Lectures - Theoretical Questions Flashcards
1
Q
What are the consequences of Chronic Right Heart failure
A
Systemic Congestion - Hepatomegaly, Splenomegaly, Renomegaly
Skin cyanosis
Acites
2
Q
What are the consequences of Chronic Left Heart failure
A
Congestion of the Lungs
Heart Failure cells in sputum
Dyspnea
3
Q
Definition of Shock
A
State of significant Hypo-perfusion resulting in a cell Injury due to Hypoxia and lack of waste metabolites removal
4
Q
Short term effects of Shock
A
Syncope, Orthostatic collapse, Carotis Hyperesthesia, Electric shock, Spinal cord Injury
5
Q
Stages of shock
A
Compensated - maintaining perfusion.
Progressive - Inadequate perfusion levels start to show.
Irreversible - Cell and tissue damage, Multi-organ failure.
6
Q
Pathophysiology of Shock - Progression of events in the various stages
A
Stage 1 - Pathogenesis causes low CO or low TPR, Hypotension compensated.
Stage 2 - Decreased perfusion and Major end-organ dysfunction, Hypotension Decompensated.
Stage 3 - Microcirculatory failure and endothelial damage leading to cellular membrane Injury and death.
7
Q
Clinical markers of shock
A
Brachial systolic BP - less than 100mmHg Sinus Tachycardia Metabolic Acidemia Hypoxemia Low urine output and High respiratory rate.
8
Q
Classification of shocks
A
Hypovolemic shock - Loss of blood or body fluids
Obstructive shock - Embolism
Cardiogenic Shock - Heart failure
Distributive Shock - Neurogenic, Anaphylactic, Septic
9
Q
Shock Index
A
SI = RR Interval divided by Pulse
Should be 2 a Normal conditions.
It is lower than 1 in case of shock.
10
Q
Further classification of Irreversible and Progressive stages of shock
A
Subacute reversible - Oxygen delivery could overtime return to normal with medical attention
Subacute Irreversible - with time and medical care no normal oxygen delivery could be achieved, although an initial improvement may appear.
Acute Irreversible - No Improvement whatsoever and only deterioration of the supply and demand of oxygen ratio.
11
Q
Hypovolemic shock - causes
A
Hemorrhage, Vomiting or Diarrhea, Diabetes or Diuretics, Burns or Inflammation of skin, Loss of interstitial fluids
12
Q
Hemorrhagic shock Initial Compensation - Neural
A
Alpha Adrenergic- Vasoconstriction of GI, Muscle, Adipose, KIdney vessels
Beta Adrenergic- Bronchodilation and cardiac stimulation
Pale skin, Decreased Diuresis, Muscle weakness
13
Q
Hemorrhagic shock - Progressive Compensation efforts, Humeral
A
Blood Glucose elevation and Capillary pressure lowering.
ADH and Renin-Angiotensin- Aldosterone sys
14
Q
Hemorrhagic Shock - Irreversible stage
A
Cell death metabolites diffuses easily to systemic circulation due to high vasodilation causing irreversible damage and death
15
Q
Cardiogenic shock cause and possible treatment
A
Heart (pump) Failure - 40% of Myocardium damaged by AMI
Alternative Pumping - Transplant or Synthetic Device
16
Q
Distributive Shock - symptoms
A
Normovolmia Normotension Low TPR High CO Redness fever
17
Q
Distributive Shock
Anaphylactic
Causes and Events
A
Immunogenic Inappropriate Vasodilation causes fluid shift into cells from capillaries.
Micro clots are formed and hazardous SMC contraction occurs like Bronchospasm.
17
Q
Distributive Shock
Septic
Causes and Events
A
The same events of Anaphylactic shock occur due to overwhelming infection reactions.
19
Q
Hyperdynamic stage of Distributive Shock
A
Accumulation of Lactic Acid
Changes in Amino acid metabolism - Tyrosine becomes Octopamine that inhibits alpha receptors
Increased NO - By cytokines
Relative oxygen deficits - Cardiac failure
19
Q
Distributive Shock
Neurogenic
Causes and Events
A
Spinal cord Lesion, Poisoning or Drug abuse causing inability of NS to maintain Vascular tone.
21
Q
Anaphylaxis
A
Sensitized Individual exposed to Antigen triggers an IgE mediated activation of Mast cells - Histamine and Other Inflammatory Cytokines are getting involved.
High inflammatory response causes Bronchoconstriction and Peripheral Vasodilation
21
Q
Obstructive Shock causes
A
Pulmonary Embolism - Blocked pulmonary Circulation
Tension Pneumothorax - Increased Intrathoracic Pressure
Cardiac Temponade - Pressure on Myocardium, Decreased Preload
22
Q
Possible Reperfusion Injury problems in order
A
Hypoxia - Tissue Injury (Endothelial cells)
Liberation of Mediators - Inflammatory Cytokines or Calcium elevation in cells
Free radicals and iNOS activation.
23
Q
Role of Muscles in Shock
A
Release of Amino acids, Pyruvate and Lactate to Circulation.
24
Roles of Lungs in Shock
Overreaction of Immune response - ARDS
| Liquid sequestration in alveoli
25
Adipose tissue Role in Shock
Negative factor - Centralized due to high alpha 1 receptors
26
Causes of ARDS
Alveolar Membrane damage, DIC, Overreacted Immunogenicity response
27
Possible Negative Feedback mechanism allowing for compensation in Trauma
```
Baroreceptor reflexes
Chemoreceptors reflexes
Cerebral Ischemia
Reabsorption of Tissue fluids
Endogenous Vasoconstrictors
Renal conservation of Water
```
28
Role of the Liver in shock
Hyperglycemia
Amino acid release
Coagulatory, Complement and Fibrinilytic proteins
Acute phase reaction proteins and C-reactive Protein
29
```
What is NOT a cause of Ketosis?
● fasting, starvation
● cocaine
● untreated DM type 1: DKA
● alcoholism
● ketogenic diet
● vomiting (mostly in children)
```
cocaine will not cause Ketosis
30
List the chronic malnutrition disease and the abnormal eating diseases accordingly: Anorexia, Cachexia, Kwashiorkor, Bulimia ,Pica, Marasmus.
Abnormal eating diseases - Bulimia and Pica
| Chronic malnutrition diseases - Anorexia, Cachexia, Kwashiorkor and Marasmus
31
Symptoms of Cachexia
loss of muscle mass and of subcutaneous fat tissue
32
Cachexia causes
Malignant tumors, Anorexia with increase of catabolic processes - IL6, TNF-alpha and PIF cause UPS overactivation.
33
What is a key way to differentiate between Marasmus and Kwashiorkor?
Kwashiorkor involves Edema and Ascites and Marasmus doesn't.
34
Kwashiorkor Symptoms
```
●low albumin level
● fatty liver
● ascites, edema
● hair and skin symptoms
● infections
● apathy
```
35
When is the usual onset of Anorexia and what is the treatment?
Anorexia onset is in puberty and the treatment is psychotherapy which is in 90% of cases saves lives.
36
What are the lab findings in general Malnutrition?
```
● low albumin level
● low transferrin level
● lymphocyte count < 1 G/l
● low Zn, Mg plasma level
● BMI < 18,5 kg/m2
```
37
BMI Calculation and Normal Range
body mass [kg] / (height [m])^2
| 18.5-24.9 is the Normal Range
38
What are the components of the Metabolic Syndrome ?
```
Central Obesity
Insulin Resistance
High Blood Pressure
High Triglycerides
Low HDL Cholesterol
Hypertension
```
39
Pathogenesis of obesity:
```
● Genetic background
● Simple overeating
● Imbalance in energy expenditure
● Socioeconomic factors
● Defective thermogenesis
● Leptin
● Thrifty gene hypothesis
● Intestinal flora
```
40
What is the precentages of primary and secondary hyperlipidemia
Primary - 10-40%
| Secondary - 60-90%
41
What is the right sequence of lipoprotein molecule based on their size?
CHY-VLDL-IDL-LDL-HDL
42
Which Apolipoproteins are found on Chylomicrons?
Apo-B48, Apo-A, Apo-C, Apo-E
43
Which Apolipoproteins C-2's Job?
Activation of LPL
44
Function of Apo-C2
Activation of LPL
45
Lipoproteins containing Apo-E?
CHY, VLDL, IDL, and LDL
46
Function of Apo-A1
LCAT Activator
47
Function of Apo-B100 and Apo-B48
Structural for all Lipoproteins (Except HDL), LDLR bind
48
Mutant Gene, Frequency and Inheritance of Familial Hypercholesterolemia:
LDLR
1/500
Autosomal Dominant
49
Mutant Gene, Frequency and Inheritance of Familial Combined Hyperlipidemia:
Not Known yet
1/100
Autosomal Dominant
50
Mutant Gene, Frequency and Inheritance of Familial Type 3 Hyperlipidemia:
Apo E
1/10,000
Autosomal Recessive
51
Genetic Deficiency and Symptoms of Familial Hyperchylomicronemia (Type 1 Dyslipidemia):
LPL or Apo-C2
| Severe elevation of TGs - Lipemia Retinalis, Eruptive Xanthomata, Hepatosplenomegaly, Pancreatitis Risk.
52
Genetic Deficiency and Symptoms of Familial Hypercholesterolemia (Type 2 Dyslipidemia):
Most commonly LDLR but PCSK9 or ApoB as well.
| Tendon and Tuberous Xanthomas, Eyelid Xanthelasma, Elevated risk for Cardiovascular Diseases.
53
Genetic Deficiency and Symptoms of Dysbetalipoproteinemia (Type 3 Dyslipidemia):
Apo-E2 - Both Cholesterol and TG increased
| Xanthomas (Palm, Tuberous), Premature Atherosclerosis.
54
Renal Diseases that Cause of Secondary Hyperlipidemias:
Nephrotic Syndrome
| Chronic Renal Failure
55
Endocrine Causes of Secondary Hyperlipidemias:
Diabetes Mellitus
Thyroid Disease (Hypothyroidism)
Pituitary Disease (Cushing Syndrome)
Pregnancy (Transient)
56
Hepatic Diseases that Cause of Secondary Hyperlipidemias:
Cholestasis
Hepatocellular Diseases
Cholelthiasis
57
Immunoglobulin Excess that Cause of Secondary Hyperlipidemias:
Myeloma Multiplex
Macroglobulinemia
SLE
58
Metabolic Disorders that Cause of Secondary Hyperlipidemias:
Hyperuricemia
Glycogen Storage Diseases
Lipodystrophies
59
Nutritional factors that Cause of Secondary Hyperlipidemias:
Obesity
Alcohol
Anorexia Nervosa
60
How is obesity Linked to Secondary Hyperlipidemias?
Increased Adipose Tissue and High Carbohydrates Intake causes Liver to Produce more VLDL and TG and Less HDL. Metabolic X syndrome: Central Obesity and Insulin Resistance.
61
How is DM Linked to Secondary Hyperlipidemias?
DM-I : Only if Untreated, Ketone and FFA ↑
| DM-II : Insulin Resistance; LPL Activity↓, VLDL↑, FFA ↑ - Metabolic X Syndrome.
62
How is Hypothyroidism Linked to Secondary Hyperlipidemias?
LDLR Synthesis and Activity↓ Leading to LDL↑, IDL↑, CHY↑
63
How is Alcohol Linked to Secondary Hyperlipidemias?
Cause of Ethanol Metabolism - Beta Oxidation↑ leads to TG↑.
| Activity of LPL↑ leads to HDL↑.
64
How are Nephrotic Syndrome and Chronic Renal Failure Linked to Secondary Hyperlipidemias?
Hypoalbuminemia - Apo-B Synthesis↑ - Hyperlipidemia.
65
How are Liver Diseases Linked to Secondary Hyperlipidemias?
Serum Cholesterol↑
66
How is Pregnancy Linked to Secondary Hyperlipidemias?
Estrogen↑ leads to Synthesis of VLDL↑ and Hepatic Lipase↓
67
How is Cushing Syndrome Linked to Secondary Hyperlipidemias?
Cortisol↑ leads to Synthesis of VLDL↑ (Central Obesity in long term Stress).
68
How is Von-Gierke-Disease Linked to Secondary Hyperlipidemias?
Glucose-6-Phosphatase Deficiency- Glucose Release↓ - Compensation Eflux of FFA↑ leads to TG Synthesis↑
69
Causes of Primary Hypoalphalipoproteinemias
Rare Hereditary Diseases:
| Tangier-Disease, Familial Type, Fish-Eye Disease, LCAT Def.
70
Causes of Secondary Hypoalphalipoproteinemias
```
Obesity and Physical Inactivity
DMII
Smoking
Excess Carbohydrates
Beta-Blockers, Anabolic Steroids and Other drugs
```
71
Causes of Primary Hypobetalipoproteinemias
Hereditary Diseases:
| Bassen-Kornzweig-Disease (All ApoB containing lipoproteins are Missing) , ApoB Def.
72
Causes of Secondary Hypobetalipoproteinemias
```
Liver diseases
Hyperthyroidism
Malnutrition
Malignancy(CML)
Rheumatic Arthritis or SLE (Inflammatory Diseases)
Fever
```
73
What is Lipidosis?
Any Disorder of lipid Metabolism involving abnormal accumulation of lipids in the reticuloendothelial cells.
74
4 Examples for Genetic Disorders that cause Lipidosis:
| Prognosis of Each
Tay-Sachs Disease - Death at age of 4 from Infections
Gaucher's Disease -May Reach Adulthood
Niemann-Pick Disease -Neuro. Disorders Premature Death
Fabry Disease - CVD Premature Death
75
What are the 4 Major Phases of Atherosclerosis and what are their corresponding symptomes?
1) Fatty Streak (Teenage years) - Silent Clinically
2) Fibrous Plaque - Effort Angina Claudication
3) Occlusive Atheroscleric Plaque - Effort Angina Claudication
4) Plaque Complications - MI/Unstable Angina/Stroke
76
What are the Most common locations for Atherosclerosis to develop?
1) Coronary Arteries
2) Abdominal Aorta
3) Carotid Arteries
77
Non-Modifiable Risk Factors for Atherosclerosis
Age
Gender - (Male more then Female up to 60 years)
Family History
78
Potentially Controllable Risk Factors for Atherosclerosis
```
Hyperlipidemia
Hypertension
Cigarette Smoking
Diabetes Mellitus
Elevated Homocysteine
Infections; Chlamydia/Herpes/Pneumoniae
Obesity, Inactivity, Stress
```
79
What are the components of the Fibrous Cap in atherosclerotic plaques?
```
SMCs
Macrophages
Foam cells
Lymphocytes
Collagen and Elastin
```
80
What are the components of the Necrotic Center in atherosclerotic plaques?
Cell Debris
Cholesterol Crystals
Foam cells
Calcium
81
Atherosclerosis Thrombogenic Theory: In short
Micro Injuries develop on vascular Intima - Vasoactive substances from Adhesed platelets (TXA and PGI) Promote Lipid Infiltration.
82
Atherosclerosis Mesenchymal Theory: In short
Hyaluronic Acid↓ causes BM permeability↑ and Lipid infiltration↑ = which causes Metabolic Functions in wall↓
Heparan sulphate↓ - Anti-thromic Activity↓
83
Atherosclerosis Monoclonal Theory: In short
Proposing that atherosclerotic lesions are benign SMC Tumors -G6PD Monoclonality checked. Therefore Risk factors: Smoking,Age,Free radicals,Infections all apply.
84
Atherosclerosis Inflammation Theory: In short
"Pathogen Burden" Cytokines↑ cause eventual Cross Reactivity with Self Antigens and Autoimmunity.
85
Atherosclerosis "Response to Injury" (Unifying) Theory: Possible causes of Endothelial Dysfunction?
LDL/ Modifed LDL↑
Genetic Alteration
Plasma Homocysteine ↑
Herpes Viruses/Chlamydia Pneumoniae Infections
86
What are the Effects of Homocysteine?
Endothelial Injury
Prothrombotic
Increase synthesis of collagen
Free Nitric Oxide ↓
87
What are Circulating EPCs?
Endothelial Protecting Cells in bloodstream:
CD34+, CD133+ and VEGF2R+ (Mononuclear WBCs)
Repair of Vascular or Myocardial Injury (Angiogenesis)
88
Which two organs play fundamental roles in the pathogenesis of fever?
a. Brain
b. Blood vessels
c. Skeletal muscles
d. Brown adipose tissue
c. Skeletal muscles
| d. Brown adipose tissue
89
Which inflammatory signs help discriminate bacterial and viral infections?
a. Leukocytosis
b. Raised CRP
c. Raised ESR
d. Response to treatment
Raised CRP- low in Viral
| also Response to treatment
90
What proves the essential role of the body in the development of inflammation?
a. That bacterial infections trigger an inflammatory response
b. The heredity of LPS resistance
c. The efficacy of bactericidal antibiotics
d. The efficacy of bacteriostatic antibiotics
The heredity of LPS resistance
91
What are the earliest laboratory markers of severe inflammation?
a. Decreased serum albumin level
b. Raised CRP
c. Increase in the number of neutrophil leukocytes in the blood
d. Raised ESR
Increase in the number of neutrophil leukocytes in the blood,Raised CRP and Raised ESR
92
How does the body recognize tissue damage?
a. Lymphocytes recognize the damage via foreign antigens presented on the surface of MHC II molecules
b. Proteins and DNA molecules released by damaged cells activate the macrophages and the dendritic cells
c. Proteins released by the damaged cells bind to cell surface receptors and activate the immune sentinel cells
d. Tissue damage changes the cellular ATP concentration that is sensed by the macrophages
Proteins and DNA molecules released by damaged cells activate the macrophages and the dendritic cells
+
Tissue damage changes the cellular ATP concentration that is sensed by the macrophages
93
How do polymorphonuclear cells kill pathogens?
a. Neutrophils form a net using their nuclear material to trap bacteria or fungi
b. Neutrophils phagocytose bacteria and in the intracellular compartment kill them via
mitochondrial oxidants
c. Neutrophils secrete proteolytic enzymes, hydrogen peroxide and perchloric acid
that can damage extracellular pathogens
d. Neutrophils activate specific killer cells of the body: the natural killer (NK) cells and the cytotoxic lymphocytes
Neutrophils form a net using their nuclear material to trap bacteria or fungi and secrete proteolytic enzymes, hydrogen peroxide and perchloric acid
94
Which statements are true about the initiation of inflammation?
a. Inflammation is primarily a vessel reaction, which is followed by a cellular phase that involves the activation of inflammatory cells
b. The activation of neutrophils (neutrophilia) is the primary event that is followed by the extravasation of monocytes and finally leads to the activation of macrophages
c. Chemokines derived from the vessels attract inflammatory cells to the site of the injury and they trigger the inflammatory response
d. Resident macrophages and dendritic cells initiate the inflammation via the secretion of cytokines
Resident macrophages and dendritic cells initiate the inflammation via the secretion of cytokines.
Inflammation is primarily a vessel reaction, which is followed by a cellular phase that involves the activation of inflammatory cells.
(A and D)
95
Why don’t we see any difference between the clinical presentation of sepsis caused by Gram positive and that of Gram negative bacteria?
a. Because the body shows the same reaction to LPS released from the cell walls of Gram positive and Gram negative bacteria
b. Because the inflammatory reaction shows convergence at the level of intracellular signaling, they both share the same signaling events
c. Because they equally trigger the release of damage associated molecular pattern (DAMP) molecules
Because the inflammatory reaction shows convergence at the level of intracellular signaling, they both share the same signaling events
96
How does the immune system detect a viral infection?
a. Viral RNA molecules are recognized via intracellular receptors
b. Intracellular receptors detect viral DNA molecules via their alternative methylation pattern
c. Viral capsids are recognized by cell surface receptors
d. Viruses are not sensed directly, but an indirect recognition system is in effect, which relies on cell and tissue damage (e.g. cell death of infected cells)
Viral RNA molecules are recognized via intracellular receptors and Viruses are not sensed directly, but an indirect recognition system is in effect, which relies on cell and tissue damage (e.g. cell death of infected cells)
97
Which statements are true about the blockage of TNF-α?
a. Anti-TNF-α therapy (Infliximab, Remicade) is ineffective in sepsis, because TNF-α is an early cytokine, and its serum level is normalized by the time symptoms occur
b. Anti-TNF-α therapy (Infliximab, Remicade) is effective in autoimmune inflammatory diseases (e.g. IBD, Rheumatoid arthritis), because it blocks TNF-α that
is released during tissue injury
c. Anti-TNF-α therapy (Infliximab, Remicade) cannot be used in chronic inflammatory diseases (e.g. in IBD, Rheumatoid arthritis), because TNF-α is an early
mediator
d. Anti-TNF-α therapy (Infliximab, Remicade) should not be used in sepsis, because it completely blocks the immune system of the body and may promote a fulminant infection
Anti-TNF-α therapy (Infliximab, Remicade) is effective in autoimmune inflammatory diseases (e.g. IBD, Rheumatoid arthritis), because it blocks TNF-α that
is released during tissue injury and Anti-TNF-α therapy (Infliximab, Remicade) should not be used in sepsis, because it completely blocks the immune system of the body and may promote a fulminant infection
98
Which statements are true about high-mobility group box-1 (HMGB-1)?
a. HMGB-1 is a transcription factor that induces late cytokine response
b. HMGB-1 precursor is activated by the inflammasome and the active HMGB-1 is released by the cells
c. HMGB-1, as a prototypical PAMP (pathogen associated molecular pattern), activates the inflammatory cascade the same way as LPS does
d. Inactivation or binding of HMGB-1 suppresses the inflammatory responses
HMGB-1, as a prototypical PAMP (pathogen associated molecular pattern), activates the inflammatory cascade the same way as LPS does.
Inactivation or binding of HMGB-1 suppresses the inflammatory responses.
99
Which treatment modalities may have a significant anti-inflammatory effect?
a. Surgical interventions
b. Antibiotics
c. Non-steroidal anti-inflammatory drugs and steroids
d. Anti-cytokine (e.g. anti-TNF-α) therapy and immunomodulatory drugs
Anti-cytokine (e.g. anti-TNF-α) therapy and immunomodulatory drugs.
Non-steroidal anti-inflammatory drugs and steroids.
100
Which statements are true about monocytes and macrophages?
a. Tissue macrophages originate from circulatory monocytes and play a role in the late phase of inflammation; they phagocytose pathogens and remove the injured cells
b. The reticuloendothelial system (RES), or with other words the mononuclear phagocyte system (MPS), is the term that describes all monocytes and macrophages
of the body, because these cells have a common precursor and they are functionally almost identical
c. Monocytes make up 4-10% of the total amount of white blood cells
d. Monocytes (similarly to the neutrophil cells) develop in bone marrow but they remain in the circulation for a longer period than the neutrophils
The reticuloendothelial system (RES), or with other words the mononuclear phagocyte system (MPS), is the term that describes all monocytes and macrophages
of the body, because these cells have a common precursor and they are functionally almost identical.
Monocytes make up 4-10% of the total amount of white blood cells.
101
Which statements are true about the natural killer (NK) cells?
a. NK cells constitute approximately 10% of circulatory lymphocytes
b. NK cells are not true lymphocytes, because they do not express a T cell receptor, therefore we call them lymphoid cells instead
c. NK cells possess an immune effector function: they kill infected or damaged cells
d. NK cells produce TNF-α and IFN-γ and they play a role in the regulation of immune responses
NK cells possess an immune effector function: they kill infected or damaged cells.
NK cells are not true lymphocytes, because they do not express a T cell receptor, therefore we call them lymphoid cells instead.
102
Inhibition or deficiency of which molecules disrupt the LPS-induced cytokine (TNF-α) response?
a. LPS binding protein (LBP)
b. glucocorticoid steroids
c. Myeloid differentiation-2 (MD-2)
d. MyD88 (Myeloid differentiation primary response 88)
e. CD14
f. I-kappaB
g. Toll like receptor 5 (TLR5)
h. Toll like receptor 3 (TLR3)
```
LPS binding protein (LBP)
MyD88 (Myeloid differentiation primary response 88)
Toll like receptor 5 (TLR5)
Toll like receptor 3 (TLR3)
CD14 (LPS Binding)
```
103
Prevelance of DM?
8 to 9%
104
Genes play a strong role in the development of - DM Type 1 or 2?
DM type 2
105
What Percentage of health care costs is spent on diabetes care?
15%
| Cause of the late complications
106
Diabetes is the likely diagnosis if Fasting blood glucose is greater than?
7 mMole/L
107
Treatment goal for HbA1c in DM is ? (Value)
<7%
108
Reason for polyuria in DM?
Osmotic Diuresis from elevated plasma glucose
109
Possible complications of DM?
| 6
```
Retinopathy
Nephropathy
Stroke
Cardiovascular
Neuropathy
Cancer
```
110
How many diabetic patients die from Cardiovascular diseases?
80%
111
Causes of weight loss in DM?
Fat and Muscle catabolism is increased
112
Causes of Coma in Dm?
Dehydration or Ketonemia
113
MODY
Maturity onset diabetes in the young
114
LADA
Latent autoimmune diabetes in adults
115
Type 2 DM
| Why is it not called NIDDM anymore?
Some Type 2 DM patients needed Insulin treatments which confused the NON INSULIN DEPENDENT term.
More complex than the old categorization.
116
Percentage of DM types in overall cases?
1 - 5,10%
| 2 - 90,95%
117
Insulin Production in each type of DM?
1 - low or abscent
| 2 - High or Normal
118
Ketosis in each DM type? (Presence)
1 - Common to have ketosis
| 2 - Rare to have Ketosis
119
Obesity prescience in each DM type?
1 - Not a characteristic
| 2 - Common to have obesity
120
Presence of Autoantibodies and HLA involvement in each DM type?
1 - common to have Autoantibodies and HLH involvement
| 2- Not related
121
Characteristic of DM type 1A ?
Autoimmunity (majority of cases)
122
Characteristics of DM type 1B?
Idiopathic - No known cause
| Mostly in Asian or African origin patients
123
Symptoms of DM type 1 (A) ?
```
Polyuria and Polydipsia
Weight loss
Weakness
Ketosis
Ketoacidotic coma
```
124
Probable reasons for the Autoimmunity in DM type 1?
```
Gene predisposition (30%)
Viral infection
```
125
Honeymoon period of treatment of DM1 ?
Episodic halt of Beta cells destruction upon constant administration of Insulin. But it continues afterwards unfortunately.
126
Age distribution for DM type 1
No actual definitive appearance in juvenile!
| Abrupt onset could happen at any age.
127
How long until DM1 shows symptoms after autoimmunity?
May take years, variable
128
Is there always eradication of the beta cells in DM1A?
Not always
129
DM Type 2 - important characteristic
Insulin Resistance - Less of an effect of the same dose of Insulin in a healthy person
130
IFG and IGT appear in which phase of DM2 development?
Prediabetic stage
131
What Is the mathematical relationship between Insulin sensitivity and Secretion?
Hyperbolic
132
Gestational Diabetes - Major risk, time of termination
Congenital abnormalities and complications as well as DM2 for the mother.
Terminated after birth.
133
Why Insulin resistance in DM2 is believed to be Enviormental and life style related?
Out of the 19 genes related to DM2 only 1 is related to Resistance
134
Genes related to DM2
| Try to remember at least 3
```
GCK - Glucokinase
Wolframin - Ca transporter
IGF2BP2 - Protein binding to IGF2 mRNA
SLC30A8 - Zinc transporter
KCNJ11 - ATP sensitive K channel
```
135
Monogenic forms of DM
MODY
MIDD
Insulin receptor defects
136
Etiology of DM2
```
Monogenic factors - 3%
Polygenic - most
Obesity
Lifestyle
Fetal malnutrition
```
137
Prevention of DM
Lifestyle activity and Metformin
138
Possible causes of Beta cells failure in late DM2?
| Still in speculation
Genetic
Obesity
Glucose toxicity
139
Glucose toxicity
Glycation of Proteins leading to Microangiopathy
140
How much does Incretins effect the insulin response?
| Examples for Incretins?
GIP and GLP - Decreased in DM2
| 70% of the insulin response
141
Twin cycle of Insulin Resistnace - Hypothesis
Positive energy balance leads to fatty liver that leads to eventual visceral fat increase and Beta cells increase in TGA and De-differentiation of them.
142
What determines the reversibility of DM2?
Length of the disease progression
143
The genes that cause DM2 are mostly responsible for
Decreased ability to secrete insulin
144
What is the share of the CO received by the liver?
| Why?
25%
| Filter and Important enzymatic functions
145
Exocrine functions of the liver
Cholesterol
Bilirubin
Copper
146
Storage done by the liver?
Glycogen
| Iron
147
Why Detoxification not a proper term for the liver function?
Bio transformation is a process that can cause formation of harmful substances (ROS) out of drugs or other xneobiotics. Not always safe entirely.
148
Zone of the Lobules of liver
| Zone 1 - Outermost
Good oxygenation
Gluconeogenesis and Urea cycle
Sensitive to Direct toxin
149
Zone of the Lobules of liver
| Zone 3 - Innermost
Poor Oxygenation
Glycolysis and Lipogenesis
Sensitive to secondary toxins and circulatory problems or bile obstruction
150
What is the percent of all tissue residual macrophage represented by Kupffer cells? Why?
80%
| High CO percentage allows attack on Microbes infections
151
SBP - What is it and in which patients?
Spontaneous bacterial Peritonitis
| Happens more commonly in liver disease patients (Kupffer cells shortage)
152
What happens if Activation and Hydroxylation are not coupled correctly in the bio transformation pathway? What patients experience that?
Increase in Reactive substances - TIssue Damage
| Alcoholics
153
What carbohydrate metabolic pathway is inhibited in alcoholics?
Gluconogensis
154
What are the crucial protein productions damaged in Liver disease?
Albumin
| Coagulation Factors
155
Chronic Liver disease causes symptoms that are related to hormonal metabolism - which are they?
Estrogen metabolism - Hairless skin and Gynecomastia on males
156
Physical Examination of Liver disease patients
Palpable, Tender liver, Splenomegaly
Jaundice, Palmar Erythema, Spider Navi
Foetor Hepatis
157
Portal Hypertension symptoms
Acites
Caput Medusae
Esophagial Varices
158
Hepatocellular liver disease clinical appearance
| Parenchyma
Acute liver Injury - Atrophia Hepatis Flava
Chronic Hepatitis
Cirrhosis - Can progress to liver cancer
159
Hepatobilliary (Cholestatic) liver disease clinical symptomes
Obstructive Jaudice
160
Why are ASAT and ALAT could be elevated in blood?
Parenchymal Liver damage
| Liver cells die and release it
161
Cytotoxicity of Alcohol or the Acetaldehyde Metabolite
Cirrhosis, Cardiomyopathy, PNS and CNS damage, Oral cancer, Gastritis, Anemia
162
Which hepatocellular system is activated in alcoholics?
MEOS - Microsomal ethanol oxidizing system
163
Effects of the NADH/NAD ratio elevation of Alcoholics in liver
Lactic acidosis
Hypoglycemia
TCA and Beta oxidation inhibition
164
Why is it common for anesthesiologists to know if a person is alcoholic or not?
In sober state the Biotransformation of Barbiturates is elevated .
Anesthesia is could be tolerated.
165
What is the difference in sensitivity to alcohol doses between men and women?
Maximal dose causing Cirrhosis-
Men - 240 g/d
Women - 81 g/d
166
What is the most common cause for acute liver injury?
Paracetamol Poisoning
167
HepA Virus and HepE Virus
Fecal oral and Water
Never chronic
Vaccine possible
168
HepB and HepD Virus
Precutaneous, Perinatal, Sexual
Can progress to Chronic - Cirrhosis and cancer ultimately
Vaccine is available
169
HepC
Precutneous
More than 50% of cases become chronic!
No vaccine
170
Cholestatic problem enzymes elevated
GGT and ALP
171
How can we diagnose cirrhosis ?
Ultrasound (used to be only Biopsy)
172
NAFLD
| Consequence
Non alcoholic fatty liver
| Could progress to Hepatitis and ultimately to Cirrhois
173
Clinical consequences of Cirrhocis
Portal Hypertension
Loss of liver Parenchyma
Hepatorenal syndrome and Hepatocellular Carcinoma
174
Hepatorenal Syndrome
Perfectly functioning kidneys (if transplanted in healthy person)that can not function in the liver diseased patient.
175
Gastritis - Possible Causes
* Alcoholic
* Viral
* Bacterial (H. Pylori)
* Drug induced
176
Common Symptoms of Gastric Diseases
* Vomiting
* Epigastric pain
* hyperacidity (reflux)/ hypoacidity
* bleeding - Melena (in stool)
* Vitamin-B12 deficiency
177
Etiology of Peptic ulcer disease (PUD)
* Helicobacter pylori infection
* NSAIDs consumption
* Viral Infections
* Gastrinoma (Zollinger-Ellison S.)
178
Where does H.Pylori attack in infections?
Antrum of Stomach
179
How does Aspirin causes Peptic Ulcers?
Causes inhibition of PGE2 formation by COX1 therefore less activation of the PGE2R on Parietal Cell - Increased HCl production!
180
Complications of Peptic Ulcers
* GERD
* Bleeding
* Perforation of Bowel Wall
* Gastric Cancer in rare cases
181
Secondary lactose malabsorption:
* Small intestinal bacterial overgrowth or Infectious
* Celiac disease
* IBD (especially Crohn)
* Drug-induced enteritis
* Irradiation induced enteritis
182
Primary lactose malabsorption:
* Acquired primary lactase deficiency
* Developmental lactose malabsorption
* Congenital lactase deficiency
183
Celiac disease - Prevalence Correlates with:
Genetic Predisposition: HLA-DQ2>HLA-DQ8
| Lifestyle Predisposition: High wheat consumption
184
Celiac disease - Serum autoantibodies:
IgA anti-gliadin
| IgA anti-tTG(tissue transglutaminase)
185
Celiac - Classic symptoms: (6)
* Diarrhea, abdominal pain
* Growth failure in children, weight loss in adults
* High temperature
* Severe anemia
* Neurologic disorders from deficiencies of B vitamins
* Osteopenia from deficiency of vitamin D and calcium
186
Celiac - Subclinical disease symptoms (3)
* fatigue
* borderline iron deficiency
* unexplained elevations in serum aminotransferases
187
Non-GI manifestations of Celiac:
* Arthritis
* Iron deficiency
* Metabolic bone disease
* Kidney Disease: (glomerular IgA deposition in 33% of patients)
188
Celiac Associated - Dermatitis herpetiformis:
Autoantibodies against epidermal transglutaminase (homologue to tTG). Responses to Gluten Withdrawal!
189
Celiac Associated - DM type 1:
Share the genetic Risk region - HLA-DQ
190
Celiac Associated - Selective IgA Deficiency:
Celiac disease is found in 8% of them
191
Celiac Associated - Down Syndrome:
20x risk of developing Celiac Disease
192
Celiac Associated - Hashimoto:
Increased Incidence in Celiac
193
Celiac Associated - IBD:
10x risk of developing IBD
194
Celiac Disease Terminal Conditions:
Increased Risk of Lymphoma, GI Cancer and General Mortality .
195
What is the dominant Cytokine appearing in IBD (UC,CD)?
IL17
196
GI Clinical Manifestations of Ulcerative Colitis:
* Diarrhea, usually associated with blood
* Colicky abdominal pain, urgency, tenesmus, and incontinence.
* Frequent Discharge of blood and mucus.
* Systemic Symptoms: fever, fatigue, weight loss
197
Non-GI Clinical Manifestations of Ulcerative Colitis:
* Arthritis (most frequent)
* Uveitis and Episcleritis
* Skin lesions
* Hepatobiliary: primary sclerosing cholangitis, fatty liver
* autoimmune liver disease
* Venous And arterial thromboembolism
* Autoimmune hemolytic anemia
198
Hallmarks of Crohn Disease:
* Fatigue
* Prolonged Diarrhea with crampy abdominal pain
* Weight loss and malabsorption(steatorrhea)
* Fever
* Occult Bleeding (gross bleeding is infrequent).
199
Pathological Findings on Intestine (commonly on distal ileum) in Crohn's:
* Fat Wrapping around
* Muscle Hypertrophy
* Cobblestone Appearance
* Fissures
200
Crohn's Differential diagnoses:
* IBS
* Lactose Intolerance
* Infectious Colitis
* UC
201
Irritable bowel syndrome (IBS) diagnosis:
Exclusion of other GI diseases!
202
Symptoms of Irritable bowel syndrome (IBS) :
Chronic abdominal pain and Altered bowel habits
203
Risk Factors for Colorectal Cancer:
* APC chromosome 5.: Germline mutations - 5% of cases
| * IBD, obesity, smoking, irradiation, alcohol, diabetes, infectious agents and Kidney Transplantation.
204
Familial adenomatous polyposis (FAP):
* <1%of CRC(!)
* Numerous colonic adenomas appear in childhood.
* First symptoms at age of ~16 years
* Colon cancer in 90%of untreated patients by the age of 45.
205
Role of APC in CRC initiation:
Transcription Factor that Prevents the WNT - Beta Catenin pathway from causing transcribing Cell proliferation and Migration.
206
Hereditary risk factors of CRC:MAP - MUTYH associated polyposis
MUTYH repairs oxidative DNA damage
•APC gene is susceptible to oxidative damage
•MUTYH failure leads to somatic mutations in APC, and to a polyposis phenotype.
207
Hereditary risk factors of CRC: Lynch syndrome
Genetic defect in one of the DNA mismatch repair genes - Increased risk of multiple cancer kinds.
208
Protective factors from CRC: Mannyyy
* Physical activity
* Diet high in fruits and vegetables (50% lower risk!!!!)
* Higher fiber intake:10 g/day increase in dietary fiber reduces CRC risk by 10%(!)
* Fish consumption: omega-3 fatty acids
* Folate intake:inhibits pathogenesis of cancer
* Vitamin B6 intake: ~20% decrease in CRC risk
* Vitamin D:Vitamin D and its metabolites inhibit CRC.
* NSAID regular use: reduces risk of colonic adenomas and CRC by 20-40%
