, etc.
Malformations can be detected visually
Specificity is high, certain of defect
Sensitivity is still low, improving
Many types of disorders can be found
New versions give 3-D image

Front 70

70. Maternal serum screening

AFP and hCG

Back 70

High levels of AFP indicative of spina bifida or neural tube defects

Low levels of AFP indicative of Down syndrome, trisomy 18, and triploidy.

Also associated w/lower serum concentration of hCG

Very High levels of hCG indicative of hydatiform mole.

Front 71

71. Amniocentesis

Back 71

Sample amniotic fluid and amniocytes
Usually done 15 to 17 weeks
Visualize fetus with ultrasound
Sample taken with syringe and needle
Biochemical measurement on fluid
Cells grown for karyotyping and other tests
Cytogenetic tests take 10 to 12 days
Pregnancy loss about 0.5% above background

Front 72

72. Complications of Amniocentesis

Back 72

Cannot be done early in pregnancy

Long wait for cytogenetic results delays decision-making

Cytogenetic changes may occur during culture

Must be assessed to differentiate mosaicism from pseudomosaicism

Front 73

73. Chorionic villus sampling (CVS)

Back 73

Can be done earlier, 10 – 11 weeks
Transcervical approach possible
Samples placental tissue
No fluid obtained for tests
Can be complicated by confined placental mosaicism
May require follow-up with amniocentesis

Front 74

74. Fetal blood sampling

Back 74

Cordocentesis or percutaneous umbilical blood sampling (PUBS)
Obtain blood from umbilical
Can test hematologic disorders directly
Hemoglobinopathies, etc.
Rapid cytogenetic results
Distinguish between fetal mosaicism and other types caused in vitro

Front 75

75. Fetal treatment

Back 75

Early diagnosis could mean early treatment
Treating mother may aid fetus
Sometimes surgery is possible
Stem cells can be transplanted
Repairing defective genes is long-term goal
Current gene therapy is early attempt at this

Congenital adrenal hyperplasia can masculinize female fetuses, dexamethasone can prevent this

Front 76

76. Conduction system of the heart

Back 76

1. SA node
2. AV node
4. His-Purkinje system

Front 77

77. SA node

Back 77

A collection of specialized pacemaker cells measuring 1 to 2 cm in length located high in the right atrium between the SVC and the right atrial appendage.

Impulse spreads from here through preferential internodal tracts, ultimately reaching the AV node

Front 78

78. AV node

Back 78

Consists of a meshwork of cells located at the inferior aspect of the right atrium between the coronary sinus and the septal leaflet of the tricuspid valve.

Provides the only normal electrical connection between the atria and ventricles.

Conduction transiently slows and then proceeds to the ventricles by means of His-Purkinje system.

Front 79

79. Bundle of His

Back 79

Extends from the AV node down the membranous IV septum to the muscular septum, where it divides into the left and right bundle branches

Ultimately, both the right and left bundle branches terminate in Purkinje cells.

Front 80

80. Right bundle branch

Back 80

A discrete structure that extends along the IV septum and enters the moderator band on its way towards the anterolateral papillary muscle of the right ventricle.

Front 81

81. Left bundle branch

Back 81

Less distinct; it consists of an array of fibers organized into an anterior fascicle, which proceeeds towards the anterolateral papillary muscles of the left ventricle, and a posterior fascicle, which proceeds posteriorly in the septum towards to the posteromedial papillary muscle.

Front 82

82. Purkinje cells

Back 82

Large cells with well developed intercellular connections that allow for the rapid propagation of electrical impulses.

These impulse generating cells then directly stimulate myocytes.

Front 83

83. Contraction of myocytes

Back 83

Begins w/electrical depolarization of the sarcolemma, which results in an influx of Ca into the cell thru channels in the T tubules.

Initial Ca entry stimulates the release of CA from the sarcoplasmic reticulum.

The Ca then binds to troponin C on the actin filaments of the sarcomere, resulting in a conformational change in the troponin-tropomyosin complex.

This facilitates the actin-myosin interaction, which results in cellular contraction

Front 84

84. ATP and myocyte contraction

Back 84

ATP is needed to dissociate myosin from actin, thereby permitting the sliding of thick filaments past thin filaments as the sarcomere shortens.

Myocardial metabolism is aerobic and thus requires a constant supply of O2.

Front 85

85. Cardiac cycle

Back 85

A repeating series of contractile and valvular events during which the valves open and close in response to pressure gradients between different cardiac chambers.

Can be divided into systole (ventricular contraction) and diastole (ventricular relaxation)

Front 86

86. Ventricular contraction

Back 86

The pressure in the ventricles increases and exceeds that in the atria, at which time the AV valves close.

Intraventricular pressure continues to rise, initially without a change in ventricular volume (isovolumic contraction) until the intraventricular pressures exceed the pressures in the aorta and pulmonary artery, at which time the semilunar valves open and ventricular ejection of blood occurs.

Front 87

87. Ventricular relaxation

Back 87

The pressure int eh ventricles falls until the pressure int he arterial chambers exceeds that in the ventricles, and the semilunar valves close.

Ventricular relaxation continues, initially w/o a change in ventricular volume (isovolumic relaxation).

When the pressure in the ventricles falls below the pressure in the atria, the AV valves open and a rapid phase of ventricular filling occurs.
(Active atrial contraction augments ventricular filling)

Front 88

88. Blood pressure during diastole

Back 88

During diastole, the arterial pressure gradually falls as blood flows distally and elastic recoil of the arteries occurs.

However, in the ventricle, the pressure gradually increases as blood enters the ventricles form the atria during diastole.

Front 89

89. Cardiac output

Back 89

Amount of blood ejected by the heart each minute

Is the product of stroke volume (SV) and the heart rate (HR)

Front 90

90. Stroke volume

Back 90

Amount of blood ejected w/each ventricular contraction

Is a measure of the mechanical function of the heart and is affected by preload, afterload, and contractility.

Front 91

91. Cardiac index

Back 91

Is the CO divided by the body surface area; it is measured in liters per minute per square meter and is a way of normalizing CO to body size.

Normal value is 4 to 6 L/min, although this value can increase 4x during exercise.

Front 92

92. Preload

Back 92

Is the volume of blood in the ventricle at the end of diastole and is primarily a reflection of venous return.

Affected by volume and vascular tone.

Volume can be increased via IV fluid; decreased by diuretics.

Tone can be decreased by nitroglycerin.

Front 93

93. Frank-Starling relationship

Back 93

Within limits, as the preload increases, the ventricle stretches and the ensuing ventricular contraction becomes more rapid and forceful.

Front 94

94. Afterload

Back 94

Is the force against which the ventricles must contract to eject blood.

The arterial pressure is often used as a practical measure of afterload; although, the size of the ventricular cavity, and the thickness of the ventricular walls determine afterload.

Afterload is increased with systemic hypertension or peripheral vascular resistance

Front 95

95. Contractility or inotropy

Back 95

Represents the force of ventricular contraction independent of loading conditions.

Can be affected by sympathetics or parasympathetics and pharmacologics

Front 96

96. Quantification of overall ventricular systolic function

Back 96

Frequently quantified by the ejection fraction, which is the ratio of the SV to the end-diastolic volume

That is, the fraction of blood in the ventricle ejected w/each ventricular contraction.

The normal ejection fraction is approx 60%

Front 97

97. Mvo2

Back 97

Myocardial oxygen consumption; under normal conditions the oxygen supply to the heart should match the Mvo2

Front 98

98. Main determinants of Mvo2

Back 98

Mvo2= HR, contractility and wall stress

Thus, Mvo2 parallels changes in HR, blood pressure, contractility, and heart size.

Front 99

99. Wall stress

Back 99

Determined by Laplace's law, and is directly related to the systolic pressure and the heart size.

Wall stress = (pressure*radius)/(2*wall thickness)

Front 100

100. When does the majority of coronary flow occur?

What does this have to do w/tachycardia?

Back 100

During diastole

Therefore, diastolic pressure is the major pressure driving the coronary circulation.

Tachycardia primarily shortens the duration of diastole, resulting in reduced time for coronary flow.

Front 101

101. Regulation of coronary blood flow

Back 101

Occurs primarily through changes in coronary vascular resistance.

In response to a change in Mvo2, the coronary arteries can dilate or constrict to allow for appropriate change in coronary flow.

Front 102

102. Neurotransmitters that affect the coronary arteries

Back 102

Sympathetic: norepinephrine; may have opposing effects on the coronary vasculature; α-receptors results in vasoconstriction while β-receptors results in vasodilation

Parasympathetics via vagus: acetylcholine; results in vasodilation.

Front 103

103. What allows the coronary vasculature to mediate changes in blood flow?

Back 103

It depends in large part on an intact, normally functioning endothelium.

The endothelium produces several potent vasodilators, including endothelium derived relaxing factor (EDRF) and prostacyclin.

Disturbances in these normal properties of the endothelium are likely to play an important role in conditions i.e. coronary atherosclerosis and thrombosis.

Front 104

104. Important function of arterioles

Back 104

Arterioles function as resistance vessels, owing to the presence of muscular sphincters and control the flow of blood to the capillary systems.

Front 105

105. Dual control of the arterioles

Back 105

1. Centrally thru the autonomic nervous system

2. Locally by means of conditions int he immediate vicinity of the blood vessels.

α-adrenergic system results in vasoconstriction while the β-adrenergic or vagal stimulation results in vasodilation

Front 106

106. Systemic vascular resistance (SVR)

Back 106

SVR is a measure of total vascular tone and is defined as the pressure drop across the peripheral capillary beds divided by the blood flow across the beds

In practice, this is calculated as the mean arterial pressure minus the right atrial pressure divided by the cardiac output and is normally in the range of 800 to 1500 dynes-sec/cm^5

Front 107

107. Important function of peripheral veins

Back 107

Have thinner walls than arteries and function as capacitance vessels; they are able to accommodate a significantly larger volume of blood than the arterial system.

Front 108

108. Pulmonary capillaries

Back 108

The pulmonary capillaries are separated from the alveoli by a thin alveolar capillary membrane through which gas exchange occurs. CO2 diffuses from the capillary blood into the alveoli, and O2 diffuses from the alveoli into the blood.

Front 109

109. Pumonary vascular resistance

Back 109

As a result of the extensive nature of the pulmonary capillary system and the distensibility of the pulmonary vasculature, the resistance across the pulmonary system is approximately 1/10 that of the systemic circulation.

As a result, the pulmonary system is able to tolerate significant increases in blood flow with little or no rise in pulmonary pressure.

Thus, atrial septal defects may be associated with normal pulmonary pressure.

Front 110

110. Physiologic right-to-left shunt

Back 110

The bronchial veins drain partly into the pulmonary veins; thus a small amount of deoxygenated blood normally enters the systemic circulation and accounts for a physiologic right-to-left shunt.

In the normal setting, this shunt is insignificant, accounting for only 1% of total systemic blood flow.

Front 111

111. Anticipation of exercise

Back 111

Neural centers in the brain stimulate vagal withdrawal and an increase in sympathetic tone, resulting in an increase in HR and contractility (Thus an increase in CO) before exercise even starts

Front 112

112. Exercise

What does this have to do w/the Frank Starling relationship?

Back 112

Sympathetic venoconstriction, augmented pumping action of skeletal muscles, and increased respiratory movements of the chest wall all result in an increase in venous return to the heart.

Through the Frank-Starling relationship, this increase in venous return results in an increase in contractility, thus augmenting CO.

However, the majority of the increase in CO during exercise is from an increased HR.

Front 113

113. Which pressure remains constant during exercise?

Back 113

Diastolic blood pressure.

Front 114

114. Most common congenital defects

Back 114

Atrial septal defects; represent 10 to 17% of cases with a higher prevalence in women (60%).

Front 115

115. Atrial septal defects

Back 115

ASD defects are classified according to their location in the interatrial septum.

Most common ASD (the ostium secundum defect) involves the fossa ovalis

Ostium primum defects (20%) involve the atrioventricular junction and are at one of the spectrum of AV septal defects

Front 116

116. Ostium secundum defect

Back 116

(60%) Involves the fossa ovalis

Left-to-right shunting of blood.

Front 117

117. Ostium primun defects

Back 117

(20%) involve the atrioventricular junction and are at one of the spectrum of AV septal defects.

Primum ASDs are usually associated with a cleft mitral valve and mitral regurgitation.

Left-to-right shunting of blood.

In rare cases, can also be associated w/a large VSD and a single AV valve, forming an AV septal defect.

Front 118

118. Larger ASDs

Back 118

If the defect is large, then the right atrium and right ventricle dilate to accommodate the increased volume of shunted blood.

Pressure in the pulmonary artery increases secondary to the increased volume of blood.

Front 119

119. Signs of ASDs

Back 119

1. A prominent right ventricular pulsation may be heard on physical exam along the left sternal border

2. A dilated hyperdynamic right ventricle

3. The S2 sound is widely split and fixed.

4. An ejection quality murmur that increases with inspiration is commonly heard at the left sternal border and is secondary to increased blood flow across the pulmonary valve.

Front 120

120. Indications for ASD closures

Contraindications?

Back 120

1. Cardiac enlargement by chest XRay
2. Right ventricular enlargement by ECG
3. Elevation of pulmonary artery pressure
4. Defects greater than 8mm in diameter

Contraindication for closure:
Pulmonary hypertension

Front 121

121. Ventricular septal defects

Back 121

A common congenital abnormality in newborns and is present in approx 1/500 normal births.

Left-to-right shunting of blood

50% close spontaneously during childhood.

Most VSDs involve the membranous septum.

Less common types of VSD involve the AV canal, which is often associate w/ostium primum ASDs

Front 122

122. Large VSDs

Back 122

If the defect is large, the right ventricle dilate to accommodate blood flow increases.

If the condition is uncorrected, then pulmonary vascular obstruction may develop and lead to pulmonary artery hypertension

Front 123

123. Signs of VSD

Back 123

1. Hyperdynamic precordium
2. Palpable thrill along the left sternal border
3. Holosystolic left parasternal murmur
4. Right ventricular hypertrophy

Front 124

124. Eisenmerger syndrome

Back 124

The ES is characterized by elevated pulmonary vascular resistance and right-to-left shunting of blood through a systemic-to-pulmonary circulation connection such as PDA, VSD, ASD, and aorticopulmonary septal defect.

Not a candidate for surgical correction of VSD!

Front 125

125. Congenital aortic stenosis or bicuspid aortic valve

Back 125

Decreased carotid upstroke
2. Sustained apical impulse
3. Single S2, S4
4. Systolic ejection murmur
5. Left ventricular hypertrophy (prominent on chest XR)

Front 126

126. Subaortic stenosis

Back 126

Often diagnosed in adulthood and is characterized by the presence of a discrete, fibrous diaphragm that encircles the left ventricular outflow tract btwn the mitral annulus and the basal IV septum

Patients w/this defect have a characteristic outflow murmur but not the systolic ejection click appreciated in patients w/bicuspid aortic valves.

Requires endocarditis prophlylaxis

Front 127

127. Supravalvar aortic stenosis (SVAS)

Back 127

SVAS is a rare form of outflow obstruction characterized by varying degrees of ascending aortic root stricture. Loss of function mutations in the ECM protein, elastin, are responsible for smooth muscle hypertrophy in SVAS.

Requires endocarditis prophlylaxis

Front 128

128. Pulmonic valve stenosis

Back 128

Most common cause of obstruction to right ventricular outflow and usually occurs as an isolated congenital lesion.

Fusion of the pulmonary leaflets creates the pressure overloaded state and results in right ventricular hypertrophy.

Front 129

129. Signs of pulmonic valve stenosis

Back 129

1. Right ventricular lift on palpation of the precordium
2. S1 sound is usually normal and is followed by an opening click that becomes louder w/expiration
3. P2 sound becomes softer and is delayed as the severity of the stenosis increases.
4. Systolic ejection murmur at left sternal border that increases w/inspiration

Requires endocarditis prophlylaxis; valve replacement is rarely necessary.

Front 130

130. Ebstein's anomaly

Back 130

A rare condition characterized by apical displacement of the tricuspid valve into the right ventricle.

As a result, the basal portion of the right ventricle forms part of the right atrium and leaves a small function right ventricle.

A patent formamen ovale or ostium secundum ASD is present in more than 50% of cases and may result in right-to-left shunt flow as right atrial pressure increases.

Front 131

131. Signs of Ebstein's anomaly

Back 131

1. Acyanotic or cyanotic
2. Increased jugular venous pressure
3. Prominent v wave
4. Systolic murmur at sternal border, increases w/inspiration
5. Right atrium abnormality (enlarged)
6. Right bundle branch block

Front 132

132. Coarctation of the aorta

Back 132

A fibrotic narrowing of the aortic lumen usually located distal to the left subclavian artery in the region of the ligamentum arteriosus.

Produces obstruction to left ventricular outflow and results in a rise in blood pressure int he proximal aorta and great vessels relative to the distal aorta and lower extremities

Front 133

133. Signs of coarctation of aorta

Back 133

1. Delayed femoral pulses
2. Reduced blood pressure in lower extremities
3. Findings associated w/bicuspid aortic valve
4. Left ventricular hypertrophy
5. Post stenotic aortic dilation
6. Prominent ascending aorta

Front 134

134. Can a coarctation of aorta be left untreated?

Back 134

More than two thirds of patients will develop left ventricular dysfunction and congestive heart failure by the fourth decade of life if left untreated.

Front 135

135. Patent ductus arteriosus (PDA)

Back 135

A persistent communication between the aorta and pulmonary artery is the result of the failure of the ductus arteriosus to close.

Closure is indicated in all cases except in those patients with silent PDAs and in those with large PDAs associated w/severe, irreversible pulmonary vascular disease

Front 136

136. Large PDA defect

Back 136

If the defect is large, blood flow thru the pulmonary circulation returning to the left side of the heart is significantly increased, resulting in left ventricular volume overload and pulmonary congestion.

Front 137

137. Signs of PDA defect

Back 137

1. Hyperdynamic apical impulse
2. Continuous machinery-like murmur
3. Left ventricular hypertrophy
4. Prominent pulmonary artery
5. Enlarged LA and LV

Front 138

138. Signs of an Eisenmerger PDA

Back 138

Characterized by:
Loss of the continuous murmur, signs of pulmonary hypertension, and differnetial cyanosis and clubbing.

Front 139

139. Tetralogy of Fallot

Back 139

Tetralogy is the result of a malalignment of the aorticopulmonary septum that divides the truncus arteriosus into the aorta and pulmonary artery during development, resulting in deviation of the aorta anteriorly towards the pulmonary artery

Results in right-to-left shunting of blood

Front 140

140. Four characteristics of Tetralogy

Back 140

1. Overriding of the aorta in relation to the ventricular septum
2. Pulmonary stenosis (due to right ventricular outflow obstruction)
3. Membranous VSD
4. Right ventricular hypertrophy

Front 141

141. Signs of Tetralogy of Fallot

Back 141

1. Usually cyanotic
2. Possible clubbing
3. Prominent ejection murmur at left sternal border
4. Soft or absent P2
5. RV hypertrophy
6. RA abnormality
7. Boot shaped heart
8. Small pulmonary artery

Front 142

142. Complete transposition of the great arteries

Back 142

AKA D-transposition

Most common cyanotic congenital heart disease.

Characterized by abnormal ventriculoarterial connections w/the aorta arising from the right ventricle and the pulmonary artery arising from the left.

Can support fetal development, but serious consequences result on closure of the foramen ovale and ductus arteriosus shortly after birth.

Front 143

143. Corrected transposition of the great arteries

Back 143

Inversion of the ventricles and abnormal positioning of the great arteries characterize congenital-corrected transposition of the great arteries (L-transposition).

The anatomic right ventricle lies on the left and receives oxygenated blood from the left atrium. Blood is ejected into an anteriorly displaced aorta. The anatomic left ventricle lies on the right and receives venous blood from the right atrium and ejects it into the posteriorly displaced pulmonary artery.

Front 144

144. Single ventricle

Back 144

Tricuspid atresia, double-inlet left ventricle w/VSD, and large atrioventriclular septal defect may all have similar consequences to the patient.

The cardiac output is directed in common to both the aorta and the pulmonary artery, w/the balance between the two circulatory beds determined by the degree of outflow tract obstruction.

Front 145

145. Fontan procedure

Back 145

Goal is to optimize pulmonary blood flow w/o volume loading the ventricle. The Fontan procedure and its modifications connect all systemic venous return to the pulmonary artery w/o an intervening ventricular pump.

Effectively separates the two ciruclartion and provides relief of cyanosis w/o providing a volume load on the left ventricle on a pressure load on the pulmonary arteries.

Front 146

146. Requirements for digestion

Back 146

1. Movement of food through the alimentary tract
2. Secretion of digestive juices and digestion of the food
3. Absorption of water
4. Circulation of blood through the GI organs to carry way the absorbed substances
5. Control of all these function by local, nervous and hormonal systems

Front 147

147. Layers of the intestinal wall from outer surface inward

Back 147

1. Serosa
2. Longitudinal muscle layer
3. Circular muscle layer
4. Submucosa
5. Mucosa

Front 148

148. GI smooth muscle

Back 148

Functions as a syncytium
Individual smooth muscle fibers in the GI tract are 200 to 500 um in length and 2 to 10 um in diameter.

In the longitudinal muscle layer, the bundles extend longitudinally down the intestinal tract; in the circular muscle layer, they extend around the gut.

A few connections exist btwn the two layers so that excitation of one often excites the other.

Front 149

149. Gap junctions

Back 149

Within each bundle, the muscle fibers are electrically connected w/one another thru large numbers of gap junctions that allow low-resistance movement of ions form one muscle cell to the next.

Front 150

150. Action potential travel

Back 150

Since each muscle layer functions as a syncytium, when an action potential is elicited anywhere w/in the muscle mass, it generally travels in all directions in the muscle.

Front 151

151. Electrical activity of GI smooth muscle

Back 151

The smooth muscle of the GI tract is excited by continual slow, intrinsic electrical activity along the membranes of the muscle fibers.

Has two basic types of electrical waves:
1. slow waves
2. spikes

Front 152

152. Slow waves

Back 152

Most GI contractions occur rhythmically, and this rhythm is determined mainly by the freq of slow waves of smooth muscle membrane potential.

*Are not action potentials. Instead, they are slow, undulating changes in the resting membrane potential. Varies 5-10 mV and freq are about 3-12 per minute.

Do not cause muscle contraction by themselves (except in the stomach)

Front 153

153. Cause of slow waves

Back 153

Appear to be cause by complex interactions among the smooth muscle cells and specialized cells, called the interstitial cells of Cajal, that are believed to act as electrical pacemakers for smooth muscle cells.

Front 154

154. Cells of Cajal

Back 154

These interstitial cells form a network with each other and are interposed between the smooth muscle layers, w/synaptic like contacts to smooth muscle cells.

Undergo cyclic changes in membrane potential due to unique ion channels that periodically open and produced inward currents that may generate slow wave activity.

Front 155

155. Spike potentials

Back 155

Are true action potentials.

Occur automatically when the resting membrane potential of the GI smooth muscle becomes more positive than about -40 mV.

(normal resting membrane potential in the smooth muscle fibers of the gut is between -50 and -60 mV)

Front 156

156. Relationship of slow waves to spike potentials

Back 156

The higher the slow wave potential rises, the greater the frequency of the spike potentials, usually ranging btwn 1 and 10 spikes per second.

Front 157

157. Differences between action potentials in the GI tract and skeletal muscle

Back 157

They last 10 to 40 times as long in GI muscle as the action potentials in large nerve fibers.

In nerve fibers, the action potentials are caused almost entirely by rapid entry of Na ions through Na channels to the interior of the fibers.

In GI smooth muscle fibers, the channels responsible for the action potentials allow especially large numbers of Ca ions to enter along w/smaller numbers of Na ions and therefore are called calcium-sodium channels.

Front 158

158. Calcium-sodium channel opening/closing

Back 158

These channels are much slower to open and close than are the rapid sodium channels of large nerve fibers.

The slowness of opening and closing accounts for the long duration of the action potentials.

Front 159

159. Factors that depolarize the membrane (make it more excitable)

Back 159

1. Stretching of the muscle
2. Stimulation by acetylcholine
3. Stimulation by parasympathetic nerves that secrete acetylcholine at their endings
4. Stimulation by several specific GI hormones

Front 160

160. Factors that hyperpolarize the membrane

Back 160

1. The effect of norepinephrine or epinephrine on the fiber membrane
2. Stimulation of the sympathetic nerves that secrete mainly norepinephrine at their endings

Front 161

161. Tonic contraction

Back 161

Some smooth muscle of the GI tract exhibits tonic contraction as well as or instead of rhythmical contractions.

Tonic contraction is continuous, not associated w/the basic electrical rhythm of the slow waves but often lasting several minutes or even hours.

Front 162

162. Causes of tonic contraction

Back 162

1. Sometimes caused by continuous repetitive spike potentials - the greater the freq the greater the degree of contraction.
2. Hormones or other factors that bring about continuous partial depolarization of the membrane w/o causing action potentials
3. Continuous entry of calcium ions into the interior of the cell brought about in ways not associated w/changes in membrane potential.

Front 163

163. Enteric nervous system

Back 163

The GI system's own nervous system

Lies in the wall of the gut, beginning in the esophagus and extending all the way to the anus.

Highly developed and controls GI movements and secretions

Front 164

164. Composition of enteric nervous system

Back 164

1. An outer plexus lying between the longitudinal and circular muscle layers, called the myenteric plexus or Auerbach's plexus

2. An inner plexus, call the submucosal plexus or Meissner's plexus, that lies in the submucosa.

Front 165

165. Myenteric plexus and submucosal plexus

Back 165

Myenteric controls mainly the GI movements

Submucosal controls mainly GI secretion and local blood flow.

Front 166

166. Myenteric plexus in detail

Back 166

Consists mostly of a linear chain of many interconnecting neurons that extends the entire length of the GI tract.

When stimulated, its principal effects are:
1. increased tonic contraction or "tone" of the gut wall
2. increase intensity of the rhythmical contractions
3. slightly increased rate of the rhythm of contraction
4. increased velocity of conduction of excitatory waves along the gut wall, causing more rapid movement of the gut peristaltic waves.

Front 167

167. Myenteric plexus: inhibitory or excitatory?

Back 167

Should not be considered entirely excitatory b/c some of its neurons are inhibitory.

Inhibitory signals are especially useful for inhibiting some of the intestinal sphincter muscles that impede movements of food along successive segments of the GI tract.

Front 168

168. Submucosal plexus in detail

Back 168

Is mainly concerned w/controlling function w/in the inner wall fo each minute segment of the intestine.

Help control:
1. Local intestinal secretion
2. Local absorption
3. Local contraction o the submucosal muscle that causes various degrees of infolding of the GI mucosa.

Front 169

169. Types of neurotransmiters secreted by eneric neurons

Back 169

1. acetylcholine
2. norepinephrine
3. adeonsine triphosphate
4. serotonin
5. dopamine
6. cholecystokinin
7. substance P
8. vasoactive intestinal polypeptide
9. somatostatin
10. leu-enkephalin
11. metenkaphalin
12. bobesin

Front 170

170. Acetylcholine, norepinephrine

Back 170

Acetylcholine almost always excites GI activity;

Norepinephrine almost always inhibits GI activity.

Front 171

171. Parasympathetic innervation of the GI tract

Back 171

1. Cranial parasympathetic nerves (vagus)
2. Sacral parasympathetics
3. Pelvic nerves

Postganglionic parasympathetic neurons are located mainly in the myenteric and submucosal plexuses.

Mainly excitatory

Front 172

172. Sympathetic innervation of the GI tract

Back 172

Originate in the spinal cord between segments T5 and L2

Preganglionic sympathetic fibers located along sympathetic trunk and go to celiac ganglion and various mesenteric ganglia.

The postganglionic sympathetic neuron bodies are in their ganglia, and postganglionic fibers then spread through to all parts of the gut.

Generally inhibits activity of the GI tract

Front 173

173. Afferent sensory nerve fibers from the gut

Back 173

Can be stimulated by:
1. Irritation of the gut mucosa
2. Excessive distension of the gut
3. Presence of specific chemical substances in the gut

*80% of the nerve fibers in the vagus nerves are afferent rather than efferent.

Front 174

174. GI reflexes

Back 174

1. Reflexes that are integrated entirely within the gut wall enteric nervous system
2. Reflexes from the gut to the prevertebral sympathetic ganglia and then back to the GI tract
3. Reflexes from the gut to the spinal cord or brain stem and then back to the GI tract.

Front 175

175. Gastrin

Back 175

Secreted by the "G" cells of the antrum fo the stomach in response to stimuli associated w/ingestion of a meal, such as distention fo the stomach, the products of proteins, and gastrin releasing peptide which is released during vagal stimulation

Actions:
1. Stimulation of gastric acid secretion
2. Stimulation of growth by the gastric mucosa

Front 176

176. Cholecystokinin

Back 176

Secreted by the "I" cells in the mucosa of the duodenum and jejunum mainly in resposne to digestive products of fat, fatty acids, and monoglycerides in the intestinal contents.

Also interacts w/the gallbladder, expelling bile into the small intestine; also inhibits stomach contraction

Front 177

177. Secretin

Back 177

Secreted by "S" cells in the mucosa of the duodenum in response to acidic gastric juice emptying in to the duodenum from the pylorus of the stomach.

Has a mild effect on motility of the GI tract and acts to promote pancreatic secretion of bicarbonate

Front 178

178. Gastric inhibitory peptide

Back 178

Secreted by the mucosa of the upper small intestine mainly in response to fatty acids and amino acids.

It has a mild effect in decreasing motor activity of the stomach as therefore slows emptying of gastric contents into the duodenum when the upper small intestine is already overloaded w/food.

Front 179

179. Motilin

Back 179

Secreted by the upper duodenum during fasting, and the only known function of this hormone is to increase GI motility

Front 180

180. Two types of movements that occur in the GI tract

Back 180

1. Propulsive movements, which cause food to move forward along the tract at an appropriate rate to accommodate digestion and absorption

2. Mixing movements, which keep the intestinal contents thoroughly mixed at all times

Front 181

181. Peristalsis

Back 181

A contractile ring appears around the gut and then moves forward;

It is an inherent property of many syncytial smooth muscle tubes; stimulation at any point in the gut can cause a contractile ring to appear in the circular muscle.

The usual stimulus for peristalsis is distention of the gut which stimulates the myenteric nervous system

Front 182

182. Function of the myenteric plexus in peristalsis?

Back 182

The myenteric plexus is required for effectual peristalsis;

Can inhibit peristalsis by depressing the activity of the myenteric plexus, i.e. congenital absence or atropine administration that paralyzes the cholinergic nerve endings in the plexus.

Front 183

183. Directional movement of peristaltic waves towards the anus

Back 183

Peristalsis can occur in either direction from stimulated point, but it normally continues for a considerable distance towards the anus.

Due to probable polarization in the anal direction

Front 184

184. Law of the gut

Back 184

AKA "Myenteric reflex" or "Peristaltic reflex"

When a segment of the intestinal tract is excited by distention and initiates peristalsis, the contractile ring begins on the orad side of the distended segment and moves toward the distended segment, pushing the intestinal contents downstream.

At the same time the gut sometimes relaxes several cm downstream toward the anus which is call "receptive relaxation" thus allowing the food to be propelled more easily downstream.

Front 185

185. Splanchnic circulation

Back 185

The blood vessels fo the GI system are part of the splanchnic circulation, which includes the blood flow thru the gut itself plus blood flow thru the spleen, pancreas and liver.

This system is designed so all the blood flows through these organs and then immediately to the liver by way of the portal system.

Front 186

186. Flow of blood thru the liver

Back 186

1. Portal vein

2. Liver sinusoids
-lined with reticuloendothelial cells which remove bacteria and harmful agents

3. Hepatic veins

4. Vena cava

Front 187

187. Nonfat, water soluble nutrients

Back 187

Absorbed from the gut and are transported in the portal venous blood to the liver sinusoids.

Here, the reticuloendothelial cells and the hepatic cells absorb and store temporarily 1/2 to 3/4 of the nutrients

Front 188

188. Fats, non-soluble nutrients

Back 188

NOT carried in the portal blood but are instead absorbed in the intestinal lymphatics and then conducted to the systemic circulation by way of the thoracic duct.

Fat bypasses the liver.

Front 189

189. Causes of increased blood flow during GI activity

Back 189

Several vasodilator substances are released from the mucosa; include peptide hormones: CCK, Gastrin, Secretin, etc..

Some of the GI glands also release two kinins, kallidin and bradykinin which are also powerful vasodilators

Decreased O2 concentration in the gut wall can increase intestinal blood flow at least 50 to 100%
-decreased O2 can also lead to a release of adenosine which is also a vasodilator

Front 190

190. Countercurrent blood flow in the GI tract

Back 190

The arterial and venous flow into and out of the villus are in opposite directions and they lie close to one another.

B/c of this, much of the blood O2 diffuses out of the arterioles directly into the adjacent venules w/o ever being carried in the blood to the tips of the villi.

As much as 80% of the O2 takes this shortcut.

Under normal conditions, this shunting is not harmful to the villi, but in diseased conditions blood flow to the gut becomes greatly reduced.

Front 191

191. Stimulation of the parasympathetics/sympathetics going to the stomach and lower colon leads to...

Back 191

Parasympathetic: Increased blood flow and glandular secretion

*Sympathetic: Intense vasoconstriction of the arterioles and greatly decreased blood flow.
-regulated by "autoregulatory escape", in which the flow returns to normal

*Important for heavy exercise or times in which blood is needed elsewhere as intestinal and mesenteric veins can provide as much as 200 to 400 mL of extra blood to sustain the circulation.